miladalsh/processed_scinews_dataset · Datasets at Hugging Face

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Chemical imaging based on mid-infrared (MIR) spectroscopic contrast is an important technique with a myriad of applications, including biomedical imaging and environmental monitoring. Current MIR cameras, however, lack performance and are much less affordable than mature Si-based devices, which operate in the visible and near-infrared regions. Here, we demonstrate fast MIR chemical imaging through non-degenerate two-photon absorption (NTA) in a standard Si-based charge-coupled device (CCD). We show that wide-field MIR images can be obtained at 100 ms exposure times using picosecond pulse energies of only a few femtojoules per pixel through NTA directly on the CCD chip. Because this on-chip approach does not rely on phase matching, it is alignment-free and does not necessitate complex postprocessing of the images. We emphasize the utility of this technique through chemically selective MIR imaging of polymers and biological samples, including MIR videos of moving targets, physical processes and live nematodes. Introduction Many fundamental molecular vibrations have energies in the mid-infrared (MIR) window—a wavelength region that stretches from approximately 2 to 10 μm. For this reason, the MIR range is of particular interest for spectroscopic imaging. The ability to generate images with chemical selectivity is of direct relevance to a myriad of fields, including the implementation of MIR-based imaging for biomedical mapping of tissues 1 , 2 , 3 , inspection of industrial ceramics 4 , stand-off detection of materials 5 , mineral sensing 6 , 7 , and environmental monitoring 8 , among others. Given its unique analytical capabilities, it is perhaps surprising that MIR-based imaging is not a more widely adopted technology for chemical mapping. The relatively scarce implementation of MIR imaging has been due in part to the lack of bright and affordable light sources in this range, although recent developments in MIR light source technology have largely overcome this problem 9 , 10 , 11 . Nonetheless, a remaining limitation is the performance and high cost of the MIR cameras. Current cameras are based on low bandgap materials, such as HgCdTe (MCT) or InSb, which inherently suffer from thermally excited electronic noise 12 . Cryogenic cooling helps to suppress this noise, but it renders the MIR camera a much less practical and affordable detector than mature Si-based detectors for the visible and near-IR. Electronically cooled MCT detectors are a promising alternative, although the matrixes of such detector arrays are still of low density and are not yet on par with high definition Si-based CCD cameras. Recognizing the attractive features of Si-based cameras, several strategies have been developed that aim to convert information from the MIR range into the visible/NIR range, thus making it possible to indirectly capture MIR signatures with a Si detector. A very recent development is the use of an entangled MIR/visible photon pair, which allows MIR imaging and microscopy utilizing nonlinear interferometry for detecting visible photons entangled to their MIR counterparts on a Si-based camera 13 , 14 , 15 . Another strategy accomplishes the MIR-to-visible conversion by using a nonlinear optical (NLO) response of the sample, such as in third-order sum-frequency generation (TSFG) microscopy 16 . Photothermal imaging, which probes the MIR-induced changes in the sample with a secondary visible beam, is another example of this approach 17 , 18 , 19 , 20 , 21 . An alternative but related method is the acoustic detection of the MIR photothermal effect, which has recently been demonstrated 22 . Another technique uses a nonlinear optical crystal placed after the sample to up-convert the MIR radiation with an additional pump beam through the process of sum-frequency generation (SFG) 23 , 24 , 25 , 26 , 27 , 28 , 29 . The visible/NIR radiation produced can be efficiently registered with a high bandgap semiconductor detector. Elegant video-rate MIR up-conversion imaging has recently been accomplished with a Si-based camera at room temperature, offering an attractive alternative to imaging with MCT focal plane arrays 30 . A possible downside of SFG up-conversion techniques is the requirement of phase matching of the MIR radiation with the pump beam in the NLO medium. This requirement implies crystal rotation to enable the multiple projections needed for capturing a single image and postprocessing for each measured frame for image reconstruction. An alternative to utilizing an optical nonlinearity of the sample or a dedicated conversion crystal for indirect MIR detection (SFG up-conversion) is the use of the NLO properties of the detector itself. In particular, the process of non-degenerate two-photon absorption (NTA) in wide bandgap semiconductor materials has been shown to permit the detection of MIR radiation at room temperature with the help of an additional visible or NIR probe beam 31 , 32 , 33 , 34 . In NTA, the signal scales linearly with the MIR intensity with detection sensitivities that rival those of cooled MCT detectors 31 . Compared with SFG-based up-conversion, NTA does not depend on phase matching and avoids the need for an NLO crystal altogether, offering a much simpler detection strategy. Moreover, the nonlinear absorption coefficient drastically increases with the energy ratio of the interacting photons 35 , 36 , 37 , 38 , 39 , allowing detection over multiple spectral octaves. Although NTA has been shown to enable efficient MIR detection with single pixel detectors, its advantages have not yet been translated to imaging with efficient Si-based cameras. Here, we report rapid, chemically selective MIR imaging using NTA in a standard CCD camera at room temperature. The nature of nonlinear absorption enhancement for direct-band semiconductors has been modelled with allowed-forbidden transitions between two parabolic bands 37 , 38 , 39 , 40 . The nonlinear absorption coefficient α 2 for photon energies ħω pump and ħω MIR can be written as 40 : $$\\begin{array}{l}\\alpha _2\\left( {\\omega _{\\mathrm{p}},\\omega _{{\\mathrm{MIR}}}} \\right) = K\\frac{{\\sqrt {E_{\\mathrm{p}}} }}{{n_{\\mathrm{p}}n_{{\\mathrm{MIR}}}E_{\\mathrm{g}}^3}}F\\left( {x_{\\mathrm{p}},x_{{\\mathrm{MIR}}}} \\right)\\\\ F = \\frac{{\\left( {x_{\\mathrm{p}} + x_{{\\mathrm{MIR}}} - 1} \\right)^{3/2}}}{{2^7x_{\\mathrm{p}}\\left( {x_{{\\mathrm{MIR}}}} \\right)^2}}\\left( {\\frac{1}{{x_{\\mathrm{p}}}} + \\frac{1}{{x_{{\\mathrm{MIR}}}}}} \\right)^2,x_{\\mathrm{p}} = \\frac{{\\hbar \\omega _{\\mathrm{p}}}}{{E_{\\mathrm{g}}}},x_{{\\mathrm{MIR}}} = \\frac{{\\hbar \\omega _{{\\mathrm{MIR}}}}}{{E_{\\mathrm{g}}}}\\end{array}$$ (1) where E p is the Kane energy parameter, n p and n MIR are refractive indices and", "role": "user" }, { "content": "The MIR range of the electromagnetic spectrum, which roughly covers light in the wavelength regime between 3 to 10 micrometers, coincides with the energies of fundamental molecular vibrations. Utilizing this light for the purpose of imaging can produce stills with chemical specificity, i.e. images with contrast derived from the chemical composition of the sample. Unfortunately, detecting MIR light is not as simple as detecting light in the visible regime. Current MIR cameras exhibit excellent sensitivity but are very sensitive to thermal noise. In addition, the fastest MIR cameras suitable for chemical mapping have sensors with low pixel numbers, thus limiting imaging at high definition. To overcome this problem, several strategies have been developed for shifting the information carried by MIR light into the visible range, followed by efficient detection with a modern Si-based camera. Unlike MIR cameras, Si-based cameras exhibit low noise characteristics and have high pixel densities, making them more attractive candidates for high performance imaging applications. The required MIR-to-visible conversion scheme, however, can be rather complicated. Presently, the most direct way for achieving the desired color conversion is through the use of a nonlinear optical crystal. When the MIR light and an additional near-infrared (NIR) light beam are coincident in the crystal, a visible light beam is generated through the process of sum-frequency generation, or SFG for short. Although the SFG up-conversion trick works well, it is sensitive to alignment and it requires numerous orientations of the crystal to produce a single MIR-derived image on the Si camera. In a new paper published in Light Science & Applications, a team of scientists from the University of California, Irvine, describes a simple method for detecting MIR images with a Si camera. Instead of using the optical nonlinearity of a crystal, they used the nonlinear optical properties of the Si chip itself to enable a MIR specific response in the camera. In particular, they used the process of non-degenerate two-photon absorption (NTA), which, with the help of an additional NIR 'pump' beam, triggers the generation of photo-induced charge carriers in Si when the MIR light illuminates the sensor. Compared to SFG up-conversion, the NTA method avoids the use of nonlinear up-conversion crystals altogether and it is virtually free of alignment artifacts, making MIR imaging with Si-based cameras significantly simpler. The team, led by Dr. Dmitry Fishman and Dr. Eric Potma, first established that Si is a material suitable for MIR detection through NTA. Using MIR light with pulse energies in the femtojoule (fJ, 10-12 J) range, they found that NTA in silicon is sufficiently efficient for detecting MIR. This principle enabled them to perform vibrational spectroscopy measurements of organic liquids employing just a simple Si photodiode as the detector. The team then moved to replace the photodiode with a charge-coupled device (CDD) camera, which also uses silicon as the photosensitive material. Through NTA, they were able to capture MIR-derived images on a 1392x1040 pixel sensor at 100 ms exposure times, yielding chemically selective images of several polymer and biological materials as well as living nematodes. Despite using technology not specifically optimized for NTA, the team observed the ability to detect small (10-2) changes in optical density (OD) in the image. \"We are excited to offer this new detection strategy to those who use MIR light for imaging,\" says David Knez, one of the team members. \"We have high hopes that the simplicity and versatility of this approach allows for the broad adoption and development of the technology.\" Adding that NTA may speed up analysis in a wide variety of fields, such as pharmaceutical quality assurance, geologic mineral sampling, or microscopic inspection of biological samples. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Chemical imaging based on mid-infrared (MIR) spectroscopic contrast is an important technique with a myriad of applications, including biomedical imaging and environmental monitoring. Current MIR cameras, however, lack performance and are much less affordable than mature Si-based devices, which operate in the visible and near-infrared regions. Here, we demonstrate fast MIR chemical imaging through non-degenerate two-photon absorption (NTA) in a standard Si-based charge-coupled device (CCD). We show that wide-field MIR images can be obtained at 100 ms exposure times using picosecond pulse energies of only a few femtojoules per pixel through NTA directly on the CCD chip. Because this on-chip approach does not rely on phase matching, it is alignment-free and does not necessitate complex postprocessing of the images. We emphasize the utility of this technique through chemically selective MIR imaging of polymers and biological samples, including MIR videos of moving targets, physical processes and live nematodes. Introduction Many fundamental molecular vibrations have energies in the mid-infrared (MIR) window—a wavelength region that stretches from approximately 2 to 10 μm. For this reason, the MIR range is of particular interest for spectroscopic imaging. The ability to generate images with chemical selectivity is of direct relevance to a myriad of fields, including the implementation of MIR-based imaging for biomedical mapping of tissues 1 , 2 , 3 , inspection of industrial ceramics 4 , stand-off detection of materials 5 , mineral sensing 6 , 7 , and environmental monitoring 8 , among others. Given its unique analytical capabilities, it is perhaps surprising that MIR-based imaging is not a more widely adopted technology for chemical mapping. The relatively scarce implementation of MIR imaging has been due in part to the lack of bright and affordable light sources in this range, although recent developments in MIR light source technology have largely overcome this problem 9 , 10 , 11 . Nonetheless, a remaining limitation is the performance and high cost of the MIR cameras. Current cameras are based on low bandgap materials, such as HgCdTe (MCT) or InSb, which inherently suffer from thermally excited electronic noise 12 . Cryogenic cooling helps to suppress this noise, but it renders the MIR camera a much less practical and affordable detector than mature Si-based detectors for the visible and near-IR. Electronically cooled MCT detectors are a promising alternative, although the matrixes of such detector arrays are still of low density and are not yet on par with high definition Si-based CCD cameras. Recognizing the attractive features of Si-based cameras, several strategies have been developed that aim to convert information from the MIR range into the visible/NIR range, thus making it possible to indirectly capture MIR signatures with a Si detector. A very recent development is the use of an entangled MIR/visible photon pair, which allows MIR imaging and microscopy utilizing nonlinear interferometry for detecting visible photons entangled to their MIR counterparts on a Si-based camera 13 , 14 , 15 . Another strategy accomplishes the MIR-to-visible conversion by using a nonlinear optical (NLO) response of the sample, such as in third-order sum-frequency generation (TSFG) microscopy 16 . Photothermal imaging, which probes the MIR-induced changes in the sample with a secondary visible beam, is another example of this approach 17 , 18 , 19 , 20 , 21 . An alternative but related method is the acoustic detection of the MIR photothermal effect, which has recently been demonstrated 22 . Another technique uses a nonlinear optical crystal placed after the sample to up-convert the MIR radiation with an additional pump beam through the process of sum-frequency generation (SFG) 23 , 24 , 25 , 26 , 27 , 28 , 29 . The visible/NIR radiation produced can be efficiently registered with a high bandgap semiconductor detector. Elegant video-rate MIR up-conversion imaging has recently been accomplished with a Si-based camera at room temperature, offering an attractive alternative to imaging with MCT focal plane arrays 30 . A possible downside of SFG up-conversion techniques is the requirement of phase matching of the MIR radiation with the pump beam in the NLO medium. This requirement implies crystal rotation to enable the multiple projections needed for capturing a single image and postprocessing for each measured frame for image reconstruction. An alternative to utilizing an optical nonlinearity of the sample or a dedicated conversion crystal for indirect MIR detection (SFG up-conversion) is the use of the NLO properties of the detector itself. In particular, the process of non-degenerate two-photon absorption (NTA) in wide bandgap semiconductor materials has been shown to permit the detection of MIR radiation at room temperature with the help of an additional visible or NIR probe beam 31 , 32 , 33 , 34 . In NTA, the signal scales linearly with the MIR intensity with detection sensitivities that rival those of cooled MCT detectors 31 . Compared with SFG-based up-conversion, NTA does not depend on phase matching and avoids the need for an NLO crystal altogether, offering a much simpler detection strategy. Moreover, the nonlinear absorption coefficient drastically increases with the energy ratio of the interacting photons 35 , 36 , 37 , 38 , 39 , allowing detection over multiple spectral octaves. Although NTA has been shown to enable efficient MIR detection with single pixel detectors, its advantages have not yet been translated to imaging with efficient Si-based cameras. Here, we report rapid, chemically selective MIR imaging using NTA in a standard CCD camera at room temperature. The nature of nonlinear absorption enhancement for direct-band semiconductors has been modelled with allowed-forbidden transitions between two parabolic bands 37 , 38 , 39 , 40 . The nonlinear absorption coefficient α 2 for photon energies ħω pump and ħω MIR can be written as 40 : $$\begin{array}{l}\alpha _2\left( {\omega _{\mathrm{p}},\omega _{{\mathrm{MIR}}}} \right) = K\frac{{\sqrt {E_{\mathrm{p}}} }}{{n_{\mathrm{p}}n_{{\mathrm{MIR}}}E_{\mathrm{g}}^3}}F\left( {x_{\mathrm{p}},x_{{\mathrm{MIR}}}} \right)\\ F = \frac{{\left( {x_{\mathrm{p}} + x_{{\mathrm{MIR}}} - 1} \right)^{3/2}}}{{2^7x_{\mathrm{p}}\left( {x_{{\mathrm{MIR}}}} \right)^2}}\left( {\frac{1}{{x_{\mathrm{p}}}} + \frac{1}{{x_{{\mathrm{MIR}}}}}} \right)^2,x_{\mathrm{p}} = \frac{{\hbar \omega _{\mathrm{p}}}}{{E_{\mathrm{g}}}},x_{{\mathrm{MIR}}} = \frac{{\hbar \omega _{{\mathrm{MIR}}}}}{{E_{\mathrm{g}}}}\end{array}$$ (1) where E p is the Kane energy parameter, n p and n MIR are refractive indices and<|im_end|> <|im_start|>assistant The MIR range of the electromagnetic spectrum, which roughly covers light in the wavelength regime between 3 to 10 micrometers, coincides with the energies of fundamental molecular vibrations. Utilizing this light for the purpose of imaging can produce stills with chemical specificity, i.e. images with contrast derived from the chemical composition of the sample. Unfortunately, detecting MIR light is not as simple as detecting light in the visible regime. Current MIR cameras exhibit excellent sensitivity but are very sensitive to thermal noise. In addition, the fastest MIR cameras suitable for chemical mapping have sensors with low pixel numbers, thus limiting imaging at high definition. To overcome this problem, several strategies have been developed for shifting the information carried by MIR light into the visible range, followed by efficient detection with a modern Si-based camera. Unlike MIR cameras, Si-based cameras exhibit low noise characteristics and have high pixel densities, making them more attractive candidates for high performance imaging applications. The required MIR-to-visible conversion scheme, however, can be rather complicated. Presently, the most direct way for achieving the desired color conversion is through the use of a nonlinear optical crystal. When the MIR light and an additional near-infrared (NIR) light beam are coincident in the crystal, a visible light beam is generated through the process of sum-frequency generation, or SFG for short. Although the SFG up-conversion trick works well, it is sensitive to alignment and it requires numerous orientations of the crystal to produce a single MIR-derived image on the Si camera. In a new paper published in Light Science & Applications, a team of scientists from the University of California, Irvine, describes a simple method for detecting MIR images with a Si camera. Instead of using the optical nonlinearity of a crystal, they used the nonlinear optical properties of the Si chip itself to enable a MIR specific response in the camera. In particular, they used the process of non-degenerate two-photon absorption (NTA), which, with the help of an additional NIR 'pump' beam, triggers the generation of photo-induced charge carriers in Si when the MIR light illuminates the sensor. Compared to SFG up-conversion, the NTA method avoids the use of nonlinear up-conversion crystals altogether and it is virtually free of alignment artifacts, making MIR imaging with Si-based cameras significantly simpler. The team, led by Dr. Dmitry Fishman and Dr. Eric Potma, first established that Si is a material suitable for MIR detection through NTA. Using MIR light with pulse energies in the femtojoule (fJ, 10-12 J) range, they found that NTA in silicon is sufficiently efficient for detecting MIR. This principle enabled them to perform vibrational spectroscopy measurements of organic liquids employing just a simple Si photodiode as the detector. The team then moved to replace the photodiode with a charge-coupled device (CDD) camera, which also uses silicon as the photosensitive material. Through NTA, they were able to capture MIR-derived images on a 1392x1040 pixel sensor at 100 ms exposure times, yielding chemically selective images of several polymer and biological materials as well as living nematodes. Despite using technology not specifically optimized for NTA, the team observed the ability to detect small (10-2) changes in optical density (OD) in the image. "We are excited to offer this new detection strategy to those who use MIR light for imaging," says David Knez, one of the team members. "We have high hopes that the simplicity and versatility of this approach allows for the broad adoption and development of the technology." Adding that NTA may speed up analysis in a wide variety of fields, such as pharmaceutical quality assurance, geologic mineral sampling, or microscopic inspection of biological samples. <|im_end|>

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1105, 706, 1027, 1646, 839, 449, 5535, 15548, 22886, 34692, 1990, 1403, 1370, 57565, 21562, 220, 1806, 1174, 220, 1987, 1174, 220, 2137, 1174, 220, 1272, 662, 578, 75098, 44225, 36706, 19581, 220, 17, 369, 69010, 49969, 10044, 100, 57971, 14155, 323, 10044, 100, 57971, 386, 2871, 649, 387, 5439, 439, 220, 1272, 551, 27199, 59, 7413, 90, 1686, 15523, 75, 11281, 7288, 721, 17, 59, 2414, 7, 29252, 33796, 721, 36802, 92650, 90, 79, 39254, 59, 33796, 721, 3052, 59, 92650, 90, 44, 2871, 3500, 3500, 1144, 1315, 8, 284, 735, 59, 38118, 3052, 59, 27986, 314, 36, 15511, 59, 92650, 90, 79, 76642, 3954, 3052, 77, 15511, 59, 92650, 90, 79, 3500, 77, 62, 3052, 59, 92650, 90, 44, 2871, 76642, 36, 15511, 59, 92650, 90, 70, 3500, 61, 18, 3500, 37, 59, 2414, 7, 314, 87, 15511, 59, 92650, 90, 79, 39254, 87, 62, 3052, 59, 92650, 90, 44, 2871, 3500, 3500, 1144, 1315, 8, 3505, 435, 284, 1144, 38118, 3052, 59, 2414, 7, 314, 87, 15511, 59, 92650, 90, 79, 3500, 489, 865, 62, 3052, 59, 92650, 90, 44, 2871, 76642, 482, 220, 16, 92, 1144, 1315, 30876, 90, 18, 14, 17, 76642, 3052, 17, 61, 22, 87, 15511, 59, 92650, 90, 79, 3500, 59, 2414, 7, 314, 87, 62, 3052, 59, 92650, 90, 44, 2871, 3500, 3500, 1144, 1315, 30876, 17, 3500, 59, 2414, 7, 29252, 38118, 90, 16, 92, 3052, 87, 15511, 59, 92650, 90, 79, 3500, 3500, 489, 1144, 38118, 90, 16, 92, 3052, 87, 62, 3052, 59, 92650, 90, 44, 2871, 3500, 3500, 3500, 1144, 1315, 30876, 17, 13095, 15511, 59, 92650, 90, 79, 3500, 284, 1144, 38118, 3052, 59, 71, 2308, 1144, 33796, 721, 36802, 92650, 90, 79, 3500, 78386, 36, 15511, 59, 92650, 90, 70, 3500, 39254, 87, 62, 3052, 59, 92650, 90, 44, 2871, 76642, 284, 1144, 38118, 3052, 59, 71, 2308, 1144, 33796, 721, 3052, 59, 92650, 90, 44, 2871, 3500, 76642, 3052, 36, 15511, 59, 92650, 90, 70, 3500, 3500, 59, 408, 90, 1686, 92, 14415, 320, 16, 8, 1405, 469, 281, 374, 279, 46656, 4907, 5852, 11, 308, 281, 323, 308, 386, 2871, 527, 19914, 3104, 15285, 323, 128257, 198, 128256, 78191, 198, 791, 386, 2871, 2134, 315, 279, 66669, 20326, 11, 902, 17715, 14861, 3177, 304, 279, 46406, 17942, 1990, 220, 18, 311, 220, 605, 19748, 442, 2481, 11, 23828, 3422, 449, 279, 49969, 315, 16188, 31206, 78352, 13, 10377, 4954, 420, 3177, 369, 279, 7580, 315, 32758, 649, 8356, 2103, 82, 449, 11742, 76041, 11, 602, 1770, 13, 5448, 449, 13168, 14592, 505, 279, 11742, 18528, 315, 279, 6205, 13, 19173, 11, 54626, 386, 2871, 3177, 374, 539, 439, 4382, 439, 54626, 3177, 304, 279, 9621, 17942, 13, 9303, 386, 2871, 18632, 31324, 9250, 27541, 719, 527, 1633, 16614, 311, 29487, 12248, 13, 763, 5369, 11, 279, 26731, 386, 2871, 18632, 14791, 369, 11742, 13021, 617, 26148, 449, 3428, 13252, 5219, 11, 8617, 33994, 32758, 520, 1579, 7419, 13, 2057, 23075, 420, 3575, 11, 3892, 15174, 617, 1027, 8040, 369, 32931, 279, 2038, 11953, 555, 386, 2871, 3177, 1139, 279, 9621, 2134, 11, 8272, 555, 11297, 18468, 449, 264, 6617, 12095, 6108, 6382, 13, 27140, 386, 2871, 18632, 11, 12095, 6108, 18632, 31324, 3428, 12248, 17910, 323, 617, 1579, 13252, 90816, 11, 3339, 1124, 810, 19411, 11426, 369, 1579, 5178, 32758, 8522, 13, 578, 2631, 386, 2871, 4791, 92236, 14747, 13155, 11, 4869, 11, 649, 387, 4856, 17395, 13, 27740, 398, 11, 279, 1455, 2167, 1648, 369, 32145, 279, 12974, 1933, 14747, 374, 1555, 279, 1005, 315, 264, 75098, 29393, 26110, 13, 3277, 279, 386, 2871, 3177, 323, 459, 5217, 3221, 3502, 82482, 320, 45, 2871, 8, 3177, 24310, 527, 23828, 1748, 304, 279, 26110, 11, 264, 9621, 3177, 24310, 374, 8066, 1555, 279, 1920, 315, 2694, 79412, 9659, 11, 477, 328, 12270, 369, 2875, 13, 10541, 279, 328, 12270, 709, 15204, 4464, 14397, 4375, 1664, 11, 433, 374, 16614, 311, 17632, 323, 433, 7612, 12387, 89935, 315, 279, 26110, 311, 8356, 264, 3254, 386, 2871, 72286, 2217, 389, 279, 12095, 6382, 13, 763, 264, 502, 5684, 4756, 304, 8828, 10170, 612, 32625, 11, 264, 2128, 315, 14248, 505, 279, 3907, 315, 7188, 11, 72385, 11, 16964, 264, 4382, 1749, 369, 54626, 386, 2871, 5448, 449, 264, 12095, 6382, 13, 12361, 315, 1701, 279, 29393, 2536, 1074, 10981, 315, 264, 26110, 11, 814, 1511, 279, 75098, 29393, 6012, 315, 279, 12095, 16797, 5196, 311, 7431, 264, 386, 2871, 3230, 2077, 304, 279, 6382, 13, 763, 4040, 11, 814, 1511, 279, 1920, 315, 2536, 6953, 19927, 1403, 63837, 26934, 44225, 320, 6542, 32, 705, 902, 11, 449, 279, 1520, 315, 459, 5217, 99854, 364, 79, 1538, 6, 24310, 11, 31854, 279, 9659, 315, 6685, 38973, 6900, 35991, 304, 12095, 994, 279, 386, 2871, 3177, 44087, 988, 279, 12271, 13, 59813, 311, 328, 12270, 709, 15204, 4464, 11, 279, 452, 15559, 1749, 55952, 279, 1005, 315, 75098, 709, 15204, 4464, 48473, 31155, 323, 433, 374, 21907, 1949, 315, 17632, 36136, 11, 3339, 386, 2871, 32758, 449, 12095, 6108, 18632, 12207, 35388, 13, 578, 2128, 11, 6197, 555, 2999, 13, 88231, 17019, 1543, 323, 2999, 13, 16645, 14020, 1764, 11, 1176, 9749, 430, 12095, 374, 264, 3769, 14791, 369, 386, 2871, 18468, 1555, 452, 15559, 13, 12362, 386, 2871, 3177, 449, 28334, 49969, 304, 279, 5103, 998, 73, 283, 273, 320, 69, 41, 11, 220, 605, 12, 717, 622, 8, 2134, 11, 814, 1766, 430, 452, 15559, 304, 51692, 374, 40044, 11297, 369, 54626, 386, 2871, 13, 1115, 17966, 9147, 1124, 311, 2804, 17358, 1697, 66425, 51856, 22323, 315, 17808, 67849, 51297, 1120, 264, 4382, 12095, 4604, 31559, 536, 439, 279, 32314, 13, 578, 2128, 1243, 7882, 311, 8454, 279, 4604, 31559, 536, 449, 264, 6900, 1824, 283, 50185, 3756, 320, 34, 4195, 8, 6382, 11, 902, 1101, 5829, 51692, 439, 279, 7397, 19245, 3769, 13, 17331, 452, 15559, 11, 814, 1051, 3025, 311, 12602, 386, 2871, 72286, 5448, 389, 264, 220, 10125, 17, 87, 6849, 15, 13252, 12271, 520, 220, 1041, 10030, 14675, 3115, 11, 78504, 8590, 2740, 44010, 5448, 315, 3892, 47393, 323, 24156, 7384, 439, 1664, 439, 5496, 24566, 266, 2601, 13, 18185, 1701, 5557, 539, 11951, 34440, 369, 452, 15559, 11, 279, 2128, 13468, 279, 5845, 311, 11388, 2678, 320, 605, 12, 17, 8, 4442, 304, 29393, 17915, 320, 2114, 8, 304, 279, 2217, 13, 330, 1687, 527, 12304, 311, 3085, 420, 502, 18468, 8446, 311, 1884, 889, 1005, 386, 2871, 3177, 369, 32758, 1359, 2795, 6941, 735, 55506, 11, 832, 315, 279, 2128, 3697, 13, 330, 1687, 617, 1579, 16388, 430, 279, 40075, 323, 60112, 315, 420, 5603, 6276, 369, 279, 7353, 25375, 323, 4500, 315, 279, 5557, 1210, 31470, 430, 452, 15559, 1253, 4732, 709, 6492, 304, 264, 7029, 8205, 315, 5151, 11, 1778, 439, 35410, 4367, 44701, 11, 3980, 39227, 25107, 25936, 11, 477, 90090, 26767, 315, 24156, 10688, 13, 220, 128257, 198 ]

2,367

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Objective To identify all known ties between the medical product industry and the healthcare ecosystem. Design Scoping review. Methods From initial literature searches and expert input, a map was created to show the network of medical product industry ties across parties and activities in the healthcare ecosystem. Through a scoping review, the ties were then verified, cataloged, and characterized, with data abstracted on types of industry ties (financial, non-financial), applicable policies for conflict of interests, and publicly available data sources. Main outcome measures Presence and types of medical product industry ties to activities and parties, presence of policies for conflict of interests, and publicly available data. Results A map derived through synthesis of 538 articles from 37 countries shows an extensive network of medical product industry ties to activities and parties in the healthcare ecosystem. Key activities include research, healthcare education, guideline development, formulary selection, and clinical care. Parties include non-profit entities, the healthcare profession, the market supply chain, and government. The medical product industry has direct ties to all parties and some activities through multiple pathways; direct ties extend through interrelationships among parties and activities. The most frequently identified parties were within the healthcare profession, with individual professionals described in 422 (78%) of the included studies. More than half (303, 56%) of the publications documented medical product industry ties to research, with clinical care (156, 29%), health professional education (145, 27%), guideline development (33, 6%), and formulary selection (8, 1%) appearing less often. Policies for conflict of interests exist for some financial and a few non-financial ties; publicly available data sources seldom describe or quantify these ties. Conclusions An extensive network of medical product industry ties to activities and parties exists in the healthcare ecosystem. Policies for conflict of interests and publicly available data are lacking, suggesting that enhanced oversight and transparency are needed to protect patient care from commercial influence and to ensure public trust. Introduction In an influential 2009 report, the Institute of Medicine described a multifaceted healthcare ecosystem rife with industry influence. 1 Central to the ecosystem are healthcare providers, researchers, clinical care facilities, journals, professional societies, and other healthcare institutions and supporting organizations engaged in medicine’s core professional activities: providing beneficial care to patients, conducting valid research, and providing evidence based clinical education and guidance. In so doing, these individuals and institutions frequently collaborate with pharmaceutical, medical device, and biotechnology product manufacturers. 1 2 3 4 5 Although these for profit entities play a crucial role in the ecosystem, particularly in developing new tests and treatments, their primary objective is to ensure financial returns to shareholders. Thus, industry collaborations inevitably introduce potential commercial bias into the healthcare ecosystem. With absent rigorous conflict of interest oversight across the entire system, the Institute of Medicine warned that medicine’s extensive ties to the medical product industry “threaten the integrity of scientific investigations, the objectivity of medical education, the quality of patient care, and the public’s trust in medicine.” 1 Controlling conflict of interest across the ecosystem, however, requires a system level understanding of how influence can enter and circulate through it. Research on the influence of the medical product industry is voluminous and expanding, aided in no small part by new data sources such as Open Payments, 6 7 8 9 a US federal database that makes public nearly all payments to physicians and teaching hospitals by pharmaceutical, medical device, and other healthcare product manufacturers. Other lines of inquiry have begun to explore the ties between medical product companies and regulators, patient advocacy groups, and other influential parties in the healthcare ecosystem. 3 4 10 11 12 And the analytic lens has broadened to include not only financial ties but also non-financial ones, such as medical product manufacturers offering healthcare professionals research data, authorship, and other opportunities for professional advancement. 13 14 15 Yet, with few exceptions, 1 2 16 17 most analyses focus on one or two narrow types of ties between the medical product industry and a single party, such as healthcare professionals, hospitals, or journals, or a single activity, such as research, education, or clinical care. The reality is that companies take a multipronged approach to developing and marketing products, enlisting the assistance of multiple influential parties throughout the healthcare ecosystem. The US opioid epidemic, for example, provides numerous instances of pharmaceutical manufacturers strategically developing financial ties with multiple entities in the healthcare ecosystem and leveraging those to create secondary influences, resulting in profound patient harm. 16 17 The complex interactions evident in the case of opioids, however, are seldom documented or explored in the literature on conflict of interests. We are unaware of any study that has endeavored to identify and characterize the full extent of medical product industry ties across the healthcare ecosystem, which involves individuals who and organizations that deliver healthcare, as well as politicians, regulators, supply chain entities, and others who shape the practice of medicine indirectly. The entire spectrum of direct ties, and subsequent indirect pathways for potential influence, could result in cumulative effects on patient care and public trust and are thus important to systematically document and assess. We therefore developed an evidence based map to encompass the complex network of ties between the pharmaceutical, medical device, and biotechnology industries and healthcare ecosystem. To identify all known pathways that could enable companies to ultimately influence patient care, we systematically explored the full range of direct industry ties, both financial and non-financial, across the ecosystem, as well as indirect ties to and from other parties and activities within the healthcare ecosystem. We also cataloged the presence of conflict of interests oversight along these routes, as well as the extent to which industry ties are transparent to regulators, the public, and other key audiences. Our results provide a system level view of the medical product industry’s potential for influence across the healthcare ecosystem, ultimately culminating at patient care. Methods Our methods were twofold. First, we used targeted literature searches and expert input to draft a map depicting the ties between", "role": "user" }, { "content": "The medical product industry maintains an extensive network of financial and non-financial ties with all major healthcare parties and activities, reveals a study published by The BMJ today. This network seems to be mostly unregulated and opaque, and the researchers call for enhanced oversight and transparency \"to shield patient care from commercial influence and to preserve public trust in healthcare.\" Although the medical product industry is a critical partner in advancing healthcare, particularly in developing new tests and treatments, their main objective is to ensure financial returns to shareholders. In an influential 2009 report, the Institute of Medicine described a multifaceted healthcare ecosystem rife with industry influence. Yet most studies of conflict of interests related to pharmaceutical, medical device, and biotechnology companies have focused on a single party (eg. healthcare professionals, hospitals, or journals) or a single activity (eg. research, education, or clinical care). The full extent of industry ties across the healthcare ecosystem is therefore still uncertain. To address this gap, a team of US researchers set out to identify all known ties between the medical product industry and the healthcare ecosystem. They searched the medical literature for evidence of ties between pharmaceutical, medical device, and biotechnology companies and parties (including hospitals, prescribers and professional societies) and activities (including research, health professional education and guideline development) in the healthcare ecosystem. Data in 538 articles from 37 countries, along with expert input, was used to create a map depicting these ties. These ties were then verified, cataloged, and characterized to ascertain types of industry ties (financial, non-financial), applicable policies on conflict of interests, and publicly available data sources. The results show an extensive network of medical product industry ties—often unregulated and non-transparent—to all major activities and parties in the healthcare ecosystem. Key activities include research, healthcare education, guideline development, formulary selection (prescription drugs that are covered by a health plan or stocked by a healthcare facility), and clinical care. Parties include non-profit entities (eg. foundations and advocacy groups), the healthcare profession, the market supply chain (eg. payers, purchasing and distribution agents), and government. For example, the researchers describe how opioid manufacturers provided funding and other assets to prescribers, patients, public officials, advocacy organizations, and other healthcare parties, who, in turn, pressured regulators and public health agencies to quash or undermine opioid related guidelines and regulations. And they warn that many other examples of harm from industry promoted products remain unexplored. The results show that all party types have financial ties to medical product companies, with only payers and distribution agents lacking additional, non-financial ties. They also show that policies for conflict of interests exist for some financial and a few non-financial ties, but publicly available data sources seldom describe or quantify these ties. The researchers acknowledge that their findings are limited to known or documented industry ties, and that some data might have been missed. However, they say their strategy of systematic, duplicative searching and feedback from an international panel of experts is unlikely to have missed common or important ties. As such, they conclude: \"An extensive network of medical product industry ties to activities and parties exists in the healthcare ecosystem. Policies for conflict of interests and publicly available data are lacking, suggesting that enhanced oversight and transparency are needed to protect patients from commercial influence and to ensure public trust.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Objective To identify all known ties between the medical product industry and the healthcare ecosystem. Design Scoping review. Methods From initial literature searches and expert input, a map was created to show the network of medical product industry ties across parties and activities in the healthcare ecosystem. Through a scoping review, the ties were then verified, cataloged, and characterized, with data abstracted on types of industry ties (financial, non-financial), applicable policies for conflict of interests, and publicly available data sources. Main outcome measures Presence and types of medical product industry ties to activities and parties, presence of policies for conflict of interests, and publicly available data. Results A map derived through synthesis of 538 articles from 37 countries shows an extensive network of medical product industry ties to activities and parties in the healthcare ecosystem. Key activities include research, healthcare education, guideline development, formulary selection, and clinical care. Parties include non-profit entities, the healthcare profession, the market supply chain, and government. The medical product industry has direct ties to all parties and some activities through multiple pathways; direct ties extend through interrelationships among parties and activities. The most frequently identified parties were within the healthcare profession, with individual professionals described in 422 (78%) of the included studies. More than half (303, 56%) of the publications documented medical product industry ties to research, with clinical care (156, 29%), health professional education (145, 27%), guideline development (33, 6%), and formulary selection (8, 1%) appearing less often. Policies for conflict of interests exist for some financial and a few non-financial ties; publicly available data sources seldom describe or quantify these ties. Conclusions An extensive network of medical product industry ties to activities and parties exists in the healthcare ecosystem. Policies for conflict of interests and publicly available data are lacking, suggesting that enhanced oversight and transparency are needed to protect patient care from commercial influence and to ensure public trust. Introduction In an influential 2009 report, the Institute of Medicine described a multifaceted healthcare ecosystem rife with industry influence. 1 Central to the ecosystem are healthcare providers, researchers, clinical care facilities, journals, professional societies, and other healthcare institutions and supporting organizations engaged in medicine’s core professional activities: providing beneficial care to patients, conducting valid research, and providing evidence based clinical education and guidance. In so doing, these individuals and institutions frequently collaborate with pharmaceutical, medical device, and biotechnology product manufacturers. 1 2 3 4 5 Although these for profit entities play a crucial role in the ecosystem, particularly in developing new tests and treatments, their primary objective is to ensure financial returns to shareholders. Thus, industry collaborations inevitably introduce potential commercial bias into the healthcare ecosystem. With absent rigorous conflict of interest oversight across the entire system, the Institute of Medicine warned that medicine’s extensive ties to the medical product industry “threaten the integrity of scientific investigations, the objectivity of medical education, the quality of patient care, and the public’s trust in medicine.” 1 Controlling conflict of interest across the ecosystem, however, requires a system level understanding of how influence can enter and circulate through it. Research on the influence of the medical product industry is voluminous and expanding, aided in no small part by new data sources such as Open Payments, 6 7 8 9 a US federal database that makes public nearly all payments to physicians and teaching hospitals by pharmaceutical, medical device, and other healthcare product manufacturers. Other lines of inquiry have begun to explore the ties between medical product companies and regulators, patient advocacy groups, and other influential parties in the healthcare ecosystem. 3 4 10 11 12 And the analytic lens has broadened to include not only financial ties but also non-financial ones, such as medical product manufacturers offering healthcare professionals research data, authorship, and other opportunities for professional advancement. 13 14 15 Yet, with few exceptions, 1 2 16 17 most analyses focus on one or two narrow types of ties between the medical product industry and a single party, such as healthcare professionals, hospitals, or journals, or a single activity, such as research, education, or clinical care. The reality is that companies take a multipronged approach to developing and marketing products, enlisting the assistance of multiple influential parties throughout the healthcare ecosystem. The US opioid epidemic, for example, provides numerous instances of pharmaceutical manufacturers strategically developing financial ties with multiple entities in the healthcare ecosystem and leveraging those to create secondary influences, resulting in profound patient harm. 16 17 The complex interactions evident in the case of opioids, however, are seldom documented or explored in the literature on conflict of interests. We are unaware of any study that has endeavored to identify and characterize the full extent of medical product industry ties across the healthcare ecosystem, which involves individuals who and organizations that deliver healthcare, as well as politicians, regulators, supply chain entities, and others who shape the practice of medicine indirectly. The entire spectrum of direct ties, and subsequent indirect pathways for potential influence, could result in cumulative effects on patient care and public trust and are thus important to systematically document and assess. We therefore developed an evidence based map to encompass the complex network of ties between the pharmaceutical, medical device, and biotechnology industries and healthcare ecosystem. To identify all known pathways that could enable companies to ultimately influence patient care, we systematically explored the full range of direct industry ties, both financial and non-financial, across the ecosystem, as well as indirect ties to and from other parties and activities within the healthcare ecosystem. We also cataloged the presence of conflict of interests oversight along these routes, as well as the extent to which industry ties are transparent to regulators, the public, and other key audiences. Our results provide a system level view of the medical product industry’s potential for influence across the healthcare ecosystem, ultimately culminating at patient care. Methods Our methods were twofold. First, we used targeted literature searches and expert input to draft a map depicting the ties between<|im_end|> <|im_start|>assistant The medical product industry maintains an extensive network of financial and non-financial ties with all major healthcare parties and activities, reveals a study published by The BMJ today. This network seems to be mostly unregulated and opaque, and the researchers call for enhanced oversight and transparency "to shield patient care from commercial influence and to preserve public trust in healthcare." Although the medical product industry is a critical partner in advancing healthcare, particularly in developing new tests and treatments, their main objective is to ensure financial returns to shareholders. In an influential 2009 report, the Institute of Medicine described a multifaceted healthcare ecosystem rife with industry influence. Yet most studies of conflict of interests related to pharmaceutical, medical device, and biotechnology companies have focused on a single party (eg. healthcare professionals, hospitals, or journals) or a single activity (eg. research, education, or clinical care). The full extent of industry ties across the healthcare ecosystem is therefore still uncertain. To address this gap, a team of US researchers set out to identify all known ties between the medical product industry and the healthcare ecosystem. They searched the medical literature for evidence of ties between pharmaceutical, medical device, and biotechnology companies and parties (including hospitals, prescribers and professional societies) and activities (including research, health professional education and guideline development) in the healthcare ecosystem. Data in 538 articles from 37 countries, along with expert input, was used to create a map depicting these ties. These ties were then verified, cataloged, and characterized to ascertain types of industry ties (financial, non-financial), applicable policies on conflict of interests, and publicly available data sources. The results show an extensive network of medical product industry ties—often unregulated and non-transparent—to all major activities and parties in the healthcare ecosystem. Key activities include research, healthcare education, guideline development, formulary selection (prescription drugs that are covered by a health plan or stocked by a healthcare facility), and clinical care. Parties include non-profit entities (eg. foundations and advocacy groups), the healthcare profession, the market supply chain (eg. payers, purchasing and distribution agents), and government. For example, the researchers describe how opioid manufacturers provided funding and other assets to prescribers, patients, public officials, advocacy organizations, and other healthcare parties, who, in turn, pressured regulators and public health agencies to quash or undermine opioid related guidelines and regulations. And they warn that many other examples of harm from industry promoted products remain unexplored. The results show that all party types have financial ties to medical product companies, with only payers and distribution agents lacking additional, non-financial ties. They also show that policies for conflict of interests exist for some financial and a few non-financial ties, but publicly available data sources seldom describe or quantify these ties. The researchers acknowledge that their findings are limited to known or documented industry ties, and that some data might have been missed. However, they say their strategy of systematic, duplicative searching and feedback from an international panel of experts is unlikely to have missed common or important ties. As such, they conclude: "An extensive network of medical product industry ties to activities and parties exists in the healthcare ecosystem. Policies for conflict of interests and publicly available data are lacking, suggesting that enhanced oversight and transparency are needed to protect patients from commercial influence and to ensure public trust." <|im_end|>

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1,932

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract High latitude ocean gateway changes are thought to play a key role in Cenozoic climate evolution. However, the underlying ocean dynamics are poorly understood. Here we use a fully coupled atmosphere-ocean model to investigate the effect of ocean gateway formation that is associated with the subsidence of the Greenland–Scotland Ridge. We find a threshold in sill depth ( ∼ 50 m) that is linked to the influence of wind mixing. Sill depth changes within the wind mixed layer establish lagoonal and estuarine conditions with limited exchange across the sill resulting in brackish or even fresher Arctic conditions. Close to the threshold the ocean regime is highly sensitive to changes in atmospheric CO 2 and the associated modulation in the hydrological cycle. For larger sill depths a bi-directional flow regime across the ridge develops, providing a baseline for the final step towards the establishment of a modern prototype North Atlantic-Arctic water exchange. Introduction The tectonic evolution of ocean gateways and CO 2 changes are key controls of Cenozoic (from 65 Myr ago until present) climate change and ocean circulation. The last 65 Myr ago (Ma) of the earth’s history are characterized by a gradual long-term cooling trend, and the superposition of relatively abrupt climate changes that occurred on much faster timescales 1 , 2 , 3 . However, it remains a major challenge to identify to which extent tectonic events and CO 2 changes controlled the different trends and climate variations. Especially during the late Eocene to early Miocene interval ( ∼ 35–16 Ma), the climate of the North Atlantic-Arctic sector is prone to instabilities 4 , 5 , 6 , 7 , 8 , 9 . Therein, the subsidence of the Greenland–Scotland Ridge (GSR) from subaerial conditions towards a submarine rise constitutes an active ocean gateway control of North Atlantic-Arctic water exchange 9 , 10 , 11 , 12 , 13 . The long-term subsidence history of the GSR is, however, interfered by recurrent Icelandic mantle plume activity, causing topographic uplift in response to thermal variations in the mantle 13 , 14 . Periodic uplifting of the seafloor through the Neogene, driven by frequent mantle plume intensity, has shown to correlate with excursions in Atlantic deep sea δ 13 C records indicating a moderated southward sill overflow of Northern Component Water—a predecessor of modern North Atlantic Deep Water 13 , 15 . Although the long-term evolution of such ocean gateway developments on adjacent ocean water mass characteristics are generally accepted to induce basin-scale reorganizations 6 , 9 , 12 , 13 , 16 , 17 , the climatic impacts, as well as the associated mechanisms of climate changes remain largely elusive. Using a fully coupled Earth System Model (ESM) 18 , we investigate the effect of the GSR subsidence during an interval between ∼ 35 and 16 Ma. In our simulations we use Miocene background climate conditions ( ∼ 20–15 Ma), as a basis and apply different GSR depths and CO 2 concentrations as a surrogate for different conditions during the subsidence interval. We find a non-linear impact of ocean gateway depth controls on the water mass exchange and Arctic Ocean circulation that is mainly controlled by the effect of sill depth on mixed layer characteristics. For gateway depths close to the depth of the mixed layer, additional simulations of different atmospheric CO 2 concentrations show a modulation of the atmospheric hydrological cycle, controlling the overall Arctic salinity and ocean gyre circulation in the sub-polar Arctic (Greenland and Norwegian Seas). The critical threshold in gateway depth is constrained by the characteristic depth of wind driven mixing, unravelling the underlying processes that allow a theoretical assessment of the circulation system of semi-enclosed ocean basins throughout Earth’s history. Results Experimental approach In this study we apply an ESM (see model description in Methods) to simulate the subsidence of the GSR by incremental changes of the mean ridge height, starting from a quasi-enclosed towards a deep Miocene topographic configuration of the Greenland–Scotland ocean gateway ( Fig. 1 ). The ocean component of the ESM is characterized by a curve-linear grid that provides a maximum horizontal resolution of ∼ 30 km near the grid pole at Greenland 18 . This ocean grid space is too coarse to resolve non-rotational meso-scale flow patterns, as defined by the internal Rossby radius of deformation. However, in our model the GSR gateway is wide enough to simulate a rotationally controlled flow regime across the gateway. Related to considerable uncertainties of the GSR subsidence history, the model is setup with alternative boundary conditions (early Miocene ∼ 20–15 Ma) 19 compared with present-day representing a template used in our ocean gateway studies (for details on the model scenarios and boundary conditions, see Methods). This setting includes a closed Bering Strait and Canadian Archipelago configuration, providing a single ocean gateway control of the GSR. The final model setup is further advanced by embedding a high resolution bathymetry reconstruction of the northern North Atlantic-Arctic Ocean 20 into the global topographic dataset ( Fig. 1 ). Figure 1: Geographical settings of Miocene topography circa 20 to 15 Ma. ( a ) Global compilation of Miocene geography 19 (elevation and depth in metres); ( b ) A high resolution (0.5°; depth in metres) bathymetric dataset is embedded in the global setup comprising the northern North Atlantic, subpolar Arctic (Greenland and Norwegian Seas) and the Eurasian Basin in the Arctic Ocean 20 . The Arctic Ocean is defined by the central Arctic and the Greenland and Norwegian Seas as shown by the stippled lines. The schematic circulation shows pathways of the North Atlantic Current (NAC), the Norwegian Current (NC) and the East Greenland Current (EGC). The yellow star reflects the location of site 336 of the Deep Sea Drilling Project 21 at the northern flank of the GSR. Full size image Within a set of model scenarios we consider a gradual deepening of the GSR by stepwise changes (between 22 and 200 m below sea level, mbsl; see Methods and Supplementary Table 1 )", "role": "user" }, { "content": "The Arctic Ocean was once a gigantic freshwater lake. Only after the land bridge between Greenland and Scotland had submerged far enough did vast quantities of salt water pour in from the Atlantic. With the help of a climate model, researchers from the Alfred Wegener Institute have demonstrated how this process took place, allowing us for the first time to understand more accurately how Atlantic circulation, as we know it today came about. The results of the study have now been published in the journal Nature Communications. Every year, ca. 3,300 cubic kilometres of fresh water flows into the Arctic Ocean. This is equivalent to ten percent of the total volume of water that all the world's rivers transport to the oceans per year. In the warm and humid climate of the Eocene (ca. 56 to 34 million years ago), the inflow of freshwater was probably even greater. However, in contrast to today, during that geological period there was no exchange of water with other oceans. The influx of saline Atlantic and Pacific water, which today finds its way into the Arctic Ocean from the Pacific via the Bering Strait and from the North Atlantic via the Greenland-Scotland Ridge, wasn't possible - the region that is today completely submerged was above the sea at that time. Only once the land bridge between Greenland and Scotland disappeared did the first ocean passages emerge, connecting the Arctic with the North Atlantic and making water exchange possible. Using a climate model, researchers from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) have now successfully simulated the effect of this geological transformation on the climate. In their simulations, they gradually submerged the land bridge to a depth of 200 metres. \"In reality, this tectonic submersion process lasted several million years,\" says Climate Scientist Michael Stärz, first author of the study. \"Interestingly, the greatest changes in the circulation patterns and characteristics of the of the Arctic Ocean only occurred when the land bridge had reached a depth of over 50 metres below the surface.\" This threshold depth corresponds to the depth of the surface mixed layer, and determines where the relatively light Arctic surface water ends and the underlying layer of inflowing North Atlantic water begins. \"Only when the oceanic ridge lies below the surface mixed layer can the heavier saline water of the North Atlantic flow into the Arctic with relatively little hindrance,\" explains Stärz. \"Once the ocean passage between Greenland and Scotland had reached this critical depth, the saline Arctic Ocean as we know it today was created.\" The formation of ocean passages plays a vital role in global climate history, as it leads to changes in heat transport in the ocean between the middle and polar latitudes. The theory that the Arctic Basin was once isolated is supported by the discovery of freshwater algae fossils in Eocene deep-sea sediments that have been obtained during international drilling near the North Pole in 2004. What was once a land bridge now lies ca. 500 metres under the ocean and consists almost entirely of volcanic basalt. Iceland is the only section remaining above the surface. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract High latitude ocean gateway changes are thought to play a key role in Cenozoic climate evolution. However, the underlying ocean dynamics are poorly understood. Here we use a fully coupled atmosphere-ocean model to investigate the effect of ocean gateway formation that is associated with the subsidence of the Greenland–Scotland Ridge. We find a threshold in sill depth ( ∼ 50 m) that is linked to the influence of wind mixing. Sill depth changes within the wind mixed layer establish lagoonal and estuarine conditions with limited exchange across the sill resulting in brackish or even fresher Arctic conditions. Close to the threshold the ocean regime is highly sensitive to changes in atmospheric CO 2 and the associated modulation in the hydrological cycle. For larger sill depths a bi-directional flow regime across the ridge develops, providing a baseline for the final step towards the establishment of a modern prototype North Atlantic-Arctic water exchange. Introduction The tectonic evolution of ocean gateways and CO 2 changes are key controls of Cenozoic (from 65 Myr ago until present) climate change and ocean circulation. The last 65 Myr ago (Ma) of the earth’s history are characterized by a gradual long-term cooling trend, and the superposition of relatively abrupt climate changes that occurred on much faster timescales 1 , 2 , 3 . However, it remains a major challenge to identify to which extent tectonic events and CO 2 changes controlled the different trends and climate variations. Especially during the late Eocene to early Miocene interval ( ∼ 35–16 Ma), the climate of the North Atlantic-Arctic sector is prone to instabilities 4 , 5 , 6 , 7 , 8 , 9 . Therein, the subsidence of the Greenland–Scotland Ridge (GSR) from subaerial conditions towards a submarine rise constitutes an active ocean gateway control of North Atlantic-Arctic water exchange 9 , 10 , 11 , 12 , 13 . The long-term subsidence history of the GSR is, however, interfered by recurrent Icelandic mantle plume activity, causing topographic uplift in response to thermal variations in the mantle 13 , 14 . Periodic uplifting of the seafloor through the Neogene, driven by frequent mantle plume intensity, has shown to correlate with excursions in Atlantic deep sea δ 13 C records indicating a moderated southward sill overflow of Northern Component Water—a predecessor of modern North Atlantic Deep Water 13 , 15 . Although the long-term evolution of such ocean gateway developments on adjacent ocean water mass characteristics are generally accepted to induce basin-scale reorganizations 6 , 9 , 12 , 13 , 16 , 17 , the climatic impacts, as well as the associated mechanisms of climate changes remain largely elusive. Using a fully coupled Earth System Model (ESM) 18 , we investigate the effect of the GSR subsidence during an interval between ∼ 35 and 16 Ma. In our simulations we use Miocene background climate conditions ( ∼ 20–15 Ma), as a basis and apply different GSR depths and CO 2 concentrations as a surrogate for different conditions during the subsidence interval. We find a non-linear impact of ocean gateway depth controls on the water mass exchange and Arctic Ocean circulation that is mainly controlled by the effect of sill depth on mixed layer characteristics. For gateway depths close to the depth of the mixed layer, additional simulations of different atmospheric CO 2 concentrations show a modulation of the atmospheric hydrological cycle, controlling the overall Arctic salinity and ocean gyre circulation in the sub-polar Arctic (Greenland and Norwegian Seas). The critical threshold in gateway depth is constrained by the characteristic depth of wind driven mixing, unravelling the underlying processes that allow a theoretical assessment of the circulation system of semi-enclosed ocean basins throughout Earth’s history. Results Experimental approach In this study we apply an ESM (see model description in Methods) to simulate the subsidence of the GSR by incremental changes of the mean ridge height, starting from a quasi-enclosed towards a deep Miocene topographic configuration of the Greenland–Scotland ocean gateway ( Fig. 1 ). The ocean component of the ESM is characterized by a curve-linear grid that provides a maximum horizontal resolution of ∼ 30 km near the grid pole at Greenland 18 . This ocean grid space is too coarse to resolve non-rotational meso-scale flow patterns, as defined by the internal Rossby radius of deformation. However, in our model the GSR gateway is wide enough to simulate a rotationally controlled flow regime across the gateway. Related to considerable uncertainties of the GSR subsidence history, the model is setup with alternative boundary conditions (early Miocene ∼ 20–15 Ma) 19 compared with present-day representing a template used in our ocean gateway studies (for details on the model scenarios and boundary conditions, see Methods). This setting includes a closed Bering Strait and Canadian Archipelago configuration, providing a single ocean gateway control of the GSR. The final model setup is further advanced by embedding a high resolution bathymetry reconstruction of the northern North Atlantic-Arctic Ocean 20 into the global topographic dataset ( Fig. 1 ). Figure 1: Geographical settings of Miocene topography circa 20 to 15 Ma. ( a ) Global compilation of Miocene geography 19 (elevation and depth in metres); ( b ) A high resolution (0.5°; depth in metres) bathymetric dataset is embedded in the global setup comprising the northern North Atlantic, subpolar Arctic (Greenland and Norwegian Seas) and the Eurasian Basin in the Arctic Ocean 20 . The Arctic Ocean is defined by the central Arctic and the Greenland and Norwegian Seas as shown by the stippled lines. The schematic circulation shows pathways of the North Atlantic Current (NAC), the Norwegian Current (NC) and the East Greenland Current (EGC). The yellow star reflects the location of site 336 of the Deep Sea Drilling Project 21 at the northern flank of the GSR. Full size image Within a set of model scenarios we consider a gradual deepening of the GSR by stepwise changes (between 22 and 200 m below sea level, mbsl; see Methods and Supplementary Table 1 )<|im_end|> <|im_start|>assistant The Arctic Ocean was once a gigantic freshwater lake. Only after the land bridge between Greenland and Scotland had submerged far enough did vast quantities of salt water pour in from the Atlantic. With the help of a climate model, researchers from the Alfred Wegener Institute have demonstrated how this process took place, allowing us for the first time to understand more accurately how Atlantic circulation, as we know it today came about. The results of the study have now been published in the journal Nature Communications. Every year, ca. 3,300 cubic kilometres of fresh water flows into the Arctic Ocean. This is equivalent to ten percent of the total volume of water that all the world's rivers transport to the oceans per year. In the warm and humid climate of the Eocene (ca. 56 to 34 million years ago), the inflow of freshwater was probably even greater. However, in contrast to today, during that geological period there was no exchange of water with other oceans. The influx of saline Atlantic and Pacific water, which today finds its way into the Arctic Ocean from the Pacific via the Bering Strait and from the North Atlantic via the Greenland-Scotland Ridge, wasn't possible - the region that is today completely submerged was above the sea at that time. Only once the land bridge between Greenland and Scotland disappeared did the first ocean passages emerge, connecting the Arctic with the North Atlantic and making water exchange possible. Using a climate model, researchers from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) have now successfully simulated the effect of this geological transformation on the climate. In their simulations, they gradually submerged the land bridge to a depth of 200 metres. "In reality, this tectonic submersion process lasted several million years," says Climate Scientist Michael Stärz, first author of the study. "Interestingly, the greatest changes in the circulation patterns and characteristics of the of the Arctic Ocean only occurred when the land bridge had reached a depth of over 50 metres below the surface." This threshold depth corresponds to the depth of the surface mixed layer, and determines where the relatively light Arctic surface water ends and the underlying layer of inflowing North Atlantic water begins. "Only when the oceanic ridge lies below the surface mixed layer can the heavier saline water of the North Atlantic flow into the Arctic with relatively little hindrance," explains Stärz. "Once the ocean passage between Greenland and Scotland had reached this critical depth, the saline Arctic Ocean as we know it today was created." The formation of ocean passages plays a vital role in global climate history, as it leads to changes in heat transport in the ocean between the middle and polar latitudes. The theory that the Arctic Basin was once isolated is supported by the discovery of freshwater algae fossils in Eocene deep-sea sediments that have been obtained during international drilling near the North Pole in 2004. What was once a land bridge now lies ca. 500 metres under the ocean and consists almost entirely of volcanic basalt. Iceland is the only section remaining above the surface. <|im_end|>

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1,951

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Changes in the Atlantic Meridional Overturning Circulation, which have the potential to drive societally-important climate impacts, have traditionally been linked to the strength of deep water formation in the subpolar North Atlantic. Yet there is neither clear observational evidence nor agreement among models about how changes in deep water formation influence overturning. Here, we use data from a trans-basin mooring array (OSNAP—Overturning in the Subpolar North Atlantic Program) to show that winter convection during 2014–2018 in the interior basin had minimal impact on density changes in the deep western boundary currents in the subpolar basins. Contrary to previous modeling studies, we find no discernable relationship between western boundary changes and subpolar overturning variability over the observational time scales. Our results require a reconsideration of the notion of deep western boundary changes representing overturning characteristics, with implications for constraining the source of overturning variability within and downstream of the subpolar region. Introduction The high-latitude North Atlantic is a key region in the global ocean circulation system. Strong buoyancy loss creates North Atlantic Deep Water (NADW) that subsequently spreads to other ocean basins via the Deep Western Boundary Current (DWBC) 1 , 2 and interior (as opposed to DWBC) pathways 3 . The formation and spreading of NADW are essential elements of the Atlantic Meridional Overturning Circulation (MOC) 4 , 5 . Paleoclimate studies have suggested a strong association between abrupt climate changes during the last glacial cycle and changes in MOC strength, the latter attributed to the strength and location of deep water formation in the subpolar region 6 . On modern time scales, the cessation of deep water formation by winter convection in the Labrador Sea has been proposed as a potential tipping point for future climate change 7 . Moreover, a recent study has suggested an emerging impact of increased freshwater export on weakened deep water formation in the subpolar region 8 . Thus, deciphering relationships between the formation and export of deep water and the MOC’s structure as well as variability is of central importance to understanding and predicting the effects of a warming climate. Recent results from a new trans-basin ocean observing system in the subpolar North Atlantic (OSNAP; Fig. 1 ) 9 , 10 showed that water mass transformation in the eastern subpolar gyre (east of Greenland) dominated subpolar overturning over the period from 2014 to 2016. Surprisingly, winter convection in the Labrador Sea contributed minimally to the mean and variability of the subpolar MOC, even though unusually strong convection occurred in that basin during winter 2014/2015 11 , 12 . These results contradict the view of convection in the Labrador Sea as the major contributor to MOC variability throughout the North Atlantic 13 , 14 via the propagation of density anomalies created by the varying strength of deep convection in this basin 15 , 16 , 17 , 18 , 19 . Though models disagree as to the strength of the linkage between Labrador Sea convection and the MOC, this linkage is a consistent model feature 20 . These new observations raise the question about the source of Labrador Sea density anomalies and their impact on MOC variability in the subpolar basin. Fig. 1: OSNAP array. a Locations of OSNAP moorings (yellow dots) and glider survey domain (yellow line) on bathymetry (1000 m intervals). Arrows indicate the major currents intercepted by the OSNAP array from west to east: LC Labrador Current, WGC West Greenland Current, EGC East Greenland Current, IC Irminger Current, ERRC East Reykjanes Ridge Current, NAC North Atlantic Current. b 2014–2018 Mean velocity perpendicular to the OSNAP section (units: m s −1 ; positive poleward), overlaid by isopycnals (contoured). The isopycnal of 27.65 kg m −3 delimits the upper and lower limbs of the subpolar Meridional Overturning Circulation (MOC), which is slightly different for subsections (27.70 and 27.55 kg m −3 for OSNAP West and East respectively). The OSNAP moorings are marked by vertical black lines. Three moorings from the French Reykjanes Ridge Experiment (RREX) program are marked by vertical purple lines. Hatching in the eastern Iceland basin indicates the glider survey domain. Full size image Because there is the possibility of a delayed impact of strong convection on the overturning due to a residence time of ~2–3 years for newly-formed upper NADW (UNADW) in the Labrador Sea interior 21 , 22 , there is a valid argument that the initial OSNAP record, 21 months in duration, was insufficient to capture this impact. Thus, in this study we use the extended OSNAP data between August 2014 and May 2018 (46 months) now available to further examine the linkage between wintertime convection and MOC variability. Namely, we first assess the impact of subpolar convection on western boundary density anomalies and then, in turn, quantify the impact of those western boundary anomalies on the subpolar MOC variability. We analyze OSNAP array observations to assess this variability on monthly to interannual time scales and define the MOC as the maximum of the overturning stream function in density ( σ θ ) space (Supplementary Fig. 1 ). Details of the OSNAP array design and calculations can be found in Methods. Results Subpolar overturning circulation Over our study period, the MOC across the OSNAP array has a time-mean of \$16.6\\,\\pm\\, 0.7\\,{{{\\rm{Sv}}}}\$ ( \$1\\,{{{\\rm{Sv}}}}\\,=\\,\\,{10}^{6}\\,{{{{\\rm{m}}}}}^{3}\\,{s}^{-1}\$ ) and exhibits strong monthly variability overlaid by year-to-year differences (Fig. 2 ). The quoted uncertainty is the standard error in the mean, estimated via Monte Carlo simulations based on the mean and uncertainty in individual months 10 . Although the 2014–2018 mean MOC is larger than the 2014–2016 mean 10 , the difference is not statistically significant at the 95% level (Methods). Composite monthly means, constructed by averaging the values of the same month for all years, appear to show seasonal MOC cycles (Supplementary Fig. 2 ), but the seasonal changes are not statistically significant (Methods). Fig. 2: Subpolar Meridional Overturning Circulation (MOC) time series. 30-day MOC estimates across the full array, OSNAP West and East, respectively. Shading indicates uncertainty in the 30-day", "role": "user" }, { "content": "A new international study has cast doubts on the view that variations in the density of some of the deepest currents of the subpolar North Atlantic Ocean are caused by winter surface conditions and represent changes in the strength of the Meridional Overturning Circulation (MOC). The study included the efforts of 15 research institutes and was led by Dr. Feili Li and Professor Susan Lozier from Georgia Institute of Technology, in partnership withProfessor Penny Holliday, from the National Oceanography Center (NOC). Research published on 24 May 2021 in Nature Communications shows observations made over four years from 2014 in the subpolar North Atlantic reveal no sign of strong winter cooling at the surface of the ocean on the density of the deepest boundary currents found in the western regions of ocean basins. Surprisingly, the authors also found no visible relationship between changes in those deep western boundary currents and variations in the strength of the MOC. Knowledge of the physical processes that govern changes in the MOC are essential for accurate climate projections. The MOC brings vast amounts of heat and salt into the northern Atlantic via the Gulf Stream and North Atlantic Current. Changes in the strength of the MOC directly affect sea level, climate and weather for Europe, North America and parts of the African continent. Climate projections all predict a slowing of the MOC as a result of greenhouse gas emissions, with potentially damaging impact on coastal communities and land. Scientists recovering instruments that have been collecting data in deep ocean for 2 years on the OSNAP array (Photo Credit NOC and GEOMAR). Credit: NOC and GEOMAR Previous analysis of models has led scientists to think that changes in the strength of the MOC are associated with changes in the density of the deep western boundary currents which make up the majority of the southward return flow of the MOC loop. In models, density can be strongly affected by a winter process called deep convection or deep water formation, where cold winds cool the surface water causing it to become very dense and sink to great depths (more than 2km). The relationship in models between convection, changes in deep western boundary currents and the strength of the MOC also underpins evidence from palaeoclimate proxies for periods of reduced MOC and low European temperatures. Retrieving data from the Labrador Sea. The OSNAP array consists of over 50 moorings between Canada, Greenland and Scotland, in ocean basins up to 3km deep. Each mooring takes several hours to bring back on board a research vessel. Credit: NOC and GEOMAR In 2014 scientific equipment was placed in the subpolar North Atlantic (OSNAP) to observe these processes in real life. The surprising new results will stimulate a reconsideration of the view that deep western boundary changes represent overturning characteristics, with implications for future climate projections as well as the interpretation of past climate change. Prof. Susan Lozier, overall lead of the international OSNAP program said: \"It is gratifying to see what an international community of oceanographers can achieve with a concentrated effort of collaboration and determination. Programs such as OSNAP and RAPID are blueprints for how oceanographers across the globe can collectively study the ocean's role in climate change in the years and decades ahead.\" Prof. Penny Holliday, Associate Head of Marine Physics and Ocean Climate from the National Oceanography Center commented: \"it is incredibly exciting to see how new observations from the OSNAP array are accelerating our knowledge of how these major ocean currents work, so that we can be more confident in our understanding of past climate change and in future climate projections.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Changes in the Atlantic Meridional Overturning Circulation, which have the potential to drive societally-important climate impacts, have traditionally been linked to the strength of deep water formation in the subpolar North Atlantic. Yet there is neither clear observational evidence nor agreement among models about how changes in deep water formation influence overturning. Here, we use data from a trans-basin mooring array (OSNAP—Overturning in the Subpolar North Atlantic Program) to show that winter convection during 2014–2018 in the interior basin had minimal impact on density changes in the deep western boundary currents in the subpolar basins. Contrary to previous modeling studies, we find no discernable relationship between western boundary changes and subpolar overturning variability over the observational time scales. Our results require a reconsideration of the notion of deep western boundary changes representing overturning characteristics, with implications for constraining the source of overturning variability within and downstream of the subpolar region. Introduction The high-latitude North Atlantic is a key region in the global ocean circulation system. Strong buoyancy loss creates North Atlantic Deep Water (NADW) that subsequently spreads to other ocean basins via the Deep Western Boundary Current (DWBC) 1 , 2 and interior (as opposed to DWBC) pathways 3 . The formation and spreading of NADW are essential elements of the Atlantic Meridional Overturning Circulation (MOC) 4 , 5 . Paleoclimate studies have suggested a strong association between abrupt climate changes during the last glacial cycle and changes in MOC strength, the latter attributed to the strength and location of deep water formation in the subpolar region 6 . On modern time scales, the cessation of deep water formation by winter convection in the Labrador Sea has been proposed as a potential tipping point for future climate change 7 . Moreover, a recent study has suggested an emerging impact of increased freshwater export on weakened deep water formation in the subpolar region 8 . Thus, deciphering relationships between the formation and export of deep water and the MOC’s structure as well as variability is of central importance to understanding and predicting the effects of a warming climate. Recent results from a new trans-basin ocean observing system in the subpolar North Atlantic (OSNAP; Fig. 1 ) 9 , 10 showed that water mass transformation in the eastern subpolar gyre (east of Greenland) dominated subpolar overturning over the period from 2014 to 2016. Surprisingly, winter convection in the Labrador Sea contributed minimally to the mean and variability of the subpolar MOC, even though unusually strong convection occurred in that basin during winter 2014/2015 11 , 12 . These results contradict the view of convection in the Labrador Sea as the major contributor to MOC variability throughout the North Atlantic 13 , 14 via the propagation of density anomalies created by the varying strength of deep convection in this basin 15 , 16 , 17 , 18 , 19 . Though models disagree as to the strength of the linkage between Labrador Sea convection and the MOC, this linkage is a consistent model feature 20 . These new observations raise the question about the source of Labrador Sea density anomalies and their impact on MOC variability in the subpolar basin. Fig. 1: OSNAP array. a Locations of OSNAP moorings (yellow dots) and glider survey domain (yellow line) on bathymetry (1000 m intervals). Arrows indicate the major currents intercepted by the OSNAP array from west to east: LC Labrador Current, WGC West Greenland Current, EGC East Greenland Current, IC Irminger Current, ERRC East Reykjanes Ridge Current, NAC North Atlantic Current. b 2014–2018 Mean velocity perpendicular to the OSNAP section (units: m s −1 ; positive poleward), overlaid by isopycnals (contoured). The isopycnal of 27.65 kg m −3 delimits the upper and lower limbs of the subpolar Meridional Overturning Circulation (MOC), which is slightly different for subsections (27.70 and 27.55 kg m −3 for OSNAP West and East respectively). The OSNAP moorings are marked by vertical black lines. Three moorings from the French Reykjanes Ridge Experiment (RREX) program are marked by vertical purple lines. Hatching in the eastern Iceland basin indicates the glider survey domain. Full size image Because there is the possibility of a delayed impact of strong convection on the overturning due to a residence time of ~2–3 years for newly-formed upper NADW (UNADW) in the Labrador Sea interior 21 , 22 , there is a valid argument that the initial OSNAP record, 21 months in duration, was insufficient to capture this impact. Thus, in this study we use the extended OSNAP data between August 2014 and May 2018 (46 months) now available to further examine the linkage between wintertime convection and MOC variability. Namely, we first assess the impact of subpolar convection on western boundary density anomalies and then, in turn, quantify the impact of those western boundary anomalies on the subpolar MOC variability. We analyze OSNAP array observations to assess this variability on monthly to interannual time scales and define the MOC as the maximum of the overturning stream function in density ( σ θ ) space (Supplementary Fig. 1 ). Details of the OSNAP array design and calculations can be found in Methods. Results Subpolar overturning circulation Over our study period, the MOC across the OSNAP array has a time-mean of $16.6\,\pm\, 0.7\,{{{\rm{Sv}}}}$ ( $1\,{{{\rm{Sv}}}}\,=\,\,{10}^{6}\,{{{{\rm{m}}}}}^{3}\,{s}^{-1}$ ) and exhibits strong monthly variability overlaid by year-to-year differences (Fig. 2 ). The quoted uncertainty is the standard error in the mean, estimated via Monte Carlo simulations based on the mean and uncertainty in individual months 10 . Although the 2014–2018 mean MOC is larger than the 2014–2016 mean 10 , the difference is not statistically significant at the 95% level (Methods). Composite monthly means, constructed by averaging the values of the same month for all years, appear to show seasonal MOC cycles (Supplementary Fig. 2 ), but the seasonal changes are not statistically significant (Methods). Fig. 2: Subpolar Meridional Overturning Circulation (MOC) time series. 30-day MOC estimates across the full array, OSNAP West and East, respectively. Shading indicates uncertainty in the 30-day<|im_end|> <|im_start|>assistant A new international study has cast doubts on the view that variations in the density of some of the deepest currents of the subpolar North Atlantic Ocean are caused by winter surface conditions and represent changes in the strength of the Meridional Overturning Circulation (MOC). The study included the efforts of 15 research institutes and was led by Dr. Feili Li and Professor Susan Lozier from Georgia Institute of Technology, in partnership withProfessor Penny Holliday, from the National Oceanography Center (NOC). Research published on 24 May 2021 in Nature Communications shows observations made over four years from 2014 in the subpolar North Atlantic reveal no sign of strong winter cooling at the surface of the ocean on the density of the deepest boundary currents found in the western regions of ocean basins. Surprisingly, the authors also found no visible relationship between changes in those deep western boundary currents and variations in the strength of the MOC. Knowledge of the physical processes that govern changes in the MOC are essential for accurate climate projections. The MOC brings vast amounts of heat and salt into the northern Atlantic via the Gulf Stream and North Atlantic Current. Changes in the strength of the MOC directly affect sea level, climate and weather for Europe, North America and parts of the African continent. Climate projections all predict a slowing of the MOC as a result of greenhouse gas emissions, with potentially damaging impact on coastal communities and land. Scientists recovering instruments that have been collecting data in deep ocean for 2 years on the OSNAP array (Photo Credit NOC and GEOMAR). Credit: NOC and GEOMAR Previous analysis of models has led scientists to think that changes in the strength of the MOC are associated with changes in the density of the deep western boundary currents which make up the majority of the southward return flow of the MOC loop. In models, density can be strongly affected by a winter process called deep convection or deep water formation, where cold winds cool the surface water causing it to become very dense and sink to great depths (more than 2km). The relationship in models between convection, changes in deep western boundary currents and the strength of the MOC also underpins evidence from palaeoclimate proxies for periods of reduced MOC and low European temperatures. Retrieving data from the Labrador Sea. The OSNAP array consists of over 50 moorings between Canada, Greenland and Scotland, in ocean basins up to 3km deep. Each mooring takes several hours to bring back on board a research vessel. Credit: NOC and GEOMAR In 2014 scientific equipment was placed in the subpolar North Atlantic (OSNAP) to observe these processes in real life. The surprising new results will stimulate a reconsideration of the view that deep western boundary changes represent overturning characteristics, with implications for future climate projections as well as the interpretation of past climate change. Prof. Susan Lozier, overall lead of the international OSNAP program said: "It is gratifying to see what an international community of oceanographers can achieve with a concentrated effort of collaboration and determination. Programs such as OSNAP and RAPID are blueprints for how oceanographers across the globe can collectively study the ocean's role in climate change in the years and decades ahead." Prof. Penny Holliday, Associate Head of Marine Physics and Ocean Climate from the National Oceanography Center commented: "it is incredibly exciting to see how new observations from the OSNAP array are accelerating our knowledge of how these major ocean currents work, so that we can be more confident in our understanding of past climate change and in future climate projections." <|im_end|>

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2,233

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Here we report the discovery of recurrent mutations concentrated at an ultraviolet signature hotspot in KNSTRN , which encodes a kinetochore protein, in 19% of cutaneous squamous cell carcinomas (SCCs). Cancer-associated KNSTRN mutations, most notably those encoding p.Ser24Phe, disrupt chromatid cohesion in normal cells, occur in SCC precursors, correlate with increased aneuploidy in primary tumors and enhance tumorigenesis in vivo . These findings suggest a role for KNSTRN mutagenesis in SCC development. Main Cutaneous SCC is the second most common cancer, with an annual global incidence exceeding 1 million 1 . To identify recurrent genomic aberrations that underlie the development of this malignancy, we used single-nucleotide variant (SNV) determinations from the whole-exome sequencing of 12 SCC-normal pairs ( Supplementary Tables 1 and 2 ; ref. 2 ) to distill a list of 336 candidate genes that were then resequenced in 100 matched SCC-normal pairs as well as in 5 SCC cell lines with an average depth exceeding 1,200× ( Supplementary Tables 1 , 2 , 3 , 4 ). Analysis of mutation type showed that the majority of tumors had a mutational profile characteristic of exposure to ultraviolet (UV) light ( Fig. 1a ), consistent with the known association of this cancer with sunlight. The mutation frequencies in TP53 , CDKN2A and HRAS —the three genes most studied in this cancer thus far—were consistent with those previously reported, confirming that the sequenced samples were genetically representative of this malignancy ( Fig. 1b and Supplementary Fig. 1 ). The number of mutations found in archived formalin-fixed, paraffin-embedded samples was not statistically different from that detected in fresh samples ( P = 0.55) ( Fig. 1b ). Previously reported SCC-associated inactivating mutations in TP53 and CDKN2A were identified as well as activating HRAS mutations and frequent disruption of the NOTCH1 and NOTCH2 genes ( Fig. 1b and Supplementary Table 2 ). Figure 1: Recurrent mutations in KNSTRN encoding p.Ser24Phe in cutaneous SCC. ( a ) The percentages of somatic point mutations in 100 primary cutaneous SCCs that are transitions compared to transversions. ( b ) Characterization of SCC–matched normal pairs. Mutation frequency is shown in parentheses next to each gene name. FFPE, formalin fixed and paraffin embedded. ( c ) Distribution of the SCC-associated alterations identified in this study across the kinastrin coding sequence. SXLP, SXLP motif; CC, coiled-coil region. ( d ) Detection of KNSTRN mutation encoding p.Ser24Phe in SCC precursor actinic keratoses (AKs) as well as primary SCCs by allelic discrimination quantitative PCR. NL, freshly excised normal skin. Data shown represent technical triplicates. WT, wild type. Full size image Among the recurrently mutated genes in SCC, KNSTRN ranked third behind CDKN2A and TP53 after normalizing for ORF length ( Fig. 1b ). KNSTRN encodes a kinetochore-associated protein that modulates anaphase onset and chromosome segregation during mitosis 3 . It is expressed in a broad range of human tissues, including in skin ( Supplementary Fig. 2 ). Somatic mutations in KNSTRN were present in 2 of 12 (17%) and 19 of 100 (19%) SCCs analyzed by whole-exome and targeted sequencing, respectively. Over half of these mutations mapped to a 17-amino-acid N-terminal region, with a 'hotspot' serine-to-phenylalanine substitution present at codon 24 (p.Ser24Phe) ( Fig. 1c and Supplementary Fig. 3 ) that was also detected in the cutaneous SCC cell line SCC-12B.2 ( Supplementary Table 4 ). This pattern of clustered somatic missense mutations is characteristic of dominant mutations in oncogenes 4 , although KNSTRN has thus far not been implicated in any published study of human cancer. Notably, the KNSTRN mutation encoding p.Ser24Phe involves a C>T transition that is characteristic of UV-induced mutagenesis. To determine whether KNSTRN mutagenesis might be an early event in SCC development, we screened 38 additional primary SCCs as well as 27 actinic keratoses, representing the earliest SCC precursor, for the presence of KNSTRN mutation encoding p.Ser24Phe. The mutation was detected in 5 of 27 (19%) and 5 of 38 (13%) actinic keratoses and SCCs, respectively, but was never identified in normal skin (0 of 122), indicating that it arises early in tumorigenesis ( Fig. 1d ). We next parsed all publicly available data sets from The Cancer Genome Atlas (TCGA). We identified KNSTRN mutations in 23 of 490 (4.7%) melanomas, another major sunlight-associated cancer, with 15 (65%) mapping to the 17-amino-acid N-terminal region and 10 (44%) specifically inducing the p.Ser24Phe substitution ( Supplementary Fig. 4 and Supplementary Table 5 ). KNSTRN mutations were rare events in the other surveyed cancers, with none displaying mutations resulting in the p.Ser24Phe substitution ( Supplementary Fig. 4a ). Thus, recurrent mutation of KNSTRN and, in particular, mutation encoding p.Ser24Phe appear selective for UV-associated malignancies. Aberrant KNSTRN expression has previously been shown to result in loss of chromatid cohesion in HeLa cells 3 , 5 ; however, the effects of mutant kinastrin protein in normal primary cells have not been described. To evaluate whether Ser24Phe kinastrin is functionally relevant in this context, we expressed wild-type or Ser24Phe kinastrin in primary human keratinocytes ( Fig. 2a and Supplementary Fig. 5 ) and assessed chromosome segregation during mitosis. Expression of mutant kinastrin disrupted sister chromatid cohesion, as demonstrated by a subset of cells containing unpaired chromatids in normal cells as well as SCC-13 cells ( P = 0.0002) ( Fig. 2b and Supplementary Fig. 6 ). Kinastrin proteins corresponding to four additional cancer-associated KNSTRN mutations (encoding p.Arg11Lys, p.Pro26Ser, p.Pro28Ser and p.Ala40Glu substitutions), including those present in melanoma, similarly disrupted chromosome segregation ( Supplementary Figs. 4b and 7 ). These functional data support a role for cancer-associated KNSTRN mutations in controlling chromosomal stability in normal as well as cancer cells. Figure 2: Ser24Phe kinastrin promotes aneuploidy and enhances tumorigenesis in vivo . ( a ) Disrupted sister chromatid cohesion in early-passage, primary human keratinocytes pooled from multiple donors and transduced to express wild-type or Ser24Phe kinastrin. Arrowheads mark unpaired chromatids. Scale bars, 5 μm. ( b ) Quantification of unpaired chromatids ( n = 2 biological replicates). *P = 0.0002. ( c )", "role": "user" }, { "content": "A genetic mutation caused by ultraviolet light is likely the driving force behind millions of human skin cancers, according to researchers at the Stanford University School of Medicine. The mutation occurs in a gene called KNSTRN, which is involved in helping cells divide their DNA equally during cell division. Genes that cause cancer when mutated are known as oncogenes. Although KNSTRN hasn't been previously implicated as a cause of human cancers, the research suggests it may be one of the most commonly mutated oncogenes in the world. \"This previously unknown oncogene is activated by sunlight and drives the development of cutaneous squamous cell carcinomas,\" said Paul Khavari, MD, PhD, the Carl J. Herzog Professor in Dermatology in the School of Medicine and chair of the Department of Dermatology. \"Our research shows that skin cancers arise differently from other cancers, and that a single mutation can cause genomic catastrophe.\" Cutaneous squamous cell carcinoma is the second most common cancer in humans. More than 1 million new cases are diagnosed globally each year. The researchers found that a particular region of KNSTRN is mutated in about 20 percent of cutaneous squamous cell carcinomas and in about 5 percent of melanomas. A paper describing the research will be published online Sept. 7 in Nature Genetics. Khavari, who is also a member of the Stanford Cancer Institute and chief of the dermatology service at the Veterans Affairs Palo Alto Health Care System, is the senior author of the paper. Postdoctoral scholar Carolyn Lee, MD, PhD, is the lead author. Lee and Khavari made the discovery while investigating the genetic causes of cutaneous squamous cell carcinoma. They compared the DNA sequences of genes from the tumor cells with those of normal skin and looked for mutations that occurred only in the tumors. They found 336 candidate genes for further study, including some familiar culprits. The top two most commonly mutated genes were CDKN2A and TP53, which were already known to be associated with squamous cell carcinoma. The third most commonly mutated gene, KNSTRN, was a surprise. It encodes a protein that helps to form the kinetochore—a structure that serves as a kind of handle used to pull pairs of newly replicated chromosomes to either end of the cell during cell division. Sequestering the DNA at either end of the cell allows the cell to split along the middle to form two daughter cells, each with the proper complement of chromosomes. If the chromosomes don't separate correctly, the daughter cells will have abnormal amounts of DNA. These cells with extra or missing chromosomes are known as aneuploid, and they are often severely dysfunctional. They tend to misread cellular cues and to behave erratically. Aneuploidy is a critical early step toward the development of many types of cancer. The mutation in the KNSTRN gene was caused by the replacement of a single nucleotide, called a cytosine, with another, called a thymine, within a specific, short stretch of DNA. The swap is indicative of a cell's attempt to repair damage from high-energy ultraviolet rays, such as those found in sunlight. \"Mutations at this UV hotspot are not found in any of the other cancers we investigated,\" said Khavari. \"They occur only in skin cancers.\" The researchers found the UV-induced KNSTRN mutation in about 20 percent of actinic keratoses—a premalignant skin condition that often progresses to squamous cell carcinoma—but never in 122 samples of normal skin, indicating the mutation is likely to be an early event in the development of squamous cell carcinomas. Furthermore, overexpression of mutant KNSTRN in laboratory-grown human skin cells disrupted their ability to segregate their DNA during cell division and enhanced the growth of cancer cells in a mouse model of squamous cell carcinoma. Finally, Lee compared five patient-derived squamous cell carcinomas that had the KNSTRN mutation with five samples that did not have the mutation. Although both sets of cells were aneuploid, those with the mutation had the most severely abnormal genomes. The identification of a new oncogene will allow researchers to better understand how these types of skin cancers develop. It may also give them clues about how to develop new therapies for the disease. In this case, it also neatly connects the dots between sun exposure and skin cancer. \"Essentially, one ultraviolet-mediated mutation in this region promotes aneuploidy and subsequent tumorigenesis,\" said Khavari. \"It is critical to protect the skin from the sun.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Here we report the discovery of recurrent mutations concentrated at an ultraviolet signature hotspot in KNSTRN , which encodes a kinetochore protein, in 19% of cutaneous squamous cell carcinomas (SCCs). Cancer-associated KNSTRN mutations, most notably those encoding p.Ser24Phe, disrupt chromatid cohesion in normal cells, occur in SCC precursors, correlate with increased aneuploidy in primary tumors and enhance tumorigenesis in vivo . These findings suggest a role for KNSTRN mutagenesis in SCC development. Main Cutaneous SCC is the second most common cancer, with an annual global incidence exceeding 1 million 1 . To identify recurrent genomic aberrations that underlie the development of this malignancy, we used single-nucleotide variant (SNV) determinations from the whole-exome sequencing of 12 SCC-normal pairs ( Supplementary Tables 1 and 2 ; ref. 2 ) to distill a list of 336 candidate genes that were then resequenced in 100 matched SCC-normal pairs as well as in 5 SCC cell lines with an average depth exceeding 1,200× ( Supplementary Tables 1 , 2 , 3 , 4 ). Analysis of mutation type showed that the majority of tumors had a mutational profile characteristic of exposure to ultraviolet (UV) light ( Fig. 1a ), consistent with the known association of this cancer with sunlight. The mutation frequencies in TP53 , CDKN2A and HRAS —the three genes most studied in this cancer thus far—were consistent with those previously reported, confirming that the sequenced samples were genetically representative of this malignancy ( Fig. 1b and Supplementary Fig. 1 ). The number of mutations found in archived formalin-fixed, paraffin-embedded samples was not statistically different from that detected in fresh samples ( P = 0.55) ( Fig. 1b ). Previously reported SCC-associated inactivating mutations in TP53 and CDKN2A were identified as well as activating HRAS mutations and frequent disruption of the NOTCH1 and NOTCH2 genes ( Fig. 1b and Supplementary Table 2 ). Figure 1: Recurrent mutations in KNSTRN encoding p.Ser24Phe in cutaneous SCC. ( a ) The percentages of somatic point mutations in 100 primary cutaneous SCCs that are transitions compared to transversions. ( b ) Characterization of SCC–matched normal pairs. Mutation frequency is shown in parentheses next to each gene name. FFPE, formalin fixed and paraffin embedded. ( c ) Distribution of the SCC-associated alterations identified in this study across the kinastrin coding sequence. SXLP, SXLP motif; CC, coiled-coil region. ( d ) Detection of KNSTRN mutation encoding p.Ser24Phe in SCC precursor actinic keratoses (AKs) as well as primary SCCs by allelic discrimination quantitative PCR. NL, freshly excised normal skin. Data shown represent technical triplicates. WT, wild type. Full size image Among the recurrently mutated genes in SCC, KNSTRN ranked third behind CDKN2A and TP53 after normalizing for ORF length ( Fig. 1b ). KNSTRN encodes a kinetochore-associated protein that modulates anaphase onset and chromosome segregation during mitosis 3 . It is expressed in a broad range of human tissues, including in skin ( Supplementary Fig. 2 ). Somatic mutations in KNSTRN were present in 2 of 12 (17%) and 19 of 100 (19%) SCCs analyzed by whole-exome and targeted sequencing, respectively. Over half of these mutations mapped to a 17-amino-acid N-terminal region, with a 'hotspot' serine-to-phenylalanine substitution present at codon 24 (p.Ser24Phe) ( Fig. 1c and Supplementary Fig. 3 ) that was also detected in the cutaneous SCC cell line SCC-12B.2 ( Supplementary Table 4 ). This pattern of clustered somatic missense mutations is characteristic of dominant mutations in oncogenes 4 , although KNSTRN has thus far not been implicated in any published study of human cancer. Notably, the KNSTRN mutation encoding p.Ser24Phe involves a C>T transition that is characteristic of UV-induced mutagenesis. To determine whether KNSTRN mutagenesis might be an early event in SCC development, we screened 38 additional primary SCCs as well as 27 actinic keratoses, representing the earliest SCC precursor, for the presence of KNSTRN mutation encoding p.Ser24Phe. The mutation was detected in 5 of 27 (19%) and 5 of 38 (13%) actinic keratoses and SCCs, respectively, but was never identified in normal skin (0 of 122), indicating that it arises early in tumorigenesis ( Fig. 1d ). We next parsed all publicly available data sets from The Cancer Genome Atlas (TCGA). We identified KNSTRN mutations in 23 of 490 (4.7%) melanomas, another major sunlight-associated cancer, with 15 (65%) mapping to the 17-amino-acid N-terminal region and 10 (44%) specifically inducing the p.Ser24Phe substitution ( Supplementary Fig. 4 and Supplementary Table 5 ). KNSTRN mutations were rare events in the other surveyed cancers, with none displaying mutations resulting in the p.Ser24Phe substitution ( Supplementary Fig. 4a ). Thus, recurrent mutation of KNSTRN and, in particular, mutation encoding p.Ser24Phe appear selective for UV-associated malignancies. Aberrant KNSTRN expression has previously been shown to result in loss of chromatid cohesion in HeLa cells 3 , 5 ; however, the effects of mutant kinastrin protein in normal primary cells have not been described. To evaluate whether Ser24Phe kinastrin is functionally relevant in this context, we expressed wild-type or Ser24Phe kinastrin in primary human keratinocytes ( Fig. 2a and Supplementary Fig. 5 ) and assessed chromosome segregation during mitosis. Expression of mutant kinastrin disrupted sister chromatid cohesion, as demonstrated by a subset of cells containing unpaired chromatids in normal cells as well as SCC-13 cells ( P = 0.0002) ( Fig. 2b and Supplementary Fig. 6 ). Kinastrin proteins corresponding to four additional cancer-associated KNSTRN mutations (encoding p.Arg11Lys, p.Pro26Ser, p.Pro28Ser and p.Ala40Glu substitutions), including those present in melanoma, similarly disrupted chromosome segregation ( Supplementary Figs. 4b and 7 ). These functional data support a role for cancer-associated KNSTRN mutations in controlling chromosomal stability in normal as well as cancer cells. Figure 2: Ser24Phe kinastrin promotes aneuploidy and enhances tumorigenesis in vivo . ( a ) Disrupted sister chromatid cohesion in early-passage, primary human keratinocytes pooled from multiple donors and transduced to express wild-type or Ser24Phe kinastrin. Arrowheads mark unpaired chromatids. Scale bars, 5 μm. ( b ) Quantification of unpaired chromatids ( n = 2 biological replicates). *P = 0.0002. ( c )<|im_end|> <|im_start|>assistant A genetic mutation caused by ultraviolet light is likely the driving force behind millions of human skin cancers, according to researchers at the Stanford University School of Medicine. The mutation occurs in a gene called KNSTRN, which is involved in helping cells divide their DNA equally during cell division. Genes that cause cancer when mutated are known as oncogenes. Although KNSTRN hasn't been previously implicated as a cause of human cancers, the research suggests it may be one of the most commonly mutated oncogenes in the world. "This previously unknown oncogene is activated by sunlight and drives the development of cutaneous squamous cell carcinomas," said Paul Khavari, MD, PhD, the Carl J. Herzog Professor in Dermatology in the School of Medicine and chair of the Department of Dermatology. "Our research shows that skin cancers arise differently from other cancers, and that a single mutation can cause genomic catastrophe." Cutaneous squamous cell carcinoma is the second most common cancer in humans. More than 1 million new cases are diagnosed globally each year. The researchers found that a particular region of KNSTRN is mutated in about 20 percent of cutaneous squamous cell carcinomas and in about 5 percent of melanomas. A paper describing the research will be published online Sept. 7 in Nature Genetics. Khavari, who is also a member of the Stanford Cancer Institute and chief of the dermatology service at the Veterans Affairs Palo Alto Health Care System, is the senior author of the paper. Postdoctoral scholar Carolyn Lee, MD, PhD, is the lead author. Lee and Khavari made the discovery while investigating the genetic causes of cutaneous squamous cell carcinoma. They compared the DNA sequences of genes from the tumor cells with those of normal skin and looked for mutations that occurred only in the tumors. They found 336 candidate genes for further study, including some familiar culprits. The top two most commonly mutated genes were CDKN2A and TP53, which were already known to be associated with squamous cell carcinoma. The third most commonly mutated gene, KNSTRN, was a surprise. It encodes a protein that helps to form the kinetochore—a structure that serves as a kind of handle used to pull pairs of newly replicated chromosomes to either end of the cell during cell division. Sequestering the DNA at either end of the cell allows the cell to split along the middle to form two daughter cells, each with the proper complement of chromosomes. If the chromosomes don't separate correctly, the daughter cells will have abnormal amounts of DNA. These cells with extra or missing chromosomes are known as aneuploid, and they are often severely dysfunctional. They tend to misread cellular cues and to behave erratically. Aneuploidy is a critical early step toward the development of many types of cancer. The mutation in the KNSTRN gene was caused by the replacement of a single nucleotide, called a cytosine, with another, called a thymine, within a specific, short stretch of DNA. The swap is indicative of a cell's attempt to repair damage from high-energy ultraviolet rays, such as those found in sunlight. "Mutations at this UV hotspot are not found in any of the other cancers we investigated," said Khavari. "They occur only in skin cancers." The researchers found the UV-induced KNSTRN mutation in about 20 percent of actinic keratoses—a premalignant skin condition that often progresses to squamous cell carcinoma—but never in 122 samples of normal skin, indicating the mutation is likely to be an early event in the development of squamous cell carcinomas. Furthermore, overexpression of mutant KNSTRN in laboratory-grown human skin cells disrupted their ability to segregate their DNA during cell division and enhanced the growth of cancer cells in a mouse model of squamous cell carcinoma. Finally, Lee compared five patient-derived squamous cell carcinomas that had the KNSTRN mutation with five samples that did not have the mutation. Although both sets of cells were aneuploid, those with the mutation had the most severely abnormal genomes. The identification of a new oncogene will allow researchers to better understand how these types of skin cancers develop. It may also give them clues about how to develop new therapies for the disease. In this case, it also neatly connects the dots between sun exposure and skin cancer. "Essentially, one ultraviolet-mediated mutation in this region promotes aneuploidy and subsequent tumorigenesis," said Khavari. "It is critical to protect the skin from the sun." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The development of two-dimensional (2D) materials has opened up possibilities for their application in electronics, optoelectronics and photovoltaics, because they can provide devices with smaller size, higher speed and additional functionalities compared with conventional silicon-based devices 1 . The ability to grow large, high-quality single crystals for 2D components—that is, conductors, semiconductors and insulators—is essential for the industrial application of 2D devices 2 , 3 , 4 . Atom-layered hexagonal boron nitride (hBN), with its excellent stability, flat surface and large bandgap, has been reported to be the best 2D insulator 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 . However, the size of 2D hBN single crystals is typically limited to less than one millimetre 13 , 14 , 15 , 16 , 17 , 18 , mainly because of difficulties in the growth of such crystals; these include excessive nucleation, which precludes growth from a single nucleus to large single crystals, and the threefold symmetry of the hBN lattice, which leads to antiparallel domains and twin boundaries on most substrates 19 . Here we report the epitaxial growth of a 100-square-centimetre single-crystal hBN monolayer on a low-symmetry Cu (110) vicinal surface, obtained by annealing an industrial copper foil. Structural characterizations and theoretical calculations indicate that epitaxial growth was achieved by the coupling of Cu <211> step edges with hBN zigzag edges, which breaks the equivalence of antiparallel hBN domains, enabling unidirectional domain alignment better than 99 per cent. The growth kinetics, unidirectional alignment and seamless stitching of the hBN domains are unambiguously demonstrated using centimetre- to atomic-scale characterization techniques. Our findings are expected to facilitate the wide application of 2D devices and lead to the epitaxial growth of broad non-centrosymmetric 2D materials, such as various transition-metal dichalcogenides 20 , 21 , 22 , 23 , to produce large single crystals. Main Recently, a macro-sized (with a length of up to 0.5 m) single-crystal Cu (111) foil and the epitaxial growth of single-crystal graphene on that substrate have been demonstrated, paving the way for the epitaxial growth of single crystals of various 2D materials 2 , 3 . However, the Cu (111) surface is not an appropriate template for the growth of single-crystal hBN owing to the nucleation of antiparallel hBN domains 19 . This is because the epitaxial growth of unidirectionally aligned domains requires the 2D material to adopt the symmetry of the substrate precisely to avoid changes in lattice orientation during a symmetric operation of the substrate. In contrast to graphene, most 2D materials, including hBN, have a lower symmetry (C 3 v for hBN) and therefore are not compatible with the C 6 v symmetry of the top-layer atoms of the Cu (111) surface. Thus, the ideal substrate for hBN growth must have C 3 v , C 3 , σ v or C 1 symmetry. Because the Cu (111) surface cannot be used to grow hBN single crystals, we have to choose a substrate with only σ v or C 1 symmetry, that is, without a regular low-index face-centred cubic (fcc) surface. To address this challenge, in this study we performed the successful synthesis of a Cu (110) vicinal surface, on which the presence of metal steps along the <211> direction led to a C 1 symmetry. This enabled the coupling of Cu <211> step edges with hBN zigzag edges, resulting in the unidirectional alignment of millions of hBN nuclei over a large 10 × 10 cm 2 area. In our experiment, 10 × 10 cm 2 single-crystal Cu foils of the Cu (110) vicinal surface were prepared by annealing industrial Cu foils using a designed high-temperature (1,060 °C) pre-treatment process before long-time standard annealing treatment (details in Methods and Extended Data Fig. 1a–g ). Such a large-area Cu (110) surface can be easily observed by optical imaging after mild oxidization in air (Fig. 1a ), because different surfaces form Cu 2 O with different oxidization rates and show characteristic colours 24 . The sharp Cu (220) peak in the X-ray diffraction (XRD) pattern in the 2 θ scan (Fig. 1b ) and the presence of only two peaks at an interval of exactly 180° in the ϕ scan (Fig. 1c ; fixed along Cu <100>) unambiguously confirmed that the single-crystal foil had no in-plane rotation (2 θ is the angle between the incident X-rays and the detector and ϕ is the in-plane rotation angle of the sample). Furthermore, at different positions (as marked in Extended Data Fig. 2a ), electron backscatter diffraction (EBSD) maps (Fig. 1d , Extended Data Fig. 2b, c ), low-energy electron diffraction (LEED) patterns (Fig. 1e , Extended Data Fig. 2d ) and scanning transmission electron microscopy (STEM) images (Fig. 1f ) revealed the single-crystal nature of the Cu (110) substrate. Here, we note that the exact surface index and the deviation of the tilt angle from ideal Cu (110) is difficult to observe, which means that the tilt angle is smaller than the experimental accuracy of about 1°. We have chosen, however, to call the substrate Cu (110) unless otherwise specified. Fig. 1: Characterization of single-crystal Cu (110) obtained by annealing an industrial Cu foil. a , Optical image of the as-annealed Cu foil after mild oxidation in air. Owing to their different oxidation rates, the Cu (110) and Cu (111) domains have a different thickness of Cu 2 O on their surfaces and are therefore different colours. Typical Cu (110) single crystals with areas of 10 × 10 cm 2 were obtained. b , c , XRD patterns obtained by a 2 θ scan of the Cu (110) foil ( b ) and a ϕ scan fixed along the Cu <100> direction ( c ), confirming the single-crystal nature of the Cu (110) foil, without in-plane rotation. d , Representative EBSD maps of as-annealed Cu (110) foils (upper panel, along the [001] direction; lower panel, along the [010] direction) measured at position 1 shown in Extended Data Fig. 2a .", "role": "user" }, { "content": "What makes something a crystal? A transparent and glittery gemstone? Not necessarily, in the microscopic world. When all of its atoms are arranged in accordance with specific mathematical rules, we call the material a single crystal. As the natural world has its unique symmetry, e.g., snowflakes or honeycombs, the atomic world of crystals is designed by its own rules of structure and symmetry. This material structure has a profound effect on its physical properties as well. Specifically, single crystals play an important role in inducing a material's intrinsic properties to its full extent. Faced with the coming end of the miniaturization process that the silicon-based integrated circuit has allowed up to this point, major efforts have been dedicated to find a single crystalline replacement for silicon. In the search for the transistor of the future, two-dimensional (2-D) materials, especially graphene, have been the subject of intense research around the world. Being thin and flexible as a result of being only a single layer of atoms, this 2-D version of carbon even features unprecedented electricity and heat conductivity. However, the last decade's efforts for graphene transistors have been held up by physical restraints—graphene allows no control over electricity flow due to the lack of band gap. So then, what about other 2-D materials? A number of interesting 2-D materials have been reported to have similar or even superior properties. Still, the lack of understanding in creating ideal experimental conditions for large-area 2-D materials has limited their maximum size to just a few millimeters. Scientists at the Center for Multidimensional Carbon Material (CMCM) within the Institute for Basic Science (IBS) have presented a novel approach to synthesize on a large scale, silicon-wafer-size, single crystalline 2-D materials. Prof. Feng Ding and Ms. Leining Zhang in collaboration with their colleagues at Peking University, China and other institutions have found a substrate with a lower order of symmetry than that of a 2-D material that facilitates the synthesis of single crystalline 2-D materials in a large area. \"It was critical to find the right balance of rotational symmetries between a substrate and a 2-D material,\" notes Prof. Feng Ding, one of corresponding authors of this study. The researchers successfully synthesized hBN single crystals of 10 x 10 cm2 by using a new substrate: a surface near Cu(110) that has a lower symmetry of (1) than hBN with (3). (a-c), schematic of edge-coupling-guided hBN growth on a Cu (110) vicinal surface with atomic step edges along the <211> direction. (b) shows the top view and (c) shows a side view. Credit: IBS Why does symmetry matters? Symmetry, in particular rotational symmetry, describes how many times a certain shape fits on to itself during a full rotation of 360 degrees. The most efficient method to synthesize large-area and single crystals of 2-D materials is to arrange layers over layers of small single crystals and grow them upon a substrate. In this epitaxial growth, it is quite challenging to ensure all of the single crystals are aligned in a single direction. Orientation of the crystals is often affected by the underlying substrate. By theoretical analysis, the IBS scientists found that an hBN island (or a group of hBN atoms forming a single triangle shape) has two equivalent alignments on the Cu(111) surface that has a very high symmetry of (6). \"It was a common view that a substrate with high symmetry may lead to the growth of materials with a high symmetry. It seemed to make sense intuitively, but this study found it is incorrect,\" says Ms. Leining Zhang, the first author of the study. Previously, various substrates such as Cu(111) have been used to synthesize single crystalline hBN in a large area, but none of them were successful. Every effort ended with hBN islands aligning in several different directions on the surfaces. Convinced by the fact that the key to achieve unidirectional alignment is to reduce the symmetry of the substrate, the researchers made tremendous efforts to obtain vicinal surfaces of a Cu(110) orientation; a surface obtained by cutting a Cu(110) with a small tilt angle. It is like forming physical steps on Cu. As an hBN island tends to position in parallel to the edge of each step, it gets only one preferred alignment. The small tilt angle lowers the symmetry of the surface as well. The researchers eventually found that a class of vicinal surfaces of Cu (110) can be used to support the growth of hBN with perfect alignment. On a carefully selected substrate with the lowest symmetry (or the surface will repeat itself only after a 360 degree rotation), hBN has only one preferred direction of alignment. The research team of Prof. Kaihui Liu at Peking University has developed a unique method to anneal a large Cu foil, up to 10 x 10 cm2, into a single crystal with the vicinal Cu (110) surface, and with it, they have achieved the synthesis of hBN single crystals of the same size. (a) large area single-crystal copper foil with a low symmetric surface, a vicinal surface of Cu(110) orientation, namely V-(110). (b) the growth of large number of unidirectional aligned hBN islands on the vicinal Cu(110) surface. (c) SEM and AFM images of hBN islands on vicinal Cu (110). Credit: IBS Besides flexibility and ultrathin thickness, emerging 2-D materials can present extraordinary properties when they are enlarged as single crystals. \"This study provides a general guideline for the experimental synthesis of various 2-D materials. Besides the hBN, many other 2-D materials could be synthesized with large area single crystalline substrates with low symmetry,\" says Prof. Feng Ding. Notably, hBN is the most representative 2-D insulator, which is different from the conductive 2-D materials, such as graphene, and 2-D semiconductors, such as molybdenum disulfide (MoS2). The vertical stacking of various types of 2-D materials, such as hBN, graphene and MoS2, would lead to a large number of new materials with exceptional properties and can be used for numerous applications, such as high-performance electronics, sensors, or wearable electronics.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The development of two-dimensional (2D) materials has opened up possibilities for their application in electronics, optoelectronics and photovoltaics, because they can provide devices with smaller size, higher speed and additional functionalities compared with conventional silicon-based devices 1 . The ability to grow large, high-quality single crystals for 2D components—that is, conductors, semiconductors and insulators—is essential for the industrial application of 2D devices 2 , 3 , 4 . Atom-layered hexagonal boron nitride (hBN), with its excellent stability, flat surface and large bandgap, has been reported to be the best 2D insulator 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 . However, the size of 2D hBN single crystals is typically limited to less than one millimetre 13 , 14 , 15 , 16 , 17 , 18 , mainly because of difficulties in the growth of such crystals; these include excessive nucleation, which precludes growth from a single nucleus to large single crystals, and the threefold symmetry of the hBN lattice, which leads to antiparallel domains and twin boundaries on most substrates 19 . Here we report the epitaxial growth of a 100-square-centimetre single-crystal hBN monolayer on a low-symmetry Cu (110) vicinal surface, obtained by annealing an industrial copper foil. Structural characterizations and theoretical calculations indicate that epitaxial growth was achieved by the coupling of Cu <211> step edges with hBN zigzag edges, which breaks the equivalence of antiparallel hBN domains, enabling unidirectional domain alignment better than 99 per cent. The growth kinetics, unidirectional alignment and seamless stitching of the hBN domains are unambiguously demonstrated using centimetre- to atomic-scale characterization techniques. Our findings are expected to facilitate the wide application of 2D devices and lead to the epitaxial growth of broad non-centrosymmetric 2D materials, such as various transition-metal dichalcogenides 20 , 21 , 22 , 23 , to produce large single crystals. Main Recently, a macro-sized (with a length of up to 0.5 m) single-crystal Cu (111) foil and the epitaxial growth of single-crystal graphene on that substrate have been demonstrated, paving the way for the epitaxial growth of single crystals of various 2D materials 2 , 3 . However, the Cu (111) surface is not an appropriate template for the growth of single-crystal hBN owing to the nucleation of antiparallel hBN domains 19 . This is because the epitaxial growth of unidirectionally aligned domains requires the 2D material to adopt the symmetry of the substrate precisely to avoid changes in lattice orientation during a symmetric operation of the substrate. In contrast to graphene, most 2D materials, including hBN, have a lower symmetry (C 3 v for hBN) and therefore are not compatible with the C 6 v symmetry of the top-layer atoms of the Cu (111) surface. Thus, the ideal substrate for hBN growth must have C 3 v , C 3 , σ v or C 1 symmetry. Because the Cu (111) surface cannot be used to grow hBN single crystals, we have to choose a substrate with only σ v or C 1 symmetry, that is, without a regular low-index face-centred cubic (fcc) surface. To address this challenge, in this study we performed the successful synthesis of a Cu (110) vicinal surface, on which the presence of metal steps along the <211> direction led to a C 1 symmetry. This enabled the coupling of Cu <211> step edges with hBN zigzag edges, resulting in the unidirectional alignment of millions of hBN nuclei over a large 10 × 10 cm 2 area. In our experiment, 10 × 10 cm 2 single-crystal Cu foils of the Cu (110) vicinal surface were prepared by annealing industrial Cu foils using a designed high-temperature (1,060 °C) pre-treatment process before long-time standard annealing treatment (details in Methods and Extended Data Fig. 1a–g ). Such a large-area Cu (110) surface can be easily observed by optical imaging after mild oxidization in air (Fig. 1a ), because different surfaces form Cu 2 O with different oxidization rates and show characteristic colours 24 . The sharp Cu (220) peak in the X-ray diffraction (XRD) pattern in the 2 θ scan (Fig. 1b ) and the presence of only two peaks at an interval of exactly 180° in the ϕ scan (Fig. 1c ; fixed along Cu <100>) unambiguously confirmed that the single-crystal foil had no in-plane rotation (2 θ is the angle between the incident X-rays and the detector and ϕ is the in-plane rotation angle of the sample). Furthermore, at different positions (as marked in Extended Data Fig. 2a ), electron backscatter diffraction (EBSD) maps (Fig. 1d , Extended Data Fig. 2b, c ), low-energy electron diffraction (LEED) patterns (Fig. 1e , Extended Data Fig. 2d ) and scanning transmission electron microscopy (STEM) images (Fig. 1f ) revealed the single-crystal nature of the Cu (110) substrate. Here, we note that the exact surface index and the deviation of the tilt angle from ideal Cu (110) is difficult to observe, which means that the tilt angle is smaller than the experimental accuracy of about 1°. We have chosen, however, to call the substrate Cu (110) unless otherwise specified. Fig. 1: Characterization of single-crystal Cu (110) obtained by annealing an industrial Cu foil. a , Optical image of the as-annealed Cu foil after mild oxidation in air. Owing to their different oxidation rates, the Cu (110) and Cu (111) domains have a different thickness of Cu 2 O on their surfaces and are therefore different colours. Typical Cu (110) single crystals with areas of 10 × 10 cm 2 were obtained. b , c , XRD patterns obtained by a 2 θ scan of the Cu (110) foil ( b ) and a ϕ scan fixed along the Cu <100> direction ( c ), confirming the single-crystal nature of the Cu (110) foil, without in-plane rotation. d , Representative EBSD maps of as-annealed Cu (110) foils (upper panel, along the [001] direction; lower panel, along the [010] direction) measured at position 1 shown in Extended Data Fig. 2a .<|im_end|> <|im_start|>assistant What makes something a crystal? A transparent and glittery gemstone? Not necessarily, in the microscopic world. When all of its atoms are arranged in accordance with specific mathematical rules, we call the material a single crystal. As the natural world has its unique symmetry, e.g., snowflakes or honeycombs, the atomic world of crystals is designed by its own rules of structure and symmetry. This material structure has a profound effect on its physical properties as well. Specifically, single crystals play an important role in inducing a material's intrinsic properties to its full extent. Faced with the coming end of the miniaturization process that the silicon-based integrated circuit has allowed up to this point, major efforts have been dedicated to find a single crystalline replacement for silicon. In the search for the transistor of the future, two-dimensional (2-D) materials, especially graphene, have been the subject of intense research around the world. Being thin and flexible as a result of being only a single layer of atoms, this 2-D version of carbon even features unprecedented electricity and heat conductivity. However, the last decade's efforts for graphene transistors have been held up by physical restraints—graphene allows no control over electricity flow due to the lack of band gap. So then, what about other 2-D materials? A number of interesting 2-D materials have been reported to have similar or even superior properties. Still, the lack of understanding in creating ideal experimental conditions for large-area 2-D materials has limited their maximum size to just a few millimeters. Scientists at the Center for Multidimensional Carbon Material (CMCM) within the Institute for Basic Science (IBS) have presented a novel approach to synthesize on a large scale, silicon-wafer-size, single crystalline 2-D materials. Prof. Feng Ding and Ms. Leining Zhang in collaboration with their colleagues at Peking University, China and other institutions have found a substrate with a lower order of symmetry than that of a 2-D material that facilitates the synthesis of single crystalline 2-D materials in a large area. "It was critical to find the right balance of rotational symmetries between a substrate and a 2-D material," notes Prof. Feng Ding, one of corresponding authors of this study. The researchers successfully synthesized hBN single crystals of 10 x 10 cm2 by using a new substrate: a surface near Cu(110) that has a lower symmetry of (1) than hBN with (3). (a-c), schematic of edge-coupling-guided hBN growth on a Cu (110) vicinal surface with atomic step edges along the <211> direction. (b) shows the top view and (c) shows a side view. Credit: IBS Why does symmetry matters? Symmetry, in particular rotational symmetry, describes how many times a certain shape fits on to itself during a full rotation of 360 degrees. The most efficient method to synthesize large-area and single crystals of 2-D materials is to arrange layers over layers of small single crystals and grow them upon a substrate. In this epitaxial growth, it is quite challenging to ensure all of the single crystals are aligned in a single direction. Orientation of the crystals is often affected by the underlying substrate. By theoretical analysis, the IBS scientists found that an hBN island (or a group of hBN atoms forming a single triangle shape) has two equivalent alignments on the Cu(111) surface that has a very high symmetry of (6). "It was a common view that a substrate with high symmetry may lead to the growth of materials with a high symmetry. It seemed to make sense intuitively, but this study found it is incorrect," says Ms. Leining Zhang, the first author of the study. Previously, various substrates such as Cu(111) have been used to synthesize single crystalline hBN in a large area, but none of them were successful. Every effort ended with hBN islands aligning in several different directions on the surfaces. Convinced by the fact that the key to achieve unidirectional alignment is to reduce the symmetry of the substrate, the researchers made tremendous efforts to obtain vicinal surfaces of a Cu(110) orientation; a surface obtained by cutting a Cu(110) with a small tilt angle. It is like forming physical steps on Cu. As an hBN island tends to position in parallel to the edge of each step, it gets only one preferred alignment. The small tilt angle lowers the symmetry of the surface as well. The researchers eventually found that a class of vicinal surfaces of Cu (110) can be used to support the growth of hBN with perfect alignment. On a carefully selected substrate with the lowest symmetry (or the surface will repeat itself only after a 360 degree rotation), hBN has only one preferred direction of alignment. The research team of Prof. Kaihui Liu at Peking University has developed a unique method to anneal a large Cu foil, up to 10 x 10 cm2, into a single crystal with the vicinal Cu (110) surface, and with it, they have achieved the synthesis of hBN single crystals of the same size. (a) large area single-crystal copper foil with a low symmetric surface, a vicinal surface of Cu(110) orientation, namely V-(110). (b) the growth of large number of unidirectional aligned hBN islands on the vicinal Cu(110) surface. (c) SEM and AFM images of hBN islands on vicinal Cu (110). Credit: IBS Besides flexibility and ultrathin thickness, emerging 2-D materials can present extraordinary properties when they are enlarged as single crystals. "This study provides a general guideline for the experimental synthesis of various 2-D materials. Besides the hBN, many other 2-D materials could be synthesized with large area single crystalline substrates with low symmetry," says Prof. Feng Ding. Notably, hBN is the most representative 2-D insulator, which is different from the conductive 2-D materials, such as graphene, and 2-D semiconductors, such as molybdenum disulfide (MoS2). The vertical stacking of various types of 2-D materials, such as hBN, graphene and MoS2, would lead to a large number of new materials with exceptional properties and can be used for numerous applications, such as high-performance electronics, sensors, or wearable electronics." <|im_end|>

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8, 7389, 6062, 5300, 13, 23966, 13, 220, 16, 25, 16007, 2065, 315, 3254, 48689, 14272, 27560, 320, 5120, 8, 12457, 555, 86997, 6260, 459, 13076, 27560, 47499, 13, 264, 1174, 75939, 2217, 315, 279, 439, 19415, 818, 5962, 27560, 47499, 1306, 23900, 71162, 304, 3805, 13, 507, 24510, 311, 872, 2204, 71162, 7969, 11, 279, 27560, 320, 5120, 8, 323, 27560, 320, 5037, 8, 31576, 617, 264, 2204, 26839, 315, 27560, 220, 17, 507, 389, 872, 27529, 323, 527, 9093, 2204, 27230, 13, 74025, 27560, 320, 5120, 8, 3254, 48473, 449, 5789, 315, 220, 605, 25800, 220, 605, 10166, 220, 17, 1051, 12457, 13, 293, 1174, 272, 1174, 1630, 37790, 12912, 12457, 555, 264, 220, 17, 101174, 8737, 315, 279, 27560, 320, 5120, 8, 47499, 320, 293, 883, 323, 264, 17839, 243, 8737, 8521, 3235, 279, 27560, 366, 1041, 29, 5216, 320, 272, 7026, 50096, 279, 3254, 48689, 14272, 7138, 315, 279, 27560, 320, 5120, 8, 47499, 11, 2085, 304, 90649, 12984, 13, 294, 1174, 38366, 469, 31129, 14370, 315, 439, 19415, 818, 5962, 27560, 320, 5120, 8, 12018, 8839, 320, 13886, 7090, 11, 3235, 279, 510, 4119, 60, 5216, 26, 4827, 7090, 11, 3235, 279, 510, 7755, 60, 5216, 8, 17303, 520, 2361, 220, 16, 6982, 304, 41665, 2956, 23966, 13, 220, 17, 64, 662, 128257, 198, 128256, 78191, 198, 3923, 3727, 2555, 264, 26110, 30, 362, 18300, 323, 55251, 88, 19269, 11046, 30, 2876, 14647, 11, 304, 279, 90090, 1917, 13, 3277, 682, 315, 1202, 33299, 527, 28902, 304, 18859, 449, 3230, 37072, 5718, 11, 584, 1650, 279, 3769, 264, 3254, 26110, 13, 1666, 279, 5933, 1917, 706, 1202, 5016, 46220, 11, 384, 1326, 2637, 12056, 1517, 2094, 477, 26828, 884, 1302, 11, 279, 25524, 1917, 315, 48473, 374, 6319, 555, 1202, 1866, 5718, 315, 6070, 323, 46220, 13, 1115, 3769, 6070, 706, 264, 28254, 2515, 389, 1202, 7106, 6012, 439, 1664, 13, 45863, 11, 3254, 48473, 1514, 459, 3062, 3560, 304, 96811, 264, 3769, 596, 47701, 6012, 311, 1202, 2539, 13112, 13, 435, 4535, 449, 279, 5108, 842, 315, 279, 13726, 2693, 2065, 1920, 430, 279, 51692, 6108, 18751, 16622, 706, 5535, 709, 311, 420, 1486, 11, 3682, 9045, 617, 1027, 12514, 311, 1505, 264, 3254, 64568, 483, 14039, 369, 51692, 13, 763, 279, 2778, 369, 279, 99041, 315, 279, 3938, 11, 1403, 33520, 320, 17, 9607, 8, 7384, 11, 5423, 66192, 11, 617, 1027, 279, 3917, 315, 19428, 3495, 2212, 279, 1917, 13, 21347, 15792, 323, 19303, 439, 264, 1121, 315, 1694, 1193, 264, 3254, 6324, 315, 33299, 11, 420, 220, 17, 9607, 2373, 315, 12782, 1524, 4519, 31069, 18200, 323, 8798, 98971, 13, 4452, 11, 279, 1566, 13515, 596, 9045, 369, 66192, 1380, 380, 1105, 617, 1027, 5762, 709, 555, 7106, 312, 7610, 2345, 4539, 1994, 6276, 912, 2585, 927, 18200, 6530, 4245, 311, 279, 6996, 315, 7200, 13225, 13, 2100, 1243, 11, 1148, 922, 1023, 220, 17, 9607, 7384, 30, 362, 1396, 315, 7185, 220, 17, 9607, 7384, 617, 1027, 5068, 311, 617, 4528, 477, 1524, 16757, 6012, 13, 16782, 11, 279, 6996, 315, 8830, 304, 6968, 10728, 22772, 4787, 369, 3544, 30122, 220, 17, 9607, 7384, 706, 7347, 872, 7340, 1404, 311, 1120, 264, 2478, 2606, 55336, 13, 57116, 520, 279, 5955, 369, 22950, 307, 29321, 22208, 10441, 320, 10190, 10190, 8, 2949, 279, 10181, 369, 14967, 10170, 320, 3336, 50, 8, 617, 10666, 264, 11775, 5603, 311, 6925, 27985, 389, 264, 3544, 5569, 11, 51692, 2695, 64, 809, 7321, 11, 3254, 64568, 483, 220, 17, 9607, 7384, 13, 8626, 13, 43758, 80473, 323, 16450, 13, 2009, 5859, 37120, 304, 20632, 449, 872, 18105, 520, 393, 59952, 3907, 11, 5734, 323, 1023, 14673, 617, 1766, 264, 54057, 449, 264, 4827, 2015, 315, 46220, 1109, 430, 315, 264, 220, 17, 9607, 3769, 430, 73633, 279, 39975, 315, 3254, 64568, 483, 220, 17, 9607, 7384, 304, 264, 3544, 3158, 13, 330, 2181, 574, 9200, 311, 1505, 279, 1314, 8335, 315, 92371, 8045, 4150, 4108, 1990, 264, 54057, 323, 264, 220, 17, 9607, 3769, 1359, 8554, 8626, 13, 43758, 80473, 11, 832, 315, 12435, 12283, 315, 420, 4007, 13, 578, 12074, 7946, 92106, 305, 15967, 3254, 48473, 315, 220, 605, 865, 220, 605, 10166, 17, 555, 1701, 264, 502, 54057, 25, 264, 7479, 3221, 27560, 7, 5120, 8, 430, 706, 264, 4827, 46220, 315, 320, 16, 8, 1109, 305, 15967, 449, 320, 18, 570, 320, 64, 1824, 705, 68144, 315, 6964, 1824, 283, 12127, 84792, 291, 305, 15967, 6650, 389, 264, 27560, 320, 5120, 8, 32531, 992, 7479, 449, 25524, 3094, 13116, 3235, 279, 366, 11483, 29, 5216, 13, 320, 65, 8, 5039, 279, 1948, 1684, 323, 320, 66, 8, 5039, 264, 3185, 1684, 13, 16666, 25, 358, 7497, 8595, 1587, 46220, 13146, 30, 11629, 33342, 11, 304, 4040, 92371, 46220, 11, 16964, 1268, 1690, 3115, 264, 3738, 6211, 18809, 389, 311, 5196, 2391, 264, 2539, 12984, 315, 220, 6843, 12628, 13, 578, 1455, 11297, 1749, 311, 6925, 27985, 3544, 30122, 323, 3254, 48473, 315, 220, 17, 9607, 7384, 374, 311, 31993, 13931, 927, 13931, 315, 2678, 3254, 48473, 323, 3139, 1124, 5304, 264, 54057, 13, 763, 420, 67422, 710, 532, 6650, 11, 433, 374, 5115, 17436, 311, 6106, 682, 315, 279, 3254, 48473, 527, 27210, 304, 264, 3254, 5216, 13, 55234, 315, 279, 48473, 374, 3629, 11754, 555, 279, 16940, 54057, 13, 3296, 32887, 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1139, 264, 3254, 26110, 449, 279, 32531, 992, 27560, 320, 5120, 8, 7479, 11, 323, 449, 433, 11, 814, 617, 17427, 279, 39975, 315, 305, 15967, 3254, 48473, 315, 279, 1890, 1404, 13, 320, 64, 8, 3544, 3158, 3254, 48689, 14272, 24166, 47499, 449, 264, 3428, 55443, 7479, 11, 264, 32531, 992, 7479, 315, 27560, 7, 5120, 8, 17140, 11, 32125, 650, 8172, 5120, 570, 320, 65, 8, 279, 6650, 315, 3544, 1396, 315, 653, 307, 45770, 27210, 305, 15967, 30100, 389, 279, 32531, 992, 27560, 7, 5120, 8, 7479, 13, 320, 66, 8, 46544, 323, 20479, 44, 5448, 315, 305, 15967, 30100, 389, 32531, 992, 27560, 320, 5120, 570, 16666, 25, 358, 7497, 31909, 25152, 323, 37232, 589, 258, 26839, 11, 24084, 220, 17, 9607, 7384, 649, 3118, 24674, 6012, 994, 814, 527, 74117, 439, 3254, 48473, 13, 330, 2028, 4007, 5825, 264, 4689, 73545, 369, 279, 22772, 39975, 315, 5370, 220, 17, 9607, 7384, 13, 31909, 279, 305, 15967, 11, 1690, 1023, 220, 17, 9607, 7384, 1436, 387, 92106, 449, 3544, 3158, 3254, 64568, 483, 16146, 988, 449, 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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Genetic variants conferring risk for autism spectrum disorder (ASD) have been identified, but the role of post-transcriptional mechanisms in ASD is not well understood. We performed genome-wide microRNA (miRNA) expression profiling in post-mortem brains from individuals with ASD and controls and identified miRNAs and co-regulated modules that were perturbed in ASD. Putative targets of these ASD-affected miRNAs were enriched for genes that have been implicated in ASD risk. We confirmed regulatory relationships between several miRNAs and their putative target mRNAs in primary human neural progenitors. These include hsa-miR-21-3p, a miRNA of unknown CNS function that is upregulated in ASD and that targets neuronal genes downregulated in ASD, and hsa_can_1002-m, a previously unknown, primate-specific miRNA that is downregulated in ASD and that regulates the epidermal growth factor receptor and fibroblast growth factor receptor signaling pathways involved in neural development and immune function. Our findings support a role for miRNA dysregulation in ASD pathophysiology and provide a rich data set and framework for future analyses of miRNAs in neuropsychiatric diseases. Main ASD is a group of clinically heterogeneous neurodevelopmental disorders characterized by deficits in social functioning and the presence of repetitive and restricted behaviors or interests 1 , 2 . ASD also manifests substantial genetic heterogeneity; hundreds of genomic loci have been implicated 1 , 2 . Dozens of rare Mendelian disorders, including fragile X syndrome, neurofibromatosis, Rett syndrome, tuberous sclerosis complex and structural chromosomal variants, confer a high risk for ASD 1 , 2 . Recent studies have also revealed the contribution of rare, de novo single-nucleotide mutations, none of which account for more than a small fraction of ASD cases 1 , 2 . Thousands of common variants are also estimated to contribute to ASD, although the effect size of individual loci is small 1 , 2 , 3 , 4 . Despite this remarkable heterogeneity, ASD-associated mutations have been suggested to target a few convergent biological processes, including synaptic function and neuronal activity, postsynaptic density protein metabolism, neuronal cell adhesion, WNT signaling, and chromatin remodeling during neurogenesis 1 , 2 . In contrast, much less is known about the contribution of post-transcriptional regulatory mechanisms to ASD. miRNAs, which are small non-coding regulatory RNAs that mediate mRNA destabilization and/or translational repression 5 , represent a sparsely studied class of putative contributors to ASD pathophysiology. Each miRNA can target up to hundreds of genes; collectively, miRNAs are predicted to target >60% of the transcriptome, establishing them as potential regulators of complex gene networks 5 , 6 . miRNAs have been shown to regulate processes that are pivotal to brain development and function, including neurogenesis, neuronal maturation and synaptic plasticity 7 . To assess the potential role of miRNAs in ASD, we performed genome-wide miRNA expression profiling in post-mortem brains from individuals with ASD and controls. We found a shared pattern of miRNA dysregulation in a majority of ASD-affected brains. The targets of ASD-associated miRNAs were enriched in ASD risk genes. Using bioinformatic and gene network analyses, we were able to link these perturbations with transcriptomic changes in ASD-affected brain. Results Differential expression of miRNAs in ASD brain We profiled miRNAs in 242 post-mortem brain tissue samples from 55 ASD cases and 42 controls (CTL) ( Fig. 1a and Supplementary Table 1 ) using Illumina small RNA sequencing (sRNA-seq; Online Methods ). Up to three brain regions from each individual were assessed: frontal cortex (FC, Brodmann area (BA) 9), temporal cortex (TC, BA41/42/22) and cerebellar vermis ( Fig. 1a ), all of which have been implicated in ASD 8 . After quality control ( Supplementary Fig. 1a,b ; Online Methods ), mature miRNAs documented in miRBase release 20 ( ) were identified and quantified using the miRDeep2 algorithm 9 (Online Methods ). We also included in our analysis previously unknown miRNAs that were identified in a recent study based on 94 human sRNA-seq data sets and supported by experimental evidence 10 , as well as previously unknown miRNAs predicted from our sequencing data with high confidence using two different methods (Online Methods and Supplementary Table 2 ). 699 miRNAs (552 in miRBase 20 and 147 previously unknown) were detected (Online Methods and Supplementary Table 2 ). Figure 1: miRNA expression changes in post-mortem ASD cortex. ( a ) Flow chart of the overall approach. ( b ) miRNA expression fold changes (>0 if higher in ASD, <0 if lower in ASD) between ASD and control cerebral cortex, plotted against the percentile rank of mean expression levels across 95 cortex samples (47 samples from 28 ASD cases and 48 samples from 28 controls) used for DGE analysis. Differentially expressed (linear mixed-effects model, FDR < 0.05) miRNAs are highlighted in red. ( c ) Comparison of miRNA expression fold changes in the temporal and the frontal cortex. Green dots, 58 miRNAs differentially expressed (FDR < 0.05) in 95 combined cortex samples; gray dots, non-differentially expressed miRNAs; black line, regression line between fold changes in the temporal and the frontal cortex for the differentially expressed miRNAs; red line, y = x . The Pearson correlation coefficient ( R ) and P value are also shown. ( d ) Dendrogram showing hierarchical clustering of 95 cortex samples based on top differentially expressed (FDR < 0.05, |log 2 (fold change)| ≥ 0.3) miRNAs. Information on diagnosis, age, sex, brain region, co-morbidity of seizures, psychiatric medication, RIN and brain bank is indicated with color bars below the dendrogram according to the legend on the right. Heat map on the bottom shows scaled (mean extracted and divided by s.d.) expression values (color-coded according to the legend on the right) for miRNAs used for clustering. Full size image The miRNA expression profiles were very similar between the frontal and temporal cortex, but were distinct in the cerebellum ( Supplementary Fig. 2a–f ), consistent with previous observations for mRNAs 11 , 12 . We therefore combined 95 covariate-matched samples (47 samples from 28 ASD cases and 48 samples from 28 controls; Supplementary Fig. 1c and Supplementary Table 1 ) from", "role": "user" }, { "content": "In an important new study, scientists at UCLA have found that the brains of people with autism spectrum disorders show distinctive changes in the levels of tiny regulator molecules known as microRNAs, which control the activities of large gene networks. The study is the first to demonstrate the broad importance of microRNAs in autism disorders. The researchers found evidence that the individual microRNAs implicated in the study regulate many genes previously linked to autism. The study thus brings researchers closer to understanding the causes of autism disorders, and in particular why the activities of so many genes are abnormal in these disorders. In principle, microRNAs or related molecules could someday be targeted with drugs to treat or prevent autism. \"These findings add a new layer to our understanding of the molecular changes that occur in the brains of patients with autism spectrum disorders, and give us a good framework for more detailed investigations of microRNAs' contributions to these disorders,\" said Dr. Daniel Geschwind, principal investigator and the Gordon and Virginia MacDonald Distinguished Professor of Human Genetics in the David Geffen School of Medicine at UCLA. The new research, published online in Nature Neuroscience, is by far the most comprehensive autism-related study of microRNAs, small molecules made of single-stranded RNA (ribonucleic acid), DNA's more primitive cousin. Almost nothing was known about microRNAs before 2001, but researchers have since determined that hundreds of different microRNAs exist in human cells, and collectively regulate the activity of most of our genes. Because a typical microRNA reduces the activities of dozens to hundreds of genes, too much or too little of that microRNA can disrupt the normal workings of many cellular processes at once. Unsurprisingly, microRNA abnormalities have already been linked to a variety of disorders, including Alzheimer's and cancers. \"Autism is in a sense a good place to look for microRNA abnormalities, because prior studies from our laboratory and others have linked autism disorders to changes in the expression levels of a large number of genes,\" said Geschwind, who is also a professor of neurology and psychiatry. For the study, Geschwind and colleagues measured levels of nearly 700 microRNAs in samples of brain tissue taken during autopsies of 55 people with autism spectrum disorders, and 42 control subjects without autism disorders. The analysis focused on samples from the cortex, which in most of the autism spectrum disorder cases showed a distinctive \"signature\" of abnormalities, involving 58 microRNAs—17 with lower than normal levels and 41 with higher than normal levels. Looking at groupings or \"modules\" of microRNAs that seem to work together in cells, the team found another autism spectrum disorder signature: two distinct modules whose microRNAs were at abnormally high levels in the autism spectrum disorder samples, and one whose microRNAs were at abnormally low levels. The affected microRNAs are thought collectively to regulate hundreds of different genes. Among them, the scientists found a disproportionately large number that are already considered \"autism risk\" genes—typically because mutations or uncommon variants of those genes have been linked to autism spectrum disorders. The genes thought to be regulated by the autism-linked microRNAs also include many whose activity is known to be abnormal in autism, even when there is no obvious autism-risk mutation. Geschwind's team selected several of the most strongly ASD-linked microRNAs, and confirmed with experiments in cultured brain cells that altering their levels—in the direction seen in the autism spectrum disorder samples—caused the kinds of changes in gene activity that were also seen in these samples. \"From all this it seems likely that abnormalities in the levels of these microRNAs contribute to the broad gene expression changes we see in the brain in autism,\" said Emily Wu, a postdoctoral scholar in the Geschwind Laboratory who was first author of the study and performed most of the experiments. The study employed advanced RNA sequencing techniques and was thorough enough to uncover, and link to the autism disorder cases, several microRNAs that had never been described before. One of them, hsa_can_1002-m, turned out to be specific for primates and thus couldn't have been detected in mouse studies. The team plans to follow up by studying these ASD-linked microRNAs in more detail, to better characterize the effects of their altered levels on gene activity, brain development, cognition and behavior. \"It would be interesting to test whether manipulating the levels of these microRNAs in animal models of autism can reverse autism-related signs,\" Wu said. Any clinical payoff from the new research is many years away at best. But success in targeting microRNAs in animal model studies might eventually lead to the development of autism spectrum disorder treatments or even preventive measures. Autism spectrum disorders currently affect about one in 40 boys and one in 200 girls in the United States, and there are no specific therapies. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Genetic variants conferring risk for autism spectrum disorder (ASD) have been identified, but the role of post-transcriptional mechanisms in ASD is not well understood. We performed genome-wide microRNA (miRNA) expression profiling in post-mortem brains from individuals with ASD and controls and identified miRNAs and co-regulated modules that were perturbed in ASD. Putative targets of these ASD-affected miRNAs were enriched for genes that have been implicated in ASD risk. We confirmed regulatory relationships between several miRNAs and their putative target mRNAs in primary human neural progenitors. These include hsa-miR-21-3p, a miRNA of unknown CNS function that is upregulated in ASD and that targets neuronal genes downregulated in ASD, and hsa_can_1002-m, a previously unknown, primate-specific miRNA that is downregulated in ASD and that regulates the epidermal growth factor receptor and fibroblast growth factor receptor signaling pathways involved in neural development and immune function. Our findings support a role for miRNA dysregulation in ASD pathophysiology and provide a rich data set and framework for future analyses of miRNAs in neuropsychiatric diseases. Main ASD is a group of clinically heterogeneous neurodevelopmental disorders characterized by deficits in social functioning and the presence of repetitive and restricted behaviors or interests 1 , 2 . ASD also manifests substantial genetic heterogeneity; hundreds of genomic loci have been implicated 1 , 2 . Dozens of rare Mendelian disorders, including fragile X syndrome, neurofibromatosis, Rett syndrome, tuberous sclerosis complex and structural chromosomal variants, confer a high risk for ASD 1 , 2 . Recent studies have also revealed the contribution of rare, de novo single-nucleotide mutations, none of which account for more than a small fraction of ASD cases 1 , 2 . Thousands of common variants are also estimated to contribute to ASD, although the effect size of individual loci is small 1 , 2 , 3 , 4 . Despite this remarkable heterogeneity, ASD-associated mutations have been suggested to target a few convergent biological processes, including synaptic function and neuronal activity, postsynaptic density protein metabolism, neuronal cell adhesion, WNT signaling, and chromatin remodeling during neurogenesis 1 , 2 . In contrast, much less is known about the contribution of post-transcriptional regulatory mechanisms to ASD. miRNAs, which are small non-coding regulatory RNAs that mediate mRNA destabilization and/or translational repression 5 , represent a sparsely studied class of putative contributors to ASD pathophysiology. Each miRNA can target up to hundreds of genes; collectively, miRNAs are predicted to target >60% of the transcriptome, establishing them as potential regulators of complex gene networks 5 , 6 . miRNAs have been shown to regulate processes that are pivotal to brain development and function, including neurogenesis, neuronal maturation and synaptic plasticity 7 . To assess the potential role of miRNAs in ASD, we performed genome-wide miRNA expression profiling in post-mortem brains from individuals with ASD and controls. We found a shared pattern of miRNA dysregulation in a majority of ASD-affected brains. The targets of ASD-associated miRNAs were enriched in ASD risk genes. Using bioinformatic and gene network analyses, we were able to link these perturbations with transcriptomic changes in ASD-affected brain. Results Differential expression of miRNAs in ASD brain We profiled miRNAs in 242 post-mortem brain tissue samples from 55 ASD cases and 42 controls (CTL) ( Fig. 1a and Supplementary Table 1 ) using Illumina small RNA sequencing (sRNA-seq; Online Methods ). Up to three brain regions from each individual were assessed: frontal cortex (FC, Brodmann area (BA) 9), temporal cortex (TC, BA41/42/22) and cerebellar vermis ( Fig. 1a ), all of which have been implicated in ASD 8 . After quality control ( Supplementary Fig. 1a,b ; Online Methods ), mature miRNAs documented in miRBase release 20 ( ) were identified and quantified using the miRDeep2 algorithm 9 (Online Methods ). We also included in our analysis previously unknown miRNAs that were identified in a recent study based on 94 human sRNA-seq data sets and supported by experimental evidence 10 , as well as previously unknown miRNAs predicted from our sequencing data with high confidence using two different methods (Online Methods and Supplementary Table 2 ). 699 miRNAs (552 in miRBase 20 and 147 previously unknown) were detected (Online Methods and Supplementary Table 2 ). Figure 1: miRNA expression changes in post-mortem ASD cortex. ( a ) Flow chart of the overall approach. ( b ) miRNA expression fold changes (>0 if higher in ASD, <0 if lower in ASD) between ASD and control cerebral cortex, plotted against the percentile rank of mean expression levels across 95 cortex samples (47 samples from 28 ASD cases and 48 samples from 28 controls) used for DGE analysis. Differentially expressed (linear mixed-effects model, FDR < 0.05) miRNAs are highlighted in red. ( c ) Comparison of miRNA expression fold changes in the temporal and the frontal cortex. Green dots, 58 miRNAs differentially expressed (FDR < 0.05) in 95 combined cortex samples; gray dots, non-differentially expressed miRNAs; black line, regression line between fold changes in the temporal and the frontal cortex for the differentially expressed miRNAs; red line, y = x . The Pearson correlation coefficient ( R ) and P value are also shown. ( d ) Dendrogram showing hierarchical clustering of 95 cortex samples based on top differentially expressed (FDR < 0.05, |log 2 (fold change)| ≥ 0.3) miRNAs. Information on diagnosis, age, sex, brain region, co-morbidity of seizures, psychiatric medication, RIN and brain bank is indicated with color bars below the dendrogram according to the legend on the right. Heat map on the bottom shows scaled (mean extracted and divided by s.d.) expression values (color-coded according to the legend on the right) for miRNAs used for clustering. Full size image The miRNA expression profiles were very similar between the frontal and temporal cortex, but were distinct in the cerebellum ( Supplementary Fig. 2a–f ), consistent with previous observations for mRNAs 11 , 12 . We therefore combined 95 covariate-matched samples (47 samples from 28 ASD cases and 48 samples from 28 controls; Supplementary Fig. 1c and Supplementary Table 1 ) from<|im_end|> <|im_start|>assistant In an important new study, scientists at UCLA have found that the brains of people with autism spectrum disorders show distinctive changes in the levels of tiny regulator molecules known as microRNAs, which control the activities of large gene networks. The study is the first to demonstrate the broad importance of microRNAs in autism disorders. The researchers found evidence that the individual microRNAs implicated in the study regulate many genes previously linked to autism. The study thus brings researchers closer to understanding the causes of autism disorders, and in particular why the activities of so many genes are abnormal in these disorders. In principle, microRNAs or related molecules could someday be targeted with drugs to treat or prevent autism. "These findings add a new layer to our understanding of the molecular changes that occur in the brains of patients with autism spectrum disorders, and give us a good framework for more detailed investigations of microRNAs' contributions to these disorders," said Dr. Daniel Geschwind, principal investigator and the Gordon and Virginia MacDonald Distinguished Professor of Human Genetics in the David Geffen School of Medicine at UCLA. The new research, published online in Nature Neuroscience, is by far the most comprehensive autism-related study of microRNAs, small molecules made of single-stranded RNA (ribonucleic acid), DNA's more primitive cousin. Almost nothing was known about microRNAs before 2001, but researchers have since determined that hundreds of different microRNAs exist in human cells, and collectively regulate the activity of most of our genes. Because a typical microRNA reduces the activities of dozens to hundreds of genes, too much or too little of that microRNA can disrupt the normal workings of many cellular processes at once. Unsurprisingly, microRNA abnormalities have already been linked to a variety of disorders, including Alzheimer's and cancers. "Autism is in a sense a good place to look for microRNA abnormalities, because prior studies from our laboratory and others have linked autism disorders to changes in the expression levels of a large number of genes," said Geschwind, who is also a professor of neurology and psychiatry. For the study, Geschwind and colleagues measured levels of nearly 700 microRNAs in samples of brain tissue taken during autopsies of 55 people with autism spectrum disorders, and 42 control subjects without autism disorders. The analysis focused on samples from the cortex, which in most of the autism spectrum disorder cases showed a distinctive "signature" of abnormalities, involving 58 microRNAs—17 with lower than normal levels and 41 with higher than normal levels. Looking at groupings or "modules" of microRNAs that seem to work together in cells, the team found another autism spectrum disorder signature: two distinct modules whose microRNAs were at abnormally high levels in the autism spectrum disorder samples, and one whose microRNAs were at abnormally low levels. The affected microRNAs are thought collectively to regulate hundreds of different genes. Among them, the scientists found a disproportionately large number that are already considered "autism risk" genes—typically because mutations or uncommon variants of those genes have been linked to autism spectrum disorders. The genes thought to be regulated by the autism-linked microRNAs also include many whose activity is known to be abnormal in autism, even when there is no obvious autism-risk mutation. Geschwind's team selected several of the most strongly ASD-linked microRNAs, and confirmed with experiments in cultured brain cells that altering their levels—in the direction seen in the autism spectrum disorder samples—caused the kinds of changes in gene activity that were also seen in these samples. "From all this it seems likely that abnormalities in the levels of these microRNAs contribute to the broad gene expression changes we see in the brain in autism," said Emily Wu, a postdoctoral scholar in the Geschwind Laboratory who was first author of the study and performed most of the experiments. The study employed advanced RNA sequencing techniques and was thorough enough to uncover, and link to the autism disorder cases, several microRNAs that had never been described before. One of them, hsa_can_1002-m, turned out to be specific for primates and thus couldn't have been detected in mouse studies. The team plans to follow up by studying these ASD-linked microRNAs in more detail, to better characterize the effects of their altered levels on gene activity, brain development, cognition and behavior. "It would be interesting to test whether manipulating the levels of these microRNAs in animal models of autism can reverse autism-related signs," Wu said. Any clinical payoff from the new research is many years away at best. But success in targeting microRNAs in animal model studies might eventually lead to the development of autism spectrum disorder treatments or even preventive measures. Autism spectrum disorders currently affect about one in 40 boys and one in 200 girls in the United States, and there are no specific therapies. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Polypeptide toxins have played a central part in understanding physiological and physiopathological functions of ion channels 1 , 2 . In the field of pain, they led to important advances in basic research 3 , 4 , 5 , 6 and even to clinical applications 7 , 8 . Acid-sensing ion channels (ASICs) are generally considered principal players in the pain pathway 9 , including in humans 10 . A snake toxin activating peripheral ASICs in nociceptive neurons has been recently shown to evoke pain 11 . Here we show that a new class of three-finger peptides from another snake, the black mamba, is able to abolish pain through inhibition of ASICs expressed either in central or peripheral neurons. These peptides, which we call mambalgins, are not toxic in mice but show a potent analgesic effect upon central and peripheral injection that can be as strong as morphine. This effect is, however, resistant to naloxone, and mambalgins cause much less tolerance than morphine and no respiratory distress. Pharmacological inhibition by mambalgins combined with the use of knockdown and knockout animals indicates that blockade of heteromeric channels made of ASIC1a and ASIC2a subunits in central neurons and of ASIC1b-containing channels in nociceptors is involved in the analgesic effect of mambalgins. These findings identify new potential therapeutic targets for pain and introduce natural peptides that block them to produce a potent analgesia. Main In a screen to discover new blockers of ASIC channels from animal venoms, we identified the venom of black mamba ( Dendroaspis polylepis polylepis ) as a potent and reversible inhibitor of the ASIC1a channel expressed in Xenopus oocytes ( Fig. 1a ). After purification, two active fractions were collected ( Supplementary Fig. 1a, b ). A partial amino-acid sequence was used to clone by degenerated PCR the corresponding complementary DNA (cDNA) from lyophilized venom ( Supplementary Fig. 1c ). Two isopeptides were identified and named mambalgin-1 and mambalgin-2. They are composed of 57 amino acids with eight cysteine residues, and only differ by one residue at position 4 ( Supplementary Fig. 1d ). Figure 1: Mambalgins represent a new class of three-finger toxins targeting ASIC channels. a , Black mamba venom (0.1 mg ml −1 ) reversibly inhibits rat ASIC1a current expressed in Xenopus oocytes. b , Three-dimensional model of mambalgin-1 (disulphide bridges in yellow). c , Electrostatic properties of mambalgin-1 and human ASIC1a channel (on the basis of the three-dimensional structure of chicken ASIC1a 29 ) with positive and negative isosurfaces in blue and red, respectively. d , e , Inhibition of rat ASIC channels expressed in COS-7 cells ( n = 4–15; peptides applied before the pH drop as in a ). Hill coefficients of 0.7–1 suggest a 1:1 stoichiometry between mambalgins and channels. f , Effect of mambalgin-1 on the pH-dependent activation and inactivation of ASIC1a current recorded in Xenopus oocytes (protocol shown in inset). g , h , Inhibition of native ASIC currents in dorsal spinal cord neurons ( g ) and DRG neurons ( h ) by mambalgin-1 (674 nM) and PcTx1 (20 nM), n = 14–34. Right panels: effect of mambalgin-1 on neurons expressing no PcTx1-sensitive current. ( V h = −60 mV in a , d , e and −50 mV in f – h .) Mean ± s.e.m. PowerPoint slide Full size image Mambalgins belong to the family of three-finger toxins 12 ( Supplementary Fig. 1d, e ). They have no sequence homology with either PcTx1 or APETx2, two toxins that we previously identified to target ASIC channels 13 , 14 . A three-dimensional model of mambalgin-1 has been established from a pool of five templates with known structures ( Supplementary Fig. 1e ), which shows a triple-stranded and short double-stranded antiparallel β-sheets connecting loops II and III, and loop I, respectively, the three loops emerging from the core of the toxin like fingers from a palm ( Fig. 1b ). The model structure presents a concave face commonly found in neurotoxins and is stabilized by four disulphide bonds with a pattern identical to that observed in the crystal structure template (Cys 1–Cys 3, Cys 2–Cys 4, Cys 5–Cys 6 and Cys 7–Cys 8; Fig. 1b and Supplementary Fig. 1f ). Mambalgins show a strong positive electrostatic potential that may contribute to binding to negatively charged ASIC channels ( Fig. 1c ). Mambalgins have the unique property of being potent, rapid and reversible inhibitors of recombinant homomeric ASIC1a and heteromeric ASIC1a + ASIC2a or ASIC1a + ASIC2b channels, that is, all the ASIC channel subtypes expressed in the central nervous system 15 , 16 , 17 , 18 , with a similar potency for both isopeptides and IC 50 values (the toxin concentration half-maximally inhibiting the current) of 55 nM, 246 nM and 61 nM, respectively ( Fig. 1d ). Mambalgins also inhibit human ASIC channels ( Supplementary Fig. 2a ). The peptides inhibit ASIC1b and ASIC1a + ASIC1b channels that are specific of sensory neurons 19 with IC 50 values of 192 nM and 72 nM, respectively ( Fig. 1e ). Mambalgins, which bind to the closed and/or inactivated state of the channels ( Supplementary Fig. 2b ), modify the affinity for protons (pH 0.5act shifted from 6.35 ± 0.04 to 5.58 ± 0.02, and pH 0.5inact shifted from 7.10 ± 0.01 to 7.17 ± 0.01, n = 4, P < 0.001 and n = 5, P < 0.05, respectively; Fig. 1f ) and act as gating modifier toxins. They potently inhibit native ASIC currents in spinal cord, hippocampal and sensory neurons ( Fig. 1g, h and Supplementary Fig. 3 ). In central spinal cord neurons, mambalgin-1 (674 nM) decreased ASIC current amplitude to 13.0 ± 2.0% ( n = 14) of the control ( Fig. 1g ) and reduced the excitability in response to acidic pH without unspecific effect on basal neuronal excitability (resting potential) or on the threshold and the shape of evoked or spontaneous action potentials and on spontaneous postsynaptic currents ( Supplementary Fig. 4", "role": "user" }, { "content": "Scientists have used the venom of Africa's lethal black mamba to produce a surprising outcome in mice which they hope to replicate in humans—effective pain relief without toxic side effects. French researchers wrote in the journal Nature Wednesday that peptides isolated from black mamba venom may be a safer pain killer than morphine. In mice at least, the peptides bypass the receptors in the brain that are targeted by morphine and other opioid compounds which sometimes cause side-effects like breathing difficulties or nausea. Nor do the peptides pose the same risk of addiction or drug abuse. \"We have identified new natural peptides, mambalgins, from the venom of the snake Black Mamba that are able to significantly reduce pain in mice without toxic effect,\" study co-author Anne Baron of France's Centre national de la recherche scientifique (national research institute) told AFP. \"It is remarkable that this was made possible from the deadly venom of one of the most venomous snakes,\" she said of the study published in the journal Nature. \"(It) is surprising that mambalgins, which represent less than 0.5 percent of the total venom protein content, has analgesic (pain-relief) properties without neurotoxicity in mice, whereas the total venom of black mamba is lethal and among the most neurotoxic ones.\" Morphine is often regarded as the best drug to relieve severe pain and suffering, but it has several side effects and can be habit-forming. The black mamba's venom is among the fastest acting of any snake species, and a bite will be fatal if not treated with antivenom—the poison attacking the central nervous system and causing respiratory paralysis. Mice are among the agile adder's favourite prey in the wild in eastern and southern Africa. Baron said researchers were confident the peptides would also work in humans \"and are very interesting candidates as painkillers\", but much work remains to be done. A patent has been issued and a pharmaceutical company is examining the possibilities, she said. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Polypeptide toxins have played a central part in understanding physiological and physiopathological functions of ion channels 1 , 2 . In the field of pain, they led to important advances in basic research 3 , 4 , 5 , 6 and even to clinical applications 7 , 8 . Acid-sensing ion channels (ASICs) are generally considered principal players in the pain pathway 9 , including in humans 10 . A snake toxin activating peripheral ASICs in nociceptive neurons has been recently shown to evoke pain 11 . Here we show that a new class of three-finger peptides from another snake, the black mamba, is able to abolish pain through inhibition of ASICs expressed either in central or peripheral neurons. These peptides, which we call mambalgins, are not toxic in mice but show a potent analgesic effect upon central and peripheral injection that can be as strong as morphine. This effect is, however, resistant to naloxone, and mambalgins cause much less tolerance than morphine and no respiratory distress. Pharmacological inhibition by mambalgins combined with the use of knockdown and knockout animals indicates that blockade of heteromeric channels made of ASIC1a and ASIC2a subunits in central neurons and of ASIC1b-containing channels in nociceptors is involved in the analgesic effect of mambalgins. These findings identify new potential therapeutic targets for pain and introduce natural peptides that block them to produce a potent analgesia. Main In a screen to discover new blockers of ASIC channels from animal venoms, we identified the venom of black mamba ( Dendroaspis polylepis polylepis ) as a potent and reversible inhibitor of the ASIC1a channel expressed in Xenopus oocytes ( Fig. 1a ). After purification, two active fractions were collected ( Supplementary Fig. 1a, b ). A partial amino-acid sequence was used to clone by degenerated PCR the corresponding complementary DNA (cDNA) from lyophilized venom ( Supplementary Fig. 1c ). Two isopeptides were identified and named mambalgin-1 and mambalgin-2. They are composed of 57 amino acids with eight cysteine residues, and only differ by one residue at position 4 ( Supplementary Fig. 1d ). Figure 1: Mambalgins represent a new class of three-finger toxins targeting ASIC channels. a , Black mamba venom (0.1 mg ml −1 ) reversibly inhibits rat ASIC1a current expressed in Xenopus oocytes. b , Three-dimensional model of mambalgin-1 (disulphide bridges in yellow). c , Electrostatic properties of mambalgin-1 and human ASIC1a channel (on the basis of the three-dimensional structure of chicken ASIC1a 29 ) with positive and negative isosurfaces in blue and red, respectively. d , e , Inhibition of rat ASIC channels expressed in COS-7 cells ( n = 4–15; peptides applied before the pH drop as in a ). Hill coefficients of 0.7–1 suggest a 1:1 stoichiometry between mambalgins and channels. f , Effect of mambalgin-1 on the pH-dependent activation and inactivation of ASIC1a current recorded in Xenopus oocytes (protocol shown in inset). g , h , Inhibition of native ASIC currents in dorsal spinal cord neurons ( g ) and DRG neurons ( h ) by mambalgin-1 (674 nM) and PcTx1 (20 nM), n = 14–34. Right panels: effect of mambalgin-1 on neurons expressing no PcTx1-sensitive current. ( V h = −60 mV in a , d , e and −50 mV in f – h .) Mean ± s.e.m. PowerPoint slide Full size image Mambalgins belong to the family of three-finger toxins 12 ( Supplementary Fig. 1d, e ). They have no sequence homology with either PcTx1 or APETx2, two toxins that we previously identified to target ASIC channels 13 , 14 . A three-dimensional model of mambalgin-1 has been established from a pool of five templates with known structures ( Supplementary Fig. 1e ), which shows a triple-stranded and short double-stranded antiparallel β-sheets connecting loops II and III, and loop I, respectively, the three loops emerging from the core of the toxin like fingers from a palm ( Fig. 1b ). The model structure presents a concave face commonly found in neurotoxins and is stabilized by four disulphide bonds with a pattern identical to that observed in the crystal structure template (Cys 1–Cys 3, Cys 2–Cys 4, Cys 5–Cys 6 and Cys 7–Cys 8; Fig. 1b and Supplementary Fig. 1f ). Mambalgins show a strong positive electrostatic potential that may contribute to binding to negatively charged ASIC channels ( Fig. 1c ). Mambalgins have the unique property of being potent, rapid and reversible inhibitors of recombinant homomeric ASIC1a and heteromeric ASIC1a + ASIC2a or ASIC1a + ASIC2b channels, that is, all the ASIC channel subtypes expressed in the central nervous system 15 , 16 , 17 , 18 , with a similar potency for both isopeptides and IC 50 values (the toxin concentration half-maximally inhibiting the current) of 55 nM, 246 nM and 61 nM, respectively ( Fig. 1d ). Mambalgins also inhibit human ASIC channels ( Supplementary Fig. 2a ). The peptides inhibit ASIC1b and ASIC1a + ASIC1b channels that are specific of sensory neurons 19 with IC 50 values of 192 nM and 72 nM, respectively ( Fig. 1e ). Mambalgins, which bind to the closed and/or inactivated state of the channels ( Supplementary Fig. 2b ), modify the affinity for protons (pH 0.5act shifted from 6.35 ± 0.04 to 5.58 ± 0.02, and pH 0.5inact shifted from 7.10 ± 0.01 to 7.17 ± 0.01, n = 4, P < 0.001 and n = 5, P < 0.05, respectively; Fig. 1f ) and act as gating modifier toxins. They potently inhibit native ASIC currents in spinal cord, hippocampal and sensory neurons ( Fig. 1g, h and Supplementary Fig. 3 ). In central spinal cord neurons, mambalgin-1 (674 nM) decreased ASIC current amplitude to 13.0 ± 2.0% ( n = 14) of the control ( Fig. 1g ) and reduced the excitability in response to acidic pH without unspecific effect on basal neuronal excitability (resting potential) or on the threshold and the shape of evoked or spontaneous action potentials and on spontaneous postsynaptic currents ( Supplementary Fig. 4<|im_end|> <|im_start|>assistant Scientists have used the venom of Africa's lethal black mamba to produce a surprising outcome in mice which they hope to replicate in humans—effective pain relief without toxic side effects. French researchers wrote in the journal Nature Wednesday that peptides isolated from black mamba venom may be a safer pain killer than morphine. In mice at least, the peptides bypass the receptors in the brain that are targeted by morphine and other opioid compounds which sometimes cause side-effects like breathing difficulties or nausea. Nor do the peptides pose the same risk of addiction or drug abuse. "We have identified new natural peptides, mambalgins, from the venom of the snake Black Mamba that are able to significantly reduce pain in mice without toxic effect," study co-author Anne Baron of France's Centre national de la recherche scientifique (national research institute) told AFP. "It is remarkable that this was made possible from the deadly venom of one of the most venomous snakes," she said of the study published in the journal Nature. "(It) is surprising that mambalgins, which represent less than 0.5 percent of the total venom protein content, has analgesic (pain-relief) properties without neurotoxicity in mice, whereas the total venom of black mamba is lethal and among the most neurotoxic ones." Morphine is often regarded as the best drug to relieve severe pain and suffering, but it has several side effects and can be habit-forming. The black mamba's venom is among the fastest acting of any snake species, and a bite will be fatal if not treated with antivenom—the poison attacking the central nervous system and causing respiratory paralysis. Mice are among the agile adder's favourite prey in the wild in eastern and southern Africa. Baron said researchers were confident the peptides would also work in humans "and are very interesting candidates as painkillers", but much work remains to be done. A patent has been issued and a pharmaceutical company is examining the possibilities, she said. <|im_end|>

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1,960

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Genetic and epigenetic variation, together with transcriptional plasticity, contribute to intratumour heterogeneity 1 . The interplay of these biological processes and their respective contributions to tumour evolution remain unknown. Here we show that intratumour genetic ancestry only infrequently affects gene expression traits and subclonal evolution in colorectal cancer (CRC). Using spatially resolved paired whole-genome and transcriptome sequencing, we find that the majority of intratumour variation in gene expression is not strongly heritable but rather ‘plastic’. Somatic expression quantitative trait loci analysis identified a number of putative genetic controls of expression by cis -acting coding and non-coding mutations, the majority of which were clonal within a tumour, alongside frequent structural alterations. Consistently, computational inference on the spatial patterning of tumour phylogenies finds that a considerable proportion of CRCs did not show evidence of subclonal selection, with only a subset of putative genetic drivers associated with subclone expansions. Spatial intermixing of clones is common, with some tumours growing exponentially and others only at the periphery. Together, our data suggest that most genetic intratumour variation in CRC has no major phenotypic consequence and that transcriptional plasticity is, instead, widespread within a tumour. Main Genetic intratumour heterogeneity (gITH) is an inevitable consequence of tumour evolution 2 . Extensive gITH has been documented across human cancer types 1 , and its precise pattern within an individual cancer is a direct consequence of the evolutionary dynamics driving the development of the tumour 3 . Consequently, clones that undergo positive, negative or neutral selection can be identified through analysis of gITH 4 , 5 , 6 . However, clonal selection in cancer operates on the phenotypic characteristics of a cell—for example, the ability of a cancer cell to evade predation by the immune system 7 or to survive in oxygen-poor environments 8 , 9 and can be modulated by spatial competition 9 , 10 , 11 , 12 , 13 , 14 . Knowledge of the genotype–phenotype map of cancer cells is limited and thus, while genomics offers us a window into determination of which clones are selected, the methodology provides limited information on precisely why they are selected. Interrelatedly, the extent to which subclonal mutations in tumours lead to phenotypic change is unclear. RNA sequencing (RNA-seq) enables high-throughput profiling of phenotypic characteristics of cancer cells by quantitative measurement of gene expression levels 15 . Historically, studies have focused on intertumour differences in gene expression patterns and have led to the identification of gene expression signatures that correlate with clinical outcomes. In colorectal cancer (CRC), the focus of this study, consensus molecular subtypes (CMS) 16 or cancer cell-intrinsic gene expression subtypes (CRIS) 17 exemplify this approach. Because the transcriptome is a feature of the cancer cell phenotype, it is natural to view changes in expression, and the pattern of transcriptomic intratumour heterogeneity (tITH), as ‘functional’ and the substrate for tumour evolution. Potentially tITH could be driven entirely by underlying heritable (epi)genetic variation that evolves during tumour growth. However, the observation that local invasion is polyclonal in both CRC 18 and early breast cancer 19 challenges the notion that cancer cell phenotype (here, the ability to invade) is driven solely by the accrual of genetic mutations. Furthermore, observations of rapid transcriptional shifts following treatment (for example, in melanoma 20 ) and, in CRC, variation in subclone proliferation rates through serial retransplantation despite largely stable patterns of genetic alterations 21 , discount the notion that transcriptomic phenotypes are determined solely by clonal replacement. It has previously been determined that most driver mutations are clonal in metastatic CRC, meaning that intratumoral transcriptional variation often happens in the absence of the acquisition of new key driver mutations 22 . Collectively, these studies suggest that phenotypic characteristics are at least partially plastic—they can vary without acquiring a new heritable (epi)genetic alteration to drive expression changes, for instance as a response to the cellular environment. In patient samples we cannot measure longitudinally the exact same clones or cells, and so here we define a trait as plastic if it varies independently of evolutionary history. Conversely, non-plastic traits are fixed through tumour evolution. Here we analyse spatially resolved paired genomic (whole-genome sequencing), epigenomic (assay for transposase-accessible chromatin using sequencing, or ATAC-seq), and transcriptomic (whole-transcript RNA-seq) profiling, coupled with computational modelling, to characterize the evolution of phenotypic heterogeneity in CRC. Paired DNA–RNA data enable assessment of the interrelationship between genetic evolution and gene expression patterns, and of the functional consequence of gene expression change for cancer evolution. We analysed our spatially resolved, multiomic, single-gland profiling dataset from primary CRCs 23 that were part of our Evolutionary Predictions in Colorectal Cancer (EPICC) study. Single-gland profiling allowed multimodal DNA, chromatin and RNA characterization of the same small clonal unit of tissue (glands or crypts). We focused our analysis on 297 samples from 27 CRCs (mean, 11 samples per tumour; range, 1–38) in which we had obtained high-quality, full-transcript RNA-seq data. Paired deep and shallow whole-genome sequencing and chromatin accessibility analysis by ATAC-seq were available for a subset of these samples. An analysis of the ATAC-seq data is available in the associated paper 23 . Expression heterogeneity in CRC First, we explored the heterogeneity of gene expression within and between CRCs. We clustered a filtered set of 11,401 genes (including removal of very lowly expressed genes and those significantly negatively correlated with purity; Methods ) using both the mean and variance of gene expression within each tumour (Fig. 1a ), and separated the dendrogram into four groups ( Methods ): group 1 had high average expression and relatively low variance in gene expression (‘highly expressed, limited heterogeneity’); groups 2 and 3 had progressively lower average gene expression and high variance in expression, whereas group 4 genes had low average gene expression and low variability between samples from the same tumour (Fig. 1b,c and Supplementary Table 1 ). Meta-pathway analysis showed weak, non-significant enrichment for pathways involved in cell growth and death in group 1, and significant enrichment for cancer-related genes in group 2 and pathways related to", "role": "user" }, { "content": "Two teams of researchers working independently from one another have conducted studies to learn more about the role that epigenetics plays in the behavior of cancerous tumors. The first group, a team at the Institute of Cancer Research in the U.K., working with colleagues from several other institutions in the U.K. analyzed thousands of samples of bowel cancers from different patients looking for instances of epigenetic changes. The second team, with members from around the globe, focused on multiple samples taken from the same tumor—they also looked for changes due to epigenetics. Both teams have published papers outlining their work in the journal Nature. For many years, medical scientists have believed that most, if not all, cancers develop due to mutations in DNA, leading to abnormal tissue growth in the form of tumors. In more recent years, researchers have found evidence showing that not all cancers have a simple genetic origin. Instead, evidence has shown that some have an epigenetic factor. Through epigenetics, age or environment exert an influence on the way that DNA code in cancer cells is expressed. In this new effort, both teams looked to better understand the role of epigenetics in the development and progression of cancerous tumors. In the first study, the researchers collected and studied tissue from various types of bowel cancer collected from 30 different patients. In all, they looked at 1,370 samples. Each was subjected to both whole-transcript RNA-seq and whole genome sequencing. They were able to track down which tumors were purely DNA based and which were not. They found that only 166 of them could be traced to underlying genetics. In the second study, the researchers used spatially resolved, paired whole-genome and transcriptome sequencing on multiple tissue samples taken from the same tumor. They found evidence showing that the majority of variations they identified could not be blamed on underlying genetics. Both teams acknowledge that their work did not prove that epigenetics leads directly to changes in the behavior of cancers, but both found evidence that suggests that is the case. They also both note that much more work is required to better understand the role that epigenetics plays in cancer development and progression. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Genetic and epigenetic variation, together with transcriptional plasticity, contribute to intratumour heterogeneity 1 . The interplay of these biological processes and their respective contributions to tumour evolution remain unknown. Here we show that intratumour genetic ancestry only infrequently affects gene expression traits and subclonal evolution in colorectal cancer (CRC). Using spatially resolved paired whole-genome and transcriptome sequencing, we find that the majority of intratumour variation in gene expression is not strongly heritable but rather ‘plastic’. Somatic expression quantitative trait loci analysis identified a number of putative genetic controls of expression by cis -acting coding and non-coding mutations, the majority of which were clonal within a tumour, alongside frequent structural alterations. Consistently, computational inference on the spatial patterning of tumour phylogenies finds that a considerable proportion of CRCs did not show evidence of subclonal selection, with only a subset of putative genetic drivers associated with subclone expansions. Spatial intermixing of clones is common, with some tumours growing exponentially and others only at the periphery. Together, our data suggest that most genetic intratumour variation in CRC has no major phenotypic consequence and that transcriptional plasticity is, instead, widespread within a tumour. Main Genetic intratumour heterogeneity (gITH) is an inevitable consequence of tumour evolution 2 . Extensive gITH has been documented across human cancer types 1 , and its precise pattern within an individual cancer is a direct consequence of the evolutionary dynamics driving the development of the tumour 3 . Consequently, clones that undergo positive, negative or neutral selection can be identified through analysis of gITH 4 , 5 , 6 . However, clonal selection in cancer operates on the phenotypic characteristics of a cell—for example, the ability of a cancer cell to evade predation by the immune system 7 or to survive in oxygen-poor environments 8 , 9 and can be modulated by spatial competition 9 , 10 , 11 , 12 , 13 , 14 . Knowledge of the genotype–phenotype map of cancer cells is limited and thus, while genomics offers us a window into determination of which clones are selected, the methodology provides limited information on precisely why they are selected. Interrelatedly, the extent to which subclonal mutations in tumours lead to phenotypic change is unclear. RNA sequencing (RNA-seq) enables high-throughput profiling of phenotypic characteristics of cancer cells by quantitative measurement of gene expression levels 15 . Historically, studies have focused on intertumour differences in gene expression patterns and have led to the identification of gene expression signatures that correlate with clinical outcomes. In colorectal cancer (CRC), the focus of this study, consensus molecular subtypes (CMS) 16 or cancer cell-intrinsic gene expression subtypes (CRIS) 17 exemplify this approach. Because the transcriptome is a feature of the cancer cell phenotype, it is natural to view changes in expression, and the pattern of transcriptomic intratumour heterogeneity (tITH), as ‘functional’ and the substrate for tumour evolution. Potentially tITH could be driven entirely by underlying heritable (epi)genetic variation that evolves during tumour growth. However, the observation that local invasion is polyclonal in both CRC 18 and early breast cancer 19 challenges the notion that cancer cell phenotype (here, the ability to invade) is driven solely by the accrual of genetic mutations. Furthermore, observations of rapid transcriptional shifts following treatment (for example, in melanoma 20 ) and, in CRC, variation in subclone proliferation rates through serial retransplantation despite largely stable patterns of genetic alterations 21 , discount the notion that transcriptomic phenotypes are determined solely by clonal replacement. It has previously been determined that most driver mutations are clonal in metastatic CRC, meaning that intratumoral transcriptional variation often happens in the absence of the acquisition of new key driver mutations 22 . Collectively, these studies suggest that phenotypic characteristics are at least partially plastic—they can vary without acquiring a new heritable (epi)genetic alteration to drive expression changes, for instance as a response to the cellular environment. In patient samples we cannot measure longitudinally the exact same clones or cells, and so here we define a trait as plastic if it varies independently of evolutionary history. Conversely, non-plastic traits are fixed through tumour evolution. Here we analyse spatially resolved paired genomic (whole-genome sequencing), epigenomic (assay for transposase-accessible chromatin using sequencing, or ATAC-seq), and transcriptomic (whole-transcript RNA-seq) profiling, coupled with computational modelling, to characterize the evolution of phenotypic heterogeneity in CRC. Paired DNA–RNA data enable assessment of the interrelationship between genetic evolution and gene expression patterns, and of the functional consequence of gene expression change for cancer evolution. We analysed our spatially resolved, multiomic, single-gland profiling dataset from primary CRCs 23 that were part of our Evolutionary Predictions in Colorectal Cancer (EPICC) study. Single-gland profiling allowed multimodal DNA, chromatin and RNA characterization of the same small clonal unit of tissue (glands or crypts). We focused our analysis on 297 samples from 27 CRCs (mean, 11 samples per tumour; range, 1–38) in which we had obtained high-quality, full-transcript RNA-seq data. Paired deep and shallow whole-genome sequencing and chromatin accessibility analysis by ATAC-seq were available for a subset of these samples. An analysis of the ATAC-seq data is available in the associated paper 23 . Expression heterogeneity in CRC First, we explored the heterogeneity of gene expression within and between CRCs. We clustered a filtered set of 11,401 genes (including removal of very lowly expressed genes and those significantly negatively correlated with purity; Methods ) using both the mean and variance of gene expression within each tumour (Fig. 1a ), and separated the dendrogram into four groups ( Methods ): group 1 had high average expression and relatively low variance in gene expression (‘highly expressed, limited heterogeneity’); groups 2 and 3 had progressively lower average gene expression and high variance in expression, whereas group 4 genes had low average gene expression and low variability between samples from the same tumour (Fig. 1b,c and Supplementary Table 1 ). Meta-pathway analysis showed weak, non-significant enrichment for pathways involved in cell growth and death in group 1, and significant enrichment for cancer-related genes in group 2 and pathways related to<|im_end|> <|im_start|>assistant Two teams of researchers working independently from one another have conducted studies to learn more about the role that epigenetics plays in the behavior of cancerous tumors. The first group, a team at the Institute of Cancer Research in the U.K., working with colleagues from several other institutions in the U.K. analyzed thousands of samples of bowel cancers from different patients looking for instances of epigenetic changes. The second team, with members from around the globe, focused on multiple samples taken from the same tumor—they also looked for changes due to epigenetics. Both teams have published papers outlining their work in the journal Nature. For many years, medical scientists have believed that most, if not all, cancers develop due to mutations in DNA, leading to abnormal tissue growth in the form of tumors. In more recent years, researchers have found evidence showing that not all cancers have a simple genetic origin. Instead, evidence has shown that some have an epigenetic factor. Through epigenetics, age or environment exert an influence on the way that DNA code in cancer cells is expressed. In this new effort, both teams looked to better understand the role of epigenetics in the development and progression of cancerous tumors. In the first study, the researchers collected and studied tissue from various types of bowel cancer collected from 30 different patients. In all, they looked at 1,370 samples. Each was subjected to both whole-transcript RNA-seq and whole genome sequencing. They were able to track down which tumors were purely DNA based and which were not. They found that only 166 of them could be traced to underlying genetics. In the second study, the researchers used spatially resolved, paired whole-genome and transcriptome sequencing on multiple tissue samples taken from the same tumor. They found evidence showing that the majority of variations they identified could not be blamed on underlying genetics. Both teams acknowledge that their work did not prove that epigenetics leads directly to changes in the behavior of cancers, but both found evidence that suggests that is the case. They also both note that much more work is required to better understand the role that epigenetics plays in cancer development and progression. <|im_end|>

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2530, 3063, 311, 14345, 37941, 292, 2349, 374, 25420, 13, 41214, 62119, 320, 31820, 7962, 80, 8, 20682, 1579, 43847, 631, 56186, 315, 14345, 37941, 292, 17910, 315, 9572, 7917, 555, 47616, 19179, 315, 15207, 7645, 5990, 220, 868, 662, 22425, 2740, 11, 7978, 617, 10968, 389, 958, 83, 372, 414, 12062, 304, 15207, 7645, 12912, 323, 617, 6197, 311, 279, 22654, 315, 15207, 7645, 33728, 430, 81584, 449, 14830, 20124, 13, 763, 79887, 95081, 9572, 320, 84439, 705, 279, 5357, 315, 420, 4007, 11, 24811, 31206, 1207, 9426, 320, 54357, 8, 220, 845, 477, 9572, 2849, 3502, 46102, 15207, 7645, 1207, 9426, 320, 9150, 1669, 8, 220, 1114, 39039, 1463, 420, 5603, 13, 9393, 279, 36815, 638, 374, 264, 4668, 315, 279, 9572, 2849, 82423, 11, 433, 374, 5933, 311, 1684, 4442, 304, 7645, 11, 323, 279, 5497, 315, 36815, 3151, 10805, 27349, 414, 30548, 76730, 320, 83, 4243, 705, 439, 3451, 50328, 529, 323, 279, 54057, 369, 15756, 414, 15740, 13, 14020, 31668, 259, 4243, 1436, 387, 16625, 11622, 555, 16940, 1077, 15729, 320, 752, 72, 8, 4469, 5411, 23851, 430, 93054, 2391, 15756, 414, 6650, 13, 4452, 11, 279, 22695, 430, 2254, 30215, 374, 1499, 6310, 25180, 304, 2225, 30495, 220, 972, 323, 4216, 17659, 9572, 220, 777, 11774, 279, 23035, 430, 9572, 2849, 82423, 320, 6881, 11, 279, 5845, 311, 75272, 8, 374, 16625, 21742, 555, 279, 86659, 940, 315, 19465, 34684, 13, 24296, 11, 24654, 315, 11295, 46940, 278, 29735, 2768, 6514, 320, 2000, 3187, 11, 304, 68012, 7942, 220, 508, 883, 323, 11, 304, 30495, 11, 23851, 304, 1207, 20579, 53840, 7969, 1555, 6275, 312, 1485, 21494, 367, 8994, 14090, 15528, 12912, 315, 19465, 61086, 220, 1691, 1174, 11336, 279, 23035, 430, 36815, 3151, 14345, 22583, 527, 11075, 21742, 555, 1206, 25180, 14039, 13, 1102, 706, 8767, 1027, 11075, 430, 1455, 5696, 34684, 527, 1206, 25180, 304, 68370, 780, 30495, 11, 7438, 430, 10805, 27349, 10020, 46940, 278, 23851, 3629, 8741, 304, 279, 19821, 315, 279, 24279, 315, 502, 1401, 5696, 34684, 220, 1313, 662, 21153, 3210, 11, 1521, 7978, 4284, 430, 14345, 37941, 292, 17910, 527, 520, 3325, 26310, 12466, 71201, 649, 13592, 2085, 42990, 264, 502, 1077, 15729, 320, 752, 72, 8, 4469, 5411, 73681, 311, 6678, 7645, 4442, 11, 369, 2937, 439, 264, 2077, 311, 279, 35693, 4676, 13, 763, 8893, 10688, 584, 4250, 6767, 49704, 38745, 279, 4839, 1890, 67007, 477, 7917, 11, 323, 779, 1618, 584, 7124, 264, 18027, 439, 12466, 422, 433, 35327, 29235, 315, 41993, 3925, 13, 82671, 11, 2536, 33207, 5174, 25022, 527, 8521, 1555, 15756, 414, 15740, 13, 5810, 584, 49586, 29079, 398, 20250, 35526, 81064, 320, 67733, 37564, 638, 62119, 705, 4248, 6569, 3151, 320, 395, 352, 369, 1380, 981, 521, 43256, 1260, 22083, 15111, 1701, 62119, 11, 477, 7520, 1741, 7962, 80, 705, 323, 36815, 3151, 320, 67733, 39160, 1250, 41214, 7962, 80, 8, 56186, 11, 34356, 449, 55580, 61966, 11, 311, 70755, 279, 15740, 315, 14345, 37941, 292, 30548, 76730, 304, 30495, 13, 16056, 2757, 15922, 4235, 31820, 828, 7431, 15813, 315, 279, 958, 37195, 1990, 19465, 15740, 323, 15207, 7645, 12912, 11, 323, 315, 279, 16003, 29774, 315, 15207, 7645, 2349, 369, 9572, 15740, 13, 1226, 67458, 1057, 29079, 398, 20250, 11, 7447, 3151, 11, 3254, 2427, 1974, 56186, 10550, 505, 6156, 30495, 82, 220, 1419, 430, 1051, 961, 315, 1057, 38321, 661, 33810, 919, 304, 4349, 461, 95081, 26211, 320, 9377, 88302, 8, 4007, 13, 11579, 2427, 1974, 56186, 5535, 80149, 58697, 15922, 11, 22083, 15111, 323, 41214, 60993, 315, 279, 1890, 2678, 1206, 25180, 5089, 315, 20438, 320, 70, 8329, 477, 14774, 82, 570, 1226, 10968, 1057, 6492, 389, 220, 18163, 10688, 505, 220, 1544, 30495, 82, 320, 14622, 11, 220, 806, 10688, 824, 15756, 414, 26, 2134, 11, 220, 16, 4235, 1987, 8, 304, 902, 584, 1047, 12457, 1579, 22867, 11, 2539, 39160, 1250, 41214, 7962, 80, 828, 13, 16056, 2757, 5655, 323, 26682, 4459, 37564, 638, 62119, 323, 22083, 15111, 40800, 6492, 555, 7520, 1741, 7962, 80, 1051, 2561, 369, 264, 27084, 315, 1521, 10688, 13, 1556, 6492, 315, 279, 7520, 1741, 7962, 80, 828, 374, 2561, 304, 279, 5938, 5684, 220, 1419, 662, 16783, 30548, 76730, 304, 30495, 5629, 11, 584, 36131, 279, 30548, 76730, 315, 15207, 7645, 2949, 323, 1990, 30495, 82, 13, 1226, 93858, 264, 18797, 743, 315, 220, 806, 11, 10841, 21389, 320, 16564, 17065, 315, 1633, 3428, 398, 13605, 21389, 323, 1884, 12207, 48291, 49393, 449, 53500, 26, 19331, 883, 1701, 2225, 279, 3152, 323, 33373, 315, 15207, 7645, 2949, 1855, 15756, 414, 320, 30035, 13, 220, 16, 64, 7026, 323, 19180, 279, 90052, 87220, 1139, 3116, 5315, 320, 19331, 16919, 1912, 220, 16, 1047, 1579, 5578, 7645, 323, 12309, 3428, 33373, 304, 15207, 7645, 320, 14336, 12156, 398, 13605, 11, 7347, 30548, 76730, 529, 1237, 5315, 220, 17, 323, 220, 18, 1047, 72859, 4827, 5578, 15207, 7645, 323, 1579, 33373, 304, 7645, 11, 20444, 1912, 220, 19, 21389, 1047, 3428, 5578, 15207, 7645, 323, 3428, 54709, 1990, 10688, 505, 279, 1890, 15756, 414, 320, 30035, 13, 220, 16, 65, 10317, 323, 99371, 6771, 220, 16, 7609, 16197, 34195, 3195, 6492, 8710, 7621, 11, 2536, 29053, 34828, 70272, 369, 44014, 6532, 304, 2849, 6650, 323, 4648, 304, 1912, 220, 16, 11, 323, 5199, 70272, 369, 9572, 14228, 21389, 304, 1912, 220, 17, 323, 44014, 5552, 311, 128257, 198, 128256, 78191, 198, 11874, 7411, 315, 12074, 3318, 29235, 505, 832, 2500, 617, 13375, 7978, 311, 4048, 810, 922, 279, 3560, 430, 4248, 6569, 25265, 11335, 304, 279, 7865, 315, 9572, 788, 56071, 13, 578, 1176, 1912, 11, 264, 2128, 520, 279, 10181, 315, 26211, 8483, 304, 279, 549, 11606, 2637, 3318, 449, 18105, 505, 3892, 1023, 14673, 304, 279, 549, 11606, 13, 30239, 9214, 315, 10688, 315, 66358, 51423, 505, 2204, 6978, 3411, 369, 13422, 315, 4248, 6569, 5411, 4442, 13, 578, 2132, 2128, 11, 449, 3697, 505, 2212, 279, 24867, 11, 10968, 389, 5361, 10688, 4529, 505, 279, 1890, 36254, 71201, 1101, 7111, 369, 4442, 4245, 311, 4248, 6569, 25265, 13, 11995, 7411, 617, 4756, 16064, 79774, 872, 990, 304, 279, 8486, 22037, 13, 1789, 1690, 1667, 11, 6593, 14248, 617, 11846, 430, 1455, 11, 422, 539, 682, 11, 51423, 2274, 4245, 311, 34684, 304, 15922, 11, 6522, 311, 35663, 20438, 6650, 304, 279, 1376, 315, 56071, 13, 763, 810, 3293, 1667, 11, 12074, 617, 1766, 6029, 9204, 430, 539, 682, 51423, 617, 264, 4382, 19465, 6371, 13, 12361, 11, 6029, 706, 6982, 430, 1063, 617, 459, 4248, 6569, 5411, 8331, 13, 17331, 4248, 6569, 25265, 11, 4325, 477, 4676, 43844, 459, 10383, 389, 279, 1648, 430, 15922, 2082, 304, 9572, 7917, 374, 13605, 13, 763, 420, 502, 5149, 11, 2225, 7411, 7111, 311, 2731, 3619, 279, 3560, 315, 4248, 6569, 25265, 304, 279, 4500, 323, 33824, 315, 9572, 788, 56071, 13, 763, 279, 1176, 4007, 11, 279, 12074, 14890, 323, 20041, 20438, 505, 5370, 4595, 315, 66358, 9572, 14890, 505, 220, 966, 2204, 6978, 13, 763, 682, 11, 814, 7111, 520, 220, 16, 11, 14648, 10688, 13, 9062, 574, 38126, 311, 2225, 4459, 39160, 1250, 41214, 7962, 80, 323, 4459, 33869, 62119, 13, 2435, 1051, 3025, 311, 3839, 1523, 902, 56071, 1051, 32227, 15922, 3196, 323, 902, 1051, 539, 13, 2435, 1766, 430, 1193, 220, 11247, 315, 1124, 1436, 387, 51400, 311, 16940, 56104, 13, 763, 279, 2132, 4007, 11, 279, 12074, 1511, 29079, 398, 20250, 11, 35526, 4459, 37564, 638, 323, 36815, 638, 62119, 389, 5361, 20438, 10688, 4529, 505, 279, 1890, 36254, 13, 2435, 1766, 6029, 9204, 430, 279, 8857, 315, 27339, 814, 11054, 1436, 539, 387, 36197, 389, 16940, 56104, 13, 11995, 7411, 25670, 430, 872, 990, 1550, 539, 12391, 430, 4248, 6569, 25265, 11767, 6089, 311, 4442, 304, 279, 7865, 315, 51423, 11, 719, 2225, 1766, 6029, 430, 13533, 430, 374, 279, 1162, 13, 2435, 1101, 2225, 5296, 430, 1790, 810, 990, 374, 2631, 311, 2731, 3619, 279, 3560, 430, 4248, 6569, 25265, 11335, 304, 9572, 4500, 323, 33824, 13, 220, 128257, 198 ]

1,855

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Background Blow flies (Diptera: Calliphoridae) are important medical, veterinary and forensic insects encompassing 8 % of the species diversity observed in the calyptrate insects. Few genomic resources exist to understand the diversity and evolution of this group. Results We present the hybrid (short and long reads) draft assemblies of the male and female genomes of the common North American blow fly, Phormia regina (Diptera: Calliphoridae). The 550 and 534 Mb draft assemblies contained 8312 and 9490 predicted genes in the female and male genomes, respectively; including > 93 % conserved eukaryotic genes. Putative X and Y chromosomes (21 and 14 Mb, respectively) were assembled and annotated. The P. regina genomes appear to contain few mobile genetic elements, an almost complete absence of SINEs, and most of the repetitive landscape consists of simple repetitive sequences. Candidate gene approaches were undertaken to annotate insecticide resistance, sex-determining, chemoreceptors, and antimicrobial peptides. Conclusions This work yielded a robust, reliable reference calliphorid genome from a species located in the middle of a calliphorid phylogeny. By adding an additional blow fly genome, the ability to tease apart what might be true of general calliphorids vs. what is specific of two distinct lineages now exists. This resource will provide a strong foundation for future studies into the evolution, population structure, behavior, and physiology of all blow flies. Background One in ten species on earth are flies (Diptera). They are the most derived group within arthropods, and have experienced an explosive radiation in the last 50 million years [ 1 , 2 ]. Over the past decade, dipteran draft genomes including the fruit fly ( Drosophila melanogaster , [ 3 ]), the house fly ( Musca domestica , [ 4 ]), and the malaria mosquito ( Anopheles gambiae , [ 5 ]) have been published. Within Diptera, the family Calliphoridae, commonly known as blow flies, comprises ~1500 species [ 6 , 7 ], and contributes 8 % of species diversity in calyptrate flies [ 8 ]. Calliphorids are ubiquitous, distributed world-wide, and are important in the medical [ 9 – 12 ], veterinary/agricultural [ 13 – 16 ] and forensic fields [ 17 , 18 ]. For example, blow flies are responsible for the transmission of human disease [ 19 – 22 ]. Mihalyi’s danger-index was calculated for seven blow fly species in South America, with consideration for the synanthropic index. Six of the seven species posed a greater sanitary risk than the house fly [ 23 ], a known disease vector [ 24 , 25 ]. Interestingly, other closely related blow fly species have been shown to be medically advantageous as a means of wound debridement, otherwise known as maggot therapy [ 9 , 12 , 26 , 27 ]. In these cases, maggots physically debride the wound of decaying tissue while simultaneously excreting antimicrobial compounds [ 26 , 28 – 36 ] effective against antibiotic resistant bacteria such as methicillin resistant Staphylococcus aureus (MRSA) [ 29 , 37 ]. Recently, the first calliphorid genome, from the sheep blow fly ( Lucilia cuprina, [ 38 ]), was released. The publication of the L. cuprina draft genome brings with it the potential for studying a group of flies that have evolved recently [ 1 , 2 , 39 ], and have adopted many different life histories [ 6 ]. For example, the sheep blow fly specimen(s) that was sequenced was from a location in which it is predominantly, if not exclusively, an obligate ectoparasite (infestation of living vertebrate tissue by fly larvae) [ 38 ], and has presumably adapted under selective pressures from subsisting on carrion to infesting live animals. Calliphorid genomes will provide the necessary resources needed to understand the basic biological processes of lineage-specific traits in myiasis-causing flies. The black blow fly, Phormia regina (Meigen), is a Palearctic fly with records throughout North America and Northern Europe, and is the dominant carrion fly for most of Canada and the United States [ 40 ]. We chose to examine the genome of this species because 1) it plays an important role in ecosystems via carrion decomposition and nutrient recycling [ 41 ], 2) its’ abundance in North America, and 3) because it exhibits no specialized parasitic adaptations or unusual sex determination strategies (i.e. it is not monogenic), though the sex determination strategy for Phormia regina is largely unknown. Like other calliphorid flies, P. regina contains 2n = 12 chromosomes, including heteromorphic sex chromosomes [ 42 , 43 ]. These characteristics make it a good candidate for comparisons with species that have more specialized life histories. Furthermore, providing an additional reference genome from Calliphoridae will allow for a more complete understanding of the clade and adaptive processes that take place within it. We sequenced the male and female genomes (~40X), allowing us to characterize sex chromosomes and sex determining pathways, as well as evolutionary relationships of chemoreceptors, antimicrobial peptides, and insecticide resistance pathways in relation to other calliphorids and dipterans. Methods Genome sequencing – short reads Genomic DNA was extracted from whole flies using the DNeasy Blood and Tissue DNA Extraction kit (Qiagen Inc., Valencia, CA) and pooled from five female and five male Phormia regina flies housed in a laboratory colony (approximately 4–6 months old). The founders originated from Indianapolis, IN (39.7684° N, 86.1581° W) and were collected during the summer of 2012. The extracted DNA from each individual was quantified using a Qubit fluorometer (ThermoFisher Scientific, Grand Island, NY) and mixed in equal proportions to yield the two pooled extracts, one for each sex. DNA libraries were prepared using TruSeq DNA sample preparation (Illumina, San Diego, CA) and sequenced (2 × 100 bp) using one half lane of an Illumina HiSeq2000 platform at the Purdue University Genomics Core Facility (West Lafayette, IN). Additional 454 reads were obtained as described in [ 44 ]. Genome sequencing – long reads Genomic DNA was extracted from a whole single male P. regina specimen that had been in colony for >15 generations (different colony from above, but same originating", "role": "user" }, { "content": "Researchers at the School of Science at Indiana University-Purdue University Indianapolis have sequenced the genome of the black blow fly, an insect commonly found throughout the United States, southern Canada and parts of northern Europe. Black blow flies have environmental, medical and forensic uses, functioning as nature's recyclers, as wound cleansers and as forensic timekeepers. They have a blue or green sheen and are similar in size to common houseflies. The female genome was found to contain 8,312 genes; the male genome had 9,490 genes. \"There is nothing special about black blow flies (scientific name Phormia regina), but that lack of uniqueness is why scientists are interested in studying them,\" said Christine Picard, assistant professor of biology and forensic scientist, who led the team that sequenced the genome. Picard offers the following analogy to explain her research interest in black blow flies: \"If you are interested in studying a particular human disease, for instance, you don't start by studying people with the disease. You start by studying healthy individuals, and then you look for differences between the healthy and the sick to make sure any differences that you observe are actually due to the disease and not due to other factors. \"The first step is to figure out what the normal is. That's why I have been studying this fly for a decade and we have been working on sequencing its genome for the past five years: because this is an essentially unremarkable insect. It doesn't do anything that is abnormal. Having sequenced the black blow fly genome, we are providing a major resource for all of the researchers who are studying other insects that have unusual or dangerous characteristics, such as a species of fly that fatally attacks livestock.\" Black blow flies are active insects that perform three tasks that benefit humans: recycling carrion, debriding human wounds and laying eggs on freshly dead bodies. They have no harmful or parasitic behaviors. Researchers at the School of Science at Indiana University-Purdue University Indianapolis led by Christine Picard have sequenced the genome of the black blow fly, an insect commonly found throughout the United States, southern Canada and parts of northern Europe. Credit: Whitney Walker, IUPUI Black blow flies feed on decaying flesh and help consume dead vertebrates throughout the environment. Black blow fly larvae, or maggots, are used medically to debride human wounds, as the insects physically remove dead tissue while simultaneously excreting antimicrobial compounds into the wound. With an excellent sense for smelling recently dead tissue, black blow flies are usually the first insects to colonize a human body, frequently within minutes after death. Females lay eggs on recently deceased corpses, setting a \"clock\" that enables forensic investigators to estimate the postmortem interval, or minimum time since death. Other gene-mapping projects have been conducted by large, often international consortiums, with one group working on one aspect and others on different aspects, as a collaborative project. IUPUI's black blow fly genome sequencing was primarily conducted over four years by biology doctoral candidate Anne Andere under Picard's mentorship, with input from Texas Tech University biologists R.N. Platt II and David A. Ray. \"Genome sequence of Phormia regina Meigen (Diptera: Calliphoridae): Implications for medical, veterinary and forensic research\" is published online in BMC Genomics. Graduate student Andere is the first author. Picard, the corresponding author, is assistant professor in the Department of Biology and the Forensic and Investigative Sciences Program. She works at the interface of forensic entomology and molecular biology. Insects constitute slightly more than half of all living species on Earth. In 2011, i5K, an initiative to sequence the genomes of 5,000 insects and other arthropods within five years, was launched. Thus far, however, only 239 arthropod genomes have been sequenced, with now the black blow fly genome available. \"Now that we have described the genome,\" said Picard, \"I plan to continue working toward a better understanding of black blow fly population variation from location to location, and show how the variations influence postmortem interval estimates, with the goal of making these important determinations more accurate.\" Picard said the mapping of the black blow fly genome will also help researchers gain better insight into insecticide sensitivity and resistance. Knowledge of the genome will advance understanding of the antimicrobial compounds secreted by these specific insects as well. The black blow fly gene-mapping results completed at IUPUI have been deposited with the National Center for Biotechnology Information's Sequence Read Archive Database and are accessible to researchers around the world. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Background Blow flies (Diptera: Calliphoridae) are important medical, veterinary and forensic insects encompassing 8 % of the species diversity observed in the calyptrate insects. Few genomic resources exist to understand the diversity and evolution of this group. Results We present the hybrid (short and long reads) draft assemblies of the male and female genomes of the common North American blow fly, Phormia regina (Diptera: Calliphoridae). The 550 and 534 Mb draft assemblies contained 8312 and 9490 predicted genes in the female and male genomes, respectively; including > 93 % conserved eukaryotic genes. Putative X and Y chromosomes (21 and 14 Mb, respectively) were assembled and annotated. The P. regina genomes appear to contain few mobile genetic elements, an almost complete absence of SINEs, and most of the repetitive landscape consists of simple repetitive sequences. Candidate gene approaches were undertaken to annotate insecticide resistance, sex-determining, chemoreceptors, and antimicrobial peptides. Conclusions This work yielded a robust, reliable reference calliphorid genome from a species located in the middle of a calliphorid phylogeny. By adding an additional blow fly genome, the ability to tease apart what might be true of general calliphorids vs. what is specific of two distinct lineages now exists. This resource will provide a strong foundation for future studies into the evolution, population structure, behavior, and physiology of all blow flies. Background One in ten species on earth are flies (Diptera). They are the most derived group within arthropods, and have experienced an explosive radiation in the last 50 million years [ 1 , 2 ]. Over the past decade, dipteran draft genomes including the fruit fly ( Drosophila melanogaster , [ 3 ]), the house fly ( Musca domestica , [ 4 ]), and the malaria mosquito ( Anopheles gambiae , [ 5 ]) have been published. Within Diptera, the family Calliphoridae, commonly known as blow flies, comprises ~1500 species [ 6 , 7 ], and contributes 8 % of species diversity in calyptrate flies [ 8 ]. Calliphorids are ubiquitous, distributed world-wide, and are important in the medical [ 9 – 12 ], veterinary/agricultural [ 13 – 16 ] and forensic fields [ 17 , 18 ]. For example, blow flies are responsible for the transmission of human disease [ 19 – 22 ]. Mihalyi’s danger-index was calculated for seven blow fly species in South America, with consideration for the synanthropic index. Six of the seven species posed a greater sanitary risk than the house fly [ 23 ], a known disease vector [ 24 , 25 ]. Interestingly, other closely related blow fly species have been shown to be medically advantageous as a means of wound debridement, otherwise known as maggot therapy [ 9 , 12 , 26 , 27 ]. In these cases, maggots physically debride the wound of decaying tissue while simultaneously excreting antimicrobial compounds [ 26 , 28 – 36 ] effective against antibiotic resistant bacteria such as methicillin resistant Staphylococcus aureus (MRSA) [ 29 , 37 ]. Recently, the first calliphorid genome, from the sheep blow fly ( Lucilia cuprina, [ 38 ]), was released. The publication of the L. cuprina draft genome brings with it the potential for studying a group of flies that have evolved recently [ 1 , 2 , 39 ], and have adopted many different life histories [ 6 ]. For example, the sheep blow fly specimen(s) that was sequenced was from a location in which it is predominantly, if not exclusively, an obligate ectoparasite (infestation of living vertebrate tissue by fly larvae) [ 38 ], and has presumably adapted under selective pressures from subsisting on carrion to infesting live animals. Calliphorid genomes will provide the necessary resources needed to understand the basic biological processes of lineage-specific traits in myiasis-causing flies. The black blow fly, Phormia regina (Meigen), is a Palearctic fly with records throughout North America and Northern Europe, and is the dominant carrion fly for most of Canada and the United States [ 40 ]. We chose to examine the genome of this species because 1) it plays an important role in ecosystems via carrion decomposition and nutrient recycling [ 41 ], 2) its’ abundance in North America, and 3) because it exhibits no specialized parasitic adaptations or unusual sex determination strategies (i.e. it is not monogenic), though the sex determination strategy for Phormia regina is largely unknown. Like other calliphorid flies, P. regina contains 2n = 12 chromosomes, including heteromorphic sex chromosomes [ 42 , 43 ]. These characteristics make it a good candidate for comparisons with species that have more specialized life histories. Furthermore, providing an additional reference genome from Calliphoridae will allow for a more complete understanding of the clade and adaptive processes that take place within it. We sequenced the male and female genomes (~40X), allowing us to characterize sex chromosomes and sex determining pathways, as well as evolutionary relationships of chemoreceptors, antimicrobial peptides, and insecticide resistance pathways in relation to other calliphorids and dipterans. Methods Genome sequencing – short reads Genomic DNA was extracted from whole flies using the DNeasy Blood and Tissue DNA Extraction kit (Qiagen Inc., Valencia, CA) and pooled from five female and five male Phormia regina flies housed in a laboratory colony (approximately 4–6 months old). The founders originated from Indianapolis, IN (39.7684° N, 86.1581° W) and were collected during the summer of 2012. The extracted DNA from each individual was quantified using a Qubit fluorometer (ThermoFisher Scientific, Grand Island, NY) and mixed in equal proportions to yield the two pooled extracts, one for each sex. DNA libraries were prepared using TruSeq DNA sample preparation (Illumina, San Diego, CA) and sequenced (2 × 100 bp) using one half lane of an Illumina HiSeq2000 platform at the Purdue University Genomics Core Facility (West Lafayette, IN). Additional 454 reads were obtained as described in [ 44 ]. Genome sequencing – long reads Genomic DNA was extracted from a whole single male P. regina specimen that had been in colony for >15 generations (different colony from above, but same originating<|im_end|> <|im_start|>assistant Researchers at the School of Science at Indiana University-Purdue University Indianapolis have sequenced the genome of the black blow fly, an insect commonly found throughout the United States, southern Canada and parts of northern Europe. Black blow flies have environmental, medical and forensic uses, functioning as nature's recyclers, as wound cleansers and as forensic timekeepers. They have a blue or green sheen and are similar in size to common houseflies. The female genome was found to contain 8,312 genes; the male genome had 9,490 genes. "There is nothing special about black blow flies (scientific name Phormia regina), but that lack of uniqueness is why scientists are interested in studying them," said Christine Picard, assistant professor of biology and forensic scientist, who led the team that sequenced the genome. Picard offers the following analogy to explain her research interest in black blow flies: "If you are interested in studying a particular human disease, for instance, you don't start by studying people with the disease. You start by studying healthy individuals, and then you look for differences between the healthy and the sick to make sure any differences that you observe are actually due to the disease and not due to other factors. "The first step is to figure out what the normal is. That's why I have been studying this fly for a decade and we have been working on sequencing its genome for the past five years: because this is an essentially unremarkable insect. It doesn't do anything that is abnormal. Having sequenced the black blow fly genome, we are providing a major resource for all of the researchers who are studying other insects that have unusual or dangerous characteristics, such as a species of fly that fatally attacks livestock." Black blow flies are active insects that perform three tasks that benefit humans: recycling carrion, debriding human wounds and laying eggs on freshly dead bodies. They have no harmful or parasitic behaviors. Researchers at the School of Science at Indiana University-Purdue University Indianapolis led by Christine Picard have sequenced the genome of the black blow fly, an insect commonly found throughout the United States, southern Canada and parts of northern Europe. Credit: Whitney Walker, IUPUI Black blow flies feed on decaying flesh and help consume dead vertebrates throughout the environment. Black blow fly larvae, or maggots, are used medically to debride human wounds, as the insects physically remove dead tissue while simultaneously excreting antimicrobial compounds into the wound. With an excellent sense for smelling recently dead tissue, black blow flies are usually the first insects to colonize a human body, frequently within minutes after death. Females lay eggs on recently deceased corpses, setting a "clock" that enables forensic investigators to estimate the postmortem interval, or minimum time since death. Other gene-mapping projects have been conducted by large, often international consortiums, with one group working on one aspect and others on different aspects, as a collaborative project. IUPUI's black blow fly genome sequencing was primarily conducted over four years by biology doctoral candidate Anne Andere under Picard's mentorship, with input from Texas Tech University biologists R.N. Platt II and David A. Ray. "Genome sequence of Phormia regina Meigen (Diptera: Calliphoridae): Implications for medical, veterinary and forensic research" is published online in BMC Genomics. Graduate student Andere is the first author. Picard, the corresponding author, is assistant professor in the Department of Biology and the Forensic and Investigative Sciences Program. She works at the interface of forensic entomology and molecular biology. Insects constitute slightly more than half of all living species on Earth. In 2011, i5K, an initiative to sequence the genomes of 5,000 insects and other arthropods within five years, was launched. Thus far, however, only 239 arthropod genomes have been sequenced, with now the black blow fly genome available. "Now that we have described the genome," said Picard, "I plan to continue working toward a better understanding of black blow fly population variation from location to location, and show how the variations influence postmortem interval estimates, with the goal of making these important determinations more accurate." Picard said the mapping of the black blow fly genome will also help researchers gain better insight into insecticide sensitivity and resistance. Knowledge of the genome will advance understanding of the antimicrobial compounds secreted by these specific insects as well. The black blow fly gene-mapping results completed at IUPUI have been deposited with the National Center for Biotechnology Information's Sequence Read Archive Database and are accessible to researchers around the world. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The development of next-generation organic electronic materials critically relies on understanding structure-function relationships in conjugated polymers. However, unlocking the full potential of organic materials requires access to their vast chemical space while efficiently managing the large synthetic workload to survey new materials. In this work, we use automated synthesis to prepare a library of conjugated oligomers with systematically varied side chain composition followed by single-molecule characterization of charge transport. Our results show that molecular junctions with long alkyl side chains exhibit a concentration-dependent bimodal conductance with an unexpectedly high conductance state that arises due to surface adsorption and backbone planarization, which is supported by a series of control experiments using asymmetric, planarized, and sterically hindered molecules. Density functional theory simulations and experiments using different anchors and alkoxy side chains highlight the role of side chain chemistry on charge transport. Overall, this work opens new avenues for using automated synthesis for the development and understanding of organic electronic materials. Introduction The development of high-performance organic electronic devices critically relies on a fundamental understanding of intra- and intermolecular charge transport 1 , 2 . Organic electronic materials are typically designed for high charge-carrier mobilities and generally have highly delocalized conjugated backbones, with common building blocks including acenes, fluorenes, phenylene vinylene derivatives, thiophene derivatives, diketopyrrolopyrrole, isoindigo, and their donor-acceptor copolymers 1 , 2 . Strong pi–pi interactions in these systems significantly decrease their solubility in organic solvents, which hinders solution processing. To overcome this issue, flexible side chains such as alkyl, fluoroalkyl, and oligo(ethylene glycol) chains are appended to pi-conjugated backbones to enhance solubility, facilitate solution processing, and tune intermolecular packing 3 , 4 . In recent years, side chain engineering has been pursued organic electronic materials, which highlights the importance of side chain length, bulkiness, branching, substitution, and chain-end functionalization on charge transport in conjugated polymers 3 , 4 . However, the majority of prior work has focused on understanding the role of backbone composition and side chain chemistry on the macroscopic or device-level properties of these materials. Despite recent progress, the role of side chain chemistry on the molecular charge transport properties of conjugated organics is not fully understood. Unlocking the full potential of organic materials relies on accessing their vast chemical space, but the synthetic workload to make large numbers of new compounds presents a practical barrier to properly survey conjugated organic derivatives. In recent years, automated iterative coupling has emerged as a promising avenue to achieve precise sequence control and enable high-throughput synthesis of oligomeric small molecules 5 . Recent efforts have leveraged general Suzuki cross-coupling reactions using stable and accessible chemical building blocks in the development of an automated small-molecule synthesizer 6 . In this way, automated synthesis platforms have emerged as powerful tools to advance our understanding of functional materials properties, but these methods have not yet been widely applied to the field of organic electronics. In general, we lack a full systematic understanding of structure-property relationships for organic electronic materials due to the tedious and challenging nature of chemical synthesis. In this work, we systematically investigate the role of side chain chemistry on the charge transport properties of conjugated oligomers using a combination of automated synthesis and single-molecule charge transport experiments. A library of terphenyl derivatives with different side chain compositions and anchors was synthesized using automated iterative Suzuki coupling. Following synthesis and chemical characterization, a scanning tunneling microscope-break junction (STM-BJ) technique was used to directly characterize the charge transport properties of these molecules. STM-BJ methods provide an ideal approach for understanding charge transport at the molecular level, thereby enabling quantitative structure-property relationships for organic materials 7 , 8 , 9 . Our results show that molecular junctions with long alkyl side chains exhibit a bimodal conductance distribution with an unexpectedly high conductance state upon increasing concentration. Systematic control experiments using asymmetric, planarized, and sterically encumbered molecules indicate that the high conductance state results from surface adsorption and molecular planarization facilitated by long alkyl side chains. Our results further show that the choice of chemical anchors and side chains directly affects molecular adsorption, and density functional theory (DFT) simulations are in reasonable agreement with experiments. Taken together, these results highlight the use of automated chemical synthesis to/understand molecular charge transport for the development of new organic electronic materials. Results and discussion Automated synthesis of terphenyl derivatives with varying alkyl side chains We used automated iterative Suzuki-Miyaura cross-coupling to prepare a library of terphenyl derivatives using stable and easily accessible molecular building blocks containing methyliminodiacetic acid (MIDA) boronates and dihalide groups (Supplementary Information, Sections S.1 and S.2 and Supplementary Figs. S16 – S81 ). Building blocks contained phenyl rings with pre-installed alkyl side chains and terminal anchor moieties to facilitate STM-BJ experiments. Building on the first-generation automated small-molecule synthesizer designed by Burke and coworkers 6 , we developed a second-generation small-molecule synthesizer capable of parallel runs of deprotections, couplings, and purifications (Fig. 1a ). Briefly, the synthesis strategy relies on the MIDA protecting group rendering boron unreactive until deprotected with mild aqueous base, analogous to the Fmoc group in iterative peptide synthesis (Fig. 1b ). The new automated synthesis instrument leverages advances in hardware and software to enable up to 12 fully parallelized, simultaneous preparative-scale iterative Suzuki reactions. Importantly, the increased throughput allows for the screening of large regions of chemical space in a single automated synthetic run. Using this approach, a library of symmetric terphenyl derivatives with different alkyl side chains ( Rn ) and an asymmetric target molecule ( R6-H ) were prepared using two automated procedures in conjunction with the standard building block set (Fig. 1c ). Fig. 1: Automated chemical synthesis of terphenyl derivatives with different side chain compositions. a Picture of the automated synthesis instrument in our lab. b Iterative coupling strategy for small-molecule synthesis using MIDA boronates. c Synthesis schemes for C2-symmetric and non-C2-symmetric terphenyl derivatives via iterative Suzuki coupling. Full size image Role of alkyl side chain length on molecular charge transport We began by studying the molecular conductance", "role": "user" }, { "content": "A cross-disciplinary University of Illinois at Urbana-Champaign (UIUC) team has demonstrated a major breakthrough in using automated synthesis to discover new molecules for organic electronics applications. The technology that enabled the discovery relies on an automated platform for rapid molecular synthesis at scale—which is a game-changer in the field of organic electronics and beyond. Using automated synthesis, the team was able to rapidly scan through a library of molecules with precisely defined structures, thereby uncovering, via single-molecule characterization experiments, a new mechanism for high conductance. The work was just reported in Nature Communications and is the first major result to emerge from the Molecule Maker Lab, which is located in the Beckman Institute for Advanced Science and Technology at the University of Illinois Urbana-Champaign. The unexpectedly high conductance was uncovered in experiments led by Charles M. Schroeder, who is the James Economy Professor in materials science & engineering and a professor in chemical & biomolecular engineering. The project's goal was to seek out new molecules with strong conductivity that might be suitable for use in molecular electronics or organic electronics applications. The team's approach was to systematically append many different side chains to molecular backbones to understand how the side chains affected conductance. The first stage of the project consisted of synthesizing a large library of molecules to be characterized using single-molecule electronics experiments. If the synthesis had been done with conventional methods, it would have been a long, cumbersome process. That effort was avoided through use of the Molecule Maker Lab's automated synthesis platform, which was designed to facilitate molecular discovery research that requires testing of large numbers of candidate molecules. Edward R. Jira, a Ph.D. student in chemical & biomolecular engineering who had a leading role in the project, explained the synthesis platform's concept. \"What's really powerful... is that it leverages a building-block-based strategy where all of the chemical functionality that we're interested in is pre-encoded in building blocks that are bench-stable, and you can have a large library of them sitting on a shelf,\" he said. A single type of reaction is used repeatedly to couple the building blocks together as needed, and \"because we have this diverse building block library that encodes a lot of different functionality, we can access a huge array of different structures for different applications.\" As Schroeder put it, \"Imagine snapping Legos together.\" Co-author Martin D. Burke extended the Lego-brick analogy to explain why the synthesizer was so valuable to the experiments—and it wasn't only because of the rapid production of the initial molecular library. \"Because of the Lego-like approach for making these molecules, the team was able to understand why they are super-fast,\" he explained. Once the surprisingly fast state was discovered, \"using the 'Legos,' we could take the molecules apart piece by piece, and swap in different 'Lego' bricks—and thereby systematically understand the structure/function relationships that led to this ultrafast conductivity.\" Ph.D. student Jialing (Caroline) Li, an expert in single-molecule electronics characterization who studied the molecules generated by the synthesizer, explained the essence of the conductivity discovery. \"We observed that the side chains have a huge impact on how the molecule behaves and how this affects charge transport efficiency across the entire molecule,\" she said. Specifically, the team discovered that molecular junctions with long alkyl side chains have unexpectedly high conductance, which is dependent on concentration. They also figured out the reason for the high conductivity: The long alkyl side chains promote surface adsorption (the molecule's ability to adhere to a surface), which results in planarization (in effect, flattening out) of the molecules such that electrons can flow through them more efficiently. Burke, who is the May and Ving Lee Professor for Chemical Innovation and a professor of chemistry, called the building-block approach a \"one-two punch\": it makes the platform \"a powerful engine for both discovering function, and then understanding the function.\" The conductance discovery represents a significant advance for the field of organic electronics. \"Semiconductor-metal interfaces are ubiquitous in electronic devices. The surprising find of a high conductance state induced by metallic interfaces can pave the way to new molecular design for highly efficient charge injection and collection across a wide range of electronic applications,\" said co-author Ying Diao, an I. C. Gunsalus Scholar, Dow Chemical Company Faculty Scholar, and associate professor of chemical & biomolecular engineering. Schroeder explained that organic electronic materials have multiple benefits. To begin with, their use avoids the need for metals or other inorganic electronics. But organic electronics also offer much more: deformation and elastic properties that can be vital to some applications, such as implantable medical devices that could bend and flex along with, for example, a beating heart. Such organic devices could even be designed to degrade within the body, so that they break down and disappear after their job is done. Some organic electronics are already available in commercial products. For example, organic light-emitting diodes (OLED) can be found in the screens of smart phones, smart watches, and OLED TVs. It's anticipated that organic solar cells are on their way to becoming a commercial success as well. But the research community has only scratched the surface of organic electronics' potential; progress has been slowed by the lack of key materials discoveries like the one just made by the UIUC team. Schroeder said that it's significant to have proven that \"we can design and synthesize large libraries for various applications.\" The paper \"showcases the fact that we successfully did it for a class of molecules for molecular electronics.\" He admitted, \"I didn't expect to see something as interesting on this first study.\" Co-author Jeffrey S. Moore, who is a Stanley O. Ikenberry Endowed Chair, professor of chemistry, and Howard Hughes Medical Institute Professor, reflected on the work: \"Advancing basic science and technology by combining new facilities with a collaborative team is what makes the Beckman Institute so special. This discovery is the first of many that will come from the Molecule Maker Lab.\" Schroeder believes that the Molecule Maker Lab facilities—which also offer artificial intelligence capabilities for predicting what molecules are likely to be worth making—will open up a new approach to research in that \"you can start thinking about designing based on a function instead of a structure.\" Whereas researchers today might start by saying, \"I need to make this particular structure because I think it's going to do something,\" it will be possible to tell the system, \"I want to get this ultimate function,\" and then let it help you figure out what structures you should make to get that function. The intent is eventually to make the Molecule Maker Lab facilities available to researchers outside UIUC. Burke said he'd like to see the Lab \"become a global epicenter of democratized molecular innovation,\" empowering people who are not molecular synthesis specialists to solve important research problems. \"I think this is the beginning of something really special,\" Burke said. \"The journey has begun.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The development of next-generation organic electronic materials critically relies on understanding structure-function relationships in conjugated polymers. However, unlocking the full potential of organic materials requires access to their vast chemical space while efficiently managing the large synthetic workload to survey new materials. In this work, we use automated synthesis to prepare a library of conjugated oligomers with systematically varied side chain composition followed by single-molecule characterization of charge transport. Our results show that molecular junctions with long alkyl side chains exhibit a concentration-dependent bimodal conductance with an unexpectedly high conductance state that arises due to surface adsorption and backbone planarization, which is supported by a series of control experiments using asymmetric, planarized, and sterically hindered molecules. Density functional theory simulations and experiments using different anchors and alkoxy side chains highlight the role of side chain chemistry on charge transport. Overall, this work opens new avenues for using automated synthesis for the development and understanding of organic electronic materials. Introduction The development of high-performance organic electronic devices critically relies on a fundamental understanding of intra- and intermolecular charge transport 1 , 2 . Organic electronic materials are typically designed for high charge-carrier mobilities and generally have highly delocalized conjugated backbones, with common building blocks including acenes, fluorenes, phenylene vinylene derivatives, thiophene derivatives, diketopyrrolopyrrole, isoindigo, and their donor-acceptor copolymers 1 , 2 . Strong pi–pi interactions in these systems significantly decrease their solubility in organic solvents, which hinders solution processing. To overcome this issue, flexible side chains such as alkyl, fluoroalkyl, and oligo(ethylene glycol) chains are appended to pi-conjugated backbones to enhance solubility, facilitate solution processing, and tune intermolecular packing 3 , 4 . In recent years, side chain engineering has been pursued organic electronic materials, which highlights the importance of side chain length, bulkiness, branching, substitution, and chain-end functionalization on charge transport in conjugated polymers 3 , 4 . However, the majority of prior work has focused on understanding the role of backbone composition and side chain chemistry on the macroscopic or device-level properties of these materials. Despite recent progress, the role of side chain chemistry on the molecular charge transport properties of conjugated organics is not fully understood. Unlocking the full potential of organic materials relies on accessing their vast chemical space, but the synthetic workload to make large numbers of new compounds presents a practical barrier to properly survey conjugated organic derivatives. In recent years, automated iterative coupling has emerged as a promising avenue to achieve precise sequence control and enable high-throughput synthesis of oligomeric small molecules 5 . Recent efforts have leveraged general Suzuki cross-coupling reactions using stable and accessible chemical building blocks in the development of an automated small-molecule synthesizer 6 . In this way, automated synthesis platforms have emerged as powerful tools to advance our understanding of functional materials properties, but these methods have not yet been widely applied to the field of organic electronics. In general, we lack a full systematic understanding of structure-property relationships for organic electronic materials due to the tedious and challenging nature of chemical synthesis. In this work, we systematically investigate the role of side chain chemistry on the charge transport properties of conjugated oligomers using a combination of automated synthesis and single-molecule charge transport experiments. A library of terphenyl derivatives with different side chain compositions and anchors was synthesized using automated iterative Suzuki coupling. Following synthesis and chemical characterization, a scanning tunneling microscope-break junction (STM-BJ) technique was used to directly characterize the charge transport properties of these molecules. STM-BJ methods provide an ideal approach for understanding charge transport at the molecular level, thereby enabling quantitative structure-property relationships for organic materials 7 , 8 , 9 . Our results show that molecular junctions with long alkyl side chains exhibit a bimodal conductance distribution with an unexpectedly high conductance state upon increasing concentration. Systematic control experiments using asymmetric, planarized, and sterically encumbered molecules indicate that the high conductance state results from surface adsorption and molecular planarization facilitated by long alkyl side chains. Our results further show that the choice of chemical anchors and side chains directly affects molecular adsorption, and density functional theory (DFT) simulations are in reasonable agreement with experiments. Taken together, these results highlight the use of automated chemical synthesis to/understand molecular charge transport for the development of new organic electronic materials. Results and discussion Automated synthesis of terphenyl derivatives with varying alkyl side chains We used automated iterative Suzuki-Miyaura cross-coupling to prepare a library of terphenyl derivatives using stable and easily accessible molecular building blocks containing methyliminodiacetic acid (MIDA) boronates and dihalide groups (Supplementary Information, Sections S.1 and S.2 and Supplementary Figs. S16 – S81 ). Building blocks contained phenyl rings with pre-installed alkyl side chains and terminal anchor moieties to facilitate STM-BJ experiments. Building on the first-generation automated small-molecule synthesizer designed by Burke and coworkers 6 , we developed a second-generation small-molecule synthesizer capable of parallel runs of deprotections, couplings, and purifications (Fig. 1a ). Briefly, the synthesis strategy relies on the MIDA protecting group rendering boron unreactive until deprotected with mild aqueous base, analogous to the Fmoc group in iterative peptide synthesis (Fig. 1b ). The new automated synthesis instrument leverages advances in hardware and software to enable up to 12 fully parallelized, simultaneous preparative-scale iterative Suzuki reactions. Importantly, the increased throughput allows for the screening of large regions of chemical space in a single automated synthetic run. Using this approach, a library of symmetric terphenyl derivatives with different alkyl side chains ( Rn ) and an asymmetric target molecule ( R6-H ) were prepared using two automated procedures in conjunction with the standard building block set (Fig. 1c ). Fig. 1: Automated chemical synthesis of terphenyl derivatives with different side chain compositions. a Picture of the automated synthesis instrument in our lab. b Iterative coupling strategy for small-molecule synthesis using MIDA boronates. c Synthesis schemes for C2-symmetric and non-C2-symmetric terphenyl derivatives via iterative Suzuki coupling. Full size image Role of alkyl side chain length on molecular charge transport We began by studying the molecular conductance<|im_end|> <|im_start|>assistant A cross-disciplinary University of Illinois at Urbana-Champaign (UIUC) team has demonstrated a major breakthrough in using automated synthesis to discover new molecules for organic electronics applications. The technology that enabled the discovery relies on an automated platform for rapid molecular synthesis at scale—which is a game-changer in the field of organic electronics and beyond. Using automated synthesis, the team was able to rapidly scan through a library of molecules with precisely defined structures, thereby uncovering, via single-molecule characterization experiments, a new mechanism for high conductance. The work was just reported in Nature Communications and is the first major result to emerge from the Molecule Maker Lab, which is located in the Beckman Institute for Advanced Science and Technology at the University of Illinois Urbana-Champaign. The unexpectedly high conductance was uncovered in experiments led by Charles M. Schroeder, who is the James Economy Professor in materials science & engineering and a professor in chemical & biomolecular engineering. The project's goal was to seek out new molecules with strong conductivity that might be suitable for use in molecular electronics or organic electronics applications. The team's approach was to systematically append many different side chains to molecular backbones to understand how the side chains affected conductance. The first stage of the project consisted of synthesizing a large library of molecules to be characterized using single-molecule electronics experiments. If the synthesis had been done with conventional methods, it would have been a long, cumbersome process. That effort was avoided through use of the Molecule Maker Lab's automated synthesis platform, which was designed to facilitate molecular discovery research that requires testing of large numbers of candidate molecules. Edward R. Jira, a Ph.D. student in chemical & biomolecular engineering who had a leading role in the project, explained the synthesis platform's concept. "What's really powerful... is that it leverages a building-block-based strategy where all of the chemical functionality that we're interested in is pre-encoded in building blocks that are bench-stable, and you can have a large library of them sitting on a shelf," he said. A single type of reaction is used repeatedly to couple the building blocks together as needed, and "because we have this diverse building block library that encodes a lot of different functionality, we can access a huge array of different structures for different applications." As Schroeder put it, "Imagine snapping Legos together." Co-author Martin D. Burke extended the Lego-brick analogy to explain why the synthesizer was so valuable to the experiments—and it wasn't only because of the rapid production of the initial molecular library. "Because of the Lego-like approach for making these molecules, the team was able to understand why they are super-fast," he explained. Once the surprisingly fast state was discovered, "using the 'Legos,' we could take the molecules apart piece by piece, and swap in different 'Lego' bricks—and thereby systematically understand the structure/function relationships that led to this ultrafast conductivity." Ph.D. student Jialing (Caroline) Li, an expert in single-molecule electronics characterization who studied the molecules generated by the synthesizer, explained the essence of the conductivity discovery. "We observed that the side chains have a huge impact on how the molecule behaves and how this affects charge transport efficiency across the entire molecule," she said. Specifically, the team discovered that molecular junctions with long alkyl side chains have unexpectedly high conductance, which is dependent on concentration. They also figured out the reason for the high conductivity: The long alkyl side chains promote surface adsorption (the molecule's ability to adhere to a surface), which results in planarization (in effect, flattening out) of the molecules such that electrons can flow through them more efficiently. Burke, who is the May and Ving Lee Professor for Chemical Innovation and a professor of chemistry, called the building-block approach a "one-two punch": it makes the platform "a powerful engine for both discovering function, and then understanding the function." The conductance discovery represents a significant advance for the field of organic electronics. "Semiconductor-metal interfaces are ubiquitous in electronic devices. The surprising find of a high conductance state induced by metallic interfaces can pave the way to new molecular design for highly efficient charge injection and collection across a wide range of electronic applications," said co-author Ying Diao, an I. C. Gunsalus Scholar, Dow Chemical Company Faculty Scholar, and associate professor of chemical & biomolecular engineering. Schroeder explained that organic electronic materials have multiple benefits. To begin with, their use avoids the need for metals or other inorganic electronics. But organic electronics also offer much more: deformation and elastic properties that can be vital to some applications, such as implantable medical devices that could bend and flex along with, for example, a beating heart. Such organic devices could even be designed to degrade within the body, so that they break down and disappear after their job is done. Some organic electronics are already available in commercial products. For example, organic light-emitting diodes (OLED) can be found in the screens of smart phones, smart watches, and OLED TVs. It's anticipated that organic solar cells are on their way to becoming a commercial success as well. But the research community has only scratched the surface of organic electronics' potential; progress has been slowed by the lack of key materials discoveries like the one just made by the UIUC team. Schroeder said that it's significant to have proven that "we can design and synthesize large libraries for various applications." The paper "showcases the fact that we successfully did it for a class of molecules for molecular electronics." He admitted, "I didn't expect to see something as interesting on this first study." Co-author Jeffrey S. Moore, who is a Stanley O. Ikenberry Endowed Chair, professor of chemistry, and Howard Hughes Medical Institute Professor, reflected on the work: "Advancing basic science and technology by combining new facilities with a collaborative team is what makes the Beckman Institute so special. This discovery is the first of many that will come from the Molecule Maker Lab." Schroeder believes that the Molecule Maker Lab facilities—which also offer artificial intelligence capabilities for predicting what molecules are likely to be worth making—will open up a new approach to research in that "you can start thinking about designing based on a function instead of a structure." Whereas researchers today might start by saying, "I need to make this particular structure because I think it's going to do something," it will be possible to tell the system, "I want to get this ultimate function," and then let it help you figure out what structures you should make to get that function. The intent is eventually to make the Molecule Maker Lab facilities available to researchers outside UIUC. Burke said he'd like to see the Lab "become a global epicenter of democratized molecular innovation," empowering people who are not molecular synthesis specialists to solve important research problems. "I think this is the beginning of something really special," Burke said. "The journey has begun." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Serving over three billion passengers annually, air travel serves as a conduit for infectious disease spread, including emerging infections and pandemics. Over two dozen cases of in-flight transmissions have been documented. To understand these risks, a characterization of the airplane cabin microbiome is necessary. Our study team collected 229 environmental samples on ten transcontinental US flights with subsequent 16S rRNA sequencing. We found that bacterial communities were largely derived from human skin and oral commensals, as well as environmental generalist bacteria. We identified clear signatures for air versus touch surface microbiome, but not for individual types of touch surfaces. We also found large flight-to-flight beta diversity variations with no distinguishing signatures of individual flights, rather a high between-flight diversity for all touch surfaces and particularly for air samples. There was no systematic pattern of microbial community change from pre- to post-flight. Our findings are similar to those of other recent studies of the microbiome of built environments. In summary, the airplane cabin microbiome has immense airplane to airplane variability. The vast majority of airplane-associated microbes are human commensals or non-pathogenic, and the results provide a baseline for non-crisis-level airplane microbiome conditions. Working on a manuscript? Avoid the common mistakes Introduction With over three billion airline passengers annually, the risk of in-flight transmission of infectious disease is a vital global health concern [ 1 , 2 ]. Over two dozen cases of in-flight transmission have been documented, including influenza [ 3 , 4 , 5 , 6 , 7 ], measles [ 8 , 9 ], meningococcal infections [ 10 ], norovirus [ 11 ], SARS [ 12 , 13 ], shigellosis [ 14 ], cholera [ 15 ], and multi-drug resistant tuberculosis [ 1 , 16 , 17 , 18 ]. Studies of SARS [ 12 , 13 ] and pandemic influenza (H1N1p) [ 19 ] transmission on airplanes indicate that air travel can serve as a conduit for the rapid spread of newly emerging infections and pandemics. Further, some of these studies suggest that the movements of passengers and crew (and their close contacts) may be an important factor in disease transmission. In 2014, a passenger infected with Ebola flew on Frontier airlines the night before being admitted to a hospital [ 20 ]. Luckily, she did not infect anybody during that trip. Despite many sensational media stories and anecdotes, e.g., “Flying The Filthy Skies” [ 21 ] or “The Gross Truth About Germs and Airplanes” [ 22 ], the true risks of in-flight transmission are unknown. An essential component of risk assessment and public health guidance is characterizing the background microbial communities present, in particular those in the air and on common touch surfaces. Next-generation sequencing has the potential to identify all bacteria present via their genomes, commonly called the microbiome. There have been a few previous studies of the bacterial community in cabin air [ 23 , 24 , 25 , 26 ], but none, to our knowledge, on airplane touch surfaces. These studies estimated total bacterial burden of culturable cells present, and applied early forms of 16S rRNA sequencing and bioinformatics, claiming species-level resolution. At the time of these studies, there were far fewer reference genomes with which to align. Although these were at the vanguard of research of the microbiome of built environments, 10 years later, current methods and protocols are significantly more rigorous. The microbiome of the built environment is an active research area. Using a wide range of methods, authors have studied the microbiomes of classrooms [ 27 , 28 , 29 ], homes [ 30 , 31 , 32 ], offices [ 33 , 34 ], hospitals [ 35 ], museums [ 36 ], nursing homes [ 37 ], stores [ 38 ], and subways [ 39 , 40 , 41 ]. Several of these studies, particularly those of classrooms and offices, identified significant quantities of Lactobacillus on seats. With the exception of the hospital microbiome, all of these studies indicate that the main microbiome constituents, at the family level, are human commensal and environmental bacteria. What else could they be? Airplane environments are unique to the examples listed above. Special features include very dry air, periodic high occupant densities, exposure to the microbiota of the high atmosphere, and long periods during which occupants have extremely limited mobility. Thus, one might expect that the airplane cabin microbiome might differ considerably from those of other built environments. Another key difference is that in an airplane cabin, it is difficult to avoid a mobile sick person, or one sitting in close proximity. In another publication [ 42 ], we describe behaviors and close contacts of all passengers and flight attendants in the economy cabin on ten flights of duration 4 hours or more, the FlyHealthy™ Study. FlyHealthy™ has provided first detailed understanding of infectious disease transmission opportunities in an airplane cabin. In addition to quantifying the opportunities, we wanted to understand the infectious agents present in an airplane cabin that might be transmitted during these opportunities. To this end, we identified the microbiota present on these flights, allowing characterization of the airplane cabin microbiome. We hypothesized that the airplane cabin microbiome differs from that of other built environments due to the above-stated reasons. Since the majority of flights were during the seasonal flu epidemic in either the originating city or the destination city, we were interested to determine if we could detect influenza virus in our samples. Since the transmission opportunities we characterized in the first part of the FlyHealthy™ study were those that would allow transmission by large droplets, we were interested in sampling air as well as touch surfaces (fomites). Key questions related to differences between types of samples (air versus touch surfaces), pre- to post-flight changes, and changes from flight-to-flight in the “core” airplane cabin microbiome. Results Airplane Cabin Bacterial Communities in the Air and on Touch Surfaces Skin commensals in the family Propionibacteriaceae dominate both air (~ 20% post-filtered reads) and touch surfaces (~ 27% post-filtered reads). There is", "role": "user" }, { "content": "What does flying in a commercial airliner have in common with working at the office or relaxing at home? According to a new study, the answer is the microbiome—the community of bacteria found in homes, offices and aircraft cabins. Believed to be the first to comprehensively assess the microbiome of aircraft, the study found that the bacterial communities accompanying airline passengers at 30,000 feet have much in common with the bacterial communities surrounding people in their homes and offices. Using advanced sequencing technology, researchers from the Georgia Institute of Technology and Emory University studied the bacteria found on three components of an airliner cabin that are commonly touched by passengers: tray tables, seat belt buckles and the handles of lavatory doors. They swabbed those items before and after 10 transcontinental flights and also sampled air in the rear of the cabin during flight. What they found was surprisingly unexciting. \"Airline passengers should not be frightened by sensational stories about germs on a plane,\" said Vicki Stover Hertzberg, a professor in Emory University's Nell Hodgson Woodruff School of Nursing and a co-author of the study. \"They should recognize that microbes are everywhere and that an airplane is no better and no worse than an office building, a subway car, home or a classroom. These environments all have microbiomes that look like places occupied by people.\" The results of the FlyHealthy study are reported June 6, 2018, in the journal Microbial Ecology. In March, the researchers reported on a separate part of the study that examined potential routes for transmitting certain respiratory viruses—such as the flu—on commercial flights. Credit: Georgia Tech Given the unusual nature of an aircraft cabin, the researchers hadn't known what to expect from their microbiome study. On transcontinental flights, passengers spend four or five hours in close proximity breathing a very dry mix of outdoor air and recycled cabin air that has been passed through special filters, similar to those found in operating rooms. \"There were reasons to believe that the communities of bacteria in an aircraft cabin might be different from those in other parts of the built environment, so it surprised me that what we found was very similar to what other researchers have found in homes and offices,\" said Howard Weiss, a professor in Georgia Tech's School of Mathematics and the study's corresponding author. \"What we found was bacterial communities that were mostly derived from human skin, the human mouth—and some environmental bacteria.\" The sampling found significant variations from flight to flight, which is consistent with the differences other researchers have found among the cars of passenger trains, Weiss noted. Each aircraft seemed to have its own microbiome, but the researchers did not detect statistically significant differences between preflight and post-flight conditions on the flights studied. \"We identified a core airplane microbiome—the genera that were present in every sample we studied,\" Weiss added. The core microbiome included genera Propionibacterium, Burkholderia, Staphylococcus, and Strepococcus (oralis). Though the study revealed bacteria common to other parts of the built environment, Weiss still suggests travelers exercise reasonable caution. \"I carry a bottle of hand sanitizer in my computer bag whenever I travel,\" said Weiss. \"It's a good practice to wash or sanitize your hands, avoid touching your face, and get a flu shot ever year.\" This new information on the aircraft microbiome provides a baseline for further study, and could lead to improved techniques for maintaining healthy aircraft. How samples were taken from airline tray tables to study the microbiome of aircraft. Credit: John Toon, Georgia Tech \"The finding that airplanes have their own unique microbiome should not be totally surprising since we have been exploring the unique microbiome of everything from humans to spacecraft to salt ponds in Australia. The study does have important implications for industrial cleaning and sterilization standards for airplanes,\" said Christopher Dupont, another co-author and an associate professor in the Microbial and Environmental Genomics Department at the J. Craig Venter Institute, which provided bioinformatics analysis of the study's data. The 229 samples obtained from the aircraft cabin testing were subjected to 16S rRNA sequencing, which was done at the HudsonAlpha Institute for Biotechnology in Huntsville, Alabama. The small amount of genetic material captured on the swabs and air sampling limited the level of detail the testing could provide to identifying genera of bacteria, Weiss said. The extensive bioinformatics, or sequence analysis, was carried out at the J. Craig Venter Institute in La Jolla, Calif. In the March 19 issue of the journal Proceedings of the National Academy of Sciences, the researchers reported on the results of another component of the FlyHealthy study that looked at potential transmission of respiratory viruses on aircraft. They found that an infectious passenger with influenza or other droplet-transmitted respiratory infection will most likely not transmit infection to passengers seated farther away than two seats laterally and one row in front or back on an aircraft. That portion of the study was designed to assess rates and routes of possible infectious disease transmission during flights, using a model that combines estimated infectivity and patterns of contact among aircraft passengers and crew members to determine likelihood of infection. FlyHealthy team members were assigned to monitor specific areas of the passenger cabin, developing information about contacts between passengers as they moved around. Among next steps, the researchers would like to study the microbiome of airport areas, especially the departure lounges where passengers congregate before boarding. They would also like to study long-haul international flights in which passengers spend more time together—and are more likely to move about the cabin. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Serving over three billion passengers annually, air travel serves as a conduit for infectious disease spread, including emerging infections and pandemics. Over two dozen cases of in-flight transmissions have been documented. To understand these risks, a characterization of the airplane cabin microbiome is necessary. Our study team collected 229 environmental samples on ten transcontinental US flights with subsequent 16S rRNA sequencing. We found that bacterial communities were largely derived from human skin and oral commensals, as well as environmental generalist bacteria. We identified clear signatures for air versus touch surface microbiome, but not for individual types of touch surfaces. We also found large flight-to-flight beta diversity variations with no distinguishing signatures of individual flights, rather a high between-flight diversity for all touch surfaces and particularly for air samples. There was no systematic pattern of microbial community change from pre- to post-flight. Our findings are similar to those of other recent studies of the microbiome of built environments. In summary, the airplane cabin microbiome has immense airplane to airplane variability. The vast majority of airplane-associated microbes are human commensals or non-pathogenic, and the results provide a baseline for non-crisis-level airplane microbiome conditions. Working on a manuscript? Avoid the common mistakes Introduction With over three billion airline passengers annually, the risk of in-flight transmission of infectious disease is a vital global health concern [ 1 , 2 ]. Over two dozen cases of in-flight transmission have been documented, including influenza [ 3 , 4 , 5 , 6 , 7 ], measles [ 8 , 9 ], meningococcal infections [ 10 ], norovirus [ 11 ], SARS [ 12 , 13 ], shigellosis [ 14 ], cholera [ 15 ], and multi-drug resistant tuberculosis [ 1 , 16 , 17 , 18 ]. Studies of SARS [ 12 , 13 ] and pandemic influenza (H1N1p) [ 19 ] transmission on airplanes indicate that air travel can serve as a conduit for the rapid spread of newly emerging infections and pandemics. Further, some of these studies suggest that the movements of passengers and crew (and their close contacts) may be an important factor in disease transmission. In 2014, a passenger infected with Ebola flew on Frontier airlines the night before being admitted to a hospital [ 20 ]. Luckily, she did not infect anybody during that trip. Despite many sensational media stories and anecdotes, e.g., “Flying The Filthy Skies” [ 21 ] or “The Gross Truth About Germs and Airplanes” [ 22 ], the true risks of in-flight transmission are unknown. An essential component of risk assessment and public health guidance is characterizing the background microbial communities present, in particular those in the air and on common touch surfaces. Next-generation sequencing has the potential to identify all bacteria present via their genomes, commonly called the microbiome. There have been a few previous studies of the bacterial community in cabin air [ 23 , 24 , 25 , 26 ], but none, to our knowledge, on airplane touch surfaces. These studies estimated total bacterial burden of culturable cells present, and applied early forms of 16S rRNA sequencing and bioinformatics, claiming species-level resolution. At the time of these studies, there were far fewer reference genomes with which to align. Although these were at the vanguard of research of the microbiome of built environments, 10 years later, current methods and protocols are significantly more rigorous. The microbiome of the built environment is an active research area. Using a wide range of methods, authors have studied the microbiomes of classrooms [ 27 , 28 , 29 ], homes [ 30 , 31 , 32 ], offices [ 33 , 34 ], hospitals [ 35 ], museums [ 36 ], nursing homes [ 37 ], stores [ 38 ], and subways [ 39 , 40 , 41 ]. Several of these studies, particularly those of classrooms and offices, identified significant quantities of Lactobacillus on seats. With the exception of the hospital microbiome, all of these studies indicate that the main microbiome constituents, at the family level, are human commensal and environmental bacteria. What else could they be? Airplane environments are unique to the examples listed above. Special features include very dry air, periodic high occupant densities, exposure to the microbiota of the high atmosphere, and long periods during which occupants have extremely limited mobility. Thus, one might expect that the airplane cabin microbiome might differ considerably from those of other built environments. Another key difference is that in an airplane cabin, it is difficult to avoid a mobile sick person, or one sitting in close proximity. In another publication [ 42 ], we describe behaviors and close contacts of all passengers and flight attendants in the economy cabin on ten flights of duration 4 hours or more, the FlyHealthy™ Study. FlyHealthy™ has provided first detailed understanding of infectious disease transmission opportunities in an airplane cabin. In addition to quantifying the opportunities, we wanted to understand the infectious agents present in an airplane cabin that might be transmitted during these opportunities. To this end, we identified the microbiota present on these flights, allowing characterization of the airplane cabin microbiome. We hypothesized that the airplane cabin microbiome differs from that of other built environments due to the above-stated reasons. Since the majority of flights were during the seasonal flu epidemic in either the originating city or the destination city, we were interested to determine if we could detect influenza virus in our samples. Since the transmission opportunities we characterized in the first part of the FlyHealthy™ study were those that would allow transmission by large droplets, we were interested in sampling air as well as touch surfaces (fomites). Key questions related to differences between types of samples (air versus touch surfaces), pre- to post-flight changes, and changes from flight-to-flight in the “core” airplane cabin microbiome. Results Airplane Cabin Bacterial Communities in the Air and on Touch Surfaces Skin commensals in the family Propionibacteriaceae dominate both air (~ 20% post-filtered reads) and touch surfaces (~ 27% post-filtered reads). There is<|im_end|> <|im_start|>assistant What does flying in a commercial airliner have in common with working at the office or relaxing at home? According to a new study, the answer is the microbiome—the community of bacteria found in homes, offices and aircraft cabins. Believed to be the first to comprehensively assess the microbiome of aircraft, the study found that the bacterial communities accompanying airline passengers at 30,000 feet have much in common with the bacterial communities surrounding people in their homes and offices. Using advanced sequencing technology, researchers from the Georgia Institute of Technology and Emory University studied the bacteria found on three components of an airliner cabin that are commonly touched by passengers: tray tables, seat belt buckles and the handles of lavatory doors. They swabbed those items before and after 10 transcontinental flights and also sampled air in the rear of the cabin during flight. What they found was surprisingly unexciting. "Airline passengers should not be frightened by sensational stories about germs on a plane," said Vicki Stover Hertzberg, a professor in Emory University's Nell Hodgson Woodruff School of Nursing and a co-author of the study. "They should recognize that microbes are everywhere and that an airplane is no better and no worse than an office building, a subway car, home or a classroom. These environments all have microbiomes that look like places occupied by people." The results of the FlyHealthy study are reported June 6, 2018, in the journal Microbial Ecology. In March, the researchers reported on a separate part of the study that examined potential routes for transmitting certain respiratory viruses—such as the flu—on commercial flights. Credit: Georgia Tech Given the unusual nature of an aircraft cabin, the researchers hadn't known what to expect from their microbiome study. On transcontinental flights, passengers spend four or five hours in close proximity breathing a very dry mix of outdoor air and recycled cabin air that has been passed through special filters, similar to those found in operating rooms. "There were reasons to believe that the communities of bacteria in an aircraft cabin might be different from those in other parts of the built environment, so it surprised me that what we found was very similar to what other researchers have found in homes and offices," said Howard Weiss, a professor in Georgia Tech's School of Mathematics and the study's corresponding author. "What we found was bacterial communities that were mostly derived from human skin, the human mouth—and some environmental bacteria." The sampling found significant variations from flight to flight, which is consistent with the differences other researchers have found among the cars of passenger trains, Weiss noted. Each aircraft seemed to have its own microbiome, but the researchers did not detect statistically significant differences between preflight and post-flight conditions on the flights studied. "We identified a core airplane microbiome—the genera that were present in every sample we studied," Weiss added. The core microbiome included genera Propionibacterium, Burkholderia, Staphylococcus, and Strepococcus (oralis). Though the study revealed bacteria common to other parts of the built environment, Weiss still suggests travelers exercise reasonable caution. "I carry a bottle of hand sanitizer in my computer bag whenever I travel," said Weiss. "It's a good practice to wash or sanitize your hands, avoid touching your face, and get a flu shot ever year." This new information on the aircraft microbiome provides a baseline for further study, and could lead to improved techniques for maintaining healthy aircraft. How samples were taken from airline tray tables to study the microbiome of aircraft. Credit: John Toon, Georgia Tech "The finding that airplanes have their own unique microbiome should not be totally surprising since we have been exploring the unique microbiome of everything from humans to spacecraft to salt ponds in Australia. The study does have important implications for industrial cleaning and sterilization standards for airplanes," said Christopher Dupont, another co-author and an associate professor in the Microbial and Environmental Genomics Department at the J. Craig Venter Institute, which provided bioinformatics analysis of the study's data. The 229 samples obtained from the aircraft cabin testing were subjected to 16S rRNA sequencing, which was done at the HudsonAlpha Institute for Biotechnology in Huntsville, Alabama. The small amount of genetic material captured on the swabs and air sampling limited the level of detail the testing could provide to identifying genera of bacteria, Weiss said. The extensive bioinformatics, or sequence analysis, was carried out at the J. Craig Venter Institute in La Jolla, Calif. In the March 19 issue of the journal Proceedings of the National Academy of Sciences, the researchers reported on the results of another component of the FlyHealthy study that looked at potential transmission of respiratory viruses on aircraft. They found that an infectious passenger with influenza or other droplet-transmitted respiratory infection will most likely not transmit infection to passengers seated farther away than two seats laterally and one row in front or back on an aircraft. That portion of the study was designed to assess rates and routes of possible infectious disease transmission during flights, using a model that combines estimated infectivity and patterns of contact among aircraft passengers and crew members to determine likelihood of infection. FlyHealthy team members were assigned to monitor specific areas of the passenger cabin, developing information about contacts between passengers as they moved around. Among next steps, the researchers would like to study the microbiome of airport areas, especially the departure lounges where passengers congregate before boarding. They would also like to study long-haul international flights in which passengers spend more time together—and are more likely to move about the cabin. <|im_end|>

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2,436

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract We designed a liquid biopsy (LB) platform employing low-pass whole genome sequencing (LP-WGS) and targeted sequencing of cell-free (cf) DNA from plasma to detect genome-wide copy number alterations (CNAs) and gene fusions in pediatric solid tumors. A total of 143 plasma samples were analyzed from 19 controls and 73 patients, including 44 bone or soft-tissue sarcomas and 12 renal, 10 germ cell, five hepatic, and two thyroid tumors. cfDNA was isolated from plasma collected at diagnosis, during and after therapy, and/or at relapse. Twenty-six of 37 (70%) patients enrolled at diagnosis without prior therapy (radiation, surgery, or chemotherapy) had circulating tumor DNA (ctDNA), based on the detection of CNAs from LP-WGS, including 18 of 27 (67%) patients with localized disease and eight of 10 (80%) patients with metastatic disease. None of the controls had detectable somatic CNAs. There was a high concordance of CNAs identified by LP-WGS to CNAs detected by chromosomal microarray analysis in the matching tumors. Mutations identified in tumor samples with our next-generation sequencing (NGS) panel, OncoKids®, were also detected by LP-WGS of ctDNA in 14 of 26 plasma samples. Finally, we developed a hybridization-based capture panel to target EWSR1 and FOXO1 fusions from patients with Ewing sarcoma or alveolar rhabdomyosarcoma (ARMS), respectively. Fusions were detected in the plasma from 10 of 12 patients with Ewing sarcoma and in two of two patients with ARMS. Combined, these data demonstrate the clinical applicability of our LB platform to evaluate pediatric patients with a variety of solid tumors. Introduction Pediatric solid tumors encompass a heterogeneous group of rare malignancies that constitute approximately 40% of all childhood cancers 1 . Among them, soft-tissue tumors including embryonal tumors, germ cell tumors, and renal tumors account for approximately 10% of cases, whereas bone and soft-tissue sarcomas comprise ~20% of all cases 2 , 3 , 4 . The cytogenetic and molecular genetic characterization of pediatric solid tumors is used clinically to aid in diagnosis and determine prognosis, and in certain cases, guide treatment 5 . Identification of germline copy number alterations (CNAs) and sequence variants in cancer predisposition genes are also important for patient management, specifically to address the risk for second malignancies in the patient or cancer in a family member. Liquid biopsy (LB) assays for pediatric patients with solid tumors have the potential to transform patient care by providing a less invasive alternative to diagnostic biopsies for identifying genomic aberrations that can inform diagnosis, risk stratification, and therapeutic options as well as enable earlier detection of disease progression compared with conventional radiographic imaging 6 , 7 , 8 , 9 , 10 , 11 . The clinical effectiveness of plasma-based LB approaches, however, depends on optimizing the detection of circulating tumor DNA (ctDNA) fragments and distinguishing them from cfDNA derived predominantly from hematopoietic cells 12 , 13 . Recent advances in LB test development have focused primarily on adult-type malignant epithelial tumors defined by a spectrum of recurrent dominant activating mutations 14 , 15 , 16 . Pediatric tumors, however, are more often characterized by CNAs, loss of tumor suppressor genes, epigenetic modifications, and large-scale structural rearrangements with breakpoints that are variable and located in the intronic regions of the genome 5 , 17 , 18 . Furthermore, the incidence of pediatric solid tumors is low, and the number of histologic, genomic, and clinical subtypes is large, suggesting that the combined use of a pan-cancer assay and a target-specific approach may be better suited for clinical applications. Most importantly, the clinical development of LB assays for pediatric solid tumor patients has been limited by the requirement for relatively large volumes of blood, urine, or cerebrospinal fluid (CSF) to isolate sufficient amounts of cancer-derived nucleic acids for analysis. The feasibility of employing NGS and droplet digital PCR-based assays utilizing cfDNA derived from CSF, plasma, or the aqueous humor of the eye for pediatric central nervous system (CNS) tumors, solid tumors, or retinoblastoma, respectively, has recently been described 10 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 . In the diagnostic setting, ultra-low-pass WGS (ULP-WGS) analysis of plasma ctDNA was effectively used to distinguish malignant peripheral nerve sheath tumors (MPNST) from the benign lesion, plexiform neurofibroma (PN), in patients with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome 28 . By using in silico enrichment of short cfDNA fragments and copy number analysis, MPNST samples were found to be enriched with ctDNA when compared to PN, and treatment response was correlated with the ctDNA-derived estimate of tumor burden 28 . To assess response to treatment, Liu et al. assessed measurable residual disease (MRD) in 123 children with medulloblastoma using LP-WGS of cfDNA derived from CSF 10 . The presence of MRD in the CSF was found to be associated with a higher risk of relapse. The presence of ctDNA in plasma has been proposed as a prognostic biomarker in pediatric solid tumors (reviewed in ref. 7 ), and targeted detection of EWSR1 and FOXO1 fusions in Ewing sarcoma and alveolar rhabdomyosarcoma (ARMS) has been demonstrated in small cohorts of patients 29 , 30 . The Precision Medicine Program in Pediatric and Adolescent Patients with Recurrent Malignancies (MAPPYACTS) employed whole exome sequencing (WES) of tumor tissue and cfDNA from plasma to identify targeted therapies in patients with relapsed/recurrent non-CNS solid tumors 31 . Notably, 57% of the somatic SNVs were detected in both the tumor and the cfDNA, whereas 31% were specific to the tumor and 11% were specific to the cfDNA, reflecting tumor heterogeneity, or possibly technical limitations of the assays 31 . Significantly more mutations were detected in patients with metastatic (66%) vs localized (47%) disease. The studies published to date have demonstrated the feasibility of using cfDNA from plasma to detect CNAs, sequence variants, and/or gene fusions, but have focused on disease-specific cohorts, or patients with recurrent/refractory disease. The aim of the present study was to evaluate the potential clinical applicability of a plasma-based LB assay for newly diagnosed", "role": "user" }, { "content": "Pediatric solid tumors make up approximately 40% of all childhood cancers. While pediatric cancer is rare, children can develop a wide range of tumor types, located in different parts of the body, which can make the differential diagnosis challenging. Investigators at Children's Hospital Los Angeles have developed a liquid biopsy for solid tumors that has the potential to aid in reaching a specific diagnosis when surgery or a tissue biopsy is not feasible. The study findings were published in the journal npj Precision Oncology. \"This is one of the first clinically validated liquid biopsy tests to be launched at a pediatric academic medical center,\" says Jaclyn Biegel, Ph.D., Chief of Genomic Medicine and Director of the Center for Personalized Medicine at CHLA. \"We created a test that may be helpful in making a diagnosis, determining prognosis, and potentially identifying an effective therapy for children with solid tumors,\" says Fariba Navid, MD, Medical Director of Clinical Research in the Cancer and Blood Disease Institute at CHLA. Dr. Navid and Dr. Biegel are co-senior authors of this study. A specific test for pediatric tumors is required because the genetics of tumors that affect adults differ from those in children. Adult tumors tend to be caused by mutations—sequence-based changes in a gene— so most liquid biopsy tests have been developed specifically to identify these mutations. However, pediatric tumors arising from mutations are less common. In children, copy number changes—losing or having extra copies of one or more genes—or rearrangements of genes that result in gene fusions, are more characteristic. For their research study, the CHLA team combined a technique known as Low-Pass Whole Genome Sequencing (LP-WGS) with targeted sequencing of cell-free DNA from plasma to detect copy number changes, as well as mutations and gene fusions, that are characteristic of pediatric solid tumors. An important feature of the study was that it required a much smaller volume of sample than is required for liquid biopsy studies in adults. Since an infant or young child has a smaller blood volume, the assays needed to be scaled down to accommodate this difference. To create the test, the researchers collaborated with clinical teams and research investigators at CHLA including Jesse Berry, MD, Director of Ocular Oncology and CHLA's Retinoblastoma Program, as well as investigators involved in Oncology, Neurosurgery and Pathology and Laboratory Medicine. Leo Mascarenhas, MD, MS, Deputy Director of the Cancer and Blood Disease Institute at CHLA was also involved in the design and support of the project. The first version of the test, launched in Nov. 2022, evaluates chromosomal copy number changes in blood samples, cerebrospinal fluid and the aqueous humor of the eye to aid in the clinical diagnosis for patients with solid tumors, brain tumors and retinoblastoma, respectively. The next version of the clinical assay, available in about six months, will include detection of mutations and gene fusions. The liquid biopsy-based genetic tests join the CHLA-developed OncoKids cancer panel, a next-generation sequencing-based assay designed to detect changes in DNA or RNA that are associated with pediatric leukemias, brain and solid tumors; the CHLA Cancer Predisposition Panel; RNAseq for cancer, a transcriptome-based assay using RNA sequencing; VMD4Kids, a panel for vascular and mosaic disorders; as well as methylation array-based profiling for pediatric brain tumors. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract We designed a liquid biopsy (LB) platform employing low-pass whole genome sequencing (LP-WGS) and targeted sequencing of cell-free (cf) DNA from plasma to detect genome-wide copy number alterations (CNAs) and gene fusions in pediatric solid tumors. A total of 143 plasma samples were analyzed from 19 controls and 73 patients, including 44 bone or soft-tissue sarcomas and 12 renal, 10 germ cell, five hepatic, and two thyroid tumors. cfDNA was isolated from plasma collected at diagnosis, during and after therapy, and/or at relapse. Twenty-six of 37 (70%) patients enrolled at diagnosis without prior therapy (radiation, surgery, or chemotherapy) had circulating tumor DNA (ctDNA), based on the detection of CNAs from LP-WGS, including 18 of 27 (67%) patients with localized disease and eight of 10 (80%) patients with metastatic disease. None of the controls had detectable somatic CNAs. There was a high concordance of CNAs identified by LP-WGS to CNAs detected by chromosomal microarray analysis in the matching tumors. Mutations identified in tumor samples with our next-generation sequencing (NGS) panel, OncoKids®, were also detected by LP-WGS of ctDNA in 14 of 26 plasma samples. Finally, we developed a hybridization-based capture panel to target EWSR1 and FOXO1 fusions from patients with Ewing sarcoma or alveolar rhabdomyosarcoma (ARMS), respectively. Fusions were detected in the plasma from 10 of 12 patients with Ewing sarcoma and in two of two patients with ARMS. Combined, these data demonstrate the clinical applicability of our LB platform to evaluate pediatric patients with a variety of solid tumors. Introduction Pediatric solid tumors encompass a heterogeneous group of rare malignancies that constitute approximately 40% of all childhood cancers 1 . Among them, soft-tissue tumors including embryonal tumors, germ cell tumors, and renal tumors account for approximately 10% of cases, whereas bone and soft-tissue sarcomas comprise ~20% of all cases 2 , 3 , 4 . The cytogenetic and molecular genetic characterization of pediatric solid tumors is used clinically to aid in diagnosis and determine prognosis, and in certain cases, guide treatment 5 . Identification of germline copy number alterations (CNAs) and sequence variants in cancer predisposition genes are also important for patient management, specifically to address the risk for second malignancies in the patient or cancer in a family member. Liquid biopsy (LB) assays for pediatric patients with solid tumors have the potential to transform patient care by providing a less invasive alternative to diagnostic biopsies for identifying genomic aberrations that can inform diagnosis, risk stratification, and therapeutic options as well as enable earlier detection of disease progression compared with conventional radiographic imaging 6 , 7 , 8 , 9 , 10 , 11 . The clinical effectiveness of plasma-based LB approaches, however, depends on optimizing the detection of circulating tumor DNA (ctDNA) fragments and distinguishing them from cfDNA derived predominantly from hematopoietic cells 12 , 13 . Recent advances in LB test development have focused primarily on adult-type malignant epithelial tumors defined by a spectrum of recurrent dominant activating mutations 14 , 15 , 16 . Pediatric tumors, however, are more often characterized by CNAs, loss of tumor suppressor genes, epigenetic modifications, and large-scale structural rearrangements with breakpoints that are variable and located in the intronic regions of the genome 5 , 17 , 18 . Furthermore, the incidence of pediatric solid tumors is low, and the number of histologic, genomic, and clinical subtypes is large, suggesting that the combined use of a pan-cancer assay and a target-specific approach may be better suited for clinical applications. Most importantly, the clinical development of LB assays for pediatric solid tumor patients has been limited by the requirement for relatively large volumes of blood, urine, or cerebrospinal fluid (CSF) to isolate sufficient amounts of cancer-derived nucleic acids for analysis. The feasibility of employing NGS and droplet digital PCR-based assays utilizing cfDNA derived from CSF, plasma, or the aqueous humor of the eye for pediatric central nervous system (CNS) tumors, solid tumors, or retinoblastoma, respectively, has recently been described 10 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 . In the diagnostic setting, ultra-low-pass WGS (ULP-WGS) analysis of plasma ctDNA was effectively used to distinguish malignant peripheral nerve sheath tumors (MPNST) from the benign lesion, plexiform neurofibroma (PN), in patients with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome 28 . By using in silico enrichment of short cfDNA fragments and copy number analysis, MPNST samples were found to be enriched with ctDNA when compared to PN, and treatment response was correlated with the ctDNA-derived estimate of tumor burden 28 . To assess response to treatment, Liu et al. assessed measurable residual disease (MRD) in 123 children with medulloblastoma using LP-WGS of cfDNA derived from CSF 10 . The presence of MRD in the CSF was found to be associated with a higher risk of relapse. The presence of ctDNA in plasma has been proposed as a prognostic biomarker in pediatric solid tumors (reviewed in ref. 7 ), and targeted detection of EWSR1 and FOXO1 fusions in Ewing sarcoma and alveolar rhabdomyosarcoma (ARMS) has been demonstrated in small cohorts of patients 29 , 30 . The Precision Medicine Program in Pediatric and Adolescent Patients with Recurrent Malignancies (MAPPYACTS) employed whole exome sequencing (WES) of tumor tissue and cfDNA from plasma to identify targeted therapies in patients with relapsed/recurrent non-CNS solid tumors 31 . Notably, 57% of the somatic SNVs were detected in both the tumor and the cfDNA, whereas 31% were specific to the tumor and 11% were specific to the cfDNA, reflecting tumor heterogeneity, or possibly technical limitations of the assays 31 . Significantly more mutations were detected in patients with metastatic (66%) vs localized (47%) disease. The studies published to date have demonstrated the feasibility of using cfDNA from plasma to detect CNAs, sequence variants, and/or gene fusions, but have focused on disease-specific cohorts, or patients with recurrent/refractory disease. The aim of the present study was to evaluate the potential clinical applicability of a plasma-based LB assay for newly diagnosed<|im_end|> <|im_start|>assistant Pediatric solid tumors make up approximately 40% of all childhood cancers. While pediatric cancer is rare, children can develop a wide range of tumor types, located in different parts of the body, which can make the differential diagnosis challenging. Investigators at Children's Hospital Los Angeles have developed a liquid biopsy for solid tumors that has the potential to aid in reaching a specific diagnosis when surgery or a tissue biopsy is not feasible. The study findings were published in the journal npj Precision Oncology. "This is one of the first clinically validated liquid biopsy tests to be launched at a pediatric academic medical center," says Jaclyn Biegel, Ph.D., Chief of Genomic Medicine and Director of the Center for Personalized Medicine at CHLA. "We created a test that may be helpful in making a diagnosis, determining prognosis, and potentially identifying an effective therapy for children with solid tumors," says Fariba Navid, MD, Medical Director of Clinical Research in the Cancer and Blood Disease Institute at CHLA. Dr. Navid and Dr. Biegel are co-senior authors of this study. A specific test for pediatric tumors is required because the genetics of tumors that affect adults differ from those in children. Adult tumors tend to be caused by mutations—sequence-based changes in a gene— so most liquid biopsy tests have been developed specifically to identify these mutations. However, pediatric tumors arising from mutations are less common. In children, copy number changes—losing or having extra copies of one or more genes—or rearrangements of genes that result in gene fusions, are more characteristic. For their research study, the CHLA team combined a technique known as Low-Pass Whole Genome Sequencing (LP-WGS) with targeted sequencing of cell-free DNA from plasma to detect copy number changes, as well as mutations and gene fusions, that are characteristic of pediatric solid tumors. An important feature of the study was that it required a much smaller volume of sample than is required for liquid biopsy studies in adults. Since an infant or young child has a smaller blood volume, the assays needed to be scaled down to accommodate this difference. To create the test, the researchers collaborated with clinical teams and research investigators at CHLA including Jesse Berry, MD, Director of Ocular Oncology and CHLA's Retinoblastoma Program, as well as investigators involved in Oncology, Neurosurgery and Pathology and Laboratory Medicine. Leo Mascarenhas, MD, MS, Deputy Director of the Cancer and Blood Disease Institute at CHLA was also involved in the design and support of the project. The first version of the test, launched in Nov. 2022, evaluates chromosomal copy number changes in blood samples, cerebrospinal fluid and the aqueous humor of the eye to aid in the clinical diagnosis for patients with solid tumors, brain tumors and retinoblastoma, respectively. The next version of the clinical assay, available in about six months, will include detection of mutations and gene fusions. The liquid biopsy-based genetic tests join the CHLA-developed OncoKids cancer panel, a next-generation sequencing-based assay designed to detect changes in DNA or RNA that are associated with pediatric leukemias, brain and solid tumors; the CHLA Cancer Predisposition Panel; RNAseq for cancer, a transcriptome-based assay using RNA sequencing; VMD4Kids, a panel for vascular and mosaic disorders; as well as methylation array-based profiling for pediatric brain tumors. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Communication by means of diffusible signaling molecules facilitates higher-level organization of cellular populations. Gram-positive bacteria frequently use signaling peptides, which are either detected at the cell surface or ‘probed’ by intracellular receptors after being pumped into the cytoplasm. While the former type is used to monitor cell density, the functions of pump-probe networks are less clear. Here we show that pump-probe networks can, in principle, perform different tasks and mediate quorum-sensing, chronometric and ratiometric control. We characterize the properties of the prototypical PhrA-RapA system in Bacillus subtilis using FRET. We find that changes in extracellular PhrA concentrations are tracked rather poorly; instead, cells accumulate and strongly amplify the signal in a dose-dependent manner. This suggests that the PhrA-RapA system, and others like it, have evolved to sense changes in the composition of heterogeneous populations and infer the fraction of signal-producing cells in a mixed population to coordinate cellular behaviors. Introduction Cell-to-cell communication by diffusible signaling molecules is a central component of higher-level organization of populations in time and space. Specific signaling peptides are frequently used for this purpose, both in eukaryotes and prokaryotes. In Gram-positive bacteria, these signals are either detected at the cell surface by histidine kinases or they are sensed inside the cell by RRNPP-type receptors after uptake by oligopeptide permeases 1 , 2 . When signals bind reversibly to receptors on the cell surface, the extracellular concentration of signaling molecules is the primary source of information, and the affinity of the receptor for its ligand controls signal transduction. In contrast, when signaling molecules are irreversibly pumped into the cell to activate an intracellular receptor, the extracellular signal concentration may not correlate with the concentrations sensed by the receptor. Thus, it is far from obvious what kinds of information cells can extract with the help of these networks to coordinate population-level behavior. There has been tremendous progress in elucidating the molecular organization of the RRNPP signaling networks in recent years. RRNPP systems are widespread among Firmicutes and regulate traits which are commonly controlled by bacterial communication, such as cell differentiation, various forms of horizontal gene transfer, and the synthesis of (exo)factors that shape the interactions of these bacteria with other microbes and their hosts 2 , 3 . Binding of the signaling peptide to the receptor induces a conformational change that alters the activity of the receptor’s output domain(s), which, depending on the receptor subtype, is either a DNA-binding domain or a protein-interaction domain or both 4 , 5 , 6 . Thus, some systems control gene expression directly, others indirectly, and a few do so in both ways. However, all systems share a common feature—namely, that the signals are produced by an export–import circuit. Cells express precursor peptides, which are subsequently secreted and cleaved by different proteases to produce the mature signaling peptides. These signals are then actively pumped into the cells by the conserved oligopeptide permease Opp 7 , 8 , an ABC-type transporter that hydrolyzes ATP to drive the import of short oligopeptides 9 . Thus, RRNPP signaling networks represent prototypes for “pump–probe” networks, since signals are first “pumped” into the cell before they are “probed” (interpreted) by the respective RRNPP-type receptors. The systems-level functions that are performed by these signaling networks are still unclear. They are commonly thought to facilitate “quorum sensing” in a bacterial population, i.e., the population-wide coordination of gene expression in response to changes in cell density 10 , 11 . Theoretically, they could indeed function as sensitive devices for cell-density monitoring 12 , but whether RRNPP signaling networks actually implement a “quorum-sensing” type of regulation has been questioned 13 , 14 . They have also been hypothesized to function as timers for (multi-)cellular development 15 , 16 , 17 , to coordinate the development of cellular subpopulations 18 , 19 and, under certain conditions, signaling could be self-directed and act in cis rather than in trans 20 . It is indeed conceivable that the more complex pump–probe network architecture allows for different types of extracellular information processing. However, this has not been systematically investigated. One of the best characterized pump–probe network is the PhrA-RapA-Spo0F signaling pathway in Bacillus subtilis . The Rap proteins represent evolutionarily ancient RRNPP-type receptors 21 that are found in many Bacilli 22 . RapA and several other Rap homologs control the initiation of endospore formation by modulating the flux of phosphoryl groups through the sporulation phosphorelay to the master regulator Spo0A 23 . RapA binds to the response regulator Spo0F and stimulates the auto-dephosphorylation of Spo0F 23 , 24 . PhrA, the hydrophilic linear pentapeptide ARNQT that is derived from the phrA gene, binds to the RapA receptor at an allosteric site 14 , 15 , 25 . This induces a conformational change, which alters the interaction of the RapA with its response-regulator target Spo0F 4 , 24 , 25 , 26 . The rapA-phrA operon is highly regulated 27 , 28 , 29 , 30 , 31 , 32 and is activated under both non-sporulating 30 , 31 and sporulating 16 , 27 , 28 , 33 conditions, indicating that signaling takes place in different situations. Interestingly, under some conditions the operon is expressed heterogeneously across the population 18 (a phenomenon that has been observed for other rap-phr -signaling systems 16 ), which might point at a signaling function beyond classical quorum sensing 34 . Specifically, in a heterogeneous population its composition might be a relevant parameter for cellular decision-making. Here we ask what regulatory functions pump–probe networks serve. To answer this question, we employ a combination of theoretical modeling of generic pump–probe networks and specific experiments on the PhrA-RapA-Spo0F pathway under non-sporulating conditions. We use Förster (fluorescence) resonance energy transfer (FRET) to monitor changes in the interaction of the RapA receptor with its response-regulator target Spo0F upon extracellular stimulation of B. subtilis cells with PhrA. We show that, in theory, pump–probe networks can exhibit different sensory modes that could mediate diverse functions, including quorum sensing, as well as chronometrically and ratiometrically controlled modes", "role": "user" }, { "content": "Bacteria have a sense of their own number. They release and sense signaling molecules that accumulate with increasing cell numbers, which allows them to change their behavior when a certain group size is reached. A team of researchers from the Max Planck Institute for Terrestrial Microbiology in Marburg and Heidelberg University has now been able to show that bacteria might be capable of even more: they could perceive the proportions of different groups of bacteria in their environment. In nature, bacteria often live in complex communities, surrounded by other cells that can differ from each other, even within a species. The principal investigator, Ilka Bischofs, explains: \"Imagine yourself in a ballroom full of people. Their sheer number is only of limited relevance to you; it is the gender ratio that tells you how hard it will be to find a dancing partner. Bacteria also collect information about their environment. Information about group ratios could help them make decisions and adapt in the best possible way.\" The research team studied information retrieval in the bacterium Bacillus subtilis. This species possesses a large number of identically constructed chemical signaling systems that were previously thought to measure cell numbers. Instead the bacteria may utilize these systems to determine the proportions of different groups within a mixed population. The respective signaling molecules are often produced by a subset of cells, but are taken up by all bacteria. Therefore, cells compete with each other for the signaling molecules. The larger the ratio of signal producers in the population, the more signaling molecules will accumulate in the cells where they are being detected. However, as with computers, the specific function of a system depends on its settings. The research team was able to show experimentally that at least the example investigated bacterial signal system is indeed correctly configured for facilitating ratio-sensing. Using high-resolution methods of flurorescence microscopy (Förster Resonance Energy Transfer, FRET), they analysed the signal transduction in detail. The ratio-sensing ability could confer decisive advantages to the bacterium. As research in recent years has shown, Bacillus subtilis often splits its population into subgroups of cells with different properties and functions. Similar to a stock broker, the bacterium diversifies its portfolio of phenotypes. Knowing the composition of a portfolio obviously enables to respond adequately to environmental changes—a strategy that bacteria may have already discovered during evolution. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Communication by means of diffusible signaling molecules facilitates higher-level organization of cellular populations. Gram-positive bacteria frequently use signaling peptides, which are either detected at the cell surface or ‘probed’ by intracellular receptors after being pumped into the cytoplasm. While the former type is used to monitor cell density, the functions of pump-probe networks are less clear. Here we show that pump-probe networks can, in principle, perform different tasks and mediate quorum-sensing, chronometric and ratiometric control. We characterize the properties of the prototypical PhrA-RapA system in Bacillus subtilis using FRET. We find that changes in extracellular PhrA concentrations are tracked rather poorly; instead, cells accumulate and strongly amplify the signal in a dose-dependent manner. This suggests that the PhrA-RapA system, and others like it, have evolved to sense changes in the composition of heterogeneous populations and infer the fraction of signal-producing cells in a mixed population to coordinate cellular behaviors. Introduction Cell-to-cell communication by diffusible signaling molecules is a central component of higher-level organization of populations in time and space. Specific signaling peptides are frequently used for this purpose, both in eukaryotes and prokaryotes. In Gram-positive bacteria, these signals are either detected at the cell surface by histidine kinases or they are sensed inside the cell by RRNPP-type receptors after uptake by oligopeptide permeases 1 , 2 . When signals bind reversibly to receptors on the cell surface, the extracellular concentration of signaling molecules is the primary source of information, and the affinity of the receptor for its ligand controls signal transduction. In contrast, when signaling molecules are irreversibly pumped into the cell to activate an intracellular receptor, the extracellular signal concentration may not correlate with the concentrations sensed by the receptor. Thus, it is far from obvious what kinds of information cells can extract with the help of these networks to coordinate population-level behavior. There has been tremendous progress in elucidating the molecular organization of the RRNPP signaling networks in recent years. RRNPP systems are widespread among Firmicutes and regulate traits which are commonly controlled by bacterial communication, such as cell differentiation, various forms of horizontal gene transfer, and the synthesis of (exo)factors that shape the interactions of these bacteria with other microbes and their hosts 2 , 3 . Binding of the signaling peptide to the receptor induces a conformational change that alters the activity of the receptor’s output domain(s), which, depending on the receptor subtype, is either a DNA-binding domain or a protein-interaction domain or both 4 , 5 , 6 . Thus, some systems control gene expression directly, others indirectly, and a few do so in both ways. However, all systems share a common feature—namely, that the signals are produced by an export–import circuit. Cells express precursor peptides, which are subsequently secreted and cleaved by different proteases to produce the mature signaling peptides. These signals are then actively pumped into the cells by the conserved oligopeptide permease Opp 7 , 8 , an ABC-type transporter that hydrolyzes ATP to drive the import of short oligopeptides 9 . Thus, RRNPP signaling networks represent prototypes for “pump–probe” networks, since signals are first “pumped” into the cell before they are “probed” (interpreted) by the respective RRNPP-type receptors. The systems-level functions that are performed by these signaling networks are still unclear. They are commonly thought to facilitate “quorum sensing” in a bacterial population, i.e., the population-wide coordination of gene expression in response to changes in cell density 10 , 11 . Theoretically, they could indeed function as sensitive devices for cell-density monitoring 12 , but whether RRNPP signaling networks actually implement a “quorum-sensing” type of regulation has been questioned 13 , 14 . They have also been hypothesized to function as timers for (multi-)cellular development 15 , 16 , 17 , to coordinate the development of cellular subpopulations 18 , 19 and, under certain conditions, signaling could be self-directed and act in cis rather than in trans 20 . It is indeed conceivable that the more complex pump–probe network architecture allows for different types of extracellular information processing. However, this has not been systematically investigated. One of the best characterized pump–probe network is the PhrA-RapA-Spo0F signaling pathway in Bacillus subtilis . The Rap proteins represent evolutionarily ancient RRNPP-type receptors 21 that are found in many Bacilli 22 . RapA and several other Rap homologs control the initiation of endospore formation by modulating the flux of phosphoryl groups through the sporulation phosphorelay to the master regulator Spo0A 23 . RapA binds to the response regulator Spo0F and stimulates the auto-dephosphorylation of Spo0F 23 , 24 . PhrA, the hydrophilic linear pentapeptide ARNQT that is derived from the phrA gene, binds to the RapA receptor at an allosteric site 14 , 15 , 25 . This induces a conformational change, which alters the interaction of the RapA with its response-regulator target Spo0F 4 , 24 , 25 , 26 . The rapA-phrA operon is highly regulated 27 , 28 , 29 , 30 , 31 , 32 and is activated under both non-sporulating 30 , 31 and sporulating 16 , 27 , 28 , 33 conditions, indicating that signaling takes place in different situations. Interestingly, under some conditions the operon is expressed heterogeneously across the population 18 (a phenomenon that has been observed for other rap-phr -signaling systems 16 ), which might point at a signaling function beyond classical quorum sensing 34 . Specifically, in a heterogeneous population its composition might be a relevant parameter for cellular decision-making. Here we ask what regulatory functions pump–probe networks serve. To answer this question, we employ a combination of theoretical modeling of generic pump–probe networks and specific experiments on the PhrA-RapA-Spo0F pathway under non-sporulating conditions. We use Förster (fluorescence) resonance energy transfer (FRET) to monitor changes in the interaction of the RapA receptor with its response-regulator target Spo0F upon extracellular stimulation of B. subtilis cells with PhrA. We show that, in theory, pump–probe networks can exhibit different sensory modes that could mediate diverse functions, including quorum sensing, as well as chronometrically and ratiometrically controlled modes<|im_end|> <|im_start|>assistant Bacteria have a sense of their own number. They release and sense signaling molecules that accumulate with increasing cell numbers, which allows them to change their behavior when a certain group size is reached. A team of researchers from the Max Planck Institute for Terrestrial Microbiology in Marburg and Heidelberg University has now been able to show that bacteria might be capable of even more: they could perceive the proportions of different groups of bacteria in their environment. In nature, bacteria often live in complex communities, surrounded by other cells that can differ from each other, even within a species. The principal investigator, Ilka Bischofs, explains: "Imagine yourself in a ballroom full of people. Their sheer number is only of limited relevance to you; it is the gender ratio that tells you how hard it will be to find a dancing partner. Bacteria also collect information about their environment. Information about group ratios could help them make decisions and adapt in the best possible way." The research team studied information retrieval in the bacterium Bacillus subtilis. This species possesses a large number of identically constructed chemical signaling systems that were previously thought to measure cell numbers. Instead the bacteria may utilize these systems to determine the proportions of different groups within a mixed population. The respective signaling molecules are often produced by a subset of cells, but are taken up by all bacteria. Therefore, cells compete with each other for the signaling molecules. The larger the ratio of signal producers in the population, the more signaling molecules will accumulate in the cells where they are being detected. However, as with computers, the specific function of a system depends on its settings. The research team was able to show experimentally that at least the example investigated bacterial signal system is indeed correctly configured for facilitating ratio-sensing. Using high-resolution methods of flurorescence microscopy (Förster Resonance Energy Transfer, FRET), they analysed the signal transduction in detail. The ratio-sensing ability could confer decisive advantages to the bacterium. As research in recent years has shown, Bacillus subtilis often splits its population into subgroups of cells with different properties and functions. Similar to a stock broker, the bacterium diversifies its portfolio of phenotypes. Knowing the composition of a portfolio obviously enables to respond adequately to environmental changes—a strategy that bacteria may have already discovered during evolution. <|im_end|>

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1,905

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract In the bottom-up synthesis of graphene nanoribbons (GNRs) from self-assembled linear polymer intermediates, surface-assisted cyclodehydrogenations usually take place on catalytic metal surfaces. Here we demonstrate the formation of GNRs from quasi-freestanding polymers assisted by hole injections from a scanning tunnelling microscope (STM) tip. While catalytic cyclodehydrogenations typically occur in a domino-like conversion process during the thermal annealing, the hole-injection-assisted reactions happen at selective molecular sites controlled by the STM tip. The charge injections lower the cyclodehydrogenation barrier in the catalyst-free formation of graphitic lattices, and the orbital symmetry conservation rules favour hole rather than electron injections for the GNR formation. The created polymer–GNR intraribbon heterostructures have a type-I energy level alignment and strongly localized interfacial states. This finding points to a new route towards controllable synthesis of freestanding graphitic layers, facilitating the design of on-surface reactions for GNR-based structures. Introduction In the pursuit of atomically precise and bottom-up fabrication of graphene-based electronics 1 , 2 , 3 , graphene nanoribbons (GNRs) with a variety of widths 4 , 5 , edge structures 6 , 7 and heterojunctions 8 , 9 have been synthesized with self-assembled molecular precursors on different catalytic metal substrates, such as Au (refs 10 , 11 , 12 ), Ag (ref. 13 ) and Cu (refs 14 , 15 ). Surface-assisted cyclodehydrogenations 16 , 17 , 18 , a key step in GNR formation, appear to take place only on the catalytic metal substrates 19 , 20 . Efforts of growing GNRs from molecular precursors directly on an insulating TiO 2 substrate only succeeded in deriving polymerization but not the cyclodehydrogenation 20 . The metallic substrates are found to be essential not only for the GNR growth process, but also for the electronic behaviours of synthesized GNRs. The orbital hybridization between substrate and edge atoms can largely affect the predicted edge states and magnetism of GNRs 21 , 22 , and the dielectric screening interaction from the substrate can greatly modify the quasiparticle bandgaps of GNRs. For example, the armchair GNRs with a width of seven carbon (7-aGNRs) on Au(111) are reported to have an energy gap ranging from 1.8 to 2.8 eV (refs 4 , 10 , 13 , 23 , 24 , 25 , 26 ). These values are much smaller than expected from electronic structure calculations within many-body perturbation theory in the GW approximation, which predicts a gap of ∼ 3.7 eV (ref. 27 ). Controlling the substrate interaction is thus considered a prerequisite for studying the on-surface synthesis process and accessing the intrinsic electronic structure of GNRs. Here we focus on the controllable conversion of quasi-freestanding polymers to form atomically precise armchair graphene nanoribbons, 7-aGNRs. To decouple their electronic structure from the metal substrate, we grow the polymers atop first-layer (1st-layer) GNRs that are in direct contact with the metal substrate. The polymers are isolated from the metal substrate by the 1st-layer GNRs, leading to their quasi-freestanding nature. Using scanning tunnelling microscopy (STM), we find that electronic decoupling of the polymer can greatly slow down the cyclodehydrogenation and an STM tip can be used to inject charges at the selected molecular sites to trigger the reaction and thus create intraribbon heterojunctions. Based on nudged elastic band (NEB) simulations, we reveal a hole-assisted cyclodehydrogenation reaction path that points to an avenue towards the controllable on-surface synthesis of freestanding GNRs and precise intraribbon heterojunctions. Results Synthesis of quasi-freestanding polymer chains The polyanthrylene chains were synthesized on Au(111) using 10,10′-dibromo-9,9′-bianthryl (DBBA) molecules as precursors with a bottom-up method described by Cai et al . 11 (Methods). Figure 1a schematically illustrates the stepwise annealing process for growing the 7-aGNRs and quasi-freestanding polymer chains atop the GNRs. With a molecule coverage θ >1, the sample is subsequently annealed to enable colligation/polymerization (at 470 K) ( Supplementary Fig. 1 ) and cyclodehydrogenation/graphitization (at 670 K), resulting in the polymer chains atop the GNRs ( Fig. 1b ). The STM images in Fig. 1c,d show the 1st-layer 7-aGNRs adsorbed on Au(111) and the second-layer (2nd-layer) polymer chains, respectively. The 2nd-layer polymer chains mainly grow along the GNRs, showing a period of about 8.4 Å, consistent with the simulated STM image shown in Fig. 1e and with previous reports for polymers directly adsorbed on Au(111) surface 11 . The sub-hexagon-ring features in the STM image ( Fig. 1f ) are reproduced by the simulated charge density distribution of the highest occupied crystal orbital of the polymer (HOCO p , Fig. 1g ). The 2nd-layer polymer chains are effectively decoupled from the Au substrate due to the GNRs underneath, which enables imaging of the quasi-atomic polymer structures. Figure 1: Bottom-up synthesis of polymer chains on armchair graphene nanoribbons with a width of seven carbon (7-aGNRs). ( a ) Sketch for synthesis of the second-layer (2nd-layer) polyanthrylene chains on 7-aGNRs from 10,10′-dibromo-9,9′-bianthryl (DBBA) molecules with stepwise annealing at 470 and 670 K, respectively. ( b ) Large-area scanning tunnelling microscopy (STM) image showing the polymer chains on 7-aGNRs (sample voltage V s =−2 V, tunnelling current I t =60 pA). Scale bar, 20 nm. ( c ) High-resolution STM image of the first-layer (1st-layer) 7-aGNR ( V s =−0.6 V, I t =100 pA) superposed with an atomic structure. Scale bar, 1 nm. ( d ) Small-scale STM image of the 2nd-layer polymer chains ( V s =+1 V, I t =60 pA). Scale bar, 2 nm. ( e ) The simulated STM image and an atomic structure of the polymer superposed on the magnified image of the top polymer chain in d . Scale bar, 1 nm. ( f ) High-resolution STM image showing the detailed structure of the polymer ( V s =−2 V, I t =10 pA). Scale bar, 2 nm. ( g ) Charge density distribution of the highest occupied crystal orbital of the polymer (HOCO p ). Dashed boxes mark the polymer unit in the polymer. Full size image The freestanding nature of the 2nd-layer polymer chains becomes clearer by comparing their geometric and electronic structures with", "role": "user" }, { "content": "A new way to grow narrow ribbons of graphene, a lightweight and strong structure of single-atom-thick carbon atoms linked into hexagons, may address a shortcoming that has prevented the material from achieving its full potential in electronic applications. Graphene nanoribbons, mere billionths of a meter wide, exhibit different electronic properties than two-dimensional sheets of the material. \"Confinement changes graphene's behavior,\" said An-Ping Li, a physicist at the Department of Energy's Oak Ridge National Laboratory. Graphene in sheets is an excellent electrical conductor, but narrowing graphene can turn the material into a semiconductor if the ribbons are made with a specific edge shape. Previous efforts to make graphene nanoribbons employed a metal substrate that hindered the ribbons' useful electronic properties. Now, scientists at ORNL and North Carolina State University report in the journal Nature Communications that they are the first to grow graphene nanoribbons without a metal substrate. Instead, they injected charge carriers that promote a chemical reaction that converts a polymer precursor into a graphene nanoribbon. At selected sites, this new technique can create interfaces between materials with different electronic properties. Such interfaces are the basis of semiconductor electronic devices from integrated circuits and transistors to light-emitting diodes and solar cells. \"Graphene is wonderful, but it has limits,\" said Li. \"In wide sheets, it doesn't have an energy gap—an energy range in a solid where no electronic states can exist. That means you cannot turn it on or off.\" When a voltage is applied to a sheet of graphene in a device, electrons flow freely as they do in metals, severely limiting graphene's application in digital electronics. \"When graphene becomes very narrow, it creates an energy gap,\" Li said. \"The narrower the ribbon is, the wider is the energy gap.\" A graphene nanoribbon is born. A scanning tunneling microscope injects charge carriers called “holes” into a polymer precursor, triggering a reaction called cyclodehydrogenation at that site, creating a specific place at which a freestanding graphene nanoribbon forms from the bottom up. Credit: Oak Ridge National Laboratory, U.S. Dept. of Energy In very narrow graphene nanoribbons, with a width of a nanometer or even less, how structures terminate at the edge of the ribbon is important too. For example, cutting graphene along the side of a hexagon creates an edge that resembles an armchair; this material can act like a semiconductor. Excising triangles from graphene creates a zigzag edge—and a material with metallic behavior. To grow graphene nanoribbons with controlled width and edge structure from polymer precursors, previous researchers had used a metal substrate to catalyze a chemical reaction. However, the metal substrate suppresses useful edge states and shrinks the desired band gap. Li and colleagues set out to get rid of this troublesome metal substrate. At the Center for Nanophase Materials Sciences, a DOE Office of Science User Facility at ORNL, they used the tip of a scanning tunneling microscope to inject either negative charge carriers (electrons) or positive charge carriers (\"holes\") to try to trigger the key chemical reaction. They discovered that only holes triggered it. They were subsequently able to make a ribbon that was only seven carbon atoms wide—less than one nanometer wide—with edges in the armchair conformation. \"We figured out the fundamental mechanism, that is, how charge injection can lower the reaction barrier to promote this chemical reaction,\" Li said. Moving the tip along the polymer chain, the researchers could select where they triggered this reaction and convert one hexagon of the graphene lattice at a time. Next, the researchers will make heterojunctions with different precursor molecules and explore functionalities. They are also eager to see how long electrons can travel in these ribbons before scattering, and will compare it with a graphene nanoribbon made another way and known to conduct electrons extremely well. Using electrons like photons could provide the basis for a new electronic device that could carry current with virtually no resistance, even at room temperature. \"It's a way to tailor physical properties for energy applications,\" Li said. \"This is an excellent example of direct writing. You can direct the transformation process at the molecular or atomic level.\" Plus, the process could be scaled up and automated. The title of the current paper is \"Controllable conversion of quasi-freestanding polymer chains to graphene nanoribbons.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract In the bottom-up synthesis of graphene nanoribbons (GNRs) from self-assembled linear polymer intermediates, surface-assisted cyclodehydrogenations usually take place on catalytic metal surfaces. Here we demonstrate the formation of GNRs from quasi-freestanding polymers assisted by hole injections from a scanning tunnelling microscope (STM) tip. While catalytic cyclodehydrogenations typically occur in a domino-like conversion process during the thermal annealing, the hole-injection-assisted reactions happen at selective molecular sites controlled by the STM tip. The charge injections lower the cyclodehydrogenation barrier in the catalyst-free formation of graphitic lattices, and the orbital symmetry conservation rules favour hole rather than electron injections for the GNR formation. The created polymer–GNR intraribbon heterostructures have a type-I energy level alignment and strongly localized interfacial states. This finding points to a new route towards controllable synthesis of freestanding graphitic layers, facilitating the design of on-surface reactions for GNR-based structures. Introduction In the pursuit of atomically precise and bottom-up fabrication of graphene-based electronics 1 , 2 , 3 , graphene nanoribbons (GNRs) with a variety of widths 4 , 5 , edge structures 6 , 7 and heterojunctions 8 , 9 have been synthesized with self-assembled molecular precursors on different catalytic metal substrates, such as Au (refs 10 , 11 , 12 ), Ag (ref. 13 ) and Cu (refs 14 , 15 ). Surface-assisted cyclodehydrogenations 16 , 17 , 18 , a key step in GNR formation, appear to take place only on the catalytic metal substrates 19 , 20 . Efforts of growing GNRs from molecular precursors directly on an insulating TiO 2 substrate only succeeded in deriving polymerization but not the cyclodehydrogenation 20 . The metallic substrates are found to be essential not only for the GNR growth process, but also for the electronic behaviours of synthesized GNRs. The orbital hybridization between substrate and edge atoms can largely affect the predicted edge states and magnetism of GNRs 21 , 22 , and the dielectric screening interaction from the substrate can greatly modify the quasiparticle bandgaps of GNRs. For example, the armchair GNRs with a width of seven carbon (7-aGNRs) on Au(111) are reported to have an energy gap ranging from 1.8 to 2.8 eV (refs 4 , 10 , 13 , 23 , 24 , 25 , 26 ). These values are much smaller than expected from electronic structure calculations within many-body perturbation theory in the GW approximation, which predicts a gap of ∼ 3.7 eV (ref. 27 ). Controlling the substrate interaction is thus considered a prerequisite for studying the on-surface synthesis process and accessing the intrinsic electronic structure of GNRs. Here we focus on the controllable conversion of quasi-freestanding polymers to form atomically precise armchair graphene nanoribbons, 7-aGNRs. To decouple their electronic structure from the metal substrate, we grow the polymers atop first-layer (1st-layer) GNRs that are in direct contact with the metal substrate. The polymers are isolated from the metal substrate by the 1st-layer GNRs, leading to their quasi-freestanding nature. Using scanning tunnelling microscopy (STM), we find that electronic decoupling of the polymer can greatly slow down the cyclodehydrogenation and an STM tip can be used to inject charges at the selected molecular sites to trigger the reaction and thus create intraribbon heterojunctions. Based on nudged elastic band (NEB) simulations, we reveal a hole-assisted cyclodehydrogenation reaction path that points to an avenue towards the controllable on-surface synthesis of freestanding GNRs and precise intraribbon heterojunctions. Results Synthesis of quasi-freestanding polymer chains The polyanthrylene chains were synthesized on Au(111) using 10,10′-dibromo-9,9′-bianthryl (DBBA) molecules as precursors with a bottom-up method described by Cai et al . 11 (Methods). Figure 1a schematically illustrates the stepwise annealing process for growing the 7-aGNRs and quasi-freestanding polymer chains atop the GNRs. With a molecule coverage θ >1, the sample is subsequently annealed to enable colligation/polymerization (at 470 K) ( Supplementary Fig. 1 ) and cyclodehydrogenation/graphitization (at 670 K), resulting in the polymer chains atop the GNRs ( Fig. 1b ). The STM images in Fig. 1c,d show the 1st-layer 7-aGNRs adsorbed on Au(111) and the second-layer (2nd-layer) polymer chains, respectively. The 2nd-layer polymer chains mainly grow along the GNRs, showing a period of about 8.4 Å, consistent with the simulated STM image shown in Fig. 1e and with previous reports for polymers directly adsorbed on Au(111) surface 11 . The sub-hexagon-ring features in the STM image ( Fig. 1f ) are reproduced by the simulated charge density distribution of the highest occupied crystal orbital of the polymer (HOCO p , Fig. 1g ). The 2nd-layer polymer chains are effectively decoupled from the Au substrate due to the GNRs underneath, which enables imaging of the quasi-atomic polymer structures. Figure 1: Bottom-up synthesis of polymer chains on armchair graphene nanoribbons with a width of seven carbon (7-aGNRs). ( a ) Sketch for synthesis of the second-layer (2nd-layer) polyanthrylene chains on 7-aGNRs from 10,10′-dibromo-9,9′-bianthryl (DBBA) molecules with stepwise annealing at 470 and 670 K, respectively. ( b ) Large-area scanning tunnelling microscopy (STM) image showing the polymer chains on 7-aGNRs (sample voltage V s =−2 V, tunnelling current I t =60 pA). Scale bar, 20 nm. ( c ) High-resolution STM image of the first-layer (1st-layer) 7-aGNR ( V s =−0.6 V, I t =100 pA) superposed with an atomic structure. Scale bar, 1 nm. ( d ) Small-scale STM image of the 2nd-layer polymer chains ( V s =+1 V, I t =60 pA). Scale bar, 2 nm. ( e ) The simulated STM image and an atomic structure of the polymer superposed on the magnified image of the top polymer chain in d . Scale bar, 1 nm. ( f ) High-resolution STM image showing the detailed structure of the polymer ( V s =−2 V, I t =10 pA). Scale bar, 2 nm. ( g ) Charge density distribution of the highest occupied crystal orbital of the polymer (HOCO p ). Dashed boxes mark the polymer unit in the polymer. Full size image The freestanding nature of the 2nd-layer polymer chains becomes clearer by comparing their geometric and electronic structures with<|im_end|> <|im_start|>assistant A new way to grow narrow ribbons of graphene, a lightweight and strong structure of single-atom-thick carbon atoms linked into hexagons, may address a shortcoming that has prevented the material from achieving its full potential in electronic applications. Graphene nanoribbons, mere billionths of a meter wide, exhibit different electronic properties than two-dimensional sheets of the material. "Confinement changes graphene's behavior," said An-Ping Li, a physicist at the Department of Energy's Oak Ridge National Laboratory. Graphene in sheets is an excellent electrical conductor, but narrowing graphene can turn the material into a semiconductor if the ribbons are made with a specific edge shape. Previous efforts to make graphene nanoribbons employed a metal substrate that hindered the ribbons' useful electronic properties. Now, scientists at ORNL and North Carolina State University report in the journal Nature Communications that they are the first to grow graphene nanoribbons without a metal substrate. Instead, they injected charge carriers that promote a chemical reaction that converts a polymer precursor into a graphene nanoribbon. At selected sites, this new technique can create interfaces between materials with different electronic properties. Such interfaces are the basis of semiconductor electronic devices from integrated circuits and transistors to light-emitting diodes and solar cells. "Graphene is wonderful, but it has limits," said Li. "In wide sheets, it doesn't have an energy gap—an energy range in a solid where no electronic states can exist. That means you cannot turn it on or off." When a voltage is applied to a sheet of graphene in a device, electrons flow freely as they do in metals, severely limiting graphene's application in digital electronics. "When graphene becomes very narrow, it creates an energy gap," Li said. "The narrower the ribbon is, the wider is the energy gap." A graphene nanoribbon is born. A scanning tunneling microscope injects charge carriers called “holes” into a polymer precursor, triggering a reaction called cyclodehydrogenation at that site, creating a specific place at which a freestanding graphene nanoribbon forms from the bottom up. Credit: Oak Ridge National Laboratory, U.S. Dept. of Energy In very narrow graphene nanoribbons, with a width of a nanometer or even less, how structures terminate at the edge of the ribbon is important too. For example, cutting graphene along the side of a hexagon creates an edge that resembles an armchair; this material can act like a semiconductor. Excising triangles from graphene creates a zigzag edge—and a material with metallic behavior. To grow graphene nanoribbons with controlled width and edge structure from polymer precursors, previous researchers had used a metal substrate to catalyze a chemical reaction. However, the metal substrate suppresses useful edge states and shrinks the desired band gap. Li and colleagues set out to get rid of this troublesome metal substrate. At the Center for Nanophase Materials Sciences, a DOE Office of Science User Facility at ORNL, they used the tip of a scanning tunneling microscope to inject either negative charge carriers (electrons) or positive charge carriers ("holes") to try to trigger the key chemical reaction. They discovered that only holes triggered it. They were subsequently able to make a ribbon that was only seven carbon atoms wide—less than one nanometer wide—with edges in the armchair conformation. "We figured out the fundamental mechanism, that is, how charge injection can lower the reaction barrier to promote this chemical reaction," Li said. Moving the tip along the polymer chain, the researchers could select where they triggered this reaction and convert one hexagon of the graphene lattice at a time. Next, the researchers will make heterojunctions with different precursor molecules and explore functionalities. They are also eager to see how long electrons can travel in these ribbons before scattering, and will compare it with a graphene nanoribbon made another way and known to conduct electrons extremely well. Using electrons like photons could provide the basis for a new electronic device that could carry current with virtually no resistance, even at room temperature. "It's a way to tailor physical properties for energy applications," Li said. "This is an excellent example of direct writing. You can direct the transformation process at the molecular or atomic level." Plus, the process could be scaled up and automated. The title of the current paper is "Controllable conversion of quasi-freestanding polymer chains to graphene nanoribbons." <|im_end|>

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2,514

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The quantitative analysis of lubricant transferred from disk to slider is important in understanding the interaction in head-disk interface and designing a stable head-disk system. When applying ellipsometric technology to determine the lubricant thickness on slider, the measurement accuracy is of concern due to the location-to-location variations of slider optical constants. This paper carried out a systematic and quantitative study on how the variations of slider optical constants affect the measurement accuracy of lubricant thickness. In this study, the distribution of slider optical constant was obtained; a differential method was used to calculate the uncertainty in lubricant thickness and the calculated results were experimentally verified. The results show that for the state-of-art sliders, the uncertainty in lubricant thickness is about 20 % for below 2 nm thicknesses and less than 15 % for around 3 nm thicknesses when measured at 632.8 nm wavelength. The results of this study might be also useful for the other optical instruments used to determine the amount of the transferred lubricant. Access provided by DEAL DE / Springer Compact Clearingstelle Uni Freiburg _ Working on a manuscript? Avoid the common mistakes 1 Introduction The continuing pursuit for higher magnetic recording areal density of hard disk drive (HDD) demands the smaller head-media spacing (HMS) (Ambeka and Bogy 2008 ). The lubricant transfer from the disk surface to a flying magnetic head slider (“slider” for short) increases with decreasing slider flying height. Transferred lubricant will affect HMS and deteriorate the slider flying stability, causing overall HDD reliability issues. The quantitative analysis of transferred lubricant is important in helping to understand the physical mechanism of interaction between lubricant and slider and design a stable head-disk interface system. Nowadays, several nanometrological techniques have been applied to determine the lubricant amount or thickness on slider (Kim et al. 2009 ; Leavitt 1992 ; Yanagisawa et al. 2010 ; Chiba and Ogata 2008 ; Tani et al. 2011 ). These include time-of-flight secondary ion mass spectroscope (TOF–SIMS), X-ray photoelectron spectroscope (XPS), optical surface analyzer (OSA), interferometry and spectroscopic ellipsometry (SE). Of these techniques, TOF–SIMS, XPS and SE have spot sizes small enough to directly measure lubricant thickness on slider. TOF–SIMS and XPS must be performed under the ultra-high vacuum conditions which might cause the evaporation and/or redistribution of transferred lubricant, whereas SE enables a fast and non-destructive measurement under ambient environment. However, when applied to determine the lubricant thickness on slider, the measurement accuracy is of concern due to the location-to-location variations of slider optical constants (refractive index n and extinction coefficient k ). SE is not direct measurement technique, it is impossible to measure the optical constants and thickness of a given sample directly with light. Instead, it measures the change of polarization in light reflected from or tramsmitted through the given sample. The polarization change is described by an amplitude ratio tanΨ and phase difference Δ between light oriented in the p- and s- directions relative to the sample surface. These measured data must be modeled in order to determine the sample properties of interest (optical constants or thickness of the film). The model-generated data are then compared to the measured data while the sample properties are varied. Through specific regression analysis, the unknown sample properties whose response best match the measured data are found. Generally, an optical model consists of the optical constants of both substrate and sample layers as well as the thicknesses of sample layers, in which the substrate is treated as a special type of layer having 1 mm optical thickness and accurately known optical constants. In SE measurement, the accuracy of an optical model usually contributes the significant accuracy to the measurement. In other word, if the optical model is not accurate, then its model fit result is not good and even might be completely wrong as through the original measured data are accurate and error free. To ensure the model accuracy, substrate optical constants used in the optical model should be the same as the measured ones for a given sample. For a case where substrate optical constants are not uniformly distributed, the location-to-location measurement should be applied, namely, before and after film deposition the same spot on the substrate will be measured and analyzed. Slider material is a two-phase composite consisting of Al 2 O 3 and TiC grains. The TiC grains are of random size, shape and separation at the order of micrometers, which makes slider optical constants vary with the measured locations and thus causes the variations in optical constants (Yuan et al. 2008 ). As stated above, the location-to-location measurement should be carried out for this case. However, the presence of positioning errors induced by the cycle of loading/unloading slider makes it very difficult to exactly get back to the original location before and after lubricant transfer, as a result, slider optical constants in the optical model might be not the same as the measured ones, thus causing the inaccurate result of determined lubricant thickness. There has not been a systematic and quantitative study on how the variation of slider optical constants affects the accuracy of the measured thickness. This paper presents a systematic and quantitative study on this problem. In this study, the statistical distribution of slider optical constants was obtained first. Then a differential method was described which was used to calculate the uncertainty (%) in lubricant thickness induced mainly by the variation of slider optical constants. The calculated results were finally verified experimentally. The results of this study might be also useful for the other optical instruments such as interferometry and reflectometry when they are used to determine the amount of the transferred lubricant (Tani et al. 2011 ). 2 Slider optical constants Normally, sliders are coated with ~0.5 nm-thick amorphous-Si adhesive layer and ~1.5 nm-thick diamond-like carbon (DLC) layer orderly. We treat them as part of slider substrate and use a combined pseudo substrate approximation to simulate the DLC/a-Si/AlTiC structure. Ellipsometry is the only technology to uniquely determine the optical constants for slider substrate.", "role": "user" }, { "content": "To keep pace with the rapidly growing consumer demand for data storage, hardware engineers are striving to cram as much electronic information into as small a space as possible. Jinmin Zhao, Mingsheng Zhang and co‐workers at the A*STAR Data Storage Institute, Singapore, have now devised a technique to assess the impact of making these devices more compact. Insights resulting from this work will guide the future design of stable disk drives. The primary components of a hard disk drive are a rotating disk coated with a thin film of magnetic material and a magnetic head on a moving arm, also called a slider (see image). The slider includes magnetic write/read elements that can encode a single bit of binary information by altering the properties of the thin film at a small spot on the surface. A smaller spot enables a higher density of data storage. Current technology is rapidly approaching one trillion bits per square inch, but this requires the separation between the head and disk to be less than 2 nanometers. This narrow requirement, however, creates its own problems. Lubricant used on the surface of the disk to protect it from corrosion can attach to the slider, which adversely affects the reliability of the hard disk drive. \"We have carried out a systematic and quantitative study on how the variation of slider optical properties affects the accuracy of the measured lubricant thickness on the slider surface,\" says Zhang. Zhao, Zhang and their co-workers analyzed a lubricant-coated slider using a technique known as spectroscopic ellipsometry. Measuring the intensity of light reflected from a sample slider provided a highly accurate estimate of the thickness of the lubricant film. Ellipsometry is a fast and non-destructive technique that, unlike some of the alternative approaches, does not require ultra-high vacuum conditions. This technique, however, does require accurate knowledge of the optical properties of the slider. A typical slider is made of aluminum oxide and grains of titanium carbide of many different shapes and sizes; thus, its optical properties vary from position to position. Zhao and the team's study demonstrated that the uncertainty in lubricant thickness is approximately proportional to the uncertainty in the slider's optical constants, and it becomes particularly pronounced for thicknesses below 2 nanometers. \"This lubricant transfer will be more serious in future heat-assisted magnetic recording,\" explains Zhang. \"The next step in this research will focus on how to reduce the lubricant transfer, especially in this type of device.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The quantitative analysis of lubricant transferred from disk to slider is important in understanding the interaction in head-disk interface and designing a stable head-disk system. When applying ellipsometric technology to determine the lubricant thickness on slider, the measurement accuracy is of concern due to the location-to-location variations of slider optical constants. This paper carried out a systematic and quantitative study on how the variations of slider optical constants affect the measurement accuracy of lubricant thickness. In this study, the distribution of slider optical constant was obtained; a differential method was used to calculate the uncertainty in lubricant thickness and the calculated results were experimentally verified. The results show that for the state-of-art sliders, the uncertainty in lubricant thickness is about 20 % for below 2 nm thicknesses and less than 15 % for around 3 nm thicknesses when measured at 632.8 nm wavelength. The results of this study might be also useful for the other optical instruments used to determine the amount of the transferred lubricant. Access provided by DEAL DE / Springer Compact Clearingstelle Uni Freiburg _ Working on a manuscript? Avoid the common mistakes 1 Introduction The continuing pursuit for higher magnetic recording areal density of hard disk drive (HDD) demands the smaller head-media spacing (HMS) (Ambeka and Bogy 2008 ). The lubricant transfer from the disk surface to a flying magnetic head slider (“slider” for short) increases with decreasing slider flying height. Transferred lubricant will affect HMS and deteriorate the slider flying stability, causing overall HDD reliability issues. The quantitative analysis of transferred lubricant is important in helping to understand the physical mechanism of interaction between lubricant and slider and design a stable head-disk interface system. Nowadays, several nanometrological techniques have been applied to determine the lubricant amount or thickness on slider (Kim et al. 2009 ; Leavitt 1992 ; Yanagisawa et al. 2010 ; Chiba and Ogata 2008 ; Tani et al. 2011 ). These include time-of-flight secondary ion mass spectroscope (TOF–SIMS), X-ray photoelectron spectroscope (XPS), optical surface analyzer (OSA), interferometry and spectroscopic ellipsometry (SE). Of these techniques, TOF–SIMS, XPS and SE have spot sizes small enough to directly measure lubricant thickness on slider. TOF–SIMS and XPS must be performed under the ultra-high vacuum conditions which might cause the evaporation and/or redistribution of transferred lubricant, whereas SE enables a fast and non-destructive measurement under ambient environment. However, when applied to determine the lubricant thickness on slider, the measurement accuracy is of concern due to the location-to-location variations of slider optical constants (refractive index n and extinction coefficient k ). SE is not direct measurement technique, it is impossible to measure the optical constants and thickness of a given sample directly with light. Instead, it measures the change of polarization in light reflected from or tramsmitted through the given sample. The polarization change is described by an amplitude ratio tanΨ and phase difference Δ between light oriented in the p- and s- directions relative to the sample surface. These measured data must be modeled in order to determine the sample properties of interest (optical constants or thickness of the film). The model-generated data are then compared to the measured data while the sample properties are varied. Through specific regression analysis, the unknown sample properties whose response best match the measured data are found. Generally, an optical model consists of the optical constants of both substrate and sample layers as well as the thicknesses of sample layers, in which the substrate is treated as a special type of layer having 1 mm optical thickness and accurately known optical constants. In SE measurement, the accuracy of an optical model usually contributes the significant accuracy to the measurement. In other word, if the optical model is not accurate, then its model fit result is not good and even might be completely wrong as through the original measured data are accurate and error free. To ensure the model accuracy, substrate optical constants used in the optical model should be the same as the measured ones for a given sample. For a case where substrate optical constants are not uniformly distributed, the location-to-location measurement should be applied, namely, before and after film deposition the same spot on the substrate will be measured and analyzed. Slider material is a two-phase composite consisting of Al 2 O 3 and TiC grains. The TiC grains are of random size, shape and separation at the order of micrometers, which makes slider optical constants vary with the measured locations and thus causes the variations in optical constants (Yuan et al. 2008 ). As stated above, the location-to-location measurement should be carried out for this case. However, the presence of positioning errors induced by the cycle of loading/unloading slider makes it very difficult to exactly get back to the original location before and after lubricant transfer, as a result, slider optical constants in the optical model might be not the same as the measured ones, thus causing the inaccurate result of determined lubricant thickness. There has not been a systematic and quantitative study on how the variation of slider optical constants affects the accuracy of the measured thickness. This paper presents a systematic and quantitative study on this problem. In this study, the statistical distribution of slider optical constants was obtained first. Then a differential method was described which was used to calculate the uncertainty (%) in lubricant thickness induced mainly by the variation of slider optical constants. The calculated results were finally verified experimentally. The results of this study might be also useful for the other optical instruments such as interferometry and reflectometry when they are used to determine the amount of the transferred lubricant (Tani et al. 2011 ). 2 Slider optical constants Normally, sliders are coated with ~0.5 nm-thick amorphous-Si adhesive layer and ~1.5 nm-thick diamond-like carbon (DLC) layer orderly. We treat them as part of slider substrate and use a combined pseudo substrate approximation to simulate the DLC/a-Si/AlTiC structure. Ellipsometry is the only technology to uniquely determine the optical constants for slider substrate.<|im_end|> <|im_start|>assistant To keep pace with the rapidly growing consumer demand for data storage, hardware engineers are striving to cram as much electronic information into as small a space as possible. Jinmin Zhao, Mingsheng Zhang and co‐workers at the A*STAR Data Storage Institute, Singapore, have now devised a technique to assess the impact of making these devices more compact. Insights resulting from this work will guide the future design of stable disk drives. The primary components of a hard disk drive are a rotating disk coated with a thin film of magnetic material and a magnetic head on a moving arm, also called a slider (see image). The slider includes magnetic write/read elements that can encode a single bit of binary information by altering the properties of the thin film at a small spot on the surface. A smaller spot enables a higher density of data storage. Current technology is rapidly approaching one trillion bits per square inch, but this requires the separation between the head and disk to be less than 2 nanometers. This narrow requirement, however, creates its own problems. Lubricant used on the surface of the disk to protect it from corrosion can attach to the slider, which adversely affects the reliability of the hard disk drive. "We have carried out a systematic and quantitative study on how the variation of slider optical properties affects the accuracy of the measured lubricant thickness on the slider surface," says Zhang. Zhao, Zhang and their co-workers analyzed a lubricant-coated slider using a technique known as spectroscopic ellipsometry. Measuring the intensity of light reflected from a sample slider provided a highly accurate estimate of the thickness of the lubricant film. Ellipsometry is a fast and non-destructive technique that, unlike some of the alternative approaches, does not require ultra-high vacuum conditions. This technique, however, does require accurate knowledge of the optical properties of the slider. A typical slider is made of aluminum oxide and grains of titanium carbide of many different shapes and sizes; thus, its optical properties vary from position to position. Zhao and the team's study demonstrated that the uncertainty in lubricant thickness is approximately proportional to the uncertainty in the slider's optical constants, and it becomes particularly pronounced for thicknesses below 2 nanometers. "This lubricant transfer will be more serious in future heat-assisted magnetic recording," explains Zhang. "The next step in this research will focus on how to reduce the lubricant transfer, especially in this type of device." <|im_end|>

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1,793

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Insects have presented human society with some of its greatest development challenges by spreading diseases, consuming crops and damaging infrastructure. Despite the massive human and financial toll of invasive insects, cost estimates of their impacts remain sporadic, spatially incomplete and of questionable quality. Here we compile a comprehensive database of economic costs of invasive insects. Taking all reported goods and service estimates, invasive insects cost a minimum of US$70.0 billion per year globally, while associated health costs exceed US$6.9 billion per year. Total costs rise as the number of estimate increases, although many of the worst costs have already been estimated (especially those related to human health). A lack of dedicated studies, especially for reproducible goods and service estimates, implies gross underestimation of global costs. Global warming as a consequence of climate change, rising human population densities and intensifying international trade will allow these costly insects to spread into new areas, but substantial savings could be achieved by increasing surveillance, containment and public awareness. Introduction For millennia, insects have been responsible for spreading devastating infectious diseases in both humans 1 and livestock 2 , ravaging crops and food stocks 3 , damaging forests 4 , destroying infrastructure 5 , altering ecosystem functions 6 and weakening the resilience of ecosystems to other disturbances 7 . This single invertebrate class ( ∼ 2.5 million species 8 ) is therefore probably the costliest animal group to human society. A global challenge this century will be meeting the world’s food requirements while maintaining economic productivity and conserving biodiversity. Globally, insect pests have been reported to reduce agricultural yields by 10–16% before harvest, and to consume a similar amount following harvest 9 . In fact, the largest food-producing countries, China and the United States, exhibit the highest potential losses from invasive insects 10 . Several other insect pests defoliate trees 4 and degrade plant biodiversity, threaten commercial forestry and hamper climate change mitigation via increased tree mortality and associated increases in greenhouse-gas emissions 11 . Many other insects are nuisance species or disease vectors that directly erode public health—from the Seventeenth to Twentieth centuries, insect-borne diseases caused more human disease and death than all other causes combined 12 . Insects are also among the most pervasive of invasive species. For example, 87% of the ∼ 2,500 non-native terrestrial invertebrates in Europe are insects 13 . Yet, reliable estimates of their impacts are difficult to obtain, in particular for economic assessments. Most cost estimates are disparate, regionally focused, cover variable periods and are not always grounded in verifiable data (see Methods). The types of costs also vary and include both direct and indirect components ( Fig. 1 ). Consequently, extrapolating local costs to global scales is challenging and few have attempted to overcome the many inherent flaws in this approach. Figure 1: Market and non-market cost categories associated with invasive insect damages. Costs are subdivided into ‘goods and services’ (yellow) and ‘human health’ (red), ‘regulating services’ ( sensu non-commercial, but potentially monetizable, such as carbon regulation and pollination not otherwise quantified in agricultural yield estimates; blue) and ‘ecological’ costs (not typically monetizable; green). Owing mainly to a lack of monetary estimates, we could not compile costs for the categories and subcategories coloured in grey. The inner circle (darkest colours) encapsulates costs associated with prevention; the middle circle (mid-range colours) includes costs associated with damage from invasive insects; the outer circle (lightest colours) covers costs associated with responses or follow-up to invasive insect incursions. The outermost purple arrow indicates the general increase in our ability to estimate monetizable costs, and the direct relevance to human commerce and well being. DALY, disability-adjusted life year (lifespan lost because of burden of insect-borne disease; not assessed). Full size image Reliable global cost summaries therefore remain a major challenge. Indeed, there are currently only 86 insect species listed in the International Union for Conservation of Nature (IUCN) Global Invasive Species Database 14 , and of those there are no cost estimates for 81.4%, while 12.8% of them have insufficient (unsourced) estimates. We therefore compiled the most comprehensive database of economic costs for invasive insects available to date (737 screened articles, chapters and reports), standardizing historical estimates as annual 2014 US dollars (US$; Methods). We determined the reproducibility of each study’s cost estimates by identifying the source of all values used to extrapolate regional costs. When values were based on actual measures as opposed to non-sourced estimates and had a clear methodology provided, we deemed the resulting costs ‘reproducible’ (although we did not assess quality per se because of a lack of standard, objective criteria to assess the accuracy of published estimates; Methods). We categorized studies that did not meet these criteria as ‘irreproducible’. We further divided all costs into two main categories: ‘goods and services’ (including production of agricultural and forestry goods, and cultural services; Fig. 1 ) and ‘human health’, further splitting the former into agriculture, forestry, infrastructure, mixed or urban categories, and the latter into seven disease categories (Methods). Taking all reported goods and services estimates, and avoiding the extrapolation of limited data, invasive insects cost a minimum of US$70.0 billion per year globally, while associated health costs exceed US$6.9 billion per year. Total costs rise as the number of estimates increases; therefore, the true costs of invasive insects to human society are substantially larger (but by a currently unquantifiable amount) than we report here. Further, future costs are likely to increase as invasive insects expand their ranges in response to climate change, as well as to increasing human movements and international trade. Results Goods and services We determined that invasive insects cost a minimum of US$70.0 billion per year globally for goods and services, of which US$25.2 billion per year comes from reproducible studies ( Fig. 2 and Supplementary Data 1 ). There was no temporal pattern in annual cost rates ( Supplementary Fig. 1 ), and most estimates were direct measures (although estimated costs were higher for extrapolated costs; see ‘Expenditure types and targets’ in the", "role": "user" }, { "content": "Invasive insects cause at least 69 billion euros of damage per annum worldwide. Such is the estimation made by an international research team led by Franck Courchamp, CNRS research director at Laboratoire Ecologie, Systématique et Evolution (Université Paris-Sud/CNRS/AgroParisTech) and notably including entomologists from IRD Montpellier and a CNRS economist. Their study brought together the largest database ever developed on economic damage attributable to invasive insects worldwide. Covering damage to goods and services, health care costs and agricultural losses, this study, conducted with the support of ANR and the BNP Paribas Foundation, considered 737 articles, books and reports. This work was published in Nature Communications on 4 October 2016. Why study insects? For thousands of years, insects have been responsible for the spread of diseases in humans and livestock, and cause considerable damage on many levels: from attacks on crops and stocks, through the destruction of infrastructure, to the devastation of forests, altering and weakening ecosystems. In the living world, insects alone (about 2.5 million species) are probably the group responsible for the greatest expense. In addition, they are among the most aggressive invasive species: 87% of 2500 terrestrial invertebrates that have colonized new territories are insects. Underestimated damage The scientists estimated the minimum economic damage caused by invasive insects to be 69 billion euros per year. Of the insects studied, the Formosan termite (Coptotermes formosanus) is one of the most destructive, causing over 26.7 billion euros of damage per year in the world. However, according to the research group, this estimate is based on a study that was insufficiently documented. Studies that were more soundly based (considered reproducible by the scientists) also put the cabbage moth (Plutella xylostella), with a cost of 4.1 billion euros per year, in a high-ranking position, like the brown spruce longhorn beetle (Tetropium fuscum), which costs 4 billion euros in Canada alone. Cabbage moth (Plutella xylostella). Credit: Mike Pennington Furthermore, according to this study, North America suffers the largest financial losses, at 24.5 billion euros a year, while Europe is currently at only 3.2 billion euros per year. This difference, however, can be explained more by a lack of evaluation sources than by a difference in exposure to these dangers. Thus, according to the researchers, the total annual cost estimation of 69 billion euros is largely underevaluated. Many parts of the world do not offer enough economic data to produce an accurate estimate, which is therefore minimized. In addition, the research team focused on the study of the ten most costly invasive species, not counting the very large number that cause less damage. Finally, considering the estimated values of ecosystem services on a global scale (hundreds of billions of dollars for crop pollination alone), the disruption caused by invasive insects could reach a level far beyond the current estimate. Health and agriculture are the most affected Insects overall take a heavy toll on agriculture by consuming 40% of the harvest (enough to feed one billion people). As for health, the total cost attributable to invasive insects exceeds 6.1 billion euros per year (without counting malaria, Zika virus, or economic impacts on tourism or productivity, etc.). From a geographic point of view, the regions of the world where medical expenses related to invasive insects prove to be the greatest are Asia (2.55 billion euros a year), North America (1.85 billion euros per year) and the whole of Central and South America (1.66 billion euros a year). Among the diseases that have the greatest economic impact, we firstly find dengue fever, for which the costs account for 84% of the 6.1 billion euros. According to the authors, greater vigilance and the development of procedures to respond to biological invasions would save society tens of billions of euros. These preventive measures could divide the cost of diseases caused by mosquitoes by at least tenfold. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Insects have presented human society with some of its greatest development challenges by spreading diseases, consuming crops and damaging infrastructure. Despite the massive human and financial toll of invasive insects, cost estimates of their impacts remain sporadic, spatially incomplete and of questionable quality. Here we compile a comprehensive database of economic costs of invasive insects. Taking all reported goods and service estimates, invasive insects cost a minimum of US$70.0 billion per year globally, while associated health costs exceed US$6.9 billion per year. Total costs rise as the number of estimate increases, although many of the worst costs have already been estimated (especially those related to human health). A lack of dedicated studies, especially for reproducible goods and service estimates, implies gross underestimation of global costs. Global warming as a consequence of climate change, rising human population densities and intensifying international trade will allow these costly insects to spread into new areas, but substantial savings could be achieved by increasing surveillance, containment and public awareness. Introduction For millennia, insects have been responsible for spreading devastating infectious diseases in both humans 1 and livestock 2 , ravaging crops and food stocks 3 , damaging forests 4 , destroying infrastructure 5 , altering ecosystem functions 6 and weakening the resilience of ecosystems to other disturbances 7 . This single invertebrate class ( ∼ 2.5 million species 8 ) is therefore probably the costliest animal group to human society. A global challenge this century will be meeting the world’s food requirements while maintaining economic productivity and conserving biodiversity. Globally, insect pests have been reported to reduce agricultural yields by 10–16% before harvest, and to consume a similar amount following harvest 9 . In fact, the largest food-producing countries, China and the United States, exhibit the highest potential losses from invasive insects 10 . Several other insect pests defoliate trees 4 and degrade plant biodiversity, threaten commercial forestry and hamper climate change mitigation via increased tree mortality and associated increases in greenhouse-gas emissions 11 . Many other insects are nuisance species or disease vectors that directly erode public health—from the Seventeenth to Twentieth centuries, insect-borne diseases caused more human disease and death than all other causes combined 12 . Insects are also among the most pervasive of invasive species. For example, 87% of the ∼ 2,500 non-native terrestrial invertebrates in Europe are insects 13 . Yet, reliable estimates of their impacts are difficult to obtain, in particular for economic assessments. Most cost estimates are disparate, regionally focused, cover variable periods and are not always grounded in verifiable data (see Methods). The types of costs also vary and include both direct and indirect components ( Fig. 1 ). Consequently, extrapolating local costs to global scales is challenging and few have attempted to overcome the many inherent flaws in this approach. Figure 1: Market and non-market cost categories associated with invasive insect damages. Costs are subdivided into ‘goods and services’ (yellow) and ‘human health’ (red), ‘regulating services’ ( sensu non-commercial, but potentially monetizable, such as carbon regulation and pollination not otherwise quantified in agricultural yield estimates; blue) and ‘ecological’ costs (not typically monetizable; green). Owing mainly to a lack of monetary estimates, we could not compile costs for the categories and subcategories coloured in grey. The inner circle (darkest colours) encapsulates costs associated with prevention; the middle circle (mid-range colours) includes costs associated with damage from invasive insects; the outer circle (lightest colours) covers costs associated with responses or follow-up to invasive insect incursions. The outermost purple arrow indicates the general increase in our ability to estimate monetizable costs, and the direct relevance to human commerce and well being. DALY, disability-adjusted life year (lifespan lost because of burden of insect-borne disease; not assessed). Full size image Reliable global cost summaries therefore remain a major challenge. Indeed, there are currently only 86 insect species listed in the International Union for Conservation of Nature (IUCN) Global Invasive Species Database 14 , and of those there are no cost estimates for 81.4%, while 12.8% of them have insufficient (unsourced) estimates. We therefore compiled the most comprehensive database of economic costs for invasive insects available to date (737 screened articles, chapters and reports), standardizing historical estimates as annual 2014 US dollars (US$; Methods). We determined the reproducibility of each study’s cost estimates by identifying the source of all values used to extrapolate regional costs. When values were based on actual measures as opposed to non-sourced estimates and had a clear methodology provided, we deemed the resulting costs ‘reproducible’ (although we did not assess quality per se because of a lack of standard, objective criteria to assess the accuracy of published estimates; Methods). We categorized studies that did not meet these criteria as ‘irreproducible’. We further divided all costs into two main categories: ‘goods and services’ (including production of agricultural and forestry goods, and cultural services; Fig. 1 ) and ‘human health’, further splitting the former into agriculture, forestry, infrastructure, mixed or urban categories, and the latter into seven disease categories (Methods). Taking all reported goods and services estimates, and avoiding the extrapolation of limited data, invasive insects cost a minimum of US$70.0 billion per year globally, while associated health costs exceed US$6.9 billion per year. Total costs rise as the number of estimates increases; therefore, the true costs of invasive insects to human society are substantially larger (but by a currently unquantifiable amount) than we report here. Further, future costs are likely to increase as invasive insects expand their ranges in response to climate change, as well as to increasing human movements and international trade. Results Goods and services We determined that invasive insects cost a minimum of US$70.0 billion per year globally for goods and services, of which US$25.2 billion per year comes from reproducible studies ( Fig. 2 and Supplementary Data 1 ). There was no temporal pattern in annual cost rates ( Supplementary Fig. 1 ), and most estimates were direct measures (although estimated costs were higher for extrapolated costs; see ‘Expenditure types and targets’ in the<|im_end|> <|im_start|>assistant Invasive insects cause at least 69 billion euros of damage per annum worldwide. Such is the estimation made by an international research team led by Franck Courchamp, CNRS research director at Laboratoire Ecologie, Systématique et Evolution (Université Paris-Sud/CNRS/AgroParisTech) and notably including entomologists from IRD Montpellier and a CNRS economist. Their study brought together the largest database ever developed on economic damage attributable to invasive insects worldwide. Covering damage to goods and services, health care costs and agricultural losses, this study, conducted with the support of ANR and the BNP Paribas Foundation, considered 737 articles, books and reports. This work was published in Nature Communications on 4 October 2016. Why study insects? For thousands of years, insects have been responsible for the spread of diseases in humans and livestock, and cause considerable damage on many levels: from attacks on crops and stocks, through the destruction of infrastructure, to the devastation of forests, altering and weakening ecosystems. In the living world, insects alone (about 2.5 million species) are probably the group responsible for the greatest expense. In addition, they are among the most aggressive invasive species: 87% of 2500 terrestrial invertebrates that have colonized new territories are insects. Underestimated damage The scientists estimated the minimum economic damage caused by invasive insects to be 69 billion euros per year. Of the insects studied, the Formosan termite (Coptotermes formosanus) is one of the most destructive, causing over 26.7 billion euros of damage per year in the world. However, according to the research group, this estimate is based on a study that was insufficiently documented. Studies that were more soundly based (considered reproducible by the scientists) also put the cabbage moth (Plutella xylostella), with a cost of 4.1 billion euros per year, in a high-ranking position, like the brown spruce longhorn beetle (Tetropium fuscum), which costs 4 billion euros in Canada alone. Cabbage moth (Plutella xylostella). Credit: Mike Pennington Furthermore, according to this study, North America suffers the largest financial losses, at 24.5 billion euros a year, while Europe is currently at only 3.2 billion euros per year. This difference, however, can be explained more by a lack of evaluation sources than by a difference in exposure to these dangers. Thus, according to the researchers, the total annual cost estimation of 69 billion euros is largely underevaluated. Many parts of the world do not offer enough economic data to produce an accurate estimate, which is therefore minimized. In addition, the research team focused on the study of the ten most costly invasive species, not counting the very large number that cause less damage. Finally, considering the estimated values of ecosystem services on a global scale (hundreds of billions of dollars for crop pollination alone), the disruption caused by invasive insects could reach a level far beyond the current estimate. Health and agriculture are the most affected Insects overall take a heavy toll on agriculture by consuming 40% of the harvest (enough to feed one billion people). As for health, the total cost attributable to invasive insects exceeds 6.1 billion euros per year (without counting malaria, Zika virus, or economic impacts on tourism or productivity, etc.). From a geographic point of view, the regions of the world where medical expenses related to invasive insects prove to be the greatest are Asia (2.55 billion euros a year), North America (1.85 billion euros per year) and the whole of Central and South America (1.66 billion euros a year). Among the diseases that have the greatest economic impact, we firstly find dengue fever, for which the costs account for 84% of the 6.1 billion euros. According to the authors, greater vigilance and the development of procedures to respond to biological invasions would save society tens of billions of euros. These preventive measures could divide the cost of diseases caused by mosquitoes by at least tenfold. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Metal halide perovskites are an important class of emerging semiconductors. Their charge carrier dynamics is poorly understood due to limited knowledge of defect physics and charge carrier recombination mechanisms. Nevertheless, classical ABC and Shockley-Read-Hall (SRH) models are ubiquitously applied to perovskites without considering their validity. Herein, an advanced technique mapping photoluminescence quantum yield (PLQY) as a function of both the excitation pulse energy and repetition frequency is developed and employed to examine the validity of these models. While ABC and SRH fail to explain the charge dynamics in a broad range of conditions, the addition of Auger recombination and trapping to the SRH model enables a quantitative fitting of PLQY maps and low-power PL decay kinetics, and extracting trap concentrations and efficacies. However, PL kinetics at high power are too fast and cannot be explained. The proposed PLQY mapping technique is ideal for a comprehensive testing of theories and applicable to any semiconductor. Introduction Semiconducting materials often exhibit complex charge dynamics, which strongly depends on the concentration of charge carriers due to the co-existence of both linear and non-linear charge recombination mechanisms 1 , 2 . The emergence of novel semiconductors like metal halide perovskites (MHPs), exhibiting intriguing and often unexpected electronic properties 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , triggered a renewed interest in revisiting the classical textbook theories of charge recombination and the development of more complete, accurate models 11 , 12 , 13 , 14 , 15 , 16 , 17 . Moreover, modern technical advances in experimental and computational capabilities 4 , 18 , 19 , 20 , 21 allow for a detailed quantitative comparison between experiment and theory, far beyond what was once possible. MHP are a novel solution-processable material class with enormous promise for application in a broad range of optoelectronic devices 22 , 23 , 24 . Driven in particular by their remarkable performance in photovoltaics, with power conversion efficiencies surpassing 25% demonstrated to date 25 , significant research efforts have been devoted to study the fundamental electronic properties of these materials 4 , 5 , 7 , 13 , 15 , 18 , 26 , 27 , 28 , 29 , 30 . It was established that for many MHP compositions—with the most notable example being the methylammonium lead triiodide (MA = CH 3 NH 3 + , also referred to as MAPbI 3 or MAPI)—they can be considered as classical crystalline semiconductors at room temperature, in which photoexcitation leads to the formation of charge carriers that exist independently from each other due to the low exciton binding energy 30 . Consequently, conventional models that describe the charge carrier dynamics are ubiquitously used to describe the dynamics of charge carriers in MHPs 11 , 13 , 14 , 15 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 . Historically, the first model describing the kinetics of charge carrier concentrations in a semiconductor was proposed by Shockley and Read 40 and independently by Hall 41 , and is known as the Shockley–Read–Hall (SRH) model. This model considers only the first-order process (trapping of electrons or holes) and the second-order kinetic processes (radiative electron–hole recombination and non-radiative (NR) recombination of the trapped electrons and free holes). It is noteworthy that the SRH model allows the concentrations of free charge carriers to differ due to the presence of trapping. In an intrinsic semiconductor, trapping of, for example, electrons generated by photoexcitation creates an excess of free holes at the valence band. This effect is often referred to as photodoping, in analogy with chemical doping, with the important difference, however, that the material becomes doped only under light irradiation and the degree of doping depends on the light irradiation intensity. Third-order processes, such as NR Auger recombination, via which two charge carriers recombine in the presence of a third charge that uptakes the released energy, have been recognized as particularly important at a high charge carrier concentration regime. To account for this process, Shen et al., instead of adding the Auger recombination term into the SRH model, proposed a simplified ABC model named after the coefficients A, B and C for the first-order (monomolecular), second-order (bi-molecular) and third-order Auger recombination, respectively 42 . These coefficients are also sometimes referred to as k 1 , k 2 and k 3 . Importantly, the concentrations of free electrons and holes in the ABC model are assumed to be equal, thus neglecting the possible influences of chemical and photodoping effects. The ABC model is widely applied in a broad range of semiconductors and in particular, is commonly used to rationalize properties and efficiency limits of LEDs 42 , 43 . The simplicity of the ABC model led to its extreme popularity also for MHPs (see e.g. ref. 15 and references therein) with fewer reports employing SRH or its modifications 13 , 14 , 16 , 17 , 31 , 36 , 39 , 44 , 45 . The ABC and SRH kinetic models are typically employed to describe experimentally acquired data such as the excitation power density dependence of photoluminescence (PL) quantum yield (PLQY) measured upon continuous wave (CW) or pulsed excitation, time-resolved PL decay kinetics and kinetics of the transient absorption signal. These models are applied to semi-quantitatively explain the experimental results and extract different rate constants 13 , 14 , 15 , 20 , 31 , 32 , 33 , 34 , 46 , 47 , often without necessarily considering the models’ limitations. Despite the very large number of published studies describing electronic processes in MHPs using the terminology of classical semiconductor physics, to the best of our knowledge, there have been only very few attempts to fit both PL decay and PLQY dependencies of excitation power using ABC/SRH-based models or at least compare the experimental data with theory 14 , 16 , 17 , 31 , 39 . These attempts, however, were of limited success because", "role": "user" }, { "content": "Metal halide perovskites have been under intense investigation over the last decade due to the remarkable rise in their performance in optoelectronic devices such as solar cells or light-emitting diodes. Despite tremendous progress in this field, many fundamental aspects of the photophysics of perovskite materials remain unknown, such as a detailed understanding of their defect physics and charge recombination mechanisms. These are typically studied by measuring the photoluminescence—i.e., the emission of light upon photoexcitation—of the material in both the steady-state and transient regimes. While such measurements are ubiquitous in literature, they do not capture the full range of the photophysical processes that occur in metal halide perovskites and thus represent only a partial picture of their charge carrier dynamics. Moreover, while several theories are commonly applied to interpret these results, their validity and limitations have not been explored, raising concerns regarding the insights they offer. To tackle this challenging question, a trinational team of researchers from Lund University (Sweden), the Russian Academy of Science (Russia) and the Technical University of Dresden (Germany) have developed a new methodology for the study of lead halide perovskites. This methodology is based on the complete mapping of the photoluminescence quantum yield and decay dynamics in the two-dimensional (2D) space of both fluence and frequency of the excitation light pulse. Such 2D maps not only offer a complete representation of the sample's photophysics, but also allow to examine the validity of theories, by applying a single set of theoretical equations and parameters to the entire data set. \"Mapping a perovskite film using our new method is like taking its fingerprints—it provides us with a great deal of information about each individual sample.\" says Prof. Ivan Scheblykin, a Professor of Chemical Physics at Lund University. \"Interestingly, each map resembles the shape of a horse's neck and mane, leading us to fondly refer to them as 'perovskite horses,\" which are all unique in their own way.\" \"The wealth of information contained in each 2D map allows us to explore different possible theories that may explain the complex behavior of charge carriers in metal halide perovskites\" adds Dr. Pavel Frantsuzov from the Siberian Brunch of the Russian Academy of Science. Indeed, the researchers discovered that the two most commonly applied theories (the so called \"ABC theory' and the Shockley-Read-Hall theory) cannot explain the 2D maps across the entire range of excitation parameters. They propose a more advanced theory that includes additional nonlinear processes to explain the photophysics of metal halide perovskites. The diagram depicts a typical 2D photoluminescence map that resembles the shape of a horse's neck and mane. Credit: I. Scheblykin / Y. Vaynzof. The researchers show that their method has important implications for the development of more efficient perovskite solar cells. Prof. Dr. Yana Vaynzof, Chair for Emerging Electronic Technologies at the Institute for Applied Physics and Photonic Materials and the Center for Advancing Electronics Dresden (cfaed) explains: \"By applying the new methodology to perovskite samples with modified interfaces, we were able to quantify their influence on the charge carrier dynamics in the perovskite layer by changing, for example, the density and efficacy of traps. This will allow us to develop interfacial modification procedures that will lead to optimal properties and more efficient photovoltaic devices.\" Importantly, the new method is not limited to the study of metal halide perovskites and can be applied to any semiconducting material. \"The versatility of our method and the ease with which we can apply it to new material systems is very exciting! We anticipate many new discoveries of fascinating photophysics in novel semiconductors.\" adds Prof. Scheblykin. The work was now published in Nature Communications. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Metal halide perovskites are an important class of emerging semiconductors. Their charge carrier dynamics is poorly understood due to limited knowledge of defect physics and charge carrier recombination mechanisms. Nevertheless, classical ABC and Shockley-Read-Hall (SRH) models are ubiquitously applied to perovskites without considering their validity. Herein, an advanced technique mapping photoluminescence quantum yield (PLQY) as a function of both the excitation pulse energy and repetition frequency is developed and employed to examine the validity of these models. While ABC and SRH fail to explain the charge dynamics in a broad range of conditions, the addition of Auger recombination and trapping to the SRH model enables a quantitative fitting of PLQY maps and low-power PL decay kinetics, and extracting trap concentrations and efficacies. However, PL kinetics at high power are too fast and cannot be explained. The proposed PLQY mapping technique is ideal for a comprehensive testing of theories and applicable to any semiconductor. Introduction Semiconducting materials often exhibit complex charge dynamics, which strongly depends on the concentration of charge carriers due to the co-existence of both linear and non-linear charge recombination mechanisms 1 , 2 . The emergence of novel semiconductors like metal halide perovskites (MHPs), exhibiting intriguing and often unexpected electronic properties 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , triggered a renewed interest in revisiting the classical textbook theories of charge recombination and the development of more complete, accurate models 11 , 12 , 13 , 14 , 15 , 16 , 17 . Moreover, modern technical advances in experimental and computational capabilities 4 , 18 , 19 , 20 , 21 allow for a detailed quantitative comparison between experiment and theory, far beyond what was once possible. MHP are a novel solution-processable material class with enormous promise for application in a broad range of optoelectronic devices 22 , 23 , 24 . Driven in particular by their remarkable performance in photovoltaics, with power conversion efficiencies surpassing 25% demonstrated to date 25 , significant research efforts have been devoted to study the fundamental electronic properties of these materials 4 , 5 , 7 , 13 , 15 , 18 , 26 , 27 , 28 , 29 , 30 . It was established that for many MHP compositions—with the most notable example being the methylammonium lead triiodide (MA = CH 3 NH 3 + , also referred to as MAPbI 3 or MAPI)—they can be considered as classical crystalline semiconductors at room temperature, in which photoexcitation leads to the formation of charge carriers that exist independently from each other due to the low exciton binding energy 30 . Consequently, conventional models that describe the charge carrier dynamics are ubiquitously used to describe the dynamics of charge carriers in MHPs 11 , 13 , 14 , 15 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 . Historically, the first model describing the kinetics of charge carrier concentrations in a semiconductor was proposed by Shockley and Read 40 and independently by Hall 41 , and is known as the Shockley–Read–Hall (SRH) model. This model considers only the first-order process (trapping of electrons or holes) and the second-order kinetic processes (radiative electron–hole recombination and non-radiative (NR) recombination of the trapped electrons and free holes). It is noteworthy that the SRH model allows the concentrations of free charge carriers to differ due to the presence of trapping. In an intrinsic semiconductor, trapping of, for example, electrons generated by photoexcitation creates an excess of free holes at the valence band. This effect is often referred to as photodoping, in analogy with chemical doping, with the important difference, however, that the material becomes doped only under light irradiation and the degree of doping depends on the light irradiation intensity. Third-order processes, such as NR Auger recombination, via which two charge carriers recombine in the presence of a third charge that uptakes the released energy, have been recognized as particularly important at a high charge carrier concentration regime. To account for this process, Shen et al., instead of adding the Auger recombination term into the SRH model, proposed a simplified ABC model named after the coefficients A, B and C for the first-order (monomolecular), second-order (bi-molecular) and third-order Auger recombination, respectively 42 . These coefficients are also sometimes referred to as k 1 , k 2 and k 3 . Importantly, the concentrations of free electrons and holes in the ABC model are assumed to be equal, thus neglecting the possible influences of chemical and photodoping effects. The ABC model is widely applied in a broad range of semiconductors and in particular, is commonly used to rationalize properties and efficiency limits of LEDs 42 , 43 . The simplicity of the ABC model led to its extreme popularity also for MHPs (see e.g. ref. 15 and references therein) with fewer reports employing SRH or its modifications 13 , 14 , 16 , 17 , 31 , 36 , 39 , 44 , 45 . The ABC and SRH kinetic models are typically employed to describe experimentally acquired data such as the excitation power density dependence of photoluminescence (PL) quantum yield (PLQY) measured upon continuous wave (CW) or pulsed excitation, time-resolved PL decay kinetics and kinetics of the transient absorption signal. These models are applied to semi-quantitatively explain the experimental results and extract different rate constants 13 , 14 , 15 , 20 , 31 , 32 , 33 , 34 , 46 , 47 , often without necessarily considering the models’ limitations. Despite the very large number of published studies describing electronic processes in MHPs using the terminology of classical semiconductor physics, to the best of our knowledge, there have been only very few attempts to fit both PL decay and PLQY dependencies of excitation power using ABC/SRH-based models or at least compare the experimental data with theory 14 , 16 , 17 , 31 , 39 . These attempts, however, were of limited success because<|im_end|> <|im_start|>assistant Metal halide perovskites have been under intense investigation over the last decade due to the remarkable rise in their performance in optoelectronic devices such as solar cells or light-emitting diodes. Despite tremendous progress in this field, many fundamental aspects of the photophysics of perovskite materials remain unknown, such as a detailed understanding of their defect physics and charge recombination mechanisms. These are typically studied by measuring the photoluminescence—i.e., the emission of light upon photoexcitation—of the material in both the steady-state and transient regimes. While such measurements are ubiquitous in literature, they do not capture the full range of the photophysical processes that occur in metal halide perovskites and thus represent only a partial picture of their charge carrier dynamics. Moreover, while several theories are commonly applied to interpret these results, their validity and limitations have not been explored, raising concerns regarding the insights they offer. To tackle this challenging question, a trinational team of researchers from Lund University (Sweden), the Russian Academy of Science (Russia) and the Technical University of Dresden (Germany) have developed a new methodology for the study of lead halide perovskites. This methodology is based on the complete mapping of the photoluminescence quantum yield and decay dynamics in the two-dimensional (2D) space of both fluence and frequency of the excitation light pulse. Such 2D maps not only offer a complete representation of the sample's photophysics, but also allow to examine the validity of theories, by applying a single set of theoretical equations and parameters to the entire data set. "Mapping a perovskite film using our new method is like taking its fingerprints—it provides us with a great deal of information about each individual sample." says Prof. Ivan Scheblykin, a Professor of Chemical Physics at Lund University. "Interestingly, each map resembles the shape of a horse's neck and mane, leading us to fondly refer to them as 'perovskite horses," which are all unique in their own way." "The wealth of information contained in each 2D map allows us to explore different possible theories that may explain the complex behavior of charge carriers in metal halide perovskites" adds Dr. Pavel Frantsuzov from the Siberian Brunch of the Russian Academy of Science. Indeed, the researchers discovered that the two most commonly applied theories (the so called "ABC theory' and the Shockley-Read-Hall theory) cannot explain the 2D maps across the entire range of excitation parameters. They propose a more advanced theory that includes additional nonlinear processes to explain the photophysics of metal halide perovskites. The diagram depicts a typical 2D photoluminescence map that resembles the shape of a horse's neck and mane. Credit: I. Scheblykin / Y. Vaynzof. The researchers show that their method has important implications for the development of more efficient perovskite solar cells. Prof. Dr. Yana Vaynzof, Chair for Emerging Electronic Technologies at the Institute for Applied Physics and Photonic Materials and the Center for Advancing Electronics Dresden (cfaed) explains: "By applying the new methodology to perovskite samples with modified interfaces, we were able to quantify their influence on the charge carrier dynamics in the perovskite layer by changing, for example, the density and efficacy of traps. This will allow us to develop interfacial modification procedures that will lead to optimal properties and more efficient photovoltaic devices." Importantly, the new method is not limited to the study of metal halide perovskites and can be applied to any semiconducting material. "The versatility of our method and the ease with which we can apply it to new material systems is very exciting! We anticipate many new discoveries of fascinating photophysics in novel semiconductors." adds Prof. Scheblykin. The work was now published in Nature Communications. <|im_end|>

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28415, 520, 69281, 3907, 13, 330, 82990, 11, 1855, 2472, 53291, 279, 6211, 315, 264, 15580, 596, 13272, 323, 53460, 11, 6522, 603, 311, 21901, 398, 8464, 311, 1124, 439, 364, 716, 869, 4991, 635, 27928, 1359, 902, 527, 682, 5016, 304, 872, 1866, 1648, 1210, 330, 791, 12205, 315, 2038, 13282, 304, 1855, 220, 17, 35, 2472, 6276, 603, 311, 13488, 2204, 3284, 26018, 430, 1253, 10552, 279, 6485, 7865, 315, 6900, 35991, 304, 9501, 15104, 579, 824, 869, 4991, 3695, 1, 11621, 2999, 13, 79369, 2939, 1821, 5308, 869, 505, 279, 68600, 1122, 3320, 3265, 315, 279, 8690, 16192, 315, 10170, 13, 23150, 11, 279, 12074, 11352, 430, 279, 1403, 1455, 17037, 9435, 26018, 320, 1820, 779, 2663, 330, 26484, 10334, 6, 323, 279, 48083, 3258, 12, 4518, 11529, 543, 10334, 8, 4250, 10552, 279, 220, 17, 35, 14370, 4028, 279, 4553, 2134, 315, 3521, 7709, 5137, 13, 2435, 30714, 264, 810, 11084, 10334, 430, 5764, 5217, 75098, 11618, 311, 10552, 279, 4604, 5237, 17688, 315, 9501, 15104, 579, 824, 869, 4991, 3695, 13, 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13516, 18007, 11, 279, 502, 1749, 374, 539, 7347, 311, 279, 4007, 315, 9501, 15104, 579, 824, 869, 4991, 3695, 323, 649, 387, 9435, 311, 904, 5347, 1965, 1076, 287, 3769, 13, 330, 791, 60112, 315, 1057, 1749, 323, 279, 14553, 449, 902, 584, 649, 3881, 433, 311, 502, 3769, 6067, 374, 1633, 13548, 0, 1226, 48248, 1690, 502, 54098, 315, 27387, 4604, 5237, 17688, 304, 11775, 5347, 1965, 1076, 1105, 1210, 11621, 8626, 13, 54772, 65, 398, 8148, 13, 578, 990, 574, 1457, 4756, 304, 22037, 26545, 13, 220, 128257, 198 ]

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract DOI Classify Address Funds Advanced Search ngRepeat: newsColumn in topMenus ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' Journal Information ngIf: newsColumn.subColumns.length > 0 ngIf: newsColumn.abbreviation == 'journals' ngIf: newsColumn.subColumns.length > 0 end ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' end ngRepeat: newsColumn in topMenus ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' For Authors ngIf: newsColumn.subColumns.length > 0 ngIf: newsColumn.abbreviation == 'journals' ngIf: newsColumn.subColumns.length > 0 end ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' end ngRepeat: newsColumn in topMenus ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' end ngRepeat: newsColumn in topMenus ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' For Referees ngIf: newsColumn.subColumns.length > 0 ngIf: newsColumn.abbreviation == 'journals' ngIf: newsColumn.subColumns.length > 0 end ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' end ngRepeat: newsColumn in topMenus E-mail Alert RSS 手机菜单 Opto-Electronic Advances <img src=\"/style/web/images/logo-new_03.png\" alt=\"\"> Advanced Search ngRepeat: newsColumn in topMenus ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' Journal Information <ol class=\"data-show i-menu-journals\" ng-if=\"newsColumn.abbreviation == 'journals'\"></ol> <ol class=\"data-show\" ng-controller=\"j-content-journals\" ng-if=\"newsColumn.abbreviation == 'journals'\"> <li ng-repeat=\"journal in journalTypes\" > <a ng-if=\"journal.linkedWebsite != null && journal.linkedWebsite !=''\" href=\"{{journal.linkedWebsite}}\" target=\"_blank\"> {{journal.titleEn}} </a> <a ng-if=\"journal.dblLanguage != 1 && journal.language == 'cn' && (journal.linkedWebsite == null || journal.linkedWebsite =='')\" href=\" {{journal.titleEn}} </a> <a ng-if=\"journal.dblLanguage != 1 && journal.language == 'en' && (journal.linkedWebsite == null || journal.linkedWebsite =='')\" href=\" {{journal.titleEn}} </a> <a ng-if=\"journal.dblLanguage == 1 && (journal.linkedWebsite == null || journal.linkedWebsite =='')\" href=\"/{{journal.publisherId}}\"> {{journal.titleEn}} </a> </li> </ol> ngIf: newsColumn.subColumns.length > 0 end ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' end ngRepeat: newsColumn in topMenus ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' For Authors <ol class=\"data-show i-menu-journals\" ng-if=\"newsColumn.abbreviation == 'journals'\"></ol> <ol class=\"data-show\" ng-controller=\"j-content-journals\" ng-if=\"newsColumn.abbreviation == 'journals'\"> <li ng-repeat=\"journal in journalTypes\" > <a ng-if=\"journal.linkedWebsite != null && journal.linkedWebsite !=''\" href=\"{{journal.linkedWebsite}}\" target=\"_blank\"> {{journal.titleEn}} </a> <a ng-if=\"journal.dblLanguage != 1 && journal.language == 'cn' && (journal.linkedWebsite == null || journal.linkedWebsite =='')\" href=\" {{journal.titleEn}} </a> <a ng-if=\"journal.dblLanguage != 1 && journal.language == 'en' && (journal.linkedWebsite == null || journal.linkedWebsite =='')\" href=\" {{journal.titleEn}} </a> <a ng-if=\"journal.dblLanguage == 1 && (journal.linkedWebsite == null || journal.linkedWebsite =='')\" href=\"/{{journal.publisherId}}\"> {{journal.titleEn}} </a> </li> </ol> ngIf: newsColumn.subColumns.length > 0 end ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' end ngRepeat: newsColumn in topMenus ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' end ngRepeat: newsColumn in topMenus ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' For Referees <ol class=\"data-show i-menu-journals\" ng-if=\"newsColumn.abbreviation == 'journals'\"></ol> <ol class=\"data-show\" ng-controller=\"j-content-journals\" ng-if=\"newsColumn.abbreviation == 'journals'\"> <li ng-repeat=\"journal in journalTypes\" > <a ng-if=\"journal.linkedWebsite != null && journal.linkedWebsite !=''\" href=\"{{journal.linkedWebsite}}\" target=\"_blank\"> {{journal.titleEn}} </a> <a ng-if=\"journal.dblLanguage != 1 && journal.language == 'cn' && (journal.linkedWebsite == null || journal.linkedWebsite =='')\" href=\" {{journal.titleEn}} </a> <a ng-if=\"journal.dblLanguage != 1 && journal.language == 'en' && (journal.linkedWebsite == null || journal.linkedWebsite =='')\" href=\" {{journal.titleEn}} </a> <a ng-if=\"journal.dblLanguage == 1 && (journal.linkedWebsite == null || journal.linkedWebsite =='')\" href=\"/{{journal.publisherId}}\"> {{journal.titleEn}} </a> </li> </ol> ngIf: newsColumn.subColumns.length > 0 end ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' end ngRepeat: newsColumn in topMenus Home 头部结束底部暂时渲染在这电脑端开始 Previous Article Next Article PDF Cite Share facebook twitter google LinkedIn weibo wechat Share the QR code with wechat scanning code to friends and circle of friends. All Title Author Keyword Abstract DOI Category Address Fund Article navigation > Opto-Electronic Advances > 2023 Vol. 6 > No. 4 > 220034 Next Article Previous Article Pei JJ, Liu X, del Águila AG, Bao D, Liu S et al. Switching of K-Q intervalley trions fine structure and their dynamics in n-doped monolayer WS2. Opto-Electron Adv 6, 220034 (2023). doi: 10.29026/oea.2023.220034 Citation: Pei JJ, Liu X, del Águila AG, Bao D, Liu S et al. Switching of K-Q intervalley trions fine structure and their dynamics in n-doped monolayer WS 2 . Opto-Electron Adv 6 , 220034 (2023). doi: 10.29026/oea.2023.220034 Article Open Access Switching of K-Q intervalley trions fine structure and their dynamics in n-doped monolayer WS 2 Jiajie Pei 1,2 , Xue Liu 3 , Andrés Granados del Águila 3 , Di Bao 3 , Sheng Liu 3 , Mohamed-Raouf Amara 3 , Weijie Zhao 3 , Feng Zhang 1 , Congya You 4 , Yongzhe Zhang 4 , Kenji Watanabe 5 , Takashi Taniguchi 5 , Han Zhang 1 , , , Qihua Xiong 6 , , 英文作者地址 1. Collaborative Innovation Center for Optoelectronic Science and Technology, International Collaborative Laboratory of 2D Materials for Optoelectronic Science and Technology of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China 2. College of Materials Science and Engineering, Fuzhou University, Fuzhou 350108, China 3. Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore 4. College of Materials Science and Engineering, Beijing University of Technology, Beijing 100124, China 5. Research Center for Functional Materials, International Center for Materials Nanoarchitectonics, National Institute for Materials Science, Tsukuba, Ibaraki 305-0044, Japan 6. State Key Laboratory of Low Dimensional Quantum Physics and Department of Physics, Tsinghua University, Beijing 100084, China More Information 作者简介和通讯作者 Corresponding authors: H Zhang, E-mail: [email protected] ; QH Xiong, E-mail: [email protected] <li class=\"com-author-info\"> </li> 稿件日期和基金项目11 稿件日期 Received Date 12 February 2022 Accepted Date 11 May 2022 Available Online 28 October 2022 Published Date 28 April 2023 摘要 Abstract Abstract Monolayer group VI transition metal dichalcogenides (TMDs) have recently emerged as promising candidates for photonic and opto-valleytronic applications. The optoelectronic properties of these atomically-thin semiconducting crystals are strongly governed by the tightly bound electron-hole pairs such as excitons and trions (charged excitons). The anomalous spin and valley configurations at the conduction band edges in monolayer WS 2 give rise to even more fascinating valley many-body complexes. Here we find that the indirect Q valley in the first Brillouin zone of monolayer WS 2 plays a critical role in the formation of a new excitonic state, which has not been well studied. By employing a high-quality h-BN encapsulated WS 2 field-effect transistor, we are able to switch the electron concentration within K-Q valleys at conduction band edges. Consequently, a distinct emission feature could be excited at the high electron doping region. Such feature has a competing population with the K valley trion, and experiences nonlinear power-law response and", "role": "user" }, { "content": "Drawing on the research idea of electron spin degree of freedom, the valley degree of freedom can be used as an information carrier to design and realize related functional devices. Monolayer group VI transition metal dichalcogenides (TMDs) have recently emerged as promising candidates for photonic and opto-valleytronic applications due to their excellent photoelectric properties and peculiar energy valley structure. On the other hand, the optoelectronic properties of these atomically-thin semiconducting crystals are strongly governed by the tightly bound electron-hole pairs such as excitons and trions (charged excitons) as a result of the enhanced Coulomb interactions in the 2D limit. The anomalous spin and valley configurations at the conduction band edges in monolayer WS2 give rise to even more fascinating valley many-body complexes. The coupling of charges, spins, energy valleys, and many-body complex quasiparticles offers opportunities to manipulate quantum information by an optical method. Among them, the control of these many-body complexes by regulating the valley charge by external fields is an effective means to realize the development of novel quantum devices, which is expected to be applied in the fields of quantum computing and quantum communication. The authors of an article now published in Opto-Electronic Advances found that the indirect Q valley in the first Brillouin zone of monolayer WS2 plays a critical role in the formation of a new excitonic state. By employing a high-quality h-BN encapsulated WS2 field-effect transistor, it is able to switch the electron concentration within K-Q valleys at conduction band edges. Consequently, a distinct emission feature could be excited at the high electron doping region. This feature is competitive with the traditional K-valley trions and obeys the Boltzmann distribution law. Further studies have proved that this feature is from the luminescence of the indirect Q-valley trions. Such a feature differs from the previously reported trion-exciton complex (XX-), which only appeared at the very low doping region of the sample, although they have very close energies. It is found that the actual doping level of the sample has a significant impact on the power-law response of this emission feature. With increasing Fermi level, the scattering of electrons to the Q valley becomes more efficient facilitating the formation of such a charged state. Consequently, it is able to tune its power-law response from linear (α~0.95) to superlinear (α~1.42), and radiative lifetime τ2 from 880 ps to 250 ps efficiently by gate modulation. The study suggests that the indirect Q valley has a significant impact on the relaxation pathways of exciton complexes when its energy level is lower or close to that of the direct K valley, which provides a new perspective for understanding the material. The authors also note that the Q valley at the first Brillouin zone results from the strong hybridization of p- and d-orbitals between the chalcogen atom X and the transition metal atom M, which makes these valleys highly sensitive to the environmental stimulus, such as the strain, doping, magnetic field, dielectric field, etc. The strong Q-K valley interaction suggests that such states are good candidates for tuning the spin/valley entanglement in these materials and their heterostructures. These findings open up a new avenue for the study of valley many-body physics and quantum optics in semiconducting 2D materials, as well as provide a promising way of valley manipulation for next-generation entangled photonic devices. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract DOI Classify Address Funds Advanced Search ngRepeat: newsColumn in topMenus ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' Journal Information ngIf: newsColumn.subColumns.length > 0 ngIf: newsColumn.abbreviation == 'journals' ngIf: newsColumn.subColumns.length > 0 end ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' end ngRepeat: newsColumn in topMenus ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' For Authors ngIf: newsColumn.subColumns.length > 0 ngIf: newsColumn.abbreviation == 'journals' ngIf: newsColumn.subColumns.length > 0 end ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' end ngRepeat: newsColumn in topMenus ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' end ngRepeat: newsColumn in topMenus ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' For Referees ngIf: newsColumn.subColumns.length > 0 ngIf: newsColumn.abbreviation == 'journals' ngIf: newsColumn.subColumns.length > 0 end ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' end ngRepeat: newsColumn in topMenus E-mail Alert RSS 手机菜单 Opto-Electronic Advances <img src="/style/web/images/logo-new_03.png" alt=""> Advanced Search ngRepeat: newsColumn in topMenus ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' Journal Information <ol class="data-show i-menu-journals" ng-if="newsColumn.abbreviation == 'journals'"></ol> <ol class="data-show" ng-controller="j-content-journals" ng-if="newsColumn.abbreviation == 'journals'"> <li ng-repeat="journal in journalTypes" > <a ng-if="journal.linkedWebsite != null && journal.linkedWebsite !=''" href="{{journal.linkedWebsite}}" target="_blank"> {{journal.titleEn}} </a> <a ng-if="journal.dblLanguage != 1 && journal.language == 'cn' && (journal.linkedWebsite == null || journal.linkedWebsite =='')" href=" {{journal.titleEn}} </a> <a ng-if="journal.dblLanguage != 1 && journal.language == 'en' && (journal.linkedWebsite == null || journal.linkedWebsite =='')" href=" {{journal.titleEn}} </a> <a ng-if="journal.dblLanguage == 1 && (journal.linkedWebsite == null || journal.linkedWebsite =='')" href="/{{journal.publisherId}}"> {{journal.titleEn}} </a> </li> </ol> ngIf: newsColumn.subColumns.length > 0 end ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' end ngRepeat: newsColumn in topMenus ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' For Authors <ol class="data-show i-menu-journals" ng-if="newsColumn.abbreviation == 'journals'"></ol> <ol class="data-show" ng-controller="j-content-journals" ng-if="newsColumn.abbreviation == 'journals'"> <li ng-repeat="journal in journalTypes" > <a ng-if="journal.linkedWebsite != null && journal.linkedWebsite !=''" href="{{journal.linkedWebsite}}" target="_blank"> {{journal.titleEn}} </a> <a ng-if="journal.dblLanguage != 1 && journal.language == 'cn' && (journal.linkedWebsite == null || journal.linkedWebsite =='')" href=" {{journal.titleEn}} </a> <a ng-if="journal.dblLanguage != 1 && journal.language == 'en' && (journal.linkedWebsite == null || journal.linkedWebsite =='')" href=" {{journal.titleEn}} </a> <a ng-if="journal.dblLanguage == 1 && (journal.linkedWebsite == null || journal.linkedWebsite =='')" href="/{{journal.publisherId}}"> {{journal.titleEn}} </a> </li> </ol> ngIf: newsColumn.subColumns.length > 0 end ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' end ngRepeat: newsColumn in topMenus ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' end ngRepeat: newsColumn in topMenus ngIf: 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newsColumn.subColumns.length > 0 end ngIf: newsColumn.columnNewsShowLocation == '1' && newsColumn.abbreviation !='journals' end ngRepeat: newsColumn in topMenus Home 头部结束底部暂时渲染在这电脑端开始 Previous Article Next Article PDF Cite Share facebook twitter google LinkedIn weibo wechat Share the QR code with wechat scanning code to friends and circle of friends. All Title Author Keyword Abstract DOI Category Address Fund Article navigation > Opto-Electronic Advances > 2023 Vol. 6 > No. 4 > 220034 Next Article Previous Article Pei JJ, Liu X, del Águila AG, Bao D, Liu S et al. Switching of K-Q intervalley trions fine structure and their dynamics in n-doped monolayer WS2. Opto-Electron Adv 6, 220034 (2023). doi: 10.29026/oea.2023.220034 Citation: Pei JJ, Liu X, del Águila AG, Bao D, Liu S et al. Switching of K-Q intervalley trions fine structure and their dynamics in n-doped monolayer WS 2 . Opto-Electron Adv 6 , 220034 (2023). doi: 10.29026/oea.2023.220034 Article Open Access Switching of K-Q intervalley trions fine structure and their dynamics in n-doped monolayer WS 2 Jiajie Pei 1,2 , Xue Liu 3 , Andrés Granados del Águila 3 , Di Bao 3 , Sheng Liu 3 , Mohamed-Raouf Amara 3 , Weijie Zhao 3 , Feng Zhang 1 , Congya You 4 , Yongzhe Zhang 4 , Kenji Watanabe 5 , Takashi Taniguchi 5 , Han Zhang 1 , , , Qihua Xiong 6 , , 英文作者地址 1. Collaborative Innovation Center for Optoelectronic Science and Technology, International Collaborative Laboratory of 2D Materials for Optoelectronic Science and Technology of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China 2. College of Materials Science and Engineering, Fuzhou University, Fuzhou 350108, China 3. Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore 4. College of Materials Science and Engineering, Beijing University of Technology, Beijing 100124, China 5. Research Center for Functional Materials, International Center for Materials Nanoarchitectonics, National Institute for Materials Science, Tsukuba, Ibaraki 305-0044, Japan 6. State Key Laboratory of Low Dimensional Quantum Physics and Department of Physics, Tsinghua University, Beijing 100084, China More Information 作者简介和通讯作者 Corresponding authors: H Zhang, E-mail: [email protected] ; QH Xiong, E-mail: [email protected] <li class="com-author-info"> </li> 稿件日期和基金项目11 稿件日期 Received Date 12 February 2022 Accepted Date 11 May 2022 Available Online 28 October 2022 Published Date 28 April 2023 摘要 Abstract Abstract Monolayer group VI transition metal dichalcogenides (TMDs) have recently emerged as promising candidates for photonic and opto-valleytronic applications. The optoelectronic properties of these atomically-thin semiconducting crystals are strongly governed by the tightly bound electron-hole pairs such as excitons and trions (charged excitons). The anomalous spin and valley configurations at the conduction band edges in monolayer WS 2 give rise to even more fascinating valley many-body complexes. Here we find that the indirect Q valley in the first Brillouin zone of monolayer WS 2 plays a critical role in the formation of a new excitonic state, which has not been well studied. By employing a high-quality h-BN encapsulated WS 2 field-effect transistor, we are able to switch the electron concentration within K-Q valleys at conduction band edges. Consequently, a distinct emission feature could be excited at the high electron doping region. Such feature has a competing population with the K valley trion, and experiences nonlinear power-law response and<|im_end|> <|im_start|>assistant Drawing on the research idea of electron spin degree of freedom, the valley degree of freedom can be used as an information carrier to design and realize related functional devices. Monolayer group VI transition metal dichalcogenides (TMDs) have recently emerged as promising candidates for photonic and opto-valleytronic applications due to their excellent photoelectric properties and peculiar energy valley structure. On the other hand, the optoelectronic properties of these atomically-thin semiconducting crystals are strongly governed by the tightly bound electron-hole pairs such as excitons and trions (charged excitons) as a result of the enhanced Coulomb interactions in the 2D limit. The anomalous spin and valley configurations at the conduction band edges in monolayer WS2 give rise to even more fascinating valley many-body complexes. The coupling of charges, spins, energy valleys, and many-body complex quasiparticles offers opportunities to manipulate quantum information by an optical method. Among them, the control of these many-body complexes by regulating the valley charge by external fields is an effective means to realize the development of novel quantum devices, which is expected to be applied in the fields of quantum computing and quantum communication. The authors of an article now published in Opto-Electronic Advances found that the indirect Q valley in the first Brillouin zone of monolayer WS2 plays a critical role in the formation of a new excitonic state. By employing a high-quality h-BN encapsulated WS2 field-effect transistor, it is able to switch the electron concentration within K-Q valleys at conduction band edges. Consequently, a distinct emission feature could be excited at the high electron doping region. This feature is competitive with the traditional K-valley trions and obeys the Boltzmann distribution law. Further studies have proved that this feature is from the luminescence of the indirect Q-valley trions. Such a feature differs from the previously reported trion-exciton complex (XX-), which only appeared at the very low doping region of the sample, although they have very close energies. It is found that the actual doping level of the sample has a significant impact on the power-law response of this emission feature. With increasing Fermi level, the scattering of electrons to the Q valley becomes more efficient facilitating the formation of such a charged state. Consequently, it is able to tune its power-law response from linear (α~0.95) to superlinear (α~1.42), and radiative lifetime τ2 from 880 ps to 250 ps efficiently by gate modulation. The study suggests that the indirect Q valley has a significant impact on the relaxation pathways of exciton complexes when its energy level is lower or close to that of the direct K valley, which provides a new perspective for understanding the material. The authors also note that the Q valley at the first Brillouin zone results from the strong hybridization of p- and d-orbitals between the chalcogen atom X and the transition metal atom M, which makes these valleys highly sensitive to the environmental stimulus, such as the strain, doping, magnetic field, dielectric field, etc. The strong Q-K valley interaction suggests that such states are good candidates for tuning the spin/valley entanglement in these materials and their heterostructures. These findings open up a new avenue for the study of valley many-body physics and quantum optics in semiconducting 2D materials, as well as provide a promising way of valley manipulation for next-generation entangled photonic devices. <|im_end|>

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2,997

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Understanding the age structure and population dynamics of harvested species is crucial for sustainability, especially in fisheries. The Bigmouth Buffalo ( Ictiobus cyprinellus ) is a fish endemic to the Mississippi and Hudson Bay drainages. A valued food-fish for centuries, they are now a prized sportfish as night bowfishing has become a million-dollar industry in the past decade. All harvest is virtually unregulated and unstudied, and Bigmouth Buffalo are declining while little is known about their biology. Using thin-sectioned otoliths and bomb-radiocarbon dating, we find Bigmouth Buffalo can reach 112 years of age, more than quadrupling previous longevity estimates, making this the oldest known freshwater teleost (~12,000 species). We document numerous populations that are comprised largely (85–90%) of individuals over 80 years old, suggesting long-term recruitment failure since dam construction in the 1930s. Our findings indicate Bigmouth Buffalo require urgent attention, while other understudied fishes may be threatened by similar ecological neglect. Introduction The Bigmouth Buffalo ( Ictiobus cyprinellus ) is one of the largest freshwater fishes endemic to North America, reaching lengths exceeding 1.25 m and body masses >36 kg 1 . Indeed, it is the largest of all catostomids (Cypriniformes: Catostomidae). Bigmouth Buffalo are also unique as the only catostomid with a terminal mouth and planktivorous, filter-feeding tendencies. All other catostomids are benthivorous 2 . The life history of I. cyprinellus was described previously as fast-paced 2 , despite apparent conflicting evidence from two studies reporting failure of some mature females to spawn every year 2 , 3 . One study reported a maximum estimated age of 26 years 4 , but previous reports suggested a younger maximum age (10–20 years), and reproductive maturity occurring as early as the first year of growth 2 , 5 , 6 . This exclusively freshwater species inhabits shallow (<4 m) warm-water lakes and pond-like areas of rivers, and is tolerant of eutrophication and high turbidity 1 , 2 . Shallow habitats are not typically associated with a long lifespan 7 , 8 . Bigmouth Buffalo have been important to human cultures in North America. Several lake names in Minnesota use the word niigijiikaag , the Ojibwe (a regional Native American tribe) name for buffalofish (Klimah, C., Minnesota Department of Natural Resources Fisheries Biologist, 2018, personal communication). Other Minnesota lakes and one county were named Kandiyohi by the Dakota tribe, meaning “where the buffalofish come.” In addition, the city of Buffalo, MN is named after this species 9 . In 1804, Lewis and Clark harvested buffalofish in Nebraska 10 and they have been of commercial importance since the 1800s 11 , 12 . This fishery is valued in the 21st Century at over 1 million USD per year in the Upper Mississippi Basin alone 13 . Despite its value, Bigmouth Buffalo have become increasingly misunderstood over the past century as they became commonly categorized as a “rough fish.” This imprecise term is used in much of the USA to lump many endemic, traditionally nongame fishes, along with unwanted invasive fishes, for purposes of harvest regulation 14 . This pejorative designation has led to the misconception by the general public of Bigmouth Buffalo as an “invasive species” or “a carp,” encouraging its persecution as a sacrificial or unimportant species. Contrary to this treatment in the USA, Bigmouth Buffalo were given Special Concern status in the Hudson Bay drainage of Canada in 1989 by the Committee on the Status of Endangered Wildlife in Canada following documented population decline concomitant with increases in invasive Common Carp ( Cyprinus carpio ) 15 . Bigmouth Buffalo serve as a competitor to the invasive Bighead Carp ( Hypophthalmichthys nobilis ) and Silver Carp ( H. molitrix ) 5 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , as well as the invasive Common Carp 2 , 24 , thus these three invasive species pose threats in addition to overharvest. Hence there is a basis for considering Bigmouth Buffalo as an ecological asset, and reason for concern about declining populations of Bigmouth Buffalo that have been documented in the northern parts of their range, including Canada, Minnesota, and North Dakota 1 , 15 . Unfortunately, other North American catostomids may also warrant such concern, with 42 out of 76 species already classified as endangered, threatened, vulnerable, or extinct, according to a recent synthesis on the conservation status of this family 25 . Current harvest of Bigmouth Buffalo is largely unregulated. This is partly because Bigmouth Buffalo have long been unpopular with recreational anglers, as these pelagic filter-feeders rarely take a baited hook or lure and thus are seldom caught by hook-and-line. However, legislative changes in the past decade coincide with a sharp increase in the popularity of bowfishing 26 . Across the USA, bowfishing is now permitted at night; archers can shoot “rough fish” with a bow and arrow under powerful lights, despite little to no regulation or study of this new harvest method 27 . While Bigmouth Buffalo and several other endemic taxa have become prized catches for bowfishers 28 , angler harvest of Bigmouth Buffalo in the USA is currently unregulated in 19 of the 22 states to which they are endemic, where recreational anglers can harvest unlimited numbers. Exceptions include Missouri and Louisiana with established take limits, and in Pennsylvania where Bigmouth Buffalo are considered endangered and are illegal to possess 14 . Furthermore, commercial anglers face no limits on the total number of Bigmouth Buffalo harvested in any U.S. state except Pennsylvania, and fish size restrictions on commercial harvest exist only in Louisiana and Mississippi 14 . Given the largely unregulated harvest of this ecologically important and historically valued endemic fish, it is crucial to validate its life history characteristics. We use otoliths (earstones) to estimate demographic characteristics of I. cyprinellus collected from 12 populations in two major drainages in Minnesota, and annulus counts on thin-sectioned otoliths to estimate fish age. The validity of these age estimates is tested using bomb radiocarbon ( 14 C) dating,", "role": "user" }, { "content": "Research recently completed at North Dakota State University has proven that the Bigmouth Buffalo (Ictiobus cyprinellus), a fish native to North America, lives more than eight decades longer than previously thought. The study published in Communications Biology documents several individuals more than 100 years of age, with one at 112 years, which more than quadruples all previous age estimates for this species. In addition, many populations were documented to be 85-90% comprised of individuals more than 80 years old, suggesting unsuccessful reproduction since the 1930s. The Bigmouth Buffalo is now known as the longest-lived freshwater teleost (a group of approximately 12,000 species) and the oldest age-validated freshwater fish (a group of about 14,000 species). A research team led by Alec R. Lackmann, Ph.D., Department of Biological Sciences at NDSU, recently published their work about aging the fish (Lackmann, Andrews, Butler, Bielak-Lackmann, & Clark 2019. \"Bigmouth Buffalo Ictiobus cyprinellus sets freshwater teleost record as improved age analysis reveals centenarian longevity.\" Communications Biology). Methodology In order to determine the age of the fish, the team employed a relatively new approach utilizing thin-sectioned otoliths (stones from the inner ears of the fish) and carbon dating of a sequential set of microsamples from individual otoliths. Otoliths are present in the ear anatomy of most fish species and they grow continuously as a fish ages. Traditional methods of aging fish by counting rings on scales and fin rays (similar to the process of aging trees) placed a typical age for Bigmouth Buffalo at 5 to 20 years. One very small study of Bigmouth Buffalo in Oklahoma published in 1999 found a maximum age of 26 years via thin-sectioned otoliths. Lackmann et al. 2019 utilized bomb radiocarbon dating to validate their otolith readings of Bigmouth Buffalo from Minnesota. This radiocarbon dating method shows time-specific markers in living creatures that are a result of the bomb-produced radiocarbon from atmospheric thermonuclear testing in the 1950s and 1960s. Using this method, the team conclusively validated their otolith age readings of Bigmouth Buffalo. Nearly 400 fish were aged in the study with five exceeding 100 years and the oldest at 112 years of age. Nearly 200 fish were aged in their 80s or 90s. 90 year old male Bigmouth Buffalo showing orange pigmentation spots. Credit: Alec Lackmann Cultural impact Found in 22 states across the upper Midwest and into Canada, Bigmouth Buffalo have historically been a part of human culture. The Minnesota county and city name of Kandiyohi means \"where the buffalofish come;\" the city of Buffalo, MN is named after the fish; and Lewis and Clark harvested them during their famous journey. The fish has been a commercially valued product since the 1800s and a fishery in the upper Mississippi Basin places a value on their harvest at more than $1 million annually. Despite their historic commercial food importance, today Bigmouth Buffalo are often incorrectly grouped with other invasive species of \"rough fish\" such as the Bighead Carp, Silver Carp, and Common Carp. While superficially similar in appearance to those species, Bigmouth Buffalo actually serve an important ecological role by displacing and keeping these invasive species in check, and belong to an entirely different family. In addition, the filter-feeding Bigmouth Buffalo consume other invasive creatures such as larval stage Zebra Mussels (Lackmann et al. in preparation). Virtually unregulated harvest While Bigmouth Buffalo were given special concern status in the 1980s and their harvest remains regulated to this day in Canada, Bigmouth Buffalo harvest in the United States today is almost totally unregulated with no limits established in almost every state. Traditionally unpopular with anglers, the fish has rapidly become a premier (and easy) target for bowfishers given recent legal changes in the past 5-7 years that have allowed night bowfishing and an extended season that includes their vulnerable spawning period. \"We need to start recognizing Bigmouth Buffalo for the native, ecological asset that they are\", said Lackmann. \"Our neglect of under-appreciated, native species needs to be addressed immediately. For example, the term 'rough fish' should be eliminated from harvest regulation terminology because it promotes an inappropriate, negative image for the native species lumped together with real invasives. Our research has shown that the Bigmouth Buffalo is one of the longest-lived vertebrates. That alone is something worth preserving and understanding. Among freshwater fish, the Bigmouth Buffalo is quite exceptional, and they deserve some protection like many other native species in North America have already achieved. The Bigmouth Buffalo could be treasured one day.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Understanding the age structure and population dynamics of harvested species is crucial for sustainability, especially in fisheries. The Bigmouth Buffalo ( Ictiobus cyprinellus ) is a fish endemic to the Mississippi and Hudson Bay drainages. A valued food-fish for centuries, they are now a prized sportfish as night bowfishing has become a million-dollar industry in the past decade. All harvest is virtually unregulated and unstudied, and Bigmouth Buffalo are declining while little is known about their biology. Using thin-sectioned otoliths and bomb-radiocarbon dating, we find Bigmouth Buffalo can reach 112 years of age, more than quadrupling previous longevity estimates, making this the oldest known freshwater teleost (~12,000 species). We document numerous populations that are comprised largely (85–90%) of individuals over 80 years old, suggesting long-term recruitment failure since dam construction in the 1930s. Our findings indicate Bigmouth Buffalo require urgent attention, while other understudied fishes may be threatened by similar ecological neglect. Introduction The Bigmouth Buffalo ( Ictiobus cyprinellus ) is one of the largest freshwater fishes endemic to North America, reaching lengths exceeding 1.25 m and body masses >36 kg 1 . Indeed, it is the largest of all catostomids (Cypriniformes: Catostomidae). Bigmouth Buffalo are also unique as the only catostomid with a terminal mouth and planktivorous, filter-feeding tendencies. All other catostomids are benthivorous 2 . The life history of I. cyprinellus was described previously as fast-paced 2 , despite apparent conflicting evidence from two studies reporting failure of some mature females to spawn every year 2 , 3 . One study reported a maximum estimated age of 26 years 4 , but previous reports suggested a younger maximum age (10–20 years), and reproductive maturity occurring as early as the first year of growth 2 , 5 , 6 . This exclusively freshwater species inhabits shallow (<4 m) warm-water lakes and pond-like areas of rivers, and is tolerant of eutrophication and high turbidity 1 , 2 . Shallow habitats are not typically associated with a long lifespan 7 , 8 . Bigmouth Buffalo have been important to human cultures in North America. Several lake names in Minnesota use the word niigijiikaag , the Ojibwe (a regional Native American tribe) name for buffalofish (Klimah, C., Minnesota Department of Natural Resources Fisheries Biologist, 2018, personal communication). Other Minnesota lakes and one county were named Kandiyohi by the Dakota tribe, meaning “where the buffalofish come.” In addition, the city of Buffalo, MN is named after this species 9 . In 1804, Lewis and Clark harvested buffalofish in Nebraska 10 and they have been of commercial importance since the 1800s 11 , 12 . This fishery is valued in the 21st Century at over 1 million USD per year in the Upper Mississippi Basin alone 13 . Despite its value, Bigmouth Buffalo have become increasingly misunderstood over the past century as they became commonly categorized as a “rough fish.” This imprecise term is used in much of the USA to lump many endemic, traditionally nongame fishes, along with unwanted invasive fishes, for purposes of harvest regulation 14 . This pejorative designation has led to the misconception by the general public of Bigmouth Buffalo as an “invasive species” or “a carp,” encouraging its persecution as a sacrificial or unimportant species. Contrary to this treatment in the USA, Bigmouth Buffalo were given Special Concern status in the Hudson Bay drainage of Canada in 1989 by the Committee on the Status of Endangered Wildlife in Canada following documented population decline concomitant with increases in invasive Common Carp ( Cyprinus carpio ) 15 . Bigmouth Buffalo serve as a competitor to the invasive Bighead Carp ( Hypophthalmichthys nobilis ) and Silver Carp ( H. molitrix ) 5 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , as well as the invasive Common Carp 2 , 24 , thus these three invasive species pose threats in addition to overharvest. Hence there is a basis for considering Bigmouth Buffalo as an ecological asset, and reason for concern about declining populations of Bigmouth Buffalo that have been documented in the northern parts of their range, including Canada, Minnesota, and North Dakota 1 , 15 . Unfortunately, other North American catostomids may also warrant such concern, with 42 out of 76 species already classified as endangered, threatened, vulnerable, or extinct, according to a recent synthesis on the conservation status of this family 25 . Current harvest of Bigmouth Buffalo is largely unregulated. This is partly because Bigmouth Buffalo have long been unpopular with recreational anglers, as these pelagic filter-feeders rarely take a baited hook or lure and thus are seldom caught by hook-and-line. However, legislative changes in the past decade coincide with a sharp increase in the popularity of bowfishing 26 . Across the USA, bowfishing is now permitted at night; archers can shoot “rough fish” with a bow and arrow under powerful lights, despite little to no regulation or study of this new harvest method 27 . While Bigmouth Buffalo and several other endemic taxa have become prized catches for bowfishers 28 , angler harvest of Bigmouth Buffalo in the USA is currently unregulated in 19 of the 22 states to which they are endemic, where recreational anglers can harvest unlimited numbers. Exceptions include Missouri and Louisiana with established take limits, and in Pennsylvania where Bigmouth Buffalo are considered endangered and are illegal to possess 14 . Furthermore, commercial anglers face no limits on the total number of Bigmouth Buffalo harvested in any U.S. state except Pennsylvania, and fish size restrictions on commercial harvest exist only in Louisiana and Mississippi 14 . Given the largely unregulated harvest of this ecologically important and historically valued endemic fish, it is crucial to validate its life history characteristics. We use otoliths (earstones) to estimate demographic characteristics of I. cyprinellus collected from 12 populations in two major drainages in Minnesota, and annulus counts on thin-sectioned otoliths to estimate fish age. The validity of these age estimates is tested using bomb radiocarbon ( 14 C) dating,<|im_end|> <|im_start|>assistant Research recently completed at North Dakota State University has proven that the Bigmouth Buffalo (Ictiobus cyprinellus), a fish native to North America, lives more than eight decades longer than previously thought. The study published in Communications Biology documents several individuals more than 100 years of age, with one at 112 years, which more than quadruples all previous age estimates for this species. In addition, many populations were documented to be 85-90% comprised of individuals more than 80 years old, suggesting unsuccessful reproduction since the 1930s. The Bigmouth Buffalo is now known as the longest-lived freshwater teleost (a group of approximately 12,000 species) and the oldest age-validated freshwater fish (a group of about 14,000 species). A research team led by Alec R. Lackmann, Ph.D., Department of Biological Sciences at NDSU, recently published their work about aging the fish (Lackmann, Andrews, Butler, Bielak-Lackmann, & Clark 2019. "Bigmouth Buffalo Ictiobus cyprinellus sets freshwater teleost record as improved age analysis reveals centenarian longevity." Communications Biology). Methodology In order to determine the age of the fish, the team employed a relatively new approach utilizing thin-sectioned otoliths (stones from the inner ears of the fish) and carbon dating of a sequential set of microsamples from individual otoliths. Otoliths are present in the ear anatomy of most fish species and they grow continuously as a fish ages. Traditional methods of aging fish by counting rings on scales and fin rays (similar to the process of aging trees) placed a typical age for Bigmouth Buffalo at 5 to 20 years. One very small study of Bigmouth Buffalo in Oklahoma published in 1999 found a maximum age of 26 years via thin-sectioned otoliths. Lackmann et al. 2019 utilized bomb radiocarbon dating to validate their otolith readings of Bigmouth Buffalo from Minnesota. This radiocarbon dating method shows time-specific markers in living creatures that are a result of the bomb-produced radiocarbon from atmospheric thermonuclear testing in the 1950s and 1960s. Using this method, the team conclusively validated their otolith age readings of Bigmouth Buffalo. Nearly 400 fish were aged in the study with five exceeding 100 years and the oldest at 112 years of age. Nearly 200 fish were aged in their 80s or 90s. 90 year old male Bigmouth Buffalo showing orange pigmentation spots. Credit: Alec Lackmann Cultural impact Found in 22 states across the upper Midwest and into Canada, Bigmouth Buffalo have historically been a part of human culture. The Minnesota county and city name of Kandiyohi means "where the buffalofish come;" the city of Buffalo, MN is named after the fish; and Lewis and Clark harvested them during their famous journey. The fish has been a commercially valued product since the 1800s and a fishery in the upper Mississippi Basin places a value on their harvest at more than $1 million annually. Despite their historic commercial food importance, today Bigmouth Buffalo are often incorrectly grouped with other invasive species of "rough fish" such as the Bighead Carp, Silver Carp, and Common Carp. While superficially similar in appearance to those species, Bigmouth Buffalo actually serve an important ecological role by displacing and keeping these invasive species in check, and belong to an entirely different family. In addition, the filter-feeding Bigmouth Buffalo consume other invasive creatures such as larval stage Zebra Mussels (Lackmann et al. in preparation). Virtually unregulated harvest While Bigmouth Buffalo were given special concern status in the 1980s and their harvest remains regulated to this day in Canada, Bigmouth Buffalo harvest in the United States today is almost totally unregulated with no limits established in almost every state. Traditionally unpopular with anglers, the fish has rapidly become a premier (and easy) target for bowfishers given recent legal changes in the past 5-7 years that have allowed night bowfishing and an extended season that includes their vulnerable spawning period. "We need to start recognizing Bigmouth Buffalo for the native, ecological asset that they are", said Lackmann. "Our neglect of under-appreciated, native species needs to be addressed immediately. For example, the term 'rough fish' should be eliminated from harvest regulation terminology because it promotes an inappropriate, negative image for the native species lumped together with real invasives. Our research has shown that the Bigmouth Buffalo is one of the longest-lived vertebrates. That alone is something worth preserving and understanding. Among freshwater fish, the Bigmouth Buffalo is quite exceptional, and they deserve some protection like many other native species in North America have already achieved. The Bigmouth Buffalo could be treasured one day." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Itch triggers scratching, a behavioural defence mechanism that aids in the removal of harmful irritants and parasites 1 . Chemical itch is triggered by many endogenous and exogenous cues, such as pro-inflammatory histamine, which is released during an allergic reaction 1 . Mechanical itch can be triggered by light sensations such as wool fibres or a crawling insect 2 . In contrast to chemical itch pathways, which have been extensively studied, the mechanisms that underlie the transduction of mechanical itch are largely unknown. Here we show that the mechanically activated ion channel PIEZO1 (ref. 3 ) is selectively expressed by itch-specific sensory neurons and is required for their mechanically activated currents. Loss of PIEZO1 function in peripheral neurons greatly reduces mechanically evoked scratching behaviours and both acute and chronic itch-evoked sensitization. Finally, mice expressing a gain-of-function Piezo1 allele 4 exhibit enhanced mechanical itch behaviours. Our studies reveal the polymodal nature of itch sensory neurons and identify a role for PIEZO1 in the sensation of itch. Main Discrete subsets of somatosensory neurons within the dorsal root ganglion (DRG) and trigeminal ganglion selectively drive itch behaviours in mice 5 , 6 . These pruriceptors are thought to be chemosensory rather than mechanosensory and, as such, are selectively implicated in chemical itch 1 . Chemical pruriceptors are marked by the expression of the neuropeptide genes somatostatin ( Sst ) and natriuretic polypeptide precursor B ( Nppb ), or the MAS-related G-protein coupled receptor A3 ( Mrgpra3 ), along with other marker genes identified from single-cell RNA sequencing (RNA-seq) studies 7 , 8 , 9 . Previous work elucidated chemical itch transduction pathways in these neurons 5 , 10 , 11 , 12 , 13 . By contrast, the molecular and cellular basis of mechanical itch in the periphery is relatively unknown, although its circuitry is well described in the spinal cord. For example, mechanical itch can be triggered by the activation of Toll-like receptor 5-positive Aβ-low threshold mechanoreceptors (LTMRs) and the engagement of urocortin 3- and neuropeptide Y receptor 1-positive excitatory spinal pathways, and/or by the inhibition of spinal neuropeptide Y-positive inhibitory interneurons that receive LTMR input 14 , 15 , 16 . Furthermore, age-dependent loss of Merkel cell–neurite complexes enhances mechanical itch, presumably through the loss of LTMR-dependent inhibition of itch spinal circuitry 17 . The contributions of other somatosensory neurons, including chemical pruriceptors, to mechanical itch and itch sensitization are unknown. Itch neurons express functional PIEZO1 Early work on the expression of Piezo genes unequivocally demonstrated that Piezo2 transcript is present at high levels in somatosensory neurons and suggested that Piezo1 was expressed at only background levels 3 , 18 . In response to the publication of several single-cell RNA-seq datasets reporting low but detectable expression of Piezo1 transcript in mouse DRG neurons 7 , 8 , 19 (Extended Data Fig. 1 ), we revisited our previous experiments using single-molecule fluorescence in situ hybridization (smFISH) to more thoroughly characterize the expression of Piezo1 in sensory neurons. Notably, we observed that Piezo1 is expressed in 92% of Nppb + DRG neurons (Fig. 1a–f and Extended Data Fig. 2a–d ), and in non-neuronal cells that are likely to comprise vascular endothelium 20 . This specific expression pattern suggested that PIEZO1 has a role in itch. We also observed the expression of Piezo1 in a subset of MAS-related G-protein coupled receptor D ( Mrgprd + ) neurons (Extended Data Fig. 2a ), which have previously been implicated in mechanical pain and in chemical itch evoked by the compound β-alanine 21 , 22 ; however, we did not observe Piezo1 in the Mrgpra3 + chloroquine-sensitive chemical itch neurons (Fig. 1d–f and Extended Data Fig. 3a ). By contrast, Piezo2 was expressed in a smaller percentage of Nppb + neurons (Fig. 1d–f and Extended Data Fig. 3b ). Substantial differences have been identified between human and mouse DRG neurons 23 , 24 and the role—if any—of NPPB in human itch transmission is unknown. smFISH of sections from a human DRG revealed PIEZO1 transcript in 83.6% of NPPB + neurons (Fig. 1h and Extended Data Fig. 4a,b ), suggestive of a conserved pattern of expression. Using a mouse line that expresses a PIEZO1 tdTomato C-terminal fusion protein 25 , we observed robust expression of PIEZO1 tdTomato in platelet endothelial cell adhesion molecule 1 (PECAM1 + ) vascular endothelial cells of the DRG and trigeminal ganglion capillaries (as expected) 20 , as well as within a subset of neuronal cell bodies and nerve fibres, consistent with the expression of PIEZO1 protein in mouse somatosensory neurons (Fig. 1i–l and Extended Data Fig. 5a–c ). Fig. 1: PIEZO1 is expressed in mouse and human putative itch receptors. a – c , Representative images (five images from two mice) of sectioned mouse DRG smFISH for Piezo1 ( a ), Nppb ( b ) and merged with DAPI ( c ). White arrowheads indicate Piezo1 + or Nppb + cells. d , Quantification of mouse DRG smFISH images showing the percentage of cells expressing a given marker (bar labels) that were co-labelled with Piezo1 transcript. The number of analysed neurons is indicated above the bar (four to six images per marker from two mice). e , Data from d presented as the percentage of Piezo1 + neurons that co-express a given marker. f , Percentage of Nppb + neurons expressing Piezo1 or Piezo2 . g , Comparison of Piezo2 expression in Nppb + versus Mrgpra3 + neurons. h , Quantification of human smFISH images (seven to eight images per marker from one donor; see Extended Data Fig. 4a,b ). i – l , Representative images of sectioned mouse DRGs labelled with antibodies against tdTomato (images show PIEZO1 ( i ), PECAM1 ( j ), neurofilament H (NEFH; k ) and the merged image ( l )). Asterisks indicate blood vessels and arrowheads indicate a PIEZO1 + neuron and nerve fibre. The experiment was repeated one additional time. All images are presented as maximum intensity z -projections of confocal images. Scale bars,", "role": "user" }, { "content": "Scientists at Scripps Research Institute have identified a protein in sensory nerves that works as a key detector of itch—specifically the \"mechanical\" itch stimulus of crawling insects, wool fibers, or other irritating objects that touch the skin. The discovery, published June 22, 2022, in Nature, is the first identification of a sensor for mechanical itch rather than chemically-triggered itch. It could lead to better treatments for itch conditions such as eczema and psoriasis. \"These findings help us untangle the complexity of itch sensation, and suggest that PIEZO1 inhibitors could be very useful clinically,\" says study senior author Ardem Patapoutian, Ph.D., a professor in the Department of Neuroscience at Scripps Research, and a Howard Hughes Medical Institute investigator. Itch is a distinct sensation with its own nerve circuitry and evolutionary purpose—likely to alert organisms to potentially harmful chemicals, insects and parasites. Researchers over the past decade or so have identified itch-specific subsets of spinal neurons that extend nerve fibers into the skin and are sensitive to chemical triggers of itch such as the allergy mediator histamine. But so far, relatively little has been discovered about the circuitry of mechanical itch. PIEZO1's role in mechanical itch was unexpected. Patapoutian won a share of last year's Nobel Prize for Medicine or Physiology for his lab's pioneering research on PIEZO1 and its sister-protein PIEZO2. These unique, propeller-shaped \"mechanosensor\" ion channels are embedded in the outer membranes of many cell types. They become activated when mechanically distorted, opening their ion channels and triggering various downstream events. Since 2010, Patapoutian and colleagues have shown that PIEZO2 is a key mechanosensor for light touch, the feeling of the positioning of the body and limbs, and the urge to urinate—all via nerves in various tissues and organs. By contrast, the researchers have found that PIEZO1 has a variety of non-sensory roles throughout the body, for example in blood vessels and red blood cells. While their initial studies suggested that PIEZO1 was not expressed in sensory neurons, other recent investigations have suggested that it is expressed at low levels in some subsets of these neurons. In the new study, Patapoutian and his team, including study first author Rose Hill, Ph.D., a postdoctoral research associate, followed up on this surprising lead. In experiments in mice, they confirmed that PIEZO1 is expressed, and appears to be a functional, mechanical pressure-sensitive ion channel protein in two different types of sensory neuron that were already implicated in chemical itch. Mice with an overactive form of PIEZO1 were markedly more sensitive to itch sensations. By contrast, mice lacking PIEZO1 in their sensory neurons scratched themselves far less when stimulated on the skin with filaments that normally would trigger strong itch sensations. The researchers also showed that a PIEZO1-blocking compound alleviates scratching behaviors in mice with the equivalent of eczema. \"We did see a dramatic effect on itch with this compound, and though it wasn't specific enough against PIEZO1 to develop into a drug, we hope eventually to develop a much more PIEZO1-specific compound for treating itch conditions,\" Hill says. Curiously, the absence or enhancement of PIEZO1 activity in mice caused at least a small reduction or increase of scratching due to chemical itch triggers such as histamine—implying that mechanical and chemical itch signals are indeed transmitted in some cases by the same sensory neurons. The researchers are now investigating whether variants of the PIEZO1 gene in the human population are related to itch sensitivity. The Patapoutian lab published a paper in 2018 showing that a mildly overactive form of PIEZO1, which also has the effect of making red blood cells relatively resistant to malaria parasites, is present in about a third of people of African ancestry. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Itch triggers scratching, a behavioural defence mechanism that aids in the removal of harmful irritants and parasites 1 . Chemical itch is triggered by many endogenous and exogenous cues, such as pro-inflammatory histamine, which is released during an allergic reaction 1 . Mechanical itch can be triggered by light sensations such as wool fibres or a crawling insect 2 . In contrast to chemical itch pathways, which have been extensively studied, the mechanisms that underlie the transduction of mechanical itch are largely unknown. Here we show that the mechanically activated ion channel PIEZO1 (ref. 3 ) is selectively expressed by itch-specific sensory neurons and is required for their mechanically activated currents. Loss of PIEZO1 function in peripheral neurons greatly reduces mechanically evoked scratching behaviours and both acute and chronic itch-evoked sensitization. Finally, mice expressing a gain-of-function Piezo1 allele 4 exhibit enhanced mechanical itch behaviours. Our studies reveal the polymodal nature of itch sensory neurons and identify a role for PIEZO1 in the sensation of itch. Main Discrete subsets of somatosensory neurons within the dorsal root ganglion (DRG) and trigeminal ganglion selectively drive itch behaviours in mice 5 , 6 . These pruriceptors are thought to be chemosensory rather than mechanosensory and, as such, are selectively implicated in chemical itch 1 . Chemical pruriceptors are marked by the expression of the neuropeptide genes somatostatin ( Sst ) and natriuretic polypeptide precursor B ( Nppb ), or the MAS-related G-protein coupled receptor A3 ( Mrgpra3 ), along with other marker genes identified from single-cell RNA sequencing (RNA-seq) studies 7 , 8 , 9 . Previous work elucidated chemical itch transduction pathways in these neurons 5 , 10 , 11 , 12 , 13 . By contrast, the molecular and cellular basis of mechanical itch in the periphery is relatively unknown, although its circuitry is well described in the spinal cord. For example, mechanical itch can be triggered by the activation of Toll-like receptor 5-positive Aβ-low threshold mechanoreceptors (LTMRs) and the engagement of urocortin 3- and neuropeptide Y receptor 1-positive excitatory spinal pathways, and/or by the inhibition of spinal neuropeptide Y-positive inhibitory interneurons that receive LTMR input 14 , 15 , 16 . Furthermore, age-dependent loss of Merkel cell–neurite complexes enhances mechanical itch, presumably through the loss of LTMR-dependent inhibition of itch spinal circuitry 17 . The contributions of other somatosensory neurons, including chemical pruriceptors, to mechanical itch and itch sensitization are unknown. Itch neurons express functional PIEZO1 Early work on the expression of Piezo genes unequivocally demonstrated that Piezo2 transcript is present at high levels in somatosensory neurons and suggested that Piezo1 was expressed at only background levels 3 , 18 . In response to the publication of several single-cell RNA-seq datasets reporting low but detectable expression of Piezo1 transcript in mouse DRG neurons 7 , 8 , 19 (Extended Data Fig. 1 ), we revisited our previous experiments using single-molecule fluorescence in situ hybridization (smFISH) to more thoroughly characterize the expression of Piezo1 in sensory neurons. Notably, we observed that Piezo1 is expressed in 92% of Nppb + DRG neurons (Fig. 1a–f and Extended Data Fig. 2a–d ), and in non-neuronal cells that are likely to comprise vascular endothelium 20 . This specific expression pattern suggested that PIEZO1 has a role in itch. We also observed the expression of Piezo1 in a subset of MAS-related G-protein coupled receptor D ( Mrgprd + ) neurons (Extended Data Fig. 2a ), which have previously been implicated in mechanical pain and in chemical itch evoked by the compound β-alanine 21 , 22 ; however, we did not observe Piezo1 in the Mrgpra3 + chloroquine-sensitive chemical itch neurons (Fig. 1d–f and Extended Data Fig. 3a ). By contrast, Piezo2 was expressed in a smaller percentage of Nppb + neurons (Fig. 1d–f and Extended Data Fig. 3b ). Substantial differences have been identified between human and mouse DRG neurons 23 , 24 and the role—if any—of NPPB in human itch transmission is unknown. smFISH of sections from a human DRG revealed PIEZO1 transcript in 83.6% of NPPB + neurons (Fig. 1h and Extended Data Fig. 4a,b ), suggestive of a conserved pattern of expression. Using a mouse line that expresses a PIEZO1 tdTomato C-terminal fusion protein 25 , we observed robust expression of PIEZO1 tdTomato in platelet endothelial cell adhesion molecule 1 (PECAM1 + ) vascular endothelial cells of the DRG and trigeminal ganglion capillaries (as expected) 20 , as well as within a subset of neuronal cell bodies and nerve fibres, consistent with the expression of PIEZO1 protein in mouse somatosensory neurons (Fig. 1i–l and Extended Data Fig. 5a–c ). Fig. 1: PIEZO1 is expressed in mouse and human putative itch receptors. a – c , Representative images (five images from two mice) of sectioned mouse DRG smFISH for Piezo1 ( a ), Nppb ( b ) and merged with DAPI ( c ). White arrowheads indicate Piezo1 + or Nppb + cells. d , Quantification of mouse DRG smFISH images showing the percentage of cells expressing a given marker (bar labels) that were co-labelled with Piezo1 transcript. The number of analysed neurons is indicated above the bar (four to six images per marker from two mice). e , Data from d presented as the percentage of Piezo1 + neurons that co-express a given marker. f , Percentage of Nppb + neurons expressing Piezo1 or Piezo2 . g , Comparison of Piezo2 expression in Nppb + versus Mrgpra3 + neurons. h , Quantification of human smFISH images (seven to eight images per marker from one donor; see Extended Data Fig. 4a,b ). i – l , Representative images of sectioned mouse DRGs labelled with antibodies against tdTomato (images show PIEZO1 ( i ), PECAM1 ( j ), neurofilament H (NEFH; k ) and the merged image ( l )). Asterisks indicate blood vessels and arrowheads indicate a PIEZO1 + neuron and nerve fibre. The experiment was repeated one additional time. All images are presented as maximum intensity z -projections of confocal images. Scale bars,<|im_end|> <|im_start|>assistant Scientists at Scripps Research Institute have identified a protein in sensory nerves that works as a key detector of itch—specifically the "mechanical" itch stimulus of crawling insects, wool fibers, or other irritating objects that touch the skin. The discovery, published June 22, 2022, in Nature, is the first identification of a sensor for mechanical itch rather than chemically-triggered itch. It could lead to better treatments for itch conditions such as eczema and psoriasis. "These findings help us untangle the complexity of itch sensation, and suggest that PIEZO1 inhibitors could be very useful clinically," says study senior author Ardem Patapoutian, Ph.D., a professor in the Department of Neuroscience at Scripps Research, and a Howard Hughes Medical Institute investigator. Itch is a distinct sensation with its own nerve circuitry and evolutionary purpose—likely to alert organisms to potentially harmful chemicals, insects and parasites. Researchers over the past decade or so have identified itch-specific subsets of spinal neurons that extend nerve fibers into the skin and are sensitive to chemical triggers of itch such as the allergy mediator histamine. But so far, relatively little has been discovered about the circuitry of mechanical itch. PIEZO1's role in mechanical itch was unexpected. Patapoutian won a share of last year's Nobel Prize for Medicine or Physiology for his lab's pioneering research on PIEZO1 and its sister-protein PIEZO2. These unique, propeller-shaped "mechanosensor" ion channels are embedded in the outer membranes of many cell types. They become activated when mechanically distorted, opening their ion channels and triggering various downstream events. Since 2010, Patapoutian and colleagues have shown that PIEZO2 is a key mechanosensor for light touch, the feeling of the positioning of the body and limbs, and the urge to urinate—all via nerves in various tissues and organs. By contrast, the researchers have found that PIEZO1 has a variety of non-sensory roles throughout the body, for example in blood vessels and red blood cells. While their initial studies suggested that PIEZO1 was not expressed in sensory neurons, other recent investigations have suggested that it is expressed at low levels in some subsets of these neurons. In the new study, Patapoutian and his team, including study first author Rose Hill, Ph.D., a postdoctoral research associate, followed up on this surprising lead. In experiments in mice, they confirmed that PIEZO1 is expressed, and appears to be a functional, mechanical pressure-sensitive ion channel protein in two different types of sensory neuron that were already implicated in chemical itch. Mice with an overactive form of PIEZO1 were markedly more sensitive to itch sensations. By contrast, mice lacking PIEZO1 in their sensory neurons scratched themselves far less when stimulated on the skin with filaments that normally would trigger strong itch sensations. The researchers also showed that a PIEZO1-blocking compound alleviates scratching behaviors in mice with the equivalent of eczema. "We did see a dramatic effect on itch with this compound, and though it wasn't specific enough against PIEZO1 to develop into a drug, we hope eventually to develop a much more PIEZO1-specific compound for treating itch conditions," Hill says. Curiously, the absence or enhancement of PIEZO1 activity in mice caused at least a small reduction or increase of scratching due to chemical itch triggers such as histamine—implying that mechanical and chemical itch signals are indeed transmitted in some cases by the same sensory neurons. The researchers are now investigating whether variants of the PIEZO1 gene in the human population are related to itch sensitivity. The Patapoutian lab published a paper in 2018 showing that a mildly overactive form of PIEZO1, which also has the effect of making red blood cells relatively resistant to malaria parasites, is present in about a third of people of African ancestry. <|im_end|>

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3339, 2579, 6680, 7917, 12309, 31785, 311, 69263, 79383, 11, 374, 3118, 304, 922, 264, 4948, 315, 1274, 315, 11904, 66004, 13, 220, 128257, 198 ]

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Various species of the intestinal microbiota have been associated with the development of colorectal cancer 1 , 2 , but it has not been demonstrated that bacteria have a direct role in the occurrence of oncogenic mutations. Escherichia coli can carry the pathogenicity island pks , which encodes a set of enzymes that synthesize colibactin 3 . This compound is believed to alkylate DNA on adenine residues 4 , 5 and induces double-strand breaks in cultured cells 3 . Here we expose human intestinal organoids to genotoxic pks + E. coli by repeated luminal injection over five months. Whole-genome sequencing of clonal organoids before and after this exposure revealed a distinct mutational signature that was absent from organoids injected with isogenic pks -mutant bacteria. The same mutational signature was detected in a subset of 5,876 human cancer genomes from two independent cohorts, predominantly in colorectal cancer. Our study describes a distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island. Main The intestinal microbiome has long been suggested to be involved in colorectal cancer (CRC) tumorigenesis 1 , 2 . Various bacterial species have been reported to be enriched in stool and biopsy samples from patients with CRC 6 , 7 , 8 , 9 , including genotoxic strains of E . coli 3 , 6 , 10 , 11 . The genome of these genotoxic E. coli harbours a 50-kb hybrid polyketide-nonribosomal peptide synthase operon ( pks , also referred to as clb ) that is responsible for the production of the genotoxin colibactin. pks + E. coli are present in a substantial fraction of individuals (about 20% of healthy individuals, about 40% of patients with inflammatory bowel disease, and about 60% of patients with familial adenomatous polyposis or CRC) 6 , 10 , 11 . pks + E. coli induce—among other things—interstrand crosslinks (ICLs) and double-strand breaks (DSBs) in epithelial cell lines 3 , 10 , 11 , 12 and in gnotobiotic mouse models of CRC, in which they can also contribute to tumorigenesis 6 , 11 . Recently, two studies have reported that colibactin–adenine adducts are formed in mammalian cells exposed to pks + E. coli 4 , 5 . Whereas the chemistry of the interaction between colibactin and DNA is thus well-established, the outcome of this process in terms of recognizable mutations remains to be determined. Recent advances in sequencing technologies and the application of novel mathematical approaches allow somatic mutational patterns to be classified. More than 50 mutational signatures have been defined in using a mutational signature analysis that includes the bases immediately 5′ and 3′ to a single-base substitution (SBS), and a number of different contexts that characterize insertions and deletions (indels) 13 , 14 . For some of these mutational signatures, the underlying causes (for example, tobacco smoke, UV light, specific genetic DNA repair defects) are known 13 , 15 , 16 . However, for many the underlying aetiology remains unclear. Human intestinal organoids, which are established from primary crypt stem cells 17 , have been useful for identifying the underlying causes of mutational signatures 18 : After being exposed to a specific mutational agent in culture, the organoids can be subcloned and analysed by whole-genome sequencing (WGS) to identify the resulting mutational signature 16 , 19 , 20 . To define the mutagenic characteristics of pks + E. coli , we developed a co-culture protocol in which a pks + E. coli strain (originally derived from a CRC biopsy 21 ) was microinjected into the lumen of clonal human intestinal organoids 22 (Fig. 1a, b ). An isogenic clbQ knockout strain that cannot produce active colibactin 21 , 23 served as a negative control. Both bacterial strains were viable for at least three days in co-culture and followed similar growth dynamics (Fig. 1c ). DSBs and ICLs, visualized by γH2AX and FANCD2 immunofluorescence, respectively, were induced specifically in epithelial cells exposed to pks + E. coli (Fig. 1d, e , Extended Data Fig. 1a ), confirming that pks + E. coli induced DNA damage in our model. There was no substantial difference in viability between organoids exposed to pks + E. coli and those exposed to pks Δ clbQ E. coli , although there was a modest decrease for both when compared to the organoids injected with dye only (Extended Data Fig. 1b, c ). We then performed repeated injections (with pks + E. coli , pks Δ clbQ E. coli or dye only) into single cell-derived organoids, in order to achieve long-term exposure over a period of five months. Subsequently, we established subclonal organoids from individual cells extracted from the exposed organoids. For each condition, three subclones were subjected to WGS (Fig. 2a ). We also subjected the original clonal cultures to WGS to subtract somatic mutations that were already present before co-culture. Organoids exposed to pks + E. coli presented increased numbers of SBSs compared to those exposed to pks Δ clbQ E. coli , with a bias towards T > N substitutions (Fig. 2b ). These T > N substitutions occurred preferentially in A T A, A T T and T T T (with the middle base mutated). From this, we defined a pks -specific single-base substitution signature (SBS- pks ; Fig. 2c ). This mutational signature was not observed in organoids exposed to pks Δ clbQ E. coli or dye only (Fig. 2b, c , Extended Data Fig. 2a–c ), proving that it is a direct consequence of exposure to pks + E. coli . Furthermore, exposure to pks + E. coli induced a characteristic small indel signature (ID- pks ), which was characterized by single T deletions at T homopolymers (Fig. 2d, e , Extended Data Fig. 2d–f ). SBS- pks and ID- pks were replicated in an independent human intestinal organoid line (Extended Data Fig. 3a–d ; SBS cosine similarity, 0.77; ID cosine similarity, 0.93) and with a clbQ", "role": "user" }, { "content": "A common type of bacteria found in our guts could contribute to bowel cancer, according to research funded by a £20 million Cancer Research UK Grand Challenge award and published in Nature today. Scientists in The Netherlands, the UK and USA have shown that a toxin released by a strain of E. coli causes unique patterns, or 'fingerprints', of DNA damage to the cells lining the gut. The fingerprints were also seen in bowel cancer tumours, showing for the first time a direct link between the bacterial toxin and the genetic changes that drive cancer development. The team suggests that detecting this specific DNA damage in the cells lining the gut could one day allow doctors to identify people at higher risk of the disease and become used alongside current bowel cancer screening tests. Other bacterial toxins from gut bacteria might have similar effects and the hunt for them is now on as researchers seek to determine whether this mechanism of DNA damage is widespread. There are around 42,000 new bowel cancer cases in the UK every year, where it remains the second most common cause of cancer death. Understanding the early triggers that could lead to bowel cancer may help doctors prevent its development and detect it at its earliest stage, when treatment is most likely to be successful. This has led scientists to investigate the role that the microbiome—trillions of bacteria, viruses, fungi and other single-celled organisms—plays in the development of bowel cancer. Cayetano Pleguezuelos-Manzano, Jens Puschhof and Axel Rosendahl Huber explain their research on genotoxic E. coli bacteria Credit: DEMCON | nymus 3D and Melanie Fremery, ©Hubrecht Institute Professor Hans Clevers and his team at the Hubrecht Institute in The Netherlands focused on one strain of E. coli producing a toxin called colibactin, and which is more often present in the stool samples of people with bowel cancer compared to healthy people. Because colibactin can cause DNA damage in cells grown in the lab, they thought the toxin might be doing the same to cells lining the gut. The team used human intestinal organoids, miniature replicas of the gut grown in the lab, and exposed them to colibactin-producing E. coli. They analysed the DNA sequence of the gut cells in the organoids after 5 months and found about double the DNA damage in them, compared to organoids exposed to 'regular' E. coli that didn't produce the colibactin. The researchers also found that the DNA damage caused by colibactin followed two very specific patterns—like fingerprints—which were unique to the toxin. To determine whether the DNA damage caused by the bacterium played a role in bowel cancer, the researchers then analysed the DNA sequences of more than 5500 tumour samples from the UK and Netherlands, with the help of Dr. Henry Wood and Professor Philip Quirke from the University of Leeds. First, they checked for the two colibactin DNA damage fingerprints in over 3600 Dutch samples of various cancer types. The fingerprints were present in multiple tumours, and much more often in bowel cancers than other cancer types. Illustration of colibactin binding to specific DNA sequence. Credit: DEMCON | nymus3D, ©Hubrecht Institute The researchers then refined their investigation on bowel cancer tumours specifically, and analysed over 2000 bowel cancer samples from the UK, collected as part of the 100,000 Genomes Project run by Genomics England. Among these samples, the colibactin fingerprints were present in 4-5% of patients. This suggests that colibactin-producing E. coli may contribute to 1 in 20 bowel cancer cases in the UK. It will be up to further studies to shed light on just how much of a role the toxin could play in these cases, and what other components of the microbiome may be involved in the early stages of bowel cancer. Professor Hans Clevers, Grand Challenge co-investigator at the Hubrecht Institute, said: \"Things like tobacco or UV light are known to cause specific patterns of DNA damage, and these fingerprints can tell us a lot about past exposures that may have caused cancer to start. But this is the first time we've seen such a distinctive pattern of DNA damage in bowel cancer, which has been caused by a bacterium that lives in our gut.\" Further down the line, the researchers say that looking for DNA damage fingerprints like the ones associated with colibactin in the cells of the gut lining could be used to identify those who are at a greater risk of developing the disease. Professor Philip Quirke, Grand Challenge co-investigator at the University of Leeds, said: \"Our goal is to understand the causes of bowel cancer, so discovering the role of colibactin represents an important step. As a Grand Challenge team, we are now looking at other bacteria and their toxins associated with bowel cancer, and we hope to identify more DNA damage fingerprints to paint a better picture of risk factors. We will then need to work out how we can reduce the presence of high-risk bacteria in the gut. But this is all in the future, so for now people should continue to eat a healthy diet and participate in bowel cancer screening.\" John Barnes, patient advocate for Grand Challenge said: \"As a cancer survivor, I don't want others to go through what I've gone through. Catching bowel cancer at an earlier stage while it's still treatable has the potential to save thousands of people's lives. This brilliant research gives me hope that people may not have to suffer from bowel cancer in the future.\" Nicola Smith, senior health information manager at Cancer Research UK, said: \"The more doctors understand about how bowel cancer develops, the better they will be at detecting it and helping people reduce their risk. \"But there are already things that people can do right now to help reduce their risk of bowel cancer. Not smoking, keeping a healthy weight, eating a diet high in fibre and low in red and processed meat will all help. And for those who are eligible, participating in bowel screening can help to detect the disease at an early stage.\" This discovery of a direct link between a bacterium and bowel cancer tumours is the first major outcome of a £20 million Grand Challenge project striving to understand how the microbiome impacts on cancer risk, development and treatment. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Various species of the intestinal microbiota have been associated with the development of colorectal cancer 1 , 2 , but it has not been demonstrated that bacteria have a direct role in the occurrence of oncogenic mutations. Escherichia coli can carry the pathogenicity island pks , which encodes a set of enzymes that synthesize colibactin 3 . This compound is believed to alkylate DNA on adenine residues 4 , 5 and induces double-strand breaks in cultured cells 3 . Here we expose human intestinal organoids to genotoxic pks + E. coli by repeated luminal injection over five months. Whole-genome sequencing of clonal organoids before and after this exposure revealed a distinct mutational signature that was absent from organoids injected with isogenic pks -mutant bacteria. The same mutational signature was detected in a subset of 5,876 human cancer genomes from two independent cohorts, predominantly in colorectal cancer. Our study describes a distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island. Main The intestinal microbiome has long been suggested to be involved in colorectal cancer (CRC) tumorigenesis 1 , 2 . Various bacterial species have been reported to be enriched in stool and biopsy samples from patients with CRC 6 , 7 , 8 , 9 , including genotoxic strains of E . coli 3 , 6 , 10 , 11 . The genome of these genotoxic E. coli harbours a 50-kb hybrid polyketide-nonribosomal peptide synthase operon ( pks , also referred to as clb ) that is responsible for the production of the genotoxin colibactin. pks + E. coli are present in a substantial fraction of individuals (about 20% of healthy individuals, about 40% of patients with inflammatory bowel disease, and about 60% of patients with familial adenomatous polyposis or CRC) 6 , 10 , 11 . pks + E. coli induce—among other things—interstrand crosslinks (ICLs) and double-strand breaks (DSBs) in epithelial cell lines 3 , 10 , 11 , 12 and in gnotobiotic mouse models of CRC, in which they can also contribute to tumorigenesis 6 , 11 . Recently, two studies have reported that colibactin–adenine adducts are formed in mammalian cells exposed to pks + E. coli 4 , 5 . Whereas the chemistry of the interaction between colibactin and DNA is thus well-established, the outcome of this process in terms of recognizable mutations remains to be determined. Recent advances in sequencing technologies and the application of novel mathematical approaches allow somatic mutational patterns to be classified. More than 50 mutational signatures have been defined in using a mutational signature analysis that includes the bases immediately 5′ and 3′ to a single-base substitution (SBS), and a number of different contexts that characterize insertions and deletions (indels) 13 , 14 . For some of these mutational signatures, the underlying causes (for example, tobacco smoke, UV light, specific genetic DNA repair defects) are known 13 , 15 , 16 . However, for many the underlying aetiology remains unclear. Human intestinal organoids, which are established from primary crypt stem cells 17 , have been useful for identifying the underlying causes of mutational signatures 18 : After being exposed to a specific mutational agent in culture, the organoids can be subcloned and analysed by whole-genome sequencing (WGS) to identify the resulting mutational signature 16 , 19 , 20 . To define the mutagenic characteristics of pks + E. coli , we developed a co-culture protocol in which a pks + E. coli strain (originally derived from a CRC biopsy 21 ) was microinjected into the lumen of clonal human intestinal organoids 22 (Fig. 1a, b ). An isogenic clbQ knockout strain that cannot produce active colibactin 21 , 23 served as a negative control. Both bacterial strains were viable for at least three days in co-culture and followed similar growth dynamics (Fig. 1c ). DSBs and ICLs, visualized by γH2AX and FANCD2 immunofluorescence, respectively, were induced specifically in epithelial cells exposed to pks + E. coli (Fig. 1d, e , Extended Data Fig. 1a ), confirming that pks + E. coli induced DNA damage in our model. There was no substantial difference in viability between organoids exposed to pks + E. coli and those exposed to pks Δ clbQ E. coli , although there was a modest decrease for both when compared to the organoids injected with dye only (Extended Data Fig. 1b, c ). We then performed repeated injections (with pks + E. coli , pks Δ clbQ E. coli or dye only) into single cell-derived organoids, in order to achieve long-term exposure over a period of five months. Subsequently, we established subclonal organoids from individual cells extracted from the exposed organoids. For each condition, three subclones were subjected to WGS (Fig. 2a ). We also subjected the original clonal cultures to WGS to subtract somatic mutations that were already present before co-culture. Organoids exposed to pks + E. coli presented increased numbers of SBSs compared to those exposed to pks Δ clbQ E. coli , with a bias towards T > N substitutions (Fig. 2b ). These T > N substitutions occurred preferentially in A T A, A T T and T T T (with the middle base mutated). From this, we defined a pks -specific single-base substitution signature (SBS- pks ; Fig. 2c ). This mutational signature was not observed in organoids exposed to pks Δ clbQ E. coli or dye only (Fig. 2b, c , Extended Data Fig. 2a–c ), proving that it is a direct consequence of exposure to pks + E. coli . Furthermore, exposure to pks + E. coli induced a characteristic small indel signature (ID- pks ), which was characterized by single T deletions at T homopolymers (Fig. 2d, e , Extended Data Fig. 2d–f ). SBS- pks and ID- pks were replicated in an independent human intestinal organoid line (Extended Data Fig. 3a–d ; SBS cosine similarity, 0.77; ID cosine similarity, 0.93) and with a clbQ<|im_end|> <|im_start|>assistant A common type of bacteria found in our guts could contribute to bowel cancer, according to research funded by a £20 million Cancer Research UK Grand Challenge award and published in Nature today. Scientists in The Netherlands, the UK and USA have shown that a toxin released by a strain of E. coli causes unique patterns, or 'fingerprints', of DNA damage to the cells lining the gut. The fingerprints were also seen in bowel cancer tumours, showing for the first time a direct link between the bacterial toxin and the genetic changes that drive cancer development. The team suggests that detecting this specific DNA damage in the cells lining the gut could one day allow doctors to identify people at higher risk of the disease and become used alongside current bowel cancer screening tests. Other bacterial toxins from gut bacteria might have similar effects and the hunt for them is now on as researchers seek to determine whether this mechanism of DNA damage is widespread. There are around 42,000 new bowel cancer cases in the UK every year, where it remains the second most common cause of cancer death. Understanding the early triggers that could lead to bowel cancer may help doctors prevent its development and detect it at its earliest stage, when treatment is most likely to be successful. This has led scientists to investigate the role that the microbiome—trillions of bacteria, viruses, fungi and other single-celled organisms—plays in the development of bowel cancer. Cayetano Pleguezuelos-Manzano, Jens Puschhof and Axel Rosendahl Huber explain their research on genotoxic E. coli bacteria Credit: DEMCON | nymus 3D and Melanie Fremery, ©Hubrecht Institute Professor Hans Clevers and his team at the Hubrecht Institute in The Netherlands focused on one strain of E. coli producing a toxin called colibactin, and which is more often present in the stool samples of people with bowel cancer compared to healthy people. Because colibactin can cause DNA damage in cells grown in the lab, they thought the toxin might be doing the same to cells lining the gut. The team used human intestinal organoids, miniature replicas of the gut grown in the lab, and exposed them to colibactin-producing E. coli. They analysed the DNA sequence of the gut cells in the organoids after 5 months and found about double the DNA damage in them, compared to organoids exposed to 'regular' E. coli that didn't produce the colibactin. The researchers also found that the DNA damage caused by colibactin followed two very specific patterns—like fingerprints—which were unique to the toxin. To determine whether the DNA damage caused by the bacterium played a role in bowel cancer, the researchers then analysed the DNA sequences of more than 5500 tumour samples from the UK and Netherlands, with the help of Dr. Henry Wood and Professor Philip Quirke from the University of Leeds. First, they checked for the two colibactin DNA damage fingerprints in over 3600 Dutch samples of various cancer types. The fingerprints were present in multiple tumours, and much more often in bowel cancers than other cancer types. Illustration of colibactin binding to specific DNA sequence. Credit: DEMCON | nymus3D, ©Hubrecht Institute The researchers then refined their investigation on bowel cancer tumours specifically, and analysed over 2000 bowel cancer samples from the UK, collected as part of the 100,000 Genomes Project run by Genomics England. Among these samples, the colibactin fingerprints were present in 4-5% of patients. This suggests that colibactin-producing E. coli may contribute to 1 in 20 bowel cancer cases in the UK. It will be up to further studies to shed light on just how much of a role the toxin could play in these cases, and what other components of the microbiome may be involved in the early stages of bowel cancer. Professor Hans Clevers, Grand Challenge co-investigator at the Hubrecht Institute, said: "Things like tobacco or UV light are known to cause specific patterns of DNA damage, and these fingerprints can tell us a lot about past exposures that may have caused cancer to start. But this is the first time we've seen such a distinctive pattern of DNA damage in bowel cancer, which has been caused by a bacterium that lives in our gut." Further down the line, the researchers say that looking for DNA damage fingerprints like the ones associated with colibactin in the cells of the gut lining could be used to identify those who are at a greater risk of developing the disease. Professor Philip Quirke, Grand Challenge co-investigator at the University of Leeds, said: "Our goal is to understand the causes of bowel cancer, so discovering the role of colibactin represents an important step. As a Grand Challenge team, we are now looking at other bacteria and their toxins associated with bowel cancer, and we hope to identify more DNA damage fingerprints to paint a better picture of risk factors. We will then need to work out how we can reduce the presence of high-risk bacteria in the gut. But this is all in the future, so for now people should continue to eat a healthy diet and participate in bowel cancer screening." John Barnes, patient advocate for Grand Challenge said: "As a cancer survivor, I don't want others to go through what I've gone through. Catching bowel cancer at an earlier stage while it's still treatable has the potential to save thousands of people's lives. This brilliant research gives me hope that people may not have to suffer from bowel cancer in the future." Nicola Smith, senior health information manager at Cancer Research UK, said: "The more doctors understand about how bowel cancer develops, the better they will be at detecting it and helping people reduce their risk. "But there are already things that people can do right now to help reduce their risk of bowel cancer. Not smoking, keeping a healthy weight, eating a diet high in fibre and low in red and processed meat will all help. And for those who are eligible, participating in bowel screening can help to detect the disease at an early stage." This discovery of a direct link between a bacterium and bowel cancer tumours is the first major outcome of a £20 million Grand Challenge project striving to understand how the microbiome impacts on cancer risk, development and treatment. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Several animal species demonstrate remarkable locomotive capabilities on land, on water, and under water. A hybrid terrestrial-aquatic robot with similar capabilities requires multimodal locomotive strategies that reconcile the constraints imposed by the different environments. Here we report the development of a 1.6 g quadrupedal microrobot that can walk on land, swim on water, and transition between the two. This robot utilizes a combination of surface tension and buoyancy to support its weight and generates differential drag using passive flaps to swim forward and turn. Electrowetting is used to break the water surface and transition into water by reducing the contact angle, and subsequently inducing spontaneous wetting. Finally, several design modifications help the robot overcome surface tension and climb a modest incline to transition back onto land. Our results show that microrobots can demonstrate unique locomotive capabilities by leveraging their small size, mesoscale fabrication methods, and surface effects. Introduction Many animal species 1 , 2 , 3 , 4 , 5 exhibit multimodal locomotive capabilities in terrestrial and aquatic environments to evade predators or search for prey. A few arachnids 3 and insects 4 can move on the surface of water by exploiting static surface tension. The surface tension force significantly exceeds (over 10 times) their body weight, enabling rapid locomotion and even jumping without breaking the water surface 6 . Remarkably some insects, such as diving flies 4 and diving beetles 7 , 8 , can also generate enough force to spontaneously break the water surface to swim, feed, and lay eggs underwater. The ability to move on the water surface, controllably transition into water, and swim underwater enable these creatures to live in complex environments (e.g., high salinity environment such as the Mono Lake 4 ) that most animals cannot survive. Robots that can traverse complex terrains, such as hybrid terrestrial-aquatic environments, are suitable for diverse applications in environmental monitoring and the exploration of confined spaces. Taking inspiration from nature, many robotic prototypes 9 , 10 , 11 , 12 have been developed for terrestrial-aquatic locomotion. Most of these amphibious robots, however, weigh over 100 g and cannot move on the water surface due to their large weight-to-size ratio 9 , 10 , 11 , 12 . Microrobots (mass<20 g, length<15 cm) have a smaller weight-to-size ratio, and they can leverage surface effects, such as electrostatics or surface tension, to perch on compliant surfaces 13 or move on the surface of water 14 , 15 , 16 , 17 , 18 , 19 . This confers several potential advantages; for example, microrobots can avoid submerged obstacles by returning to the water surface. Furthermore, microrobots experience smaller drag on the water surface due to reduced wetted area, which leads to higher locomotion speed compared to swimming underwater. These hybrid locomotion capabilities could potentially allow microrobots to explore diverse environments that are inaccessible to larger robots. Previous work 14 , 15 , 16 , 17 , 18 , 19 , 20 on water strider-inspired microrobots leveraged insights from studies of biological water striders 21 . These robots weigh 6–20 g, are 8–15 cm long, and use hydrophobic wires for support on the water surface. These devices were used to investigate the biomechanics of water striders 22 , 23 , study the associated fluid mechanics 21 , and enable microrobot locomotion on the water surface. Actual water striders are ~1 cm long and weigh 4.5 mg, and they are over 10 times smaller and 1000 times lighter than these microrobots. Since the surface tension force scales linearly with the leg contact length and mass scales with length cubed, these robots need to use supporting legs that are substantially longer than their bodies. These supporting legs create challenges for locomotion in other environments, such as on land or underwater. In this study, we develop a 1.6 g quadrupedal microrobot that is capable of walking on land, moving on the surface of water, and transitioning between land, the water surface, and aquatic environments (Supplementary Movie 1 ). We address two challenges that are unexamined in previous studies: gait design for multimodal locomotion 24 in terrestrial and aquatic environments, and strategies for transitions between these environments. First, we develop gaits for locomotion on land and the water surface utilizing a quadrupedal robot with two independently controlled degrees-of-freedom (DOFs) in each leg. Second, we design “feet” that utilize both surface tension and surface tension induced buoyancy to generate the necessary supporting force without inhibiting terrestrial locomotion. The “feet” utilize electrowetting 25 , 26 , 27 to break the water surface. Electrowetting refers to the changing of the liquid to solid surface contact angle in response to an applied voltage, and it is commonly found in microfluidics or electronic paper display applications 26 . We further examine the influence of surface tension on the robot during underwater-to-land transitions. Design changes to the robot’s legs and transmission (compared to a previous version 28 ) allow it to overcome a force that is twice its body weight and break the water surface to transition back onto land. In summary, this work develops multimodal strategies for locomotion in terrestrial and aquatic environments, describes novel mesoscale devices for water surface to underwater transitions, and analyzes the influence of surface tension on microrobot aquatic to terrestrial transitions. These studies culminate in the first terrestrial-aquatic microrobot that adapts to complex environments, representing advances in mesoscale fabrication and microrobot locomotive capabilities. Results Robot design and demonstration We base our robot design on the Harvard Ambulatory MicroRobot (HAMR), which is a 1.43 g quadrupedal robot with eight independently actuated DOFs 29 . Two piezoelectric actuators control the swing (fore/aft) and lift (vertical) motion of each leg. The robot is fabricated based on the PC-MEMS process 28 , 30 and the robot transmissions are made of compliant 25 µm polyimide flexures (Kapton, Dupont). In previous studies 28 , 29 , a number of walking gaits such as the trot, pronk, and jump are shown to be capable of high speed locomotion on land. Several design", "role": "user" }, { "content": "In nature, cockroaches can survive underwater for up to 30 minutes. Now, a robotic cockroach can do even better. Harvard's Ambulatory Microrobot, known as HAMR, can walk on land, swim on the surface of water, and walk underwater for as long as necessary, opening up new environments for this little bot to explore. This next generation HAMR uses multifunctional foot pads that rely on surface tension and surface tension induced buoyancy when HAMR needs to swim but can also apply a voltage to break the water surface when HAMR needs to sink. This process is called electrowetting, which is the reduction of the contact angle between a material and the water surface under an applied voltage. This change of contact angle makes it easier for objects to break the water surface. Moving on the surface of water allows a microrobot to evade submerged obstacles and reduces drag. Using four pairs of asymmetric flaps and custom designed swimming gaits, HAMR robo-paddles on the water surface to swim. Exploiting the unsteady interaction between the robot's passive flaps and the surrounding water, the robot generates swimming gaits similar to that of a diving beetle. This allows the robot to effectively swim forward and turn. \"This research demonstrates that microrobotics can leverage small-scale physics—in this case surface tension—to perform functions and capabilities that are challenging for larger robots,\" said Kevin Chen, a postdoctoral fellow at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and first author of the paper. HAMR's multifunctional foot pads rely on surface tension and surface tension induced buoyancy when HAMR needs to swim but can also apply a voltage to break the water surface when HAMR needs to sink. Credit: Yufeng Chen, Neel Doshi, and Benjamin Goldberg/Harvard University The most recent research is published in the journal Nature Communications. \"HAMR's size is key to its performance,\" said Neel Doshi, graduate student at SEAS and co-author of the paper. \"If it were much bigger, it would be challenging to support the robot with surface tension and if it were much smaller, the robot might not be able to generate enough force to break it.\" HAMR weighs 1.65 grams (about as much as a large paper clip), can carry 1.44 grams of additional payload without sinking and can paddle its legs with a frequency up to 10 Hz. It's coated in Parylene to keep it from shorting under water. Once below the surface of the water, HAMR uses the same gait to walk as it does on dry land and is just as mobile. To return to dry land HAMR faces enormous challenge from the water's hold. A water surface tension force that is twice the robot weight pushes down on the robot, and in addition the induced torque causes a dramatic increase of friction on the robot's hind legs. The researchers stiffened the robot's transmission and installed soft pads to the robot's front legs to increase payload capacity and redistribute friction during climbing. Finally, walking up a modest incline, the robot is able break out of the water's hold. \"This robot nicely illustrates some of the challenges and opportunities with small-scale robots,\" said senior author Robert Wood, Charles River Professor of Engineering and Applied Sciences at SEAS and core faculty member of the Harvard Wyss Institute for Biologically Inspired Engineering. \"Shrinking brings opportunities for increased mobility—such as walking on the surface of water—but also challenges since the forces that we take for granted at larger scales can start to dominate at the size of an insect.\" Next, the researchers hope to further improve HAMR's locomotion and find a way to return to land without a ramp, perhaps incorporating gecko-inspired adhesives or impulsive jumping mechanisms. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Several animal species demonstrate remarkable locomotive capabilities on land, on water, and under water. A hybrid terrestrial-aquatic robot with similar capabilities requires multimodal locomotive strategies that reconcile the constraints imposed by the different environments. Here we report the development of a 1.6 g quadrupedal microrobot that can walk on land, swim on water, and transition between the two. This robot utilizes a combination of surface tension and buoyancy to support its weight and generates differential drag using passive flaps to swim forward and turn. Electrowetting is used to break the water surface and transition into water by reducing the contact angle, and subsequently inducing spontaneous wetting. Finally, several design modifications help the robot overcome surface tension and climb a modest incline to transition back onto land. Our results show that microrobots can demonstrate unique locomotive capabilities by leveraging their small size, mesoscale fabrication methods, and surface effects. Introduction Many animal species 1 , 2 , 3 , 4 , 5 exhibit multimodal locomotive capabilities in terrestrial and aquatic environments to evade predators or search for prey. A few arachnids 3 and insects 4 can move on the surface of water by exploiting static surface tension. The surface tension force significantly exceeds (over 10 times) their body weight, enabling rapid locomotion and even jumping without breaking the water surface 6 . Remarkably some insects, such as diving flies 4 and diving beetles 7 , 8 , can also generate enough force to spontaneously break the water surface to swim, feed, and lay eggs underwater. The ability to move on the water surface, controllably transition into water, and swim underwater enable these creatures to live in complex environments (e.g., high salinity environment such as the Mono Lake 4 ) that most animals cannot survive. Robots that can traverse complex terrains, such as hybrid terrestrial-aquatic environments, are suitable for diverse applications in environmental monitoring and the exploration of confined spaces. Taking inspiration from nature, many robotic prototypes 9 , 10 , 11 , 12 have been developed for terrestrial-aquatic locomotion. Most of these amphibious robots, however, weigh over 100 g and cannot move on the water surface due to their large weight-to-size ratio 9 , 10 , 11 , 12 . Microrobots (mass<20 g, length<15 cm) have a smaller weight-to-size ratio, and they can leverage surface effects, such as electrostatics or surface tension, to perch on compliant surfaces 13 or move on the surface of water 14 , 15 , 16 , 17 , 18 , 19 . This confers several potential advantages; for example, microrobots can avoid submerged obstacles by returning to the water surface. Furthermore, microrobots experience smaller drag on the water surface due to reduced wetted area, which leads to higher locomotion speed compared to swimming underwater. These hybrid locomotion capabilities could potentially allow microrobots to explore diverse environments that are inaccessible to larger robots. Previous work 14 , 15 , 16 , 17 , 18 , 19 , 20 on water strider-inspired microrobots leveraged insights from studies of biological water striders 21 . These robots weigh 6–20 g, are 8–15 cm long, and use hydrophobic wires for support on the water surface. These devices were used to investigate the biomechanics of water striders 22 , 23 , study the associated fluid mechanics 21 , and enable microrobot locomotion on the water surface. Actual water striders are ~1 cm long and weigh 4.5 mg, and they are over 10 times smaller and 1000 times lighter than these microrobots. Since the surface tension force scales linearly with the leg contact length and mass scales with length cubed, these robots need to use supporting legs that are substantially longer than their bodies. These supporting legs create challenges for locomotion in other environments, such as on land or underwater. In this study, we develop a 1.6 g quadrupedal microrobot that is capable of walking on land, moving on the surface of water, and transitioning between land, the water surface, and aquatic environments (Supplementary Movie 1 ). We address two challenges that are unexamined in previous studies: gait design for multimodal locomotion 24 in terrestrial and aquatic environments, and strategies for transitions between these environments. First, we develop gaits for locomotion on land and the water surface utilizing a quadrupedal robot with two independently controlled degrees-of-freedom (DOFs) in each leg. Second, we design “feet” that utilize both surface tension and surface tension induced buoyancy to generate the necessary supporting force without inhibiting terrestrial locomotion. The “feet” utilize electrowetting 25 , 26 , 27 to break the water surface. Electrowetting refers to the changing of the liquid to solid surface contact angle in response to an applied voltage, and it is commonly found in microfluidics or electronic paper display applications 26 . We further examine the influence of surface tension on the robot during underwater-to-land transitions. Design changes to the robot’s legs and transmission (compared to a previous version 28 ) allow it to overcome a force that is twice its body weight and break the water surface to transition back onto land. In summary, this work develops multimodal strategies for locomotion in terrestrial and aquatic environments, describes novel mesoscale devices for water surface to underwater transitions, and analyzes the influence of surface tension on microrobot aquatic to terrestrial transitions. These studies culminate in the first terrestrial-aquatic microrobot that adapts to complex environments, representing advances in mesoscale fabrication and microrobot locomotive capabilities. Results Robot design and demonstration We base our robot design on the Harvard Ambulatory MicroRobot (HAMR), which is a 1.43 g quadrupedal robot with eight independently actuated DOFs 29 . Two piezoelectric actuators control the swing (fore/aft) and lift (vertical) motion of each leg. The robot is fabricated based on the PC-MEMS process 28 , 30 and the robot transmissions are made of compliant 25 µm polyimide flexures (Kapton, Dupont). In previous studies 28 , 29 , a number of walking gaits such as the trot, pronk, and jump are shown to be capable of high speed locomotion on land. Several design<|im_end|> <|im_start|>assistant In nature, cockroaches can survive underwater for up to 30 minutes. Now, a robotic cockroach can do even better. Harvard's Ambulatory Microrobot, known as HAMR, can walk on land, swim on the surface of water, and walk underwater for as long as necessary, opening up new environments for this little bot to explore. This next generation HAMR uses multifunctional foot pads that rely on surface tension and surface tension induced buoyancy when HAMR needs to swim but can also apply a voltage to break the water surface when HAMR needs to sink. This process is called electrowetting, which is the reduction of the contact angle between a material and the water surface under an applied voltage. This change of contact angle makes it easier for objects to break the water surface. Moving on the surface of water allows a microrobot to evade submerged obstacles and reduces drag. Using four pairs of asymmetric flaps and custom designed swimming gaits, HAMR robo-paddles on the water surface to swim. Exploiting the unsteady interaction between the robot's passive flaps and the surrounding water, the robot generates swimming gaits similar to that of a diving beetle. This allows the robot to effectively swim forward and turn. "This research demonstrates that microrobotics can leverage small-scale physics—in this case surface tension—to perform functions and capabilities that are challenging for larger robots," said Kevin Chen, a postdoctoral fellow at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and first author of the paper. HAMR's multifunctional foot pads rely on surface tension and surface tension induced buoyancy when HAMR needs to swim but can also apply a voltage to break the water surface when HAMR needs to sink. Credit: Yufeng Chen, Neel Doshi, and Benjamin Goldberg/Harvard University The most recent research is published in the journal Nature Communications. "HAMR's size is key to its performance," said Neel Doshi, graduate student at SEAS and co-author of the paper. "If it were much bigger, it would be challenging to support the robot with surface tension and if it were much smaller, the robot might not be able to generate enough force to break it." HAMR weighs 1.65 grams (about as much as a large paper clip), can carry 1.44 grams of additional payload without sinking and can paddle its legs with a frequency up to 10 Hz. It's coated in Parylene to keep it from shorting under water. Once below the surface of the water, HAMR uses the same gait to walk as it does on dry land and is just as mobile. To return to dry land HAMR faces enormous challenge from the water's hold. A water surface tension force that is twice the robot weight pushes down on the robot, and in addition the induced torque causes a dramatic increase of friction on the robot's hind legs. The researchers stiffened the robot's transmission and installed soft pads to the robot's front legs to increase payload capacity and redistribute friction during climbing. Finally, walking up a modest incline, the robot is able break out of the water's hold. "This robot nicely illustrates some of the challenges and opportunities with small-scale robots," said senior author Robert Wood, Charles River Professor of Engineering and Applied Sciences at SEAS and core faculty member of the Harvard Wyss Institute for Biologically Inspired Engineering. "Shrinking brings opportunities for increased mobility—such as walking on the surface of water—but also challenges since the forces that we take for granted at larger scales can start to dominate at the size of an insect." Next, the researchers hope to further improve HAMR's locomotion and find a way to return to land without a ramp, perhaps incorporating gecko-inspired adhesives or impulsive jumping mechanisms. <|im_end|>

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2,183

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Background Our understanding of the molecular underpinnings of chronic traumatic encephalopathy (CTE) and its associated pathology in post-mortem brain is incomplete. Factors including years of play and genetic risk variants influence the extent of tau pathology associated with disease expression, but how these factors affect gene expression, and whether those effects are consistent across the development of disease, is unknown. Methods To address these questions, we conducted an analysis of the largest post-mortem brain CTE mRNASeq whole-transcriptome dataset available to date. We examined the genes and biological processes associated with disease by comparing individuals with CTE with control individuals with a history of repetitive head impacts that lack CTE pathology. We then identified genes and biological processes associated with total years of play as a measure of exposure, amount of tau pathology present at time of death, and the presence of APOE and TMEM106B risk variants. Samples were stratified into low and high pathology groups based on McKee CTE staging criteria to model early versus late changes in response to exposure, and the relative effects associated with these factors were compared between these groups. Results Substantial gene expression changes were associated with severe disease for most of these factors, primarily implicating diverse, strongly involved neuroinflammatory and neuroimmune processes. In contrast, low pathology groups had many fewer genes and processes implicated and show striking differences for some factors when compared with severe disease. Specifically, gene expression associated with amount of tau pathology showed a nearly perfect inverse relationship when compared between these two groups. Conclusions Together, these results suggest the early CTE disease process may be mechanistically different than what occurs in late stages, that total years of play and tau pathology influence disease expression differently, and that related pathology-modifying risk variants may do so via distinct biological pathways. Peer Review reports Background Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that is caused at least in part by exposure to repeated traumatic head impacts most commonly observed in the brains of athletes of contact sports and combat veterans. CTE pathology is associated with many clinical symptoms, including behavioral, personality and mood changes as well as memory and cognitive function deficits. Upon autopsy, CTE is diagnosed by the presence of neurofibrillary tangles found around blood vessels and in the depths of the cortical sulcus. The primary risk factor for developing CTE is the duration of exposure to repetitive head impacts (RHI), which can be measured as total years of play for contact sport athletes [ 1 ]. The neurological symptoms of CTE often only manifest decades after players have retired, suggesting the effects of RHI set in motion a progression of pathological events ultimately leading to disease. However, not all individuals with a similar degree of exposure will go on to develop CTE, and while some genetic evidence suggests specific genes are associated with increased risk of disease, the mechanisms underlying the disease process are currently unknown. It is also currently unknown whether early disease states differ from those that are coincident with severe pathology. Our previous work showed that two genetic risk variants in the Apolipoprotein E (APOE) and Transmembrane Protein 106B (TMEM106B) genes also influence the frequency and severity of CTE. The association of the APOE e4 allele with increased Alzheimer’s Disease (AD) risk is well documented [ 2 ] and APOE e4 has also been shown to be associated with increased severity of CTE pathology [ 3 ]. Variants in TMEM106B are associated with increased neuroinflammation in aging [ 4 ], frontotemporal lobar degeneration (FTLD)-TDP [ 5 ], and with AD [ 6 , 7 ] and our prior study suggested a protective role of the TMEM106B variant rs3173615 in CTE [ 8 ]. While prior research has provided some information about the functional roles of APOE [ 9 ] and to a lesser extent TMEM106B [ 10 , 11 , 12 , 13 ] in both normal and disease contexts, the role they play in the development of CTE is poorly understood. To address these knowledge gaps, we profiled whole transcriptome gene expression of prefrontal cortex (Brodmann Area 9) by mRNASeq in a cohort of 66 CTE and 10 RHI controls. The CTE samples were subdivided into 13 low (CTE-L, Stages I & II) and 53 high (CTE-H, Stages III & IV) pathology groups using the McKee staging criteria [ 14 , 15 ], with the goal of identifying molecular changes associated with early versus late disease. The RHI controls are individuals who experienced a similar level of repetitive head impacts exposure as the disease groups but displayed no CTE pathology upon autopsy. In this study, we sought to identify genes and biological processes associated with differences between CTE and RHI controls, repetitive head impacts exposure as measured by total years of play, amount of tau pathology using immunohistological quantification of Phospho-Tau (AT8), and between APOE and TMEM106B risk variant carrier groups. Methods Sample characteristics Autopsy participants with a history of RHI exposure were drawn from the from the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) study. Inclusion criteria for UNITE include a history of contact sports participation, military service, or domestic violence [ 16 ]. Participants were excluded if they lacked fresh frozen prefrontal cortex, died from drug overdose, hanging, or gunshot wound to the head, or had motor neuron disease or other significant neurodegenerative disease in the absence of CTE. For this study, contact sports included American football (n=67), boxing (n=2), ice hockey (n=2), and professional wrestling (n=1). Years of consecutive contact sport participation was used as a proxy for RHI. Two participants without CTE had RHI from non-contact sports exposures (e.g. multiple traumatic brain injuries during military service) and were not included in the years of play analyses. Sample statistics are included in Table 5 . This study has been approved by the VA Bedford Healthcare System and Boston University School of Medicine Institutional Review Boards. CTE-L and CTE-H samples were categorized based on the McKee staging criteria [ 14 , 15", "role": "user" }, { "content": "Millions of people, including athletes who play contact sports, members of the military and victims of domestic violence, are exposed to repetitive head impacts (RHI), which is the primary risk factor for developing chronic traumatic encephalopathy (CTE). Symptoms of CTE often manifest years to decades after exposure to RHI and very little is known about what happens in the brain in the interim. The brains of people who die with CTE are marked by the accumulation of a protein called tau, the same protein found to aggregate in Alzheimer's disease (AD) brain. The amount of tau pathology in CTE correlates with severity of disease, where early-stage brains have very little pathology and late stage show severe, widespread involvement. The amount of RHI exposure, which for athletes can be measured in terms of the number of years they played a violent sport, as well as genetic risk variants influence the extent of tau pathology and associated disease severity. However, the molecular and genetic mechanisms that underly the development disease, and to what extent those effects are consistent throughout disease progression, are poorly understood. To address these questions, researchers from Boston University Chobanian & Avedisian School of Medicine conducted genetic analysis of the largest collection of post-mortem CTE brains, primarily from professional athletes, donated to the BU CTE Brain Bank. They found evidence that early and late CTE brains are similar in some ways but dramatically different in others. In particular, neuro-inflammation and neuronal stress are strongly implicated in disease, albeit to different extents and in different directions depending on the severity of disease. This is the first study to show that the molecular pathways involved in early CTE are different from those involved in late-stage disease. \"A better understanding of the early CTE disease process may lead to more informative diagnostics, biomarkers and ultimately therapies,\" said co-corresponding author Adam Thomas Labadorf, Ph.D., assistant professor of neurology. \"In addition, since the type of pathology found in the brains of people with CTE is similar to that found in AD, a better understanding of how the brain responds to this kind of pathology in CTE is likely to better inform our understanding AD as well.\" The researchers studied the prefrontal cortex tissue from 76 individuals (66 CTE, 10 control) who donated their brains to the BU UNITE Brain Bank. The sample set contained brains that spanned the full range of disease severity, affording the researchers the unique opportunity to see whether the gene expression in people with early stage CTE differ from those with late stage. The researchers generated gene expression data for each individual and then performed bioinformatic and statistical analyses of the different subsets of these samples to look for gene expression patterns that are associated with different clinical, histological and genetic markers that are relevant to CTE. They then identified genes and biological processes associated with total years of play as a measure of exposure, amount of tau pathology present at time of death, and the presence of APOE and TMEM106B risk variants. The researchers found substantial gene expression changes were associated with severe disease for most of these factors, primarily implicating diverse, strongly involved neuro-inflammatory and neuro-immune processes. In contrast, low pathology groups had many fewer gene expression changes and neuroimmune or inflammatory processes implicated and showed striking differences for some factors when compared with severe disease. According to the researchers, if the active disease process in early disease differs substantially from late-stage disease, this could have important implications for both diagnostic and therapeutic targets. \"This might explain why therapeutic targets identified from late-stage human tissue have largely failed to influence disease progression in clinical trials for many neurodegenerative diseases. In addition, if there are distinct markers of early disease progression that are absent in late disease, this would provide an opportunity to explore different diagnostics and biomarkers that we otherwise wouldn't know to look for,\" explained co-corresponding author Thor Stein, MD, Ph.D., a neuropathologist at VA Boston Healthcare System and associate professor of pathology and laboratory medicine. These findings appear online in the journal BMC Medical Genomics. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Background Our understanding of the molecular underpinnings of chronic traumatic encephalopathy (CTE) and its associated pathology in post-mortem brain is incomplete. Factors including years of play and genetic risk variants influence the extent of tau pathology associated with disease expression, but how these factors affect gene expression, and whether those effects are consistent across the development of disease, is unknown. Methods To address these questions, we conducted an analysis of the largest post-mortem brain CTE mRNASeq whole-transcriptome dataset available to date. We examined the genes and biological processes associated with disease by comparing individuals with CTE with control individuals with a history of repetitive head impacts that lack CTE pathology. We then identified genes and biological processes associated with total years of play as a measure of exposure, amount of tau pathology present at time of death, and the presence of APOE and TMEM106B risk variants. Samples were stratified into low and high pathology groups based on McKee CTE staging criteria to model early versus late changes in response to exposure, and the relative effects associated with these factors were compared between these groups. Results Substantial gene expression changes were associated with severe disease for most of these factors, primarily implicating diverse, strongly involved neuroinflammatory and neuroimmune processes. In contrast, low pathology groups had many fewer genes and processes implicated and show striking differences for some factors when compared with severe disease. Specifically, gene expression associated with amount of tau pathology showed a nearly perfect inverse relationship when compared between these two groups. Conclusions Together, these results suggest the early CTE disease process may be mechanistically different than what occurs in late stages, that total years of play and tau pathology influence disease expression differently, and that related pathology-modifying risk variants may do so via distinct biological pathways. Peer Review reports Background Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that is caused at least in part by exposure to repeated traumatic head impacts most commonly observed in the brains of athletes of contact sports and combat veterans. CTE pathology is associated with many clinical symptoms, including behavioral, personality and mood changes as well as memory and cognitive function deficits. Upon autopsy, CTE is diagnosed by the presence of neurofibrillary tangles found around blood vessels and in the depths of the cortical sulcus. The primary risk factor for developing CTE is the duration of exposure to repetitive head impacts (RHI), which can be measured as total years of play for contact sport athletes [ 1 ]. The neurological symptoms of CTE often only manifest decades after players have retired, suggesting the effects of RHI set in motion a progression of pathological events ultimately leading to disease. However, not all individuals with a similar degree of exposure will go on to develop CTE, and while some genetic evidence suggests specific genes are associated with increased risk of disease, the mechanisms underlying the disease process are currently unknown. It is also currently unknown whether early disease states differ from those that are coincident with severe pathology. Our previous work showed that two genetic risk variants in the Apolipoprotein E (APOE) and Transmembrane Protein 106B (TMEM106B) genes also influence the frequency and severity of CTE. The association of the APOE e4 allele with increased Alzheimer’s Disease (AD) risk is well documented [ 2 ] and APOE e4 has also been shown to be associated with increased severity of CTE pathology [ 3 ]. Variants in TMEM106B are associated with increased neuroinflammation in aging [ 4 ], frontotemporal lobar degeneration (FTLD)-TDP [ 5 ], and with AD [ 6 , 7 ] and our prior study suggested a protective role of the TMEM106B variant rs3173615 in CTE [ 8 ]. While prior research has provided some information about the functional roles of APOE [ 9 ] and to a lesser extent TMEM106B [ 10 , 11 , 12 , 13 ] in both normal and disease contexts, the role they play in the development of CTE is poorly understood. To address these knowledge gaps, we profiled whole transcriptome gene expression of prefrontal cortex (Brodmann Area 9) by mRNASeq in a cohort of 66 CTE and 10 RHI controls. The CTE samples were subdivided into 13 low (CTE-L, Stages I & II) and 53 high (CTE-H, Stages III & IV) pathology groups using the McKee staging criteria [ 14 , 15 ], with the goal of identifying molecular changes associated with early versus late disease. The RHI controls are individuals who experienced a similar level of repetitive head impacts exposure as the disease groups but displayed no CTE pathology upon autopsy. In this study, we sought to identify genes and biological processes associated with differences between CTE and RHI controls, repetitive head impacts exposure as measured by total years of play, amount of tau pathology using immunohistological quantification of Phospho-Tau (AT8), and between APOE and TMEM106B risk variant carrier groups. Methods Sample characteristics Autopsy participants with a history of RHI exposure were drawn from the from the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) study. Inclusion criteria for UNITE include a history of contact sports participation, military service, or domestic violence [ 16 ]. Participants were excluded if they lacked fresh frozen prefrontal cortex, died from drug overdose, hanging, or gunshot wound to the head, or had motor neuron disease or other significant neurodegenerative disease in the absence of CTE. For this study, contact sports included American football (n=67), boxing (n=2), ice hockey (n=2), and professional wrestling (n=1). Years of consecutive contact sport participation was used as a proxy for RHI. Two participants without CTE had RHI from non-contact sports exposures (e.g. multiple traumatic brain injuries during military service) and were not included in the years of play analyses. Sample statistics are included in Table 5 . This study has been approved by the VA Bedford Healthcare System and Boston University School of Medicine Institutional Review Boards. CTE-L and CTE-H samples were categorized based on the McKee staging criteria [ 14 , 15<|im_end|> <|im_start|>assistant Millions of people, including athletes who play contact sports, members of the military and victims of domestic violence, are exposed to repetitive head impacts (RHI), which is the primary risk factor for developing chronic traumatic encephalopathy (CTE). Symptoms of CTE often manifest years to decades after exposure to RHI and very little is known about what happens in the brain in the interim. The brains of people who die with CTE are marked by the accumulation of a protein called tau, the same protein found to aggregate in Alzheimer's disease (AD) brain. The amount of tau pathology in CTE correlates with severity of disease, where early-stage brains have very little pathology and late stage show severe, widespread involvement. The amount of RHI exposure, which for athletes can be measured in terms of the number of years they played a violent sport, as well as genetic risk variants influence the extent of tau pathology and associated disease severity. However, the molecular and genetic mechanisms that underly the development disease, and to what extent those effects are consistent throughout disease progression, are poorly understood. To address these questions, researchers from Boston University Chobanian & Avedisian School of Medicine conducted genetic analysis of the largest collection of post-mortem CTE brains, primarily from professional athletes, donated to the BU CTE Brain Bank. They found evidence that early and late CTE brains are similar in some ways but dramatically different in others. In particular, neuro-inflammation and neuronal stress are strongly implicated in disease, albeit to different extents and in different directions depending on the severity of disease. This is the first study to show that the molecular pathways involved in early CTE are different from those involved in late-stage disease. "A better understanding of the early CTE disease process may lead to more informative diagnostics, biomarkers and ultimately therapies," said co-corresponding author Adam Thomas Labadorf, Ph.D., assistant professor of neurology. "In addition, since the type of pathology found in the brains of people with CTE is similar to that found in AD, a better understanding of how the brain responds to this kind of pathology in CTE is likely to better inform our understanding AD as well." The researchers studied the prefrontal cortex tissue from 76 individuals (66 CTE, 10 control) who donated their brains to the BU UNITE Brain Bank. The sample set contained brains that spanned the full range of disease severity, affording the researchers the unique opportunity to see whether the gene expression in people with early stage CTE differ from those with late stage. The researchers generated gene expression data for each individual and then performed bioinformatic and statistical analyses of the different subsets of these samples to look for gene expression patterns that are associated with different clinical, histological and genetic markers that are relevant to CTE. They then identified genes and biological processes associated with total years of play as a measure of exposure, amount of tau pathology present at time of death, and the presence of APOE and TMEM106B risk variants. The researchers found substantial gene expression changes were associated with severe disease for most of these factors, primarily implicating diverse, strongly involved neuro-inflammatory and neuro-immune processes. In contrast, low pathology groups had many fewer gene expression changes and neuroimmune or inflammatory processes implicated and showed striking differences for some factors when compared with severe disease. According to the researchers, if the active disease process in early disease differs substantially from late-stage disease, this could have important implications for both diagnostic and therapeutic targets. "This might explain why therapeutic targets identified from late-stage human tissue have largely failed to influence disease progression in clinical trials for many neurodegenerative diseases. In addition, if there are distinct markers of early disease progression that are absent in late disease, this would provide an opportunity to explore different diagnostics and biomarkers that we otherwise wouldn't know to look for," explained co-corresponding author Thor Stein, MD, Ph.D., a neuropathologist at VA Boston Healthcare System and associate professor of pathology and laboratory medicine. These findings appear online in the journal BMC Medical Genomics. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The globally recognized need to advance more sustainable agriculture and food systems has motivated the emergence of transdisciplinary solutions, which include methodologies that utilize the properties of materials at the nanoscale to address extensive and inefficient resource use. Despite the promising prospects of these nanoscale materials, the potential for large-scale applications directly to the environment and to crops necessitates precautionary measures to avoid unintended consequences. Further, the effects of using engineered nanomaterials (ENMs) in agricultural practices cascade throughout their life cycle and include effects from upstream-embodied resources and emissions from ENM production as well as their potential downstream environmental implications. Building on decades-long research in ENM synthesis, biological and environmental interactions, fate, transport and transformation, there is the opportunity to inform the sustainable design of nano-enabled agrochemicals. Here we perform a screening-level analysis that considers the system-wide benefits and costs for opportunities in which ENMs can advance the sustainability of crop-based agriculture. These include their on-farm use as (1) soil amendments to offset nitrogen fertilizer inputs, (2) seed coatings to increase germination rates and (3) foliar sprays to enhance yields. In each analysis, the nano-enabled alternatives are compared against the current practice on the basis of performance and embodied energy. In addition to identifying the ENM compositions and application approaches with the greatest potential to sustainably advance crop production, we present a holistic, prospective, systems-based approach that promotes emerging alternatives that have net performance and environmental benefits. Main The global agriculture system is complex and integrated, and touches nearly all aspects of our daily lives, both directly and indirectly. Agriculture is the cornerstone of a prosperous global society and, therefore, it is critical to maintain and protect it for future generations. Sustainable development of the agriculture and food system has become a priority of prominent national and global organizations. For example, the United Nations Food and Agriculture Organization recognizes the need to advance sustainable agriculture alongside goals to eradicate food insecurity and malnourishment 1 , and half of the United Nations Sustainable Development Goals pertain to food systems, which include directly addressing hunger (Goal 2), clean water (Goal 6) and responsible consumption and production (Goal 12) 2 . In addition, the National Academies of Engineering identify nitrogen (N)-cycle management as one of 14 Grand Challenges for Engineering 3 , and the National Science Foundation recently recognized the critical imbalance of the anthropogenically altered phosphorus (P) cycle 4 . Given the current resource inefficiencies of food-system processes—upstream processing energy, on-farm agrochemical and water resources, and downstream food distribution and waste—innovative approaches are needed to increase the agricultural productivity while minimizing its resource intensity and environmental implications. The 2020 forecasted global agrochemical annual use is 120 × 10 6 t (metric tonnes) for N-based fertilizers 5 , 50 × 10 6 t for phosphate-based fertilizers 5 and over 2.6 × 10 6 t for pesticides 6 . Without efforts to mitigate the environmental impacts of agriculture and technological advancements, food-system impacts (that is, greenhouse gas emissions, cropland and water use, and N and P applications as fertilizers) are estimated to increase 50–90% by 2050 7 . Agrochemicals, which include fertilizers and pesticides, are critical to crop development, and conventional farming practices often overapply to maximize crop yields. Currently, more than 50% of the applied N and 85% of the applied P are not assimilated by crops 8 , 9 , and less than 10% of the applied pesticides reach their targets 10 , 11 , 12 , 13 . Although this practice of overapplication is a feasible on-farm practice in many parts of the world under current raw material costs and availability (for example, primary fertilizer prices per tonne dropped an average of 40% between 2013 and 2017/2018 14 , 15 to as low as US$350 t –1 of potash), more efficient delivery technologies will be needed in the future and are estimated to result in multibillion dollar benefits 16 . Net losses of agrochemicals to the environment introduce contamination to the surrounding ecosystems—soils, surface water and groundwater—which carries substantial adverse human health and environmental consequences (for example, anoxic water bodies, ecotoxicity, loss of biodiversity and contaminated drinking-water sources) 17 , 18 , 19 , 20 . Further, agrochemical losses translate into a substantial waste of embodied resources, both materials and energy. For example, the energy-intense ammonia production by the Haber–Bosch process requires 41.8 GJ t –1 of ammonia 21 , 22 , which translates into 158 PJ annually (based on 2014 US consumption values 23 ). Ammonia production accounts for 80% of the energy consumed by the N-fertilizer industry 24 . The increased investments in innovation and technology that increase N-utilization efficiencies are predicted to aid in achieving future targets with respect to both managing the N cycle and meeting food demands 25 . This will include technical innovations, such as nano-enabled agrochemicals, and the following analysis demonstrates the criticality of considering environmental trade-offs of the entire technology life cycle. Nanoscale material properties can be leveraged to develop agricultural intensification solutions, which is the increase in food production per unit resource (for example, agrochemical and water input, and land area) 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 . Although nanotechnology is also being developed for use across the food system (for example, in chemical and biological sensors, food packaging and water treatment) 12 , 27 , 28 , 35 , 36 , we focus here on the potential for nano-enabled solutions to increase agrochemical use efficiency and enhance crop production. Specifically, we compare the performance, environmental and economic trade-offs of engineered nanomaterials (ENMs) and conventional alternatives in three applications, (1) soil amendments, (2) seed coatings and (3) foliar treatment. The benefits of using ENMs to facilitate crop growth have been reported and attributed to their potential for a targeted delivery to plants and improvements in agrochemical utilization efficiencies 28 , 37 , 38 , 39 , 40 , 41 , 42 , 43 . Yet, the development of nanotechnology to", "role": "user" }, { "content": "A team of researchers affiliated with several institutions in the U.S. has conducted an analysis of the system-wide costs and benefits of using engineered nanomaterials (ENMs) on crop-based agriculture. In their paper published in the journal Nature Nanotechnology, the group describes their analysis and what they found. As scientists have come to realize that vast improvements in agricultural practices are needed if future generations are going to be able to grow enough food to feed the expected rise in population. They have increasingly turned to technology-based solutions, rather than just looking for biological advances. One such approach involves the design and use of ENMs on crops as a means of improving pest control and fertilizer efficiency. Prior research has shown that some ENMs can be mixed into the soil as a form of pest control or as a means of diverting fertilizer directly to the roots, reducing the amount required. In a similar vein, some prior research has shown that ENMs can be applied to parts of the plant above-ground as a means of pest control. What has been less well studied, the researchers note, is the overall impact of ENMs on crops and the environment. In this new effort, they have tested the impact of ENM use on various crops and how they impacted the environment in which they were used. The researchers tested metal-oxide-based ENMs and carbon nanotubes that have been designed to improve fertilizer efficiency, and found their use was no better than crops with no ENMs added. They did, however, find that when ENMs were used as seed coatings or as a leaf spray, they provided additional protection from pests. They next attempted to test the impact of ENM use on the environment and found that there was a potential for such materials to make their way into the water system. They also found there was a potential for ingestion by humans eating the treated crops, with unknown consequences. But they also found that there appeared to be more of an impact on the environment during the manufacture of the ENMs than during their use. They conclude by suggesting that much more research is required on ENMs before they are used as commercial products. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The globally recognized need to advance more sustainable agriculture and food systems has motivated the emergence of transdisciplinary solutions, which include methodologies that utilize the properties of materials at the nanoscale to address extensive and inefficient resource use. Despite the promising prospects of these nanoscale materials, the potential for large-scale applications directly to the environment and to crops necessitates precautionary measures to avoid unintended consequences. Further, the effects of using engineered nanomaterials (ENMs) in agricultural practices cascade throughout their life cycle and include effects from upstream-embodied resources and emissions from ENM production as well as their potential downstream environmental implications. Building on decades-long research in ENM synthesis, biological and environmental interactions, fate, transport and transformation, there is the opportunity to inform the sustainable design of nano-enabled agrochemicals. Here we perform a screening-level analysis that considers the system-wide benefits and costs for opportunities in which ENMs can advance the sustainability of crop-based agriculture. These include their on-farm use as (1) soil amendments to offset nitrogen fertilizer inputs, (2) seed coatings to increase germination rates and (3) foliar sprays to enhance yields. In each analysis, the nano-enabled alternatives are compared against the current practice on the basis of performance and embodied energy. In addition to identifying the ENM compositions and application approaches with the greatest potential to sustainably advance crop production, we present a holistic, prospective, systems-based approach that promotes emerging alternatives that have net performance and environmental benefits. Main The global agriculture system is complex and integrated, and touches nearly all aspects of our daily lives, both directly and indirectly. Agriculture is the cornerstone of a prosperous global society and, therefore, it is critical to maintain and protect it for future generations. Sustainable development of the agriculture and food system has become a priority of prominent national and global organizations. For example, the United Nations Food and Agriculture Organization recognizes the need to advance sustainable agriculture alongside goals to eradicate food insecurity and malnourishment 1 , and half of the United Nations Sustainable Development Goals pertain to food systems, which include directly addressing hunger (Goal 2), clean water (Goal 6) and responsible consumption and production (Goal 12) 2 . In addition, the National Academies of Engineering identify nitrogen (N)-cycle management as one of 14 Grand Challenges for Engineering 3 , and the National Science Foundation recently recognized the critical imbalance of the anthropogenically altered phosphorus (P) cycle 4 . Given the current resource inefficiencies of food-system processes—upstream processing energy, on-farm agrochemical and water resources, and downstream food distribution and waste—innovative approaches are needed to increase the agricultural productivity while minimizing its resource intensity and environmental implications. The 2020 forecasted global agrochemical annual use is 120 × 10 6 t (metric tonnes) for N-based fertilizers 5 , 50 × 10 6 t for phosphate-based fertilizers 5 and over 2.6 × 10 6 t for pesticides 6 . Without efforts to mitigate the environmental impacts of agriculture and technological advancements, food-system impacts (that is, greenhouse gas emissions, cropland and water use, and N and P applications as fertilizers) are estimated to increase 50–90% by 2050 7 . Agrochemicals, which include fertilizers and pesticides, are critical to crop development, and conventional farming practices often overapply to maximize crop yields. Currently, more than 50% of the applied N and 85% of the applied P are not assimilated by crops 8 , 9 , and less than 10% of the applied pesticides reach their targets 10 , 11 , 12 , 13 . Although this practice of overapplication is a feasible on-farm practice in many parts of the world under current raw material costs and availability (for example, primary fertilizer prices per tonne dropped an average of 40% between 2013 and 2017/2018 14 , 15 to as low as US$350 t –1 of potash), more efficient delivery technologies will be needed in the future and are estimated to result in multibillion dollar benefits 16 . Net losses of agrochemicals to the environment introduce contamination to the surrounding ecosystems—soils, surface water and groundwater—which carries substantial adverse human health and environmental consequences (for example, anoxic water bodies, ecotoxicity, loss of biodiversity and contaminated drinking-water sources) 17 , 18 , 19 , 20 . Further, agrochemical losses translate into a substantial waste of embodied resources, both materials and energy. For example, the energy-intense ammonia production by the Haber–Bosch process requires 41.8 GJ t –1 of ammonia 21 , 22 , which translates into 158 PJ annually (based on 2014 US consumption values 23 ). Ammonia production accounts for 80% of the energy consumed by the N-fertilizer industry 24 . The increased investments in innovation and technology that increase N-utilization efficiencies are predicted to aid in achieving future targets with respect to both managing the N cycle and meeting food demands 25 . This will include technical innovations, such as nano-enabled agrochemicals, and the following analysis demonstrates the criticality of considering environmental trade-offs of the entire technology life cycle. Nanoscale material properties can be leveraged to develop agricultural intensification solutions, which is the increase in food production per unit resource (for example, agrochemical and water input, and land area) 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 . Although nanotechnology is also being developed for use across the food system (for example, in chemical and biological sensors, food packaging and water treatment) 12 , 27 , 28 , 35 , 36 , we focus here on the potential for nano-enabled solutions to increase agrochemical use efficiency and enhance crop production. Specifically, we compare the performance, environmental and economic trade-offs of engineered nanomaterials (ENMs) and conventional alternatives in three applications, (1) soil amendments, (2) seed coatings and (3) foliar treatment. The benefits of using ENMs to facilitate crop growth have been reported and attributed to their potential for a targeted delivery to plants and improvements in agrochemical utilization efficiencies 28 , 37 , 38 , 39 , 40 , 41 , 42 , 43 . Yet, the development of nanotechnology to<|im_end|> <|im_start|>assistant A team of researchers affiliated with several institutions in the U.S. has conducted an analysis of the system-wide costs and benefits of using engineered nanomaterials (ENMs) on crop-based agriculture. In their paper published in the journal Nature Nanotechnology, the group describes their analysis and what they found. As scientists have come to realize that vast improvements in agricultural practices are needed if future generations are going to be able to grow enough food to feed the expected rise in population. They have increasingly turned to technology-based solutions, rather than just looking for biological advances. One such approach involves the design and use of ENMs on crops as a means of improving pest control and fertilizer efficiency. Prior research has shown that some ENMs can be mixed into the soil as a form of pest control or as a means of diverting fertilizer directly to the roots, reducing the amount required. In a similar vein, some prior research has shown that ENMs can be applied to parts of the plant above-ground as a means of pest control. What has been less well studied, the researchers note, is the overall impact of ENMs on crops and the environment. In this new effort, they have tested the impact of ENM use on various crops and how they impacted the environment in which they were used. The researchers tested metal-oxide-based ENMs and carbon nanotubes that have been designed to improve fertilizer efficiency, and found their use was no better than crops with no ENMs added. They did, however, find that when ENMs were used as seed coatings or as a leaf spray, they provided additional protection from pests. They next attempted to test the impact of ENM use on the environment and found that there was a potential for such materials to make their way into the water system. They also found there was a potential for ingestion by humans eating the treated crops, with unknown consequences. But they also found that there appeared to be more of an impact on the environment during the manufacture of the ENMs than during their use. They conclude by suggesting that much more research is required on ENMs before they are used as commercial products. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Deep intracontinental earthquakes are poorly understood, despite their potential to cause significant destruction. Although lower crustal strength is currently a topic of debate, dry lower continental crust may be strong under high-grade conditions. Such strength could enable earthquake slip at high differential stress within a predominantly viscous regime, but requires further documentation in nature. Here, we analyse geological observations of seismic structures in exhumed lower crustal rocks. A granulite facies shear zone network dissects an anorthosite intrusion in Lofoten, northern Norway, and separates relatively undeformed, microcracked blocks of anorthosite. In these blocks, pristine pseudotachylytes decorate fault sets that link adjacent or intersecting shear zones. These fossil seismogenic faults are rarely >15 m in length, yet record single-event displacements of tens of centimetres, a slip/length ratio that implies >1 GPa stress drops. These pseudotachylytes represent direct identification of earthquake nucleation as a transient consequence of ongoing, localised aseismic creep. Introduction Earthquake mechanics are mostly studied in the context of the brittle upper crust, where earthquakes predominately occur 1 . However, earthquakes also nucleate in the continental lower crust in mechanically strong lithologies 2 , 3 , 4 . Deep continental earthquakes tend to nucleate along intraplate faults, or faults cutting thick, cold cratons 5 , 6 , 7 , 8 . Earthquakes in continental interiors have resulted in significantly higher casualties than earthquakes at plate boundaries 9 . Thus, a thorough understanding of the earthquake cycle in intracontinental settings is essential, and requires knowledge of the mechanical behaviour and seismogenic potential of the lower crust. The occurrence of pseudotachylytes (solidified frictional melts) formed at lower crustal conditions has been taken as geological evidence of both high mechanical strength and the occurrence of seismic rupture below the typical seismogenic zone 10 , 11 , 12 , 13 , 14 . Seismological observations of lower crustal earthquakes, e.g. in East Africa 2 and in the India-Tibet collision zone 3 , compare favourably with geological studies suggesting a dry, metastable, strong and seismic lower crust 15 , 16 . Earthquakes in dry (e.g. <0.1 wt. % H 2 O 17 ) lower crustal rocks at depths ≥25–30 km require either transiently high differential stresses or local weakening mechanisms (e.g. high pore fluid pressure 5 ). One explanation for transient high stresses is the downward propagation of an earthquake rupture from the shallower seismogenic zone 4 , 18 . These stress spikes account for transient post-mainshock deformation including rapid postseismic strain rates 19 and clusters of aftershocks beneath the mainshock rupture area 4 , 20 , 21 . Whilst large continental earthquakes that nucleate in the upper crust and propagate downwards to depths of 20–25 km are not uncommon 7 , 22 , 23 , 24 , the mechanisms of earthquakes that nucleate within the lower crust are still intensely debated. Proposed mechanisms include thermal-runaway plastic instabilities 25 , dehydration reactions leading to increased fluid pressure 26 and/or local stress redistributions 27 , or eclogitisation reactions 28 . These examples, however, require syn-deformational reactions that may not be occurring in all locations hosting local, lower crustal seismicity. Here we suggest a mechanism where earthquakes nucleate within dry and strong lower crustal rocks without the need of syn-deformational reactions or seismic loading from shallower crustal levels, but rather as a direct consequence of loading of low strain domains during deformation along a network of intersecting ductile shear zones. This is an important advance in our understanding, because this mechanism can explain lower crustal seismicity in regions without shallow seismicity or evidence for fluids, such as deep earthquakes observed in the northern Central Alpine foreland 29 . We characterise an exhumed network of highly localised shear zones recording viscous deformation at lower crustal conditions. We describe the geometry of pseudotachylyte veins that cut between shear zones of varying orientations, outline the evidence that these markers of seismicity were coeval with viscous creep of the shear zones at lower crustal conditions, and use measurements of fault length and displacement to calculate the moment magnitudes and static stress drops of these seismic events. We interpret this mechanism of seismicity to be a mechanical response to strain incompatibility across the shear zone network during localised viscous shear, with strong blocks undergoing seismic failure at points of local stress amplification. This is the first evidence for in-situ, high stress drop earthquake nucleation in the lower crust driven predominantly by the geometry of a shear zone network, as a consequence of differential creep rates and high viscosity contrasts. Results The Nusfjord shear zone network The Lofoten-Vesterålen islands of Norway expose a 1.9–1.7-Ga Anorthosite-Mangerite-Charnockite-Granite suite that extensively preserves an anhydrous granulite facies assemblages 30 . In the SE of Flakstadøy (Supplementary Fig. 1 ) the Nusfjord coarse-grained anorthosite is cut by mylonitic shear zones that were active at 650–750 °C and 0.7–0.8 GPa 31 . The mylonitic shear zones, concentrated within an E-W striking high strain zone of ~1 km apparent thickness, occur in three main sets (Sets 1–3) that match the orientations of regional tectonic lineaments (Fig. 1 ). This high strain zone comprises mylonitic shear zones ranging from numerous narrow (typically 5–20 cm thick) structures to less frequent wider structures consisting of multiple shear zone strands (Figs. 1 and 2 ). Most Set 1 shear zones (average foliation dip/dip direction of 54°/156° and average lineation plunge/azimuth of 48°/184°) include mylonitised pseudotachylytes (type-1 pseudotachylytes) and have accumulated appreciable oblique normal displacement (Fig. 2 ). Set 2 shear zones strike NW-SE (average foliation 82°/050°, and lineation 18°/328°), contain fewer type-1 pseudotachylytes and show sinistral strike-slip movement. Set 3 shear zones are generally minor structures with strike varying from N-S to NE-SW (average foliation orientation of 88°/278°, Fig. 1 ). Fig. 1: Structure of the Nusfjord region. a Map of Nusfjord anorthosite showing locations of shear zones and large dykes. Red shading indicates the extent of the high strain zone containing frequent cross-cutting shear zones. Basemap © OpenStreetMap contributors (openstreetmap.org.uk/copyright). b Block diagram showing three-dimensional structure of interlocking shear zones in various orientations.", "role": "user" }, { "content": "A major international study has shed new light on the mechanisms through which earthquakes are triggered up to 40km beneath the earth's surface. While such earthquakes are unusual, because rocks at those depth are expected to creep slowly and aseismically, they account for around 30 percent of intracontinental seismic activity. Recent examples include a significant proportion of seismicity in the Himalaya as well as aftershocks associated with the 2001 Bhuj earthquake in India. However, very little is presently known about what causes them, in large part due to the fact that any effects are normally hidden deep underground. The current study, published in Nature Communications and funded by the Natural Environment Research Council, sought to understand how such deep earthquakes may be generated. They showed that earthquake ruptures may be encouraged by the interaction of different shear zones that are creeping slowly and aseismically. This interaction loads the adjacent blocks of stiff rocks in the deep crust, until they cannot sustain the rising stress anymore, and snap—generating earthquakes. Emphasising observations of quite complex networks created by earthquake-generated faults, they suggest that this context is characterised by repeating cycles of deformation, with long-term slow creep on the shear zones punctuated by episodic earthquakes. Although only a transient component of such deformation cycles, the earthquakes release a significant proportion of the accumulated stress across the region. The research was led by the University of Plymouth (UK) and University of Oslo (Norway), with scientists conducting geological observations of seismic structures in exhumed lower crustal rocks on the Lofoten Islands. Project scientists in the Lofoton Islands shown in a still from the film Pseudotachylyte. Credit: Heidi Morstang, University of Plymouth The region is home to one of the few well-exposed large sections of exhumed continental lower crust in the world, exposed during the opening of the North Atlantic Ocean. Scientists spent several months in the region, conducting a detailed analysis of the exposed rock and in particular pristine pseudotachylytes (solidified melt produced during seismic slip regarded as 'fossil earthquakes') which decorate fault sets linking adjacent or intersecting shear zones. They also collected samples from the region which were then analysed using cutting edge technology in the University's Plymouth Electron Microscopy Centre. Lead author Dr. Lucy Campbell, Post-Doctoral Research Fellow at the University of Plymouth, said: \"The Lofoten Islands provide an almost unique location in which to examine the impact of earthquakes in the lower crust. But by looking at sections of exposed rock less than 15 metres wide, we were able to see examples of slow-forming rock deformation working to trigger earthquakes generated up to 30km beneath the surface. The model we have now developed provides a novel explanation of the causes and effects of such earthquakes that could be applied at many locations where they occur.\" Project lead Dr. Luca Menegon, Associate Professor at the University of Plymouth and the University of Oslo, added: \"Deep earthquakes can be as destructive as those nucleating closer to the Earth's surface. They often occur in highly populated areas in the interior of the continents, like in Central Asia for example. But while a lot is known about what causes seismic activity in the upper crust, we know far less about those which occur lower. This study gives us a fascinating insight into what is happening deep below the Earth's surface, and our challenge is now to take this research forward and see if we can use it to make at-risk communities more aware of the dangers posed by such activity.\" A trailer for the film Pseuodtachylyte. Credit: Heidi Morstang, University of Plymouth As part of the study, scientists also worked with University of Plymouth filmmaker Heidi Morstang to produce a 60-minute documentary film about their work. Pseudotachylyte premiered at the 2019 Bergen International Film Festival, and will be distributed internationally once it has screened at various other festivals globally. The study, \"Earthquake nucleation in the lower crust by local stress amplification by Campbell et al,\" is published in Nature Communications. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Deep intracontinental earthquakes are poorly understood, despite their potential to cause significant destruction. Although lower crustal strength is currently a topic of debate, dry lower continental crust may be strong under high-grade conditions. Such strength could enable earthquake slip at high differential stress within a predominantly viscous regime, but requires further documentation in nature. Here, we analyse geological observations of seismic structures in exhumed lower crustal rocks. A granulite facies shear zone network dissects an anorthosite intrusion in Lofoten, northern Norway, and separates relatively undeformed, microcracked blocks of anorthosite. In these blocks, pristine pseudotachylytes decorate fault sets that link adjacent or intersecting shear zones. These fossil seismogenic faults are rarely >15 m in length, yet record single-event displacements of tens of centimetres, a slip/length ratio that implies >1 GPa stress drops. These pseudotachylytes represent direct identification of earthquake nucleation as a transient consequence of ongoing, localised aseismic creep. Introduction Earthquake mechanics are mostly studied in the context of the brittle upper crust, where earthquakes predominately occur 1 . However, earthquakes also nucleate in the continental lower crust in mechanically strong lithologies 2 , 3 , 4 . Deep continental earthquakes tend to nucleate along intraplate faults, or faults cutting thick, cold cratons 5 , 6 , 7 , 8 . Earthquakes in continental interiors have resulted in significantly higher casualties than earthquakes at plate boundaries 9 . Thus, a thorough understanding of the earthquake cycle in intracontinental settings is essential, and requires knowledge of the mechanical behaviour and seismogenic potential of the lower crust. The occurrence of pseudotachylytes (solidified frictional melts) formed at lower crustal conditions has been taken as geological evidence of both high mechanical strength and the occurrence of seismic rupture below the typical seismogenic zone 10 , 11 , 12 , 13 , 14 . Seismological observations of lower crustal earthquakes, e.g. in East Africa 2 and in the India-Tibet collision zone 3 , compare favourably with geological studies suggesting a dry, metastable, strong and seismic lower crust 15 , 16 . Earthquakes in dry (e.g. <0.1 wt. % H 2 O 17 ) lower crustal rocks at depths ≥25–30 km require either transiently high differential stresses or local weakening mechanisms (e.g. high pore fluid pressure 5 ). One explanation for transient high stresses is the downward propagation of an earthquake rupture from the shallower seismogenic zone 4 , 18 . These stress spikes account for transient post-mainshock deformation including rapid postseismic strain rates 19 and clusters of aftershocks beneath the mainshock rupture area 4 , 20 , 21 . Whilst large continental earthquakes that nucleate in the upper crust and propagate downwards to depths of 20–25 km are not uncommon 7 , 22 , 23 , 24 , the mechanisms of earthquakes that nucleate within the lower crust are still intensely debated. Proposed mechanisms include thermal-runaway plastic instabilities 25 , dehydration reactions leading to increased fluid pressure 26 and/or local stress redistributions 27 , or eclogitisation reactions 28 . These examples, however, require syn-deformational reactions that may not be occurring in all locations hosting local, lower crustal seismicity. Here we suggest a mechanism where earthquakes nucleate within dry and strong lower crustal rocks without the need of syn-deformational reactions or seismic loading from shallower crustal levels, but rather as a direct consequence of loading of low strain domains during deformation along a network of intersecting ductile shear zones. This is an important advance in our understanding, because this mechanism can explain lower crustal seismicity in regions without shallow seismicity or evidence for fluids, such as deep earthquakes observed in the northern Central Alpine foreland 29 . We characterise an exhumed network of highly localised shear zones recording viscous deformation at lower crustal conditions. We describe the geometry of pseudotachylyte veins that cut between shear zones of varying orientations, outline the evidence that these markers of seismicity were coeval with viscous creep of the shear zones at lower crustal conditions, and use measurements of fault length and displacement to calculate the moment magnitudes and static stress drops of these seismic events. We interpret this mechanism of seismicity to be a mechanical response to strain incompatibility across the shear zone network during localised viscous shear, with strong blocks undergoing seismic failure at points of local stress amplification. This is the first evidence for in-situ, high stress drop earthquake nucleation in the lower crust driven predominantly by the geometry of a shear zone network, as a consequence of differential creep rates and high viscosity contrasts. Results The Nusfjord shear zone network The Lofoten-Vesterålen islands of Norway expose a 1.9–1.7-Ga Anorthosite-Mangerite-Charnockite-Granite suite that extensively preserves an anhydrous granulite facies assemblages 30 . In the SE of Flakstadøy (Supplementary Fig. 1 ) the Nusfjord coarse-grained anorthosite is cut by mylonitic shear zones that were active at 650–750 °C and 0.7–0.8 GPa 31 . The mylonitic shear zones, concentrated within an E-W striking high strain zone of ~1 km apparent thickness, occur in three main sets (Sets 1–3) that match the orientations of regional tectonic lineaments (Fig. 1 ). This high strain zone comprises mylonitic shear zones ranging from numerous narrow (typically 5–20 cm thick) structures to less frequent wider structures consisting of multiple shear zone strands (Figs. 1 and 2 ). Most Set 1 shear zones (average foliation dip/dip direction of 54°/156° and average lineation plunge/azimuth of 48°/184°) include mylonitised pseudotachylytes (type-1 pseudotachylytes) and have accumulated appreciable oblique normal displacement (Fig. 2 ). Set 2 shear zones strike NW-SE (average foliation 82°/050°, and lineation 18°/328°), contain fewer type-1 pseudotachylytes and show sinistral strike-slip movement. Set 3 shear zones are generally minor structures with strike varying from N-S to NE-SW (average foliation orientation of 88°/278°, Fig. 1 ). Fig. 1: Structure of the Nusfjord region. a Map of Nusfjord anorthosite showing locations of shear zones and large dykes. Red shading indicates the extent of the high strain zone containing frequent cross-cutting shear zones. Basemap © OpenStreetMap contributors (openstreetmap.org.uk/copyright). b Block diagram showing three-dimensional structure of interlocking shear zones in various orientations.<|im_end|> <|im_start|>assistant A major international study has shed new light on the mechanisms through which earthquakes are triggered up to 40km beneath the earth's surface. While such earthquakes are unusual, because rocks at those depth are expected to creep slowly and aseismically, they account for around 30 percent of intracontinental seismic activity. Recent examples include a significant proportion of seismicity in the Himalaya as well as aftershocks associated with the 2001 Bhuj earthquake in India. However, very little is presently known about what causes them, in large part due to the fact that any effects are normally hidden deep underground. The current study, published in Nature Communications and funded by the Natural Environment Research Council, sought to understand how such deep earthquakes may be generated. They showed that earthquake ruptures may be encouraged by the interaction of different shear zones that are creeping slowly and aseismically. This interaction loads the adjacent blocks of stiff rocks in the deep crust, until they cannot sustain the rising stress anymore, and snap—generating earthquakes. Emphasising observations of quite complex networks created by earthquake-generated faults, they suggest that this context is characterised by repeating cycles of deformation, with long-term slow creep on the shear zones punctuated by episodic earthquakes. Although only a transient component of such deformation cycles, the earthquakes release a significant proportion of the accumulated stress across the region. The research was led by the University of Plymouth (UK) and University of Oslo (Norway), with scientists conducting geological observations of seismic structures in exhumed lower crustal rocks on the Lofoten Islands. Project scientists in the Lofoton Islands shown in a still from the film Pseudotachylyte. Credit: Heidi Morstang, University of Plymouth The region is home to one of the few well-exposed large sections of exhumed continental lower crust in the world, exposed during the opening of the North Atlantic Ocean. Scientists spent several months in the region, conducting a detailed analysis of the exposed rock and in particular pristine pseudotachylytes (solidified melt produced during seismic slip regarded as 'fossil earthquakes') which decorate fault sets linking adjacent or intersecting shear zones. They also collected samples from the region which were then analysed using cutting edge technology in the University's Plymouth Electron Microscopy Centre. Lead author Dr. Lucy Campbell, Post-Doctoral Research Fellow at the University of Plymouth, said: "The Lofoten Islands provide an almost unique location in which to examine the impact of earthquakes in the lower crust. But by looking at sections of exposed rock less than 15 metres wide, we were able to see examples of slow-forming rock deformation working to trigger earthquakes generated up to 30km beneath the surface. The model we have now developed provides a novel explanation of the causes and effects of such earthquakes that could be applied at many locations where they occur." Project lead Dr. Luca Menegon, Associate Professor at the University of Plymouth and the University of Oslo, added: "Deep earthquakes can be as destructive as those nucleating closer to the Earth's surface. They often occur in highly populated areas in the interior of the continents, like in Central Asia for example. But while a lot is known about what causes seismic activity in the upper crust, we know far less about those which occur lower. This study gives us a fascinating insight into what is happening deep below the Earth's surface, and our challenge is now to take this research forward and see if we can use it to make at-risk communities more aware of the dangers posed by such activity." A trailer for the film Pseuodtachylyte. Credit: Heidi Morstang, University of Plymouth As part of the study, scientists also worked with University of Plymouth filmmaker Heidi Morstang to produce a 60-minute documentary film about their work. Pseudotachylyte premiered at the 2019 Bergen International Film Festival, and will be distributed internationally once it has screened at various other festivals globally. The study, "Earthquake nucleation in the lower crust by local stress amplification by Campbell et al," is published in Nature Communications. <|im_end|>

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2,340

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Historically, graphene-based transistor fabrication has been time-consuming due to the high demand for carefully controlled Raman spectroscopy, physical vapor deposition, and lift-off processes. For the first time in a three-terminal graphene field-effect transistor embodiment, we introduce a rapid fabrication technique that implements non-toxic eutectic liquid-metal Galinstan interconnects and an electrolytic gate dielectric comprised of honey. The goal is to minimize cost and turnaround time between fabrication runs; thereby, allowing researchers to focus on the characterization of graphene phenomena that drives innovation rather than a lengthy device fabrication process that hinders it. We demonstrate characteristic Dirac peaks for a single-gate graphene field-effect transistor embodiment that exhibits hole and electron mobilities of 213 ± 15 and 166 ± 5 cm 2 / V · s respectively. We discuss how our methods can be used for the rapid determination of graphene quality and can complement Raman Spectroscopy techniques. Lastly, we explore a PN junction embodiment which further validates that our fabrication techniques can rapidly adapt to alternative device architectures and greatly broaden the research applicability. Introduction The lowering cost of graphene synthesis has created opportunities that include lightweight electronics such as wearable, flexible, and electromagnetic sensors 1 . However, to explore such scientific phenomena one must be trained and certified in sophisticated optical characterization and microfabrication techniques to design and fabricate graphene devices such as graphene field-effect transistors (GFETs). Furthermore, the complexity of the required fabrication steps must be conducted in a controlled environment to increase device yield and minimize exposure to harmful chemicals. This process can be quite time-consuming and demanding depending on the scope of the device architecture and the allotted time given for expenditure of project funds. Such drawbacks reduce the accessibility of graphene research across academic and private institutions. In a typical GFET fabrication process, graphene is synthesized via chemical vapor deposition and transferred onto a target substrate via delamination and the graphene quality is measured via Raman Spectroscopy. Lift-off processes are then used to construct contact electrodes, gate-dielectrics, and gate-contacts 2 , 3 , 4 , 5 , 6 , 7 . Unfortunately, numerous articles have reported degradation in graphene transistor performance due to mechanical and electrical strain put on graphene that is a direct result of photolithography and physical vapor deposition 8 , 9 , 10 . In addition, graphene has been shown to exhibit high contact resistance with standard electrode materials relative to its size that create non-ideal performance across the board 11 . This performance limitation will potentially force a researcher back into the cleanroom to identify drawbacks in his or her fabrication process. In this paper, we demonstrate the rapid fabrication of a three-terminal graphene-field effect transistor embodiment with the use of commercially available eutectic liquid-metal Galinstan interconnects and electrolytic gate dielectric comprised of honey ( LM-GFET ). We demonstrate comparable GFET performance with the proposed inexpensive, non-traditional materials to much more common ionic gel materials 12 , 13 . Galinstan is a non-toxic liquid-metal alloy consisting of 68.5% gallium, 21.5% indium, and 10% tin 14 that possesses desirable conformal properties. In a previous study, Galinstan device interconnects exhibited less than a 5.5% change in resistance for a graphene two-terminal device when subjected to repeated deformations as small as 4.5 mm radius of curvature 15 . Moreover, graphene transistors can greatly benefit from the conductivity of Galinstan (2.30 × 10 6 S / m ), a desirable vapor pressure (<1 × 10 −6 Pa at 500 ° C ) compared with mercury (0.1713 Pa at 20 ° C ), and a stable liquid state across a broad temperature range (−19 ° C to 1300 ° C ) 16 . Honey is typically produced via sugary secretions from bees, harvested, and packaged under various brand names for commercial food consumption. Honey contains various concentrations of water, vitamins, minerals, amino acids, and sugars: fructose, glucose, sucrose that can be controlled via bee production and honey extraction techniques 17 . To our benefit, honey formulates an ionic gel-like solution analogous to ion gels. Ion gels consist of room-temperature ionic liquids and gelating triblock copolymers 12 , 13 . Recently, ion gels have demonstrated ideal performance as electrolytic gate dielectrics for flexible GFET devices due to an ability to produce extremely high capacitance and high dielectric constants required for high on-current and low-voltage operation 12 . The introduction of honey as an electrolytic gate dielectric is advantageous for rapid fabrication of GFET devices due to the commercial availability, non-toxicity, control of ionic content that can be used to alter dielectric properties, and quick mixing that reduces preparation time of honey. Currently, ion gels require special preparation in an atmospheric controlled environment to mitigate outgassing and combustion, which only adds to its complexity. Results and Discussion Transistor Architecture and Operation The transistor architecture of the LM-GFET device is shown in Fig. 1a and an image of the LM-GFET is shown in Fig. 1c . The device is comprised of liquid-metal Galinstan source and drain electrodes that are overlaid on monolayer graphene transferred to Polyethylene Terephthalate (PET). A detailed fabrication process for the LM-GFET device is described in the Methods Section. Honey, was used as a gel-like electrolytic gate dielectric to generate an enhanced electric field-effect response above graphene. Due to the presence of ions and high polarizability of honey, a diffusion of charge is formed at the thin layer between honey and graphene. This layer forms an electric double layer and is typical when ionic liquids contact conductive materials 12 , 13 . Due to the nanoscale separation distance of the electric double layer, usually from 1-10 nm , a large charge gradient is formed on the surface of graphene. For example, in the case a gate electrode is positively charged and submerged in honey, anions will accumulate at the gate/honey interface and cations will accumulate at the honey/graphene interface. The resultant electrical double layer at the honey/graphene interface will then alter the graphene conductivity, Fig. 1d . The opposite is true for the case in which the", "role": "user" }, { "content": "Dr. Richard Ordonez, a nanomaterials scientist at the Space and Naval Warfare Systems Center Pacific (SSC Pacific), was having stomach pains last year. So begins the story of the accidental discovery that honey—yes, the bee byproduct—is an effective, non-toxic substitute for the manipulation of the current and voltage characteristics of graphene. Ordonez' lab mate and friend Cody Hayashi gave him some store-bought honey as a Christmas gift and anti-inflammatory for his stomach, and Ordonez kept it near his work station for daily use. One day in the lab, the duo was investigating various dielectric materials they could use to fabricate a graphene transistor. First, the team tried to utilize water as a top-gate dielectric to manipulate graphene's electrical conductivity. This approach was unsuccessful, so they proceeded with various compositions of sugar and deionized water, another electrolyte, which still resulted in negligible performance. That's when the honey caught Ordonez' eye, and an accidental scientific breakthrough was realized. The finding is detailed in a paper in Nature Scientific Reports, in which the team describes how honey produces a nanometer-sized electric double layer at the interface with graphene that can be used to gate the ambipolar transport of graphene. \"As a top-gate dielectric, water is much too conductive, so we moved to sugar and de-ionized water to control the ionic composition in hopes we could reduce conductivity,\" Ordonez explained. \"However, sugar water didn't work for us either because, as a gate-dielectric, there was still too much leakage current. Out of frustration, literally inches away from me was the honey Cody had bought, so we decided to drop-cast the honey on graphene to act as top-gate dielectric— I thought maybe the honey would mimic dielectric gels I read about in literature. To our surprise—everyone said it's not going to work—we tried and it did.\" Ordonez, Hayashi, and a team of researchers from SSC Pacific, in collaboration with the University of Hawai′i at Mānoa, have been developing novel graphene devices as part of a Navy Innovative Science and Engineering (NISE)-funded effort to imbue the Navy with inexpensive, lightweight, flexible graphene-based devices that can be used as next-generation sensors and wearable devices. \"Traditionally, electrolytic gate transistors are made with ionic gel materials,\" Hayashi said. \"But you must be proficient with the processes to synthesize them, and it can take several months to figure out the correct recipe that is required for these gels to function in the environment. Some of the liquids are toxic, so experimentation must be conducted in an atmospheric-controlled environment. Honey is completely different—it performs similarly to these much more sophisticated materials, but is safe, inexpensive, and easier to use. The honey was an intermediate step towards using ionic gels, and possibly a replacement for certain applications.\" Ordonez and Hayashi envision the honey-based version of graphene products being used for rapid prototyping of devices, since the devices can be created quickly and easily redesigned based on results. Instead of having to spend months developing the materials before even beginning to incorporate it into devices, using honey allows the team to get initial tests underway without waiting for costly fabrication equipment. Ordonez also sees a use for such products in science, technology, engineering and math (STEM) outreach efforts, since the honey is non-toxic and could be used to teach students about graphene. This latest innovation and publication was a follow-on from the group's discovery last year that liquid metals can be used in place of rigid electrodes such as gold and silver to electrically contact graphene. This, coupled with research on graphene and multi-spectral detection, earned them the Federal Laboratory Consortium Far West Regional Award in the category of Outstanding Technology Development. SSC Pacific is the naval research and development lab responsible for ensuring Information Warfare superiority for warfighters, including the areas of cyber, command and control, intelligence, surveillance and reconnaissance, and space systems. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Historically, graphene-based transistor fabrication has been time-consuming due to the high demand for carefully controlled Raman spectroscopy, physical vapor deposition, and lift-off processes. For the first time in a three-terminal graphene field-effect transistor embodiment, we introduce a rapid fabrication technique that implements non-toxic eutectic liquid-metal Galinstan interconnects and an electrolytic gate dielectric comprised of honey. The goal is to minimize cost and turnaround time between fabrication runs; thereby, allowing researchers to focus on the characterization of graphene phenomena that drives innovation rather than a lengthy device fabrication process that hinders it. We demonstrate characteristic Dirac peaks for a single-gate graphene field-effect transistor embodiment that exhibits hole and electron mobilities of 213 ± 15 and 166 ± 5 cm 2 / V · s respectively. We discuss how our methods can be used for the rapid determination of graphene quality and can complement Raman Spectroscopy techniques. Lastly, we explore a PN junction embodiment which further validates that our fabrication techniques can rapidly adapt to alternative device architectures and greatly broaden the research applicability. Introduction The lowering cost of graphene synthesis has created opportunities that include lightweight electronics such as wearable, flexible, and electromagnetic sensors 1 . However, to explore such scientific phenomena one must be trained and certified in sophisticated optical characterization and microfabrication techniques to design and fabricate graphene devices such as graphene field-effect transistors (GFETs). Furthermore, the complexity of the required fabrication steps must be conducted in a controlled environment to increase device yield and minimize exposure to harmful chemicals. This process can be quite time-consuming and demanding depending on the scope of the device architecture and the allotted time given for expenditure of project funds. Such drawbacks reduce the accessibility of graphene research across academic and private institutions. In a typical GFET fabrication process, graphene is synthesized via chemical vapor deposition and transferred onto a target substrate via delamination and the graphene quality is measured via Raman Spectroscopy. Lift-off processes are then used to construct contact electrodes, gate-dielectrics, and gate-contacts 2 , 3 , 4 , 5 , 6 , 7 . Unfortunately, numerous articles have reported degradation in graphene transistor performance due to mechanical and electrical strain put on graphene that is a direct result of photolithography and physical vapor deposition 8 , 9 , 10 . In addition, graphene has been shown to exhibit high contact resistance with standard electrode materials relative to its size that create non-ideal performance across the board 11 . This performance limitation will potentially force a researcher back into the cleanroom to identify drawbacks in his or her fabrication process. In this paper, we demonstrate the rapid fabrication of a three-terminal graphene-field effect transistor embodiment with the use of commercially available eutectic liquid-metal Galinstan interconnects and electrolytic gate dielectric comprised of honey ( LM-GFET ). We demonstrate comparable GFET performance with the proposed inexpensive, non-traditional materials to much more common ionic gel materials 12 , 13 . Galinstan is a non-toxic liquid-metal alloy consisting of 68.5% gallium, 21.5% indium, and 10% tin 14 that possesses desirable conformal properties. In a previous study, Galinstan device interconnects exhibited less than a 5.5% change in resistance for a graphene two-terminal device when subjected to repeated deformations as small as 4.5 mm radius of curvature 15 . Moreover, graphene transistors can greatly benefit from the conductivity of Galinstan (2.30 × 10 6 S / m ), a desirable vapor pressure (<1 × 10 −6 Pa at 500 ° C ) compared with mercury (0.1713 Pa at 20 ° C ), and a stable liquid state across a broad temperature range (−19 ° C to 1300 ° C ) 16 . Honey is typically produced via sugary secretions from bees, harvested, and packaged under various brand names for commercial food consumption. Honey contains various concentrations of water, vitamins, minerals, amino acids, and sugars: fructose, glucose, sucrose that can be controlled via bee production and honey extraction techniques 17 . To our benefit, honey formulates an ionic gel-like solution analogous to ion gels. Ion gels consist of room-temperature ionic liquids and gelating triblock copolymers 12 , 13 . Recently, ion gels have demonstrated ideal performance as electrolytic gate dielectrics for flexible GFET devices due to an ability to produce extremely high capacitance and high dielectric constants required for high on-current and low-voltage operation 12 . The introduction of honey as an electrolytic gate dielectric is advantageous for rapid fabrication of GFET devices due to the commercial availability, non-toxicity, control of ionic content that can be used to alter dielectric properties, and quick mixing that reduces preparation time of honey. Currently, ion gels require special preparation in an atmospheric controlled environment to mitigate outgassing and combustion, which only adds to its complexity. Results and Discussion Transistor Architecture and Operation The transistor architecture of the LM-GFET device is shown in Fig. 1a and an image of the LM-GFET is shown in Fig. 1c . The device is comprised of liquid-metal Galinstan source and drain electrodes that are overlaid on monolayer graphene transferred to Polyethylene Terephthalate (PET). A detailed fabrication process for the LM-GFET device is described in the Methods Section. Honey, was used as a gel-like electrolytic gate dielectric to generate an enhanced electric field-effect response above graphene. Due to the presence of ions and high polarizability of honey, a diffusion of charge is formed at the thin layer between honey and graphene. This layer forms an electric double layer and is typical when ionic liquids contact conductive materials 12 , 13 . Due to the nanoscale separation distance of the electric double layer, usually from 1-10 nm , a large charge gradient is formed on the surface of graphene. For example, in the case a gate electrode is positively charged and submerged in honey, anions will accumulate at the gate/honey interface and cations will accumulate at the honey/graphene interface. The resultant electrical double layer at the honey/graphene interface will then alter the graphene conductivity, Fig. 1d . The opposite is true for the case in which the<|im_end|> <|im_start|>assistant Dr. Richard Ordonez, a nanomaterials scientist at the Space and Naval Warfare Systems Center Pacific (SSC Pacific), was having stomach pains last year. So begins the story of the accidental discovery that honey—yes, the bee byproduct—is an effective, non-toxic substitute for the manipulation of the current and voltage characteristics of graphene. Ordonez' lab mate and friend Cody Hayashi gave him some store-bought honey as a Christmas gift and anti-inflammatory for his stomach, and Ordonez kept it near his work station for daily use. One day in the lab, the duo was investigating various dielectric materials they could use to fabricate a graphene transistor. First, the team tried to utilize water as a top-gate dielectric to manipulate graphene's electrical conductivity. This approach was unsuccessful, so they proceeded with various compositions of sugar and deionized water, another electrolyte, which still resulted in negligible performance. That's when the honey caught Ordonez' eye, and an accidental scientific breakthrough was realized. The finding is detailed in a paper in Nature Scientific Reports, in which the team describes how honey produces a nanometer-sized electric double layer at the interface with graphene that can be used to gate the ambipolar transport of graphene. "As a top-gate dielectric, water is much too conductive, so we moved to sugar and de-ionized water to control the ionic composition in hopes we could reduce conductivity," Ordonez explained. "However, sugar water didn't work for us either because, as a gate-dielectric, there was still too much leakage current. Out of frustration, literally inches away from me was the honey Cody had bought, so we decided to drop-cast the honey on graphene to act as top-gate dielectric— I thought maybe the honey would mimic dielectric gels I read about in literature. To our surprise—everyone said it's not going to work—we tried and it did." Ordonez, Hayashi, and a team of researchers from SSC Pacific, in collaboration with the University of Hawai′i at Mānoa, have been developing novel graphene devices as part of a Navy Innovative Science and Engineering (NISE)-funded effort to imbue the Navy with inexpensive, lightweight, flexible graphene-based devices that can be used as next-generation sensors and wearable devices. "Traditionally, electrolytic gate transistors are made with ionic gel materials," Hayashi said. "But you must be proficient with the processes to synthesize them, and it can take several months to figure out the correct recipe that is required for these gels to function in the environment. Some of the liquids are toxic, so experimentation must be conducted in an atmospheric-controlled environment. Honey is completely different—it performs similarly to these much more sophisticated materials, but is safe, inexpensive, and easier to use. The honey was an intermediate step towards using ionic gels, and possibly a replacement for certain applications." Ordonez and Hayashi envision the honey-based version of graphene products being used for rapid prototyping of devices, since the devices can be created quickly and easily redesigned based on results. Instead of having to spend months developing the materials before even beginning to incorporate it into devices, using honey allows the team to get initial tests underway without waiting for costly fabrication equipment. Ordonez also sees a use for such products in science, technology, engineering and math (STEM) outreach efforts, since the honey is non-toxic and could be used to teach students about graphene. This latest innovation and publication was a follow-on from the group's discovery last year that liquid metals can be used in place of rigid electrodes such as gold and silver to electrically contact graphene. This, coupled with research on graphene and multi-spectral detection, earned them the Federal Laboratory Consortium Far West Regional Award in the category of Outstanding Technology Development. SSC Pacific is the naval research and development lab responsible for ensuring Information Warfare superiority for warfighters, including the areas of cyber, command and control, intelligence, surveillance and reconnaissance, and space systems. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract We present orbital bistatic radar observations of a small-body, acquired during occultation by the Dawn spacecraft at asteroid Vesta. The radar forward-scattering properties of different reflection sites are used to assess the textural properties of Vesta’s surface at centimeter-to-decimeter scales and are compared to subsurface hydrogen concentrations observed by Dawnʼs Gamma Ray and Neutron Detector to assess potential volatile occurrence in the surface and shallow subsurface. We observe significant differences in surface radar reflectivity, implying substantial spatial variations in centimeter-to-decimeter-scale surface roughness. Our results suggest that unlike the Moon, Vesta’s surface roughness variations cannot be explained by cratering processes only. In particular, the occurrence of heightened hydrogen concentrations within large smoother terrains (over hundreds of square kilometers) suggests that potential ground-ice presence may have contributed to the formation of Vesta’s current surface texture. Our observations are consistent with geomorphological evidence of transient water flow from Dawn Framing Camera images. Introduction Using the communications antenna aboard the NASA Dawn spacecraft, we conducted the first orbital bistatic radar (BSR) observations of a small body at asteroid Vesta at grazing incidence angles during entry and exit from occultations. In this configuration, Dawn’s high-gain telecommunications antenna (HGA) transmitted X-band radio waves during its orbit of Vesta, while the Deep Space Network (DSN) 70-meter antennas received the signal on Earth. Dawn’s orbital trajectory was designed to ensure that the spacecraft’s HGA communications antenna would almost constantly be in the line of sight with ground stations on Earth 1 , but on occasion, the spacecraft inevitably passed into occultation behind Vesta—lasting as briefly as 5 min or as long as 33 min. By continuously transmitting basic telemetry data from Dawn’s antennas during these events, the opportunity arose to observe surface reflections of HGA-transmitted radar waves from Vesta’s surface. Over the past decades, orbital BSR experiments have been used to assess the textural (and in some cases, dielectric) properties of the surfaces of terrestrial bodies such as Mercury 2 , Venus 3 , the Moon 4 , 5 , 6 , Mars 7 , 8 , Saturn’s moon Titan 9 , and now comet 67P/CG 10 . In contrast to most orbital BSR experiments, Dawn’s HGA beam intersected Vesta’s surface at grazing angles of incidence near 89° and in a microgravity environment with substantial variability in its gravity field 11 , leading to a low and variable orbital velocity and hence a more challenging detection of the Doppler-shifted surface echo (hereafter simply referred to as the “surface echo”). While the Mars Global Surveyor (MGS), for instance, orbited at ~3,400 m s −1 with respect to Mars’ rotating surface during its BSR experiment, Dawn orbited Vesta at a relative velocity of only ~200 m s −1 . A high orbital velocity like that of the MGS results in a large Doppler shift between surface-reflected echoes and the direct signal, which greatly simplifies the need to distinguish the two peaks during spectral analysis. In the case of Dawn’s BSR observations of Vesta, however, much shorter averaging time and higher frequency resolution is needed to distinguish surface echoes 12 . Through radar power spectral signal analysis of each surface echo, we assess relative surface roughness at centimeter-to-decimeter scales on Vesta and address its application to understanding the textural evolution of the surface. This is accomplished by measuring the radar cross section σ of each area that is illuminated by the radar lobe of Dawn’s HGA (hereafter referred to as the “site” or the “echo site”), which quantifies the cross-sectional surface area that—if equally scattering in all directions—would reflect the echo power measured at the receiver. Hence, larger values of σ are associated with stronger echoes. In turn, echo strength depends on the roughness of the surface at wavelength scales, the angle of incidence, and the intrinsic reflective and absorptive (dielectric) properties of Vesta’s surface material at radar wavelengths. Assuming each surface echo is measured at the same angle of incidence and is reflected from equal surface area, we normalize σ to the site of strongest reflection and use estimated dielectric properties of the surface material to assess relative centimeter-to-decimeter-scale surface roughness on Vesta with respect to a given reference site. Through the comparison of relative surface roughness with estimated surface ages of geologic units based on two crater counting methods 13 , we assess the physical processes that shaped Vesta’s surface roughness at the same scales as done previously for the Moon (e.g., ref. 14 ). In turn, surface roughness provides insight into the shock history of the body 15 and identification of fracturing mechanisms, such as those resulting from thermal erosion caused by diurnal expansion and contraction of volatiles within the surface host rocks 16 . The comparison of relative roughness with observations of hydrogen concentration [H] from Dawn’s Gamma Ray and Neutron Detector (GRaND 17 ); with hydrated material distribution from Dawn’s Visible and Infrared Mapping Spectrometer (VIR 18 ); and with surface thermal inertia and associated multi-meter-scale topography modeled from VIR data 19 enable further investigation into the relationship between volatile presence and centimeter-to-decimeter-scale surface roughness. Characterizing the roughness properties of Vesta’s surface and of other small bodies is also key to assessing landing, anchoring, sampling, and surface trafficability in future missions 20 . Given the low risk, low operational constraints, and opportunistic nature of the orbital BSR experiment by Dawn, other planetary missions can conduct similar observations even in the case of unlikely major science payload failure. Orbital BSR can also be used to constrain ambiguities associated with surface roughness and, potentially, surface dielectric properties of other small bodies as is proposed for the Jupiter Icy Moons Explorer (JUICE) mission at Ganymede 21 . In our study of Dawn’s BSR observations of asteroid Vesta, we successfully detect radar echoes from Vesta’s surface and find significant variations of radar reflectivity across the surface—where stronger surface echoes suggest smoother surfaces. Unlike the Moon, however, Vesta’s surface roughness variations cannot be explained by cratering only—particularly where smoother areas overlap areas of heightened [H], suggesting that volatile-involved processes have", "role": "user" }, { "content": "Research at the USC Viterbi School of Engineering has revealed new evidence for the occurrence of ground ice on the protoplanet Vesta. The work, under the sponsorship of NASA's Planetary Geology and Geophysics program, is part of ongoing efforts at USC Viterbi to improve water detectability techniques in terrestrial and planetary subsurfaces using radar and microwave imaging techniques. The study, conducted at USC Viterbi in the Ming Hsieh Department of Electrical Engineering by research scientist Essam Heggy and graduate student Elizabeth Palmer from Western Michigan University, took over three years to complete and was featured in the journal Nature Communications on its Sept. 12 release. Heggy is a member of the Ming Hsieh Department of Electrical Engineering's Mixil Lab, which is led by professor Mahta Moghaddam and specializes in radar and microwave imaging. Vesta is located in the asteroid belt between Mars and Jupiter and, due to its large size, is believed to be a differentiated body with a core and a mantle just like our own planet. Collisions between asteroids in the belt enable them to leave their orbits and travel great distances in the solar system, potentially colliding with other planetary bodies. Finding ice on these bodies is of major importance to understanding the transport and evolution of water-rich materials in our solar system. The team used a special technique called \"bistatic radar\" on the Dawn spacecraft to explore the surface texture of Vesta at the scale of a few inches. On some orbits, when the spacecraft was about to travel behind Vesta from Earth's perspective, its radio communications waves bounced off Vesta's surface, and mission personnel on the ground at NASA's Jet Propulsion Laboratory (JPL) received the signals back on Earth. According to Heggy, this system of radar signaling was like \"seeing a flame from a lighter in the middle of day from the opposite side of the United States.\" Despite the challenges in measuring such a weak signal from the Dawn Spacecraft communication antenna from nearly 300 million miles away, the team assessed the occurrence of large, smooth areas on Vesta that correlated with the occurrence of higher concentration of hydrogen as measured by the gamma ray and neutron detector (GRaND) instrument onboard. \"I am excited that we were able to perform such an observation on Vesta. At USC we have been contributing to testing and developing several bistatic radar methods to explore water and ice on planetary surfaces and arid areas of Earth. As the largest research university located in an arid area of the planet, this effort is a natural outgrowth of our focus on understanding water evolution,\" Heggy said. The USC researchers hope their work will get the public excited not just about water in space, but also about the importance of understanding water evolution in arid areas under changing climatic conditions. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract We present orbital bistatic radar observations of a small-body, acquired during occultation by the Dawn spacecraft at asteroid Vesta. The radar forward-scattering properties of different reflection sites are used to assess the textural properties of Vesta’s surface at centimeter-to-decimeter scales and are compared to subsurface hydrogen concentrations observed by Dawnʼs Gamma Ray and Neutron Detector to assess potential volatile occurrence in the surface and shallow subsurface. We observe significant differences in surface radar reflectivity, implying substantial spatial variations in centimeter-to-decimeter-scale surface roughness. Our results suggest that unlike the Moon, Vesta’s surface roughness variations cannot be explained by cratering processes only. In particular, the occurrence of heightened hydrogen concentrations within large smoother terrains (over hundreds of square kilometers) suggests that potential ground-ice presence may have contributed to the formation of Vesta’s current surface texture. Our observations are consistent with geomorphological evidence of transient water flow from Dawn Framing Camera images. Introduction Using the communications antenna aboard the NASA Dawn spacecraft, we conducted the first orbital bistatic radar (BSR) observations of a small body at asteroid Vesta at grazing incidence angles during entry and exit from occultations. In this configuration, Dawn’s high-gain telecommunications antenna (HGA) transmitted X-band radio waves during its orbit of Vesta, while the Deep Space Network (DSN) 70-meter antennas received the signal on Earth. Dawn’s orbital trajectory was designed to ensure that the spacecraft’s HGA communications antenna would almost constantly be in the line of sight with ground stations on Earth 1 , but on occasion, the spacecraft inevitably passed into occultation behind Vesta—lasting as briefly as 5 min or as long as 33 min. By continuously transmitting basic telemetry data from Dawn’s antennas during these events, the opportunity arose to observe surface reflections of HGA-transmitted radar waves from Vesta’s surface. Over the past decades, orbital BSR experiments have been used to assess the textural (and in some cases, dielectric) properties of the surfaces of terrestrial bodies such as Mercury 2 , Venus 3 , the Moon 4 , 5 , 6 , Mars 7 , 8 , Saturn’s moon Titan 9 , and now comet 67P/CG 10 . In contrast to most orbital BSR experiments, Dawn’s HGA beam intersected Vesta’s surface at grazing angles of incidence near 89° and in a microgravity environment with substantial variability in its gravity field 11 , leading to a low and variable orbital velocity and hence a more challenging detection of the Doppler-shifted surface echo (hereafter simply referred to as the “surface echo”). While the Mars Global Surveyor (MGS), for instance, orbited at ~3,400 m s −1 with respect to Mars’ rotating surface during its BSR experiment, Dawn orbited Vesta at a relative velocity of only ~200 m s −1 . A high orbital velocity like that of the MGS results in a large Doppler shift between surface-reflected echoes and the direct signal, which greatly simplifies the need to distinguish the two peaks during spectral analysis. In the case of Dawn’s BSR observations of Vesta, however, much shorter averaging time and higher frequency resolution is needed to distinguish surface echoes 12 . Through radar power spectral signal analysis of each surface echo, we assess relative surface roughness at centimeter-to-decimeter scales on Vesta and address its application to understanding the textural evolution of the surface. This is accomplished by measuring the radar cross section σ of each area that is illuminated by the radar lobe of Dawn’s HGA (hereafter referred to as the “site” or the “echo site”), which quantifies the cross-sectional surface area that—if equally scattering in all directions—would reflect the echo power measured at the receiver. Hence, larger values of σ are associated with stronger echoes. In turn, echo strength depends on the roughness of the surface at wavelength scales, the angle of incidence, and the intrinsic reflective and absorptive (dielectric) properties of Vesta’s surface material at radar wavelengths. Assuming each surface echo is measured at the same angle of incidence and is reflected from equal surface area, we normalize σ to the site of strongest reflection and use estimated dielectric properties of the surface material to assess relative centimeter-to-decimeter-scale surface roughness on Vesta with respect to a given reference site. Through the comparison of relative surface roughness with estimated surface ages of geologic units based on two crater counting methods 13 , we assess the physical processes that shaped Vesta’s surface roughness at the same scales as done previously for the Moon (e.g., ref. 14 ). In turn, surface roughness provides insight into the shock history of the body 15 and identification of fracturing mechanisms, such as those resulting from thermal erosion caused by diurnal expansion and contraction of volatiles within the surface host rocks 16 . The comparison of relative roughness with observations of hydrogen concentration [H] from Dawn’s Gamma Ray and Neutron Detector (GRaND 17 ); with hydrated material distribution from Dawn’s Visible and Infrared Mapping Spectrometer (VIR 18 ); and with surface thermal inertia and associated multi-meter-scale topography modeled from VIR data 19 enable further investigation into the relationship between volatile presence and centimeter-to-decimeter-scale surface roughness. Characterizing the roughness properties of Vesta’s surface and of other small bodies is also key to assessing landing, anchoring, sampling, and surface trafficability in future missions 20 . Given the low risk, low operational constraints, and opportunistic nature of the orbital BSR experiment by Dawn, other planetary missions can conduct similar observations even in the case of unlikely major science payload failure. Orbital BSR can also be used to constrain ambiguities associated with surface roughness and, potentially, surface dielectric properties of other small bodies as is proposed for the Jupiter Icy Moons Explorer (JUICE) mission at Ganymede 21 . In our study of Dawn’s BSR observations of asteroid Vesta, we successfully detect radar echoes from Vesta’s surface and find significant variations of radar reflectivity across the surface—where stronger surface echoes suggest smoother surfaces. Unlike the Moon, however, Vesta’s surface roughness variations cannot be explained by cratering only—particularly where smoother areas overlap areas of heightened [H], suggesting that volatile-involved processes have<|im_end|> <|im_start|>assistant Research at the USC Viterbi School of Engineering has revealed new evidence for the occurrence of ground ice on the protoplanet Vesta. The work, under the sponsorship of NASA's Planetary Geology and Geophysics program, is part of ongoing efforts at USC Viterbi to improve water detectability techniques in terrestrial and planetary subsurfaces using radar and microwave imaging techniques. The study, conducted at USC Viterbi in the Ming Hsieh Department of Electrical Engineering by research scientist Essam Heggy and graduate student Elizabeth Palmer from Western Michigan University, took over three years to complete and was featured in the journal Nature Communications on its Sept. 12 release. Heggy is a member of the Ming Hsieh Department of Electrical Engineering's Mixil Lab, which is led by professor Mahta Moghaddam and specializes in radar and microwave imaging. Vesta is located in the asteroid belt between Mars and Jupiter and, due to its large size, is believed to be a differentiated body with a core and a mantle just like our own planet. Collisions between asteroids in the belt enable them to leave their orbits and travel great distances in the solar system, potentially colliding with other planetary bodies. Finding ice on these bodies is of major importance to understanding the transport and evolution of water-rich materials in our solar system. The team used a special technique called "bistatic radar" on the Dawn spacecraft to explore the surface texture of Vesta at the scale of a few inches. On some orbits, when the spacecraft was about to travel behind Vesta from Earth's perspective, its radio communications waves bounced off Vesta's surface, and mission personnel on the ground at NASA's Jet Propulsion Laboratory (JPL) received the signals back on Earth. According to Heggy, this system of radar signaling was like "seeing a flame from a lighter in the middle of day from the opposite side of the United States." Despite the challenges in measuring such a weak signal from the Dawn Spacecraft communication antenna from nearly 300 million miles away, the team assessed the occurrence of large, smooth areas on Vesta that correlated with the occurrence of higher concentration of hydrogen as measured by the gamma ray and neutron detector (GRaND) instrument onboard. "I am excited that we were able to perform such an observation on Vesta. At USC we have been contributing to testing and developing several bistatic radar methods to explore water and ice on planetary surfaces and arid areas of Earth. As the largest research university located in an arid area of the planet, this effort is a natural outgrowth of our focus on understanding water evolution," Heggy said. The USC researchers hope their work will get the public excited not just about water in space, but also about the importance of understanding water evolution in arid areas under changing climatic conditions. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract A life table is a tabulated expression of life expectancy and mortality-related information at specified ages in a given population. This study utilised VetCompass data to develop life tables for the UK companion dog population and broken down by sex, Kennel Club breed group, and common breeds. Among 30,563 dogs that died between 1st January 2016 and 31st July 2020, life expectancy at age 0 was 11.23 [95% confidence interval (CI): 11.19–11.27] years. Female dogs (11.41 years; 95% CI: 11.35–11.47) had a greater life expectancy than males (11.07 years; 95% CI: 11.01–11.13) at age 0. Life tables varied widely between breeds. Jack Russell Terrier (12.72 years; 95% CI: 12.53–12.90) and French Bulldog (4.53 years; 95% CI: 4.14–5.01) had the longest and shortest life expectancy at age 0, respectively. Life tables generated by the current study allow a deeper understanding of the varied life trajectory across many types of dogs and offer novel insights and applications to improve canine health and welfare. The current study helps promote further understanding of life expectancy, which will benefit pet owners and the veterinary profession, along with many other sectors. Introduction A deeper understanding of life expectancies at different ages within the United Kingdom (UK) companion dog population, further categorised by sex and breed, is critical to the improvement of canine welfare and health management 1 , 2 . For example, existing and potential dog owners can develop realistic expectations for the typical remaining life period of their dogs through the knowledge of life expectancy. To date, much of the research on dog life expectancy has focused on reporting average overall ages at death in dogs that have been selected using referral or first opinion veterinary caseloads 1 , 3 , insurance databases 4 or owner questionnaires 5 , 6 . Among companion dogs died between 2009 and 2011 in the UK, the median age at death was estimated to be 12.0 years [interquartile range (IQR): 8.9–14.2], and the median age at death for various breeds ranged from Dogue de Bordeaux at 5.5 years (IQR: 3.3–6.1; n = 21) to Miniature Poodle at 14.2 years (IQR: 11.1–15.6; n = 20) 1 . Instead of offering a single value for the average age of at death, a life table is a tabulated expression of life expectancy and probability of death at different age groups of a given population. A life table provides much more detailed information and inference than a single summary average age at death across all ages 7 . There are two main types of life tables: (a) a cohort life table , which summarises the actual mortality experience of a group of individuals (the cohort) from the birth of the first to the death of the last member of the cohort, and (b) a current life table , which provides cross-sectional mortality and survival experience of a population during a single or few current years 8 . Cohort life tables have also been constructed using a hypothetical (i.e., not pre-determined) cohort 9 , 10 . Both types of life tables have their importance. Cohort life tables can inform the mortality situation of cohorts, but the data for current life tables are generally easier to be collected 8 . Human life tables are routinely constructed for countries, or sub-populations within a country, as a proxy indicator of the general health of the population. A decrease in life expectancy implies that events leading to mortality occur, on average, earlier and is, therefore, suggestive of a generally less healthy population 11 . Thus, life tables can be used to monitor changes in the general health of a population over time, as well as to identify vulnerable (sub-)populations, promoting targeted investigation into the reasons for the observed reduction in life expectancy 11 , 12 . Human life tables are considered an essential tool for effective public planning and policy-making 13 , e.g., estimating the future costs of the Old-Age, Survivors, and Disability Insurance federal programmes within the United States 14 . In the UK, a national current life table for humans is generated every three years whereas there is an update every year in the United States 12 , 15 . National life tables are usually constructed for the population overall, per sex, and may include ethnic groups in some countries 16 . Despite their usefulness for the management of human populations, life tables are rarely built for companion animals. Two life table studies for dogs were recently conducted in Japan 10 , 17 ; the first created current life tables for dogs in general, along with estimates for differing sizes, using pet insurance data, whilst the other created a hypothetical cohort life table using pet cemetery data. These life tables have advanced the knowledge of dog life trajectory 18 and have been applied in studies that required information on the life expectancy of dogs of different ages, such as a quantitative risk assessment of the introduction of rabies 19 and the quantification of welfare impact caused by diseases 2 . However, given that the breed structure of dog populations can vary widely between countries, the international generalisability of lifetables needs to be considered carefully. In addition, the average lifespan and mortality profiles of individual breeds may differ among national dog populations for a wide range of genetic and healthcare reasons. For instance, on average, Labrador Retrievers lived 14.1 years (mean) in Japan 10 , 12.5 years (median) in the UK 1 , and 10.5 (median) years in Denmark 20 . The construction of a life table for companion dogs in the UK could facilitate the understanding of the life expectancy and health of the UK companion dog population in a similar way to the application of such life tables in human populations 12 , 15 . A reliable canine life table can enhance our understanding of the life expectancy at different ages, as it demonstrates that life expectancy at each age is not the same as the average lifespan minus that age. There are practical", "role": "user" }, { "content": "Jack Russell Terriers and Yorkshire Terriers have the highest life expectancies of dog breeds in the UK, according to a new study published in the journal Scientific Reports. However, flat-faced breeds such as French Bulldogs and Pugs have some of the lowest life expectancies. Kendy Tzu-yun Teng, Dan O'Neill and colleagues analyzed 30,563 records of dog deaths from veterinary practices across the UK between 2016 and 2020 using the VetCompass database, categorized into 18 dog breeds recognized by the Kennel Club and also a group of crossbreed dogs. They created life tables which calculate life expectancy throughout the life cycle, starting at birth (0 years). Jack Russell Terriers had the highest life expectancy at birth (12.72 years), followed by Yorkshire Terriers (12.54 years), Border Collies (12.10 years), and Springer Spaniels (11.92 years). In contrast, French Bulldogs had the lowest life expectancy at birth (4.53 years). This is approximately three years less than other flat-faced breeds that showed low life expectancies at birth including English Bulldogs (7.39 years) and Pugs (7.65 years). The authors propose that these short life expectancies could result from the high health risks known to occur in these flat-faced breeds. Across all dog breeds, the average life expectancy at age 0 for male dogs was 11.1 years, four months shorter than the estimate for female dogs. Dogs that had been neutered had a higher life expectancy (11.98 years for females and 11.49 years for males) than those that were not neutered (10.50 years for females and 10.58 years for males). The authors discuss the potential benefits of neutering and associated increased life expectancy and whether neutering could possibly reflect more responsible dog owners and better care. The authors conclude their work now enables dog life expectancies to be tracked at different ages, similarly to humans, and may improve predictions for different breeds in the UK. There could also be other practical benefits such as helping dog shelters to provide accurate estimates of a dog's remaining life expectancy during rehoming. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract A life table is a tabulated expression of life expectancy and mortality-related information at specified ages in a given population. This study utilised VetCompass data to develop life tables for the UK companion dog population and broken down by sex, Kennel Club breed group, and common breeds. Among 30,563 dogs that died between 1st January 2016 and 31st July 2020, life expectancy at age 0 was 11.23 [95% confidence interval (CI): 11.19–11.27] years. Female dogs (11.41 years; 95% CI: 11.35–11.47) had a greater life expectancy than males (11.07 years; 95% CI: 11.01–11.13) at age 0. Life tables varied widely between breeds. Jack Russell Terrier (12.72 years; 95% CI: 12.53–12.90) and French Bulldog (4.53 years; 95% CI: 4.14–5.01) had the longest and shortest life expectancy at age 0, respectively. Life tables generated by the current study allow a deeper understanding of the varied life trajectory across many types of dogs and offer novel insights and applications to improve canine health and welfare. The current study helps promote further understanding of life expectancy, which will benefit pet owners and the veterinary profession, along with many other sectors. Introduction A deeper understanding of life expectancies at different ages within the United Kingdom (UK) companion dog population, further categorised by sex and breed, is critical to the improvement of canine welfare and health management 1 , 2 . For example, existing and potential dog owners can develop realistic expectations for the typical remaining life period of their dogs through the knowledge of life expectancy. To date, much of the research on dog life expectancy has focused on reporting average overall ages at death in dogs that have been selected using referral or first opinion veterinary caseloads 1 , 3 , insurance databases 4 or owner questionnaires 5 , 6 . Among companion dogs died between 2009 and 2011 in the UK, the median age at death was estimated to be 12.0 years [interquartile range (IQR): 8.9–14.2], and the median age at death for various breeds ranged from Dogue de Bordeaux at 5.5 years (IQR: 3.3–6.1; n = 21) to Miniature Poodle at 14.2 years (IQR: 11.1–15.6; n = 20) 1 . Instead of offering a single value for the average age of at death, a life table is a tabulated expression of life expectancy and probability of death at different age groups of a given population. A life table provides much more detailed information and inference than a single summary average age at death across all ages 7 . There are two main types of life tables: (a) a cohort life table , which summarises the actual mortality experience of a group of individuals (the cohort) from the birth of the first to the death of the last member of the cohort, and (b) a current life table , which provides cross-sectional mortality and survival experience of a population during a single or few current years 8 . Cohort life tables have also been constructed using a hypothetical (i.e., not pre-determined) cohort 9 , 10 . Both types of life tables have their importance. Cohort life tables can inform the mortality situation of cohorts, but the data for current life tables are generally easier to be collected 8 . Human life tables are routinely constructed for countries, or sub-populations within a country, as a proxy indicator of the general health of the population. A decrease in life expectancy implies that events leading to mortality occur, on average, earlier and is, therefore, suggestive of a generally less healthy population 11 . Thus, life tables can be used to monitor changes in the general health of a population over time, as well as to identify vulnerable (sub-)populations, promoting targeted investigation into the reasons for the observed reduction in life expectancy 11 , 12 . Human life tables are considered an essential tool for effective public planning and policy-making 13 , e.g., estimating the future costs of the Old-Age, Survivors, and Disability Insurance federal programmes within the United States 14 . In the UK, a national current life table for humans is generated every three years whereas there is an update every year in the United States 12 , 15 . National life tables are usually constructed for the population overall, per sex, and may include ethnic groups in some countries 16 . Despite their usefulness for the management of human populations, life tables are rarely built for companion animals. Two life table studies for dogs were recently conducted in Japan 10 , 17 ; the first created current life tables for dogs in general, along with estimates for differing sizes, using pet insurance data, whilst the other created a hypothetical cohort life table using pet cemetery data. These life tables have advanced the knowledge of dog life trajectory 18 and have been applied in studies that required information on the life expectancy of dogs of different ages, such as a quantitative risk assessment of the introduction of rabies 19 and the quantification of welfare impact caused by diseases 2 . However, given that the breed structure of dog populations can vary widely between countries, the international generalisability of lifetables needs to be considered carefully. In addition, the average lifespan and mortality profiles of individual breeds may differ among national dog populations for a wide range of genetic and healthcare reasons. For instance, on average, Labrador Retrievers lived 14.1 years (mean) in Japan 10 , 12.5 years (median) in the UK 1 , and 10.5 (median) years in Denmark 20 . The construction of a life table for companion dogs in the UK could facilitate the understanding of the life expectancy and health of the UK companion dog population in a similar way to the application of such life tables in human populations 12 , 15 . A reliable canine life table can enhance our understanding of the life expectancy at different ages, as it demonstrates that life expectancy at each age is not the same as the average lifespan minus that age. There are practical<|im_end|> <|im_start|>assistant Jack Russell Terriers and Yorkshire Terriers have the highest life expectancies of dog breeds in the UK, according to a new study published in the journal Scientific Reports. However, flat-faced breeds such as French Bulldogs and Pugs have some of the lowest life expectancies. Kendy Tzu-yun Teng, Dan O'Neill and colleagues analyzed 30,563 records of dog deaths from veterinary practices across the UK between 2016 and 2020 using the VetCompass database, categorized into 18 dog breeds recognized by the Kennel Club and also a group of crossbreed dogs. They created life tables which calculate life expectancy throughout the life cycle, starting at birth (0 years). Jack Russell Terriers had the highest life expectancy at birth (12.72 years), followed by Yorkshire Terriers (12.54 years), Border Collies (12.10 years), and Springer Spaniels (11.92 years). In contrast, French Bulldogs had the lowest life expectancy at birth (4.53 years). This is approximately three years less than other flat-faced breeds that showed low life expectancies at birth including English Bulldogs (7.39 years) and Pugs (7.65 years). The authors propose that these short life expectancies could result from the high health risks known to occur in these flat-faced breeds. Across all dog breeds, the average life expectancy at age 0 for male dogs was 11.1 years, four months shorter than the estimate for female dogs. Dogs that had been neutered had a higher life expectancy (11.98 years for females and 11.49 years for males) than those that were not neutered (10.50 years for females and 10.58 years for males). The authors discuss the potential benefits of neutering and associated increased life expectancy and whether neutering could possibly reflect more responsible dog owners and better care. The authors conclude their work now enables dog life expectancies to be tracked at different ages, similarly to humans, and may improve predictions for different breeds in the UK. There could also be other practical benefits such as helping dog shelters to provide accurate estimates of a dog's remaining life expectancy during rehoming. <|im_end|>

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1,781

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The translation of batch chemistries onto continuous flow platforms requires addressing the issues of consistent fluidic behaviour, channel fouling and high-throughput processing. Droplet microfluidic technologies reduce channel fouling and provide an improved level of control over heat and mass transfer to control reaction kinetics. However, in conventional geometries, the droplet size is sensitive to changes in flow rates. Here we report a three-dimensional droplet generating device that exhibits flow invariant behaviour and is robust to fluctuations in flow rate. In addition, the droplet generator is capable of producing droplet volumes spanning four orders of magnitude. We apply this device in a parallel network to synthesize platinum nanoparticles using an ionic liquid solvent, demonstrate reproducible synthesis after recycling the ionic liquid, and double the reaction yield compared with an analogous batch synthesis. Introduction Continuous flow microfluidic reactors are powerful tools for synthesizing chemicals and materials 1 , 2 , 3 , 4 , 5 , 6 . Microreactors allow for efficient heat transfer, excellent control of local mixing conditions and provide an ideal format for studying reaction kinetics on a small scale 7 . Microfluidic systems also offer a clear and appealing route to scale-up via massively parallel operation. Scaling by parallelization has clear advantages over traditional scale-up approaches. In contrast to a scale-up approach that relies on increasing the size of a single batch reactor, scale-up by parallelization does not change the local reaction conditions in terms of mixing uniformity and temperature distribution, which are critically sensitive variables for certain chemistries. For example, the scale-up of colloidal inorganic nanoparticle syntheses to yield kg quantities is difficult to execute in conventional batch reactors because higher reagent concentrations or increased reaction volumes affect mass and thermal transport, which in turn affect nucleation and growth, leading to loss of particle quality and poor process reproducibility 8 . Microfluidic parallelization can circumvent these issues and enable a simplified and more predictable scale-up route, as demonstrated in a parallel network of planar droplet formation devices 9 . One major challenge in implementing parallel microreactor systems is developing control and design strategies that guarantee uniform fluidic behaviour across an ensemble of reactors 10 , 11 . Here, we address this issue by presenting a fluidic design based on a three-dimensional (3D)-printed channel junction that allows for geometrically controlled two-phase liquid-in-liquid droplet formation that is robust to fluctuations in driving pressure and flow rate. Microfluidic liquid-in-liquid droplet flows facilitate rapid homogenization of reactants 12 . They are, therefore, ideal for reactions that are sensitive to concentration gradients and local mixing conditions. Droplets are isolated from each other and the channel walls to eliminate dispersion effects and prevent device fouling 13 . The design presented here enables an ensemble of parallel reactors with consistent droplet formation behaviour regardless of inconsistencies in the feed pressure or flow rate across the reactor bank. In contrast, prior attempts at nanoparticle synthesis scale-up using continuous flow have focused on modifying single-channel devices to employ larger droplets and increased operating flow rates 14 , 15 . Although these approaches produce good quality nanoparticles, this strategy cannot be scaled indefinitely. An additional advantage of the droplet formation geometry we present here is that it can be rapidly reconfigured to produce a variety of droplet volumes spanning four orders of magnitude. This range of droplet sizes is used in many applications, including biomimetic vesicle formation, cell encapsulation and millifluidic reactor platforms 16 , 17 . In traditional T-junction and flow-focusing droplet formation devices, the operating parameters (that is, flow rates) allow for a relatively narrow range of droplet sizes to be accessed by a single device geometry 18 . Switching to a different droplet size regime requires redesigning (and refabricating) the device. In the device geometry we present here, droplet size is set by the diameter of an easily interchangeable outlet component. Different droplet sizes are accessible by swapping out this modular component. This control mechanism is in contrast to upstream geometrical control exhibited in planar droplet formation devices where the inlet geometry governs droplet size. Coupled with the relative insensitivity of droplet formation to flow rates, this design represents an important innovation in microfluidic droplet formation. In addition to demonstrating the robust operation of this droplet formation geometry in a parallel system, we show it operating as the key element of a droplet microreactor applied to the synthesis of metal nanoparticles. In this paper, we demonstrate the first platinum nanoparticle (PtNP) synthesis using a continuous flow droplet microreactor. A key aspect of our continuous flow synthesis is the use of ionic liquid droplets as the dispersed phase and reaction medium. Ionic liquids are gaining interest as solvents for precious metal nanoparticle synthesis because of their ability to colloidally stabilize nanoparticles and induce high nucleation rates resulting in more monodisperse nanoparticle ensembles 19 . This, coupled with their environmental health, safety and sustainability advantages over volatile and flammable organic solvents 20 , makes ionic liquids promising solvents for large-scale nanofabrication reactions. Herein, the synthesis of PtNPs is performed in ionic liquid droplets that are successfully recycled and reused to produce PtNPs over multiple runs in high fidelity. Results 3D-printed microfluidic droplet generators This microfluidic droplet generator is designed to be an easy-to-operate device that forms consistent droplet sizes across a broad range of inlet pressures or flow rates. The 3D geometry is manufactured using stereolithographic (SLA) printing technologies. This geometry is designed to interface with commercially available tubing (outer diameter (OD)=1/16 inch) to create a droplet generating chip that does not require any fabrication steps in a clean room facility and can passively form droplet volumes spanning four orders of magnitude. Tubing connections form an elastomeric seal that resists leaking for water flow rates beyond 8 l h −1 . Although the 3D printing technology is quickly advancing to create higher resolution features, a major concern is that the smallest channel feature that has been produced in the commonly used Watershed material is 400 μm. Herein, we overcome this barrier by (i) fabricating a", "role": "user" }, { "content": "Nanoparticles - tiny particles 100,000 times smaller than the width of a strand of hair - can be found in everything from drug delivery formulations to pollution controls on cars to HD TV sets. With special properties derived from their tiny size and subsequently increased surface area, they're critical to industry and scientific research. They're also expensive and tricky to make. Now, researchers at USC have created a new way to manufacture nanoparticles that will transform the process from a painstaking, batch-by-batch drudgery into a large-scale, automated assembly line. The method, developed by a team led by Noah Malmstadt of the USC Viterbi School of Engineering and Richard Brutchey of the USC Dornsife College of Letters, Arts and Sciences, was published in Nature Communications on Feb. 23. Consider, for example, gold nanoparticles. They have been shown to be able to easily penetrate cell membranes without causing any damage - an unusual feat, given that most penetrations of cell membranes by foreign objects can damage or kill the cell. Their ability to slip through the cell's membrane makes gold nanoparticles ideal delivery devices for medications to healthy cells, or fatal doses of radiation to cancer cells. However, a single milligram of gold nanoparticles currently costs about $80 (depending on the size of the nanoparticles). That places the price of gold nanoparticles at $80,000 per gram - while a gram of pure, raw gold goes for about $50. \"It's not the gold that's making it expensive,\" Malmstadt said. \"We can make them, but it's not like we can cheaply make a 50 gallon drum full of them.\" Right now, the process of manufacturing a nanoparticle typically involves a technician in a chemistry lab mixing up a batch of chemicals by hand in traditional lab flasks and beakers. Brutchey and Malmstadt's new technique instead relies on microfluidics - technology that manipulates tiny droplets of fluid in narrow channels. \"In order to go large scale, we have to go small,\" Brutchey said. Really small. The team 3D printed tubes about 250 micrometers in diameter - which they believe to be the smallest, fully enclosed 3D printed tubes anywhere. For reference, your average-sized speck of dust is 50 micrometers wide. They then built a parallel network of four of these tubes, side-by-side, and ran a combination of two non-mixing fluids (like oil and water) through them. As the two fluids fought to get out through the openings, they squeezed off tiny droplets. Each of these droplets acted as a micro-scale chemical reactor in which materials were mixed and nanoparticles were generated. Each microfluidic tube can create millions of identical droplets that perform the same reaction. This sort of system has been envisioned in the past, but its hasn't been able to be scaled up because the parallel structure meant that if one tube got jammed, it would cause a ripple effect of changing pressures along its neighbors, knocking out the entire system. Think of it like losing a single Christmas light in one of the old-style strands - lose one, and you lose them all. Brutchey and Malmstadt bypassed this problem by altering the geometry of the tubes themselves, shaping the junction between the tubes such that the particles come out a uniform size and the system is immune to pressure changes. Malmstadt and Brutchy collaborated with Malancha Gupta of USC Viterbi and USC graduate students Carson Riche and Emily Roberts. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The translation of batch chemistries onto continuous flow platforms requires addressing the issues of consistent fluidic behaviour, channel fouling and high-throughput processing. Droplet microfluidic technologies reduce channel fouling and provide an improved level of control over heat and mass transfer to control reaction kinetics. However, in conventional geometries, the droplet size is sensitive to changes in flow rates. Here we report a three-dimensional droplet generating device that exhibits flow invariant behaviour and is robust to fluctuations in flow rate. In addition, the droplet generator is capable of producing droplet volumes spanning four orders of magnitude. We apply this device in a parallel network to synthesize platinum nanoparticles using an ionic liquid solvent, demonstrate reproducible synthesis after recycling the ionic liquid, and double the reaction yield compared with an analogous batch synthesis. Introduction Continuous flow microfluidic reactors are powerful tools for synthesizing chemicals and materials 1 , 2 , 3 , 4 , 5 , 6 . Microreactors allow for efficient heat transfer, excellent control of local mixing conditions and provide an ideal format for studying reaction kinetics on a small scale 7 . Microfluidic systems also offer a clear and appealing route to scale-up via massively parallel operation. Scaling by parallelization has clear advantages over traditional scale-up approaches. In contrast to a scale-up approach that relies on increasing the size of a single batch reactor, scale-up by parallelization does not change the local reaction conditions in terms of mixing uniformity and temperature distribution, which are critically sensitive variables for certain chemistries. For example, the scale-up of colloidal inorganic nanoparticle syntheses to yield kg quantities is difficult to execute in conventional batch reactors because higher reagent concentrations or increased reaction volumes affect mass and thermal transport, which in turn affect nucleation and growth, leading to loss of particle quality and poor process reproducibility 8 . Microfluidic parallelization can circumvent these issues and enable a simplified and more predictable scale-up route, as demonstrated in a parallel network of planar droplet formation devices 9 . One major challenge in implementing parallel microreactor systems is developing control and design strategies that guarantee uniform fluidic behaviour across an ensemble of reactors 10 , 11 . Here, we address this issue by presenting a fluidic design based on a three-dimensional (3D)-printed channel junction that allows for geometrically controlled two-phase liquid-in-liquid droplet formation that is robust to fluctuations in driving pressure and flow rate. Microfluidic liquid-in-liquid droplet flows facilitate rapid homogenization of reactants 12 . They are, therefore, ideal for reactions that are sensitive to concentration gradients and local mixing conditions. Droplets are isolated from each other and the channel walls to eliminate dispersion effects and prevent device fouling 13 . The design presented here enables an ensemble of parallel reactors with consistent droplet formation behaviour regardless of inconsistencies in the feed pressure or flow rate across the reactor bank. In contrast, prior attempts at nanoparticle synthesis scale-up using continuous flow have focused on modifying single-channel devices to employ larger droplets and increased operating flow rates 14 , 15 . Although these approaches produce good quality nanoparticles, this strategy cannot be scaled indefinitely. An additional advantage of the droplet formation geometry we present here is that it can be rapidly reconfigured to produce a variety of droplet volumes spanning four orders of magnitude. This range of droplet sizes is used in many applications, including biomimetic vesicle formation, cell encapsulation and millifluidic reactor platforms 16 , 17 . In traditional T-junction and flow-focusing droplet formation devices, the operating parameters (that is, flow rates) allow for a relatively narrow range of droplet sizes to be accessed by a single device geometry 18 . Switching to a different droplet size regime requires redesigning (and refabricating) the device. In the device geometry we present here, droplet size is set by the diameter of an easily interchangeable outlet component. Different droplet sizes are accessible by swapping out this modular component. This control mechanism is in contrast to upstream geometrical control exhibited in planar droplet formation devices where the inlet geometry governs droplet size. Coupled with the relative insensitivity of droplet formation to flow rates, this design represents an important innovation in microfluidic droplet formation. In addition to demonstrating the robust operation of this droplet formation geometry in a parallel system, we show it operating as the key element of a droplet microreactor applied to the synthesis of metal nanoparticles. In this paper, we demonstrate the first platinum nanoparticle (PtNP) synthesis using a continuous flow droplet microreactor. A key aspect of our continuous flow synthesis is the use of ionic liquid droplets as the dispersed phase and reaction medium. Ionic liquids are gaining interest as solvents for precious metal nanoparticle synthesis because of their ability to colloidally stabilize nanoparticles and induce high nucleation rates resulting in more monodisperse nanoparticle ensembles 19 . This, coupled with their environmental health, safety and sustainability advantages over volatile and flammable organic solvents 20 , makes ionic liquids promising solvents for large-scale nanofabrication reactions. Herein, the synthesis of PtNPs is performed in ionic liquid droplets that are successfully recycled and reused to produce PtNPs over multiple runs in high fidelity. Results 3D-printed microfluidic droplet generators This microfluidic droplet generator is designed to be an easy-to-operate device that forms consistent droplet sizes across a broad range of inlet pressures or flow rates. The 3D geometry is manufactured using stereolithographic (SLA) printing technologies. This geometry is designed to interface with commercially available tubing (outer diameter (OD)=1/16 inch) to create a droplet generating chip that does not require any fabrication steps in a clean room facility and can passively form droplet volumes spanning four orders of magnitude. Tubing connections form an elastomeric seal that resists leaking for water flow rates beyond 8 l h −1 . Although the 3D printing technology is quickly advancing to create higher resolution features, a major concern is that the smallest channel feature that has been produced in the commonly used Watershed material is 400 μm. Herein, we overcome this barrier by (i) fabricating a<|im_end|> <|im_start|>assistant Nanoparticles - tiny particles 100,000 times smaller than the width of a strand of hair - can be found in everything from drug delivery formulations to pollution controls on cars to HD TV sets. With special properties derived from their tiny size and subsequently increased surface area, they're critical to industry and scientific research. They're also expensive and tricky to make. Now, researchers at USC have created a new way to manufacture nanoparticles that will transform the process from a painstaking, batch-by-batch drudgery into a large-scale, automated assembly line. The method, developed by a team led by Noah Malmstadt of the USC Viterbi School of Engineering and Richard Brutchey of the USC Dornsife College of Letters, Arts and Sciences, was published in Nature Communications on Feb. 23. Consider, for example, gold nanoparticles. They have been shown to be able to easily penetrate cell membranes without causing any damage - an unusual feat, given that most penetrations of cell membranes by foreign objects can damage or kill the cell. Their ability to slip through the cell's membrane makes gold nanoparticles ideal delivery devices for medications to healthy cells, or fatal doses of radiation to cancer cells. However, a single milligram of gold nanoparticles currently costs about $80 (depending on the size of the nanoparticles). That places the price of gold nanoparticles at $80,000 per gram - while a gram of pure, raw gold goes for about $50. "It's not the gold that's making it expensive," Malmstadt said. "We can make them, but it's not like we can cheaply make a 50 gallon drum full of them." Right now, the process of manufacturing a nanoparticle typically involves a technician in a chemistry lab mixing up a batch of chemicals by hand in traditional lab flasks and beakers. Brutchey and Malmstadt's new technique instead relies on microfluidics - technology that manipulates tiny droplets of fluid in narrow channels. "In order to go large scale, we have to go small," Brutchey said. Really small. The team 3D printed tubes about 250 micrometers in diameter - which they believe to be the smallest, fully enclosed 3D printed tubes anywhere. For reference, your average-sized speck of dust is 50 micrometers wide. They then built a parallel network of four of these tubes, side-by-side, and ran a combination of two non-mixing fluids (like oil and water) through them. As the two fluids fought to get out through the openings, they squeezed off tiny droplets. Each of these droplets acted as a micro-scale chemical reactor in which materials were mixed and nanoparticles were generated. Each microfluidic tube can create millions of identical droplets that perform the same reaction. This sort of system has been envisioned in the past, but its hasn't been able to be scaled up because the parallel structure meant that if one tube got jammed, it would cause a ripple effect of changing pressures along its neighbors, knocking out the entire system. Think of it like losing a single Christmas light in one of the old-style strands - lose one, and you lose them all. Brutchey and Malmstadt bypassed this problem by altering the geometry of the tubes themselves, shaping the junction between the tubes such that the particles come out a uniform size and the system is immune to pressure changes. Malmstadt and Brutchy collaborated with Malancha Gupta of USC Viterbi and USC graduate students Carson Riche and Emily Roberts. <|im_end|>

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2,047

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Earlier we showed that human genome contains many evolutionarily young or novel genes with tumor-specific or tumor-predominant expression. We suggest calling such genes T umor S pecifically E xpressed, E volutionarily N ew ( TSEEN ) genes. In this paper we performed a study of the evolutionary ages of different classes of human genes, using homology searches in genomes of different taxa in human lineage. We discovered that different classes of human genes have different evolutionary ages and confirmed the existence of TSEEN gene classes. On the other hand, we found that oncogenes, tumor-suppressor genes and differentiation genes are among the oldest gene classes in humans and their evolution occurs concurrently. These findings confirm non-trivial predictions made by our hypothesis of the possible evolutionary role of hereditary tumors. The results may be important for better understanding of tumor biology. TSEEN genes may become the best tumor markers. Introduction We are interested in the possible evolutionary role of tumors. In previous publications 1 , 2 , 3 , 4 , 5 we formulated the hypothesis of the possible evolutionary role of hereditary tumors, i.e. tumors that can be passed from parent to offspring. According to this hypothesis, hereditary tumors were the source of extra cell masses which could be used in the evolution of multicellular organisms for the expression of evolutionarily novel genes, for the origin of new differentiated cell types with novel functions and for building new structures which constitute evolutionary innovations and morphological novelties. Hereditary tumors could play an evolutionary role by providing conditions (space and resources) for the expression of genes newly evolving in the DNA of germ cells. As a result of expression of novel genes, tumor cells acquired new functions and differentiated in new directions, which might lead to the origin of new cell types, tissues and organs 5 . The new cell type was inherited in progeny generations due to genetic and transgenerational epigenetic mechanisms similar to those for pre-existing cell types 5 , 6 , 7 . Our hypothesis makes several nontrivial predictions. One of predictions is that tumors could be selected for new functional roles beneficial to the organism. This prediction was addressed in a special work 5 , 8 , in which it was shown that the “hoods” of some varieties of gold fishes such as Lionhead, Oranda, etc. are benign tumors. These tumors have been selected by breeders for hundreds of years and eventually formed a new organ, the “hood”. The other prediction of the hypothesis is that evolutionarily young and novel genes should be specifically expressed in tumors. This prediction was verified in a number of papers from our laboratory 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 . We have described several evolutionarily young or novel genes with tumor-predominant or tumor-specific expression, and even the evolutionary novelty of the class of genes – cancer/testis genes – which consists of evolutionary young and novel genes expressed predominantly in tumors (reviewed in) 9 . We suggest calling such genes Tumor Specifically Expressed, Evolutionarily New ( TSEEN ) genes 5 , 9 . TSEEN genes may become the best tumor markers 9 , 10 . In this paper, we performed a systematic study of the evolutionary ages of different functional classes of human genes in order to verify one more nontrivial prediction of the hypothesis of the possible evolutionary role of hereditary tumors, i.e. the prediction of concurrent evolution of oncogenes, tumor suppressor genes and differentiation genes 2 , 3 , 5 . Results The curves of gene age distribution for different classes of human genes obtained by the ProteinHistorian tool are represented in Figs 1 – 7 . Figure 1 Distribution of human housekeeping genes genes and all protein coding genes according to their evolutionary ages. The evolutionary ages of the gene classes are measured numerically in million years at the median of distribution, i.e. at the time point on the human evolutionary timeline that corresponds to the origin of 50% of genes in this class. Full size image Figure 2 Gene age distributions of different classes of human genes. Full size image Figure 3 Cluster I of gene age distribution and control curves. Full size image Figure 4 Cluster II of gene age distribution and control curve. Full size image Figure 5 Cluster III of gene age distribution and control curve. Full size image Figure 6 Gene age distribution for different classes of human genes between Euarchontoglires and H. sapiens. Full size image Figure 7 The proportion of different classes of human genes originated between Homininae and H. sapiens. Full size image These figures show curves sloping upward from left to right. The uppermost curve describes the gene age distribution of human housekeeping genes. The evolutionary age of this gene class, defined by the median position of the curve, is 894 million years (Ma) (Fig. 1 ). The curve of all human protein-coding genes has evolutionary age of 600 Ma (Figs 1 and 3–5 ). These curves were used as control curves in our study. Some curves are located mainly between the control curves (Fig. 3 ), others are located below the second control curve (Figs 4 and 5 ). The median ages of other groups of genes are the following: oncogenes (750 Ma), tumor suppressor genes (750 Ma), differentiation genes (693 Ma), homeobox genes (450 Ma), apoptosis genes (360 Ma), canser/testis (CT) antigen genes (autosomal) (324 Ma), Biomedical Center globally subtracted, tumor-specifically expressed (BMC GSTSE) protein-coding genes (220 Ma), BMC GSTSE non-coding sequences (130 Ma), CT antigen genes located on X chromosome (CT-X) (60 Ma) and BMC GSTSE non-coding sequences located on X chromosome (BMC GSTSE-X non-coding sequences) (50 Ma) (Fig. 2 ). In most of the cases the pairwise differences in the age distributions of genes belonging to different classes are statistically significant (see Supplementary Dataset 1 ). As follows from Figs 2 – 5 the curves are organized in clusters. The existence of", "role": "user" }, { "content": "A team of scientists from Peter the Great St.Petersburg Polytechnic University (SPbPU) studied the evolutionary ages of human genes and identified a new class of them expressed in tumors—tumor specifically expressed, evolutionarily novel (TSEEN) genes. This confirms the team's earlier theory about the evolutionary role of neoplasms. A report about the study was published in Scientific Reports. A tumor is a pathological new growth of tissues. Due to genetic changes, it has impaired cellular regulation and therefore defective functionality. Tumors can be benign or malignant. Unlike the latter, the former grow slowly, don't metastasize, and are easy to remove. Malignant tumors (cancer) are one of the primary mortality factors in the world. A team of scientists from Saint Petersburg discovered a new class of evolutionarily novel genes present in all tumors—the so-called TSEEN (Tumor Specifically Expressed Evolutionarily Novel) genes. \"The evolutionary role of these genes is to provide genetic material for the origin of new progressive characteristics. TSEEN genes are expressed in many neoplasms and therefore can be excellent tumor markers,\" said Prof. Andrei Kozlov, a Ph.D. in Biology, the head of Laboratory \"Molecular Virology and Oncology\" at Peter the Great St. Petersburg Polytechnic University. The new research confirms a theory that has been proposed by A. Kozlov earlier. According to it, the number of oncogenes in a human body should correspond to the number of differential cell types. The theory also suggested that the evolution of oncogenes, tumor suppressor genes, and the genes that determine cell differentiation goes on concurrently. The theory is based on the hypothesis of evolution through tumor neofunctionalization, according to which hereditary neoplasms might have played an important role during the early stages of metazoan evolution by providing additional cell masses for the origin of new cell types, tissues, and organs. Evolutionarily novel genes that originate in the DNA of germ cells are expressed in these extra cells. Prof. Kozlov also made a reference to the article \"Evolutionarily Novel Genes Are Expressed in Transgenic Fish Tumors and Their Orthologs Are Involved in Development of Progressive Traits in Humans\" (2019) that has recently been published by his laboratory. In this article, the team confirmed their hypothesis using transgenic fish tumors and fish evolutionarily novel genes. The orthologs of such genes are found in the human genome, but in humans they play a role in the development of progressive characteristics not encountered in fish (e.g. lungs, breasts, placenta, ventricular septum in the heart, etc). This confirms the hypothesis about the evolutionary role of tumors. The studies referred to in the article lasted for several years, and their participants used a wide range of methods from the fields of bioinformatics and molecular biology. \"Our work is of great social importance, as the cancer problem hasn't been solved yet. Our theory suggests new prevention and therapy strategies,\" said Prof. Kozlov. According to him, to fight cancer, a new paradigm should be developed in oncology. TSEEN genes may be used to create new cancer test systems and antitumor vaccines. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Earlier we showed that human genome contains many evolutionarily young or novel genes with tumor-specific or tumor-predominant expression. We suggest calling such genes T umor S pecifically E xpressed, E volutionarily N ew ( TSEEN ) genes. In this paper we performed a study of the evolutionary ages of different classes of human genes, using homology searches in genomes of different taxa in human lineage. We discovered that different classes of human genes have different evolutionary ages and confirmed the existence of TSEEN gene classes. On the other hand, we found that oncogenes, tumor-suppressor genes and differentiation genes are among the oldest gene classes in humans and their evolution occurs concurrently. These findings confirm non-trivial predictions made by our hypothesis of the possible evolutionary role of hereditary tumors. The results may be important for better understanding of tumor biology. TSEEN genes may become the best tumor markers. Introduction We are interested in the possible evolutionary role of tumors. In previous publications 1 , 2 , 3 , 4 , 5 we formulated the hypothesis of the possible evolutionary role of hereditary tumors, i.e. tumors that can be passed from parent to offspring. According to this hypothesis, hereditary tumors were the source of extra cell masses which could be used in the evolution of multicellular organisms for the expression of evolutionarily novel genes, for the origin of new differentiated cell types with novel functions and for building new structures which constitute evolutionary innovations and morphological novelties. Hereditary tumors could play an evolutionary role by providing conditions (space and resources) for the expression of genes newly evolving in the DNA of germ cells. As a result of expression of novel genes, tumor cells acquired new functions and differentiated in new directions, which might lead to the origin of new cell types, tissues and organs 5 . The new cell type was inherited in progeny generations due to genetic and transgenerational epigenetic mechanisms similar to those for pre-existing cell types 5 , 6 , 7 . Our hypothesis makes several nontrivial predictions. One of predictions is that tumors could be selected for new functional roles beneficial to the organism. This prediction was addressed in a special work 5 , 8 , in which it was shown that the “hoods” of some varieties of gold fishes such as Lionhead, Oranda, etc. are benign tumors. These tumors have been selected by breeders for hundreds of years and eventually formed a new organ, the “hood”. The other prediction of the hypothesis is that evolutionarily young and novel genes should be specifically expressed in tumors. This prediction was verified in a number of papers from our laboratory 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 . We have described several evolutionarily young or novel genes with tumor-predominant or tumor-specific expression, and even the evolutionary novelty of the class of genes – cancer/testis genes – which consists of evolutionary young and novel genes expressed predominantly in tumors (reviewed in) 9 . We suggest calling such genes Tumor Specifically Expressed, Evolutionarily New ( TSEEN ) genes 5 , 9 . TSEEN genes may become the best tumor markers 9 , 10 . In this paper, we performed a systematic study of the evolutionary ages of different functional classes of human genes in order to verify one more nontrivial prediction of the hypothesis of the possible evolutionary role of hereditary tumors, i.e. the prediction of concurrent evolution of oncogenes, tumor suppressor genes and differentiation genes 2 , 3 , 5 . Results The curves of gene age distribution for different classes of human genes obtained by the ProteinHistorian tool are represented in Figs 1 – 7 . Figure 1 Distribution of human housekeeping genes genes and all protein coding genes according to their evolutionary ages. The evolutionary ages of the gene classes are measured numerically in million years at the median of distribution, i.e. at the time point on the human evolutionary timeline that corresponds to the origin of 50% of genes in this class. Full size image Figure 2 Gene age distributions of different classes of human genes. Full size image Figure 3 Cluster I of gene age distribution and control curves. Full size image Figure 4 Cluster II of gene age distribution and control curve. Full size image Figure 5 Cluster III of gene age distribution and control curve. Full size image Figure 6 Gene age distribution for different classes of human genes between Euarchontoglires and H. sapiens. Full size image Figure 7 The proportion of different classes of human genes originated between Homininae and H. sapiens. Full size image These figures show curves sloping upward from left to right. The uppermost curve describes the gene age distribution of human housekeeping genes. The evolutionary age of this gene class, defined by the median position of the curve, is 894 million years (Ma) (Fig. 1 ). The curve of all human protein-coding genes has evolutionary age of 600 Ma (Figs 1 and 3–5 ). These curves were used as control curves in our study. Some curves are located mainly between the control curves (Fig. 3 ), others are located below the second control curve (Figs 4 and 5 ). The median ages of other groups of genes are the following: oncogenes (750 Ma), tumor suppressor genes (750 Ma), differentiation genes (693 Ma), homeobox genes (450 Ma), apoptosis genes (360 Ma), canser/testis (CT) antigen genes (autosomal) (324 Ma), Biomedical Center globally subtracted, tumor-specifically expressed (BMC GSTSE) protein-coding genes (220 Ma), BMC GSTSE non-coding sequences (130 Ma), CT antigen genes located on X chromosome (CT-X) (60 Ma) and BMC GSTSE non-coding sequences located on X chromosome (BMC GSTSE-X non-coding sequences) (50 Ma) (Fig. 2 ). In most of the cases the pairwise differences in the age distributions of genes belonging to different classes are statistically significant (see Supplementary Dataset 1 ). As follows from Figs 2 – 5 the curves are organized in clusters. The existence of<|im_end|> <|im_start|>assistant A team of scientists from Peter the Great St.Petersburg Polytechnic University (SPbPU) studied the evolutionary ages of human genes and identified a new class of them expressed in tumors—tumor specifically expressed, evolutionarily novel (TSEEN) genes. This confirms the team's earlier theory about the evolutionary role of neoplasms. A report about the study was published in Scientific Reports. A tumor is a pathological new growth of tissues. Due to genetic changes, it has impaired cellular regulation and therefore defective functionality. Tumors can be benign or malignant. Unlike the latter, the former grow slowly, don't metastasize, and are easy to remove. Malignant tumors (cancer) are one of the primary mortality factors in the world. A team of scientists from Saint Petersburg discovered a new class of evolutionarily novel genes present in all tumors—the so-called TSEEN (Tumor Specifically Expressed Evolutionarily Novel) genes. "The evolutionary role of these genes is to provide genetic material for the origin of new progressive characteristics. TSEEN genes are expressed in many neoplasms and therefore can be excellent tumor markers," said Prof. Andrei Kozlov, a Ph.D. in Biology, the head of Laboratory "Molecular Virology and Oncology" at Peter the Great St. Petersburg Polytechnic University. The new research confirms a theory that has been proposed by A. Kozlov earlier. According to it, the number of oncogenes in a human body should correspond to the number of differential cell types. The theory also suggested that the evolution of oncogenes, tumor suppressor genes, and the genes that determine cell differentiation goes on concurrently. The theory is based on the hypothesis of evolution through tumor neofunctionalization, according to which hereditary neoplasms might have played an important role during the early stages of metazoan evolution by providing additional cell masses for the origin of new cell types, tissues, and organs. Evolutionarily novel genes that originate in the DNA of germ cells are expressed in these extra cells. Prof. Kozlov also made a reference to the article "Evolutionarily Novel Genes Are Expressed in Transgenic Fish Tumors and Their Orthologs Are Involved in Development of Progressive Traits in Humans" (2019) that has recently been published by his laboratory. In this article, the team confirmed their hypothesis using transgenic fish tumors and fish evolutionarily novel genes. The orthologs of such genes are found in the human genome, but in humans they play a role in the development of progressive characteristics not encountered in fish (e.g. lungs, breasts, placenta, ventricular septum in the heart, etc). This confirms the hypothesis about the evolutionary role of tumors. The studies referred to in the article lasted for several years, and their participants used a wide range of methods from the fields of bioinformatics and molecular biology. "Our work is of great social importance, as the cancer problem hasn't been solved yet. Our theory suggests new prevention and therapy strategies," said Prof. Kozlov. According to him, to fight cancer, a new paradigm should be developed in oncology. TSEEN genes may be used to create new cancer test systems and antitumor vaccines. <|im_end|>

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24, 1174, 220, 605, 662, 763, 420, 5684, 11, 584, 10887, 264, 37538, 4007, 315, 279, 41993, 17051, 315, 2204, 16003, 6989, 315, 3823, 21389, 304, 2015, 311, 10356, 832, 810, 2536, 376, 27756, 20212, 315, 279, 31178, 315, 279, 3284, 41993, 3560, 315, 1077, 95454, 56071, 11, 602, 1770, 13, 279, 20212, 315, 35135, 15740, 315, 78970, 11968, 288, 11, 36254, 28321, 269, 21389, 323, 60038, 21389, 220, 17, 1174, 220, 18, 1174, 220, 20, 662, 18591, 578, 37033, 315, 15207, 4325, 8141, 369, 2204, 6989, 315, 3823, 21389, 12457, 555, 279, 49475, 50083, 1122, 5507, 527, 15609, 304, 435, 14801, 220, 16, 1389, 220, 22, 662, 19575, 220, 16, 35009, 315, 3823, 3838, 33494, 21389, 21389, 323, 682, 13128, 11058, 21389, 4184, 311, 872, 41993, 17051, 13, 578, 41993, 17051, 315, 279, 15207, 6989, 527, 17303, 8015, 2740, 304, 3610, 1667, 520, 279, 23369, 315, 8141, 11, 602, 1770, 13, 520, 279, 892, 1486, 389, 279, 3823, 41993, 25845, 430, 34310, 311, 279, 6371, 315, 220, 1135, 4, 315, 21389, 304, 420, 538, 13, 8797, 1404, 2217, 19575, 220, 17, 24983, 4325, 43785, 315, 2204, 6989, 315, 3823, 21389, 13, 8797, 1404, 2217, 19575, 220, 18, 36480, 358, 315, 15207, 4325, 8141, 323, 2585, 37033, 13, 8797, 1404, 2217, 19575, 220, 19, 36480, 8105, 315, 15207, 4325, 8141, 323, 2585, 16029, 13, 8797, 1404, 2217, 19575, 220, 20, 36480, 14767, 315, 15207, 4325, 8141, 323, 2585, 16029, 13, 8797, 1404, 2217, 19575, 220, 21, 24983, 4325, 8141, 369, 2204, 6989, 315, 3823, 21389, 1990, 22730, 1132, 546, 540, 747, 417, 323, 473, 13, 82295, 729, 13, 8797, 1404, 2217, 19575, 220, 22, 578, 21801, 315, 2204, 6989, 315, 3823, 21389, 44853, 1990, 473, 8129, 125887, 323, 473, 13, 82295, 729, 13, 8797, 1404, 2217, 4314, 12678, 1501, 37033, 18067, 10194, 40872, 505, 2163, 311, 1314, 13, 578, 8582, 3646, 16029, 16964, 279, 15207, 4325, 8141, 315, 3823, 3838, 33494, 21389, 13, 578, 41993, 4325, 315, 420, 15207, 538, 11, 4613, 555, 279, 23369, 2361, 315, 279, 16029, 11, 374, 220, 26227, 3610, 1667, 320, 30635, 8, 320, 30035, 13, 220, 16, 7609, 578, 16029, 315, 682, 3823, 13128, 1824, 3785, 21389, 706, 41993, 4325, 315, 220, 5067, 11583, 320, 37, 14801, 220, 16, 323, 220, 18, 4235, 20, 7609, 4314, 37033, 1051, 1511, 439, 2585, 37033, 304, 1057, 4007, 13, 4427, 37033, 527, 7559, 14918, 1990, 279, 2585, 37033, 320, 30035, 13, 220, 18, 7026, 3885, 527, 7559, 3770, 279, 2132, 2585, 16029, 320, 37, 14801, 220, 19, 323, 220, 20, 7609, 578, 23369, 17051, 315, 1023, 5315, 315, 21389, 527, 279, 2768, 25, 78970, 11968, 288, 320, 11711, 11583, 705, 36254, 28321, 269, 21389, 320, 11711, 11583, 705, 60038, 21389, 320, 25298, 11583, 705, 2162, 33560, 21389, 320, 10617, 11583, 705, 95874, 21389, 320, 6843, 11583, 705, 43732, 261, 12986, 285, 320, 1182, 8, 83089, 21389, 320, 80401, 53911, 8, 320, 16723, 11583, 705, 12371, 61860, 5955, 31550, 33356, 291, 11, 36254, 19440, 750, 13605, 320, 33, 11865, 33934, 937, 8, 13128, 1824, 3785, 21389, 320, 8610, 11583, 705, 82806, 33934, 937, 2536, 1824, 3785, 24630, 320, 5894, 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362, 1934, 922, 279, 4007, 574, 4756, 304, 38130, 29140, 13, 362, 36254, 374, 264, 89961, 502, 6650, 315, 39881, 13, 24586, 311, 19465, 4442, 11, 433, 706, 50160, 35693, 19812, 323, 9093, 64903, 15293, 13, 350, 372, 1105, 649, 387, 65309, 477, 94329, 13, 27140, 279, 15629, 11, 279, 4846, 3139, 14297, 11, 1541, 956, 68370, 300, 553, 11, 323, 527, 4228, 311, 4148, 13, 386, 6750, 519, 56071, 320, 66, 11967, 8, 527, 832, 315, 279, 6156, 29528, 9547, 304, 279, 1917, 13, 362, 2128, 315, 14248, 505, 14539, 55048, 11352, 264, 502, 538, 315, 15740, 6751, 11775, 21389, 3118, 304, 682, 56071, 22416, 779, 19434, 350, 937, 965, 320, 51, 69361, 45863, 1398, 14655, 38321, 6751, 53976, 8, 21389, 13, 330, 791, 41993, 3560, 315, 1521, 21389, 374, 311, 3493, 19465, 3769, 369, 279, 6371, 315, 502, 23053, 17910, 13, 350, 937, 965, 21389, 527, 13605, 304, 1690, 841, 454, 14833, 1026, 323, 9093, 649, 387, 9250, 36254, 24915, 1359, 1071, 8626, 13, 27525, 72, 735, 9700, 36247, 11, 264, 2405, 920, 13, 304, 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990, 374, 315, 2294, 3674, 12939, 11, 439, 279, 9572, 3575, 12775, 956, 1027, 29056, 3686, 13, 5751, 10334, 13533, 502, 27344, 323, 15419, 15174, 1359, 1071, 8626, 13, 735, 9700, 36247, 13, 10771, 311, 1461, 11, 311, 4465, 9572, 11, 264, 502, 49340, 1288, 387, 8040, 304, 78970, 2508, 13, 350, 937, 965, 21389, 1253, 387, 1511, 311, 1893, 502, 9572, 1296, 6067, 323, 3276, 275, 69361, 40300, 13, 220, 128257, 198 ]

1,993

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract hnRNPDL is a ribonucleoprotein (RNP) involved in transcription and RNA-processing that hosts missense mutations causing limb-girdle muscular dystrophy D3 (LGMD D3). Mammalian-specific alternative splicing (AS) renders three natural isoforms, hnRNPDL-2 being predominant in humans. We present the cryo-electron microscopy structure of full-length hnRNPDL-2 amyloid fibrils, which are stable, non-toxic, and bind nucleic acids. The high-resolution amyloid core consists of a single Gly/Tyr-rich and highly hydrophilic filament containing internal water channels. The RNA binding domains are located as a solenoidal coat around the core. The architecture and activity of hnRNPDL-2 fibrils are reminiscent of functional amyloids, our results suggesting that LGMD D3 might be a loss-of-function disease associated with impaired fibrillation. Strikingly, the fibril core matches exon 6, absent in the soluble hnRNPDL-3 isoform. This provides structural evidence for AS controlling hnRNPDL assembly by precisely including/skipping an amyloid exon, a mechanism that holds the potential to generate functional diversity in RNPs. Introduction Human heterogeneous ribonucleoprotein D-like (hnRNPDL) belongs to a class of conserved nuclear RNA-binding proteins (RBPs) that assemble with RNA to form ribonucleoproteins (RNPs). hnRNPDL acts as a transcriptional regulator and participates in the metabolism and biogenesis of mRNA 1 , 2 , 3 , 4 . Three isoforms of hnRNPDL are produced by alternative splicing (AS): hnRNPDL-1, hnRNPDL-2, and hnRNPDL-3 5 (Fig. 1a and Supplementary Fig. 1 ). hnRNPDL-2 is a 301 residues protein and the predominant isoform in human tissues 6 . It consists of two consecutive globular RNA recognition motifs (RRM1 and RRM2), followed by a C-terminal low-complexity domain (LCD) that maps at residues ~201–285 and a nuclear localization sequence (PY-NLS) comprising residues 281-301. hnRNPDL-1 is a longer isoform of 420 amino acids containing an additional Arg-rich N-terminal LCD 5 ; it is less abundant than hnRNPDL-2 and is present mainly in brain and testis 6 . hnRNPDL-3 is a shorter and minor isoform of 244 amino acids that lacks the N- and C- terminal LCDs but conserves the PY-NLS 7 . Fig. 1: hnRNPDL-2 aggregates into ordered amyloid fibrils. a Domain organization of human hnRNPDL isoforms. The RNA recognition motifs are labelled as RRM (pink) and N- and C-terminal low complexity domains (LCD) are indicated as R-rich LCD (orange) and Y/G-rich LCD (blue), respectively. The region and sequence of exon 6 is also indicated, according to hnRNPDL-2 numbering. D259 disease-associated amino acid is shown in red. NLS indicates the shared nuclear localization signal. b Representative confocal images of HeLa hnRNPDL KO cells transiently transfected with the different hnRNPDL isoforms (DL-1, DL-2 and DL-3). The empty GFP vector (GFP) was transfected as control. The images depict the characteristic nuclear distribution of GFP-hnRNPDL fusions (green). Nuclear DNA was stained with Hoechst (blue). White arrows indicate the location of the nucleolus. In all cases, the nucleus contour has been indicated with a white dashed line. Scale bar, 10 μm. c Th-T binding to hnRNPDL-1 (orange line), hnRNPDL-2 (blue line) and hnRNPDL-3 (purple line) after incubation at 37 °C and 600 rpm, pH 7.5 and 300 mM NaCl for 2 days. Representative negative staining TEM micrographs of the incubated solutions of ( d ) hnRNPDL-1, ( e ) hnRNPDL-2 and ( f ) hnRNPDL-3. Scale bar, 200 nm. Note that only in ( e ) individual amyloid filaments are evident. In ( b ) and ( d–f ), results are representative from three independent experiments. Full size image A point mutation in hnRNPDL exon 6 causes autosomal dominant limb-girdle muscular dystrophy D3 (LGMD D3) 8 , 9 , 10 , a rare disease characterized by slowly progressive proximal muscle weakness 11 , 12 . This mutation changes the conserved Asp259 in the C-terminal LCD to either Asn or His. Similarly, mutation of specific Asp residues to Asn or Val in the LCDs of hnRNPA1 and hnRNPA2 are linked to amyotrophic lateral sclerosis (ALS) and multisystem proteinopathy (MSP) 13 , 14 . However, unlike ALS and MSP patients, where hnRNPA1 and hnRNPA2 accumulate in cytoplasmic inclusions in muscular fibers 14 , 15 , most LGMD D3 patients do not exhibit nuclear or cytoplasmatic protein inclusions 8 . Structures of the amyloid fibrils formed by hnRNPA1 and hnRNPA2 LCDs have been recently determined 16 , 17 . For both fibrils, the PY-NLS was embedded within the ordered core. This led to suggest that, under physiological conditions, binding of the import receptor karyopherin-β2 (Kapβ2) to PY-NLS 18 would impede fibrillation, whereas its exposure under pathological conditions would allow amyloid formation 16 . However, in these studies, constructs of the LCD, alone or fused to a fluorescent protein, were used to form the fibrils, and it is unknown whether the observed assemblies would match those of the natural full-length proteins’ fibrils. Here we present the cryo-electron microscopy (cryo-EM) structure of the fibrils formed by the full-length hnRNPDL-2 isoform at an overall resolution of 2.5 Å. These fibrils are stable and bind oligonucleotides, with the associated RRM domains building an exposed solenoidal coat wrapping the structured fibril. The fibrils’ core is formed by a single highly hydrophilic filament encompassing LCD residues 226-276, including Asp259. Modeling suggests that disease-associated mutations at this residue may have limited impact on fibril stability. Importantly, the fibril core does not include the PY-NLS. The hnRNPDL-2 fibril core precisely matches exon 6 (residues 224-280), which is alternatively spliced (AS) in a mammalian-specific manner 19 . These AS events are frequent in RNPs, especially at their Y/G-rich LCDs 19 and they have been proposed to be a way to regulate protein function by controlling the formation of high-order assemblies 20 ; our results provide structural evidence supporting this hypothesis. Overall, we describe the structure of a full-length RNP in its fibrillar functional conformation, providing insight into the molecular bases of LGMD D3, and illustrating how AS can control RNPs assembly by including/excluding amyloidogenic exons at their LCDs. Results hnRNPDLs localize at the nucleus and exon 6 is key for their compartmentalization Human hnRNPDL AS renders three naturally occurring transcripts (Fig. 1a and Supplementary Fig. 1 ). When transfected into a HeLa", "role": "user" }, { "content": "Researchers at the UAB have determined the structure of amyloid fibers formed by the protein hnRNPDL-2, implicated in limb-girdle muscular dystrophy type 3, using high-resolution cryo-electron microscopy (cryo-EM). They have concluded that the inability of the protein to form amyloid fibers, and not aggregation, would be the cause of the disease. This is the first amyloid structure determined at high resolution by a Spanish research team. The study, published in Nature Communications, informs the search for molecules that stabilize or facilitate amyloid formation and opens the door to the study of other functional amyloids and their mutations using the same technique, in order to better understand their implications in health and disease. Limb-girdle muscular dystrophy type 3 (LGMD D3) is a rare disease causing progressive muscle weakness caused by point mutations in the hnRNPDL-2 protein. A member of the RNA-associated ribonucleoprotein (RNP) family, it is a little-known protein with the ability to assemble to form functional amyloid structures. Amyloids are formed by the joining of thousands of pieces of the same protein to form very stable and structured fibers (protein aggregates). Their formation is often associated with diseases such as Parkinson's and Alzheimer's, but they are also used by different organisms for functional purposes, although the number of functional amyloids described in humans is still small. Researchers at the Universitat Autònoma de Barcelona (UAB) have determined that the architecture and activity of the amyloid fibers suggest that they are stable, non-toxic amyloid fibers that bind nucleic acids in their aggregated state. The results indicate that LGMD D3 could be a protein loss-of-function disease: the inability to form the amyloid structures described in the study would cause the pathology. \"Our study challenges the hypothesis that the aggregation of this protein is the cause of the disease and proposes that it is the inability to form a fibrillar structure that has been selected by evolution to bind nucleic acids that causes the pathology,\" says Salvador Ventura, professor of Biochemistry and Molecular Biology and researcher at the Institute of Biotechnology and Biomedicine (IBB-UAB), who led the research together with the first author of the paper, Javier Garcia-Pardo, a Juan de la Cierva-Incorporación researcher at IBB-UAB. Researchers have determined the structure of the amyloid fibers of the hnRNPDL-2 protein using high-resolution cryo-electron microscopy (cryo-EM). This is the first structure of a human functional amyloid formed by the complete protein to be solved using this technique—previously, only structures formed by fragments of these proteins had been solved. It is also the first amyloid structure determined at high-resolution by a Spanish research team. The structure of the protein differs from that of other pathological amyloid proteins in that it has a highly hydrophilic nucleus, which includes the amino acid associated with LGMD D3. In this case, unlike in other diseases, amyloid formation is not toxic, but necessary for the function of the protein. The results change the concept of the origin of the disease and how it should be treated, say the researchers. \"Previously, we thought that, as in many neurodegenerative diseases, LGMD D3 originated because mutations in patients caused the initially soluble protein to form aggregates and, therefore, the search for anti-aggregant molecules could be a potential therapy. Now we know that this would be a mistake, since it is the incorrect formation of the fiber that seems to trigger the disease; therefore, molecules that stabilize this structure or facilitate its formation would be the most appropriate,\" says Salvador Ventura. Understanding the molecular structures of amyloids Certain human amyloids can undergo both functional and pathological aggregation, and it is therefore necessary to understand their molecular structures in order to determine their distinctive qualities and functions. For example, RNPs similar to the one studied in this research, such as hnRNPA1 or FUS, are able to form functional amyloid fibers in response to cellular stress, but they can also harbor mutations responsible for disease. These proteins are characterized by a modular architecture, including one or more nucleic acid binding domains, together with disordered regions that are responsible for the formation of their assembly into functional or pathological amyloid structures. \"In recent years, the structures of various amyloid fibers formed by fragments of RNPs have been solved. However, these assemblies may not necessarily coincide with those adopted in the context of complete proteins, as is the case of the structure obtained for hnRNPDL-2 solved in our group,\" explains Salvador Ventura. \"In fact, our structure differs significantly from previous ones and questions some of the assumptions that were considered valid regarding the regulation of these proteins in cells,\" he points out. Special techniques for resolving functional amyloids To resolve the structure of hnRNPDL-2 in its assembled state, the research team used the cryo-EM technique, applying special techniques to resolve amyloid structures. In the past two years, a significant number of amyloid fiber structures have been solved with this technique, but these mainly correspond to pathological amyloids involved in systemic and neurodegenerative diseases. \"Our discovery highlights the power of cryo-EM to study the function of RNPs and the reasons for their link to disease. These proteins have been little studied until now, but they are associated with diseases such as Alzheimer's, muscular dystrophies, cancer, and neurodevelopmental and neuropsychiatric disorders. Thus, our objective now is to take advantage of the experience acquired with this technique to determine the fibrillary states of other functional amyloids and study the effect of mutations, in order to better understand their implications in health and disease,\" says Salvador Ventura. The development of this new technology at the UAB will allow researchers to exploit the recently installed cryo-EM platform at the Alba synchrotron, of which the university is a partner. Solving this type of structure requires a great deal of computational power. The IBB's Protein Folding and Conformational Diseases research group led by Salvador Ventura has just acquired a high-powered computer to carry out these calculations. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract hnRNPDL is a ribonucleoprotein (RNP) involved in transcription and RNA-processing that hosts missense mutations causing limb-girdle muscular dystrophy D3 (LGMD D3). Mammalian-specific alternative splicing (AS) renders three natural isoforms, hnRNPDL-2 being predominant in humans. We present the cryo-electron microscopy structure of full-length hnRNPDL-2 amyloid fibrils, which are stable, non-toxic, and bind nucleic acids. The high-resolution amyloid core consists of a single Gly/Tyr-rich and highly hydrophilic filament containing internal water channels. The RNA binding domains are located as a solenoidal coat around the core. The architecture and activity of hnRNPDL-2 fibrils are reminiscent of functional amyloids, our results suggesting that LGMD D3 might be a loss-of-function disease associated with impaired fibrillation. Strikingly, the fibril core matches exon 6, absent in the soluble hnRNPDL-3 isoform. This provides structural evidence for AS controlling hnRNPDL assembly by precisely including/skipping an amyloid exon, a mechanism that holds the potential to generate functional diversity in RNPs. Introduction Human heterogeneous ribonucleoprotein D-like (hnRNPDL) belongs to a class of conserved nuclear RNA-binding proteins (RBPs) that assemble with RNA to form ribonucleoproteins (RNPs). hnRNPDL acts as a transcriptional regulator and participates in the metabolism and biogenesis of mRNA 1 , 2 , 3 , 4 . Three isoforms of hnRNPDL are produced by alternative splicing (AS): hnRNPDL-1, hnRNPDL-2, and hnRNPDL-3 5 (Fig. 1a and Supplementary Fig. 1 ). hnRNPDL-2 is a 301 residues protein and the predominant isoform in human tissues 6 . It consists of two consecutive globular RNA recognition motifs (RRM1 and RRM2), followed by a C-terminal low-complexity domain (LCD) that maps at residues ~201–285 and a nuclear localization sequence (PY-NLS) comprising residues 281-301. hnRNPDL-1 is a longer isoform of 420 amino acids containing an additional Arg-rich N-terminal LCD 5 ; it is less abundant than hnRNPDL-2 and is present mainly in brain and testis 6 . hnRNPDL-3 is a shorter and minor isoform of 244 amino acids that lacks the N- and C- terminal LCDs but conserves the PY-NLS 7 . Fig. 1: hnRNPDL-2 aggregates into ordered amyloid fibrils. a Domain organization of human hnRNPDL isoforms. The RNA recognition motifs are labelled as RRM (pink) and N- and C-terminal low complexity domains (LCD) are indicated as R-rich LCD (orange) and Y/G-rich LCD (blue), respectively. The region and sequence of exon 6 is also indicated, according to hnRNPDL-2 numbering. D259 disease-associated amino acid is shown in red. NLS indicates the shared nuclear localization signal. b Representative confocal images of HeLa hnRNPDL KO cells transiently transfected with the different hnRNPDL isoforms (DL-1, DL-2 and DL-3). The empty GFP vector (GFP) was transfected as control. The images depict the characteristic nuclear distribution of GFP-hnRNPDL fusions (green). Nuclear DNA was stained with Hoechst (blue). White arrows indicate the location of the nucleolus. In all cases, the nucleus contour has been indicated with a white dashed line. Scale bar, 10 μm. c Th-T binding to hnRNPDL-1 (orange line), hnRNPDL-2 (blue line) and hnRNPDL-3 (purple line) after incubation at 37 °C and 600 rpm, pH 7.5 and 300 mM NaCl for 2 days. Representative negative staining TEM micrographs of the incubated solutions of ( d ) hnRNPDL-1, ( e ) hnRNPDL-2 and ( f ) hnRNPDL-3. Scale bar, 200 nm. Note that only in ( e ) individual amyloid filaments are evident. In ( b ) and ( d–f ), results are representative from three independent experiments. Full size image A point mutation in hnRNPDL exon 6 causes autosomal dominant limb-girdle muscular dystrophy D3 (LGMD D3) 8 , 9 , 10 , a rare disease characterized by slowly progressive proximal muscle weakness 11 , 12 . This mutation changes the conserved Asp259 in the C-terminal LCD to either Asn or His. Similarly, mutation of specific Asp residues to Asn or Val in the LCDs of hnRNPA1 and hnRNPA2 are linked to amyotrophic lateral sclerosis (ALS) and multisystem proteinopathy (MSP) 13 , 14 . However, unlike ALS and MSP patients, where hnRNPA1 and hnRNPA2 accumulate in cytoplasmic inclusions in muscular fibers 14 , 15 , most LGMD D3 patients do not exhibit nuclear or cytoplasmatic protein inclusions 8 . Structures of the amyloid fibrils formed by hnRNPA1 and hnRNPA2 LCDs have been recently determined 16 , 17 . For both fibrils, the PY-NLS was embedded within the ordered core. This led to suggest that, under physiological conditions, binding of the import receptor karyopherin-β2 (Kapβ2) to PY-NLS 18 would impede fibrillation, whereas its exposure under pathological conditions would allow amyloid formation 16 . However, in these studies, constructs of the LCD, alone or fused to a fluorescent protein, were used to form the fibrils, and it is unknown whether the observed assemblies would match those of the natural full-length proteins’ fibrils. Here we present the cryo-electron microscopy (cryo-EM) structure of the fibrils formed by the full-length hnRNPDL-2 isoform at an overall resolution of 2.5 Å. These fibrils are stable and bind oligonucleotides, with the associated RRM domains building an exposed solenoidal coat wrapping the structured fibril. The fibrils’ core is formed by a single highly hydrophilic filament encompassing LCD residues 226-276, including Asp259. Modeling suggests that disease-associated mutations at this residue may have limited impact on fibril stability. Importantly, the fibril core does not include the PY-NLS. The hnRNPDL-2 fibril core precisely matches exon 6 (residues 224-280), which is alternatively spliced (AS) in a mammalian-specific manner 19 . These AS events are frequent in RNPs, especially at their Y/G-rich LCDs 19 and they have been proposed to be a way to regulate protein function by controlling the formation of high-order assemblies 20 ; our results provide structural evidence supporting this hypothesis. Overall, we describe the structure of a full-length RNP in its fibrillar functional conformation, providing insight into the molecular bases of LGMD D3, and illustrating how AS can control RNPs assembly by including/excluding amyloidogenic exons at their LCDs. Results hnRNPDLs localize at the nucleus and exon 6 is key for their compartmentalization Human hnRNPDL AS renders three naturally occurring transcripts (Fig. 1a and Supplementary Fig. 1 ). When transfected into a HeLa<|im_end|> <|im_start|>assistant Researchers at the UAB have determined the structure of amyloid fibers formed by the protein hnRNPDL-2, implicated in limb-girdle muscular dystrophy type 3, using high-resolution cryo-electron microscopy (cryo-EM). They have concluded that the inability of the protein to form amyloid fibers, and not aggregation, would be the cause of the disease. This is the first amyloid structure determined at high resolution by a Spanish research team. The study, published in Nature Communications, informs the search for molecules that stabilize or facilitate amyloid formation and opens the door to the study of other functional amyloids and their mutations using the same technique, in order to better understand their implications in health and disease. Limb-girdle muscular dystrophy type 3 (LGMD D3) is a rare disease causing progressive muscle weakness caused by point mutations in the hnRNPDL-2 protein. A member of the RNA-associated ribonucleoprotein (RNP) family, it is a little-known protein with the ability to assemble to form functional amyloid structures. Amyloids are formed by the joining of thousands of pieces of the same protein to form very stable and structured fibers (protein aggregates). Their formation is often associated with diseases such as Parkinson's and Alzheimer's, but they are also used by different organisms for functional purposes, although the number of functional amyloids described in humans is still small. Researchers at the Universitat Autònoma de Barcelona (UAB) have determined that the architecture and activity of the amyloid fibers suggest that they are stable, non-toxic amyloid fibers that bind nucleic acids in their aggregated state. The results indicate that LGMD D3 could be a protein loss-of-function disease: the inability to form the amyloid structures described in the study would cause the pathology. "Our study challenges the hypothesis that the aggregation of this protein is the cause of the disease and proposes that it is the inability to form a fibrillar structure that has been selected by evolution to bind nucleic acids that causes the pathology," says Salvador Ventura, professor of Biochemistry and Molecular Biology and researcher at the Institute of Biotechnology and Biomedicine (IBB-UAB), who led the research together with the first author of the paper, Javier Garcia-Pardo, a Juan de la Cierva-Incorporación researcher at IBB-UAB. Researchers have determined the structure of the amyloid fibers of the hnRNPDL-2 protein using high-resolution cryo-electron microscopy (cryo-EM). This is the first structure of a human functional amyloid formed by the complete protein to be solved using this technique—previously, only structures formed by fragments of these proteins had been solved. It is also the first amyloid structure determined at high-resolution by a Spanish research team. The structure of the protein differs from that of other pathological amyloid proteins in that it has a highly hydrophilic nucleus, which includes the amino acid associated with LGMD D3. In this case, unlike in other diseases, amyloid formation is not toxic, but necessary for the function of the protein. The results change the concept of the origin of the disease and how it should be treated, say the researchers. "Previously, we thought that, as in many neurodegenerative diseases, LGMD D3 originated because mutations in patients caused the initially soluble protein to form aggregates and, therefore, the search for anti-aggregant molecules could be a potential therapy. Now we know that this would be a mistake, since it is the incorrect formation of the fiber that seems to trigger the disease; therefore, molecules that stabilize this structure or facilitate its formation would be the most appropriate," says Salvador Ventura. Understanding the molecular structures of amyloids Certain human amyloids can undergo both functional and pathological aggregation, and it is therefore necessary to understand their molecular structures in order to determine their distinctive qualities and functions. For example, RNPs similar to the one studied in this research, such as hnRNPA1 or FUS, are able to form functional amyloid fibers in response to cellular stress, but they can also harbor mutations responsible for disease. These proteins are characterized by a modular architecture, including one or more nucleic acid binding domains, together with disordered regions that are responsible for the formation of their assembly into functional or pathological amyloid structures. "In recent years, the structures of various amyloid fibers formed by fragments of RNPs have been solved. However, these assemblies may not necessarily coincide with those adopted in the context of complete proteins, as is the case of the structure obtained for hnRNPDL-2 solved in our group," explains Salvador Ventura. "In fact, our structure differs significantly from previous ones and questions some of the assumptions that were considered valid regarding the regulation of these proteins in cells," he points out. Special techniques for resolving functional amyloids To resolve the structure of hnRNPDL-2 in its assembled state, the research team used the cryo-EM technique, applying special techniques to resolve amyloid structures. In the past two years, a significant number of amyloid fiber structures have been solved with this technique, but these mainly correspond to pathological amyloids involved in systemic and neurodegenerative diseases. "Our discovery highlights the power of cryo-EM to study the function of RNPs and the reasons for their link to disease. These proteins have been little studied until now, but they are associated with diseases such as Alzheimer's, muscular dystrophies, cancer, and neurodevelopmental and neuropsychiatric disorders. Thus, our objective now is to take advantage of the experience acquired with this technique to determine the fibrillary states of other functional amyloids and study the effect of mutations, in order to better understand their implications in health and disease," says Salvador Ventura. The development of this new technology at the UAB will allow researchers to exploit the recently installed cryo-EM platform at the Alba synchrotron, of which the university is a partner. Solving this type of structure requires a great deal of computational power. The IBB's Protein Folding and Conformational Diseases research group led by Salvador Ventura has just acquired a high-powered computer to carry out these calculations. <|im_end|>

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320, 3336, 33, 35681, 1905, 705, 889, 6197, 279, 3495, 3871, 449, 279, 1176, 3229, 315, 279, 5684, 11, 71309, 38810, 9483, 21106, 11, 264, 29604, 409, 1208, 32744, 46965, 32600, 6133, 4406, 5840, 32185, 520, 358, 10306, 35681, 1905, 13, 59250, 617, 11075, 279, 6070, 315, 279, 64383, 52196, 49774, 315, 279, 96338, 49, 27321, 16931, 12, 17, 13128, 1701, 1579, 64036, 16106, 78, 37081, 2298, 92914, 320, 62238, 78, 12, 2783, 570, 1115, 374, 279, 1176, 6070, 315, 264, 3823, 16003, 64383, 52196, 14454, 555, 279, 4686, 13128, 311, 387, 29056, 1701, 420, 15105, 2345, 1762, 18785, 11, 1193, 14726, 14454, 555, 35603, 315, 1521, 28896, 1047, 1027, 29056, 13, 1102, 374, 1101, 279, 1176, 64383, 52196, 6070, 11075, 520, 1579, 64036, 555, 264, 15506, 3495, 2128, 13, 578, 6070, 315, 279, 13128, 44642, 505, 430, 315, 1023, 89961, 64383, 52196, 28896, 304, 430, 433, 706, 264, 7701, 17055, 46185, 292, 62607, 11, 902, 5764, 279, 42500, 13935, 5938, 449, 24294, 6204, 423, 18, 13, 763, 420, 1162, 11, 20426, 304, 1023, 19338, 11, 64383, 52196, 18488, 374, 539, 21503, 11, 719, 5995, 369, 279, 734, 315, 279, 13128, 13, 578, 3135, 2349, 279, 7434, 315, 279, 6371, 315, 279, 8624, 323, 1268, 433, 1288, 387, 12020, 11, 2019, 279, 12074, 13, 330, 83039, 11, 584, 3463, 430, 11, 439, 304, 1690, 18247, 451, 7642, 1413, 19338, 11, 24294, 6204, 423, 18, 44853, 1606, 34684, 304, 6978, 9057, 279, 15453, 88045, 13128, 311, 1376, 71643, 323, 11, 9093, 11, 279, 2778, 369, 7294, 43085, 8157, 519, 35715, 1436, 387, 264, 4754, 15419, 13, 4800, 584, 1440, 430, 420, 1053, 387, 264, 16930, 11, 2533, 433, 374, 279, 15465, 18488, 315, 279, 24722, 430, 5084, 311, 8346, 279, 8624, 26, 9093, 11, 35715, 430, 70236, 420, 6070, 477, 28696, 1202, 18488, 1053, 387, 279, 1455, 8475, 1359, 2795, 49459, 85754, 13, 46551, 279, 31206, 14726, 315, 64383, 385, 3447, 35211, 3823, 64383, 385, 3447, 649, 37771, 2225, 16003, 323, 89961, 52729, 11, 323, 433, 374, 9093, 5995, 311, 3619, 872, 31206, 14726, 304, 2015, 311, 8417, 872, 35947, 29600, 323, 5865, 13, 1789, 3187, 11, 46916, 21051, 4528, 311, 279, 832, 20041, 304, 420, 3495, 11, 1778, 439, 96338, 51295, 8201, 16, 477, 435, 2078, 11, 527, 3025, 311, 1376, 16003, 64383, 52196, 49774, 304, 2077, 311, 35693, 8631, 11, 719, 814, 649, 1101, 57511, 34684, 8647, 369, 8624, 13, 4314, 28896, 527, 32971, 555, 264, 44993, 18112, 11, 2737, 832, 477, 810, 31484, 292, 13935, 11212, 31576, 11, 3871, 449, 834, 10767, 13918, 430, 527, 8647, 369, 279, 18488, 315, 872, 14956, 1139, 16003, 477, 89961, 64383, 52196, 14726, 13, 330, 644, 3293, 1667, 11, 279, 14726, 315, 5370, 64383, 52196, 49774, 14454, 555, 35603, 315, 46916, 21051, 617, 1027, 29056, 13, 4452, 11, 1521, 62407, 1253, 539, 14647, 72359, 449, 1884, 18306, 304, 279, 2317, 315, 4686, 28896, 11, 439, 374, 279, 1162, 315, 279, 6070, 12457, 369, 96338, 49, 27321, 16931, 12, 17, 29056, 304, 1057, 1912, 1359, 15100, 49459, 85754, 13, 330, 644, 2144, 11, 1057, 6070, 44642, 12207, 505, 3766, 6305, 323, 4860, 1063, 315, 279, 32946, 430, 1051, 6646, 2764, 9002, 279, 19812, 315, 1521, 28896, 304, 7917, 1359, 568, 3585, 704, 13, 9984, 12823, 369, 53583, 16003, 64383, 385, 3447, 2057, 9006, 279, 6070, 315, 96338, 49, 27321, 16931, 12, 17, 304, 1202, 35105, 1614, 11, 279, 3495, 2128, 1511, 279, 16106, 78, 12, 2783, 15105, 11, 19486, 3361, 12823, 311, 9006, 64383, 52196, 14726, 13, 763, 279, 3347, 1403, 1667, 11, 264, 5199, 1396, 315, 64383, 52196, 24722, 14726, 617, 1027, 29056, 449, 420, 15105, 11, 719, 1521, 14918, 8024, 311, 89961, 64383, 385, 3447, 6532, 304, 46417, 323, 18247, 451, 7642, 1413, 19338, 13, 330, 8140, 18841, 22020, 279, 2410, 315, 16106, 78, 12, 2783, 311, 4007, 279, 734, 315, 46916, 21051, 323, 279, 8125, 369, 872, 2723, 311, 8624, 13, 4314, 28896, 617, 1027, 2697, 20041, 3156, 1457, 11, 719, 814, 527, 5938, 449, 19338, 1778, 439, 44531, 596, 11, 52192, 69110, 22761, 552, 11, 9572, 11, 323, 18247, 30671, 278, 323, 21143, 98438, 23336, 24673, 13, 14636, 11, 1057, 16945, 1457, 374, 311, 1935, 9610, 315, 279, 3217, 19426, 449, 420, 15105, 311, 8417, 279, 95235, 35605, 5415, 315, 1023, 16003, 64383, 385, 3447, 323, 4007, 279, 2515, 315, 34684, 11, 304, 2015, 311, 2731, 3619, 872, 25127, 304, 2890, 323, 8624, 1359, 2795, 49459, 85754, 13, 578, 4500, 315, 420, 502, 5557, 520, 279, 549, 1905, 690, 2187, 12074, 311, 33294, 279, 6051, 10487, 16106, 78, 12, 2783, 5452, 520, 279, 1708, 4749, 6925, 331, 299, 35785, 11, 315, 902, 279, 12374, 374, 264, 8427, 13, 11730, 4504, 420, 955, 315, 6070, 7612, 264, 2294, 3568, 315, 55580, 2410, 13, 578, 358, 10306, 596, 49475, 92250, 323, 1221, 1659, 278, 70674, 3495, 1912, 6197, 555, 49459, 85754, 706, 1120, 19426, 264, 1579, 41503, 6500, 311, 6920, 704, 1521, 29217, 13, 220, 128257, 198 ]

2,912

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract There is increasing evidence that the Himalayan seismicity can be bimodal: blind earthquakes (up to Mw ~ 7.8) tend to cluster in the downdip part of the seismogenic zone, whereas infrequent great earthquakes (Mw 8+) propagate up to the Himalayan frontal thrust. To explore the causes of this bimodal seismicity, we developed a two-dimensional, seismic cycle model of the Nepal Himalaya. Our visco-elasto-plastic simulations reproduce important features of the earthquake cycle, including interseismic strain and a bimodal seismicity pattern. Bimodal seismicity emerges as a result of relatively higher friction and a non-planar geometry of the Main Himalayan Thrust fault. This introduces a region of large strength excess that can only be activated once enough stress is transferred upwards by blind earthquakes. This supports the view that most segments of the Himalaya might produce complete ruptures significantly larger than the 2015 Mw 7.8 Gorkha earthquake, which should be accounted for in future seismic hazard assessments. Introduction On 25 April 2015, an earthquake with moment magnitude Mw 7.8 struck the Nepal Himalaya 1 , 2 , 3 , rupturing a 50-km-wide segment of the Main Himalayan Thrust (MHT) fault (Fig. 1 a). The 2015 Gorkha earthquake has a similar location as the 1833 earthquake, with estimated magnitude Mw 7.6–7.7, which also caused significant damage in Kathmandu 4 , 5 . The geometry of the MHT is relatively well known in their hypocentral region from various geological and geophysical campaigns 6 , 7 , 8 . In particular, geodetic data (SAR, InSAR and GPS) and the detailed location of the Gorkha seismic sequence have provided new constraints on the geometry of the MHT 9 , 10 . This information allows us to investigate the relation between interseismic strain and seismicity—given the MHT geometry—and contribute to an ongoing debate on how the Himalayan wedge is deforming. Some authors claim that the location of the front of the high topography could be explained by a mid-crustal ramp along the MHT 11 , 12 , 13 . Conversely, others have argued for active out-of-sequence thrusting at the front of the high Himalaya 14 , 15 . Understanding how and where stresses build up in the Himalaya is important, because evaluating the balance between the interseismic strain accumulation and the elastic strain released during seismic events could potentially improve the seismic hazard assessment in central Nepal following the 2015 earthquake 16 . Fig. 1 Seismotectonic context, model setup and fault geometries. a , Topographic relief, coupling mode and historical seismicity. The white arrows show the long-term shortening across the arc. The interseismic coupling is shown as shades of red (ref. 48 ). A coupling value of 1 means the area is fully locked, while a value of 0 means fully creeping. Coloured patches indicate the supposed rupture zones since 1505 (refs. 4 , 21 , 22 ): blue patches display blind ruptures of large (Mw ≤ 7.8) earthquakes, whereas yellow patches indicate surface ruptures of great (Mw > 8) events. Black line indicates the cross-section utilised for the numerical model setup. b , Zoom of the initial reference setup (model EF) and temperature. The numerical setup represents the geological cross-section of the Nepal Himalaya constrained from the main-shock and aftershocks of the Gorkha sequence (ref. 9 ). c , Additional fault geometries employed in the numerical experiments: model DF, from Duputel et al. 10 , and a planar fault geometry (model PF) Full size image It has long been noticed that the seismicity in the Himalaya is bimodal 11 , 17 , 18 . Partial (blind) earthquakes (up to Mw ~ 7.8) tend to cluster and repeatedly rupture the deeper portion of the MHT, whereas sporadic great earthquakes (Mw > 8) completely unzip the entire width of the seismogenic zone (Fig. 1a ). The partial ruptures are generally characterised by 10–15 km focal depths and clustered along the front of the Himalaya. They seem to occur in the vicinity of the mid-crustal ramp 11 . The Mw 7.8 Gorkha earthquake is the largest known event in that category. On the other hand, paleoseismological field studies found evidence for surface ruptures at the Himalayan frontal fault (Main Frontal Thrust, MFT), probably associated with great (Mw > 8) events 16 , 19 , 20 , 21 , 22 . The 1934 Mw 8.4 Bihar Nepal 16 , 22 and the 1950 Mw 8.7 Assam earthquake 23 —the largest intracontinental earthquake ever recorded—probably fall in that category. On the basis of these observations, the mechanism driving bimodal behaviour remains poorly understood. One potential explanation is that the MHT consists of along-dip subsegments that rupture—either independently or jointly with neighbouring segments during larger earthquakes—with a non-periodic or even chaotic behaviour arising from stress transfers. This segmentation may partly be controlled by rheological 24 and geometrical complexities such as local non-planarity 5 , 25 , 26 . There is also growing evidence that fault frictional properties are also an influential and perhaps determining factor that affect the spatial extent, size and timing of megathrust ruptures 27 . Dynamic simulations over multiple earthquake cycles with a linear slip-weakening friction law show that a large event that ruptures the entire fault is preceded by a number of small events with various rupture lengths 28 . These results are in keeping with dynamic modelling of the seismic cycle based on rate-and-state friction, which produce partial ruptures even in the case of a planar fault with uniform frictional properties 29 . However, how complete ruptures relate to partial ruptures and the geometry and mechanical properties of the MHT, has not yet been investigated quantitatively. Here we report the use of a novel two-dimensional (2D) numerical approach (Methods section) to explore the seismic rupture pattern on the MHT over many earthquake cycles (Fig. 1b ). The geometry and mechanical properties of our model are defined based on constraints from structural geology and geophysical campaigns 7 and new insights gained from studies of the Gorkha sequence 1 , 5 , 9 , 10 . The temperature distribution", "role": "user" }, { "content": "Nepal was struck by an earthquake with a magnitude of 7.8 in 2015, but the country may still face the threat of much stronger temblor. This is the conclusion reached by ETH researchers based on a new model that simulates physical processes of earthquake rupture between the Eurasian and Indian Plates. In April 2015, Nepal – and especially the region around the capital city, Kathmandu – was struck by a powerful tremor. An earthquake with a magnitude of 7.8 destroyed entire villages, traffic routes and cultural monuments, with a death toll of some 9,000. However, the country may still face the threat of much stronger earthquakes with a magnitude of 8 or more. This is the conclusion reached by a group of earth scientists from ETH Zurich based on a new model of the collision zone between the Indian and Eurasian Plates in the vicinity of the Himalayas. Using this model, the team of ETH researchers working with doctoral student Luca Dal Zilio, from the group led by Professor Taras Gerya at the Institute of Geophysics, has now performed the first high-resolution simulations of earthquake cycles in a cross-section of the rupture zone. \"In the 2015 quake, there was only a partial rupture of the major Himalayan fault separating the two continental plates. The frontal, near-surface section of the rupture zone, where the Indian Plate subducts beneath the Eurasian Plate, did not slip and remains under stress,\" explains Dal Zilio, lead author of the study, which was recently published in the journal Nature Communications. Cross section through the fracture zone (black thick line) between the Indian (grey areas) and the Eurasian plate (green areas). Credit: Dal Zilio et al., Nat.Comm. 2019 Normally, a major earthquake releases almost all the stress that has built up in the vicinity of the focus as a result of displacement of the plates. \"Our model shows that, although the Gorkha earthquake reduced the stress level in part of the rupture zone, tension actually increased in the frontal section close to the foot of the Himalayas. The apparent paradox is that 'medium-sized' earthquakes such as Gorkha can create the conditions for an even larger earthquake,\" says Dal Zilio. Tremors of the magnitude of the Gorkha earthquake release stress only in the deeper subsections of the fault system over lengths of 100 kilometres. In turn, new and even greater stress builds up in the near-surface sections of the rupture zone. According to the simulations performed by Dal Zilio and his colleagues, two or three further Gorkha quakes would be needed to build up sufficient stress for an earthquake with a magnitude of 8.1 or more. In a quake of this kind, the rupture zone breaks over the entire depth range, extending up to the Earth's surface and laterally—along the Himalayan arc—for hundreds of kilometres. This ultimately leads to a complete stress release in this segment of the fault system, which extends to some 2,000 kilometres in total. Historical data shows that mega events of this kind have also occurred in the past. For example, the Assam earthquake in 1950 had a magnitude of 8.6, with the rupture zone breaking over a length of several hundred kilometres and across the entire depth range. In 1505, a giant earthquake struck with sufficient power to produce an approximately 800-kilometre rupture on the major Himalayan fault. Where plates collide: The main frontal thrust (red line) extends over the entire length of the Himalayas. Credit: NASA Earth Observatory \"The new model reveals that powerful earthquakes in the Himalayas have not just one form but at least two, and that their cycles partially overlap,\" says Edi Kissling, Professor of Seismology and Geodynamics. Super earthquakes might occur with a periodicity of 400 to 600 years, whereas \"medium-sized\" quakes such as Gorkha have a recurrence time of up to a few hundred years. As the cycles overlap, the researchers expect powerful and dangerous earthquakes to occur at irregular intervals. However, they cannot predict when another extremely large quake will next take place. \"No one can predict earthquakes, not even with the new model. However, we can improve our understanding of the seismic hazard in a specific area and take appropriate precautions,\" says Kissling. The two-dimensional and high-resolution model also includes some research findings that were published after the Gorkha earthquake. To generate the simulations, the researchers used the Euler mainframe computer at ETH Zurich. \"A three-dimensional model would be more accurate and would also allow us to make statements about the western and eastern fringes of the Himalayas. However, modelling the entire 2,000 kilometres of the rupture zone would require enormous computational power that not even the supercomputers at the CSCS can provide,\" says Dal Zilio. Nepal lies at the point where two continents meet: India and Eurasia. It is here that the Indian Plate subducts into the mantle beneath the Eurasian plate. Due to the suction effect exerted by the Indian Plate as it sinks into the mantle, the Indian subcontinent moves north by up to 4 centimetres a year. As a result, the plates rub against each other over the length of this 2,000-kilometre fault system, allowing considerable amounts of stress to build up. During an earthquake, the sudden release of this stress causes an abrupt displacement of the plates next to each other. This is why Nepal and the southern foothills of the Himalayas repeatedly experience very powerful earthquakes. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract There is increasing evidence that the Himalayan seismicity can be bimodal: blind earthquakes (up to Mw ~ 7.8) tend to cluster in the downdip part of the seismogenic zone, whereas infrequent great earthquakes (Mw 8+) propagate up to the Himalayan frontal thrust. To explore the causes of this bimodal seismicity, we developed a two-dimensional, seismic cycle model of the Nepal Himalaya. Our visco-elasto-plastic simulations reproduce important features of the earthquake cycle, including interseismic strain and a bimodal seismicity pattern. Bimodal seismicity emerges as a result of relatively higher friction and a non-planar geometry of the Main Himalayan Thrust fault. This introduces a region of large strength excess that can only be activated once enough stress is transferred upwards by blind earthquakes. This supports the view that most segments of the Himalaya might produce complete ruptures significantly larger than the 2015 Mw 7.8 Gorkha earthquake, which should be accounted for in future seismic hazard assessments. Introduction On 25 April 2015, an earthquake with moment magnitude Mw 7.8 struck the Nepal Himalaya 1 , 2 , 3 , rupturing a 50-km-wide segment of the Main Himalayan Thrust (MHT) fault (Fig. 1 a). The 2015 Gorkha earthquake has a similar location as the 1833 earthquake, with estimated magnitude Mw 7.6–7.7, which also caused significant damage in Kathmandu 4 , 5 . The geometry of the MHT is relatively well known in their hypocentral region from various geological and geophysical campaigns 6 , 7 , 8 . In particular, geodetic data (SAR, InSAR and GPS) and the detailed location of the Gorkha seismic sequence have provided new constraints on the geometry of the MHT 9 , 10 . This information allows us to investigate the relation between interseismic strain and seismicity—given the MHT geometry—and contribute to an ongoing debate on how the Himalayan wedge is deforming. Some authors claim that the location of the front of the high topography could be explained by a mid-crustal ramp along the MHT 11 , 12 , 13 . Conversely, others have argued for active out-of-sequence thrusting at the front of the high Himalaya 14 , 15 . Understanding how and where stresses build up in the Himalaya is important, because evaluating the balance between the interseismic strain accumulation and the elastic strain released during seismic events could potentially improve the seismic hazard assessment in central Nepal following the 2015 earthquake 16 . Fig. 1 Seismotectonic context, model setup and fault geometries. a , Topographic relief, coupling mode and historical seismicity. The white arrows show the long-term shortening across the arc. The interseismic coupling is shown as shades of red (ref. 48 ). A coupling value of 1 means the area is fully locked, while a value of 0 means fully creeping. Coloured patches indicate the supposed rupture zones since 1505 (refs. 4 , 21 , 22 ): blue patches display blind ruptures of large (Mw ≤ 7.8) earthquakes, whereas yellow patches indicate surface ruptures of great (Mw > 8) events. Black line indicates the cross-section utilised for the numerical model setup. b , Zoom of the initial reference setup (model EF) and temperature. The numerical setup represents the geological cross-section of the Nepal Himalaya constrained from the main-shock and aftershocks of the Gorkha sequence (ref. 9 ). c , Additional fault geometries employed in the numerical experiments: model DF, from Duputel et al. 10 , and a planar fault geometry (model PF) Full size image It has long been noticed that the seismicity in the Himalaya is bimodal 11 , 17 , 18 . Partial (blind) earthquakes (up to Mw ~ 7.8) tend to cluster and repeatedly rupture the deeper portion of the MHT, whereas sporadic great earthquakes (Mw > 8) completely unzip the entire width of the seismogenic zone (Fig. 1a ). The partial ruptures are generally characterised by 10–15 km focal depths and clustered along the front of the Himalaya. They seem to occur in the vicinity of the mid-crustal ramp 11 . The Mw 7.8 Gorkha earthquake is the largest known event in that category. On the other hand, paleoseismological field studies found evidence for surface ruptures at the Himalayan frontal fault (Main Frontal Thrust, MFT), probably associated with great (Mw > 8) events 16 , 19 , 20 , 21 , 22 . The 1934 Mw 8.4 Bihar Nepal 16 , 22 and the 1950 Mw 8.7 Assam earthquake 23 —the largest intracontinental earthquake ever recorded—probably fall in that category. On the basis of these observations, the mechanism driving bimodal behaviour remains poorly understood. One potential explanation is that the MHT consists of along-dip subsegments that rupture—either independently or jointly with neighbouring segments during larger earthquakes—with a non-periodic or even chaotic behaviour arising from stress transfers. This segmentation may partly be controlled by rheological 24 and geometrical complexities such as local non-planarity 5 , 25 , 26 . There is also growing evidence that fault frictional properties are also an influential and perhaps determining factor that affect the spatial extent, size and timing of megathrust ruptures 27 . Dynamic simulations over multiple earthquake cycles with a linear slip-weakening friction law show that a large event that ruptures the entire fault is preceded by a number of small events with various rupture lengths 28 . These results are in keeping with dynamic modelling of the seismic cycle based on rate-and-state friction, which produce partial ruptures even in the case of a planar fault with uniform frictional properties 29 . However, how complete ruptures relate to partial ruptures and the geometry and mechanical properties of the MHT, has not yet been investigated quantitatively. Here we report the use of a novel two-dimensional (2D) numerical approach (Methods section) to explore the seismic rupture pattern on the MHT over many earthquake cycles (Fig. 1b ). The geometry and mechanical properties of our model are defined based on constraints from structural geology and geophysical campaigns 7 and new insights gained from studies of the Gorkha sequence 1 , 5 , 9 , 10 . The temperature distribution<|im_end|> <|im_start|>assistant Nepal was struck by an earthquake with a magnitude of 7.8 in 2015, but the country may still face the threat of much stronger temblor. This is the conclusion reached by ETH researchers based on a new model that simulates physical processes of earthquake rupture between the Eurasian and Indian Plates. In April 2015, Nepal – and especially the region around the capital city, Kathmandu – was struck by a powerful tremor. An earthquake with a magnitude of 7.8 destroyed entire villages, traffic routes and cultural monuments, with a death toll of some 9,000. However, the country may still face the threat of much stronger earthquakes with a magnitude of 8 or more. This is the conclusion reached by a group of earth scientists from ETH Zurich based on a new model of the collision zone between the Indian and Eurasian Plates in the vicinity of the Himalayas. Using this model, the team of ETH researchers working with doctoral student Luca Dal Zilio, from the group led by Professor Taras Gerya at the Institute of Geophysics, has now performed the first high-resolution simulations of earthquake cycles in a cross-section of the rupture zone. "In the 2015 quake, there was only a partial rupture of the major Himalayan fault separating the two continental plates. The frontal, near-surface section of the rupture zone, where the Indian Plate subducts beneath the Eurasian Plate, did not slip and remains under stress," explains Dal Zilio, lead author of the study, which was recently published in the journal Nature Communications. Cross section through the fracture zone (black thick line) between the Indian (grey areas) and the Eurasian plate (green areas). Credit: Dal Zilio et al., Nat.Comm. 2019 Normally, a major earthquake releases almost all the stress that has built up in the vicinity of the focus as a result of displacement of the plates. "Our model shows that, although the Gorkha earthquake reduced the stress level in part of the rupture zone, tension actually increased in the frontal section close to the foot of the Himalayas. The apparent paradox is that 'medium-sized' earthquakes such as Gorkha can create the conditions for an even larger earthquake," says Dal Zilio. Tremors of the magnitude of the Gorkha earthquake release stress only in the deeper subsections of the fault system over lengths of 100 kilometres. In turn, new and even greater stress builds up in the near-surface sections of the rupture zone. According to the simulations performed by Dal Zilio and his colleagues, two or three further Gorkha quakes would be needed to build up sufficient stress for an earthquake with a magnitude of 8.1 or more. In a quake of this kind, the rupture zone breaks over the entire depth range, extending up to the Earth's surface and laterally—along the Himalayan arc—for hundreds of kilometres. This ultimately leads to a complete stress release in this segment of the fault system, which extends to some 2,000 kilometres in total. Historical data shows that mega events of this kind have also occurred in the past. For example, the Assam earthquake in 1950 had a magnitude of 8.6, with the rupture zone breaking over a length of several hundred kilometres and across the entire depth range. In 1505, a giant earthquake struck with sufficient power to produce an approximately 800-kilometre rupture on the major Himalayan fault. Where plates collide: The main frontal thrust (red line) extends over the entire length of the Himalayas. Credit: NASA Earth Observatory "The new model reveals that powerful earthquakes in the Himalayas have not just one form but at least two, and that their cycles partially overlap," says Edi Kissling, Professor of Seismology and Geodynamics. Super earthquakes might occur with a periodicity of 400 to 600 years, whereas "medium-sized" quakes such as Gorkha have a recurrence time of up to a few hundred years. As the cycles overlap, the researchers expect powerful and dangerous earthquakes to occur at irregular intervals. However, they cannot predict when another extremely large quake will next take place. "No one can predict earthquakes, not even with the new model. However, we can improve our understanding of the seismic hazard in a specific area and take appropriate precautions," says Kissling. The two-dimensional and high-resolution model also includes some research findings that were published after the Gorkha earthquake. To generate the simulations, the researchers used the Euler mainframe computer at ETH Zurich. "A three-dimensional model would be more accurate and would also allow us to make statements about the western and eastern fringes of the Himalayas. However, modelling the entire 2,000 kilometres of the rupture zone would require enormous computational power that not even the supercomputers at the CSCS can provide," says Dal Zilio. Nepal lies at the point where two continents meet: India and Eurasia. It is here that the Indian Plate subducts into the mantle beneath the Eurasian plate. Due to the suction effect exerted by the Indian Plate as it sinks into the mantle, the Indian subcontinent moves north by up to 4 centimetres a year. As a result, the plates rub against each other over the length of this 2,000-kilometre fault system, allowing considerable amounts of stress to build up. During an earthquake, the sudden release of this stress causes an abrupt displacement of the plates next to each other. This is why Nepal and the southern foothills of the Himalayas repeatedly experience very powerful earthquakes. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Drug resistance and tolerance greatly diminish the therapeutic potential of antibiotics against pathogens. Antibiotic tolerance by bacterial biofilms often leads to persistent infections, but its mechanisms are unclear. Here we use a proteomics approach, pulsed stable isotope labelling with amino acids (pulsed-SILAC), to quantify newly expressed proteins in colistin-tolerant subpopulations of Pseudomonas aeruginosa biofilms (colistin is a ‘last-resort’ antibiotic against multidrug-resistant Gram-negative pathogens). Migration is essential for the formation of colistin-tolerant biofilm subpopulations, with colistin-tolerant cells using type IV pili to migrate onto the top of the colistin-killed biofilm. The colistin-tolerant cells employ quorum sensing (QS) to initiate the formation of new colistin-tolerant subpopulations, highlighting multicellular behaviour in antibiotic tolerance development. The macrolide erythromycin, which has been previously shown to inhibit the motility and QS of P. aeruginosa , boosts biofilm eradication by colistin. Our work provides insights on the mechanisms underlying the formation of antibiotic-tolerant populations in bacterial biofilms and indicates research avenues for designing more efficient treatments against biofilm-associated infections. Introduction The therapeutic efficacy of antibiotics can be severely crippled by two major bacterial defence strategies. ‘Resistance’ occurs when bacteria acquire genetic mutations or mobile genetic elements that enable growth under conditions of constant antibiotic exposure 1 , while ‘tolerance’ is mediated by transient phenotypic variations (based on protein expression) that enable bacteria to survive exposures to the highest deliverable doses of antibiotics 2 , 3 . While the current view is that development of tolerance is intrinsically linked to the biofilm lifestyle, early experiments conducted on bacteria in the planktonic lifestyle revealed that tolerance can develop to a number of stresses including antibiotics 4 , 5 . However, in contrast to the planktonic mode of life, biofilms are sessile, densely populated multicellular communities embedded in biopolymeric matrix components 6 . A major advantage for bacteria that aggregate into biofilms is that a multitude of matrix components and physiological states offers additional levels of protection against immune defences and antibiotics, which cannot be obtained in the planktonic growth mode 7 , 8 , 9 . It is widely accepted that pathogenic bacteria in the biofilm mode significantly contribute to the development of nosocomial infections as they are colonizing hospital settings and chronic infection sites, where they represent a serious threat to public health 6 . Bacterial cells differentiate into several physiologically distinct subpopulations within a biofilm 10 . Antibiotic treatment often eradicates sensitive subpopulations, but leaves small antibiotic-tolerant subpopulations behind, resulting in recurring infections after antibiotic treatment has been stopped 10 . Antibiotic-tolerant bacterial cells are variants of wild-type cells that can revert back to the wild type when antimicrobial treatment has ceased 11 . Their transient nature and low abundance make it difficult to investigate their tolerance-related physiology. With only a few studies that have investigated planktonic antibiotic-tolerant cells by pre-isolating them using flow cytometry 12 , 13 , 14 , 15 , the mechanisms underlying the formation of antibiotic-tolerant subpopulation in biofilms have remained elusive. Moreover, these pre-isolation-based strategies are destructive and not feasible for studying the antibiotic-tolerant subpopulations in biofilms. This prompted us to develop an alternative, high-resolution ‘-omics’ approach to simultaneously characterize the physiologies of sensitive and antibiotic-tolerant subpopulations in biofilms. Pseudomonas aeruginosa forms biofilm with extreme tolerance to antibiotics in nosocomial infections, such as pneumonia and surgical site infections, prompting the Centers for Disease Control and Prevention to classify P. aeruginosa under ‘serious’-threat level ( ) and the Infectious Diseases Society of America to declare it as one of the six ‘top-priority dangerous, drug-resistant microbes’ 16 . Colistin is a last-resort polymyxin antibiotic available for treatment of infections caused by drug-resistant Gram-negative bacteria 17 . P. aeruginosa biofilms in flow chambers develop colistin-tolerant cells rapidly and these cells feature high expression levels of the pmr operon 18 . Here we observe the dynamic development of drug-tolerant subpopulations in P. aeruginosa biofilms after treatment with colistin. To obtain knowledge about the physiology of the colistin-tolerant biofilm cells, we apply pulsed stable isotope labelling with amino acids (pulsed-SILAC) proteomics method to selectively quantify the newly expressed proteins that incorporate and are thus labelled with heavy C13 lysine, to promote understanding of the colistin-tolerant subpopulation physiology. The colistin-tolerant populations are able to migrate to the top of the dead biofilm by employing type IV pili-dependent motility and initiate formation of new biofilm via quorum sensing (QS)-regulated group activity. Synergistic treatment by use of erythromycin, which can inhibit QS and motility with colistin, is able to boost the elimination of P. aeruginosa biofilms. Hence, our study provides key insights in developing novel treatments against biofilm-associated infections, which otherwise prove hard to eradicate. Results and Discussion Development of colistin-tolerant subpopulations in biofilms We monitored the development of live and dead subpopulations of P. aeruginosa biofilms after exposure to colistin in real-time by using time series confocal image acquisition as well as enumeration of viable cells with colony forming units (c.f.u. per ml). Colistin exposure of P. aeruginosa wild-type biofilms tagged with green fluorescent protein (GFP) led to a sudden reduction in cell viability according to the propidium iodide (PI) dead staining ( Fig. 1a and Supplementary Movies 1 and 2 ) and c.f.u. per ml counting ( Fig. 1b ). However, we noticed that a few P. aeruginosa cells localized at the substratum of the biofilms remained alive even after 24 h of colistin treatment ( Fig. 1a ), which might result from the heterogeneous compositions/structures of the exopolymeric matrix materials 19 , 20 . Certain exopolymeric matrix components might act as physical barriers and reduce the penetration of colistin into deep part of biofilms 21 , which allows a few biofilm cells at the substratum to survive and acquire colistin tolerance. Figure 1: The migration and formation of colistin-tolerant subpopulations in biofilm. ( a ) P. aeruginosa PAO1 wild-type biofilms were treated with minimal medium containing 10 μg ml −1 colistin followed by real-time CLSM observation from 2 to 32 h of treatment. Scale bars, 50 μm. Colistin-tolerant cells in P. aeruginosa PAO1 biofilms migrated onto", "role": "user" }, { "content": "Scientists at Nanyang Technological University, Singapore (NTU Singapore) have discovered that antibiotics can continue to be effective if bacteria's cell-to-cell communication and ability to latch on to each other are disrupted. This research breakthrough is a major step forward in tackling the growing concern of antibiotic resistance, opening up new treatment options for doctors to help patients fight against chronic and persistent bacterial infections. The study, led by Assistant Professor Yang Liang from the Singapore Centre for Environmental Life Sciences (SCELSE) at NTU, found that a community of bacteria, known as biofilm, can put up a strong line of defence to resist antibiotics. The NTU team has successfully demonstrated how biofilms can be disrupted to let antibiotics continue their good work. The research was published recently in Nature Communications. \"Many types of bacteria that used to be easily killed by antibiotics have started to develop antibiotic resistance or tolerance, either through acquiring the antibiotic resistant genes or by forming biofilms,\" said Asst Prof Yang, who also teaches at NTU's School of Biological Sciences. \"The US Center for Disease Control estimates that over 60 per cent of all bacterial infections are related to biofilms. Our study has shown that by disrupting the cell-to-cell communication between bacteria and their ability to latch on to each other, we can compromise the biofilms, leaving the bacteria vulnerable and easily killed by antibiotics.\" Bacterial resistance to antibiotics is rapidly growing world-wide and this puts at risk the ability to treat common infections in the community and hospitals. The World Health Organisation states on its factsheet on Antimicrobial resistance that \"without urgent, coordinated action, the world is heading towards a post-antibiotic era, in which common infections and minor injuries, which have been treatable for decades, can once again kill\". Associate Professor Kevin Pethe, an expert in antibiotic development and infectious diseases from NTU's Lee Kong Chian School of Medicine, said that this discovery may yield new treatment options that doctors can employ against chronic and persistent bacterial infections. \"Being able to disable biofilms and its protective benefits for the bacteria is a big step towards tackling the growing concern of antibiotic resistance,\" said Assoc Prof Pethe. \"While the scientific community is developing new types of antibiotics and antimicrobial treatments, this discovery may help to buy time by improving the effectiveness of older drugs.\" How the discovery was made Asst Prof Yang's team discovered the mechanisms of how bacteria are able to tolerate antibiotics by using a common bacterium Pseudomonas aeruginosa. The bacteria were allowed to form a wall of biofilm in a microfluidic system. An antibiotic was then introduced. A large portion of the bacterial cells were killed by the antibiotic, leaving only a small fraction of antibiotic-tolerant cells. However, these cells were able to reproduce rapidly and dominate the community. The scientists then used an FDA-approved drug that disrupts cell-to-cell communication (known as quorum sensing) and 'velcro'-like cells that can move and \"stick\" to each other. This drug was added to the antibiotic and together they managed to kill all the bacterial cells. The same tests were then performed on mice with infected implants. It was found that only mice treated with a combination of anti-biofilm compound and antibiotics had their infections completely eradicated. Interdisciplinary research This discovery breakthrough was made possible through an interdisciplinary approach, where experts from three different fields – microbiology ecology, systems biology and chemical biology – came together to tackle the problem. The NTU research team included proteomics expert Assoc Prof Newman Sze Siu Kwan from NTU's School of Biological Sciences. Proteomics was the key method used to discover chemical signals that bacterial cells in the biofilm use to communicate with each other. Another researcher in the team is Professor Michael Givskov, a world-leading scientist in the area of biofilm research and bacterial cell-to-cell communication at SCELSE. Together, the team found that traditional methods of isolating the bacteria from the biofilm for observation did not work, as the bacteria behave differently after being isolated from the biofilm. This study, supported by the Ministry of Education Academic Research Fund, took Asst Prof Yang and his team four years to complete. Moving forward, they will seek more ways to improve efficiency of antibiotics for persistent infections. \"What we hope to do is to develop new compounds that are able to better target biofilms. This will help existing drugs perform better at overcoming biofilm infections, which is commonly seen in cases of patients with artificial implants and chronic wounds, as they have very limited effective treatment options that are effective,\" said Asst Prof Yang. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Drug resistance and tolerance greatly diminish the therapeutic potential of antibiotics against pathogens. Antibiotic tolerance by bacterial biofilms often leads to persistent infections, but its mechanisms are unclear. Here we use a proteomics approach, pulsed stable isotope labelling with amino acids (pulsed-SILAC), to quantify newly expressed proteins in colistin-tolerant subpopulations of Pseudomonas aeruginosa biofilms (colistin is a ‘last-resort’ antibiotic against multidrug-resistant Gram-negative pathogens). Migration is essential for the formation of colistin-tolerant biofilm subpopulations, with colistin-tolerant cells using type IV pili to migrate onto the top of the colistin-killed biofilm. The colistin-tolerant cells employ quorum sensing (QS) to initiate the formation of new colistin-tolerant subpopulations, highlighting multicellular behaviour in antibiotic tolerance development. The macrolide erythromycin, which has been previously shown to inhibit the motility and QS of P. aeruginosa , boosts biofilm eradication by colistin. Our work provides insights on the mechanisms underlying the formation of antibiotic-tolerant populations in bacterial biofilms and indicates research avenues for designing more efficient treatments against biofilm-associated infections. Introduction The therapeutic efficacy of antibiotics can be severely crippled by two major bacterial defence strategies. ‘Resistance’ occurs when bacteria acquire genetic mutations or mobile genetic elements that enable growth under conditions of constant antibiotic exposure 1 , while ‘tolerance’ is mediated by transient phenotypic variations (based on protein expression) that enable bacteria to survive exposures to the highest deliverable doses of antibiotics 2 , 3 . While the current view is that development of tolerance is intrinsically linked to the biofilm lifestyle, early experiments conducted on bacteria in the planktonic lifestyle revealed that tolerance can develop to a number of stresses including antibiotics 4 , 5 . However, in contrast to the planktonic mode of life, biofilms are sessile, densely populated multicellular communities embedded in biopolymeric matrix components 6 . A major advantage for bacteria that aggregate into biofilms is that a multitude of matrix components and physiological states offers additional levels of protection against immune defences and antibiotics, which cannot be obtained in the planktonic growth mode 7 , 8 , 9 . It is widely accepted that pathogenic bacteria in the biofilm mode significantly contribute to the development of nosocomial infections as they are colonizing hospital settings and chronic infection sites, where they represent a serious threat to public health 6 . Bacterial cells differentiate into several physiologically distinct subpopulations within a biofilm 10 . Antibiotic treatment often eradicates sensitive subpopulations, but leaves small antibiotic-tolerant subpopulations behind, resulting in recurring infections after antibiotic treatment has been stopped 10 . Antibiotic-tolerant bacterial cells are variants of wild-type cells that can revert back to the wild type when antimicrobial treatment has ceased 11 . Their transient nature and low abundance make it difficult to investigate their tolerance-related physiology. With only a few studies that have investigated planktonic antibiotic-tolerant cells by pre-isolating them using flow cytometry 12 , 13 , 14 , 15 , the mechanisms underlying the formation of antibiotic-tolerant subpopulation in biofilms have remained elusive. Moreover, these pre-isolation-based strategies are destructive and not feasible for studying the antibiotic-tolerant subpopulations in biofilms. This prompted us to develop an alternative, high-resolution ‘-omics’ approach to simultaneously characterize the physiologies of sensitive and antibiotic-tolerant subpopulations in biofilms. Pseudomonas aeruginosa forms biofilm with extreme tolerance to antibiotics in nosocomial infections, such as pneumonia and surgical site infections, prompting the Centers for Disease Control and Prevention to classify P. aeruginosa under ‘serious’-threat level ( ) and the Infectious Diseases Society of America to declare it as one of the six ‘top-priority dangerous, drug-resistant microbes’ 16 . Colistin is a last-resort polymyxin antibiotic available for treatment of infections caused by drug-resistant Gram-negative bacteria 17 . P. aeruginosa biofilms in flow chambers develop colistin-tolerant cells rapidly and these cells feature high expression levels of the pmr operon 18 . Here we observe the dynamic development of drug-tolerant subpopulations in P. aeruginosa biofilms after treatment with colistin. To obtain knowledge about the physiology of the colistin-tolerant biofilm cells, we apply pulsed stable isotope labelling with amino acids (pulsed-SILAC) proteomics method to selectively quantify the newly expressed proteins that incorporate and are thus labelled with heavy C13 lysine, to promote understanding of the colistin-tolerant subpopulation physiology. The colistin-tolerant populations are able to migrate to the top of the dead biofilm by employing type IV pili-dependent motility and initiate formation of new biofilm via quorum sensing (QS)-regulated group activity. Synergistic treatment by use of erythromycin, which can inhibit QS and motility with colistin, is able to boost the elimination of P. aeruginosa biofilms. Hence, our study provides key insights in developing novel treatments against biofilm-associated infections, which otherwise prove hard to eradicate. Results and Discussion Development of colistin-tolerant subpopulations in biofilms We monitored the development of live and dead subpopulations of P. aeruginosa biofilms after exposure to colistin in real-time by using time series confocal image acquisition as well as enumeration of viable cells with colony forming units (c.f.u. per ml). Colistin exposure of P. aeruginosa wild-type biofilms tagged with green fluorescent protein (GFP) led to a sudden reduction in cell viability according to the propidium iodide (PI) dead staining ( Fig. 1a and Supplementary Movies 1 and 2 ) and c.f.u. per ml counting ( Fig. 1b ). However, we noticed that a few P. aeruginosa cells localized at the substratum of the biofilms remained alive even after 24 h of colistin treatment ( Fig. 1a ), which might result from the heterogeneous compositions/structures of the exopolymeric matrix materials 19 , 20 . Certain exopolymeric matrix components might act as physical barriers and reduce the penetration of colistin into deep part of biofilms 21 , which allows a few biofilm cells at the substratum to survive and acquire colistin tolerance. Figure 1: The migration and formation of colistin-tolerant subpopulations in biofilm. ( a ) P. aeruginosa PAO1 wild-type biofilms were treated with minimal medium containing 10 μg ml −1 colistin followed by real-time CLSM observation from 2 to 32 h of treatment. Scale bars, 50 μm. Colistin-tolerant cells in P. aeruginosa PAO1 biofilms migrated onto<|im_end|> <|im_start|>assistant Scientists at Nanyang Technological University, Singapore (NTU Singapore) have discovered that antibiotics can continue to be effective if bacteria's cell-to-cell communication and ability to latch on to each other are disrupted. This research breakthrough is a major step forward in tackling the growing concern of antibiotic resistance, opening up new treatment options for doctors to help patients fight against chronic and persistent bacterial infections. The study, led by Assistant Professor Yang Liang from the Singapore Centre for Environmental Life Sciences (SCELSE) at NTU, found that a community of bacteria, known as biofilm, can put up a strong line of defence to resist antibiotics. The NTU team has successfully demonstrated how biofilms can be disrupted to let antibiotics continue their good work. The research was published recently in Nature Communications. "Many types of bacteria that used to be easily killed by antibiotics have started to develop antibiotic resistance or tolerance, either through acquiring the antibiotic resistant genes or by forming biofilms," said Asst Prof Yang, who also teaches at NTU's School of Biological Sciences. "The US Center for Disease Control estimates that over 60 per cent of all bacterial infections are related to biofilms. Our study has shown that by disrupting the cell-to-cell communication between bacteria and their ability to latch on to each other, we can compromise the biofilms, leaving the bacteria vulnerable and easily killed by antibiotics." Bacterial resistance to antibiotics is rapidly growing world-wide and this puts at risk the ability to treat common infections in the community and hospitals. The World Health Organisation states on its factsheet on Antimicrobial resistance that "without urgent, coordinated action, the world is heading towards a post-antibiotic era, in which common infections and minor injuries, which have been treatable for decades, can once again kill". Associate Professor Kevin Pethe, an expert in antibiotic development and infectious diseases from NTU's Lee Kong Chian School of Medicine, said that this discovery may yield new treatment options that doctors can employ against chronic and persistent bacterial infections. "Being able to disable biofilms and its protective benefits for the bacteria is a big step towards tackling the growing concern of antibiotic resistance," said Assoc Prof Pethe. "While the scientific community is developing new types of antibiotics and antimicrobial treatments, this discovery may help to buy time by improving the effectiveness of older drugs." How the discovery was made Asst Prof Yang's team discovered the mechanisms of how bacteria are able to tolerate antibiotics by using a common bacterium Pseudomonas aeruginosa. The bacteria were allowed to form a wall of biofilm in a microfluidic system. An antibiotic was then introduced. A large portion of the bacterial cells were killed by the antibiotic, leaving only a small fraction of antibiotic-tolerant cells. However, these cells were able to reproduce rapidly and dominate the community. The scientists then used an FDA-approved drug that disrupts cell-to-cell communication (known as quorum sensing) and 'velcro'-like cells that can move and "stick" to each other. This drug was added to the antibiotic and together they managed to kill all the bacterial cells. The same tests were then performed on mice with infected implants. It was found that only mice treated with a combination of anti-biofilm compound and antibiotics had their infections completely eradicated. Interdisciplinary research This discovery breakthrough was made possible through an interdisciplinary approach, where experts from three different fields – microbiology ecology, systems biology and chemical biology – came together to tackle the problem. The NTU research team included proteomics expert Assoc Prof Newman Sze Siu Kwan from NTU's School of Biological Sciences. Proteomics was the key method used to discover chemical signals that bacterial cells in the biofilm use to communicate with each other. Another researcher in the team is Professor Michael Givskov, a world-leading scientist in the area of biofilm research and bacterial cell-to-cell communication at SCELSE. Together, the team found that traditional methods of isolating the bacteria from the biofilm for observation did not work, as the bacteria behave differently after being isolated from the biofilm. This study, supported by the Ministry of Education Academic Research Fund, took Asst Prof Yang and his team four years to complete. Moving forward, they will seek more ways to improve efficiency of antibiotics for persistent infections. "What we hope to do is to develop new compounds that are able to better target biofilms. This will help existing drugs perform better at overcoming biofilm infections, which is commonly seen in cases of patients with artificial implants and chronic wounds, as they have very limited effective treatment options that are effective," said Asst Prof Yang. <|im_end|>

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2,439

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Autism spectrum disorder (ASD) involves substantial genetic contributions. These contributions are profoundly heterogeneous but may converge on common pathways that are not yet well understood 1 , 2 , 3 . Here, through post-mortem genome-wide transcriptome analysis of the largest cohort of samples analysed so far, to our knowledge 4 , 5 , 6 , 7 , we interrogate the noncoding transcriptome, alternative splicing, and upstream molecular regulators to broaden our understanding of molecular convergence in ASD. Our analysis reveals ASD-associated dysregulation of primate-specific long noncoding RNAs (lncRNAs), downregulation of the alternative splicing of activity-dependent neuron-specific exons, and attenuation of normal differences in gene expression between the frontal and temporal lobes. Our data suggest that SOX5, a transcription factor involved in neuron fate specification, contributes to this reduction in regional differences. We further demonstrate that a genetically defined subtype of ASD, chromosome 15q11.2-13.1 duplication syndrome (dup15q), shares the core transcriptomic signature observed in idiopathic ASD. Co-expression network analysis reveals that individuals with ASD show age-related changes in the trajectory of microglial and synaptic function over the first two decades, and suggests that genetic risk for ASD may influence changes in regional cortical gene expression. Our findings illustrate how diverse genetic perturbations can lead to phenotypic convergence at multiple biological levels in a complex neuropsychiatric disorder. Main We performed rRNA-depleted RNA sequencing (RNA-seq) of 251 post-mortem samples of frontal and temporal cortex and cerebellum from 48 individuals with ASD and 49 control subjects (Methods and Extended Data Fig. 1a–h ). We first validated differential gene expression (DGE) between samples of cortex from control individuals and those with ASD (ASD cortex) by comparing gene expression with that of different individuals from those previously profiled by microarray 8 , and found strong concordance ( R 2 = 0.60; Fig. 1a , Extended Data Fig. 1i ). This constitutes an independent technical and biological replication of shared molecular alterations in ASD cortex. Figure 1: Transcriptome-wide differential gene expression and alternative splicing in ASD. a , Replication of DGE between ASD and control cortex from previously analysed samples (16 ASD and 16 control on microarray 8 ) with new age- and sex-matched cortex samples (15 ASD and 17 control). b , P value distribution of the linear mixed effect (LME) model DGE results for cortex and cerebellum. c , LINC00693 and LINC00689 are upregulated in ASD and downregulated during cortical development (developmental expression data from ref. 12 ). Two-sided ASD–control P values are computed by the LME model, developmental P values are computed by analysis of variance (ANOVA). FPKM, fragments per kilobase million mapped reads. d , UCSC genome browser track displaying reads per million (RPM) in ASD and control samples along with sequence conservation for LINC00693 and LINC00689 . e , Cell-type enrichment analysis of differential alternative splicing events from cortex using exons with ΔPSI (per cent spliced in) >50% in each cell type compared to the others 17 . f , g , Correlation between the first principal component (PC1) of the cortex differential splicing (DS) set and gene expression of neuronal splicing factors in cortex ( f ) and cerebellum ( g ) (DGE P value in parentheses). h , Enrichment among ASD differential splicing events and events regulated by splicing factors and neuronal activity (see Methods). i , Correlations between the PC1 across the ASD versus control analyses for different transcriptome subcategories. Bottom left: scatterplots of the principal components for ASD (red) and control (black) individuals. Top right: pairwise correlation values between principal components. PowerPoint slide Full size image We next combined covariate-matched samples from individuals with idiopathic ASD to evaluate changes across the entire transcriptome. Compared to control cortex, 584 genes showed increased expression and 558 showed decreased expression in ASD cortex ( Fig. 1b ; Benjamini–Hochberg FDR < 0.05, linear mixed effects model; see Methods). This DGE signal was consistent across methods, unrelated to major confounders, and found in more than two-thirds of ASD samples ( Extended Data Fig. 1j–m ). We performed a classification analysis to confirm that gene expression in ASD could separate samples by disease status ( Extended Data Fig. 2a ) and confirmed the technical quality of our data with qRT–PCR ( Extended Data Fig. 2b, c ). We next evaluated enrichment of the gene sets for pathways and cell types ( Extended Data Fig. 2d, e ), and found that the downregulated set was enriched in genes expressed in neurons and involved in neuronal pathways, including PVALB and SYT2 , which are highly expressed in interneurons; by contrast, the upregulated gene set was enriched in genes expressed in microglia and astrocytes 8 . Although there was no significant DGE in the cerebellum (FDR < 0.05, P distributions in Fig. 1b ), similar to observations in a smaller cohort 8 , there was a replication signal in the cerebellum and overall concordance between ASD-related fold changes in the cortex and cerebellum ( Extended Data Fig. 2f–h ). The lack of significant DGE in the cerebellum is explained by the fact that changes in expression were consistently stronger in the cortex than in the cerebellum ( Extended Data Fig. 2h ), which suggests that the cortex is more selectively vulnerable to these transcriptomic alterations. We also compared our results to an RNA-seq study of protein coding genes in the occipital cortex of individuals with ASD and control subjects 4 . Despite significant technical differences that reduce power to detect DGE, and profiling of different brain regions in that study, there was a weak but significant correlation in fold changes, which was due mostly to upregulated genes in both studies ( P = 0.038, Extended Data Fig. 2i, j ). We next explored lncRNAs, most of which have little functional annotation, and identified 60 lncRNAs in the DGE set (FDR < 0.05, Extended Data Fig. 2k ). Multiple lines of evidence, including developmental regulation in RNA-seq datasets and epigenetic annotations, support the functionality of most of these lncRNAs ( Supplementary Table 2 ). Moreover, 20 of", "role": "user" }, { "content": "Autism spectrum disorder is caused by a variety of factors, both genetic and environmental. But a new study led by UCLA scientists provides further evidence that the brains of people with the disorder tend to have the same \"signature\" of abnormalities at the molecular level. The scientists analyzed 251 brain tissue samples from nearly 100 deceased people—48 who had autism and 49 who didn't. Most of the samples from people with autism showed a distinctive pattern of unusual gene activity. The findings, published Dec. 5 in Nature, confirm and extend the results of earlier, smaller studies, and provide a clearer picture of what goes awry, at the molecular level, in the brains of people with autism. \"This pattern of unusual gene activity suggests some possible targets for future autism drugs,\" said Dr. Daniel Geschwind, the paper's senior author and UCLA's Gordon and Virginia MacDonald Distinguished Professor of Human Genetics. \"In principle, we can use the abnormal patterns we've found to screen for drugs that reverse them—and thereby hopefully treat this disorder.\" According to the Centers for Disease Control and Prevention, about 1.5 percent of children in the U.S. have autism; the disorder is characterized by impaired social interactions and other cognitive and behavioral problems. In rare cases, the disorder has been tied to specific DNA mutations, maternal infections during pregnancy or exposures to certain chemicals in the womb. But in most cases, the causes are unknown. In a much-cited study in Nature in 2011, Geschwind and colleagues found that key regions of the brain in people with different kinds of autism had the same broad pattern of abnormal gene activity. More specifically, researchers noticed that the brains of people with autism didn't have the \"normal\" pattern for which genes are active or inactive that they found in the brains of people without the disorder. What's more, the genes in brains with autism weren't randomly active or inactive in these key regions, but rather had their own consistent patterns from one brain to the next—even when the causes of the autism appear to be very different. The discovery suggested that different genetic and environmental triggers of autism disorders mostly lead to disease via the same biological pathways in brain cells. In the new study, Geschwind and his team analyzed a larger number of brain tissue samples and found the same broad pattern of abnormal gene activity in areas of the brain that are affected by autism. \"Traditionally, few genetic studies of psychiatric diseases have been replicated, so being able to confirm those initial findings in a new set of patients is very important,\" said Geschwind, who also is a professor of neurology and psychiatry at the David Geffen School of Medicine at UCLA. \"It strongly suggests that the pattern we found applies to most people with autism disorders.\" The team also looked at other aspects of cell biology, including brain cells' production of molecules called long non-coding RNAs, which can suppress or enhance the activity of many genes at once. Again, the researchers found a distinctive abnormal pattern in the autism disorder samples. Further studies may determine which abnormalities are drivers of autism, and which are merely the brain's responses to the disease process. But the findings offer some intriguing leads about how the brains of people with autism develop during the first 10 years of their lives. One is that, in people with the disorder, genes that control the formation of synapses—the ports through which neurons send signals to each other—are abnormally quiet in key regions of the brain. During the same time frame, genes that promote the activity of microglial cells, the brain's principal immune cells, are abnormally busy. This could mean that the first decade of life could be a critical time for interventions to prevent autism. The study also confirmed a previous finding that in the brains of people with autism, the patterns of gene activity in the frontal and temporal lobes are almost the same. In people who don't have autism, the two regions develop distinctly different patterns during childhood. The new study suggests that SOX5, a gene with a known role in early brain development, contributes to the failure of the two regions to diverge in people with autism. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Autism spectrum disorder (ASD) involves substantial genetic contributions. These contributions are profoundly heterogeneous but may converge on common pathways that are not yet well understood 1 , 2 , 3 . Here, through post-mortem genome-wide transcriptome analysis of the largest cohort of samples analysed so far, to our knowledge 4 , 5 , 6 , 7 , we interrogate the noncoding transcriptome, alternative splicing, and upstream molecular regulators to broaden our understanding of molecular convergence in ASD. Our analysis reveals ASD-associated dysregulation of primate-specific long noncoding RNAs (lncRNAs), downregulation of the alternative splicing of activity-dependent neuron-specific exons, and attenuation of normal differences in gene expression between the frontal and temporal lobes. Our data suggest that SOX5, a transcription factor involved in neuron fate specification, contributes to this reduction in regional differences. We further demonstrate that a genetically defined subtype of ASD, chromosome 15q11.2-13.1 duplication syndrome (dup15q), shares the core transcriptomic signature observed in idiopathic ASD. Co-expression network analysis reveals that individuals with ASD show age-related changes in the trajectory of microglial and synaptic function over the first two decades, and suggests that genetic risk for ASD may influence changes in regional cortical gene expression. Our findings illustrate how diverse genetic perturbations can lead to phenotypic convergence at multiple biological levels in a complex neuropsychiatric disorder. Main We performed rRNA-depleted RNA sequencing (RNA-seq) of 251 post-mortem samples of frontal and temporal cortex and cerebellum from 48 individuals with ASD and 49 control subjects (Methods and Extended Data Fig. 1a–h ). We first validated differential gene expression (DGE) between samples of cortex from control individuals and those with ASD (ASD cortex) by comparing gene expression with that of different individuals from those previously profiled by microarray 8 , and found strong concordance ( R 2 = 0.60; Fig. 1a , Extended Data Fig. 1i ). This constitutes an independent technical and biological replication of shared molecular alterations in ASD cortex. Figure 1: Transcriptome-wide differential gene expression and alternative splicing in ASD. a , Replication of DGE between ASD and control cortex from previously analysed samples (16 ASD and 16 control on microarray 8 ) with new age- and sex-matched cortex samples (15 ASD and 17 control). b , P value distribution of the linear mixed effect (LME) model DGE results for cortex and cerebellum. c , LINC00693 and LINC00689 are upregulated in ASD and downregulated during cortical development (developmental expression data from ref. 12 ). Two-sided ASD–control P values are computed by the LME model, developmental P values are computed by analysis of variance (ANOVA). FPKM, fragments per kilobase million mapped reads. d , UCSC genome browser track displaying reads per million (RPM) in ASD and control samples along with sequence conservation for LINC00693 and LINC00689 . e , Cell-type enrichment analysis of differential alternative splicing events from cortex using exons with ΔPSI (per cent spliced in) >50% in each cell type compared to the others 17 . f , g , Correlation between the first principal component (PC1) of the cortex differential splicing (DS) set and gene expression of neuronal splicing factors in cortex ( f ) and cerebellum ( g ) (DGE P value in parentheses). h , Enrichment among ASD differential splicing events and events regulated by splicing factors and neuronal activity (see Methods). i , Correlations between the PC1 across the ASD versus control analyses for different transcriptome subcategories. Bottom left: scatterplots of the principal components for ASD (red) and control (black) individuals. Top right: pairwise correlation values between principal components. PowerPoint slide Full size image We next combined covariate-matched samples from individuals with idiopathic ASD to evaluate changes across the entire transcriptome. Compared to control cortex, 584 genes showed increased expression and 558 showed decreased expression in ASD cortex ( Fig. 1b ; Benjamini–Hochberg FDR < 0.05, linear mixed effects model; see Methods). This DGE signal was consistent across methods, unrelated to major confounders, and found in more than two-thirds of ASD samples ( Extended Data Fig. 1j–m ). We performed a classification analysis to confirm that gene expression in ASD could separate samples by disease status ( Extended Data Fig. 2a ) and confirmed the technical quality of our data with qRT–PCR ( Extended Data Fig. 2b, c ). We next evaluated enrichment of the gene sets for pathways and cell types ( Extended Data Fig. 2d, e ), and found that the downregulated set was enriched in genes expressed in neurons and involved in neuronal pathways, including PVALB and SYT2 , which are highly expressed in interneurons; by contrast, the upregulated gene set was enriched in genes expressed in microglia and astrocytes 8 . Although there was no significant DGE in the cerebellum (FDR < 0.05, P distributions in Fig. 1b ), similar to observations in a smaller cohort 8 , there was a replication signal in the cerebellum and overall concordance between ASD-related fold changes in the cortex and cerebellum ( Extended Data Fig. 2f–h ). The lack of significant DGE in the cerebellum is explained by the fact that changes in expression were consistently stronger in the cortex than in the cerebellum ( Extended Data Fig. 2h ), which suggests that the cortex is more selectively vulnerable to these transcriptomic alterations. We also compared our results to an RNA-seq study of protein coding genes in the occipital cortex of individuals with ASD and control subjects 4 . Despite significant technical differences that reduce power to detect DGE, and profiling of different brain regions in that study, there was a weak but significant correlation in fold changes, which was due mostly to upregulated genes in both studies ( P = 0.038, Extended Data Fig. 2i, j ). We next explored lncRNAs, most of which have little functional annotation, and identified 60 lncRNAs in the DGE set (FDR < 0.05, Extended Data Fig. 2k ). Multiple lines of evidence, including developmental regulation in RNA-seq datasets and epigenetic annotations, support the functionality of most of these lncRNAs ( Supplementary Table 2 ). Moreover, 20 of<|im_end|> <|im_start|>assistant Autism spectrum disorder is caused by a variety of factors, both genetic and environmental. But a new study led by UCLA scientists provides further evidence that the brains of people with the disorder tend to have the same "signature" of abnormalities at the molecular level. The scientists analyzed 251 brain tissue samples from nearly 100 deceased people—48 who had autism and 49 who didn't. Most of the samples from people with autism showed a distinctive pattern of unusual gene activity. The findings, published Dec. 5 in Nature, confirm and extend the results of earlier, smaller studies, and provide a clearer picture of what goes awry, at the molecular level, in the brains of people with autism. "This pattern of unusual gene activity suggests some possible targets for future autism drugs," said Dr. Daniel Geschwind, the paper's senior author and UCLA's Gordon and Virginia MacDonald Distinguished Professor of Human Genetics. "In principle, we can use the abnormal patterns we've found to screen for drugs that reverse them—and thereby hopefully treat this disorder." According to the Centers for Disease Control and Prevention, about 1.5 percent of children in the U.S. have autism; the disorder is characterized by impaired social interactions and other cognitive and behavioral problems. In rare cases, the disorder has been tied to specific DNA mutations, maternal infections during pregnancy or exposures to certain chemicals in the womb. But in most cases, the causes are unknown. In a much-cited study in Nature in 2011, Geschwind and colleagues found that key regions of the brain in people with different kinds of autism had the same broad pattern of abnormal gene activity. More specifically, researchers noticed that the brains of people with autism didn't have the "normal" pattern for which genes are active or inactive that they found in the brains of people without the disorder. What's more, the genes in brains with autism weren't randomly active or inactive in these key regions, but rather had their own consistent patterns from one brain to the next—even when the causes of the autism appear to be very different. The discovery suggested that different genetic and environmental triggers of autism disorders mostly lead to disease via the same biological pathways in brain cells. In the new study, Geschwind and his team analyzed a larger number of brain tissue samples and found the same broad pattern of abnormal gene activity in areas of the brain that are affected by autism. "Traditionally, few genetic studies of psychiatric diseases have been replicated, so being able to confirm those initial findings in a new set of patients is very important," said Geschwind, who also is a professor of neurology and psychiatry at the David Geffen School of Medicine at UCLA. "It strongly suggests that the pattern we found applies to most people with autism disorders." The team also looked at other aspects of cell biology, including brain cells' production of molecules called long non-coding RNAs, which can suppress or enhance the activity of many genes at once. Again, the researchers found a distinctive abnormal pattern in the autism disorder samples. Further studies may determine which abnormalities are drivers of autism, and which are merely the brain's responses to the disease process. But the findings offer some intriguing leads about how the brains of people with autism develop during the first 10 years of their lives. One is that, in people with the disorder, genes that control the formation of synapses—the ports through which neurons send signals to each other—are abnormally quiet in key regions of the brain. During the same time frame, genes that promote the activity of microglial cells, the brain's principal immune cells, are abnormally busy. This could mean that the first decade of life could be a critical time for interventions to prevent autism. The study also confirmed a previous finding that in the brains of people with autism, the patterns of gene activity in the frontal and temporal lobes are almost the same. In people who don't have autism, the two regions develop distinctly different patterns during childhood. The new study suggests that SOX5, a gene with a known role in early brain development, contributes to the failure of the two regions to diverge in people with autism. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Manganese is one of the most abundant elements on Earth. The oxidation of manganese has long been theorized 1 —yet has not been demonstrated 2 , 3 , 4 —to fuel the growth of chemolithoautotrophic microorganisms. Here we refine an enrichment culture that exhibits exponential growth dependent on Mn(II) oxidation to a co-culture of two microbial species. Oxidation required viable bacteria at permissive temperatures, which resulted in the generation of small nodules of manganese oxide with which the cells associated. The majority member of the culture—which we designate ‘ Candidatus Manganitrophus noduliformans’—is affiliated to the phylum Nitrospirae (also known as Nitrospirota), but is distantly related to known species of Nitrospira and Leptospirillum . We isolated the minority member, a betaproteobacterium that does not oxidize Mn(II) alone, and designate it Ramlibacter lithotrophicus . Stable-isotope probing revealed 13 CO 2 fixation into cellular biomass that was dependent upon Mn(II) oxidation. Transcriptomic analysis revealed candidate pathways for coupling extracellular manganese oxidation to aerobic energy conservation and autotrophic CO 2 fixation. These findings expand the known diversity of inorganic metabolisms that support life, and complete a biogeochemical energy cycle for manganese 5 , 6 that may interface with other major global elemental cycles. Main Beijerinck and Winogradsky discovered biological redox reactions involving carbon, nitrogen, sulfur and iron over a century ago, while pioneering methods for cultivating the microbiota responsible for these reactions: this led to the concept of chemolithoautotrophy 7 , 8 . The known breadth of inorganic electron-accepting and -donating reactions in biology has continued to expand 9 , 10 , 11 , 12 , 13 . For example, the anaerobic respiratory reduction of Mn(IV) oxides to Mn(II) by diverse microorganisms is now understood to be widespread and of broad biogeochemical importance 5 , 6 , 14 , 15 . Over the past century, a multitude of studies and reviews have focused on the details of Mn(II) oxidation catalysed by diverse heterotrophs 2 , 3 , 4 ; however, the physiological roles of these activities generally remain unclear. Despite experimental hints that the oxidation might be coupled to energy conservation (Mn 2+ + 1/2O 2 + H 2 O → Mn(IV)O 2( s ) + 2H + ; Δ G° ′ = −68 kJ per mol Mn (Supplementary Note 1) in some organisms 1 , 16 , 17 , 18 , 19 , whether Mn(II) oxidation drives the growth of any chemolithotrophs has remained an open question. Cultivation of manganese oxidizers We re-examined the possibility that previously unappreciated microorganisms from the environment might oxidize Mn(II) for energy. We coated a glass jar with a slurry of Mn(II)CO 3 and allowed it to dry, before filling it with municipal tap water from Pasadena (California, USA) and leaving it to incubate at room temperature. After several months, the cream-coloured carbonate coating had oxidized to a dark manganese oxide. We serially transferred the material into a defined medium, which led to the establishment of a stable in vitro culture. Unless otherwise noted, this medium was free of alternative organic and inorganic electron donors (except for trace amounts of vitamins); for example, nitrate was used instead of ammonia as a source of nitrogen to preclude the growth of nitrifiers. To distinguish between abiological and biological oxidation, flasks of sterile, defined Mn(II) medium were either inoculated with a subculture of the enrichment or left uninoculated, and incubated under oxic conditions. Because manganese oxides have previously been suggested to contribute to the chemical auto-oxidation of Mn(II) 20 , we inoculated other replicate flasks with a steam-sterilized subculture with oxide products. Even after a year, oxidation had not occurred in uninoculated flasks or flasks containing the steam-sterilized inocula, as predicted by the known chemical stability of MnCO 3 under these conditions 21 , 22 . However, within four weeks, the flasks inoculated with ‘viable material’ had generated dark, adherent manganese oxides (Fig. 1a ). Oxidation required O 2 and occurred at temperatures up to 42 °C; oxidation occurring optimally between 34 °C to 40 °C (Extended Data Fig. 1a ), consistent with catalysis being enzymatic. Mn(II) oxidation activity was also sensitive to exposure to antibiotics, or to overnight pasteurization at 50 °C (Extended Data Fig. 1b ). Phosphate was inhibitory at concentrations above 0.3 mM. When amended with MnCO 3 , the pH of unbuffered medium ranged between 5.7 and 6.3. Although a pH buffer was not required, Mn(II) oxidation was faster in medium buffered with 5 mM 3-morpholinopropanesulfonic acid (MOPS) at its p K a (7.1 at 37 °C). In buffered cultures, the final pH ranged between 6.5 and 6.8. With or without buffer, increases in culture pH during or after oxidation—which might lead to chemical oxidation of unreacted MnCO 3 —were not observed. No growth could be detected in the MOPS-buffered basal medium without addition of MnCO 3 (Extended Data Fig. 2a ). Fig. 1: Bio-oxidation of MnCO 3 produces manganese oxide nodules to which two species associate. a , After incubation, comparison of an uninoculated control flask of basal medium containing bright, unreacted MnCO 3 (left) with the adherent dark oxide products generated in a flask that had been inoculated with viable material (right). b – e , Microscopy of manganese oxide nodules generated in agarose solidified MnCO 3 medium. b , After incubation of tubes inoculated with viable material, the cloud of bright MnCO 3 particles was clarified towards the air-exposed meniscus, concomitant with the generation of larger, discrete dark oxides (enlarged in c ). d , Transmitted light micrograph of an acridine-orange (nucleic acid)-stained manganese oxide nodule from the same agarose tube. e , Epifluorescence micrograph of the same nodule as in d , with surface visible biomass localized to the inner clefts; material in clefts appeared orange before staining. f , Scanning electron micrograph of an manganese oxide nodule produced by the co-culture. g , Epifluorescence microscopy and fluorescence in situ hybridization using species-specific rRNA-targeted probes reveal cell distributions in dissolved manganese oxide nodules. Species A, magenta; species B, green; all DNA stained", "role": "user" }, { "content": "Caltech microbiologists have discovered bacteria that feed on manganese and use the metal as their source of calories. Such microbes were predicted to exist over a century ago, but none had been found or described until now. \"These are the first bacteria found to use manganese as their source of fuel,\" says Jared Leadbetter, professor of environmental microbiology at Caltech who, in collaboration with postdoctoral scholar Hang Yu, describes the findings in the July 16 issue of the journal Nature. \"A wonderful aspect of microbes in nature is that they can metabolize seemingly unlikely materials, like metals, yielding energy useful to the cell.\" The study also reveals that the bacteria can use manganese to convert carbon dioxide into biomass, a process called chemosynthesis. Previously, researchers knew of bacteria and fungi that could oxidize manganese, or strip it of electrons, but they had only speculated that yet-to-be-identified microbes might be able to harness the process to drive growth. Leadbetter found the bacteria serendipitously after performing unrelated experiments using a light, chalk-like form of manganese. He had left a glass jar soiled with the substance to soak in tap water in his Caltech office sink before departing for several months to work off campus. When he returned, the jar was coated with a dark material. \"I thought, 'What is that?'\" he explains. \"I started to wonder if long-sought-after microbes might be responsible, so we systematically performed tests to figure that out.\" The black coating was in fact oxidized manganese generated by newfound bacteria that had likely come from the tap water itself. \"There is evidence that relatives of these creatures reside in groundwater, and a portion of Pasadena's drinking water is pumped from local aquifers,\" he says. Manganese is one of the most abundant elements on the surface of the earth. Manganese oxides take the form of a dark, clumpy substance and are common in nature; they have been found in subsurface deposits and can also form in water-distribution systems. \"There is a whole set of environmental engineering literature on drinking-water-distribution systems getting clogged by manganese oxides,\" says Leadbetter. \"But how and for what reason such material is generated there has remained an enigma. Clearly, many scientists have considered that bacteria using manganese for energy might be responsible, but evidence supporting this idea was not available until now.\" The finding helps researchers better understand the geochemistry of groundwater. It is known that bacteria can degrade pollutants in groundwater, a process called bioremediation. When doing this, several key organisms will \"reduce\" manganese oxide, which means they donate electrons to it, in a manner similar to how humans use oxygen in the air. Scientists have wondered where the manganese oxide comes from in the first place. \"The bacteria we have discovered can produce it, thus they enjoy a lifestyle that also serves to supply the other microbes with what they need to perform reactions that we consider to be beneficial and desirable,\" says Leadbetter. The research findings also have possible relevance to understanding manganese nodules that dot much of the seafloor. These round metallic balls, which can be as large as grapefruit, were known to marine researchers as early as the cruises of the HMS Challenger in the 1870s. Since then, such nodules have been found to line the bottom of many of Earth's oceans. In recent years, mining companies have been making plans to harvest and exploit these nodules, because rare metals are often found concentrated within them. But little is understood about how the nodules form in the first place. Yu and Leadbetter now wonder if microbes similar to what they have found in freshwater might play a role and they plan to further investigate the mystery. \"This underscores the need to better understand marine manganese nodules before they are decimated by mining,\" says Yu. \"This discovery from Jared and Hang fills a major intellectual gap in our understanding of Earth's elemental cycles, and adds to the diverse ways in which manganese, an abstruse but common transition metal, has shaped the evolution of life on our planet,\" says Woodward Fischer, professor of geobiology at Caltech, who was not involved with the study. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Manganese is one of the most abundant elements on Earth. The oxidation of manganese has long been theorized 1 —yet has not been demonstrated 2 , 3 , 4 —to fuel the growth of chemolithoautotrophic microorganisms. Here we refine an enrichment culture that exhibits exponential growth dependent on Mn(II) oxidation to a co-culture of two microbial species. Oxidation required viable bacteria at permissive temperatures, which resulted in the generation of small nodules of manganese oxide with which the cells associated. The majority member of the culture—which we designate ‘ Candidatus Manganitrophus noduliformans’—is affiliated to the phylum Nitrospirae (also known as Nitrospirota), but is distantly related to known species of Nitrospira and Leptospirillum . We isolated the minority member, a betaproteobacterium that does not oxidize Mn(II) alone, and designate it Ramlibacter lithotrophicus . Stable-isotope probing revealed 13 CO 2 fixation into cellular biomass that was dependent upon Mn(II) oxidation. Transcriptomic analysis revealed candidate pathways for coupling extracellular manganese oxidation to aerobic energy conservation and autotrophic CO 2 fixation. These findings expand the known diversity of inorganic metabolisms that support life, and complete a biogeochemical energy cycle for manganese 5 , 6 that may interface with other major global elemental cycles. Main Beijerinck and Winogradsky discovered biological redox reactions involving carbon, nitrogen, sulfur and iron over a century ago, while pioneering methods for cultivating the microbiota responsible for these reactions: this led to the concept of chemolithoautotrophy 7 , 8 . The known breadth of inorganic electron-accepting and -donating reactions in biology has continued to expand 9 , 10 , 11 , 12 , 13 . For example, the anaerobic respiratory reduction of Mn(IV) oxides to Mn(II) by diverse microorganisms is now understood to be widespread and of broad biogeochemical importance 5 , 6 , 14 , 15 . Over the past century, a multitude of studies and reviews have focused on the details of Mn(II) oxidation catalysed by diverse heterotrophs 2 , 3 , 4 ; however, the physiological roles of these activities generally remain unclear. Despite experimental hints that the oxidation might be coupled to energy conservation (Mn 2+ + 1/2O 2 + H 2 O → Mn(IV)O 2( s ) + 2H + ; Δ G° ′ = −68 kJ per mol Mn (Supplementary Note 1) in some organisms 1 , 16 , 17 , 18 , 19 , whether Mn(II) oxidation drives the growth of any chemolithotrophs has remained an open question. Cultivation of manganese oxidizers We re-examined the possibility that previously unappreciated microorganisms from the environment might oxidize Mn(II) for energy. We coated a glass jar with a slurry of Mn(II)CO 3 and allowed it to dry, before filling it with municipal tap water from Pasadena (California, USA) and leaving it to incubate at room temperature. After several months, the cream-coloured carbonate coating had oxidized to a dark manganese oxide. We serially transferred the material into a defined medium, which led to the establishment of a stable in vitro culture. Unless otherwise noted, this medium was free of alternative organic and inorganic electron donors (except for trace amounts of vitamins); for example, nitrate was used instead of ammonia as a source of nitrogen to preclude the growth of nitrifiers. To distinguish between abiological and biological oxidation, flasks of sterile, defined Mn(II) medium were either inoculated with a subculture of the enrichment or left uninoculated, and incubated under oxic conditions. Because manganese oxides have previously been suggested to contribute to the chemical auto-oxidation of Mn(II) 20 , we inoculated other replicate flasks with a steam-sterilized subculture with oxide products. Even after a year, oxidation had not occurred in uninoculated flasks or flasks containing the steam-sterilized inocula, as predicted by the known chemical stability of MnCO 3 under these conditions 21 , 22 . However, within four weeks, the flasks inoculated with ‘viable material’ had generated dark, adherent manganese oxides (Fig. 1a ). Oxidation required O 2 and occurred at temperatures up to 42 °C; oxidation occurring optimally between 34 °C to 40 °C (Extended Data Fig. 1a ), consistent with catalysis being enzymatic. Mn(II) oxidation activity was also sensitive to exposure to antibiotics, or to overnight pasteurization at 50 °C (Extended Data Fig. 1b ). Phosphate was inhibitory at concentrations above 0.3 mM. When amended with MnCO 3 , the pH of unbuffered medium ranged between 5.7 and 6.3. Although a pH buffer was not required, Mn(II) oxidation was faster in medium buffered with 5 mM 3-morpholinopropanesulfonic acid (MOPS) at its p K a (7.1 at 37 °C). In buffered cultures, the final pH ranged between 6.5 and 6.8. With or without buffer, increases in culture pH during or after oxidation—which might lead to chemical oxidation of unreacted MnCO 3 —were not observed. No growth could be detected in the MOPS-buffered basal medium without addition of MnCO 3 (Extended Data Fig. 2a ). Fig. 1: Bio-oxidation of MnCO 3 produces manganese oxide nodules to which two species associate. a , After incubation, comparison of an uninoculated control flask of basal medium containing bright, unreacted MnCO 3 (left) with the adherent dark oxide products generated in a flask that had been inoculated with viable material (right). b – e , Microscopy of manganese oxide nodules generated in agarose solidified MnCO 3 medium. b , After incubation of tubes inoculated with viable material, the cloud of bright MnCO 3 particles was clarified towards the air-exposed meniscus, concomitant with the generation of larger, discrete dark oxides (enlarged in c ). d , Transmitted light micrograph of an acridine-orange (nucleic acid)-stained manganese oxide nodule from the same agarose tube. e , Epifluorescence micrograph of the same nodule as in d , with surface visible biomass localized to the inner clefts; material in clefts appeared orange before staining. f , Scanning electron micrograph of an manganese oxide nodule produced by the co-culture. g , Epifluorescence microscopy and fluorescence in situ hybridization using species-specific rRNA-targeted probes reveal cell distributions in dissolved manganese oxide nodules. Species A, magenta; species B, green; all DNA stained<|im_end|> <|im_start|>assistant Caltech microbiologists have discovered bacteria that feed on manganese and use the metal as their source of calories. Such microbes were predicted to exist over a century ago, but none had been found or described until now. "These are the first bacteria found to use manganese as their source of fuel," says Jared Leadbetter, professor of environmental microbiology at Caltech who, in collaboration with postdoctoral scholar Hang Yu, describes the findings in the July 16 issue of the journal Nature. "A wonderful aspect of microbes in nature is that they can metabolize seemingly unlikely materials, like metals, yielding energy useful to the cell." The study also reveals that the bacteria can use manganese to convert carbon dioxide into biomass, a process called chemosynthesis. Previously, researchers knew of bacteria and fungi that could oxidize manganese, or strip it of electrons, but they had only speculated that yet-to-be-identified microbes might be able to harness the process to drive growth. Leadbetter found the bacteria serendipitously after performing unrelated experiments using a light, chalk-like form of manganese. He had left a glass jar soiled with the substance to soak in tap water in his Caltech office sink before departing for several months to work off campus. When he returned, the jar was coated with a dark material. "I thought, 'What is that?'" he explains. "I started to wonder if long-sought-after microbes might be responsible, so we systematically performed tests to figure that out." The black coating was in fact oxidized manganese generated by newfound bacteria that had likely come from the tap water itself. "There is evidence that relatives of these creatures reside in groundwater, and a portion of Pasadena's drinking water is pumped from local aquifers," he says. Manganese is one of the most abundant elements on the surface of the earth. Manganese oxides take the form of a dark, clumpy substance and are common in nature; they have been found in subsurface deposits and can also form in water-distribution systems. "There is a whole set of environmental engineering literature on drinking-water-distribution systems getting clogged by manganese oxides," says Leadbetter. "But how and for what reason such material is generated there has remained an enigma. Clearly, many scientists have considered that bacteria using manganese for energy might be responsible, but evidence supporting this idea was not available until now." The finding helps researchers better understand the geochemistry of groundwater. It is known that bacteria can degrade pollutants in groundwater, a process called bioremediation. When doing this, several key organisms will "reduce" manganese oxide, which means they donate electrons to it, in a manner similar to how humans use oxygen in the air. Scientists have wondered where the manganese oxide comes from in the first place. "The bacteria we have discovered can produce it, thus they enjoy a lifestyle that also serves to supply the other microbes with what they need to perform reactions that we consider to be beneficial and desirable," says Leadbetter. The research findings also have possible relevance to understanding manganese nodules that dot much of the seafloor. These round metallic balls, which can be as large as grapefruit, were known to marine researchers as early as the cruises of the HMS Challenger in the 1870s. Since then, such nodules have been found to line the bottom of many of Earth's oceans. In recent years, mining companies have been making plans to harvest and exploit these nodules, because rare metals are often found concentrated within them. But little is understood about how the nodules form in the first place. Yu and Leadbetter now wonder if microbes similar to what they have found in freshwater might play a role and they plan to further investigate the mystery. "This underscores the need to better understand marine manganese nodules before they are decimated by mining," says Yu. "This discovery from Jared and Hang fills a major intellectual gap in our understanding of Earth's elemental cycles, and adds to the diverse ways in which manganese, an abstruse but common transition metal, has shaped the evolution of life on our planet," says Woodward Fischer, professor of geobiology at Caltech, who was not involved with the study. <|im_end|>

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2,379

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Females tend to perform worse than males on math and science tests, but they perform better on verbal reading tests. Here, by analysing performance during a cognitive test, we provide evidence that females are better able to sustain their performance during a test across all of these topics, including math and science (study 1). This finding suggests that longer cognitive tests decrease the gender gap in math and science. By analysing a dataset with multiple tests that vary in test length, we find empirical support for this idea (study 2). Introduction The successful completion of a cognitive task often requires time. At the workplace, one might even work for eight consecutive hours on cognitively demanding tasks. These observations suggest that the ability to sustain performance during such tasks is a relevant aspect for individual success in current knowledge societies. Though there are some exceptions 1 , 2 , this ability has been largely understudied. In the present article, we study gender differences in the ability to sustain performance on a specific task: completing a cognitive test. We examine the hypothesis that females show more sustained performance during test-taking than males and investigate its potential implications for the gender gaps in test scores. It has been documented that, on average, female students tend to outperform male students on verbal and reading tests, while male students often perform better than female students on math and science tests 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 . Gender gaps in math test scores have received special attention because course enrolment gaps in math and related STEM-field courses are important to understand the male−female differences in socioeconomic outcomes 12 , 13 . Despite the fact that gender gaps in math test scores have been found to narrow or even vanish over recent decades 4 , 9 , 14 , they remain present in large-scale assessments such as the Programme for International Student Assessment (PISA) 15 . Similar to many other cognitive tasks, the completion of a test requires time. Consequently, gender differences in the ability to sustain performance during a test can affect these documented gender gaps in test scores. Previous research provides several reasons to expect that female students show more sustained performance during test-taking than male students. The first reason is the documented gender difference in noncognitive skills. Noncognitive skills comprise a broad category of metrics that encompass socioemotional ability, personality, motivations and behaviour, and they have recently gained attention as important aspects of human capital 16 . Females have been found to have more self-discipline 17 , have fewer behavioural problems 18 , be less overconfident 19 , and show more developed attitudes towards learning 10 . In terms of the Big Five taxonomy, females consistently report higher levels of agreeableness and neuroticism 20 , 21 , 22 , 23 . Female have also been found to report higher levels of conscientiousness 22 , but the size of this gender gap seems to differ among studies 20 , 21 , 23 and to depend on the facet of conscientiousness 24 . A second reason for the hypothesis is that male and female students may follow different strategies while completing a test. We define test-taking strategies as any reason that leads a student to answer the questions in an order different than the order being administered. For instance, a strategy might be to review all the answers before handing in the test. Although gender differences in test-taking strategies have not been directly studied before, females have been found to have an advantage in the neurocognitive ability of planning 25 . Planning includes actions and thoughts for successful task completion, such as self-monitoring, self-correction, and verification of completion 26 . Gender differences in test-taking strategies seem to also be consistent with the existing evidence on male−female differences in time management 27 , 28 . Finally, a third reason for the hypothesis is that females may be better able to maintain their effort during the test. Testing effort and motivation have been found to be an important determinant of test scores 29 , 30 , 31 , 32 , where female students have been found to exert higher effort on non-incentivized tests 31 , 33 , 34 , 35 . All of these reasons are unrelated to the specific cognitive domain evaluated in the test. Therefore, we can expect that females show more sustained performance during test-taking than male in the cognitive domains where they perform both relatively better (reading) and relatively worse (math-science). Gender differences in the ability to sustain performance can have important implications in the interpretation and framing of the previously documented gender differences in test scores. The presence of larger gender gaps in short tests has often been attributed to females being less able to cope with time pressure 36 . For instance, when the relative performance of female students increased after a 15-min time extension on math and computer science exams at Oxford University, dons argued the following in an article in The Telegraph : “female candidates might be more likely to be adversely affected by time pressure” 37 . A female advantage in sustaining performance during test-taking would provide an alternative explanation to this observation: female students might make better use of the extra time on the test because of their ability to sustain performance. In this article, we conduct two studies to analyse the gender difference in sustaining performance during a cognitive test and its potential implications for the gender gaps in test scores. In study 1, we use data from the PISA test and show that 15-year-old females are better able to sustain their performance during the test than 15-year-old males. Extending the approach proposed by previous work 1 , we compare the performance of male and female students at the beginning of and during the test, and we do so separately for math and science questions (domains favourable to males) and for reading questions (a", "role": "user" }, { "content": "A team of researchers from Universitat de les Illes Balears and Erasmus University Rotterdam, has found that female students score better than male students on tests over two hours long. In their paper published in the journal Nature Communications, the researchers describe their study of test results of students taking the Programme for International Student Assessment (PISA) and what they found. For many years, have shown female students have achieved higher PISA scores on reading and verbal tests, while boys did better on math and science. These findings have led to efforts by school administrators to improve the way students are taught, particularly girls who tend to shun STEM fields. But now, it appears there is more to the test results than was previously thought. To learn more about the differences in test taking between genders, the researchers studied PISA results from 2006 to 2015 in a new way. They noted that prior research had shown that students give their best answers at the beginning of a test and grow progressively worse as the test continues. They report that when they tracked the progression of test taking with the students, they found that the performance of the males degraded more so than did the females. This led to fewer overall performance differences for longer tests. As an example, they noted that during the early stages of math tests, the boys were outperforming girls by up to 6 percent. But by the end of the test, performance was nearly equal. The researchers suggest their findings indicate that girls are able to maintain their concentration on tests for longer periods than boys. To confirm their findings, the researchers also looked at the data from a prior study that involved performance by students who had completed 441 tests of varying lengths. They report that they found the same trend—longer tests had a smaller gender gap. The researchers suggest that girls have more self-discipline and tend to take a more serious approach to learning. They also note that prior studies have shown that women are better at planning, and might be using that ability when working on tests that take a lot of time. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Females tend to perform worse than males on math and science tests, but they perform better on verbal reading tests. Here, by analysing performance during a cognitive test, we provide evidence that females are better able to sustain their performance during a test across all of these topics, including math and science (study 1). This finding suggests that longer cognitive tests decrease the gender gap in math and science. By analysing a dataset with multiple tests that vary in test length, we find empirical support for this idea (study 2). Introduction The successful completion of a cognitive task often requires time. At the workplace, one might even work for eight consecutive hours on cognitively demanding tasks. These observations suggest that the ability to sustain performance during such tasks is a relevant aspect for individual success in current knowledge societies. Though there are some exceptions 1 , 2 , this ability has been largely understudied. In the present article, we study gender differences in the ability to sustain performance on a specific task: completing a cognitive test. We examine the hypothesis that females show more sustained performance during test-taking than males and investigate its potential implications for the gender gaps in test scores. It has been documented that, on average, female students tend to outperform male students on verbal and reading tests, while male students often perform better than female students on math and science tests 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 . Gender gaps in math test scores have received special attention because course enrolment gaps in math and related STEM-field courses are important to understand the male−female differences in socioeconomic outcomes 12 , 13 . Despite the fact that gender gaps in math test scores have been found to narrow or even vanish over recent decades 4 , 9 , 14 , they remain present in large-scale assessments such as the Programme for International Student Assessment (PISA) 15 . Similar to many other cognitive tasks, the completion of a test requires time. Consequently, gender differences in the ability to sustain performance during a test can affect these documented gender gaps in test scores. Previous research provides several reasons to expect that female students show more sustained performance during test-taking than male students. The first reason is the documented gender difference in noncognitive skills. Noncognitive skills comprise a broad category of metrics that encompass socioemotional ability, personality, motivations and behaviour, and they have recently gained attention as important aspects of human capital 16 . Females have been found to have more self-discipline 17 , have fewer behavioural problems 18 , be less overconfident 19 , and show more developed attitudes towards learning 10 . In terms of the Big Five taxonomy, females consistently report higher levels of agreeableness and neuroticism 20 , 21 , 22 , 23 . Female have also been found to report higher levels of conscientiousness 22 , but the size of this gender gap seems to differ among studies 20 , 21 , 23 and to depend on the facet of conscientiousness 24 . A second reason for the hypothesis is that male and female students may follow different strategies while completing a test. We define test-taking strategies as any reason that leads a student to answer the questions in an order different than the order being administered. For instance, a strategy might be to review all the answers before handing in the test. Although gender differences in test-taking strategies have not been directly studied before, females have been found to have an advantage in the neurocognitive ability of planning 25 . Planning includes actions and thoughts for successful task completion, such as self-monitoring, self-correction, and verification of completion 26 . Gender differences in test-taking strategies seem to also be consistent with the existing evidence on male−female differences in time management 27 , 28 . Finally, a third reason for the hypothesis is that females may be better able to maintain their effort during the test. Testing effort and motivation have been found to be an important determinant of test scores 29 , 30 , 31 , 32 , where female students have been found to exert higher effort on non-incentivized tests 31 , 33 , 34 , 35 . All of these reasons are unrelated to the specific cognitive domain evaluated in the test. Therefore, we can expect that females show more sustained performance during test-taking than male in the cognitive domains where they perform both relatively better (reading) and relatively worse (math-science). Gender differences in the ability to sustain performance can have important implications in the interpretation and framing of the previously documented gender differences in test scores. The presence of larger gender gaps in short tests has often been attributed to females being less able to cope with time pressure 36 . For instance, when the relative performance of female students increased after a 15-min time extension on math and computer science exams at Oxford University, dons argued the following in an article in The Telegraph : “female candidates might be more likely to be adversely affected by time pressure” 37 . A female advantage in sustaining performance during test-taking would provide an alternative explanation to this observation: female students might make better use of the extra time on the test because of their ability to sustain performance. In this article, we conduct two studies to analyse the gender difference in sustaining performance during a cognitive test and its potential implications for the gender gaps in test scores. In study 1, we use data from the PISA test and show that 15-year-old females are better able to sustain their performance during the test than 15-year-old males. Extending the approach proposed by previous work 1 , we compare the performance of male and female students at the beginning of and during the test, and we do so separately for math and science questions (domains favourable to males) and for reading questions (a<|im_end|> <|im_start|>assistant A team of researchers from Universitat de les Illes Balears and Erasmus University Rotterdam, has found that female students score better than male students on tests over two hours long. In their paper published in the journal Nature Communications, the researchers describe their study of test results of students taking the Programme for International Student Assessment (PISA) and what they found. For many years, have shown female students have achieved higher PISA scores on reading and verbal tests, while boys did better on math and science. These findings have led to efforts by school administrators to improve the way students are taught, particularly girls who tend to shun STEM fields. But now, it appears there is more to the test results than was previously thought. To learn more about the differences in test taking between genders, the researchers studied PISA results from 2006 to 2015 in a new way. They noted that prior research had shown that students give their best answers at the beginning of a test and grow progressively worse as the test continues. They report that when they tracked the progression of test taking with the students, they found that the performance of the males degraded more so than did the females. This led to fewer overall performance differences for longer tests. As an example, they noted that during the early stages of math tests, the boys were outperforming girls by up to 6 percent. But by the end of the test, performance was nearly equal. The researchers suggest their findings indicate that girls are able to maintain their concentration on tests for longer periods than boys. To confirm their findings, the researchers also looked at the data from a prior study that involved performance by students who had completed 441 tests of varying lengths. They report that they found the same trend—longer tests had a smaller gender gap. The researchers suggest that girls have more self-discipline and tend to take a more serious approach to learning. They also note that prior studies have shown that women are better at planning, and might be using that ability when working on tests that take a lot of time. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Planetary formation models show that terrestrial planets are formed by the accretion of tens of Moon- to Mars-sized planetary embryos through energetic giant impacts. However, relics of these large proto-planets are yet to be found. Ureilites are one of the main families of achondritic meteorites and their parent body is believed to have been catastrophically disrupted by an impact during the first 10 million years of the solar system. Here we studied a section of the Almahata Sitta ureilite using transmission electron microscopy, where large diamonds were formed at high pressure inside the parent body. We discovered chromite, phosphate, and (Fe,Ni)-sulfide inclusions embedded in diamond. The composition and morphology of the inclusions can only be explained if the formation pressure was higher than 20 GPa. Such pressures suggest that the ureilite parent body was a Mercury- to Mars-sized planetary embryo. Introduction Asteroid 2008 TC 3 fell in 2008 in the Nubian desert in Sudan 1 , and the recovered meteorites, called Almahata Sitta, are mostly dominated by ureilites along with various chondrites 2 . Ureilite fragments are coarse grained rocks mainly consisting of olivine and pyroxene, originating from the mantle of the ureilite parent body (UPB) 3 that has been disrupted following an impact in the first 10 Myr of the solar system 3 . High concentrations of carbon distinguishes ureilites from all other achondrite meteorites 3 , with graphite and diamond expressed between silicate grains. There are three mechanisms suggested for diamond formation in ureilites: (i) shock-driven transformation of graphite to diamond during a high-energy impact 4 , (ii) growth by chemical vapor deposition (CVD) of a carbon-rich gas in the solar nebula 5 , and (iii) growth under static high-pressure inside the UPB 6 . Recent observation 7 of a fragment of the Almahata Sitta ureilite (MS-170) revealed clusters of diamond single crystals that have almost identical crystallographic orientation, and separated by graphite bands. It was thus suggested that individual diamond single crystals as large as 100 μm existed in the sample, which have been later segmented through graphitization 7 . The formation of such large single-crystal diamond grains along with δ 15 N sector zoning observed in diamond segments 7 is impossible during a dynamic event 8 , 9 due to its short duration (up to a few seconds 10 ), and even more so by CVD mechanisms 11 , leaving static high-pressure growth as the only possibility for the origin of the single-crystal diamonds. Owing to their stability, mechanical strength and melting temperature, diamonds very often encapsulate and trap minerals and melts present in their formation environment, in the form of inclusions. In terrestrial diamonds, this has allowed to estimate the depth of diamond formation, and to identify the composition and petrology of phases sampled at that depth. Therefore, diamonds formed inside the UPB can potentially hold invaluable information about its size and composition. In this study, we investigated the Almahata Sitta MS-170 section using transmission electron microscopy (TEM) and electron energy-loss spectroscopy (EELS). We studied the diamond–graphite relation and discovered different types of inclusions that were chemically characterized by energy dispersive X-ray (EDX) spectroscopy, crystallographically by electron diffraction, and morphologically by TEM imaging. The composition and mineralogy of these inclusions points to pressures in excess of 20 GPa inside the UPB, which in turn implies a planetary body ranging in size between Mercury and Mars. Results Diamond–graphite relationship The diamond matrix shows plastic deformation as evidenced by the high density of dislocations, stacking faults and a large number of {111} deformation twins (Supplementary Fig. 1 ). Despite no sign of graphitization for uninterrupted twins, the deformation twins that intersect an inclusion transform to graphite (Fig. 1 , Supplementary Fig. 2 ), while keeping their original morphology. Thus, the diamond–graphite grain boundary forms parallel to the {111} planes of diamond (Supplementary Note 1 ). Fig. 1 Graphitization of diamond along twinning directions. a The high-angle annular dark-field (HAADF) STEM image shows two twinning regions indicated as twin 1 and twin 2. Twin 1 is intersecting with two inclusions (indicated by orange arrows) and graphitized, while twin 2 is purely diamond. b The graphite-diamond EELS map (from the dashed blue rectangle in panel a ) indicates that the graphitization is confined to the twinning region and around the inclusions (red = graphite, blue = diamond) Full size image The sample shown in Fig. 2 consists of several diamond segments with close crystallographic orientations, and are separated by graphite bands. Inclusion trails can be seen extending from one diamond segment into the next, while disappearing in the in-between graphite band (Fig. 2b ). This is undeniable morphological evidence that the inclusions existed in diamond before these were broken into smaller pieces by graphitization. Similar to the graphitized twins, the graphite bands in Fig. 2 have grain boundaries parallel to {111} planes of diamond (Supplementary Fig. 3 and Supplementary Note 1 ). Thus, the most likely cause of graphitization is the shock event where the diamond matrix has been severely deformed 12 , 13 . Elevated temperature during the shock, as well as stress concentration around the inclusion promotes the graphitization process 13 , 14 . Fig. 2 Inclusion trails imaged inside diamond fragments. a HAADF-STEM image from diamond segments with similar crystallographic orientation. Dashed yellow lines show the diamond–graphite boundaries. b High-magnification image corresponding to the green square in a . Diamond and inclusion trails are cut by a graphite band. The dashed orange line shows the direction of the inclusion trails Full size image Iron–sulfur type inclusions in diamond The overwhelming majority of inclusions are iron-rich sulfides, found either as isolated grains with sizes up to a few 100 nanometers, or as trails of small particles ranging from 50 nm down to a few nanometers (Fig. 3 and Supplementary Fig. 4 ). All the inclusions are faceted indicating that they were trapped as solid crystalline phases rather than melts. However, they show evidence of transformation to low-pressure phases during decompression, similarly to those found in deep", "role": "user" }, { "content": "Fragments of a meteorite that fell to Earth about a decade ago provide compelling evidence of a lost planet that once roamed our solar system, according to a study published Tuesday. Researchers from Switzerland, France and Germany examined diamonds found inside the Almahata Sitta meteorite and concluded they were most likely formed by a proto-planet at least 4.55 billion years ago. The diamonds in the meteorite, which crashed in Sudan's Nubian Desert in October 2008, have tiny crystals inside them that would have required great pressure to form, said one of the study's co-authors, Philippe Gillet. \"We demonstrate that these large diamonds cannot be the result of a shock but rather of growth that has taken place within a planet,\" he told The Associated Press in a telephone interview from Switzerland. Gillet, a planetary scientist at the Federal Institute of Technology in Lausanne, said researchers calculated a pressure of 200,000 bar (2.9 million psi) would be needed to form such diamonds, suggesting the mystery planet was as least as big as Mercury, possibly even Mars. Scientists have long theorized that the early solar system once contained many more planets—some of which were likely little more than a mass of molten magma. One of these embryo planets—dubbed Theia—is believed to have slammed into a young Earth, ejecting a large amount of debris that later formed the moon. Inclusion trails imaged inside diamond fragments. a HAADF-STEM image from diamond segments with similar crystallographic orientation. Dashed yellow lines show the diamond–graphite boundaries. b High-magnification image corresponding to the green square in a. Diamond and inclusion trails are cut by a graphite band. The dashed orange line shows the direction of the inclusion trails. Credit: Nature Communications (2018). DOI: 10.1038/s41467-018-03808-6 \"What we're claiming here,\" said Gillet, \"is that we have in our hands a remnant of this first generation of planets that are missing today because they were destroyed or incorporated in a bigger planet.\" Addi Bischoff, a meteorite expert at the University of Muenster, Germany, said the methods used for the study were sound and the conclusion was plausible. But further evidence of sustained high pressure would be expected to be found in the minerals surrounding the diamonds, he said. Bischoff wasn't involved in the study, which was published in the journal Nature Communications. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Planetary formation models show that terrestrial planets are formed by the accretion of tens of Moon- to Mars-sized planetary embryos through energetic giant impacts. However, relics of these large proto-planets are yet to be found. Ureilites are one of the main families of achondritic meteorites and their parent body is believed to have been catastrophically disrupted by an impact during the first 10 million years of the solar system. Here we studied a section of the Almahata Sitta ureilite using transmission electron microscopy, where large diamonds were formed at high pressure inside the parent body. We discovered chromite, phosphate, and (Fe,Ni)-sulfide inclusions embedded in diamond. The composition and morphology of the inclusions can only be explained if the formation pressure was higher than 20 GPa. Such pressures suggest that the ureilite parent body was a Mercury- to Mars-sized planetary embryo. Introduction Asteroid 2008 TC 3 fell in 2008 in the Nubian desert in Sudan 1 , and the recovered meteorites, called Almahata Sitta, are mostly dominated by ureilites along with various chondrites 2 . Ureilite fragments are coarse grained rocks mainly consisting of olivine and pyroxene, originating from the mantle of the ureilite parent body (UPB) 3 that has been disrupted following an impact in the first 10 Myr of the solar system 3 . High concentrations of carbon distinguishes ureilites from all other achondrite meteorites 3 , with graphite and diamond expressed between silicate grains. There are three mechanisms suggested for diamond formation in ureilites: (i) shock-driven transformation of graphite to diamond during a high-energy impact 4 , (ii) growth by chemical vapor deposition (CVD) of a carbon-rich gas in the solar nebula 5 , and (iii) growth under static high-pressure inside the UPB 6 . Recent observation 7 of a fragment of the Almahata Sitta ureilite (MS-170) revealed clusters of diamond single crystals that have almost identical crystallographic orientation, and separated by graphite bands. It was thus suggested that individual diamond single crystals as large as 100 μm existed in the sample, which have been later segmented through graphitization 7 . The formation of such large single-crystal diamond grains along with δ 15 N sector zoning observed in diamond segments 7 is impossible during a dynamic event 8 , 9 due to its short duration (up to a few seconds 10 ), and even more so by CVD mechanisms 11 , leaving static high-pressure growth as the only possibility for the origin of the single-crystal diamonds. Owing to their stability, mechanical strength and melting temperature, diamonds very often encapsulate and trap minerals and melts present in their formation environment, in the form of inclusions. In terrestrial diamonds, this has allowed to estimate the depth of diamond formation, and to identify the composition and petrology of phases sampled at that depth. Therefore, diamonds formed inside the UPB can potentially hold invaluable information about its size and composition. In this study, we investigated the Almahata Sitta MS-170 section using transmission electron microscopy (TEM) and electron energy-loss spectroscopy (EELS). We studied the diamond–graphite relation and discovered different types of inclusions that were chemically characterized by energy dispersive X-ray (EDX) spectroscopy, crystallographically by electron diffraction, and morphologically by TEM imaging. The composition and mineralogy of these inclusions points to pressures in excess of 20 GPa inside the UPB, which in turn implies a planetary body ranging in size between Mercury and Mars. Results Diamond–graphite relationship The diamond matrix shows plastic deformation as evidenced by the high density of dislocations, stacking faults and a large number of {111} deformation twins (Supplementary Fig. 1 ). Despite no sign of graphitization for uninterrupted twins, the deformation twins that intersect an inclusion transform to graphite (Fig. 1 , Supplementary Fig. 2 ), while keeping their original morphology. Thus, the diamond–graphite grain boundary forms parallel to the {111} planes of diamond (Supplementary Note 1 ). Fig. 1 Graphitization of diamond along twinning directions. a The high-angle annular dark-field (HAADF) STEM image shows two twinning regions indicated as twin 1 and twin 2. Twin 1 is intersecting with two inclusions (indicated by orange arrows) and graphitized, while twin 2 is purely diamond. b The graphite-diamond EELS map (from the dashed blue rectangle in panel a ) indicates that the graphitization is confined to the twinning region and around the inclusions (red = graphite, blue = diamond) Full size image The sample shown in Fig. 2 consists of several diamond segments with close crystallographic orientations, and are separated by graphite bands. Inclusion trails can be seen extending from one diamond segment into the next, while disappearing in the in-between graphite band (Fig. 2b ). This is undeniable morphological evidence that the inclusions existed in diamond before these were broken into smaller pieces by graphitization. Similar to the graphitized twins, the graphite bands in Fig. 2 have grain boundaries parallel to {111} planes of diamond (Supplementary Fig. 3 and Supplementary Note 1 ). Thus, the most likely cause of graphitization is the shock event where the diamond matrix has been severely deformed 12 , 13 . Elevated temperature during the shock, as well as stress concentration around the inclusion promotes the graphitization process 13 , 14 . Fig. 2 Inclusion trails imaged inside diamond fragments. a HAADF-STEM image from diamond segments with similar crystallographic orientation. Dashed yellow lines show the diamond–graphite boundaries. b High-magnification image corresponding to the green square in a . Diamond and inclusion trails are cut by a graphite band. The dashed orange line shows the direction of the inclusion trails Full size image Iron–sulfur type inclusions in diamond The overwhelming majority of inclusions are iron-rich sulfides, found either as isolated grains with sizes up to a few 100 nanometers, or as trails of small particles ranging from 50 nm down to a few nanometers (Fig. 3 and Supplementary Fig. 4 ). All the inclusions are faceted indicating that they were trapped as solid crystalline phases rather than melts. However, they show evidence of transformation to low-pressure phases during decompression, similarly to those found in deep<|im_end|> <|im_start|>assistant Fragments of a meteorite that fell to Earth about a decade ago provide compelling evidence of a lost planet that once roamed our solar system, according to a study published Tuesday. Researchers from Switzerland, France and Germany examined diamonds found inside the Almahata Sitta meteorite and concluded they were most likely formed by a proto-planet at least 4.55 billion years ago. The diamonds in the meteorite, which crashed in Sudan's Nubian Desert in October 2008, have tiny crystals inside them that would have required great pressure to form, said one of the study's co-authors, Philippe Gillet. "We demonstrate that these large diamonds cannot be the result of a shock but rather of growth that has taken place within a planet," he told The Associated Press in a telephone interview from Switzerland. Gillet, a planetary scientist at the Federal Institute of Technology in Lausanne, said researchers calculated a pressure of 200,000 bar (2.9 million psi) would be needed to form such diamonds, suggesting the mystery planet was as least as big as Mercury, possibly even Mars. Scientists have long theorized that the early solar system once contained many more planets—some of which were likely little more than a mass of molten magma. One of these embryo planets—dubbed Theia—is believed to have slammed into a young Earth, ejecting a large amount of debris that later formed the moon. Inclusion trails imaged inside diamond fragments. a HAADF-STEM image from diamond segments with similar crystallographic orientation. Dashed yellow lines show the diamond–graphite boundaries. b High-magnification image corresponding to the green square in a. Diamond and inclusion trails are cut by a graphite band. The dashed orange line shows the direction of the inclusion trails. Credit: Nature Communications (2018). DOI: 10.1038/s41467-018-03808-6 "What we're claiming here," said Gillet, "is that we have in our hands a remnant of this first generation of planets that are missing today because they were destroyed or incorporated in a bigger planet." Addi Bischoff, a meteorite expert at the University of Muenster, Germany, said the methods used for the study were sound and the conclusion was plausible. But further evidence of sustained high pressure would be expected to be found in the minerals surrounding the diamonds, he said. Bischoff wasn't involved in the study, which was published in the journal Nature Communications. <|im_end|>

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1,905

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Neural sequences are a fundamental feature of brain dynamics underlying diverse behaviours, but the mechanisms by which they develop during learning remain unknown. Songbirds learn vocalizations composed of syllables; in adult birds, each syllable is produced by a different sequence of action potential bursts in the premotor cortical area HVC. Here we carried out recordings of large populations of HVC neurons in singing juvenile birds throughout learning to examine the emergence of neural sequences. Early in vocal development, HVC neurons begin producing rhythmic bursts, temporally locked to a ‘prototype’ syllable. Different neurons are active at different latencies relative to syllable onset to form a continuous sequence. Through development, as new syllables emerge from the prototype syllable, initially highly overlapping burst sequences become increasingly distinct. We propose a mechanistic model in which multiple neural sequences can emerge from the growth and splitting of a common precursor sequence. Main Sequences of neural activity have been observed during various behaviours, including navigation 1 , 2 , 3 , 4 , short-term memory 5 , 6 , 7 , decision making 8 , 9 , and complex movements 10 , 11 , suggesting that neural sequences are a fundamental form of brain dynamics 12 , 13 . However, the circuit mechanisms underlying the generation of neural sequences and their development during learning are not well understood. The songbird is a good model system to address such questions because the song produced by adults is learned during development 14 , 15 , 16 , 17 , 18 . Furthermore, adult song is associated with neural sequences in nucleus HVC 19 , 20 , 21 , 22 , 23 , 24 , a premotor cortical area necessary for the production of stereotyped adult song 25 , 26 , 27 , 28 , 29 , 30 . Most projection neurons in HVC generate a brief burst of spikes at one specific time in the song motif and different neurons are active at different times in the song 19 , 20 , 21 , 22 , 23 , 24 , 30 ; thus, distinct syllable types are produced by largely non-overlapping neural sequences in HVC. Here we ask how these different neural sequences are constructed during vocal development. Zebra finches acquire their stereotyped song through a gradual learning process 14 , 31 . Young birds initially produce a highly variable ‘subsong’ 31 , akin to human babbling 15 . Birds then enter the protosyllable stage as they begin to incorporate syllables of a characteristic ~100 ms duration 32 , 33 , 34 , 35 . This is followed by the gradual emergence of multiple syllable types 32 , 33 , 36 , and a final ‘motif’ stage in which syllables are produced in a reliable sequence. While HVC activity is not required for subsong 27 , 34 , 35 , it is required for song components in all later stages, including protosyllables, emerging syllable types, and adult song 25 , 26 , 27 , 28 , 34 , 35 . Developmental progression of HVC activity To elucidate the mechanisms by which neural sequences in HVC develop, we recorded from populations of HVC projection neurons in juvenile and adult birds ( n = 1,149 neurons, 35 birds; Extended Data Fig. 1a ). At all stages of vocal development, HVC projection neurons generated brief bursts of spikes during singing ( Fig. 1a–c , Extended Data Fig. 1b, c ). In the subsong stage ( n = 12 birds; defined by exponential distribution of syllable durations, before the emergence of protosyllables) roughly half the neurons generated bursts not temporally locked to syllable onsets ( Extended Data Fig. 1d ), while the other half produced bursts that tended to occur at a particular latency relative to subsong syllable onsets ( Fig. 1a and Extended Data Fig. 1e–i ; 19/39 neurons exhibited syllable locking). The fraction of neurons locked to syllable onsets exhibited a gradual and significant increase throughout vocal development ( Fig. 1f ; correlation with song stage: r = 0.22, P < 10 −10 ; see Methods) until, in adult birds, virtually every projection neuron generated bursts precisely locked to syllables, as previously described 19 , 20 , 21 , 22 , 23 , 24 . Figure 1: Singing-related firing patterns of HVC projection neurons in juvenile birds. a , Neuron recorded in the subsong stage, before the formation of protosyllables (RA-projecting HVC neuron, HVC RA ; 51 dph; bird 7). Top, song spectrogram with syllables indicated above. Bottom, extracellular voltage trace. b , Neuron recorded in the protosyllable stage (HVC RA ; 62 dph; bird 2). Protosyllables indicated (grey bars). c , Neuron recorded after motif formation (HVC RA ; 68 dph; bird 8). d , Neuron bursting exclusively at bout onset (X-projecting HVC neuron, HVC X ; 61 dph; bird 2). e , Neuron bursting exclusively at bout offset (HVC RA ; 65 dph; bird 2). f , Developmental change in the fraction of neurons locked to syllable onsets (grey) and fraction of neurons with rhythmic bursting (black) (mean ± s.e.m.; n = 39, 135, 565, 378 and 32 neurons, respectively). g , Mean period of the HVC rhythmicity as a function of song stage ( n = 3, 70, 356, 298 and 25 neurons, respectively). *** P < 0.001, post-hoc comparison with the adult stage. Spectrogram vertical axis 500–8,000 Hz. Scale bars for panels a – c , 0.5 mV, 200 ms; panels d – e , 1 mV, 500 ms. Inset in panels a – c show zoom of bursts indicated by an asterisk; scale bar, 5 ms. PowerPoint slide Full size image Song development is characterized by a gradual change in song rhythm 33 , 37 , 38 . The subsong stage, which has little evidence of rhythmic song structure, ends with the emergence of a rhythmically produced protosyllable (5–10 Hz) 32 , 33 , 34 , 35 . This is followed by a subsequent increase in the period between repetitions of the same sound,", "role": "user" }, { "content": "Male zebra finches, small songbirds native to central Australia, learn their songs by copying what they hear from their fathers. These songs, often used as mating calls, develop early in life as juvenile birds experiment with mimicking the sounds they hear. MIT neuroscientists have now uncovered the brain activity that supports this learning process. Sequences of neural activity that encode the birds' first song syllable are duplicated and altered slightly, allowing the birds to produce several variations on the original syllable. Eventually these syllables are strung together into the bird's signature song, which remains constant for life. \"The advantage here is that in order to learn new syllables, you don't have to learn them from scratch. You can reuse what you've learned and modify it slightly. We think it's an efficient way to learn various types of syllables,\" says Tatsuo Okubo, a former MIT graduate student and lead author of the study, which appears in the Nov. 30 online edition of Nature. Okubo and his colleagues believe that this type of neural sequence duplication may also underlie other types of motor learning. For example, the sequence used to swing a tennis racket might be repurposed for a similar motion such as playing Ping-Pong. \"This seems like a way that sequences might be learned and reused for anything that involves timing,\" says Emily Mackevicius, an MIT graduate student who is also an author of the paper. The paper's senior author is Michale Fee, a professor of brain and cognitive sciences at MIT and a member of the McGovern Institute for Brain Research. Bursting into song Previous studies from Fee's lab have found that a part of the brain's cortex known as the HVC is critical for song production. Typically, each song lasts for about one second and consists of multiple syllables. Fee's lab has found that in adult birds, individual HVC neurons show a very brief burst of activity—about 10 milliseconds or less—at one moment during the song. Different sets of neurons are active at different times, and collectively the song is represented by this sequence of bursts. In the new Nature study, the researchers wanted to figure out how those neural patterns develop in newly hatched zebra finches. To do that, they recorded electrical activity in HVC neurons for up to three months after the birds hatched. When zebra finches begin to sing, about 30 days after hatching, they produce only nonsense syllables known as subsong, similar to the babble of human babies. At first, the duration of these syllables is highly variable, but after a week or so they turn into more consistent sounds called protosyllables, which last about 100 milliseconds. Each bird learns one protosyllable that forms a scaffold for subsequent syllables. The researchers found that within the HVC, neurons fire in a sequence of short bursts corresponding to the first protosyllable that each bird learns. Most of the neurons in the HVC participate in this original sequence, but as time goes by, some of these neurons are extracted from the original sequence and produce a new, very similar sequence. This chain of neural sequences can be repurposed to produce different syllables. \"From that short sequence it splits into new sequences for the next new syllables,\" Mackevicius says. \"It starts with that short chain that has a lot of redundancy in it, and splits off some neurons for syllable A and some neurons for syllable B.\" This splitting of neural sequences happens repeatedly until the birds can produce between three and seven different syllables, the researchers found. This entire process takes about two months, at which point each bird has settled on its final song. \"This is a very natural way for motor patterns to evolve, by repeating something and then molding it, but until now nobody had any good data to understand how the brain actually does that,\" says Ofer Tchernichovski, a professor of psychology at Hunter College who was not involved in the research. \"What's cool about this paper is they managed to follow how brain centers govern these transitions from simple repetitive patterns to more complex patterns.\" Evolution by duplication The researchers note that this process is similar to what is believed to drive the production of new genes and traits during evolution. \"If you duplicate a gene, then you could have separate mutations in both copies of the gene and they could eventually do different functions,\" Okubo says. \"It's similar with motor programs. You can duplicate the sequence and then independently modify the two daughter motor programs so that they can now each do slightly different things.\" Mackevicius is now studying how input from sound-processing parts of the brain to the HVC contributes to the formation of these neural sequences. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Neural sequences are a fundamental feature of brain dynamics underlying diverse behaviours, but the mechanisms by which they develop during learning remain unknown. Songbirds learn vocalizations composed of syllables; in adult birds, each syllable is produced by a different sequence of action potential bursts in the premotor cortical area HVC. Here we carried out recordings of large populations of HVC neurons in singing juvenile birds throughout learning to examine the emergence of neural sequences. Early in vocal development, HVC neurons begin producing rhythmic bursts, temporally locked to a ‘prototype’ syllable. Different neurons are active at different latencies relative to syllable onset to form a continuous sequence. Through development, as new syllables emerge from the prototype syllable, initially highly overlapping burst sequences become increasingly distinct. We propose a mechanistic model in which multiple neural sequences can emerge from the growth and splitting of a common precursor sequence. Main Sequences of neural activity have been observed during various behaviours, including navigation 1 , 2 , 3 , 4 , short-term memory 5 , 6 , 7 , decision making 8 , 9 , and complex movements 10 , 11 , suggesting that neural sequences are a fundamental form of brain dynamics 12 , 13 . However, the circuit mechanisms underlying the generation of neural sequences and their development during learning are not well understood. The songbird is a good model system to address such questions because the song produced by adults is learned during development 14 , 15 , 16 , 17 , 18 . Furthermore, adult song is associated with neural sequences in nucleus HVC 19 , 20 , 21 , 22 , 23 , 24 , a premotor cortical area necessary for the production of stereotyped adult song 25 , 26 , 27 , 28 , 29 , 30 . Most projection neurons in HVC generate a brief burst of spikes at one specific time in the song motif and different neurons are active at different times in the song 19 , 20 , 21 , 22 , 23 , 24 , 30 ; thus, distinct syllable types are produced by largely non-overlapping neural sequences in HVC. Here we ask how these different neural sequences are constructed during vocal development. Zebra finches acquire their stereotyped song through a gradual learning process 14 , 31 . Young birds initially produce a highly variable ‘subsong’ 31 , akin to human babbling 15 . Birds then enter the protosyllable stage as they begin to incorporate syllables of a characteristic ~100 ms duration 32 , 33 , 34 , 35 . This is followed by the gradual emergence of multiple syllable types 32 , 33 , 36 , and a final ‘motif’ stage in which syllables are produced in a reliable sequence. While HVC activity is not required for subsong 27 , 34 , 35 , it is required for song components in all later stages, including protosyllables, emerging syllable types, and adult song 25 , 26 , 27 , 28 , 34 , 35 . Developmental progression of HVC activity To elucidate the mechanisms by which neural sequences in HVC develop, we recorded from populations of HVC projection neurons in juvenile and adult birds ( n = 1,149 neurons, 35 birds; Extended Data Fig. 1a ). At all stages of vocal development, HVC projection neurons generated brief bursts of spikes during singing ( Fig. 1a–c , Extended Data Fig. 1b, c ). In the subsong stage ( n = 12 birds; defined by exponential distribution of syllable durations, before the emergence of protosyllables) roughly half the neurons generated bursts not temporally locked to syllable onsets ( Extended Data Fig. 1d ), while the other half produced bursts that tended to occur at a particular latency relative to subsong syllable onsets ( Fig. 1a and Extended Data Fig. 1e–i ; 19/39 neurons exhibited syllable locking). The fraction of neurons locked to syllable onsets exhibited a gradual and significant increase throughout vocal development ( Fig. 1f ; correlation with song stage: r = 0.22, P < 10 −10 ; see Methods) until, in adult birds, virtually every projection neuron generated bursts precisely locked to syllables, as previously described 19 , 20 , 21 , 22 , 23 , 24 . Figure 1: Singing-related firing patterns of HVC projection neurons in juvenile birds. a , Neuron recorded in the subsong stage, before the formation of protosyllables (RA-projecting HVC neuron, HVC RA ; 51 dph; bird 7). Top, song spectrogram with syllables indicated above. Bottom, extracellular voltage trace. b , Neuron recorded in the protosyllable stage (HVC RA ; 62 dph; bird 2). Protosyllables indicated (grey bars). c , Neuron recorded after motif formation (HVC RA ; 68 dph; bird 8). d , Neuron bursting exclusively at bout onset (X-projecting HVC neuron, HVC X ; 61 dph; bird 2). e , Neuron bursting exclusively at bout offset (HVC RA ; 65 dph; bird 2). f , Developmental change in the fraction of neurons locked to syllable onsets (grey) and fraction of neurons with rhythmic bursting (black) (mean ± s.e.m.; n = 39, 135, 565, 378 and 32 neurons, respectively). g , Mean period of the HVC rhythmicity as a function of song stage ( n = 3, 70, 356, 298 and 25 neurons, respectively). *** P < 0.001, post-hoc comparison with the adult stage. Spectrogram vertical axis 500–8,000 Hz. Scale bars for panels a – c , 0.5 mV, 200 ms; panels d – e , 1 mV, 500 ms. Inset in panels a – c show zoom of bursts indicated by an asterisk; scale bar, 5 ms. PowerPoint slide Full size image Song development is characterized by a gradual change in song rhythm 33 , 37 , 38 . The subsong stage, which has little evidence of rhythmic song structure, ends with the emergence of a rhythmically produced protosyllable (5–10 Hz) 32 , 33 , 34 , 35 . This is followed by a subsequent increase in the period between repetitions of the same sound,<|im_end|> <|im_start|>assistant Male zebra finches, small songbirds native to central Australia, learn their songs by copying what they hear from their fathers. These songs, often used as mating calls, develop early in life as juvenile birds experiment with mimicking the sounds they hear. MIT neuroscientists have now uncovered the brain activity that supports this learning process. Sequences of neural activity that encode the birds' first song syllable are duplicated and altered slightly, allowing the birds to produce several variations on the original syllable. Eventually these syllables are strung together into the bird's signature song, which remains constant for life. "The advantage here is that in order to learn new syllables, you don't have to learn them from scratch. You can reuse what you've learned and modify it slightly. We think it's an efficient way to learn various types of syllables," says Tatsuo Okubo, a former MIT graduate student and lead author of the study, which appears in the Nov. 30 online edition of Nature. Okubo and his colleagues believe that this type of neural sequence duplication may also underlie other types of motor learning. For example, the sequence used to swing a tennis racket might be repurposed for a similar motion such as playing Ping-Pong. "This seems like a way that sequences might be learned and reused for anything that involves timing," says Emily Mackevicius, an MIT graduate student who is also an author of the paper. The paper's senior author is Michale Fee, a professor of brain and cognitive sciences at MIT and a member of the McGovern Institute for Brain Research. Bursting into song Previous studies from Fee's lab have found that a part of the brain's cortex known as the HVC is critical for song production. Typically, each song lasts for about one second and consists of multiple syllables. Fee's lab has found that in adult birds, individual HVC neurons show a very brief burst of activity—about 10 milliseconds or less—at one moment during the song. Different sets of neurons are active at different times, and collectively the song is represented by this sequence of bursts. In the new Nature study, the researchers wanted to figure out how those neural patterns develop in newly hatched zebra finches. To do that, they recorded electrical activity in HVC neurons for up to three months after the birds hatched. When zebra finches begin to sing, about 30 days after hatching, they produce only nonsense syllables known as subsong, similar to the babble of human babies. At first, the duration of these syllables is highly variable, but after a week or so they turn into more consistent sounds called protosyllables, which last about 100 milliseconds. Each bird learns one protosyllable that forms a scaffold for subsequent syllables. The researchers found that within the HVC, neurons fire in a sequence of short bursts corresponding to the first protosyllable that each bird learns. Most of the neurons in the HVC participate in this original sequence, but as time goes by, some of these neurons are extracted from the original sequence and produce a new, very similar sequence. This chain of neural sequences can be repurposed to produce different syllables. "From that short sequence it splits into new sequences for the next new syllables," Mackevicius says. "It starts with that short chain that has a lot of redundancy in it, and splits off some neurons for syllable A and some neurons for syllable B." This splitting of neural sequences happens repeatedly until the birds can produce between three and seven different syllables, the researchers found. This entire process takes about two months, at which point each bird has settled on its final song. "This is a very natural way for motor patterns to evolve, by repeating something and then molding it, but until now nobody had any good data to understand how the brain actually does that," says Ofer Tchernichovski, a professor of psychology at Hunter College who was not involved in the research. "What's cool about this paper is they managed to follow how brain centers govern these transitions from simple repetitive patterns to more complex patterns." Evolution by duplication The researchers note that this process is similar to what is believed to drive the production of new genes and traits during evolution. "If you duplicate a gene, then you could have separate mutations in both copies of the gene and they could eventually do different functions," Okubo says. "It's similar with motor programs. You can duplicate the sequence and then independently modify the two daughter motor programs so that they can now each do slightly different things." Mackevicius is now studying how input from sound-processing parts of the brain to the HVC contributes to the formation of these neural sequences. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Underdamped terahertz-frequency delocalized phonon-like modes have long been suggested to play a role in the biological function of DNA. Such phonon modes involve the collective motion of many atoms and are prerequisite to understanding the molecular nature of macroscopic conformational changes and related biochemical phenomena. Initial predictions were based on simple theoretical models of DNA. However, such models do not take into account strong interactions with the surrounding water, which is likely to cause phonon modes to be heavily damped and localized. Here we apply state-of-the-art femtosecond optical Kerr effect spectroscopy, which is currently the only technique capable of taking low-frequency (GHz to THz) vibrational spectra in solution. We are able to demonstrate that phonon modes involving the hydrogen bond network between the strands exist in DNA at physiologically relevant conditions. In addition, the dynamics of the solvating water molecules is slowed down by about a factor of 20 compared with the bulk. Introduction The processes important to the biological function of DNA (replication, transcription, denaturation and molecular intercalation) have in common that they start with the breaking of the hydrogen bonds between the bases of the nucleic acid. Driven by the torsional stress of the molecule 1 , the destablization of the weak bonds leads to the splitting of a section of the double helix of DNA into single strands, forming a gap in the nucleic acid known as a transcriptional bubble 2 . The DNA molecule is not a static object, but vibrates and fluctuates on timescales from femtoseconds to nanoseconds. The origin of the rupture of the hydrogen bonds in DNA is thought to be low-frequency vibrational modes propagating along its length in the form of phonon-like modes that expand and contract the space between the bases 3 , 4 , 5 . Because adenine–thymine and guanine–cytosine base pairs differ in their hydrogen bonding and stacking, the physical properties of DNA that influence these waves, such as helical structure 6 or elasticity 7 , depend on the local DNA sequence 8 . It has been suggested that DNA has regions where specific sequences favour the resonance between low-frequency vibrational modes 9 , 10 , promoting the temporary splitting of a significant number of bases, even at physiological temperatures 11 , 12 , 13 . During the short period of time that the bubbles exist 14 , the bases are exposed to the surrounding solvent, which has two effects. On one hand, bubbles expose the nucleic acid to reactions of the bases with mutagens in the environment 15 , while molecular intercalators can take advantage of the gap and may insert themselves between the strands of DNA 11 . On the other hand, bubbles allow helicases access to DNA to stabilize the bubble, followed by splitting the strands to start the transcription and replication process 16 . For this reason, it is believed that DNA directs its own transcription. Despite the importance of the low-frequency vibrational modes of DNA, evidence for their existence is only indirect 17 . The relatively weak absorption of far-infrared radiation by DNA compared with the extremely strong absorption by water has limited investigation by infrared spectroscopy 18 . However, a recent report suggested a non-thermal response of cellular gene expression to terahertz radiation 19 . The presence of low-frequency vibrational modes in DNA has been shown through Raman 20 , 21 , Brillouin 22 , inelastic X-ray 23 and inelastic neutron-scattering 24 measurements. However, all of these studies have been performed in unnatural solid DNA preparations (humidified films, fibres and so on) that modify the dynamics and are likely to introduce low-frequency lattice-phonon modes associated with crystal packing. Furthermore, inelastic neutron-scattering experiments have shown great sensitivity of the speed of sound to relative humidity. No spectroscopic experiments have been carried out under relevant physiological conditions in aqueous solution except over a very narrow frequency range (10–35 cm −1 ) 25 , 26 , 27 . It seems highly likely that exposure of the nucleic acid to bulk liquid water will lead to strong damping of phonon-like modes, resulting in localization. Therefore, the importance of bubbles and the associated low-frequency phonon-like vibrational modes under physiological conditions remains unproven and unlikely. In recent work, we have shown that the technique of ultrafast optical Kerr effect (OKE) spectroscopy could be used to determine the presence of delocalized phonon-like modes in a protein and prove their relevance to biological function 28 . This technique measures the low-frequency depolarized Raman spectrum in the time domain and obtains a spectrum through numerical Fourier transformation 29 , 30 , 31 . Spontaneous scattering techniques such as Raman spectroscopy and inelastic neutron scattering when applied to liquids and solutions become unreliable at low frequencies (<1 THz) due to a very strong Rayleigh peak from elastic scattering 32 . The spectral resolution of inelastic X-ray and neutron scattering is poor ( ∼ 15 cm −1 or 0.5 THz), prohibiting spectral characterization especially below ∼ 1 THz (ref. 23 ). OKE spectroscopy has proven to be far superior at low frequencies, as it does not suffer from a large Rayleigh peak and its high signal to noise allows a detailed analysis of the spectra 29 , 30 . Furthermore, the OKE signal from liquid water is relatively weak, allowing it to be subtracted from the total signal to reveal the spectrum of the solvated biomolecule. Thus, OKE is the only technique that can reliably determine the terahertz and sub-terahertz spectra of biomolecules in physiologically relevant aqueous solution. Here we use OKE spectroscopy to investigate the low-frequency vibrational modes of DNA to determine the presence and possible role of phonon-like modes in nucleic acids in aqueous solution. We present the OKE spectra of two DNA oligomers in phosphate buffer solution, at various degrees of denaturation as a function of increasing temperature. Two phonon-like modes associated with the hydrogen bonds of the double strand of DNA are identified. To confirm the assignments given to the observed bands, the OKE spectra of two different oligomers", "role": "user" }, { "content": "Scientists have shown the weird world of quantum mechanics operating in the molecule of life, DNA. The research, which was carried out by academics from the University of Glasgow and is published today in Nature Communications, describes how double-stranded DNA splits using delocalized sound waves that are the hallmark of quantum effects. DNA contains the code to life and holds a blueprint for each and every living thing on earth. Dedicated enzymes responsible for making new proteins read the code by splitting the double strand in order to access the information. One of the big outstanding questions of biology has been how these enzymes find the initial hole or \"bubble\" in the double strand to start reading the code. Dr Mario González Jiménez, researcher, explains, \"It is believed that DNA has regions where a specific sequence of bases modifies the stiffness of the double helix favouring the formation of bubbles. This causes a break of the weak bonds between the strands showing the transcription and replication enzymes where to start their task.\" Dr Gopakumar Ramakrishnan adds: \"It had been proposed by theoreticians that such DNA bubbles might behave like sound waves, bouncing around in DNA like echoes in a cathedral. However, the current paradigm in biology is that such sound-like dynamics are irrelevant to biological function, as interaction of a biomolecule with the surrounding water will almost certainly destroy any of these effects.\" Researchers in the Ultrafast Chemical Physics group at the University of Glasgow carried out experiments with a laser that produces femtosecond laser pulses about a trillion times shorter than a camera flash. This allowed them to succeed in the detection of sound-like bubbles in DNA. They could show that these bubbles whiz around like bullets in a shooting gallery even in an environment very similar to that which can be found in a living cell. PhD student Dr Thomas Harwood, recently graduated from the University of Strathclyde, points out: \"The sound waves in DNA are not your ordinary sounds waves. They have a frequency of a few terahertz or a billion times higher than a human or a dog can hear!\" Prof Klaas Wynne, leader of the research team and Chair in Chemical Physics at the University of Glasgow, explains: \"The terahertz sound-like bubbles we have seen alter our fundamental understanding of biochemical reactions. There were earlier suggestions for a role of delocalized quantum phenomena in light harvesting, magneto reception, and olfaction. The new results now imply a much more general role for sound-like delocalized phenomena in biomolecular processes.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Underdamped terahertz-frequency delocalized phonon-like modes have long been suggested to play a role in the biological function of DNA. Such phonon modes involve the collective motion of many atoms and are prerequisite to understanding the molecular nature of macroscopic conformational changes and related biochemical phenomena. Initial predictions were based on simple theoretical models of DNA. However, such models do not take into account strong interactions with the surrounding water, which is likely to cause phonon modes to be heavily damped and localized. Here we apply state-of-the-art femtosecond optical Kerr effect spectroscopy, which is currently the only technique capable of taking low-frequency (GHz to THz) vibrational spectra in solution. We are able to demonstrate that phonon modes involving the hydrogen bond network between the strands exist in DNA at physiologically relevant conditions. In addition, the dynamics of the solvating water molecules is slowed down by about a factor of 20 compared with the bulk. Introduction The processes important to the biological function of DNA (replication, transcription, denaturation and molecular intercalation) have in common that they start with the breaking of the hydrogen bonds between the bases of the nucleic acid. Driven by the torsional stress of the molecule 1 , the destablization of the weak bonds leads to the splitting of a section of the double helix of DNA into single strands, forming a gap in the nucleic acid known as a transcriptional bubble 2 . The DNA molecule is not a static object, but vibrates and fluctuates on timescales from femtoseconds to nanoseconds. The origin of the rupture of the hydrogen bonds in DNA is thought to be low-frequency vibrational modes propagating along its length in the form of phonon-like modes that expand and contract the space between the bases 3 , 4 , 5 . Because adenine–thymine and guanine–cytosine base pairs differ in their hydrogen bonding and stacking, the physical properties of DNA that influence these waves, such as helical structure 6 or elasticity 7 , depend on the local DNA sequence 8 . It has been suggested that DNA has regions where specific sequences favour the resonance between low-frequency vibrational modes 9 , 10 , promoting the temporary splitting of a significant number of bases, even at physiological temperatures 11 , 12 , 13 . During the short period of time that the bubbles exist 14 , the bases are exposed to the surrounding solvent, which has two effects. On one hand, bubbles expose the nucleic acid to reactions of the bases with mutagens in the environment 15 , while molecular intercalators can take advantage of the gap and may insert themselves between the strands of DNA 11 . On the other hand, bubbles allow helicases access to DNA to stabilize the bubble, followed by splitting the strands to start the transcription and replication process 16 . For this reason, it is believed that DNA directs its own transcription. Despite the importance of the low-frequency vibrational modes of DNA, evidence for their existence is only indirect 17 . The relatively weak absorption of far-infrared radiation by DNA compared with the extremely strong absorption by water has limited investigation by infrared spectroscopy 18 . However, a recent report suggested a non-thermal response of cellular gene expression to terahertz radiation 19 . The presence of low-frequency vibrational modes in DNA has been shown through Raman 20 , 21 , Brillouin 22 , inelastic X-ray 23 and inelastic neutron-scattering 24 measurements. However, all of these studies have been performed in unnatural solid DNA preparations (humidified films, fibres and so on) that modify the dynamics and are likely to introduce low-frequency lattice-phonon modes associated with crystal packing. Furthermore, inelastic neutron-scattering experiments have shown great sensitivity of the speed of sound to relative humidity. No spectroscopic experiments have been carried out under relevant physiological conditions in aqueous solution except over a very narrow frequency range (10–35 cm −1 ) 25 , 26 , 27 . It seems highly likely that exposure of the nucleic acid to bulk liquid water will lead to strong damping of phonon-like modes, resulting in localization. Therefore, the importance of bubbles and the associated low-frequency phonon-like vibrational modes under physiological conditions remains unproven and unlikely. In recent work, we have shown that the technique of ultrafast optical Kerr effect (OKE) spectroscopy could be used to determine the presence of delocalized phonon-like modes in a protein and prove their relevance to biological function 28 . This technique measures the low-frequency depolarized Raman spectrum in the time domain and obtains a spectrum through numerical Fourier transformation 29 , 30 , 31 . Spontaneous scattering techniques such as Raman spectroscopy and inelastic neutron scattering when applied to liquids and solutions become unreliable at low frequencies (<1 THz) due to a very strong Rayleigh peak from elastic scattering 32 . The spectral resolution of inelastic X-ray and neutron scattering is poor ( ∼ 15 cm −1 or 0.5 THz), prohibiting spectral characterization especially below ∼ 1 THz (ref. 23 ). OKE spectroscopy has proven to be far superior at low frequencies, as it does not suffer from a large Rayleigh peak and its high signal to noise allows a detailed analysis of the spectra 29 , 30 . Furthermore, the OKE signal from liquid water is relatively weak, allowing it to be subtracted from the total signal to reveal the spectrum of the solvated biomolecule. Thus, OKE is the only technique that can reliably determine the terahertz and sub-terahertz spectra of biomolecules in physiologically relevant aqueous solution. Here we use OKE spectroscopy to investigate the low-frequency vibrational modes of DNA to determine the presence and possible role of phonon-like modes in nucleic acids in aqueous solution. We present the OKE spectra of two DNA oligomers in phosphate buffer solution, at various degrees of denaturation as a function of increasing temperature. Two phonon-like modes associated with the hydrogen bonds of the double strand of DNA are identified. To confirm the assignments given to the observed bands, the OKE spectra of two different oligomers<|im_end|> <|im_start|>assistant Scientists have shown the weird world of quantum mechanics operating in the molecule of life, DNA. The research, which was carried out by academics from the University of Glasgow and is published today in Nature Communications, describes how double-stranded DNA splits using delocalized sound waves that are the hallmark of quantum effects. DNA contains the code to life and holds a blueprint for each and every living thing on earth. Dedicated enzymes responsible for making new proteins read the code by splitting the double strand in order to access the information. One of the big outstanding questions of biology has been how these enzymes find the initial hole or "bubble" in the double strand to start reading the code. Dr Mario González Jiménez, researcher, explains, "It is believed that DNA has regions where a specific sequence of bases modifies the stiffness of the double helix favouring the formation of bubbles. This causes a break of the weak bonds between the strands showing the transcription and replication enzymes where to start their task." Dr Gopakumar Ramakrishnan adds: "It had been proposed by theoreticians that such DNA bubbles might behave like sound waves, bouncing around in DNA like echoes in a cathedral. However, the current paradigm in biology is that such sound-like dynamics are irrelevant to biological function, as interaction of a biomolecule with the surrounding water will almost certainly destroy any of these effects." Researchers in the Ultrafast Chemical Physics group at the University of Glasgow carried out experiments with a laser that produces femtosecond laser pulses about a trillion times shorter than a camera flash. This allowed them to succeed in the detection of sound-like bubbles in DNA. They could show that these bubbles whiz around like bullets in a shooting gallery even in an environment very similar to that which can be found in a living cell. PhD student Dr Thomas Harwood, recently graduated from the University of Strathclyde, points out: "The sound waves in DNA are not your ordinary sounds waves. They have a frequency of a few terahertz or a billion times higher than a human or a dog can hear!" Prof Klaas Wynne, leader of the research team and Chair in Chemical Physics at the University of Glasgow, explains: "The terahertz sound-like bubbles we have seen alter our fundamental understanding of biochemical reactions. There were earlier suggestions for a role of delocalized quantum phenomena in light harvesting, magneto reception, and olfaction. The new results now imply a much more general role for sound-like delocalized phenomena in biomolecular processes." <|im_end|>

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1,830

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract With the potential development of new disease-modifying Alzheimer’s disease (AD) therapies, simple, widely available screening tests are needed to identify which individuals, who are experiencing symptoms of cognitive or behavioral decline, should be further evaluated for initiation of treatment. A blood-based test for AD would be a less invasive and less expensive screening tool than the currently approved cerebrospinal fluid or amyloid β positron emission tomography (PET) diagnostic tests. We examined whether plasma tau phosphorylated at residue 181 (pTau181) could differentiate between clinically diagnosed or autopsy-confirmed AD and frontotemporal lobar degeneration. Plasma pTau181 concentrations were increased by 3.5-fold in AD compared to controls and differentiated AD from both clinically diagnosed (receiver operating characteristic area under the curve of 0.894) and autopsy-confirmed frontotemporal lobar degeneration (area under the curve of 0.878). Plasma pTau181 identified individuals who were amyloid β-PET-positive regardless of clinical diagnosis and correlated with cortical tau protein deposition measured by 18 F-flortaucipir PET. Plasma pTau181 may be useful to screen for tau pathology associated with AD. Main With the potential development of new disease-modifying treatments for AD 1 , screening tests that can be widely and inexpensively deployed to identify those who might benefit from treatment are urgently needed. Particularly important will be differentiating AD from other related dementias, such as frontotemporal lobar degeneration (FTLD), which can sometimes be misdiagnosed as AD in younger individuals or patients with mild or questionable symptoms, called mild cognitive impairment (MCI). Currently, two technologies are approved for differential diagnosis of AD from other dementias, expert interpretation (visual read) of measurements of brain β-amyloid (Aβ) deposition with Aβ positron emission tomography (Aβ-PET) 2 or Aβ and tau measurements in cerebrospinal fluid (CSF) 3 , 4 . These biomarkers are not widely used because of the invasiveness of lumbar punctures required for obtaining CSF and the high costs of PET imaging, often not reimbursed by third-party payers 2 . Moreover, PET scans are associated with exposure to radiation and access to PET imaging is often restricted to specialized centers. A blood-based test for AD would be a less invasive and less expensive screening tool to identify individuals who are experiencing symptoms of cognitive or behavioral decline and might benefit from more comprehensive CSF or PET testing for diagnostic purposes or before initiation of disease-modifying AD therapy. Examining the performance of a screening diagnostic test for AD in patients with FTLD is important because FTLD is similarly prevalent to AD in individuals who are less than 65 years old at onset and can be difficult to differentiate from AD because of similar clinical features, such as language and executive function impairments 5 . Moreover, at autopsy, insoluble tau deposition is present in both neuropathologically diagnosed AD (AD path ) and a subset of FTLD syndromes (FTLD-tau), including approximately half of behavioral variant frontotemporal dementia (bvFTD), most nonfluent variant primary progressive aphasia (nfvPPA) and almost all patients with progressive supranuclear palsy (PSP) 6 . Whereas, in AD path , tau pathology is associated with elevated concentrations of CSF tau species, including (total) tau and phosphorylated tau at residue 181 (pTau181) 7 , 8 in FTLD, CSF tau and pTau181 can be either elevated or decreased 9 . Insoluble tau deposition can be visualized in the brains of living individuals with AD using flortaucipir (FTP)-PET, a tracer that binds with high affinity to mixed 3 and 4 microtubule binding domain repeat (3R/4R) tau that is found in AD path neurofibrillary tangles 10 and can distinguish clinical AD (AD clin ) from other diseases 11 . However, FTP has low affinity for the predominantly 3R or 4R tau deposits found in most FTLD, limiting its usefulness 9 . In contrast, levels of neurofilament light chain (NfL) a marker of axonal damage measurable in CSF, plasma and serum 12 , 13 , 14 are increased in FTLD and correlate with survival 15 , clinical severity and brain volume 16 , 17 , 18 , 19 . CSF and serum NfL concentrations are also elevated in AD clin , but less so than in FTLD 13 , 17 , 20 , 21 . As in FTLD, serum NfL is predictive of cortical thinning and rate of disease progression in AD clin 22 , 23 . Recent studies have shown that the Aβ42/Aβ40 ratio measured in plasma can differentiate between healthy controls and patients with AD using immunoprecipitation mass spectrometry (IP–MS), but this technology is not accessible to most clinical laboratories 24 , 25 , 26 . New ultrasensitive single molecule array (Simoa) antibody-based approaches measuring Aβ in blood are easier to implement but do not yet have sufficient diagnostic precision to be useful clinically 26 . Elevated levels of total tau measured with Simoa technology in plasma are associated with cognitive decline 27 , although there is substantial overlap between concentrations measured in normal aging and AD limiting the diagnostic usefulness of such assays 28 , 29 , 30 . Recently, a new plasma pTau181 assay was found to differentiate AD clin from healthy controls 31 . We tested the differential diagnostic ability of plasma pTau181 measurements to differentiate MCI and AD clin relative to a variety of clinical FTLD phenotypes. A subset of diagnoses was verified using neuropathological examination at autopsy or by the presence of autosomal dominant mutations that lead to specific types of FTLD pathology, including mutations in the tau gene ( MAPT ) that lead to FTLD pure 4R tau or AD-like mixed 3R/4R tau deposition in the brain. We also compared plasma pTau181 to current clinical standards for dementia differential diagnosis, Aβ-PET and CSF pTau181, as well as to the research biomarkers plasma NfL, plasma Aβ42 and Aβ40, FTP-PET and brain atrophy measured with magnetic resonance imaging (MRI), to better evaluate the biological basis for elevated plasma pTau181. Results Participant characteristics Baseline demographics, clinical assessments, imaging measures and fluid biomarker levels are shown in Table 1 . The control group (HC) and the MCI group were younger than the PSP and nfvPPA groups. Plasma pTau181", "role": "user" }, { "content": "A blood test that may eventually be done in a doctor's office can swiftly reveal if a patient with memory issues has Alzheimer's disease or mild cognitive impairment and can also distinguish both conditions from frontotemporal dementia. If approved, the blood test could lead to a jump in the number of Alzheimer's patients enrolling in clinical trials and be used to monitor response to those investigational treatments. In a study led by UC San Francisco, researchers measured blood levels of phosphorylated tau 181 (pTau181), a brain protein that aggregates in tangles in patients with Alzheimer's. They found that pTau181 was 3.5-times higher in people with the disease compared to their healthy peers. In contrast, in patients with frontotemporal dementia, a condition that is often misdiagnosed as Alzheimer's, pTau181 was found to be within the same range as the control group. The study publishes in Nature Medicine on March 2, 2020. \"This test could eventually be deployed in a primary care setting for people with memory concerns to identify who should be referred to specialized centers to participate in clinical trials or to be treated with new Alzheimer's therapies, once they are approved,\" said senior author Adam Boxer, MD, Ph.D., of the UCSF Memory and Aging Center. Being able to easily diagnose Alzheimer's disease at early stages may be especially beneficial to patients with mild cognitive impairment, some of whom may have early Alzheimer's disease. Individuals with early Alzheimer's are more likely to respond to many of the new treatments that are being developed.\" Current Alzheimer's Testing Expensive, Invasive Existing methods for diagnosing Alzheimer's include measurement of the deposits of amyloid, another protein implicated in dementia, from a PET scan; or using lumbar puncture to quantify amyloid and tau in cerebrospinal fluid. PET scans are expensive, only available in specialized centers and currently not covered by insurance, and lumbar punctures are invasive, labor intensive and not easy to perform in large populations, the authors noted. There are 132 drugs in clinical trials for Alzheimer's, according to a 2019 study, including 28 that are being tested in 42 phase-3 trials—the final part of a study before approval is sought from the federal Food and Drug Administration. Among those phase-3 drugs is aducanumab, which some experts believe may be the first drug approved to slow the progression of Alzheimer's. In the study, participants underwent testing to measure pTau181 from plasma, the liquid part of blood. They were aged from 58 to 70 and included 56 who had been diagnosed with Alzheimer's, 47 with mild cognitive impairment and 69 of their healthy peers. Additionally, participants included 190 people with different types of frontotemporal dementia, a group of brain disorders caused by degeneration of the frontal and temporal lobes, areas of the brain associated with decision-making, behavioral control, emotion and language. Among adults under 65, frontotemporal dementia is as common as Alzheimer's. Blood Test Measures Up to Established Tool The researchers found that blood measures of pTau181 were 2.4 pg/ml among healthy controls, 3.7 pg/ml among those with mild cognitive impairment and 8.4 pg/ml for those with Alzheimer's. In people with variants of frontotemporal dementia, levels ranged from 1.9 to 2.8 pg/ml. These results gave similar information to the more established diagnostic tools of PET scan measures of amyloid or tau protein, Boxer said. The study follows research by other investigators published last year that found high levels of plasma amyloid were a predictor of Alzheimer's. However, amyloid accumulates in the brain many years before symptoms emerge, if they emerge, said Boxer, who is affiliated with the UCSF Weill Institute for Neurosciences. \"In contrast, the amount of tau that accumulates in the brain is very strongly linked to the onset, the severity and characteristic symptoms of the disease,\" he said. A companion study by Oskar Hansson, MD, Ph.D., of Lund University, Sweden, published in the same issue of Nature Medicine corroborated the results of the UCSF-led study. It concluded that pTau181 was a stronger predictor of developing Alzheimer's in healthy elders than amyloid. The researchers said they hope to see the blood test available in doctor's offices within five years. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract With the potential development of new disease-modifying Alzheimer’s disease (AD) therapies, simple, widely available screening tests are needed to identify which individuals, who are experiencing symptoms of cognitive or behavioral decline, should be further evaluated for initiation of treatment. A blood-based test for AD would be a less invasive and less expensive screening tool than the currently approved cerebrospinal fluid or amyloid β positron emission tomography (PET) diagnostic tests. We examined whether plasma tau phosphorylated at residue 181 (pTau181) could differentiate between clinically diagnosed or autopsy-confirmed AD and frontotemporal lobar degeneration. Plasma pTau181 concentrations were increased by 3.5-fold in AD compared to controls and differentiated AD from both clinically diagnosed (receiver operating characteristic area under the curve of 0.894) and autopsy-confirmed frontotemporal lobar degeneration (area under the curve of 0.878). Plasma pTau181 identified individuals who were amyloid β-PET-positive regardless of clinical diagnosis and correlated with cortical tau protein deposition measured by 18 F-flortaucipir PET. Plasma pTau181 may be useful to screen for tau pathology associated with AD. Main With the potential development of new disease-modifying treatments for AD 1 , screening tests that can be widely and inexpensively deployed to identify those who might benefit from treatment are urgently needed. Particularly important will be differentiating AD from other related dementias, such as frontotemporal lobar degeneration (FTLD), which can sometimes be misdiagnosed as AD in younger individuals or patients with mild or questionable symptoms, called mild cognitive impairment (MCI). Currently, two technologies are approved for differential diagnosis of AD from other dementias, expert interpretation (visual read) of measurements of brain β-amyloid (Aβ) deposition with Aβ positron emission tomography (Aβ-PET) 2 or Aβ and tau measurements in cerebrospinal fluid (CSF) 3 , 4 . These biomarkers are not widely used because of the invasiveness of lumbar punctures required for obtaining CSF and the high costs of PET imaging, often not reimbursed by third-party payers 2 . Moreover, PET scans are associated with exposure to radiation and access to PET imaging is often restricted to specialized centers. A blood-based test for AD would be a less invasive and less expensive screening tool to identify individuals who are experiencing symptoms of cognitive or behavioral decline and might benefit from more comprehensive CSF or PET testing for diagnostic purposes or before initiation of disease-modifying AD therapy. Examining the performance of a screening diagnostic test for AD in patients with FTLD is important because FTLD is similarly prevalent to AD in individuals who are less than 65 years old at onset and can be difficult to differentiate from AD because of similar clinical features, such as language and executive function impairments 5 . Moreover, at autopsy, insoluble tau deposition is present in both neuropathologically diagnosed AD (AD path ) and a subset of FTLD syndromes (FTLD-tau), including approximately half of behavioral variant frontotemporal dementia (bvFTD), most nonfluent variant primary progressive aphasia (nfvPPA) and almost all patients with progressive supranuclear palsy (PSP) 6 . Whereas, in AD path , tau pathology is associated with elevated concentrations of CSF tau species, including (total) tau and phosphorylated tau at residue 181 (pTau181) 7 , 8 in FTLD, CSF tau and pTau181 can be either elevated or decreased 9 . Insoluble tau deposition can be visualized in the brains of living individuals with AD using flortaucipir (FTP)-PET, a tracer that binds with high affinity to mixed 3 and 4 microtubule binding domain repeat (3R/4R) tau that is found in AD path neurofibrillary tangles 10 and can distinguish clinical AD (AD clin ) from other diseases 11 . However, FTP has low affinity for the predominantly 3R or 4R tau deposits found in most FTLD, limiting its usefulness 9 . In contrast, levels of neurofilament light chain (NfL) a marker of axonal damage measurable in CSF, plasma and serum 12 , 13 , 14 are increased in FTLD and correlate with survival 15 , clinical severity and brain volume 16 , 17 , 18 , 19 . CSF and serum NfL concentrations are also elevated in AD clin , but less so than in FTLD 13 , 17 , 20 , 21 . As in FTLD, serum NfL is predictive of cortical thinning and rate of disease progression in AD clin 22 , 23 . Recent studies have shown that the Aβ42/Aβ40 ratio measured in plasma can differentiate between healthy controls and patients with AD using immunoprecipitation mass spectrometry (IP–MS), but this technology is not accessible to most clinical laboratories 24 , 25 , 26 . New ultrasensitive single molecule array (Simoa) antibody-based approaches measuring Aβ in blood are easier to implement but do not yet have sufficient diagnostic precision to be useful clinically 26 . Elevated levels of total tau measured with Simoa technology in plasma are associated with cognitive decline 27 , although there is substantial overlap between concentrations measured in normal aging and AD limiting the diagnostic usefulness of such assays 28 , 29 , 30 . Recently, a new plasma pTau181 assay was found to differentiate AD clin from healthy controls 31 . We tested the differential diagnostic ability of plasma pTau181 measurements to differentiate MCI and AD clin relative to a variety of clinical FTLD phenotypes. A subset of diagnoses was verified using neuropathological examination at autopsy or by the presence of autosomal dominant mutations that lead to specific types of FTLD pathology, including mutations in the tau gene ( MAPT ) that lead to FTLD pure 4R tau or AD-like mixed 3R/4R tau deposition in the brain. We also compared plasma pTau181 to current clinical standards for dementia differential diagnosis, Aβ-PET and CSF pTau181, as well as to the research biomarkers plasma NfL, plasma Aβ42 and Aβ40, FTP-PET and brain atrophy measured with magnetic resonance imaging (MRI), to better evaluate the biological basis for elevated plasma pTau181. Results Participant characteristics Baseline demographics, clinical assessments, imaging measures and fluid biomarker levels are shown in Table 1 . The control group (HC) and the MCI group were younger than the PSP and nfvPPA groups. Plasma pTau181<|im_end|> <|im_start|>assistant A blood test that may eventually be done in a doctor's office can swiftly reveal if a patient with memory issues has Alzheimer's disease or mild cognitive impairment and can also distinguish both conditions from frontotemporal dementia. If approved, the blood test could lead to a jump in the number of Alzheimer's patients enrolling in clinical trials and be used to monitor response to those investigational treatments. In a study led by UC San Francisco, researchers measured blood levels of phosphorylated tau 181 (pTau181), a brain protein that aggregates in tangles in patients with Alzheimer's. They found that pTau181 was 3.5-times higher in people with the disease compared to their healthy peers. In contrast, in patients with frontotemporal dementia, a condition that is often misdiagnosed as Alzheimer's, pTau181 was found to be within the same range as the control group. The study publishes in Nature Medicine on March 2, 2020. "This test could eventually be deployed in a primary care setting for people with memory concerns to identify who should be referred to specialized centers to participate in clinical trials or to be treated with new Alzheimer's therapies, once they are approved," said senior author Adam Boxer, MD, Ph.D., of the UCSF Memory and Aging Center. Being able to easily diagnose Alzheimer's disease at early stages may be especially beneficial to patients with mild cognitive impairment, some of whom may have early Alzheimer's disease. Individuals with early Alzheimer's are more likely to respond to many of the new treatments that are being developed." Current Alzheimer's Testing Expensive, Invasive Existing methods for diagnosing Alzheimer's include measurement of the deposits of amyloid, another protein implicated in dementia, from a PET scan; or using lumbar puncture to quantify amyloid and tau in cerebrospinal fluid. PET scans are expensive, only available in specialized centers and currently not covered by insurance, and lumbar punctures are invasive, labor intensive and not easy to perform in large populations, the authors noted. There are 132 drugs in clinical trials for Alzheimer's, according to a 2019 study, including 28 that are being tested in 42 phase-3 trials—the final part of a study before approval is sought from the federal Food and Drug Administration. Among those phase-3 drugs is aducanumab, which some experts believe may be the first drug approved to slow the progression of Alzheimer's. In the study, participants underwent testing to measure pTau181 from plasma, the liquid part of blood. They were aged from 58 to 70 and included 56 who had been diagnosed with Alzheimer's, 47 with mild cognitive impairment and 69 of their healthy peers. Additionally, participants included 190 people with different types of frontotemporal dementia, a group of brain disorders caused by degeneration of the frontal and temporal lobes, areas of the brain associated with decision-making, behavioral control, emotion and language. Among adults under 65, frontotemporal dementia is as common as Alzheimer's. Blood Test Measures Up to Established Tool The researchers found that blood measures of pTau181 were 2.4 pg/ml among healthy controls, 3.7 pg/ml among those with mild cognitive impairment and 8.4 pg/ml for those with Alzheimer's. In people with variants of frontotemporal dementia, levels ranged from 1.9 to 2.8 pg/ml. These results gave similar information to the more established diagnostic tools of PET scan measures of amyloid or tau protein, Boxer said. The study follows research by other investigators published last year that found high levels of plasma amyloid were a predictor of Alzheimer's. However, amyloid accumulates in the brain many years before symptoms emerge, if they emerge, said Boxer, who is affiliated with the UCSF Weill Institute for Neurosciences. "In contrast, the amount of tau that accumulates in the brain is very strongly linked to the onset, the severity and characteristic symptoms of the disease," he said. A companion study by Oskar Hansson, MD, Ph.D., of Lund University, Sweden, published in the same issue of Nature Medicine corroborated the results of the UCSF-led study. It concluded that pTau181 was a stronger predictor of developing Alzheimer's in healthy elders than amyloid. The researchers said they hope to see the blood test available in doctor's offices within five years. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Reward drives motivated behaviours and is essential for survival, and therefore there is strong evolutionary pressure to retain contextual information about rewarding stimuli. This drive may be abnormally strong, such as in addiction, or weak, such as in depression, in which anhedonia (loss of pleasure in response to rewarding stimuli) is a prominent symptom. Hippocampal input to the shell of the nucleus accumbens (NAc) is important for driving NAc activity 1 , 2 and activity-dependent modulation of the strength of this input may contribute to the proper regulation of goal-directed behaviours. However, there have been few robust descriptions of the mechanisms that underlie the induction or expression of long-term potentiation (LTP) at these synapses, and there is, to our knowledge, no evidence about whether such plasticity contributes to reward-related behaviour. Here we show that high-frequency activity induces LTP at hippocampus–NAc synapses in mice via canonical, but dopamine-independent, mechanisms. The induction of LTP at this synapse in vivo drives conditioned place preference, and activity at this synapse is required for conditioned place preference in response to a natural reward. Conversely, chronic stress, which induces anhedonia, decreases the strength of this synapse and impairs LTP, whereas antidepressant treatment is accompanied by a reversal of these stress-induced changes. We conclude that hippocampus–NAc synapses show activity-dependent plasticity and suggest that their strength may be critical for contextual reward behaviour. Main Hippocampal activity is altered by changes in the contextual features of rewarding stimuli 3 , 4 , and a population of reward-associated cells has been identified in this region 5 . Activity-dependent enhancement of spike firing has been observed at hippocampus–NAc synapses 5 , 6 , and cocaine strengthens the connectivity between these two nuclei 7 , leading us to hypothesize that plasticity of these excitatory synapses is associated with reward. We first examined whether hippocampus–NAc inputs display activity-dependent synaptic potentiation. Using whole-cell voltage-clamp, we recorded excitatory postsynaptic currents (EPSCs) from medium spiny neurons (MSNs) in the ventromedial NAc shell in brain slices from mice expressing tdTomato in dopamine type 1 receptor (D1R)-expressing MSNs to differentiate between D1R- and presumptive D2R-expressing cells (D1R-MSNs and D2R-MSNs, respectively) 8 . Glutamatergic EPSCs, mediated by both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N -methyl- d -aspartate (NMDA)-type receptors, were evoked by electrical stimulation of axons of hippocampal cells that projected to the NAc via the fornix. In response to high-frequency stimulation (HFS) (Fig. 1a–c ), robust potentiation was elicited similarly in both D1R- and D2R-MSNs. LTP was accompanied by a change in the coefficient of variation and a reduction in transmission failures (Extended Data Fig. 1 ), but no change in paired-pulse ratio (Fig. 1a ), suggesting that postsynaptic expression mechanisms underlie this potentiation. Fig. 1: Mechanisms that underlie activity-dependent LTP at hippocampus–NAc synapses. a , LTP of hippocampus–NAc eEPSCs is similar in D1R- and D2R-MSNs and does not alter paired pulse ratios. b , Summary data from the last 5 min of recording. # D1: t = 2.624, P = 0.0394, n = 7 cells from 7 mice; D2: t = 3.586, P = 0.0059, n = 10 cells from 10 mice. c , Representative traces of EPSCs before and after HFS. Grey shading represents individual traces. Black represents the average. d , pHFS induces LTP of light-evoked EPSCs. e , Summary data from the last 5 min of recording. # t = 3.337, P = 0.0157, n = 7 cells from 7 mice. f , Representative traces of pEPSCs before and after HFS. Grey shading represents individual traces. Blue represents the average. g , pHFS potentiates both electrically and optogenetically evoked EPSCs. h , Summary data from the last 5 min of recording. # Two-tailed paired Wilcoxon test to compare baseline to response at 30 min: W = 21, P = 0.0313, n = 3 cells from 3 mice. i , Representative traces from electrically and optogenetically evoked EPSCs before and after HFS. j , Pre-incubation with AP5 or KN62, or chelation of intracellular Ca 2+ with BAPTA, prevents LTP induction by HFS. k , Summary data from the last 5 min of recording. AP5/control AP5 : * U = 1, P = 0.0317, n = 3, 5 mice; # control AP5 : t = 2.865, P = 0.0457, n = 5 cells; AP5: t = 1.729, P = 0.1589, n = 5 cells; BAPTA/control BAPTA : * U = 5, P = 0.0221, n = 7, 6 mice; # control BAPTA : t = 3.149, P = 0.0199, n = 7 cells; BAPTA: t = 1.172, P = 0.2942, n = 6 cells; KN62/control KN62 : ** U = 6, P = 0.0089, n = 7, 8 mice; # control KN62 : t = 2.526, P = 0.0449, n = 7 cells; KN62: t = 0.4919, P = 0.6378, n = 8 cells. l , Representative traces of EPSCs from control cells and cells treated with AP5, BAPTA or KN62. m , Pre-incubation with SCH23390 or Rp-cAMPs does not affect LTP induction in D1R-MSNs. n , Summary data from the last 5 min of recording. SCH/control SCH : U = 22, P = 0.6070, n = 6, 9 mice; # control SCH : t = 5.658, P = 0.0013, n = 7 cells; SCH: t = 2.914, P = 0.0195, n = 9 cells; Rp/control Rp : U = 13, P = 0.7922, n = 5, 6 mice; # control Rp : t = 2.611, P = 0.476, n = 6 cells; Rp: t = 2.337, P = 0.0476, n = 9 cells. o , Representative traces of EPSCs from control, SCH23390, and Rp-cAMPs-treated D1R-MSNs. *Differences between treatment and control by two-tailed Mann–Whitney U -test. # Significant increase in EPSC amplitude above baseline revealed by two-tailed paired t -test. LTP kinetics are plotted in 1-min bins. Centre values represent mean, error bars represent s.e.m. For box plots, the middle line is plotted at the median. The box shows the 25th–75th percentiles. Whiskers represent minimum and maximum. Scale bars, 10 pA/10 ms. Full size image To", "role": "user" }, { "content": "In new pre-clinical research, scientists at the University of Maryland School of Medicine (UMSOM), led by Scott Thompson, Ph.D., Professor of Physiology, have identified changes in brain activity linked to the pleasure and reward system. The research, published in the journal, Nature, provides news insights into how the brain processes rewards, and advances our understanding of addiction and depression. The research, which was conducted by Tara LeGates, Ph.D., a Research Associate in the Department of Physiology, discovered that the strength of signals between two brain regions, the hippocampus and the nucleus accumbens, is critical for processing information related to a rewarding stimulus, such as its location. \"These two parts of the brain are known to be important in processing rewarding experiences,\" said Dr. Thompson.\" The communication between these regions is stronger in addiction, although the mechanisms underlying this were unknown. We also suspected that opposite changes in the strength of this communication would occur in depression. A weakening of their connections could explain the defect in reward processing that causes the symptom of anhedonia in depressed patients.\" Anhedonia is the inability to enjoy normally pleasurable experiences, such as food, being with friends or family, and sex. This research uncovered a key circuit in the brain of mice that is important for goal-directed behaviors and shows that the strength of the signals in this circuit are changeable, a process referred to as plasticity. Reward circuits and the molecular components that underlie their plasticity represent new targets for development of treatments for disorders like addiction and depression. Using Light-Sensitive Proteins To activate or inhibit this connection, researchers used special light-sensitive proteins introduced into specific neurons in the brains of the mice. In mice with the light-sensitive protein that stimulated the neurons, just four seconds of light exposure not only activated this hippocampus-to-nucleus accumbens pathway while the light was on but persistently reinforced the strength of the signals along this pathway, creating an artificial reward memory. A day later, the mice returned to the place where the artificial memory was created, even though they never experienced an actual reward there. Researchers then used light to silence the same pathway in mice with the light-sensitive protein that inhibited the neurons and found that this pathway is required for associating a reward with its location. The mice no longer showed a preference for the place where they had interacted with another mouse. The researchers also examined this circuit in depressed mice. This pathway could not be enhanced using the stimulating light-sensitive protein. After receiving anti-depressant medication, the researchers could enhance this pathway using the light-sensitive protein and create artificial reward memories in the mice. This work was funded by the National Institutes of Health, the Whitehall Foundation, and the Brain & Behavior Research Foundation (NARSAD Young Investigator Grant). \"These exciting results bring us closer to understanding what goes wrong in the brains of clinically depressed patients,\" said UMSOM Dean E. Albert Reece, MD, Ph.D., MBA, who is also the Executive Vice President for Medical Affairs, University of Maryland, and the John Z. and Akiko K. Bowers Distinguished Professor. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Reward drives motivated behaviours and is essential for survival, and therefore there is strong evolutionary pressure to retain contextual information about rewarding stimuli. This drive may be abnormally strong, such as in addiction, or weak, such as in depression, in which anhedonia (loss of pleasure in response to rewarding stimuli) is a prominent symptom. Hippocampal input to the shell of the nucleus accumbens (NAc) is important for driving NAc activity 1 , 2 and activity-dependent modulation of the strength of this input may contribute to the proper regulation of goal-directed behaviours. However, there have been few robust descriptions of the mechanisms that underlie the induction or expression of long-term potentiation (LTP) at these synapses, and there is, to our knowledge, no evidence about whether such plasticity contributes to reward-related behaviour. Here we show that high-frequency activity induces LTP at hippocampus–NAc synapses in mice via canonical, but dopamine-independent, mechanisms. The induction of LTP at this synapse in vivo drives conditioned place preference, and activity at this synapse is required for conditioned place preference in response to a natural reward. Conversely, chronic stress, which induces anhedonia, decreases the strength of this synapse and impairs LTP, whereas antidepressant treatment is accompanied by a reversal of these stress-induced changes. We conclude that hippocampus–NAc synapses show activity-dependent plasticity and suggest that their strength may be critical for contextual reward behaviour. Main Hippocampal activity is altered by changes in the contextual features of rewarding stimuli 3 , 4 , and a population of reward-associated cells has been identified in this region 5 . Activity-dependent enhancement of spike firing has been observed at hippocampus–NAc synapses 5 , 6 , and cocaine strengthens the connectivity between these two nuclei 7 , leading us to hypothesize that plasticity of these excitatory synapses is associated with reward. We first examined whether hippocampus–NAc inputs display activity-dependent synaptic potentiation. Using whole-cell voltage-clamp, we recorded excitatory postsynaptic currents (EPSCs) from medium spiny neurons (MSNs) in the ventromedial NAc shell in brain slices from mice expressing tdTomato in dopamine type 1 receptor (D1R)-expressing MSNs to differentiate between D1R- and presumptive D2R-expressing cells (D1R-MSNs and D2R-MSNs, respectively) 8 . Glutamatergic EPSCs, mediated by both α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N -methyl- d -aspartate (NMDA)-type receptors, were evoked by electrical stimulation of axons of hippocampal cells that projected to the NAc via the fornix. In response to high-frequency stimulation (HFS) (Fig. 1a–c ), robust potentiation was elicited similarly in both D1R- and D2R-MSNs. LTP was accompanied by a change in the coefficient of variation and a reduction in transmission failures (Extended Data Fig. 1 ), but no change in paired-pulse ratio (Fig. 1a ), suggesting that postsynaptic expression mechanisms underlie this potentiation. Fig. 1: Mechanisms that underlie activity-dependent LTP at hippocampus–NAc synapses. a , LTP of hippocampus–NAc eEPSCs is similar in D1R- and D2R-MSNs and does not alter paired pulse ratios. b , Summary data from the last 5 min of recording. # D1: t = 2.624, P = 0.0394, n = 7 cells from 7 mice; D2: t = 3.586, P = 0.0059, n = 10 cells from 10 mice. c , Representative traces of EPSCs before and after HFS. Grey shading represents individual traces. Black represents the average. d , pHFS induces LTP of light-evoked EPSCs. e , Summary data from the last 5 min of recording. # t = 3.337, P = 0.0157, n = 7 cells from 7 mice. f , Representative traces of pEPSCs before and after HFS. Grey shading represents individual traces. Blue represents the average. g , pHFS potentiates both electrically and optogenetically evoked EPSCs. h , Summary data from the last 5 min of recording. # Two-tailed paired Wilcoxon test to compare baseline to response at 30 min: W = 21, P = 0.0313, n = 3 cells from 3 mice. i , Representative traces from electrically and optogenetically evoked EPSCs before and after HFS. j , Pre-incubation with AP5 or KN62, or chelation of intracellular Ca 2+ with BAPTA, prevents LTP induction by HFS. k , Summary data from the last 5 min of recording. AP5/control AP5 : * U = 1, P = 0.0317, n = 3, 5 mice; # control AP5 : t = 2.865, P = 0.0457, n = 5 cells; AP5: t = 1.729, P = 0.1589, n = 5 cells; BAPTA/control BAPTA : * U = 5, P = 0.0221, n = 7, 6 mice; # control BAPTA : t = 3.149, P = 0.0199, n = 7 cells; BAPTA: t = 1.172, P = 0.2942, n = 6 cells; KN62/control KN62 : ** U = 6, P = 0.0089, n = 7, 8 mice; # control KN62 : t = 2.526, P = 0.0449, n = 7 cells; KN62: t = 0.4919, P = 0.6378, n = 8 cells. l , Representative traces of EPSCs from control cells and cells treated with AP5, BAPTA or KN62. m , Pre-incubation with SCH23390 or Rp-cAMPs does not affect LTP induction in D1R-MSNs. n , Summary data from the last 5 min of recording. SCH/control SCH : U = 22, P = 0.6070, n = 6, 9 mice; # control SCH : t = 5.658, P = 0.0013, n = 7 cells; SCH: t = 2.914, P = 0.0195, n = 9 cells; Rp/control Rp : U = 13, P = 0.7922, n = 5, 6 mice; # control Rp : t = 2.611, P = 0.476, n = 6 cells; Rp: t = 2.337, P = 0.0476, n = 9 cells. o , Representative traces of EPSCs from control, SCH23390, and Rp-cAMPs-treated D1R-MSNs. *Differences between treatment and control by two-tailed Mann–Whitney U -test. # Significant increase in EPSC amplitude above baseline revealed by two-tailed paired t -test. LTP kinetics are plotted in 1-min bins. Centre values represent mean, error bars represent s.e.m. For box plots, the middle line is plotted at the median. The box shows the 25th–75th percentiles. Whiskers represent minimum and maximum. Scale bars, 10 pA/10 ms. Full size image To<|im_end|> <|im_start|>assistant In new pre-clinical research, scientists at the University of Maryland School of Medicine (UMSOM), led by Scott Thompson, Ph.D., Professor of Physiology, have identified changes in brain activity linked to the pleasure and reward system. The research, published in the journal, Nature, provides news insights into how the brain processes rewards, and advances our understanding of addiction and depression. The research, which was conducted by Tara LeGates, Ph.D., a Research Associate in the Department of Physiology, discovered that the strength of signals between two brain regions, the hippocampus and the nucleus accumbens, is critical for processing information related to a rewarding stimulus, such as its location. "These two parts of the brain are known to be important in processing rewarding experiences," said Dr. Thompson." The communication between these regions is stronger in addiction, although the mechanisms underlying this were unknown. We also suspected that opposite changes in the strength of this communication would occur in depression. A weakening of their connections could explain the defect in reward processing that causes the symptom of anhedonia in depressed patients." Anhedonia is the inability to enjoy normally pleasurable experiences, such as food, being with friends or family, and sex. This research uncovered a key circuit in the brain of mice that is important for goal-directed behaviors and shows that the strength of the signals in this circuit are changeable, a process referred to as plasticity. Reward circuits and the molecular components that underlie their plasticity represent new targets for development of treatments for disorders like addiction and depression. Using Light-Sensitive Proteins To activate or inhibit this connection, researchers used special light-sensitive proteins introduced into specific neurons in the brains of the mice. In mice with the light-sensitive protein that stimulated the neurons, just four seconds of light exposure not only activated this hippocampus-to-nucleus accumbens pathway while the light was on but persistently reinforced the strength of the signals along this pathway, creating an artificial reward memory. A day later, the mice returned to the place where the artificial memory was created, even though they never experienced an actual reward there. Researchers then used light to silence the same pathway in mice with the light-sensitive protein that inhibited the neurons and found that this pathway is required for associating a reward with its location. The mice no longer showed a preference for the place where they had interacted with another mouse. The researchers also examined this circuit in depressed mice. This pathway could not be enhanced using the stimulating light-sensitive protein. After receiving anti-depressant medication, the researchers could enhance this pathway using the light-sensitive protein and create artificial reward memories in the mice. This work was funded by the National Institutes of Health, the Whitehall Foundation, and the Brain & Behavior Research Foundation (NARSAD Young Investigator Grant). "These exciting results bring us closer to understanding what goes wrong in the brains of clinically depressed patients," said UMSOM Dean E. Albert Reece, MD, Ph.D., MBA, who is also the Executive Vice President for Medical Affairs, University of Maryland, and the John Z. and Akiko K. Bowers Distinguished Professor. <|im_end|>

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2,335

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Objectives To understand how device-measured sedentary behaviour and physical activity are related to all-cause mortality in older men, an age group with high levels of inactivity and sedentary behaviour. Methods Prospective population-based cohort study of men recruited from 24 UK General Practices in 1978–1980. In 2010–2012, 3137 surviving men were invited to a follow-up, 1655 (aged 71–92 years) agreed. Nurses measured height and weight, men completed health and demographic questionnaires and wore an ActiGraph GT3x accelerometer. All-cause mortality was collected through National Health Service central registers up to 1 June 2016. Results After median 5.0 years’ follow-up, 194 deaths occurred in 1181 men without pre-existing cardiovascular disease. For each additional 30 min in sedentary behaviour, or light physical activity (LIPA), or 10 min in moderate to vigorous physical activity (MVPA), HRs for mortality were 1.17 (95% CI 1.10 to 1.25), 0.83 (95% CI 0.77 to 0.90) and 0.90 (95% CI 0.84 to 0.96), respectively. Adjustments for confounders did not meaningfully change estimates. Only LIPA remained significant on mutual adjustment for all intensities. The HR for accumulating 150 min MVPA/week in sporadic minutes (achieved by 66% of men) was 0.59 (95% CI 0.43 to 0.81) and 0.58 (95% CI 0.33 to 1.00) for accumulating 150 min MVPA/week in bouts lasting ≥10 min (achieved by 16% of men). Sedentary breaks were not associated with mortality. Conclusions In older men, all activities (of light intensity upwards) were beneficial and accumulation of activity in bouts ≥10 min did not appear important beyond total volume of activity. Findings can inform physical activity guidelines for older adults. physical activity sedentary behaviour accelerometer mortality bouts. This is an open access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: googletag.cmd.push(function() { googletag.display(\"dfp-ad-mpu\"); }); Statistics from Altmetric.com See more details Picked up by 129 news outlets Blogged by 2 Referenced in 1 policy sources Tweeted by 354 On 20 Facebook pages Reddited by 1 257 readers on Mendeley Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. ?xml version=\"1.0\" encoding=\"UTF-8\" ? Request permissions physical activity sedentary behaviour accelerometer mortality bouts. Nearly all epidemiological evidence used to estimate the shape of the dose–response curve between physical activity (PA) and mortality is based on self-reported PA. 1 Moderately active compared with inactive adults have 20%–30% reductions in all-cause mortality, with greater reductions in older (>65 years) than middle-aged adults. 2 PA is a key determinant of longevity globally. 3 Current activity guidelines suggest accumulating ≥150 min moderate to vigorous PA (MVPA) per week in bouts lasting ≥10 min. 4 5 The 10 min bout requirement was based on trial data for cardiometabolic risk factors only, not clinical end points. 5 In order to test whether the accumulation of MVPA in ≥10 min bouts affects risk of mortality, prospective cohort studies with device-measured physical activity (which can provide minute by minute data for calculation of bouts) and mortality data are required, but few studies have such data. Such data can also inform whether accruing sedentary time in prolonged bouts is associated with adverse effects on mortality, as this has been identified as an important research gap. 6 Many studies report that higher levels of self-reported sedentary time are associated with mortality, 7–10 although self-reported sedentary behaviours may suffer from measurement error or recall bias. 11–15 Experimental studies suggest benefits of breaking up sedentary time for metabolic and haemostatic markers. 16 17 Hence, activity guidelines now suggest avoiding ‘long’ sedentary periods, but without quantifying how ‘long’ is detrimental. 4 Recently, prospective cohort studies using body-worn devices to measure PA report that more time spent in MVPA is associated with lower mortality risks and sedentary behaviour with higher risks. 18–28 However, few address the question of pattern of accumulation of activity rather than total volume. Most of the studies use the US National Health and Nutrition Examination Survey (NHANES) data set, 18–24 and not all findings are consistent. 18 23 There is little information from other populations and older age groups, >80 years. We address important gaps in knowledge by focusing on older men: older adults are increasingly important given global population ageing. We use a community-dwelling cohort of older British men to investigate how device-measured PA is associated with all-cause mortality (including light PA (LIPA) and sedentary behaviour which are the predominant activities in this age group 29 ). Importantly, we fill a research gap by investigating dose–response associations, 6 testing for linear and non-linear associations in order to understand whether the reductions in mortality risk for higher levels of physical activity are linear, or if there is a threshold level at which the benefits per unit of activity decrease (and conversely for sedentary behaviour). We also investigate whether, as suggested elsewhere, 30 the association of sedentary behaviour with mortality depends on PA level. Finally, a particularly novel and policy-relevant aspect of this paper is that we investigate patterns of accumulation of activity (including bout length and sedentary breaks) in relation to mortality. Answers to these questions will help inform future guidelines for older adults. Methods Sample The British Regional Heart Study is a prospective cohort study of 7735 men recruited from a single general practice in each of 24 British towns in 1978–1980 (ages 40–59 years). In 2010–2012, survivors (n=3137) were invited to a physical examination. 31 Measurements at 2010–2012 examination Objective physical activity assessment Men wore a GT3x accelerometer (ActiGraph, Pensacola, FL, USA) over the right hip for 7 days, during waking hours, removing it for bathing and swimming (2% reported swimming). Data were processed using standard methods described previously. 29 Non-wear time was excluded using the R package", "role": "user" }, { "content": "Clocking up just a few minutes at a time of any level of physical activity, including of light intensity, is linked to a lower risk of death in older men, suggests research published online in the British Journal of Sports Medicine. Providing the recommended 150 minute weekly tally of moderate to physical activity is reached, total volume, rather than activity in 10 minute bouts, as current guidelines suggest, might be key, the findings indicate. This lower level of intensity is also likely to be a better fit for older men, most of whose daily physical activity is of light intensity, say the researchers. Current exercise guidelines recommend accumulating at least 150 minutes a week of moderate to vigorous physical activity in bouts lasting 10 or more minutes. But such a pattern is not always easy for older adults to achieve, say the researchers. To find out if other patterns of activity might still contribute to lowering the risk of death, the researchers drew on data from the British Regional Heart Study. This involved 7735 participants from 24 British towns, who were aged between 40 and 59 when the study stated in 1978-80. In 2010-12, the 3137 survivors were invited for a check-up, which included a physical examination, and questions about their lifestyle, sleeping patterns, and whether they had ever been diagnosed with heart disease. They were also asked to wear an accelerometer—a portable gadget that continuously tracks the volume and intensity of physical activity—during waking hours for 7 days. Their health was then tracked until death or June 2016, whichever came first. In all, 1566 (50%) men agreed to wear the device, but after excluding those with pre-existing heart disease and those who hadn't worn their accelerometer enough during the 7 days, the final analysis was based on 1181 men, whose average age was 78. During the monitoring period, which averaged around 5 years, 194 of the men died. The accelerometer findings indicated that total volume of physical activity, from light intensity upwards, was associated with a lower risk of death from any cause. Each additional 30 minutes a day of light intensity activity, such as gentle gardening or taking the dog for a walk, for example, was associated with a 17 percent reduction in the risk of death. This association persisted even after taking account of potentially influential lifestyle factors, such as sedentary time. Whilst the equivalent reduction in the risk of death was around 33 percent for each additional 30 minutes of moderate to vigorous intensity physical activity a day, the benefits of light intensity activity were large enough to mean that this too might prolong life. And there was no evidence to suggest that clocking up moderate to vigorous activity in bouts of 10 minutes or more was better than accumulating it in shorter bouts. Sporadic bouts of activity were associated with a 41 percent lower risk of death; bouts lasting 10 or more minutes were associated with a 42 percent lower risk. Sporadic bouts seemed easier to achieve as two thirds (66%) of the men achieved their weekly total of moderate to vigorous physical activity in this way while only 16% managed to do so in bouts of 10 or more minutes. Finally, there was no evidence to suggest that breaking up sitting time was associated with a lower risk of death. This is an observational study so no firm conclusions can be drawn about cause and effect. And those who wore the accelerometer tended to be younger and have healthier lifestyles than those who didn't, so this might have skewed the results, say the researchers. Nor is it clear if the findings would be equally applicable to younger age groups or older women. Nevertheless, the results could be used to refine current physical activity guidelines and make them more achievable for older adults, suggest the researchers. Future guidance might emphasise that all physical activity, however modest, is worthwhile for extending the lifespan—something that is particularly important to recognise, given how physical activity levels tail off rapidly as people age, they point out. \"[The ] results suggest that all activities, however modest, are beneficial. The finding that [low intensity physical activity] is associated with lower risk of mortality is especially important among older men, as most of their daily physical activity is of light intensity,\" write the researchers. \"Furthermore, the pattern of accumulation of physical activity did not appear to alter the associations with mortality, suggesting that it would be beneficial to encourage older men to be active irrespective of bouts,\" they add. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Objectives To understand how device-measured sedentary behaviour and physical activity are related to all-cause mortality in older men, an age group with high levels of inactivity and sedentary behaviour. Methods Prospective population-based cohort study of men recruited from 24 UK General Practices in 1978–1980. In 2010–2012, 3137 surviving men were invited to a follow-up, 1655 (aged 71–92 years) agreed. Nurses measured height and weight, men completed health and demographic questionnaires and wore an ActiGraph GT3x accelerometer. All-cause mortality was collected through National Health Service central registers up to 1 June 2016. Results After median 5.0 years’ follow-up, 194 deaths occurred in 1181 men without pre-existing cardiovascular disease. For each additional 30 min in sedentary behaviour, or light physical activity (LIPA), or 10 min in moderate to vigorous physical activity (MVPA), HRs for mortality were 1.17 (95% CI 1.10 to 1.25), 0.83 (95% CI 0.77 to 0.90) and 0.90 (95% CI 0.84 to 0.96), respectively. Adjustments for confounders did not meaningfully change estimates. Only LIPA remained significant on mutual adjustment for all intensities. The HR for accumulating 150 min MVPA/week in sporadic minutes (achieved by 66% of men) was 0.59 (95% CI 0.43 to 0.81) and 0.58 (95% CI 0.33 to 1.00) for accumulating 150 min MVPA/week in bouts lasting ≥10 min (achieved by 16% of men). Sedentary breaks were not associated with mortality. Conclusions In older men, all activities (of light intensity upwards) were beneficial and accumulation of activity in bouts ≥10 min did not appear important beyond total volume of activity. Findings can inform physical activity guidelines for older adults. physical activity sedentary behaviour accelerometer mortality bouts. This is an open access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: googletag.cmd.push(function() { googletag.display("dfp-ad-mpu"); }); Statistics from Altmetric.com See more details Picked up by 129 news outlets Blogged by 2 Referenced in 1 policy sources Tweeted by 354 On 20 Facebook pages Reddited by 1 257 readers on Mendeley Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. ?xml version="1.0" encoding="UTF-8" ? Request permissions physical activity sedentary behaviour accelerometer mortality bouts. Nearly all epidemiological evidence used to estimate the shape of the dose–response curve between physical activity (PA) and mortality is based on self-reported PA. 1 Moderately active compared with inactive adults have 20%–30% reductions in all-cause mortality, with greater reductions in older (>65 years) than middle-aged adults. 2 PA is a key determinant of longevity globally. 3 Current activity guidelines suggest accumulating ≥150 min moderate to vigorous PA (MVPA) per week in bouts lasting ≥10 min. 4 5 The 10 min bout requirement was based on trial data for cardiometabolic risk factors only, not clinical end points. 5 In order to test whether the accumulation of MVPA in ≥10 min bouts affects risk of mortality, prospective cohort studies with device-measured physical activity (which can provide minute by minute data for calculation of bouts) and mortality data are required, but few studies have such data. Such data can also inform whether accruing sedentary time in prolonged bouts is associated with adverse effects on mortality, as this has been identified as an important research gap. 6 Many studies report that higher levels of self-reported sedentary time are associated with mortality, 7–10 although self-reported sedentary behaviours may suffer from measurement error or recall bias. 11–15 Experimental studies suggest benefits of breaking up sedentary time for metabolic and haemostatic markers. 16 17 Hence, activity guidelines now suggest avoiding ‘long’ sedentary periods, but without quantifying how ‘long’ is detrimental. 4 Recently, prospective cohort studies using body-worn devices to measure PA report that more time spent in MVPA is associated with lower mortality risks and sedentary behaviour with higher risks. 18–28 However, few address the question of pattern of accumulation of activity rather than total volume. Most of the studies use the US National Health and Nutrition Examination Survey (NHANES) data set, 18–24 and not all findings are consistent. 18 23 There is little information from other populations and older age groups, >80 years. We address important gaps in knowledge by focusing on older men: older adults are increasingly important given global population ageing. We use a community-dwelling cohort of older British men to investigate how device-measured PA is associated with all-cause mortality (including light PA (LIPA) and sedentary behaviour which are the predominant activities in this age group 29 ). Importantly, we fill a research gap by investigating dose–response associations, 6 testing for linear and non-linear associations in order to understand whether the reductions in mortality risk for higher levels of physical activity are linear, or if there is a threshold level at which the benefits per unit of activity decrease (and conversely for sedentary behaviour). We also investigate whether, as suggested elsewhere, 30 the association of sedentary behaviour with mortality depends on PA level. Finally, a particularly novel and policy-relevant aspect of this paper is that we investigate patterns of accumulation of activity (including bout length and sedentary breaks) in relation to mortality. Answers to these questions will help inform future guidelines for older adults. Methods Sample The British Regional Heart Study is a prospective cohort study of 7735 men recruited from a single general practice in each of 24 British towns in 1978–1980 (ages 40–59 years). In 2010–2012, survivors (n=3137) were invited to a physical examination. 31 Measurements at 2010–2012 examination Objective physical activity assessment Men wore a GT3x accelerometer (ActiGraph, Pensacola, FL, USA) over the right hip for 7 days, during waking hours, removing it for bathing and swimming (2% reported swimming). Data were processed using standard methods described previously. 29 Non-wear time was excluded using the R package<|im_end|> <|im_start|>assistant Clocking up just a few minutes at a time of any level of physical activity, including of light intensity, is linked to a lower risk of death in older men, suggests research published online in the British Journal of Sports Medicine. Providing the recommended 150 minute weekly tally of moderate to physical activity is reached, total volume, rather than activity in 10 minute bouts, as current guidelines suggest, might be key, the findings indicate. This lower level of intensity is also likely to be a better fit for older men, most of whose daily physical activity is of light intensity, say the researchers. Current exercise guidelines recommend accumulating at least 150 minutes a week of moderate to vigorous physical activity in bouts lasting 10 or more minutes. But such a pattern is not always easy for older adults to achieve, say the researchers. To find out if other patterns of activity might still contribute to lowering the risk of death, the researchers drew on data from the British Regional Heart Study. This involved 7735 participants from 24 British towns, who were aged between 40 and 59 when the study stated in 1978-80. In 2010-12, the 3137 survivors were invited for a check-up, which included a physical examination, and questions about their lifestyle, sleeping patterns, and whether they had ever been diagnosed with heart disease. They were also asked to wear an accelerometer—a portable gadget that continuously tracks the volume and intensity of physical activity—during waking hours for 7 days. Their health was then tracked until death or June 2016, whichever came first. In all, 1566 (50%) men agreed to wear the device, but after excluding those with pre-existing heart disease and those who hadn't worn their accelerometer enough during the 7 days, the final analysis was based on 1181 men, whose average age was 78. During the monitoring period, which averaged around 5 years, 194 of the men died. The accelerometer findings indicated that total volume of physical activity, from light intensity upwards, was associated with a lower risk of death from any cause. Each additional 30 minutes a day of light intensity activity, such as gentle gardening or taking the dog for a walk, for example, was associated with a 17 percent reduction in the risk of death. This association persisted even after taking account of potentially influential lifestyle factors, such as sedentary time. Whilst the equivalent reduction in the risk of death was around 33 percent for each additional 30 minutes of moderate to vigorous intensity physical activity a day, the benefits of light intensity activity were large enough to mean that this too might prolong life. And there was no evidence to suggest that clocking up moderate to vigorous activity in bouts of 10 minutes or more was better than accumulating it in shorter bouts. Sporadic bouts of activity were associated with a 41 percent lower risk of death; bouts lasting 10 or more minutes were associated with a 42 percent lower risk. Sporadic bouts seemed easier to achieve as two thirds (66%) of the men achieved their weekly total of moderate to vigorous physical activity in this way while only 16% managed to do so in bouts of 10 or more minutes. Finally, there was no evidence to suggest that breaking up sitting time was associated with a lower risk of death. This is an observational study so no firm conclusions can be drawn about cause and effect. And those who wore the accelerometer tended to be younger and have healthier lifestyles than those who didn't, so this might have skewed the results, say the researchers. Nor is it clear if the findings would be equally applicable to younger age groups or older women. Nevertheless, the results could be used to refine current physical activity guidelines and make them more achievable for older adults, suggest the researchers. Future guidance might emphasise that all physical activity, however modest, is worthwhile for extending the lifespan—something that is particularly important to recognise, given how physical activity levels tail off rapidly as people age, they point out. "[The ] results suggest that all activities, however modest, are beneficial. The finding that [low intensity physical activity] is associated with lower risk of mortality is especially important among older men, as most of their daily physical activity is of light intensity," write the researchers. "Furthermore, the pattern of accumulation of physical activity did not appear to alter the associations with mortality, suggesting that it would be beneficial to encourage older men to be active irrespective of bouts," they add. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The DNA sensor cyclic GMP–AMP synthase (cGAS) initiates innate immune responses following microbial infection, cellular stress and cancer 1 . Upon activation by double-stranded DNA, cytosolic cGAS produces 2′3′ cGMP–AMP, which triggers the induction of inflammatory cytokines and type I interferons 2 , 3 , 4 , 5 , 6 , 7 . cGAS is also present inside the cell nucleus, which is replete with genomic DNA 8 , where chromatin has been implicated in restricting its enzymatic activity 9 . However, the structural basis for inhibition of cGAS by chromatin remains unknown. Here we present the cryo-electron microscopy structure of human cGAS bound to nucleosomes. cGAS makes extensive contacts with both the acidic patch of the histone H2A–H2B heterodimer and nucleosomal DNA. The structural and complementary biochemical analysis also find cGAS engaged to a second nucleosome in trans . Mechanistically, binding of the nucleosome locks cGAS into a monomeric state, in which steric hindrance suppresses spurious activation by genomic DNA. We find that mutations to the cGAS–acidic patch interface are sufficient to abolish the inhibitory effect of nucleosomes in vitro and to unleash the activity of cGAS on genomic DNA in living cells. Our work uncovers the structural basis of the interaction between cGAS and chromatin and details a mechanism that permits self–non-self discrimination of genomic DNA by cGAS. Main In the cytoplasm of mammalian cells, the enzyme cGAS is crucial for the detection of double-stranded DNA (dsDNA) during infection 2 . On binding dsDNA, cGAS synthesizes the second messenger 2′3′ cyclic GMP–AMP (cGAMP), which in turn stimulates antiviral and pro-inflammatory responses through the adaptor protein stimulator of interferon genes (STING) 2 , 3 , 4 , 5 , 6 , 7 , 10 . In addition, the nucleus contains a pool of cGAS that associates strongly with chromatin (Extended Data Fig. 1a ) 8 , 9 , 11 . The chromatinized state of intact genomic DNA has been reported to limit cGAS activity 12 , 13 , and cGAS has been found to bind more tightly to nucleosomes than to the corresponding naked DNA duplexes 13 . Here we sought a mechanism that explains how cGAS can be juxtaposed to nucleosomal DNA without undergoing activation. A minimal inhibitory histone unit for cGAS We tested whether histones, the building blocks of nucleosomes, may regulate cGAS inside the nucleus. Treatment of cells with aclarubicin robustly evicts core histones from chromatin 14 ; in particular, histones H2A and H2B (Extended Data Fig. 1b ). Notably, disruption of nucleosomes by aclarubicin also led to mobilization of nuclear cGAS (Extended Data Fig. 1b ). Proximity-ligation assays (PLAs) further indicated prominent association of cGAS with histones in situ, which was partially lost upon aclarubicin treatment (Extended Data Fig. 1c, d ). Thus, histones appear to dynamically engage cGAS in the nucleus. Consistent with previous work 13 , functional analysis of the in vitro enzymatic activity of cGAS revealed that mononucleosomes (hereafter nucleosomes) inhibited DNA-induced cGAMP synthesis (Extended Data Fig. 1e ). Likewise, compact chromatin fibres (12-mer nucleosome arrays) suppressed cGAS activity (Extended Data Fig. 1e ). H2A–H2B dimers also had an inhibitory effect, but neither H2A or H2B monomers nor H3 or H4 monomers did (Extended Data Fig. 1f, g ). Thus, H2A–H2B dimers on their own can suppress cGAS, albeit with weaker overall potency than fully assembled nucleosomes (Extended Data Fig. 1h ). Additional features of chromatin are therefore necessary to exert maximal inhibition. Overall structure of the cGAS–NCP complex To determine how cGAS interacts with nucleosomes, we pursued structural studies. A 1.5:1 molar mixture of human cGAS (residues 155–522) with a 147-bp 601 DNA nucleosome core particle (NCP) resulted in heterogenous particle distribution (Extended Data Fig. 2a–d ). To select for and stabilize more homogenous cGAS–NCP complexes, we combined gradient centrifugation with chemical crosslinking (GraFix) 15 . Both wild-type (WT) cGAS and cGAS K394E, a mutant impaired in dsDNA-mediated cGAS dimerization 16 , were used for structure determination. For the cGAS K394E mutant, we obtained a 4.1 Å reconstruction that revealed two NCPs organized in an NCP1–cGAS1–cGAS2–NCP2 sandwich arrangement with an expected molecular weight of around 560 kDa, consistent with the most prominent peak fraction in multi-angle light scattering under non-crosslinked conditions (Fig. 1a, b , Extended Data Fig. 3 , Extended Data Table 1a , Supplementary Videos 1 , 2 ). The two individual nucleosomes are held together by two cGAS protomers. While the first cGAS protomer and its corresponding NCP (designated cGAS1 and NCP1) are well resolved, the second nucleosome–cGAS pair (NCP2 and cGAS2) is less ordered (Extended Data Fig. 3e ). In the dimeric NCP1–cGAS1–cGAS2–NCP2 arrangement, each cGAS protomer interacts with the histone octamer of one NCP through histones H2A and H2B and the nucleosomal DNA (for example, cGAS1 and NCP1), while contacting the second nucleosome (for example, cGAS1 and NCP2) primarily through interactions with the nucleosomal DNA (Fig. 1a, b ). In the WT cGAS structure, we observed a similar overall structural arrangement, with the NCP1–cGAS1–cGAS2–NCP2 complex at 5.1 Å and a NCP1–cGAS1 structure at 4.7 Å resolution following focused 3D classification (Extended Data Figs. 4 , 5 , Extended Data Table 1 ). Given the structural similarity, the higher-resolution cGAS K394E mutant was used for subsequent analysis (Extended Data Figs. 3 , 6 ). Fig. 1: Cryo-electron microscopy structure of cGAS bound to nucleosomes. a , 3D reconstruction of the complex containing two cGAS protomers, cGAS1 (red) and cGAS2 (orange), and two nucleosomal core particles, NCP1 and NCP2, respectively. b , c , Ribbon diagrams of the NCP1–cGAS1–cGAS2–NCP2 complex ( b ) and the cGAS1–NCP1 complex ( c ) fit into corresponding electron-density maps. The two lobes of cGAS, N-lobe and C-lobe, are shown in pink and red, respectively. d , Schematic domain architecture for human cGAS (hcGAS) as previously defined 23 . Residue numbers are shown and the dotted line indicates the construct used for structural analysis. The dsDNA-sensing regions that are involved in cGAS activation are underlined in purple, and the nucleosome-binding regions that", "role": "user" }, { "content": "How do molecules involved in activating our immune system discriminate between our own DNA and foreign pathogens? Researchers from the Thomä group, in collaboration with the EPFL, deciphered the structural and functional basis of a DNA-sensing molecule when it comes in contact with the cell's own DNA, providing crucial insights into the recognition of self vs. non-self DNA. DNA within our cells is compacted and stored in the nucleus in the form of chromatin (DNA wraped around histone proteins, forming nucleosomes, the basic unit of chromatin). DNA found outside the nucleus, in the cytoplasm, is an important signal that triggers immune responses indicating the presence of an intracellular pathogen or a potentially cancerous cell. DNA sensing is carried out by cGAS, an enzyme responsible for recognizing and binding naked DNA. When activated, cGAS synthesizes cyclic GMP-AMP, which in turn initiates the body's so-called \"innate\" immune system—the first-line-of-defense part of our immune system. Until now, cGAS was thought to function predominantly in the cytoplasm, detecting foreign, non-self, DNA such as viruses. But recent studies suggested that cGAS is also present inside the nucleus. This was puzzling given the possibility that the enzyme is activated by its own DNA triggering an unwanted inflammatory response against its own DNA. Intrigued by this observation, researchers from the Thomä group used structural biology as a discovery tool and found that cGAS is present in the nucleus in an inactive state. They teamed up with the Ablasser lab at the EPFL to decipher the mechanism of cGAS inactivation by chromatin in cells. Taking advantage of the capability of the Thomä lab in cryo-electron microscopy (cryo-EM), the researchers derived the structure of cGAS bound to a nucleosome. They found that cGAS directly engages the histone proteins of nucleosomes. Once bound to the nucleosome, cGAS is \"trapped\" in a state in which it is unable to engage or sense naked DNA. It is then also unable to synthesize GMP-AMP and remains inactivated. cGAS, when present in the nucleus of healthy cells, is thus inactivated by chromatin, and does not participate in innate immune signaling in response to its own DNA. Ganesh Pathare, a postdoc in the Thomä lab and one of the first authors of the study, comments: \"The cGAS-nucleosomes structures provide the structural and functional basis for cGAS inhibition by chromatin. cGAS is an important protein for the innate immune response in the cell, required for the fight against viruses but also for detecting transformed or cancerous cells. cGAS activity is also often misguided in autoimmune diseases. Our study provides crucial insights into cGAS regulation and the mechanism of self DNA vs. non-self DNA recognition. This creates exciting opportunities for future therapeutic intervention in a wide range of diseases\". This study was published in the 26 November 2020 issue of Nature. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The DNA sensor cyclic GMP–AMP synthase (cGAS) initiates innate immune responses following microbial infection, cellular stress and cancer 1 . Upon activation by double-stranded DNA, cytosolic cGAS produces 2′3′ cGMP–AMP, which triggers the induction of inflammatory cytokines and type I interferons 2 , 3 , 4 , 5 , 6 , 7 . cGAS is also present inside the cell nucleus, which is replete with genomic DNA 8 , where chromatin has been implicated in restricting its enzymatic activity 9 . However, the structural basis for inhibition of cGAS by chromatin remains unknown. Here we present the cryo-electron microscopy structure of human cGAS bound to nucleosomes. cGAS makes extensive contacts with both the acidic patch of the histone H2A–H2B heterodimer and nucleosomal DNA. The structural and complementary biochemical analysis also find cGAS engaged to a second nucleosome in trans . Mechanistically, binding of the nucleosome locks cGAS into a monomeric state, in which steric hindrance suppresses spurious activation by genomic DNA. We find that mutations to the cGAS–acidic patch interface are sufficient to abolish the inhibitory effect of nucleosomes in vitro and to unleash the activity of cGAS on genomic DNA in living cells. Our work uncovers the structural basis of the interaction between cGAS and chromatin and details a mechanism that permits self–non-self discrimination of genomic DNA by cGAS. Main In the cytoplasm of mammalian cells, the enzyme cGAS is crucial for the detection of double-stranded DNA (dsDNA) during infection 2 . On binding dsDNA, cGAS synthesizes the second messenger 2′3′ cyclic GMP–AMP (cGAMP), which in turn stimulates antiviral and pro-inflammatory responses through the adaptor protein stimulator of interferon genes (STING) 2 , 3 , 4 , 5 , 6 , 7 , 10 . In addition, the nucleus contains a pool of cGAS that associates strongly with chromatin (Extended Data Fig. 1a ) 8 , 9 , 11 . The chromatinized state of intact genomic DNA has been reported to limit cGAS activity 12 , 13 , and cGAS has been found to bind more tightly to nucleosomes than to the corresponding naked DNA duplexes 13 . Here we sought a mechanism that explains how cGAS can be juxtaposed to nucleosomal DNA without undergoing activation. A minimal inhibitory histone unit for cGAS We tested whether histones, the building blocks of nucleosomes, may regulate cGAS inside the nucleus. Treatment of cells with aclarubicin robustly evicts core histones from chromatin 14 ; in particular, histones H2A and H2B (Extended Data Fig. 1b ). Notably, disruption of nucleosomes by aclarubicin also led to mobilization of nuclear cGAS (Extended Data Fig. 1b ). Proximity-ligation assays (PLAs) further indicated prominent association of cGAS with histones in situ, which was partially lost upon aclarubicin treatment (Extended Data Fig. 1c, d ). Thus, histones appear to dynamically engage cGAS in the nucleus. Consistent with previous work 13 , functional analysis of the in vitro enzymatic activity of cGAS revealed that mononucleosomes (hereafter nucleosomes) inhibited DNA-induced cGAMP synthesis (Extended Data Fig. 1e ). Likewise, compact chromatin fibres (12-mer nucleosome arrays) suppressed cGAS activity (Extended Data Fig. 1e ). H2A–H2B dimers also had an inhibitory effect, but neither H2A or H2B monomers nor H3 or H4 monomers did (Extended Data Fig. 1f, g ). Thus, H2A–H2B dimers on their own can suppress cGAS, albeit with weaker overall potency than fully assembled nucleosomes (Extended Data Fig. 1h ). Additional features of chromatin are therefore necessary to exert maximal inhibition. Overall structure of the cGAS–NCP complex To determine how cGAS interacts with nucleosomes, we pursued structural studies. A 1.5:1 molar mixture of human cGAS (residues 155–522) with a 147-bp 601 DNA nucleosome core particle (NCP) resulted in heterogenous particle distribution (Extended Data Fig. 2a–d ). To select for and stabilize more homogenous cGAS–NCP complexes, we combined gradient centrifugation with chemical crosslinking (GraFix) 15 . Both wild-type (WT) cGAS and cGAS K394E, a mutant impaired in dsDNA-mediated cGAS dimerization 16 , were used for structure determination. For the cGAS K394E mutant, we obtained a 4.1 Å reconstruction that revealed two NCPs organized in an NCP1–cGAS1–cGAS2–NCP2 sandwich arrangement with an expected molecular weight of around 560 kDa, consistent with the most prominent peak fraction in multi-angle light scattering under non-crosslinked conditions (Fig. 1a, b , Extended Data Fig. 3 , Extended Data Table 1a , Supplementary Videos 1 , 2 ). The two individual nucleosomes are held together by two cGAS protomers. While the first cGAS protomer and its corresponding NCP (designated cGAS1 and NCP1) are well resolved, the second nucleosome–cGAS pair (NCP2 and cGAS2) is less ordered (Extended Data Fig. 3e ). In the dimeric NCP1–cGAS1–cGAS2–NCP2 arrangement, each cGAS protomer interacts with the histone octamer of one NCP through histones H2A and H2B and the nucleosomal DNA (for example, cGAS1 and NCP1), while contacting the second nucleosome (for example, cGAS1 and NCP2) primarily through interactions with the nucleosomal DNA (Fig. 1a, b ). In the WT cGAS structure, we observed a similar overall structural arrangement, with the NCP1–cGAS1–cGAS2–NCP2 complex at 5.1 Å and a NCP1–cGAS1 structure at 4.7 Å resolution following focused 3D classification (Extended Data Figs. 4 , 5 , Extended Data Table 1 ). Given the structural similarity, the higher-resolution cGAS K394E mutant was used for subsequent analysis (Extended Data Figs. 3 , 6 ). Fig. 1: Cryo-electron microscopy structure of cGAS bound to nucleosomes. a , 3D reconstruction of the complex containing two cGAS protomers, cGAS1 (red) and cGAS2 (orange), and two nucleosomal core particles, NCP1 and NCP2, respectively. b , c , Ribbon diagrams of the NCP1–cGAS1–cGAS2–NCP2 complex ( b ) and the cGAS1–NCP1 complex ( c ) fit into corresponding electron-density maps. The two lobes of cGAS, N-lobe and C-lobe, are shown in pink and red, respectively. d , Schematic domain architecture for human cGAS (hcGAS) as previously defined 23 . Residue numbers are shown and the dotted line indicates the construct used for structural analysis. The dsDNA-sensing regions that are involved in cGAS activation are underlined in purple, and the nucleosome-binding regions that<|im_end|> <|im_start|>assistant How do molecules involved in activating our immune system discriminate between our own DNA and foreign pathogens? Researchers from the Thomä group, in collaboration with the EPFL, deciphered the structural and functional basis of a DNA-sensing molecule when it comes in contact with the cell's own DNA, providing crucial insights into the recognition of self vs. non-self DNA. DNA within our cells is compacted and stored in the nucleus in the form of chromatin (DNA wraped around histone proteins, forming nucleosomes, the basic unit of chromatin). DNA found outside the nucleus, in the cytoplasm, is an important signal that triggers immune responses indicating the presence of an intracellular pathogen or a potentially cancerous cell. DNA sensing is carried out by cGAS, an enzyme responsible for recognizing and binding naked DNA. When activated, cGAS synthesizes cyclic GMP-AMP, which in turn initiates the body's so-called "innate" immune system—the first-line-of-defense part of our immune system. Until now, cGAS was thought to function predominantly in the cytoplasm, detecting foreign, non-self, DNA such as viruses. But recent studies suggested that cGAS is also present inside the nucleus. This was puzzling given the possibility that the enzyme is activated by its own DNA triggering an unwanted inflammatory response against its own DNA. Intrigued by this observation, researchers from the Thomä group used structural biology as a discovery tool and found that cGAS is present in the nucleus in an inactive state. They teamed up with the Ablasser lab at the EPFL to decipher the mechanism of cGAS inactivation by chromatin in cells. Taking advantage of the capability of the Thomä lab in cryo-electron microscopy (cryo-EM), the researchers derived the structure of cGAS bound to a nucleosome. They found that cGAS directly engages the histone proteins of nucleosomes. Once bound to the nucleosome, cGAS is "trapped" in a state in which it is unable to engage or sense naked DNA. It is then also unable to synthesize GMP-AMP and remains inactivated. cGAS, when present in the nucleus of healthy cells, is thus inactivated by chromatin, and does not participate in innate immune signaling in response to its own DNA. Ganesh Pathare, a postdoc in the Thomä lab and one of the first authors of the study, comments: "The cGAS-nucleosomes structures provide the structural and functional basis for cGAS inhibition by chromatin. cGAS is an important protein for the innate immune response in the cell, required for the fight against viruses but also for detecting transformed or cancerous cells. cGAS activity is also often misguided in autoimmune diseases. Our study provides crucial insights into cGAS regulation and the mechanism of self DNA vs. non-self DNA recognition. This creates exciting opportunities for future therapeutic intervention in a wide range of diseases". This study was published in the 26 November 2020 issue of Nature. <|im_end|>

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128257, 198 ]

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The adhesion of water to solid surfaces is characterized by the tendency to balance competing molecule–molecule and molecule–surface interactions. Hydroxyl groups form strong hydrogen bonds to water molecules and are known to substantially influence the wetting behaviour of oxide surfaces, but it is not well-understood how these hydroxyl groups and their distribution on a surface affect the molecular-scale structure at the interface. Here we report a study of water clustering on a moiré-structured iron oxide thin film with a controlled density of hydroxyl groups. While large amorphous monolayer islands form on the bare film, the hydroxylated iron oxide film acts as a hydrophilic nanotemplate, causing the formation of a regular array of ice-like hexameric nanoclusters. The formation of this ordered phase is localized at the nanometre scale; with increasing water coverage, ordered and amorphous water are found to coexist at adjacent hydroxylated and hydroxyl-free domains of the moiré structure. Introduction Motivated by applications in diverse fields such as electrochemistry, geochemistry, atmospheric chemistry, corrosion and catalysis, the structure of water adsorbed on solid surfaces has been a topic of strong and sustained interest over the past decades 1 , 2 , 3 , 4 . Due to the relative strength and particular directionality of interactions between water molecules, which are delicately balanced against molecule–surface interactions, the structures of water monolayers on various surfaces exhibit surprising diversity. This has been recently demonstrated in scanning tunnelling microscopy (STM) studies 5 , 6 , 7 , 8 , which allow direct visualization of hydrogen bonding networks. The most detailed insight into water adsorption has been achieved for single-crystal metal surfaces, where the structure of water layers is determined mainly by the dimensions of the surface unit cell and the strength of metal–oxygen bonding 6 . The adsorption and clustering of water on metal oxide surfaces are very relevant for applications, as these materials are ubiquitous under ambient and aqueous conditions. Oxides add an additional level of complexity compared with metals, as water molecules can bond both to metal cations and oxide anions, and in addition, adhere strongly to OH groups formed by water dissociation at lattice sites or at abundant structural defects 3 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 . Although these fundamental aspects of water adsorption on oxide surfaces have been well-established, comparatively few microscopy studies have been conducted to provide detailed information about the structures formed and the influence of defects. As a result, understanding of water adsorption on oxides remains far behind that of adsorption on metals. An additional relevant factor in the adsorption of water on the surfaces of natural or man-made materials is the fact that many such materials have nanometre-scale dimensions, and thus present an adsorption landscape for water which is inhomogeneous. Such inhomogeneity can lead to the formation of distinct nanometre-scale water structures, as observed on a boron nitride nanomesh 18 , or can disrupt the formation of an ordered phase, as observed on stepped Pt surfaces 19 . On oxide surfaces, an inhomogeneous distribution of defects or the presence of different facets can lead to a strongly varying distribution of OH groups, creating large variations in hydrophilicity over short length scales 16 . In general it is not well-understood how nanoscale variations in surface structure impact the formation and structure of the first few wetting layers on oxide surfaces. Monolayer FeO grown on Pt(111), first reported by Vurens et al. 20 , exhibits a 2.5 nm moiré superstructure due to the ~10% lattice mismatch between the FeO film and the substrate 21 . The resulting modulation in the film’s structure, best understood in terms of periodic variation in Fe-O buckling normal to the surface, creates an inhomogeneous adsorption potential 22 , so that adsorbed atoms and molecules have been found to form arrays with the periodicity of the film’s superstructure instead of forming larger, more random aggregates 23 , 24 . Although previous temperature-programmed desorption (TPD), infrared reflection absorption spectroscopy and ultraviolet photoelectron spectroscopy studies of water adsorbed on ultra-thin FeO(111) films have shown rather weak interactions between water and the surface 12 , 25 , 26 , no microscopy studies have been reported to date and the potential effect of the films’ moiré structure on the adsorption has not been considered. Additionally, as demonstrated in previous studies 27 , 28 , 29 , OH groups can be introduced to the FeO surface in a well-controlled manner by exposure to atomic hydrogen, enabling us to directly and systematically study the effects of hydroxylation on H 2 O adsorption and clustering. As will be discussed below, the OH groups formed in this manner also show a distinct spatial distribution following the film’s moiré structure, allowing us to examine the impact of nanometre-scale variations in defect density. We report here a combined experimental and theoretical study of water adsorption, clustering and desorption on bare and hydroxylated monolayer FeO/Pt(111) at low temperatures. Our results show that hydroxyl groups on the FeO film promote the formation of an ordered, ice-like phase, in contrast to the disordered structure formed on the bare surface. The OH groups are localized at one particular domain of the FeO film’s moiré unit cell, such that the surface exhibits alternating hydrophilic and hydrophobic regions with a periodicity of ~2.5 nm. Despite the small length scale, it is found that the ordered phase only forms at the hydrophilic domains—not at adjacent hydrophobic domains. Results Hydroxylation of FeO with atomic hydrogen An STM image of the bare FeO/Pt(111) surface is displayed in Fig. 1a , with a structural model of the film shown in Fig. 1b . As is clear in the STM image, the FeO film exhibits a distinct moiré superstructure, which can be described in terms of three high-symmetry domains. These domains are distinguished by the local stacking sequence of the Fe and O layers relative to the high-symmetry points of the Pt(111) surface. At the FCC domain (square), Fe ions reside above", "role": "user" }, { "content": "(Phys.org) —A multi-institutional team has resolved a long-unanswered question about how two of the world's most common substances interact. In a paper published June 30, 2014, in the journal Nature Communications, Manos Mavrikakis, the Paul A. Elfers professor of chemical and biological engineering at the University of Wisconsin-Madison, and his collaborators report fundamental discoveries about how water reacts with metal oxides. The paper, \"Water clustering on nanostructured iron oxide films,\" opens doors for greater understanding and control of chemical reactions in fields ranging from catalysis to geochemistry and atmospheric chemistry. \"These metal oxide materials are everywhere, and water is everywhere,\" Mavrikakis says. \"It would be nice to see how something so abundant as water interacts with materials that are accelerating chemical reactions.\" These reactions play a huge role in the catalysis-driven creation of common chemical platforms such as methanol, produced on the order of 10 million tons per year for uses including fuel and as raw material for chemicals production. \"Ninety percent of all catalytic processes use metal oxides as a support,\" Mavrikakis says. \"Therefore, all of the reactions including water as an impurity or reactant or product would be affected by the insights developed.\" Chemists understand how water interacts with many non-oxide metals, which are very homogeneous. Metal oxides are trickier: An occasional oxygen atom is missing, causing what Mavrikakis calls \"oxygen defects.\" When water meets with one of those defects, it forms two adjacent hydroxyls—a stable compound comprising one oxygen atom and one hydrogen atom. Mavrikakis, with assistant scientist Guowen Peng and PhD student Carrie Farberow, along with researchers at Aarhus University in Denmark and Lund University in Sweden, investigated how hydroxyls affect water molecules around them, and how that differs from water molecules contacting a pristine metal oxide surface. The Aarhus researchers generated data on the reactions using scanning tunneling microscopy (STM). The Wisconsin researchers then subjected the STM images to quantum mechanical analysis that decoded the resulting chemical structures, defining which atom is which. \"If you don't have the component of the work that we provided, there is no way that you can tell from STM alone what the atomic-scale structure of the water is, when absorbed on various surfaces\" Mavrikakis says. The project yielded two dramatically different pictures of water-metal oxide reactions. \"On a smooth surface, you form amorphous networks of water molecules, whereas on a hydroxylated surface, there are much more structured, well-ordered domains of water molecules,\" Mavrikakis says. In the latter case, the researchers realized that hydroxyl behaves as a sort of anchor, setting the template for a tidy hexameric ring of water molecules attracted to the metal's surface. Mavrikakis' next step is to examine how these differing structures react with other molecules, and to use the research to improve catalysis. Mavrikakis sees lots of possibilities outside his own field. \"Maybe others might be inspired and look at the geochemistry and/or atmospheric chemistry implications, such as how these water cluster structures on atmospheric dust nanoparticles could affect cloud formation, rain, and acid rain,\" Mavrikakis says. Other researchers might also look at whether other molecules exhibit similar behavior when they come into contact with metal oxides, he adds. \"It opens the doors to using hydrogen bonds to make surfaces hydrophilic or attracted to water, and to templating these surfaces for the selective absorption of other molecules possessing fundamental similarities to water,\" Mavrikakis says. \"Because catalysis is at the heart of engineering chemical reactions, this is also very fundamental for atomic-scale chemical reaction engineering.\" While the research fills part of the foundation of chemistry, it also owes a great deal to state-of-the-art research technology. \"The size and nature of the calculations we had to do probably was not feasible until maybe four or five years ago, and the spatial and temporal resolution of scanning tunneling microscopy was not there,\" Mavrikakis says. \"So it's advances in the methods that allow for this new information to be born.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The adhesion of water to solid surfaces is characterized by the tendency to balance competing molecule–molecule and molecule–surface interactions. Hydroxyl groups form strong hydrogen bonds to water molecules and are known to substantially influence the wetting behaviour of oxide surfaces, but it is not well-understood how these hydroxyl groups and their distribution on a surface affect the molecular-scale structure at the interface. Here we report a study of water clustering on a moiré-structured iron oxide thin film with a controlled density of hydroxyl groups. While large amorphous monolayer islands form on the bare film, the hydroxylated iron oxide film acts as a hydrophilic nanotemplate, causing the formation of a regular array of ice-like hexameric nanoclusters. The formation of this ordered phase is localized at the nanometre scale; with increasing water coverage, ordered and amorphous water are found to coexist at adjacent hydroxylated and hydroxyl-free domains of the moiré structure. Introduction Motivated by applications in diverse fields such as electrochemistry, geochemistry, atmospheric chemistry, corrosion and catalysis, the structure of water adsorbed on solid surfaces has been a topic of strong and sustained interest over the past decades 1 , 2 , 3 , 4 . Due to the relative strength and particular directionality of interactions between water molecules, which are delicately balanced against molecule–surface interactions, the structures of water monolayers on various surfaces exhibit surprising diversity. This has been recently demonstrated in scanning tunnelling microscopy (STM) studies 5 , 6 , 7 , 8 , which allow direct visualization of hydrogen bonding networks. The most detailed insight into water adsorption has been achieved for single-crystal metal surfaces, where the structure of water layers is determined mainly by the dimensions of the surface unit cell and the strength of metal–oxygen bonding 6 . The adsorption and clustering of water on metal oxide surfaces are very relevant for applications, as these materials are ubiquitous under ambient and aqueous conditions. Oxides add an additional level of complexity compared with metals, as water molecules can bond both to metal cations and oxide anions, and in addition, adhere strongly to OH groups formed by water dissociation at lattice sites or at abundant structural defects 3 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 . Although these fundamental aspects of water adsorption on oxide surfaces have been well-established, comparatively few microscopy studies have been conducted to provide detailed information about the structures formed and the influence of defects. As a result, understanding of water adsorption on oxides remains far behind that of adsorption on metals. An additional relevant factor in the adsorption of water on the surfaces of natural or man-made materials is the fact that many such materials have nanometre-scale dimensions, and thus present an adsorption landscape for water which is inhomogeneous. Such inhomogeneity can lead to the formation of distinct nanometre-scale water structures, as observed on a boron nitride nanomesh 18 , or can disrupt the formation of an ordered phase, as observed on stepped Pt surfaces 19 . On oxide surfaces, an inhomogeneous distribution of defects or the presence of different facets can lead to a strongly varying distribution of OH groups, creating large variations in hydrophilicity over short length scales 16 . In general it is not well-understood how nanoscale variations in surface structure impact the formation and structure of the first few wetting layers on oxide surfaces. Monolayer FeO grown on Pt(111), first reported by Vurens et al. 20 , exhibits a 2.5 nm moiré superstructure due to the ~10% lattice mismatch between the FeO film and the substrate 21 . The resulting modulation in the film’s structure, best understood in terms of periodic variation in Fe-O buckling normal to the surface, creates an inhomogeneous adsorption potential 22 , so that adsorbed atoms and molecules have been found to form arrays with the periodicity of the film’s superstructure instead of forming larger, more random aggregates 23 , 24 . Although previous temperature-programmed desorption (TPD), infrared reflection absorption spectroscopy and ultraviolet photoelectron spectroscopy studies of water adsorbed on ultra-thin FeO(111) films have shown rather weak interactions between water and the surface 12 , 25 , 26 , no microscopy studies have been reported to date and the potential effect of the films’ moiré structure on the adsorption has not been considered. Additionally, as demonstrated in previous studies 27 , 28 , 29 , OH groups can be introduced to the FeO surface in a well-controlled manner by exposure to atomic hydrogen, enabling us to directly and systematically study the effects of hydroxylation on H 2 O adsorption and clustering. As will be discussed below, the OH groups formed in this manner also show a distinct spatial distribution following the film’s moiré structure, allowing us to examine the impact of nanometre-scale variations in defect density. We report here a combined experimental and theoretical study of water adsorption, clustering and desorption on bare and hydroxylated monolayer FeO/Pt(111) at low temperatures. Our results show that hydroxyl groups on the FeO film promote the formation of an ordered, ice-like phase, in contrast to the disordered structure formed on the bare surface. The OH groups are localized at one particular domain of the FeO film’s moiré unit cell, such that the surface exhibits alternating hydrophilic and hydrophobic regions with a periodicity of ~2.5 nm. Despite the small length scale, it is found that the ordered phase only forms at the hydrophilic domains—not at adjacent hydrophobic domains. Results Hydroxylation of FeO with atomic hydrogen An STM image of the bare FeO/Pt(111) surface is displayed in Fig. 1a , with a structural model of the film shown in Fig. 1b . As is clear in the STM image, the FeO film exhibits a distinct moiré superstructure, which can be described in terms of three high-symmetry domains. These domains are distinguished by the local stacking sequence of the Fe and O layers relative to the high-symmetry points of the Pt(111) surface. At the FCC domain (square), Fe ions reside above<|im_end|> <|im_start|>assistant (Phys.org) —A multi-institutional team has resolved a long-unanswered question about how two of the world's most common substances interact. In a paper published June 30, 2014, in the journal Nature Communications, Manos Mavrikakis, the Paul A. Elfers professor of chemical and biological engineering at the University of Wisconsin-Madison, and his collaborators report fundamental discoveries about how water reacts with metal oxides. The paper, "Water clustering on nanostructured iron oxide films," opens doors for greater understanding and control of chemical reactions in fields ranging from catalysis to geochemistry and atmospheric chemistry. "These metal oxide materials are everywhere, and water is everywhere," Mavrikakis says. "It would be nice to see how something so abundant as water interacts with materials that are accelerating chemical reactions." These reactions play a huge role in the catalysis-driven creation of common chemical platforms such as methanol, produced on the order of 10 million tons per year for uses including fuel and as raw material for chemicals production. "Ninety percent of all catalytic processes use metal oxides as a support," Mavrikakis says. "Therefore, all of the reactions including water as an impurity or reactant or product would be affected by the insights developed." Chemists understand how water interacts with many non-oxide metals, which are very homogeneous. Metal oxides are trickier: An occasional oxygen atom is missing, causing what Mavrikakis calls "oxygen defects." When water meets with one of those defects, it forms two adjacent hydroxyls—a stable compound comprising one oxygen atom and one hydrogen atom. Mavrikakis, with assistant scientist Guowen Peng and PhD student Carrie Farberow, along with researchers at Aarhus University in Denmark and Lund University in Sweden, investigated how hydroxyls affect water molecules around them, and how that differs from water molecules contacting a pristine metal oxide surface. The Aarhus researchers generated data on the reactions using scanning tunneling microscopy (STM). The Wisconsin researchers then subjected the STM images to quantum mechanical analysis that decoded the resulting chemical structures, defining which atom is which. "If you don't have the component of the work that we provided, there is no way that you can tell from STM alone what the atomic-scale structure of the water is, when absorbed on various surfaces" Mavrikakis says. The project yielded two dramatically different pictures of water-metal oxide reactions. "On a smooth surface, you form amorphous networks of water molecules, whereas on a hydroxylated surface, there are much more structured, well-ordered domains of water molecules," Mavrikakis says. In the latter case, the researchers realized that hydroxyl behaves as a sort of anchor, setting the template for a tidy hexameric ring of water molecules attracted to the metal's surface. Mavrikakis' next step is to examine how these differing structures react with other molecules, and to use the research to improve catalysis. Mavrikakis sees lots of possibilities outside his own field. "Maybe others might be inspired and look at the geochemistry and/or atmospheric chemistry implications, such as how these water cluster structures on atmospheric dust nanoparticles could affect cloud formation, rain, and acid rain," Mavrikakis says. Other researchers might also look at whether other molecules exhibit similar behavior when they come into contact with metal oxides, he adds. "It opens the doors to using hydrogen bonds to make surfaces hydrophilic or attracted to water, and to templating these surfaces for the selective absorption of other molecules possessing fundamental similarities to water," Mavrikakis says. "Because catalysis is at the heart of engineering chemical reactions, this is also very fundamental for atomic-scale chemical reaction engineering." While the research fills part of the foundation of chemistry, it also owes a great deal to state-of-the-art research technology. "The size and nature of the calculations we had to do probably was not feasible until maybe four or five years ago, and the spatial and temporal resolution of scanning tunneling microscopy was not there," Mavrikakis says. "So it's advances in the methods that allow for this new information to be born." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Heart transplantation is the only cure for patients with terminal cardiac failure, but the supply of allogeneic donor organs falls far short of the clinical need 1 , 2 , 3 . Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative 4 . Genetically multi-modified pig hearts that lack galactose-α1,3-galactose epitopes (α1,3-galactosyltransferase knockout) and express a human membrane cofactor protein (CD46) and human thrombomodulin have survived for up to 945 days after heterotopic abdominal transplantation in baboons 5 . This model demonstrated long-term acceptance of discordant xenografts with safe immunosuppression but did not predict their life-supporting function. Despite 25 years of extensive research, the maximum survival of a baboon after heart replacement with a porcine xenograft was only 57 days and this was achieved, to our knowledge, only once 6 . Here we show that α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin require non-ischaemic preservation with continuous perfusion and control of post-transplantation growth to ensure long-term orthotopic function of the xenograft in baboons, the most stringent preclinical xenotransplantation model. Consistent life-supporting function of xenografted hearts for up to 195 days is a milestone on the way to clinical cardiac xenotransplantation 7 . Main Xenotransplantation of genetically multi-modified α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin (blood group 0) was performed using the clinically approved Shumway’s orthotopic technique 8 . Fourteen captive-bred baboons ( Papio anubis , blood groups B and AB) served as recipients. All recipients received basic immunosuppression, similar to that described previously 5 : induction therapy included anti-CD20 antibody, anti-thymocyte-globulin, and the monkey-specific anti-CD40 mouse/rhesus chimeric IgG4 monoclonal antibody (clone 2C10R4) 9 or our own humanized anti-CD40L PASylated (conjugated with a long, structurally disordered Pro-Ala-Ser amino acid chain) antigen-binding fragment (Fab) 10 . During maintenance therapy methylprednisolone was reduced gradually, whereas mycophenolate mofetil and anti-CD40 monoclonal antibody or anti-CD40L PASylated Fab treatment remained constant (Extended Data Table 1 ). Postoperative treatment of the recipients has been described elsewhere 11 . In group I ( n = 5), donor organs were preserved with two clinically approved crystalloid solutions (4 °C custodiol HTK (histidine-tryptophan-ketoglutarate) or Belzer’s UW solution), each perfused after cross-clamping the ascending aorta before excision of the porcine donor organ. The hearts were kept in plastic bags filled with ice-cold solution and surrounded by ice cubes (static preservation). The results of group I were disappointing. Despite short ischaemic preservation periods (123 ± 7 min), the animals survived for only 1 day ( n = 3), 3 days ( n = 1) and 30 days ( n = 1) (Fig. 1a ). The four short-term survivors were successfully taken off cardiopulmonary bypass (CPB) and three could be extubated, but all were lost due to severe systolic left heart failure in spite of a high dose of intravenous catecholamines (Extended Data Fig. 1 ). This so-called ‘perioperative cardiac xenograft dysfunction’ (PCXD) 12 has been observed in 40 to 60% of the orthotopic cardiac xenotransplantation experiments described in the literature 4 . The only 30-day survivor (which received a heart preserved with Belzer’s UW solution) gradually developed left ventricular myocardial hypertrophy and stiffening, resulting in progressive diastolic left ventricular failure associated with increased serum levels of troponin T, an indicator of myocardial damage (Fig. 1b ). Increased serum bilirubin levels (Fig. 1c ) and several other clinically relevant chemical parameters (Table 1 ) indicated associated terminal liver disease. Upon necropsy, marked cardiac hypertrophy (Fig. 1e ) with a thickened left ventricular myocardium and a decreased left ventricular cavity was evident (Fig. 1f ). Fig. 1: Survival, laboratory parameters, necropsy and histology after orthotopic xenotransplantation. a , Kaplan–Meier curve of survival of groups I (black; n = 5 animals), II (red; n = 4 animals) and III (magenta; n = 5 animals). Two-sided log-rank test, P = 0.0007. b , c , Serum concentrations of cardiac troponin T ( b ) and bilirubin ( c ). d , Left ventricular (LV) masses of xenografted hearts from animals 9 (group II), 11 and 13 (both group III); note increased graft growth after discontinuation of temsirolimus (arrow). e – g , Front view of the porcine donor heart and own heart of baboon 3 ( e , left and right, respectively; group I) and transverse cuts of the porcine donor hearts (left) and the baboons’ own hearts (right) of animals 3 ( f ) and 11 ( g ). Note the extensive left ventricular hypertrophy and reduction of left ventricular cavity of the donor organ of baboon 3 in contrast to animal 11. h , i , Haematoxylin and eosin staining of the left ventricular myocardium of the donor (left) and the liver of the recipient (right). Scale bars, 100 μm. h , The myocardium of animal 9 showed multifocal cell necroses with hypereosinophilia, small vessel thromboses, moderate interstitial infiltration of lymphocytes, neutrophils and macrophages. The liver of this animal had multifocal centrolobular cell vacuolizations and necroses as well as multifocal intralesional haemorrhages. i , The myocardium of baboon 11 had sporadic infiltrations of lymphocytes, multifocal minor interstitial oedema whereas the liver had small vacuolar degeneration of hepatocytes (lipid type). j , Wheat germ agglutinin-stained myocardial sections of a sham-operated porcine heart (left), and the hearts transplanted into animals 9 (centre) and 11 (right). Scale bar, 50 μm. e – j , n = 4, groups I/II; n = 3, group III; n = 1, control; one representative biological sample for each group is shown for group I/II, group III and control ( j ). k , Quantitative analysis of cardiomyocyte cross-sectional areas. Data are mean ± s.d., P values are indicated, one-way analysis of variance (ANOVA) with Holm – Sidak’s multiple comparisons test ( n = 3 biologically independent samples with 5–8 measurements each). l , Western blot analysis of myocardium from transplanted hearts of animals 11 and 12 showed reduced mTOR phosphorylation (p-mTOR) compared to age-matched control samples. n = 2, group III; n = 2, controls. For gel source data, see Supplementary Fig.", "role": "user" }, { "content": "A large team of researchers from several institutions in Germany, Sweden, Switzerland and the U.S. has transplanted pig hearts into baboons and kept them alive for an extended period of time. In their paper published in the journal Nature, the group describes changes they made to heart transplant procedures and how well they worked. Christoph Knosalla with the German Heart Center Berlin has written a News & Views piece on the work done by the team in the same journal issue. As populations age in advanced countries, medical providers confront a growing number of health issues, one of which is how to deal with cardiac damage from heart disease. Currently, the only treatment for such patients is a transplant. But every year, the list grows longer, and many people die waiting for a donor. One possible solution to this problem is to breed animals that are anatomically similar to humans and use their hearts. But thus far, research in this area has run into a wall—baboons that receive pig hearts, for example, rarely live for more than a month. In this new effort, the researchers claim to have overcome the problems associated with transplanting pig hearts into baboons, and in so doing have brought some optimism to the idea of doing the same for humans. Prior research has shown that there are two main reasons that pig hearts fail to thrive in baboons: damage that occurs during the procedure, and size differences between pigs and baboons. The normal procedure for preserving a heart after removal from an animal before transplantation has been immersing it in cold water. But this method has been found to damage heart tissue. To prevent that damage, the researchers periodically pumped a solution of blood mixed with nutrients and hormones and added extra oxygen. Doing so appeared to prevent heart damage. Pigs are bigger than baboons and thus have bigger hearts—if a pig heart grows to its normal size inside of a baboon, it runs out of room and fails. To prevent this from happening, the researchers gave the baboons medicine to bring their blood pressure down to the level found in pigs. They also gave the baboons a drug that prevents heart growth. And finally, they modified the hormone treatment given to the baboons to prevent immunosuppression—they tapered the cortisone treatments to prevent heart overgrowth. By combining the techniques, the researchers found they were able to extend the lives of the baboon recipients. Two lived for three months—the length of the study—and another two lived for six months before they were euthanized. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Heart transplantation is the only cure for patients with terminal cardiac failure, but the supply of allogeneic donor organs falls far short of the clinical need 1 , 2 , 3 . Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative 4 . Genetically multi-modified pig hearts that lack galactose-α1,3-galactose epitopes (α1,3-galactosyltransferase knockout) and express a human membrane cofactor protein (CD46) and human thrombomodulin have survived for up to 945 days after heterotopic abdominal transplantation in baboons 5 . This model demonstrated long-term acceptance of discordant xenografts with safe immunosuppression but did not predict their life-supporting function. Despite 25 years of extensive research, the maximum survival of a baboon after heart replacement with a porcine xenograft was only 57 days and this was achieved, to our knowledge, only once 6 . Here we show that α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin require non-ischaemic preservation with continuous perfusion and control of post-transplantation growth to ensure long-term orthotopic function of the xenograft in baboons, the most stringent preclinical xenotransplantation model. Consistent life-supporting function of xenografted hearts for up to 195 days is a milestone on the way to clinical cardiac xenotransplantation 7 . Main Xenotransplantation of genetically multi-modified α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin (blood group 0) was performed using the clinically approved Shumway’s orthotopic technique 8 . Fourteen captive-bred baboons ( Papio anubis , blood groups B and AB) served as recipients. All recipients received basic immunosuppression, similar to that described previously 5 : induction therapy included anti-CD20 antibody, anti-thymocyte-globulin, and the monkey-specific anti-CD40 mouse/rhesus chimeric IgG4 monoclonal antibody (clone 2C10R4) 9 or our own humanized anti-CD40L PASylated (conjugated with a long, structurally disordered Pro-Ala-Ser amino acid chain) antigen-binding fragment (Fab) 10 . During maintenance therapy methylprednisolone was reduced gradually, whereas mycophenolate mofetil and anti-CD40 monoclonal antibody or anti-CD40L PASylated Fab treatment remained constant (Extended Data Table 1 ). Postoperative treatment of the recipients has been described elsewhere 11 . In group I ( n = 5), donor organs were preserved with two clinically approved crystalloid solutions (4 °C custodiol HTK (histidine-tryptophan-ketoglutarate) or Belzer’s UW solution), each perfused after cross-clamping the ascending aorta before excision of the porcine donor organ. The hearts were kept in plastic bags filled with ice-cold solution and surrounded by ice cubes (static preservation). The results of group I were disappointing. Despite short ischaemic preservation periods (123 ± 7 min), the animals survived for only 1 day ( n = 3), 3 days ( n = 1) and 30 days ( n = 1) (Fig. 1a ). The four short-term survivors were successfully taken off cardiopulmonary bypass (CPB) and three could be extubated, but all were lost due to severe systolic left heart failure in spite of a high dose of intravenous catecholamines (Extended Data Fig. 1 ). This so-called ‘perioperative cardiac xenograft dysfunction’ (PCXD) 12 has been observed in 40 to 60% of the orthotopic cardiac xenotransplantation experiments described in the literature 4 . The only 30-day survivor (which received a heart preserved with Belzer’s UW solution) gradually developed left ventricular myocardial hypertrophy and stiffening, resulting in progressive diastolic left ventricular failure associated with increased serum levels of troponin T, an indicator of myocardial damage (Fig. 1b ). Increased serum bilirubin levels (Fig. 1c ) and several other clinically relevant chemical parameters (Table 1 ) indicated associated terminal liver disease. Upon necropsy, marked cardiac hypertrophy (Fig. 1e ) with a thickened left ventricular myocardium and a decreased left ventricular cavity was evident (Fig. 1f ). Fig. 1: Survival, laboratory parameters, necropsy and histology after orthotopic xenotransplantation. a , Kaplan–Meier curve of survival of groups I (black; n = 5 animals), II (red; n = 4 animals) and III (magenta; n = 5 animals). Two-sided log-rank test, P = 0.0007. b , c , Serum concentrations of cardiac troponin T ( b ) and bilirubin ( c ). d , Left ventricular (LV) masses of xenografted hearts from animals 9 (group II), 11 and 13 (both group III); note increased graft growth after discontinuation of temsirolimus (arrow). e – g , Front view of the porcine donor heart and own heart of baboon 3 ( e , left and right, respectively; group I) and transverse cuts of the porcine donor hearts (left) and the baboons’ own hearts (right) of animals 3 ( f ) and 11 ( g ). Note the extensive left ventricular hypertrophy and reduction of left ventricular cavity of the donor organ of baboon 3 in contrast to animal 11. h , i , Haematoxylin and eosin staining of the left ventricular myocardium of the donor (left) and the liver of the recipient (right). Scale bars, 100 μm. h , The myocardium of animal 9 showed multifocal cell necroses with hypereosinophilia, small vessel thromboses, moderate interstitial infiltration of lymphocytes, neutrophils and macrophages. The liver of this animal had multifocal centrolobular cell vacuolizations and necroses as well as multifocal intralesional haemorrhages. i , The myocardium of baboon 11 had sporadic infiltrations of lymphocytes, multifocal minor interstitial oedema whereas the liver had small vacuolar degeneration of hepatocytes (lipid type). j , Wheat germ agglutinin-stained myocardial sections of a sham-operated porcine heart (left), and the hearts transplanted into animals 9 (centre) and 11 (right). Scale bar, 50 μm. e – j , n = 4, groups I/II; n = 3, group III; n = 1, control; one representative biological sample for each group is shown for group I/II, group III and control ( j ). k , Quantitative analysis of cardiomyocyte cross-sectional areas. Data are mean ± s.d., P values are indicated, one-way analysis of variance (ANOVA) with Holm – Sidak’s multiple comparisons test ( n = 3 biologically independent samples with 5–8 measurements each). l , Western blot analysis of myocardium from transplanted hearts of animals 11 and 12 showed reduced mTOR phosphorylation (p-mTOR) compared to age-matched control samples. n = 2, group III; n = 2, controls. For gel source data, see Supplementary Fig.<|im_end|> <|im_start|>assistant A large team of researchers from several institutions in Germany, Sweden, Switzerland and the U.S. has transplanted pig hearts into baboons and kept them alive for an extended period of time. In their paper published in the journal Nature, the group describes changes they made to heart transplant procedures and how well they worked. Christoph Knosalla with the German Heart Center Berlin has written a News & Views piece on the work done by the team in the same journal issue. As populations age in advanced countries, medical providers confront a growing number of health issues, one of which is how to deal with cardiac damage from heart disease. Currently, the only treatment for such patients is a transplant. But every year, the list grows longer, and many people die waiting for a donor. One possible solution to this problem is to breed animals that are anatomically similar to humans and use their hearts. But thus far, research in this area has run into a wall—baboons that receive pig hearts, for example, rarely live for more than a month. In this new effort, the researchers claim to have overcome the problems associated with transplanting pig hearts into baboons, and in so doing have brought some optimism to the idea of doing the same for humans. Prior research has shown that there are two main reasons that pig hearts fail to thrive in baboons: damage that occurs during the procedure, and size differences between pigs and baboons. The normal procedure for preserving a heart after removal from an animal before transplantation has been immersing it in cold water. But this method has been found to damage heart tissue. To prevent that damage, the researchers periodically pumped a solution of blood mixed with nutrients and hormones and added extra oxygen. Doing so appeared to prevent heart damage. Pigs are bigger than baboons and thus have bigger hearts—if a pig heart grows to its normal size inside of a baboon, it runs out of room and fails. To prevent this from happening, the researchers gave the baboons medicine to bring their blood pressure down to the level found in pigs. They also gave the baboons a drug that prevents heart growth. And finally, they modified the hormone treatment given to the baboons to prevent immunosuppression—they tapered the cortisone treatments to prevent heart overgrowth. By combining the techniques, the researchers found they were able to extend the lives of the baboon recipients. Two lived for three months—the length of the study—and another two lived for six months before they were euthanized. <|im_end|>

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220, 806, 320, 342, 7609, 7181, 279, 16781, 2163, 10594, 57333, 48855, 58175, 323, 14278, 315, 2163, 10594, 57333, 56429, 315, 279, 35558, 2942, 315, 16993, 9186, 220, 18, 304, 13168, 311, 10065, 220, 806, 13, 305, 1174, 602, 1174, 14433, 336, 4428, 4223, 3817, 323, 62894, 258, 88896, 315, 279, 2163, 10594, 57333, 95736, 2411, 315, 279, 35558, 320, 2414, 8, 323, 279, 26587, 315, 279, 22458, 320, 1315, 570, 25635, 16283, 11, 220, 1041, 33983, 76, 13, 305, 1174, 578, 95736, 2411, 315, 10065, 220, 24, 8710, 62387, 3768, 2849, 19591, 3714, 288, 449, 9950, 486, 437, 258, 93655, 11, 2678, 27274, 84664, 65, 20274, 11, 24070, 958, 49270, 98835, 315, 43745, 57878, 11, 26878, 22761, 8839, 323, 18563, 764, 1154, 13, 578, 26587, 315, 420, 10065, 1047, 62387, 3768, 41987, 1718, 1299, 2849, 9467, 84, 337, 8200, 323, 19591, 3714, 288, 439, 1664, 439, 62387, 3768, 50938, 645, 4001, 6520, 336, 54308, 1154, 13, 602, 1174, 578, 95736, 2411, 315, 16993, 9186, 220, 806, 1047, 62016, 37314, 43364, 811, 315, 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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract For SARS-CoV-2, R0 calculations in the range of 2–3 dominate the literature, but much higher estimates have also been published. Because capacity for RT-PCR testing increased greatly in the early phase of the Covid-19 pandemic, R0 determinations based on these incidence values are subject to strong bias. We propose to use Covid-19-induced excess mortality to determine R0 regardless of RT-PCR testing capacity. We used data from the Robert Koch Institute (RKI) on the incidence of Covid cases, Covid-related deaths, number of RT-PCR tests performed, and excess mortality calculated from data from the Federal Statistical Office in Germany. We determined R0 using exponential growth estimates with a serial interval of 4.7 days. We used only datasets that were not yet under the influence of policy measures (e.g., lockdowns or school closures). The uncorrected R0 value for the spread of SARS-CoV-2 based on RT-PCR incidence data was 2.56 (95% CI 2.52–2.60) for Covid-19 cases and 2.03 (95% CI 1.96–2.10) for Covid-19-related deaths. However, because the number of RT-PCR tests increased by a growth factor of 1.381 during the same period, these R0 values must be corrected accordingly (R0corrected = R0uncorrected/1.381), yielding 1.86 for Covid-19 cases and 1.47 for Covid-19 deaths. The R0 value based on excess deaths was calculated to be 1.34 (95% CI 1.32–1.37). A sine-function-based adjustment for seasonal effects of 40% corresponds to a maximum value of R0 January = 1.68 and a minimum value of R0 July = 1.01. Our calculations show an R0 that is much lower than previously thought. This relatively low range of R0 fits very well with the observed seasonal pattern of infection across Europe in 2020 and 2021, including the emergence of more contagious escape variants such as delta or omicron. In general, our study shows that excess mortality can be used as a reliable surrogate to determine the R0 in pandemic situations. Introduction The basic replication number (R0) of a virus describes the average number of secondary infections caused by an infected individual in an immunologically still naive population 1 . R0 is a key factor in predicting the spread of a virus in a population. It is also used to estimate the proportion of individuals required in a population to achieve herd immunity 2 . In addition, the magnitude of R0 can also be used to predict whether a respiratory virus in temperate climates will develop a seasonal pattern of infection (as observed with influenza viruses and endemic coronaviruses) rather than continuous transmission throughout the year 3 . R0 is influenced not only by intrinsic characteristics of the pathogen, such as its infectivity and mode of transmission, but also by characteristics of the population under study such as the population density 4 . For respiratory viruses, there are several such extrinsic characteristics that have a significant impact on the probability of transmission and thus on R0: The density of a population, the number of persons living in a household and their average vulnerability to infections, other social factors that affect the number of close contacts between infected and uninfected persons (e.g., use of public transportation, work laws when ill, etc.), and also the climate of the area in which the population is located 5 . Based on data from 425 confirmed cases in Wuhan, R0 of SARS-CoV-2 was estimated to be 2.2 6 . Another report estimating R0 based on case reports in Wuhan yielded a higher R0 of 5.7 7 . This wide range of values is also reflected in a number of other analyses in which R0 was determined to be between 1.95 (WHO estimate) and 6.49 (all reviewed in Ref. 8 ). The German Robert-Koch-Institute (RKI) assumes an R0 in the range of 2.8–3.8 9 based on systematic reviews 10 , 11 , 12 . All these estimations of R0 have in common that they are based on incidences of SARS-CoV-2 infections detected by RT-PCR. These estimations are therefore not only dependent on the characteristics of the population under study, but also on testing strategies (e.g. representative sampling, symptom-based testing, contact-based testing of index patients, etc.) as well as rapidly increasing numbers of available and performed tests during the early weeks of the pandemic (at least, if no mathematical corrections for this increase were performed). Because SARS-CoV-2 infections have led to excess mortality in many countries worldwide 13 , the increase in excess mortality can be used as a surrogate for SARS-CoV-2 infections in order to calculate R0 independent of testing strategies and testing capacity. Here, we determined R0 for SARS-CoV-2 infections in Germany during the early phase of the pandemic in February and March 2020 based on Covid-19-associated excess mortality. For comparison, we also calculated R0 from incidence data of SARS-CoV-2 infections corrected by the increase in test capacities, as well as R0 from incidence data of RT-PCR-confirmed Covid-19-related deaths. Methods Databases The number of Covid-19 cases, Covid-19-related deaths and SARS-CoV-2-RT-PCR-tests was accessed from the Robert-Koch-Institute (RKI) website 14 . The definition of “Covid-19 case” used here is that of the RKI, which does not use the date of receipt of a positive PCR sample, but rather the date of illness, which in some cases is several days earlier 13 . In accordance with Section 11 (1) of the IfSG (Infektionsschutzgesetz), the public health authorit only reports cases of illness or death and evidence of pathogens that meet the case definition in accordance with Section11 (2) IfSG. Excess mortality was calculated from data of the Federal Statistical Office 15 . All used datasets can be downloaded as excel file from the Supplementary Material S1 . Mobility data was taken from the Apple website 16 , which provided the movement data of Apple cell phones from different countries to be used for scientific evaluation in the context of the Covid pandemic. As of April 14, 2022, Apple is no longer providing COVID-19 mobility trends reports. The datafile used for this study can be accessed in the Supplement Sect. S5 . All methods were performed in accordance with the", "role": "user" }, { "content": "In 2020, at the beginning of the pandemic, the whole of Germany was fascinated by the so-called R-value, which was published daily in the media. If it was above 1, it was clear that the pandemic would continue to spread. A value below 1, on the other hand, promised a decline in the number of infections. Values of more than 2, as calculated by the Robert Koch Institute during this time, did not bode well: they stood for an exponential spread of SARS-CoV-2. However, a study now published in the journal Scientific Reports concludes that in reality, the R-value was significantly lower than previously assumed. Scientists from the Institute of Virology and Immunobiology and the Chair of Bioinformatics at the Julius-Maximilians-Universität Würzburg (JMU) are responsible for these calculations. Lead authors are virologist Carsten Scheller and bioinformatician Thomas Dandekar. R0 value: Basis of many predictions \"The so-called basic replication number R0 of a virus describes the average number of people that an infected person infects in a population that has not yet had any contact with the virus,\" Carsten Scheller says. Accordingly, R0 is a key factor when it comes to making predictions about the spread of a virus or to estimate how many people need to become infected to achieve the goal of herd immunity. \"In addition, the R0 value can be used to predict whether a respiratory virus in temperate climates will develop more of a seasonal pattern of infection, such as influenza viruses, or whether there will be continuous transmission throughout the year,\" the virologist said. Estimates vary widely In the case of SARS-CoV-2, the R0 values determined varied significantly. An initial estimate based on data from 425 confirmed cases in Wuhan yielded a value of 2.26, while later calculations yielded 5.77. World Health Organization estimates ranged from 1.95 to 6.49, and the German Robert Koch Institute assumes an R value in the range of 2.8 to 3.89 based on systematic reviews. \"What all these estimates and calculations have in common is that they are based on the incidence of SARS-CoV-2 infections detected with a PCR test,\" says Carsten Scheller. The problem here is that these estimates depend not only on the characteristics of the population studied, but also on testing strategies and the increasing number of tests available and performed in the first weeks of the pandemic—at least if no mathematical corrections are made for this increase. Excess mortality as a basis To rid its calculations of such uncertain influencing factors, the team at the University of Würzburg decided to use a different data basis: the increase in mortality compared to pre-pandemic years, known as excess mortality. \"Since SARS-CoV-2 infection has led to increased excess mortality in many countries, these data can be used as a surrogate marker for the spread of coronavirus. And because excess mortality is independent of the number or strategy of tests performed, it provides a representative picture of the spread of infection in the general population,\" the virologist said. However, the team had to consider one important aspect: the question of the right time to collect the data. Germany, for example, had taken early measures to contain the SARS-CoV-2 epidemic—ranging from a ban on mass gatherings (March 9) to school closures (March 16) to a complete lockdown (March 23). All of these restrictions, as well as widespread media coverage, may have had an impact on the spread of the coronavirus, according to the researchers. \"For this reason, we used only deaths up to and including April 11, 2020, for our calculations. Since the infections of these deaths already occurred on average 25 days before death, the measures adopted to contain the infections could not have had any influence on the calculated value of R0,\" explains bioinformatician Thomas Dandekar. Expansion of test capacities leads to overestimation On this basis, the team concludes, \"We determined an R0 value of 1.34 for infections in March 2020, which corresponds to a seasonal range of 1.68 in January and a minimum of 1.01 in July.\" This rather low range of R0 values is much more consistent with observations of pandemic progression than many earlier and much higher estimates, according to those involved in the study. The main reasons for this overestimation, they believe, is the massive expansion of testing capacity in the early stages of the pandemic, combined with changes in testing strategy. This relatively low R0 value contributed significantly to a decline in infection numbers in the spring of 2020, according to the research group. The effects of the lockdown on the spread of the virus, therefore, may not have been as high as it might seem. Given a similar trend, therefore, any cost-benefit consideration of lockdown measures would have to be different than in the past. New virus variants may have different R-values What significance do these findings have now, given that other SARS-CoV-2 variants have long been sweeping the country? \"The new, usually more contagious variants should certainly have a different R0 value in a human population unaffected by the virus than the original variant. However, this can never be calculated again, because the population has built up a great deal of immunity through infections it has already undergone and also through vaccinations,\" explains Carsten Scheller. However, the lower R0 value of the original variant now provides a better view of the individual waves of infection. Finally, a low R value also means that herd immunity is achieved early on. Then the virus has no way to spread further, with the consequence that new variants are constantly being formed. \"So the individual waves, caused by so-called immune-escape variants, are something quite normal,\" says the virologist. Once about a third of the population is infected, these waves of the original variant break off on their own, which is important to know for planning countermeasures, he says. Limitations must be taken into account However, the authors of the study now published are aware that their model is also subject to certain limitations. For example, pandemic-related medical shortages could lead to an increase in excess mortality that is independent of a direct effect of viral infections. Such a bias would lead to an overestimation of the R value. In addition, statements about excess mortality always refer to a specific reference period, such as the previous year or, as in the case of this study, the preceding four years. Accordingly, an increase or decrease is always dependent on the development of mortality rates in the preceding years. And finally, it is a prerequisite for the determination of correct values that the share of particularly vulnerable groups in the total infection incidence does not change significantly during the analysis period. Moreover, over time, the more infectious viral variants are preferentially passed on and eventually dominate the incidence of infection. If all of these factors were taken into account, the authors of the study are convinced that excess mortality would be a valuable tool in future pandemics to determine reliable values for the rate of spread of an emerging pathogen in a population. Policy decisions could be better adapted to reality from this basis. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract For SARS-CoV-2, R0 calculations in the range of 2–3 dominate the literature, but much higher estimates have also been published. Because capacity for RT-PCR testing increased greatly in the early phase of the Covid-19 pandemic, R0 determinations based on these incidence values are subject to strong bias. We propose to use Covid-19-induced excess mortality to determine R0 regardless of RT-PCR testing capacity. We used data from the Robert Koch Institute (RKI) on the incidence of Covid cases, Covid-related deaths, number of RT-PCR tests performed, and excess mortality calculated from data from the Federal Statistical Office in Germany. We determined R0 using exponential growth estimates with a serial interval of 4.7 days. We used only datasets that were not yet under the influence of policy measures (e.g., lockdowns or school closures). The uncorrected R0 value for the spread of SARS-CoV-2 based on RT-PCR incidence data was 2.56 (95% CI 2.52–2.60) for Covid-19 cases and 2.03 (95% CI 1.96–2.10) for Covid-19-related deaths. However, because the number of RT-PCR tests increased by a growth factor of 1.381 during the same period, these R0 values must be corrected accordingly (R0corrected = R0uncorrected/1.381), yielding 1.86 for Covid-19 cases and 1.47 for Covid-19 deaths. The R0 value based on excess deaths was calculated to be 1.34 (95% CI 1.32–1.37). A sine-function-based adjustment for seasonal effects of 40% corresponds to a maximum value of R0 January = 1.68 and a minimum value of R0 July = 1.01. Our calculations show an R0 that is much lower than previously thought. This relatively low range of R0 fits very well with the observed seasonal pattern of infection across Europe in 2020 and 2021, including the emergence of more contagious escape variants such as delta or omicron. In general, our study shows that excess mortality can be used as a reliable surrogate to determine the R0 in pandemic situations. Introduction The basic replication number (R0) of a virus describes the average number of secondary infections caused by an infected individual in an immunologically still naive population 1 . R0 is a key factor in predicting the spread of a virus in a population. It is also used to estimate the proportion of individuals required in a population to achieve herd immunity 2 . In addition, the magnitude of R0 can also be used to predict whether a respiratory virus in temperate climates will develop a seasonal pattern of infection (as observed with influenza viruses and endemic coronaviruses) rather than continuous transmission throughout the year 3 . R0 is influenced not only by intrinsic characteristics of the pathogen, such as its infectivity and mode of transmission, but also by characteristics of the population under study such as the population density 4 . For respiratory viruses, there are several such extrinsic characteristics that have a significant impact on the probability of transmission and thus on R0: The density of a population, the number of persons living in a household and their average vulnerability to infections, other social factors that affect the number of close contacts between infected and uninfected persons (e.g., use of public transportation, work laws when ill, etc.), and also the climate of the area in which the population is located 5 . Based on data from 425 confirmed cases in Wuhan, R0 of SARS-CoV-2 was estimated to be 2.2 6 . Another report estimating R0 based on case reports in Wuhan yielded a higher R0 of 5.7 7 . This wide range of values is also reflected in a number of other analyses in which R0 was determined to be between 1.95 (WHO estimate) and 6.49 (all reviewed in Ref. 8 ). The German Robert-Koch-Institute (RKI) assumes an R0 in the range of 2.8–3.8 9 based on systematic reviews 10 , 11 , 12 . All these estimations of R0 have in common that they are based on incidences of SARS-CoV-2 infections detected by RT-PCR. These estimations are therefore not only dependent on the characteristics of the population under study, but also on testing strategies (e.g. representative sampling, symptom-based testing, contact-based testing of index patients, etc.) as well as rapidly increasing numbers of available and performed tests during the early weeks of the pandemic (at least, if no mathematical corrections for this increase were performed). Because SARS-CoV-2 infections have led to excess mortality in many countries worldwide 13 , the increase in excess mortality can be used as a surrogate for SARS-CoV-2 infections in order to calculate R0 independent of testing strategies and testing capacity. Here, we determined R0 for SARS-CoV-2 infections in Germany during the early phase of the pandemic in February and March 2020 based on Covid-19-associated excess mortality. For comparison, we also calculated R0 from incidence data of SARS-CoV-2 infections corrected by the increase in test capacities, as well as R0 from incidence data of RT-PCR-confirmed Covid-19-related deaths. Methods Databases The number of Covid-19 cases, Covid-19-related deaths and SARS-CoV-2-RT-PCR-tests was accessed from the Robert-Koch-Institute (RKI) website 14 . The definition of “Covid-19 case” used here is that of the RKI, which does not use the date of receipt of a positive PCR sample, but rather the date of illness, which in some cases is several days earlier 13 . In accordance with Section 11 (1) of the IfSG (Infektionsschutzgesetz), the public health authorit only reports cases of illness or death and evidence of pathogens that meet the case definition in accordance with Section11 (2) IfSG. Excess mortality was calculated from data of the Federal Statistical Office 15 . All used datasets can be downloaded as excel file from the Supplementary Material S1 . Mobility data was taken from the Apple website 16 , which provided the movement data of Apple cell phones from different countries to be used for scientific evaluation in the context of the Covid pandemic. As of April 14, 2022, Apple is no longer providing COVID-19 mobility trends reports. The datafile used for this study can be accessed in the Supplement Sect. S5 . All methods were performed in accordance with the<|im_end|> <|im_start|>assistant In 2020, at the beginning of the pandemic, the whole of Germany was fascinated by the so-called R-value, which was published daily in the media. If it was above 1, it was clear that the pandemic would continue to spread. A value below 1, on the other hand, promised a decline in the number of infections. Values of more than 2, as calculated by the Robert Koch Institute during this time, did not bode well: they stood for an exponential spread of SARS-CoV-2. However, a study now published in the journal Scientific Reports concludes that in reality, the R-value was significantly lower than previously assumed. Scientists from the Institute of Virology and Immunobiology and the Chair of Bioinformatics at the Julius-Maximilians-Universität Würzburg (JMU) are responsible for these calculations. Lead authors are virologist Carsten Scheller and bioinformatician Thomas Dandekar. R0 value: Basis of many predictions "The so-called basic replication number R0 of a virus describes the average number of people that an infected person infects in a population that has not yet had any contact with the virus," Carsten Scheller says. Accordingly, R0 is a key factor when it comes to making predictions about the spread of a virus or to estimate how many people need to become infected to achieve the goal of herd immunity. "In addition, the R0 value can be used to predict whether a respiratory virus in temperate climates will develop more of a seasonal pattern of infection, such as influenza viruses, or whether there will be continuous transmission throughout the year," the virologist said. Estimates vary widely In the case of SARS-CoV-2, the R0 values determined varied significantly. An initial estimate based on data from 425 confirmed cases in Wuhan yielded a value of 2.26, while later calculations yielded 5.77. World Health Organization estimates ranged from 1.95 to 6.49, and the German Robert Koch Institute assumes an R value in the range of 2.8 to 3.89 based on systematic reviews. "What all these estimates and calculations have in common is that they are based on the incidence of SARS-CoV-2 infections detected with a PCR test," says Carsten Scheller. The problem here is that these estimates depend not only on the characteristics of the population studied, but also on testing strategies and the increasing number of tests available and performed in the first weeks of the pandemic—at least if no mathematical corrections are made for this increase. Excess mortality as a basis To rid its calculations of such uncertain influencing factors, the team at the University of Würzburg decided to use a different data basis: the increase in mortality compared to pre-pandemic years, known as excess mortality. "Since SARS-CoV-2 infection has led to increased excess mortality in many countries, these data can be used as a surrogate marker for the spread of coronavirus. And because excess mortality is independent of the number or strategy of tests performed, it provides a representative picture of the spread of infection in the general population," the virologist said. However, the team had to consider one important aspect: the question of the right time to collect the data. Germany, for example, had taken early measures to contain the SARS-CoV-2 epidemic—ranging from a ban on mass gatherings (March 9) to school closures (March 16) to a complete lockdown (March 23). All of these restrictions, as well as widespread media coverage, may have had an impact on the spread of the coronavirus, according to the researchers. "For this reason, we used only deaths up to and including April 11, 2020, for our calculations. Since the infections of these deaths already occurred on average 25 days before death, the measures adopted to contain the infections could not have had any influence on the calculated value of R0," explains bioinformatician Thomas Dandekar. Expansion of test capacities leads to overestimation On this basis, the team concludes, "We determined an R0 value of 1.34 for infections in March 2020, which corresponds to a seasonal range of 1.68 in January and a minimum of 1.01 in July." This rather low range of R0 values is much more consistent with observations of pandemic progression than many earlier and much higher estimates, according to those involved in the study. The main reasons for this overestimation, they believe, is the massive expansion of testing capacity in the early stages of the pandemic, combined with changes in testing strategy. This relatively low R0 value contributed significantly to a decline in infection numbers in the spring of 2020, according to the research group. The effects of the lockdown on the spread of the virus, therefore, may not have been as high as it might seem. Given a similar trend, therefore, any cost-benefit consideration of lockdown measures would have to be different than in the past. New virus variants may have different R-values What significance do these findings have now, given that other SARS-CoV-2 variants have long been sweeping the country? "The new, usually more contagious variants should certainly have a different R0 value in a human population unaffected by the virus than the original variant. However, this can never be calculated again, because the population has built up a great deal of immunity through infections it has already undergone and also through vaccinations," explains Carsten Scheller. However, the lower R0 value of the original variant now provides a better view of the individual waves of infection. Finally, a low R value also means that herd immunity is achieved early on. Then the virus has no way to spread further, with the consequence that new variants are constantly being formed. "So the individual waves, caused by so-called immune-escape variants, are something quite normal," says the virologist. Once about a third of the population is infected, these waves of the original variant break off on their own, which is important to know for planning countermeasures, he says. Limitations must be taken into account However, the authors of the study now published are aware that their model is also subject to certain limitations. For example, pandemic-related medical shortages could lead to an increase in excess mortality that is independent of a direct effect of viral infections. Such a bias would lead to an overestimation of the R value. In addition, statements about excess mortality always refer to a specific reference period, such as the previous year or, as in the case of this study, the preceding four years. Accordingly, an increase or decrease is always dependent on the development of mortality rates in the preceding years. And finally, it is a prerequisite for the determination of correct values that the share of particularly vulnerable groups in the total infection incidence does not change significantly during the analysis period. Moreover, over time, the more infectious viral variants are preferentially passed on and eventually dominate the incidence of infection. If all of these factors were taken into account, the authors of the study are convinced that excess mortality would be a valuable tool in future pandemics to determine reliable values for the rate of spread of an emerging pathogen in a population. Policy decisions could be better adapted to reality from this basis. <|im_end|>

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1418, 3010, 29217, 58487, 220, 20, 13, 2813, 13, 4435, 6401, 21021, 17989, 41829, 505, 220, 16, 13, 2721, 311, 220, 21, 13, 2491, 11, 323, 279, 6063, 8563, 40593, 10181, 22204, 459, 432, 907, 304, 279, 2134, 315, 220, 17, 13, 23, 311, 220, 18, 13, 4578, 3196, 389, 37538, 8544, 13, 330, 3923, 682, 1521, 17989, 323, 29217, 617, 304, 4279, 374, 430, 814, 527, 3196, 389, 279, 39775, 315, 328, 17485, 87271, 53, 12, 17, 30020, 16914, 449, 264, 67791, 1296, 1359, 2795, 3341, 16172, 5124, 7218, 13, 578, 3575, 1618, 374, 430, 1521, 17989, 6904, 539, 1193, 389, 279, 17910, 315, 279, 7187, 20041, 11, 719, 1101, 389, 7649, 15174, 323, 279, 7859, 1396, 315, 7177, 2561, 323, 10887, 304, 279, 1176, 5672, 315, 279, 28522, 99563, 3325, 422, 912, 37072, 51479, 527, 1903, 369, 420, 5376, 13, 1398, 1140, 29528, 439, 264, 8197, 2057, 9463, 1202, 29217, 315, 1778, 36218, 66700, 9547, 11, 279, 2128, 520, 279, 3907, 315, 468, 5297, 79302, 6773, 311, 1005, 264, 2204, 828, 8197, 25, 279, 5376, 304, 29528, 7863, 311, 864, 2320, 438, 8274, 1667, 11, 3967, 439, 13937, 29528, 13, 330, 12834, 328, 17485, 87271, 53, 12, 17, 19405, 706, 6197, 311, 7319, 13937, 29528, 304, 1690, 5961, 11, 1521, 828, 649, 387, 1511, 439, 264, 73950, 11381, 369, 279, 9041, 315, 33333, 13, 1628, 1606, 13937, 29528, 374, 9678, 315, 279, 1396, 477, 8446, 315, 7177, 10887, 11, 433, 5825, 264, 18740, 6945, 315, 279, 9041, 315, 19405, 304, 279, 4689, 7187, 1359, 279, 3355, 299, 848, 380, 1071, 13, 4452, 11, 279, 2128, 1047, 311, 2980, 832, 3062, 13189, 25, 279, 3488, 315, 279, 1314, 892, 311, 6667, 279, 828, 13, 10057, 11, 369, 3187, 11, 1047, 4529, 4216, 11193, 311, 6782, 279, 328, 17485, 87271, 53, 12, 17, 42620, 2345, 81, 8764, 505, 264, 9120, 389, 3148, 66237, 320, 28623, 220, 24, 8, 311, 2978, 61000, 320, 28623, 220, 845, 8, 311, 264, 4686, 51235, 320, 28623, 220, 1419, 570, 2052, 315, 1521, 17294, 11, 439, 1664, 439, 24716, 3772, 10401, 11, 1253, 617, 1047, 459, 5536, 389, 279, 9041, 315, 279, 33333, 11, 4184, 311, 279, 12074, 13, 330, 2520, 420, 2944, 11, 584, 1511, 1193, 16779, 709, 311, 323, 2737, 5936, 220, 806, 11, 220, 2366, 15, 11, 369, 1057, 29217, 13, 8876, 279, 30020, 315, 1521, 16779, 2736, 10222, 389, 5578, 220, 914, 2919, 1603, 4648, 11, 279, 11193, 18306, 311, 6782, 279, 30020, 1436, 539, 617, 1047, 904, 10383, 389, 279, 16997, 907, 315, 432, 15, 1359, 15100, 17332, 41540, 780, 1122, 11355, 423, 438, 1247, 277, 13, 55654, 315, 1296, 59539, 11767, 311, 927, 478, 5582, 1952, 420, 8197, 11, 279, 2128, 45537, 11, 330, 1687, 11075, 459, 432, 15, 907, 315, 220, 16, 13, 1958, 369, 30020, 304, 5587, 220, 2366, 15, 11, 902, 34310, 311, 264, 36899, 2134, 315, 220, 16, 13, 2614, 304, 6186, 323, 264, 8187, 315, 220, 16, 13, 1721, 304, 5887, 1210, 1115, 4856, 3428, 2134, 315, 432, 15, 2819, 374, 1790, 810, 13263, 449, 24654, 315, 28522, 33824, 1109, 1690, 6931, 323, 1790, 5190, 17989, 11, 4184, 311, 1884, 6532, 304, 279, 4007, 13, 578, 1925, 8125, 369, 420, 927, 478, 5582, 11, 814, 4510, 11, 374, 279, 11191, 14800, 315, 7649, 8824, 304, 279, 4216, 18094, 315, 279, 28522, 11, 11093, 449, 4442, 304, 7649, 8446, 13, 1115, 12309, 3428, 432, 15, 907, 20162, 12207, 311, 264, 18174, 304, 19405, 5219, 304, 279, 10683, 315, 220, 2366, 15, 11, 4184, 311, 279, 3495, 1912, 13, 578, 6372, 315, 279, 51235, 389, 279, 9041, 315, 279, 17188, 11, 9093, 11, 1253, 539, 617, 1027, 439, 1579, 439, 433, 2643, 2873, 13, 16644, 264, 4528, 9327, 11, 9093, 11, 904, 2853, 1481, 89729, 18361, 315, 51235, 11193, 1053, 617, 311, 387, 2204, 1109, 304, 279, 3347, 13, 1561, 17188, 27103, 1253, 617, 2204, 432, 70150, 3639, 26431, 656, 1521, 14955, 617, 1457, 11, 2728, 430, 1023, 328, 17485, 87271, 53, 12, 17, 27103, 617, 1317, 1027, 42071, 279, 3224, 30, 330, 791, 502, 11, 6118, 810, 89534, 27103, 1288, 7995, 617, 264, 2204, 432, 15, 907, 304, 264, 3823, 7187, 78622, 555, 279, 17188, 1109, 279, 4113, 11678, 13, 4452, 11, 420, 649, 2646, 387, 16997, 1578, 11, 1606, 279, 7187, 706, 5918, 709, 264, 2294, 3568, 315, 40368, 1555, 30020, 433, 706, 2736, 64238, 323, 1101, 1555, 91971, 1359, 15100, 3341, 16172, 5124, 7218, 13, 4452, 11, 279, 4827, 432, 15, 907, 315, 279, 4113, 11678, 1457, 5825, 264, 2731, 1684, 315, 279, 3927, 17301, 315, 19405, 13, 17830, 11, 264, 3428, 432, 907, 1101, 3445, 430, 59213, 40368, 374, 17427, 4216, 389, 13, 5112, 279, 17188, 706, 912, 1648, 311, 9041, 4726, 11, 449, 279, 29774, 430, 502, 27103, 527, 15320, 1694, 14454, 13, 330, 4516, 279, 3927, 17301, 11, 9057, 555, 779, 19434, 22852, 12, 13295, 27103, 11, 527, 2555, 5115, 4725, 1359, 2795, 279, 3355, 299, 848, 380, 13, 9843, 922, 264, 4948, 315, 279, 7187, 374, 29374, 11, 1521, 17301, 315, 279, 4113, 11678, 1464, 1022, 389, 872, 1866, 11, 902, 374, 3062, 311, 1440, 369, 9293, 5663, 2727, 24368, 11, 568, 2795, 13, 29108, 811, 2011, 387, 4529, 1139, 2759, 4452, 11, 279, 12283, 315, 279, 4007, 1457, 4756, 527, 8010, 430, 872, 1646, 374, 1101, 3917, 311, 3738, 9669, 13, 1789, 3187, 11, 28522, 14228, 6593, 67276, 1436, 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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The RAS proteins are the most frequently mutated oncogenes in cancer, with highest frequency found in pancreatic, lung, and colon tumors. Moreover, the activity of RAS is required for the proliferation and/or survival of these tumor cells and thus represents a high-value target for therapeutic development. Direct targeting of RAS has proven challenging for multiple reasons stemming from the biology of the protein, the complexity of downstream effector pathways and upstream regulatory networks. Thus, significant efforts have been directed at identifying downstream targets on which RAS is dependent. These efforts have proven challenging, in part due to confounding factors such as reliance on two-dimensional adherent monolayer cell cultures that inadequately recapitulate the physiologic context to which cells are exposed in vivo. To overcome these issues, we implemented a high-throughput screening (HTS) approach using a spheroid-based 3-dimensional culture format, thought to more closely reflect conditions experienced by cells in vivo. Using isogenic cell pairs, differing in the status of KRAS , we identified Proscillaridin A as a selective inhibitor of cells harboring the oncogenic KRas G12V allele. Significantly, the identification of Proscillaridin A was facilitated by the 3D screening platform and would not have been discovered employing standard 2D culturing methods. Introduction The RAS proteins are a family of small GTP-binding proteins comprised of HRAS, NRAS and two splice forms of KRAS (KRAS4A and KRAS4B), which function as a switch cycling between “ON” (GTP-bound) or “OFF” (GDP-bound) conformations. They mediate signals from the extracellular environment into intracellular signaling pathways and function as master regulators in almost every aspect of cellular behavior including cell proliferation, differentiation and cell death. Given these functions, the involvement of RAS proteins in pathological conditions, such as cancer, is no surprise. Indeed, the RAS genes are the most frequently mutated oncogenes, with oncogenic mutations found in approximately 30% of all cancers [ 1 , 2 ]. Examples include mutations of KRAS found in pancreatic carcinomas (>90%), lung adenocarcinomas (>30%) and colorectal tumors (>40%). Mutations in HRAS are found mostly in bladder (>15%) and head and neck squamous cell carcinoma (>10%). NRAS mutations are found mostly in melanoma (>30%) and multiple myeloma (18%) [ 3 ]. Mutations in RAS genes cluster most frequently to codons 12, 13 and 61, all within the G-domain of the protein that is involved in nucleotide binding and hydrolysis [ 4 ]. This results in an oncogenic version of the protein that is preferentially in the “ON” state. Given the oncogenic role of RAS proteins and prevalence of mutations, they have been of great interest as therapeutic targets for decades. However, efforts to target RAS proteins directly have proven challenging [ 4 ]. The majority of efforts have focused on attacking the catalytic G-domain, as well as interference with functionally required post-translational modifications (PTMs). In the case of attacking the G-domain, the use of nucleotide analogs is problematic given the affinities of RAS proteins to GTP, the intracellular concentration of GTP and kinetics of GTP hydrolysis. Similarly, the identification of small molecules that can specifically bind to RAS proteins has proven extremely difficult. In the case of PTMs, processing of the RAS C-terminus involves farnesylation, palmitoylation, methylation and proteolysis, all processes that could potentially be targeted. Several approaches to target these processes have been attempted, again with little success [ 4 ]. Other efforts have focused on identifying indirect targets through which RAS proteins drive tumorigenesis or on which RAS proteins are dependent. Efforts to develop inhibitors of downstream effector pathways have provided a number of targets that are currently in various stages of development. Examples include the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways, which are well documented as required for RAS-driven transformation and tumorigenesis. Attempts to target these pathways have focused on development of kinase inhibitors against effectors of these pathways including RAF, mitogen-activated protein kinase (MEK) and PI3K. However, inhibition of either of these pathways alone seems to be insufficient for multiple reasons including powerful feedback mechanisms, the activation of alternate signaling pathways and the co-opting of new effectors [ 4 ]. As an alternative to targeting downstream effectors, synthetic lethality (SL) approaches have been utilized to identify targets that are non-essential when inhibited in normal cells, but are required for the viability of tumor cells expressing an oncogenic allele of KRAS [ 5 , 6 ]. Initially, the approaches taken were candidate based, relying on the known functions of select effectors. Examples include the small G-protein Rac1, the cyclin-dependent kinase CDK4, nuclear factor-κB and cyclin D1 (reviewed in Gysin et al. [ 4 ]). More recently, efforts to identify SL interactions have relied on unbiased loss-of-function approaches using RNA interference libraries to knockdown specific mRNAs in cells harboring an oncogenic RAS mutation [ 4 ]. Such efforts typically rely on lentiviral or retroviral libraries to introduce short hairpin RNA into RAS mutant cell lines. Examples include the identification of STK33—a calcium/calmodulin-dependent serine/threonine kinase [ 7 ], TBK1—a non-canonical IκB kinase [ 8 ], Polo-like kinase 1 [ 9 ], Wilm’s tumor 1 (WT1) and Snail2 [ 10 , 11 ]. These efforts have proven extremely challenging and in some cases the SL of hits could not be reproduced [ 12 , 13 , 14 ]. Another approach taken toward identification of oncogenic RAS-specific dependencies involves high-throughput screening (HTS) of small molecule libraries. The scope of these efforts has been much more limited when compared with genetic screens described above, albeit a number of compounds have been identified including sulfinyl cytidine, triphenyltetrazolium, erastin and tolperisone [ 15 , 16 , 17 , 18 , 19 ]. Further development of many of these leads is awaiting identification and confirmation of their respective targets in relevant tumor models. One potential limitation of previous screening efforts was the reliance on two-dimensional (2D) cell culture conditions, in which cells were directly plated onto plastic. These conditions vastly oversimplify the conditions to which cancer cells are exposed in vivo and are likely to be a major confounding factor. Indeed, cells grown on", "role": "user" }, { "content": "May 14, 2018—Cancer is a disease often driven by mutations in genes. As researchers learn more about these genes, and the proteins they code for, they are seeking smarter drugs to target them. The ultimate goal is to find ways to stop cancer cells from multiplying out of control, thereby blocking the growth and spread of tumors. Now researchers from The Scripps Research Institute are reporting an innovative new method to screen for potential cancer drugs. The technique makes use of tiny, three-dimensional ball-like aggregates of cells called spheroids. These structures can be used to interrogate hundreds or even thousands of compounds rapidly using a technique called high throughput screening. In fact, by using this approach, the team has already identified one potential drug for an important cancer gene. The results were reported in the journal Oncogene. \"What's important about this research is that we're able to do studies using a form of cancer cells that is more physiologically relevant and better recapitulates how these cells appear in the body,\" says Timothy Spicer, director of Lead Identification Discovery Biology and High Throughput Screening on Scripps Research's Florida campus and one of the study's corresponding authors. \"Until now, most of the research to screen for cancer drugs has used cells that are growing flat on a plate,\" adds Louis Scampavia, director of HTS Chemistry and Technologies at Scripps Research and one of the study's co-authors. \"With these 3-D spheroids, we emulate much more closely what's found in living tissues.\" The spheroids are 100 to 600 microns in diameter-equivalent to the thickness of a few sheets of paper. In contrast to single layers of cells normally used to screen for drugs, which tend to all grow at the same rate because they get the same exposure to oxygen and nutrients, the spheroids mimic what might happen in a tumor: Some cells are on the outside and some are on the inside. The researchers used a technique called confocal microscopy to confirm that the cell lines were forming spheres. Here is the BxPC-3-KRASG12V cell line. Credit: Kota et. al./The Scripps Research Institute In the new paper, the researchers focused on a cancer-driving protein called KRAS. The KRAS gene and other members of the related RAS gene family are found to be mutated in nearly one-third of all cancers. They are common in lung cancer, colorectal cancer, and especially pancreatic cancer. In fact, up to 90 percent of pancreatic cancers are driven by KRAS mutations, and the investigators used pancreatic cancer cell lines for the current study. \"In the past, KRAS has been a very tricky protein to target. People have spent several decades trying, but so far there has been little success,\" says Joseph Kissil, Ph.D., professor at Scripps Research Medicine and the other co-corresponding author. \"The KRAS protein is relatively small, and that's made it hard to attack it directly. But the method of screening that we used in this study allowed us to come at the question in a different way.\" The investigators performed what is called a phenotypic screen, which means they were looking for drugs that had an effect on cell growth, but didn't have a preconceived idea about how they might work. \"We came at this in an unbiased way,\" Kissil explains. \"We were not trying to design something to attack a specific part of the KRAS protein. We were just looking for something that acted on some part of the pathway that's driving cell growth.\" The investigators report in the new paper that they have already identified one compound that was previously not know to affect KRAS, called Proscillaridin A. The compound is similar to a class of drugs used to treat some heart conditions. Although the team says this particular drug is unlikely to be developed as a cancer treatment, it validates the approach of conducting drug screenings using spheroids. \"It's unlikely we would have discovered this connection using standard 2-D methods,\" Scampavia says. \"From our perspective, this is a proof-of-principle study,\" Kissel adds. \"It shows you can look at libraries of drugs that have already been approved for other diseases, and find drugs that may also work for cancer. In theory, you could use this screening method for any line of cancer cells, and any mutation you want.\" \"We would love to use this research to create a pipeline for new oncology drugs,\" Spicer concludes. \"Many of the most promising compounds may be overlooked with 2-D screening. This study provides direct evidence that screening for drugs using 3-D structures of cancer cells may be more appropriate.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The RAS proteins are the most frequently mutated oncogenes in cancer, with highest frequency found in pancreatic, lung, and colon tumors. Moreover, the activity of RAS is required for the proliferation and/or survival of these tumor cells and thus represents a high-value target for therapeutic development. Direct targeting of RAS has proven challenging for multiple reasons stemming from the biology of the protein, the complexity of downstream effector pathways and upstream regulatory networks. Thus, significant efforts have been directed at identifying downstream targets on which RAS is dependent. These efforts have proven challenging, in part due to confounding factors such as reliance on two-dimensional adherent monolayer cell cultures that inadequately recapitulate the physiologic context to which cells are exposed in vivo. To overcome these issues, we implemented a high-throughput screening (HTS) approach using a spheroid-based 3-dimensional culture format, thought to more closely reflect conditions experienced by cells in vivo. Using isogenic cell pairs, differing in the status of KRAS , we identified Proscillaridin A as a selective inhibitor of cells harboring the oncogenic KRas G12V allele. Significantly, the identification of Proscillaridin A was facilitated by the 3D screening platform and would not have been discovered employing standard 2D culturing methods. Introduction The RAS proteins are a family of small GTP-binding proteins comprised of HRAS, NRAS and two splice forms of KRAS (KRAS4A and KRAS4B), which function as a switch cycling between “ON” (GTP-bound) or “OFF” (GDP-bound) conformations. They mediate signals from the extracellular environment into intracellular signaling pathways and function as master regulators in almost every aspect of cellular behavior including cell proliferation, differentiation and cell death. Given these functions, the involvement of RAS proteins in pathological conditions, such as cancer, is no surprise. Indeed, the RAS genes are the most frequently mutated oncogenes, with oncogenic mutations found in approximately 30% of all cancers [ 1 , 2 ]. Examples include mutations of KRAS found in pancreatic carcinomas (>90%), lung adenocarcinomas (>30%) and colorectal tumors (>40%). Mutations in HRAS are found mostly in bladder (>15%) and head and neck squamous cell carcinoma (>10%). NRAS mutations are found mostly in melanoma (>30%) and multiple myeloma (18%) [ 3 ]. Mutations in RAS genes cluster most frequently to codons 12, 13 and 61, all within the G-domain of the protein that is involved in nucleotide binding and hydrolysis [ 4 ]. This results in an oncogenic version of the protein that is preferentially in the “ON” state. Given the oncogenic role of RAS proteins and prevalence of mutations, they have been of great interest as therapeutic targets for decades. However, efforts to target RAS proteins directly have proven challenging [ 4 ]. The majority of efforts have focused on attacking the catalytic G-domain, as well as interference with functionally required post-translational modifications (PTMs). In the case of attacking the G-domain, the use of nucleotide analogs is problematic given the affinities of RAS proteins to GTP, the intracellular concentration of GTP and kinetics of GTP hydrolysis. Similarly, the identification of small molecules that can specifically bind to RAS proteins has proven extremely difficult. In the case of PTMs, processing of the RAS C-terminus involves farnesylation, palmitoylation, methylation and proteolysis, all processes that could potentially be targeted. Several approaches to target these processes have been attempted, again with little success [ 4 ]. Other efforts have focused on identifying indirect targets through which RAS proteins drive tumorigenesis or on which RAS proteins are dependent. Efforts to develop inhibitors of downstream effector pathways have provided a number of targets that are currently in various stages of development. Examples include the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways, which are well documented as required for RAS-driven transformation and tumorigenesis. Attempts to target these pathways have focused on development of kinase inhibitors against effectors of these pathways including RAF, mitogen-activated protein kinase (MEK) and PI3K. However, inhibition of either of these pathways alone seems to be insufficient for multiple reasons including powerful feedback mechanisms, the activation of alternate signaling pathways and the co-opting of new effectors [ 4 ]. As an alternative to targeting downstream effectors, synthetic lethality (SL) approaches have been utilized to identify targets that are non-essential when inhibited in normal cells, but are required for the viability of tumor cells expressing an oncogenic allele of KRAS [ 5 , 6 ]. Initially, the approaches taken were candidate based, relying on the known functions of select effectors. Examples include the small G-protein Rac1, the cyclin-dependent kinase CDK4, nuclear factor-κB and cyclin D1 (reviewed in Gysin et al. [ 4 ]). More recently, efforts to identify SL interactions have relied on unbiased loss-of-function approaches using RNA interference libraries to knockdown specific mRNAs in cells harboring an oncogenic RAS mutation [ 4 ]. Such efforts typically rely on lentiviral or retroviral libraries to introduce short hairpin RNA into RAS mutant cell lines. Examples include the identification of STK33—a calcium/calmodulin-dependent serine/threonine kinase [ 7 ], TBK1—a non-canonical IκB kinase [ 8 ], Polo-like kinase 1 [ 9 ], Wilm’s tumor 1 (WT1) and Snail2 [ 10 , 11 ]. These efforts have proven extremely challenging and in some cases the SL of hits could not be reproduced [ 12 , 13 , 14 ]. Another approach taken toward identification of oncogenic RAS-specific dependencies involves high-throughput screening (HTS) of small molecule libraries. The scope of these efforts has been much more limited when compared with genetic screens described above, albeit a number of compounds have been identified including sulfinyl cytidine, triphenyltetrazolium, erastin and tolperisone [ 15 , 16 , 17 , 18 , 19 ]. Further development of many of these leads is awaiting identification and confirmation of their respective targets in relevant tumor models. One potential limitation of previous screening efforts was the reliance on two-dimensional (2D) cell culture conditions, in which cells were directly plated onto plastic. These conditions vastly oversimplify the conditions to which cancer cells are exposed in vivo and are likely to be a major confounding factor. Indeed, cells grown on<|im_end|> <|im_start|>assistant May 14, 2018—Cancer is a disease often driven by mutations in genes. As researchers learn more about these genes, and the proteins they code for, they are seeking smarter drugs to target them. The ultimate goal is to find ways to stop cancer cells from multiplying out of control, thereby blocking the growth and spread of tumors. Now researchers from The Scripps Research Institute are reporting an innovative new method to screen for potential cancer drugs. The technique makes use of tiny, three-dimensional ball-like aggregates of cells called spheroids. These structures can be used to interrogate hundreds or even thousands of compounds rapidly using a technique called high throughput screening. In fact, by using this approach, the team has already identified one potential drug for an important cancer gene. The results were reported in the journal Oncogene. "What's important about this research is that we're able to do studies using a form of cancer cells that is more physiologically relevant and better recapitulates how these cells appear in the body," says Timothy Spicer, director of Lead Identification Discovery Biology and High Throughput Screening on Scripps Research's Florida campus and one of the study's corresponding authors. "Until now, most of the research to screen for cancer drugs has used cells that are growing flat on a plate," adds Louis Scampavia, director of HTS Chemistry and Technologies at Scripps Research and one of the study's co-authors. "With these 3-D spheroids, we emulate much more closely what's found in living tissues." The spheroids are 100 to 600 microns in diameter-equivalent to the thickness of a few sheets of paper. In contrast to single layers of cells normally used to screen for drugs, which tend to all grow at the same rate because they get the same exposure to oxygen and nutrients, the spheroids mimic what might happen in a tumor: Some cells are on the outside and some are on the inside. The researchers used a technique called confocal microscopy to confirm that the cell lines were forming spheres. Here is the BxPC-3-KRASG12V cell line. Credit: Kota et. al./The Scripps Research Institute In the new paper, the researchers focused on a cancer-driving protein called KRAS. The KRAS gene and other members of the related RAS gene family are found to be mutated in nearly one-third of all cancers. They are common in lung cancer, colorectal cancer, and especially pancreatic cancer. In fact, up to 90 percent of pancreatic cancers are driven by KRAS mutations, and the investigators used pancreatic cancer cell lines for the current study. "In the past, KRAS has been a very tricky protein to target. People have spent several decades trying, but so far there has been little success," says Joseph Kissil, Ph.D., professor at Scripps Research Medicine and the other co-corresponding author. "The KRAS protein is relatively small, and that's made it hard to attack it directly. But the method of screening that we used in this study allowed us to come at the question in a different way." The investigators performed what is called a phenotypic screen, which means they were looking for drugs that had an effect on cell growth, but didn't have a preconceived idea about how they might work. "We came at this in an unbiased way," Kissil explains. "We were not trying to design something to attack a specific part of the KRAS protein. We were just looking for something that acted on some part of the pathway that's driving cell growth." The investigators report in the new paper that they have already identified one compound that was previously not know to affect KRAS, called Proscillaridin A. The compound is similar to a class of drugs used to treat some heart conditions. Although the team says this particular drug is unlikely to be developed as a cancer treatment, it validates the approach of conducting drug screenings using spheroids. "It's unlikely we would have discovered this connection using standard 2-D methods," Scampavia says. "From our perspective, this is a proof-of-principle study," Kissel adds. "It shows you can look at libraries of drugs that have already been approved for other diseases, and find drugs that may also work for cancer. In theory, you could use this screening method for any line of cancer cells, and any mutation you want." "We would love to use this research to create a pipeline for new oncology drugs," Spicer concludes. "Many of the most promising compounds may be overlooked with 2-D screening. This study provides direct evidence that screening for drugs using 3-D structures of cancer cells may be more appropriate." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Automated long haul trucking is being developed for commercial deployment in the United States. One possible mode of deployment for this technology is a “transfer-hub” model where the operationally less complex highway driving is automated, while human drivers drive the more complex urban segment of the route. We study the possible net impacts on tractor-trailer operator-hours from this mode of deployment. Using data from the 2017 Commodity Flow Survey, we gather information on trucking shipments and the operator-hours required to fulfill those shipments. We find that up to 94% of long haul trucking operator-hours may be impacted as the technology improves to operate in all weather conditions. If the technology is however restricted to the southern states where the majority of companies are currently testing automated trucking, we find that only 10% of operator-hours are impacted. We conduct interviews with industry stakeholders including tractor-trailer operators on the feasibility of such a system of deployment. We find that an increase in short haul operation is unlikely to compensate for the loss in long haul operator-hours, despite public claims to this effect by the developers of the technology. Policymakers should consider the impact of different scenarios of deployment on the long haul trucking workforce. Introduction Automated driving technology is currently being tested on public roads in the United States in both the light vehicle and heavy duty segments. Given the likely reduced operational complexity involved in highway driving, several companies are currently working on developing automation for long haul trucking, which is designed to work as per a “transfer-hub” model (Hickman et al., 2018 ; Transport Topics, 2018 ). This would involve an automated truck (AT) completing the highway leg of the route and human drivers undertaking the more complex suburban-urban segments at both the starting and end points of the journey. Truck ports near highways would be used to switch out the trailer from the prime mover and enable this switch at both ends. For a schematic of the possible transfer-hub model see Fig. 1 . Fig. 1: Schematic showing the possible operation of a transfer-hub model where a human driven truck drives the load from the origin to the first truck port where the load is switched to an automated prime mover shown in black. This completes the highway leg of the journey to another truck port where a human driven truck takes the load from the port to the final destination. Full size image The promise of ATs has led to widespread concern about job losses in long haul trucking, which is a common profession in the United States, particularly for men with high-school educations (Wertheim, 2020 ). On the other hand, it has also been noted, often by the companies developing this technology, that long haul trucking currently faces a labor shortage and automation will create new short haul jobs, which will more than make up for the long haul jobs lost. As a result of these conflicting claims, as well as the uncertainty over the technology itself and its limitations, there is little clarity on how automated trucking will be deployed and its economic and political ramifications, such as the impact on the long haul trucking labor market. We use data from the Commodity Flow Survey (CFS) 2017 (United States Census Bureau, 2020 ), which is a dataset jointly produced by the U.S. Census Bureau, U.S. Bureau of Transportation Statistics, and the U.S. Department of Commerce. CFS produces a sample of shipments in the United States including data on the type, origin and destination, value, weight, modes of transportation, and distance shipped. We estimate the operator-hours required for different routes using origin and destination information for trucking shipments from the CFS dataset, which enables us to estimate highway and (sub)urban splits for each shipment. We consider the technological constraints of automated trucking to make more refined estimates of the possible near term impacts of automation on long haul trucking operator-hours in the United States by assessing different scenarios of deployment. We find that contrary to strong claims by companies developing this technology (Gilroy, 2019 ), the loss in long haul operator-hours is unlikely to be compensated for by an increase in demand for short haul drivers. We find large labor impacts from the deployment of the transfer-hub model, contingent on the pace of progress of automation technology’s ability to function in different operating conditions. We compare the capabilities of automation with the tasks truck drivers are required to perform through discussions with industry stakeholders, including long haul operators. This allows us to have a realistic assessment of the tasks the technology will be required to perform over the highway legs and explore the feasibility of such deployment scenarios. In this framework, where jobs are considered as a bundle of tasks, our work builds on an extensive literature in the social sciences (Acemoglu and Autor, 2011 ; Acemoglu and Restrepo, 2019 ; Arntz et al., 2016 ). Through our limited sample of interviews, we discover reluctance to shift to new modes of operation such as short haul driving that will result from any application of the transfer-hub mode of deployment. The rest of the paper is structured as follows. Section “Literature review” reviews the existing literature on job impacts of AT. Section “Methods” describes our methods for both the analysis of operator-hour impacts and semi-structured interviews. Section “Results” presents the results and section “Conclusion and policy implications” concludes. Literature review Given the relatively recent advances in automated driving technology, there are a limited number of studies that have been conducted on the job impacts of automation on truck driver jobs. Viscelli ( 2018 ) has analyzed the impact of automation based on a similar “transfer-hub” operational model assumption shown in Fig. 1 , where highway driving is automated while human drivers perform the urban segments of the route. Using revenue data from major trucking carriers and estimates of average per driver revenue, Viscelli ( 2018 ) estimates nearly 300,000 long haul jobs to be at risk. As", "role": "user" }, { "content": "As automated truck technology continues to be developed in the United States, there are still many questions about how the technology will be deployed and what its potential impacts will be on the long-haul trucking market. A new study by researchers at the University of Michigan and Carnegie Mellon University assessed how and where automation might replace operator hours in long-haul trucking. They found that up to 94% of operator hours may be impacted if automated trucking technology improves to operate in all weather conditions across the continental United States. Currently, automated trucking is being tested mainly in the Sun Belt. \"Our results suggest that the impacts of automation may not happen all at once. If automation is restricted to Sun Belt states (including Florida, Texas and Arizona)—because the technology may not initially work well in rough weather—about 10% of the operator hours will be affected,\" said study co-author Parth Vaishnav, assistant professor of sustainable systems at the U-M School for Environment and Sustainability. Using transportation data from the 2017 Commodity Flow Survey, which is produced by the U.S. Bureau of Transportation Statistics, U.S. Census Bureau and U.S. Department of Commerce, the study authors gathered information on trucking shipments and the operator hours used to fulfill those shipments. In addition, they explored different automated trucking deployment scenarios, including deployment in southern, sunny states; deployment in spring and summer months (April 1 to Sept. 30); deployment for journeys more than 500 miles; and deployment across the United States. \"Our study is the first to combine a geospatial analysis based on shipment data with an explicit consideration of the specific capabilities of automation and how those might evolve over time,\" said co-author Aniruddh Mohan, a doctoral candidate in engineering and public policy at Carnegie Mellon. The study was published online March 15 in the journal Humanities and Social Sciences Communications. Long-haul trucking is generally defined as transport that covers more than 150 miles. Several companies are currently working on developing automation for long-haul trucking that is designed to work as a \"transfer hub\" model. It would involve an automated truck completing the highway leg of the route and human drivers undertaking the more complex suburban-urban segments at both the starting and end points of the journey. Truck ports near highways would be used to switch out the trailer from the prime mover and enable this switch at both ends. Labor accounts for about two-fifths of the cost of trucking, so deploying automated technology will be seen as an attractive option for trucking companies to save money, said Vaishnav. However, there are concerns about the potential job losses for workers. \"Because trucking is viewed as one of the few jobs that give folks with a high school education the chance to make a decent living, there is a concern that automation will eliminate these jobs,\" he said. \"Some people worry that all or most of the million or more trucking jobs might be lost. \"In terms of numbers, our analysis showed that automation could eliminate a few hundred thousand jobs (as opposed to a million or more), but there is plenty of evidence to suggest that for most people these are fleeting, poorly paid and unpleasant jobs. We think that it is possible that the number of operator hours lost at truck stops, because automated trucks will have no drivers who need to be served at truck stops, could be compensated by new employment opportunities at transfer hub ports.\" The researchers also analyzed if automated trucking could lead to an increase in short-haul driving jobs, which involve transporting shipments within a 150-mile radius, and determined that the operator hours of work lost to the automation of long-haul trucking would not be made up both in terms of quantity and quality by short-haul driving work. Short-haul jobs typically pay less than long-haul jobs, the study noted, creating the potential for a reduced livelihood for workers. \"We found that an increase in short-haul operation is unlikely to compensate for the loss in long-haul operator-hours, despite public claims to this effect by the developers of the technology,\" Vaishnav said. \"As a result of these conflicting claims, as well as the uncertainty over the technology itself and its limitations, there is little clarity on how automated trucking will be deployed and its economic and political ramifications, such as the impact on the long-haul trucking labor market. We hope to help resolve these controversies.\" As part of their study, the researchers conducted interviews with trucking industry stakeholders, including tractor-trailer operators, to determine the feasibility of automated trucking deployment. \"A key finding was just how economically attractive this technology would be and the fact that everyone, including truckers, agreed that the interstate part of the job could be automated,\" Vaishnav said. \"Ultimately, societal and political choices can determine the mode of deployment of automated trucking capabilities, as well as the winners and losers of any shift to automation of long-haul trucking.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Automated long haul trucking is being developed for commercial deployment in the United States. One possible mode of deployment for this technology is a “transfer-hub” model where the operationally less complex highway driving is automated, while human drivers drive the more complex urban segment of the route. We study the possible net impacts on tractor-trailer operator-hours from this mode of deployment. Using data from the 2017 Commodity Flow Survey, we gather information on trucking shipments and the operator-hours required to fulfill those shipments. We find that up to 94% of long haul trucking operator-hours may be impacted as the technology improves to operate in all weather conditions. If the technology is however restricted to the southern states where the majority of companies are currently testing automated trucking, we find that only 10% of operator-hours are impacted. We conduct interviews with industry stakeholders including tractor-trailer operators on the feasibility of such a system of deployment. We find that an increase in short haul operation is unlikely to compensate for the loss in long haul operator-hours, despite public claims to this effect by the developers of the technology. Policymakers should consider the impact of different scenarios of deployment on the long haul trucking workforce. Introduction Automated driving technology is currently being tested on public roads in the United States in both the light vehicle and heavy duty segments. Given the likely reduced operational complexity involved in highway driving, several companies are currently working on developing automation for long haul trucking, which is designed to work as per a “transfer-hub” model (Hickman et al., 2018 ; Transport Topics, 2018 ). This would involve an automated truck (AT) completing the highway leg of the route and human drivers undertaking the more complex suburban-urban segments at both the starting and end points of the journey. Truck ports near highways would be used to switch out the trailer from the prime mover and enable this switch at both ends. For a schematic of the possible transfer-hub model see Fig. 1 . Fig. 1: Schematic showing the possible operation of a transfer-hub model where a human driven truck drives the load from the origin to the first truck port where the load is switched to an automated prime mover shown in black. This completes the highway leg of the journey to another truck port where a human driven truck takes the load from the port to the final destination. Full size image The promise of ATs has led to widespread concern about job losses in long haul trucking, which is a common profession in the United States, particularly for men with high-school educations (Wertheim, 2020 ). On the other hand, it has also been noted, often by the companies developing this technology, that long haul trucking currently faces a labor shortage and automation will create new short haul jobs, which will more than make up for the long haul jobs lost. As a result of these conflicting claims, as well as the uncertainty over the technology itself and its limitations, there is little clarity on how automated trucking will be deployed and its economic and political ramifications, such as the impact on the long haul trucking labor market. We use data from the Commodity Flow Survey (CFS) 2017 (United States Census Bureau, 2020 ), which is a dataset jointly produced by the U.S. Census Bureau, U.S. Bureau of Transportation Statistics, and the U.S. Department of Commerce. CFS produces a sample of shipments in the United States including data on the type, origin and destination, value, weight, modes of transportation, and distance shipped. We estimate the operator-hours required for different routes using origin and destination information for trucking shipments from the CFS dataset, which enables us to estimate highway and (sub)urban splits for each shipment. We consider the technological constraints of automated trucking to make more refined estimates of the possible near term impacts of automation on long haul trucking operator-hours in the United States by assessing different scenarios of deployment. We find that contrary to strong claims by companies developing this technology (Gilroy, 2019 ), the loss in long haul operator-hours is unlikely to be compensated for by an increase in demand for short haul drivers. We find large labor impacts from the deployment of the transfer-hub model, contingent on the pace of progress of automation technology’s ability to function in different operating conditions. We compare the capabilities of automation with the tasks truck drivers are required to perform through discussions with industry stakeholders, including long haul operators. This allows us to have a realistic assessment of the tasks the technology will be required to perform over the highway legs and explore the feasibility of such deployment scenarios. In this framework, where jobs are considered as a bundle of tasks, our work builds on an extensive literature in the social sciences (Acemoglu and Autor, 2011 ; Acemoglu and Restrepo, 2019 ; Arntz et al., 2016 ). Through our limited sample of interviews, we discover reluctance to shift to new modes of operation such as short haul driving that will result from any application of the transfer-hub mode of deployment. The rest of the paper is structured as follows. Section “Literature review” reviews the existing literature on job impacts of AT. Section “Methods” describes our methods for both the analysis of operator-hour impacts and semi-structured interviews. Section “Results” presents the results and section “Conclusion and policy implications” concludes. Literature review Given the relatively recent advances in automated driving technology, there are a limited number of studies that have been conducted on the job impacts of automation on truck driver jobs. Viscelli ( 2018 ) has analyzed the impact of automation based on a similar “transfer-hub” operational model assumption shown in Fig. 1 , where highway driving is automated while human drivers perform the urban segments of the route. Using revenue data from major trucking carriers and estimates of average per driver revenue, Viscelli ( 2018 ) estimates nearly 300,000 long haul jobs to be at risk. As<|im_end|> <|im_start|>assistant As automated truck technology continues to be developed in the United States, there are still many questions about how the technology will be deployed and what its potential impacts will be on the long-haul trucking market. A new study by researchers at the University of Michigan and Carnegie Mellon University assessed how and where automation might replace operator hours in long-haul trucking. They found that up to 94% of operator hours may be impacted if automated trucking technology improves to operate in all weather conditions across the continental United States. Currently, automated trucking is being tested mainly in the Sun Belt. "Our results suggest that the impacts of automation may not happen all at once. If automation is restricted to Sun Belt states (including Florida, Texas and Arizona)—because the technology may not initially work well in rough weather—about 10% of the operator hours will be affected," said study co-author Parth Vaishnav, assistant professor of sustainable systems at the U-M School for Environment and Sustainability. Using transportation data from the 2017 Commodity Flow Survey, which is produced by the U.S. Bureau of Transportation Statistics, U.S. Census Bureau and U.S. Department of Commerce, the study authors gathered information on trucking shipments and the operator hours used to fulfill those shipments. In addition, they explored different automated trucking deployment scenarios, including deployment in southern, sunny states; deployment in spring and summer months (April 1 to Sept. 30); deployment for journeys more than 500 miles; and deployment across the United States. "Our study is the first to combine a geospatial analysis based on shipment data with an explicit consideration of the specific capabilities of automation and how those might evolve over time," said co-author Aniruddh Mohan, a doctoral candidate in engineering and public policy at Carnegie Mellon. The study was published online March 15 in the journal Humanities and Social Sciences Communications. Long-haul trucking is generally defined as transport that covers more than 150 miles. Several companies are currently working on developing automation for long-haul trucking that is designed to work as a "transfer hub" model. It would involve an automated truck completing the highway leg of the route and human drivers undertaking the more complex suburban-urban segments at both the starting and end points of the journey. Truck ports near highways would be used to switch out the trailer from the prime mover and enable this switch at both ends. Labor accounts for about two-fifths of the cost of trucking, so deploying automated technology will be seen as an attractive option for trucking companies to save money, said Vaishnav. However, there are concerns about the potential job losses for workers. "Because trucking is viewed as one of the few jobs that give folks with a high school education the chance to make a decent living, there is a concern that automation will eliminate these jobs," he said. "Some people worry that all or most of the million or more trucking jobs might be lost. "In terms of numbers, our analysis showed that automation could eliminate a few hundred thousand jobs (as opposed to a million or more), but there is plenty of evidence to suggest that for most people these are fleeting, poorly paid and unpleasant jobs. We think that it is possible that the number of operator hours lost at truck stops, because automated trucks will have no drivers who need to be served at truck stops, could be compensated by new employment opportunities at transfer hub ports." The researchers also analyzed if automated trucking could lead to an increase in short-haul driving jobs, which involve transporting shipments within a 150-mile radius, and determined that the operator hours of work lost to the automation of long-haul trucking would not be made up both in terms of quantity and quality by short-haul driving work. Short-haul jobs typically pay less than long-haul jobs, the study noted, creating the potential for a reduced livelihood for workers. "We found that an increase in short-haul operation is unlikely to compensate for the loss in long-haul operator-hours, despite public claims to this effect by the developers of the technology," Vaishnav said. "As a result of these conflicting claims, as well as the uncertainty over the technology itself and its limitations, there is little clarity on how automated trucking will be deployed and its economic and political ramifications, such as the impact on the long-haul trucking labor market. We hope to help resolve these controversies." As part of their study, the researchers conducted interviews with trucking industry stakeholders, including tractor-trailer operators, to determine the feasibility of automated trucking deployment. "A key finding was just how economically attractive this technology would be and the fact that everyone, including truckers, agreed that the interstate part of the job could be automated," Vaishnav said. "Ultimately, societal and political choices can determine the mode of deployment of automated trucking capabilities, as well as the winners and losers of any shift to automation of long-haul trucking." <|im_end|>

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2,263

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Parvalbumin-positive (PV + ) GABAergic interneurons in hippocampal microcircuits are thought to play a key role in several higher network functions, such as feedforward and feedback inhibition, network oscillations, and pattern separation. Fast lateral inhibition mediated by GABAergic interneurons may implement a winner-takes-all mechanism in the hippocampal input layer. However, it is not clear whether the functional connectivity rules of granule cells (GCs) and interneurons in the dentate gyrus are consistent with such a mechanism. Using simultaneous patch-clamp recordings from up to seven GCs and up to four PV + interneurons in the dentate gyrus, we find that connectivity is structured in space, synapse-specific, and enriched in specific disynaptic motifs. In contrast to the neocortex, lateral inhibition in the dentate gyrus (in which a GC inhibits neighboring GCs via a PV + interneuron) is ~ 10-times more abundant than recurrent inhibition (in which a GC inhibits itself). Thus, unique connectivity rules may enable the dentate gyrus to perform specific higher-order computations. Introduction Throughout the brain, fast-spiking, parvalbumin-expressing (PV + ) GABAergic interneurons play a key role in several higher functions, such as feedforward and feedback inhibition, high-frequency network oscillations, and pattern separation 1 . Understanding how PV + interneurons contribute to these complex computations requires a detailed and quantitative analysis of their synaptic connectivity. While early studies suggested that connectivity of PV + interneurons is random 2 , more recent work highlighted several specific connectivity rules 3 , 4 , 5 , 6 , 7 (Supplementary Table 1 ). Analysis of principal neuron (PN)–interneuron (IN) connectivity in the neocortex revealed that reciprocally connected pairs occurred much more frequently than expected in a random network 3 , 4 , 5 , 6 , 7 . Moreover, synaptic strength appeared to be higher in these reciprocally connected motifs 4 , 6 . Whether these connectivity rules also apply in other microcircuits, such as the hippocampus, has not been determined yet. Pattern separation is a fundamental network computation in which PV + interneurons are likely to be involved. Pattern separation is thought to be particularly important in the dentate gyrus, where conversion of overlapping synaptic input patterns into non-overlapping action potential (AP) output patterns 8 , 9 , 10 , 11 , 12 may facilitate reliable storage of information in the downstream CA3 network 9 , 13 , 14 . Previous studies suggested a model of pattern separation based on a winner-takes-all mechanism mediated by feedback inhibition 15 , 16 , 17 , 18 , 19 . Such a model has received experimental support in the olfactory system 20 , 21 , 22 . While some studies suggested that similar mechanisms may operate in the dentate gyrus 23 , 24 , it is not clear whether the rules of PN–IN connectivity are adequate to support such a model. Specifically, two forms of feedback inhibition need to be distinguished: recurrent inhibition, in which an active PN inhibits itself via reciprocal PN–IN connections, and lateral inhibition, in which an active PN inhibits neighboring PNs but not itself 25 , 26 . A winner-takes-all mechanism likely requires lateral inhibition; recurrent inhibition may be counter-productive, because it could suppress potential winners 17 , 26 , 27 . However, in both neocortex and brain areas directly connected to the hippocampus, recurrent inhibition and lateral inhibition are equally abundant 3 , 4 , 5 , 6 , 7 (Supplementary Table 1 ). Such a circuit design would seem incompatible with efficient pattern separation. To resolve this apparent contradiction, we examined the functional connectivity rules in PN–IN networks in the dentate gyrus, using simultaneous recordings from up to seven granule cells (GCs) and up to four GABAergic interneurons. Our experiments reveal a uniquely high abundance of lateral inhibition mediated by PV + interneurons. Results Octuple recordings from neurons in the dentate gyrus To determine the functional connectivity rules between PNs and INs in the dentate gyrus, we performed simultaneous whole-cell recordings from up to eight neurons (up to seven GCs and up to four INs) in vitro (Fig. 1a, b ). PV + interneurons, somatostatin-positive (SST + ), and cholecystokinin-positive (CCK + ) interneurons were identified in genetically modified mice, obtained by crossing Cre or Flp recombinase-expressing lines with tdTomato or EGFP reporter lines. PV + interneurons showed the characteristic fast-spiking AP phenotype during sustained current injection, whereas both SST + and CCK + interneurons generated APs with lower frequency, corroborating the reliability of the genetic labeling (Supplementary Figure 1 ). Fig. 1 Octuple recording from GCs and PV + interneurons in the dentate gyrus. a Octuple recording from five GCs and two PV + interneurons (seven cells successfully recorded). Infrared differential interference contrast video micrograph of the dentate gyrus in a 300-µm slice preparation, with eight recording pipettes. Shaded areas represent the 2D projections of cell bodies (blue, GCs; red and yellow, PV + interneurons). Blue dashed lines, boundaries of GC layer. b Partial reconstruction of one GC and two PV + interneurons in the same recording as shown in ( a ). Cells were filled with biocytin during recording and visualized using 3,3′-diaminobenzidine as chromogen. For clarity, only the somatodendritic domains were drawn for the PV + interneurons. Insets, biocytin-labeled putative synaptic contacts, corresponding to boxes in main figure. c Connectivity matrix of an octuple recording (all eight cells successfully recorded). Subpanels on the diagonal (AP traces) represent the presynaptic cells, subpanels outside the diagonal (EPSC or IPSC traces) indicate postsynaptic cells. In this example, 56 connections were tested; 7 excitatory GC–PV + interneuron connections, 7 inhibitory PV + interneuron–GC connections, and 42 connections between GCs. Brief transients in a subset of traces represent capacitive coupling artifacts, as shown in previous publications 5 , 14 . d Expanded view of presynaptic APs and postsynaptic currents, corresponding to the boxed areas in ( c ). In this octuple recording, an inhibitory synaptic connection was identified between the PV + interneuron (red) and GC 5 (blue) and an excitatory synaptic connection was found between GC 1 (blue) and the", "role": "user" }, { "content": "Digital reconstruction of the two parvalbumin-expressing interneurons (red and yellow) and one granular cell (blue) and visualization of the synaptic connections (black & white photographs). Credit: Espinoza et al When you park in the office car park, you usually have no problem finding your car again at the end of the day. The next day, you might park a few spots further away. However, in the evening, you find your car, even though the memories of both days are very similar. You find your car (also) because our brains are able to store memories of very similar events as distinct memories in a process called pattern separation. Researchers at the Institute of Science and Technology Austria (IST Austria) are deciphering how the brain computes this pattern separation in a brain region called the dentate gyrus. Results of their work are published today in Nature Communications. Peter Jonas and his team, including first author and Ph.D. student Claudia Espinoza, Jose Guzman and Xiaomin Zhang sought to understand how the connections between neurons in the dentate gyrus, a part of the hippocampus, enable the separation of patterns in mice. In the dentate gyrus, two types of neurons send signals: principal neurons send excitatory signals, while interneurons send inhibitory signals. The researchers sought to decipher the rules of connectivity between them—which neurons send signals to each other, whether connections between neurons are reciprocal, and whether many neurons converge to send signals to one main neuron. They recorded signaling between neurons to understand how the neurons are connected and how the local circuit works to support pattern separation. Espinoza performed octuple whole-cell recordings, in which she stimulated one neuron in a slice of the dentate gyrus, and recorded how the other seven neurons responded. By labeling all stimulated neurons, she could then reconstruct the morphology of the circuit. The researchers found that the parvalbumin-expressing interneurons are connected in a specific way only in the dentate gyrus. In the dentate gyrus, parvalbumin-expressing interneurons mainly inhibit the activity of nearby neurons in a process called lateral inhibition. In other brain regions, such as the neocortex, parvalbumin-expressing interneurons are not connected in this manner. \"We think that the unique connectivity rules established by parvalbumin-expressing interneurons, such as lateral inhibition, represent a circuit adaptation to specific network functions that occur in this brain region,\" says Claudia Espinoza. \"Our experimental data supports the idea that pattern separation works through a mechanism called 'winner-takes-all,' achieved via lateral inhibition in the dentate gyrus. However, this has not been proven yet. We need behavioral data and computational models, which we are working on.\" After the dentate gyrus separates similar memories to avoid an overlap between them, the CA3 region of the hippocampus then stores these memories. In a previous article published in Science in 2016, Peter Jonas and Jose Guzman showed that the connectivity in the CA3 region of the hippocampus is designed to recall information of stored memories in a process called pattern completion. \"At a biological level, our group found the connectivity rules that support the computational function of a brain region,\" says Espinoza, \"Our work contributes to showing how local circuits are optimized for the specific function of a brain area. While the input that reaches the dentate gyrus is important, the way in which the dentate gyrus then computes this information to achieve pattern separation is crucial.\" Claudia Espinoza is a Ph.D. student in the group of Peter Jonas. Before she joined IST Austria for her Ph.D. studies in 2013, she worked with patients with neurological disorders. This experience motivated Espinoza to pursue a Ph.D. in neuroscience: \"I realized that my work as a therapist was very limited because the treatment that we could offer to our patients was very scarce, and actually most of the available treatments are palliative and not curative. The main reason is that the information available about how the nervous system works is very limited, more than what most people believe. This fact motivated me the most for changing my career from a therapist to a researcher. I think that creating knowledge is a beautiful way of contributing something to our society and indirectly to helping people.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Parvalbumin-positive (PV + ) GABAergic interneurons in hippocampal microcircuits are thought to play a key role in several higher network functions, such as feedforward and feedback inhibition, network oscillations, and pattern separation. Fast lateral inhibition mediated by GABAergic interneurons may implement a winner-takes-all mechanism in the hippocampal input layer. However, it is not clear whether the functional connectivity rules of granule cells (GCs) and interneurons in the dentate gyrus are consistent with such a mechanism. Using simultaneous patch-clamp recordings from up to seven GCs and up to four PV + interneurons in the dentate gyrus, we find that connectivity is structured in space, synapse-specific, and enriched in specific disynaptic motifs. In contrast to the neocortex, lateral inhibition in the dentate gyrus (in which a GC inhibits neighboring GCs via a PV + interneuron) is ~ 10-times more abundant than recurrent inhibition (in which a GC inhibits itself). Thus, unique connectivity rules may enable the dentate gyrus to perform specific higher-order computations. Introduction Throughout the brain, fast-spiking, parvalbumin-expressing (PV + ) GABAergic interneurons play a key role in several higher functions, such as feedforward and feedback inhibition, high-frequency network oscillations, and pattern separation 1 . Understanding how PV + interneurons contribute to these complex computations requires a detailed and quantitative analysis of their synaptic connectivity. While early studies suggested that connectivity of PV + interneurons is random 2 , more recent work highlighted several specific connectivity rules 3 , 4 , 5 , 6 , 7 (Supplementary Table 1 ). Analysis of principal neuron (PN)–interneuron (IN) connectivity in the neocortex revealed that reciprocally connected pairs occurred much more frequently than expected in a random network 3 , 4 , 5 , 6 , 7 . Moreover, synaptic strength appeared to be higher in these reciprocally connected motifs 4 , 6 . Whether these connectivity rules also apply in other microcircuits, such as the hippocampus, has not been determined yet. Pattern separation is a fundamental network computation in which PV + interneurons are likely to be involved. Pattern separation is thought to be particularly important in the dentate gyrus, where conversion of overlapping synaptic input patterns into non-overlapping action potential (AP) output patterns 8 , 9 , 10 , 11 , 12 may facilitate reliable storage of information in the downstream CA3 network 9 , 13 , 14 . Previous studies suggested a model of pattern separation based on a winner-takes-all mechanism mediated by feedback inhibition 15 , 16 , 17 , 18 , 19 . Such a model has received experimental support in the olfactory system 20 , 21 , 22 . While some studies suggested that similar mechanisms may operate in the dentate gyrus 23 , 24 , it is not clear whether the rules of PN–IN connectivity are adequate to support such a model. Specifically, two forms of feedback inhibition need to be distinguished: recurrent inhibition, in which an active PN inhibits itself via reciprocal PN–IN connections, and lateral inhibition, in which an active PN inhibits neighboring PNs but not itself 25 , 26 . A winner-takes-all mechanism likely requires lateral inhibition; recurrent inhibition may be counter-productive, because it could suppress potential winners 17 , 26 , 27 . However, in both neocortex and brain areas directly connected to the hippocampus, recurrent inhibition and lateral inhibition are equally abundant 3 , 4 , 5 , 6 , 7 (Supplementary Table 1 ). Such a circuit design would seem incompatible with efficient pattern separation. To resolve this apparent contradiction, we examined the functional connectivity rules in PN–IN networks in the dentate gyrus, using simultaneous recordings from up to seven granule cells (GCs) and up to four GABAergic interneurons. Our experiments reveal a uniquely high abundance of lateral inhibition mediated by PV + interneurons. Results Octuple recordings from neurons in the dentate gyrus To determine the functional connectivity rules between PNs and INs in the dentate gyrus, we performed simultaneous whole-cell recordings from up to eight neurons (up to seven GCs and up to four INs) in vitro (Fig. 1a, b ). PV + interneurons, somatostatin-positive (SST + ), and cholecystokinin-positive (CCK + ) interneurons were identified in genetically modified mice, obtained by crossing Cre or Flp recombinase-expressing lines with tdTomato or EGFP reporter lines. PV + interneurons showed the characteristic fast-spiking AP phenotype during sustained current injection, whereas both SST + and CCK + interneurons generated APs with lower frequency, corroborating the reliability of the genetic labeling (Supplementary Figure 1 ). Fig. 1 Octuple recording from GCs and PV + interneurons in the dentate gyrus. a Octuple recording from five GCs and two PV + interneurons (seven cells successfully recorded). Infrared differential interference contrast video micrograph of the dentate gyrus in a 300-µm slice preparation, with eight recording pipettes. Shaded areas represent the 2D projections of cell bodies (blue, GCs; red and yellow, PV + interneurons). Blue dashed lines, boundaries of GC layer. b Partial reconstruction of one GC and two PV + interneurons in the same recording as shown in ( a ). Cells were filled with biocytin during recording and visualized using 3,3′-diaminobenzidine as chromogen. For clarity, only the somatodendritic domains were drawn for the PV + interneurons. Insets, biocytin-labeled putative synaptic contacts, corresponding to boxes in main figure. c Connectivity matrix of an octuple recording (all eight cells successfully recorded). Subpanels on the diagonal (AP traces) represent the presynaptic cells, subpanels outside the diagonal (EPSC or IPSC traces) indicate postsynaptic cells. In this example, 56 connections were tested; 7 excitatory GC–PV + interneuron connections, 7 inhibitory PV + interneuron–GC connections, and 42 connections between GCs. Brief transients in a subset of traces represent capacitive coupling artifacts, as shown in previous publications 5 , 14 . d Expanded view of presynaptic APs and postsynaptic currents, corresponding to the boxed areas in ( c ). In this octuple recording, an inhibitory synaptic connection was identified between the PV + interneuron (red) and GC 5 (blue) and an excitatory synaptic connection was found between GC 1 (blue) and the<|im_end|> <|im_start|>assistant Digital reconstruction of the two parvalbumin-expressing interneurons (red and yellow) and one granular cell (blue) and visualization of the synaptic connections (black & white photographs). Credit: Espinoza et al When you park in the office car park, you usually have no problem finding your car again at the end of the day. The next day, you might park a few spots further away. However, in the evening, you find your car, even though the memories of both days are very similar. You find your car (also) because our brains are able to store memories of very similar events as distinct memories in a process called pattern separation. Researchers at the Institute of Science and Technology Austria (IST Austria) are deciphering how the brain computes this pattern separation in a brain region called the dentate gyrus. Results of their work are published today in Nature Communications. Peter Jonas and his team, including first author and Ph.D. student Claudia Espinoza, Jose Guzman and Xiaomin Zhang sought to understand how the connections between neurons in the dentate gyrus, a part of the hippocampus, enable the separation of patterns in mice. In the dentate gyrus, two types of neurons send signals: principal neurons send excitatory signals, while interneurons send inhibitory signals. The researchers sought to decipher the rules of connectivity between them—which neurons send signals to each other, whether connections between neurons are reciprocal, and whether many neurons converge to send signals to one main neuron. They recorded signaling between neurons to understand how the neurons are connected and how the local circuit works to support pattern separation. Espinoza performed octuple whole-cell recordings, in which she stimulated one neuron in a slice of the dentate gyrus, and recorded how the other seven neurons responded. By labeling all stimulated neurons, she could then reconstruct the morphology of the circuit. The researchers found that the parvalbumin-expressing interneurons are connected in a specific way only in the dentate gyrus. In the dentate gyrus, parvalbumin-expressing interneurons mainly inhibit the activity of nearby neurons in a process called lateral inhibition. In other brain regions, such as the neocortex, parvalbumin-expressing interneurons are not connected in this manner. "We think that the unique connectivity rules established by parvalbumin-expressing interneurons, such as lateral inhibition, represent a circuit adaptation to specific network functions that occur in this brain region," says Claudia Espinoza. "Our experimental data supports the idea that pattern separation works through a mechanism called 'winner-takes-all,' achieved via lateral inhibition in the dentate gyrus. However, this has not been proven yet. We need behavioral data and computational models, which we are working on." After the dentate gyrus separates similar memories to avoid an overlap between them, the CA3 region of the hippocampus then stores these memories. In a previous article published in Science in 2016, Peter Jonas and Jose Guzman showed that the connectivity in the CA3 region of the hippocampus is designed to recall information of stored memories in a process called pattern completion. "At a biological level, our group found the connectivity rules that support the computational function of a brain region," says Espinoza, "Our work contributes to showing how local circuits are optimized for the specific function of a brain area. While the input that reaches the dentate gyrus is important, the way in which the dentate gyrus then computes this information to achieve pattern separation is crucial." Claudia Espinoza is a Ph.D. student in the group of Peter Jonas. Before she joined IST Austria for her Ph.D. studies in 2013, she worked with patients with neurological disorders. This experience motivated Espinoza to pursue a Ph.D. in neuroscience: "I realized that my work as a therapist was very limited because the treatment that we could offer to our patients was very scarce, and actually most of the available treatments are palliative and not curative. The main reason is that the information available about how the nervous system works is very limited, more than what most people believe. This fact motivated me the most for changing my career from a therapist to a researcher. I think that creating knowledge is a beautiful way of contributing something to our society and indirectly to helping people." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract While every society can be exposed to heatwaves, some people suffer far less harm and recover more quickly than others from their occurrence. Here we project indicators of global heatwave risk associated with global warming of 1.5 and 2 °C, specified by the Paris agreement, for two future pathways of societal development representing low and high vulnerability conditions. Results suggest that at the 1.5 °C warming level, heatwave exposure in 2075 estimated for the population living in low development countries is expected to be greater than exposure at the warming level of 2 °C for the population living in very high development countries. A similar result holds for an illustrative heatwave risk index. However, the projected difference in heatwave exposure and the illustrative risk index for the low and very high development countries will be significantly reduced if global warming is stabilized below 1.5 °C, and in the presence of rapid social development. Introduction The large socioeconomic costs of heatwaves make them a crucial target for impact assessments of climate change scenarios. Recent studies have focused on changes in the frequency, intensity, and duration of extreme events that affect their risk to human society 1 , 2 , 3 , 4 , 5 , 6 , in some cases differentiating the occurrence of those hazards in low income versus high income countries 7 , 8 . According to the Intergovernmental Panel on Climate Change 9 , 10 climate change risks are determined not only by climate extremes (the hazards) but also by the exposure and vulnerability of society to these hazards 10 , 11 . Here, we analyze and discuss changes in heatwave hazard, population exposure, and a vulnerability proxy. Subsequently, we derive an illustrative heatwave risk index (IRI) as the product of the probability of its occurrence (hazard) and normalized levels of exposure and a proxy for vulnerability 12 (see Eq. ( 1 )). We calculate the IRI at two different levels of warming (1.5 °C, 2 °C) and for two alternative scenarios of societal development based on the Shared Socioeconomic Pathways (SSPs) 13 designed to explore a range of exposures, potential vulnerabilities and potential capabilities to adapt to climate change. In particular, SSP1 corresponds to a society with low population growth and rapid social and economic development (low vulnerability), whereas the SSP4 represents a future society with high population growth in currently high fertility countries and a high degree of inequality (high vulnerability) 13 . As metric for heatwave hazard we use the decadal probability of experiencing an extreme heatwave. A heatwave is defined using the Heat Wave Magnitude Index daily 14 (HWMId), which takes into account both duration and temperature anomalies of a heatwave into a single number. Extreme heatwaves are those that occur on average every five hundred years under present climate conditions (hereafter HW500Y; results for 100-year return heatwaves are shown in Supplementary ). The hazard is estimated through extreme value analysis using a block maxima approach 1 , 15 , 16 , based on multi-model ensemble simulations (four models, each with 1000 years members or more) provided by the Half A degree additional warming, Prognosis and Projected Impacts (HAPPI) project for the present climate and at warming levels of 1.5 and 2 °C (see Methods). Following recent studies 8 , 17 , 18 , we combine the projected heatwave hazard with projections of spatially explicit population density consistent with the SSPs 13 , 19 to calculate exposure. Calculations of risk usually combine exposure to a particular hazard with dose-response relationships relating exposure to an outcome of interest, such as mortality or morbidity due to heatwaves. These relationships reflect the level of vulnerability of the exposed population. Lacking such dose-response relationships for heatwaves that are applicable globally, we instead adopt the Human Development Index 20 (HDI) as an indicator of broadly defined vulnerabilility. The HDI is a composite indicator introduced by the UNDP in 1990 to assess the socioeconomic development of countries. Other studies have used Gross Domestic Product (GDP) to account for vulnerability to climate change 8 , 21 , 22 , 23 ; HDI is a more comprehensive measure than GDP as it takes income, health, and education into account. Low and very high-human-development countries are defined by using the fixed cutoff points based on quartiles of HDI values introduced by the 2014 Human Development Report ( HDI < 0.55 and HDI > 0.8, respectively (see HDR_technical_notes.pdf and Methods). HDI has been shown to outperform several more recent indices as a generic national-level index of social vulnerability to climate change 24 . HDI also shows high significant correlation with historical measures of country vulnerability to climate change such as the Notre Dame-Global Adaptation Initiative Country Index (ND-GAIN) 25 (see 'HDI versus other vulnerability indices' section). However, it is important to emphasize that HDI can neither serve as a specific (or causal) vulnerability measure to heatwaves or any other climate hazard, nor does it indicate adaptive capacities to specific heatwaves per se. We use recent projections of HDI for all countries through 2075, consistent with the demographic, economic, and education assumptions in the SSPs 26 in order to calculate the IRI in a manner that illustrates how vulnerability can affect risk, not to estimate actual heatwave risk outcomes. Here, we derive IRI to illustrate relative composite spatial patterns of hazard, exposure, and vulnerability at the global scale rather than definitive or quantitative risk estimates. We calculate normalized and non-normalized versions of IRI. In the normalized IRI, present and projected HDI and population density variables are transformed to the same range of variability before aggregation by normalizing in (0, 1) using the Johnson Cumulative Distribution Function 27 (CDF) fitted to the present period (see Methods). Normalized IRI thus represents the probability of occurrence of an extreme heatwave (HW500y) scaled by normalized population density and level of social development. An IRI of zero indicates low or negligible risk relative to the other locations, for instance due to very low population density and thus low exposure,", "role": "user" }, { "content": "A new study published in Nature Communications suggests that global warming of 1.5 or 2°C will lead to more intense and frequent extreme heatwave events. Increased socio-economic development can, however, help reduce their impact on society in low development countries. The study, which was published in January, illustrates how people living in both developed and developing countries may be at risk of being affected by extreme heatwaves. This has been done by establishing and projecting an illustrative index of global heatwave risk associated with global warming of 1.5 and 2°C for two future pathways of societal development. These scenarios represent several low and high vulnerability conditions based on UN's Human Development Index (HDI), i.e. level of education, per capita income and life expectancy. \"Findings of the study indicate that with a 1.5°C mean temperature rise in 2075, the average number of people exposed to heatwave events may be larger in low-HDI countries compared to the number of people in high-HDI countries exposed to heatwave events at a 2°C rise,\" says Sebastian Sippel, researcher at NIBIO's department for Terrestrial Ecology and co-author of the study. \"The results of our study show inequality and provide a picture of where the impacts of climate change may be felt the most,\" he adds. Sippel points out that the study is illustrative and does not fully account for the different levels of vulnerability across populations, seeing as calibrated dose-response relationships for heatwaves are unavailable for most countries. This being said, the study does provide relevant information for global-scale impacts and risk assessments linked to heatwaves. In addition, it points toward ways in which analyses of a wide range of climate risks could be strengthened. More intense heatwaves Jana Sillmann, research director at CICERO Center for International Climate Research and another co-author of the study, says that the frequency and intensity of heatwaves will increase with rising global mean temperatures. The tropics and the sub-tropics, which is where most of the least developed and developing countries are located, will in the near term experience a more rapid intensification of heatwaves. \"For instance, heatwaves that are very unusual in today's climate will by 2040 occuron a regular basisif we continue emitting greenhouse gases at the current rate,\" Sillmann says. If global warming is stabilised below 1.5°C, the risk of people in developing countries suffering serious harm during heatwaves may be significantly reduced. Furthermore, the risk may be lowered if these countries experience rapid socio-economic development. Better healthcare may lower heatwave impact \"Socio-economic development strengthens healthcare and increases the number of people having higher education and a better income. This means that people will have better access to healthcare during a heatwave, and will be better equipped to deal with heatwave impacts, such as having access to air conditioning and a home that provides some shelter from the heat,\" Sillmann explains. \"Being able to escape the heat reduces the risk of suffering from heat-induced health problems such as dehydration, heat exhaustion and heat strokes, which may all lead to premature death,\" she adds. An initial attempt for further studies Vulnerability is a complex issue which is difficult to quantify. The projections presented in the study of the heatwave hazard and exposure to it can be interpreted as the distribution of the world's populations according to the likelihood of them experiencing the hazard. The study does not account for differential levels of vulnerability across populations. Sebastian Sippel from NIBIO stresses that although the study has significance, it is important to look at it for what it is: illustrative, not necessarily reality. \"Rather than paint the full picture, our work should be considered an initial attempt to quantify global differences in heatwave hazard, exposure and illustrative risk between different warming levels and socioeconomic pathways,\" he says. \"Our hope is that the study triggers discussions about how to go about real risk quantification analyses when it comes to heatwaves and other hazards at a global scale,\" he adds. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract While every society can be exposed to heatwaves, some people suffer far less harm and recover more quickly than others from their occurrence. Here we project indicators of global heatwave risk associated with global warming of 1.5 and 2 °C, specified by the Paris agreement, for two future pathways of societal development representing low and high vulnerability conditions. Results suggest that at the 1.5 °C warming level, heatwave exposure in 2075 estimated for the population living in low development countries is expected to be greater than exposure at the warming level of 2 °C for the population living in very high development countries. A similar result holds for an illustrative heatwave risk index. However, the projected difference in heatwave exposure and the illustrative risk index for the low and very high development countries will be significantly reduced if global warming is stabilized below 1.5 °C, and in the presence of rapid social development. Introduction The large socioeconomic costs of heatwaves make them a crucial target for impact assessments of climate change scenarios. Recent studies have focused on changes in the frequency, intensity, and duration of extreme events that affect their risk to human society 1 , 2 , 3 , 4 , 5 , 6 , in some cases differentiating the occurrence of those hazards in low income versus high income countries 7 , 8 . According to the Intergovernmental Panel on Climate Change 9 , 10 climate change risks are determined not only by climate extremes (the hazards) but also by the exposure and vulnerability of society to these hazards 10 , 11 . Here, we analyze and discuss changes in heatwave hazard, population exposure, and a vulnerability proxy. Subsequently, we derive an illustrative heatwave risk index (IRI) as the product of the probability of its occurrence (hazard) and normalized levels of exposure and a proxy for vulnerability 12 (see Eq. ( 1 )). We calculate the IRI at two different levels of warming (1.5 °C, 2 °C) and for two alternative scenarios of societal development based on the Shared Socioeconomic Pathways (SSPs) 13 designed to explore a range of exposures, potential vulnerabilities and potential capabilities to adapt to climate change. In particular, SSP1 corresponds to a society with low population growth and rapid social and economic development (low vulnerability), whereas the SSP4 represents a future society with high population growth in currently high fertility countries and a high degree of inequality (high vulnerability) 13 . As metric for heatwave hazard we use the decadal probability of experiencing an extreme heatwave. A heatwave is defined using the Heat Wave Magnitude Index daily 14 (HWMId), which takes into account both duration and temperature anomalies of a heatwave into a single number. Extreme heatwaves are those that occur on average every five hundred years under present climate conditions (hereafter HW500Y; results for 100-year return heatwaves are shown in Supplementary ). The hazard is estimated through extreme value analysis using a block maxima approach 1 , 15 , 16 , based on multi-model ensemble simulations (four models, each with 1000 years members or more) provided by the Half A degree additional warming, Prognosis and Projected Impacts (HAPPI) project for the present climate and at warming levels of 1.5 and 2 °C (see Methods). Following recent studies 8 , 17 , 18 , we combine the projected heatwave hazard with projections of spatially explicit population density consistent with the SSPs 13 , 19 to calculate exposure. Calculations of risk usually combine exposure to a particular hazard with dose-response relationships relating exposure to an outcome of interest, such as mortality or morbidity due to heatwaves. These relationships reflect the level of vulnerability of the exposed population. Lacking such dose-response relationships for heatwaves that are applicable globally, we instead adopt the Human Development Index 20 (HDI) as an indicator of broadly defined vulnerabilility. The HDI is a composite indicator introduced by the UNDP in 1990 to assess the socioeconomic development of countries. Other studies have used Gross Domestic Product (GDP) to account for vulnerability to climate change 8 , 21 , 22 , 23 ; HDI is a more comprehensive measure than GDP as it takes income, health, and education into account. Low and very high-human-development countries are defined by using the fixed cutoff points based on quartiles of HDI values introduced by the 2014 Human Development Report ( HDI < 0.55 and HDI > 0.8, respectively (see HDR_technical_notes.pdf and Methods). HDI has been shown to outperform several more recent indices as a generic national-level index of social vulnerability to climate change 24 . HDI also shows high significant correlation with historical measures of country vulnerability to climate change such as the Notre Dame-Global Adaptation Initiative Country Index (ND-GAIN) 25 (see 'HDI versus other vulnerability indices' section). However, it is important to emphasize that HDI can neither serve as a specific (or causal) vulnerability measure to heatwaves or any other climate hazard, nor does it indicate adaptive capacities to specific heatwaves per se. We use recent projections of HDI for all countries through 2075, consistent with the demographic, economic, and education assumptions in the SSPs 26 in order to calculate the IRI in a manner that illustrates how vulnerability can affect risk, not to estimate actual heatwave risk outcomes. Here, we derive IRI to illustrate relative composite spatial patterns of hazard, exposure, and vulnerability at the global scale rather than definitive or quantitative risk estimates. We calculate normalized and non-normalized versions of IRI. In the normalized IRI, present and projected HDI and population density variables are transformed to the same range of variability before aggregation by normalizing in (0, 1) using the Johnson Cumulative Distribution Function 27 (CDF) fitted to the present period (see Methods). Normalized IRI thus represents the probability of occurrence of an extreme heatwave (HW500y) scaled by normalized population density and level of social development. An IRI of zero indicates low or negligible risk relative to the other locations, for instance due to very low population density and thus low exposure,<|im_end|> <|im_start|>assistant A new study published in Nature Communications suggests that global warming of 1.5 or 2°C will lead to more intense and frequent extreme heatwave events. Increased socio-economic development can, however, help reduce their impact on society in low development countries. The study, which was published in January, illustrates how people living in both developed and developing countries may be at risk of being affected by extreme heatwaves. This has been done by establishing and projecting an illustrative index of global heatwave risk associated with global warming of 1.5 and 2°C for two future pathways of societal development. These scenarios represent several low and high vulnerability conditions based on UN's Human Development Index (HDI), i.e. level of education, per capita income and life expectancy. "Findings of the study indicate that with a 1.5°C mean temperature rise in 2075, the average number of people exposed to heatwave events may be larger in low-HDI countries compared to the number of people in high-HDI countries exposed to heatwave events at a 2°C rise," says Sebastian Sippel, researcher at NIBIO's department for Terrestrial Ecology and co-author of the study. "The results of our study show inequality and provide a picture of where the impacts of climate change may be felt the most," he adds. Sippel points out that the study is illustrative and does not fully account for the different levels of vulnerability across populations, seeing as calibrated dose-response relationships for heatwaves are unavailable for most countries. This being said, the study does provide relevant information for global-scale impacts and risk assessments linked to heatwaves. In addition, it points toward ways in which analyses of a wide range of climate risks could be strengthened. More intense heatwaves Jana Sillmann, research director at CICERO Center for International Climate Research and another co-author of the study, says that the frequency and intensity of heatwaves will increase with rising global mean temperatures. The tropics and the sub-tropics, which is where most of the least developed and developing countries are located, will in the near term experience a more rapid intensification of heatwaves. "For instance, heatwaves that are very unusual in today's climate will by 2040 occuron a regular basisif we continue emitting greenhouse gases at the current rate," Sillmann says. If global warming is stabilised below 1.5°C, the risk of people in developing countries suffering serious harm during heatwaves may be significantly reduced. Furthermore, the risk may be lowered if these countries experience rapid socio-economic development. Better healthcare may lower heatwave impact "Socio-economic development strengthens healthcare and increases the number of people having higher education and a better income. This means that people will have better access to healthcare during a heatwave, and will be better equipped to deal with heatwave impacts, such as having access to air conditioning and a home that provides some shelter from the heat," Sillmann explains. "Being able to escape the heat reduces the risk of suffering from heat-induced health problems such as dehydration, heat exhaustion and heat strokes, which may all lead to premature death," she adds. An initial attempt for further studies Vulnerability is a complex issue which is difficult to quantify. The projections presented in the study of the heatwave hazard and exposure to it can be interpreted as the distribution of the world's populations according to the likelihood of them experiencing the hazard. The study does not account for differential levels of vulnerability across populations. Sebastian Sippel from NIBIO stresses that although the study has significance, it is important to look at it for what it is: illustrative, not necessarily reality. "Rather than paint the full picture, our work should be considered an initial attempt to quantify global differences in heatwave hazard, exposure and illustrative risk between different warming levels and socioeconomic pathways," he says. "Our hope is that the study triggers discussions about how to go about real risk quantification analyses when it comes to heatwaves and other hazards at a global scale," he adds. <|im_end|>

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2,148

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The lowest-lying fundamental excitation of an incommensurate charge-density-wave material is believed to be a massless phason—a collective modulation of the phase of the charge-density-wave order parameter. However, long-range Coulomb interactions should push the phason energy up to the plasma energy of the charge-density-wave condensate, resulting in a massive phason and fully gapped spectrum 1 . Using time-domain terahertz emission spectroscopy, we investigate this issue in (TaSe 4 ) 2 I, a quasi-one-dimensional charge-density-wave insulator. On transient photoexcitation at low temperatures, we find the material strikingly emits coherent, narrowband terahertz radiation. The frequency, polarization and temperature dependences of the emitted radiation imply the existence of a phason that acquires mass by coupling to long-range Coulomb interactions. Our observations underscore the role of long-range interactions in determining the nature of collective excitations in materials with modulated charge or spin order. Main The fundamental collective modes (amplitudon and phason) of a broken-symmetry ordered state (Fig. 1a ) have been key in establishing foundational theories across various fields of physics, including gauge theories in particle physics, as well as superconductors, antiferromagnets and charge-density-wave (CDW) materials in condensed-matter physics 2 , 3 . The phason is typically massless, in accordance with Goldstone’s theorem, which necessitates the emergence of a massless boson for broken symmetry in systems where the ground or vacuum state is continuously degenerate. A prominent exception occurs in superconducting systems. Here, even though the ground state is continuously degenerate, the long-range Coulomb interaction pushes the longitudinal phason up to the plasma frequency 4 , and therefore, a massless Goldstone boson does not exist and the low-lying excitation spectrum is fully gapped. This behaviour is the celebrated Anderson–Higgs mechanism that established the deep connection between symmetry breaking and gauge fields, and ultimately explained how all the fundamental particles acquire mass from interactions with the Higgs field. Fig. 1: Collective modes of an incommensurate CDW phase. a , Ginzburg–Landau free energy ( \${{{\\mathcal{F}}}}\$ ) and real-space representation of the amplitudon (dashed arrow) and phason (solid line arrow) for a CDW order parameter in the absence of long-range Coulomb interactions. b , c , Dispersion relations of the CDW collective modes. Below T CDW , the otherwise undistorted acoustic phonon (LA) softens near \${\\overrightarrow{q}}_{{{{\\rm{CDW}}}}}\$ and renormalizes into the amplitudon and phason bands. At moderate T ( ≲ T CDW ), the long-range Coulomb repulsion U is screened by quasiparticles ( b ). When the system is cooled well below T CDW , the screening weakens and the spectral weight from the massless (acoustic) phason is transferred to the massive (infrared-active) phason of frequency ω LF ( c ). Full size image Unlike superconductivity, an incommensurate CDW is believed to have a massless phason, typically understood in terms of the softening of a longitudinal acoustic phonon branch around the CDW wavevector \${\\overrightarrow{q}}_{{{{\\rm{CDW}}}}}\$ (Fig. 1b ). Below the CDW transition temperature ( T CDW ), this mode softening results in the linear-in-wavevector, zero-gap dispersion of the phason, implying that the CDW can freely slide for excitation wavevector \$\\overrightarrow{q}=0\$ . In any real material, however, random impurities and disorder restrict this sliding motion, leading to a small gap in phason dispersion (pinning frequency) (Fig. 1b ). Thus, the sliding CDW motion can only be observed if a strong enough electric field is applied to first depin the phason. The resulting sliding motion of the CDW can then be measured in d.c. transport experiments as done in various systems 5 . However, the above phenomenology of a massless phason (or disorder pinned phason at low frequency) assumes the absence of long-range Coulomb interactions ( U ). This assumption is believed to be valid because the presence of normal electrons at a non-zero temperature can screen U . However, if U is sufficiently strong or if the density of normal electrons is sufficiently low, then the CDW phason at \$\\overrightarrow{q}=0\$ should be pushed to higher energies (even above the amplitudon energy) (Fig. 1c ). This behaviour was highlighted in work on CDW dynamics 6 and then formalized in a later work 1 that noted the similarity of the emergence of a massive CDW phason with the Anderson–Higgs mechanism in a superconductor. Later works 7 , 8 predicted that the massive (optical) phason could indeed dominate over the massless (acoustic) phason at sufficiently low temperatures where charged quasiparticles cannot sufficiently screen U . Within these models, the amplitudon remains unaffected by the long-range Coulomb interaction 8 . We note that in superconductors, the plasma frequency is much larger than the single-particle gap, rendering the phase mode unobservable deep in the superconducting phase. In a CDW system, however, the relevant scale is the plasma frequency of the condensate, which can lie far below the single-particle gap. To date, direct experimental evidence of a massive phason in CDW systems has been elusive. Here we present the evidence for the generation and detection of a massive phason in the CDW insulator (TaSe 4 ) 2 I, a quasi-one-dimensional (quasi-1D) material that undergoes an incommensurate CDW transition below T CDW ≈ 260 K (refs. 9 , 10 , 11 ) with a CDW gap for single-particle excitations of 2 Δ CDW ≈ 250–300 meV (refs. 12 , 13 , 14 ). (TaSe 4 ) 2 I is unique among quasi-1D CDW systems due to its unusually high resistivity in the low-temperature insulating state ( Supplementary Information ), such that the long-range Coulomb interaction can remain unscreened and the massive phason can have substantial spectral weight. To investigate the collective modes of the CDW order in (TaSe 4 ) 2 I, we performed time-domain terahertz (THz) emission spectroscopy using an ultrafast photoexcitation ‘pump’ pulse with an energy of 1.2 eV ( λ = 1,030 nm) (Fig. 2a shows the experimental geometry and Supplementary Information provides further details of the experimental setup). Note that the photoexcitation energy here is greater than 2 Δ CDW , and therefore, the pump pulse initially creates single-particle excitations across the CDW gap. As (TaSe 4 ) 2 I is structurally chiral", "role": "user" }, { "content": "Researchers at the University of Illinois Urbana-Champaign have detected the existence of a charge density wave of electrons that acquires mass as it interacts with the background lattice ions of the material over long distances. This new research, led by assistant professor Fahad Mahmood (Physics, Materials Research Laboratory) and postdoc Soyeun Kim (current postdoc at Stanford Institute for Materials and Energy Sciences, SLAC National Accelerator Laboratory), is a direct measurement of the Anderson-Higgs mechanism (of mass acquisition) and the first known demonstration of a massive phason in a charge density wave material, a prediction made more than 40 years ago. Their paper, \"Observation of a massive phason in a charge density wave insulator,\" with these results, was recently published in Nature Materials. The collective excitations of condensed phases of matter often play a foundational role in developing fundamental theories for a variety of materials, including superconductors, quantum magnets, and charge density waves. In a simple metal, electrons are distributed uniformly across space; electron density at one point in space is equal to that of another point in space. In certain metals, however, the electron density develops a sinusoidal (wave) pattern (a charge density wave). Mahmood explains that, considering the charge density wave as frozen in space, if the wave is disturbed, it is going to \"ring\" (that is, its collective excitations are generated). It can ring by a change in the amplitude of the wave pattern, or the charge density wave can slide back and forth (phase shifting). The later collective excitation is dubbed the phason and is similar to sound waves in a material—it has negligible mass. More than 40 years ago, researchers predicted that if the phason interacts strongly with the background lattice of ions over long-distances (long-range Coulomb interactions), then it will try to drag the heavy ions as it moves. As a result, the phason will require a lot more energy to get it to move—the phason is said to \"acquire mass\". This mass acquisition of a phason is believed to occur due to the same mechanism by which all fundamental massive particles in the universe acquire mass (a phenomena known as the Anderson-Higgs mechanism). Direct observation of this mass acquisition has remained elusive, primarily because long-range Coulomb interactions do not exist in most charge density wave materials. The material used in this research, tantalum selenium iodide ((TaSe4)2I), is a very good insulator at low temperatures and is one of the best-known insulators for charge density waves. Because of that, long-range Coulomb interactions are likely to be present in the system and those interactions can give mass to the otherwise massless excitation. In theory, if the material is heated, it would become less insulating, the Coulomb interactions would weaken, and the massive phason should become massless. Mahmood, Kim, and their collaborators were able to investigate the charge density wave phason in (TaSe4)2I by developing a nonlinear optical technique known as time-domain terahertz (THz) emission spectroscopy at low temperatures (less than 10 K, -442° F). Using this technique, an ultrafast infrared laser pulse, lasting less than 150 fs (1 fs is a millionth of a billionth of second), was shined on the (TaSe4)2I sample, generating the collective excitations of the system. What they detected was the massive phason radiating in the THz region of frequencies, with a very narrow bandwidth. When they heated the material, the massive phason became massless (stopped radiating), matching up with long-standing theoretical predictions. While (TaSe4)2I is conducive to hosting a massive phason, it can be a very challenging material to work with because it grows as very thin needles making sample alignment very difficult. Kim described the process \"like trying to shine a light on the side of a chopstick\". A collaborator on this research, Daniel Shoemaker (associate professor, MatSE, UIUC), was able to grow (TaSe4)2I crystals with substantially large width, which enabled the application of THz emission spectroscopy on this material. \"It is gratifying to see that a collective mode predicted many years ago is finally seen experimentally,\" commented Patrick Lee, the William & Emma Rogers Professor of Physics at MIT, and one of the pioneers of the theoretical works predicting the massive phason in charge density waves. \"It speaks to the power of modern nonlinear optical techniques and the ingenuity of the experimentalists. The method is general, and we may see applications to other collective modes as well.\" At an applied level, generating narrowband radiation in the THz region of frequencies can be very difficult. However, due to the strikingly narrow bandwidth THz radiation resulting from the massive phason in (TaSe4)2I, the possibility of developing it (and other such materials) as a THz emitter is quite promising. The frequency and intensity of this THz emission can potentially be controlled by varying sample properties, applying external magnetic fields or strain. Mahmood summarizes, \"This is the first known demonstration of a massive phason in a charge density wave material and settles the long-standing question of whether a charge density wave phason acquires mass by coupling to long-range Coulomb interactions. This is a major result that will have a profound impact on the field of strongly correlated materials, and in the understanding of the interplay between interactions, density-wave ordering and superconductivity in materials.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The lowest-lying fundamental excitation of an incommensurate charge-density-wave material is believed to be a massless phason—a collective modulation of the phase of the charge-density-wave order parameter. However, long-range Coulomb interactions should push the phason energy up to the plasma energy of the charge-density-wave condensate, resulting in a massive phason and fully gapped spectrum 1 . Using time-domain terahertz emission spectroscopy, we investigate this issue in (TaSe 4 ) 2 I, a quasi-one-dimensional charge-density-wave insulator. On transient photoexcitation at low temperatures, we find the material strikingly emits coherent, narrowband terahertz radiation. The frequency, polarization and temperature dependences of the emitted radiation imply the existence of a phason that acquires mass by coupling to long-range Coulomb interactions. Our observations underscore the role of long-range interactions in determining the nature of collective excitations in materials with modulated charge or spin order. Main The fundamental collective modes (amplitudon and phason) of a broken-symmetry ordered state (Fig. 1a ) have been key in establishing foundational theories across various fields of physics, including gauge theories in particle physics, as well as superconductors, antiferromagnets and charge-density-wave (CDW) materials in condensed-matter physics 2 , 3 . The phason is typically massless, in accordance with Goldstone’s theorem, which necessitates the emergence of a massless boson for broken symmetry in systems where the ground or vacuum state is continuously degenerate. A prominent exception occurs in superconducting systems. Here, even though the ground state is continuously degenerate, the long-range Coulomb interaction pushes the longitudinal phason up to the plasma frequency 4 , and therefore, a massless Goldstone boson does not exist and the low-lying excitation spectrum is fully gapped. This behaviour is the celebrated Anderson–Higgs mechanism that established the deep connection between symmetry breaking and gauge fields, and ultimately explained how all the fundamental particles acquire mass from interactions with the Higgs field. Fig. 1: Collective modes of an incommensurate CDW phase. a , Ginzburg–Landau free energy ( ${{{\mathcal{F}}}}$ ) and real-space representation of the amplitudon (dashed arrow) and phason (solid line arrow) for a CDW order parameter in the absence of long-range Coulomb interactions. b , c , Dispersion relations of the CDW collective modes. Below T CDW , the otherwise undistorted acoustic phonon (LA) softens near ${\overrightarrow{q}}_{{{{\rm{CDW}}}}}$ and renormalizes into the amplitudon and phason bands. At moderate T ( ≲ T CDW ), the long-range Coulomb repulsion U is screened by quasiparticles ( b ). When the system is cooled well below T CDW , the screening weakens and the spectral weight from the massless (acoustic) phason is transferred to the massive (infrared-active) phason of frequency ω LF ( c ). Full size image Unlike superconductivity, an incommensurate CDW is believed to have a massless phason, typically understood in terms of the softening of a longitudinal acoustic phonon branch around the CDW wavevector ${\overrightarrow{q}}_{{{{\rm{CDW}}}}}$ (Fig. 1b ). Below the CDW transition temperature ( T CDW ), this mode softening results in the linear-in-wavevector, zero-gap dispersion of the phason, implying that the CDW can freely slide for excitation wavevector $\overrightarrow{q}=0$ . In any real material, however, random impurities and disorder restrict this sliding motion, leading to a small gap in phason dispersion (pinning frequency) (Fig. 1b ). Thus, the sliding CDW motion can only be observed if a strong enough electric field is applied to first depin the phason. The resulting sliding motion of the CDW can then be measured in d.c. transport experiments as done in various systems 5 . However, the above phenomenology of a massless phason (or disorder pinned phason at low frequency) assumes the absence of long-range Coulomb interactions ( U ). This assumption is believed to be valid because the presence of normal electrons at a non-zero temperature can screen U . However, if U is sufficiently strong or if the density of normal electrons is sufficiently low, then the CDW phason at $\overrightarrow{q}=0$ should be pushed to higher energies (even above the amplitudon energy) (Fig. 1c ). This behaviour was highlighted in work on CDW dynamics 6 and then formalized in a later work 1 that noted the similarity of the emergence of a massive CDW phason with the Anderson–Higgs mechanism in a superconductor. Later works 7 , 8 predicted that the massive (optical) phason could indeed dominate over the massless (acoustic) phason at sufficiently low temperatures where charged quasiparticles cannot sufficiently screen U . Within these models, the amplitudon remains unaffected by the long-range Coulomb interaction 8 . We note that in superconductors, the plasma frequency is much larger than the single-particle gap, rendering the phase mode unobservable deep in the superconducting phase. In a CDW system, however, the relevant scale is the plasma frequency of the condensate, which can lie far below the single-particle gap. To date, direct experimental evidence of a massive phason in CDW systems has been elusive. Here we present the evidence for the generation and detection of a massive phason in the CDW insulator (TaSe 4 ) 2 I, a quasi-one-dimensional (quasi-1D) material that undergoes an incommensurate CDW transition below T CDW ≈ 260 K (refs. 9 , 10 , 11 ) with a CDW gap for single-particle excitations of 2 Δ CDW ≈ 250–300 meV (refs. 12 , 13 , 14 ). (TaSe 4 ) 2 I is unique among quasi-1D CDW systems due to its unusually high resistivity in the low-temperature insulating state ( Supplementary Information ), such that the long-range Coulomb interaction can remain unscreened and the massive phason can have substantial spectral weight. To investigate the collective modes of the CDW order in (TaSe 4 ) 2 I, we performed time-domain terahertz (THz) emission spectroscopy using an ultrafast photoexcitation ‘pump’ pulse with an energy of 1.2 eV ( λ = 1,030 nm) (Fig. 2a shows the experimental geometry and Supplementary Information provides further details of the experimental setup). Note that the photoexcitation energy here is greater than 2 Δ CDW , and therefore, the pump pulse initially creates single-particle excitations across the CDW gap. As (TaSe 4 ) 2 I is structurally chiral<|im_end|> <|im_start|>assistant Researchers at the University of Illinois Urbana-Champaign have detected the existence of a charge density wave of electrons that acquires mass as it interacts with the background lattice ions of the material over long distances. This new research, led by assistant professor Fahad Mahmood (Physics, Materials Research Laboratory) and postdoc Soyeun Kim (current postdoc at Stanford Institute for Materials and Energy Sciences, SLAC National Accelerator Laboratory), is a direct measurement of the Anderson-Higgs mechanism (of mass acquisition) and the first known demonstration of a massive phason in a charge density wave material, a prediction made more than 40 years ago. Their paper, "Observation of a massive phason in a charge density wave insulator," with these results, was recently published in Nature Materials. The collective excitations of condensed phases of matter often play a foundational role in developing fundamental theories for a variety of materials, including superconductors, quantum magnets, and charge density waves. In a simple metal, electrons are distributed uniformly across space; electron density at one point in space is equal to that of another point in space. In certain metals, however, the electron density develops a sinusoidal (wave) pattern (a charge density wave). Mahmood explains that, considering the charge density wave as frozen in space, if the wave is disturbed, it is going to "ring" (that is, its collective excitations are generated). It can ring by a change in the amplitude of the wave pattern, or the charge density wave can slide back and forth (phase shifting). The later collective excitation is dubbed the phason and is similar to sound waves in a material—it has negligible mass. More than 40 years ago, researchers predicted that if the phason interacts strongly with the background lattice of ions over long-distances (long-range Coulomb interactions), then it will try to drag the heavy ions as it moves. As a result, the phason will require a lot more energy to get it to move—the phason is said to "acquire mass". This mass acquisition of a phason is believed to occur due to the same mechanism by which all fundamental massive particles in the universe acquire mass (a phenomena known as the Anderson-Higgs mechanism). Direct observation of this mass acquisition has remained elusive, primarily because long-range Coulomb interactions do not exist in most charge density wave materials. The material used in this research, tantalum selenium iodide ((TaSe4)2I), is a very good insulator at low temperatures and is one of the best-known insulators for charge density waves. Because of that, long-range Coulomb interactions are likely to be present in the system and those interactions can give mass to the otherwise massless excitation. In theory, if the material is heated, it would become less insulating, the Coulomb interactions would weaken, and the massive phason should become massless. Mahmood, Kim, and their collaborators were able to investigate the charge density wave phason in (TaSe4)2I by developing a nonlinear optical technique known as time-domain terahertz (THz) emission spectroscopy at low temperatures (less than 10 K, -442° F). Using this technique, an ultrafast infrared laser pulse, lasting less than 150 fs (1 fs is a millionth of a billionth of second), was shined on the (TaSe4)2I sample, generating the collective excitations of the system. What they detected was the massive phason radiating in the THz region of frequencies, with a very narrow bandwidth. When they heated the material, the massive phason became massless (stopped radiating), matching up with long-standing theoretical predictions. While (TaSe4)2I is conducive to hosting a massive phason, it can be a very challenging material to work with because it grows as very thin needles making sample alignment very difficult. Kim described the process "like trying to shine a light on the side of a chopstick". A collaborator on this research, Daniel Shoemaker (associate professor, MatSE, UIUC), was able to grow (TaSe4)2I crystals with substantially large width, which enabled the application of THz emission spectroscopy on this material. "It is gratifying to see that a collective mode predicted many years ago is finally seen experimentally," commented Patrick Lee, the William & Emma Rogers Professor of Physics at MIT, and one of the pioneers of the theoretical works predicting the massive phason in charge density waves. "It speaks to the power of modern nonlinear optical techniques and the ingenuity of the experimentalists. The method is general, and we may see applications to other collective modes as well." At an applied level, generating narrowband radiation in the THz region of frequencies can be very difficult. However, due to the strikingly narrow bandwidth THz radiation resulting from the massive phason in (TaSe4)2I, the possibility of developing it (and other such materials) as a THz emitter is quite promising. The frequency and intensity of this THz emission can potentially be controlled by varying sample properties, applying external magnetic fields or strain. Mahmood summarizes, "This is the first known demonstration of a massive phason in a charge density wave material and settles the long-standing question of whether a charge density wave phason acquires mass by coupling to long-range Coulomb interactions. This is a major result that will have a profound impact on the field of strongly correlated materials, and in the understanding of the interplay between interactions, density-wave ordering and superconductivity in materials." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Asgard archaea are considered to be the closest known relatives of eukaryotes. Their genomes contain hundreds of eukaryotic signature proteins (ESPs), which inspired hypotheses on the evolution of the eukaryotic cell 1 , 2 , 3 . A role of ESPs in the formation of an elaborate cytoskeleton and complex cellular structures has been postulated 4 , 5 , 6 , but never visualized. Here we describe a highly enriched culture of ‘ Candidatus Lokiarchaeum ossiferum’, a member of the Asgard phylum, which thrives anaerobically at 20 °C on organic carbon sources. It divides every 7–14 days, reaches cell densities of up to 5 × 10 7 cells per ml and has a significantly larger genome compared with the single previously cultivated Asgard strain 7 . ESPs represent 5% of its protein-coding genes, including four actin homologues. We imaged the enrichment culture using cryo-electron tomography, identifying ‘ Ca . L. ossiferum’ cells on the basis of characteristic expansion segments of their ribosomes. Cells exhibited coccoid cell bodies and a network of branched protrusions with frequent constrictions. The cell envelope consists of a single membrane and complex surface structures. A long-range cytoskeleton extends throughout the cell bodies, protrusions and constrictions. The twisted double-stranded architecture of the filaments is consistent with F-actin. Immunostaining indicates that the filaments comprise Lokiactin—one of the most highly conserved ESPs in Asgard archaea. We propose that a complex actin-based cytoskeleton predated the emergence of the first eukaryotes and was a crucial feature in the evolution of the Asgard phylum by scaffolding elaborate cellular structures. Main Soon after the discovery of archaea as a separate lineage besides bacteria, molecular and phylogenetic studies suggested that there is a deep common evolutionary descent between archaea and eukaryotes 8 , 9 . However, only recently has the discovery of the first Lokiarchaeota 10 (now Lokiarchaeia 11 ) and the wider superphylum of Asgardarchaeota in metagenomic analyses 1 , 2 , 11 , 12 , 13 , 14 , 15 , 16 , 17 corroborated a distinct relationship and a possible direct emergence of eukaryotic cells from archaea. In fact, eukaryotes form a direct sister group to Asgardarchaeota or even arise within Asgardarchaeota in most phylogenomic analyses 3 , 10 , 18 . Compellingly, all members of the Asgardarchaea carry an extensive repertoire of genes that were originally assumed to be unique to eukaryotes (ESPs) 1 , 2 , 3 , 10 , 19 , 20 . These ESPs are mostly associated with features of cells with high complexity, such as cytoskeleton formation, transport and the shaping of membranes. For example, the observation that Asgard archaeal genomes encode a complete and functional ubiquitin-coupled ESCRT system 10 , 21 suggested the possibility of elaborate intracellular membrane compartments 10 . Another notable example is genes encoding several close homologues of eukaryotic actin. While F-actin-like assemblies have been identified in other archaea 22 , 23 , Asgard archaea also possess actin-related proteins (ARPs), as well as actin-binding proteins. Notably, Asgard profilins and gelsolins were found to be able to modulate the dynamics of eukaryotic actin 5 , 19 , 24 , 25 , 26 , indicating the existence of an elaborate and dynamic cytoskeleton 4 . However, the in situ structures and functions of archaeal actins remain unclear. A seminal study 7 presented the first enrichment culture of an Asgard archaeon, ‘ Candidatus Prometheoarchaeum syntrophicum’, which grows slowly to low cell densities in syntrophic consortia with molecular-hydrogen-consuming organisms. As ‘ Ca. P. syntrophicum’ cells show long branched protrusions, the authors proposed a hypothesis for eukaryogenesis, in which a primordial Asgard archaeon closely interacts with the predecessor of the bacterial endosymbiont and eventually endogenizes it 7 , 27 . These observations were consistent with the stepwise mechanism of eukaryogenesis that was first proposed as the ‘inside out’ model 28 . The role of Asgard ESPs could so far not be investigated in the natural host, making it difficult to further test these conceptual models. Although ‘ Ca. P. syntrophicum’ was shown to transcribe ESPs, characteristics regarding its intracellular architecture could not be revealed. Fundamental questions regarding the presence of a cytoskeleton or internal compartmentalization in Asgard archaea remain unclear, as does the structure of the cell envelope. Here we combine the enrichment of an experimentally tractable Asgard archaeon with state-of-the-art imaging to reveal its cellular architecture at macromolecular detail. A Lokiarchaea culture from sediment Considering that lokiarchaeal organisms and other Asgard archaea can be found in a variety of anoxic and often marine environments 29 , 30 , we screened DNA from shallow-water sediment from different locations for the presence of 16S rRNA genes of Asgard archaea to select suitable and easily reachable sampling sites for establishing enrichments. Sediments from a small estuarine canal that regularly receives water from the Mediterranean near the coast of Piran, Slovenia, were identified to have the highest relative abundance at the 13–16 cm depth layer, exhibiting up to 4% of Asgard archaea 16S rRNA genes in amplicon sequencing (Extended Data Figs. 1 and 2 ). The identified sample was used to inoculate enrichment cultures (Fig. 1a ) with media of different compositions and various headspace conditions (Supplementary Table 1 ). With periodic monitoring using quantitative PCR (qPCR) with Lokiarchaea-specific primers (Extended Data Fig. 3 ), growth could be observed after 140 days at 20 °C in serum flasks containing sterile-filtered water from the original source supplemented with complex organics (casein hydrolysate, milk powder and amino acids). However, after two transfers under these conditions, growth could no longer be detected and a second round of screening with different medium compositions was performed. Using a modification of the medium MK-D1 reported for the cultivation of ‘ Ca. P. syntrophicum’ 7 , cell growth recovered, and abundances reached repeatedly 2–8%. However, higher enrichments, were not achieved under these conditions. Only through developing a minimal medium, mostly by reducing the input of organic carbon sources to a single compound and by increasing antibiotic concentrations, lokiarchaeal relative abundances reached between 25% and 80% after", "role": "user" }, { "content": "How did the complex organisms on Earth arise? This is one of the big open questions in biology. A collaboration between the working groups of Christa Schleper at the University of Vienna and Martin Pilhofer at ETH Zurich has come a step closer to the answer. The researchers succeeded in cultivating a special archaeon and characterizing it more precisely using microscopic methods. This member of the Asgard archaea exhibits unique cellular characteristics and may represent an evolutionary \"missing link\" to more complex life forms such as animals and plants. The study was recently published in the journal Nature. All life forms on earth are divided into three major domains: eukaryotes, bacteria and archaea. Eukaryotes include the groups of animals, plants and fungi. Their cells are usually much larger and, at first glance, more complex than the cells of bacteria and archaea. The genetic material of eukaryotes, for example, is packaged in a cell nucleus and the cells also have a large number of other compartments. Cell shape and transport within the eukaryotic cell are also based on an extensive cytoskeleton. But how did the evolutionary leap to such complex eukaryotic cells come about? Most current models assume that archaea and bacteria played a central role in the evolution of eukaryotes. A eukaryotic primordial cell is believed to have evolved from a close symbiosis between archaea and bacteria about two billion years ago. In 2015, genomic studies of deep-sea environmental samples discovered the group of the so-called \"Asgard archaea\", which in the tree of life represent the closest relatives of eukaryotes. The first images of Asgard cells were published in 2020 from enrichment cultures by a Japanese group. Scanning electron micrograph of a Lokiarchaeum ossiferum cell showing the long and complex cell protrusions. Credit: Thiago Rodrigues-Oliveira, Univ. Wien Asgard archaea cultivated from marine sediments Christa Schleper's working group at the University of Vienna has now succeeded for the first time in cultivating a representative of this group in higher concentrations. It comes from marine sediments on the coast of Piran, Slovenia, but is also an inhabitant of Vienna, for example in the bank sediments of the Danube. Because of its growth to high cell densities, this representative can be studied particularly well. \"It was very tricky and laborious to obtain this extremely sensitive organism in a stable culture in the laboratory,\" reports Thiago Rodrigues-Oliveira, postdoc in the Archaea working group at the University of Vienna and one of the first authors of the study. Asgard archaea have a complex cell shape with an extensive cytoskeleton The remarkable success of the Viennese group to cultivate a highly enriched Asgard representative finally allowed a more detailed examination of the cells by microscopy. The ETH researchers in Martin Pilhofer's group used a modern cryo-electron microscope to take pictures of shock-frozen cells. One of the currently most popular evolutionary theories assumes that eukaryotes (including animals, plants and fungi) arose from the fusion of an Asgard archaeon with a bacterium. Credit: Florian Wollweber, ETH Zürich \"This method enables a three-dimensional insight into the internal cellular structures,\" explains Pilhofer. \"The cells consist of round cell bodies with thin, sometimes very long cell extensions. These tentacle-like structures sometimes even seem to connect different cell bodies with each other,\" says Florian Wollweber, who spent months tracking down the cells under the microscope. The cells also contain an extensive network of actin filaments thought to be unique to eukaryotic cells. This suggests that extensive cytoskeletal structures arose in archaea before the appearance of the first eukaryotes and fuels evolutionary theories around this important and spectacular event in the history of life. Future insights through the new model organism \"Our new organism, called 'Lokiarchaeum ossiferum', has great potential to provide further groundbreaking insights into the early evolution of eukaryotes,\" comments microbiologist Christa Schleper. \"It has taken six long years to obtain a stable and highly enriched culture, but now we can use this experience to perform many biochemical studies and to cultivate other Asgard archaea as well.\" In addition, the scientists can now use the new imaging methods developed at ETH to investigate, for example, the close interactions between Asgard archaea and their bacterial partners. Basic cell biological processes such as cell division can also be studied in the future in order to shed light on the evolutionary origin of these mechanisms in eukaryotes. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Asgard archaea are considered to be the closest known relatives of eukaryotes. Their genomes contain hundreds of eukaryotic signature proteins (ESPs), which inspired hypotheses on the evolution of the eukaryotic cell 1 , 2 , 3 . A role of ESPs in the formation of an elaborate cytoskeleton and complex cellular structures has been postulated 4 , 5 , 6 , but never visualized. Here we describe a highly enriched culture of ‘ Candidatus Lokiarchaeum ossiferum’, a member of the Asgard phylum, which thrives anaerobically at 20 °C on organic carbon sources. It divides every 7–14 days, reaches cell densities of up to 5 × 10 7 cells per ml and has a significantly larger genome compared with the single previously cultivated Asgard strain 7 . ESPs represent 5% of its protein-coding genes, including four actin homologues. We imaged the enrichment culture using cryo-electron tomography, identifying ‘ Ca . L. ossiferum’ cells on the basis of characteristic expansion segments of their ribosomes. Cells exhibited coccoid cell bodies and a network of branched protrusions with frequent constrictions. The cell envelope consists of a single membrane and complex surface structures. A long-range cytoskeleton extends throughout the cell bodies, protrusions and constrictions. The twisted double-stranded architecture of the filaments is consistent with F-actin. Immunostaining indicates that the filaments comprise Lokiactin—one of the most highly conserved ESPs in Asgard archaea. We propose that a complex actin-based cytoskeleton predated the emergence of the first eukaryotes and was a crucial feature in the evolution of the Asgard phylum by scaffolding elaborate cellular structures. Main Soon after the discovery of archaea as a separate lineage besides bacteria, molecular and phylogenetic studies suggested that there is a deep common evolutionary descent between archaea and eukaryotes 8 , 9 . However, only recently has the discovery of the first Lokiarchaeota 10 (now Lokiarchaeia 11 ) and the wider superphylum of Asgardarchaeota in metagenomic analyses 1 , 2 , 11 , 12 , 13 , 14 , 15 , 16 , 17 corroborated a distinct relationship and a possible direct emergence of eukaryotic cells from archaea. In fact, eukaryotes form a direct sister group to Asgardarchaeota or even arise within Asgardarchaeota in most phylogenomic analyses 3 , 10 , 18 . Compellingly, all members of the Asgardarchaea carry an extensive repertoire of genes that were originally assumed to be unique to eukaryotes (ESPs) 1 , 2 , 3 , 10 , 19 , 20 . These ESPs are mostly associated with features of cells with high complexity, such as cytoskeleton formation, transport and the shaping of membranes. For example, the observation that Asgard archaeal genomes encode a complete and functional ubiquitin-coupled ESCRT system 10 , 21 suggested the possibility of elaborate intracellular membrane compartments 10 . Another notable example is genes encoding several close homologues of eukaryotic actin. While F-actin-like assemblies have been identified in other archaea 22 , 23 , Asgard archaea also possess actin-related proteins (ARPs), as well as actin-binding proteins. Notably, Asgard profilins and gelsolins were found to be able to modulate the dynamics of eukaryotic actin 5 , 19 , 24 , 25 , 26 , indicating the existence of an elaborate and dynamic cytoskeleton 4 . However, the in situ structures and functions of archaeal actins remain unclear. A seminal study 7 presented the first enrichment culture of an Asgard archaeon, ‘ Candidatus Prometheoarchaeum syntrophicum’, which grows slowly to low cell densities in syntrophic consortia with molecular-hydrogen-consuming organisms. As ‘ Ca. P. syntrophicum’ cells show long branched protrusions, the authors proposed a hypothesis for eukaryogenesis, in which a primordial Asgard archaeon closely interacts with the predecessor of the bacterial endosymbiont and eventually endogenizes it 7 , 27 . These observations were consistent with the stepwise mechanism of eukaryogenesis that was first proposed as the ‘inside out’ model 28 . The role of Asgard ESPs could so far not be investigated in the natural host, making it difficult to further test these conceptual models. Although ‘ Ca. P. syntrophicum’ was shown to transcribe ESPs, characteristics regarding its intracellular architecture could not be revealed. Fundamental questions regarding the presence of a cytoskeleton or internal compartmentalization in Asgard archaea remain unclear, as does the structure of the cell envelope. Here we combine the enrichment of an experimentally tractable Asgard archaeon with state-of-the-art imaging to reveal its cellular architecture at macromolecular detail. A Lokiarchaea culture from sediment Considering that lokiarchaeal organisms and other Asgard archaea can be found in a variety of anoxic and often marine environments 29 , 30 , we screened DNA from shallow-water sediment from different locations for the presence of 16S rRNA genes of Asgard archaea to select suitable and easily reachable sampling sites for establishing enrichments. Sediments from a small estuarine canal that regularly receives water from the Mediterranean near the coast of Piran, Slovenia, were identified to have the highest relative abundance at the 13–16 cm depth layer, exhibiting up to 4% of Asgard archaea 16S rRNA genes in amplicon sequencing (Extended Data Figs. 1 and 2 ). The identified sample was used to inoculate enrichment cultures (Fig. 1a ) with media of different compositions and various headspace conditions (Supplementary Table 1 ). With periodic monitoring using quantitative PCR (qPCR) with Lokiarchaea-specific primers (Extended Data Fig. 3 ), growth could be observed after 140 days at 20 °C in serum flasks containing sterile-filtered water from the original source supplemented with complex organics (casein hydrolysate, milk powder and amino acids). However, after two transfers under these conditions, growth could no longer be detected and a second round of screening with different medium compositions was performed. Using a modification of the medium MK-D1 reported for the cultivation of ‘ Ca. P. syntrophicum’ 7 , cell growth recovered, and abundances reached repeatedly 2–8%. However, higher enrichments, were not achieved under these conditions. Only through developing a minimal medium, mostly by reducing the input of organic carbon sources to a single compound and by increasing antibiotic concentrations, lokiarchaeal relative abundances reached between 25% and 80% after<|im_end|> <|im_start|>assistant How did the complex organisms on Earth arise? This is one of the big open questions in biology. A collaboration between the working groups of Christa Schleper at the University of Vienna and Martin Pilhofer at ETH Zurich has come a step closer to the answer. The researchers succeeded in cultivating a special archaeon and characterizing it more precisely using microscopic methods. This member of the Asgard archaea exhibits unique cellular characteristics and may represent an evolutionary "missing link" to more complex life forms such as animals and plants. The study was recently published in the journal Nature. All life forms on earth are divided into three major domains: eukaryotes, bacteria and archaea. Eukaryotes include the groups of animals, plants and fungi. Their cells are usually much larger and, at first glance, more complex than the cells of bacteria and archaea. The genetic material of eukaryotes, for example, is packaged in a cell nucleus and the cells also have a large number of other compartments. Cell shape and transport within the eukaryotic cell are also based on an extensive cytoskeleton. But how did the evolutionary leap to such complex eukaryotic cells come about? Most current models assume that archaea and bacteria played a central role in the evolution of eukaryotes. A eukaryotic primordial cell is believed to have evolved from a close symbiosis between archaea and bacteria about two billion years ago. In 2015, genomic studies of deep-sea environmental samples discovered the group of the so-called "Asgard archaea", which in the tree of life represent the closest relatives of eukaryotes. The first images of Asgard cells were published in 2020 from enrichment cultures by a Japanese group. Scanning electron micrograph of a Lokiarchaeum ossiferum cell showing the long and complex cell protrusions. Credit: Thiago Rodrigues-Oliveira, Univ. Wien Asgard archaea cultivated from marine sediments Christa Schleper's working group at the University of Vienna has now succeeded for the first time in cultivating a representative of this group in higher concentrations. It comes from marine sediments on the coast of Piran, Slovenia, but is also an inhabitant of Vienna, for example in the bank sediments of the Danube. Because of its growth to high cell densities, this representative can be studied particularly well. "It was very tricky and laborious to obtain this extremely sensitive organism in a stable culture in the laboratory," reports Thiago Rodrigues-Oliveira, postdoc in the Archaea working group at the University of Vienna and one of the first authors of the study. Asgard archaea have a complex cell shape with an extensive cytoskeleton The remarkable success of the Viennese group to cultivate a highly enriched Asgard representative finally allowed a more detailed examination of the cells by microscopy. The ETH researchers in Martin Pilhofer's group used a modern cryo-electron microscope to take pictures of shock-frozen cells. One of the currently most popular evolutionary theories assumes that eukaryotes (including animals, plants and fungi) arose from the fusion of an Asgard archaeon with a bacterium. Credit: Florian Wollweber, ETH Zürich "This method enables a three-dimensional insight into the internal cellular structures," explains Pilhofer. "The cells consist of round cell bodies with thin, sometimes very long cell extensions. These tentacle-like structures sometimes even seem to connect different cell bodies with each other," says Florian Wollweber, who spent months tracking down the cells under the microscope. The cells also contain an extensive network of actin filaments thought to be unique to eukaryotic cells. This suggests that extensive cytoskeletal structures arose in archaea before the appearance of the first eukaryotes and fuels evolutionary theories around this important and spectacular event in the history of life. Future insights through the new model organism "Our new organism, called 'Lokiarchaeum ossiferum', has great potential to provide further groundbreaking insights into the early evolution of eukaryotes," comments microbiologist Christa Schleper. "It has taken six long years to obtain a stable and highly enriched culture, but now we can use this experience to perform many biochemical studies and to cultivate other Asgard archaea as well." In addition, the scientists can now use the new imaging methods developed at ETH to investigate, for example, the close interactions between Asgard archaea and their bacterial partners. Basic cell biological processes such as cell division can also be studied in the future in order to shed light on the evolutionary origin of these mechanisms in eukaryotes. <|im_end|>

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2,443

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Animal personality has been described in a range of species with ecological and evolutionary consequences. Factors shaping and maintaining variation in personality are not fully understood, but monoaminergic systems are consistently linked to personality variation. We experimentally explored how personality was influenced by alterations in two key monoamine systems: dopamine and serotonin. This was done using ropinirole and fluoxetine, two common human pharmaceuticals. Using the Mediterranean field cricket ( Gryllus bimaculatus ), we focused on the personality traits activity, exploration, and aggression, with confirmed repeatability in our study. Dopamine manipulations explained little variation in the personality traits investigated, while serotonin manipulation reduced both activity and aggression. Due to limited previous research, we created a dose-response curve for ropinirole, ranging from concentrations measured in surface waters to human therapeutic doses. No ropinirole dose level strongly influenced cricket personality, suggesting our results did not come from a dose mismatch. Our results indicate that the serotonergic system explains more variation in personality than manipulations of the dopaminergic system. Additionally, they suggest that monoamine systems differ across taxa, and confirm the importance of the mode of action of pharmaceuticals in determining their effects on behaviour. Introduction Animal personality (i.e., consistent among-individual variation in behaviour), has been described in a broad range of species 1 , 2 . Despite research demonstrating that animal personality can have important ecological and evolutionary consequences 2 , 3 , 4 , the factors shaping and maintaining variation in personality are still poorly understood. Underlying genetic variation has been demonstrated in a number of species, but our understanding of the mechanisms translating genetic variation into personality variation is generally limited 5 , 6 . This calls for rigorous experimental studies using experimental manipulations of different mechanistic pathways in order to understand how genetic variation is translated into personality variation 7 , 8 , 9 . Aspects of personality have been linked to monoaminergic systems 2 , 10 , 11 , including variation in metabolite levels, methylation, and gene polymorphisms for both dopamine and serotonin. Dopamine levels, polymorphisms and differential methylation of dopamine-associated genes are related to novelty-seeking and exploratory behaviour in mammals and birds 2 , 7 , 12 , 13 , 14 . Dopamine is also involved in the recovery of aggression after social defeat in insects 15 , 16 . Additionally, serotonin levels are negatively associated with aggressiveness in several species 2 , 10 , 17 , but positively related to activity and aggression in others 13 , 14 , 18 . Polymorphisms in serotonin transporter genes are related to aggression, anxiety, and impulsivity 2 . Such evidence suggests monoamines may be one of the mechanisms translating genetic variation into personality variation 7 , 8 . However, we cannot yet clearly describe the link between monoamines and behaviour, and further work exploring the causality of observed relationships between neuroendocrinology and personality is needed. We experimentally manipulated two key monoamine systems to determine their effect on personality. For our manipulations we used human pharmaceuticals: ropinirole, which alters the dopaminergic system, and fluoxetine, which alters the serotonergic system. Ropinirole is a dopamine receptor agonist that has been linked to motor control and is prescribed to treat Parkinson’s disease and restless legs syndrome 19 , 20 . Fluoxetine is a selective serotonin reuptake inhibitor prescribed to treat depression and anxiety 21 . We used pharmaceuticals for our manipulations because they have known effects on human personality and behaviour, and as monoamine systems are evolutionarily conserved across taxa 22 , these compounds are good candidates for potentially explaining personality variation in other species. We used the Mediterranean field cricket because they are a model species for neuroethological studies 23 , 24 , 25 , have been shown to demonstrate personality 26 , and respond to monoamine manipulations 18 , 27 , 28 . Based on previous work, we predicted that both of our monoamine manipulations would affect personality by increasing cricket activity 29 , 30 , and aggressiveness 15 , 18 , and that our serotonin manipulation would increase exploration tendency 13 , 14 . These three behaviours were chosen as they are consistent within individuals, describe personality types in a variety of species 31 , and are important to individual fitness 4 . Results All raw data can be found as Supplementary Table S1 . We confirmed that our behaviours were repeatable in our population by running repeatability analyses (for details see Methods below; Table 1 ), thus they can be classified as personality traits. This allowed us to assay individuals a single time for other parts of our study. Table 1 Comparison of repeatability of cricket behavioural traits measured on 3 consecutive days (n = 24). Full size table When comparing our dopamine-manipulated and unmanipulated individuals using linear models, there were no significant differences between groups in any of their behavioural responses measured (for details see Methods below; Table 2 ). Serotonin on the other hand did alter personality: our manipulated individuals had lower activity (distance moved in familiar environment) and lower aggression (more often lost fights) than control individuals (Table 2 , Fig. 1 ). Exploration (statistically controlled for individual level activity), however, was not influenced by our serotonin manipulation. Table 2 The influence of manipulation of monoamines (dopamine via ropinirole hydrochloride or serotonin via fluoxetine hydrochloride) on cricket personality (n = 144). Full size table Figure 1 The influence of manipulation of monoamines (dopamine via ropinirole hydrochloride, or serotonin via fluoxetine hydrochloride) on cricket personality (n = 144). Mean and standard error of raw data describing ( A ) Activity, distance moved in home environment (cm); ( B ) Exploration, distance moved in novel area (cm); ( C ) Aggression, winner of fight dyad, binomial. Full size image We created a dose response curve across 6 concentrations of ropinirole and used linear models to confirm that only intermediately low (1 µM and 33 µM) doses tended to increase aggressiveness relative to control individuals (for details see Methods below; Table 3 , Fig. 2 ). However, these results", "role": "user" }, { "content": "Crickets that are exposed to human drugs that alter serotonin levels in the brain are less active and less aggressive than crickets that have had no drug exposure, according to a new study led by researchers from Linköping University. The findings have been published in Scientific Reports. Individuals in many animal species show different personality types. Some individuals are, for example, consistently bolder than others. \"However, in biology, we still do not fully understand what causes people or animals to show differences in personality. In humans, people with different levels of brain chemicals, such as serotonin and dopamine, often behave differently. However, we do not know if these chemicals can also explain personality differences in other species, and if the chemicals cause the observed differences or if both the differences in behavior and chemical levels are caused by another underlying factor,\" says Robin Abbey-Lee, postdoctoral researcher at the Department of Physics, Chemistry and Biology, IFM, and lead author of the study. The researchers, therefore, set out to experimentally change the levels of the brain chemicals serotonin and dopamine in the crickets. They did that by giving the crickets human pharmaceuticals that are known to act on the serotonin and dopamine systems and are used to treat depression and Parkinson disease, respectively. Because dopamine and serotonin systems are similar across species, these chemicals were predicted to also affect cricket behavior. \"In this study we wanted to address an important gap in our knowledge by experimentally altering these brain chemicals and seeing if we could get a resulting behavioral change,\" says Hanne Løvlie, associate professor at IFM, and senior author. Researchers at Linköping University, Sweden, set out to experimentally change the levels of the brain chemicals serotonin and dopamine in crickets. They gave the crickets human pharmaceuticals that are known to act on the serotonin and dopamine systems. Because dopamine and serotonin systems are similar across species, these chemicals were predicted to also affect cricket behavior. Credit: Linköping University The researchers measured three different behaviors. \"First, we measured the activity of crickets in a familiar environment. This is similar to how much a person moves around their own home. Second, we measured the exploration behavior of a cricket in a new environment, similar to how a human might behave on a trip to a new city. Finally, we measured cricket fighting behavior to determine how aggressive individuals were,\" says Robin Abbey-Lee. What the researchers found was that changing the serotonin levels made crickets less active and less aggressive. But changing the dopamine levels of crickets did not change their behavior. \"This suggests that serotonin has a clearer underlying role in these behaviors,\" says Hanne Løvlie. The findings add to our understanding of why animals have personality. They also raise the issue of how pharmaceuticals leaking into nature through human waste water may affect animals. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Animal personality has been described in a range of species with ecological and evolutionary consequences. Factors shaping and maintaining variation in personality are not fully understood, but monoaminergic systems are consistently linked to personality variation. We experimentally explored how personality was influenced by alterations in two key monoamine systems: dopamine and serotonin. This was done using ropinirole and fluoxetine, two common human pharmaceuticals. Using the Mediterranean field cricket ( Gryllus bimaculatus ), we focused on the personality traits activity, exploration, and aggression, with confirmed repeatability in our study. Dopamine manipulations explained little variation in the personality traits investigated, while serotonin manipulation reduced both activity and aggression. Due to limited previous research, we created a dose-response curve for ropinirole, ranging from concentrations measured in surface waters to human therapeutic doses. No ropinirole dose level strongly influenced cricket personality, suggesting our results did not come from a dose mismatch. Our results indicate that the serotonergic system explains more variation in personality than manipulations of the dopaminergic system. Additionally, they suggest that monoamine systems differ across taxa, and confirm the importance of the mode of action of pharmaceuticals in determining their effects on behaviour. Introduction Animal personality (i.e., consistent among-individual variation in behaviour), has been described in a broad range of species 1 , 2 . Despite research demonstrating that animal personality can have important ecological and evolutionary consequences 2 , 3 , 4 , the factors shaping and maintaining variation in personality are still poorly understood. Underlying genetic variation has been demonstrated in a number of species, but our understanding of the mechanisms translating genetic variation into personality variation is generally limited 5 , 6 . This calls for rigorous experimental studies using experimental manipulations of different mechanistic pathways in order to understand how genetic variation is translated into personality variation 7 , 8 , 9 . Aspects of personality have been linked to monoaminergic systems 2 , 10 , 11 , including variation in metabolite levels, methylation, and gene polymorphisms for both dopamine and serotonin. Dopamine levels, polymorphisms and differential methylation of dopamine-associated genes are related to novelty-seeking and exploratory behaviour in mammals and birds 2 , 7 , 12 , 13 , 14 . Dopamine is also involved in the recovery of aggression after social defeat in insects 15 , 16 . Additionally, serotonin levels are negatively associated with aggressiveness in several species 2 , 10 , 17 , but positively related to activity and aggression in others 13 , 14 , 18 . Polymorphisms in serotonin transporter genes are related to aggression, anxiety, and impulsivity 2 . Such evidence suggests monoamines may be one of the mechanisms translating genetic variation into personality variation 7 , 8 . However, we cannot yet clearly describe the link between monoamines and behaviour, and further work exploring the causality of observed relationships between neuroendocrinology and personality is needed. We experimentally manipulated two key monoamine systems to determine their effect on personality. For our manipulations we used human pharmaceuticals: ropinirole, which alters the dopaminergic system, and fluoxetine, which alters the serotonergic system. Ropinirole is a dopamine receptor agonist that has been linked to motor control and is prescribed to treat Parkinson’s disease and restless legs syndrome 19 , 20 . Fluoxetine is a selective serotonin reuptake inhibitor prescribed to treat depression and anxiety 21 . We used pharmaceuticals for our manipulations because they have known effects on human personality and behaviour, and as monoamine systems are evolutionarily conserved across taxa 22 , these compounds are good candidates for potentially explaining personality variation in other species. We used the Mediterranean field cricket because they are a model species for neuroethological studies 23 , 24 , 25 , have been shown to demonstrate personality 26 , and respond to monoamine manipulations 18 , 27 , 28 . Based on previous work, we predicted that both of our monoamine manipulations would affect personality by increasing cricket activity 29 , 30 , and aggressiveness 15 , 18 , and that our serotonin manipulation would increase exploration tendency 13 , 14 . These three behaviours were chosen as they are consistent within individuals, describe personality types in a variety of species 31 , and are important to individual fitness 4 . Results All raw data can be found as Supplementary Table S1 . We confirmed that our behaviours were repeatable in our population by running repeatability analyses (for details see Methods below; Table 1 ), thus they can be classified as personality traits. This allowed us to assay individuals a single time for other parts of our study. Table 1 Comparison of repeatability of cricket behavioural traits measured on 3 consecutive days (n = 24). Full size table When comparing our dopamine-manipulated and unmanipulated individuals using linear models, there were no significant differences between groups in any of their behavioural responses measured (for details see Methods below; Table 2 ). Serotonin on the other hand did alter personality: our manipulated individuals had lower activity (distance moved in familiar environment) and lower aggression (more often lost fights) than control individuals (Table 2 , Fig. 1 ). Exploration (statistically controlled for individual level activity), however, was not influenced by our serotonin manipulation. Table 2 The influence of manipulation of monoamines (dopamine via ropinirole hydrochloride or serotonin via fluoxetine hydrochloride) on cricket personality (n = 144). Full size table Figure 1 The influence of manipulation of monoamines (dopamine via ropinirole hydrochloride, or serotonin via fluoxetine hydrochloride) on cricket personality (n = 144). Mean and standard error of raw data describing ( A ) Activity, distance moved in home environment (cm); ( B ) Exploration, distance moved in novel area (cm); ( C ) Aggression, winner of fight dyad, binomial. Full size image We created a dose response curve across 6 concentrations of ropinirole and used linear models to confirm that only intermediately low (1 µM and 33 µM) doses tended to increase aggressiveness relative to control individuals (for details see Methods below; Table 3 , Fig. 2 ). However, these results<|im_end|> <|im_start|>assistant Crickets that are exposed to human drugs that alter serotonin levels in the brain are less active and less aggressive than crickets that have had no drug exposure, according to a new study led by researchers from Linköping University. The findings have been published in Scientific Reports. Individuals in many animal species show different personality types. Some individuals are, for example, consistently bolder than others. "However, in biology, we still do not fully understand what causes people or animals to show differences in personality. In humans, people with different levels of brain chemicals, such as serotonin and dopamine, often behave differently. However, we do not know if these chemicals can also explain personality differences in other species, and if the chemicals cause the observed differences or if both the differences in behavior and chemical levels are caused by another underlying factor," says Robin Abbey-Lee, postdoctoral researcher at the Department of Physics, Chemistry and Biology, IFM, and lead author of the study. The researchers, therefore, set out to experimentally change the levels of the brain chemicals serotonin and dopamine in the crickets. They did that by giving the crickets human pharmaceuticals that are known to act on the serotonin and dopamine systems and are used to treat depression and Parkinson disease, respectively. Because dopamine and serotonin systems are similar across species, these chemicals were predicted to also affect cricket behavior. "In this study we wanted to address an important gap in our knowledge by experimentally altering these brain chemicals and seeing if we could get a resulting behavioral change," says Hanne Løvlie, associate professor at IFM, and senior author. Researchers at Linköping University, Sweden, set out to experimentally change the levels of the brain chemicals serotonin and dopamine in crickets. They gave the crickets human pharmaceuticals that are known to act on the serotonin and dopamine systems. Because dopamine and serotonin systems are similar across species, these chemicals were predicted to also affect cricket behavior. Credit: Linköping University The researchers measured three different behaviors. "First, we measured the activity of crickets in a familiar environment. This is similar to how much a person moves around their own home. Second, we measured the exploration behavior of a cricket in a new environment, similar to how a human might behave on a trip to a new city. Finally, we measured cricket fighting behavior to determine how aggressive individuals were," says Robin Abbey-Lee. What the researchers found was that changing the serotonin levels made crickets less active and less aggressive. But changing the dopamine levels of crickets did not change their behavior. "This suggests that serotonin has a clearer underlying role in these behaviors," says Hanne Løvlie. The findings add to our understanding of why animals have personality. They also raise the issue of how pharmaceuticals leaking into nature through human waste water may affect animals. <|im_end|>

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220, 128257, 198 ]

1,902

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Objective To examine whether the increase in use of electronic cigarettes in the USA, which became noticeable around 2010 and increased dramatically by 2014, was associated with a change in overall smoking cessation rate at the population level. Design Population surveys with nationally representative samples. Setting Five of the US Current Population Survey-Tobacco Use Supplement (CPS-TUS) in 2001-02, 2003, 2006-07, 2010-11, and 2014-15. Participants Data on e-cigarette use were obtained from the total sample of the 2014-15 CPS-TUS (n=161 054). Smoking cessation rates were obtained from those who reported smoking cigarettes 12 months before the survey (n=23 270). Rates from 2014-15 CPS-TUS were then compared with those from 2010-11 CPS-TUS (n=27 280) and those from three other previous surveys. Main outcome measures Rate of attempt to quit cigarette smoking and the rate of successfully quitting smoking, defined as having quit smoking for at least three months. Results Of 161 054 respondents to the 2014-15 survey, 22 548 were current smokers and 2136 recent quitters. Among them, 38.2% of current smokers and 49.3% of recent quitters had tried e-cigarettes, and 11.5% and 19.0% used them currently (every day or some days). E-cigarette users were more likely than non-users to attempt to quit smoking, 65.1% v 40.1% (change=25.0%, 95% confidence interval 23.2% to 26.9%), and more likely to succeed in quitting, 8.2% v 4.8% (3.5%, 2.5% to 4.5%). The overall population cessation rate for 2014-15 was significantly higher than that for 2010-11, 5.6% v 4.5% (1.1%, 0.6% to 1.5%), and higher than those for all other survey years (range 4.3-4.5%). Conclusion The substantial increase in e-cigarette use among US adult smokers was associated with a statistically significant increase in the smoking cessation rate at the population level. These findings need to be weighed carefully in regulatory policy making regarding e-cigarettes and in planning tobacco control interventions. Introduction Current regulatory policies on electronic cigarettes vary widely across countries. The United Kingdom provides a path for licensing e-cigarettes as a smoking cessation aid if they can pass safety standards and deliver nicotine like existing nicotine replacement therapy. 1 In contrast, Australia bans the sale of e-cigarettes containing nicotine. 2 US policy falls somewhere between. If there is no claim that e-cigarettes are a smoking cessation aid, they are treated as recreational products and regulated by the Tobacco Product Center of the Food and Drug Administration. Most manufacturers of e-cigarettes avoid making explicit claims on cessation benefits. 3 4 Thus e-cigarettes are currently sold in the US with minor restrictions, as the most recent FDA rulings on e-cigarettes give grace periods for implementation of many components. 5 The scientific community is also divided in its opinion of e-cigarettes as a smoking cessation aid. The debate is not as much about the potential efficacy of e-cigarettes for individual users as it is about the overall population impact. A recent Cochrane review suggests that e-cigarettes have a similar effect as nicotine replacement therapy for individual smokers who use them. 6 Thus e-cigarettes will have a positive impact on the population cessation rate if they function as a nicotine replacement therapy and if they increase the total proportion of smokers using nicotine replacement products. 7 8 9 10 11 Others argue the overall impact of e-cigarettes on smoking in adults will be negative, even if they help some individuals to quit smoking. 12 13 The reason is that smokers who use e-cigarettes often use them occasionally, along with cigarettes. 14 Such dual use could lessen the urgency to quit smoking, delaying the cessation process. If this is true, then the positive effect of e-cigarettes on some will be offset by the negative effect on many others, rendering the overall population impact as negative. A randomized trial at the population level could resolve the debate, but such a trial is difficult to do. Instead, population studies have only compared smokers who have used e-cigarettes with those who have not. Some found that e-cigarette users quit at higher rates 9 15 whereas others found the opposite. 16 17 18 None has reported whether the overall population cessation rate (which includes both e-cigarette users and non-users) has changed because of e-cigarettes. We examined the relation between e-cigarette use and smoking cessation in the US population using the largest representative sample of smokers and e-cigarette users available to date: the 2014-15 Current Population Survey-Tobacco Use Supplement (CPS-TUS). Population surveys in the US began to measure e-cigarette use around 2010. 14 The surveys found that most users were smokers. In 2010, about 1.4% of smokers were current users of e-cigarettes. 19 Their usage among smokers increased dramatically by 2014, with estimates from various studies ranging from 15% to 30%. 14 19 20 21 Thus a comparison between CPS-TUS 2010-11 and 2014-15 provides the best chance yet to examine the effect of e-cigarettes on the overall smoking cessation rate. We investigated two questions: First, did users of e-cigarettes in 2014-15 quit smoking at a higher rate than non-users? Second, did smokers in 2014-15 as a whole quit smoking at a higher rate than those in 2010-11? For a longer historical view, we also compared the 2014-15 survey with surveys earlier than 2010-11. Methods Data source The US Current Population Survey-Tobacco Use Supplement (CPS-TUS) is a periodic tobacco survey attached to the Current Population Survey and administered by the US Census Bureau. It provides data from a nationally representative sample of US households of non-institutionalized civilians. Details of the design are published elsewhere. 22 Our analysis included five surveys, 2001-02, 2003, 2006-07, 2010-11, and 2014-15. The sample sizes (excluding proxy respondents) were 185 568, 183 810, 172 023, 171 365, and 163 920, respectively. We did not include surveys earlier than 2001-02 because they did not assess quit attempts for all smokers. Participants For analysis of the prevalence of e-cigarette use in the 2014-15 survey, we included 161 054 of the total sample of 163 920 (we excluded those who did not answer questions on cigarettes or e-cigarettes). The analysis on smoking cessation included", "role": "user" }, { "content": "People who used e-cigarettes were more likely to kick the habit than those who didn't, a new study found. Nicotine patches, gums and medications are known to aid smoking cessation, but there's no consensus on whether vaping devices can help anti-smoking efforts. The U.S. research is the largest look yet at electronic cigarette users and it found e-cigarettes played a role in helping people quit. \"It's absolutely clear that e-cigarettes help smokers replace cigarettes,\" said Peter Hajek, director of the health and lifestyle research unit at Queen Mary University in London, who wasn't part of the study. Smoking rates have been generally declining for decades. Health experts have credited taxes on tobacco products and anti-smoking ads for the drop. E-cigarettes have been sold in the U.S. since 2007. Most devices heat a liquid nicotine solution into vapor and were promoted to smokers as a less dangerous alternative since they don't contain all the chemicals, tar or odor of regular cigarettes. Researchers analyzed and compared data collected by the U.S. Census from 2001 to 2015, including the number of adult e-cigarette users from the most recent survey. About two-thirds of e-cigarette users tried to quit smoking compared to 40 percent of non-users, the study found. E-cigarette users were more likely to succeed in quitting for at least three months than non-users—8 percent versus 5 percent. The research was published online Wednesday in the journal, BMJ. It was funded by the National Institutes of Health. The rate of people quitting smoking in the U.S. has remained steady at about 4.5 percent for years. It jumped to 5.6 percent in 2014-2015, representing about 350,000 fewer smokers. It was the first recorded rise in the smoking cessation rate in 15 years. While national anti-smoking campaigns likely helped, the results show e-cigarette use also played an important role, said lead author Shu-Hong Zhu of the University of California, San Diego. Hajek, who wasn't part of the research, said vaping devices shouldn't be strictly regulated, but instead be allowed to compete directly with cigarettes. \"That way, smokers can get what they want without killing themselves,\" he said. Earlier this month, a House panel renewed its efforts to prevent the Food and Drug Administration from requiring retroactive safety reviews of e-cigarettes already on the market. Others warned that the long-term side effects of e-cigarettes are unknown. \"We just don't know if moving to e-cigarettes is good enough to reduce the harm,\" said Aruni Bhatnagar, director of the American Heart Association's Tobacco Research and Addiction Center. Chris Bullen, who authored an accompanying editorial , said although the long-term safety of e-cigarettes is unclear, any ill effects are \"likely to be rare compared with the harms of continuing to smoke.\" The latest results strongly suggest that more lenient control of e-cigarettes could improve population health, said Bullen, a professor of public health at the University of Auckland. \"If every smoker was to change over to e-cigarettes completely, there would be a dramatic and almost immediate public health benefit,\" he said in an email. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Objective To examine whether the increase in use of electronic cigarettes in the USA, which became noticeable around 2010 and increased dramatically by 2014, was associated with a change in overall smoking cessation rate at the population level. Design Population surveys with nationally representative samples. Setting Five of the US Current Population Survey-Tobacco Use Supplement (CPS-TUS) in 2001-02, 2003, 2006-07, 2010-11, and 2014-15. Participants Data on e-cigarette use were obtained from the total sample of the 2014-15 CPS-TUS (n=161 054). Smoking cessation rates were obtained from those who reported smoking cigarettes 12 months before the survey (n=23 270). Rates from 2014-15 CPS-TUS were then compared with those from 2010-11 CPS-TUS (n=27 280) and those from three other previous surveys. Main outcome measures Rate of attempt to quit cigarette smoking and the rate of successfully quitting smoking, defined as having quit smoking for at least three months. Results Of 161 054 respondents to the 2014-15 survey, 22 548 were current smokers and 2136 recent quitters. Among them, 38.2% of current smokers and 49.3% of recent quitters had tried e-cigarettes, and 11.5% and 19.0% used them currently (every day or some days). E-cigarette users were more likely than non-users to attempt to quit smoking, 65.1% v 40.1% (change=25.0%, 95% confidence interval 23.2% to 26.9%), and more likely to succeed in quitting, 8.2% v 4.8% (3.5%, 2.5% to 4.5%). The overall population cessation rate for 2014-15 was significantly higher than that for 2010-11, 5.6% v 4.5% (1.1%, 0.6% to 1.5%), and higher than those for all other survey years (range 4.3-4.5%). Conclusion The substantial increase in e-cigarette use among US adult smokers was associated with a statistically significant increase in the smoking cessation rate at the population level. These findings need to be weighed carefully in regulatory policy making regarding e-cigarettes and in planning tobacco control interventions. Introduction Current regulatory policies on electronic cigarettes vary widely across countries. The United Kingdom provides a path for licensing e-cigarettes as a smoking cessation aid if they can pass safety standards and deliver nicotine like existing nicotine replacement therapy. 1 In contrast, Australia bans the sale of e-cigarettes containing nicotine. 2 US policy falls somewhere between. If there is no claim that e-cigarettes are a smoking cessation aid, they are treated as recreational products and regulated by the Tobacco Product Center of the Food and Drug Administration. Most manufacturers of e-cigarettes avoid making explicit claims on cessation benefits. 3 4 Thus e-cigarettes are currently sold in the US with minor restrictions, as the most recent FDA rulings on e-cigarettes give grace periods for implementation of many components. 5 The scientific community is also divided in its opinion of e-cigarettes as a smoking cessation aid. The debate is not as much about the potential efficacy of e-cigarettes for individual users as it is about the overall population impact. A recent Cochrane review suggests that e-cigarettes have a similar effect as nicotine replacement therapy for individual smokers who use them. 6 Thus e-cigarettes will have a positive impact on the population cessation rate if they function as a nicotine replacement therapy and if they increase the total proportion of smokers using nicotine replacement products. 7 8 9 10 11 Others argue the overall impact of e-cigarettes on smoking in adults will be negative, even if they help some individuals to quit smoking. 12 13 The reason is that smokers who use e-cigarettes often use them occasionally, along with cigarettes. 14 Such dual use could lessen the urgency to quit smoking, delaying the cessation process. If this is true, then the positive effect of e-cigarettes on some will be offset by the negative effect on many others, rendering the overall population impact as negative. A randomized trial at the population level could resolve the debate, but such a trial is difficult to do. Instead, population studies have only compared smokers who have used e-cigarettes with those who have not. Some found that e-cigarette users quit at higher rates 9 15 whereas others found the opposite. 16 17 18 None has reported whether the overall population cessation rate (which includes both e-cigarette users and non-users) has changed because of e-cigarettes. We examined the relation between e-cigarette use and smoking cessation in the US population using the largest representative sample of smokers and e-cigarette users available to date: the 2014-15 Current Population Survey-Tobacco Use Supplement (CPS-TUS). Population surveys in the US began to measure e-cigarette use around 2010. 14 The surveys found that most users were smokers. In 2010, about 1.4% of smokers were current users of e-cigarettes. 19 Their usage among smokers increased dramatically by 2014, with estimates from various studies ranging from 15% to 30%. 14 19 20 21 Thus a comparison between CPS-TUS 2010-11 and 2014-15 provides the best chance yet to examine the effect of e-cigarettes on the overall smoking cessation rate. We investigated two questions: First, did users of e-cigarettes in 2014-15 quit smoking at a higher rate than non-users? Second, did smokers in 2014-15 as a whole quit smoking at a higher rate than those in 2010-11? For a longer historical view, we also compared the 2014-15 survey with surveys earlier than 2010-11. Methods Data source The US Current Population Survey-Tobacco Use Supplement (CPS-TUS) is a periodic tobacco survey attached to the Current Population Survey and administered by the US Census Bureau. It provides data from a nationally representative sample of US households of non-institutionalized civilians. Details of the design are published elsewhere. 22 Our analysis included five surveys, 2001-02, 2003, 2006-07, 2010-11, and 2014-15. The sample sizes (excluding proxy respondents) were 185 568, 183 810, 172 023, 171 365, and 163 920, respectively. We did not include surveys earlier than 2001-02 because they did not assess quit attempts for all smokers. Participants For analysis of the prevalence of e-cigarette use in the 2014-15 survey, we included 161 054 of the total sample of 163 920 (we excluded those who did not answer questions on cigarettes or e-cigarettes). The analysis on smoking cessation included<|im_end|> <|im_start|>assistant People who used e-cigarettes were more likely to kick the habit than those who didn't, a new study found. Nicotine patches, gums and medications are known to aid smoking cessation, but there's no consensus on whether vaping devices can help anti-smoking efforts. The U.S. research is the largest look yet at electronic cigarette users and it found e-cigarettes played a role in helping people quit. "It's absolutely clear that e-cigarettes help smokers replace cigarettes," said Peter Hajek, director of the health and lifestyle research unit at Queen Mary University in London, who wasn't part of the study. Smoking rates have been generally declining for decades. Health experts have credited taxes on tobacco products and anti-smoking ads for the drop. E-cigarettes have been sold in the U.S. since 2007. Most devices heat a liquid nicotine solution into vapor and were promoted to smokers as a less dangerous alternative since they don't contain all the chemicals, tar or odor of regular cigarettes. Researchers analyzed and compared data collected by the U.S. Census from 2001 to 2015, including the number of adult e-cigarette users from the most recent survey. About two-thirds of e-cigarette users tried to quit smoking compared to 40 percent of non-users, the study found. E-cigarette users were more likely to succeed in quitting for at least three months than non-users—8 percent versus 5 percent. The research was published online Wednesday in the journal, BMJ. It was funded by the National Institutes of Health. The rate of people quitting smoking in the U.S. has remained steady at about 4.5 percent for years. It jumped to 5.6 percent in 2014-2015, representing about 350,000 fewer smokers. It was the first recorded rise in the smoking cessation rate in 15 years. While national anti-smoking campaigns likely helped, the results show e-cigarette use also played an important role, said lead author Shu-Hong Zhu of the University of California, San Diego. Hajek, who wasn't part of the research, said vaping devices shouldn't be strictly regulated, but instead be allowed to compete directly with cigarettes. "That way, smokers can get what they want without killing themselves," he said. Earlier this month, a House panel renewed its efforts to prevent the Food and Drug Administration from requiring retroactive safety reviews of e-cigarettes already on the market. Others warned that the long-term side effects of e-cigarettes are unknown. "We just don't know if moving to e-cigarettes is good enough to reduce the harm," said Aruni Bhatnagar, director of the American Heart Association's Tobacco Research and Addiction Center. Chris Bullen, who authored an accompanying editorial , said although the long-term safety of e-cigarettes is unclear, any ill effects are "likely to be rare compared with the harms of continuing to smoke." The latest results strongly suggest that more lenient control of e-cigarettes could improve population health, said Bullen, a professor of public health at the University of Auckland. "If every smoker was to change over to e-cigarettes completely, there would be a dramatic and almost immediate public health benefit," he said in an email. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Background Despite decades of education reform efforts, the percent of the general US population accepting biological evolution as the explanation for the diversity of life has remained relatively unchanged over the past 35 years. Previous work has shown the importance of both educational and non-educational (sociodemographic and psychological) factors on acceptance of evolution, but has often looked at such factors in isolation. Our study is among the first attempts to model quantitatively how the unique influences of evolutionary content knowledge, religiosity, epistemological sophistication, and an understanding of the nature of science collectively predict an individual’s acceptance or rejection of evolution. Results Our study population had a high acceptance of evolution, with an average score of 77.17 (95% C.I. ± 1.483) on the Measure of Acceptance of the Theory of Evolution (MATE) instrument. Our combined general linear model showed that, of the variables in our model, an understanding of the nature of science explained the greatest amount of variation in acceptance of evolution. This was followed in amount of variance explained by a measure of religiosity, openness to experience, religious denomination, number of biology courses previously taken, and knowledge of evolutionary biology terms. Conclusions Understanding of the nature of science was the single most important factor associated with acceptance of evolution in our study and explained at least four times more variation than measures of evolutionary knowledge. This suggests that educational efforts to impact evolutionary acceptance should focus on increasing an understanding of the nature of science (which may be expected to have additional benefits towards generalized science denial). Additionally, our measure of epistemological sophistication had a unique, significant impact on acceptance of evolution. Both epistemological sophistication and an understanding of the nature of science are factors that might change throughout a liberal arts education, independent of the effect of direct evolutionary instruction. Background Evolution is the unifying theme of all biology. Living organisms and the interactions between them can be understood most clearly through the lens of evolution; this is reflected in the near-universal acceptance of evolution among biologists (Graffin 2003 ), who have studied the evidence supporting evolutionary theory and use it to guide their work. However, among the general public, acceptance of evolution is much less prevalent. Despite decades of efforts toward science education reform that might be expected to improve evolutionary understanding and acceptance, little change has occurred in the number of people who accept evolutionary explanations of life’s diversity (Gallup 2014 ). This rejection of biology’s overarching theme leads to an inability to correctly understand and to reason appropriately regarding biological phenomena (Dobzhansky 1973 ). In addition, science denial by those responsible for setting policy leads to difficulties in implementation of sound science curricula in schools as well as poor potential outcomes regarding future funding for biological sciences. It is for these reasons and more that a public accepting of evolutionary biology is not only desirable, but necessary. In this study, we attempt to explore how different educational and sociodemographic factors interact with acceptance of evolution in college students. Knowledge of evolution is perhaps the most intuitive factor related to evolution acceptance. Rutledge and Warden ( 2000 ) found that among high school teachers, knowledge of evolution was significantly correlated with acceptance of evolution (see also Deniz et al. 2008 ; Glaze et al. 2015 ). This link was also found in an undergraduate sample (Carter and Wiles 2014 ). Other studies (Heddy and Nadelson 2013 ; Mazur 2004 ; Wiles 2014 ) have found more generally that higher education levels lead to greater acceptance of evolution. Barone et al. ( 2014 ) found a significant correlation between knowledge of evolutionary terms and acceptance of evolution among visitors to a natural history museum. However, other researchers have found no significant link between knowledge and acceptance of evolution, especially when other variables are considered in the same model (Cavallo and McCall 2008 ; Sinatra et al. 2003 ). Multiple studies have found an understanding of the nature of science to be significantly related to acceptance of evolution (Carter and Wiles 2014 ; Cavallo and McCall 2008 ; Glaze et al. 2015 ; Johnson and Peeples 1987 ; Rutledge and Mitchell 2002 ; Trani 2004 ). Compared to the more equivocal support of the role of evolutionary content knowledge in evolution acceptance described above, this consistent trend seems to indicate acceptance of evolution might be more strongly influenced by a general understanding of the aims and process of science. Indeed, many of the major creationist criticisms of evolutionary biology stem from a misunderstanding of the nature of science (Matthews 1997 ; Pigliucci 2008 ). Cognitive factors have also been found to have a strong effect on acceptance of evolution. Deniz et al. ( 2008 ) found thinking dispositions to be the most significant predictor of evolution acceptance in preservice biology teachers in Turkey. Sinatra et al. ( 2003 ) found a measure of epistemological sophistication and a disposition towards actively open-minded thinking to be significantly correlated with acceptance of human evolution (but no relation was found for acceptance of animal evolution). Hawley et al. ( 2011 ) found that openness to experience, a psychological metric measuring intellectualism and creativity (John et al. 2008 ), to be significantly negatively related to acceptance of creationist reasoning. In this study, we consider epistemological sophistication to be a general term referring to a mature manner of understanding the nature of knowledge. Openness to experience is used here as a proxy for epistemological sophistication. It is generally known that, at least among many Christian denominations in the United States, people who are more strongly religious tend to have greater concern over evolution, especially as it applies to humans. Many authors have found a link between strength of religious convictions and lack of acceptance of evolution (Barone et al. 2014 ; Carter and Wiles 2014 ; Glaze et al. 2015 ; Heddy and Nadelson 2013 ; Mazur 2004 ; Moore et al. 2011 ; Nehm and Schonfeld 2007 ; Trani 2004 ), although", "role": "user" }, { "content": "Understanding the nature of science is the greatest predictor of evolution acceptance in college students, a new study finds. With a minority of American adults fully accepting evolution, the fundamental principle of biological science, this research provides guidance for educators to improve science literacy. \"Asking why it is critical that students accept evolution is almost like asking why it is critical that students understand biology,\" says Ryan Dunk, biology Ph.D. candidate in the College of Arts and Sciences and the paper's lead author. Evolution's many applications include understanding human disease and impacts of climate change, he explains. The research was published online on July 17, 2017, in the open-access journal Evolution: Education & Outreach. SpringerOpen also published Dunk's invited blog post on the findings on Sept. 11, 2017. Dunk surveyed introductory anatomy and physiology students at the University of Wisconsin-Milwaukee (UWM) with co-author Benjamin Campbell, UWM associate professor of anthropology. Andrew Petto, UWM distinguished lecturer of biology, and Jason Wiles, Syracuse associate professor of biology, join as co-authors. In this study, Dunk and colleagues used statistical models to pinpoint how an individual's understanding of science, knowledge of evolution, personality traits, religiosity and demographic traits predict student acceptance of evolution. While previous research looked for single traits predicting evolution acceptance, Dunk combined all of the above variables into one comprehensive model. Unlike previous \"one variable\" models, this comprehensive approach enabled Dunk to see which variables are more important relative to each other. \"We were able to look at interactions that are actually going on in people—every individual has a level of knowledge of evolution, a level of their knowledge of nature of science, a level of religiosity, and so on,\" Dunk says. In this study, evolution acceptance was determined by student responses to a commonly used questionnaire called Measure of the Acceptance of the Theory of Evolution (MATE.) The MATE asks questions about the age of the Earth, how organisms have changed over time, how and if humans have changed over time and whether evolutionary theory is supported by historical and laboratory data. The greatest predictor of student evolution acceptance was greater understanding of the nature of science, which includes recognizing the types of questions science can answer and how the scientific method is used to test hypotheses. Intrinsic religiosity, the extent to which an individual relies on religion for decision and opinion making, was also an important factor, but to a lesser extent. Dunk explains that the study's results go against the old strategy of \"teach evolution better\" to increase acceptance: \"We know we don't just need to teach them the facts better, because we have been working on evolution curriculum reforms for decades that have moved the needle very little on wide-scale acceptance.\" Additionally, the authors don't see religion as a roadblock to fostering evolution acceptance. \"Many religious leaders have made peace with evolution,\" Wiles notes, referring to resources like the Clergy Letter Project and Voices for Evolution. Prior research from the Wiles lab found that students who had become more accepting of evolution had not become any less religiously active. Wiles explains, \"It may be that as students learn more about how science works, they rely more on scientific explanations for natural phenomena, but that doesn't mean they must abandon religion in the process.\" Dunk, who recently received a $2,492 Rosemary Grant Award (RGA) for Graduate Student Research from the Society for the Study of Evolution, will continue exploring evolution acceptance with his Ph.D. advisor, Wiles. In addition to tracking evolution acceptance across Syracuse undergraduates over two years, the RGA will fund focus groups and individual interviews with select participants. \"All the people we survey are currently students. But they're going to be educated members of the general public,\" Dunk says. \"Our work aims to help them have an appreciation for scientific inquiry and nature itself.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Background Despite decades of education reform efforts, the percent of the general US population accepting biological evolution as the explanation for the diversity of life has remained relatively unchanged over the past 35 years. Previous work has shown the importance of both educational and non-educational (sociodemographic and psychological) factors on acceptance of evolution, but has often looked at such factors in isolation. Our study is among the first attempts to model quantitatively how the unique influences of evolutionary content knowledge, religiosity, epistemological sophistication, and an understanding of the nature of science collectively predict an individual’s acceptance or rejection of evolution. Results Our study population had a high acceptance of evolution, with an average score of 77.17 (95% C.I. ± 1.483) on the Measure of Acceptance of the Theory of Evolution (MATE) instrument. Our combined general linear model showed that, of the variables in our model, an understanding of the nature of science explained the greatest amount of variation in acceptance of evolution. This was followed in amount of variance explained by a measure of religiosity, openness to experience, religious denomination, number of biology courses previously taken, and knowledge of evolutionary biology terms. Conclusions Understanding of the nature of science was the single most important factor associated with acceptance of evolution in our study and explained at least four times more variation than measures of evolutionary knowledge. This suggests that educational efforts to impact evolutionary acceptance should focus on increasing an understanding of the nature of science (which may be expected to have additional benefits towards generalized science denial). Additionally, our measure of epistemological sophistication had a unique, significant impact on acceptance of evolution. Both epistemological sophistication and an understanding of the nature of science are factors that might change throughout a liberal arts education, independent of the effect of direct evolutionary instruction. Background Evolution is the unifying theme of all biology. Living organisms and the interactions between them can be understood most clearly through the lens of evolution; this is reflected in the near-universal acceptance of evolution among biologists (Graffin 2003 ), who have studied the evidence supporting evolutionary theory and use it to guide their work. However, among the general public, acceptance of evolution is much less prevalent. Despite decades of efforts toward science education reform that might be expected to improve evolutionary understanding and acceptance, little change has occurred in the number of people who accept evolutionary explanations of life’s diversity (Gallup 2014 ). This rejection of biology’s overarching theme leads to an inability to correctly understand and to reason appropriately regarding biological phenomena (Dobzhansky 1973 ). In addition, science denial by those responsible for setting policy leads to difficulties in implementation of sound science curricula in schools as well as poor potential outcomes regarding future funding for biological sciences. It is for these reasons and more that a public accepting of evolutionary biology is not only desirable, but necessary. In this study, we attempt to explore how different educational and sociodemographic factors interact with acceptance of evolution in college students. Knowledge of evolution is perhaps the most intuitive factor related to evolution acceptance. Rutledge and Warden ( 2000 ) found that among high school teachers, knowledge of evolution was significantly correlated with acceptance of evolution (see also Deniz et al. 2008 ; Glaze et al. 2015 ). This link was also found in an undergraduate sample (Carter and Wiles 2014 ). Other studies (Heddy and Nadelson 2013 ; Mazur 2004 ; Wiles 2014 ) have found more generally that higher education levels lead to greater acceptance of evolution. Barone et al. ( 2014 ) found a significant correlation between knowledge of evolutionary terms and acceptance of evolution among visitors to a natural history museum. However, other researchers have found no significant link between knowledge and acceptance of evolution, especially when other variables are considered in the same model (Cavallo and McCall 2008 ; Sinatra et al. 2003 ). Multiple studies have found an understanding of the nature of science to be significantly related to acceptance of evolution (Carter and Wiles 2014 ; Cavallo and McCall 2008 ; Glaze et al. 2015 ; Johnson and Peeples 1987 ; Rutledge and Mitchell 2002 ; Trani 2004 ). Compared to the more equivocal support of the role of evolutionary content knowledge in evolution acceptance described above, this consistent trend seems to indicate acceptance of evolution might be more strongly influenced by a general understanding of the aims and process of science. Indeed, many of the major creationist criticisms of evolutionary biology stem from a misunderstanding of the nature of science (Matthews 1997 ; Pigliucci 2008 ). Cognitive factors have also been found to have a strong effect on acceptance of evolution. Deniz et al. ( 2008 ) found thinking dispositions to be the most significant predictor of evolution acceptance in preservice biology teachers in Turkey. Sinatra et al. ( 2003 ) found a measure of epistemological sophistication and a disposition towards actively open-minded thinking to be significantly correlated with acceptance of human evolution (but no relation was found for acceptance of animal evolution). Hawley et al. ( 2011 ) found that openness to experience, a psychological metric measuring intellectualism and creativity (John et al. 2008 ), to be significantly negatively related to acceptance of creationist reasoning. In this study, we consider epistemological sophistication to be a general term referring to a mature manner of understanding the nature of knowledge. Openness to experience is used here as a proxy for epistemological sophistication. It is generally known that, at least among many Christian denominations in the United States, people who are more strongly religious tend to have greater concern over evolution, especially as it applies to humans. Many authors have found a link between strength of religious convictions and lack of acceptance of evolution (Barone et al. 2014 ; Carter and Wiles 2014 ; Glaze et al. 2015 ; Heddy and Nadelson 2013 ; Mazur 2004 ; Moore et al. 2011 ; Nehm and Schonfeld 2007 ; Trani 2004 ), although<|im_end|> <|im_start|>assistant Understanding the nature of science is the greatest predictor of evolution acceptance in college students, a new study finds. With a minority of American adults fully accepting evolution, the fundamental principle of biological science, this research provides guidance for educators to improve science literacy. "Asking why it is critical that students accept evolution is almost like asking why it is critical that students understand biology," says Ryan Dunk, biology Ph.D. candidate in the College of Arts and Sciences and the paper's lead author. Evolution's many applications include understanding human disease and impacts of climate change, he explains. The research was published online on July 17, 2017, in the open-access journal Evolution: Education & Outreach. SpringerOpen also published Dunk's invited blog post on the findings on Sept. 11, 2017. Dunk surveyed introductory anatomy and physiology students at the University of Wisconsin-Milwaukee (UWM) with co-author Benjamin Campbell, UWM associate professor of anthropology. Andrew Petto, UWM distinguished lecturer of biology, and Jason Wiles, Syracuse associate professor of biology, join as co-authors. In this study, Dunk and colleagues used statistical models to pinpoint how an individual's understanding of science, knowledge of evolution, personality traits, religiosity and demographic traits predict student acceptance of evolution. While previous research looked for single traits predicting evolution acceptance, Dunk combined all of the above variables into one comprehensive model. Unlike previous "one variable" models, this comprehensive approach enabled Dunk to see which variables are more important relative to each other. "We were able to look at interactions that are actually going on in people—every individual has a level of knowledge of evolution, a level of their knowledge of nature of science, a level of religiosity, and so on," Dunk says. In this study, evolution acceptance was determined by student responses to a commonly used questionnaire called Measure of the Acceptance of the Theory of Evolution (MATE.) The MATE asks questions about the age of the Earth, how organisms have changed over time, how and if humans have changed over time and whether evolutionary theory is supported by historical and laboratory data. The greatest predictor of student evolution acceptance was greater understanding of the nature of science, which includes recognizing the types of questions science can answer and how the scientific method is used to test hypotheses. Intrinsic religiosity, the extent to which an individual relies on religion for decision and opinion making, was also an important factor, but to a lesser extent. Dunk explains that the study's results go against the old strategy of "teach evolution better" to increase acceptance: "We know we don't just need to teach them the facts better, because we have been working on evolution curriculum reforms for decades that have moved the needle very little on wide-scale acceptance." Additionally, the authors don't see religion as a roadblock to fostering evolution acceptance. "Many religious leaders have made peace with evolution," Wiles notes, referring to resources like the Clergy Letter Project and Voices for Evolution. Prior research from the Wiles lab found that students who had become more accepting of evolution had not become any less religiously active. Wiles explains, "It may be that as students learn more about how science works, they rely more on scientific explanations for natural phenomena, but that doesn't mean they must abandon religion in the process." Dunk, who recently received a $2,492 Rosemary Grant Award (RGA) for Graduate Student Research from the Society for the Study of Evolution, will continue exploring evolution acceptance with his Ph.D. advisor, Wiles. In addition to tracking evolution acceptance across Syracuse undergraduates over two years, the RGA will fund focus groups and individual interviews with select participants. "All the people we survey are currently students. But they're going to be educated members of the general public," Dunk says. "Our work aims to help them have an appreciation for scientific inquiry and nature itself." <|im_end|>

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2,083

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Widespread mRNA 3′ UTR shortening through alternative polyadenylation 1 promotes tumor growth in vivo 2 . A prevailing hypothesis is that it induces proto-oncogene expression in cis through escaping microRNA-mediated repression. Here we report a surprising enrichment of 3′UTR shortening among transcripts that are predicted to act as competing-endogenous RNAs (ceRNAs) for tumor-suppressor genes. Our model-based analysis of the trans effect of 3′ UTR shortening (MAT3UTR) reveals a significant role in altering ceRNA expression. MAT3UTR predicts many trans-targets of 3′ UTR shortening, including PTEN , a crucial tumor-suppressor gene 3 involved in ceRNA crosstalk 4 with nine 3′UTR-shortening genes, including EPS15 and NFIA . Knockdown of NUDT21 , a master 3′ UTR-shortening regulator 2 , represses tumor-suppressor genes such as PHF6 and LARP1 in trans in a miRNA-dependent manner. Together, the results of our analysis suggest a major role of 3′ UTR shortening in repressing tumor-suppressor genes in trans by disrupting ceRNA crosstalk, rather than inducing proto-oncogenes in cis. Main Widespread 3′ UTR shortening (3′US) through alternative polyadenylation (APA) occurs during enhanced cellular proliferation and transformation 1 , 5 , 6 , 7 , 8 . Recently, we reported that NUDT21 -mediated 3′US promotes glioblastoma growth, further underscoring its significance to tumorigenesis 2 . A prevailing hypothesis is that a shortened 3′ UTR results in activation of proto-oncogenes in cis through escaping microRNA (miRNA)-mediated repression. Indeed, several well-characterized oncogenes, such as CCND1 , have been shown to use 3′US to increase their protein levels, but mostly in cell lines 5 . However, in recent PolyA sequencing 7 and our TCGA RNA sequencing (RNA-Seq) APA analysis 1 (5 and 358 tumor/normal pairs, respectively), most oncogenes with 3′US previously identified in vitro 5 displayed almost no changes in their 3′UTR lengths in tumors (Fig. 1a ). For example, we identified 1,346 recurrent (occurrence rate >20%) 3′US genes in 358 tumor/normal pairs 1 . However, CCND1 is not on that list as its 3′US occurred in only a very small portion (8 out of 358; 2.2%) of tumors (Fig. 1b ) . Furthermore, similar to random genes, 3′US genes from all 5 previous APA studies have little overlap with the top 500 ( P < 0.01) high-confidence oncogenes as defined on the basis of distinct somatic mutational patterns of >8,200 tumor/normal pairs 9 (Fig. 1c ). These results challenge the previous hypothesis and suggest a different function of 3′US for tumorigenesis. Fig. 1: 3′US genes are not strongly associated with oncogenes. a , TCGA RNA-Seq data for CCND1 demonstrates no change in 3′UTR usage between tumors (yellow) and matched normal samples (blue). A similar pattern was also observed in PolyA-seq 7 of CCND1 . b , ΔPDUI values for 3′US genes (red) and all genes (gray) in 358 TCGA tumor/normal pairs 1 (upper panel). A negative ΔPDUI represents 3′UTR shortening. The lower panel shows ΔPDUI values for CCND1 across 358 tumor/normal pairs 1 . Significant CCND1 3′ UTR shortening occurred only in a very small portion (8 out of 358; 2.2%) of tumors. c , Overlap P values and the ratios between previously identified 3′US genes and oncogenes. ‘Random ( n = 100)’ represents the averaged P value from 100 random sampling of 100 RefSeq genes. The error bar represents standard variation values of P values from 100 random trials. Full size image Aside from regulating its cognate transcript in cis, the 3′UTR has also been implicated in competing-endogenous RNA (ceRNA) regulation in trans 10 . Although the scope is not fully understood, ceRNA is generally thought to form global regulatory networks (ceRNETs) controlling important biological processes 11 . For example, the tumor suppressor PTEN ’s ceRNAs, CNOT6L and VAPA , have been shown to regulate PTEN and phenocopy its tumor-suppressive properties 12 . As the ceRNA’s regulatory axis is mostly based on miRNA-binding sites on 3′ UTRs, we hypothesize that when genes with shortened 3′ UTRs no longer sequester miRNAs, the released miRNAs would then be directed to repress their ceRNA partners, such as tumor-suppressor genes, in trans, thereby contributing to tumorigenesis. To test this hypothesis, we first used well-established strategies to reconstruct two ceRNETs from 97 TCGA breast tumors and their matched normal tissues, respectively, based on miRNA-binding-site overlap and co-expression 13 , 14 between genes of active ceRNA regulation ( Methods ). In general, transcripts are less correlated between each other in tumors than in normal tissues, partially due to tumor heterogeneity 15 and global reduction of miRNA expression in tumors 16 (Fig. 2a ). As expected, the loss of co-expression results in a much smaller (tenfold reduced) ceRNET for tumors than for normal tissues (Fig. 2b ). Fig. 2: 3′UTR shortening contributes to ceRNET disruption. a , Pearson’s correlation coefficients of 100,000 randomly selected transcript pairs with significant miRNA-binding-site overlap in breast tumors and matched normal tissues. b , The number of ceRNA pairs in breast tumor and the matched normal ceRNETs. The numbers in parentheses are normalized to the number of edges shared between tumor and normal. c , Gene expression of EPS15 (3′US gene) and PTEN (ceRNA partner) on 68 estrogen-receptor-positive (ERP) breast tumors and matched normal samples. The horizontal lines represent the mean expression values of PTEN , which is decreased in tumors (FDR = 2.1 × 10 −10 ). d , The upper heatmap exhibits significant APA events (rows) across 68 ERP tumor/normal pairs (columns), ranked by the number of 3′US genes. The Venn diagrams show the number of ceRNA pairs in the normal and tumor ceRNET. The numbers in parentheses are normalized to the number of edges shared between tumor and normal tissues. The P value was calculated from a one-tailed Pearson’s chi-squared test. Full size image To investigate the role of 3′US in ceRNET disruption, we focused on estrogen-receptor-positive (ER + ) breast tumors, which comprise the majority (68/97) of TCGA breast tumor samples. We built normal and tumor ceRNETs using the same procedure as above. Using the DaPars algorithm 1 , we identified 427 3′US genes recurring in >20% of tumors.", "role": "user" }, { "content": "A collaborative research team has uncovered new information that more accurately explains how cancerous tumors grow within the body. This study is currently available in Nature Genetics. Researchers led by scientists at The University of Texas Medical Branch at Galveston and Baylor College of Medicine found that a losing a section of messenger RNA that was previously thought to transform normal cells into cancerous ones actually acts by blocking a body's ability suppress the formation of tumors. The finding could completely alter the way that medical science approaches the formation of tumors. In molecules throughout the body, the three-prime untranslated region, or 3'UTR, is a section of messenger RNA that can alter gene expression. It's known that shortening this RNA section promotes cancerous tumor growth. \"Researchers have historically thought that this was because 3'UTR shortening induces the expression of proto-oncogenes, normal genes that when altered by mutation or expressed too high, become oncogenes that can transform a normal cell into a cancer cell,\" said Eric Wagner, UTMB associate professor in the department of biochemistry and molecular biology. \"However, using a combination of computational approaches and cancer cell models, we found that 3'UTR shortening in tumors actually causes tumor-suppressing genes to be turned off.\" In the study, the researchers used \"Big data\" analyses to reconstruct the RNA thought to form global regulatory networks within breast tumor cells and their matched normal tissues. This approach identified the fact that 3'UTRs are vital in regulating these global regulatory networks. Using this new information, they then disrupted these networks within breast cancer cells to test the effects on tumor growth. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Widespread mRNA 3′ UTR shortening through alternative polyadenylation 1 promotes tumor growth in vivo 2 . A prevailing hypothesis is that it induces proto-oncogene expression in cis through escaping microRNA-mediated repression. Here we report a surprising enrichment of 3′UTR shortening among transcripts that are predicted to act as competing-endogenous RNAs (ceRNAs) for tumor-suppressor genes. Our model-based analysis of the trans effect of 3′ UTR shortening (MAT3UTR) reveals a significant role in altering ceRNA expression. MAT3UTR predicts many trans-targets of 3′ UTR shortening, including PTEN , a crucial tumor-suppressor gene 3 involved in ceRNA crosstalk 4 with nine 3′UTR-shortening genes, including EPS15 and NFIA . Knockdown of NUDT21 , a master 3′ UTR-shortening regulator 2 , represses tumor-suppressor genes such as PHF6 and LARP1 in trans in a miRNA-dependent manner. Together, the results of our analysis suggest a major role of 3′ UTR shortening in repressing tumor-suppressor genes in trans by disrupting ceRNA crosstalk, rather than inducing proto-oncogenes in cis. Main Widespread 3′ UTR shortening (3′US) through alternative polyadenylation (APA) occurs during enhanced cellular proliferation and transformation 1 , 5 , 6 , 7 , 8 . Recently, we reported that NUDT21 -mediated 3′US promotes glioblastoma growth, further underscoring its significance to tumorigenesis 2 . A prevailing hypothesis is that a shortened 3′ UTR results in activation of proto-oncogenes in cis through escaping microRNA (miRNA)-mediated repression. Indeed, several well-characterized oncogenes, such as CCND1 , have been shown to use 3′US to increase their protein levels, but mostly in cell lines 5 . However, in recent PolyA sequencing 7 and our TCGA RNA sequencing (RNA-Seq) APA analysis 1 (5 and 358 tumor/normal pairs, respectively), most oncogenes with 3′US previously identified in vitro 5 displayed almost no changes in their 3′UTR lengths in tumors (Fig. 1a ). For example, we identified 1,346 recurrent (occurrence rate >20%) 3′US genes in 358 tumor/normal pairs 1 . However, CCND1 is not on that list as its 3′US occurred in only a very small portion (8 out of 358; 2.2%) of tumors (Fig. 1b ) . Furthermore, similar to random genes, 3′US genes from all 5 previous APA studies have little overlap with the top 500 ( P < 0.01) high-confidence oncogenes as defined on the basis of distinct somatic mutational patterns of >8,200 tumor/normal pairs 9 (Fig. 1c ). These results challenge the previous hypothesis and suggest a different function of 3′US for tumorigenesis. Fig. 1: 3′US genes are not strongly associated with oncogenes. a , TCGA RNA-Seq data for CCND1 demonstrates no change in 3′UTR usage between tumors (yellow) and matched normal samples (blue). A similar pattern was also observed in PolyA-seq 7 of CCND1 . b , ΔPDUI values for 3′US genes (red) and all genes (gray) in 358 TCGA tumor/normal pairs 1 (upper panel). A negative ΔPDUI represents 3′UTR shortening. The lower panel shows ΔPDUI values for CCND1 across 358 tumor/normal pairs 1 . Significant CCND1 3′ UTR shortening occurred only in a very small portion (8 out of 358; 2.2%) of tumors. c , Overlap P values and the ratios between previously identified 3′US genes and oncogenes. ‘Random ( n = 100)’ represents the averaged P value from 100 random sampling of 100 RefSeq genes. The error bar represents standard variation values of P values from 100 random trials. Full size image Aside from regulating its cognate transcript in cis, the 3′UTR has also been implicated in competing-endogenous RNA (ceRNA) regulation in trans 10 . Although the scope is not fully understood, ceRNA is generally thought to form global regulatory networks (ceRNETs) controlling important biological processes 11 . For example, the tumor suppressor PTEN ’s ceRNAs, CNOT6L and VAPA , have been shown to regulate PTEN and phenocopy its tumor-suppressive properties 12 . As the ceRNA’s regulatory axis is mostly based on miRNA-binding sites on 3′ UTRs, we hypothesize that when genes with shortened 3′ UTRs no longer sequester miRNAs, the released miRNAs would then be directed to repress their ceRNA partners, such as tumor-suppressor genes, in trans, thereby contributing to tumorigenesis. To test this hypothesis, we first used well-established strategies to reconstruct two ceRNETs from 97 TCGA breast tumors and their matched normal tissues, respectively, based on miRNA-binding-site overlap and co-expression 13 , 14 between genes of active ceRNA regulation ( Methods ). In general, transcripts are less correlated between each other in tumors than in normal tissues, partially due to tumor heterogeneity 15 and global reduction of miRNA expression in tumors 16 (Fig. 2a ). As expected, the loss of co-expression results in a much smaller (tenfold reduced) ceRNET for tumors than for normal tissues (Fig. 2b ). Fig. 2: 3′UTR shortening contributes to ceRNET disruption. a , Pearson’s correlation coefficients of 100,000 randomly selected transcript pairs with significant miRNA-binding-site overlap in breast tumors and matched normal tissues. b , The number of ceRNA pairs in breast tumor and the matched normal ceRNETs. The numbers in parentheses are normalized to the number of edges shared between tumor and normal. c , Gene expression of EPS15 (3′US gene) and PTEN (ceRNA partner) on 68 estrogen-receptor-positive (ERP) breast tumors and matched normal samples. The horizontal lines represent the mean expression values of PTEN , which is decreased in tumors (FDR = 2.1 × 10 −10 ). d , The upper heatmap exhibits significant APA events (rows) across 68 ERP tumor/normal pairs (columns), ranked by the number of 3′US genes. The Venn diagrams show the number of ceRNA pairs in the normal and tumor ceRNET. The numbers in parentheses are normalized to the number of edges shared between tumor and normal tissues. The P value was calculated from a one-tailed Pearson’s chi-squared test. Full size image To investigate the role of 3′US in ceRNET disruption, we focused on estrogen-receptor-positive (ER + ) breast tumors, which comprise the majority (68/97) of TCGA breast tumor samples. We built normal and tumor ceRNETs using the same procedure as above. Using the DaPars algorithm 1 , we identified 427 3′US genes recurring in >20% of tumors.<|im_end|> <|im_start|>assistant A collaborative research team has uncovered new information that more accurately explains how cancerous tumors grow within the body. This study is currently available in Nature Genetics. Researchers led by scientists at The University of Texas Medical Branch at Galveston and Baylor College of Medicine found that a losing a section of messenger RNA that was previously thought to transform normal cells into cancerous ones actually acts by blocking a body's ability suppress the formation of tumors. The finding could completely alter the way that medical science approaches the formation of tumors. In molecules throughout the body, the three-prime untranslated region, or 3'UTR, is a section of messenger RNA that can alter gene expression. It's known that shortening this RNA section promotes cancerous tumor growth. "Researchers have historically thought that this was because 3'UTR shortening induces the expression of proto-oncogenes, normal genes that when altered by mutation or expressed too high, become oncogenes that can transform a normal cell into a cancer cell," said Eric Wagner, UTMB associate professor in the department of biochemistry and molecular biology. "However, using a combination of computational approaches and cancer cell models, we found that 3'UTR shortening in tumors actually causes tumor-suppressing genes to be turned off." In the study, the researchers used "Big data" analyses to reconstruct the RNA thought to form global regulatory networks within breast tumor cells and their matched normal tissues. This approach identified the fact that 3'UTRs are vital in regulating these global regulatory networks. Using this new information, they then disrupted these networks within breast cancer cells to test the effects on tumor growth. <|im_end|>

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279, 42338, 1990, 8767, 11054, 220, 18, 39615, 2078, 21389, 323, 78970, 11968, 288, 13, 3451, 14326, 320, 308, 284, 220, 1041, 8, 529, 11105, 279, 37956, 393, 907, 505, 220, 1041, 4288, 25936, 315, 220, 1041, 8718, 20794, 21389, 13, 578, 1493, 3703, 11105, 5410, 23851, 2819, 315, 393, 2819, 505, 220, 1041, 4288, 19622, 13, 8797, 1404, 2217, 57194, 505, 58499, 1202, 19329, 349, 36815, 304, 67504, 11, 279, 220, 18, 39615, 1406, 49, 706, 1101, 1027, 69702, 304, 27260, 13368, 53595, 41214, 320, 346, 31820, 8, 19812, 304, 1380, 220, 605, 662, 10541, 279, 7036, 374, 539, 7373, 16365, 11, 3846, 31820, 374, 8965, 3463, 311, 1376, 3728, 23331, 14488, 320, 346, 49, 15734, 82, 8, 26991, 3062, 24156, 11618, 220, 806, 662, 1789, 3187, 11, 279, 36254, 28321, 269, 19932, 965, 18217, 82, 3846, 51295, 2170, 11, 356, 14394, 21, 43, 323, 650, 89769, 1174, 617, 1027, 6982, 311, 37377, 19932, 965, 323, 14345, 511, 1289, 1202, 36254, 59615, 69563, 6012, 220, 717, 662, 1666, 279, 3846, 31820, 753, 23331, 8183, 374, 10213, 3196, 389, 9686, 31820, 65500, 6732, 389, 220, 18, 39615, 549, 2434, 82, 11, 584, 22601, 27985, 430, 994, 21389, 449, 66663, 220, 18, 39615, 549, 2434, 82, 912, 5129, 513, 724, 261, 9686, 51295, 2170, 11, 279, 6004, 9686, 51295, 2170, 1053, 1243, 387, 15910, 311, 312, 1911, 872, 3846, 31820, 8717, 11, 1778, 439, 36254, 59615, 57320, 21389, 11, 304, 1380, 11, 28592, 29820, 311, 15756, 4775, 268, 14093, 13, 2057, 1296, 420, 31178, 11, 584, 1176, 1511, 1664, 64868, 15174, 311, 44928, 1403, 3846, 49, 15734, 82, 505, 220, 3534, 350, 8974, 32, 17659, 56071, 323, 872, 18545, 4725, 39881, 11, 15947, 11, 3196, 389, 9686, 31820, 65500, 29654, 28347, 323, 1080, 82593, 220, 1032, 1174, 220, 975, 1990, 21389, 315, 4642, 3846, 31820, 19812, 320, 19331, 7609, 763, 4689, 11, 61412, 527, 2753, 49393, 1990, 1855, 1023, 304, 56071, 1109, 304, 4725, 39881, 11, 26310, 4245, 311, 36254, 30548, 76730, 220, 868, 323, 3728, 14278, 315, 9686, 31820, 7645, 304, 56071, 220, 845, 320, 30035, 13, 220, 17, 64, 7609, 1666, 3685, 11, 279, 4814, 315, 1080, 82593, 3135, 304, 264, 1790, 9333, 320, 2002, 20557, 11293, 8, 3846, 49, 15734, 369, 56071, 1109, 369, 4725, 39881, 320, 30035, 13, 220, 17, 65, 7609, 23966, 13, 220, 17, 25, 220, 18, 39615, 1406, 49, 2875, 6147, 44072, 311, 3846, 49, 15734, 44219, 13, 264, 1174, 59642, 753, 26670, 37929, 315, 220, 1041, 11, 931, 27716, 4183, 36815, 13840, 449, 5199, 9686, 31820, 65500, 29654, 28347, 304, 17659, 56071, 323, 18545, 4725, 39881, 13, 293, 1174, 578, 1396, 315, 3846, 31820, 13840, 304, 17659, 36254, 323, 279, 18545, 4725, 3846, 49, 15734, 82, 13, 578, 5219, 304, 75075, 527, 30510, 311, 279, 1396, 315, 13116, 6222, 1990, 36254, 323, 4725, 13, 272, 1174, 24983, 7645, 315, 41707, 868, 320, 18, 39615, 2078, 15207, 8, 323, 19932, 965, 320, 346, 31820, 8427, 8, 389, 220, 2614, 70180, 5621, 15709, 69788, 320, 85358, 8, 17659, 56071, 323, 18545, 4725, 10688, 13, 578, 16600, 5238, 4097, 279, 3152, 7645, 2819, 315, 19932, 965, 1174, 902, 374, 25983, 304, 56071, 320, 37, 7842, 284, 220, 17, 13, 16, 25800, 220, 605, 25173, 605, 7609, 294, 1174, 578, 8582, 97723, 50829, 5199, 84640, 4455, 320, 1849, 8, 4028, 220, 2614, 66279, 36254, 14, 8416, 13840, 320, 16773, 705, 21682, 555, 279, 1396, 315, 220, 18, 39615, 2078, 21389, 13, 578, 650, 2734, 47287, 1501, 279, 1396, 315, 3846, 31820, 13840, 304, 279, 4725, 323, 36254, 3846, 49, 15734, 13, 578, 5219, 304, 75075, 527, 30510, 311, 279, 1396, 315, 13116, 6222, 1990, 36254, 323, 4725, 39881, 13, 578, 393, 907, 574, 16997, 505, 264, 832, 2442, 5805, 59642, 753, 26883, 1355, 35349, 1296, 13, 8797, 1404, 2217, 2057, 19874, 279, 3560, 315, 220, 18, 39615, 2078, 304, 3846, 49, 15734, 44219, 11, 584, 10968, 389, 70180, 5621, 15709, 69788, 320, 643, 489, 883, 17659, 56071, 11, 902, 54350, 279, 8857, 320, 2614, 14, 3534, 8, 315, 350, 8974, 32, 17659, 36254, 10688, 13, 1226, 5918, 4725, 323, 36254, 3846, 49, 15734, 82, 1701, 279, 1890, 10537, 439, 3485, 13, 12362, 279, 14569, 47, 1590, 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7917, 311, 1296, 279, 6372, 389, 36254, 6650, 13, 220, 128257, 198 ]

1,945

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Coherent ultraviolet light is important for applications in environmental and life sciences. However, direct ultraviolet lasing is constrained by the fabrication challenge and operation cost. Herein, we present a strategy for the indirect generation of deep-ultraviolet lasing through a tandem upconversion process. A core–shell–shell nanoparticle is developed to achieve deep-ultraviolet emission at 290 nm by excitation in the telecommunication wavelength range at 1550 nm. The ultralarge anti-Stokes shift of 1260 nm (~3.5 eV) stems from a tandem combination of distinct upconversion processes that are integrated into separate layers of the core–shell–shell structure. By incorporating the core–shell–shell nanoparticles as gain media into a toroid microcavity, single-mode lasing at 289.2 nm is realized by pumping at 1550 nm. As various optical components are readily available in the mature telecommunication industry, our findings provide a viable solution for constructing miniaturized short-wavelength lasers that are suitable for device applications. Introduction Luminescent materials that convert excitation photons into prescribed emissions are at the core of many photonics technologies such as varicolored displays and programmable photoactivation 1 , 2 . Amongst various luminescence processes, photon upconversion characterized by high-energy emission upon excitation of lower-energy photons is of exceptional interest. Upconversion primarily takes advantage of lanthanide-doped materials, in which the stepwise excitation through the energy levels of the lanthanide activators results in visible and ultraviolet emissions by successive absorption of multiple near-infrared photons 3 , 4 , 5 , 6 , 7 . The unique upconversion process has enabled a diversity of applications ranging from bioimaging to solar energy conversion and optical storage 8 , 9 , 10 , 11 , 12 , 13 . In particular, upconversion is considered as a promising solution to generating short-wavelength lasing by pumping with longer-wavelength light sources that are more readily acquired 14 , 15 . Frequency upconversion holds potential for cost-effective construction of miniaturized deep-ultraviolet (UV) emission devices that find enormous medical and industrial applications, such as microbial sterilization and biomedical instrumentation 16 , 17 , 18 , 19 . However, the implementation of such a technique has been constrained by the limited spectral tunability of upconversion, which occurs in special lanthanide ions comprising fixed sets of energy levels. For example, one important class of light sources are lasers operating in the telecommunication wavelengths (1260 to 1675 nm) 20 , 21 , which are extensively used in fiber-optic communication and photonic circuits because of minimal optical attenuation, ready accessibility in various forms, and low cost for device fabrication. In addition, the wavelengths fall in the second near-infrared window (NIR-II) that is favorable for high-resolution in vivo bioimaging owing to maximal tissue transparency and minimal autofluorescence 22 , 23 . However, only a small number of Er 3+ -sensitized materials are capable of upconverting excitation light in this wavelength range, which displays dominated Er 3+ emissions across a limited spectrum 24 , 25 , 26 , 27 , 28 . It remains a daunting challenge to achieve deep-UV emission by excitation in the telecommunication wavelengths. To expand the spectral tunability of upconversion, herein we propose a domino upconversion (DU) scheme, in which energy amassed in one upconversion course triggers another succeeding upconversion process (Fig. 1 ). By a tandem combination of Er 3+ - and Tm 3+ -based upconversion in a core–shell–shell nanostructure, deep-ultraviolet emission is realized by excitation at 1550 nm with an ultralarge anti-Stokes shift of up to 1260 nm. We systematically investigate the energy cascade processes in the core–shell–shell nanostructures and demonstrate deep-ultraviolet lasing at 289.2 nm through the DU scheme by excitation at the telecommunication wavelength. Fig. 1: Comparison of the conventional energy transfer upconversion (ETU) and the proposed domino upconversion (DU) processes. a In an ETU process, the excitation energy is only amassed in one type of lanthanide upconverting ion. b In a DU process, the excitation energy amassed in one upconverting ion triggers energy amassment in a second upconverting ion, leading to an ultralarge anti-Stokes shift. Full size image Results Synthesis and characterization As a proof-of-concept experiment, we constructed a NaYF 4 :Yb/Tm@NaErF 4 :Ce @NaYF 4 core−shell−shell nanoparticle with the Tm 3+ - and Er 3+ -based upconversion processes separately incorporated into the core and interlayer of the nanoparticle, respectively (Fig. 2a ). The outermost shell of NaYF 4 was designed to protect the nanoparticle against surface quenching 29 , 30 . The spatial separation of the dopant ions was intended to minimize the cross-talk between different upconversion processes 31 , 32 , which were independently optimized in their respective doping domains. To facilitate the DU process through interfacial energy transfer, we also employed high concentrations of Er 3+ and Yb 3+ dopants that are highly resistant to concentration quenching (Fig. 2a ) 25 , 33 , 34 . Fig. 2: Ultralarge anti-Stokes emission through DU in core–shell–shell nanoparticles. a Schematic design of a NaYF 4 :Yb/Tm@NaErF 4 :Ce@NaYF 4 core–shell–shell nanoparticle for DU (left panel) and proposed energy transfer mechanism in the nanoparticle. b HAADF-STEM image of the NaYF 4 :Yb/Tm@NaErF 4 :Ce@NaYF 4 nanoparticles highlighting the layered structure. c Digitally processed high-resolution TEM image of a NaYF 4 :Yb/Tm@NaErF 4 :Ce@NaYF 4 nanoparticle showing the single crystalline nature. d An enlarged view of the selected area in c , indicated by a white box, showing the hexagonal structure of the lattice in accord with the NaYF 4 crystal (right panel). e Schematic illustration of the waveguide circuit for excitation of upconversion nanoparticles. Due to the convergence of the laser beam, the power density in the waveguide circuit ( I W ) was amplified relative to that in the incident fiber ( I F ). f Emission spectrum of the NaYF 4 :Yb/Tm@NaErF 4 :Ce@NaYF 4 nanoparticles by excitation of the waveguide circuit at 1550 nm with a high-power density of 2073 kW cm −2 . Full size image The nanoparticles were synthesized by a layer-by-layer epitaxial growth protocol 35 , which involved the preparation of NaYF 4 :Yb/Tm core nanoparticle followed by the epitaxial growth of the NaErF 4 :Ce", "role": "user" }, { "content": "Strong and coherent ultraviolet light emission devices have enormous medical and industrial application potential, but generating ultraviolet light emission in an effective way has been challenging. Recently, a collaborative research team co-led by researchers from City University of Hong Kong (CityU) developed a new approach to generate deep-ultraviolet lasing through a \"domino upconversion\" processing of nanoparticles using near-infrared light, which is commonly used in telecommunication devices. The findings provide a solution for constructing miniaturized high energy lasers for bio-detection and photonic devices. In the world of nanomaterials, \"photon upconversion\" means that when nanomaterial is excited by light or photons with a long wavelength and low energy, it emits light with a shorter wavelength and higher energy, such as ultraviolet light. Challenge in achieving photon upconversion Photon upconversion characterized by high-energy emission upon excitation of lower-energy photons is of exceptional interest among scientists. This is because it holds potential for cost-effective construction of miniaturized deep-ultraviolet emission devices, which have enormous medical and industrial application potential, such as microbial sterilization and biomedical instrumentation. However, the photon upconversion process has limited flexibility, as it occurs mainly in special lanthanide ions comprising fixed sets of energy levels. A research team co-led by Professor Wang Feng, from Department of Materials Science and Engineering, and Professor Chu Sai-tak, from Department of Physics at CityU, together with Dr. Jin Limin from the Harbin Institute of Technology (Shenzhen), overcame the obstacle by introducing a \"domino upconversion\" tactic. Special structural design of nanoparticles Domino upconversion is like a chain reaction, in which energy amassed in one upconversion course triggers another succeeding upconversion process. By using a doughnut-shaped microresonator, incorporated with specially designed \"upconversion nanoparticles,\" the team successfully generated high-energy, deep-ultraviolet light emission at 290 nm by excitation of low-energy infrared photons at 1550nm. \"As the excitation wavelength was in the telecommunication wavelength range, the nanoparticles can be readily used and integrated into existing fiber-optic communication and photonic circuits without complicated modification or adaptation,\" said Professor Wang. The findings were published in the journal Nature Communications, titled \"Ultralarge anti-Stokes lasing through tandem upconversion.\" The idea of constructing \"domino upconversion\" was inspired by a previous study of energy transfer in core-shell nanoparticles by Professors Wang and Chu. The core-shell structure design of the nanoparticle allows the multiphoton luminescence process in erbium (Er3+) ions. By adapting a similar synthetic protocol, the team successfully constructed \"core-shell-shell\" nanoparticles through a wet-chemistry method to explore the energy-transfer mechanism of lanthanide ions, including thulium (Tm3+) ions. Doughnut-shaped microresonator Through the careful design of doping composition and concentration in different layers or shells of the upconversion nanoparticles, the team successfully achieved a tandem combination of Er3+ and Tm3+ ions-based upconversion processes (domino upconversion). In the experiment, the Er3+ ions contained in the outer shell responded to 1550 nm near-infrared photon excitation, a wavelength located in the telecommunication range. By incorporating the nanoparticles into a doughnut-shaped microresonator cavity, the team further generated a high-quality ultraviolet microlaser, demonstrating lasing action at 289 nm by 1550 nm excitation. \"The upconversion nanoparticles act as 'wavelength converters' to multiply the energy of incident infrared photons,\" explained Professor Wang. He expects the findings to pave the way for the construction of miniaturized short-wavelength lasers and says they may inspire new ideas for designing photonic circuits. He added that the miniaturized ultraviolet laser using this domino upconversion technology can provide a platform for sensitive bio-detection, such as the detection of cancer cell secretion, by monitoring the lasing intensity and threshold, which offers great biomedical application potential in the future. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Coherent ultraviolet light is important for applications in environmental and life sciences. However, direct ultraviolet lasing is constrained by the fabrication challenge and operation cost. Herein, we present a strategy for the indirect generation of deep-ultraviolet lasing through a tandem upconversion process. A core–shell–shell nanoparticle is developed to achieve deep-ultraviolet emission at 290 nm by excitation in the telecommunication wavelength range at 1550 nm. The ultralarge anti-Stokes shift of 1260 nm (~3.5 eV) stems from a tandem combination of distinct upconversion processes that are integrated into separate layers of the core–shell–shell structure. By incorporating the core–shell–shell nanoparticles as gain media into a toroid microcavity, single-mode lasing at 289.2 nm is realized by pumping at 1550 nm. As various optical components are readily available in the mature telecommunication industry, our findings provide a viable solution for constructing miniaturized short-wavelength lasers that are suitable for device applications. Introduction Luminescent materials that convert excitation photons into prescribed emissions are at the core of many photonics technologies such as varicolored displays and programmable photoactivation 1 , 2 . Amongst various luminescence processes, photon upconversion characterized by high-energy emission upon excitation of lower-energy photons is of exceptional interest. Upconversion primarily takes advantage of lanthanide-doped materials, in which the stepwise excitation through the energy levels of the lanthanide activators results in visible and ultraviolet emissions by successive absorption of multiple near-infrared photons 3 , 4 , 5 , 6 , 7 . The unique upconversion process has enabled a diversity of applications ranging from bioimaging to solar energy conversion and optical storage 8 , 9 , 10 , 11 , 12 , 13 . In particular, upconversion is considered as a promising solution to generating short-wavelength lasing by pumping with longer-wavelength light sources that are more readily acquired 14 , 15 . Frequency upconversion holds potential for cost-effective construction of miniaturized deep-ultraviolet (UV) emission devices that find enormous medical and industrial applications, such as microbial sterilization and biomedical instrumentation 16 , 17 , 18 , 19 . However, the implementation of such a technique has been constrained by the limited spectral tunability of upconversion, which occurs in special lanthanide ions comprising fixed sets of energy levels. For example, one important class of light sources are lasers operating in the telecommunication wavelengths (1260 to 1675 nm) 20 , 21 , which are extensively used in fiber-optic communication and photonic circuits because of minimal optical attenuation, ready accessibility in various forms, and low cost for device fabrication. In addition, the wavelengths fall in the second near-infrared window (NIR-II) that is favorable for high-resolution in vivo bioimaging owing to maximal tissue transparency and minimal autofluorescence 22 , 23 . However, only a small number of Er 3+ -sensitized materials are capable of upconverting excitation light in this wavelength range, which displays dominated Er 3+ emissions across a limited spectrum 24 , 25 , 26 , 27 , 28 . It remains a daunting challenge to achieve deep-UV emission by excitation in the telecommunication wavelengths. To expand the spectral tunability of upconversion, herein we propose a domino upconversion (DU) scheme, in which energy amassed in one upconversion course triggers another succeeding upconversion process (Fig. 1 ). By a tandem combination of Er 3+ - and Tm 3+ -based upconversion in a core–shell–shell nanostructure, deep-ultraviolet emission is realized by excitation at 1550 nm with an ultralarge anti-Stokes shift of up to 1260 nm. We systematically investigate the energy cascade processes in the core–shell–shell nanostructures and demonstrate deep-ultraviolet lasing at 289.2 nm through the DU scheme by excitation at the telecommunication wavelength. Fig. 1: Comparison of the conventional energy transfer upconversion (ETU) and the proposed domino upconversion (DU) processes. a In an ETU process, the excitation energy is only amassed in one type of lanthanide upconverting ion. b In a DU process, the excitation energy amassed in one upconverting ion triggers energy amassment in a second upconverting ion, leading to an ultralarge anti-Stokes shift. Full size image Results Synthesis and characterization As a proof-of-concept experiment, we constructed a NaYF 4 :Yb/Tm@NaErF 4 :Ce @NaYF 4 core−shell−shell nanoparticle with the Tm 3+ - and Er 3+ -based upconversion processes separately incorporated into the core and interlayer of the nanoparticle, respectively (Fig. 2a ). The outermost shell of NaYF 4 was designed to protect the nanoparticle against surface quenching 29 , 30 . The spatial separation of the dopant ions was intended to minimize the cross-talk between different upconversion processes 31 , 32 , which were independently optimized in their respective doping domains. To facilitate the DU process through interfacial energy transfer, we also employed high concentrations of Er 3+ and Yb 3+ dopants that are highly resistant to concentration quenching (Fig. 2a ) 25 , 33 , 34 . Fig. 2: Ultralarge anti-Stokes emission through DU in core–shell–shell nanoparticles. a Schematic design of a NaYF 4 :Yb/Tm@NaErF 4 :Ce@NaYF 4 core–shell–shell nanoparticle for DU (left panel) and proposed energy transfer mechanism in the nanoparticle. b HAADF-STEM image of the NaYF 4 :Yb/Tm@NaErF 4 :Ce@NaYF 4 nanoparticles highlighting the layered structure. c Digitally processed high-resolution TEM image of a NaYF 4 :Yb/Tm@NaErF 4 :Ce@NaYF 4 nanoparticle showing the single crystalline nature. d An enlarged view of the selected area in c , indicated by a white box, showing the hexagonal structure of the lattice in accord with the NaYF 4 crystal (right panel). e Schematic illustration of the waveguide circuit for excitation of upconversion nanoparticles. Due to the convergence of the laser beam, the power density in the waveguide circuit ( I W ) was amplified relative to that in the incident fiber ( I F ). f Emission spectrum of the NaYF 4 :Yb/Tm@NaErF 4 :Ce@NaYF 4 nanoparticles by excitation of the waveguide circuit at 1550 nm with a high-power density of 2073 kW cm −2 . Full size image The nanoparticles were synthesized by a layer-by-layer epitaxial growth protocol 35 , which involved the preparation of NaYF 4 :Yb/Tm core nanoparticle followed by the epitaxial growth of the NaErF 4 :Ce<|im_end|> <|im_start|>assistant Strong and coherent ultraviolet light emission devices have enormous medical and industrial application potential, but generating ultraviolet light emission in an effective way has been challenging. Recently, a collaborative research team co-led by researchers from City University of Hong Kong (CityU) developed a new approach to generate deep-ultraviolet lasing through a "domino upconversion" processing of nanoparticles using near-infrared light, which is commonly used in telecommunication devices. The findings provide a solution for constructing miniaturized high energy lasers for bio-detection and photonic devices. In the world of nanomaterials, "photon upconversion" means that when nanomaterial is excited by light or photons with a long wavelength and low energy, it emits light with a shorter wavelength and higher energy, such as ultraviolet light. Challenge in achieving photon upconversion Photon upconversion characterized by high-energy emission upon excitation of lower-energy photons is of exceptional interest among scientists. This is because it holds potential for cost-effective construction of miniaturized deep-ultraviolet emission devices, which have enormous medical and industrial application potential, such as microbial sterilization and biomedical instrumentation. However, the photon upconversion process has limited flexibility, as it occurs mainly in special lanthanide ions comprising fixed sets of energy levels. A research team co-led by Professor Wang Feng, from Department of Materials Science and Engineering, and Professor Chu Sai-tak, from Department of Physics at CityU, together with Dr. Jin Limin from the Harbin Institute of Technology (Shenzhen), overcame the obstacle by introducing a "domino upconversion" tactic. Special structural design of nanoparticles Domino upconversion is like a chain reaction, in which energy amassed in one upconversion course triggers another succeeding upconversion process. By using a doughnut-shaped microresonator, incorporated with specially designed "upconversion nanoparticles," the team successfully generated high-energy, deep-ultraviolet light emission at 290 nm by excitation of low-energy infrared photons at 1550nm. "As the excitation wavelength was in the telecommunication wavelength range, the nanoparticles can be readily used and integrated into existing fiber-optic communication and photonic circuits without complicated modification or adaptation," said Professor Wang. The findings were published in the journal Nature Communications, titled "Ultralarge anti-Stokes lasing through tandem upconversion." The idea of constructing "domino upconversion" was inspired by a previous study of energy transfer in core-shell nanoparticles by Professors Wang and Chu. The core-shell structure design of the nanoparticle allows the multiphoton luminescence process in erbium (Er3+) ions. By adapting a similar synthetic protocol, the team successfully constructed "core-shell-shell" nanoparticles through a wet-chemistry method to explore the energy-transfer mechanism of lanthanide ions, including thulium (Tm3+) ions. Doughnut-shaped microresonator Through the careful design of doping composition and concentration in different layers or shells of the upconversion nanoparticles, the team successfully achieved a tandem combination of Er3+ and Tm3+ ions-based upconversion processes (domino upconversion). In the experiment, the Er3+ ions contained in the outer shell responded to 1550 nm near-infrared photon excitation, a wavelength located in the telecommunication range. By incorporating the nanoparticles into a doughnut-shaped microresonator cavity, the team further generated a high-quality ultraviolet microlaser, demonstrating lasing action at 289 nm by 1550 nm excitation. "The upconversion nanoparticles act as 'wavelength converters' to multiply the energy of incident infrared photons," explained Professor Wang. He expects the findings to pave the way for the construction of miniaturized short-wavelength lasers and says they may inspire new ideas for designing photonic circuits. He added that the miniaturized ultraviolet laser using this domino upconversion technology can provide a platform for sensitive bio-detection, such as the detection of cancer cell secretion, by monitoring the lasing intensity and threshold, which offers great biomedical application potential in the future. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Active brood-warming in army ant nests (bivouacs) is well documented for surface-dwelling Eciton burchellii and E. hamatum colonies in lowland tropical forests. However, little is known about thermoregulation by the below-ground bivouacking army ants that comprise all other species in subfamily Dorylinae. Here we report the first observations of subterranean Labidus praedator bivouacs in tropical montane and premontane conditions (Monteverde, Costa Rica), and present the first evidence for active nest warming in underground bivouacs. We measured bivouac temperatures at depth increments of 10 cm through the center of a 1565 m elevation bivouac and compared these to simultaneous measurements at the same soil depths 1 m outside the bivouac. The bivouac was actively heated to over 6 °C higher than the adjacent soil. Another bivouac showed warming of up to 3.7 °C above surface ambient. We measured critical thermal maxima (CT max ) and minima (CT min ) of L. praedator workers of a range of body sizes including callows, as well as thermal tolerances of inquiline millipedes from the bivouac. CT max varied positively with worker body size. CT min was lower for mature than for callow workers. Symbiotic millipedes had lower CT max and higher CT min than ant workers. Temperatures below the thermal tolerance ranges of symbiotic millipedes and near the bottom thermal tolerance range for callow workers were recorded in the bivouac periphery and in adjacent soil, suggesting active bivouac warming protects some members of L. praedator bivouac communities from cold-limitation at high elevations in the tropics. Access provided by Universität des es, -und Working on a manuscript? Avoid the common mistakes Introduction The typically soft-bodied, altricial brood of many social insects are more sensitive to thermal variation than adult nest mates (Nalepa 2011 ). Social insect nests are often thermally homeostatic with temperature control achieved by passive and/or active thermoregulation (Seeley and Heinrich 1981 ; Jones and Oldroyd 2007 ). Passive thermoregulation involves behavioral responses to environmental thermal gradients (Jones and Oldroyd 2007 ). Examples of passive thermoregulation among social insects include foraging site and nest site selection, nest construction and orientation, and relocation of brood within nests (Coenen-Stass, Schaarschmidt and Lamprecht 1980 ; Frouz 2000 ; Penick and Tschinkel 2008 ; McGlynn et al. 2010 ; Jílková and Frouz 2014 ). Actively thermoregulating organisms use physiology to modify internal or ambient temperatures via metabolic heating or physical activity (Seeley and Heinrich 1981 ; Jones and Oldroyd 2007 ). Examples of active thermoregulation among social insects include worker clustering, flight muscle twitching to generate heat, and wing-fanning to promote evaporative cooling (Heinrich 1993 ; Anderson, Theraulaz and Deneubourg 2002 ; Weiner et al. 2010 ). Most ant species rely on passive thermoregulation to modify nest temperatures because workers are wingless, preventing active thermoregulation via fanning or flight muscle shivering (Hölldobler and Wilson 1990 ). However, some Neotropical army ants in the subfamily Dorylinae create homeostatic thermal conditions within their temporary nests (bivouacs) via active thermoregulation (Jones and Oldroyd 2007 ). In two above-ground active species, Eciton burchellii and E. hamatum , bivouacs are composed of hundreds of thousands of clustering worker bodies that surround and insulate the brood and queen. These bivouacs are actively warmed via collective metabolic heat, and bivouac temperature variation is lower than ambient (Schneirla, Brown and Brown 1954 ; Jackson 1957 ; Coenen-Stass, Schaarschmidt and Lamprecht 1980 ; Franks 1985 , 1989 ; Anderson, Theraulaz and Deneubourg 2002 ; Jones and Oldroyd 2007 ; Kadochová and Frouz 2014 ). All other army ant species bivouac below ground (Rettenmeyer 1963 ). Here, we present the first measurements of subterranean bivouac thermal physiology and brood developmental synchrony in the army ant Labidus praedator (Smith 1858). Previous studies of army ant thermoregulation have primarily focused on above-ground E. burchellii and E. hamatum bivouacs (Schneirla, Brown and Brown 1954 ; Jackson 1957 ; Rettenmeyer 1963 ). Lowland E. burchellii bivouacs thermoregulated their brood at relatively stable elevated temperatures of 28 ± 1 °C (average 2 °C higher than ambient, maximum 6 °C higher than nocturnal low temperatures) (Schneirla, Brown and Brown 1954 ; Franks 1989 ), while lowland bivouacs of E. hamatum were on average 1 °C higher and less thermally variable than ambient conditions of 22–29°C (Jackson 1957 ). Active bivouac thermoregulation and homeostasis is thought to be tightly linked to the synchronous brood development cycles that characterize the dichotomous statary (egg/pupal) and nomadic (larval) phases of Eciton colony activity (Schneirla, Brown and Brown 1954 ; Jackson 1957 ; Franks 1989 ). Whether active or passive bivouac thermoregulation and brood synchrony occur in other species of Dorylinae is unknown. Eciton species are not representative of Dorylinae, in part because they raid and frequently bivouac above ground (Schneirla 1933 ; Schneirla, Brown and Brown 1954 ; Rettenmeyer 1963 ; Gotwald Jr 1995 ). In contrast, most Neotropical army ant species are at least partly subterranean, bivouacking underground and raiding partly or entirely below ground (Rettenmeyer 1963 ; Gotwald Jr 1995 ). These differences in foraging and bivouacking soil microhabitat correspond to differences in sensory investment and thermal tolerance (Baudier et al. 2015 ; Bulova et al 2016 ). Due to the challenge of tracking underground mobile nests, the subterranean bivouacs of many common army ants remain undescribed (Rettenmeyer 1963 ; Berghoff et al. 2002 ; Dunn 2003 ). Above-ground bivouacking in Eciton is a derived state among army ants (Brady 2003 ; Brady et al. 2014 ). Therefore, data on bivouacking behavior in other doryline genera can provide evidence of how bivouac thermoregulation evolved in the above-ground species. Labidus praedator is an abundant subterranean-bivouacking army ant that raids both on the surface of the forest floor and underground (Rettenmeyer 1963 ; Kaspari and O’Donnell 2003 ; O’Donnell et al. 2007 ). Labidus praedator ranges from the southern United States (N30°50′, W93°45′) to Argentina and Southern Brazil (S30°2′, W51°12′). Labidus praedator occurs in the lowlands near sea level, though this species is most abundant from 1000 to 1600 masl in Costa Rica (Schneirla 1949 ;", "role": "user" }, { "content": "For their colonies to survive at high altitudes, army ants keep their underground nests as much as 13 degrees F warmer than surface temperatures, according to a new study by Drexel University scientists. Although they're a nomadic species—which is relatively rare for ants—Labidus praedator create underground nests (called bivouacs) that harbor their eggs and young offspring (brood). How hot or cold that bivouac gets may be critical for the ability of the ants to stay mobile and raise their young. \"As is the case for most insects, army ant brood temperature is a key determiner of the time required for each hatched egg to reach adulthood,\" said Kaitlin Baudier, a graduate student in Drexel's College of Arts and Sciences, who teamed with Drexel professor Sean O'Donnell, PhD, to publish their findings in Insectes Sociaux. L. praedator carefully time the lifecycle of their young. Efficiency is key. When their young are larvae (freshly hatched offspring), the colony can remain on the move. But when those larvae become pupae (similar to a chrysalis in butterflies, the stage just before the ants become adults), the colony is tied down to one bivouac for weeks. Since there is an ideal temperature range that best facilitates offspring growth, it's important for the ants to keep their nest nice and toasty. And when those bivouacs occur at higher elevations that becomes especially vital. \"At high elevations, bivouac heating may be even more important than at low elevations because ambient air temperatures are further below optimum growth temperatures,\" Baudier explained. Studying army ant colonies in Costa Rica, Baudier and O'Donnell tracked three different bivouacs, the lowest constructed at 950 meters above sea level and the highest at 1,565. While Drexel's researchers measured surface and soil temperatures that frequently dropped too low for the ants' young, the bivouacs were consistently kept warm enough to remain in their ideal temperature range. In fact, the warmest temperatures were recorded lower in the nest, about 40 centimeters down, where the youngest offspring resided. Underground areas near the bivouac were only slightly warmer than above-ground—just about 1 degree F. Meanwhile, the bivouacs' mean temperature was 13 degrees F above the surface. Higher temperatures didn't just result from residual heat energy in the ground—the ants' bodies were warming it. While previous research focused on above-ground army ants who make their bivouacs at lower (and warmer) elevations, Baudier and O'Donnell's research showed the resiliency of army ants when confronting colder mountain environments. \"This study lifts the roof on what we thought army ants were capable of in terms of warming their young in the face of the more extreme cold and wet conditions at high elevations,\" Baudier said. Still, that doesn't mean that the ants are ready to climb Mount Everest. Army ants do a good job of warming their nests, but there might be a ceiling to their capabilities. In the lower bivouac the researchers studied (constructed at 950 meters above sea level) even the coolest portions were consistently warmer than the highest temperatures recorded in the bivouac at 1,565 meters above sea level. \"The record high elevation for an army ant in Costa Rica was a specimen of Labidus coecus—a close relative, though more subterranean than L. praedator—that was found at 3,000 meters above sea level. However, in the case of L. praedator, the highest I'm aware of is about 1,750 meters above sea level,\" Baudier said. \"I do suspect that cold temperatures are a major factor in setting these upper elevational ranges. The highest bivouacs seem to struggle to keep warm in wet, cold soil.\" \"We suspect ants in the mountains have to expend a lot of energy to keep their nests warm,\" O'Donnell added. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Active brood-warming in army ant nests (bivouacs) is well documented for surface-dwelling Eciton burchellii and E. hamatum colonies in lowland tropical forests. However, little is known about thermoregulation by the below-ground bivouacking army ants that comprise all other species in subfamily Dorylinae. Here we report the first observations of subterranean Labidus praedator bivouacs in tropical montane and premontane conditions (Monteverde, Costa Rica), and present the first evidence for active nest warming in underground bivouacs. We measured bivouac temperatures at depth increments of 10 cm through the center of a 1565 m elevation bivouac and compared these to simultaneous measurements at the same soil depths 1 m outside the bivouac. The bivouac was actively heated to over 6 °C higher than the adjacent soil. Another bivouac showed warming of up to 3.7 °C above surface ambient. We measured critical thermal maxima (CT max ) and minima (CT min ) of L. praedator workers of a range of body sizes including callows, as well as thermal tolerances of inquiline millipedes from the bivouac. CT max varied positively with worker body size. CT min was lower for mature than for callow workers. Symbiotic millipedes had lower CT max and higher CT min than ant workers. Temperatures below the thermal tolerance ranges of symbiotic millipedes and near the bottom thermal tolerance range for callow workers were recorded in the bivouac periphery and in adjacent soil, suggesting active bivouac warming protects some members of L. praedator bivouac communities from cold-limitation at high elevations in the tropics. Access provided by Universität des es, -und Working on a manuscript? Avoid the common mistakes Introduction The typically soft-bodied, altricial brood of many social insects are more sensitive to thermal variation than adult nest mates (Nalepa 2011 ). Social insect nests are often thermally homeostatic with temperature control achieved by passive and/or active thermoregulation (Seeley and Heinrich 1981 ; Jones and Oldroyd 2007 ). Passive thermoregulation involves behavioral responses to environmental thermal gradients (Jones and Oldroyd 2007 ). Examples of passive thermoregulation among social insects include foraging site and nest site selection, nest construction and orientation, and relocation of brood within nests (Coenen-Stass, Schaarschmidt and Lamprecht 1980 ; Frouz 2000 ; Penick and Tschinkel 2008 ; McGlynn et al. 2010 ; Jílková and Frouz 2014 ). Actively thermoregulating organisms use physiology to modify internal or ambient temperatures via metabolic heating or physical activity (Seeley and Heinrich 1981 ; Jones and Oldroyd 2007 ). Examples of active thermoregulation among social insects include worker clustering, flight muscle twitching to generate heat, and wing-fanning to promote evaporative cooling (Heinrich 1993 ; Anderson, Theraulaz and Deneubourg 2002 ; Weiner et al. 2010 ). Most ant species rely on passive thermoregulation to modify nest temperatures because workers are wingless, preventing active thermoregulation via fanning or flight muscle shivering (Hölldobler and Wilson 1990 ). However, some Neotropical army ants in the subfamily Dorylinae create homeostatic thermal conditions within their temporary nests (bivouacs) via active thermoregulation (Jones and Oldroyd 2007 ). In two above-ground active species, Eciton burchellii and E. hamatum , bivouacs are composed of hundreds of thousands of clustering worker bodies that surround and insulate the brood and queen. These bivouacs are actively warmed via collective metabolic heat, and bivouac temperature variation is lower than ambient (Schneirla, Brown and Brown 1954 ; Jackson 1957 ; Coenen-Stass, Schaarschmidt and Lamprecht 1980 ; Franks 1985 , 1989 ; Anderson, Theraulaz and Deneubourg 2002 ; Jones and Oldroyd 2007 ; Kadochová and Frouz 2014 ). All other army ant species bivouac below ground (Rettenmeyer 1963 ). Here, we present the first measurements of subterranean bivouac thermal physiology and brood developmental synchrony in the army ant Labidus praedator (Smith 1858). Previous studies of army ant thermoregulation have primarily focused on above-ground E. burchellii and E. hamatum bivouacs (Schneirla, Brown and Brown 1954 ; Jackson 1957 ; Rettenmeyer 1963 ). Lowland E. burchellii bivouacs thermoregulated their brood at relatively stable elevated temperatures of 28 ± 1 °C (average 2 °C higher than ambient, maximum 6 °C higher than nocturnal low temperatures) (Schneirla, Brown and Brown 1954 ; Franks 1989 ), while lowland bivouacs of E. hamatum were on average 1 °C higher and less thermally variable than ambient conditions of 22–29°C (Jackson 1957 ). Active bivouac thermoregulation and homeostasis is thought to be tightly linked to the synchronous brood development cycles that characterize the dichotomous statary (egg/pupal) and nomadic (larval) phases of Eciton colony activity (Schneirla, Brown and Brown 1954 ; Jackson 1957 ; Franks 1989 ). Whether active or passive bivouac thermoregulation and brood synchrony occur in other species of Dorylinae is unknown. Eciton species are not representative of Dorylinae, in part because they raid and frequently bivouac above ground (Schneirla 1933 ; Schneirla, Brown and Brown 1954 ; Rettenmeyer 1963 ; Gotwald Jr 1995 ). In contrast, most Neotropical army ant species are at least partly subterranean, bivouacking underground and raiding partly or entirely below ground (Rettenmeyer 1963 ; Gotwald Jr 1995 ). These differences in foraging and bivouacking soil microhabitat correspond to differences in sensory investment and thermal tolerance (Baudier et al. 2015 ; Bulova et al 2016 ). Due to the challenge of tracking underground mobile nests, the subterranean bivouacs of many common army ants remain undescribed (Rettenmeyer 1963 ; Berghoff et al. 2002 ; Dunn 2003 ). Above-ground bivouacking in Eciton is a derived state among army ants (Brady 2003 ; Brady et al. 2014 ). Therefore, data on bivouacking behavior in other doryline genera can provide evidence of how bivouac thermoregulation evolved in the above-ground species. Labidus praedator is an abundant subterranean-bivouacking army ant that raids both on the surface of the forest floor and underground (Rettenmeyer 1963 ; Kaspari and O’Donnell 2003 ; O’Donnell et al. 2007 ). Labidus praedator ranges from the southern United States (N30°50′, W93°45′) to Argentina and Southern Brazil (S30°2′, W51°12′). Labidus praedator occurs in the lowlands near sea level, though this species is most abundant from 1000 to 1600 masl in Costa Rica (Schneirla 1949 ;<|im_end|> <|im_start|>assistant For their colonies to survive at high altitudes, army ants keep their underground nests as much as 13 degrees F warmer than surface temperatures, according to a new study by Drexel University scientists. Although they're a nomadic species—which is relatively rare for ants—Labidus praedator create underground nests (called bivouacs) that harbor their eggs and young offspring (brood). How hot or cold that bivouac gets may be critical for the ability of the ants to stay mobile and raise their young. "As is the case for most insects, army ant brood temperature is a key determiner of the time required for each hatched egg to reach adulthood," said Kaitlin Baudier, a graduate student in Drexel's College of Arts and Sciences, who teamed with Drexel professor Sean O'Donnell, PhD, to publish their findings in Insectes Sociaux. L. praedator carefully time the lifecycle of their young. Efficiency is key. When their young are larvae (freshly hatched offspring), the colony can remain on the move. But when those larvae become pupae (similar to a chrysalis in butterflies, the stage just before the ants become adults), the colony is tied down to one bivouac for weeks. Since there is an ideal temperature range that best facilitates offspring growth, it's important for the ants to keep their nest nice and toasty. And when those bivouacs occur at higher elevations that becomes especially vital. "At high elevations, bivouac heating may be even more important than at low elevations because ambient air temperatures are further below optimum growth temperatures," Baudier explained. Studying army ant colonies in Costa Rica, Baudier and O'Donnell tracked three different bivouacs, the lowest constructed at 950 meters above sea level and the highest at 1,565. While Drexel's researchers measured surface and soil temperatures that frequently dropped too low for the ants' young, the bivouacs were consistently kept warm enough to remain in their ideal temperature range. In fact, the warmest temperatures were recorded lower in the nest, about 40 centimeters down, where the youngest offspring resided. Underground areas near the bivouac were only slightly warmer than above-ground—just about 1 degree F. Meanwhile, the bivouacs' mean temperature was 13 degrees F above the surface. Higher temperatures didn't just result from residual heat energy in the ground—the ants' bodies were warming it. While previous research focused on above-ground army ants who make their bivouacs at lower (and warmer) elevations, Baudier and O'Donnell's research showed the resiliency of army ants when confronting colder mountain environments. "This study lifts the roof on what we thought army ants were capable of in terms of warming their young in the face of the more extreme cold and wet conditions at high elevations," Baudier said. Still, that doesn't mean that the ants are ready to climb Mount Everest. Army ants do a good job of warming their nests, but there might be a ceiling to their capabilities. In the lower bivouac the researchers studied (constructed at 950 meters above sea level) even the coolest portions were consistently warmer than the highest temperatures recorded in the bivouac at 1,565 meters above sea level. "The record high elevation for an army ant in Costa Rica was a specimen of Labidus coecus—a close relative, though more subterranean than L. praedator—that was found at 3,000 meters above sea level. However, in the case of L. praedator, the highest I'm aware of is about 1,750 meters above sea level," Baudier said. "I do suspect that cold temperatures are a major factor in setting these upper elevational ranges. The highest bivouacs seem to struggle to keep warm in wet, cold soil." "We suspect ants in the mountains have to expend a lot of energy to keep their nests warm," O'Donnell added. <|im_end|>

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323, 9859, 37314, 320, 14115, 838, 8, 35530, 315, 37211, 63537, 42036, 5820, 320, 31224, 818, 2881, 64, 11, 10690, 323, 10690, 220, 6280, 19, 2652, 13972, 220, 6280, 22, 2652, 2939, 4129, 220, 3753, 24, 7609, 13440, 4642, 477, 28979, 293, 344, 283, 582, 30945, 461, 70, 2987, 323, 2967, 347, 14453, 88, 12446, 304, 1023, 9606, 315, 423, 683, 75, 125887, 374, 9987, 13, 37211, 63537, 9606, 527, 539, 18740, 315, 423, 683, 75, 125887, 11, 304, 961, 1606, 814, 25834, 323, 14134, 293, 344, 283, 582, 3485, 5015, 320, 31224, 818, 2881, 64, 220, 7285, 18, 2652, 5124, 818, 2881, 64, 11, 10690, 323, 10690, 220, 6280, 19, 2652, 10608, 2002, 76, 35472, 220, 5162, 18, 2652, 25545, 54006, 16014, 220, 2550, 20, 7609, 763, 13168, 11, 1455, 4275, 354, 51172, 13695, 3276, 9606, 527, 520, 3325, 28135, 1207, 69769, 33561, 11, 293, 344, 283, 9162, 26326, 323, 25834, 287, 28135, 477, 11622, 3770, 5015, 320, 12289, 2002, 76, 35472, 220, 5162, 18, 2652, 25545, 54006, 16014, 220, 2550, 20, 7609, 4314, 12062, 304, 369, 4210, 323, 293, 344, 283, 9162, 17614, 8162, 10796, 48877, 8024, 311, 12062, 304, 49069, 9341, 323, 29487, 25065, 320, 33, 8039, 1291, 1880, 453, 13, 220, 679, 20, 2652, 13805, 12949, 1880, 453, 220, 679, 21, 7609, 24586, 311, 279, 8815, 315, 15194, 26326, 6505, 96221, 11, 279, 1207, 69769, 33561, 293, 344, 283, 19807, 315, 1690, 4279, 13695, 61495, 7293, 56838, 17890, 320, 12289, 2002, 76, 35472, 220, 5162, 18, 2652, 9084, 876, 1885, 1880, 453, 13, 220, 1049, 17, 2652, 64845, 220, 1049, 18, 7609, 44710, 79255, 293, 344, 283, 9162, 304, 37211, 63537, 374, 264, 14592, 1614, 4315, 13695, 61495, 320, 6971, 7759, 220, 1049, 18, 2652, 36470, 1880, 453, 13, 220, 679, 19, 7609, 15636, 11, 828, 389, 293, 344, 283, 9162, 7865, 304, 1023, 294, 683, 1074, 84535, 649, 3493, 6029, 315, 1268, 293, 344, 283, 582, 30945, 461, 70, 2987, 28995, 304, 279, 3485, 79255, 9606, 13, 11868, 307, 355, 45103, 291, 859, 374, 459, 44611, 1207, 69769, 33561, 1481, 344, 283, 9162, 13695, 3276, 430, 52581, 2225, 389, 279, 7479, 315, 279, 13952, 6558, 323, 26326, 320, 12289, 2002, 76, 35472, 220, 5162, 18, 2652, 38642, 1768, 72, 323, 507, 529, 8161, 49565, 220, 1049, 18, 2652, 507, 529, 8161, 49565, 1880, 453, 13, 220, 1049, 22, 7609, 11868, 307, 355, 45103, 291, 859, 21986, 505, 279, 18561, 3723, 4273, 320, 45, 966, 11877, 1135, 39615, 11, 468, 6365, 11877, 1774, 39615, 8, 311, 32164, 323, 16642, 16327, 320, 50, 966, 11877, 17, 39615, 11, 468, 3971, 11877, 717, 39615, 570, 11868, 307, 355, 45103, 291, 859, 13980, 304, 279, 3428, 8329, 3221, 9581, 2237, 11, 3582, 420, 9606, 374, 1455, 44611, 505, 220, 1041, 15, 311, 220, 6330, 15, 9427, 75, 304, 32380, 53049, 320, 31224, 818, 2881, 64, 220, 6393, 24, 2652, 128257, 198, 128256, 78191, 198, 2520, 872, 49028, 311, 18167, 520, 1579, 4902, 21237, 11, 13695, 61495, 2567, 872, 26326, 96221, 439, 1790, 439, 220, 1032, 12628, 435, 46039, 1109, 7479, 20472, 11, 4184, 311, 264, 502, 4007, 555, 423, 38639, 301, 3907, 14248, 13, 10541, 814, 2351, 264, 9859, 37314, 9606, 50004, 374, 12309, 9024, 369, 61495, 2345, 30146, 307, 355, 45103, 291, 859, 1893, 26326, 96221, 320, 44982, 293, 344, 283, 19807, 8, 430, 57511, 872, 19335, 323, 3995, 46471, 320, 15222, 347, 570, 2650, 4106, 477, 9439, 430, 293, 344, 283, 582, 5334, 1253, 387, 9200, 369, 279, 5845, 315, 279, 61495, 311, 4822, 6505, 323, 4933, 872, 3995, 13, 330, 2170, 374, 279, 1162, 369, 1455, 41911, 11, 13695, 3276, 2967, 347, 9499, 374, 264, 1401, 6449, 261, 315, 279, 892, 2631, 369, 1855, 305, 35344, 19151, 311, 5662, 64033, 1359, 1071, 735, 1339, 3817, 426, 8039, 1291, 11, 264, 19560, 5575, 304, 423, 38639, 301, 596, 9304, 315, 17979, 323, 23199, 11, 889, 61310, 449, 423, 38639, 301, 14561, 26044, 507, 28805, 27476, 616, 11, 30661, 11, 311, 3498, 872, 14955, 304, 763, 9885, 288, 27670, 83391, 13, 445, 13, 45103, 291, 859, 15884, 892, 279, 48608, 315, 872, 3995, 13, 67667, 374, 1401, 13, 3277, 872, 3995, 527, 83861, 320, 72408, 398, 305, 35344, 46471, 705, 279, 42036, 649, 7293, 389, 279, 3351, 13, 2030, 994, 1884, 83861, 3719, 15241, 6043, 320, 65387, 311, 264, 523, 894, 19776, 285, 304, 81776, 11, 279, 6566, 1120, 1603, 279, 61495, 3719, 12884, 705, 279, 42036, 374, 17791, 1523, 311, 832, 293, 344, 283, 582, 369, 5672, 13, 8876, 1070, 374, 459, 10728, 9499, 2134, 430, 1888, 73633, 46471, 6650, 11, 433, 596, 3062, 369, 279, 61495, 311, 2567, 872, 23634, 6555, 323, 311, 15329, 13, 1628, 994, 1884, 293, 344, 283, 19807, 12446, 520, 5190, 12231, 811, 430, 9221, 5423, 16595, 13, 330, 1688, 1579, 12231, 811, 11, 293, 344, 283, 582, 24494, 1253, 387, 1524, 810, 3062, 1109, 520, 3428, 12231, 811, 1606, 35288, 3805, 20472, 527, 4726, 3770, 54767, 6650, 20472, 1359, 426, 8039, 1291, 11497, 13, 7814, 7169, 13695, 3276, 49028, 304, 32380, 53049, 11, 426, 8039, 1291, 323, 507, 28805, 27476, 616, 34156, 2380, 2204, 293, 344, 283, 19807, 11, 279, 15821, 20968, 520, 220, 15862, 20645, 3485, 9581, 2237, 323, 279, 8592, 520, 220, 16, 11, 20943, 13, 6104, 423, 38639, 301, 596, 12074, 17303, 7479, 323, 17614, 20472, 430, 14134, 12504, 2288, 3428, 369, 279, 61495, 6, 3995, 11, 279, 293, 344, 283, 19807, 1051, 21356, 8774, 8369, 3403, 311, 7293, 304, 872, 10728, 9499, 2134, 13, 763, 2144, 11, 279, 8369, 478, 20472, 1051, 12715, 4827, 304, 279, 23634, 11, 922, 220, 1272, 2960, 55336, 1523, 11, 1405, 279, 39637, 46471, 594, 4591, 13, 54987, 5789, 3221, 279, 293, 344, 283, 582, 1051, 1193, 10284, 46039, 1109, 3485, 79255, 2345, 4345, 922, 220, 16, 8547, 435, 13, 26982, 11, 279, 293, 344, 283, 19807, 6, 3152, 9499, 574, 220, 1032, 12628, 435, 3485, 279, 7479, 13, 35321, 20472, 3287, 956, 1120, 1121, 505, 33247, 8798, 4907, 304, 279, 5015, 22416, 61495, 6, 13162, 1051, 24808, 433, 13, 6104, 3766, 3495, 10968, 389, 3485, 79255, 13695, 61495, 889, 1304, 872, 293, 344, 283, 19807, 520, 4827, 320, 438, 46039, 8, 12231, 811, 11, 426, 8039, 1291, 323, 507, 28805, 27476, 616, 596, 3495, 8710, 279, 594, 4008, 2301, 315, 13695, 61495, 994, 75867, 76214, 16700, 22484, 13, 330, 2028, 4007, 54166, 279, 15485, 389, 1148, 584, 3463, 13695, 61495, 1051, 13171, 315, 304, 3878, 315, 24808, 872, 3995, 304, 279, 3663, 315, 279, 810, 14560, 9439, 323, 14739, 4787, 520, 1579, 12231, 811, 1359, 426, 8039, 1291, 1071, 13, 16782, 11, 430, 3250, 956, 3152, 430, 279, 61495, 527, 5644, 311, 26438, 10640, 87578, 13, 13309, 61495, 656, 264, 1695, 2683, 315, 24808, 872, 96221, 11, 719, 1070, 2643, 387, 264, 22959, 311, 872, 17357, 13, 763, 279, 4827, 293, 344, 283, 582, 279, 12074, 20041, 320, 82678, 520, 220, 15862, 20645, 3485, 9581, 2237, 8, 1524, 279, 74534, 19885, 1051, 21356, 46039, 1109, 279, 8592, 20472, 12715, 304, 279, 293, 344, 283, 582, 520, 220, 16, 11, 20943, 20645, 3485, 9581, 2237, 13, 330, 791, 3335, 1579, 27255, 369, 459, 13695, 3276, 304, 32380, 53049, 574, 264, 58184, 315, 11868, 307, 355, 1080, 762, 355, 29096, 3345, 8844, 11, 3582, 810, 1207, 69769, 33561, 1109, 445, 13, 45103, 291, 859, 41128, 574, 1766, 520, 220, 18, 11, 931, 20645, 3485, 9581, 2237, 13, 4452, 11, 304, 279, 1162, 315, 445, 13, 45103, 291, 859, 11, 279, 8592, 358, 2846, 8010, 315, 374, 922, 220, 16, 11, 11711, 20645, 3485, 9581, 2237, 1359, 426, 8039, 1291, 1071, 13, 330, 40, 656, 15562, 430, 9439, 20472, 527, 264, 3682, 8331, 304, 6376, 1521, 8582, 12231, 1697, 21986, 13, 578, 8592, 293, 344, 283, 19807, 2873, 311, 14993, 311, 2567, 8369, 304, 14739, 11, 9439, 17614, 1210, 330, 1687, 15562, 61495, 304, 279, 24405, 617, 311, 28410, 264, 2763, 315, 4907, 311, 2567, 872, 96221, 8369, 1359, 507, 28805, 27476, 616, 3779, 13, 220, 128257, 198 ]

2,565

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Applications such as microwave wireless communications, optical light fidelity, and light detection and ranging systems require advanced interfaces that can couple guided waves from in-plane sources into free space and manipulate the extracted free-space waves. Spatiotemporally modulated metasurfaces can control electromagnetic waves, but such systems are typically limited to free-space-only and waveguide-only platforms. Here we report a 1-bit space–time-coding metasurface antenna that can extract and mould guided waves into any desired free-space waves in both space and frequency domains. The waveguide-integrated metasurface antenna also provides a self-filtering phenomenon that overcomes the issue of sideband pollution found in traditional spatiotemporally modulated metasurfaces. To illustrate the capabilities of the approach, we use the metasurface antenna for high-efficiency frequency conversion, fundamental-frequency continuous beam scanning and independent control of multiple harmonics. Main Metamaterials are artificial materials that typically consist of subwavelength structures arranged to achieve macroscopic electromagnetic (EM) properties 1 , 2 . Metasurfaces—the two-dimensional (2D) counterpart of metamaterials—can offer distinct advantages over metamaterials such as low insertion loss, easy fabrication and conformability 3 , 4 , 5 . Metasurfaces can manipulate EM waves—including their amplitude, phase and polarization—and can dynamically control EM waves by integrating functional materials. In particular, spatial gradient metasurfaces can tailor the momentum of EM waves, enabling a wide variety of functions including abnormal deflection 5 , 6 , orbital angular momentum generation 7 , 8 , holography 9 , 10 and cloaking 11 , 12 . By loading tunable components into metasurfaces, the wavefront of EM waves can be switched on demand 13 , 14 , 15 . Recently, time-varying metasurfaces with space modulation—that is, spatiotemporally modulated metasurfaces (STMMs)—have been developed. STMMs have one or more spatially and temporally variant parameters, such as the reflection/transmission phase, amplitude, surface impedance and conductivity of the constitutive material 16 , 17 , 18 , 19 , 20 , 21 . Compared with conventional gradient metasurfaces, STMMs add an additional dimension—time—into the metasurface design, enabling new physical phenomena and a new level of EM wave manipulation in the momentum and frequency spaces. STMMs can be divided into three categories according to whether their excitation and output are guided waves or free-space waves. The first type controls the waves inside waveguides. Waveguide-based STMMs can break time-reversal symmetry and Lorentz reciprocity by cascading two standing-wave modulators with a relative phase shift 22 , 23 or by the unidirectional-propagating permittivity 19 , 20 /conductivity 17 , 18 of the constructive medium. Non-reciprocal STMMs can behave as optical isolators or circulators, potentially for on-chip integrated photonics 22 . In addition, space–time modulation allows the spectrums of guided waves to be controlled by forming photonic gauge potentials, leading to diverse phenomena, such as frequency comb generation, negative refraction, perfect focusing and Bloch oscillations in the synthetic frequency dimensions 24 , 25 , 26 . In these cases, both input and output are guided modes propagating inside the waveguides. The second type of STMM is excited by external free-space waves and offers novel physical phenomena such as the ability to overcome Lorentz reciprocity constraints 27 , 28 , 29 , 30 , Doppler cloaks 31 , 32 , 33 , harmonic generation 16 , 34 , 35 , 36 , frequency conversion 37 , 38 , 39 , 40 and direct information modulation 41 , 42 , 43 . For these situations, both input and output are free-space waves, making further on-chip integration difficult. The third type of STMM aims to bridge the gap between free-space and guided modes 18 , 44 , 45 . We term this type as a ‘metasurface antenna’ to distinguish it from the other two types and to emphasize its unique property that links guided waves in transmission lines and free space. Such STMMs have received limited attention to date, and only the breakdown of Lorentz reciprocity has been experimentally demonstrated 44 . Other wave-based spatiotemporal manipulations have yet to be explored. Such metasurface antennas, however, have a range of potential applications including microwave wireless communications, optical light fidelity, and light detection and ranging systems. These systems require advanced interfaces that can couple guided waves from in-plane sources into free space and manipulate the extracted free-space waves on demand. Phased arrays 46 , 47 are well explored at microwave frequencies to implement beamforming and steering, but they are costly and power hungry. Alternatively, edge couplers 48 and surface gratings 49 used for optical on-chip guided-to-space coupling have limited functionalities in terms of light control. Metasurfaces offer powerful opportunities to bridge the gap between waveguides and free space, but most metasurface antennas have space-only modulation and do not exploit the time dimension 50 , 51 , 52 , 53 . Sideband pollution is a key bottleneck in the broad application of STMMs. In particular, periodic temporal modulation in STMMs and time-modulated arrays 54 , 55 , 56 produce unwanted harmonic radiations, severely interfering with the useful signals. In this Article, we report a self-filtering phenomenon for waveguide-integrated metasurface antennas. Our space–time-coding (STC) metasurface antennas can achieve a versatile and complex guide to free-space functions in both spectral and spatial domains and are free of sideband pollution. We also theoretically predict and experimentally demonstrate that a 1-bit coding scheme—the simplest digital version of metasurfaces—can achieve full control of the frequency and momentum contents of EM waves, which typically requires continuous or multibit spatiotemporal modulations for conventional free-space-only STMMs. We illustrate the flexibility in frequency and space manipulation of our STC metasurface antenna by using it for high-efficiency frequency conversion, fundamental-frequency continuous beam scanning, and multiharmonic independent control. Our STC metasurface antenna could be of use in wireless communications, cognitive radar and integrated photonics. Theoretical formulation A conceptual illustration of the waveguide-integrated STC metasurface antenna, consisting of a one-dimensional array of meta-atoms, is shown in Fig. 1 . The propagating guided waves inside the waveguide can be extracted and moulded into desired out-of-plane free-space waves in both spatial and frequency domains. Positive–intrinsic–negative (PIN) diodes are utilized as the active components embedded into each meta-atom to independently", "role": "user" }, { "content": "Antennas that can couple guided waves emitted from different sources in free space and manipulate these waves are crucial to the development of numerous technologies, including wireless communication, optical communication and ranging systems. Metasurfaces, thin films made up of several elements, have shown promise for developing these types of antennas. Researchers at City University of Hong Kong and Southeast University have recently created a new metasurface antenna that can extract and manipulate guided waves to create desired free-space waves in both the spatial and frequency domains. This antenna, introduced in a paper published in Nature Electronics, combines two different research advancements, namely amplitude-modulated (AM) leaky-wave antennas and space-time coding techniques. \"Our paper is based on the invention of the amplitude-modulated leaky-wave antenna reported in the Ph.D. thesis of Dr. Gengbo WU at the City University of Hong Kong (CityU) and the groundbreaking research on space-time-coding metasurface led by Academician Tie Jun Cui at Southeast University,\" Prof. Chi Hou Chan, one of the researchers who carried out the study, told TechXplore. \"The AM leaky-wave antennas are inspired by the amplitude modulation in classical communications theory. \" A key advantage of AM leaky-wave antennas is that their radiation pattern can easily be synthesized or tailored for specific uses, by changing the antenna's shape and structure. Once an antenna is fabricated, however, its radiation characteristics will typically remain fixed. \"Around the same time when the AM leaky-wave antennas were presented in 2020, Dr. Jun Yan Dai joined the CityU research group from Southeast University for a postdoctoral research fellow appointment,\" Prof. Chan said. \"He came from the research group led by Academician Tie Jun Cui and Professor Qiang Cheng and brought us the use of space-time coding, or software control, to dynamically reconfigure the antenna performance.\" Measurement setup of the space-time-coding metasurface antenna in a microwave anechoic chamber. Credit: Wu et al. Space-time coding, or space-time block coding, is a technique that allows engineers to transmit multiple copies of a data stream across several antennas, using the different versions of the original data to transfer data more reliably. Prof. Chan and his colleagues combined space-time coding techniques with AM leaky-wave antenna design to enable the modulation of emitted radiation patterns. \"By combining the two approaches, we achieve a designated radiation characteristic by controlling the on-off sequences and durations of the switches on the leaky-wave antenna through a space-time matrix that can be generated via analytical means,\" Prof. Chan explained. \"Due to the guided-wave nature of the leaky-wave antenna, unwanted harmonics generated by the switches can be filtered out by the waveguide, leading to sideband suppression. The reported research results are generated with synergistic efforts and complementary expertise by the two research teams at City University of Hong Kong and Southeast University.\" The new sideband-free and space-time coding metasurface antennas introduced by the researchers ultimately allow users to attain different radiation characteristics through software control, without requiring physical alterations to the antenna's structure. This means that the unwanted sidebands or harmonics that hinder the performance of conventional antennas based on reconfigurable metasurfaces can be eradicated. \"For example, the same frequency beam steering is achievable with our antenna,\" Prof. Chan said. \"As the space-time matrix is linear, different beams radiating at different frequencies can be generated simultaneously by the superposition of different space-time matrices. As the space-time matrix is linear, different beams radiating at different frequencies can be generated simultaneously by the superposition of different space-time matrices.\" Prof. Chan and his colleagues assessed the effectiveness of their antenna design in a series of tests and found that it enabled high-efficiency frequency conversion, fundamental-frequency continuous beam scanning and the independent control of multiple harmonics. In the future, their antenna could be combined with different base-band modulation schemes to achieve highly efficient and secure communications. \"In our next studies, we plan to modify the antenna's structure to achieve more control over the radiation characteristics, including polarization of the radiated beams,\" Prof. Chan added. \"One unique feature of the antennas is that we can control the amplitude and phase distributions on the antenna aperture. Therefore, we can create all kinds of radiation characteristics, including linear sweeping of a focused spot along the length or perpendicular to the antenna surface.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Applications such as microwave wireless communications, optical light fidelity, and light detection and ranging systems require advanced interfaces that can couple guided waves from in-plane sources into free space and manipulate the extracted free-space waves. Spatiotemporally modulated metasurfaces can control electromagnetic waves, but such systems are typically limited to free-space-only and waveguide-only platforms. Here we report a 1-bit space–time-coding metasurface antenna that can extract and mould guided waves into any desired free-space waves in both space and frequency domains. The waveguide-integrated metasurface antenna also provides a self-filtering phenomenon that overcomes the issue of sideband pollution found in traditional spatiotemporally modulated metasurfaces. To illustrate the capabilities of the approach, we use the metasurface antenna for high-efficiency frequency conversion, fundamental-frequency continuous beam scanning and independent control of multiple harmonics. Main Metamaterials are artificial materials that typically consist of subwavelength structures arranged to achieve macroscopic electromagnetic (EM) properties 1 , 2 . Metasurfaces—the two-dimensional (2D) counterpart of metamaterials—can offer distinct advantages over metamaterials such as low insertion loss, easy fabrication and conformability 3 , 4 , 5 . Metasurfaces can manipulate EM waves—including their amplitude, phase and polarization—and can dynamically control EM waves by integrating functional materials. In particular, spatial gradient metasurfaces can tailor the momentum of EM waves, enabling a wide variety of functions including abnormal deflection 5 , 6 , orbital angular momentum generation 7 , 8 , holography 9 , 10 and cloaking 11 , 12 . By loading tunable components into metasurfaces, the wavefront of EM waves can be switched on demand 13 , 14 , 15 . Recently, time-varying metasurfaces with space modulation—that is, spatiotemporally modulated metasurfaces (STMMs)—have been developed. STMMs have one or more spatially and temporally variant parameters, such as the reflection/transmission phase, amplitude, surface impedance and conductivity of the constitutive material 16 , 17 , 18 , 19 , 20 , 21 . Compared with conventional gradient metasurfaces, STMMs add an additional dimension—time—into the metasurface design, enabling new physical phenomena and a new level of EM wave manipulation in the momentum and frequency spaces. STMMs can be divided into three categories according to whether their excitation and output are guided waves or free-space waves. The first type controls the waves inside waveguides. Waveguide-based STMMs can break time-reversal symmetry and Lorentz reciprocity by cascading two standing-wave modulators with a relative phase shift 22 , 23 or by the unidirectional-propagating permittivity 19 , 20 /conductivity 17 , 18 of the constructive medium. Non-reciprocal STMMs can behave as optical isolators or circulators, potentially for on-chip integrated photonics 22 . In addition, space–time modulation allows the spectrums of guided waves to be controlled by forming photonic gauge potentials, leading to diverse phenomena, such as frequency comb generation, negative refraction, perfect focusing and Bloch oscillations in the synthetic frequency dimensions 24 , 25 , 26 . In these cases, both input and output are guided modes propagating inside the waveguides. The second type of STMM is excited by external free-space waves and offers novel physical phenomena such as the ability to overcome Lorentz reciprocity constraints 27 , 28 , 29 , 30 , Doppler cloaks 31 , 32 , 33 , harmonic generation 16 , 34 , 35 , 36 , frequency conversion 37 , 38 , 39 , 40 and direct information modulation 41 , 42 , 43 . For these situations, both input and output are free-space waves, making further on-chip integration difficult. The third type of STMM aims to bridge the gap between free-space and guided modes 18 , 44 , 45 . We term this type as a ‘metasurface antenna’ to distinguish it from the other two types and to emphasize its unique property that links guided waves in transmission lines and free space. Such STMMs have received limited attention to date, and only the breakdown of Lorentz reciprocity has been experimentally demonstrated 44 . Other wave-based spatiotemporal manipulations have yet to be explored. Such metasurface antennas, however, have a range of potential applications including microwave wireless communications, optical light fidelity, and light detection and ranging systems. These systems require advanced interfaces that can couple guided waves from in-plane sources into free space and manipulate the extracted free-space waves on demand. Phased arrays 46 , 47 are well explored at microwave frequencies to implement beamforming and steering, but they are costly and power hungry. Alternatively, edge couplers 48 and surface gratings 49 used for optical on-chip guided-to-space coupling have limited functionalities in terms of light control. Metasurfaces offer powerful opportunities to bridge the gap between waveguides and free space, but most metasurface antennas have space-only modulation and do not exploit the time dimension 50 , 51 , 52 , 53 . Sideband pollution is a key bottleneck in the broad application of STMMs. In particular, periodic temporal modulation in STMMs and time-modulated arrays 54 , 55 , 56 produce unwanted harmonic radiations, severely interfering with the useful signals. In this Article, we report a self-filtering phenomenon for waveguide-integrated metasurface antennas. Our space–time-coding (STC) metasurface antennas can achieve a versatile and complex guide to free-space functions in both spectral and spatial domains and are free of sideband pollution. We also theoretically predict and experimentally demonstrate that a 1-bit coding scheme—the simplest digital version of metasurfaces—can achieve full control of the frequency and momentum contents of EM waves, which typically requires continuous or multibit spatiotemporal modulations for conventional free-space-only STMMs. We illustrate the flexibility in frequency and space manipulation of our STC metasurface antenna by using it for high-efficiency frequency conversion, fundamental-frequency continuous beam scanning, and multiharmonic independent control. Our STC metasurface antenna could be of use in wireless communications, cognitive radar and integrated photonics. Theoretical formulation A conceptual illustration of the waveguide-integrated STC metasurface antenna, consisting of a one-dimensional array of meta-atoms, is shown in Fig. 1 . The propagating guided waves inside the waveguide can be extracted and moulded into desired out-of-plane free-space waves in both spatial and frequency domains. Positive–intrinsic–negative (PIN) diodes are utilized as the active components embedded into each meta-atom to independently<|im_end|> <|im_start|>assistant Antennas that can couple guided waves emitted from different sources in free space and manipulate these waves are crucial to the development of numerous technologies, including wireless communication, optical communication and ranging systems. Metasurfaces, thin films made up of several elements, have shown promise for developing these types of antennas. Researchers at City University of Hong Kong and Southeast University have recently created a new metasurface antenna that can extract and manipulate guided waves to create desired free-space waves in both the spatial and frequency domains. This antenna, introduced in a paper published in Nature Electronics, combines two different research advancements, namely amplitude-modulated (AM) leaky-wave antennas and space-time coding techniques. "Our paper is based on the invention of the amplitude-modulated leaky-wave antenna reported in the Ph.D. thesis of Dr. Gengbo WU at the City University of Hong Kong (CityU) and the groundbreaking research on space-time-coding metasurface led by Academician Tie Jun Cui at Southeast University," Prof. Chi Hou Chan, one of the researchers who carried out the study, told TechXplore. "The AM leaky-wave antennas are inspired by the amplitude modulation in classical communications theory. " A key advantage of AM leaky-wave antennas is that their radiation pattern can easily be synthesized or tailored for specific uses, by changing the antenna's shape and structure. Once an antenna is fabricated, however, its radiation characteristics will typically remain fixed. "Around the same time when the AM leaky-wave antennas were presented in 2020, Dr. Jun Yan Dai joined the CityU research group from Southeast University for a postdoctoral research fellow appointment," Prof. Chan said. "He came from the research group led by Academician Tie Jun Cui and Professor Qiang Cheng and brought us the use of space-time coding, or software control, to dynamically reconfigure the antenna performance." Measurement setup of the space-time-coding metasurface antenna in a microwave anechoic chamber. Credit: Wu et al. Space-time coding, or space-time block coding, is a technique that allows engineers to transmit multiple copies of a data stream across several antennas, using the different versions of the original data to transfer data more reliably. Prof. Chan and his colleagues combined space-time coding techniques with AM leaky-wave antenna design to enable the modulation of emitted radiation patterns. "By combining the two approaches, we achieve a designated radiation characteristic by controlling the on-off sequences and durations of the switches on the leaky-wave antenna through a space-time matrix that can be generated via analytical means," Prof. Chan explained. "Due to the guided-wave nature of the leaky-wave antenna, unwanted harmonics generated by the switches can be filtered out by the waveguide, leading to sideband suppression. The reported research results are generated with synergistic efforts and complementary expertise by the two research teams at City University of Hong Kong and Southeast University." The new sideband-free and space-time coding metasurface antennas introduced by the researchers ultimately allow users to attain different radiation characteristics through software control, without requiring physical alterations to the antenna's structure. This means that the unwanted sidebands or harmonics that hinder the performance of conventional antennas based on reconfigurable metasurfaces can be eradicated. "For example, the same frequency beam steering is achievable with our antenna," Prof. Chan said. "As the space-time matrix is linear, different beams radiating at different frequencies can be generated simultaneously by the superposition of different space-time matrices. As the space-time matrix is linear, different beams radiating at different frequencies can be generated simultaneously by the superposition of different space-time matrices." Prof. Chan and his colleagues assessed the effectiveness of their antenna design in a series of tests and found that it enabled high-efficiency frequency conversion, fundamental-frequency continuous beam scanning and the independent control of multiple harmonics. In the future, their antenna could be combined with different base-band modulation schemes to achieve highly efficient and secure communications. "In our next studies, we plan to modify the antenna's structure to achieve more control over the radiation characteristics, including polarization of the radiated beams," Prof. Chan added. "One unique feature of the antennas is that we can control the amplitude and phase distributions on the antenna aperture. Therefore, we can create all kinds of radiation characteristics, including linear sweeping of a focused spot along the length or perpendicular to the antenna surface." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Models developed for gross domestic product (GDP) growth forecasting tend to be extremely complex, relying on a large number of variables and parameters. Such complexity is not always to the benefit of the accuracy of the forecast. Economic complexity constitutes a framework that builds on methods developed for the study of complex systems to construct approaches that are less demanding than standard macroeconomic ones in terms of data requirements, but whose accuracy remains to be systematically benchmarked. Here we develop a forecasting scheme that is shown to outperform the accuracy of the five-year forecast issued by the International Monetary Fund (IMF) by more than 25% on the available data. The model is based on effectively representing economic growth as a two-dimensional dynamical system, defined by GDP per capita and ‘fitness’, a variable computed using only publicly available product-level export data. We show that forecasting errors produced by the method are generally predictable and are also uncorrelated to IMF errors, suggesting that our method is extracting information that is complementary to standard approaches. We believe that our findings are of a very general nature and we plan to extend our validations on larger datasets in future works. Main In recent years a new approach to macroeconomic analysis and forecasting has been developed in the context of complex systems. This new framework, which goes under the name of economic complexity (EC), provides a concise description of global macroeconomic relations, technological trends and growth dynamics. By contrast with standard macroeconomics, EC is parsimonious in terms of data requirements, both in terms of quantity and diversity. EC leverages the ability of network algorithms to extract information from reliable and standardized datasets on global trade to build a metrics of national industrial competitiveness, called economic fitness (EF). In this work we show how EF can be combined with techniques from dynamical systems to provide a novel approach to gross domestic product growth forecasting that is concise and reproducible, surpasses the accuracy of mainstream institutions such as the IMF, and provides a clearer understanding and interpretation of the dynamics of growth. Besides providing extensive validation, we show how this new approach is complementary to standard ones, and how its combination with mainstream models further improves accuracy. These results imply that further effort should be made in order to integrate EC in the standard framework, and the fact that such accuracy arises from the dynamics of low-dimensional systems can help improve and rethink our vision of the forces that drive long-term growth. Less data is more Models developed for GDP growth forecasting are very complex. These typically make use of a large number of variables (up to hundreds of them), and for each of those there is at least one parameter to be fitted to data, or assigned by assumptions. Such variables range from socio-economic indicators (labour productivity, employment, schooling, population age, and so on) to financial indicators (fiscal policies, interest rates, public debt) and global trade indicators (raw material prices, trade openness, exchange rates) among others 1 , 2 , 3 . To have such complex models, with so many variables, offers the illusion to be able to capture all the components that drive economic growth and therefore to deliver the best possible forecasting. However, this is in general not the case, for two reasons: first, it is in practice very hard to find the right ‘recipe’ to mix all these variables (that is, the right functional form and the right parameters) in order to have an accurate forecast of growth. There is in fact scarcely a principle that can drive the choice of how to combine schooling with raw material prices for instance. Second, increasing the number of input variables exponentially increases the dimensionality of the space over which one would like to fit a function (the model) that predicts economic growth 4 : this implies that the ability to systematically sample observations from this space is very limited. In many cases, not only in economics, theoretical modelling and forecasting are not tightly related 5 . Most of the modelling efforts are in the direction of oversimplified representations that aim only at understanding the potential effects of a single variable, or of a limited set of them, in a controlled setting. Although these models may help grasp many isolated implications, they are rarely used directly to predict precise dynamics of complex systems such as, in the case of economics, countries’ growth or crisis. On the other side, the approaches explicitly developed for forecasting often depart from rigorous theoretical models, and are typically grounded on econometric or statistical techniques. From a physicist’s perspective, such a situation can be mapped to the more general problem of forecasting the evolution of a dynamical system of which we do not know the actual laws of motion. The state of the system, in the case of growth forecasting, is the GDP of the country, together with all the other socio-economic variables that are used in the model, and we suppose the dynamics to be ruled by some kind of coupling among such variables. The only knowledge we have about the system is a collection of previously observed states, together with their evolution after a fixed time delay (possibly only along the GDP direction, if we do not know the evolution of the other indicators). In such a situation, to perform a prediction for the evolution of a new and previously unseen state, the most basic approach would be to look for the most similar state of which we know the evolution from past data (an analogue) and use that evolution as a prediction. This approach goes under the name of ‘method of analogues’, and has a long story of successful and failed applications 6 , 7 , 8 . This model requires only a rule to chose the analogues and a procedure to extract the information from them. In light of basic considerations about dynamical systems, such as those exposed in ref. 4 , it is easy to see", "role": "user" }, { "content": "A team of Italian physicists has used economic complexity theory to produce five-year gross domestic product (GDP) estimates for several countries around the world. In their paper published in the journal Nature Physics, Andrea Tacchella, D. Mazzilli and Luciano Pietronero describe how they applied the theory to economic forecasting and how well it has worked thus far. Currently, economists use a variety of models to produce GDP estimates, which are often used by law and policy makers to inform decisions about future events. Such models typically require a host of variable inputs and are quite complex. In sharp contrast, the estimates made by the Italian team used just two variables: current GDP and another they describe as \"economic fitness.\" The researchers calculated a number for a given country's economic fitness using physics principles applied to export products. Such factors as diversification and the complexity of the products were taken into account, offering a means of gauging the relative strength of a given economy. The idea was to rate a country's economic strength—the wider the range of products being exported and the more complex they were, the more likely GDP was likely to grow—and used that to forecast future prosperity. The team reports that they have been running their models for approximately six years—long enough for them to see how well their estimates matched actual GDP numbers over time. They report that their estimates were on average 25 percent more accurate than were those made by the International Monetary Fund. They report also that their models accurately predicted the booming Chinese economy in 2015 when more traditional models suggested the country was headed for a slowdown. The researchers explain that the field of economic complexity involves studying the behavior of economies over time and the factors that cause them to change. Doing so includes using tools such as those that have been developed to measure turbulence in fluids and traffic jams. The philosophy of such research, they explain, revolves around the idea that complex systems with a large number of elements that interact in non-linear ways tend to have emergent properties. Learning to understand such properties, they further note, can offer insights into relationships such as the one between exports and GDP trends. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Models developed for gross domestic product (GDP) growth forecasting tend to be extremely complex, relying on a large number of variables and parameters. Such complexity is not always to the benefit of the accuracy of the forecast. Economic complexity constitutes a framework that builds on methods developed for the study of complex systems to construct approaches that are less demanding than standard macroeconomic ones in terms of data requirements, but whose accuracy remains to be systematically benchmarked. Here we develop a forecasting scheme that is shown to outperform the accuracy of the five-year forecast issued by the International Monetary Fund (IMF) by more than 25% on the available data. The model is based on effectively representing economic growth as a two-dimensional dynamical system, defined by GDP per capita and ‘fitness’, a variable computed using only publicly available product-level export data. We show that forecasting errors produced by the method are generally predictable and are also uncorrelated to IMF errors, suggesting that our method is extracting information that is complementary to standard approaches. We believe that our findings are of a very general nature and we plan to extend our validations on larger datasets in future works. Main In recent years a new approach to macroeconomic analysis and forecasting has been developed in the context of complex systems. This new framework, which goes under the name of economic complexity (EC), provides a concise description of global macroeconomic relations, technological trends and growth dynamics. By contrast with standard macroeconomics, EC is parsimonious in terms of data requirements, both in terms of quantity and diversity. EC leverages the ability of network algorithms to extract information from reliable and standardized datasets on global trade to build a metrics of national industrial competitiveness, called economic fitness (EF). In this work we show how EF can be combined with techniques from dynamical systems to provide a novel approach to gross domestic product growth forecasting that is concise and reproducible, surpasses the accuracy of mainstream institutions such as the IMF, and provides a clearer understanding and interpretation of the dynamics of growth. Besides providing extensive validation, we show how this new approach is complementary to standard ones, and how its combination with mainstream models further improves accuracy. These results imply that further effort should be made in order to integrate EC in the standard framework, and the fact that such accuracy arises from the dynamics of low-dimensional systems can help improve and rethink our vision of the forces that drive long-term growth. Less data is more Models developed for GDP growth forecasting are very complex. These typically make use of a large number of variables (up to hundreds of them), and for each of those there is at least one parameter to be fitted to data, or assigned by assumptions. Such variables range from socio-economic indicators (labour productivity, employment, schooling, population age, and so on) to financial indicators (fiscal policies, interest rates, public debt) and global trade indicators (raw material prices, trade openness, exchange rates) among others 1 , 2 , 3 . To have such complex models, with so many variables, offers the illusion to be able to capture all the components that drive economic growth and therefore to deliver the best possible forecasting. However, this is in general not the case, for two reasons: first, it is in practice very hard to find the right ‘recipe’ to mix all these variables (that is, the right functional form and the right parameters) in order to have an accurate forecast of growth. There is in fact scarcely a principle that can drive the choice of how to combine schooling with raw material prices for instance. Second, increasing the number of input variables exponentially increases the dimensionality of the space over which one would like to fit a function (the model) that predicts economic growth 4 : this implies that the ability to systematically sample observations from this space is very limited. In many cases, not only in economics, theoretical modelling and forecasting are not tightly related 5 . Most of the modelling efforts are in the direction of oversimplified representations that aim only at understanding the potential effects of a single variable, or of a limited set of them, in a controlled setting. Although these models may help grasp many isolated implications, they are rarely used directly to predict precise dynamics of complex systems such as, in the case of economics, countries’ growth or crisis. On the other side, the approaches explicitly developed for forecasting often depart from rigorous theoretical models, and are typically grounded on econometric or statistical techniques. From a physicist’s perspective, such a situation can be mapped to the more general problem of forecasting the evolution of a dynamical system of which we do not know the actual laws of motion. The state of the system, in the case of growth forecasting, is the GDP of the country, together with all the other socio-economic variables that are used in the model, and we suppose the dynamics to be ruled by some kind of coupling among such variables. The only knowledge we have about the system is a collection of previously observed states, together with their evolution after a fixed time delay (possibly only along the GDP direction, if we do not know the evolution of the other indicators). In such a situation, to perform a prediction for the evolution of a new and previously unseen state, the most basic approach would be to look for the most similar state of which we know the evolution from past data (an analogue) and use that evolution as a prediction. This approach goes under the name of ‘method of analogues’, and has a long story of successful and failed applications 6 , 7 , 8 . This model requires only a rule to chose the analogues and a procedure to extract the information from them. In light of basic considerations about dynamical systems, such as those exposed in ref. 4 , it is easy to see<|im_end|> <|im_start|>assistant A team of Italian physicists has used economic complexity theory to produce five-year gross domestic product (GDP) estimates for several countries around the world. In their paper published in the journal Nature Physics, Andrea Tacchella, D. Mazzilli and Luciano Pietronero describe how they applied the theory to economic forecasting and how well it has worked thus far. Currently, economists use a variety of models to produce GDP estimates, which are often used by law and policy makers to inform decisions about future events. Such models typically require a host of variable inputs and are quite complex. In sharp contrast, the estimates made by the Italian team used just two variables: current GDP and another they describe as "economic fitness." The researchers calculated a number for a given country's economic fitness using physics principles applied to export products. Such factors as diversification and the complexity of the products were taken into account, offering a means of gauging the relative strength of a given economy. The idea was to rate a country's economic strength—the wider the range of products being exported and the more complex they were, the more likely GDP was likely to grow—and used that to forecast future prosperity. The team reports that they have been running their models for approximately six years—long enough for them to see how well their estimates matched actual GDP numbers over time. They report that their estimates were on average 25 percent more accurate than were those made by the International Monetary Fund. They report also that their models accurately predicted the booming Chinese economy in 2015 when more traditional models suggested the country was headed for a slowdown. The researchers explain that the field of economic complexity involves studying the behavior of economies over time and the factors that cause them to change. Doing so includes using tools such as those that have been developed to measure turbulence in fluids and traffic jams. The philosophy of such research, they explain, revolves around the idea that complex systems with a large number of elements that interact in non-linear ways tend to have emergent properties. Learning to understand such properties, they further note, can offer insights into relationships such as the one between exports and GDP trends. <|im_end|>

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1,621

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Over the past two centuries, the human population has grown sevenfold and the experts anticipate the addition of 2–3 billion more during the twenty-first century. In the present overview, I take a historical glance at how humans supported such extraordinary population growth first through the invention of agriculture and more recently through the rapid deployment of scientific and technological advances in agriculture. I then identify future challenges posed by continued population growth and climate warming on a finite planet. I end by discussing both how we can meet such challenges and what stands in the way. Background Today we have enough food to meet the world’s needs. Indeed, we have an extraordinary global food system that brings food from all over the planet to consumers who can afford to buy it. The food price spike of 2008 and the resurgence of high food prices in recent years have had little impact on the affluent citizens of the developed world who spend a small fraction of their income on food. By contrast, food prices have a profound impact on the world’s poorest people. Many of them spend half or more of their income on food. During the food price crisis of 2008, there were food riots in more than 30 countries. Unrest in the Middle East and North Africa tracks with the price of food, as is dramatically illustrated in Fig. 1 . Spiraling food prices drive the world’s poorest into chronic hunger even in a world of relative plenty. Fig. 1 Food price spikes are correlated with increases in food riots. Red dashed vertical lines correspond to beginning dates of “food riots” and protests associated with the major recent unrest in North Africa and the Middle East. The overall death toll is reported in parentheses . The blue vertical line indicates the date on which the authors of the cited report [ 1 ] submitted a report to the U.S. government warning of the link between food prices, social unrest, and political instability. The inset shows the FAO Food Price Index from 1990 to 2011. (The figure is reproduced with permission from [ 1 ]). Full size image Does this mean we need worry only about poverty, not about the global food supply, as suggested in a recent editorial by the influential New York Times food commentator Mark Bittman [ 2 ]? Analyses of the most recent United Nations projections indicate that the human population will expand from roughly 7.2 billion today to 9.6 billion in 2050 and 10.9 billion by 2100 [ 3 , 4 ]. Current yield growth trends are simply insufficient to keep up with growing demand [ 5 ]. As well, the rapid expansion of agriculture over the past century to feed today’s population has had a devastating impact on biodiversity [ 6 ]. As a result, there is an acute need to intensify agricultural productivity, while at the same time decreasing the deleterious impact of agriculture on biodiversity and the services provided by complex ecosystems [ 7 ]. Historical perspective For most of our evolutionary history, our numbers were small and we were mobile hunter-gatherers. We spent our time finding and capturing enough food to feed ourselves and our closest kin. Then sometime between 10 and 20,000 years ago—maybe even more—that started to change. We began to shape plants and animals to our own advantage and settled down to grow and herd them [ 8 ]. The process by which we have modified plants and animals to suit our needs, traditionally called “domestication,” is a process of genetic modification [ 9 ]. Early peoples selected variant organisms—plants, animals, and microbes—with useful traits, such as seeds that adhere to plants until they are harvested and animals tame enough to herd. Domestication is a process of modification that is possible because of the genetic variation constantly arising in all living organisms. While hunter-gatherers were quite sophisticated in their resource management, it was systematic planting and harvesting of crops that marks the origin of what we now call “agriculture” [ 10 ]. Agriculture allowed people to produce more food than they consumed; cities and civilization followed. Thus human civilization emerged because we figured out how to produce surplus food. We could feed artisans and scribes and warriors and kings. For the next 10 millennia, people built cities and civilizations, wore out the land, invaded their neighbors or abandoned the cities and civilizations, eventually rebuilding on fresh land [ 11 ]. It was often the fertility of the land that determined how long a civilization lasted. Plants extract nutrients from the soil and crop yields decline, making it harder and harder to produce enough food as the number of people grows [ 8 ]. Concern about access to sufficient food, today called “food security,” is as old as mankind. Thomas Malthus’ famous Essay on Population, published in 1798, crystallized the problem of balancing food and human population for the modern era [ 12 ]. Malthus believed that humanity was doomed to food insecurity because our numbers increased exponentially, while our ability to produce food could only increase linearly. Curiously, Malthus penned his essay at about the time that science began to play a major role in boosting agricultural productivity. Late eighteenth century milestones were Joseph Priestley’s discovery that plants emit oxygen and Nicholas-Théodore de Saussure’s definition of the chemical composition of plants [ 13 , 14 ]. Malthus could not have envisioned the extraordinary increases in productivity that the integration of science and technology into agricultural practice would stimulate over the ensuing two centuries. Both organic- and mineral fertilization of plants have been practiced since ancient times. Farmers knew that certain chemicals and biological materials, ranging from fish and oyster shells to manure and bones, stimulated plant growth [ 15 , 16 ]. Justus von Liebig made important contributions to the study of plant nutrient requirements, understanding that biological sources of nitrogen could be replaced with purely chemical sources. But supplying nitrogen in the forms that plants use", "role": "user" }, { "content": "A former adviser to the US Secretary of State says that genetic modification (GM) is the most critical technology in agriculture for meeting the challenges of feeding a growing global population, writing in the open access journal Agriculture & Food Security. Nina Fedoroff, molecular biologist and former Science and Technology Adviser to Hillary Clinton and Condoleezza Rice, warns of the detrimental influence of politics and misinformation on the safety of GM crops. Instead, Fedoroff says that: \"GM crops are arguably the safest new crops ever introduced into the human and animal food chains.\" Addressing safety concerns, Fedoroff highlights recent studies that have revealed that plant modification by molecular techniques has less impact on gene expression, protein and metabolite levels than conventional genetic crosses. New methods are also rapidly being developed that promise to further increase the specificity and precision of genetic modification. \"The overwhelming evidence is that the GM foods now on the market are as safe, or safer, than non-GM foods,\" argues Fedoroff. She also cites a recent overview by the European Union of more than 130 research projects over 25 years concluding that GM methods are not inherently more risky than conventional plant breeding technologies. Fedoroff adds: \"Every credible scientific body that has examined the evidence has come to the same conclusion.\" In her commentary, Fedoroff explains that the human population has grown seven-fold over the past two centuries, with the addition of a further 2-3 billion anticipated during the 21st century. The UN's Food and Agriculture Organization has estimated that food production will need to increase by 70% by 2050 to meet this demand. She writes: \"Current yield growth trends are simply insufficient to keep up with growing demand...To live sustainably within planetary constraints, we must grow more on the same amount of land using less water, energy and chemicals. The molecular genetic revolution of the late 20th century that powered the development of precise GM methods is the most critical technology for meeting these challenges.\" The negative impact of climate change on agriculture is also predicted to worsen, warns Fedoroff, and arable land continues to be lost to urbanization, salinization, and desertification. \"Supplies of fresh water for agriculture are under pressure, as well,\" writes Fedoroff. \"Today, about a third of the global population lives in arid and semi-arid areas, which cover roughly 40% of the land area... Yet the major crops that now feed the world - corn, wheat, rice, soy - require a substantial amount of water.\" The advances in knowledge of plant stress responses and tools for plant breeding have already resulted in the introduction of new drought-tolerant crop varieties, both GM and non-GM, says Fedoroff. But opposition to GM crops within the political systems of Japan and most European and African countries impeded progress, suggests Fedoroff: \"European influence has been especially detrimental in Africa, causing African leaders to be excessively precautionary in approving GM crops and even to ban the import of GM grain to alleviate famine.\" Fedoroff discusses missed opportunities in using GM technology for addressing global malnutrition. Severe vitamin A deficiency causes up to 2.8 million preventable deaths and blindness in half a million children annually. The GM crop 'Golden Rice' produces enough β-carotene so that a few ounces of cooked rice could eliminate the morbidity and mortality of vitamin A deficiency. \"Golden Rice remains mired in controversy and has been tied up in the regulatory process for more than a decade,\" argues Fedoroff. \"Millions suffer and die while Golden Rice remains in test plots.\" More positive stories on the adoption of GM crops are highlighted by Fedoroff, citing studies showing that more than 90% of farmers growing biotech crops today are smallholder, resource-poor farmers, and others concluding that, over 20 years, GM crops have reduced pesticide use by 37%, increased crop yields by 22% and increase farmers' profits by 68%: \"The simple reasons that farmers migrate to GM crops are that their yields increase and their costs decrease.\" Taking a historical perspective, Fedoroff suggests that much of the opposition to GM crops could lie in our understanding of what constitutes 'genetic modification'. \"Humans practiced genetic modification long before chemistry entered agriculture,\" explains Fedoroff, \"transforming inedible wild plants into crop plants, wild animals into domestic animals and harnessing microbes to produce everything from cheese to wine and beer. Oddly, it is only our contemporary methods of bending organisms' genetic constitution to suit our needs that are today recognized as genetic modification.\" In conclusion, Fedoroff asks: \"Will we have the wisdom to overcome our fear of new technologies and re-invest in the kind of agricultural research and development that can simultaneously increase agricultural productivity and decrease its environmental impact, so that we might preserve what remains of our extraordinary biological heritage?...The answers to these questions will, for better or worse, shape our future civilizations.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Over the past two centuries, the human population has grown sevenfold and the experts anticipate the addition of 2–3 billion more during the twenty-first century. In the present overview, I take a historical glance at how humans supported such extraordinary population growth first through the invention of agriculture and more recently through the rapid deployment of scientific and technological advances in agriculture. I then identify future challenges posed by continued population growth and climate warming on a finite planet. I end by discussing both how we can meet such challenges and what stands in the way. Background Today we have enough food to meet the world’s needs. Indeed, we have an extraordinary global food system that brings food from all over the planet to consumers who can afford to buy it. The food price spike of 2008 and the resurgence of high food prices in recent years have had little impact on the affluent citizens of the developed world who spend a small fraction of their income on food. By contrast, food prices have a profound impact on the world’s poorest people. Many of them spend half or more of their income on food. During the food price crisis of 2008, there were food riots in more than 30 countries. Unrest in the Middle East and North Africa tracks with the price of food, as is dramatically illustrated in Fig. 1 . Spiraling food prices drive the world’s poorest into chronic hunger even in a world of relative plenty. Fig. 1 Food price spikes are correlated with increases in food riots. Red dashed vertical lines correspond to beginning dates of “food riots” and protests associated with the major recent unrest in North Africa and the Middle East. The overall death toll is reported in parentheses . The blue vertical line indicates the date on which the authors of the cited report [ 1 ] submitted a report to the U.S. government warning of the link between food prices, social unrest, and political instability. The inset shows the FAO Food Price Index from 1990 to 2011. (The figure is reproduced with permission from [ 1 ]). Full size image Does this mean we need worry only about poverty, not about the global food supply, as suggested in a recent editorial by the influential New York Times food commentator Mark Bittman [ 2 ]? Analyses of the most recent United Nations projections indicate that the human population will expand from roughly 7.2 billion today to 9.6 billion in 2050 and 10.9 billion by 2100 [ 3 , 4 ]. Current yield growth trends are simply insufficient to keep up with growing demand [ 5 ]. As well, the rapid expansion of agriculture over the past century to feed today’s population has had a devastating impact on biodiversity [ 6 ]. As a result, there is an acute need to intensify agricultural productivity, while at the same time decreasing the deleterious impact of agriculture on biodiversity and the services provided by complex ecosystems [ 7 ]. Historical perspective For most of our evolutionary history, our numbers were small and we were mobile hunter-gatherers. We spent our time finding and capturing enough food to feed ourselves and our closest kin. Then sometime between 10 and 20,000 years ago—maybe even more—that started to change. We began to shape plants and animals to our own advantage and settled down to grow and herd them [ 8 ]. The process by which we have modified plants and animals to suit our needs, traditionally called “domestication,” is a process of genetic modification [ 9 ]. Early peoples selected variant organisms—plants, animals, and microbes—with useful traits, such as seeds that adhere to plants until they are harvested and animals tame enough to herd. Domestication is a process of modification that is possible because of the genetic variation constantly arising in all living organisms. While hunter-gatherers were quite sophisticated in their resource management, it was systematic planting and harvesting of crops that marks the origin of what we now call “agriculture” [ 10 ]. Agriculture allowed people to produce more food than they consumed; cities and civilization followed. Thus human civilization emerged because we figured out how to produce surplus food. We could feed artisans and scribes and warriors and kings. For the next 10 millennia, people built cities and civilizations, wore out the land, invaded their neighbors or abandoned the cities and civilizations, eventually rebuilding on fresh land [ 11 ]. It was often the fertility of the land that determined how long a civilization lasted. Plants extract nutrients from the soil and crop yields decline, making it harder and harder to produce enough food as the number of people grows [ 8 ]. Concern about access to sufficient food, today called “food security,” is as old as mankind. Thomas Malthus’ famous Essay on Population, published in 1798, crystallized the problem of balancing food and human population for the modern era [ 12 ]. Malthus believed that humanity was doomed to food insecurity because our numbers increased exponentially, while our ability to produce food could only increase linearly. Curiously, Malthus penned his essay at about the time that science began to play a major role in boosting agricultural productivity. Late eighteenth century milestones were Joseph Priestley’s discovery that plants emit oxygen and Nicholas-Théodore de Saussure’s definition of the chemical composition of plants [ 13 , 14 ]. Malthus could not have envisioned the extraordinary increases in productivity that the integration of science and technology into agricultural practice would stimulate over the ensuing two centuries. Both organic- and mineral fertilization of plants have been practiced since ancient times. Farmers knew that certain chemicals and biological materials, ranging from fish and oyster shells to manure and bones, stimulated plant growth [ 15 , 16 ]. Justus von Liebig made important contributions to the study of plant nutrient requirements, understanding that biological sources of nitrogen could be replaced with purely chemical sources. But supplying nitrogen in the forms that plants use<|im_end|> <|im_start|>assistant A former adviser to the US Secretary of State says that genetic modification (GM) is the most critical technology in agriculture for meeting the challenges of feeding a growing global population, writing in the open access journal Agriculture & Food Security. Nina Fedoroff, molecular biologist and former Science and Technology Adviser to Hillary Clinton and Condoleezza Rice, warns of the detrimental influence of politics and misinformation on the safety of GM crops. Instead, Fedoroff says that: "GM crops are arguably the safest new crops ever introduced into the human and animal food chains." Addressing safety concerns, Fedoroff highlights recent studies that have revealed that plant modification by molecular techniques has less impact on gene expression, protein and metabolite levels than conventional genetic crosses. New methods are also rapidly being developed that promise to further increase the specificity and precision of genetic modification. "The overwhelming evidence is that the GM foods now on the market are as safe, or safer, than non-GM foods," argues Fedoroff. She also cites a recent overview by the European Union of more than 130 research projects over 25 years concluding that GM methods are not inherently more risky than conventional plant breeding technologies. Fedoroff adds: "Every credible scientific body that has examined the evidence has come to the same conclusion." In her commentary, Fedoroff explains that the human population has grown seven-fold over the past two centuries, with the addition of a further 2-3 billion anticipated during the 21st century. The UN's Food and Agriculture Organization has estimated that food production will need to increase by 70% by 2050 to meet this demand. She writes: "Current yield growth trends are simply insufficient to keep up with growing demand...To live sustainably within planetary constraints, we must grow more on the same amount of land using less water, energy and chemicals. The molecular genetic revolution of the late 20th century that powered the development of precise GM methods is the most critical technology for meeting these challenges." The negative impact of climate change on agriculture is also predicted to worsen, warns Fedoroff, and arable land continues to be lost to urbanization, salinization, and desertification. "Supplies of fresh water for agriculture are under pressure, as well," writes Fedoroff. "Today, about a third of the global population lives in arid and semi-arid areas, which cover roughly 40% of the land area... Yet the major crops that now feed the world - corn, wheat, rice, soy - require a substantial amount of water." The advances in knowledge of plant stress responses and tools for plant breeding have already resulted in the introduction of new drought-tolerant crop varieties, both GM and non-GM, says Fedoroff. But opposition to GM crops within the political systems of Japan and most European and African countries impeded progress, suggests Fedoroff: "European influence has been especially detrimental in Africa, causing African leaders to be excessively precautionary in approving GM crops and even to ban the import of GM grain to alleviate famine." Fedoroff discusses missed opportunities in using GM technology for addressing global malnutrition. Severe vitamin A deficiency causes up to 2.8 million preventable deaths and blindness in half a million children annually. The GM crop 'Golden Rice' produces enough β-carotene so that a few ounces of cooked rice could eliminate the morbidity and mortality of vitamin A deficiency. "Golden Rice remains mired in controversy and has been tied up in the regulatory process for more than a decade," argues Fedoroff. "Millions suffer and die while Golden Rice remains in test plots." More positive stories on the adoption of GM crops are highlighted by Fedoroff, citing studies showing that more than 90% of farmers growing biotech crops today are smallholder, resource-poor farmers, and others concluding that, over 20 years, GM crops have reduced pesticide use by 37%, increased crop yields by 22% and increase farmers' profits by 68%: "The simple reasons that farmers migrate to GM crops are that their yields increase and their costs decrease." Taking a historical perspective, Fedoroff suggests that much of the opposition to GM crops could lie in our understanding of what constitutes 'genetic modification'. "Humans practiced genetic modification long before chemistry entered agriculture," explains Fedoroff, "transforming inedible wild plants into crop plants, wild animals into domestic animals and harnessing microbes to produce everything from cheese to wine and beer. Oddly, it is only our contemporary methods of bending organisms' genetic constitution to suit our needs that are today recognized as genetic modification." In conclusion, Fedoroff asks: "Will we have the wisdom to overcome our fear of new technologies and re-invest in the kind of agricultural research and development that can simultaneously increase agricultural productivity and decrease its environmental impact, so that we might preserve what remains of our extraordinary biological heritage?...The answers to these questions will, for better or worse, shape our future civilizations." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Timely perception of adverse environmental changes is critical for survival. Dynamic changes in gases are important cues for plants to sense environmental perturbations, such as submergence. In Arabidopsis thaliana , changes in oxygen and nitric oxide (NO) control the stability of ERFVII transcription factors. ERFVII proteolysis is regulated by the N-degron pathway and mediates adaptation to flooding-induced hypoxia. However, how plants detect and transduce early submergence signals remains elusive. Here we show that plants can rapidly detect submergence through passive ethylene entrapment and use this signal to pre-adapt to impending hypoxia. Ethylene can enhance ERFVII stability prior to hypoxia by increasing the NO-scavenger PHYTOGLOBIN1. This ethylene-mediated NO depletion and consequent ERFVII accumulation pre-adapts plants to survive subsequent hypoxia. Our results reveal the biological link between three gaseous signals for the regulation of flooding survival and identifies key regulatory targets for early stress perception that could be pivotal for developing flood-tolerant crops. Introduction The increasing frequency of floods due to climate change 1 has devastating effects on agricultural productivity worldwide 2 . Due to restricted gas diffusion underwater, flooded plants experience cellular oxygen (O 2 ) deprivation (hypoxia) and survival strongly depends on molecular responses that enhance hypoxia tolerance 2 , 3 . In submerged plant tissues the limited gas diffusion causes passive ethylene accumulation. This rapid ethylene build-up can occur prior to the onset of severe hypoxia, making it a timely and reliable signal for submergence 4 , 5 . In several plant species, ethylene regulates adaptive responses to flooding by inducing morphological and anatomical modifications that prevent hypoxia 5 . Surprisingly, ethylene has so far not been linked to metabolic responses that reduce hypoxia damage. In addition, how plants perceive early submergence to subsequently increase survival remains elusive. Here we show that plants can quickly sense submergence using passive ethylene accumulation and integrate this signal to acclimate to subsequent hypoxia. This ethylene-mediated hypoxia acclimation is dependent on enhanced group VII Ethylene Response Factor (ERFVII) stability prior to hypoxia. We show that ethylene limits ERFVII proteolysis under normoxic conditions by increasing the NO-scavenger PHYTOGLOBIN1 (PGB1). Our results reveal a molecular mechanism that plants use to integrate early stress signals to pre-adapt to forthcoming severe stress. Results Early ethylene signalling enhances hypoxia acclimation To unravel the spatial and temporal dynamics of ethylene signalling upon plant submergence, we monitored the nuclear accumulation of ETHYLENE INSENSITIVE 3 (EIN3) 6 , 7 , 8 , 9 , an essential transcription factor for mediating ethylene responses. We show, through an increase in EIN3-GFP fluorescence signal, that ethylene is rapidly perceived (within 1–2 h) in Arabidopsis thaliana (hereafter Arabidopsis) root tips upon submergence (Supplementary Fig. 1a-c ). An ethylene or submergence pre-treatment of only 4 h was sufficient to increase root meristem survival during subsequent hypoxia ( < 0.01% O 2 ). These responses were abolished in ethylene signalling mutants or via chemical inhibition of ethylene action (Supplementary Fig. 1d–e ). Ethylene-induced acclimation to hypoxia was observed in both roots and shoots and was accompanied by a reduction in cellular damage in response to hypoxia (Fig. 1 , Supplementary Figs. 2 & 3 ). Furthermore, enhanced hypoxia tolerance after ethylene pre-treatment is conserved within Arabidopsis accessions and taxonomically diverse flowering plant species, although variation in capacity to benefit from an ethylene pre-treatment exists (Supplementary Fig. 4 ; 10 ). These results demonstrate that ethylene enhances tolerance of multiple plant organs and species to hypoxia. Next, we aimed to unravel how early ethylene signalling leads to enhanced hypoxia tolerance in Arabidopsis root tips. Fig. 1 Ethylene pre-treatment enhances hypoxia tolerance. a , b Arabidopsis (Col-0) seedling root tip a and adult rosette b survival after 4 h of air (white) or ~5μllˉ¹ ethylene (blue) followed by hypoxia and recovery (3 days for root tips, 7 days for rosettes). Values are relative to control (normoxia) plants (mean ± sem). Asterisks indicate significant differences between air and ethylene ( p < 0.05, Generalized linear model, negative binomial error structure, n = 4-8 rows consisting of ~23 seedlings a , n = 30 plants b ). c Arabidopsis (Col-0) rosette phenotypes after 4 h of pre-treatment (air/ ~5μllˉ¹ ethylene) followed by hypoxia and 7 days recovery. All experiments were replicated at least 3 times Full size image Ethylene stabilizes group VII Ethylene Response Factors Hypoxia acclimation in plants involves the up-regulation of hypoxia adaptive genes that control energy maintenance and oxidative stress homeostasis 11 . Interestingly, most of these genes were not induced by ethylene alone, but showed increased transcript abundance upon hypoxia following a pre-treatment with ethylene (Supplementary Fig. 5 ). Hypoxia adaptive genes are regulated by the ERFVII transcription factors that are components of a mechanism that senses O 2 and NO via the Cys-branch of the PROTEOLYSIS 6 (PRT6) N-degron pathway 12 , 13 , 14 . ERFVIIs are degraded following oxidation of amino terminal (Nt-) Cysteine in the presence of O 2 and NO, catalysed by PLANT CYSTEINE OXIDASEs (PCOs) 15 . The N-recognin E3 ligase PRT6 promotes degradation of oxidized ERFVIIs by the 26 S proteasome 16 , 17 . A decline in either O 2 or NO stabilizes ERFVIIs, leading to transcriptional up-regulation of hypoxia adaptive genes and other environmental and developmental responses 12 , 13 , 14 , 18 . The constitutively synthesized ERVIIs RELATED TO APETALA2.12 (RAP2.12), RAP2.2 and RAP2.3 redundantly act as the principal activators of many hypoxia adaptive genes 19 , 20 , 21 . In contrast, HYPOXIA RESPONSIVE ERF1 (HRE1) and HRE2 function downstream of RAP-type ERFVIIs, being transcriptionally induced once hypoxia occurs 22 . We investigated whether ethylene-induced hypoxia tolerance depends on the constitutively synthesized RAP-type ERFVIIs. Single loss-of-function mutants of RAP2.12 , RAP2.2 and RAP2.3 , and the hre1 hre2 double mutant, responded to ethylene pre-treatment similarly to their WT backgrounds (Supplementary Fig. 6a ). However, two independent rap2.2 rap2.12 loss-of-function double mutants 20 showed no improved hypoxia tolerance after ethylene pre-treatment (Fig. 2a ), while their WT background crosses did (Supplementary Fig. 6b ). In", "role": "user" }, { "content": "Scientists at Utrecht University have discovered how some plants can quickly detect that they are under water when flooded, and initiate processes that prevents them from drowning. Floods cause widespread yield losses annually due to the extreme flood sensitivity of most major crops. In a study published in Nature Communications, the researchers demonstrate how plants use the gaseous hormone ethylene as a signal to trigger underwater survival reactions. The identification of this signaling mechanism and the genes involved can potentially pave the way towards stress resilient, flood-proof crops that can sustain yields even under stressful conditions. Global warming results in the increased incidence of not just drought and heatwaves, but also increased rainfall and higher flood risk. This is a major problem for crops. Just like humans, plants need oxygen to survive and the lack of it underwater causes them to suffocate. The devastating agricultural impact of floods is therefore just as immense as other extreme weather events such as drought. For instance, flooding of a potato field can cause complete yield loss within just 24 hours. It is therefore absolutely essential to understand plant resilience mechanisms in order to progress towards flood resistant crops. This can make a world of difference with regards to food security and mitigating major economic losses. Survival response \"If plants can quickly detect that they are flooded, they can initiate processes that increase their chances of survival. One strategy, for example, is the so-called snorkel response, in which leaves and stems increase upwards growth to emerge from the water and restore contact with air. Another strategy is to suppress growth and metabolism in order to minimize oxygen and energy consumption until the floods recede,\" says first author Sjon Hartman, plant biologist at the Plant Ecophysiology group at Utrecht University. \"We recently demonstrated that the gaseous plant hormone ethylene plays a very important role in this. Ethylene entrapped in the cells of flooded plants serves as a flood signal for the plant.\" Together with colleagues from Nijmegen, Denmark, the United Kingdom and the U.S., the researchers now report their findings in Nature Communications, and describe the series of molecular events that are triggered upon a flood in plants and the genes involved. They demonstrate that ethylene accumulation in flooded plants triggers a survival response in the plants at an early stage, even before the oxygen levels actually drop. \"This is very useful: a plant that goes into survival mode early can last longer under water and that can make the difference between life and death,\" says Hartman. Future-proof crops The discovery of this tolerance mechanism holds great potential for the future development of flood-tolerant crops. \"Now that we know the genes associated with flooding survival, we can introduce them back into plants that lack them and thus program flooded plants to go into survival mode sooner,\" say research leaders Dr. Rashmi Sasidharan and Prof. Rens Voesenek of Utrecht University. \"This will enable us to make future-proof crops that are better able to withstand flooding.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Timely perception of adverse environmental changes is critical for survival. Dynamic changes in gases are important cues for plants to sense environmental perturbations, such as submergence. In Arabidopsis thaliana , changes in oxygen and nitric oxide (NO) control the stability of ERFVII transcription factors. ERFVII proteolysis is regulated by the N-degron pathway and mediates adaptation to flooding-induced hypoxia. However, how plants detect and transduce early submergence signals remains elusive. Here we show that plants can rapidly detect submergence through passive ethylene entrapment and use this signal to pre-adapt to impending hypoxia. Ethylene can enhance ERFVII stability prior to hypoxia by increasing the NO-scavenger PHYTOGLOBIN1. This ethylene-mediated NO depletion and consequent ERFVII accumulation pre-adapts plants to survive subsequent hypoxia. Our results reveal the biological link between three gaseous signals for the regulation of flooding survival and identifies key regulatory targets for early stress perception that could be pivotal for developing flood-tolerant crops. Introduction The increasing frequency of floods due to climate change 1 has devastating effects on agricultural productivity worldwide 2 . Due to restricted gas diffusion underwater, flooded plants experience cellular oxygen (O 2 ) deprivation (hypoxia) and survival strongly depends on molecular responses that enhance hypoxia tolerance 2 , 3 . In submerged plant tissues the limited gas diffusion causes passive ethylene accumulation. This rapid ethylene build-up can occur prior to the onset of severe hypoxia, making it a timely and reliable signal for submergence 4 , 5 . In several plant species, ethylene regulates adaptive responses to flooding by inducing morphological and anatomical modifications that prevent hypoxia 5 . Surprisingly, ethylene has so far not been linked to metabolic responses that reduce hypoxia damage. In addition, how plants perceive early submergence to subsequently increase survival remains elusive. Here we show that plants can quickly sense submergence using passive ethylene accumulation and integrate this signal to acclimate to subsequent hypoxia. This ethylene-mediated hypoxia acclimation is dependent on enhanced group VII Ethylene Response Factor (ERFVII) stability prior to hypoxia. We show that ethylene limits ERFVII proteolysis under normoxic conditions by increasing the NO-scavenger PHYTOGLOBIN1 (PGB1). Our results reveal a molecular mechanism that plants use to integrate early stress signals to pre-adapt to forthcoming severe stress. Results Early ethylene signalling enhances hypoxia acclimation To unravel the spatial and temporal dynamics of ethylene signalling upon plant submergence, we monitored the nuclear accumulation of ETHYLENE INSENSITIVE 3 (EIN3) 6 , 7 , 8 , 9 , an essential transcription factor for mediating ethylene responses. We show, through an increase in EIN3-GFP fluorescence signal, that ethylene is rapidly perceived (within 1–2 h) in Arabidopsis thaliana (hereafter Arabidopsis) root tips upon submergence (Supplementary Fig. 1a-c ). An ethylene or submergence pre-treatment of only 4 h was sufficient to increase root meristem survival during subsequent hypoxia ( < 0.01% O 2 ). These responses were abolished in ethylene signalling mutants or via chemical inhibition of ethylene action (Supplementary Fig. 1d–e ). Ethylene-induced acclimation to hypoxia was observed in both roots and shoots and was accompanied by a reduction in cellular damage in response to hypoxia (Fig. 1 , Supplementary Figs. 2 & 3 ). Furthermore, enhanced hypoxia tolerance after ethylene pre-treatment is conserved within Arabidopsis accessions and taxonomically diverse flowering plant species, although variation in capacity to benefit from an ethylene pre-treatment exists (Supplementary Fig. 4 ; 10 ). These results demonstrate that ethylene enhances tolerance of multiple plant organs and species to hypoxia. Next, we aimed to unravel how early ethylene signalling leads to enhanced hypoxia tolerance in Arabidopsis root tips. Fig. 1 Ethylene pre-treatment enhances hypoxia tolerance. a , b Arabidopsis (Col-0) seedling root tip a and adult rosette b survival after 4 h of air (white) or ~5μllˉ¹ ethylene (blue) followed by hypoxia and recovery (3 days for root tips, 7 days for rosettes). Values are relative to control (normoxia) plants (mean ± sem). Asterisks indicate significant differences between air and ethylene ( p < 0.05, Generalized linear model, negative binomial error structure, n = 4-8 rows consisting of ~23 seedlings a , n = 30 plants b ). c Arabidopsis (Col-0) rosette phenotypes after 4 h of pre-treatment (air/ ~5μllˉ¹ ethylene) followed by hypoxia and 7 days recovery. All experiments were replicated at least 3 times Full size image Ethylene stabilizes group VII Ethylene Response Factors Hypoxia acclimation in plants involves the up-regulation of hypoxia adaptive genes that control energy maintenance and oxidative stress homeostasis 11 . Interestingly, most of these genes were not induced by ethylene alone, but showed increased transcript abundance upon hypoxia following a pre-treatment with ethylene (Supplementary Fig. 5 ). Hypoxia adaptive genes are regulated by the ERFVII transcription factors that are components of a mechanism that senses O 2 and NO via the Cys-branch of the PROTEOLYSIS 6 (PRT6) N-degron pathway 12 , 13 , 14 . ERFVIIs are degraded following oxidation of amino terminal (Nt-) Cysteine in the presence of O 2 and NO, catalysed by PLANT CYSTEINE OXIDASEs (PCOs) 15 . The N-recognin E3 ligase PRT6 promotes degradation of oxidized ERFVIIs by the 26 S proteasome 16 , 17 . A decline in either O 2 or NO stabilizes ERFVIIs, leading to transcriptional up-regulation of hypoxia adaptive genes and other environmental and developmental responses 12 , 13 , 14 , 18 . The constitutively synthesized ERVIIs RELATED TO APETALA2.12 (RAP2.12), RAP2.2 and RAP2.3 redundantly act as the principal activators of many hypoxia adaptive genes 19 , 20 , 21 . In contrast, HYPOXIA RESPONSIVE ERF1 (HRE1) and HRE2 function downstream of RAP-type ERFVIIs, being transcriptionally induced once hypoxia occurs 22 . We investigated whether ethylene-induced hypoxia tolerance depends on the constitutively synthesized RAP-type ERFVIIs. Single loss-of-function mutants of RAP2.12 , RAP2.2 and RAP2.3 , and the hre1 hre2 double mutant, responded to ethylene pre-treatment similarly to their WT backgrounds (Supplementary Fig. 6a ). However, two independent rap2.2 rap2.12 loss-of-function double mutants 20 showed no improved hypoxia tolerance after ethylene pre-treatment (Fig. 2a ), while their WT background crosses did (Supplementary Fig. 6b ). In<|im_end|> <|im_start|>assistant Scientists at Utrecht University have discovered how some plants can quickly detect that they are under water when flooded, and initiate processes that prevents them from drowning. Floods cause widespread yield losses annually due to the extreme flood sensitivity of most major crops. In a study published in Nature Communications, the researchers demonstrate how plants use the gaseous hormone ethylene as a signal to trigger underwater survival reactions. The identification of this signaling mechanism and the genes involved can potentially pave the way towards stress resilient, flood-proof crops that can sustain yields even under stressful conditions. Global warming results in the increased incidence of not just drought and heatwaves, but also increased rainfall and higher flood risk. This is a major problem for crops. Just like humans, plants need oxygen to survive and the lack of it underwater causes them to suffocate. The devastating agricultural impact of floods is therefore just as immense as other extreme weather events such as drought. For instance, flooding of a potato field can cause complete yield loss within just 24 hours. It is therefore absolutely essential to understand plant resilience mechanisms in order to progress towards flood resistant crops. This can make a world of difference with regards to food security and mitigating major economic losses. Survival response "If plants can quickly detect that they are flooded, they can initiate processes that increase their chances of survival. One strategy, for example, is the so-called snorkel response, in which leaves and stems increase upwards growth to emerge from the water and restore contact with air. Another strategy is to suppress growth and metabolism in order to minimize oxygen and energy consumption until the floods recede," says first author Sjon Hartman, plant biologist at the Plant Ecophysiology group at Utrecht University. "We recently demonstrated that the gaseous plant hormone ethylene plays a very important role in this. Ethylene entrapped in the cells of flooded plants serves as a flood signal for the plant." Together with colleagues from Nijmegen, Denmark, the United Kingdom and the U.S., the researchers now report their findings in Nature Communications, and describe the series of molecular events that are triggered upon a flood in plants and the genes involved. They demonstrate that ethylene accumulation in flooded plants triggers a survival response in the plants at an early stage, even before the oxygen levels actually drop. "This is very useful: a plant that goes into survival mode early can last longer under water and that can make the difference between life and death," says Hartman. Future-proof crops The discovery of this tolerance mechanism holds great potential for the future development of flood-tolerant crops. "Now that we know the genes associated with flooding survival, we can introduce them back into plants that lack them and thus program flooded plants to go into survival mode sooner," say research leaders Dr. Rashmi Sasidharan and Prof. Rens Voesenek of Utrecht University. "This will enable us to make future-proof crops that are better able to withstand flooding." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract First described as a medusoid jellyfish, the “star-shaped” Brooksella from the Conasauga shale Lagerstätten, Southeastern USA, was variously reconsidered as algae, feeding traces, gas bubbles, and most recently hexactinellid sponges. In this work, we present new morphological, chemical, and structural data to evaluate its hexactinellid affinities, as well as whether it could be a trace fossil or pseudofossil. External and cross-sectional surfaces, thin sections, X-ray computed tomography (CT) and micro-CT imaging, revealed no evidence that Brooksella is a hexactinellid sponge or a trace fossil. Although internally Brooksella contains abundant voids and variously orientated tubes consistent with multiple burrowing or bioeroding organisms, these structures have no relation to Brooksella ’s external lobe-like morphology. Furthermore, Brooksella has no pattern of growth comparable to the linear growth of early Paleozoic hexactinellids; rather, its growth is similar to syndepositional concretions. Lastly, Brooksella , except for its lobes and occasional central depression, is no different in microstructure to the silica concretions of the Conasauga Formation, strongly indicating it is a morphologically unusual endmember of the silica concretions of the formation. These findings highlight the need for thorough and accurate descriptions in Cambrian paleontology; wherein care must be taken to examine the full range of biotic and abiotic hypotheses for these compelling and unique fossils. Cite this as Nolan MR, Walker SE, Selly T, Schiffbauer J. 2023 . Is the middle Cambrian Brooksella a hexactinellid sponge, trace fossil or pseudofossil? PeerJ 11 : e14796 Main article text Introduction Sponges that produce siliceous skeletons are the only benthic animals that secrete copious amounts of silica and are recently recognized as important sinks for biogenic silica and nutrient cycling in the oceans ( Chu et al., 2011 ; Maldonado et al., 2011 ; Maldonado et al., 2021 ). The fossil record and molecular clock history of putative sponges extends back to the late Proterozoic, possibly to 890 million years, making them potentially among the first animals on Earth ( e.g. , keratose demosponges; Turner, 2021 ), though many fossils of purported precambrian sponges are subject to significant controversy ( Antcliffe, Callow & Brasier, 2014 ; Botting & Muir, 2018 ). The earliest fossils of partially biomineralized, siliceous spicules date to the early Cambrian or the latest Ediacaran, indicating either a later evolution of spicule biomineralization or a taphonomic bias against these structural components that are essential to sponge taxonomy prior to that time ( Sperling et al., 2010 ; Chang et al., 2019 ; Tang et al., 2019 ). Disarticulated and articulated sponge spicules are known from a variety of early-to-middle Cambrian Burgess Shale-type deposits ( e.g. , Burgess Shale Lagerstätte of Canada and the earlier Series 2 Sirius Passet Lagerstätte of Greenland; Finks, 2003 ; Botting & Peel, 2016 ), though it was not until the middle Cambrian that the taxonomic affinities of these sponges become clearer. Most of these early and middle Cambrian sponges are preserved as compressions or impressions on shale with abundant spicules ( Finks, 2003 ) except for an enigmatic star-shaped fossil interpreted as a hexactinellid sponge, Brooksella alternata , from the middle Cambrian Conasauga Lagerstätte of the southeastern US (northeastern Alabama, northwestern Georgia; Ciampaglio et al., 2006 ; Schwimmer & Montante, 2007 ). Brooksella is considered to have exceptional three-dimensional (3-D) preservation in chert concretions with radial morphology and numerous lobes ( Ciampaglio et al., 2006 ). However, its identity has generated controversy since its discovery in the late 1800s by Charles Doolittle Walcott ( Walcott, 1896 ; Walcott, 1898 ). Brooksella was originally described by Walcott in 1896 as a jellyfish with tentacles, an umbrella (bell), and a gastric cavity. However, he also considered whether these medusoid forms were hexactinellid sponges despite finding no spicules or traces of spicules in his “large number” of thin sections of Brooksella ( Walcott, 1898 , his p. 21)—although he mentions finding a few hexactinellid-like spicule casts on the outer surface of non-medusoid concretions ( Walcott, 1898 , his p. 22). Since Walcott’s work, the taxonomic identity of Brooksella has been reevaluated many times ( Table S1 and Fig. S1 ). The most recent reevaluation by Ciampaglio et al. (2006) suggests that Brooksella is a Protospongia -type reticulosan hexactinellid sponge (though later researchers have suggested that Protospongia specifically and reticulosans, and in general, are not hexactinellids, e.g. , Botting & Muir, 2018 ; Page, Butterfield & Harvey, 2009 ; and J Botting, pers. comm., 2022), which Walcott also suggested but later rejected, over a century earlier. As a consequence of this new taxonomic assignment, the Conasauga Formation is interpreted to be an exceptional fossil Lagerstätte with fossils preserved by extensive sponge-produced biogenic silica ( Schwimmer & Montante, 2007 ). The question regarding Brooksella’s placement as a sponge, and more specifically, a hexactinellid sponge that could have produced enough biogenic silica to preserve an entire middle Cambrian Lagerstätte, might not yet be settled. Ciampaglio et al. (2006) observed that the external surfaces and cross sections of Brooksella had white Protospongia -type spicules, four-rayed spicules of siliceous composition. Even so, others suggest the presence of such hexactine spicules are not sufficiently diagnostic for hexactinellids ( e.g. , Botting & Muir, 2018 ) and Protospongia had calcitic or biminerallic, but not necessarily siliceous spicules ( e.g. , Page, Butterfield & Harvey, 2009 ). This calls into question what Walcott keenly observed, however: despite the hundreds of specimens he examined, he found no spicules in thin-section, and, based on a compression of Brooksella in shale, he favored a jellyfish fossil over a sponge identity ( Walcott, 1898 , his p. 21–22). Ciampaglio et al. (2006) also noted ostia (incurrent pores), a central canal (spongocoel), radial canals in each of the numerous lobes, and openings at the tips of the lobes into these canals (refer to their Fig. 3). They also inferred that the concave side of Brooksella with the central depression was the top of the specimen, contrary to Walcott’s medusoid interpretation ( Ciampaglio et al., 2006 , their p. 264). Lastly, Ciampaglio et al. (2006) synonymized three", "role": "user" }, { "content": "More than 100 years ago, Charles Doolittle Walcott from the Smithsonian Institution was asked to examine strange star-shaped fossils with lobes hailing from the ~ 514-million-year-old Conasauga Formation in Alabama. Walcott described these odd fossils as jellyfish that likely floated in the middle Cambrian seas of what is now the southeastern United States. Little did he know that the Cambrian fossil he named would cause more than 100 years of controversy. The controversy hinged on the interpretation of what Brooksella really was: Was it truly a jellyfish that would be important for middle Cambrian marine ecosystems, a time when animals were originating and diversifying for the first time on Earth? Or was Brooksella just preserved gas bubbles? Or maybe it was a type of bulbous algae? Or a glass sponge made of opaline silica? Or, as hypothesized, perhaps Brooksella was not a fossil at all. Using shape and chemical analyses combined with high-resolution 3D imaging, we evaluated whether Brooksella was a fossil, like a sponge, a trace fossil, representing the burrows of worm-like animals, or not a fossil. We found that Brooksella lacked characteristics of glass sponges, specifically, the opaline-fused spicules that compose the body. Nor did it grow as a sponge would be expected to over its lifetime. Importantly, in the field, its purported excurrent canal (osculum) was always oriented down in the sediment, which would make it very hard—if not impossible— to filter water for food. We also did not find any indication that worms made the iconic star-shaped lobes. We then compared the composition and internal structure of Brooksella to silica concretions from the same middle Cambrian rock beds. We did not find any difference between Brooksella and the concretions, other than Brooksella had lobes and the concretions did not. We thus concluded that Brooksella was not part of early sponge diversification in middle Cambrian seas, but rather, was an unusual type of silica concretion. Concretions can be all kinds of shapes to the point some look like they were organically formed. The significance of our finding is two-fold: First, there are numerous enigmatic Cambrian fossils that need to be scrutinized to determine if they are really fossils to help paleontologists refine biodiversity estimates for the Cambrian when most of Earth's major animal groups originated. Second, this is not the first time that unusual fossils and rocks from the Cambrian have puzzled scientists, and our findings highlight the necessity of close scrutiny of early fossil materials, especially using newer, powerful analytical techniques like micro-CT in combination with classic lab and field approaches. Sunset at Weiss Lake where Brooksella alternata were collected. Credit: Morrison R. Nolan Morrison Nolan, Department of Geosciences, Virginia Tech, says, \"Brooksella alternata interests me because so many scientists have worked on identifying it and have come to very different conclusions. It really illustrates how difficult it can be to distinguish one type of life from another, and even life from non-life, which is especially challenging for early materials in the geologic record. \"Amateur paleontological/geological groups like the Georgia Mineral Society helped me learn about Brooksella and other interesting geological features around me. Such groups do a great job of teaching the public about the geologic past and bringing people to the field to see and learn about these features.\" Sally Walker, Professor of Paleontology at the University of Georgia in Athens, Georgia, U.S., says, \"Brooksella intrigued me because, unlike most fossils, it had a 3D shape like a star-shaped puffed pastry that is unusual for soft-squishy animals like a sponge. A sponge usually gets flattened like roadkill during the fossilization process—especially a fossil more than 500 million years old. \"Also puzzling was the fact that no one inspected Brooksella where it lived and its orientation; if they did, they would find that most lobes were oriented downward, which does not make sense for a sponge to be eating mud. Lastly, the puzzle of Brooksella continues: What are the physical, chemical and perhaps biological processes that actually formed these strange Brooksella concretions? That is for a future paleontologist to solve. James Schiffbauer, Associate Professor of Geological Sciences, University of Missouri, says, \"While the applications for microCT have been nearly endless in the materials sciences and engineering fields, its capacities for elucidating the fossil record are really just beginning to be explored. This project is an excellent example of the types of fossil mysteries we can solve with applications of microCT. When we can scrutinize the internal construction of Brooksella with reference to its many past interpretations, it becomes increasingly apparent that none of them really match.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract First described as a medusoid jellyfish, the “star-shaped” Brooksella from the Conasauga shale Lagerstätten, Southeastern USA, was variously reconsidered as algae, feeding traces, gas bubbles, and most recently hexactinellid sponges. In this work, we present new morphological, chemical, and structural data to evaluate its hexactinellid affinities, as well as whether it could be a trace fossil or pseudofossil. External and cross-sectional surfaces, thin sections, X-ray computed tomography (CT) and micro-CT imaging, revealed no evidence that Brooksella is a hexactinellid sponge or a trace fossil. Although internally Brooksella contains abundant voids and variously orientated tubes consistent with multiple burrowing or bioeroding organisms, these structures have no relation to Brooksella ’s external lobe-like morphology. Furthermore, Brooksella has no pattern of growth comparable to the linear growth of early Paleozoic hexactinellids; rather, its growth is similar to syndepositional concretions. Lastly, Brooksella , except for its lobes and occasional central depression, is no different in microstructure to the silica concretions of the Conasauga Formation, strongly indicating it is a morphologically unusual endmember of the silica concretions of the formation. These findings highlight the need for thorough and accurate descriptions in Cambrian paleontology; wherein care must be taken to examine the full range of biotic and abiotic hypotheses for these compelling and unique fossils. Cite this as Nolan MR, Walker SE, Selly T, Schiffbauer J. 2023 . Is the middle Cambrian Brooksella a hexactinellid sponge, trace fossil or pseudofossil? PeerJ 11 : e14796 Main article text Introduction Sponges that produce siliceous skeletons are the only benthic animals that secrete copious amounts of silica and are recently recognized as important sinks for biogenic silica and nutrient cycling in the oceans ( Chu et al., 2011 ; Maldonado et al., 2011 ; Maldonado et al., 2021 ). The fossil record and molecular clock history of putative sponges extends back to the late Proterozoic, possibly to 890 million years, making them potentially among the first animals on Earth ( e.g. , keratose demosponges; Turner, 2021 ), though many fossils of purported precambrian sponges are subject to significant controversy ( Antcliffe, Callow & Brasier, 2014 ; Botting & Muir, 2018 ). The earliest fossils of partially biomineralized, siliceous spicules date to the early Cambrian or the latest Ediacaran, indicating either a later evolution of spicule biomineralization or a taphonomic bias against these structural components that are essential to sponge taxonomy prior to that time ( Sperling et al., 2010 ; Chang et al., 2019 ; Tang et al., 2019 ). Disarticulated and articulated sponge spicules are known from a variety of early-to-middle Cambrian Burgess Shale-type deposits ( e.g. , Burgess Shale Lagerstätte of Canada and the earlier Series 2 Sirius Passet Lagerstätte of Greenland; Finks, 2003 ; Botting & Peel, 2016 ), though it was not until the middle Cambrian that the taxonomic affinities of these sponges become clearer. Most of these early and middle Cambrian sponges are preserved as compressions or impressions on shale with abundant spicules ( Finks, 2003 ) except for an enigmatic star-shaped fossil interpreted as a hexactinellid sponge, Brooksella alternata , from the middle Cambrian Conasauga Lagerstätte of the southeastern US (northeastern Alabama, northwestern Georgia; Ciampaglio et al., 2006 ; Schwimmer & Montante, 2007 ). Brooksella is considered to have exceptional three-dimensional (3-D) preservation in chert concretions with radial morphology and numerous lobes ( Ciampaglio et al., 2006 ). However, its identity has generated controversy since its discovery in the late 1800s by Charles Doolittle Walcott ( Walcott, 1896 ; Walcott, 1898 ). Brooksella was originally described by Walcott in 1896 as a jellyfish with tentacles, an umbrella (bell), and a gastric cavity. However, he also considered whether these medusoid forms were hexactinellid sponges despite finding no spicules or traces of spicules in his “large number” of thin sections of Brooksella ( Walcott, 1898 , his p. 21)—although he mentions finding a few hexactinellid-like spicule casts on the outer surface of non-medusoid concretions ( Walcott, 1898 , his p. 22). Since Walcott’s work, the taxonomic identity of Brooksella has been reevaluated many times ( Table S1 and Fig. S1 ). The most recent reevaluation by Ciampaglio et al. (2006) suggests that Brooksella is a Protospongia -type reticulosan hexactinellid sponge (though later researchers have suggested that Protospongia specifically and reticulosans, and in general, are not hexactinellids, e.g. , Botting & Muir, 2018 ; Page, Butterfield & Harvey, 2009 ; and J Botting, pers. comm., 2022), which Walcott also suggested but later rejected, over a century earlier. As a consequence of this new taxonomic assignment, the Conasauga Formation is interpreted to be an exceptional fossil Lagerstätte with fossils preserved by extensive sponge-produced biogenic silica ( Schwimmer & Montante, 2007 ). The question regarding Brooksella’s placement as a sponge, and more specifically, a hexactinellid sponge that could have produced enough biogenic silica to preserve an entire middle Cambrian Lagerstätte, might not yet be settled. Ciampaglio et al. (2006) observed that the external surfaces and cross sections of Brooksella had white Protospongia -type spicules, four-rayed spicules of siliceous composition. Even so, others suggest the presence of such hexactine spicules are not sufficiently diagnostic for hexactinellids ( e.g. , Botting & Muir, 2018 ) and Protospongia had calcitic or biminerallic, but not necessarily siliceous spicules ( e.g. , Page, Butterfield & Harvey, 2009 ). This calls into question what Walcott keenly observed, however: despite the hundreds of specimens he examined, he found no spicules in thin-section, and, based on a compression of Brooksella in shale, he favored a jellyfish fossil over a sponge identity ( Walcott, 1898 , his p. 21–22). Ciampaglio et al. (2006) also noted ostia (incurrent pores), a central canal (spongocoel), radial canals in each of the numerous lobes, and openings at the tips of the lobes into these canals (refer to their Fig. 3). They also inferred that the concave side of Brooksella with the central depression was the top of the specimen, contrary to Walcott’s medusoid interpretation ( Ciampaglio et al., 2006 , their p. 264). Lastly, Ciampaglio et al. (2006) synonymized three<|im_end|> <|im_start|>assistant More than 100 years ago, Charles Doolittle Walcott from the Smithsonian Institution was asked to examine strange star-shaped fossils with lobes hailing from the ~ 514-million-year-old Conasauga Formation in Alabama. Walcott described these odd fossils as jellyfish that likely floated in the middle Cambrian seas of what is now the southeastern United States. Little did he know that the Cambrian fossil he named would cause more than 100 years of controversy. The controversy hinged on the interpretation of what Brooksella really was: Was it truly a jellyfish that would be important for middle Cambrian marine ecosystems, a time when animals were originating and diversifying for the first time on Earth? Or was Brooksella just preserved gas bubbles? Or maybe it was a type of bulbous algae? Or a glass sponge made of opaline silica? Or, as hypothesized, perhaps Brooksella was not a fossil at all. Using shape and chemical analyses combined with high-resolution 3D imaging, we evaluated whether Brooksella was a fossil, like a sponge, a trace fossil, representing the burrows of worm-like animals, or not a fossil. We found that Brooksella lacked characteristics of glass sponges, specifically, the opaline-fused spicules that compose the body. Nor did it grow as a sponge would be expected to over its lifetime. Importantly, in the field, its purported excurrent canal (osculum) was always oriented down in the sediment, which would make it very hard—if not impossible— to filter water for food. We also did not find any indication that worms made the iconic star-shaped lobes. We then compared the composition and internal structure of Brooksella to silica concretions from the same middle Cambrian rock beds. We did not find any difference between Brooksella and the concretions, other than Brooksella had lobes and the concretions did not. We thus concluded that Brooksella was not part of early sponge diversification in middle Cambrian seas, but rather, was an unusual type of silica concretion. Concretions can be all kinds of shapes to the point some look like they were organically formed. The significance of our finding is two-fold: First, there are numerous enigmatic Cambrian fossils that need to be scrutinized to determine if they are really fossils to help paleontologists refine biodiversity estimates for the Cambrian when most of Earth's major animal groups originated. Second, this is not the first time that unusual fossils and rocks from the Cambrian have puzzled scientists, and our findings highlight the necessity of close scrutiny of early fossil materials, especially using newer, powerful analytical techniques like micro-CT in combination with classic lab and field approaches. Sunset at Weiss Lake where Brooksella alternata were collected. Credit: Morrison R. Nolan Morrison Nolan, Department of Geosciences, Virginia Tech, says, "Brooksella alternata interests me because so many scientists have worked on identifying it and have come to very different conclusions. It really illustrates how difficult it can be to distinguish one type of life from another, and even life from non-life, which is especially challenging for early materials in the geologic record. "Amateur paleontological/geological groups like the Georgia Mineral Society helped me learn about Brooksella and other interesting geological features around me. Such groups do a great job of teaching the public about the geologic past and bringing people to the field to see and learn about these features." Sally Walker, Professor of Paleontology at the University of Georgia in Athens, Georgia, U.S., says, "Brooksella intrigued me because, unlike most fossils, it had a 3D shape like a star-shaped puffed pastry that is unusual for soft-squishy animals like a sponge. A sponge usually gets flattened like roadkill during the fossilization process—especially a fossil more than 500 million years old. "Also puzzling was the fact that no one inspected Brooksella where it lived and its orientation; if they did, they would find that most lobes were oriented downward, which does not make sense for a sponge to be eating mud. Lastly, the puzzle of Brooksella continues: What are the physical, chemical and perhaps biological processes that actually formed these strange Brooksella concretions? That is for a future paleontologist to solve. James Schiffbauer, Associate Professor of Geological Sciences, University of Missouri, says, "While the applications for microCT have been nearly endless in the materials sciences and engineering fields, its capacities for elucidating the fossil record are really just beginning to be explored. This project is an excellent example of the types of fossil mysteries we can solve with applications of microCT. When we can scrutinize the internal construction of Brooksella with reference to its many past interpretations, it becomes increasingly apparent that none of them really match." <|im_end|>

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2,626

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Previous research on speech perception has found an effect of ethnicity, such that the same audio clip may be rated more accented when presented with an Asian face (Rubin, Donald L. 1992. Nonlanguage factors affecting undergraduates’ judgments of nonnative English-speaking teaching assistants. Research in Higher Education 33(4). 511–531. doi: 10.1007/bf00973770). However, most previous work has concentrated on Asian non-native English speakers, and Caucasian speakers remain under-explored. In this study, listeners carried out an accentedness rating task using stimuli from first language Korean, German, and English speakers in 3 conditions: audio only, video only, and audiovisual . Korean speakers received similar accentedness ratings regardless of condition, but German speakers were rated significantly less accented in the video condition and more accented in the audiovisual condition than the audio one. This result is explained as an expectation mismatch effect, whereby, when the listeners saw a Caucasian speaker they did not expect to hear a foreign accent, but if they actually heard one it was made more salient by their expectation to the contrary. Keywords: Speech perception ; sociophonetics ; foreign accentedness ; ethnicity ; variation 1 Introduction There is a growing body of research on sociophonetic variation in speech perception (see Campbell-Kibler 2010 ; Drager 2010 ; for a review). Previous studies have shown a strong link between social and linguistic information such that, on the one hand, the perceived linguistic information influences the listeners’ assumptions about the speaker’s social information (e.g., Campbell-Kibler 2007 ) and, on the other hand, assumed social information may affect how linguistic information is perceived (e.g., Hay et al. 2006a ; Hay et al. 2006b ; Niedzielski 1999 ; see discussion below). The existing relationship between social and linguistic information may be explained by usage-based models of speech perception. Exemplar theory (e.g., Johnson 1997 ; Johnson 2006 ; Pierrehumbert 2003 ) suggests that our brain stores clouds of representations, exemplars , for a given category; and that these clouds are updated constantly through the perception-production loop. Sociolinguistic information, such as different speaker characteristics (sex, age, origin, etc.) and contextual information (speech styles, etc.), is associated and stored together with these exemplars. The sociolinguistic information is activated when associated exemplars are activated, and it can activate associated exemplars when it is accessed ( Hay et al. 2006a : 370). In non-native speakers, previous research has also shown that assumed social information may affect perceived linguistic information, such as degree of accent (e.g., see a discussion of Rubin 1992 below). An accent is a “cumulative auditory effect of those features of pronunciation which identify where a person is from, regionally or socially” ( Vishnevskaya 2008 : 235). When listeners hear substantial differences in a speaker’s production, they can identify the person as coming from a different background. A specific example of that would be the accent of a non-native speaker (NNS), whose first language is different from that of the listeners, which I will call here a foreign accent. In perception studies, accentedness is conceptualized as a subjective measure of how strong listeners rate a speaker’s accent. A usage-based account is potentially insightful when considering not just the first language (L1) perception studies discussed above, but also studies of second language (L2) variation, including foreign-accentedness rating tasks. Usage-based models would predict that in a foreign accentedness rating task the items that activated the representations most similar to the ones associated with the listener or other native speakers would be judged as less foreign-accented whereas the items different from them or similar to the representations that have previously been identified as foreign-accented would be judged as more foreign-accented. Accentedness perception has been shown to be influenced by a number of stimulus-independent factors ( Kraut and Wulff 2013 ; Levi et al. 2007 ). A speaker’s perceived ethnicity is one of such factors influencing his/her perceived accentedness. Anecdotes of native English speakers of a non-white background being perceived to have an accent are abundant: in Lippi-Green (1997) a monolingual English-speaking woman of Asian Indian decent is asked by a shopkeeper to speak more slowly because of her “accent”. Several studies have explored the effect of ethnicity on reverse linguistic stereotyping, which is the idea that perceived social characteristics may influence perceived linguistic characteristics ( Kang and Rubin 2009 ). Rubin (1992) and McGowan (2015) have shown that the assumed ethnicity of the speaker influenced their perceived accentedness and intelligibility ratings, respectively. Rubin (1992) showed that the same native speaker (NS) of American English was rated as more accented when the listeners were presented with a picture of an Asian woman compared to when they were presented with a picture of a Caucasian woman, and this was attributed to listeners’ negative bias. That is, listeners’ negative bias towards Asian faces was said to influence their accentedness rating even when presented with audio stimuli from a native speaker with a Standard American English accent. McGowan (2015) finds a different effect, such that when presented with Asian-accented speech stimuli, listeners’ intelligibility ratings are higher when they are shown a picture of an Asian face rather than a Caucasian face. This is not seen to be an effect of negative bias, then, but instead an effect of matching the types of stimuli: an audio clip from a native speaker of Standard American English mismatched with a picture of an Asian face increases accentedness ratings, but an audio clip from an Asian-accented speaker matched with a picture of an Asian face increases intelligibility scores. These studies provide us with important information about how a speaker’s assumed ethnicity can impact upon listeners’ reaction to speech stimuli, but they both focus on a minority ethnicity (i.e. Asian speakers in the USA). Much less is known about the perceptual effects of presenting listeners with foreign-accented speech along with pictures of Caucasian faces. Specifically, little is known about the perceptual effects of reverse linguistic stereotyping when listeners are presented with visual stimuli of a Caucasian speaker but audio stimuli of a non-standard variety, such as foreign-accented speech. The effects", "role": "user" }, { "content": "New research from The Australian National University (ANU) has shown people demonstrate unconscious negative biases when they encounter a person of ethnic appearance or hear a foreign accent. Dr. Ksenia Gnevsheva of the ANU School of Literature, Languages and Linguistics asked research participants to watch videos of ethnically diverse people speaking and rate the level of accent they detected. She found participants rated a person of Asian appearance as accented, even though a video of them speaking was played to them mute. They also rated a Caucasian-looking person as not at all accented without hearing their audio, when they were actually a native German speaking English with an accent. \"I wanted to see how accents interacted with ethnicity and I found that when people responded to visual cues only; what a person looks like, they make assumptions about a person's accent. They rated an Asian person's accent stronger than that of a Caucasian-looking person's, without even hearing the audio,\" said Dr. Gnevsheva. While both Korean and German speakers were rated to have a similar degree of accent in English when the participants were played the audio-recordings (without vision), these ratings changed when the video track was added. When participants both saw and heard the non-native speakers of English, they rated the Asian person with the same level of accent as when there was no video track, but rated the German English speaker as more accented than just the audio-recording. \"This was a new and unexpected finding,\" said Dr. Gnevsheva and it tells me that people don't expect to hear an accent from a Caucasian looking person so they get a surprise when they hear one and rate it as more highly accented. \"I call this an expectation mis-match and it goes some way to showing that our unconscious biases can work against a large cross section of society, not just people of ethnic appearance,\" she said. Dr. Gnevsheva hopes the research will raise people's awareness of inherent biases they have in relation to ethnic appearance and linguistic ability. \"You could say this is linguistic discrimination. People often base hiring and promotion decisions on communicative ability and we have shown that ethnicity affects our perception of communicative ability.\" \"Racial discrimination laws don't actually cover linguistic discrimination. People can substitute other types of discrimination for linguistic discrimination,\" she said. Dr. Gnevsheva says linguists are divided over whether the results are the product of inherent negative biases or due simply to a limited experience and exposure to a diversity of languages. \"I think as a society and as individuals we are cautious of 'the other'; things we haven't experienced or don't understand, but as they become more common and we begin to see them more frequently, we grow to know, understand and accept diversity and multiculturalism.\" Dr. Gnevsheva's research is published in Linguistics. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Previous research on speech perception has found an effect of ethnicity, such that the same audio clip may be rated more accented when presented with an Asian face (Rubin, Donald L. 1992. Nonlanguage factors affecting undergraduates’ judgments of nonnative English-speaking teaching assistants. Research in Higher Education 33(4). 511–531. doi: 10.1007/bf00973770). However, most previous work has concentrated on Asian non-native English speakers, and Caucasian speakers remain under-explored. In this study, listeners carried out an accentedness rating task using stimuli from first language Korean, German, and English speakers in 3 conditions: audio only, video only, and audiovisual . Korean speakers received similar accentedness ratings regardless of condition, but German speakers were rated significantly less accented in the video condition and more accented in the audiovisual condition than the audio one. This result is explained as an expectation mismatch effect, whereby, when the listeners saw a Caucasian speaker they did not expect to hear a foreign accent, but if they actually heard one it was made more salient by their expectation to the contrary. Keywords: Speech perception ; sociophonetics ; foreign accentedness ; ethnicity ; variation 1 Introduction There is a growing body of research on sociophonetic variation in speech perception (see Campbell-Kibler 2010 ; Drager 2010 ; for a review). Previous studies have shown a strong link between social and linguistic information such that, on the one hand, the perceived linguistic information influences the listeners’ assumptions about the speaker’s social information (e.g., Campbell-Kibler 2007 ) and, on the other hand, assumed social information may affect how linguistic information is perceived (e.g., Hay et al. 2006a ; Hay et al. 2006b ; Niedzielski 1999 ; see discussion below). The existing relationship between social and linguistic information may be explained by usage-based models of speech perception. Exemplar theory (e.g., Johnson 1997 ; Johnson 2006 ; Pierrehumbert 2003 ) suggests that our brain stores clouds of representations, exemplars , for a given category; and that these clouds are updated constantly through the perception-production loop. Sociolinguistic information, such as different speaker characteristics (sex, age, origin, etc.) and contextual information (speech styles, etc.), is associated and stored together with these exemplars. The sociolinguistic information is activated when associated exemplars are activated, and it can activate associated exemplars when it is accessed ( Hay et al. 2006a : 370). In non-native speakers, previous research has also shown that assumed social information may affect perceived linguistic information, such as degree of accent (e.g., see a discussion of Rubin 1992 below). An accent is a “cumulative auditory effect of those features of pronunciation which identify where a person is from, regionally or socially” ( Vishnevskaya 2008 : 235). When listeners hear substantial differences in a speaker’s production, they can identify the person as coming from a different background. A specific example of that would be the accent of a non-native speaker (NNS), whose first language is different from that of the listeners, which I will call here a foreign accent. In perception studies, accentedness is conceptualized as a subjective measure of how strong listeners rate a speaker’s accent. A usage-based account is potentially insightful when considering not just the first language (L1) perception studies discussed above, but also studies of second language (L2) variation, including foreign-accentedness rating tasks. Usage-based models would predict that in a foreign accentedness rating task the items that activated the representations most similar to the ones associated with the listener or other native speakers would be judged as less foreign-accented whereas the items different from them or similar to the representations that have previously been identified as foreign-accented would be judged as more foreign-accented. Accentedness perception has been shown to be influenced by a number of stimulus-independent factors ( Kraut and Wulff 2013 ; Levi et al. 2007 ). A speaker’s perceived ethnicity is one of such factors influencing his/her perceived accentedness. Anecdotes of native English speakers of a non-white background being perceived to have an accent are abundant: in Lippi-Green (1997) a monolingual English-speaking woman of Asian Indian decent is asked by a shopkeeper to speak more slowly because of her “accent”. Several studies have explored the effect of ethnicity on reverse linguistic stereotyping, which is the idea that perceived social characteristics may influence perceived linguistic characteristics ( Kang and Rubin 2009 ). Rubin (1992) and McGowan (2015) have shown that the assumed ethnicity of the speaker influenced their perceived accentedness and intelligibility ratings, respectively. Rubin (1992) showed that the same native speaker (NS) of American English was rated as more accented when the listeners were presented with a picture of an Asian woman compared to when they were presented with a picture of a Caucasian woman, and this was attributed to listeners’ negative bias. That is, listeners’ negative bias towards Asian faces was said to influence their accentedness rating even when presented with audio stimuli from a native speaker with a Standard American English accent. McGowan (2015) finds a different effect, such that when presented with Asian-accented speech stimuli, listeners’ intelligibility ratings are higher when they are shown a picture of an Asian face rather than a Caucasian face. This is not seen to be an effect of negative bias, then, but instead an effect of matching the types of stimuli: an audio clip from a native speaker of Standard American English mismatched with a picture of an Asian face increases accentedness ratings, but an audio clip from an Asian-accented speaker matched with a picture of an Asian face increases intelligibility scores. These studies provide us with important information about how a speaker’s assumed ethnicity can impact upon listeners’ reaction to speech stimuli, but they both focus on a minority ethnicity (i.e. Asian speakers in the USA). Much less is known about the perceptual effects of presenting listeners with foreign-accented speech along with pictures of Caucasian faces. Specifically, little is known about the perceptual effects of reverse linguistic stereotyping when listeners are presented with visual stimuli of a Caucasian speaker but audio stimuli of a non-standard variety, such as foreign-accented speech. The effects<|im_end|> <|im_start|>assistant New research from The Australian National University (ANU) has shown people demonstrate unconscious negative biases when they encounter a person of ethnic appearance or hear a foreign accent. Dr. Ksenia Gnevsheva of the ANU School of Literature, Languages and Linguistics asked research participants to watch videos of ethnically diverse people speaking and rate the level of accent they detected. She found participants rated a person of Asian appearance as accented, even though a video of them speaking was played to them mute. They also rated a Caucasian-looking person as not at all accented without hearing their audio, when they were actually a native German speaking English with an accent. "I wanted to see how accents interacted with ethnicity and I found that when people responded to visual cues only; what a person looks like, they make assumptions about a person's accent. They rated an Asian person's accent stronger than that of a Caucasian-looking person's, without even hearing the audio," said Dr. Gnevsheva. While both Korean and German speakers were rated to have a similar degree of accent in English when the participants were played the audio-recordings (without vision), these ratings changed when the video track was added. When participants both saw and heard the non-native speakers of English, they rated the Asian person with the same level of accent as when there was no video track, but rated the German English speaker as more accented than just the audio-recording. "This was a new and unexpected finding," said Dr. Gnevsheva and it tells me that people don't expect to hear an accent from a Caucasian looking person so they get a surprise when they hear one and rate it as more highly accented. "I call this an expectation mis-match and it goes some way to showing that our unconscious biases can work against a large cross section of society, not just people of ethnic appearance," she said. Dr. Gnevsheva hopes the research will raise people's awareness of inherent biases they have in relation to ethnic appearance and linguistic ability. "You could say this is linguistic discrimination. People often base hiring and promotion decisions on communicative ability and we have shown that ethnicity affects our perception of communicative ability." "Racial discrimination laws don't actually cover linguistic discrimination. People can substitute other types of discrimination for linguistic discrimination," she said. Dr. Gnevsheva says linguists are divided over whether the results are the product of inherent negative biases or due simply to a limited experience and exposure to a diversity of languages. "I think as a society and as individuals we are cautious of 'the other'; things we haven't experienced or don't understand, but as they become more common and we begin to see them more frequently, we grow to know, understand and accept diversity and multiculturalism." Dr. Gnevsheva's research is published in Linguistics. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Myeloid-derived suppressor cells (MDSCs) play critical roles in primary and metastatic cancer progression. MDSC regulation is widely variable even among patients harbouring the same type of malignancy, and the mechanisms governing such heterogeneity are largely unknown. Here, integrating human tumour genomics and syngeneic mammary tumour models, we demonstrate that mTOR signalling in cancer cells dictates a mammary tumour’s ability to stimulate MDSC accumulation through regulating G-CSF. Inhibiting this pathway or its activators (for example, FGFR) impairs tumour progression, which is partially rescued by restoring MDSCs or G-CSF. Tumour-initiating cells (TICs) exhibit elevated G-CSF. MDSCs reciprocally increase TIC frequency through activating Notch in tumour cells, forming a feedforward loop. Analyses of primary breast cancers and patient-derived xenografts corroborate these mechanisms in patients. These findings establish a non-canonical oncogenic role of mTOR signalling in recruiting pro-tumorigenic MDSCs and show how defined cancer subsets may evolve to promote and depend on a distinct immune microenvironment. Main Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population defined as CD11b + Gr1 + cells. They can be roughly divided into granulocytic and monocytic subsets using Ly6G and Ly6C as markers, respectively. Both CD11b + Ly6G + and CD11b + Ly6C + cells have immunosuppressive activities, although different mechanisms may be used. The granulocytic subset is more often found expanded in tumour models and is involved in promoting tumour progression 1 , 2 , 3 , 4 , although anti-tumour effects have also been observed 5 . In the clinic, MDSCs were first identified in the peripheral blood of cancer patients as non-lymphoid haematopoietic suppressor cells 6 that have been subsequently shown to increase during progression in many cancer types 7 , 8 . Similar to mouse, most human MDSCs carry markers of immature myeloid lineage cells and qualify as either granulocytic (CD11b + CD33 + CD15 + HDLA low ) or monocytic (CD11b + CD14 + HDLA low ) subsets 3 , 4 , 9 . Considerable information has been obtained about the biogenesis and functions of MDSCs. The cytokines responsible for MDSC accumulation include G-CSF 10 , 11 , 12 , 13 , 14 , GM-CSF 15 , IL-1β 16 , 17 , IL-6 18 , PGE2 19 , IFN-γ 20 , IL-4 21 and VEGF 22 . The immunosuppressive mechanisms used by MDSCs involve secretion of TGFβ, generation of nitric oxide and reactive oxygen species, and metabolic depletion of L -arginine by arginase 1 (refs 1 , 2 ). These activities can blunt cytotoxicity, block proliferation or induce apoptosis of cytotoxic T lymphocytes and natural killer cells. Other MDSC functions include formation of a pre-metastatic niche 23 , enhancement of tumour invasion 24 , 25 and stimulation of angiogenesis 25 . Despite this knowledge, we have a limited understanding of why and how individual tumours vary widely in their propensity to induce MDSCs. Here, we demonstrate that this propensity is determined by an oncogenic signalling pathway and linked to the subpopulation of tumour-initiating cells (TICs). RESULTS Inter-tumoral heterogeneity of MDSC infiltration We examined myeloid cells in a variety of syngeneic mammary tumour models of diverse genetic backgrounds and tumorigenic drivers. MMTV–WNT1, MMTV–WNT1–iFGFR and P53–PTEN double knockout (DKO) are genetically engineered mouse models in the FVB background. MMTV–WNT1 is a widely used model of basal-like tumours. WNT1–iFGFR is a bigenic model based on MMTV–WNT1, in which FGFR signalling can be inducibly activated 26 , 27 . The P53–PTEN DKO was generated by conditional deletion of these tumour suppressors using a MMTV-driven Cre. P53N tumour lines initially arose from transplanted P53-null mammary gland tissues in BALB/c mice, and are maintained through mouse-to-mouse orthotopic transplantation. Despite the common loss of P53, P53N lines exhibited remarkable inter-tumoral heterogeneity in genomic copy number, gene expression profiles and TIC frequencies 28 . The 67NR–4TO7–4T1 series are established cell lines derived from a spontaneous tumour in BALB/c mice. Taken together, these reagents provide an unbiased representation of available syngeneic models. Mammary tumours were generated either by spontaneous tumorigenesis (MMTV–WNT1, WNT1–iFGFR and P53–PTEN DKO), or orthotopic transplantation of primary tumour tissues (P53N series) or cell suspensions (67NR, 4TO7, and 4T1). When tumours reached 1 cm 3 , we examined myeloid cell infiltration by immunofluorescence staining of S100A8, which was predominantly expressed by CD11b + Gr1 + cells rather than tumour cells ( Supplementary Fig. 1b ). Significant inter-tumoral heterogeneity was discovered ( Fig. 1a and Supplementary Fig. 1a ). Quantification of CD11b + Gr1 + cells in dissociated tumours was largely consistent with S100A8 staining ( Fig. 1b ). The accumulation of CD11b + Gr1 + cells is systemic, as they were also found in peripheral blood and the frequencies closely correlated with the tumour-infiltrating myeloid cells ( Fig. 1c, d ). Overall, the inter-model variations of CD11b + Gr1 + cells were as high as 50- to 100-fold. In contrast, tumours of the same model exhibited only a 2- to 5-fold variation ( Fig. 1b ). Thus, the local and systemic accumulation of CD11b + Gr1 + cells seems to be a stable trait of each tumour line. Figure 1: Inter-tumoral heterogeneity of MDSC infiltration. ( a ) Representative immunofluorescence staining of S100A8 in the indicated tumours. Green, S100A8; blue, DAPI (nucleus). Scale bar, 100 μm. ( b ) Flow cytometry quantification of tumour-infiltrating CD11b + Gr1 + cells. Animal numbers ( n ) in each model are indicated. Five independent experiments were performed with consistent results and one representative experiment is shown. ( c , d ) Flow cytometry quantification of CD11b + Gr1 + cells in peripheral blood. Animal numbers: ( c ) tumour-free: n = 4, MMTV–Wnt1: n = 5, MMTV–Wnt1–iFGFR: n = 7; ( d ) tumour-free: n = 4, P53N-A: n = 4, P53N-B: n = 2, P53N-C: n = 5. Three independent experiments were performed with consistent results and a representative experiment is shown. NS, not significant. ( e ) FACS analyses show that CD11b + cells in blood of P53N-C tumour-bearing mice express Ly6C at a lower and more variable level compared with", "role": "user" }, { "content": "Not every breast cancer tumor follows the same path to grow. Some tumors have the assistance of myeloid-derived suppressor cells (MDSCs), a diverse type of immune cell involved in the suppression of the body's response against tumors. How breast cancer cells recruit MDSCs is not completely understood, but in a paper released today in Nature Cell Biology, Baylor College of Medicine researchers report a new mechanism that helps cancer cells engage MDSCs. \"There are alternative paths a tumor may take without the MDSCs, but those cancer cells that take the mTOR path of activity tend to have more MDSCs through the production of granulocyte-colony stimulating factor (G-CSF), which drives the accumulation of MDSCs,\" said corresponding author Dr. Xiang Zhang, a McNair Scholar and assistant professor of molecular and cellular biology at Baylor College of Medicine. Knowing how cancer cells and MDSCs interact with each other helps researchers understand the events that may lead to tumor growth and metastasis and identify potential therapeutic targets. For instance, \"determining that a patient's tumor is using the mTOR pathway would indicate that the cancer cells are more likely to depend on MDSCs for progression,\" said Zhang, who also is with the Lester and Sue Smith Breast Center at Baylor. \"This information suggests that, in this case, available therapies for mTOR combined with therapies for MDSCs represent potential therapeutic strategies.\" Tumors that do not use the mTOR signaling pathway would not be expected to respond as well to the same therapies. The discovery of Zhang and colleagues is much in line with the concept of personalized medicine. \"People talk about the specific mutations one patient's tumor has that are not in another patient's tumor. The same type of tumors having different mutations may warrant different treatments; that is personalized medicine,\" explained Zhang. \"We are trying to come from a different angle. We are trying to enrich this concept by saying that not only tumor-intrinsic characteristics are different from patient to patient, but, related to that, there is also diversity in terms of the immune components. Different tumors may evolve via different characteristics of the tumor and the immune response.\" MDCSs are just one type of aberrant immune cell associated with the tumor. \"In addition, there are other immune cells associated with the tumor - monocytes, macrophages, different subsets of T cells - that can either attack or help the tumor. All those cells may vary from patient to patient, and we don't really understand that yet,\" said Zhang. In addition, MDSCs also play a role in non-cancer situations. For instance, in chronic inflammation, these cells try to suppress the inflammation; in this case, they play a pro-health role. So, \"simply eliminating all MDSCs to treat cancer may likely result in negative side effects, such as autoimmune disease. That's why it's necessary to further characterize the diversity, to find the specific subsets of MDSCs that are tumor specific,\" said Zhang. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Myeloid-derived suppressor cells (MDSCs) play critical roles in primary and metastatic cancer progression. MDSC regulation is widely variable even among patients harbouring the same type of malignancy, and the mechanisms governing such heterogeneity are largely unknown. Here, integrating human tumour genomics and syngeneic mammary tumour models, we demonstrate that mTOR signalling in cancer cells dictates a mammary tumour’s ability to stimulate MDSC accumulation through regulating G-CSF. Inhibiting this pathway or its activators (for example, FGFR) impairs tumour progression, which is partially rescued by restoring MDSCs or G-CSF. Tumour-initiating cells (TICs) exhibit elevated G-CSF. MDSCs reciprocally increase TIC frequency through activating Notch in tumour cells, forming a feedforward loop. Analyses of primary breast cancers and patient-derived xenografts corroborate these mechanisms in patients. These findings establish a non-canonical oncogenic role of mTOR signalling in recruiting pro-tumorigenic MDSCs and show how defined cancer subsets may evolve to promote and depend on a distinct immune microenvironment. Main Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population defined as CD11b + Gr1 + cells. They can be roughly divided into granulocytic and monocytic subsets using Ly6G and Ly6C as markers, respectively. Both CD11b + Ly6G + and CD11b + Ly6C + cells have immunosuppressive activities, although different mechanisms may be used. The granulocytic subset is more often found expanded in tumour models and is involved in promoting tumour progression 1 , 2 , 3 , 4 , although anti-tumour effects have also been observed 5 . In the clinic, MDSCs were first identified in the peripheral blood of cancer patients as non-lymphoid haematopoietic suppressor cells 6 that have been subsequently shown to increase during progression in many cancer types 7 , 8 . Similar to mouse, most human MDSCs carry markers of immature myeloid lineage cells and qualify as either granulocytic (CD11b + CD33 + CD15 + HDLA low ) or monocytic (CD11b + CD14 + HDLA low ) subsets 3 , 4 , 9 . Considerable information has been obtained about the biogenesis and functions of MDSCs. The cytokines responsible for MDSC accumulation include G-CSF 10 , 11 , 12 , 13 , 14 , GM-CSF 15 , IL-1β 16 , 17 , IL-6 18 , PGE2 19 , IFN-γ 20 , IL-4 21 and VEGF 22 . The immunosuppressive mechanisms used by MDSCs involve secretion of TGFβ, generation of nitric oxide and reactive oxygen species, and metabolic depletion of L -arginine by arginase 1 (refs 1 , 2 ). These activities can blunt cytotoxicity, block proliferation or induce apoptosis of cytotoxic T lymphocytes and natural killer cells. Other MDSC functions include formation of a pre-metastatic niche 23 , enhancement of tumour invasion 24 , 25 and stimulation of angiogenesis 25 . Despite this knowledge, we have a limited understanding of why and how individual tumours vary widely in their propensity to induce MDSCs. Here, we demonstrate that this propensity is determined by an oncogenic signalling pathway and linked to the subpopulation of tumour-initiating cells (TICs). RESULTS Inter-tumoral heterogeneity of MDSC infiltration We examined myeloid cells in a variety of syngeneic mammary tumour models of diverse genetic backgrounds and tumorigenic drivers. MMTV–WNT1, MMTV–WNT1–iFGFR and P53–PTEN double knockout (DKO) are genetically engineered mouse models in the FVB background. MMTV–WNT1 is a widely used model of basal-like tumours. WNT1–iFGFR is a bigenic model based on MMTV–WNT1, in which FGFR signalling can be inducibly activated 26 , 27 . The P53–PTEN DKO was generated by conditional deletion of these tumour suppressors using a MMTV-driven Cre. P53N tumour lines initially arose from transplanted P53-null mammary gland tissues in BALB/c mice, and are maintained through mouse-to-mouse orthotopic transplantation. Despite the common loss of P53, P53N lines exhibited remarkable inter-tumoral heterogeneity in genomic copy number, gene expression profiles and TIC frequencies 28 . The 67NR–4TO7–4T1 series are established cell lines derived from a spontaneous tumour in BALB/c mice. Taken together, these reagents provide an unbiased representation of available syngeneic models. Mammary tumours were generated either by spontaneous tumorigenesis (MMTV–WNT1, WNT1–iFGFR and P53–PTEN DKO), or orthotopic transplantation of primary tumour tissues (P53N series) or cell suspensions (67NR, 4TO7, and 4T1). When tumours reached 1 cm 3 , we examined myeloid cell infiltration by immunofluorescence staining of S100A8, which was predominantly expressed by CD11b + Gr1 + cells rather than tumour cells ( Supplementary Fig. 1b ). Significant inter-tumoral heterogeneity was discovered ( Fig. 1a and Supplementary Fig. 1a ). Quantification of CD11b + Gr1 + cells in dissociated tumours was largely consistent with S100A8 staining ( Fig. 1b ). The accumulation of CD11b + Gr1 + cells is systemic, as they were also found in peripheral blood and the frequencies closely correlated with the tumour-infiltrating myeloid cells ( Fig. 1c, d ). Overall, the inter-model variations of CD11b + Gr1 + cells were as high as 50- to 100-fold. In contrast, tumours of the same model exhibited only a 2- to 5-fold variation ( Fig. 1b ). Thus, the local and systemic accumulation of CD11b + Gr1 + cells seems to be a stable trait of each tumour line. Figure 1: Inter-tumoral heterogeneity of MDSC infiltration. ( a ) Representative immunofluorescence staining of S100A8 in the indicated tumours. Green, S100A8; blue, DAPI (nucleus). Scale bar, 100 μm. ( b ) Flow cytometry quantification of tumour-infiltrating CD11b + Gr1 + cells. Animal numbers ( n ) in each model are indicated. Five independent experiments were performed with consistent results and one representative experiment is shown. ( c , d ) Flow cytometry quantification of CD11b + Gr1 + cells in peripheral blood. Animal numbers: ( c ) tumour-free: n = 4, MMTV–Wnt1: n = 5, MMTV–Wnt1–iFGFR: n = 7; ( d ) tumour-free: n = 4, P53N-A: n = 4, P53N-B: n = 2, P53N-C: n = 5. Three independent experiments were performed with consistent results and a representative experiment is shown. NS, not significant. ( e ) FACS analyses show that CD11b + cells in blood of P53N-C tumour-bearing mice express Ly6C at a lower and more variable level compared with<|im_end|> <|im_start|>assistant Not every breast cancer tumor follows the same path to grow. Some tumors have the assistance of myeloid-derived suppressor cells (MDSCs), a diverse type of immune cell involved in the suppression of the body's response against tumors. How breast cancer cells recruit MDSCs is not completely understood, but in a paper released today in Nature Cell Biology, Baylor College of Medicine researchers report a new mechanism that helps cancer cells engage MDSCs. "There are alternative paths a tumor may take without the MDSCs, but those cancer cells that take the mTOR path of activity tend to have more MDSCs through the production of granulocyte-colony stimulating factor (G-CSF), which drives the accumulation of MDSCs," said corresponding author Dr. Xiang Zhang, a McNair Scholar and assistant professor of molecular and cellular biology at Baylor College of Medicine. Knowing how cancer cells and MDSCs interact with each other helps researchers understand the events that may lead to tumor growth and metastasis and identify potential therapeutic targets. For instance, "determining that a patient's tumor is using the mTOR pathway would indicate that the cancer cells are more likely to depend on MDSCs for progression," said Zhang, who also is with the Lester and Sue Smith Breast Center at Baylor. "This information suggests that, in this case, available therapies for mTOR combined with therapies for MDSCs represent potential therapeutic strategies." Tumors that do not use the mTOR signaling pathway would not be expected to respond as well to the same therapies. The discovery of Zhang and colleagues is much in line with the concept of personalized medicine. "People talk about the specific mutations one patient's tumor has that are not in another patient's tumor. The same type of tumors having different mutations may warrant different treatments; that is personalized medicine," explained Zhang. "We are trying to come from a different angle. We are trying to enrich this concept by saying that not only tumor-intrinsic characteristics are different from patient to patient, but, related to that, there is also diversity in terms of the immune components. Different tumors may evolve via different characteristics of the tumor and the immune response." MDCSs are just one type of aberrant immune cell associated with the tumor. "In addition, there are other immune cells associated with the tumor - monocytes, macrophages, different subsets of T cells - that can either attack or help the tumor. All those cells may vary from patient to patient, and we don't really understand that yet," said Zhang. In addition, MDSCs also play a role in non-cancer situations. For instance, in chronic inflammation, these cells try to suppress the inflammation; in this case, they play a pro-health role. So, "simply eliminating all MDSCs to treat cancer may likely result in negative side effects, such as autoimmune disease. That's why it's necessary to further characterize the diversity, to find the specific subsets of MDSCs that are tumor specific," said Zhang. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Electrochemical conversions at fuel cell electrodes are complex processes. In particular, the oxygen reduction reaction has substantial overpotential limiting the electrical power output efficiency. Effective and inexpensive catalytic interfaces are therefore essential for increased performance. Taking inspiration from enzymes, earth-abundant metal centres embedded in organic environments present remarkable catalytic active sites. Here we show that these enzyme-inspired centres can be effectively mimicked in two-dimensional metal-organic coordination networks self-assembled on electrode surfaces. Networks consisting of trimesic acid and bis-pyridyl-bispyrimidine coordinating to single iron and manganese atoms on Au(111) effectively catalyse the oxygen reduction and reveal distinctive catalytic activity in alkaline media. These results demonstrate the potential of surface-engineered metal-organic networks for electrocatalytic conversions. Specifically designed coordination complexes at surfaces inspired by enzyme cofactors represent a new class of nanocatalysts with promising applications in electrocatalysis. Introduction Energy and climate change have become one of the biggest preoccupations attracting the common interest of science, engineering and society. In this important field, electrochemistry provides a bridge for efficient interconversion of chemical to electrical energy, that is, fuel cells 1 , 2 , 3 . Fuel cells based on oxidation of H 2 and reduction of O 2 require electrocatalytic surfaces since the electrode processes are not simple reactions and show a strong dependence on the nature of the electrode material. For instance, a direct relationship between the kinetic rates of the oxygen reduction reaction (ORR) and the surface electrode structure was found for gold single crystals 4 , 5 . ORR is a complex reaction and an effective and inexpensive catalyst that can compete with or exceed the efficiency of platinum remains an ongoing challenge. The physical and economic requirements of low overpotential, long-term stability, pH working conditions, non-toxic and earth-abundant elements, and so on impose severe boundaries on the usable material combinations. Nature provides an alternative and efficient solution to this problem, that is, the O 2 in our atmosphere is biogenic—the result of a catalytic process in the photosynthetic machinery of green plants 6 . With increasing atmospheric oxygen levels, higher life-forms with oxygen-metabolizing enzymes evolved. These naturally occurring oxygen activation catalysts, which have been utilized in biological processes for several hundred millions of years, are considered as viable substitutes for precious metals in ORR catalysts for fuel cells 7 , 8 , 9 . Considering both biological and classical inorganic catalysts, one finds close relation between structure and function. In the case of the enzymatic ORR catalysts, nature uses, first, molecules containing electron-donating functional groups that prevent the formation and release of detrimental partially reduced oxygen by-products and intermediates 10 . Second, bulky protein chains sufficiently separate the ORR inorganic active sites, preventing site overlap and catalytic deactivation 9 . The active sites, mostly composed of first-row transition metal atoms and clusters, share a common and important feature with classical inorganic catalysts, that is, the presence of coordinatively unsaturated sites, which play a prominent role in heterogeneous catalytic transformations 11 , 12 . Thus, new catalytic materials can be designed that are inspired by both natural and classical ORR catalysts by using organic molecules with specific molecular backbones (adequately separating the active sites) and selected functional groups (electron withdrawing or donating) to coordinate transition metal atoms or clusters directly on surfaces. Thus, two-dimensional metal-organic coordination networks (2D-MOCNs), that is, organic molecules and metal centres self-assembled on surfaces under well-controlled conditions, constitute a promising route to fabricate functional low-dimensional bio-inspired architectures 13 . 2D-MOCNs were created using organic ligands with different functional groups (carboxylic acid, pyridyl, cyano and hydroxyl end groups) and metal centres (Mn, Fe, Co, Ni and Cu) on various noble metal substrates like Au, Ag, Cu or highly ordered pyrolytic graphite 13 , 14 , 15 , 16 . An example of a 2D-MOCN is presented in Fig. 1 showing a Scanning tunnelling microscopy (STM) image of biphenyl-dicarboxylic acid self-assembled with Fe atoms on Cu(100) 17 . The biphenyl-dicarboxylic acid ligand coordinates with its two-terminal carboxylate groups to dimeric Fe centres, thus forming an extended and periodic 2D coordination polymer. The network presents open cavities where the underlying substrate is exposed. Each network node consists of two coordinatively unsaturated Fe centres with each atom being threefold coordinated to carboxylate oxygen atoms (see Fig. 1 ). The network is chemisorbed to the copper surface but the top binding position of the Fe centres remains open. Moreover, the hybridization of the metal centres with the metal surface is significantly reduced yielding atomic-like electronic configurations for the Fe ions as found for isolated metal–organic complexes 18 . Figure 1: Example of 2D-MOCNs. Scanning tunneling microscopy image of Fe-biphenyl-dicarboxylic acid on Cu (100) self-assembled under UHV conditions. The main features of 2D-MOCNs are indicated: metal centre, organic ligand and cavity. The expansion illustrates the Fe coordination environment 17 . Full size image Engineering of the synthetic ligands in combination with the judicious choice of the metal centres and substrates allows complete control on the network structure, separation and coordination geometry of the metal centres as well as the size of the generated cavities 17 , 19 . To date, the most explored application of surface-supported 2D networks so far is the accommodation of guest molecules inside the cavities 20 , 21 . Initial experiments on the reactivity of the metal centres towards O 2 adsorbed from the gas phase 22 indicate the high potential of 2D-MOCNs as tailor-made heterogeneous electrocatalysts. In the present work, we show that rationally designed 2D−MOCN exhibit substantial electrocatalytic activity for the ORR in alkaline media. The electrochemical behaviour differs from bare Au(111) and the ORR mechanism depends strongly on the choice of the metal centre, while the stability of the network is determined by the organic molecule. The networks containing Fe atoms exhibit a (2+2)e − pathway for the complete reduction to H 2 O, while the coordinated Mn atoms show evidence for a direct 4e − route to convert O 2 to H 2 O. Results Formation of metal–organic networks on Au(111) The networks consist of", "role": "user" }, { "content": "Fuel cells represent an important component of the energy transition, as they supply electrical energy without first having to create heat and steam from fossil fuels. Instead, they create the energy directly from a reaction of hydrogen and oxygen to form water. For that reason, they can create energy more efficiently than coal-fired or gas-fired power plants. Today's fuel cells require, however, costly platinum as a catalyst for this reaction, which restricts their more widespread use. A team at the Max Planck Institute for Solid State Research in Stuttgart has been inspired by nature to develop an alternative catalyst. It consists of organic molecules as well as iron or manganese on a metallic substrate. These materials are less costly and more easily available than platinum. Humans and animals obtain energy from the same reaction as fuel cells: they breathe in oxygen and bind hydrogen with it in their cells to form water. In this chemical conversion, energy is released, which the organism uses to live. Therefore, the idea to search in nature for a catalyst as a substitute for expensive platinum is logical. This noble metal drives a specific partial reaction during the energy conversion in a fuel cell: the so-called reduction of oxygen. During this reaction, oxygen picks up either two or four electrons, depending on whether it reacts directly with hydrogen or via an intermediate hydrogen peroxide molecule to form water. Natural oxygen-reducing enzymes contain metals like iron and manganese, which are easily obtained through nutritional sources. Organic molecules associated with this enzyme hold on tightly to the atoms of these metals, so that the oxygen can dock there and be reduced. Klaus Kern and his staff member Doris Grumelli from the Max Planck Institute for Solid State Research have now evaporated iron and manganese atoms together with organic molecules onto a gold substrate. In doing this, they established that the organic molecules and the metal atoms become ordered in patterns that strongly resemble the functional centres of enzymes. Networks formed in which individual iron or manganese atoms are surrounded by several organic molecules, like the intersecting points in a lattice fence. The iron atoms (blue) and the organic molecules (green, black) form a lattice pattern on the gold substrate. Credit: Grumelli et al., Nat. Comm. 2013 In order to be able to test how the catalyst functions in the networks, the researchers had to develop a transport system with which they can move the samples from vacuum into liquids. This is because the new surface structures were formed under a very high vacuum, while the tests took place outside the vacuum chamber in an electrochemical cell. It turned out that the catalytic activity depended of the kind of metallic centre, while, on the other hand, the stability of the structure depended on the type of organic molecules that form the network. Iron atoms led to a two-level reaction via the intermediate hydrogen peroxide molecule, while manganese atoms produced a direct reaction of oxygen to water. The latter reaction would be interest for fuel cells, as experts expect higher efficiency in converting the chemical energy to electrical energy through the direct reaction. \"However, the other variant could also have applications,\" says Grumelli, \"even serving to modulate or interrupt the reaction.\" This can play a role in biosensors, for example. In any event, the Group has succeeded in making a new class of nanocatalysts that are cost-effective to manufacture, and whose raw materials are plentiful. Doris Grumelli is already working on a new variant of these kinds of structures: with the help of special organic molecules which each contain a metal atom, and the use of additional metal atoms, she hopes to create a surface structure that simultaneously contains two types of metal atoms. \"Such structures could serve as models for biological research,\" says the scientist. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Electrochemical conversions at fuel cell electrodes are complex processes. In particular, the oxygen reduction reaction has substantial overpotential limiting the electrical power output efficiency. Effective and inexpensive catalytic interfaces are therefore essential for increased performance. Taking inspiration from enzymes, earth-abundant metal centres embedded in organic environments present remarkable catalytic active sites. Here we show that these enzyme-inspired centres can be effectively mimicked in two-dimensional metal-organic coordination networks self-assembled on electrode surfaces. Networks consisting of trimesic acid and bis-pyridyl-bispyrimidine coordinating to single iron and manganese atoms on Au(111) effectively catalyse the oxygen reduction and reveal distinctive catalytic activity in alkaline media. These results demonstrate the potential of surface-engineered metal-organic networks for electrocatalytic conversions. Specifically designed coordination complexes at surfaces inspired by enzyme cofactors represent a new class of nanocatalysts with promising applications in electrocatalysis. Introduction Energy and climate change have become one of the biggest preoccupations attracting the common interest of science, engineering and society. In this important field, electrochemistry provides a bridge for efficient interconversion of chemical to electrical energy, that is, fuel cells 1 , 2 , 3 . Fuel cells based on oxidation of H 2 and reduction of O 2 require electrocatalytic surfaces since the electrode processes are not simple reactions and show a strong dependence on the nature of the electrode material. For instance, a direct relationship between the kinetic rates of the oxygen reduction reaction (ORR) and the surface electrode structure was found for gold single crystals 4 , 5 . ORR is a complex reaction and an effective and inexpensive catalyst that can compete with or exceed the efficiency of platinum remains an ongoing challenge. The physical and economic requirements of low overpotential, long-term stability, pH working conditions, non-toxic and earth-abundant elements, and so on impose severe boundaries on the usable material combinations. Nature provides an alternative and efficient solution to this problem, that is, the O 2 in our atmosphere is biogenic—the result of a catalytic process in the photosynthetic machinery of green plants 6 . With increasing atmospheric oxygen levels, higher life-forms with oxygen-metabolizing enzymes evolved. These naturally occurring oxygen activation catalysts, which have been utilized in biological processes for several hundred millions of years, are considered as viable substitutes for precious metals in ORR catalysts for fuel cells 7 , 8 , 9 . Considering both biological and classical inorganic catalysts, one finds close relation between structure and function. In the case of the enzymatic ORR catalysts, nature uses, first, molecules containing electron-donating functional groups that prevent the formation and release of detrimental partially reduced oxygen by-products and intermediates 10 . Second, bulky protein chains sufficiently separate the ORR inorganic active sites, preventing site overlap and catalytic deactivation 9 . The active sites, mostly composed of first-row transition metal atoms and clusters, share a common and important feature with classical inorganic catalysts, that is, the presence of coordinatively unsaturated sites, which play a prominent role in heterogeneous catalytic transformations 11 , 12 . Thus, new catalytic materials can be designed that are inspired by both natural and classical ORR catalysts by using organic molecules with specific molecular backbones (adequately separating the active sites) and selected functional groups (electron withdrawing or donating) to coordinate transition metal atoms or clusters directly on surfaces. Thus, two-dimensional metal-organic coordination networks (2D-MOCNs), that is, organic molecules and metal centres self-assembled on surfaces under well-controlled conditions, constitute a promising route to fabricate functional low-dimensional bio-inspired architectures 13 . 2D-MOCNs were created using organic ligands with different functional groups (carboxylic acid, pyridyl, cyano and hydroxyl end groups) and metal centres (Mn, Fe, Co, Ni and Cu) on various noble metal substrates like Au, Ag, Cu or highly ordered pyrolytic graphite 13 , 14 , 15 , 16 . An example of a 2D-MOCN is presented in Fig. 1 showing a Scanning tunnelling microscopy (STM) image of biphenyl-dicarboxylic acid self-assembled with Fe atoms on Cu(100) 17 . The biphenyl-dicarboxylic acid ligand coordinates with its two-terminal carboxylate groups to dimeric Fe centres, thus forming an extended and periodic 2D coordination polymer. The network presents open cavities where the underlying substrate is exposed. Each network node consists of two coordinatively unsaturated Fe centres with each atom being threefold coordinated to carboxylate oxygen atoms (see Fig. 1 ). The network is chemisorbed to the copper surface but the top binding position of the Fe centres remains open. Moreover, the hybridization of the metal centres with the metal surface is significantly reduced yielding atomic-like electronic configurations for the Fe ions as found for isolated metal–organic complexes 18 . Figure 1: Example of 2D-MOCNs. Scanning tunneling microscopy image of Fe-biphenyl-dicarboxylic acid on Cu (100) self-assembled under UHV conditions. The main features of 2D-MOCNs are indicated: metal centre, organic ligand and cavity. The expansion illustrates the Fe coordination environment 17 . Full size image Engineering of the synthetic ligands in combination with the judicious choice of the metal centres and substrates allows complete control on the network structure, separation and coordination geometry of the metal centres as well as the size of the generated cavities 17 , 19 . To date, the most explored application of surface-supported 2D networks so far is the accommodation of guest molecules inside the cavities 20 , 21 . Initial experiments on the reactivity of the metal centres towards O 2 adsorbed from the gas phase 22 indicate the high potential of 2D-MOCNs as tailor-made heterogeneous electrocatalysts. In the present work, we show that rationally designed 2D−MOCN exhibit substantial electrocatalytic activity for the ORR in alkaline media. The electrochemical behaviour differs from bare Au(111) and the ORR mechanism depends strongly on the choice of the metal centre, while the stability of the network is determined by the organic molecule. The networks containing Fe atoms exhibit a (2+2)e − pathway for the complete reduction to H 2 O, while the coordinated Mn atoms show evidence for a direct 4e − route to convert O 2 to H 2 O. Results Formation of metal–organic networks on Au(111) The networks consist of<|im_end|> <|im_start|>assistant Fuel cells represent an important component of the energy transition, as they supply electrical energy without first having to create heat and steam from fossil fuels. Instead, they create the energy directly from a reaction of hydrogen and oxygen to form water. For that reason, they can create energy more efficiently than coal-fired or gas-fired power plants. Today's fuel cells require, however, costly platinum as a catalyst for this reaction, which restricts their more widespread use. A team at the Max Planck Institute for Solid State Research in Stuttgart has been inspired by nature to develop an alternative catalyst. It consists of organic molecules as well as iron or manganese on a metallic substrate. These materials are less costly and more easily available than platinum. Humans and animals obtain energy from the same reaction as fuel cells: they breathe in oxygen and bind hydrogen with it in their cells to form water. In this chemical conversion, energy is released, which the organism uses to live. Therefore, the idea to search in nature for a catalyst as a substitute for expensive platinum is logical. This noble metal drives a specific partial reaction during the energy conversion in a fuel cell: the so-called reduction of oxygen. During this reaction, oxygen picks up either two or four electrons, depending on whether it reacts directly with hydrogen or via an intermediate hydrogen peroxide molecule to form water. Natural oxygen-reducing enzymes contain metals like iron and manganese, which are easily obtained through nutritional sources. Organic molecules associated with this enzyme hold on tightly to the atoms of these metals, so that the oxygen can dock there and be reduced. Klaus Kern and his staff member Doris Grumelli from the Max Planck Institute for Solid State Research have now evaporated iron and manganese atoms together with organic molecules onto a gold substrate. In doing this, they established that the organic molecules and the metal atoms become ordered in patterns that strongly resemble the functional centres of enzymes. Networks formed in which individual iron or manganese atoms are surrounded by several organic molecules, like the intersecting points in a lattice fence. The iron atoms (blue) and the organic molecules (green, black) form a lattice pattern on the gold substrate. Credit: Grumelli et al., Nat. Comm. 2013 In order to be able to test how the catalyst functions in the networks, the researchers had to develop a transport system with which they can move the samples from vacuum into liquids. This is because the new surface structures were formed under a very high vacuum, while the tests took place outside the vacuum chamber in an electrochemical cell. It turned out that the catalytic activity depended of the kind of metallic centre, while, on the other hand, the stability of the structure depended on the type of organic molecules that form the network. Iron atoms led to a two-level reaction via the intermediate hydrogen peroxide molecule, while manganese atoms produced a direct reaction of oxygen to water. The latter reaction would be interest for fuel cells, as experts expect higher efficiency in converting the chemical energy to electrical energy through the direct reaction. "However, the other variant could also have applications," says Grumelli, "even serving to modulate or interrupt the reaction." This can play a role in biosensors, for example. In any event, the Group has succeeded in making a new class of nanocatalysts that are cost-effective to manufacture, and whose raw materials are plentiful. Doris Grumelli is already working on a new variant of these kinds of structures: with the help of special organic molecules which each contain a metal atom, and the use of additional metal atoms, she hopes to create a surface structure that simultaneously contains two types of metal atoms. "Such structures could serve as models for biological research," says the scientist. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Quantum teleportation 1 allows for the transfer of arbitrary unknown quantum states from a sender to a spatially distant receiver, provided that the two parties share an entangled state and can communicate classically. It is the essence of many sophisticated protocols for quantum communication and computation 2 , 3 , 4 , 5 . Photons are an optimal choice for carrying information in the form of ‘flying qubits’, but the teleportation of photonic quantum bits 6 , 7 , 8 , 9 , 10 , 11 (qubits) has been limited by experimental inefficiencies and restrictions. Main disadvantages include the fundamentally probabilistic nature of linear-optics Bell measurements 12 , as well as the need either to destroy the teleported qubit or attenuate the input qubit when the detectors do not resolve photon numbers 13 . Here we experimentally realize fully deterministic quantum teleportation of photonic qubits without post-selection. The key step is to make use of a hybrid technique involving continuous-variable teleportation 14 , 15 , 16 of a discrete-variable, photonic qubit. When the receiver’s feedforward gain is optimally tuned, the continuous-variable teleporter acts as a pure loss channel 17 , 18 , and the input dual-rail-encoded qubit, based on a single photon, represents a quantum error detection code against photon loss 19 and hence remains completely intact for most teleportation events. This allows for a faithful qubit transfer even with imperfect continuous-variable entangled states: for four qubits the overall transfer fidelities range from 0.79 to 0.82 and all of them exceed the classical limit of teleportation. Furthermore, even for a relatively low level of the entanglement, qubits are teleported much more efficiently than in previous experiments, albeit post-selectively (taking into account only the qubit subspaces), and with a fidelity comparable to the previously reported values. Main Since originally being proposed 1 , the concept of quantum teleportation has attracted a lot of attention and has become one of the central elements of advanced and practical realizations of quantum information protocols. It is essential for long-distance quantum communication by means of quantum repeaters 2 , and it has been shown to be a useful tool for realizing universal quantum logic gates in a measurement-based fashion 3 . Many proposals and models for quantum computation rely on quantum teleportation, such as the efficient linear-optics quantum computing scheme of ref. 4 and the ‘one-way’ quantum computer using cluster states 5 . Although much progress has been made in demonstrating quantum teleportation of photonic qubits 6 , 7 , 8 , 9 , 10 , 11 , most of these schemes share one fundamental restriction: an unambiguous two-qubit Bell-state measurement (BSM), as is needed to teleport a qubit using two-qubit entanglement, is always probabilistic when linear optics is used, even if photon-number-resolving detectors are available 12 , 13 . There are two experiments avoiding this constraint, but in these either a qubit can no longer be teleported when it is delivered independently from an external resource 7 or an extra nonlinear element leads to extremely low measurement efficiencies, of the order of 10 −10 (ref. 8 ). A further experimental limitation, rendering these schemes fairly inefficient, is the probabilistic nature of the entangled resource states 13 . Efficient, near-deterministic quantum teleportation, however, is of great benefit in quantum communication, where it can be used to reduce the storage times of quantum memories in a quantum repeater, and it is a necessity in teleportation-based quantum computation. An additional drawback of the previous experiments, owing to the lack of photon-number-resolving detectors, was the need either to destroy the teleported qubit 20 or to attenuate the input qubit 10 , thus further decreasing the success rate of teleportation. We overcome all the above limitations by taking a different approach: continuous-variable quantum teleportation of a photonic qubit. The strength of continuous-variable teleportation lies in the on-demand availability of the quadrature-entangled states and the completeness of a BSM in the quadrature bases using linear optics and homodyne detections 15 . So far, these tools have been used to unconditionally teleport continuous-variable quantum states such as coherent states 16 , 21 . However, it has not yet been possible to apply them to qubits 18 , 22 , because typical pulsed-laser-based qubits (such as those in refs 6–11 ) have a broad frequency bandwidth that is incompatible with the original continuous-wave-based continuous-variable teleporter, which works only on narrow sidebands 16 , 21 . We overcome this incompatibility by using very recent, advanced technology: a broadband continuous-variable teleporter 23 and a narrowband time-bin qubit compatible with that teleporter 24 . Importantly, this qubit uses two temporal modes to represent a dual-rail-encoded qubit 13 where |0, 1〉 and |1, 0〉 refer to the temporal modes of the photon (expressed in the two-mode photon-number basis, with | α | 2 + | β | 2 = 1). Therefore, teleportation of both modes of the qubit is accomplished by means of a single continuous-variable teleporter acting subsequently on the temporal modes of the time-bin qubits ( Fig. 1 ). Figure 1: Experimental set-up. A time-bin qubit is heralded by detecting one half of an entangled photon pair produced by an optical parametric oscillator (OPO). The continuous-variable teleporter ( g , feedforward gain) always transfers this qubit, albeit with non-unit fidelity. The teleported qubit is finally characterized by single or dual homodyne measurement to verify the success of teleportation. See Methods Summary for details. APD, avalanche photodiode; EOM, electro-optic modulator; HD, homodyne detector; LO- x and LO- p , local oscillators to measure x and p quadratures, respectively. PowerPoint slide Full size image Remarkably, the main weakness of continuous-variable teleportation, namely the intrinsic imperfection of the finitely squeezed, entangled states, can be circumvented to a great extent in the present ‘hybrid’ setting when the input to the continuous-variable teleporter is a dual-rail qubit. The entangled state of the teleporter is a two-mode squeezed, quadrature-entangled state, , here written in the number basis with g opt ≡ tanh( r ), where r is the squeezing", "role": "user" }, { "content": "By means of the quantum-mechanical entanglement of spatially separated light fields, researchers in Tokyo and Mainz have managed to teleport photonic qubits with extreme reliability. This means that a decisive breakthrough has been achieved some 15 years after the first experiments in the field of optical teleportation. The success of the experiment conducted in Tokyo is attributable to the use of a hybrid technique in which two conceptually different and previously incompatible approaches were combined. \"Discrete digital optical quantum information can now be transmitted continuously – at the touch of a button, if you will,\" explained Professor Peter van Loock of Johannes Gutenberg University Mainz (JGU). As a theoretical physicist, van Loock advised the experimental physicists in the research team headed by Professor Akira Furusawa of the University of Tokyo on how they could most efficiently perform the teleportation experiment to ultimately verify the success of quantum teleportation. Their findings have now been published in the prestigious specialist journal Nature. Quantum teleportation involves the transfer of arbitrary quantum states from a sender, dubbed Alice, to a spatially distant receiver, named Bob. This requires that Alice and Bob initially share an entangled quantum state across the space in question, e.g., in the form of entangled photons. Quantum teleportation is of fundamental importance to the processing of quantum information (quantum computing) and quantum communication. Photons are especially valued as ideal information carriers for quantum communication since they can be used to transmit signals at the speed of light. A photon can represent a quantum bit or qubit analogous to a binary digit (bit) in standard classical information processing. Such photons are known as 'flying quantum bits'. The first attempts to teleport single photons or light particles were made by the Austrian physicist Anton Zeilinger. Various other related experiments have been performed in the meantime. However, teleportation of photonic quantum bits using conventional methods proved to have its limitations because of experimental deficiencies and difficulties with fundamental principles. What makes the experiment in Tokyo so different is the use of a hybrid technique. With its help, a completely deterministic and highly reliable quantum teleportation of photonic qubits has been achieved. The accuracy of the transfer was 79 to 82 percent for four different qubits. In addition, the qubits were teleported much more efficiently than in previous experiments, even at a low degree of entanglement. Entanglement 'on demand' using squeezed light The concept of entanglement was first formulated by Erwin Schrödinger and involves a situation in which two quantum systems, such as two light particles for example, are in a joint state, so that their behavior is mutually dependent to a greater extent than is normally (classically) possible. In the Tokyo experiment, continuous entanglement was achieved by means of entangling many photons with many other photons. This meant that the complete amplitudes and phases of two light fields were quantum correlated. Previous experiments only had a single photon entangled with another single photon – a less efficient solution. \"The entanglement of photons functioned very well in the Tokyo experiment – practically at the press of a button, as soon as the laser was switched on,\" said van Loock, Professor for Theory of Quantum Optics and Quantum Information at Mainz University. This continuous entanglement was accomplished with the aid of so-called 'squeezed light', which takes the form of an ellipse in the phase space of the light field. Once entanglement has been achieved, a third light field can be attached to the transmitter. From there, in principle, any state and any number of states can be transmitted to the receiver. \"In our experiment, there were precisely four sufficiently representative test states that were transferred from Alice to Bob using entanglement. Thanks to continuous entanglement, it was possible to transmit the photonic qubits in a deterministic fashion to Bob, in other words, in each run,\" added van Loock. Earlier attempts to achieve optical teleportation were performed differently and, before now, the concepts used have proved to be incompatible. Although in theory it had already been assumed that the two different strategies, from the discrete and the continuous world, needed to be combined, it represents a technological breakthrough that this has actually now been experimentally demonstrated with the help of the hybrid technique. \"The two separate worlds, the discrete and the continuous, are starting to converge,\" concluded van Loock. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Quantum teleportation 1 allows for the transfer of arbitrary unknown quantum states from a sender to a spatially distant receiver, provided that the two parties share an entangled state and can communicate classically. It is the essence of many sophisticated protocols for quantum communication and computation 2 , 3 , 4 , 5 . Photons are an optimal choice for carrying information in the form of ‘flying qubits’, but the teleportation of photonic quantum bits 6 , 7 , 8 , 9 , 10 , 11 (qubits) has been limited by experimental inefficiencies and restrictions. Main disadvantages include the fundamentally probabilistic nature of linear-optics Bell measurements 12 , as well as the need either to destroy the teleported qubit or attenuate the input qubit when the detectors do not resolve photon numbers 13 . Here we experimentally realize fully deterministic quantum teleportation of photonic qubits without post-selection. The key step is to make use of a hybrid technique involving continuous-variable teleportation 14 , 15 , 16 of a discrete-variable, photonic qubit. When the receiver’s feedforward gain is optimally tuned, the continuous-variable teleporter acts as a pure loss channel 17 , 18 , and the input dual-rail-encoded qubit, based on a single photon, represents a quantum error detection code against photon loss 19 and hence remains completely intact for most teleportation events. This allows for a faithful qubit transfer even with imperfect continuous-variable entangled states: for four qubits the overall transfer fidelities range from 0.79 to 0.82 and all of them exceed the classical limit of teleportation. Furthermore, even for a relatively low level of the entanglement, qubits are teleported much more efficiently than in previous experiments, albeit post-selectively (taking into account only the qubit subspaces), and with a fidelity comparable to the previously reported values. Main Since originally being proposed 1 , the concept of quantum teleportation has attracted a lot of attention and has become one of the central elements of advanced and practical realizations of quantum information protocols. It is essential for long-distance quantum communication by means of quantum repeaters 2 , and it has been shown to be a useful tool for realizing universal quantum logic gates in a measurement-based fashion 3 . Many proposals and models for quantum computation rely on quantum teleportation, such as the efficient linear-optics quantum computing scheme of ref. 4 and the ‘one-way’ quantum computer using cluster states 5 . Although much progress has been made in demonstrating quantum teleportation of photonic qubits 6 , 7 , 8 , 9 , 10 , 11 , most of these schemes share one fundamental restriction: an unambiguous two-qubit Bell-state measurement (BSM), as is needed to teleport a qubit using two-qubit entanglement, is always probabilistic when linear optics is used, even if photon-number-resolving detectors are available 12 , 13 . There are two experiments avoiding this constraint, but in these either a qubit can no longer be teleported when it is delivered independently from an external resource 7 or an extra nonlinear element leads to extremely low measurement efficiencies, of the order of 10 −10 (ref. 8 ). A further experimental limitation, rendering these schemes fairly inefficient, is the probabilistic nature of the entangled resource states 13 . Efficient, near-deterministic quantum teleportation, however, is of great benefit in quantum communication, where it can be used to reduce the storage times of quantum memories in a quantum repeater, and it is a necessity in teleportation-based quantum computation. An additional drawback of the previous experiments, owing to the lack of photon-number-resolving detectors, was the need either to destroy the teleported qubit 20 or to attenuate the input qubit 10 , thus further decreasing the success rate of teleportation. We overcome all the above limitations by taking a different approach: continuous-variable quantum teleportation of a photonic qubit. The strength of continuous-variable teleportation lies in the on-demand availability of the quadrature-entangled states and the completeness of a BSM in the quadrature bases using linear optics and homodyne detections 15 . So far, these tools have been used to unconditionally teleport continuous-variable quantum states such as coherent states 16 , 21 . However, it has not yet been possible to apply them to qubits 18 , 22 , because typical pulsed-laser-based qubits (such as those in refs 6–11 ) have a broad frequency bandwidth that is incompatible with the original continuous-wave-based continuous-variable teleporter, which works only on narrow sidebands 16 , 21 . We overcome this incompatibility by using very recent, advanced technology: a broadband continuous-variable teleporter 23 and a narrowband time-bin qubit compatible with that teleporter 24 . Importantly, this qubit uses two temporal modes to represent a dual-rail-encoded qubit 13 where |0, 1〉 and |1, 0〉 refer to the temporal modes of the photon (expressed in the two-mode photon-number basis, with | α | 2 + | β | 2 = 1). Therefore, teleportation of both modes of the qubit is accomplished by means of a single continuous-variable teleporter acting subsequently on the temporal modes of the time-bin qubits ( Fig. 1 ). Figure 1: Experimental set-up. A time-bin qubit is heralded by detecting one half of an entangled photon pair produced by an optical parametric oscillator (OPO). The continuous-variable teleporter ( g , feedforward gain) always transfers this qubit, albeit with non-unit fidelity. The teleported qubit is finally characterized by single or dual homodyne measurement to verify the success of teleportation. See Methods Summary for details. APD, avalanche photodiode; EOM, electro-optic modulator; HD, homodyne detector; LO- x and LO- p , local oscillators to measure x and p quadratures, respectively. PowerPoint slide Full size image Remarkably, the main weakness of continuous-variable teleportation, namely the intrinsic imperfection of the finitely squeezed, entangled states, can be circumvented to a great extent in the present ‘hybrid’ setting when the input to the continuous-variable teleporter is a dual-rail qubit. The entangled state of the teleporter is a two-mode squeezed, quadrature-entangled state, , here written in the number basis with g opt ≡ tanh( r ), where r is the squeezing<|im_end|> <|im_start|>assistant By means of the quantum-mechanical entanglement of spatially separated light fields, researchers in Tokyo and Mainz have managed to teleport photonic qubits with extreme reliability. This means that a decisive breakthrough has been achieved some 15 years after the first experiments in the field of optical teleportation. The success of the experiment conducted in Tokyo is attributable to the use of a hybrid technique in which two conceptually different and previously incompatible approaches were combined. "Discrete digital optical quantum information can now be transmitted continuously – at the touch of a button, if you will," explained Professor Peter van Loock of Johannes Gutenberg University Mainz (JGU). As a theoretical physicist, van Loock advised the experimental physicists in the research team headed by Professor Akira Furusawa of the University of Tokyo on how they could most efficiently perform the teleportation experiment to ultimately verify the success of quantum teleportation. Their findings have now been published in the prestigious specialist journal Nature. Quantum teleportation involves the transfer of arbitrary quantum states from a sender, dubbed Alice, to a spatially distant receiver, named Bob. This requires that Alice and Bob initially share an entangled quantum state across the space in question, e.g., in the form of entangled photons. Quantum teleportation is of fundamental importance to the processing of quantum information (quantum computing) and quantum communication. Photons are especially valued as ideal information carriers for quantum communication since they can be used to transmit signals at the speed of light. A photon can represent a quantum bit or qubit analogous to a binary digit (bit) in standard classical information processing. Such photons are known as 'flying quantum bits'. The first attempts to teleport single photons or light particles were made by the Austrian physicist Anton Zeilinger. Various other related experiments have been performed in the meantime. However, teleportation of photonic quantum bits using conventional methods proved to have its limitations because of experimental deficiencies and difficulties with fundamental principles. What makes the experiment in Tokyo so different is the use of a hybrid technique. With its help, a completely deterministic and highly reliable quantum teleportation of photonic qubits has been achieved. The accuracy of the transfer was 79 to 82 percent for four different qubits. In addition, the qubits were teleported much more efficiently than in previous experiments, even at a low degree of entanglement. Entanglement 'on demand' using squeezed light The concept of entanglement was first formulated by Erwin Schrödinger and involves a situation in which two quantum systems, such as two light particles for example, are in a joint state, so that their behavior is mutually dependent to a greater extent than is normally (classically) possible. In the Tokyo experiment, continuous entanglement was achieved by means of entangling many photons with many other photons. This meant that the complete amplitudes and phases of two light fields were quantum correlated. Previous experiments only had a single photon entangled with another single photon – a less efficient solution. "The entanglement of photons functioned very well in the Tokyo experiment – practically at the press of a button, as soon as the laser was switched on," said van Loock, Professor for Theory of Quantum Optics and Quantum Information at Mainz University. This continuous entanglement was accomplished with the aid of so-called 'squeezed light', which takes the form of an ellipse in the phase space of the light field. Once entanglement has been achieved, a third light field can be attached to the transmitter. From there, in principle, any state and any number of states can be transmitted to the receiver. "In our experiment, there were precisely four sufficiently representative test states that were transferred from Alice to Bob using entanglement. Thanks to continuous entanglement, it was possible to transmit the photonic qubits in a deterministic fashion to Bob, in other words, in each run," added van Loock. Earlier attempts to achieve optical teleportation were performed differently and, before now, the concepts used have proved to be incompatible. Although in theory it had already been assumed that the two different strategies, from the discrete and the continuous world, needed to be combined, it represents a technological breakthrough that this has actually now been experimentally demonstrated with the help of the hybrid technique. "The two separate worlds, the discrete and the continuous, are starting to converge," concluded van Loock. <|im_end|>

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2,294

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Two-neutrino double electron capture (2 ν ECEC) is a second-order weak-interaction process with a predicted half-life that surpasses the age of the Universe by many orders of magnitude 1 . Until now, indications of 2 ν ECEC decays have only been seen for two isotopes 2 , 3 , 4 , 5 , 78 Kr and 130 Ba, and instruments with very low background levels are needed to detect them directly with high statistical significance 6 , 7 . The 2 ν ECEC half-life is an important observable for nuclear structure models 8 , 9 , 10 , 11 , 12 , 13 , 14 and its measurement represents a meaningful step in the search for neutrinoless double electron capture—the detection of which would establish the Majorana nature of the neutrino and would give access to the absolute neutrino mass 15 , 16 , 17 . Here we report the direct observation of 2 ν ECEC in 124 Xe with the XENON1T dark-matter detector. The significance of the signal is 4.4 standard deviations and the corresponding half-life of 1.8 × 10 22 years (statistical uncertainty, 0.5 × 10 22 years; systematic uncertainty, 0.1 × 10 22 years) is the longest measured directly so far. This study demonstrates that the low background and large target mass of xenon-based dark-matter detectors make them well suited for measuring rare processes and highlights the broad physics reach of larger next-generation experiments 18 , 19 , 20 . Main The long half-life of double electron capture makes it extremely rare, and the process has escaped detection for decades. In 2 ν ECEC, two protons in a nucleus are simultaneously converted into neutrons by the absorption of two electrons from one of the atomic shells and the emission of two electron neutrinos 1 ( ν e ). After the capture of the two atomic electrons, mostly from the K shell 21 , the filling of vacancies results in a detectable cascade of X-rays and Auger electrons 22 . The nuclear binding energy Q released in the process (on the order of 1 MeV) is carried away mostly by the two neutrinos, which are not detected within the detector. Thus, the experimental signature appears in the kiloelectronvolt, rather than the megaelectronvolt, range. The process is illustrated in Fig. 1 . Fig. 1: Schematic of two-neutrino double electron capture. In the 2 ν ECEC process the nucleus captures two atomic-shell electrons (black), usually from the K shell, and simultaneously converts two protons (red) to neutrons (white). Two neutrinos (black) are emitted in the nuclear process and carry away most of the decay energy while the atomic shell is left in an excited state with two holes in the K shell. A cascade of X-rays (red, ‘X’) and Auger electrons (red, ‘ e ’) are emitted during atomic relaxation, when the K shell is refilled from the higher-energy L, M and N shells. In turn, vacancies are created in the refilling shells and are refilled with electrons from the higher-energy shells (arrows). Full size image 2 ν ECEC is allowed in the standard model of particle physics and is related to double β decay as a second-order weak-interaction process. However, few experimental indications exist. Geochemical studies 4 , 5 for 130 Ba and a direct measurement 2 , 3 for 78 Kr quote half-lives of the order of 10 20 –10 22 yr. Even longer timescales are expected for a hypothetical double electron capture without neutrino emission (0 ν ECEC) 16 , 17 . A detection of this decay would show that neutrinos are Majorana particles 15 (that is, their own anti-particles) and could help us to understand the dominance of matter over antimatter in our Universe by means of leptogenesis 23 . A Majorana nature would give access to the absolute neutrino mass, but only with theoretical nuclear-matrix-element calculations. A plethora of different nuclear models 8 , 9 , 10 , 11 , 12 , 13 , 14 can also be applied to predict the 2 ν ECEC half-life; thus, its measurement would provide a vital experimental constraint for these models, as well as insight into double-β-decay processes on the proton-rich side of the nuclide chart. Here we study the 2 ν ECEC decay of 124 Xe. Natural xenon is a radiopure and scalable detector medium that contains about 1 kg of 124 Xe per tonne. 124 Xe undergoes 2 ν ECEC to 124 Te with 24 Q = 2,857 keV. Because the amount of energy released by the recoiling nucleus is negligible (on the order of 10 eV) and the neutrinos carrying away the energy Q are undetected, only the X-rays and Auger electrons are measured. The total energy for double K-shell-electron capture 24 is 64.3 keV. This value has already been corrected for energy depositions that do not exceed the xenon excitation threshold 22 . Previous searches for the 2 ν ECEC decay of 124 Xe were carried out with gas proportional counters using enriched xenon 6 , as well as large detectors originally designed for dark-matter searches 25 . The currently leading lower limit on the half-life of this decay comes from the XMASS collaboration at \${T}_{1/2}^{2\\nu {\\rm{ECEC}}} > 2.1\\times 1{0}^{22}\\hspace{2.77626pt}{\\rm{yr}}\$ (90% confidence level) 7 . XENON1T 26 was built to detect interactions of dark matter in the form of weakly interacting massive particles (WIMPs) and has recently placed the most stringent limits on the coherent elastic scattering of WIMPs with xenon nuclei 27 . XENON1T uses 3.2 t of ultra-pure liquid xenon (LXe), of which 2 t are within the sensitive volume of the time-projection chamber (TPC): a cylinder with diameter and height of about 96 cm and with walls of highly reflective polytetrafluoroethylene, equipped with 248 photomultiplier tubes (PMTs). The TPC is used for the measurement of the scintillation (S1) and ionization signals (S2) induced by particle interactions—the latter by converting ionization electrons into light by means of proportional scintillation. It provides calorimetry and three-dimensional position reconstruction and measures the scatter multiplicity.", "role": "user" }, { "content": "How do you observe a process that takes more than one trillion times longer than the age of the universe? The XENON Collaboration research team did it with an instrument built to find the most elusive particle in the universe—dark matter. In a paper to be published tomorrow in the journal Nature, researchers announce that they have observed the radioactive decay of xenon-124, which has a half-life of 1.8 X 1022 years. \"We actually saw this decay happen. It's the longest, slowest process that has ever been directly observed, and our dark matter detector was sensitive enough to measure it,\" said Ethan Brown, an assistant professor of physics at Rensselaer, and co-author of the study. \"It's an amazing to have witnessed this process, and it says that our detector can measure the rarest thing ever recorded.\" The XENON Collaboration runs XENON1T, a 1,300-kilogram vat of super-pure liquid xenon shielded from cosmic rays in a cryostat submerged in water deep 1,500 meters beneath the Gran Sasso mountains of Italy. The researchers search for dark matter (which is five times more abundant than ordinary matter, but seldom interacts with ordinary matter) by recording tiny flashes of light created when particles interact with xenon inside the detector. And while XENON1T was built to capture the interaction between a dark matter particle and the nucleus of a xenon atom, the detector actually picks up signals from any interactions with the xenon. The evidence for xenon decay was produced as a proton inside the nucleus of a xenon atom converted into a neutron. In most elements subject to decay, that happens when one electron is pulled into the nucleus. But a proton in a xenon atom must absorb two electrons to convert into a neutron, an event called \"double-electron capture.\" Double-electron capture only happens when two of the electrons are right next to the nucleus at just the right time, Brown said, which is \"a rare thing multiplied by another rare thing, making it ultra-rare.\" When the ultra-rare happened, and a double-electron capture occurred inside the detector, instruments picked up the signal of electrons in the atom re-arranging to fill in for the two that were absorbed into the nucleus. The photodetectors of the inner detecor of XENON1T were tested in liquid xenon in the UZH laboratory. Credit: Xenon Collaboration \"Electrons in double-capture are removed from the innermost shell around the nucleus, and that creates room in that shell,\" said Brown. \"The remaining electrons collapse to the ground state, and we saw this collapse process in our detector.\" The achievement is the first time scientists have measured the half-life of this xenon isotope based on a direct observation of its radioactive decay. \"This is a fascinating finding that advances the frontiers of knowledge about the most fundamental characteristics of matter,\" said Curt Breneman, dean of the School of Science. \"Dr. Brown's work in calibrating the detector and ensuring that the xenon is scrubbed to the highest possible standard of purity was critical to making this important observation.\" The electronics to select the photodetectors were developed and built at the UZH. (Image: Xenon Collaboration) Credit: Xenon Collaboration The XENON Collaboration includes more than 160 scientists from Europe, the United States, and the Middle East, and, since 2002, has operated three successively more sensitive liquid xenon detectors in the Gran Sasso National Laboratory in Italy. XENON1T, the largest detector of its type ever built, acquired data from 2016 until December 2018, when it was switched off. Scientists are currently upgrading the experiment for the new XENONnT phase, which will feature an active detector mass three times larger than XENON1T. Together with a reduced background level, this will boost the detector's sensitivity by an order of magnitude. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Two-neutrino double electron capture (2 ν ECEC) is a second-order weak-interaction process with a predicted half-life that surpasses the age of the Universe by many orders of magnitude 1 . Until now, indications of 2 ν ECEC decays have only been seen for two isotopes 2 , 3 , 4 , 5 , 78 Kr and 130 Ba, and instruments with very low background levels are needed to detect them directly with high statistical significance 6 , 7 . The 2 ν ECEC half-life is an important observable for nuclear structure models 8 , 9 , 10 , 11 , 12 , 13 , 14 and its measurement represents a meaningful step in the search for neutrinoless double electron capture—the detection of which would establish the Majorana nature of the neutrino and would give access to the absolute neutrino mass 15 , 16 , 17 . Here we report the direct observation of 2 ν ECEC in 124 Xe with the XENON1T dark-matter detector. The significance of the signal is 4.4 standard deviations and the corresponding half-life of 1.8 × 10 22 years (statistical uncertainty, 0.5 × 10 22 years; systematic uncertainty, 0.1 × 10 22 years) is the longest measured directly so far. This study demonstrates that the low background and large target mass of xenon-based dark-matter detectors make them well suited for measuring rare processes and highlights the broad physics reach of larger next-generation experiments 18 , 19 , 20 . Main The long half-life of double electron capture makes it extremely rare, and the process has escaped detection for decades. In 2 ν ECEC, two protons in a nucleus are simultaneously converted into neutrons by the absorption of two electrons from one of the atomic shells and the emission of two electron neutrinos 1 ( ν e ). After the capture of the two atomic electrons, mostly from the K shell 21 , the filling of vacancies results in a detectable cascade of X-rays and Auger electrons 22 . The nuclear binding energy Q released in the process (on the order of 1 MeV) is carried away mostly by the two neutrinos, which are not detected within the detector. Thus, the experimental signature appears in the kiloelectronvolt, rather than the megaelectronvolt, range. The process is illustrated in Fig. 1 . Fig. 1: Schematic of two-neutrino double electron capture. In the 2 ν ECEC process the nucleus captures two atomic-shell electrons (black), usually from the K shell, and simultaneously converts two protons (red) to neutrons (white). Two neutrinos (black) are emitted in the nuclear process and carry away most of the decay energy while the atomic shell is left in an excited state with two holes in the K shell. A cascade of X-rays (red, ‘X’) and Auger electrons (red, ‘ e ’) are emitted during atomic relaxation, when the K shell is refilled from the higher-energy L, M and N shells. In turn, vacancies are created in the refilling shells and are refilled with electrons from the higher-energy shells (arrows). Full size image 2 ν ECEC is allowed in the standard model of particle physics and is related to double β decay as a second-order weak-interaction process. However, few experimental indications exist. Geochemical studies 4 , 5 for 130 Ba and a direct measurement 2 , 3 for 78 Kr quote half-lives of the order of 10 20 –10 22 yr. Even longer timescales are expected for a hypothetical double electron capture without neutrino emission (0 ν ECEC) 16 , 17 . A detection of this decay would show that neutrinos are Majorana particles 15 (that is, their own anti-particles) and could help us to understand the dominance of matter over antimatter in our Universe by means of leptogenesis 23 . A Majorana nature would give access to the absolute neutrino mass, but only with theoretical nuclear-matrix-element calculations. A plethora of different nuclear models 8 , 9 , 10 , 11 , 12 , 13 , 14 can also be applied to predict the 2 ν ECEC half-life; thus, its measurement would provide a vital experimental constraint for these models, as well as insight into double-β-decay processes on the proton-rich side of the nuclide chart. Here we study the 2 ν ECEC decay of 124 Xe. Natural xenon is a radiopure and scalable detector medium that contains about 1 kg of 124 Xe per tonne. 124 Xe undergoes 2 ν ECEC to 124 Te with 24 Q = 2,857 keV. Because the amount of energy released by the recoiling nucleus is negligible (on the order of 10 eV) and the neutrinos carrying away the energy Q are undetected, only the X-rays and Auger electrons are measured. The total energy for double K-shell-electron capture 24 is 64.3 keV. This value has already been corrected for energy depositions that do not exceed the xenon excitation threshold 22 . Previous searches for the 2 ν ECEC decay of 124 Xe were carried out with gas proportional counters using enriched xenon 6 , as well as large detectors originally designed for dark-matter searches 25 . The currently leading lower limit on the half-life of this decay comes from the XMASS collaboration at ${T}_{1/2}^{2\nu {\rm{ECEC}}} > 2.1\times 1{0}^{22}\hspace{2.77626pt}{\rm{yr}}$ (90% confidence level) 7 . XENON1T 26 was built to detect interactions of dark matter in the form of weakly interacting massive particles (WIMPs) and has recently placed the most stringent limits on the coherent elastic scattering of WIMPs with xenon nuclei 27 . XENON1T uses 3.2 t of ultra-pure liquid xenon (LXe), of which 2 t are within the sensitive volume of the time-projection chamber (TPC): a cylinder with diameter and height of about 96 cm and with walls of highly reflective polytetrafluoroethylene, equipped with 248 photomultiplier tubes (PMTs). The TPC is used for the measurement of the scintillation (S1) and ionization signals (S2) induced by particle interactions—the latter by converting ionization electrons into light by means of proportional scintillation. It provides calorimetry and three-dimensional position reconstruction and measures the scatter multiplicity.<|im_end|> <|im_start|>assistant How do you observe a process that takes more than one trillion times longer than the age of the universe? The XENON Collaboration research team did it with an instrument built to find the most elusive particle in the universe—dark matter. In a paper to be published tomorrow in the journal Nature, researchers announce that they have observed the radioactive decay of xenon-124, which has a half-life of 1.8 X 1022 years. "We actually saw this decay happen. It's the longest, slowest process that has ever been directly observed, and our dark matter detector was sensitive enough to measure it," said Ethan Brown, an assistant professor of physics at Rensselaer, and co-author of the study. "It's an amazing to have witnessed this process, and it says that our detector can measure the rarest thing ever recorded." The XENON Collaboration runs XENON1T, a 1,300-kilogram vat of super-pure liquid xenon shielded from cosmic rays in a cryostat submerged in water deep 1,500 meters beneath the Gran Sasso mountains of Italy. The researchers search for dark matter (which is five times more abundant than ordinary matter, but seldom interacts with ordinary matter) by recording tiny flashes of light created when particles interact with xenon inside the detector. And while XENON1T was built to capture the interaction between a dark matter particle and the nucleus of a xenon atom, the detector actually picks up signals from any interactions with the xenon. The evidence for xenon decay was produced as a proton inside the nucleus of a xenon atom converted into a neutron. In most elements subject to decay, that happens when one electron is pulled into the nucleus. But a proton in a xenon atom must absorb two electrons to convert into a neutron, an event called "double-electron capture." Double-electron capture only happens when two of the electrons are right next to the nucleus at just the right time, Brown said, which is "a rare thing multiplied by another rare thing, making it ultra-rare." When the ultra-rare happened, and a double-electron capture occurred inside the detector, instruments picked up the signal of electrons in the atom re-arranging to fill in for the two that were absorbed into the nucleus. The photodetectors of the inner detecor of XENON1T were tested in liquid xenon in the UZH laboratory. Credit: Xenon Collaboration "Electrons in double-capture are removed from the innermost shell around the nucleus, and that creates room in that shell," said Brown. "The remaining electrons collapse to the ground state, and we saw this collapse process in our detector." The achievement is the first time scientists have measured the half-life of this xenon isotope based on a direct observation of its radioactive decay. "This is a fascinating finding that advances the frontiers of knowledge about the most fundamental characteristics of matter," said Curt Breneman, dean of the School of Science. "Dr. Brown's work in calibrating the detector and ensuring that the xenon is scrubbed to the highest possible standard of purity was critical to making this important observation." The electronics to select the photodetectors were developed and built at the UZH. (Image: Xenon Collaboration) Credit: Xenon Collaboration The XENON Collaboration includes more than 160 scientists from Europe, the United States, and the Middle East, and, since 2002, has operated three successively more sensitive liquid xenon detectors in the Gran Sasso National Laboratory in Italy. XENON1T, the largest detector of its type ever built, acquired data from 2016 until December 2018, when it was switched off. Scientists are currently upgrading the experiment for the new XENONnT phase, which will feature an active detector mass three times larger than XENON1T. Together with a reduced background level, this will boost the detector's sensitivity by an order of magnitude. <|im_end|>

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2,286

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The prevailing mid-latitude westerly winds, known as the westerlies, are a fundamental component of the climate system because they have a crucial role in driving surface ocean circulation 1 and modulating air–sea heat, momentum and carbon exchange 1 , 2 , 3 . Recent work suggests that westerly wind belts are migrating polewards in response to anthropogenic forcing 4 , 5 . Reconstructing the westerlies during past warm periods such as the Pliocene epoch, in which atmospheric carbon dioxide (CO 2 ) was about 350 to 450 parts per million 6 and temperatures were about 2 to 4 degrees Celsius higher than today 7 , can improve our understanding of changes in the position and strength of these wind systems as the climate continues to warm. Here we show that the westerlies were weaker and more poleward during the warm Pliocene than during glacial periods after the intensification of Northern Hemisphere glaciation (iNHG), which occurred around 2.73 million years ago 8 . Our results, which are based on dust and export productivity reconstructions, indicate that major ice sheet development during the iNHG was accompanied by substantial increases in dust fluxes in the mid-latitude North Pacific Ocean, especially compared to those in the subarctic North Pacific. Following this shift, changes in dust and productivity largely track the glacial–interglacial cycles of the late Pliocene and early Pleistocene epochs. On the basis of this pattern, we infer that shifts in the westerlies were primarily driven by variations in Plio-Pleistocene thermal gradients and ice volume. By combining this relationship with other dust records 9 , 10 , 11 and climate modelling results 12 , we find that the proposed changes in the westerlies were globally synchronous. If the Pliocene is predictive of future warming, we posit that continued poleward movement and weakening of the present-day westerlies in both hemispheres can be expected. Main Over the past 40 years, numerous studies have found that the Southern Hemisphere westerly winds have been moving towards Antarctica 4 , 5 and strengthening 13 , with both trends being predominantly attributed to anthropogenic forcing. Meridional shifts in mid-latitude winds have, to a lesser degree, also been recognized in the Northern Hemisphere 5 , 14 . Whether the poleward movement and enhancement of the westerlies will continue as temperatures and atmospheric CO 2 increase further under future warming scenarios is still widely debated 1 , 15 . Currently, our understanding of the dynamics influencing the westerlies in different climate states relies primarily on the past 20,000 years (~20 kyr), when Earth’s climate was colder than at present. Previous work focusing on this interval using marine proxies 3 , 16 , dust records 17 and modelling approaches 18 , 19 has suggested that changes to the location and intensity of the westerly winds are predominantly affected by changing equator-to-pole temperature gradients and/or the extent of major ice sheets, although the sign and magnitude of the shifts are disputed 15 , 18 . Reconstructions of the response of westerlies to identified glacial–interglacial forcing mechanisms during warmer-than-present conditions in Earth’s history will aid in better quantifying future changes in mid-latitude circulation. A promising analogue for predicted warming over the next century is the Pliocene, spanning ~3–5 million years ago (Ma) 20 . The climate of this interval was predominately warmer than today, culminating with the mid-Pliocene warm period at about 3–3.3 Ma (refs. 7 , 21 ), when average surface air temperatures were about 2–4 °C higher than preindustrial conditions 7 . Atmospheric CO 2 levels were similar to today, ranging from about 350 ppm to 450 ppm (ref. 6 ). Following this warm interval, there was a dramatic shift in global climate to cooler conditions, and expansive Northern Hemisphere ice sheets developed for the first time—a period referred to as the iNHG 8 , 22 . The Pliocene and early Pleistocene thus offer the opportunity to study the response of the westerlies to fluctuations in climate that are potentially relevant to future climate change. Available modelling and geochemical studies focusing on the position and strength of Pliocene and early Pleistocene westerlies are sparse 12 , 23 . Reconstructions of aeolian dust fluxes offer a promising solution to this deficiency because mineral aerosols trace the paths and strength of atmospheric circulation. Marine sediments are valuable recorders of dust deposition because they accumulate continuously, are relatively well dated and provide wide spatial coverage. Assembling data from the North Pacific in particular is advantageous, as it lies downwind of Eastern Asia, one of the largest dust sources today 24 and a dust-generating region before the Pliocene 25 . Furthermore, this mid-latitude zone of arid basins would not suffer from substantial changes to dust production mechanisms during the Pliocene and early Pleistocene such as the presence of ice sheets, a potential complicating factor for regions downwind of North America and Patagonia 10 , 11 , 26 . Pliocene dust in the North Pacific Pioneering single-core studies of aeolian deposition in the North Pacific during the Pliocene, in which dust fluxes were determined from concentrations of insoluble sedimentary components and age model-derived sediment mass accumulation rates (MARs), show variations in total lithogenic inputs through time 27 , 28 , 29 . Much of this variability is attributed to fluctuations in Eastern Asia aridity. Although aridity certainly affects dust production and deposition, the methodology and use of a single core in many of these studies limits their potential to offer insight into tracing the westerlies through time (see Methods ). To overcome this limitation, we use dust records from two marine sediment cores separated by about 9° latitude to unravel the variability in westerly winds over the North Pacific. We analyse isotope and elemental signatures of dust combined with a constant flux proxy (CFP) to reconstruct North Pacific dust fluxes for the period of about 2.5–4.5 Ma at Ocean Drilling Program (ODP) sites 1208 (36.1° N, 158.2° E, 3,346 m water depth) and 885/886 (44.7° N, 168.2° W, 5,709/5,714 m water depth), located in the western and", "role": "user" }, { "content": "The westerlies—or westerly winds—play an important role in weather and climate both locally and on a global scale, by influencing precipitation patterns, impacting ocean circulation and steering tropical cyclones. So, finding a way to assess how they will change as the climate warms is crucial. Typically, the westerlies blow from west to east across the planet's middle latitudes. But scientists have noticed that over the last several decades, these winds are changing, migrating poleward. Research suggests this is because of climate change. But, scientists have been debating whether the poleward movement of the westerlies will continue as temperatures and atmospheric carbon dioxide (CO2) increase further under future warming scenarios. It's been difficult to resolve this scientific question because our knowledge of the westerlies in past warm climates has until now been limited. In a paper published January 6 in Nature, climate researchers from Columbia University's Lamont-Doherty Earth Observatory describe a new method of tracking the ancient history of the westerly winds—a proxy for what we may experience in a future warming world. The lead author, Lamont graduate student Jordan Abell and his advisor, Gisela Winckler, developed a way to apply paleoclimatology—the study of past climate—to the question of the behavior of the westerly winds, and found evidence suggesting that atmospheric circulation patterns will change with climate warming. Sediment cores like the one shown here, drilled from the bottom of the ocean, contain records of past climate conditions within their layers. Dust in cores collected by the research vessel JOIDES Resolution and stored at Texas A&M University helped to reveal changing patterns in the westerly winds. Credit: Jordan Abell/Lamont-Doherty Earth Observatory The finding represents a breakthrough in our understanding of how the winds changed in the past, and how they may continue to change in the future. By using dust in ancient, deep sea sediments as an indirect tracer of wind, the researchers were able to reconstruct wind patterns that occurred three to five million years ago. Knowing that winds—in this case the westerlies—transport dust from desert regions to faraway locations, the authors examined cores from the North Pacific Ocean. This area is downwind from Eastern Asia, one of the largest dust sources today and a known dust-generating region for the past several million years. By measuring the dust in cores from two different sites thousands of kilometers apart, the researchers were able to map changes in dust, and in turn the westerly winds. \"We could immediately see the patterns. The data are so clear. Our work is consistent with modern observations, and suggests that wind patterns will change with climate warming,\" said Abell. The researchers found that during the warm parts of the Pliocene (3-5 million years ago), the westerlies were located closer to the poles. The image on the right shows how the westerlies moved toward the equator during colder intervals afterward. Recent observations indicate that as the planet warms due to climate change, the westerlies are once again shifting poleward. Credit: Abell et al., Nature 2021 They found that during the warm parts of the Pliocene (a period three to five million years ago, when the Earth was about two to four degrees Celsius warmer than today but had approximately the same concentration of CO2 in the air as we do now), the westerlies, globally, were located closer towards the poles than during the colder intervals afterwards. \"By using the Pliocene as an analogue for modern global warming, it seems likely that the movement of the westerlies towards the poles observed in the modern era will continue with further human-induced warming,\" explained Winckler. The movement of these winds have huge implications for storm systems and precipitation patterns. And while this research does not indicate exactly where it will rain more or less, it confirms that the wind and precipitation patterns will change with climate warming. \"In the Earth history record, tracking down movements of wind and how they've changed, that's been elusive because we didn't have a tracer for it,\" said Winckler. \"Now we do.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The prevailing mid-latitude westerly winds, known as the westerlies, are a fundamental component of the climate system because they have a crucial role in driving surface ocean circulation 1 and modulating air–sea heat, momentum and carbon exchange 1 , 2 , 3 . Recent work suggests that westerly wind belts are migrating polewards in response to anthropogenic forcing 4 , 5 . Reconstructing the westerlies during past warm periods such as the Pliocene epoch, in which atmospheric carbon dioxide (CO 2 ) was about 350 to 450 parts per million 6 and temperatures were about 2 to 4 degrees Celsius higher than today 7 , can improve our understanding of changes in the position and strength of these wind systems as the climate continues to warm. Here we show that the westerlies were weaker and more poleward during the warm Pliocene than during glacial periods after the intensification of Northern Hemisphere glaciation (iNHG), which occurred around 2.73 million years ago 8 . Our results, which are based on dust and export productivity reconstructions, indicate that major ice sheet development during the iNHG was accompanied by substantial increases in dust fluxes in the mid-latitude North Pacific Ocean, especially compared to those in the subarctic North Pacific. Following this shift, changes in dust and productivity largely track the glacial–interglacial cycles of the late Pliocene and early Pleistocene epochs. On the basis of this pattern, we infer that shifts in the westerlies were primarily driven by variations in Plio-Pleistocene thermal gradients and ice volume. By combining this relationship with other dust records 9 , 10 , 11 and climate modelling results 12 , we find that the proposed changes in the westerlies were globally synchronous. If the Pliocene is predictive of future warming, we posit that continued poleward movement and weakening of the present-day westerlies in both hemispheres can be expected. Main Over the past 40 years, numerous studies have found that the Southern Hemisphere westerly winds have been moving towards Antarctica 4 , 5 and strengthening 13 , with both trends being predominantly attributed to anthropogenic forcing. Meridional shifts in mid-latitude winds have, to a lesser degree, also been recognized in the Northern Hemisphere 5 , 14 . Whether the poleward movement and enhancement of the westerlies will continue as temperatures and atmospheric CO 2 increase further under future warming scenarios is still widely debated 1 , 15 . Currently, our understanding of the dynamics influencing the westerlies in different climate states relies primarily on the past 20,000 years (~20 kyr), when Earth’s climate was colder than at present. Previous work focusing on this interval using marine proxies 3 , 16 , dust records 17 and modelling approaches 18 , 19 has suggested that changes to the location and intensity of the westerly winds are predominantly affected by changing equator-to-pole temperature gradients and/or the extent of major ice sheets, although the sign and magnitude of the shifts are disputed 15 , 18 . Reconstructions of the response of westerlies to identified glacial–interglacial forcing mechanisms during warmer-than-present conditions in Earth’s history will aid in better quantifying future changes in mid-latitude circulation. A promising analogue for predicted warming over the next century is the Pliocene, spanning ~3–5 million years ago (Ma) 20 . The climate of this interval was predominately warmer than today, culminating with the mid-Pliocene warm period at about 3–3.3 Ma (refs. 7 , 21 ), when average surface air temperatures were about 2–4 °C higher than preindustrial conditions 7 . Atmospheric CO 2 levels were similar to today, ranging from about 350 ppm to 450 ppm (ref. 6 ). Following this warm interval, there was a dramatic shift in global climate to cooler conditions, and expansive Northern Hemisphere ice sheets developed for the first time—a period referred to as the iNHG 8 , 22 . The Pliocene and early Pleistocene thus offer the opportunity to study the response of the westerlies to fluctuations in climate that are potentially relevant to future climate change. Available modelling and geochemical studies focusing on the position and strength of Pliocene and early Pleistocene westerlies are sparse 12 , 23 . Reconstructions of aeolian dust fluxes offer a promising solution to this deficiency because mineral aerosols trace the paths and strength of atmospheric circulation. Marine sediments are valuable recorders of dust deposition because they accumulate continuously, are relatively well dated and provide wide spatial coverage. Assembling data from the North Pacific in particular is advantageous, as it lies downwind of Eastern Asia, one of the largest dust sources today 24 and a dust-generating region before the Pliocene 25 . Furthermore, this mid-latitude zone of arid basins would not suffer from substantial changes to dust production mechanisms during the Pliocene and early Pleistocene such as the presence of ice sheets, a potential complicating factor for regions downwind of North America and Patagonia 10 , 11 , 26 . Pliocene dust in the North Pacific Pioneering single-core studies of aeolian deposition in the North Pacific during the Pliocene, in which dust fluxes were determined from concentrations of insoluble sedimentary components and age model-derived sediment mass accumulation rates (MARs), show variations in total lithogenic inputs through time 27 , 28 , 29 . Much of this variability is attributed to fluctuations in Eastern Asia aridity. Although aridity certainly affects dust production and deposition, the methodology and use of a single core in many of these studies limits their potential to offer insight into tracing the westerlies through time (see Methods ). To overcome this limitation, we use dust records from two marine sediment cores separated by about 9° latitude to unravel the variability in westerly winds over the North Pacific. We analyse isotope and elemental signatures of dust combined with a constant flux proxy (CFP) to reconstruct North Pacific dust fluxes for the period of about 2.5–4.5 Ma at Ocean Drilling Program (ODP) sites 1208 (36.1° N, 158.2° E, 3,346 m water depth) and 885/886 (44.7° N, 168.2° W, 5,709/5,714 m water depth), located in the western and<|im_end|> <|im_start|>assistant The westerlies—or westerly winds—play an important role in weather and climate both locally and on a global scale, by influencing precipitation patterns, impacting ocean circulation and steering tropical cyclones. So, finding a way to assess how they will change as the climate warms is crucial. Typically, the westerlies blow from west to east across the planet's middle latitudes. But scientists have noticed that over the last several decades, these winds are changing, migrating poleward. Research suggests this is because of climate change. But, scientists have been debating whether the poleward movement of the westerlies will continue as temperatures and atmospheric carbon dioxide (CO2) increase further under future warming scenarios. It's been difficult to resolve this scientific question because our knowledge of the westerlies in past warm climates has until now been limited. In a paper published January 6 in Nature, climate researchers from Columbia University's Lamont-Doherty Earth Observatory describe a new method of tracking the ancient history of the westerly winds—a proxy for what we may experience in a future warming world. The lead author, Lamont graduate student Jordan Abell and his advisor, Gisela Winckler, developed a way to apply paleoclimatology—the study of past climate—to the question of the behavior of the westerly winds, and found evidence suggesting that atmospheric circulation patterns will change with climate warming. Sediment cores like the one shown here, drilled from the bottom of the ocean, contain records of past climate conditions within their layers. Dust in cores collected by the research vessel JOIDES Resolution and stored at Texas A&M University helped to reveal changing patterns in the westerly winds. Credit: Jordan Abell/Lamont-Doherty Earth Observatory The finding represents a breakthrough in our understanding of how the winds changed in the past, and how they may continue to change in the future. By using dust in ancient, deep sea sediments as an indirect tracer of wind, the researchers were able to reconstruct wind patterns that occurred three to five million years ago. Knowing that winds—in this case the westerlies—transport dust from desert regions to faraway locations, the authors examined cores from the North Pacific Ocean. This area is downwind from Eastern Asia, one of the largest dust sources today and a known dust-generating region for the past several million years. By measuring the dust in cores from two different sites thousands of kilometers apart, the researchers were able to map changes in dust, and in turn the westerly winds. "We could immediately see the patterns. The data are so clear. Our work is consistent with modern observations, and suggests that wind patterns will change with climate warming," said Abell. The researchers found that during the warm parts of the Pliocene (3-5 million years ago), the westerlies were located closer to the poles. The image on the right shows how the westerlies moved toward the equator during colder intervals afterward. Recent observations indicate that as the planet warms due to climate change, the westerlies are once again shifting poleward. Credit: Abell et al., Nature 2021 They found that during the warm parts of the Pliocene (a period three to five million years ago, when the Earth was about two to four degrees Celsius warmer than today but had approximately the same concentration of CO2 in the air as we do now), the westerlies, globally, were located closer towards the poles than during the colder intervals afterwards. "By using the Pliocene as an analogue for modern global warming, it seems likely that the movement of the westerlies towards the poles observed in the modern era will continue with further human-induced warming," explained Winckler. The movement of these winds have huge implications for storm systems and precipitation patterns. And while this research does not indicate exactly where it will rain more or less, it confirms that the wind and precipitation patterns will change with climate warming. "In the Earth history record, tracking down movements of wind and how they've changed, that's been elusive because we didn't have a tracer for it," said Winckler. "Now we do." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Direct visualization of ultrafast coupling between charge carriers and lattice degrees of freedom in photoexcited semiconductors has remained a long-standing challenge and is critical for understanding the light-induced physical behaviour of materials under extreme non-equilibrium conditions. Here we obtain a direct visualization of the structural dynamics in monocrystalline 2D perovskites. We achieve this by monitoring the evolution of wavevector-resolved ultrafast electron diffraction intensity following above-bandgap high-density photoexcitation. Our analysis reveals a light-induced ultrafast reduction in antiferro-distortion resulting from a strong interaction between the electron–hole plasma and perovskite lattice, which induces an in-plane octahedra rotation towards a more symmetric phase. Correlated ultrafast spectroscopy performed at the same carrier density as ultrafast electron diffraction reveals that the creation of a dense electron–hole plasma triggers the relaxation of lattice distortion at shorter timescales by modulating the crystal cohesive energy. Finally, we show that the interaction between carrier gas and lattice can be altered by tailoring the rigidity of the 2D perovskite by choosing an appropriate organic spacer layer. Main Organic–inorganic (hybrid) two-dimensional (2D) halide perovskites (2DP) are constructed by a superlattice of interlocking organic and inorganic nanometre-thick layers and have demonstrated unique and non-classical behaviours; they are being extensively explored for a wide range of technologies such as photovoltaics, photodetectors, photocatalysts, light-emitting diodes, lasers and quantum emitters 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 . The underlying design principles for each of these devices are strongly correlated to the exact details of how photoexcited or electronically injected charge carriers dissipate their energy via electron–phonon coupling. For example, it has been recently shown that unusual electron–phonon coupling mechanisms probably promote the emission of single photons or correlated photon pairs from perovskite quantum sources 10 . There have only been a handful of experimental studies based on ultrafast or temperature-dependent optical spectroscopies to elucidate the carrier dynamics in 2D perovskites. These studies reveal the different facets of electron–phonon coupling, which could strongly govern the exciton polaronic effects 11 , hot-carrier dynamics 12 , vibrational relaxation dynamics 13 , and carrier trapping and recombination rates 5 . Moreover, these measurements indicate that the presence of an organic cation in close proximity to the inorganic perovskite lattice strongly modulates the nature of electron–phonon interactions 5 , 11 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , and suggest that electron–phonon scattering in 2D perovskites occurs via local dynamic disorder 6 . These short-range carrier–lattice interactions modulate the quantum-well thickness and octahedral tilts, leading to, for example, exciton self-trapping and broadband emission, as well as the unique photophysical properties under extreme 9 non-equilibrium. However, there exists no direct ultrafast structural measurement of 2D perovskites, which elucidates the underlying carrier–lattice interaction mechanisms on optical excitation. Moreover, the exact geometry and dynamics of these lattice distortions are unknown. This is largely due to the challenges in visualizing the carrier–lattice coupling and dynamics at ultra-short times after optical excitation above the bandgap. Here we report a direct measurement of the structural dynamics in 2D perovskites obtained by monitoring the change in femtosecond-scale ultrafast electron diffraction (UED) after optical excitation. This technique enables the picosecond time-resolved structural evolution of 2D perovskites by tracking the changes in diffraction pattern, thus providing a direct visualization of lattice response after photodoping. A detailed analysis of the Bragg peak intensities and temporal signatures reveals an ultrafast reduction in antiferro-distortion at early times (rise-time constant τ ≤ 1 ps), which is attributed to the light-induced in-plane rotation of the perovskite octahedra from a distorted to symmetrical (ordered) phase. Complementary transient absorption (TA) measurements further reveal a high-excitation regime (beyond Mott transition) 20 , 21 in which a dense electron–hole plasma strongly modulates the crystal cohesive energy 22 , leading to an ultrafast lattice ordering. In parallel, a classical energy transfer to the whole phonon bath via thermal atomic displacements was observed, which was attributed to the Debye–Waller effect. The latter was associated with a slower rise time ( τ ≈ 5 ps) of thermal dissipation (or lattice heating). Additionally, the observed long-lived coherent acoustic oscillations suggest the long lifetime of the observed lattice response. Concomitant with the Debye–Waller effect, we also observe an increase in diffused scattering, which confirms the activation of thermal transfer to the phonon bath. Finally, we show that the mechanism and dynamics of the interaction between the charge carriers and lattice are acutely tunable and sensitive to the initial lattice distortion of 2D perovskites dictated by the choice of the organic spacer layers. These findings reveal distinct carrier–lattice interactions and counterintuitive mechanisms in 2D perovskites at room temperature, which have not been reported in conventional non-polar/weakly polar semiconductors such as Si and GaAs or even in three-dimensional (3D) iodide perovskites 23 , 24 . UED experiments on 2D perovskites The UED experiments are performed in a pump–probe setup in which sub-micrometre-thick 2D hybrid perovskite single crystals are photoexcited with a 75 fs pulsed laser and the structural dynamics are probed with a pulsed electron beam with 150 fs temporal width after specific delay times ( t ) (Fig. 1a ). A diffraction image is acquired at each delay time after above-bandgap excitation (Fig. 1b ), which reflects the instantaneous 2D perovskite crystal structure. Monitoring the characteristics of the diffraction peaks (or Bragg peaks) on the image allows us to directly probe the dynamic changes in the lattice structure after light excitation, revealing the carrier–lattice interactions during energy relaxation (cooling) to the band edge of 2D perovskite semiconductors. We start with a phase-pure (homogeneous perovskite-layer thickness) 2D perovskite crystal of Dion–Jacobson 4AMP-MAPb 2 I 7 (DJ n = 2) with a thickness of 270 nm (Fig. 1a and Supplementary Fig. 1 ), which is excited with 3.1 eV light, that is, 0.9 eV above its ground-state optical transition 25 . The diffraction pattern of DJ n = 2 at rest is consistent with the static crystal structure reported previously (Fig. 1c,d and Supplementary Fig. 2 ) 25", "role": "user" }, { "content": "Rice University researchers already knew the atoms in perovskites react favorably to light. Now they can see precisely how those atoms move. A breakthrough in visualization supports their efforts to squeeze every possible drop of utility out of perovskite-based materials, including solar cells, a long-standing project that only recently yielded an advance to make the devices far more durable. A study published in Nature Physics details the first direct measurement of structural dynamics under light-induced excitation in 2D perovskites. Perovskites are layered materials that have well-ordered crystal lattices. They are highly efficient harvesters of light that are being explored for use as solar cells, photodetectors, photocatalysts, light-emitting diodes, quantum emitters and more. \"The next frontier in light-to-energy conversion devices is harvesting hot carriers,\" said Rice University's Aditya Mohite, a corresponding author of the study. \"Studies have shown that hot carriers in perovskite can live up to 10–100 times longer than in classical semiconductors. However, the mechanisms and design principles for the energy transfer and how they interact with the lattice are not understood.\" Hot carriers are short-lived, high-energy charge carriers, either electrons for negative charges or electron \"holes\" for positive charges, and having the ability to harvest their energy would allow light-harvesting devices to \"surpass thermodynamic efficiency,\" said Mohite, an associate professor of chemical and biomolecular engineering in Rice's George R. Brown School of Engineering. Mohite and three members of his research group, senior scientist Jean-Christophe Blancon and graduate students Hao Zhang and Wenbin Li, worked with colleagues at the SLAC National Accelerator Laboratory to see how atoms in a perovskite lattice rearranged themselves when a hot carrier was created in their midst. They visualized lattice reorganization in real time using ultrafast electron diffraction. \"Whenever you expose these soft semiconductors to stimuli like electric fields, interesting things happen,\" Mohite said. \"When you generate electrons and holes, they tend to couple to the lattice in unusual and really strong ways, which is not the case for classical materials and semiconductors. \"So there was a fundamental physics question,\" he said. \"Can we visualize these interactions? Can we see how the structure is actually responding at very fast timescales as you put light onto this material?\" The answer was yes, but only with a strong input. SLAC's mega-electron-volt ultrafast electron diffraction (MeV-UED) facility is one of the few places in the world with pulsed lasers capable of creating the electron-hole plasma in perovskites that was needed to reveal how the lattice structure changed in less than a billionth of a second in response to a hot carrier. \"The way this experiment works is that you shoot a laser through the material and then you send an electron beam that goes past it at a very short time delay,\" Mohite explained. \"You start to see exactly what you would in a TEM (transmission electron microscope) image. With the high-energy electrons at SLAC, you can see diffraction patterns from thicker samples, and that allows you to monitor what happens to those electrons and holes and how they interact with the lattice.\" The experiments at SLAC produced before-and-after diffraction patterns that Mohite's team interpreted to show how the lattice changed. They found that after the lattice was excited by light, it relaxed and literally straightened up in as little as one picosecond, or one-trillionth of a second. Zhang said, \"There's a subtle tilting of the perovskite octahedra, which triggers this transient lattice reorganization towards a higher symmetric phase.\" By demonstrating that a perovskite lattice can suddenly become less distorted in response to light, the research showed it should be possible to tune how perovskite lattices interact with light, and it suggested a way to accomplish the tuning. Li said, \"This effect is very dependent on the type of structure and type of organic spacer cation.\" There are many recipes for making perovskites, but all contain organic cations, an ingredient that acts as a spacer between the materials' semiconducting layers. By substituting or subtly changing organic cations, researchers could tailor lattice rigidity, dialing it up or down to alter how the material responds to light, Li said. Mohite said the experiments also show that tuning a perovskite's lattice alters its heat-transfer properties. \"What is generally expected is that when you excite electrons at a very high energy level, they lose their energy to the lattice,\" he said. \"Some of that energy is converted to whatever process you want, but a lot of it is lost as heat, which shows in the diffraction pattern as a loss in intensity. \"The lattice is getting more energy from thermal energy,\" Mohite said. \"That's the classical effect, which is expected, and is well-known as the Debye-Waller factor. But because we can now know exactly what's happening in every direction of the crystal lattice, we see the lattice starts to get more crystalline or ordered. And that's totally counterintuitive.\" A better understanding of how excited perovskites handle heat is a bonus of the research, he said. \"As we make devices smaller and smaller, one of the biggest challenges from a microelectronics perspective is heat management,\" Mohite said. \"Understanding this heat generation and how it's being transported through materials is important. \"When people talk about stacking devices, they need to be able to extract heat very fast,\" he said. \"As we move to new technologies that consume less power and generate less heat, these types of measurements will allow us to directly probe how heat is flowing.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Direct visualization of ultrafast coupling between charge carriers and lattice degrees of freedom in photoexcited semiconductors has remained a long-standing challenge and is critical for understanding the light-induced physical behaviour of materials under extreme non-equilibrium conditions. Here we obtain a direct visualization of the structural dynamics in monocrystalline 2D perovskites. We achieve this by monitoring the evolution of wavevector-resolved ultrafast electron diffraction intensity following above-bandgap high-density photoexcitation. Our analysis reveals a light-induced ultrafast reduction in antiferro-distortion resulting from a strong interaction between the electron–hole plasma and perovskite lattice, which induces an in-plane octahedra rotation towards a more symmetric phase. Correlated ultrafast spectroscopy performed at the same carrier density as ultrafast electron diffraction reveals that the creation of a dense electron–hole plasma triggers the relaxation of lattice distortion at shorter timescales by modulating the crystal cohesive energy. Finally, we show that the interaction between carrier gas and lattice can be altered by tailoring the rigidity of the 2D perovskite by choosing an appropriate organic spacer layer. Main Organic–inorganic (hybrid) two-dimensional (2D) halide perovskites (2DP) are constructed by a superlattice of interlocking organic and inorganic nanometre-thick layers and have demonstrated unique and non-classical behaviours; they are being extensively explored for a wide range of technologies such as photovoltaics, photodetectors, photocatalysts, light-emitting diodes, lasers and quantum emitters 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 . The underlying design principles for each of these devices are strongly correlated to the exact details of how photoexcited or electronically injected charge carriers dissipate their energy via electron–phonon coupling. For example, it has been recently shown that unusual electron–phonon coupling mechanisms probably promote the emission of single photons or correlated photon pairs from perovskite quantum sources 10 . There have only been a handful of experimental studies based on ultrafast or temperature-dependent optical spectroscopies to elucidate the carrier dynamics in 2D perovskites. These studies reveal the different facets of electron–phonon coupling, which could strongly govern the exciton polaronic effects 11 , hot-carrier dynamics 12 , vibrational relaxation dynamics 13 , and carrier trapping and recombination rates 5 . Moreover, these measurements indicate that the presence of an organic cation in close proximity to the inorganic perovskite lattice strongly modulates the nature of electron–phonon interactions 5 , 11 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , and suggest that electron–phonon scattering in 2D perovskites occurs via local dynamic disorder 6 . These short-range carrier–lattice interactions modulate the quantum-well thickness and octahedral tilts, leading to, for example, exciton self-trapping and broadband emission, as well as the unique photophysical properties under extreme 9 non-equilibrium. However, there exists no direct ultrafast structural measurement of 2D perovskites, which elucidates the underlying carrier–lattice interaction mechanisms on optical excitation. Moreover, the exact geometry and dynamics of these lattice distortions are unknown. This is largely due to the challenges in visualizing the carrier–lattice coupling and dynamics at ultra-short times after optical excitation above the bandgap. Here we report a direct measurement of the structural dynamics in 2D perovskites obtained by monitoring the change in femtosecond-scale ultrafast electron diffraction (UED) after optical excitation. This technique enables the picosecond time-resolved structural evolution of 2D perovskites by tracking the changes in diffraction pattern, thus providing a direct visualization of lattice response after photodoping. A detailed analysis of the Bragg peak intensities and temporal signatures reveals an ultrafast reduction in antiferro-distortion at early times (rise-time constant τ ≤ 1 ps), which is attributed to the light-induced in-plane rotation of the perovskite octahedra from a distorted to symmetrical (ordered) phase. Complementary transient absorption (TA) measurements further reveal a high-excitation regime (beyond Mott transition) 20 , 21 in which a dense electron–hole plasma strongly modulates the crystal cohesive energy 22 , leading to an ultrafast lattice ordering. In parallel, a classical energy transfer to the whole phonon bath via thermal atomic displacements was observed, which was attributed to the Debye–Waller effect. The latter was associated with a slower rise time ( τ ≈ 5 ps) of thermal dissipation (or lattice heating). Additionally, the observed long-lived coherent acoustic oscillations suggest the long lifetime of the observed lattice response. Concomitant with the Debye–Waller effect, we also observe an increase in diffused scattering, which confirms the activation of thermal transfer to the phonon bath. Finally, we show that the mechanism and dynamics of the interaction between the charge carriers and lattice are acutely tunable and sensitive to the initial lattice distortion of 2D perovskites dictated by the choice of the organic spacer layers. These findings reveal distinct carrier–lattice interactions and counterintuitive mechanisms in 2D perovskites at room temperature, which have not been reported in conventional non-polar/weakly polar semiconductors such as Si and GaAs or even in three-dimensional (3D) iodide perovskites 23 , 24 . UED experiments on 2D perovskites The UED experiments are performed in a pump–probe setup in which sub-micrometre-thick 2D hybrid perovskite single crystals are photoexcited with a 75 fs pulsed laser and the structural dynamics are probed with a pulsed electron beam with 150 fs temporal width after specific delay times ( t ) (Fig. 1a ). A diffraction image is acquired at each delay time after above-bandgap excitation (Fig. 1b ), which reflects the instantaneous 2D perovskite crystal structure. Monitoring the characteristics of the diffraction peaks (or Bragg peaks) on the image allows us to directly probe the dynamic changes in the lattice structure after light excitation, revealing the carrier–lattice interactions during energy relaxation (cooling) to the band edge of 2D perovskite semiconductors. We start with a phase-pure (homogeneous perovskite-layer thickness) 2D perovskite crystal of Dion–Jacobson 4AMP-MAPb 2 I 7 (DJ n = 2) with a thickness of 270 nm (Fig. 1a and Supplementary Fig. 1 ), which is excited with 3.1 eV light, that is, 0.9 eV above its ground-state optical transition 25 . The diffraction pattern of DJ n = 2 at rest is consistent with the static crystal structure reported previously (Fig. 1c,d and Supplementary Fig. 2 ) 25<|im_end|> <|im_start|>assistant Rice University researchers already knew the atoms in perovskites react favorably to light. Now they can see precisely how those atoms move. A breakthrough in visualization supports their efforts to squeeze every possible drop of utility out of perovskite-based materials, including solar cells, a long-standing project that only recently yielded an advance to make the devices far more durable. A study published in Nature Physics details the first direct measurement of structural dynamics under light-induced excitation in 2D perovskites. Perovskites are layered materials that have well-ordered crystal lattices. They are highly efficient harvesters of light that are being explored for use as solar cells, photodetectors, photocatalysts, light-emitting diodes, quantum emitters and more. "The next frontier in light-to-energy conversion devices is harvesting hot carriers," said Rice University's Aditya Mohite, a corresponding author of the study. "Studies have shown that hot carriers in perovskite can live up to 10–100 times longer than in classical semiconductors. However, the mechanisms and design principles for the energy transfer and how they interact with the lattice are not understood." Hot carriers are short-lived, high-energy charge carriers, either electrons for negative charges or electron "holes" for positive charges, and having the ability to harvest their energy would allow light-harvesting devices to "surpass thermodynamic efficiency," said Mohite, an associate professor of chemical and biomolecular engineering in Rice's George R. Brown School of Engineering. Mohite and three members of his research group, senior scientist Jean-Christophe Blancon and graduate students Hao Zhang and Wenbin Li, worked with colleagues at the SLAC National Accelerator Laboratory to see how atoms in a perovskite lattice rearranged themselves when a hot carrier was created in their midst. They visualized lattice reorganization in real time using ultrafast electron diffraction. "Whenever you expose these soft semiconductors to stimuli like electric fields, interesting things happen," Mohite said. "When you generate electrons and holes, they tend to couple to the lattice in unusual and really strong ways, which is not the case for classical materials and semiconductors. "So there was a fundamental physics question," he said. "Can we visualize these interactions? Can we see how the structure is actually responding at very fast timescales as you put light onto this material?" The answer was yes, but only with a strong input. SLAC's mega-electron-volt ultrafast electron diffraction (MeV-UED) facility is one of the few places in the world with pulsed lasers capable of creating the electron-hole plasma in perovskites that was needed to reveal how the lattice structure changed in less than a billionth of a second in response to a hot carrier. "The way this experiment works is that you shoot a laser through the material and then you send an electron beam that goes past it at a very short time delay," Mohite explained. "You start to see exactly what you would in a TEM (transmission electron microscope) image. With the high-energy electrons at SLAC, you can see diffraction patterns from thicker samples, and that allows you to monitor what happens to those electrons and holes and how they interact with the lattice." The experiments at SLAC produced before-and-after diffraction patterns that Mohite's team interpreted to show how the lattice changed. They found that after the lattice was excited by light, it relaxed and literally straightened up in as little as one picosecond, or one-trillionth of a second. Zhang said, "There's a subtle tilting of the perovskite octahedra, which triggers this transient lattice reorganization towards a higher symmetric phase." By demonstrating that a perovskite lattice can suddenly become less distorted in response to light, the research showed it should be possible to tune how perovskite lattices interact with light, and it suggested a way to accomplish the tuning. Li said, "This effect is very dependent on the type of structure and type of organic spacer cation." There are many recipes for making perovskites, but all contain organic cations, an ingredient that acts as a spacer between the materials' semiconducting layers. By substituting or subtly changing organic cations, researchers could tailor lattice rigidity, dialing it up or down to alter how the material responds to light, Li said. Mohite said the experiments also show that tuning a perovskite's lattice alters its heat-transfer properties. "What is generally expected is that when you excite electrons at a very high energy level, they lose their energy to the lattice," he said. "Some of that energy is converted to whatever process you want, but a lot of it is lost as heat, which shows in the diffraction pattern as a loss in intensity. "The lattice is getting more energy from thermal energy," Mohite said. "That's the classical effect, which is expected, and is well-known as the Debye-Waller factor. But because we can now know exactly what's happening in every direction of the crystal lattice, we see the lattice starts to get more crystalline or ordered. And that's totally counterintuitive." A better understanding of how excited perovskites handle heat is a bonus of the research, he said. "As we make devices smaller and smaller, one of the biggest challenges from a microelectronics perspective is heat management," Mohite said. "Understanding this heat generation and how it's being transported through materials is important. "When people talk about stacking devices, they need to be able to extract heat very fast," he said. "As we move to new technologies that consume less power and generate less heat, these types of measurements will allow us to directly probe how heat is flowing." <|im_end|>

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2,732

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Recently, nanotechnology has been effectively used in the field of road pavement. Oxidation and aging of asphalt cause deterioration of road pavements and increase asphalt-related emissions. We propose an anti-aging strategy to interrupt the asphalt deterioration by using engineered clay/fumed silica nanocomposites. In this research, the morphological, chemical, thermal, mechanical, and rheological properties of nano-modified asphalt binders are meticulously analyzed in various conditions. The experiment results proved that this composite efficiently disrupts the chemical oxidation and decomposition in the mixture and reduces the aging rate. Remarkably, asphalt binder rheology experiments revealed that the addition of 0.2–0.3 wt% of nano-reinforced materials maximized their rheological resistance after short- and long-term aging. Moreover, nanoparticles improve the moisture resistance efficiency and in turn overcome the critical issue of moisture in low production temperature within the framework of warm mix asphalt technology. This cost-effective, facile, and scalable approach in warm mix asphalt mixtures can contribute to increased sustainability and lifespan of pavements and a reduction in greenhouse gas emissions. Graphical abstract Keywords: nano clay ; modified bitumen ; thermal oxidation aging ; nano-modification ; nanocomposites 1 Introduction Bitumen is generally used as the glue in road asphalt mixtures, due to its appropriate rheological properties [ 1 , 2 , 3 ]. However, modification of bitumen has developed an emerging field in road material technology, mainly in connection with re-using reclaimed asphalt paving, with low-energy concepts for asphalt mixture production, and with the increasing wish to at least partially replace the bitumen through more sustainable and bio-based binders. A significant issue when identifying the most appropriate bitumen modifiers is to investigate their aging resistance. As road asphalt materials are exposed not only to hot temperatures during mixture production but also to severe sun radiation, and oxygen and other radicals that promote binder aging during their entire in-service life [ 4 , 5 , 6 , 7 ], the durability of asphalt binders in terms of aging resistance is an important material property. Binder aging includes ultraviolet, thermal long-term aging, and thermo oxidative short-term aging. To influence asphalt binder performance, a huge variety of different types of additives can be added to bitumen, such as polymers, fibers, recycled materials, and nanomaterials [ 8 , 9 ]. This study focuses on nanomaterials. Among these materials, usually, nanomaterials significantly change chemical binder properties and in consequence mechanical rheological performance properties. Among the most important parameters describing nanoparticles (NPs), which cause physical properties of nanocomposites unique and different from conventional materials, are their ratio of surface area to volume, shape, chemical composition, and their capability to increase interactions at phase interfaces [ 10 , 11 ]. Metal oxide, inorganic, nanofibers, and nanocomposites are the main class of nanomaterials particularly used in asphalt mixture to modify asphaltene binders [ 12 , 13 ]. Metal oxide NPs including zinc oxide (ZnO) and titanium dioxide (TiO 2 ) are reported to enhance the asphalt mixture’s resistance to rutting and cracking [ 13 , 14 ]. Inorganic NPs such as silica (SiO 2 ), carbon nanotubes (CNTs), and nano-clay are seen to have excellent potential in the reinforcement of asphalt materials and improving their durability [ 15 , 16 ]. The rheological performance of bitumen – and consequently the performance of the corresponding asphalt mixture – was successfully improved through the addition of SiO 2 NPs. The thermal and mechanical stabilities of the asphalt mixture were also improved by incorporating clay NPs [ 17 , 18 ]. To the best of our knowledge, clay and silica families are the most widely used inorganic NPs to improve the binder resistance to aging [ 19 , 20 , 21 , 22 ]. Clay and silica families were reported to be one of the excellent inorganic NPs in improving binder aging properties. Based on the results of different reports, nano-silica-modified asphalt binders slightly decreased viscosity and complex modulus, while improving fatigue and rutting resistance after short-term aging [ 19 , 20 , 21 ]. In addition, some investigations have shown that nano-silica-modified binder has a higher resistance to thermal aging, ultimately leading to increased durability of asphalt pavements [ 21 , 22 ]. SiO 2 NPs have advantages such as nonphotocatalytic, inorganic shielding, and nontoxic, which are of crucial importance for use in asphalt mixtures [ 23 , 24 ]. However, fumed SiO 2 NPs are one class of synthetic nanomaterials that has environmentally friendly and economic justification to use on large scale. Fumed silica is a synthetic amorphous structure nanomaterial with a large surface area and nano-size scale [ 25 ]. Therefore, this study focuses on clay/fumed silica nanoparticles (CSNPs). In comparison to the conventional way, warm mix asphalt (WMA) technology works in an efficient eco-friendly manner. In this case, asphalt is produced at a temperature of approximately 30–60°C, which is lower than usual. This technology reduces the emission of harmful vapors and leads to 20–35 and 35% less greenhouse gas emissions and energy consumption, respectively [ 13 , 26 ]. However, moisture susceptibility is a common disadvantage of WMA technology, leading to a decrease in its performance [ 27 , 28 ]. The objective of this research is to identify the potential impacts of CSNPs on the aging resistance of road asphalt binders that are used for road asphalt mixtures produced by WMA technology. In detail, the morphological, chemical, thermal, rheological, and mechanical properties of CSNP-modified asphalt binders are meticulously analyzed in various conditions. New insights are presented toward a further understanding of potential changes in mechanical and rheological binder properties due to thermal aging. Figure 1 schematically illustrates the experimental techniques applied in this study. Figure 1 Schematic overview of experimental techniques applied in this study. 2 Materials and methods 2.1 Materials The synthesis process of CSNPs was selected according to the authors’ previous research (as shown in Figure S1) [ 29 ]. Nano fumed silica (Aerosil A300, Degussa Co., Germany), sodium bentonite (Sigma Aldrich Ltd., Germany; see Table S1), and Bitumen 50/70 (Total Co., France) were used in this research. The particle", "role": "user" }, { "content": "A novel and eco-friendly nano asphalt binder has been developed by researchers at Swansea University and the Technical University of Braunschweig. The product generates a new class of warm mix asphalt (WMA) additive that significantly reduces energy consumption while simultaneously minimizing vapors and greenhouse gas emissions during the production of asphalt mixtures when compared to conventional asphalt, it also works effectively at a large scale. To achieve net-zero carbon emissions, Highways UK is increasing the adoption of WMA as a standard across its supply chain. When compared to conventional hot-mix asphalts, WMA technologies can provide increased efficiency and reduce carbon production, with CO2 reductions of up to 15%. WMAs are produced at temperatures of up to 40°C lower than ordinary asphalt, therefore, switching to them would save roughly 61,000 tons of CO2 each year in the UK, which is the equivalent of reducing 300 million miles of automobile travel. To address these issues in WMA technology, a team from the Braunschweig Pavement Engineering Centre (ISBS) at the Technische Universität Braunschweig and Energy Safety Research Institute (ESRI) at Swansea University have discovered the potential for engineered clay/fumed silica nanocomposites to be used as an anti-aging binder that can not only serve to reduce temperatures but also overcome significant limitations caused by moisture susceptibility. Lead researcher Dr. Gِoshtasp Cheraghian of the Technical University of Braunschweig said: \"The study given fills the technical gap in WMA technology. Our nanocomposite is a cost-effective and non-toxic substance that can have a significant impact on WMA stability.\" \"Typically, asphalt binders are susceptible to aging due to heat, air, sunlight, and water, that have a detrimental effect on the pavement quality, reducing durability.\" Dr. Sajad Kiani of ESRI said, \"We found that the addition of mineral-reinforced particle will not only decrease oxidation and aging of asphalt but also improve road pavement lifespan and decrease asphalt-related emissions.\" Professor Andrew Barron, the Founder and Director of ESRI and the Sêr Cymru Chair of Low Carbon Energy and Environment at Swansea University, said: \"Compared to commercial materials, our solution requires lower concentrations (less than 0.3 wt.%) of additives due to their superior surface activity, and as such has the potential to solve some of the challenges associated with, less durable the roads.\" Dr. Cheraghian summarizes: \"Our results on the molecular interaction between nanoparticles and asphalt binders could pave the way for novel nanotechnology applications in asphalt engineering.\" The article can be read in Nanotechnology Reviews. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Recently, nanotechnology has been effectively used in the field of road pavement. Oxidation and aging of asphalt cause deterioration of road pavements and increase asphalt-related emissions. We propose an anti-aging strategy to interrupt the asphalt deterioration by using engineered clay/fumed silica nanocomposites. In this research, the morphological, chemical, thermal, mechanical, and rheological properties of nano-modified asphalt binders are meticulously analyzed in various conditions. The experiment results proved that this composite efficiently disrupts the chemical oxidation and decomposition in the mixture and reduces the aging rate. Remarkably, asphalt binder rheology experiments revealed that the addition of 0.2–0.3 wt% of nano-reinforced materials maximized their rheological resistance after short- and long-term aging. Moreover, nanoparticles improve the moisture resistance efficiency and in turn overcome the critical issue of moisture in low production temperature within the framework of warm mix asphalt technology. This cost-effective, facile, and scalable approach in warm mix asphalt mixtures can contribute to increased sustainability and lifespan of pavements and a reduction in greenhouse gas emissions. Graphical abstract Keywords: nano clay ; modified bitumen ; thermal oxidation aging ; nano-modification ; nanocomposites 1 Introduction Bitumen is generally used as the glue in road asphalt mixtures, due to its appropriate rheological properties [ 1 , 2 , 3 ]. However, modification of bitumen has developed an emerging field in road material technology, mainly in connection with re-using reclaimed asphalt paving, with low-energy concepts for asphalt mixture production, and with the increasing wish to at least partially replace the bitumen through more sustainable and bio-based binders. A significant issue when identifying the most appropriate bitumen modifiers is to investigate their aging resistance. As road asphalt materials are exposed not only to hot temperatures during mixture production but also to severe sun radiation, and oxygen and other radicals that promote binder aging during their entire in-service life [ 4 , 5 , 6 , 7 ], the durability of asphalt binders in terms of aging resistance is an important material property. Binder aging includes ultraviolet, thermal long-term aging, and thermo oxidative short-term aging. To influence asphalt binder performance, a huge variety of different types of additives can be added to bitumen, such as polymers, fibers, recycled materials, and nanomaterials [ 8 , 9 ]. This study focuses on nanomaterials. Among these materials, usually, nanomaterials significantly change chemical binder properties and in consequence mechanical rheological performance properties. Among the most important parameters describing nanoparticles (NPs), which cause physical properties of nanocomposites unique and different from conventional materials, are their ratio of surface area to volume, shape, chemical composition, and their capability to increase interactions at phase interfaces [ 10 , 11 ]. Metal oxide, inorganic, nanofibers, and nanocomposites are the main class of nanomaterials particularly used in asphalt mixture to modify asphaltene binders [ 12 , 13 ]. Metal oxide NPs including zinc oxide (ZnO) and titanium dioxide (TiO 2 ) are reported to enhance the asphalt mixture’s resistance to rutting and cracking [ 13 , 14 ]. Inorganic NPs such as silica (SiO 2 ), carbon nanotubes (CNTs), and nano-clay are seen to have excellent potential in the reinforcement of asphalt materials and improving their durability [ 15 , 16 ]. The rheological performance of bitumen – and consequently the performance of the corresponding asphalt mixture – was successfully improved through the addition of SiO 2 NPs. The thermal and mechanical stabilities of the asphalt mixture were also improved by incorporating clay NPs [ 17 , 18 ]. To the best of our knowledge, clay and silica families are the most widely used inorganic NPs to improve the binder resistance to aging [ 19 , 20 , 21 , 22 ]. Clay and silica families were reported to be one of the excellent inorganic NPs in improving binder aging properties. Based on the results of different reports, nano-silica-modified asphalt binders slightly decreased viscosity and complex modulus, while improving fatigue and rutting resistance after short-term aging [ 19 , 20 , 21 ]. In addition, some investigations have shown that nano-silica-modified binder has a higher resistance to thermal aging, ultimately leading to increased durability of asphalt pavements [ 21 , 22 ]. SiO 2 NPs have advantages such as nonphotocatalytic, inorganic shielding, and nontoxic, which are of crucial importance for use in asphalt mixtures [ 23 , 24 ]. However, fumed SiO 2 NPs are one class of synthetic nanomaterials that has environmentally friendly and economic justification to use on large scale. Fumed silica is a synthetic amorphous structure nanomaterial with a large surface area and nano-size scale [ 25 ]. Therefore, this study focuses on clay/fumed silica nanoparticles (CSNPs). In comparison to the conventional way, warm mix asphalt (WMA) technology works in an efficient eco-friendly manner. In this case, asphalt is produced at a temperature of approximately 30–60°C, which is lower than usual. This technology reduces the emission of harmful vapors and leads to 20–35 and 35% less greenhouse gas emissions and energy consumption, respectively [ 13 , 26 ]. However, moisture susceptibility is a common disadvantage of WMA technology, leading to a decrease in its performance [ 27 , 28 ]. The objective of this research is to identify the potential impacts of CSNPs on the aging resistance of road asphalt binders that are used for road asphalt mixtures produced by WMA technology. In detail, the morphological, chemical, thermal, rheological, and mechanical properties of CSNP-modified asphalt binders are meticulously analyzed in various conditions. New insights are presented toward a further understanding of potential changes in mechanical and rheological binder properties due to thermal aging. Figure 1 schematically illustrates the experimental techniques applied in this study. Figure 1 Schematic overview of experimental techniques applied in this study. 2 Materials and methods 2.1 Materials The synthesis process of CSNPs was selected according to the authors’ previous research (as shown in Figure S1) [ 29 ]. Nano fumed silica (Aerosil A300, Degussa Co., Germany), sodium bentonite (Sigma Aldrich Ltd., Germany; see Table S1), and Bitumen 50/70 (Total Co., France) were used in this research. The particle<|im_end|> <|im_start|>assistant A novel and eco-friendly nano asphalt binder has been developed by researchers at Swansea University and the Technical University of Braunschweig. The product generates a new class of warm mix asphalt (WMA) additive that significantly reduces energy consumption while simultaneously minimizing vapors and greenhouse gas emissions during the production of asphalt mixtures when compared to conventional asphalt, it also works effectively at a large scale. To achieve net-zero carbon emissions, Highways UK is increasing the adoption of WMA as a standard across its supply chain. When compared to conventional hot-mix asphalts, WMA technologies can provide increased efficiency and reduce carbon production, with CO2 reductions of up to 15%. WMAs are produced at temperatures of up to 40°C lower than ordinary asphalt, therefore, switching to them would save roughly 61,000 tons of CO2 each year in the UK, which is the equivalent of reducing 300 million miles of automobile travel. To address these issues in WMA technology, a team from the Braunschweig Pavement Engineering Centre (ISBS) at the Technische Universität Braunschweig and Energy Safety Research Institute (ESRI) at Swansea University have discovered the potential for engineered clay/fumed silica nanocomposites to be used as an anti-aging binder that can not only serve to reduce temperatures but also overcome significant limitations caused by moisture susceptibility. Lead researcher Dr. Gِoshtasp Cheraghian of the Technical University of Braunschweig said: "The study given fills the technical gap in WMA technology. Our nanocomposite is a cost-effective and non-toxic substance that can have a significant impact on WMA stability." "Typically, asphalt binders are susceptible to aging due to heat, air, sunlight, and water, that have a detrimental effect on the pavement quality, reducing durability." Dr. Sajad Kiani of ESRI said, "We found that the addition of mineral-reinforced particle will not only decrease oxidation and aging of asphalt but also improve road pavement lifespan and decrease asphalt-related emissions." Professor Andrew Barron, the Founder and Director of ESRI and the Sêr Cymru Chair of Low Carbon Energy and Environment at Swansea University, said: "Compared to commercial materials, our solution requires lower concentrations (less than 0.3 wt.%) of additives due to their superior surface activity, and as such has the potential to solve some of the challenges associated with, less durable the roads." Dr. Cheraghian summarizes: "Our results on the molecular interaction between nanoparticles and asphalt binders could pave the way for novel nanotechnology applications in asphalt engineering." The article can be read in Nanotechnology Reviews. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Animals exhibit various physiological and behavioural strategies for minimizing travel costs. Fins of aquatic animals play key roles in efficient travel and, for sharks, the functions of dorsal and pectoral fins are considered well divided: the former assists propulsion and generates lateral hydrodynamic forces during turns and the latter generates vertical forces that offset sharks’ negative buoyancy. Here we show that great hammerhead sharks drastically reconfigure the function of these structures, using an exaggerated dorsal fin to generate lift by swimming rolled on their side. Tagged wild sharks spend up to 90% of time swimming at roll angles between 50° and 75°, and hydrodynamic modelling shows that doing so reduces drag—and in turn, the cost of transport—by around 10% compared with traditional upright swimming. Employment of such a strongly selected feature for such a unique purpose raises interesting questions about evolutionary pathways to hydrodynamic adaptations, and our perception of form and function. Introduction Like other mobile aquatic animals, sharks have evolved a set of morphological traits that facilitate efficient travel in water; a streamlined body shape and assortment of fins are conspicuous examples. Almost all sharks are negatively buoyant 1 , 2 , and use their pectoral fins to generate vertical hydrodynamic force that counteracts gravity 3 , 4 . In contrast, the dorsal fin assists in propulsion 5 and turning 6 through the generation of lateral forces 6 , 7 . The prevailing view is that the roles of the pectoral and dorsal fins in sharks are clearly divided in this way. By measuring body posture of great hammerhead sharks Sphyrna mokarran swimming in the wild, we show that this species regularly swims rolled on their side. Because this implies a reconfiguration of the function of their fins during locomotion, we conducted a series of modelling experiments to explore the hydrodynamic consequences of this unusual rolled swimming. Our results show that S. mokarran generate lift with their dorsal fin by swimming on their side, and that doing so is a more efficient way to travel than is swimming upright. These findings question the paradigm of the division of labour in shark fins, and highlight that efficient travel is a strong selective agent in driving the evolution of animals. Results Observations of rolled swimming We tagged two wild great hammerhead sharks with accelerometer loggers that allow the estimation of body pitch and roll angles as they swim freely in their environment (see Methods, Supplementary Fig. 1 and Supplementary Notes 1 and 2 ); one at the Great Barrier Reef, Australia, and another off the Mesoamerican Reef, Belize. Unexpectedly, the shark tagged at the Great Barrier Reef spent ∼ 90% of the 18 h deployment period (which was from early evening till late morning) swimming on its side at absolute roll angles between 50° and 75° ( Fig. 1a,b and Supplementary Fig. 2 ). The shark exhibited this rolling behaviour whether it was ascending, descending or swimming at constant depth, and alternated between rolling to the left and right sides approximately every 5–10 min. An onboard video camera visually confirmed the observations ( Supplementary Movie 1 ). The shark tagged off Belize exhibited a very similar pattern; it was monitored for almost 3 days, and spent the majority of night-time hours swimming at roll angles between 30° and 80°, and tended to swim more upright during daylight hours ( Supplementary Fig. 3 and Supplementary Note 2 ). It is unlikely that this behaviour is a response to the capture, handling and tagging procedure because a further three sharks fitted with onboard video cameras via SCUBA (that is, cameras were fitted to the shark’s dorsal fins underwater without being captured or handled) in the Bahamas also exhibited frequent rolled swimming throughout the 2–3 h of each daytime video deployment ( Fig. 1e,f and Supplementary Movie 2 ), and untagged specimens of this species in public aquaria invariably spend a large proportion of time swimming at the same roll angles seen in our wild, tagged animals ( Supplementary Movie 3 ). Ostensibly, this seems a bizarre and unexpected mode of swimming, and has no precedent in the literature. What possible advantage could be obtained by swimming rolled in this way? Doing so would presumably inhibit use of their cephalofoil for detecting electrical signals from benthic prey; therefore, rather than representing a foraging strategy, our hypothesis was that the rolled swimming confers hydrodynamic advantages. Figure 1: Rolled swimming in great hammerhead sharks Sphyrna mokarran . For a to d , roll and pitch angles were measured by an electronic tag attached to a 295 cm shark’s dorsal fin, and monitored as it swam freely at the Great Barrier Reef, northern Australia. ( a , c ) A typical hour-long time series for that animal. ( b , d ) Probability distributions of roll and pitch angles based on the last 15 h of the monitoring period for the Great Barrier Reef shark. Images in e , f were taken with a fin-mounted video camera attached to another wild S. mokarran ( ∼ 350 cm) as it swam rolled to the left and right (respectively) at South Bimini Island, the Bahamas, at absolute roll angles of ∼ 60° (see Supplementary Movie 2 for examples of this and other wild S. mokarran swimming rolled). Full size image Hydrodynamics of a swimming shark Hydrodynamic forces acting on a swimming shark can be conveniently divided into lift L , drag D , thrust T and buoyancy B . For simplicity, we will assume that the thrust is generated mainly by the caudal, anal and the second dorsal fins, and is directed along the swimming path, whereas lift and drag are generated by all other fins and by the body of the shark; they are directed perpendicular and parallel to the swimming path, respectively. When swimming at constant speed along a straight horizontal path, all forces cancel out with gravity, G : Lift and drag are commonly expressed in terms of the respective coefficients C L and C", "role": "user" }, { "content": "Hammerhead sharks swim on their sides up to 90 per cent of the time to save energy, a Murdoch University researcher has found. Dr Adrian Gleiss from the Centre for Fish and Fisheries Research, collaborated on an international study which found the great hammerhead species spends up to 90 per cent of its time swimming at angles of between 50 and 70 degrees. This is thanks to an exaggerated dorsal fin which generates lift and helps to reduce drag when the sharks are rolled on their sides. Most sharks use their dorsal fins on their backs like a rudder on a boat, to facilitate quick turns. Their large pectoral fins on their sides are used like aircraft wings to keep them from sinking. It was thought this was how all sharks functioned until this study, which was led by Dr Nicholas Payne from the University of Roehampton, London. Dr Gleiss and the research team used video cameras and tagging to measure roll angles in hammerhead sharks in Belize, Australia and The Bahamas. \"The co-lead author on our paper, Associate Professor Gil Iosilevskii, developed hydrodynamic modeling to show this swimming method reduces energy use by around 10 per cent, compared with traditional upright swimming,\" said Dr Gleiss. \"Gil also conducted a series of experiments in a wind tunnel using a scale model of a hammerhead to find that minimal drag could be achieved at roll angles between 50 and 70 degrees, which closely matched the range of roll angles at which our tagged sharks swam in the wild.\" Dr Gleiss said understanding how animals reduce the effects of drag on their mobility could help mechanical engineers striving to find biometric solutions for man made designs. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Animals exhibit various physiological and behavioural strategies for minimizing travel costs. Fins of aquatic animals play key roles in efficient travel and, for sharks, the functions of dorsal and pectoral fins are considered well divided: the former assists propulsion and generates lateral hydrodynamic forces during turns and the latter generates vertical forces that offset sharks’ negative buoyancy. Here we show that great hammerhead sharks drastically reconfigure the function of these structures, using an exaggerated dorsal fin to generate lift by swimming rolled on their side. Tagged wild sharks spend up to 90% of time swimming at roll angles between 50° and 75°, and hydrodynamic modelling shows that doing so reduces drag—and in turn, the cost of transport—by around 10% compared with traditional upright swimming. Employment of such a strongly selected feature for such a unique purpose raises interesting questions about evolutionary pathways to hydrodynamic adaptations, and our perception of form and function. Introduction Like other mobile aquatic animals, sharks have evolved a set of morphological traits that facilitate efficient travel in water; a streamlined body shape and assortment of fins are conspicuous examples. Almost all sharks are negatively buoyant 1 , 2 , and use their pectoral fins to generate vertical hydrodynamic force that counteracts gravity 3 , 4 . In contrast, the dorsal fin assists in propulsion 5 and turning 6 through the generation of lateral forces 6 , 7 . The prevailing view is that the roles of the pectoral and dorsal fins in sharks are clearly divided in this way. By measuring body posture of great hammerhead sharks Sphyrna mokarran swimming in the wild, we show that this species regularly swims rolled on their side. Because this implies a reconfiguration of the function of their fins during locomotion, we conducted a series of modelling experiments to explore the hydrodynamic consequences of this unusual rolled swimming. Our results show that S. mokarran generate lift with their dorsal fin by swimming on their side, and that doing so is a more efficient way to travel than is swimming upright. These findings question the paradigm of the division of labour in shark fins, and highlight that efficient travel is a strong selective agent in driving the evolution of animals. Results Observations of rolled swimming We tagged two wild great hammerhead sharks with accelerometer loggers that allow the estimation of body pitch and roll angles as they swim freely in their environment (see Methods, Supplementary Fig. 1 and Supplementary Notes 1 and 2 ); one at the Great Barrier Reef, Australia, and another off the Mesoamerican Reef, Belize. Unexpectedly, the shark tagged at the Great Barrier Reef spent ∼ 90% of the 18 h deployment period (which was from early evening till late morning) swimming on its side at absolute roll angles between 50° and 75° ( Fig. 1a,b and Supplementary Fig. 2 ). The shark exhibited this rolling behaviour whether it was ascending, descending or swimming at constant depth, and alternated between rolling to the left and right sides approximately every 5–10 min. An onboard video camera visually confirmed the observations ( Supplementary Movie 1 ). The shark tagged off Belize exhibited a very similar pattern; it was monitored for almost 3 days, and spent the majority of night-time hours swimming at roll angles between 30° and 80°, and tended to swim more upright during daylight hours ( Supplementary Fig. 3 and Supplementary Note 2 ). It is unlikely that this behaviour is a response to the capture, handling and tagging procedure because a further three sharks fitted with onboard video cameras via SCUBA (that is, cameras were fitted to the shark’s dorsal fins underwater without being captured or handled) in the Bahamas also exhibited frequent rolled swimming throughout the 2–3 h of each daytime video deployment ( Fig. 1e,f and Supplementary Movie 2 ), and untagged specimens of this species in public aquaria invariably spend a large proportion of time swimming at the same roll angles seen in our wild, tagged animals ( Supplementary Movie 3 ). Ostensibly, this seems a bizarre and unexpected mode of swimming, and has no precedent in the literature. What possible advantage could be obtained by swimming rolled in this way? Doing so would presumably inhibit use of their cephalofoil for detecting electrical signals from benthic prey; therefore, rather than representing a foraging strategy, our hypothesis was that the rolled swimming confers hydrodynamic advantages. Figure 1: Rolled swimming in great hammerhead sharks Sphyrna mokarran . For a to d , roll and pitch angles were measured by an electronic tag attached to a 295 cm shark’s dorsal fin, and monitored as it swam freely at the Great Barrier Reef, northern Australia. ( a , c ) A typical hour-long time series for that animal. ( b , d ) Probability distributions of roll and pitch angles based on the last 15 h of the monitoring period for the Great Barrier Reef shark. Images in e , f were taken with a fin-mounted video camera attached to another wild S. mokarran ( ∼ 350 cm) as it swam rolled to the left and right (respectively) at South Bimini Island, the Bahamas, at absolute roll angles of ∼ 60° (see Supplementary Movie 2 for examples of this and other wild S. mokarran swimming rolled). Full size image Hydrodynamics of a swimming shark Hydrodynamic forces acting on a swimming shark can be conveniently divided into lift L , drag D , thrust T and buoyancy B . For simplicity, we will assume that the thrust is generated mainly by the caudal, anal and the second dorsal fins, and is directed along the swimming path, whereas lift and drag are generated by all other fins and by the body of the shark; they are directed perpendicular and parallel to the swimming path, respectively. When swimming at constant speed along a straight horizontal path, all forces cancel out with gravity, G : Lift and drag are commonly expressed in terms of the respective coefficients C L and C<|im_end|> <|im_start|>assistant Hammerhead sharks swim on their sides up to 90 per cent of the time to save energy, a Murdoch University researcher has found. Dr Adrian Gleiss from the Centre for Fish and Fisheries Research, collaborated on an international study which found the great hammerhead species spends up to 90 per cent of its time swimming at angles of between 50 and 70 degrees. This is thanks to an exaggerated dorsal fin which generates lift and helps to reduce drag when the sharks are rolled on their sides. Most sharks use their dorsal fins on their backs like a rudder on a boat, to facilitate quick turns. Their large pectoral fins on their sides are used like aircraft wings to keep them from sinking. It was thought this was how all sharks functioned until this study, which was led by Dr Nicholas Payne from the University of Roehampton, London. Dr Gleiss and the research team used video cameras and tagging to measure roll angles in hammerhead sharks in Belize, Australia and The Bahamas. "The co-lead author on our paper, Associate Professor Gil Iosilevskii, developed hydrodynamic modeling to show this swimming method reduces energy use by around 10 per cent, compared with traditional upright swimming," said Dr Gleiss. "Gil also conducted a series of experiments in a wind tunnel using a scale model of a hammerhead to find that minimal drag could be achieved at roll angles between 50 and 70 degrees, which closely matched the range of roll angles at which our tagged sharks swam in the wild." Dr Gleiss said understanding how animals reduce the effects of drag on their mobility could help mechanical engineers striving to find biometric solutions for man made designs. <|im_end|>

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1,607

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Tritium labelling is a critical tool for investigating the pharmacokinetic and pharmacodynamic properties of drugs, autoradiography, receptor binding and receptor occupancy studies 1 . Tritium gas is the preferred source of tritium for the preparation of labelled molecules because it is available in high isotopic purity 2 . The introduction of tritium labels from tritium gas is commonly achieved by heterogeneous transition-metal-catalysed tritiation of aryl (pseudo)halides. However, heterogeneous catalysts such as palladium supported on carbon operate through a reaction mechanism that also results in the reduction of other functional groups that are prominently featured in pharmaceuticals 3 . Homogeneous palladium catalysts can react chemoselectively with aryl (pseudo)halides but have not been used for hydrogenolysis reactions because, after required oxidative addition, they cannot split dihydrogen 4 . Here we report a homogenous hydrogenolysis reaction with a well defined, molecular palladium catalyst. We show how the thianthrene leaving group—which can be introduced selectively into pharmaceuticals by late-stage C–H functionalization 5 —differs in its coordinating ability to relevant palladium(II) catalysts from conventional leaving groups to enable the previously unrealized catalysis with dihydrogen. This distinct reactivity combined with the chemoselectivity of a well defined molecular palladium catalyst enables the tritiation of small-molecule pharmaceuticals that contain functionality that may otherwise not be tolerated by heterogeneous catalysts. The tritiation reaction does not require an inert atmosphere or dry conditions and is therefore practical and robust to execute, and could have an immediate impact in the discovery and development of pharmaceuticals. Main Tritium ( 3 H) labelling allows the direct incorporation of a radioactive tag into pharmaceutical candidates without substantial changes in their chemical and physical properties and biological activity 6 . However, many reliable hydrogenation or hydrogenolysis reactions cannot be suitably used for tritium labelling owing to a lack of reagents, low molar activity, restricted functional-group tolerance or safety concerns. Tritiated water ( 3 H 2 O) is problematic owing to fast washout of the label from omnipresent water and safety concerns regarding the potential fast uptake of radioactive water by experimentalists. The preferred source of tritium labels is tritium gas ( 3 H 2 ), which is available in high isotopic purity and practical to handle with commercially available manifolds on the small scale typically used for labelling 2 , 7 . Hydrogenation with hydrogen gas is one of the most extensively studied reactions in chemistry, with numerous important applications ranging from biomass degradation 8 to hydrogenolysis of otherwise persistent halogenated pollutants 9 . Several well defined, homogeneous transition-metal catalysts based on rhodium 10 , iridium 11 and ruthenium 12 can split the strong hydrogen–hydrogen bond for countless productive hydrogenation reactions of unsaturated bonds. However, appropriate unsaturated bonds are often not present in pharmaceuticals or would be destroyed by hydrogenation, and the same hydrogenation catalysts are generally not useful for the hydrogenolysis of carbon–halide bonds because most transition-metal hydrides are inactive towards the oxidative addition of carbon–heteroatom bonds. In the presence of both dihydrogen and aryl(pseudo)halides, dihydrogen oxidative addition is commonly faster, which results in metal hydrides in higher oxidation states that are not suitable for aryl (pseudo)halide oxidative addition 13 , 14 . Therefore, for the hydrogenolysis of carbon–heteroatom bonds 15 , chemists select heterogeneous catalysts, such as palladium supported on carbon, which can effectively reduce aryl(pseudo)halides through a mechanistically distinct pathway 16 , 17 . The reactivity of the active hydrogen chemisorbed on the catalyst surface results in low chemoselectivity, and the undesired reduction of other functional groups typically found in pharmaceuticals(Fig. 1a ) 3 . Fig. 1: Palladium-catalysed hydrogenolysis with molecular hydrogen. a , Heterogeneous Pd-catalysed hydrogenolysis with H 2 . b , Homogeneous Pd-catalysed hydrogenolysis of aryl halide. L, neutral 2-electron ligand. c , Homogeneous Pd-catalysed hydrogenolysis of aryl thianthrenium salt. d , Chemo- and site-selective C–H tritiation via arylthianthrenium salt by homogeneous palladium catalysis. X, conventional (pseudo)halide. Full size image Tritium for hydrogen exchange is a desirable way for tritium incorporation because prior functionalization is not required 18 . Several impressive hydrogen isotope exchange reactions have been developed with transition-metal catalysts, maybe most notably those based on iridium 19 , 20 and nickel 21 ; however, they require the presence of directing groups or heterocycles for efficient transformations. An aromatic hydrogen isotope exchange reaction that does not require directing groups was developed based on an iron catalyst, which provides successful tritiation complementary to the iridium-catalysed methods 22 . At present, the low-valent iron catalyst does not tolerate protic functional groups and requires an inert atmosphere, which complicates its routine, practical application in pharmaceutical development 23 , 24 . In addition, all hydrogen isotope exchange reactions typically afford several constitutional isomers with more than one label incorporated, which can be advantageous because high molar activity can be reached 25 , but may also render interpretation of imaging studies difficult when the labelled molecule is metabolized 26 . In that sense, a robust, practical, site-selective functionalization would be complementary to the hydrogen exchange reactions and could add significant value to the field 27 . Metal-catalysed hydrogenolysis proceeds through metal-hydride intermediates 28 that can be formed by dihydrogen oxidative addition. Transition-metal complexes that react with aryl (pseudo)halides through oxidative addition do not engage with dihydrogen in a second oxidative reaction to form metal hydrides. Heterolytic cleavage of the hydrogen–hydrogen bond can also result in the formation of metal hydrides 29 . For example, electrophilic transition-metal complexes of iridium 30 and ruthenium 31 can substantially acidify dihydrogen through complexation owing to a strong σ donor–acceptor interaction 29 , 32 , which can result in the formation of metal hydrides through deprotonation of the metal η 2 -dihydrogen complexes 33 . Only a few examples of palladium (Pd) dihydrogen complexes are known 4 , and no electrophilic Pd(II) catalysts—generated through oxidative addition of an aryl (pseudo)halide to low-valent palladium—have been shown to heterolyse dihydrogen 34 , 35 , 36 . Upon oxidative addition to a ligated Pd(0), no appropriate coordination site is available at square planar d 8 Pd(II) tetracoordinate complexes for dihydrogen coordination", "role": "user" }, { "content": "Tritium 3H, a radioactive isotope of hydrogen, is commonly used in medicinal chemistry as a label to follow the course of a drug in the human body. Chemists like to use the technique to evaluate drug candidates and their metabolism. A team led of researchers at the Max-Planck-Institut für Kohlenforschung in Mühlheim, Germany, has now found a new way to label complex small molecules with tritium. In a joint research project with the research and early development organization of the Swiss pharmaceutical company Roche, they investigated ways to incorporate tritium into pharmaceuticals and other similar molecules that are important derivatives for drug development. The team took advantage of the special properties of arylthianthrenium salts that they developed two years ago. The thianthrene group can be introduced into pharmaceuticals selectively and at a late stage in a direct and predictable manner. The new approach does not require an inert atmosphere or dry conditions, making it practical to use. \"The unusual feature of this work is the reaction of arylpseudohalides with hydrogen, catalyzed for the first time by a homogeneous catalyst,\" explains Tobias Ritter from the Max Planck Institute for Coal Research. \"Such reactions were previously unknown with conventional groups that can be introduced into pharmaceuticals. Normally, chemists use heterogeneous catalysts but those also often destroy other functional groups, which are frequently found in pharmaceuticals,\" the director annotates. The study is published in Nature. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Tritium labelling is a critical tool for investigating the pharmacokinetic and pharmacodynamic properties of drugs, autoradiography, receptor binding and receptor occupancy studies 1 . Tritium gas is the preferred source of tritium for the preparation of labelled molecules because it is available in high isotopic purity 2 . The introduction of tritium labels from tritium gas is commonly achieved by heterogeneous transition-metal-catalysed tritiation of aryl (pseudo)halides. However, heterogeneous catalysts such as palladium supported on carbon operate through a reaction mechanism that also results in the reduction of other functional groups that are prominently featured in pharmaceuticals 3 . Homogeneous palladium catalysts can react chemoselectively with aryl (pseudo)halides but have not been used for hydrogenolysis reactions because, after required oxidative addition, they cannot split dihydrogen 4 . Here we report a homogenous hydrogenolysis reaction with a well defined, molecular palladium catalyst. We show how the thianthrene leaving group—which can be introduced selectively into pharmaceuticals by late-stage C–H functionalization 5 —differs in its coordinating ability to relevant palladium(II) catalysts from conventional leaving groups to enable the previously unrealized catalysis with dihydrogen. This distinct reactivity combined with the chemoselectivity of a well defined molecular palladium catalyst enables the tritiation of small-molecule pharmaceuticals that contain functionality that may otherwise not be tolerated by heterogeneous catalysts. The tritiation reaction does not require an inert atmosphere or dry conditions and is therefore practical and robust to execute, and could have an immediate impact in the discovery and development of pharmaceuticals. Main Tritium ( 3 H) labelling allows the direct incorporation of a radioactive tag into pharmaceutical candidates without substantial changes in their chemical and physical properties and biological activity 6 . However, many reliable hydrogenation or hydrogenolysis reactions cannot be suitably used for tritium labelling owing to a lack of reagents, low molar activity, restricted functional-group tolerance or safety concerns. Tritiated water ( 3 H 2 O) is problematic owing to fast washout of the label from omnipresent water and safety concerns regarding the potential fast uptake of radioactive water by experimentalists. The preferred source of tritium labels is tritium gas ( 3 H 2 ), which is available in high isotopic purity and practical to handle with commercially available manifolds on the small scale typically used for labelling 2 , 7 . Hydrogenation with hydrogen gas is one of the most extensively studied reactions in chemistry, with numerous important applications ranging from biomass degradation 8 to hydrogenolysis of otherwise persistent halogenated pollutants 9 . Several well defined, homogeneous transition-metal catalysts based on rhodium 10 , iridium 11 and ruthenium 12 can split the strong hydrogen–hydrogen bond for countless productive hydrogenation reactions of unsaturated bonds. However, appropriate unsaturated bonds are often not present in pharmaceuticals or would be destroyed by hydrogenation, and the same hydrogenation catalysts are generally not useful for the hydrogenolysis of carbon–halide bonds because most transition-metal hydrides are inactive towards the oxidative addition of carbon–heteroatom bonds. In the presence of both dihydrogen and aryl(pseudo)halides, dihydrogen oxidative addition is commonly faster, which results in metal hydrides in higher oxidation states that are not suitable for aryl (pseudo)halide oxidative addition 13 , 14 . Therefore, for the hydrogenolysis of carbon–heteroatom bonds 15 , chemists select heterogeneous catalysts, such as palladium supported on carbon, which can effectively reduce aryl(pseudo)halides through a mechanistically distinct pathway 16 , 17 . The reactivity of the active hydrogen chemisorbed on the catalyst surface results in low chemoselectivity, and the undesired reduction of other functional groups typically found in pharmaceuticals(Fig. 1a ) 3 . Fig. 1: Palladium-catalysed hydrogenolysis with molecular hydrogen. a , Heterogeneous Pd-catalysed hydrogenolysis with H 2 . b , Homogeneous Pd-catalysed hydrogenolysis of aryl halide. L, neutral 2-electron ligand. c , Homogeneous Pd-catalysed hydrogenolysis of aryl thianthrenium salt. d , Chemo- and site-selective C–H tritiation via arylthianthrenium salt by homogeneous palladium catalysis. X, conventional (pseudo)halide. Full size image Tritium for hydrogen exchange is a desirable way for tritium incorporation because prior functionalization is not required 18 . Several impressive hydrogen isotope exchange reactions have been developed with transition-metal catalysts, maybe most notably those based on iridium 19 , 20 and nickel 21 ; however, they require the presence of directing groups or heterocycles for efficient transformations. An aromatic hydrogen isotope exchange reaction that does not require directing groups was developed based on an iron catalyst, which provides successful tritiation complementary to the iridium-catalysed methods 22 . At present, the low-valent iron catalyst does not tolerate protic functional groups and requires an inert atmosphere, which complicates its routine, practical application in pharmaceutical development 23 , 24 . In addition, all hydrogen isotope exchange reactions typically afford several constitutional isomers with more than one label incorporated, which can be advantageous because high molar activity can be reached 25 , but may also render interpretation of imaging studies difficult when the labelled molecule is metabolized 26 . In that sense, a robust, practical, site-selective functionalization would be complementary to the hydrogen exchange reactions and could add significant value to the field 27 . Metal-catalysed hydrogenolysis proceeds through metal-hydride intermediates 28 that can be formed by dihydrogen oxidative addition. Transition-metal complexes that react with aryl (pseudo)halides through oxidative addition do not engage with dihydrogen in a second oxidative reaction to form metal hydrides. Heterolytic cleavage of the hydrogen–hydrogen bond can also result in the formation of metal hydrides 29 . For example, electrophilic transition-metal complexes of iridium 30 and ruthenium 31 can substantially acidify dihydrogen through complexation owing to a strong σ donor–acceptor interaction 29 , 32 , which can result in the formation of metal hydrides through deprotonation of the metal η 2 -dihydrogen complexes 33 . Only a few examples of palladium (Pd) dihydrogen complexes are known 4 , and no electrophilic Pd(II) catalysts—generated through oxidative addition of an aryl (pseudo)halide to low-valent palladium—have been shown to heterolyse dihydrogen 34 , 35 , 36 . Upon oxidative addition to a ligated Pd(0), no appropriate coordination site is available at square planar d 8 Pd(II) tetracoordinate complexes for dihydrogen coordination<|im_end|> <|im_start|>assistant Tritium 3H, a radioactive isotope of hydrogen, is commonly used in medicinal chemistry as a label to follow the course of a drug in the human body. Chemists like to use the technique to evaluate drug candidates and their metabolism. A team led of researchers at the Max-Planck-Institut für Kohlenforschung in Mühlheim, Germany, has now found a new way to label complex small molecules with tritium. In a joint research project with the research and early development organization of the Swiss pharmaceutical company Roche, they investigated ways to incorporate tritium into pharmaceuticals and other similar molecules that are important derivatives for drug development. The team took advantage of the special properties of arylthianthrenium salts that they developed two years ago. The thianthrene group can be introduced into pharmaceuticals selectively and at a late stage in a direct and predictable manner. The new approach does not require an inert atmosphere or dry conditions, making it practical to use. "The unusual feature of this work is the reaction of arylpseudohalides with hydrogen, catalyzed for the first time by a homogeneous catalyst," explains Tobias Ritter from the Max Planck Institute for Coal Research. "Such reactions were previously unknown with conventional groups that can be introduced into pharmaceuticals. Normally, chemists use heterogeneous catalysts but those also often destroy other functional groups, which are frequently found in pharmaceuticals," the director annotates. The study is published in Nature. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The strong interaction is not well understood at low energies or for interactions with low momentum transfer. Chiral perturbation theory gives testable predictions for the nucleonic generalized polarizabilities, which are fundamental quantities describing the nucleon’s response to an external field. We report a measurement of the proton’s generalized spin polarizabilities extracted with a polarized electron beam and a polarized solid ammonia target in the region where chiral perturbation theory is expected to be valid. The investigated structure function g 2 characterizes the internal spin structure of the proton. From its moments, we extract the longitudinal–transverse spin polarizability δ LT and twist-3 matrix element and polarizability \$\\overline{{d}_{2}}\$ . Our results provide discriminating power between existing chiral perturbation theory calculations and will help provide a better understanding of this strong quantum chromodynamics regime. Main The proton accounts for the vast majority of ordinary matter in the Universe, but how its fundamental properties such as mass and spin arise from the interactions of its constituents remains an open question. The proton’s sub-structure is well understood in the high-energy short-distance region of asymptotic freedom 1 . Conversely, in the low-energy regime where the quantum chromodynamics (QCD) coupling becomes truly strong, quark–quark and quark–gluon correlations invalidate the simple picture of the parton model. Unresolved questions about the structure of the proton can be probed with spin-polarized electron–proton scattering, but this region carries a number of experimental challenges that make data scarce. These challenges are especially difficult at low energy for transversely polarized protons, as a low-energy incident electron beam will suffer severe bending in the transverse target magnetic field, introducing a number of systematic issues. The nucleons are not yet well understood in this regime. For example, neutron data 2 revealed a large discrepancy between moments of the spin structure functions and early calculations of chiral perturbation theory (χPT). This discrepancy became known as the ‘ δ LT puzzle’ and stimulated a rigorous new generation of theoretical efforts and low- Q 2 experiments such as the present measurement. Though some light has been shed on the initial disagreement, the newest neutron data 3 still show a large deviation from χPT, making it very important to examine if similar issues exist for the proton. Several recently published experiments 3 , 4 have probed the low- and medium-energy regions of the spin structure function \${g}_{1}^{\\mathrm{p}}\$ and the medium-energy region of the spin structure function \${g}_{2}^{\\mathrm{p}}\$ . Our experiment expands on those results with low-energy measurements of \${g}_{2}^{\\mathrm{p}}\$ and its associated moments. Sum rules and moments of the nucleon spin structure functions allow for a direct comparison between experiment and theory. In recent years, the Bjorken sum rule 5 at large Q 2 and the Gerasimov–Drell–Hearn (GDH) sum rule 6 at Q 2 = 0 have been extensively investigated 7 , 8 , 9 , 10 , 11 . Less well studied for the proton is another class of sum rules addressing the spin polarizabilities 12 , 13 . Spin polarizabilities are fundamental properties of the nucleons, making their measurement and comparison to theory of great interest. Polarizabilities, in general, describe the proton’s response to an external field. The electric and magnetic polarizabilities are relatively well measured for the proton, but less well understood are the spin and colour polarizabilities. Spin polarizabilities describe a spin-dependent response of the nucleon to an electromagnetic field, whereas colour polarizabilities contain information on how the nucleon’s spin affects the colour electric and magnetic fields on average 14 , 15 . Of particular interest is the spin polarizability δ LT and the higher moment \$\\overline{{d}_{2}}\$ related to the colour polarizabilities at large Q 2 . The sum rules used to obtain these moments are based on unsubtracted dispersion relations, which use the optical theorem to relate moments of the spin structure functions to real or virtual Compton amplitudes 16 . The doubly virtual Compton-scattering dispersion relations are used to form a low-energy expansion of the spin-flip Compton amplitudes f TT and f LT (ref. 17 ), giving rise to a number of spin structure function moments. The next-to-leading order term of the f LT low-energy expansion contains the following generalized longitudinal–transverse spin polarizability: $${\\delta }_{\\mathrm{LT}}({Q}^{2})=\\frac{16\\alpha {M}^{2}}{{Q}^{6}}\\int\\nolimits_{0}^{{x}_{0}}{x}^{2}\\left({g}_{1}(x,{Q}^{2})+{g}_{2}(x,{Q}^{2})\\right)\\mathrm{d}x.$$ (1) Here Q 2 is the four-momentum transfer, α is the fine-structure constant, M represents the proton mass and x 0 represents the Bjorken x value associated with the pion production threshold at an invariant mass (defined as W 2 = M 2 + 2 M ν − Q 2 ) for W = 1,073.2 MeV. This limit ensures that the elastic response is excluded from the integral as is required for pure polarizability 15 . A measurement of the generalized longitudinal–transverse polarizability is considered a benchmark test of χPT because it is a fundamental nucleon observable and was initially expected to be insensitive to contributions from virtual π – Δ intermediate states 18 , 19 . The actual contribution of these states has ultimately proved to be more complicated. The χPT predictions for δ LT at leading order and next-to-leading order are, in principle, parameter-free predictions, the accuracy of which is only determined by the convergence properties of chiral expansion. Precise comparisons of this quantity between data and theory are, therefore, extremely valuable to test χPT and other low-energy theories. Also of interest is the \$\\overline{{d}_{2}}\$ spin polarizability, a higher moment identified at high Q 2 with the twist-3 matrix element d 2 (ref. 14 ). We can access a truncated moment of this quantity through a sum rule: $$\\overline{{d}_{2}}({Q}^{2})=\\int\\nolimits_{0}^{{x}_{0}}{x}^{2}\\left(2{g}_{1}(x,{Q}^{2})+3{g}_{2}(x,{Q}^{2})\\right)\\mathrm{d}x.$$ (2) At high Q 2 , this moment describes the ‘colour Lorentz force’ and gives us information on the colour polarizabilities discussed above. Consequently, \$\\overline{{d}_{2}}\$ helps to describe how the colour electric and magnetic fields interact with the nucleon spin 14 . In this regime, \$\\overline{{d}_{2}}\$ becomes a twist-3 quantity and thus quantifies the quark–gluon correlations of the nucleon 20 . At low Q 2 , the partonic description of \$\\overline{{d}_{2}}\$ fails, but it remains pure polarizability that contains information on the nucleon’s bulk properties", "role": "user" }, { "content": "Quantum chromodynamics is an area of study that explores the strong interactions between quarks mediated by gluons. Quarks are elementary particles with an electric charge, which are building blocks of composite particles, such as hadrons and protons. Some aspects of the strong interactions in the quantum chromodynamics regime are still poorly understood, particularly when it comes to interactions at low energies and with low momentum transfer. One theory that makes predictions about nucleonic generalized polarizabilities (i.e., fundamental quantities describing the nucleon's response to an external field in quantum chromodynamics), is chiral perturbation theory. Chiral perturbation is an effective field theory aligned with the estimated chiral symmetry of quantum chromodynamics. This theory is often used to study low-energy interactions in the quantum chromodynamics regime, particularly in terms of their underlying chiral symmetry. Researchers at University of New Hampshire, University of Virginia, The College of William and Mary, and other institutes in the U.S. and China have recently tested the predictions of chiral perturbation theory in an experimental setting. Their paper, published in Nature Physics, offers a measurement of the spin structure and generalized polarizabilities of a proton in the strong quantum chromodynamics regime. \"There are only a handful of characteristics that summarize the properties of the proton— the mass, charge, etc.,\" Karl Slifer, one of the researchers who carried out the study, told Phys.org. \"Given the proton's role as a foundational particle in all visible matter, it's really important that we understand these few properties well. About a decade ago it became clear that the theoretical understanding of one of these quantities—known as a generalized spin polarizability—was very unsatisfactory.\" The key objective of the recent work by Slifer and his colleagues was to measure generalized a proton's spin polarizability in a reliable way. To do this, they used a solid polarized ammonia (NH3) target with a strong magnetic field, oriented perpendicular to the direction of an incident electron beam. \"Our design causes a large deflection of the beam as it passes through the field on the way to the target,\" Slifer explained. \"Therefore, it required a lot of engineering to deliver the beam onto the target and years of analysis to extract the reaction cross section from the scattered electrons that emerged from the target.\" Using the measurements they collected, Slifer and his colleagues were able to characterize the internal spin structure of individual protons (i.e., subatomic particles found in the nucleus of atoms). From their data, they also extracted the proton's longitudinal-transverse spin polarizability, twist-3 matrix element, and polarizability d2, crucial parameters estimated by chiral perturbation theory. \"There are two main groups of theorists who are performing calculations for this quantity,\" Slifer said. \"These groups employ slightly different approaches, but both predictions in principle follow directly from the same assumptions and symmetries as Quantum Chromodynamics (QCD). QCD is the theory of the strong force—one of only four known forces in nature—and direct tests of QCD are notoriously hard to come by.\" Ultimately, to ascertain the validity of theoretical predictions, these predictions need to be tested in an experimental setting. The findings gathered by Slifer and his colleagues can be used to validate predictions made by chiral perturbation theory, which can in turn improve our understanding the strong quantum chromodynamics regime, including the spin structure and generalized spin polarizabilities of protons. \"Transversely polarized proton data is historically scarce because these experiments are so difficult to run and to analyze,\" Slifer added. \"But our results show that this kind of data is really helpful to clarify how exactly the spin-dependent properties of the proton arise. We've been asked by our theory colleagues to expand these measurements to higher energy. It's another very difficult experiment that will take years to run and analyze, but it should be completed.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The strong interaction is not well understood at low energies or for interactions with low momentum transfer. Chiral perturbation theory gives testable predictions for the nucleonic generalized polarizabilities, which are fundamental quantities describing the nucleon’s response to an external field. We report a measurement of the proton’s generalized spin polarizabilities extracted with a polarized electron beam and a polarized solid ammonia target in the region where chiral perturbation theory is expected to be valid. The investigated structure function g 2 characterizes the internal spin structure of the proton. From its moments, we extract the longitudinal–transverse spin polarizability δ LT and twist-3 matrix element and polarizability $\overline{{d}_{2}}$ . Our results provide discriminating power between existing chiral perturbation theory calculations and will help provide a better understanding of this strong quantum chromodynamics regime. Main The proton accounts for the vast majority of ordinary matter in the Universe, but how its fundamental properties such as mass and spin arise from the interactions of its constituents remains an open question. The proton’s sub-structure is well understood in the high-energy short-distance region of asymptotic freedom 1 . Conversely, in the low-energy regime where the quantum chromodynamics (QCD) coupling becomes truly strong, quark–quark and quark–gluon correlations invalidate the simple picture of the parton model. Unresolved questions about the structure of the proton can be probed with spin-polarized electron–proton scattering, but this region carries a number of experimental challenges that make data scarce. These challenges are especially difficult at low energy for transversely polarized protons, as a low-energy incident electron beam will suffer severe bending in the transverse target magnetic field, introducing a number of systematic issues. The nucleons are not yet well understood in this regime. For example, neutron data 2 revealed a large discrepancy between moments of the spin structure functions and early calculations of chiral perturbation theory (χPT). This discrepancy became known as the ‘ δ LT puzzle’ and stimulated a rigorous new generation of theoretical efforts and low- Q 2 experiments such as the present measurement. Though some light has been shed on the initial disagreement, the newest neutron data 3 still show a large deviation from χPT, making it very important to examine if similar issues exist for the proton. Several recently published experiments 3 , 4 have probed the low- and medium-energy regions of the spin structure function ${g}_{1}^{\mathrm{p}}$ and the medium-energy region of the spin structure function ${g}_{2}^{\mathrm{p}}$ . Our experiment expands on those results with low-energy measurements of ${g}_{2}^{\mathrm{p}}$ and its associated moments. Sum rules and moments of the nucleon spin structure functions allow for a direct comparison between experiment and theory. In recent years, the Bjorken sum rule 5 at large Q 2 and the Gerasimov–Drell–Hearn (GDH) sum rule 6 at Q 2 = 0 have been extensively investigated 7 , 8 , 9 , 10 , 11 . Less well studied for the proton is another class of sum rules addressing the spin polarizabilities 12 , 13 . Spin polarizabilities are fundamental properties of the nucleons, making their measurement and comparison to theory of great interest. Polarizabilities, in general, describe the proton’s response to an external field. The electric and magnetic polarizabilities are relatively well measured for the proton, but less well understood are the spin and colour polarizabilities. Spin polarizabilities describe a spin-dependent response of the nucleon to an electromagnetic field, whereas colour polarizabilities contain information on how the nucleon’s spin affects the colour electric and magnetic fields on average 14 , 15 . Of particular interest is the spin polarizability δ LT and the higher moment $\overline{{d}_{2}}$ related to the colour polarizabilities at large Q 2 . The sum rules used to obtain these moments are based on unsubtracted dispersion relations, which use the optical theorem to relate moments of the spin structure functions to real or virtual Compton amplitudes 16 . The doubly virtual Compton-scattering dispersion relations are used to form a low-energy expansion of the spin-flip Compton amplitudes f TT and f LT (ref. 17 ), giving rise to a number of spin structure function moments. The next-to-leading order term of the f LT low-energy expansion contains the following generalized longitudinal–transverse spin polarizability: $${\delta }_{\mathrm{LT}}({Q}^{2})=\frac{16\alpha {M}^{2}}{{Q}^{6}}\int\nolimits_{0}^{{x}_{0}}{x}^{2}\left({g}_{1}(x,{Q}^{2})+{g}_{2}(x,{Q}^{2})\right)\mathrm{d}x.$$ (1) Here Q 2 is the four-momentum transfer, α is the fine-structure constant, M represents the proton mass and x 0 represents the Bjorken x value associated with the pion production threshold at an invariant mass (defined as W 2 = M 2 + 2 M ν − Q 2 ) for W = 1,073.2 MeV. This limit ensures that the elastic response is excluded from the integral as is required for pure polarizability 15 . A measurement of the generalized longitudinal–transverse polarizability is considered a benchmark test of χPT because it is a fundamental nucleon observable and was initially expected to be insensitive to contributions from virtual π – Δ intermediate states 18 , 19 . The actual contribution of these states has ultimately proved to be more complicated. The χPT predictions for δ LT at leading order and next-to-leading order are, in principle, parameter-free predictions, the accuracy of which is only determined by the convergence properties of chiral expansion. Precise comparisons of this quantity between data and theory are, therefore, extremely valuable to test χPT and other low-energy theories. Also of interest is the $\overline{{d}_{2}}$ spin polarizability, a higher moment identified at high Q 2 with the twist-3 matrix element d 2 (ref. 14 ). We can access a truncated moment of this quantity through a sum rule: $$\overline{{d}_{2}}({Q}^{2})=\int\nolimits_{0}^{{x}_{0}}{x}^{2}\left(2{g}_{1}(x,{Q}^{2})+3{g}_{2}(x,{Q}^{2})\right)\mathrm{d}x.$$ (2) At high Q 2 , this moment describes the ‘colour Lorentz force’ and gives us information on the colour polarizabilities discussed above. Consequently, $\overline{{d}_{2}}$ helps to describe how the colour electric and magnetic fields interact with the nucleon spin 14 . In this regime, $\overline{{d}_{2}}$ becomes a twist-3 quantity and thus quantifies the quark–gluon correlations of the nucleon 20 . At low Q 2 , the partonic description of $\overline{{d}_{2}}$ fails, but it remains pure polarizability that contains information on the nucleon’s bulk properties<|im_end|> <|im_start|>assistant Quantum chromodynamics is an area of study that explores the strong interactions between quarks mediated by gluons. Quarks are elementary particles with an electric charge, which are building blocks of composite particles, such as hadrons and protons. Some aspects of the strong interactions in the quantum chromodynamics regime are still poorly understood, particularly when it comes to interactions at low energies and with low momentum transfer. One theory that makes predictions about nucleonic generalized polarizabilities (i.e., fundamental quantities describing the nucleon's response to an external field in quantum chromodynamics), is chiral perturbation theory. Chiral perturbation is an effective field theory aligned with the estimated chiral symmetry of quantum chromodynamics. This theory is often used to study low-energy interactions in the quantum chromodynamics regime, particularly in terms of their underlying chiral symmetry. Researchers at University of New Hampshire, University of Virginia, The College of William and Mary, and other institutes in the U.S. and China have recently tested the predictions of chiral perturbation theory in an experimental setting. Their paper, published in Nature Physics, offers a measurement of the spin structure and generalized polarizabilities of a proton in the strong quantum chromodynamics regime. "There are only a handful of characteristics that summarize the properties of the proton— the mass, charge, etc.," Karl Slifer, one of the researchers who carried out the study, told Phys.org. "Given the proton's role as a foundational particle in all visible matter, it's really important that we understand these few properties well. About a decade ago it became clear that the theoretical understanding of one of these quantities—known as a generalized spin polarizability—was very unsatisfactory." The key objective of the recent work by Slifer and his colleagues was to measure generalized a proton's spin polarizability in a reliable way. To do this, they used a solid polarized ammonia (NH3) target with a strong magnetic field, oriented perpendicular to the direction of an incident electron beam. "Our design causes a large deflection of the beam as it passes through the field on the way to the target," Slifer explained. "Therefore, it required a lot of engineering to deliver the beam onto the target and years of analysis to extract the reaction cross section from the scattered electrons that emerged from the target." Using the measurements they collected, Slifer and his colleagues were able to characterize the internal spin structure of individual protons (i.e., subatomic particles found in the nucleus of atoms). From their data, they also extracted the proton's longitudinal-transverse spin polarizability, twist-3 matrix element, and polarizability d2, crucial parameters estimated by chiral perturbation theory. "There are two main groups of theorists who are performing calculations for this quantity," Slifer said. "These groups employ slightly different approaches, but both predictions in principle follow directly from the same assumptions and symmetries as Quantum Chromodynamics (QCD). QCD is the theory of the strong force—one of only four known forces in nature—and direct tests of QCD are notoriously hard to come by." Ultimately, to ascertain the validity of theoretical predictions, these predictions need to be tested in an experimental setting. The findings gathered by Slifer and his colleagues can be used to validate predictions made by chiral perturbation theory, which can in turn improve our understanding the strong quantum chromodynamics regime, including the spin structure and generalized spin polarizabilities of protons. "Transversely polarized proton data is historically scarce because these experiments are so difficult to run and to analyze," Slifer added. "But our results show that this kind of data is really helpful to clarify how exactly the spin-dependent properties of the proton arise. We've been asked by our theory colleagues to expand these measurements to higher energy. It's another very difficult experiment that will take years to run and analyze, but it should be completed." <|im_end|>

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2,376

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Many rotating stars have magnetic fields that interact with the winds they produce. The Sun is no exception. The interaction between the Sun’s magnetic field and the solar wind gives rise to the heliospheric magnetic field—a spiralling magnetic structure, known as the Parker spiral, which pervades the Solar System. This magnetic field is critical for governing plasma processes that source the solar wind. Here, we report the creation of a laboratory model of the Parker spiral system based on a rapidly rotating plasma magnetosphere and the measurement of its global structure and dynamic behaviour. This laboratory system exhibits regions where the plasma flows evolve in a similar manner to many magnetized stellar winds. We observe the advection of the magnetic field into an Archimedean spiral and the ejection of quasi-periodic plasma blobs into the stellar outflow, which mimics the observed plasmoids that fuel the slow solar wind. This process involves magnetic reconnection and can be modelled numerically by the inclusion of two-fluid effects in the simulation. The Parker spiral system mimicked in the laboratory can be used for studying solar wind dynamics in a complementary fashion to conventional space missions such as NASA’s Parker Solar Probe mission. Main In 1958, Eugene Parker first predicted the existence of the supersonic solar wind 1 , which was subsequently verified by early spacecraft missions 2 , 3 . He also theorized how this solar wind interacts with the dynamo-generated magnetic field of the Sun—carrying the magnetic field lines away from the star, while their footpoints are frozen into the corona and twisted into an Archimedean spiral by stellar rotation. This magnetic topology is now known as the Parker spiral and is the largest magnetic structure in the heliosphere. The transition between the magnetic field co-rotating with a star and the field advected by the wind is thought to occur near the so-called Alfvén surface, where inertial forces in the wind can stretch and bend the magnetic field. According to the governing equations of magnetohydrodynamics (MHD), this transition in a magnetic field like that of the Sun is singular in nature and therefore suspected to be highly dynamic 4 , 5 . However, this region has rarely been observed in situ by spacecraft and is presently the primary focus of the Parker Solar Probe mission 6 , 7 . Here we show, in a synergistic approach to studying solar wind dynamics, that the large-scale magnetic topology of the Parker spiral can also be created and studied in the laboratory. By generating a rotating magnetosphere with Alfvénic flows, magnetic field lines are advected into an Archimedean spiral, giving rise to a dynamic current sheet that undergoes magnetic reconnection and plasmoid ejection. These plasmoids are born near the Alfvén surface, at the tip of the helmet streamer, and carry blobs of plasma outwards at super-Alfvénic speeds, mimicking the dynamics of unstable coronal helmet streamers, which are thought to fuel a significant portion of the slow solar wind 8 , 9 , 10 . As the solar wind evolves from the lower corona to 1 au , the governing dynamics change dramatically as the plasma is accelerated outward and the magnetic field of the Sun decreases. The solar wind experiences three primary dynamical interfaces—regions where the dominant plasma forces change in nature. These three interfaces are the transonic, trans-Alfvénic and trans- β zones 1 , 11 , 12 . They characterize where the solar wind speed becomes supersonic, where it becomes super-Alfvénic (inertial forces dominate magnetic forces, that is \$V_{{\\mathrm{Alfven}}} = B/\\sqrt {\\mu _0m_{\\mathrm{i}}n} < V_{\\mathrm{sw}}\$ ), and where the plasma pressure overcomes the magnetic pressure (that is, β = 2 μ 0 nT / B 2 > 1), respectively. These transition zones depend on the magnetic field strength B , the plasma density n , the plasma temperature T , the ion mass m i and the local solar wind speed V sw . As a result, the transitions are governed by the interaction between the magnetic topology of the Sun and the plasma acceleration and heating mechanisms in the corona. This interaction results in complex, often overlapping, transition zones that vary wildly with heliographic latitude as well as heliocentric distance and give rise to the wide range of characteristics exhibited by the solar wind 13 , 14 . Many spacecraft missions since the early 1960s have been dedicated to observing and categorizing the composition, speed, density and magnetic field of the solar wind from various vantage points to gain insight into the origins and acceleration of the solar wind 15 . Possibly none of these missions is more famous than Ulysses, which was the first to fly over the solar poles and discovered that the ‘fast’ solar wind tends to come from the open field lines of coronal holes, whereas the ‘slow’ solar wind has its origins in the equatorial streamer belt 16 . However, the mechanisms that transport the slow solar wind plasma from closed field lines in the streamer belt to the open field lines of the Parker spiral are more ambiguous and have motivated theoretical, computational and observational work dedicated to elucidating this issue 5 , 17 , 18 , 19 , 20 . Despite the fundamental role these dynamical interfaces play in the origin and evolution of the solar wind, they have received little experimental attention. Nevertheless, a laboratory model of this system is not only possible, but provides new insight into the behaviour of dynamical interfaces relevant to the evolution of stellar winds, with special attention given to the dynamics near the Alfvén and β = 1 surfaces. In this Article, we report the creation of a laboratory model of the Parker spiral system and the measurement of its global structure and dynamic behaviour. This system is realized by producing a rotating plasma magnetosphere whose magnetic topology evolves from a closed magnetosphere into an Archimedean spiral. We show that this system develops interface regions where V ≈ V Alfvén and β ≈ 1, which become highly dynamic and result", "role": "user" }, { "content": "The sun's solar wind affects nearly everything in the solar system. It can disrupt the function of Earth's satellites and creates the lights of the auroras. A new study by University of Wisconsin-Madison physicists mimicked solar winds in the lab, confirming how they develop and providing an Earth-bound model for the future study of solar physics. Our sun is essentially a big ball of hot plasma—an energetic state of matter made up of ionized gas. As the sun spins, the plasma spins along, too. This plasma movement in the core of the sun produces a magnetic field that fills the solar atmosphere. At some distance from the sun's surface, known as the Alfvén surface, this magnetic field weakens and plasma breaks away from the sun, creating the solar wind. \"The solar wind is highly variable, but there are essentially two types: fast and slow,\" explains Ethan Peterson, a graduate student in the department of physics at UW-Madison and lead author of the study published online July 29 in Nature Physics. \"Satellite missions have documented pretty well where the fast wind comes from, so we were trying to study specifically how the slow solar wind is generated and how it evolves as it travels toward Earth.\" Peterson and his colleagues, including physics professor Cary Forest, may not have direct access to the big plasma ball of the sun, but they do have access to the next best thing: the Big Red Ball. The Big Red Ball is a three-meter-wide hollow sphere, with a strong magnet at its center and various probes inside. The researchers pump helium gas in, ionize it to create a plasma, and then apply an electric current that, along with the magnetic field, stirs the plasma, creating a near-perfect mimic of the spinning plasma and electromagnetic fields of the sun. With their mini-sun in place, the researchers can take measurements at many points inside the ball, allowing them to study solar phenomena in three dimensions. First, they were able to recreate the Parker Spiral, a magnetic field that fills the entire solar system named for the scientist who first described the solar wind. Below the Alfvén surface, the magnetic field radiates straight out from the Sun. But at that surface, solar wind dynamics take over, dragging the magnetic field into a spiral. \"Satellite measurements are pretty consistent with the Parker Spiral model, but only at one point at a time, so you'd never be able to make a simultaneous, large-scale map of it like we can in the lab.\" Peterson says. \"Our experimental measurements confirm Parker's theory of how it is created by these plasma flows.\" The researchers were also able to identify the source of the Sun's plasma \"burps,\" small, periodic ejections of plasma that fuel the slow solar wind. With the plasma spinning, they probed the magnetic field and the speed of the plasma. Their data mapped a region where the plasma was moving fast enough and the magnetic field was weak enough that the plasma could break off and eject radially. \"These ejections are observed by satellites, but no one knows what drives them,\" Peterson says. \"We ended up seeing very similar burps in our experiment, and identified how they develop.\" The researchers stress that their Earth-bound experiments complement, but don't replaceme, satellite missions. For example, the Parker Solar Probe, launched in August 2018, is expected to reach and even dip below the Alfvén surface. It will provide direct measurements of solar wind never obtained before. \"Our work shows that laboratory experiments can also get at the fundamental physics of these processes,\" Peterson says. \"And because the Big Red Ball is now funded as a National User Facility, it says to the science community: If you want to study the physics of solar wind, you can do that here.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Many rotating stars have magnetic fields that interact with the winds they produce. The Sun is no exception. The interaction between the Sun’s magnetic field and the solar wind gives rise to the heliospheric magnetic field—a spiralling magnetic structure, known as the Parker spiral, which pervades the Solar System. This magnetic field is critical for governing plasma processes that source the solar wind. Here, we report the creation of a laboratory model of the Parker spiral system based on a rapidly rotating plasma magnetosphere and the measurement of its global structure and dynamic behaviour. This laboratory system exhibits regions where the plasma flows evolve in a similar manner to many magnetized stellar winds. We observe the advection of the magnetic field into an Archimedean spiral and the ejection of quasi-periodic plasma blobs into the stellar outflow, which mimics the observed plasmoids that fuel the slow solar wind. This process involves magnetic reconnection and can be modelled numerically by the inclusion of two-fluid effects in the simulation. The Parker spiral system mimicked in the laboratory can be used for studying solar wind dynamics in a complementary fashion to conventional space missions such as NASA’s Parker Solar Probe mission. Main In 1958, Eugene Parker first predicted the existence of the supersonic solar wind 1 , which was subsequently verified by early spacecraft missions 2 , 3 . He also theorized how this solar wind interacts with the dynamo-generated magnetic field of the Sun—carrying the magnetic field lines away from the star, while their footpoints are frozen into the corona and twisted into an Archimedean spiral by stellar rotation. This magnetic topology is now known as the Parker spiral and is the largest magnetic structure in the heliosphere. The transition between the magnetic field co-rotating with a star and the field advected by the wind is thought to occur near the so-called Alfvén surface, where inertial forces in the wind can stretch and bend the magnetic field. According to the governing equations of magnetohydrodynamics (MHD), this transition in a magnetic field like that of the Sun is singular in nature and therefore suspected to be highly dynamic 4 , 5 . However, this region has rarely been observed in situ by spacecraft and is presently the primary focus of the Parker Solar Probe mission 6 , 7 . Here we show, in a synergistic approach to studying solar wind dynamics, that the large-scale magnetic topology of the Parker spiral can also be created and studied in the laboratory. By generating a rotating magnetosphere with Alfvénic flows, magnetic field lines are advected into an Archimedean spiral, giving rise to a dynamic current sheet that undergoes magnetic reconnection and plasmoid ejection. These plasmoids are born near the Alfvén surface, at the tip of the helmet streamer, and carry blobs of plasma outwards at super-Alfvénic speeds, mimicking the dynamics of unstable coronal helmet streamers, which are thought to fuel a significant portion of the slow solar wind 8 , 9 , 10 . As the solar wind evolves from the lower corona to 1 au , the governing dynamics change dramatically as the plasma is accelerated outward and the magnetic field of the Sun decreases. The solar wind experiences three primary dynamical interfaces—regions where the dominant plasma forces change in nature. These three interfaces are the transonic, trans-Alfvénic and trans- β zones 1 , 11 , 12 . They characterize where the solar wind speed becomes supersonic, where it becomes super-Alfvénic (inertial forces dominate magnetic forces, that is $V_{{\mathrm{Alfven}}} = B/\sqrt {\mu _0m_{\mathrm{i}}n} < V_{\mathrm{sw}}$ ), and where the plasma pressure overcomes the magnetic pressure (that is, β = 2 μ 0 nT / B 2 > 1), respectively. These transition zones depend on the magnetic field strength B , the plasma density n , the plasma temperature T , the ion mass m i and the local solar wind speed V sw . As a result, the transitions are governed by the interaction between the magnetic topology of the Sun and the plasma acceleration and heating mechanisms in the corona. This interaction results in complex, often overlapping, transition zones that vary wildly with heliographic latitude as well as heliocentric distance and give rise to the wide range of characteristics exhibited by the solar wind 13 , 14 . Many spacecraft missions since the early 1960s have been dedicated to observing and categorizing the composition, speed, density and magnetic field of the solar wind from various vantage points to gain insight into the origins and acceleration of the solar wind 15 . Possibly none of these missions is more famous than Ulysses, which was the first to fly over the solar poles and discovered that the ‘fast’ solar wind tends to come from the open field lines of coronal holes, whereas the ‘slow’ solar wind has its origins in the equatorial streamer belt 16 . However, the mechanisms that transport the slow solar wind plasma from closed field lines in the streamer belt to the open field lines of the Parker spiral are more ambiguous and have motivated theoretical, computational and observational work dedicated to elucidating this issue 5 , 17 , 18 , 19 , 20 . Despite the fundamental role these dynamical interfaces play in the origin and evolution of the solar wind, they have received little experimental attention. Nevertheless, a laboratory model of this system is not only possible, but provides new insight into the behaviour of dynamical interfaces relevant to the evolution of stellar winds, with special attention given to the dynamics near the Alfvén and β = 1 surfaces. In this Article, we report the creation of a laboratory model of the Parker spiral system and the measurement of its global structure and dynamic behaviour. This system is realized by producing a rotating plasma magnetosphere whose magnetic topology evolves from a closed magnetosphere into an Archimedean spiral. We show that this system develops interface regions where V ≈ V Alfvén and β ≈ 1, which become highly dynamic and result<|im_end|> <|im_start|>assistant The sun's solar wind affects nearly everything in the solar system. It can disrupt the function of Earth's satellites and creates the lights of the auroras. A new study by University of Wisconsin-Madison physicists mimicked solar winds in the lab, confirming how they develop and providing an Earth-bound model for the future study of solar physics. Our sun is essentially a big ball of hot plasma—an energetic state of matter made up of ionized gas. As the sun spins, the plasma spins along, too. This plasma movement in the core of the sun produces a magnetic field that fills the solar atmosphere. At some distance from the sun's surface, known as the Alfvén surface, this magnetic field weakens and plasma breaks away from the sun, creating the solar wind. "The solar wind is highly variable, but there are essentially two types: fast and slow," explains Ethan Peterson, a graduate student in the department of physics at UW-Madison and lead author of the study published online July 29 in Nature Physics. "Satellite missions have documented pretty well where the fast wind comes from, so we were trying to study specifically how the slow solar wind is generated and how it evolves as it travels toward Earth." Peterson and his colleagues, including physics professor Cary Forest, may not have direct access to the big plasma ball of the sun, but they do have access to the next best thing: the Big Red Ball. The Big Red Ball is a three-meter-wide hollow sphere, with a strong magnet at its center and various probes inside. The researchers pump helium gas in, ionize it to create a plasma, and then apply an electric current that, along with the magnetic field, stirs the plasma, creating a near-perfect mimic of the spinning plasma and electromagnetic fields of the sun. With their mini-sun in place, the researchers can take measurements at many points inside the ball, allowing them to study solar phenomena in three dimensions. First, they were able to recreate the Parker Spiral, a magnetic field that fills the entire solar system named for the scientist who first described the solar wind. Below the Alfvén surface, the magnetic field radiates straight out from the Sun. But at that surface, solar wind dynamics take over, dragging the magnetic field into a spiral. "Satellite measurements are pretty consistent with the Parker Spiral model, but only at one point at a time, so you'd never be able to make a simultaneous, large-scale map of it like we can in the lab." Peterson says. "Our experimental measurements confirm Parker's theory of how it is created by these plasma flows." The researchers were also able to identify the source of the Sun's plasma "burps," small, periodic ejections of plasma that fuel the slow solar wind. With the plasma spinning, they probed the magnetic field and the speed of the plasma. Their data mapped a region where the plasma was moving fast enough and the magnetic field was weak enough that the plasma could break off and eject radially. "These ejections are observed by satellites, but no one knows what drives them," Peterson says. "We ended up seeing very similar burps in our experiment, and identified how they develop." The researchers stress that their Earth-bound experiments complement, but don't replaceme, satellite missions. For example, the Parker Solar Probe, launched in August 2018, is expected to reach and even dip below the Alfvén surface. It will provide direct measurements of solar wind never obtained before. "Our work shows that laboratory experiments can also get at the fundamental physics of these processes," Peterson says. "And because the Big Red Ball is now funded as a National User Facility, it says to the science community: If you want to study the physics of solar wind, you can do that here." <|im_end|>

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2,058

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Repeated episodes of binge-like alcohol consumption produce anxiety, depression and various deleterious effects including alterations in neurogenesis. While the involvement of the serotonin receptor 1 A (5-HT 1A ) in the regulation of anxiety-like behavior and neurogenesis is well documented, its contribution to alcohol withdrawal-induced anxiety and alcohol-induced deficits in neurogenesis is less documented. Using the Drinking-In-the-Dark (DID) paradigm to model chronic long-term (12 weeks) binge-like voluntary alcohol consumption in mice, we show that the selective partial activation of 5-HT 1A receptors by tandospirone (3 mg/kg) prevents alcohol withdrawal-induced anxiety in a battery of behavioral tests (marble burying, elevated-plus-maze, open-field), which is accompanied by a robust decrease in binge-like ethanol intake (1 and 3 mg/kg). Furthermore, using triple immunolabelling of proliferation and neuronal differentiation markers, we show that long-term DID elicits profound deficits in neurogenesis and neuronal fate specification in the dorsal hippocampus that are entirely reversed by a 2-week chronic treatment with the 5-HT 1A partial agonist tandospirone (3 mg/kg/day). Together, our results confirm previous observations that 5-HT 1A receptors play a pivotal role in alcohol drinking behavior and the associated emotional and neurogenic impairments, and suggest that 5-HT 1A partial agonists represent a promising treatment strategy for alcohol abuse. Introduction Alcoholism is regarded as a chronic relapsing disorder, with the development of alcohol addiction a progressive cycle involving extended periods of heavy alcohol use, with repeated episodes of binge-like consumption and abstinence 1 . In society, alcohol abuse is highly prevalent with significantly higher rates of co-occurrence with emotional and mood disorders including anxiety and depression 2 . In turn, increased anxiety levels following alcohol withdrawal are key factors contributing to craving and relapse 3 . Animal studies using non-contingent/forced alcohol delivery (e.g., vapor inhalation, injection, gavage) or contingent models based on continuous access to alcohol (2-bottle choice) have also revealed that withdrawal from chronic alcohol exposure increases stress responsiveness 4 , anxiety- 5 and depression-like behaviors 6 , and alters hippocampal neurogenesis 7 . However, no study to date has investigated the consequences of prolonged periods (12 weeks) of voluntary binge-like alcohol consumption and abstinence on anxiety-like behaviors and hippocampal neuron proliferation or differentiation. The “Drinking-In-the-Dark” (DID) paradigm is a model of voluntary binge-like alcohol drinking, in which animals have a daily 2-hour limited access to ethanol followed by a 24-hour abstinence period. Using this procedure, the high-drinking C57Bl/6 J mouse strain consumes pharmacologically relevant levels of ethanol (blood ethanol concentration ≥1.0 g/L) and shows signs of behavioral intoxication 8 . In adult mice chronically exposed for short term periods (6 weeks), this procedure was shown to elicit increased anxiety- and depression-like behaviors as early as 24 hours after the last drinking session and up to 21 days into protracted withdrawal 9 . The serotonin (5-hydroxytryptamine, 5-HT) system has been widely implicated in the regulation of emotion, impulsivity, mood, reward and arousal. As such, dysregulation of serotonin homeostasis is distinctly involved in the development of anxiety- and depression-related disorders. In line with this, profound functional changes in 5-HT signaling have been observed in the limbic system following acute and chronic alcohol exposure 10 . Since selective serotonin reuptake inhibitor (SSRI) antidepressants elevate 5-HT availability and promote hippocampal neurogenesis, which is required for antidepressant effects 11 , a positive relationship between 5-HT signaling and hippocampal neurogenesis has been established, with the role of the 5-HT 1A receptor becoming well elucidated in both anxiety/depression 12 , 13 and neurogenesis 14 . Chronic alcohol exposure downregulates 5-HT 1A receptor expression in the hippocampus but upregulates 5-HT 1A receptor expression and function in the raphé 15 , 16 . Interestingly, 5-HT 1A receptor activation by the non-selective partial agonists buspirone was shown to reduce alcohol drinking 17 and alcohol withdrawal-induced anxiety 18 , 19 , 20 in rodents. These particular studies however, used a protocol in which animals are forced to consume alcohol by including ethanol in a liquid diet as the sole source of nutrient, making their motivation to drink ethanol in relation to emotional deficits questionable. Additionally, it is now well accepted that buspirone is not selective for 5-HT 1A receptors but also displays an antagonist activity at dopamine D 2 -like receptors 21 , 22 . Indeed, the effect of buspirone on alcohol drinking as well as some anxiety-related behaviors are mediated by D2-like receptor blockade 23 , 24 . Furthermore, we and others have demonstrated that buspirone has a complex action with both anxiolytic and anxiogenic, or motor effects in rodents 25 , 26 , 27 , 28 , 29 , 30 , which could explain the inconsistent results on the benefit of buspirone reported in human alcoholics 31 . Together, these data suggest that that further work is needed to clarify the specific contribution of 5-HT 1A receptors in both alcohol drinking behaviour and alcohol-withdrawal induced anxiety. Tandospirone is a 5-HT 1A partial agonist that, unlike buspirone, presents a high selectivity of two to three orders of magnitude over dopamine, adrenergic and other 5-HT receptors 32 . Tandospirone is an effective anxiolytic drug marketed as Sediel in China and Japan, that is well tolerated and presents limited adverse effects and low abuse liability 33 . Animal studies have also demonstrated that chronic tandospirone treatment improves hippocampal neurogenesis 34 and inhibits stress-induced anxiety and neurogenic deficits 35 . However, the ability of tandospirone to reduce anxiety-like behavior and neurogenic deficits following long-term binge-like alcohol consumption has not been described. To address this question, we used the long-term DID (12 to 15 weeks) model to investigate the effect of tandospirone on (1) alcohol withdrawal-induced anxiety in a battery of behavioral tests (marble burying, elevated-plus-maze and open-field), (2) the maintenance of alcohol binge-like drinking and (3) alcohol-induced deficits in hippocampal neurogenesis. Here, we report for the first time that the selective partial activation of 5-HT 1A receptors by tandospirone reverses alcohol withdrawal-induced anxiety-like behaviors following 12 weeks of exposure, which is accompanied by a robust decrease in alcohol binge-like consumption. In addition, we show that a 2-week tandospirone", "role": "user" }, { "content": "QUT researchers have identified a drug that could potentially help our brains reboot and reverse the damaging impacts of heavy alcohol consumption on regeneration of brain cells. Their studies in adult mice show that two weeks of daily treatment with the drug tandospirone reversed the effects of 15 weeks of binge-like alcohol consumption on neurogenesis – the ability of the brain to grow and replace neurons (brain cells). The findings have been published in Scientific Reports. This is the first time tandospirone has be shown to reverse the deficit in brain neurogenesis induced by heavy alcohol consumptionTandospirone acts selectively on a serotonin receptor (5-HT1A)The researchers also showed in mice that the drug was effective in stopping anxiety-like behaviours associated with alcohol withdrawal, and this was accompanied by a significant decrease in binge-like alcohol intake \"This is a novel discovery that tandospirone can reverse the deficit in neurogenesis caused by alcohol,\" said study leader neuroscientist Professor Selena Bartlett from QUT's Institute of Health and Biomedical Innovation. \"We know that with heavy drinking you are inhibiting your ability to grow new neurons, brain cells. Alcohol is specifically very damaging for neurons. \"Other studies in mice have shown that tandospirone improves brain neurogenesis, but this is the first time it has been shown that it can totally reverse the neurogenic deficits induced by alcohol. Credit: Queensland University of Technology \"This opens the way to look at if neurogenesis is associated with other substance-abuse deficits, such as in memory and learning, and whether this compound can reverse these.\" Professor Bartlett, who is based at the Translational Research Institute, said the discovery by study co-authors QUT postdoctoral research fellows Dr. Arnauld Belmer and Dr. Omkar Patkar came about serendipitously, after research started in a different direction. \"It was surprising, and exciting,\" Dr. Belmer said. \"This drug is relatively new and available only in China and Japan. It is commonly used there and shown to be highly effective in treating general anxiety and well tolerated with limited adverse effects.\" Professor Bartlett said researchers are constantly looking at new treatment strategies for alcohol abuse and addiction, which is characterised by extended periods of heavy alcohol use, binges and abstinence, and anxiety and depression which contribute to relapse. \"This is not just another drug that shows promise in helping to reduce binge drinking,\" she said. \"While it could possibly have that effect, it might be able to help reboot the brain and reverse the deficits the alcohol abuse causes – both the inhibition to the brain's ability to regenerate, and the behavioural consequences that come from what alcohol is doing to the brain, like increases in anxiety and depression.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Repeated episodes of binge-like alcohol consumption produce anxiety, depression and various deleterious effects including alterations in neurogenesis. While the involvement of the serotonin receptor 1 A (5-HT 1A ) in the regulation of anxiety-like behavior and neurogenesis is well documented, its contribution to alcohol withdrawal-induced anxiety and alcohol-induced deficits in neurogenesis is less documented. Using the Drinking-In-the-Dark (DID) paradigm to model chronic long-term (12 weeks) binge-like voluntary alcohol consumption in mice, we show that the selective partial activation of 5-HT 1A receptors by tandospirone (3 mg/kg) prevents alcohol withdrawal-induced anxiety in a battery of behavioral tests (marble burying, elevated-plus-maze, open-field), which is accompanied by a robust decrease in binge-like ethanol intake (1 and 3 mg/kg). Furthermore, using triple immunolabelling of proliferation and neuronal differentiation markers, we show that long-term DID elicits profound deficits in neurogenesis and neuronal fate specification in the dorsal hippocampus that are entirely reversed by a 2-week chronic treatment with the 5-HT 1A partial agonist tandospirone (3 mg/kg/day). Together, our results confirm previous observations that 5-HT 1A receptors play a pivotal role in alcohol drinking behavior and the associated emotional and neurogenic impairments, and suggest that 5-HT 1A partial agonists represent a promising treatment strategy for alcohol abuse. Introduction Alcoholism is regarded as a chronic relapsing disorder, with the development of alcohol addiction a progressive cycle involving extended periods of heavy alcohol use, with repeated episodes of binge-like consumption and abstinence 1 . In society, alcohol abuse is highly prevalent with significantly higher rates of co-occurrence with emotional and mood disorders including anxiety and depression 2 . In turn, increased anxiety levels following alcohol withdrawal are key factors contributing to craving and relapse 3 . Animal studies using non-contingent/forced alcohol delivery (e.g., vapor inhalation, injection, gavage) or contingent models based on continuous access to alcohol (2-bottle choice) have also revealed that withdrawal from chronic alcohol exposure increases stress responsiveness 4 , anxiety- 5 and depression-like behaviors 6 , and alters hippocampal neurogenesis 7 . However, no study to date has investigated the consequences of prolonged periods (12 weeks) of voluntary binge-like alcohol consumption and abstinence on anxiety-like behaviors and hippocampal neuron proliferation or differentiation. The “Drinking-In-the-Dark” (DID) paradigm is a model of voluntary binge-like alcohol drinking, in which animals have a daily 2-hour limited access to ethanol followed by a 24-hour abstinence period. Using this procedure, the high-drinking C57Bl/6 J mouse strain consumes pharmacologically relevant levels of ethanol (blood ethanol concentration ≥1.0 g/L) and shows signs of behavioral intoxication 8 . In adult mice chronically exposed for short term periods (6 weeks), this procedure was shown to elicit increased anxiety- and depression-like behaviors as early as 24 hours after the last drinking session and up to 21 days into protracted withdrawal 9 . The serotonin (5-hydroxytryptamine, 5-HT) system has been widely implicated in the regulation of emotion, impulsivity, mood, reward and arousal. As such, dysregulation of serotonin homeostasis is distinctly involved in the development of anxiety- and depression-related disorders. In line with this, profound functional changes in 5-HT signaling have been observed in the limbic system following acute and chronic alcohol exposure 10 . Since selective serotonin reuptake inhibitor (SSRI) antidepressants elevate 5-HT availability and promote hippocampal neurogenesis, which is required for antidepressant effects 11 , a positive relationship between 5-HT signaling and hippocampal neurogenesis has been established, with the role of the 5-HT 1A receptor becoming well elucidated in both anxiety/depression 12 , 13 and neurogenesis 14 . Chronic alcohol exposure downregulates 5-HT 1A receptor expression in the hippocampus but upregulates 5-HT 1A receptor expression and function in the raphé 15 , 16 . Interestingly, 5-HT 1A receptor activation by the non-selective partial agonists buspirone was shown to reduce alcohol drinking 17 and alcohol withdrawal-induced anxiety 18 , 19 , 20 in rodents. These particular studies however, used a protocol in which animals are forced to consume alcohol by including ethanol in a liquid diet as the sole source of nutrient, making their motivation to drink ethanol in relation to emotional deficits questionable. Additionally, it is now well accepted that buspirone is not selective for 5-HT 1A receptors but also displays an antagonist activity at dopamine D 2 -like receptors 21 , 22 . Indeed, the effect of buspirone on alcohol drinking as well as some anxiety-related behaviors are mediated by D2-like receptor blockade 23 , 24 . Furthermore, we and others have demonstrated that buspirone has a complex action with both anxiolytic and anxiogenic, or motor effects in rodents 25 , 26 , 27 , 28 , 29 , 30 , which could explain the inconsistent results on the benefit of buspirone reported in human alcoholics 31 . Together, these data suggest that that further work is needed to clarify the specific contribution of 5-HT 1A receptors in both alcohol drinking behaviour and alcohol-withdrawal induced anxiety. Tandospirone is a 5-HT 1A partial agonist that, unlike buspirone, presents a high selectivity of two to three orders of magnitude over dopamine, adrenergic and other 5-HT receptors 32 . Tandospirone is an effective anxiolytic drug marketed as Sediel in China and Japan, that is well tolerated and presents limited adverse effects and low abuse liability 33 . Animal studies have also demonstrated that chronic tandospirone treatment improves hippocampal neurogenesis 34 and inhibits stress-induced anxiety and neurogenic deficits 35 . However, the ability of tandospirone to reduce anxiety-like behavior and neurogenic deficits following long-term binge-like alcohol consumption has not been described. To address this question, we used the long-term DID (12 to 15 weeks) model to investigate the effect of tandospirone on (1) alcohol withdrawal-induced anxiety in a battery of behavioral tests (marble burying, elevated-plus-maze and open-field), (2) the maintenance of alcohol binge-like drinking and (3) alcohol-induced deficits in hippocampal neurogenesis. Here, we report for the first time that the selective partial activation of 5-HT 1A receptors by tandospirone reverses alcohol withdrawal-induced anxiety-like behaviors following 12 weeks of exposure, which is accompanied by a robust decrease in alcohol binge-like consumption. In addition, we show that a 2-week tandospirone<|im_end|> <|im_start|>assistant QUT researchers have identified a drug that could potentially help our brains reboot and reverse the damaging impacts of heavy alcohol consumption on regeneration of brain cells. Their studies in adult mice show that two weeks of daily treatment with the drug tandospirone reversed the effects of 15 weeks of binge-like alcohol consumption on neurogenesis – the ability of the brain to grow and replace neurons (brain cells). The findings have been published in Scientific Reports. This is the first time tandospirone has be shown to reverse the deficit in brain neurogenesis induced by heavy alcohol consumptionTandospirone acts selectively on a serotonin receptor (5-HT1A)The researchers also showed in mice that the drug was effective in stopping anxiety-like behaviours associated with alcohol withdrawal, and this was accompanied by a significant decrease in binge-like alcohol intake "This is a novel discovery that tandospirone can reverse the deficit in neurogenesis caused by alcohol," said study leader neuroscientist Professor Selena Bartlett from QUT's Institute of Health and Biomedical Innovation. "We know that with heavy drinking you are inhibiting your ability to grow new neurons, brain cells. Alcohol is specifically very damaging for neurons. "Other studies in mice have shown that tandospirone improves brain neurogenesis, but this is the first time it has been shown that it can totally reverse the neurogenic deficits induced by alcohol. Credit: Queensland University of Technology "This opens the way to look at if neurogenesis is associated with other substance-abuse deficits, such as in memory and learning, and whether this compound can reverse these." Professor Bartlett, who is based at the Translational Research Institute, said the discovery by study co-authors QUT postdoctoral research fellows Dr. Arnauld Belmer and Dr. Omkar Patkar came about serendipitously, after research started in a different direction. "It was surprising, and exciting," Dr. Belmer said. "This drug is relatively new and available only in China and Japan. It is commonly used there and shown to be highly effective in treating general anxiety and well tolerated with limited adverse effects." Professor Bartlett said researchers are constantly looking at new treatment strategies for alcohol abuse and addiction, which is characterised by extended periods of heavy alcohol use, binges and abstinence, and anxiety and depression which contribute to relapse. "This is not just another drug that shows promise in helping to reduce binge drinking," she said. "While it could possibly have that effect, it might be able to help reboot the brain and reverse the deficits the alcohol abuse causes – both the inhibition to the brain's ability to regenerate, and the behavioural consequences that come from what alcohol is doing to the brain, like increases in anxiety and depression." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Topological superconductors are an essential component for topologically protected quantum computation and information processing. Although signatures of topological superconductivity have been reported in heterostructures, material realizations of intrinsic topological superconductors are rather rare. Here we use scanning tunnelling spectroscopy to study the transition metal dichalcogenide 4Hb-TaS 2 that interleaves superconducting 1H-TaS 2 layers with strongly correlated 1T-TaS 2 layers, and find spectroscopic evidence for the existence of topological surface superconductivity. These include edge modes running along the 1H-layer terminations as well as under the 1T-layer terminations, where they separate between superconducting regions of distinct topological nature. We also observe signatures of zero-bias states in vortex cores. All the boundary modes exhibit crystallographic anisotropy, which—together with a finite in-gap density of states throughout the 1H layers—allude to the presence of a topological nodal-point superconducting state. Our theoretical modelling attributes this phenomenology to an inter-orbital pairing channel that necessitates the combination of surface mirror symmetry breaking and strong interactions. It, thus, suggests a topological superconducting state realized in a natural compound. Main Topological superconductors are extensively explored with the aim to induce and manipulate Majorana zero modes that are essential to realize topological quantum information processing. The non-local nature of these zero modes and their intrinsic non-Abelian braiding statistics allow for quantum information to be stored and manipulated in a non-local manner, which protects it from the influence of the local environment 1 , 2 . A growing body of realizations of topological superconductors in one-dimensional (1D) systems have been reported so far, including hybrid nanowires 3 , atomic chains 4 , proximitized helical edge modes 5 and planar Josephson junctions 6 , 7 . In these systems, Majorana zero modes manifest themselves as zero-energy conductance anomalies localized at the ends of the topological superconducting segment. In two-dimensional (2D) systems, Majorana zero modes may be manifested as zero-bias conductance (ZBC) peaks at the centre of vortex cores 8 , 9 , 10 , 11 , 12 . A complementary hallmark of a 2D topological superconductor is the existence of gapless Majorana edge modes bound to its 1D boundaries 13 , 14 , 15 . These could be the physical boundaries of the system or separate superconducting regions with distinct topological nature. So far, signatures of 1D Majorana edge modes have been mostly observed in heterostructures or hybrid systems 16 , 17 , 18 , in which topological superconductivity emerges from the interplay of magnetism, superconductivity and spin–orbit coupling that are provided by the different device components. To date, evidence for topological superconductivity in naturally occurring materials has been scarce 19 , 20 . Transition metal dichalcogenides (TMDs) are strongly correlated materials exhibiting numerous different intriguing phases such as superconductivity, charge-density-wave (CDW) order and spin liquid state 21 , 22 , 23 , 24 , 25 . The combination of strong spin–orbit interactions and strong electron interactions renders them to be an ideal hunting ground for topological superconductivity 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 . Their van der Waals nature further allows one to mix and match various materials with diverse phenomenologies either in growth or via exfoliation and stacking 35 . We use scanning tunnelling microscopy (STM) and scanning tunnelling spectroscopy to study the superconducting state in TMD 4Hb-TaS 2 , which comprises the alternating stacking of 1T-TaS 2 and 1H-TaS 2 layers (Fig. 1a ). While bulk 1T-TaS 2 is expected to host a quantum spin liquid state 36 , bulk 2H-TaS 2 is well known for its quasi-2D Ising superconductivity 23 . Furthermore, the observation of increased muon spin rotation concurrently rising with the superconducting state of 4Hb-TaS 2 has raised the possibility of non-trivial topology 37 . Our measurements reveal the presence of 1D boundary edge modes as well as ZBC peaks at the vortex cores. These have the phenomenology of a nodal-point topological superconductor 34 stemming from inter-orbital Cooper pairing 14 , 38 , 39 , 40 . Fig. 1: CDW, superconductivity and ZBC peaks in vortex cores. a , Crystal structure of 4Hb-TaS 2 . b , Topography of a cleaved surface showing both 1H and 1T terminations along with their commensurate CDW patterns. c , d , Zoomed-in topography of the 1T ( c ) and 1H ( d ) terminations (top) and their corresponding Fourier transforms (bottom). The Ta and S atoms are overlaid on the topography along with the CDW unit cell (green rhombus). The Fourier transform clearly shows the atomic Bragg peak (yellow), the 1T CDW peak (green) and the 1H CDW peak (pink). e , Spatially averaged d I /d V in arbitrary units (a.u.) measured on the 1T and 1H terminations at 4.2 K. f , The d I /d V spectrum normalized by its value above the gap dI / dV N (blue dots) measured on the 1H termination at temperature T = 0.38 K showing the superconducting gap fitted with a BCS spectrum and an offset BCS spectrum (dotted and solid lines, respectively). The gap vanishes above the superconducting critical temperature, T c , and critical field, H c2 (orange and purple dots, respectively). g , Spatial mapping of ZBC in d I /d V on the 1H termination with a 100 mT out-of-plane magnetic field shows an ordered Abrikosov vortex lattice. h , The energy dependent spectrum, d I /d V (E) at a linecut across the vortex marked by the dashed line in g shows enhanced the zero-bias DOS at the core. i , The d I /d V profiles at the vortex core (red) and far from it (blue). The corresponding locations are marked by red and blue arrows in h . j , Zoomed-in view of the shaded box marked in i , showing a zero-bias peak fitted to a single Gaussian profile including instrumental broadening. Full size image Results We cleave single crystals along the [001] orientation under an ultrahigh vacuum. Due to the alternating layer structure of 4Hb-TaS 2 , the", "role": "user" }, { "content": "Topological superconductors are a class of superconducting materials characterized by sub-gap zero energy localized modes, known as Majorana boundary states (MBSs). These materials are promising for the development of quantum computing technology. Past studies have observed signatures of topological superconductivity in a variety of heterostructures. However, so far, physicists and material scientists have only been able to create a few intrinsically topological superconductors. Researchers at Weizmann Institute of Science and Technion in Israel have recently gathered evidence of topological superconductivity in 4Hb-TaS2, a new material realized by one of their colleagues. Their paper, published in Nature Physics, could have important implications for the future development of various quantum devices. \"In early 2019, Amit Kanigel at Technion institute of technology gave a seminar at the Weizmann institute of science on 4Hb-TaS2, an intriguing compound that he had recently grown and measured,\" Nurit Avraham, Abhay Kumar Nayak and Haim Beidenkopf, three of the researchers who carried out the study, told Phys.org. \"One exciting observation he presented was an onset of increased muon spin relaxation, possibly signifying time reversal symmetry breaking, concurrently with superconductivity, which alluded towards the existence of topological superconductivity in this compound.\" After attending Kanigel's seminar, the team at Weizmann set out to examine the exotic compound he uncovered using a technique known as scanning tunneling microscopy (STM). Scanning tunneling microscopes are instruments that can be used to collect atomic-scale images and spectroscopic measurements of a material's surface. A key hallmark of topological superconductivity is the presence of Majorana edge modes on a material's edges, which can be directly observed and characterized using STM techniques. Kanigel's seminar at Technion thus inspired the researchers to seek for experimental evidence of topological superconductivity in 4Hb-TaS2. \"In our lab, we use scanning tunneling microscopy and spectroscopic mappings,\" Beidenkopf said. \"What was particularly exciting in the 4Hb polytype of TaS2 was that it interleaves 1H superconducting layers with 1T Mott insulating layers. Therefore, simply by cleaving and exposing the various terminations we could explore the mutual interaction between these distinct correlated states.\" 12 nodes are induced by the cross-orbital pairing term within the Brilluin zone. Their projection to various edges gives rise to the anisotropic character of the edge modesCredit: Nayak et al. In the first topographic images they collected, the researchers observed a hint of the strong interaction between the 1T and 1H layers in the material synthesized by Kanigel. More specifically, they unveiled the imprint of charge density waves on the 1H layer, due to its proximity with the 1T layer beneath it. The team then measured the superconductivity of the 1H layer and found that the superconducting gap was significantly shallow. This suggested that this gap was filled by in-gap electronic states. \"We later identified the existence of edge modes along boundaries of the superconducting layer,\" Avraham said \"The most intriguing one was an edge mode we observed on the interface between superconducting regions of the 1H layer, that are encapsulated by 1T layers from both sides, and exposed regions with no 1T layer on top. This relates to our first observation, suggesting that even though superconductivity remains continuous throughout the 1H layer, it changes its topological classification due to the interaction with the adjacent 1T layers.\" An additional result that supported the topological nature of the superconductivity in the 1H layer of the material was the visualization of zero-bias conductance peaks at vortex cores. The researchers were thus able to collect very strong evidence of the intrinsic topological superconductivity of 4Hb-TaS2. Subsequently, they started collaborating with a group of theorists to come up with hypotheses about the inter-orbital pairing mechanisms that may support the exotic phenomena they observed. \"While topological insulators, and even semimetals, are by now abundant, the list of topological superconductors in natural materials is extremely short,\" Nayak said. \"It includes SrO2 and FeSeTe and several other candidates as UTe2. Therefore, adding 4Hb-TaS2 to this list is exciting news, as it also hosts strongly correlated states and its layer structure can be changed from 1T to 1H by local tip manipulations.\" The findings gathered by this team of researchers suggest that the exotic compound realized by Kanigel is intrinsically a topological superconductor. In the future, this material could thus prove particularly valuable for the development of quantum computers and other quantum information processing tools. Meanwhile, the team at Weizmann and their colleagues plan to continue examining 4Hb-TaS2, specifically looking at the fate of the Mott insulating state on the 1T layer in presence of the metallic 1H layer. \"We have preliminary indications of an exotic state that forms on the 1T layer. Its evolution with superconductivity is also unresolved.\" Avraham, Nayak and Beidenkopf added. \"Perhaps these additional insights will bring us closer to a wholesome comprehension of 4Hb-TaS2, in which topological superconductivity on the 1H terminations is one exciting aspect.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Topological superconductors are an essential component for topologically protected quantum computation and information processing. Although signatures of topological superconductivity have been reported in heterostructures, material realizations of intrinsic topological superconductors are rather rare. Here we use scanning tunnelling spectroscopy to study the transition metal dichalcogenide 4Hb-TaS 2 that interleaves superconducting 1H-TaS 2 layers with strongly correlated 1T-TaS 2 layers, and find spectroscopic evidence for the existence of topological surface superconductivity. These include edge modes running along the 1H-layer terminations as well as under the 1T-layer terminations, where they separate between superconducting regions of distinct topological nature. We also observe signatures of zero-bias states in vortex cores. All the boundary modes exhibit crystallographic anisotropy, which—together with a finite in-gap density of states throughout the 1H layers—allude to the presence of a topological nodal-point superconducting state. Our theoretical modelling attributes this phenomenology to an inter-orbital pairing channel that necessitates the combination of surface mirror symmetry breaking and strong interactions. It, thus, suggests a topological superconducting state realized in a natural compound. Main Topological superconductors are extensively explored with the aim to induce and manipulate Majorana zero modes that are essential to realize topological quantum information processing. The non-local nature of these zero modes and their intrinsic non-Abelian braiding statistics allow for quantum information to be stored and manipulated in a non-local manner, which protects it from the influence of the local environment 1 , 2 . A growing body of realizations of topological superconductors in one-dimensional (1D) systems have been reported so far, including hybrid nanowires 3 , atomic chains 4 , proximitized helical edge modes 5 and planar Josephson junctions 6 , 7 . In these systems, Majorana zero modes manifest themselves as zero-energy conductance anomalies localized at the ends of the topological superconducting segment. In two-dimensional (2D) systems, Majorana zero modes may be manifested as zero-bias conductance (ZBC) peaks at the centre of vortex cores 8 , 9 , 10 , 11 , 12 . A complementary hallmark of a 2D topological superconductor is the existence of gapless Majorana edge modes bound to its 1D boundaries 13 , 14 , 15 . These could be the physical boundaries of the system or separate superconducting regions with distinct topological nature. So far, signatures of 1D Majorana edge modes have been mostly observed in heterostructures or hybrid systems 16 , 17 , 18 , in which topological superconductivity emerges from the interplay of magnetism, superconductivity and spin–orbit coupling that are provided by the different device components. To date, evidence for topological superconductivity in naturally occurring materials has been scarce 19 , 20 . Transition metal dichalcogenides (TMDs) are strongly correlated materials exhibiting numerous different intriguing phases such as superconductivity, charge-density-wave (CDW) order and spin liquid state 21 , 22 , 23 , 24 , 25 . The combination of strong spin–orbit interactions and strong electron interactions renders them to be an ideal hunting ground for topological superconductivity 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 . Their van der Waals nature further allows one to mix and match various materials with diverse phenomenologies either in growth or via exfoliation and stacking 35 . We use scanning tunnelling microscopy (STM) and scanning tunnelling spectroscopy to study the superconducting state in TMD 4Hb-TaS 2 , which comprises the alternating stacking of 1T-TaS 2 and 1H-TaS 2 layers (Fig. 1a ). While bulk 1T-TaS 2 is expected to host a quantum spin liquid state 36 , bulk 2H-TaS 2 is well known for its quasi-2D Ising superconductivity 23 . Furthermore, the observation of increased muon spin rotation concurrently rising with the superconducting state of 4Hb-TaS 2 has raised the possibility of non-trivial topology 37 . Our measurements reveal the presence of 1D boundary edge modes as well as ZBC peaks at the vortex cores. These have the phenomenology of a nodal-point topological superconductor 34 stemming from inter-orbital Cooper pairing 14 , 38 , 39 , 40 . Fig. 1: CDW, superconductivity and ZBC peaks in vortex cores. a , Crystal structure of 4Hb-TaS 2 . b , Topography of a cleaved surface showing both 1H and 1T terminations along with their commensurate CDW patterns. c , d , Zoomed-in topography of the 1T ( c ) and 1H ( d ) terminations (top) and their corresponding Fourier transforms (bottom). The Ta and S atoms are overlaid on the topography along with the CDW unit cell (green rhombus). The Fourier transform clearly shows the atomic Bragg peak (yellow), the 1T CDW peak (green) and the 1H CDW peak (pink). e , Spatially averaged d I /d V in arbitrary units (a.u.) measured on the 1T and 1H terminations at 4.2 K. f , The d I /d V spectrum normalized by its value above the gap dI / dV N (blue dots) measured on the 1H termination at temperature T = 0.38 K showing the superconducting gap fitted with a BCS spectrum and an offset BCS spectrum (dotted and solid lines, respectively). The gap vanishes above the superconducting critical temperature, T c , and critical field, H c2 (orange and purple dots, respectively). g , Spatial mapping of ZBC in d I /d V on the 1H termination with a 100 mT out-of-plane magnetic field shows an ordered Abrikosov vortex lattice. h , The energy dependent spectrum, d I /d V (E) at a linecut across the vortex marked by the dashed line in g shows enhanced the zero-bias DOS at the core. i , The d I /d V profiles at the vortex core (red) and far from it (blue). The corresponding locations are marked by red and blue arrows in h . j , Zoomed-in view of the shaded box marked in i , showing a zero-bias peak fitted to a single Gaussian profile including instrumental broadening. Full size image Results We cleave single crystals along the [001] orientation under an ultrahigh vacuum. Due to the alternating layer structure of 4Hb-TaS 2 , the<|im_end|> <|im_start|>assistant Topological superconductors are a class of superconducting materials characterized by sub-gap zero energy localized modes, known as Majorana boundary states (MBSs). These materials are promising for the development of quantum computing technology. Past studies have observed signatures of topological superconductivity in a variety of heterostructures. However, so far, physicists and material scientists have only been able to create a few intrinsically topological superconductors. Researchers at Weizmann Institute of Science and Technion in Israel have recently gathered evidence of topological superconductivity in 4Hb-TaS2, a new material realized by one of their colleagues. Their paper, published in Nature Physics, could have important implications for the future development of various quantum devices. "In early 2019, Amit Kanigel at Technion institute of technology gave a seminar at the Weizmann institute of science on 4Hb-TaS2, an intriguing compound that he had recently grown and measured," Nurit Avraham, Abhay Kumar Nayak and Haim Beidenkopf, three of the researchers who carried out the study, told Phys.org. "One exciting observation he presented was an onset of increased muon spin relaxation, possibly signifying time reversal symmetry breaking, concurrently with superconductivity, which alluded towards the existence of topological superconductivity in this compound." After attending Kanigel's seminar, the team at Weizmann set out to examine the exotic compound he uncovered using a technique known as scanning tunneling microscopy (STM). Scanning tunneling microscopes are instruments that can be used to collect atomic-scale images and spectroscopic measurements of a material's surface. A key hallmark of topological superconductivity is the presence of Majorana edge modes on a material's edges, which can be directly observed and characterized using STM techniques. Kanigel's seminar at Technion thus inspired the researchers to seek for experimental evidence of topological superconductivity in 4Hb-TaS2. "In our lab, we use scanning tunneling microscopy and spectroscopic mappings," Beidenkopf said. "What was particularly exciting in the 4Hb polytype of TaS2 was that it interleaves 1H superconducting layers with 1T Mott insulating layers. Therefore, simply by cleaving and exposing the various terminations we could explore the mutual interaction between these distinct correlated states." 12 nodes are induced by the cross-orbital pairing term within the Brilluin zone. Their projection to various edges gives rise to the anisotropic character of the edge modesCredit: Nayak et al. In the first topographic images they collected, the researchers observed a hint of the strong interaction between the 1T and 1H layers in the material synthesized by Kanigel. More specifically, they unveiled the imprint of charge density waves on the 1H layer, due to its proximity with the 1T layer beneath it. The team then measured the superconductivity of the 1H layer and found that the superconducting gap was significantly shallow. This suggested that this gap was filled by in-gap electronic states. "We later identified the existence of edge modes along boundaries of the superconducting layer," Avraham said "The most intriguing one was an edge mode we observed on the interface between superconducting regions of the 1H layer, that are encapsulated by 1T layers from both sides, and exposed regions with no 1T layer on top. This relates to our first observation, suggesting that even though superconductivity remains continuous throughout the 1H layer, it changes its topological classification due to the interaction with the adjacent 1T layers." An additional result that supported the topological nature of the superconductivity in the 1H layer of the material was the visualization of zero-bias conductance peaks at vortex cores. The researchers were thus able to collect very strong evidence of the intrinsic topological superconductivity of 4Hb-TaS2. Subsequently, they started collaborating with a group of theorists to come up with hypotheses about the inter-orbital pairing mechanisms that may support the exotic phenomena they observed. "While topological insulators, and even semimetals, are by now abundant, the list of topological superconductors in natural materials is extremely short," Nayak said. "It includes SrO2 and FeSeTe and several other candidates as UTe2. Therefore, adding 4Hb-TaS2 to this list is exciting news, as it also hosts strongly correlated states and its layer structure can be changed from 1T to 1H by local tip manipulations." The findings gathered by this team of researchers suggest that the exotic compound realized by Kanigel is intrinsically a topological superconductor. In the future, this material could thus prove particularly valuable for the development of quantum computers and other quantum information processing tools. Meanwhile, the team at Weizmann and their colleagues plan to continue examining 4Hb-TaS2, specifically looking at the fate of the Mott insulating state on the 1T layer in presence of the metallic 1H layer. "We have preliminary indications of an exotic state that forms on the 1T layer. Its evolution with superconductivity is also unresolved." Avraham, Nayak and Beidenkopf added. "Perhaps these additional insights will bring us closer to a wholesome comprehension of 4Hb-TaS2, in which topological superconductivity on the 1H terminations is one exciting aspect." <|im_end|>

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16, 39, 2307, 77752, 287, 13931, 449, 220, 16, 51, 386, 1751, 1672, 15853, 13931, 13, 15636, 11, 5042, 555, 11551, 2370, 323, 47066, 279, 5370, 10415, 811, 584, 1436, 13488, 279, 27848, 16628, 1990, 1521, 12742, 49393, 5415, 1210, 220, 717, 7954, 527, 36572, 555, 279, 5425, 27609, 65, 2223, 48813, 4751, 2949, 279, 67744, 75721, 10353, 13, 11205, 22343, 311, 5370, 13116, 6835, 10205, 311, 279, 459, 285, 79432, 3752, 315, 279, 6964, 20362, 34593, 25, 99173, 587, 1880, 453, 13, 763, 279, 1176, 1948, 12968, 5448, 814, 14890, 11, 279, 12074, 13468, 264, 13310, 315, 279, 3831, 16628, 1990, 279, 220, 16, 51, 323, 220, 16, 39, 13931, 304, 279, 3769, 92106, 555, 31663, 50639, 13, 4497, 11951, 11, 814, 39297, 279, 79967, 315, 6900, 17915, 17301, 389, 279, 220, 16, 39, 6324, 11, 4245, 311, 1202, 37843, 449, 279, 220, 16, 51, 6324, 24923, 433, 13, 578, 2128, 1243, 17303, 279, 2307, 77752, 1968, 315, 279, 220, 16, 39, 6324, 323, 1766, 430, 279, 2307, 77752, 287, 13225, 574, 12207, 26682, 13, 1115, 12090, 430, 420, 13225, 574, 10409, 555, 304, 89657, 14683, 5415, 13, 330, 1687, 3010, 11054, 279, 14209, 315, 6964, 20362, 3235, 23546, 315, 279, 2307, 77752, 287, 6324, 1359, 7671, 17012, 1071, 330, 791, 1455, 41765, 832, 574, 459, 6964, 3941, 584, 13468, 389, 279, 3834, 1990, 2307, 77752, 287, 13918, 315, 279, 220, 16, 39, 6324, 11, 430, 527, 43669, 7913, 555, 220, 16, 51, 13931, 505, 2225, 11314, 11, 323, 15246, 13918, 449, 912, 220, 16, 51, 6324, 389, 1948, 13, 1115, 36716, 311, 1057, 1176, 22695, 11, 23377, 430, 1524, 3582, 2307, 77752, 1968, 8625, 19815, 6957, 279, 220, 16, 39, 6324, 11, 433, 4442, 1202, 1948, 5848, 24790, 4245, 311, 279, 16628, 449, 279, 24894, 220, 16, 51, 13931, 1210, 1556, 5217, 1121, 430, 7396, 279, 1948, 5848, 7138, 315, 279, 2307, 77752, 1968, 304, 279, 220, 16, 39, 6324, 315, 279, 3769, 574, 279, 42148, 315, 7315, 1481, 3557, 6929, 685, 40035, 520, 87627, 36804, 13, 578, 12074, 1051, 8617, 3025, 311, 6667, 1633, 3831, 6029, 315, 279, 47701, 1948, 5848, 2307, 77752, 1968, 315, 220, 19, 39, 65, 44195, 50, 17, 13, 3804, 39742, 11, 814, 3940, 73301, 449, 264, 1912, 315, 84062, 311, 2586, 709, 449, 74513, 922, 279, 958, 27609, 65, 2223, 48813, 24717, 430, 1253, 1862, 279, 39418, 44247, 814, 13468, 13, 330, 8142, 1948, 5848, 1672, 42391, 11, 323, 1524, 5347, 86366, 1147, 11, 527, 555, 1457, 44611, 11, 279, 1160, 315, 1948, 5848, 2307, 77752, 1105, 304, 5933, 7384, 374, 9193, 2875, 1359, 99173, 587, 1071, 13, 330, 2181, 5764, 34688, 46, 17, 323, 3926, 1542, 6777, 323, 3892, 1023, 11426, 439, 549, 6777, 17, 13, 15636, 11, 7999, 220, 19, 39, 65, 44195, 50, 17, 311, 420, 1160, 374, 13548, 3754, 11, 439, 433, 1101, 18939, 16917, 49393, 5415, 323, 1202, 6324, 6070, 649, 387, 5614, 505, 220, 16, 51, 311, 220, 16, 39, 555, 2254, 11813, 14951, 7607, 1210, 578, 14955, 20802, 555, 420, 2128, 315, 12074, 4284, 430, 279, 39418, 24549, 15393, 555, 31663, 50639, 374, 10805, 1354, 2740, 264, 1948, 5848, 2307, 444, 36869, 13, 763, 279, 3938, 11, 420, 3769, 1436, 8617, 12391, 8104, 15525, 369, 279, 4500, 315, 31228, 19002, 323, 1023, 31228, 2038, 8863, 7526, 13, 26982, 11, 279, 2128, 520, 1226, 450, 18022, 323, 872, 18105, 3197, 311, 3136, 38936, 220, 19, 39, 65, 44195, 50, 17, 11, 11951, 3411, 520, 279, 25382, 315, 279, 386, 1751, 1672, 15853, 1614, 389, 279, 220, 16, 51, 6324, 304, 9546, 315, 279, 46258, 220, 16, 39, 6324, 13, 330, 1687, 617, 33269, 56190, 315, 459, 39418, 1614, 430, 7739, 389, 279, 220, 16, 51, 6324, 13, 11699, 15740, 449, 2307, 77752, 1968, 374, 1101, 81261, 1210, 7671, 17012, 11, 99173, 587, 323, 2893, 12770, 84698, 69, 3779, 13, 330, 32576, 1521, 5217, 26793, 690, 4546, 603, 12401, 311, 264, 88318, 62194, 315, 220, 19, 39, 65, 44195, 50, 17, 11, 304, 902, 1948, 5848, 2307, 77752, 1968, 389, 279, 220, 16, 39, 10415, 811, 374, 832, 13548, 13189, 1210, 220, 128257, 198 ]

2,632

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract El Niño Southern Oscillation (ENSO) events modulate oceanographic processes that control temperature and productivity in tropical waters, yet potential interactions with low frequency climate variability, such as the Pacific Decadal Oscillation (PDO), are poorly understood. We show that ENSO and PDO together predicted (i) maximum sea-surface temperatures (SST), which were associated with coral bleaching and declines in coral cover, and (ii) maximum chlorophyll-a concentrations, which were associated with high densities of coral-predatory Acanthaster starfish, across the tropical north Pacific Ocean since 1980. Asynchrony between the positive PDO and negative ENSO (i.e., La Niña) was associated with peaks in annual SST. By contrast, synchrony between the positive PDO and positive ENSO (i.e., El Niño) was associated with peaks in chlorophyll-a. Both conditions led to ecological disturbances and significant loss of coral cover, however, spatial models revealed where impacts to reefs were expected under varying climate scenarios. The 2015/17 ENSO event was coupled with a positive PDO and resulted in high SST and Acanthaster abundances in eastern Micronesia, while positive coral growth occurred in western Micronesia. Our novel approach for forecasting coral growth into the future may be applicable to other oceanic regions with differing oceanographic modulators. Introduction Coral bleaching is a consequence of anomalous thermal-stress events that have led to coral mortality in extreme conditions and to changes in the composition of remaining coral assemblages 1 , 2 . A recent increase in the frequency and intensity of thermal-stress events in the Pacific Ocean is attributed to the overprint of ocean warming on El Niño Southern Oscillation (ENSO) 2 , 3 , 4 . The overprint of warming in the central Pacific reduce the threshold and increase the likelihood of extreme ENSO events 5 , 6 . Yet, predicting where and when coral reefs are susceptible to ENSO events is challenging 2 , 7 , 8 . Consider for example the coral reefs in Micronesia that were exposed to strong ENSO events in 1997/98 and again in 2015/17. The 1997/98 ENSO was attributed to extensive coral bleaching in western Micronesia 9 , 10 , whereas the 2015/17 event impacted central and eastern Micronesia 2000 km farther eastward. These disturbance patterns suggest that our ability to predict reef futures relies on a better understanding of how ENSO combines with secondary, low frequency climate variability to regulate ocean temperatures across the tropical Pacific Ocean 11 . Short-term predictive models can accurately forecast ocean temperatures 3–4 months into the future using autoregressive and linear inverse models that are extensions of recent climate observations 12 . These types of models, for example, predict thermal stress events and form the basis for coral bleaching alerts that are derived from satellite SST data 13 , 14 , 15 . By contrast, longer-term predictions that reveal the likelihood of future thermal anomalies are based on past temperature records from geological coral cores and on historical patterns of past temperatures (Thompson and van Woesik 2009). Representative concentration pathway (RCP) models, for example, predict SST trajectories over the next 50 to 100 years under varying CO 2 emissions scenarios 8 , 16 . RCP models provide novel insight into patterns and processes associated with SST variation and rely upon smoothed annual trends over low-resolution geographic projections. The present study differs from both approaches and sought to predict changes in ocean temperatures across years to decades that were driven by climate oscillations associated with ENSO and the Pacific Decadal Oscillation (PDO). While bleaching events are commonly associated with ENSO cycles 1 , 2 , the PDO represents a low frequency climate variability that is associated with changes in SST and productivity along a north-to-south gradient in the tropical and temperate Pacific Ocean. The north-to-south climatic shifts are associated with cool and warm PDO phases that can augment or diminish the influence of ENSO 17 , 18 . Although the atmospheric and oceanic processes driving the PDO are poorly understood, at least compared with ENSO, the present study relies upon the PDO indices as a measure of predictable oceanographic change as the science surrounding the PDO and other interdecadal oscillations continue to evolve 19 . In addition to thermal stressors, coral reefs in the Pacific and Indian Oceans are subjected to repeated outbreaks of the coral-eating seastar Acanthaster . Several studies have demonstrated that the density of these coral predators are proportional to the extent of coral mortality, and that Acanthaster frequently spread across reefs like fires spread through forests 20 , 21 . These episodes of intensive coral predation have been linked to high nutrient concentrations for brachiolaria larvae of Acanthaster 22 . Such high nutrient concentrations are associated with river discharge 23 , 24 or anomalous oceanographic conditions generating high coastal productivity, frequently detected as high chlorophyll-a concentrations 25 , 26 . Enhanced primary productivity can occur during ENSO events in some coral-reef localities that are otherwise nutrient depauperate 25 . For example, ENSO can cause dynamic shifts in coastal upwelling, currents, and regional rainfall 26 . Here, we modelled the relationships between indices of climate modulators, thermal stress and chlorophyll-a concentrations, and the resultant change in coral cover across the tropical North Pacific (1° to 11°N, 130° to 165°E, Fig. 1 ). Our study revealed a strong interaction between these indices and changes to the coral reefs of Micronesia, demonstrating how ENSO cycles influence both heat transfer and productivity in a predictable, but spatially inconsistent manner. Figure 1 Map of the western Pacific Ocean with a geographical box surrounding the tropical North Pacific study region of Micronesia. Numbers indicate islands where long-term biological data were collected: (1) Palau, (2) Yap, (3) Chuuk, (4) Pohnpei, and (5) Kosrae. Map was created by author PH using ArcGIS software 10.2.2 and freely available base maps associated with the online account. Full size image Materials and Methods The present study was conducted in Micronesia, tropical northwestern Pacific Ocean (1° to 11°N, 130° to 165°E) (Fig. 1 ). Micronesia has a long history of disturbances impacting coral reefs. Widespread thermal-stress related coral bleaching", "role": "user" }, { "content": "A new study by the Marine Laboratory at the University of Guam may help researchers predict coral bleaching months earlier than current tools, and, for the first time, may help predict invasion events of coral-eating crown-of-thorns starfish. The study was published on May 8 in Scientific Reports. Coral bleaching and the crown-of-thorns starfish represent the two biggest disturbances coral reefs face, while local stressors like pollution and overfishing represent the two biggest impediments to recovery following disturbances. Unlike other prediction tools, this study used the interaction of two major oceanographic modulators—El Nino and Pacific Decadal Oscillation, or PDO—to predict how \"warm blobs\" of seawater and excess nutrients move around the tropical Western Pacific to cause these two destructive events. Existing tools typically provide bleaching warnings two to three weeks in advance; however, this new tool extends the warning period to between three and five months. Important implications Advanced warnings have important implications for coral reef management efforts in the Pacific region and potentially beyond. \"It takes management from a reactive position to a more proactive one,\" said senior author Peter Houk, an associate professor of marine biology in the Marine Lab. \"Not a lot can be accomplished with only a couple weeks' notice, but predicting bleaching and starfish disturbance events a few months out may give governments and other agencies more time to acquire supplies, create legislation, and create support networks to ensure reefs are better equipped to handle these forces.\" For example, it allows more time to revise temporary fisheries regulations, raise funds for the removal of starfish, and procure supplies needed to support these acts. The authors have predicted outbreaks of starfish to emerge in Eastern Micronesia this year, providing time for Kosrae's tourism industry and resources agencies to gather supplies and build monitoring and removal plans now. Further, the authors can provide warnings for other islands down current to be on the lookout as starfish outbreaks are known to spread across islands and reefs in the direction of prevailing currents. Piis Patch Reef on the Micronesian Island of Chuuk is shown in August 2018 following a coral bleaching event associated with El Niño, or the warming phase of sea temperatures. Credit: University of Guam An unanswered question Above-average sea-surface temperatures are common across the tropical Pacific following El Nino Southern Oscillation events, which are increasingly exacerbated by climate change. However, islands—from Palau to Kosrae—can be affected differently. One may bleach, while another experiences little to none. That question motivated researchers to study the impact of El Nino interacting with the PDO. Together, the two patterns predict maximum sea-surface temperatures and also the movement of \"nutrient plumes\" filled with what is known as \"chlorophyll a\" around the Pacific Ocean that attract plankton and cause the crown-of-thorns starfish outbreaks that wreak havoc on coral. Both sea-surface temperatures and nutrient plumes have been mapped by satellites for years; however, predicting their future has been a challenge. Predictions based on decades of data The researchers analyzed sea temperatures dating back to 1980 and biological data dating back to 1998, including coral cover and chlorophyll a plumes, from 82 survey sites on the main islands of Micronesia to track how they are influenced by the interaction of these two cycles. Lorenzo Stephan, a coral reef monitoring team member in Chuuk, holds one of many coral-eating crown-of-thorns starfish found during the El Niño-Southern Oscillation event of 2015-2017. A recently published study out of the University of Guam Marine Laboratory found a predictable pattern between starfish invasions and the interaction of El Niño and Pacific Decadal Oscillation climate events. Credit: University of Guam Using those observations, they built models that accurately predicted both sea surface temperatures and nutrients. The models accounted for 77% of the variation in sea temperature and 55% of the variation in chlorophyll a concentrations between 1980 to the present, both of which support strong predictions. The study shows that including PDO events into forecasts may improve predictions of when and where bleaching and starfish outbreaks will occur. The next step will be to build an online resource to host the predictive model for scientists and resources managers to access and to keep improving the model to the extent possible. \"We provide the first insight into how PDO and El Niño cycles predicted sea-surface temperatures, chlorophyll a concentrations, and changes to coral cover across the tropical north Pacific Ocean,\" the authors said. \"These results may be transferrable to other oceanic regions to help predict coral reef status at even larger scales.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract El Niño Southern Oscillation (ENSO) events modulate oceanographic processes that control temperature and productivity in tropical waters, yet potential interactions with low frequency climate variability, such as the Pacific Decadal Oscillation (PDO), are poorly understood. We show that ENSO and PDO together predicted (i) maximum sea-surface temperatures (SST), which were associated with coral bleaching and declines in coral cover, and (ii) maximum chlorophyll-a concentrations, which were associated with high densities of coral-predatory Acanthaster starfish, across the tropical north Pacific Ocean since 1980. Asynchrony between the positive PDO and negative ENSO (i.e., La Niña) was associated with peaks in annual SST. By contrast, synchrony between the positive PDO and positive ENSO (i.e., El Niño) was associated with peaks in chlorophyll-a. Both conditions led to ecological disturbances and significant loss of coral cover, however, spatial models revealed where impacts to reefs were expected under varying climate scenarios. The 2015/17 ENSO event was coupled with a positive PDO and resulted in high SST and Acanthaster abundances in eastern Micronesia, while positive coral growth occurred in western Micronesia. Our novel approach for forecasting coral growth into the future may be applicable to other oceanic regions with differing oceanographic modulators. Introduction Coral bleaching is a consequence of anomalous thermal-stress events that have led to coral mortality in extreme conditions and to changes in the composition of remaining coral assemblages 1 , 2 . A recent increase in the frequency and intensity of thermal-stress events in the Pacific Ocean is attributed to the overprint of ocean warming on El Niño Southern Oscillation (ENSO) 2 , 3 , 4 . The overprint of warming in the central Pacific reduce the threshold and increase the likelihood of extreme ENSO events 5 , 6 . Yet, predicting where and when coral reefs are susceptible to ENSO events is challenging 2 , 7 , 8 . Consider for example the coral reefs in Micronesia that were exposed to strong ENSO events in 1997/98 and again in 2015/17. The 1997/98 ENSO was attributed to extensive coral bleaching in western Micronesia 9 , 10 , whereas the 2015/17 event impacted central and eastern Micronesia 2000 km farther eastward. These disturbance patterns suggest that our ability to predict reef futures relies on a better understanding of how ENSO combines with secondary, low frequency climate variability to regulate ocean temperatures across the tropical Pacific Ocean 11 . Short-term predictive models can accurately forecast ocean temperatures 3–4 months into the future using autoregressive and linear inverse models that are extensions of recent climate observations 12 . These types of models, for example, predict thermal stress events and form the basis for coral bleaching alerts that are derived from satellite SST data 13 , 14 , 15 . By contrast, longer-term predictions that reveal the likelihood of future thermal anomalies are based on past temperature records from geological coral cores and on historical patterns of past temperatures (Thompson and van Woesik 2009). Representative concentration pathway (RCP) models, for example, predict SST trajectories over the next 50 to 100 years under varying CO 2 emissions scenarios 8 , 16 . RCP models provide novel insight into patterns and processes associated with SST variation and rely upon smoothed annual trends over low-resolution geographic projections. The present study differs from both approaches and sought to predict changes in ocean temperatures across years to decades that were driven by climate oscillations associated with ENSO and the Pacific Decadal Oscillation (PDO). While bleaching events are commonly associated with ENSO cycles 1 , 2 , the PDO represents a low frequency climate variability that is associated with changes in SST and productivity along a north-to-south gradient in the tropical and temperate Pacific Ocean. The north-to-south climatic shifts are associated with cool and warm PDO phases that can augment or diminish the influence of ENSO 17 , 18 . Although the atmospheric and oceanic processes driving the PDO are poorly understood, at least compared with ENSO, the present study relies upon the PDO indices as a measure of predictable oceanographic change as the science surrounding the PDO and other interdecadal oscillations continue to evolve 19 . In addition to thermal stressors, coral reefs in the Pacific and Indian Oceans are subjected to repeated outbreaks of the coral-eating seastar Acanthaster . Several studies have demonstrated that the density of these coral predators are proportional to the extent of coral mortality, and that Acanthaster frequently spread across reefs like fires spread through forests 20 , 21 . These episodes of intensive coral predation have been linked to high nutrient concentrations for brachiolaria larvae of Acanthaster 22 . Such high nutrient concentrations are associated with river discharge 23 , 24 or anomalous oceanographic conditions generating high coastal productivity, frequently detected as high chlorophyll-a concentrations 25 , 26 . Enhanced primary productivity can occur during ENSO events in some coral-reef localities that are otherwise nutrient depauperate 25 . For example, ENSO can cause dynamic shifts in coastal upwelling, currents, and regional rainfall 26 . Here, we modelled the relationships between indices of climate modulators, thermal stress and chlorophyll-a concentrations, and the resultant change in coral cover across the tropical North Pacific (1° to 11°N, 130° to 165°E, Fig. 1 ). Our study revealed a strong interaction between these indices and changes to the coral reefs of Micronesia, demonstrating how ENSO cycles influence both heat transfer and productivity in a predictable, but spatially inconsistent manner. Figure 1 Map of the western Pacific Ocean with a geographical box surrounding the tropical North Pacific study region of Micronesia. Numbers indicate islands where long-term biological data were collected: (1) Palau, (2) Yap, (3) Chuuk, (4) Pohnpei, and (5) Kosrae. Map was created by author PH using ArcGIS software 10.2.2 and freely available base maps associated with the online account. Full size image Materials and Methods The present study was conducted in Micronesia, tropical northwestern Pacific Ocean (1° to 11°N, 130° to 165°E) (Fig. 1 ). Micronesia has a long history of disturbances impacting coral reefs. Widespread thermal-stress related coral bleaching<|im_end|> <|im_start|>assistant A new study by the Marine Laboratory at the University of Guam may help researchers predict coral bleaching months earlier than current tools, and, for the first time, may help predict invasion events of coral-eating crown-of-thorns starfish. The study was published on May 8 in Scientific Reports. Coral bleaching and the crown-of-thorns starfish represent the two biggest disturbances coral reefs face, while local stressors like pollution and overfishing represent the two biggest impediments to recovery following disturbances. Unlike other prediction tools, this study used the interaction of two major oceanographic modulators—El Nino and Pacific Decadal Oscillation, or PDO—to predict how "warm blobs" of seawater and excess nutrients move around the tropical Western Pacific to cause these two destructive events. Existing tools typically provide bleaching warnings two to three weeks in advance; however, this new tool extends the warning period to between three and five months. Important implications Advanced warnings have important implications for coral reef management efforts in the Pacific region and potentially beyond. "It takes management from a reactive position to a more proactive one," said senior author Peter Houk, an associate professor of marine biology in the Marine Lab. "Not a lot can be accomplished with only a couple weeks' notice, but predicting bleaching and starfish disturbance events a few months out may give governments and other agencies more time to acquire supplies, create legislation, and create support networks to ensure reefs are better equipped to handle these forces." For example, it allows more time to revise temporary fisheries regulations, raise funds for the removal of starfish, and procure supplies needed to support these acts. The authors have predicted outbreaks of starfish to emerge in Eastern Micronesia this year, providing time for Kosrae's tourism industry and resources agencies to gather supplies and build monitoring and removal plans now. Further, the authors can provide warnings for other islands down current to be on the lookout as starfish outbreaks are known to spread across islands and reefs in the direction of prevailing currents. Piis Patch Reef on the Micronesian Island of Chuuk is shown in August 2018 following a coral bleaching event associated with El Niño, or the warming phase of sea temperatures. Credit: University of Guam An unanswered question Above-average sea-surface temperatures are common across the tropical Pacific following El Nino Southern Oscillation events, which are increasingly exacerbated by climate change. However, islands—from Palau to Kosrae—can be affected differently. One may bleach, while another experiences little to none. That question motivated researchers to study the impact of El Nino interacting with the PDO. Together, the two patterns predict maximum sea-surface temperatures and also the movement of "nutrient plumes" filled with what is known as "chlorophyll a" around the Pacific Ocean that attract plankton and cause the crown-of-thorns starfish outbreaks that wreak havoc on coral. Both sea-surface temperatures and nutrient plumes have been mapped by satellites for years; however, predicting their future has been a challenge. Predictions based on decades of data The researchers analyzed sea temperatures dating back to 1980 and biological data dating back to 1998, including coral cover and chlorophyll a plumes, from 82 survey sites on the main islands of Micronesia to track how they are influenced by the interaction of these two cycles. Lorenzo Stephan, a coral reef monitoring team member in Chuuk, holds one of many coral-eating crown-of-thorns starfish found during the El Niño-Southern Oscillation event of 2015-2017. A recently published study out of the University of Guam Marine Laboratory found a predictable pattern between starfish invasions and the interaction of El Niño and Pacific Decadal Oscillation climate events. Credit: University of Guam Using those observations, they built models that accurately predicted both sea surface temperatures and nutrients. The models accounted for 77% of the variation in sea temperature and 55% of the variation in chlorophyll a concentrations between 1980 to the present, both of which support strong predictions. The study shows that including PDO events into forecasts may improve predictions of when and where bleaching and starfish outbreaks will occur. The next step will be to build an online resource to host the predictive model for scientists and resources managers to access and to keep improving the model to the extent possible. "We provide the first insight into how PDO and El Niño cycles predicted sea-surface temperatures, chlorophyll a concentrations, and changes to coral cover across the tropical north Pacific Ocean," the authors said. "These results may be transferrable to other oceanic regions to help predict coral reef status at even larger scales." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The ancestral origins of the lytic cell death mode, necroptosis, lie in host defense. However, the dysregulation of necroptosis in inflammatory diseases has led to widespread interest in targeting the pathway therapeutically. This mode of cell death is executed by the terminal effector, the MLKL pseudokinase, which is licensed to kill following phosphorylation by its upstream regulator, RIPK3 kinase. The precise molecular details underlying MLKL activation are still emerging and, intriguingly, appear to mechanistically-diverge between species. Here, we report the structure of the human RIPK3 kinase domain alone and in complex with the MLKL pseudokinase. These structures reveal how human RIPK3 structurally differs from its mouse counterpart, and how human RIPK3 maintains MLKL in an inactive conformation prior to induction of necroptosis. Residues within the RIPK3:MLKL C-lobe interface are crucial to complex assembly and necroptotic signaling in human cells, thereby rationalizing the strict species specificity governing RIPK3 activation of MLKL. Introduction Necroptosis is a lytic, caspase-independent programmed cell death modality 1 , 2 , 3 , 4 , 5 , 6 that has ancestral origins in innate immunity 7 , 8 , 9 , 10 , 11 . Recent studies have implicated the dysregulation of necroptosis signaling in a range of human pathologies, including inflammatory diseases 12 , 13 , 14 , 15 , renal injury 16 , 17 , diabetes 18 , and inflammatory bowel disease 19 , raising interest in the pathway as a therapeutic target 20 . Necroptotic signaling is initiated upon ligation of death or pathogen receptors, such as tumor necrosis factor (TNF) receptor 1 or Toll-like receptors, and the subsequent assembly of a cytoplasmic signaling platform termed the necrosome. Necrosome formation occurs in scenarios where the cellular inhibitors of apoptosis (cIAP) E3 Ubiquitin ligase family or Caspase-8 protease are disabled, preventing the involvement of the apical kinase, receptor-interacting serine/threonine protein kinase (RIPK)-1, in nuclear factor-κB (NF-κB) or apoptotic signaling. The necrosome is a high molecular weight complex in which the RIPK1 and RIPK3 kinases assemble as core proteins via their C-terminal functional amyloid-forming RIP homotypic interaction motifs (RHIMs) 21 , 22 , 23 . Although the details of the underlying cues for assembly are incompletely understood, necroptotic signaling induces autophosphorylation of the RIPK1 kinase domain, which permits recruitment and auto-activation of RIPK3 (refs. 5 , 24 , 25 ) and subsequent engagement of the terminal pathway effector, the Mixed Lineage Kinase domain-Like (MLKL) pseudokinase 4 , 6 , 26 , 27 . RIPK3-mediated phosphorylation of MLKL permits its dissociation from the necrosome, prior to trafficking to the plasma membrane where MLKL accumulates into hotspots and permeabilizes the cell, manifesting in a lytic, pro-inflammatory form of death 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 . Although the core principles of necroptotic signaling are conserved between mammals, there is remarkable species specificity 38 , 39 , such that rat MLKL cannot substitute for mouse MLKL in mouse cells despite their 86% amino acid identity 40 . Such divergence is consistent with an ancestral origin for the pathway in host defense, where exposure to necroptosis-interfering proteins encoded by different pathogens may have driven the co-evolution, and interspecies divergence, of RIPK3 and MLKL cognate pairs 7 , 8 , 9 , 10 , 11 , 41 , 42 , 43 , 44 . The precise nature of the interactions between RIPK3 and MLKL are of immense interest, because recognition of MLKL is a key checkpoint in the execution of the necroptosis pathway. To date, our understanding of this interaction has been limited by a dearth of RIPK3:MLKL complex structures, with only the mouse complex reported, and by the availability of only the mouse RIPK3 structure 45 , 46 . Recent data indicate that human MLKL occurs in the cytoplasm in complex with RIPK3 prior to initiation of necroptosis 47 . Upon receipt of necroptotic signals, this complex is recruited to the necrosome where RIPK3 phosphorylates and activates MLKL. Phosphorylation was proposed to induce MLKL release from the necrosome, which could be detected by a recently-described synthetic protein ligand termed Monobody-27 (ref. 47 ). The Monobody-27 recognition site on human MLKL was proposed to overlap the RIPK3-binding site on MLKL, because Monobody-27 binding was occluded prior to MLKL activation and necrosome disengagement. Additionally, this process was proposed to involve a structural interconversion of MLKL from an open to a closed conformation 47 . However, which form represents the dormant form bound by RIPK3, and which is the activated form following RIPK3-mediated phosphorylation, required validation. Further, owing to primary sequence divergence between mouse and human MLKL and RIPK3, knowledge of the RIPK3-binding site on MLKL has relied on the identification of synthetic binding proteins, termed monobodies, that compete with RIPK3 for binding to MLKL 47 . However, a precise definition of how human RIPK3 recognizes human MLKL, and how this differs from the mouse counterpart, has been lacking in the absence of a complex structure. Here, we report the crystal structure of the human RIPK3 kinase domain alone and in complex with the human MLKL pseudokinase domain. Human RIPK3 and MLKL bound in a face-to-face arrangement mediated by parallel N-lobe:N-lobe and C-lobe:C-lobe contacts, which lead to their activation loops and ATP-binding sites facing towards each other. Interestingly, despite only 70% sequence identity and different autophosphorylation sites between human and mouse RIPK3 kinase domains, the C-lobes of human and mouse RIPK3 exhibited comparable topology and modes of interaction with MLKL, while the N-lobes diverged structurally and formed a distinct interface in the human RIPK3:MLKL complex. These differences could be attributed to human MLKL assuming an open conformation with a helical activation loop that displaces the key regulatory element, the αC helix. In contrast, in the orthologous mouse RIPK3:MLKL complex structure, the mouse MLKL activation loop forms a shorter helix that packs against the MLKL C-lobe in a distinct orientation. The different positions of the human and mouse MLKL activation loop helices impart distinct modes of interaction with the N-lobe", "role": "user" }, { "content": "A team of WEHI researchers has for the first time visualized a human cell death complex linked to autoimmune and inflammatory conditions, such as inflammatory bowel disease, and injuries associated with excessive cell death. Using the Australian Synchrotron, the team solved the structure of the human cell death proteins MLKL and RIPK3 bound to each other, as well as human RIPK3 alone. When RIPK3 activates MLKL, it triggers a type of inflammatory cell death called necroptosis that kills the cell and alerts the immune system that it is under attack. However, when uncontrolled, necroptosis has been linked to human inflammatory diseases. The findings will help scientists discover drugs that can target and suppress cell death by necroptosis, which could lead to new treatments for a range of autoimmune and inflammatory diseases including inflammatory bowel disease, renal injury and diabetes. The research, published in Nature Communications, was led by WEHI researchers Yanxiang Meng, Dr. Katherine Davies, Associate Professor Peter Czabotar and Associate Professor James Murphy. The discovery is the latest in an almost 15-year-long journey to understand necroptosis for treating disease. 'The cell death pathway' Necroptosis is a type of inflammatory cell death process that helps protect the body against infection. Most often triggered when a cell is infected by a virus or bacteria, the cell is instructed to die and send inflammatory signals to warn the immune system of foreign invaders. However, when necroptosis is uncontrolled or excessive, the inflammatory response can trigger disease. Ph.D. student Yanxiang Meng said that MLKL and RIPK3 are bound in an inert state in all cells of the body, waiting to be activated. Credit: Walter and Eliza Hall Institute of Medical Research \"MLKL and RIPK3 form an inert complex, with RIPK3 'holding' MLKL in an inactive state to prevent necroptotic cell death,\" he said. \"When the cell is infected, RIPK3 chemically modifies MLKL then detaches, giving it a 'licence to kill' the infected or damaged cell for the greater good,\" he said. He said the Australian Synchrotron and Collaborative Crystallisation Centre (C3) facility at CSIRO were crucial to visualize the structure of human forms of RIPK3 bound to human MLKL for the first time. \"The necroptotic cell death proteins are conserved across different organisms, however there are differences between the proteins' structures in different animals and how they bind to each other. \"We showed that the human versions of these proteins bind differently to what we have seen in other species. This is something the scientific community has been waiting many years for.\" New targets for drug discovery Dr. Davies said the team hoped this structural information would, in the future, lead to new treatment options for patients suffering from diseases linked to excessive necroptosis. \"We now have a picture of how two key proteins in this death pathway are maintained in their dormant state. It would be interesting to know how this is regulated and leads to disease and whether this could be targeted with small molecule drugs,\" she said. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The ancestral origins of the lytic cell death mode, necroptosis, lie in host defense. However, the dysregulation of necroptosis in inflammatory diseases has led to widespread interest in targeting the pathway therapeutically. This mode of cell death is executed by the terminal effector, the MLKL pseudokinase, which is licensed to kill following phosphorylation by its upstream regulator, RIPK3 kinase. The precise molecular details underlying MLKL activation are still emerging and, intriguingly, appear to mechanistically-diverge between species. Here, we report the structure of the human RIPK3 kinase domain alone and in complex with the MLKL pseudokinase. These structures reveal how human RIPK3 structurally differs from its mouse counterpart, and how human RIPK3 maintains MLKL in an inactive conformation prior to induction of necroptosis. Residues within the RIPK3:MLKL C-lobe interface are crucial to complex assembly and necroptotic signaling in human cells, thereby rationalizing the strict species specificity governing RIPK3 activation of MLKL. Introduction Necroptosis is a lytic, caspase-independent programmed cell death modality 1 , 2 , 3 , 4 , 5 , 6 that has ancestral origins in innate immunity 7 , 8 , 9 , 10 , 11 . Recent studies have implicated the dysregulation of necroptosis signaling in a range of human pathologies, including inflammatory diseases 12 , 13 , 14 , 15 , renal injury 16 , 17 , diabetes 18 , and inflammatory bowel disease 19 , raising interest in the pathway as a therapeutic target 20 . Necroptotic signaling is initiated upon ligation of death or pathogen receptors, such as tumor necrosis factor (TNF) receptor 1 or Toll-like receptors, and the subsequent assembly of a cytoplasmic signaling platform termed the necrosome. Necrosome formation occurs in scenarios where the cellular inhibitors of apoptosis (cIAP) E3 Ubiquitin ligase family or Caspase-8 protease are disabled, preventing the involvement of the apical kinase, receptor-interacting serine/threonine protein kinase (RIPK)-1, in nuclear factor-κB (NF-κB) or apoptotic signaling. The necrosome is a high molecular weight complex in which the RIPK1 and RIPK3 kinases assemble as core proteins via their C-terminal functional amyloid-forming RIP homotypic interaction motifs (RHIMs) 21 , 22 , 23 . Although the details of the underlying cues for assembly are incompletely understood, necroptotic signaling induces autophosphorylation of the RIPK1 kinase domain, which permits recruitment and auto-activation of RIPK3 (refs. 5 , 24 , 25 ) and subsequent engagement of the terminal pathway effector, the Mixed Lineage Kinase domain-Like (MLKL) pseudokinase 4 , 6 , 26 , 27 . RIPK3-mediated phosphorylation of MLKL permits its dissociation from the necrosome, prior to trafficking to the plasma membrane where MLKL accumulates into hotspots and permeabilizes the cell, manifesting in a lytic, pro-inflammatory form of death 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 . Although the core principles of necroptotic signaling are conserved between mammals, there is remarkable species specificity 38 , 39 , such that rat MLKL cannot substitute for mouse MLKL in mouse cells despite their 86% amino acid identity 40 . Such divergence is consistent with an ancestral origin for the pathway in host defense, where exposure to necroptosis-interfering proteins encoded by different pathogens may have driven the co-evolution, and interspecies divergence, of RIPK3 and MLKL cognate pairs 7 , 8 , 9 , 10 , 11 , 41 , 42 , 43 , 44 . The precise nature of the interactions between RIPK3 and MLKL are of immense interest, because recognition of MLKL is a key checkpoint in the execution of the necroptosis pathway. To date, our understanding of this interaction has been limited by a dearth of RIPK3:MLKL complex structures, with only the mouse complex reported, and by the availability of only the mouse RIPK3 structure 45 , 46 . Recent data indicate that human MLKL occurs in the cytoplasm in complex with RIPK3 prior to initiation of necroptosis 47 . Upon receipt of necroptotic signals, this complex is recruited to the necrosome where RIPK3 phosphorylates and activates MLKL. Phosphorylation was proposed to induce MLKL release from the necrosome, which could be detected by a recently-described synthetic protein ligand termed Monobody-27 (ref. 47 ). The Monobody-27 recognition site on human MLKL was proposed to overlap the RIPK3-binding site on MLKL, because Monobody-27 binding was occluded prior to MLKL activation and necrosome disengagement. Additionally, this process was proposed to involve a structural interconversion of MLKL from an open to a closed conformation 47 . However, which form represents the dormant form bound by RIPK3, and which is the activated form following RIPK3-mediated phosphorylation, required validation. Further, owing to primary sequence divergence between mouse and human MLKL and RIPK3, knowledge of the RIPK3-binding site on MLKL has relied on the identification of synthetic binding proteins, termed monobodies, that compete with RIPK3 for binding to MLKL 47 . However, a precise definition of how human RIPK3 recognizes human MLKL, and how this differs from the mouse counterpart, has been lacking in the absence of a complex structure. Here, we report the crystal structure of the human RIPK3 kinase domain alone and in complex with the human MLKL pseudokinase domain. Human RIPK3 and MLKL bound in a face-to-face arrangement mediated by parallel N-lobe:N-lobe and C-lobe:C-lobe contacts, which lead to their activation loops and ATP-binding sites facing towards each other. Interestingly, despite only 70% sequence identity and different autophosphorylation sites between human and mouse RIPK3 kinase domains, the C-lobes of human and mouse RIPK3 exhibited comparable topology and modes of interaction with MLKL, while the N-lobes diverged structurally and formed a distinct interface in the human RIPK3:MLKL complex. These differences could be attributed to human MLKL assuming an open conformation with a helical activation loop that displaces the key regulatory element, the αC helix. In contrast, in the orthologous mouse RIPK3:MLKL complex structure, the mouse MLKL activation loop forms a shorter helix that packs against the MLKL C-lobe in a distinct orientation. The different positions of the human and mouse MLKL activation loop helices impart distinct modes of interaction with the N-lobe<|im_end|> <|im_start|>assistant A team of WEHI researchers has for the first time visualized a human cell death complex linked to autoimmune and inflammatory conditions, such as inflammatory bowel disease, and injuries associated with excessive cell death. Using the Australian Synchrotron, the team solved the structure of the human cell death proteins MLKL and RIPK3 bound to each other, as well as human RIPK3 alone. When RIPK3 activates MLKL, it triggers a type of inflammatory cell death called necroptosis that kills the cell and alerts the immune system that it is under attack. However, when uncontrolled, necroptosis has been linked to human inflammatory diseases. The findings will help scientists discover drugs that can target and suppress cell death by necroptosis, which could lead to new treatments for a range of autoimmune and inflammatory diseases including inflammatory bowel disease, renal injury and diabetes. The research, published in Nature Communications, was led by WEHI researchers Yanxiang Meng, Dr. Katherine Davies, Associate Professor Peter Czabotar and Associate Professor James Murphy. The discovery is the latest in an almost 15-year-long journey to understand necroptosis for treating disease. 'The cell death pathway' Necroptosis is a type of inflammatory cell death process that helps protect the body against infection. Most often triggered when a cell is infected by a virus or bacteria, the cell is instructed to die and send inflammatory signals to warn the immune system of foreign invaders. However, when necroptosis is uncontrolled or excessive, the inflammatory response can trigger disease. Ph.D. student Yanxiang Meng said that MLKL and RIPK3 are bound in an inert state in all cells of the body, waiting to be activated. Credit: Walter and Eliza Hall Institute of Medical Research "MLKL and RIPK3 form an inert complex, with RIPK3 'holding' MLKL in an inactive state to prevent necroptotic cell death," he said. "When the cell is infected, RIPK3 chemically modifies MLKL then detaches, giving it a 'licence to kill' the infected or damaged cell for the greater good," he said. He said the Australian Synchrotron and Collaborative Crystallisation Centre (C3) facility at CSIRO were crucial to visualize the structure of human forms of RIPK3 bound to human MLKL for the first time. "The necroptotic cell death proteins are conserved across different organisms, however there are differences between the proteins' structures in different animals and how they bind to each other. "We showed that the human versions of these proteins bind differently to what we have seen in other species. This is something the scientific community has been waiting many years for." New targets for drug discovery Dr. Davies said the team hoped this structural information would, in the future, lead to new treatment options for patients suffering from diseases linked to excessive necroptosis. "We now have a picture of how two key proteins in this death pathway are maintained in their dormant state. It would be interesting to know how this is regulated and leads to disease and whether this could be targeted with small molecule drugs," she said. <|im_end|>

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2,168

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Hepatitis C virus (HCV) infection is a causal agent of chronic liver disease, cirrhosis and hepatocellular carcinoma in humans, and afflicts more than 70 million people worldwide. The HCV envelope glycoproteins E1 and E2 are responsible for the binding of the virus to the host cell, but the exact entry process remains undetermined 1 . The majority of broadly neutralizing antibodies block interaction between HCV E2 and the large extracellular loop (LEL) of the cellular receptor CD81 (CD81-LEL) 2 . Here we show that low pH enhances the binding of CD81-LEL to E2, and we determine the crystal structure of E2 in complex with an antigen-binding fragment (2A12) and CD81-LEL (E2–2A12–CD81-LEL); E2 in complex with 2A12 (E2–2A12); and CD81-LEL alone. After binding CD81, residues 418–422 in E2 are displaced, which allows for the extension of an internal loop consisting of residues 520–539. Docking of the E2–CD81-LEL complex onto a membrane-embedded, full-length CD81 places the residues Tyr529 and Trp531 of E2 proximal to the membrane. Liposome flotation assays show that low pH and CD81-LEL increase the interaction of E2 with membranes, whereas structure-based mutants of Tyr529, Trp531 and Ile422 in the amino terminus of E2 abolish membrane binding. These data support a model in which acidification and receptor binding result in a conformational change in E2 in preparation for membrane fusion. Main HCV enters hepatocytes through a multistep process that requires a series of host cellular factors and the viral envelope glycoproteins E1 and E2 (reviewed previously 1 ). The HCV glycoproteins mediate cell targeting, endocytosis and membrane fusion, which is ultimately stimulated by endosomal acidification 3 . At least four cellular factors are critical for HCV attachment and entry: CD81, scavenger receptor class B type I (SRBI), claudin-1 (CLDN) and occludin (OCLN); however, blocking the E2–CD81 interaction is the primary means of antibody-mediated neutralization 2 . CD81 is ubiquitously expressed in a variety of cell lines, indicating that it has a role secondary to hepatocyte-specific receptor binding. CD81 translocates with the virion to tight junctions and engages with the late-entry factors CLDN and OCLN in the endosome for acidification and entry. CD81 is an integral membrane protein of the tetraspanin family that contains four transmembrane helices. The CD81-LEL—a globular domain made of five helices (A–E)—binds E2, and residues that are essential for the interaction have previously been identified 4 , 5 , 6 , 7 , 8 , 9 . The molecular mechanisms thereafter, which mediate the cell entry and membrane fusion of HCV, remain to our knowledge undefined. Initial crystallization trials showed that the presence of low pH is a critical determinant for crystal formation. We therefore measured the affinity of human and tamarin CD81-LEL (hCD81-LEL and tCD81-LEL, respectively) for the ectodomain of E2 (eE2) at neutral and low pH. Differing from human CD81 by only five amino acids (Extended Data Fig. 1 ), tamarin CD81 supports HCV infection and binds E2 more effectively 10 , 11 . tCD81-LEL showed a fourfold increase in affinity for eE2 compared to hCD81-LEL (175 nM and 773 nM, respectively) (Extended Data Table 1 , Extended Data Fig. 2 ). Low pH (5.0) increased the affinity of tCD81-LEL for eE2 by 4.7-fold (175 nM at pH 7.5 to 37 nM at pH 5.0), whereas hCD81-LEL showed only a modest 1.1-fold increase in affinity (773 nM at pH 7.5 to 681 nM at pH 5.0) (Extended Data Table 1 , Extended Data Fig. 2 ). A low-pH complex of tCD81-LEL–eE2(ΔHVR1) (in which ΔHVR1 indicates deletion of the hypervariable region 1 of eE2) with 2A12 (an antigen-binding fragment (Fab) of a non-neutralizing antibody) 12 as a crystallization chaperone yielded crystals that diffracted to a resolution of about 3.3 Å. To assist in the identification of changes after complex formation, structures of full-length, fully glycosylated eE2–2A12 as well as tCD81-LEL alone were also determined (Fig. 1 , Extended Data Table 2 ). Fig. 1: Ribbon diagrams of the tCD81-LEL–eE2(ΔHVR1)–2A12, eE2–2A12 and tCD81-LEL X-ray crystal structures. a , b , The tCD81-LEL (blue) and eE2(ΔHVR1) (red and green) complex ( a ) and eE2 alone (pink and grey) ( b ), highlighting the location of the CD81-binding loop (green in a and grey in b ). The 2A12 Fab is not shown. Carbohydrate molecules are coloured by heteroatom. c , The homodimeric, asymmetric unit of tCD81-LEL, free form, with helices A–E labelled on the intermediate (violet) and open (olive) conformations. The unwound helix D in the open conformation is labelled with a crossed-out D. d , The tCD81-LEL(blue) and eE2(ΔHVR1) (red and green) interface in detail with the side chains of the CD81-binding loop residues (green and heteroatom) represented in sticks. The CD81-binding loop sequence is shown at the top. Full size image Conformational changes in E2 and CD81 The tCD81-LEL–eE2(ΔHVR1)–2A12 structure has two complexes in the asymmetric unit, which allows two independent observations of the interaction (Fig. 1a , Extended Data Fig. 3 ). The non-crystallographic, two-fold symmetry axis resembles the homodimer that is observed in the tCD81-LEL structure (Fig. 1c ) and in previously reported hCD81-LEL structures 13 , 14 , and is likely to be a biochemical artifact as the interface clashes with the transmembrane helices of the full-length CD81 structures 15 , 16 . Each tCD81-LEL is bound to a copy of eE2(ΔHVR1), and each eE2(ΔHVR1) is, in turn, bound to a 2A12 Fab. There are no contacts between the E2 molecules in the asymmetric unit (Extended Data Fig. 3 ) but the complexes are highly similar, with an alpha carbon root mean squared deviation (r.m.s.d.) of 1.0 Å. The overall structure of E2 in the eE2–2A12 and tCD81-LEL–eE2(ΔHVR1)–2A12 complexes (Fig. 1a, b ) is similar to that reported previously 12 , 17 , 18 , 19 , 20 . We observed two noteworthy conformational changes in residues 418–422 and 520–539 (the CD81-binding loop) of E2 (Fig. 1a, b, d, Extended Data Fig. 4 ). In the absence of CD81, residues 384–421 (HVR1 and antigenic site (AS) 412) of eE2 are disordered,", "role": "user" }, { "content": "In a new paper published in Nature, scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, describe the structure of a key protein on the surface of the hepatitis C virus (HCV) and how it interacts with its receptor found on some human cells. The findings provide new leads for developing an HCV vaccine. Hepatitis C is one of the most common bloodborne infections in the United States. Although it may not cause any symptoms in its early stages, untreated chronic infections can lead to severe liver damage, cancer, and death. Concerningly, infections are on the rise among young adults, largely due to exposure resulting from shared drug-injectables. No vaccine is available to prevent HCV infection. HCV is usually transmitted via blood, such as during birth or when drug-injection equipment is shared. Because HCV may not cause any symptoms for years after initial infection, infections often go undetected. According to the U.S. Centers for Disease Control and Prevention, an estimated 2.4 million people are living with hepatitis C infection in the United States. More than half of all people infected with HCV are thought to develop chronic infection. HCV is a leading cause of cirrhosis, liver failure requiring transplant, and the leading cause of death from liver disease. Although effective antiviral drugs are available to treat HCV infection, they are expensive and do not prevent reinfection. In their new paper in Nature, researchers from NIAID and other organizations describe the interaction between a protein expressed on the surface of the HCV, known as HCV E2, and a receptor called CD81 found on the surface of some human cells. Prior research had shown that antibodies interfered with interactions between these two proteins. This suggested that the interaction between HCV E2 and CD81 allowed HCV to enter and infect human cells. However, exactly how this occurred was unknown. The researchers determined the exact structure of HCV E2 and CD81 and studied how the two proteins interacted when exposed to each other under different conditions. They found that under acidic conditions, HCV E2 easily binds to the CD81 receptor. Once the interaction between virus and receptor begins, HCV E2 changes shape, facilitating its entrance into the cell by putting the virus in closer contact with the cell membrane. Identifying these structures and the ways they interact with each other may provide the foundation for a vaccine against HCV, the researchers say. A vaccine potentially could cause a person to make specific antibodies that prevent HCV E2 from binding with CD81, stopping the virus from entering the cell, and preventing HCV infection. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Hepatitis C virus (HCV) infection is a causal agent of chronic liver disease, cirrhosis and hepatocellular carcinoma in humans, and afflicts more than 70 million people worldwide. The HCV envelope glycoproteins E1 and E2 are responsible for the binding of the virus to the host cell, but the exact entry process remains undetermined 1 . The majority of broadly neutralizing antibodies block interaction between HCV E2 and the large extracellular loop (LEL) of the cellular receptor CD81 (CD81-LEL) 2 . Here we show that low pH enhances the binding of CD81-LEL to E2, and we determine the crystal structure of E2 in complex with an antigen-binding fragment (2A12) and CD81-LEL (E2–2A12–CD81-LEL); E2 in complex with 2A12 (E2–2A12); and CD81-LEL alone. After binding CD81, residues 418–422 in E2 are displaced, which allows for the extension of an internal loop consisting of residues 520–539. Docking of the E2–CD81-LEL complex onto a membrane-embedded, full-length CD81 places the residues Tyr529 and Trp531 of E2 proximal to the membrane. Liposome flotation assays show that low pH and CD81-LEL increase the interaction of E2 with membranes, whereas structure-based mutants of Tyr529, Trp531 and Ile422 in the amino terminus of E2 abolish membrane binding. These data support a model in which acidification and receptor binding result in a conformational change in E2 in preparation for membrane fusion. Main HCV enters hepatocytes through a multistep process that requires a series of host cellular factors and the viral envelope glycoproteins E1 and E2 (reviewed previously 1 ). The HCV glycoproteins mediate cell targeting, endocytosis and membrane fusion, which is ultimately stimulated by endosomal acidification 3 . At least four cellular factors are critical for HCV attachment and entry: CD81, scavenger receptor class B type I (SRBI), claudin-1 (CLDN) and occludin (OCLN); however, blocking the E2–CD81 interaction is the primary means of antibody-mediated neutralization 2 . CD81 is ubiquitously expressed in a variety of cell lines, indicating that it has a role secondary to hepatocyte-specific receptor binding. CD81 translocates with the virion to tight junctions and engages with the late-entry factors CLDN and OCLN in the endosome for acidification and entry. CD81 is an integral membrane protein of the tetraspanin family that contains four transmembrane helices. The CD81-LEL—a globular domain made of five helices (A–E)—binds E2, and residues that are essential for the interaction have previously been identified 4 , 5 , 6 , 7 , 8 , 9 . The molecular mechanisms thereafter, which mediate the cell entry and membrane fusion of HCV, remain to our knowledge undefined. Initial crystallization trials showed that the presence of low pH is a critical determinant for crystal formation. We therefore measured the affinity of human and tamarin CD81-LEL (hCD81-LEL and tCD81-LEL, respectively) for the ectodomain of E2 (eE2) at neutral and low pH. Differing from human CD81 by only five amino acids (Extended Data Fig. 1 ), tamarin CD81 supports HCV infection and binds E2 more effectively 10 , 11 . tCD81-LEL showed a fourfold increase in affinity for eE2 compared to hCD81-LEL (175 nM and 773 nM, respectively) (Extended Data Table 1 , Extended Data Fig. 2 ). Low pH (5.0) increased the affinity of tCD81-LEL for eE2 by 4.7-fold (175 nM at pH 7.5 to 37 nM at pH 5.0), whereas hCD81-LEL showed only a modest 1.1-fold increase in affinity (773 nM at pH 7.5 to 681 nM at pH 5.0) (Extended Data Table 1 , Extended Data Fig. 2 ). A low-pH complex of tCD81-LEL–eE2(ΔHVR1) (in which ΔHVR1 indicates deletion of the hypervariable region 1 of eE2) with 2A12 (an antigen-binding fragment (Fab) of a non-neutralizing antibody) 12 as a crystallization chaperone yielded crystals that diffracted to a resolution of about 3.3 Å. To assist in the identification of changes after complex formation, structures of full-length, fully glycosylated eE2–2A12 as well as tCD81-LEL alone were also determined (Fig. 1 , Extended Data Table 2 ). Fig. 1: Ribbon diagrams of the tCD81-LEL–eE2(ΔHVR1)–2A12, eE2–2A12 and tCD81-LEL X-ray crystal structures. a , b , The tCD81-LEL (blue) and eE2(ΔHVR1) (red and green) complex ( a ) and eE2 alone (pink and grey) ( b ), highlighting the location of the CD81-binding loop (green in a and grey in b ). The 2A12 Fab is not shown. Carbohydrate molecules are coloured by heteroatom. c , The homodimeric, asymmetric unit of tCD81-LEL, free form, with helices A–E labelled on the intermediate (violet) and open (olive) conformations. The unwound helix D in the open conformation is labelled with a crossed-out D. d , The tCD81-LEL(blue) and eE2(ΔHVR1) (red and green) interface in detail with the side chains of the CD81-binding loop residues (green and heteroatom) represented in sticks. The CD81-binding loop sequence is shown at the top. Full size image Conformational changes in E2 and CD81 The tCD81-LEL–eE2(ΔHVR1)–2A12 structure has two complexes in the asymmetric unit, which allows two independent observations of the interaction (Fig. 1a , Extended Data Fig. 3 ). The non-crystallographic, two-fold symmetry axis resembles the homodimer that is observed in the tCD81-LEL structure (Fig. 1c ) and in previously reported hCD81-LEL structures 13 , 14 , and is likely to be a biochemical artifact as the interface clashes with the transmembrane helices of the full-length CD81 structures 15 , 16 . Each tCD81-LEL is bound to a copy of eE2(ΔHVR1), and each eE2(ΔHVR1) is, in turn, bound to a 2A12 Fab. There are no contacts between the E2 molecules in the asymmetric unit (Extended Data Fig. 3 ) but the complexes are highly similar, with an alpha carbon root mean squared deviation (r.m.s.d.) of 1.0 Å. The overall structure of E2 in the eE2–2A12 and tCD81-LEL–eE2(ΔHVR1)–2A12 complexes (Fig. 1a, b ) is similar to that reported previously 12 , 17 , 18 , 19 , 20 . We observed two noteworthy conformational changes in residues 418–422 and 520–539 (the CD81-binding loop) of E2 (Fig. 1a, b, d, Extended Data Fig. 4 ). In the absence of CD81, residues 384–421 (HVR1 and antigenic site (AS) 412) of eE2 are disordered,<|im_end|> <|im_start|>assistant In a new paper published in Nature, scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, describe the structure of a key protein on the surface of the hepatitis C virus (HCV) and how it interacts with its receptor found on some human cells. The findings provide new leads for developing an HCV vaccine. Hepatitis C is one of the most common bloodborne infections in the United States. Although it may not cause any symptoms in its early stages, untreated chronic infections can lead to severe liver damage, cancer, and death. Concerningly, infections are on the rise among young adults, largely due to exposure resulting from shared drug-injectables. No vaccine is available to prevent HCV infection. HCV is usually transmitted via blood, such as during birth or when drug-injection equipment is shared. Because HCV may not cause any symptoms for years after initial infection, infections often go undetected. According to the U.S. Centers for Disease Control and Prevention, an estimated 2.4 million people are living with hepatitis C infection in the United States. More than half of all people infected with HCV are thought to develop chronic infection. HCV is a leading cause of cirrhosis, liver failure requiring transplant, and the leading cause of death from liver disease. Although effective antiviral drugs are available to treat HCV infection, they are expensive and do not prevent reinfection. In their new paper in Nature, researchers from NIAID and other organizations describe the interaction between a protein expressed on the surface of the HCV, known as HCV E2, and a receptor called CD81 found on the surface of some human cells. Prior research had shown that antibodies interfered with interactions between these two proteins. This suggested that the interaction between HCV E2 and CD81 allowed HCV to enter and infect human cells. However, exactly how this occurred was unknown. The researchers determined the exact structure of HCV E2 and CD81 and studied how the two proteins interacted when exposed to each other under different conditions. They found that under acidic conditions, HCV E2 easily binds to the CD81 receptor. Once the interaction between virus and receptor begins, HCV E2 changes shape, facilitating its entrance into the cell by putting the virus in closer contact with the cell membrane. Identifying these structures and the ways they interact with each other may provide the foundation for a vaccine against HCV, the researchers say. A vaccine potentially could cause a person to make specific antibodies that prevent HCV E2 from binding with CD81, stopping the virus from entering the cell, and preventing HCV infection. <|im_end|>

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13, 15, 705, 20444, 305, 6620, 5932, 12, 877, 43, 8710, 1193, 264, 27946, 220, 16, 13, 16, 24325, 5376, 304, 51552, 320, 23267, 308, 44, 520, 37143, 220, 22, 13, 20, 311, 220, 25091, 308, 44, 520, 37143, 220, 20, 13, 15, 8, 320, 54290, 2956, 6771, 220, 16, 1174, 41665, 2956, 23966, 13, 220, 17, 7609, 362, 3428, 2320, 39, 6485, 315, 259, 6620, 5932, 12, 877, 43, 4235, 68, 36, 17, 7, 101561, 39, 19330, 16, 8, 320, 258, 902, 82263, 39, 19330, 16, 15151, 37166, 315, 279, 9950, 651, 277, 2205, 5654, 220, 16, 315, 384, 36, 17, 8, 449, 220, 17, 32, 717, 320, 276, 83089, 65500, 12569, 320, 53267, 8, 315, 264, 2536, 92322, 4954, 63052, 8, 220, 717, 439, 264, 64568, 2065, 523, 3271, 606, 58487, 48473, 430, 1422, 1658, 22955, 311, 264, 11175, 315, 922, 220, 18, 13, 18, 80352, 13, 2057, 7945, 304, 279, 22654, 315, 4442, 1306, 6485, 18488, 11, 14726, 315, 2539, 30425, 11, 7373, 37807, 9594, 4010, 660, 384, 36, 17, 4235, 17, 32, 717, 439, 1664, 439, 259, 6620, 5932, 12, 877, 43, 7636, 1051, 1101, 11075, 320, 30035, 13, 220, 16, 1174, 41665, 2956, 6771, 220, 17, 7609, 23966, 13, 220, 16, 25, 77567, 47287, 315, 279, 259, 6620, 5932, 12, 877, 43, 4235, 68, 36, 17, 7, 101561, 39, 19330, 16, 8, 4235, 17, 32, 717, 11, 384, 36, 17, 4235, 17, 32, 717, 323, 259, 6620, 5932, 12, 877, 43, 1630, 30630, 26110, 14726, 13, 264, 1174, 293, 1174, 578, 259, 6620, 5932, 12, 877, 43, 320, 12481, 8, 323, 384, 36, 17, 7, 101561, 39, 19330, 16, 8, 320, 1171, 323, 6307, 8, 6485, 320, 264, 883, 323, 384, 36, 17, 7636, 320, 64349, 323, 20366, 8, 320, 293, 7026, 39686, 279, 3813, 315, 279, 11325, 5932, 65500, 6471, 320, 13553, 304, 264, 323, 20366, 304, 293, 7609, 578, 220, 17, 32, 717, 19797, 374, 539, 6982, 13, 3341, 34658, 349, 35715, 527, 58919, 555, 30548, 78, 22612, 13, 272, 1174, 578, 5105, 347, 3212, 292, 11, 97929, 5089, 315, 259, 6620, 5932, 12, 877, 43, 11, 1949, 1376, 11, 449, 11591, 1238, 362, 4235, 36, 61336, 389, 279, 29539, 320, 85, 32012, 8, 323, 1825, 320, 337, 535, 8, 26965, 811, 13, 578, 15375, 801, 11591, 953, 423, 304, 279, 1825, 390, 1659, 374, 61336, 449, 264, 28129, 9994, 423, 13, 294, 1174, 578, 259, 6620, 5932, 12, 877, 43, 30911, 361, 8, 323, 384, 36, 17, 7, 101561, 39, 19330, 16, 8, 320, 1171, 323, 6307, 8, 3834, 304, 7872, 449, 279, 3185, 27271, 315, 279, 11325, 5932, 65500, 6471, 71783, 320, 13553, 323, 30548, 78, 22612, 8, 15609, 304, 34240, 13, 578, 11325, 5932, 65500, 6471, 8668, 374, 6982, 520, 279, 1948, 13, 8797, 1404, 2217, 1221, 1659, 278, 4442, 304, 469, 17, 323, 11325, 5932, 578, 259, 6620, 5932, 12, 877, 43, 4235, 68, 36, 17, 7, 101561, 39, 19330, 16, 8, 4235, 17, 32, 717, 6070, 706, 1403, 69125, 304, 279, 97929, 5089, 11, 902, 6276, 1403, 9678, 24654, 315, 279, 16628, 320, 30035, 13, 220, 16, 64, 1174, 41665, 2956, 23966, 13, 220, 18, 7609, 578, 2536, 48689, 14272, 848, 79173, 11, 1403, 24325, 46220, 8183, 53291, 279, 5105, 347, 3212, 430, 374, 13468, 304, 279, 259, 6620, 5932, 12, 877, 43, 6070, 320, 30035, 13, 220, 16, 66, 883, 323, 304, 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6522, 5353, 315, 30570, 41196, 10934, 11, 26587, 8060, 23537, 43929, 11, 323, 279, 6522, 5353, 315, 4648, 505, 26587, 8624, 13, 10541, 7524, 3276, 344, 37478, 11217, 527, 2561, 311, 4322, 473, 20161, 19405, 11, 814, 527, 11646, 323, 656, 539, 5471, 15601, 13421, 13, 763, 872, 502, 5684, 304, 22037, 11, 12074, 505, 452, 5987, 926, 323, 1023, 11351, 7664, 279, 16628, 1990, 264, 13128, 13605, 389, 279, 7479, 315, 279, 473, 20161, 11, 3967, 439, 473, 20161, 469, 17, 11, 323, 264, 35268, 2663, 11325, 5932, 1766, 389, 279, 7479, 315, 1063, 3823, 7917, 13, 32499, 3495, 1047, 6982, 430, 59854, 41305, 291, 449, 22639, 1990, 1521, 1403, 28896, 13, 1115, 12090, 430, 279, 16628, 1990, 473, 20161, 469, 17, 323, 11325, 5932, 5535, 473, 20161, 311, 3810, 323, 34527, 3823, 7917, 13, 4452, 11, 7041, 1268, 420, 10222, 574, 9987, 13, 578, 12074, 11075, 279, 4839, 6070, 315, 473, 20161, 469, 17, 323, 11325, 5932, 323, 20041, 1268, 279, 1403, 28896, 16681, 291, 994, 15246, 311, 1855, 1023, 1234, 2204, 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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Wide-gap semiconductors have received significant attention for their advantages over existing semiconductors in energy-efficient power devices. To realize stable and reliable wide-gap semiconductor devices, the basic physical properties, such as the electric properties on the surface and at the interface, should be revealed. Here, we report visualization of terahertz (THz) emission from the surface of GaN, which is excited by ultraviolet femtosecond laser pulses. We found that the THz emission is enhanced by defects related to yellow luminescence and this phenomenon is explained through the modification of band structures in the surface depletion layer owing to trapped electrons at defect sites. Our results demonstrate that the surface potential in a GaN surface could be detected by laser-induced THz emission. Moreover, this method enables feasible evaluation of the distribution of non-radiative defects, which are undetectable with photoluminescence and it contributes to the realization normally-off GaN devices. Introduction As a material for next generation devices, such as light sources, high-power devices and solar cells, wide-gap semiconductors have attracted significant attention over the years. Blue light sources manufactured from gallium nitride (GaN), which is a typical wide-gap semiconductor, have already been used in many industrial applications. For higher luminous efficiency, the crystal quality of GaN must be improved. In addition, power devices made from GaN have many superiorities over existing power devices, e.g., high-frequency operation, break-down field and heat conductivity, however there are still some problems to be solved such as a current collapse 1 and a normally-on property 2 . Among these, the normally-on characteristics, i.e., a high electric field exists without external bias voltage due to polarization 3 in the interface of the hetero-junction, have been a serious problem for practical applications. Therefore, control of the surface and the interface polarization is required. However, there is no convenient method for measuring the “local” polarization without electrical contacts. On the other hand, terahertz (THz) spectroscopy is expected to evaluate semiconductor materials and devices. The optical and electrical properties of various semiconductors have been investigated by THz time-domain spectroscopy 4 , 5 , 6 and by laser-induced THz emission spectroscopy 7 , 8 , 9 . The laser THz emission microscope (LTEM), which images the amplitude of THz emission from materials and devices, is also used for evaluating semiconductor devices 10 , 11 . Here, we measured THz emission from GaN surfaces excited by ultraviolet (UV) femtosecond laser pulses and found enhancement of THz emission due to defects in the GaN surface by comparing the photoluminescence (PL) measurements. The enhancement is explained by modification of the band bending induced by the accumulated negative charges in the surface depletion layer. Accordingly, the present results suggest that LTEM is capable of measuring not only the defect density but also the local surface potential. Results Figure 1a,b respectively show the LTEM image of the Ga-polar (0001) surface of n-type GaN, which was provided by Sumitomo Electric Industries and the waveforms of THz emissions at the two points, which are shown as sky blue and orange marks in the LTEM image. All the measurements in this study were performed at room temperature. The excitation wavelength and the photon density per pulse are 260 nm and 3.4 × 10 13 /cm 2 , respectively. Because the band gap energy of GaN is 3.4 eV, the incident photon energy (4.8 eV) is sufficient to excite an electron from the valence band to the conduction band. The LTEM image corresponds to the mapping of the negative peak amplitude at 0 ps, as shown in Fig. 1b . Figure 1 ( a ) The LTEM image of n-type GaN with an excitation wavelength of 260 nm. ( b ) The THz waveforms at two points in ( a ). Line colors correspond to point colors in ( a ). Full size image As shown in Fig. 1a , a noticeable distribution of the THz amplitude in the plane can be observed in the LTEM image, even though pulse widths were almost unchanged. Figure 2a shows PL spectra measured at two points in the same GaN sample. The PL measurement was performed at room temperature and the excitation wavelength and photon density per pulse were 345 nm and 4.8 × 10 13 /cm 2 , respectively. These spectra contain the excitation source at 345 nm, the near-band-edge (NBE) emission peak at 365 nm, the luminescence peak by donor-acceptor pair (DAP) or conduction-band-to-acceptor (e -A) transition at 390 nm and the broad luminescence around 500 nm, corresponding to photon energy of 2.2–2.4 eV. This broad luminescence is called “yellow luminescence” (YL) and is primarily attributed to defects that function as deep acceptors. However, the origin of the deep acceptor has not been determined and some models have been proposed, e.g., Ga vacancy, V Ga 12 , 13 , 14 , carbon substituting nitrogen, C N 15 and C N -O N complex 16 . The intensities of YL depend on measured points on the GaN surface, which are depicted by a sky blue line and an orange line in Fig. 2a , seem to reflect the density of defects on the GaN surface. To clarify the distribution of YL intensity, we have performed PL intensity mapping with YL of the GaN in the same area as the THz mapping in Fig. 1a . The YL intensity mapping shown in Fig. 2b has almost the same contrast as the LTEM image. Thus, the intensity of THz emission from the region with high defect density (HDD) is higher than that from the region with low defect density (LDD). The results suggest that an enhancement of the THz emission is induced by the defects in the GaN surface. Figure 2 ( a ) The PL spectra of GaN at two characteristic points shown in Fig. 2 ( b ) as blue and orange points. The excitation wavelength is 345 nm. ( b ) PL 2D mapping using the intensity of YL peak with the excitation wavelength of 345 nm. Full size image Figure 3a shows", "role": "user" }, { "content": "Wide-gap semiconductors such as gallium nitride (GaN) are widely used for optical devices such as blue LED and are also anticipated as materials for next-generation energy saving power devices and solar cells. However, the quality of GaN crystals does not come up to that of conventional semiconductor materials such as silicon (Si) and this prevents GaN from being used for power devices. For that reason, the establishment of technology for producing high-quality crystals with fewer defects and rearrangement is expected, and the development of a new evaluation technology is crucial. A group of researchers led by Iwao Kawayama, an associate professor of the Institute of Laser Engineering at Osaka University, in cooperation with Screen Holdings Co., Ltd., succeeded in visualizing changes in defect density on the surface of GaN through the laser terahertz emission microscope (LTEM) which measures THz waves generated by laser emission. This group's discovery shows that LTEM is useful as a new method for evaluating the quality of wide-gap semiconductors and it is also expected that LTEM will bring a breakthrough in the development of next-generation optical devices, super high frequency devices, and energy devices. The group examined the intensity distribution of THz generated by radiating ultraviolet femtosecond laser pulses on the surface of GaN crystal through LTEM. As a result, it was found that there were regions with high intensity of THz emission and ones with low intensity of THz emission. Additionally, when the LTEM image was compared with the image obtained through photoluminescence (PL) using a conventional method, it was found that there was a strong correlation between the distribution of emission intensity due to lattice defects and the intensity distribution of THz wave emission. Furthermore, from results measurement through modification of excited lasers, it was confirmed that THz emission needs excitation light with larger energy than the band gap energy. This research was featured in the electronic version of Scientific Reports on September 9, 2015. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Wide-gap semiconductors have received significant attention for their advantages over existing semiconductors in energy-efficient power devices. To realize stable and reliable wide-gap semiconductor devices, the basic physical properties, such as the electric properties on the surface and at the interface, should be revealed. Here, we report visualization of terahertz (THz) emission from the surface of GaN, which is excited by ultraviolet femtosecond laser pulses. We found that the THz emission is enhanced by defects related to yellow luminescence and this phenomenon is explained through the modification of band structures in the surface depletion layer owing to trapped electrons at defect sites. Our results demonstrate that the surface potential in a GaN surface could be detected by laser-induced THz emission. Moreover, this method enables feasible evaluation of the distribution of non-radiative defects, which are undetectable with photoluminescence and it contributes to the realization normally-off GaN devices. Introduction As a material for next generation devices, such as light sources, high-power devices and solar cells, wide-gap semiconductors have attracted significant attention over the years. Blue light sources manufactured from gallium nitride (GaN), which is a typical wide-gap semiconductor, have already been used in many industrial applications. For higher luminous efficiency, the crystal quality of GaN must be improved. In addition, power devices made from GaN have many superiorities over existing power devices, e.g., high-frequency operation, break-down field and heat conductivity, however there are still some problems to be solved such as a current collapse 1 and a normally-on property 2 . Among these, the normally-on characteristics, i.e., a high electric field exists without external bias voltage due to polarization 3 in the interface of the hetero-junction, have been a serious problem for practical applications. Therefore, control of the surface and the interface polarization is required. However, there is no convenient method for measuring the “local” polarization without electrical contacts. On the other hand, terahertz (THz) spectroscopy is expected to evaluate semiconductor materials and devices. The optical and electrical properties of various semiconductors have been investigated by THz time-domain spectroscopy 4 , 5 , 6 and by laser-induced THz emission spectroscopy 7 , 8 , 9 . The laser THz emission microscope (LTEM), which images the amplitude of THz emission from materials and devices, is also used for evaluating semiconductor devices 10 , 11 . Here, we measured THz emission from GaN surfaces excited by ultraviolet (UV) femtosecond laser pulses and found enhancement of THz emission due to defects in the GaN surface by comparing the photoluminescence (PL) measurements. The enhancement is explained by modification of the band bending induced by the accumulated negative charges in the surface depletion layer. Accordingly, the present results suggest that LTEM is capable of measuring not only the defect density but also the local surface potential. Results Figure 1a,b respectively show the LTEM image of the Ga-polar (0001) surface of n-type GaN, which was provided by Sumitomo Electric Industries and the waveforms of THz emissions at the two points, which are shown as sky blue and orange marks in the LTEM image. All the measurements in this study were performed at room temperature. The excitation wavelength and the photon density per pulse are 260 nm and 3.4 × 10 13 /cm 2 , respectively. Because the band gap energy of GaN is 3.4 eV, the incident photon energy (4.8 eV) is sufficient to excite an electron from the valence band to the conduction band. The LTEM image corresponds to the mapping of the negative peak amplitude at 0 ps, as shown in Fig. 1b . Figure 1 ( a ) The LTEM image of n-type GaN with an excitation wavelength of 260 nm. ( b ) The THz waveforms at two points in ( a ). Line colors correspond to point colors in ( a ). Full size image As shown in Fig. 1a , a noticeable distribution of the THz amplitude in the plane can be observed in the LTEM image, even though pulse widths were almost unchanged. Figure 2a shows PL spectra measured at two points in the same GaN sample. The PL measurement was performed at room temperature and the excitation wavelength and photon density per pulse were 345 nm and 4.8 × 10 13 /cm 2 , respectively. These spectra contain the excitation source at 345 nm, the near-band-edge (NBE) emission peak at 365 nm, the luminescence peak by donor-acceptor pair (DAP) or conduction-band-to-acceptor (e -A) transition at 390 nm and the broad luminescence around 500 nm, corresponding to photon energy of 2.2–2.4 eV. This broad luminescence is called “yellow luminescence” (YL) and is primarily attributed to defects that function as deep acceptors. However, the origin of the deep acceptor has not been determined and some models have been proposed, e.g., Ga vacancy, V Ga 12 , 13 , 14 , carbon substituting nitrogen, C N 15 and C N -O N complex 16 . The intensities of YL depend on measured points on the GaN surface, which are depicted by a sky blue line and an orange line in Fig. 2a , seem to reflect the density of defects on the GaN surface. To clarify the distribution of YL intensity, we have performed PL intensity mapping with YL of the GaN in the same area as the THz mapping in Fig. 1a . The YL intensity mapping shown in Fig. 2b has almost the same contrast as the LTEM image. Thus, the intensity of THz emission from the region with high defect density (HDD) is higher than that from the region with low defect density (LDD). The results suggest that an enhancement of the THz emission is induced by the defects in the GaN surface. Figure 2 ( a ) The PL spectra of GaN at two characteristic points shown in Fig. 2 ( b ) as blue and orange points. The excitation wavelength is 345 nm. ( b ) PL 2D mapping using the intensity of YL peak with the excitation wavelength of 345 nm. Full size image Figure 3a shows<|im_end|> <|im_start|>assistant Wide-gap semiconductors such as gallium nitride (GaN) are widely used for optical devices such as blue LED and are also anticipated as materials for next-generation energy saving power devices and solar cells. However, the quality of GaN crystals does not come up to that of conventional semiconductor materials such as silicon (Si) and this prevents GaN from being used for power devices. For that reason, the establishment of technology for producing high-quality crystals with fewer defects and rearrangement is expected, and the development of a new evaluation technology is crucial. A group of researchers led by Iwao Kawayama, an associate professor of the Institute of Laser Engineering at Osaka University, in cooperation with Screen Holdings Co., Ltd., succeeded in visualizing changes in defect density on the surface of GaN through the laser terahertz emission microscope (LTEM) which measures THz waves generated by laser emission. This group's discovery shows that LTEM is useful as a new method for evaluating the quality of wide-gap semiconductors and it is also expected that LTEM will bring a breakthrough in the development of next-generation optical devices, super high frequency devices, and energy devices. The group examined the intensity distribution of THz generated by radiating ultraviolet femtosecond laser pulses on the surface of GaN crystal through LTEM. As a result, it was found that there were regions with high intensity of THz emission and ones with low intensity of THz emission. Additionally, when the LTEM image was compared with the image obtained through photoluminescence (PL) using a conventional method, it was found that there was a strong correlation between the distribution of emission intensity due to lattice defects and the intensity distribution of THz wave emission. Furthermore, from results measurement through modification of excited lasers, it was confirmed that THz emission needs excitation light with larger energy than the band gap energy. This research was featured in the electronic version of Scientific Reports on September 9, 2015. <|im_end|>

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1,792

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract We describe and share a device, methodology and image analysis algorithms, which allow up to 66 spheroids to be arranged into a gel-based array directly from a culture plate for downstream processing and analysis. Compared to processing individual samples, the technique uses 11-fold less reagents, saves time and enables automated imaging. To illustrate the power of the technology, we showcase applications of the methodology for investigating 3D spheroid morphology and marker expression and for in vitro safety and efficacy screens. First, spheroid arrays of 11 cell-lines were rapidly assessed for differences in spheroid morphology. Second, highly-positive (SOX-2), moderately-positive (Ki-67) and weakly-positive (βIII-tubulin) protein targets were detected and quantified. Third, the arrays enabled screening of ten media compositions for inducing differentiation in human neurospheres. Last, the application of spheroid microarrays for spheroid-based drug screens was demonstrated by quantifying the dose-dependent drop in proliferation and increase in differentiation in etoposide-treated neurospheres. Introduction Current preclinical studies for drugs and safety assessments for chemicals use in vitro cell cultures and animal data to predict human response. In vitro data generated in 2D models are notoriously unreliable due to the reductionist way of culturing cells as a monolayer on plastic, and animal studies often fail to predict how drugs will behave in humans due to substantial interspecies differences 1 . Three-dimensional in vitro spheroid and organoid models are considered to be more physiologically relevant models of normal and diseased human tissues compared to cells cultured in 2D 2 . Although three-dimensional cultures offer more realistic cell-cell and cell-matrix interactions, there have been two main obstacles for their adoption in drug screening. First, the methods for their culture were low-throughput and resulted in large variation in spheroid size. This has recently been overcome with the introduction of high-throughput plate-based platforms for 3D culture. Second, the techniques to analyze spheroid viability, morphology, gene and protein expression were also slow and laborious. Here, we present a device which overcomes this issue by allowing users to arrange up to 66 spheroids in a single plane for high-throughput downstream analysis of three-dimensional cell cultures. Three-dimensional aggregate cultures were first described in the 1950s by Moscona 3 , and the advantages of using spheroids in cancer research were recognized in the 1970s by Sutherland 4 . The introduction of plate-based platforms for spheroid culture in hanging-drop 5 , 6 or liquid overlay 7 , 8 has enabled researchers to produce a single-spheroid per well and control spheroid size in a high-throughput format. The increased adoption of spheroid screens has mostly relied on plate-based viability measurements 9 , 10 , 11 , 12 . While cytotoxicity assays may be useful in assessing the effectiveness of anticancer drugs, they do not provide clues on the mechanisms behind tumor drug resistance and the adverse outcome pathways leading to toxicity in normal tissues 13 . The next research frontier is to move away from simplistic viability assays and analyze spheroid morphology and biological function at the single cell level within their 3D context. Spheroid morphology and single cell protein/gene analysis can identify spatial patterns in expression due to nutrient and oxygen gradients and the phenotype of small populations of cells resistant to drug therapy. These properties can be examined using histological and immunohistochemistry techniques. To this end, many technical replicate spheroids are cultured under the same conditions, fixed, embedded in matrix (e.g. agarose gel), frozen or paraffin-embedded, then sectioned, stained and imaged 7 , 12 . When more than two conditions are examined (e.g. compound screens, dose-response curves) or if many different cell types are used, the replicates from each condition need to be embedded as separate samples ( Fig. 1a ). In this way a single dose-response assay in a 96-well plate with nine drug levels and one untreated control would yield 10 separate samples per plate and would require at least 30 (3 per condition) microscope slides per protein( Fig. 1a , bottom panel). The increase in number of samples means researchers waste more time to section and stain the samples and use greater amounts of expensive reagents, such as antibodies. Moreover, the random distribution of spheroids in the embedding media necessitates manual imaging, further increasing the time for analysis. The whole process becomes very low-throughput, and requires a big investment in researcher hands-on time and reagents. Figure 1: Spheroid microarray technology overview and mold making procedure. ( a ) The current workflow to analyze spheroid histology requires separate processing of spheroids representing different conditions and results in many samples which need to be embedded (I), processed (II), sectioned (III), stained(IV) and imaged (V) separately. The random distribution of spheroids in different planes requires manual imaging and further takes up researcher and equipment time. Embedding multiple conditions on the same array (top) reduces the number of samples 11 times resulting in economies in reagents and hands-on time as well as the possibility for automated imaging of all spheroids located in the same plane. ( b ) Spheroid microarrays are made by pouring liquid agarose solution in histology molds and floating the Mold-maker on top of the solution. Once the agarose cools down and gels, the Mold-maker is removed and the spheroids are loaded into the wells of the resulting agarose mold. The mold is sealed with low-gelling agarose and is processed for histology. Full size image We have developed and share the designs of a device which creates spheroid microarrays by transferring previously-fixed spheroids from the cell culture plate to a precast agarose mold ( Fig. 1b ). The mold-making device (Mold-maker) produces agarose molds with 66 holes arranged in 6 rows and 11 columns. The holes have a paraboloid shape and equal depth and serve to arrange up to 66 spheroids in the same plane. Embedding all spheroids in a common plane reduces the chances for sample mix-up and allows researchers to cut sections containing all 66 spheroids at the same time for simultaneous staining and analysis. Compared to embedding technical replicates in separate blocks, the techniques uses 11 times less", "role": "user" }, { "content": "A new technology that could speed up the testing of drugs and reduce the use of animals in the lab has been developed by scientists at The University of Nottingham. The researchers in the University's Division of Cancer and Stem Cells have designed a device that allows dozens of tiny balls of cells, called spheroids, to be sliced simultaneously to examine their structure and function. The method, which is detailed in the academic journal Scientific Reports, will enable other scientists to more rapidly assess whether new therapies and tissue engineering are likely to work in the real world, and could be up to 11 times more efficient than current methods. Dr Delyan Ivanov said: \"When I started exploring spheroids by slicing them, I was frustrated by the slow and gruelling nature of the process. I had to cut spheroids cultured in many different drugs and it was taking me months, there were many manual steps. \"Inspired by the principle of 3D printing, I decided to design my own tool for arranging all spheroids from an experiment in the same plane in a microchip-like pattern in a gel.\" Overcoming limitations Dr Ivanov, who designed the device during his EPSRC-funded doctoral prize fellowship (Engineering and Physical Sciences Research Council), was able to refine the design after enlisting the help of Joseph White, a research technician in the University's Additive Manufacturing group, who printed 20 different versions of the prototype for testing. The team will now be sharing the design files and methodology openly with the scientific community to ensure that everyone can immediately benefit from the technology. New drugs for cancer and strategies to build tissues from stem cells have historically been tested in the laboratory in human cells grown as a 'carpet' on plastic. In contrast to the natural behaviour in the human body, the cells in these two-dimensional cultures have limited interaction with each other and produce little of the natural 'glue' called extracellular matrix. To overcome these limitations, tiny three-dimensional balls of cells (spheroids) which are smaller than a pinhead, interact more closely with one another and behave more like their natural counterparts in the human body are now being used. Scientists are growing spheroids derived from tumour and normal tissues and have even developed improved, more organised structures which resemble organs, called organoids. The catch was that, while two-dimensional structures can be examined just by looking down the microscope, the 3D spheroids need to be sliced into hundreds of thin slices just 0.005mm (5 µm) thick in order to get a reliable picture of their structure and function. Reducing animal testing The Nottingham invention allows researchers to arrange 66 spheroids grown in the presence of different drugs and molecules and slice simultaneously and more quickly, allowing scientists to answer more questions using the same set of laboratory-grown tissues. Many experiments currently done in animals could be done in these spheroid and organoid cultures reducing and ultimately replacing some animal testing in cancer research and tissue engineering. Dr Anna Grabowska, who mentored Dr Ivanov at Nottingham during his post-doc, added: \"We would like to create cell-based models in the laboratory which closely mimic the natural behaviour of cells in the human body. We are doing this not only by culturing cells as spheroids but by including multiple cell types and the right extracellular matrix. Delyan's technology would allow us to monitor the behaviour of laboratory models of human tissues and organs in a faster, more efficient way.\" The paper being published in Scientific Reports includes the blueprints of the device, demonstration of the possibilities of the new technology and offers an instructional video to show researchers how to make their own spheroid microarrays. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract We describe and share a device, methodology and image analysis algorithms, which allow up to 66 spheroids to be arranged into a gel-based array directly from a culture plate for downstream processing and analysis. Compared to processing individual samples, the technique uses 11-fold less reagents, saves time and enables automated imaging. To illustrate the power of the technology, we showcase applications of the methodology for investigating 3D spheroid morphology and marker expression and for in vitro safety and efficacy screens. First, spheroid arrays of 11 cell-lines were rapidly assessed for differences in spheroid morphology. Second, highly-positive (SOX-2), moderately-positive (Ki-67) and weakly-positive (βIII-tubulin) protein targets were detected and quantified. Third, the arrays enabled screening of ten media compositions for inducing differentiation in human neurospheres. Last, the application of spheroid microarrays for spheroid-based drug screens was demonstrated by quantifying the dose-dependent drop in proliferation and increase in differentiation in etoposide-treated neurospheres. Introduction Current preclinical studies for drugs and safety assessments for chemicals use in vitro cell cultures and animal data to predict human response. In vitro data generated in 2D models are notoriously unreliable due to the reductionist way of culturing cells as a monolayer on plastic, and animal studies often fail to predict how drugs will behave in humans due to substantial interspecies differences 1 . Three-dimensional in vitro spheroid and organoid models are considered to be more physiologically relevant models of normal and diseased human tissues compared to cells cultured in 2D 2 . Although three-dimensional cultures offer more realistic cell-cell and cell-matrix interactions, there have been two main obstacles for their adoption in drug screening. First, the methods for their culture were low-throughput and resulted in large variation in spheroid size. This has recently been overcome with the introduction of high-throughput plate-based platforms for 3D culture. Second, the techniques to analyze spheroid viability, morphology, gene and protein expression were also slow and laborious. Here, we present a device which overcomes this issue by allowing users to arrange up to 66 spheroids in a single plane for high-throughput downstream analysis of three-dimensional cell cultures. Three-dimensional aggregate cultures were first described in the 1950s by Moscona 3 , and the advantages of using spheroids in cancer research were recognized in the 1970s by Sutherland 4 . The introduction of plate-based platforms for spheroid culture in hanging-drop 5 , 6 or liquid overlay 7 , 8 has enabled researchers to produce a single-spheroid per well and control spheroid size in a high-throughput format. The increased adoption of spheroid screens has mostly relied on plate-based viability measurements 9 , 10 , 11 , 12 . While cytotoxicity assays may be useful in assessing the effectiveness of anticancer drugs, they do not provide clues on the mechanisms behind tumor drug resistance and the adverse outcome pathways leading to toxicity in normal tissues 13 . The next research frontier is to move away from simplistic viability assays and analyze spheroid morphology and biological function at the single cell level within their 3D context. Spheroid morphology and single cell protein/gene analysis can identify spatial patterns in expression due to nutrient and oxygen gradients and the phenotype of small populations of cells resistant to drug therapy. These properties can be examined using histological and immunohistochemistry techniques. To this end, many technical replicate spheroids are cultured under the same conditions, fixed, embedded in matrix (e.g. agarose gel), frozen or paraffin-embedded, then sectioned, stained and imaged 7 , 12 . When more than two conditions are examined (e.g. compound screens, dose-response curves) or if many different cell types are used, the replicates from each condition need to be embedded as separate samples ( Fig. 1a ). In this way a single dose-response assay in a 96-well plate with nine drug levels and one untreated control would yield 10 separate samples per plate and would require at least 30 (3 per condition) microscope slides per protein( Fig. 1a , bottom panel). The increase in number of samples means researchers waste more time to section and stain the samples and use greater amounts of expensive reagents, such as antibodies. Moreover, the random distribution of spheroids in the embedding media necessitates manual imaging, further increasing the time for analysis. The whole process becomes very low-throughput, and requires a big investment in researcher hands-on time and reagents. Figure 1: Spheroid microarray technology overview and mold making procedure. ( a ) The current workflow to analyze spheroid histology requires separate processing of spheroids representing different conditions and results in many samples which need to be embedded (I), processed (II), sectioned (III), stained(IV) and imaged (V) separately. The random distribution of spheroids in different planes requires manual imaging and further takes up researcher and equipment time. Embedding multiple conditions on the same array (top) reduces the number of samples 11 times resulting in economies in reagents and hands-on time as well as the possibility for automated imaging of all spheroids located in the same plane. ( b ) Spheroid microarrays are made by pouring liquid agarose solution in histology molds and floating the Mold-maker on top of the solution. Once the agarose cools down and gels, the Mold-maker is removed and the spheroids are loaded into the wells of the resulting agarose mold. The mold is sealed with low-gelling agarose and is processed for histology. Full size image We have developed and share the designs of a device which creates spheroid microarrays by transferring previously-fixed spheroids from the cell culture plate to a precast agarose mold ( Fig. 1b ). The mold-making device (Mold-maker) produces agarose molds with 66 holes arranged in 6 rows and 11 columns. The holes have a paraboloid shape and equal depth and serve to arrange up to 66 spheroids in the same plane. Embedding all spheroids in a common plane reduces the chances for sample mix-up and allows researchers to cut sections containing all 66 spheroids at the same time for simultaneous staining and analysis. Compared to embedding technical replicates in separate blocks, the techniques uses 11 times less<|im_end|> <|im_start|>assistant A new technology that could speed up the testing of drugs and reduce the use of animals in the lab has been developed by scientists at The University of Nottingham. The researchers in the University's Division of Cancer and Stem Cells have designed a device that allows dozens of tiny balls of cells, called spheroids, to be sliced simultaneously to examine their structure and function. The method, which is detailed in the academic journal Scientific Reports, will enable other scientists to more rapidly assess whether new therapies and tissue engineering are likely to work in the real world, and could be up to 11 times more efficient than current methods. Dr Delyan Ivanov said: "When I started exploring spheroids by slicing them, I was frustrated by the slow and gruelling nature of the process. I had to cut spheroids cultured in many different drugs and it was taking me months, there were many manual steps. "Inspired by the principle of 3D printing, I decided to design my own tool for arranging all spheroids from an experiment in the same plane in a microchip-like pattern in a gel." Overcoming limitations Dr Ivanov, who designed the device during his EPSRC-funded doctoral prize fellowship (Engineering and Physical Sciences Research Council), was able to refine the design after enlisting the help of Joseph White, a research technician in the University's Additive Manufacturing group, who printed 20 different versions of the prototype for testing. The team will now be sharing the design files and methodology openly with the scientific community to ensure that everyone can immediately benefit from the technology. New drugs for cancer and strategies to build tissues from stem cells have historically been tested in the laboratory in human cells grown as a 'carpet' on plastic. In contrast to the natural behaviour in the human body, the cells in these two-dimensional cultures have limited interaction with each other and produce little of the natural 'glue' called extracellular matrix. To overcome these limitations, tiny three-dimensional balls of cells (spheroids) which are smaller than a pinhead, interact more closely with one another and behave more like their natural counterparts in the human body are now being used. Scientists are growing spheroids derived from tumour and normal tissues and have even developed improved, more organised structures which resemble organs, called organoids. The catch was that, while two-dimensional structures can be examined just by looking down the microscope, the 3D spheroids need to be sliced into hundreds of thin slices just 0.005mm (5 µm) thick in order to get a reliable picture of their structure and function. Reducing animal testing The Nottingham invention allows researchers to arrange 66 spheroids grown in the presence of different drugs and molecules and slice simultaneously and more quickly, allowing scientists to answer more questions using the same set of laboratory-grown tissues. Many experiments currently done in animals could be done in these spheroid and organoid cultures reducing and ultimately replacing some animal testing in cancer research and tissue engineering. Dr Anna Grabowska, who mentored Dr Ivanov at Nottingham during his post-doc, added: "We would like to create cell-based models in the laboratory which closely mimic the natural behaviour of cells in the human body. We are doing this not only by culturing cells as spheroids but by including multiple cell types and the right extracellular matrix. Delyan's technology would allow us to monitor the behaviour of laboratory models of human tissues and organs in a faster, more efficient way." The paper being published in Scientific Reports includes the blueprints of the device, demonstration of the possibilities of the new technology and offers an instructional video to show researchers how to make their own spheroid microarrays. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Accurate estimates of the burden of SARS-CoV-2 infection are critical to informing pandemic response. Confirmed COVID-19 case counts in the U.S. do not capture the total burden of the pandemic because testing has been primarily restricted to individuals with moderate to severe symptoms due to limited test availability. Here, we use a semi-Bayesian probabilistic bias analysis to account for incomplete testing and imperfect diagnostic accuracy. We estimate 6,454,951 cumulative infections compared to 721,245 confirmed cases (1.9% vs. 0.2% of the population) in the United States as of April 18, 2020. Accounting for uncertainty, the number of infections during this period was 3 to 20 times higher than the number of confirmed cases. 86% (simulation interval: 64–99%) of this difference is due to incomplete testing, while 14% (0.3–36%) is due to imperfect test accuracy. The approach can readily be applied in future studies in other locations or at finer spatial scale to correct for biased testing and imperfect diagnostic accuracy to provide a more realistic assessment of COVID-19 burden. Introduction The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) pandemic is reported to have caused 2,003,930 confirmed cases of coronavirus disease 2019 (COVID-19) in the U.S. by June 11, 2020. The first known case in the U.S. was confirmed on January 21, 2020. In February, SARS-CoV-2 testing remained limited due to flawed test kits. For the first few months of the pandemic, the U.S. Centers for Disease Control and Prevention (CDC) recommended that physicians prioritize testing hospitalized patients, who tend to have moderate to severe symptoms. Most state testing policies were consistent with this recommendation (Supplementary Table 1 ). Yet, evidence from studies that conducted broader testing suggest that 30–70% of individuals who test positive have mild or no symptoms 1 , 2 , 3 , 4 and that asymptomatic and pre-symptomatic individuals can transmit SARS-CoV-2 5 , 6 , 7 . Thus, a substantial number of mild or asymptomatic infections in the U.S. may be undetected 8 . Furthermore, initial evidence suggests that tests based on nasopharyngeal and throat swabs may produce false negative results 9 , 10 , 11 , 12 . Thus, counts of confirmed cases are biased due to incomplete testing and imperfect test sensitivity. Accurate estimates of the burden of SARS-CoV-2 infection are critical to understanding the course of the pandemic and informing public health response 8 , 13 . Furthermore, limited and biased testing can influence estimates of SARS-CoV-2 transmissibility, which typically rely upon observed counts of cumulative infections 14 . To date, the majority of studies that have estimated the burden of SARS-CoV-2 infection have used mathematical models (e.g., compartmental or agent-based models) 15 , 16 , 17 , 18 , 19 . Mathematical modeling studies attempt to mimic natural disease transmission systems by modeling age and social structure, travel and commuting patterns, and immune dynamics. Such models are particularly useful for projecting transmission patterns under hypothetical interventions but can be highly complex; when sufficient data do not exist to parameterize such models, results can be quite biased 20 , 21 . In addition, model outputs are sensitive to assumed population structure and contact patterns, which are difficult to validate, particularly in a novel pathogen setting. We estimate the total number of SARS-CoV-2 infections in each U.S. state from February 28 to April 18, 2020 using probabilistic bias analysis, a semi-Bayesian approach, to correct empirical confirmed case counts for bias due to incomplete testing and imperfect test accuracy. This method is commonly used to quantify the impact of and correct for measurement bias in observational epidemiologic studies 22 . Our objective is to estimate infection burden from empirical data rather than to forecast future dynamics. In the absence of systematic random sampling or robust surveillance, true COVID-19 incidence is unknown and “we are operating in the dark” 23 . This being the case, our method provides an estimate of the true number of infections, which can help not only determine what kind of response is appropriate, but also evaluate the progress or failure of mitigation or containment efforts. Further, the simplicity of our approach facilitates transparent assessment of modeling assumptions. Results SARS-CoV-2 testing rates varied widely by state We quantified the SARS-CoV-2 testing rate per 1000 persons using daily counts of tests in each state and 2019 projected state populations from the 2010 U.S. Census 24 . By April 18, 2020, the SARS-CoV-2 testing rate was 11 per 1000 in the U.S. However, there were large discrepancies in testing between states, with state-level testing rates of 6 per 1000 in Kansas to 31 per 1000 in Rhode Island (Fig. 1 ). Generally, testing rates were higher in the Northwest and Northeast and lower in the Midwest and South. Fig. 1: Daily SARS-CoV-2 tests per 1000 population in the United States by state and region. SARS-CoV-2 testing rates in US states increased from close to 0 in early March to 6 per 1000 in Kansas to 31 per 1000 in Rhode Island by April 18, 2020. Generally, testing rates were higher in the Northwest and Northeast and lower in the Midwest and South. We estimated the cumulative population tested in each state by date by dividing the number of tests performed by 2019 population projections from the U.S. 2010 Census. Each open circle indicates the number of individuals tested in a state on a given day per 1000. Line, point, and text colors are based on quintiles of the distribution of testing per 1000 population on April 18, 2020 across all states. Testing quintile from lowest to highest is mapped to color from warmest to coolest (such that quintile 1, the lowest, maps to yellow (warmest), and quintile 5, the highest, maps to dark purple (coolest)). In each panel, state names are sorted in descending order by the population tested per 1000. Quality of daily estimates of the number of tests performed varied by state; see Supplementary Table 3 for details. See interactive plot at . Full size image Confirmed COVID-19 case counts underestimate infections When", "role": "user" }, { "content": "The United States may have experienced more than 6.4 million cases of COVID-19 by April 18, 2020, according to a probability analysis conducted by UC Berkeley School of Public Health researchers and published in Nature Communications. That is nine time more than the number of confirmed cases in the same period, which was 721,245. \"The majority of this discrepancy was due to undertesting,\" says Jade Benjamin-Chung, study co-author and professor of epidemiology & biostatistics at Berkeley Public Health. \"Our findings highlight the urgent need for more SARS-CoV-2 [the virus that causes COVID-19] testing—including testing of asymptomatic individuals exposed to COVID-19—to help stop the spread of the virus.\" The first known case of COVID-19 in the US was confirmed on January 21, 2020. For the first few months of the pandemic, the US Centers for Disease Control recommended that testing be prioritized for patients in the hospital who presented moderate or severe symptoms. However, studies suggest that 30–70% of individuals who test positive for the virus present with mild symptoms or may have none at all. \"We know that in the US, earlier on in the epidemic, the people who were getting tested had moderate to severe symptoms,\" Benjamin-Chung said. \"And we know that since then, we have a larger number of asymptomatic people who are affecting the total number of infections but may not be included in confirmed case counts.\" Berkeley Public Health's Benjamin-Chung, Sean Wu, and colleagues estimated the total number of SARS-CoV-2 infections in each US state from February 28 to April 18, 2020, using a probabilistic bias analysis to account for incomplete testing and less than 100% test accuracy. The authors estimate that there were 6,454,951 cases of SARS-CoV-2 infection (19 per 1,000 people). This estimate is about 9 times larger than the number of confirmed cases during the same period (2 per 1,000 people) and suggests that 89% of infections were undocumented. The majority of this difference (approximately 86%) was due to incomplete testing, with the remainder due to limited test accuracy. The authors found that COVID-19 incidence was highest in the Northeast, Midwest, and the state of Louisiana when using confirmed case counts or the estimated number of infections. Underestimation of the number of cases was more common in Puerto Rico, California, and some southern states. In 33 states, the estimated number of infections was at least 10 times higher than the number of confirmed cases. The authors note that their methodology does not incorporate a transmission model and so they are unable to make forecasts about the spread of the virus. However, they argue that their method provides a more realistic picture of infection burden at a given point in time. \"The method that we used can't forecast the number of cases in the future. For future forecasts, we would need to use a transmission model,\" said co-author and Berkeley Public Health Ph.D. candidate Wu. \"The number of cases we estimated in April could be used as a baseline for a transmission model that started then and would predict what would happen in the future.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Accurate estimates of the burden of SARS-CoV-2 infection are critical to informing pandemic response. Confirmed COVID-19 case counts in the U.S. do not capture the total burden of the pandemic because testing has been primarily restricted to individuals with moderate to severe symptoms due to limited test availability. Here, we use a semi-Bayesian probabilistic bias analysis to account for incomplete testing and imperfect diagnostic accuracy. We estimate 6,454,951 cumulative infections compared to 721,245 confirmed cases (1.9% vs. 0.2% of the population) in the United States as of April 18, 2020. Accounting for uncertainty, the number of infections during this period was 3 to 20 times higher than the number of confirmed cases. 86% (simulation interval: 64–99%) of this difference is due to incomplete testing, while 14% (0.3–36%) is due to imperfect test accuracy. The approach can readily be applied in future studies in other locations or at finer spatial scale to correct for biased testing and imperfect diagnostic accuracy to provide a more realistic assessment of COVID-19 burden. Introduction The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) pandemic is reported to have caused 2,003,930 confirmed cases of coronavirus disease 2019 (COVID-19) in the U.S. by June 11, 2020. The first known case in the U.S. was confirmed on January 21, 2020. In February, SARS-CoV-2 testing remained limited due to flawed test kits. For the first few months of the pandemic, the U.S. Centers for Disease Control and Prevention (CDC) recommended that physicians prioritize testing hospitalized patients, who tend to have moderate to severe symptoms. Most state testing policies were consistent with this recommendation (Supplementary Table 1 ). Yet, evidence from studies that conducted broader testing suggest that 30–70% of individuals who test positive have mild or no symptoms 1 , 2 , 3 , 4 and that asymptomatic and pre-symptomatic individuals can transmit SARS-CoV-2 5 , 6 , 7 . Thus, a substantial number of mild or asymptomatic infections in the U.S. may be undetected 8 . Furthermore, initial evidence suggests that tests based on nasopharyngeal and throat swabs may produce false negative results 9 , 10 , 11 , 12 . Thus, counts of confirmed cases are biased due to incomplete testing and imperfect test sensitivity. Accurate estimates of the burden of SARS-CoV-2 infection are critical to understanding the course of the pandemic and informing public health response 8 , 13 . Furthermore, limited and biased testing can influence estimates of SARS-CoV-2 transmissibility, which typically rely upon observed counts of cumulative infections 14 . To date, the majority of studies that have estimated the burden of SARS-CoV-2 infection have used mathematical models (e.g., compartmental or agent-based models) 15 , 16 , 17 , 18 , 19 . Mathematical modeling studies attempt to mimic natural disease transmission systems by modeling age and social structure, travel and commuting patterns, and immune dynamics. Such models are particularly useful for projecting transmission patterns under hypothetical interventions but can be highly complex; when sufficient data do not exist to parameterize such models, results can be quite biased 20 , 21 . In addition, model outputs are sensitive to assumed population structure and contact patterns, which are difficult to validate, particularly in a novel pathogen setting. We estimate the total number of SARS-CoV-2 infections in each U.S. state from February 28 to April 18, 2020 using probabilistic bias analysis, a semi-Bayesian approach, to correct empirical confirmed case counts for bias due to incomplete testing and imperfect test accuracy. This method is commonly used to quantify the impact of and correct for measurement bias in observational epidemiologic studies 22 . Our objective is to estimate infection burden from empirical data rather than to forecast future dynamics. In the absence of systematic random sampling or robust surveillance, true COVID-19 incidence is unknown and “we are operating in the dark” 23 . This being the case, our method provides an estimate of the true number of infections, which can help not only determine what kind of response is appropriate, but also evaluate the progress or failure of mitigation or containment efforts. Further, the simplicity of our approach facilitates transparent assessment of modeling assumptions. Results SARS-CoV-2 testing rates varied widely by state We quantified the SARS-CoV-2 testing rate per 1000 persons using daily counts of tests in each state and 2019 projected state populations from the 2010 U.S. Census 24 . By April 18, 2020, the SARS-CoV-2 testing rate was 11 per 1000 in the U.S. However, there were large discrepancies in testing between states, with state-level testing rates of 6 per 1000 in Kansas to 31 per 1000 in Rhode Island (Fig. 1 ). Generally, testing rates were higher in the Northwest and Northeast and lower in the Midwest and South. Fig. 1: Daily SARS-CoV-2 tests per 1000 population in the United States by state and region. SARS-CoV-2 testing rates in US states increased from close to 0 in early March to 6 per 1000 in Kansas to 31 per 1000 in Rhode Island by April 18, 2020. Generally, testing rates were higher in the Northwest and Northeast and lower in the Midwest and South. We estimated the cumulative population tested in each state by date by dividing the number of tests performed by 2019 population projections from the U.S. 2010 Census. Each open circle indicates the number of individuals tested in a state on a given day per 1000. Line, point, and text colors are based on quintiles of the distribution of testing per 1000 population on April 18, 2020 across all states. Testing quintile from lowest to highest is mapped to color from warmest to coolest (such that quintile 1, the lowest, maps to yellow (warmest), and quintile 5, the highest, maps to dark purple (coolest)). In each panel, state names are sorted in descending order by the population tested per 1000. Quality of daily estimates of the number of tests performed varied by state; see Supplementary Table 3 for details. See interactive plot at . Full size image Confirmed COVID-19 case counts underestimate infections When<|im_end|> <|im_start|>assistant The United States may have experienced more than 6.4 million cases of COVID-19 by April 18, 2020, according to a probability analysis conducted by UC Berkeley School of Public Health researchers and published in Nature Communications. That is nine time more than the number of confirmed cases in the same period, which was 721,245. "The majority of this discrepancy was due to undertesting," says Jade Benjamin-Chung, study co-author and professor of epidemiology & biostatistics at Berkeley Public Health. "Our findings highlight the urgent need for more SARS-CoV-2 [the virus that causes COVID-19] testing—including testing of asymptomatic individuals exposed to COVID-19—to help stop the spread of the virus." The first known case of COVID-19 in the US was confirmed on January 21, 2020. For the first few months of the pandemic, the US Centers for Disease Control recommended that testing be prioritized for patients in the hospital who presented moderate or severe symptoms. However, studies suggest that 30–70% of individuals who test positive for the virus present with mild symptoms or may have none at all. "We know that in the US, earlier on in the epidemic, the people who were getting tested had moderate to severe symptoms," Benjamin-Chung said. "And we know that since then, we have a larger number of asymptomatic people who are affecting the total number of infections but may not be included in confirmed case counts." Berkeley Public Health's Benjamin-Chung, Sean Wu, and colleagues estimated the total number of SARS-CoV-2 infections in each US state from February 28 to April 18, 2020, using a probabilistic bias analysis to account for incomplete testing and less than 100% test accuracy. The authors estimate that there were 6,454,951 cases of SARS-CoV-2 infection (19 per 1,000 people). This estimate is about 9 times larger than the number of confirmed cases during the same period (2 per 1,000 people) and suggests that 89% of infections were undocumented. The majority of this difference (approximately 86%) was due to incomplete testing, with the remainder due to limited test accuracy. The authors found that COVID-19 incidence was highest in the Northeast, Midwest, and the state of Louisiana when using confirmed case counts or the estimated number of infections. Underestimation of the number of cases was more common in Puerto Rico, California, and some southern states. In 33 states, the estimated number of infections was at least 10 times higher than the number of confirmed cases. The authors note that their methodology does not incorporate a transmission model and so they are unable to make forecasts about the spread of the virus. However, they argue that their method provides a more realistic picture of infection burden at a given point in time. "The method that we used can't forecast the number of cases in the future. For future forecasts, we would need to use a transmission model," said co-author and Berkeley Public Health Ph.D. candidate Wu. "The number of cases we estimated in April could be used as a baseline for a transmission model that started then and would predict what would happen in the future." <|im_end|>

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2,068

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The adenohypophysis (anterior pituitary) is a major centre for systemic hormones. At present, no efficient stem-cell culture for its generation is available, partly because of insufficient knowledge about how the pituitary primordium (Rathke’s pouch) is induced in the embryonic head ectoderm. Here we report efficient self-formation of three-dimensional adenohypophysis tissues in an aggregate culture of mouse embryonic stem (ES) cells. ES cells were stimulated to differentiate into non-neural head ectoderm and hypothalamic neuroectoderm in adjacent layers within the aggregate, and treated with hedgehog signalling. Self-organization of Rathke’s-pouch-like three-dimensional structures occurred at the interface of these two epithelia, as seen in vivo , and various endocrine cells including corticotrophs and somatotrophs were subsequently produced. The corticotrophs efficiently secreted adrenocorticotropic hormone in response to corticotrophin releasing hormone and, when grafted in vivo , these cells rescued the systemic glucocorticoid level in hypopituitary mice. Thus, functional anterior pituitary tissue self-forms in ES cell culture, recapitulating local tissue interactions. Main The adenohypophysis, corresponding to the anterior and intermediate lobes of the pituitary gland, contains several types of endocrine cells, which secrete systemic hormones such as adenocorticotropic hormone (ACTH), GH, LH/FSH, TSH and prolactin 1 , 2 , 3 in response to hypothalamus-derived releasing hormones. In contrast, the neurohypophysis (posterior pituitary) consists of the axons and secretory termini of hypothalamic vasopressin and oxytocin neurons. During early mammalian development, the adenohypophysis anlage originates as a placode in the non-neural head ectoderm rostral and adjacent to the anterior neural plate 4 , 5 ( Supplementary Fig. 1a ) (hereafter, this part of non-neural ectoderm, expressing region-specific markers Pitx1 and Pitx2, is simply referred to as rostral head ectoderm; this includes the oral ectoderm as a large part). The thickened placodal epithelium invaginates and subsequently detaches from the oral ectoderm, becoming a hollowed epithelial vesicle, Rathke’s pouch ( Fig. 1a, b and Supplementary Fig. 1b, c ). The development of Rathke’s pouch depends on tissue interactions between the rostral head ectoderm and the rostral hypothalamus 3 , 4 , 5 , 6 , 7 , 8 . We sought to recapitulate this interactive microenvironment of the pituitary-forming morphogenetic field using three-dimensional ES cell culture. Figure 1: Adjacent formation of head ectoderm and hypothalamic epithelia in ES cell culture. a , Schematic of pituitary development, sagittal view. A, anterior; D, dorsal; P, posterior; V, ventral. b , In vivo expression of Pitx1 and Rx on embryonic day 13 (E13). c , Little expression of Pitx2 in SFEBq/CDM-cultured ES cells (qPCR; n = 3 experiments). d, day. d , Pitx2 expression in aggregates cultured under the LCA condition (red) or treated with 0.5 nM BMP4 (blue) ( n = 3). e , f , Immunostaining of day-6 LCA aggregates for Pitx1 (red), and Rx (green, f ). g , Schematic of the result. h , Induction of Lim3 expression by SAG (qPCR; n = 9). i , FACS analysis of the Lim3::venus + population in day-10 LCA aggregates with SAG treatment (green). Grey, day-1 aggregate. j , Lim3::venus expression in LCA aggregates with SAG treatment. k , Clusters of Lim3::venus + vesicles (arrowheads) in day-13 SAG-treated LCA aggregates. Arrows, vesicles forming on the other side. l , Lim3 + pouch is Pitx1 + but Tuj1 − . Scale bars, 100 µm ( b , e , f , k , l ); 500 µm ( h ). The values shown on graphs represent the mean ± s.e.m. NS, not significant. *, P < 0.05; **, P < 0.01; ***, P < 0.001. PowerPoint slide Full size image Juxtaposing ectodermal layers formed in culture Mouse ES cells can be induced to differentiate into rostral hypothalamic tissues when cultured as floating aggregates (typically 3,000 cells per aggregate) in a chemically defined medium lacking extrinsic growth factors (including no insulin; hereafter referred to as SFEBq culture 9 ). However, quantitative polymerase chain reaction (qPCR) analysis found only low expression levels of the rostral head ectoderm marker Pitx2 in SFEBq-cultured ES cells ( Fig. 1c ). Because the embryonic anlage for rostral head ectoderm and hypothalamic neuroectoderm are adjacent ( Supplementary Fig. 1a–c ), we wondered if a slight shift in positional information could promote the simultaneous generation of both tissues within the same aggregate in SFEBq culture. We experimentally tested several culture conditions known to affect early ectodermal patterning 9 , 10 , 11 , 12 , and found two that substantially increased Pitx2 expression levels ( Fig. 1d and data not shown): a large cell-aggregation (LCA) culture (red; starting differentiation culture at 10,000 cells per aggregate, instead of 3,000; Supplementary Fig. 2a ) and bone morphogenetic protein 4 (BMP4) treatment (blue; 0.5 µM, days 0–7). BMP4 plus LCA also increased Pitx2 expression, but no clear additive effects were seen over LCA alone ( Supplementary Fig. 2b ). In the LCA culture, both Pitx1/2 + rostral head ectoderm tissue and Rx + neural tissue formed continuous epithelia within the ES cell aggregates ( Fig. 1e–g ; Supplementary Fig. 2c and data not shown). The Rx + tissues were Chx10 − nestin + (Chx10 also known as Vsx2; Supplementary Fig. 2d ), characteristic of rostral hypothalamic epithelia (retinal epithelia are Rx + but Chx10 + nestin − ) 9 , 13 . Importantly, a layer of Pitx1/2 + epithelium reproducibly formed on the surface of the ES cell aggregates, adjacent and exterior to the Rx + neuroepithelia, which formed inner layers ( Fig. 1f, g ). In contrast, treatment with exogenous BMP4, which is generally known to promote differentiation of non-neural ectoderm at the cost of neural differentiation 10 , 12 , inhibited the formation of hypothalamic tissues even at 0.5 nM, regardless of the aggregation size ( Supplementary Fig. 2e ). Conversely, treatment with the BMP antagonist dorsomorphin inhibited the generation of Pitx2 + ectoderm, which was promoted in the LCA culture ( Supplementary Fig. 2f ). Given that the expression of Bmp2 and Bmp4 (refs 8 , 14 ) was increased under LCA conditions ( Supplementary Fig. 2g–i ), the moderate", "role": "user" }, { "content": "(Medical Xpress) -- A new study published in Nature reports that scientists have been able to grow working pituitary glands from embryonic stem cells from mice. When these were transplanted into mice with defects in the pituitary gland, the levels of hormones missing in the body were raised. The pituitary gland is a pea-sized endocrine gland at the base of the brain and secretes different hormones including Human Growth Hormone, or HGH and thyroid-stimulating hormone, or TSH. The release of these hormones plays a role in things such as growth, blood pressure, pregnancy and thyroid function. Inadequate release of certain hormones by the pituitary gland can lead to various hormone disorders. The team of researchers, led by Dr. Yoshiki Sasai from the RIKEN Centre for Developmental Biology in Kobe, Japan has created a way to grow these little organs using embryonic stem cells from mice. Using a three dimensional culture, the team arranged the mouse stem cells in a way that mimicked the way a pituitary gland grows naturally in the embryo. When the pituitary gland grows in the embryo, it is made from two different tissue types in the brain. Where these two different tissues come together is where the pituitary gland forms. The researchers set up the culture so these two tissues would come together similar to the way they do in the brain. The fold of tissue known as Rathke’s pouch formed naturally and grew into the pituitary gland. This pituitary gland took three weeks to grow and included all the cell types that are found in a normal pituitary gland. The researchers then transplanted the tissue into mice that had pituitary problems and the hormone levels soon returned to normal. While these pituitary glands were created with embryonic stem cells, the researchers believe they can use the same process successfully with stem cells taken from adults and avoid possible ethical concerns with the use of embryonic stem cells. Research is planned to develop human pituitary glands though Sasai says that will take another four to five years. If successful, these lab-grown pituitary glands could be used to replace ones that have been damaged or do not function properly. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The adenohypophysis (anterior pituitary) is a major centre for systemic hormones. At present, no efficient stem-cell culture for its generation is available, partly because of insufficient knowledge about how the pituitary primordium (Rathke’s pouch) is induced in the embryonic head ectoderm. Here we report efficient self-formation of three-dimensional adenohypophysis tissues in an aggregate culture of mouse embryonic stem (ES) cells. ES cells were stimulated to differentiate into non-neural head ectoderm and hypothalamic neuroectoderm in adjacent layers within the aggregate, and treated with hedgehog signalling. Self-organization of Rathke’s-pouch-like three-dimensional structures occurred at the interface of these two epithelia, as seen in vivo , and various endocrine cells including corticotrophs and somatotrophs were subsequently produced. The corticotrophs efficiently secreted adrenocorticotropic hormone in response to corticotrophin releasing hormone and, when grafted in vivo , these cells rescued the systemic glucocorticoid level in hypopituitary mice. Thus, functional anterior pituitary tissue self-forms in ES cell culture, recapitulating local tissue interactions. Main The adenohypophysis, corresponding to the anterior and intermediate lobes of the pituitary gland, contains several types of endocrine cells, which secrete systemic hormones such as adenocorticotropic hormone (ACTH), GH, LH/FSH, TSH and prolactin 1 , 2 , 3 in response to hypothalamus-derived releasing hormones. In contrast, the neurohypophysis (posterior pituitary) consists of the axons and secretory termini of hypothalamic vasopressin and oxytocin neurons. During early mammalian development, the adenohypophysis anlage originates as a placode in the non-neural head ectoderm rostral and adjacent to the anterior neural plate 4 , 5 ( Supplementary Fig. 1a ) (hereafter, this part of non-neural ectoderm, expressing region-specific markers Pitx1 and Pitx2, is simply referred to as rostral head ectoderm; this includes the oral ectoderm as a large part). The thickened placodal epithelium invaginates and subsequently detaches from the oral ectoderm, becoming a hollowed epithelial vesicle, Rathke’s pouch ( Fig. 1a, b and Supplementary Fig. 1b, c ). The development of Rathke’s pouch depends on tissue interactions between the rostral head ectoderm and the rostral hypothalamus 3 , 4 , 5 , 6 , 7 , 8 . We sought to recapitulate this interactive microenvironment of the pituitary-forming morphogenetic field using three-dimensional ES cell culture. Figure 1: Adjacent formation of head ectoderm and hypothalamic epithelia in ES cell culture. a , Schematic of pituitary development, sagittal view. A, anterior; D, dorsal; P, posterior; V, ventral. b , In vivo expression of Pitx1 and Rx on embryonic day 13 (E13). c , Little expression of Pitx2 in SFEBq/CDM-cultured ES cells (qPCR; n = 3 experiments). d, day. d , Pitx2 expression in aggregates cultured under the LCA condition (red) or treated with 0.5 nM BMP4 (blue) ( n = 3). e , f , Immunostaining of day-6 LCA aggregates for Pitx1 (red), and Rx (green, f ). g , Schematic of the result. h , Induction of Lim3 expression by SAG (qPCR; n = 9). i , FACS analysis of the Lim3::venus + population in day-10 LCA aggregates with SAG treatment (green). Grey, day-1 aggregate. j , Lim3::venus expression in LCA aggregates with SAG treatment. k , Clusters of Lim3::venus + vesicles (arrowheads) in day-13 SAG-treated LCA aggregates. Arrows, vesicles forming on the other side. l , Lim3 + pouch is Pitx1 + but Tuj1 − . Scale bars, 100 µm ( b , e , f , k , l ); 500 µm ( h ). The values shown on graphs represent the mean ± s.e.m. NS, not significant. *, P < 0.05; **, P < 0.01; ***, P < 0.001. PowerPoint slide Full size image Juxtaposing ectodermal layers formed in culture Mouse ES cells can be induced to differentiate into rostral hypothalamic tissues when cultured as floating aggregates (typically 3,000 cells per aggregate) in a chemically defined medium lacking extrinsic growth factors (including no insulin; hereafter referred to as SFEBq culture 9 ). However, quantitative polymerase chain reaction (qPCR) analysis found only low expression levels of the rostral head ectoderm marker Pitx2 in SFEBq-cultured ES cells ( Fig. 1c ). Because the embryonic anlage for rostral head ectoderm and hypothalamic neuroectoderm are adjacent ( Supplementary Fig. 1a–c ), we wondered if a slight shift in positional information could promote the simultaneous generation of both tissues within the same aggregate in SFEBq culture. We experimentally tested several culture conditions known to affect early ectodermal patterning 9 , 10 , 11 , 12 , and found two that substantially increased Pitx2 expression levels ( Fig. 1d and data not shown): a large cell-aggregation (LCA) culture (red; starting differentiation culture at 10,000 cells per aggregate, instead of 3,000; Supplementary Fig. 2a ) and bone morphogenetic protein 4 (BMP4) treatment (blue; 0.5 µM, days 0–7). BMP4 plus LCA also increased Pitx2 expression, but no clear additive effects were seen over LCA alone ( Supplementary Fig. 2b ). In the LCA culture, both Pitx1/2 + rostral head ectoderm tissue and Rx + neural tissue formed continuous epithelia within the ES cell aggregates ( Fig. 1e–g ; Supplementary Fig. 2c and data not shown). The Rx + tissues were Chx10 − nestin + (Chx10 also known as Vsx2; Supplementary Fig. 2d ), characteristic of rostral hypothalamic epithelia (retinal epithelia are Rx + but Chx10 + nestin − ) 9 , 13 . Importantly, a layer of Pitx1/2 + epithelium reproducibly formed on the surface of the ES cell aggregates, adjacent and exterior to the Rx + neuroepithelia, which formed inner layers ( Fig. 1f, g ). In contrast, treatment with exogenous BMP4, which is generally known to promote differentiation of non-neural ectoderm at the cost of neural differentiation 10 , 12 , inhibited the formation of hypothalamic tissues even at 0.5 nM, regardless of the aggregation size ( Supplementary Fig. 2e ). Conversely, treatment with the BMP antagonist dorsomorphin inhibited the generation of Pitx2 + ectoderm, which was promoted in the LCA culture ( Supplementary Fig. 2f ). Given that the expression of Bmp2 and Bmp4 (refs 8 , 14 ) was increased under LCA conditions ( Supplementary Fig. 2g–i ), the moderate<|im_end|> <|im_start|>assistant (Medical Xpress) -- A new study published in Nature reports that scientists have been able to grow working pituitary glands from embryonic stem cells from mice. When these were transplanted into mice with defects in the pituitary gland, the levels of hormones missing in the body were raised. The pituitary gland is a pea-sized endocrine gland at the base of the brain and secretes different hormones including Human Growth Hormone, or HGH and thyroid-stimulating hormone, or TSH. The release of these hormones plays a role in things such as growth, blood pressure, pregnancy and thyroid function. Inadequate release of certain hormones by the pituitary gland can lead to various hormone disorders. The team of researchers, led by Dr. Yoshiki Sasai from the RIKEN Centre for Developmental Biology in Kobe, Japan has created a way to grow these little organs using embryonic stem cells from mice. Using a three dimensional culture, the team arranged the mouse stem cells in a way that mimicked the way a pituitary gland grows naturally in the embryo. When the pituitary gland grows in the embryo, it is made from two different tissue types in the brain. Where these two different tissues come together is where the pituitary gland forms. The researchers set up the culture so these two tissues would come together similar to the way they do in the brain. The fold of tissue known as Rathke’s pouch formed naturally and grew into the pituitary gland. This pituitary gland took three weeks to grow and included all the cell types that are found in a normal pituitary gland. The researchers then transplanted the tissue into mice that had pituitary problems and the hormone levels soon returned to normal. While these pituitary glands were created with embryonic stem cells, the researchers believe they can use the same process successfully with stem cells taken from adults and avoid possible ethical concerns with the use of embryonic stem cells. Research is planned to develop human pituitary glands though Sasai says that will take another four to five years. If successful, these lab-grown pituitary glands could be used to replace ones that have been damaged or do not function properly. <|im_end|>

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44481, 14338, 1938, 220, 1032, 320, 36, 1032, 570, 272, 1174, 15013, 7645, 315, 40079, 87, 17, 304, 24360, 8428, 80, 14, 6620, 44, 1824, 495, 3149, 19844, 7917, 320, 80, 74256, 26, 308, 284, 220, 18, 21896, 570, 294, 11, 1938, 13, 294, 1174, 40079, 87, 17, 7645, 304, 71643, 89948, 1234, 279, 445, 5158, 3044, 320, 1171, 8, 477, 12020, 449, 220, 15, 13, 20, 308, 44, 76294, 19, 320, 12481, 8, 320, 308, 284, 220, 18, 570, 384, 1174, 282, 1174, 67335, 537, 2101, 315, 1938, 12, 21, 445, 5158, 71643, 369, 40079, 87, 16, 320, 1171, 705, 323, 36476, 320, 13553, 11, 282, 7609, 342, 1174, 328, 82149, 315, 279, 1121, 13, 305, 1174, 2314, 2720, 315, 13903, 18, 7645, 555, 328, 1929, 320, 80, 74256, 26, 308, 284, 220, 24, 570, 602, 1174, 435, 63787, 6492, 315, 279, 13903, 18, 487, 1055, 355, 489, 7187, 304, 1938, 12, 605, 445, 5158, 71643, 449, 328, 1929, 6514, 320, 13553, 570, 26769, 11, 1938, 12, 16, 24069, 13, 503, 1174, 13903, 18, 487, 1055, 355, 7645, 304, 445, 5158, 71643, 449, 328, 1929, 6514, 13, 597, 1174, 2493, 14947, 315, 13903, 18, 487, 1055, 355, 489, 65635, 4440, 320, 6172, 36910, 8, 304, 1938, 12, 1032, 328, 1929, 88186, 445, 5158, 71643, 13, 1676, 1849, 11, 65635, 4440, 30164, 389, 279, 1023, 3185, 13, 326, 1174, 13903, 18, 489, 56952, 374, 40079, 87, 16, 489, 719, 350, 9832, 16, 25173, 662, 25635, 16283, 11, 220, 1041, 64012, 76, 320, 293, 1174, 384, 1174, 282, 1174, 597, 1174, 326, 7048, 220, 2636, 64012, 76, 320, 305, 7609, 578, 2819, 6982, 389, 40099, 4097, 279, 3152, 20903, 274, 1770, 749, 13, 3119, 11, 539, 5199, 13, 12039, 393, 366, 220, 15, 13, 2304, 26, 3146, 11, 393, 366, 220, 15, 13, 1721, 26, 3146, 12594, 393, 366, 220, 15, 13, 4119, 13, 54600, 15332, 8797, 1404, 2217, 622, 93462, 14759, 77594, 347, 18558, 13931, 14454, 304, 7829, 18191, 19844, 7917, 649, 387, 36572, 311, 54263, 1139, 938, 56070, 45455, 278, 4079, 39881, 994, 89948, 439, 19596, 71643, 320, 87184, 220, 18, 11, 931, 7917, 824, 24069, 8, 304, 264, 8590, 2740, 4613, 11298, 32161, 11741, 28692, 6650, 9547, 320, 16564, 912, 32152, 26, 1618, 10924, 14183, 311, 439, 24360, 8428, 80, 7829, 220, 24, 7609, 4452, 11, 47616, 47393, 521, 8957, 13010, 320, 80, 74256, 8, 6492, 1766, 1193, 3428, 7645, 5990, 315, 279, 938, 56070, 2010, 77594, 347, 4289, 11381, 40079, 87, 17, 304, 24360, 8428, 80, 1824, 495, 3149, 19844, 7917, 320, 23966, 13, 220, 16, 66, 7609, 9393, 279, 44481, 14338, 459, 56854, 369, 938, 56070, 2010, 77594, 347, 4289, 323, 45455, 278, 4079, 18247, 440, 347, 4289, 527, 24894, 320, 99371, 23966, 13, 220, 16, 64, 4235, 66, 7026, 584, 31156, 422, 264, 8275, 6541, 304, 68647, 2038, 1436, 12192, 279, 58632, 9659, 315, 2225, 39881, 2949, 279, 1890, 24069, 304, 24360, 8428, 80, 7829, 13, 1226, 9526, 750, 12793, 3892, 7829, 4787, 3967, 311, 7958, 4216, 77594, 347, 18558, 93093, 1251, 220, 24, 1174, 220, 605, 1174, 220, 806, 1174, 220, 717, 1174, 323, 1766, 1403, 430, 32302, 7319, 40079, 87, 17, 7645, 5990, 320, 23966, 13, 220, 16, 67, 323, 828, 539, 6982, 1680, 264, 3544, 2849, 43085, 35542, 320, 43, 5158, 8, 7829, 320, 1171, 26, 6041, 60038, 7829, 520, 220, 605, 11, 931, 7917, 824, 24069, 11, 4619, 315, 220, 18, 11, 931, 26, 99371, 23966, 13, 220, 17, 64, 883, 323, 17685, 27448, 11968, 5411, 13128, 220, 19, 320, 33, 5901, 19, 8, 6514, 320, 12481, 26, 220, 15, 13, 20, 64012, 44, 11, 2919, 220, 15, 4235, 22, 570, 76294, 19, 5636, 445, 5158, 1101, 7319, 40079, 87, 17, 7645, 11, 719, 912, 2867, 64338, 6372, 1051, 3970, 927, 445, 5158, 7636, 320, 99371, 23966, 13, 220, 17, 65, 7609, 763, 279, 445, 5158, 7829, 11, 2225, 40079, 87, 16, 14, 17, 489, 938, 56070, 2010, 77594, 347, 4289, 20438, 323, 36476, 489, 30828, 20438, 14454, 19815, 64779, 37029, 2949, 279, 19844, 2849, 71643, 320, 23966, 13, 220, 16, 68, 4235, 70, 2652, 99371, 23966, 13, 220, 17, 66, 323, 828, 539, 6982, 570, 578, 36476, 489, 39881, 1051, 921, 87, 605, 25173, 23634, 258, 489, 320, 1163, 87, 605, 1101, 3967, 439, 44082, 87, 17, 26, 99371, 23966, 13, 220, 17, 67, 7026, 29683, 315, 938, 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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The flipping of membrane-embedded lipids containing large, polar head groups is slow and energetically unfavourable, and is therefore catalysed by flippases, the mechanisms of which are unknown. A prominent example of a flipping reaction is the translocation of lipid-linked oligosaccharides that serve as donors in N -linked protein glycosylation. In Campylobacter jejuni , this process is catalysed by the ABC transporter PglK. Here we present a mechanism of PglK-catalysed lipid-linked oligosaccharide flipping based on crystal structures in distinct states, a newly devised in vitro flipping assay, and in vivo studies. PglK can adopt inward- and outward-facing conformations in vitro , but only outward-facing states are required for flipping. While the pyrophosphate-oligosaccharide head group of lipid-linked oligosaccharides enters the translocation cavity and interacts with positively charged side chains, the lipidic polyprenyl tail binds and activates the transporter but remains exposed to the lipid bilayer during the reaction. The proposed mechanism is distinct from the classical alternating-access model applied to other transporters. Main The translocation of lipids across the bilayer, termed flipping, is not only essential for maintaining lipid asymmetry in membranes, but also underpins various processes including signalling, vesicle formation in secretory and endocytic pathways, the regulation of membrane protein activity, and asparagine-linked protein glycosylation 1 , 2 , 3 , 4 , 5 . In animals, trans -bilayer lipid asymmetry affects processes such as blood coagulation, macrophage recognition 6 and apoptosis 7 . In bacteria, precursors of cell wall components are coupled to lipid carriers and exported by flippases, which is essential for cell wall assembly 8 , 9 , 10 . Flipping reactions are catalysed by passive or active transporter proteins 11 . These include energy-independent scramblases that randomize the orientation of lipids across the bilayer 12 , 13 , proton- or sodium-driven secondary antiporters 14 , and ATP-driven, vectorial transporters that actively translocate specific lipids. The latter include P4-ATPases 15 and ATP-binding cassette (ABC) transporters 11 , 16 . Despite extensive research, remarkably little is known about the structure and mechanism of active, flippase-catalysed lipid translocation. Until now, crystal structures have only been reported for the MsbA protein 16 , 17 , the bacterial flippase of lipid A-core, but no mechanism could be deduced from the structural data. In addition to the scarcity of structures, there are few reliable in vitro assays that allow the study of native substrate flipping. A prominent substrate of flippases in eukaryotes is the lipid-linked-oligosaccharide (LLO) Man 5 GlcNAc 2 -PP-dolichol, which is translocated from the cytosolic to the luminal side of the endoplasmic reticulum membrane, where the oligosaccharide is transferred to asparagine residues of nascent polypeptide chains in protein N -glycosylation 1 , 2 . In the homologous bacterial N -glycosylation pathway, a chemically similar LLO (GlcGalNAc 5 Bac-PP-undecaprenyl; Extended Data Fig. 1 ) is flipped in the human pathogen C. jejuni 18 , 19 . The responsible flippase, PglK, is a homodimeric ABC transporter and an essential component of the bacterial protein N -glycosylation machinery 20 . The translocated LLO is handed over to the oligosaccharyltransferase PglB, which catalyses oligosaccharide transfer to acceptor proteins 21 . Undecaprenyl-pyrophosophate is subsequently hydrolysed to the monophosphate by undecaprenyl-pyrophosphatase 22 ( Extended Data Fig. 2 ). To understand the mechanism of ATP-driven LLO flipping, we have developed an in vitro assay and determined the crystal structures of C. jejuni PglK in distinct states. Our results suggest a mechanism in which only the outward-facing conformations are relevant for flipping, thereby allowing the passage of the oligosaccharide moiety through the transporter while the polyprenyl tail remains partially embedded in the lipid bilayer but attached to the surface of PglK. This newly proposed mechanism is distinct from the alternating-access model that underlies the mechanism of most primary and secondary transporters studied so far. PglK in vitro LLO flipping and ATPase activity Flipping of polyprenyl-linked oligosaccharides has previously been investigated using radiolabelled natural lipids 23 , 24 . By contrast, we exploited the fact that PglK can process LLOs with shortened oligosaccharides both in vivo and in vitro 20 , 25 , 26 . We therefore generated proteoliposomes by co-reconstituting PglK and a trisaccharide LLO (tLLO), which contained a reducing-end bacillosamine and two N -acetylgalactosamine (GalNAc) moieties ( Fig. 1a and Extended Data Fig. 1 ). To determine the rate of ATP-driven, PglK-dependent tLLO flipping, the amount of tLLO molecules in the outer, accessible leaflet of the proteoliposomes was quantified by radiolabelling using purified glycosyltransferase PglH 27 , 28 , 29 , an enzyme of the C. jejuni N -glycosylation machinery that was shown to attach up to three GalNAc residues to the non-reducing end of tLLO ( Extended Data Fig. 2 ). We used excess UDP-GalNAc, thereby forcing three GalNAc molecules to be added to each tLLO molecule, allowing accurate determination of tLLO flipping to the liposome lumen ( Fig. 1b and Extended Data Fig. 9a ). The conversion of tLLO to hexa-saccharide LLO was confirmed by transferring the resulting oligosaccharides to fluorescently labelled acceptor peptides using purified oligosaccharyltransferase PglB, followed by SDS–PAGE analysis 26 , 30 , 31 . PglK-catalysed in vitro tLLO flipping was strictly dependent on ATP hydrolysis. A PglK mutant containing a glutamine residue in the Walker-B motif (E510Q) exhibited an almost 100-fold decrease in the flipping rate, which correlated with strongly reduced in vivo activity ( Extended Data Fig. 3a–c ). The ATPase activity of PglK in the presence of LLO follows Michaelis–Menten kinetics, with a K m value of 0.46 ± 0.08 mM (mean ± s.d.), matching the K m of ATP-dependent tLLO flipping of 0.36 ± 0.03 mM ( Extended Data Fig. 3d ). This corroborates the interpretation that ATP hydrolysis is required and driving PglK-catalysed LLO flipping. As was observed with other ABC transporters, binding of native substrate can stimulate the ATPase activity. PglK-catalysed ATP hydrolysis is stimulated ∼ 2.5-fold by full-length LLO and tLLO both in detergent and in liposomes, demonstrating that the terminal GalNAc and the branching glucose residues of native LLO are not relevant for ATPase", "role": "user" }, { "content": "A team of researchers at ETH Zurich and the University of Bern has succeeded in determining the structure of a lipid flippase at high resolution, which has provided insight into how this membrane protein transports lipids by flipping. Biological membranes have a fundamental role in separating the interior of cells from the extracellular space and in helping determine cellular shape and size. They consist of a double layer (\"bilayer\") of lipids that contain a hydrophilic head group and generally two long, hydrophobic tails. Whereas the head groups face outwards, the hydrophobic tail face each other. Numerous other components are embedded in membranes, including pore-forming proteins and transport proteins. Countless vital processes occur at membranes, including the transport of various substances. The transport of phospholipids and lipid-linked oligosaccharides (LLO) is particularly difficult to achieve due to the bipolar nature of the lipid bilayer - hydrophobic interior, hydrophilic surface. This is why flippases are required to transport lipids from one side of the membrane to the other, essentially flipping their orientation. Flippases have important roles in maintaining the asymmetry of cellular membranes, i.e. in the different lipid composition of the outer and inner sides. In mammals, this affects various processes such as blood coagulation, immune recognition and programmed cell death, or apoptosis. Flippases are also essential for transporting lipid-linked oligosaccharides (\"LLOs\"), which are transferred onto acceptor proteins during N-linked protein glycosylation. Flippase structure revealed for the first time Until now biologists knew neither the high-resolution structures of flippases nor the exact mechanism used to flip LLOs. Three research teams from ETH Zurich and the University of Bern, led by ETH professor Kaspar Locher, have now determined the structure of one such flippase, the PglK protein from the bacterium Campylobacter jejuni. The study has been published in the journal Nature. This required the researchers to purify the flippase from bacterial membranes and generate three-dimensional crystals, which were then analysed using X-ray crystallography to determine the positions of all atoms. The scientists determined three distinct structures that corresponded to different states of the flippase during the reaction. Their data allowed the researchers to deduce a molecular mechanism of how PglK flips LLOs. The researchers show that PglK consists of two identical subunits that move like a pair of scissors when energy (ATP) is consumed. Similar to a credit card reader, the oligosaccharide moiety of the lipid-linked oligosaccharide is then pulled into a hydrophilic channel within the flippase. The hydrophobic, lipidic tail of the LLO molecule remains exposed to the lipidic membrane, causing the LLO to change its orientation so that the sugar part ends up on the outside of the membrane. The flippase itself does not change its orientation during translocation reaction and therefore acts as a catalyst. Fundamentally different mechanism The newly-discovered mechanism fundamentally differs from previously known transport processes that catalyze import or export of soluble substrates. \"The flipping of lipids in membranes has always fascinated biochemists and cell biologists; the biological solution to this problem thrills us!\" says co-author Markus Aebi, Professor of Microbiology at ETH Zurich. The research groups from ETH Zurich and the University of Bern are the first to have solved the fundamental biological puzzle of how LLOs are flipped. They developed a novel method for studying the reaction in vitro. ETH Professor Aebi insists that only through the cooperation of structural biologists, chemists and microbiologists was it possible to decipher this basic mechanism. \"Every group brought their own expertise from their respective fields. This was the only way we could succeed.\" Therapeutic applications? Although the present work constitutes basic research, there are diseases associated with mutations in a human flippase, explains Aebi. These diseases are termed 'congenital disorders of glycosylation'. More than 10,000 glycosylation sites in various proteins have been identified in humans, \"which is why changes in glycosylation in which flippase plays a crucial role affect so many processes in the body,\" says the ETH professor. Examples of this include the development and maturation of the central nervous system. Whether the newly acquired knowledge of the bacterial flippase PglK leads to novel therapeutic approaches is unclear at present. However, flippases already form an essential part of biotechnological systems that are used to generate glycoproteins desigend for various uses in diagnostics and potential therapeutic agents. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The flipping of membrane-embedded lipids containing large, polar head groups is slow and energetically unfavourable, and is therefore catalysed by flippases, the mechanisms of which are unknown. A prominent example of a flipping reaction is the translocation of lipid-linked oligosaccharides that serve as donors in N -linked protein glycosylation. In Campylobacter jejuni , this process is catalysed by the ABC transporter PglK. Here we present a mechanism of PglK-catalysed lipid-linked oligosaccharide flipping based on crystal structures in distinct states, a newly devised in vitro flipping assay, and in vivo studies. PglK can adopt inward- and outward-facing conformations in vitro , but only outward-facing states are required for flipping. While the pyrophosphate-oligosaccharide head group of lipid-linked oligosaccharides enters the translocation cavity and interacts with positively charged side chains, the lipidic polyprenyl tail binds and activates the transporter but remains exposed to the lipid bilayer during the reaction. The proposed mechanism is distinct from the classical alternating-access model applied to other transporters. Main The translocation of lipids across the bilayer, termed flipping, is not only essential for maintaining lipid asymmetry in membranes, but also underpins various processes including signalling, vesicle formation in secretory and endocytic pathways, the regulation of membrane protein activity, and asparagine-linked protein glycosylation 1 , 2 , 3 , 4 , 5 . In animals, trans -bilayer lipid asymmetry affects processes such as blood coagulation, macrophage recognition 6 and apoptosis 7 . In bacteria, precursors of cell wall components are coupled to lipid carriers and exported by flippases, which is essential for cell wall assembly 8 , 9 , 10 . Flipping reactions are catalysed by passive or active transporter proteins 11 . These include energy-independent scramblases that randomize the orientation of lipids across the bilayer 12 , 13 , proton- or sodium-driven secondary antiporters 14 , and ATP-driven, vectorial transporters that actively translocate specific lipids. The latter include P4-ATPases 15 and ATP-binding cassette (ABC) transporters 11 , 16 . Despite extensive research, remarkably little is known about the structure and mechanism of active, flippase-catalysed lipid translocation. Until now, crystal structures have only been reported for the MsbA protein 16 , 17 , the bacterial flippase of lipid A-core, but no mechanism could be deduced from the structural data. In addition to the scarcity of structures, there are few reliable in vitro assays that allow the study of native substrate flipping. A prominent substrate of flippases in eukaryotes is the lipid-linked-oligosaccharide (LLO) Man 5 GlcNAc 2 -PP-dolichol, which is translocated from the cytosolic to the luminal side of the endoplasmic reticulum membrane, where the oligosaccharide is transferred to asparagine residues of nascent polypeptide chains in protein N -glycosylation 1 , 2 . In the homologous bacterial N -glycosylation pathway, a chemically similar LLO (GlcGalNAc 5 Bac-PP-undecaprenyl; Extended Data Fig. 1 ) is flipped in the human pathogen C. jejuni 18 , 19 . The responsible flippase, PglK, is a homodimeric ABC transporter and an essential component of the bacterial protein N -glycosylation machinery 20 . The translocated LLO is handed over to the oligosaccharyltransferase PglB, which catalyses oligosaccharide transfer to acceptor proteins 21 . Undecaprenyl-pyrophosophate is subsequently hydrolysed to the monophosphate by undecaprenyl-pyrophosphatase 22 ( Extended Data Fig. 2 ). To understand the mechanism of ATP-driven LLO flipping, we have developed an in vitro assay and determined the crystal structures of C. jejuni PglK in distinct states. Our results suggest a mechanism in which only the outward-facing conformations are relevant for flipping, thereby allowing the passage of the oligosaccharide moiety through the transporter while the polyprenyl tail remains partially embedded in the lipid bilayer but attached to the surface of PglK. This newly proposed mechanism is distinct from the alternating-access model that underlies the mechanism of most primary and secondary transporters studied so far. PglK in vitro LLO flipping and ATPase activity Flipping of polyprenyl-linked oligosaccharides has previously been investigated using radiolabelled natural lipids 23 , 24 . By contrast, we exploited the fact that PglK can process LLOs with shortened oligosaccharides both in vivo and in vitro 20 , 25 , 26 . We therefore generated proteoliposomes by co-reconstituting PglK and a trisaccharide LLO (tLLO), which contained a reducing-end bacillosamine and two N -acetylgalactosamine (GalNAc) moieties ( Fig. 1a and Extended Data Fig. 1 ). To determine the rate of ATP-driven, PglK-dependent tLLO flipping, the amount of tLLO molecules in the outer, accessible leaflet of the proteoliposomes was quantified by radiolabelling using purified glycosyltransferase PglH 27 , 28 , 29 , an enzyme of the C. jejuni N -glycosylation machinery that was shown to attach up to three GalNAc residues to the non-reducing end of tLLO ( Extended Data Fig. 2 ). We used excess UDP-GalNAc, thereby forcing three GalNAc molecules to be added to each tLLO molecule, allowing accurate determination of tLLO flipping to the liposome lumen ( Fig. 1b and Extended Data Fig. 9a ). The conversion of tLLO to hexa-saccharide LLO was confirmed by transferring the resulting oligosaccharides to fluorescently labelled acceptor peptides using purified oligosaccharyltransferase PglB, followed by SDS–PAGE analysis 26 , 30 , 31 . PglK-catalysed in vitro tLLO flipping was strictly dependent on ATP hydrolysis. A PglK mutant containing a glutamine residue in the Walker-B motif (E510Q) exhibited an almost 100-fold decrease in the flipping rate, which correlated with strongly reduced in vivo activity ( Extended Data Fig. 3a–c ). The ATPase activity of PglK in the presence of LLO follows Michaelis–Menten kinetics, with a K m value of 0.46 ± 0.08 mM (mean ± s.d.), matching the K m of ATP-dependent tLLO flipping of 0.36 ± 0.03 mM ( Extended Data Fig. 3d ). This corroborates the interpretation that ATP hydrolysis is required and driving PglK-catalysed LLO flipping. As was observed with other ABC transporters, binding of native substrate can stimulate the ATPase activity. PglK-catalysed ATP hydrolysis is stimulated ∼ 2.5-fold by full-length LLO and tLLO both in detergent and in liposomes, demonstrating that the terminal GalNAc and the branching glucose residues of native LLO are not relevant for ATPase<|im_end|> <|im_start|>assistant A team of researchers at ETH Zurich and the University of Bern has succeeded in determining the structure of a lipid flippase at high resolution, which has provided insight into how this membrane protein transports lipids by flipping. Biological membranes have a fundamental role in separating the interior of cells from the extracellular space and in helping determine cellular shape and size. They consist of a double layer ("bilayer") of lipids that contain a hydrophilic head group and generally two long, hydrophobic tails. Whereas the head groups face outwards, the hydrophobic tail face each other. Numerous other components are embedded in membranes, including pore-forming proteins and transport proteins. Countless vital processes occur at membranes, including the transport of various substances. The transport of phospholipids and lipid-linked oligosaccharides (LLO) is particularly difficult to achieve due to the bipolar nature of the lipid bilayer - hydrophobic interior, hydrophilic surface. This is why flippases are required to transport lipids from one side of the membrane to the other, essentially flipping their orientation. Flippases have important roles in maintaining the asymmetry of cellular membranes, i.e. in the different lipid composition of the outer and inner sides. In mammals, this affects various processes such as blood coagulation, immune recognition and programmed cell death, or apoptosis. Flippases are also essential for transporting lipid-linked oligosaccharides ("LLOs"), which are transferred onto acceptor proteins during N-linked protein glycosylation. Flippase structure revealed for the first time Until now biologists knew neither the high-resolution structures of flippases nor the exact mechanism used to flip LLOs. Three research teams from ETH Zurich and the University of Bern, led by ETH professor Kaspar Locher, have now determined the structure of one such flippase, the PglK protein from the bacterium Campylobacter jejuni. The study has been published in the journal Nature. This required the researchers to purify the flippase from bacterial membranes and generate three-dimensional crystals, which were then analysed using X-ray crystallography to determine the positions of all atoms. The scientists determined three distinct structures that corresponded to different states of the flippase during the reaction. Their data allowed the researchers to deduce a molecular mechanism of how PglK flips LLOs. The researchers show that PglK consists of two identical subunits that move like a pair of scissors when energy (ATP) is consumed. Similar to a credit card reader, the oligosaccharide moiety of the lipid-linked oligosaccharide is then pulled into a hydrophilic channel within the flippase. The hydrophobic, lipidic tail of the LLO molecule remains exposed to the lipidic membrane, causing the LLO to change its orientation so that the sugar part ends up on the outside of the membrane. The flippase itself does not change its orientation during translocation reaction and therefore acts as a catalyst. Fundamentally different mechanism The newly-discovered mechanism fundamentally differs from previously known transport processes that catalyze import or export of soluble substrates. "The flipping of lipids in membranes has always fascinated biochemists and cell biologists; the biological solution to this problem thrills us!" says co-author Markus Aebi, Professor of Microbiology at ETH Zurich. The research groups from ETH Zurich and the University of Bern are the first to have solved the fundamental biological puzzle of how LLOs are flipped. They developed a novel method for studying the reaction in vitro. ETH Professor Aebi insists that only through the cooperation of structural biologists, chemists and microbiologists was it possible to decipher this basic mechanism. "Every group brought their own expertise from their respective fields. This was the only way we could succeed." Therapeutic applications? Although the present work constitutes basic research, there are diseases associated with mutations in a human flippase, explains Aebi. These diseases are termed 'congenital disorders of glycosylation'. More than 10,000 glycosylation sites in various proteins have been identified in humans, "which is why changes in glycosylation in which flippase plays a crucial role affect so many processes in the body," says the ETH professor. Examples of this include the development and maturation of the central nervous system. Whether the newly acquired knowledge of the bacterial flippase PglK leads to novel therapeutic approaches is unclear at present. However, flippases already form an essential part of biotechnological systems that are used to generate glycoproteins desigend for various uses in diagnostics and potential therapeutic agents. <|im_end|>

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2,591

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The use of precision medicine is poised to increase in complex injuries such as traumatic brain injury (TBI), whose multifaceted comorbidities and personal circumstances create significant challenges in the domains of surveillance, management, and environmental mapping. Population-wide health administrative data remains a rather unexplored, but accessible data source for identifying clinical associations and environmental patterns that could lead to a better understanding of TBIs. However, the amount of data structured and coded by the International Classification of Disease poses a challenge to its successful interpretation. The emerging field of data mining can be instrumental in helping to meet the daunting challenges faced by the TBI community. The report outlines novel areas for data mining relevant to TBI, and offers insight into how the above approach can be applied to solve pressing healthcare problems. Future work should focus on confirmatory analyses, which subsequently can guide precision medicine and preventive frameworks. Introduction With the enormous progress in the consolidation of large clinical datasets and national registries in modern healthcare 1 , 2 , vast amounts of personal, clinical, and environmental data are increasingly becoming available for research 3 . This presents an opportunity to identify novel associations and complex patterns of patient morbidity, personal circumstances, treatment seeking behaviours, and care over time, promoting scientific advancements in personalized medicine for the most complex disorders and injuries 3 , 4 , 5 . Traumatic brain injury (TBI), defined as structural and/or physiological disruption of brain function as a result of an external force 6 , is rapidly becoming a major challenge faced by healthcare systems worldwide 7 . When internationally reported numbers are extrapolated, it is estimated that 50–60 million individuals are affected each year, and it is predicted that close to 50% of the world’s population will sustain a TBI in their lifetime 8 . The clinical view of TBI has shifted in the last decade from that of an injury event, to a chronic disorder with lifelong effects on both morbidity and mortality 9 , which expedites development of new clinical entities (comorbidities) over time, bringing complexity to its management 10 . Recently, TBI has been recognized as a consequence of multiple comorbid disorders which can potentiate or modify the risks associated with falls or adverse behaviors (e.g., assault and domestic abuse), including but not limited to depressive and substance-use disorders, epilepsy, vascular disease, psychosis, and medication effects 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 . Adding to this complexity, any single known adverse determinant of health (e.g. advanced age, socioeconomic deprivation, and gender inequality) 21 can be implicated in the development of multiple comorbid disorders, thus increasing vulnerability to injury as a result of decreased physical and cognitive reserves 22 . The World Health Organization (WHO) identified the prevention of injuries as a priority given the projected 40% increase in global deaths due to injury between 2002 and 2030 23 . Likewise, the United States Congress, through Public Law 110–252 24 , highlighted injury surveillance as a federal priority given drastic increase in emergency department visits and hospitalizations for TBI over the past decades 25 . Primary prevention efforts are those designed to prevent the initial injury 26 . Although several studies describe medical and environmental factors associated with an increased risk of TBI including low socioeconomic status, youngest and oldest age groups, male sex, and place of residence 27 , 28 , 29 , 30 , these studies are not population-based, and their results may impose a ceiling effect based on the research hypotheses, selected populations with a wide variety of providers and specialists, as well as researcher knowledge and expertise. Based on the fundamental assumption that causal factors of TBI can be identified through the systematic examination of different populations, or of subgroups within populations 31 , successful prevention of TBI is theoretically possible with comprehensive concurrent evaluation of personal, clinical, and environmental contexts in the period prior to TBI 32 in populations and population subgroups. Here we describe exploratory research utilizing a data mining non-hypothesis driven approach used in genomics 33 , 34 applied to a population which used emergency and acute care resources following TBI, and comparing them to a matched population (individually matched based on age, sex, income level, and place of residence) who used emergency and acute care resources for reasons other than TBI. The focus of this research is not only the data mining methodology, but also the results obtained through data mining approach sequencing more than 70,000 diagnosis codes within the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes within the five years preceding TBI event. Methods Data sources Residents of Ontario, Canada’s largest province, have universal public health insurance covering all medically necessary services. The Institute for Clinical Evaluative Sciences (ICES) 35 houses high quality health administrative data on a wide variety of publicly funded services provided to residents, including but not limited to individual-level information on emergency departments (ED) (identified in the National Ambulatory Care Reporting System, NACRS), and acute care visits (identified in the Discharge Abstract Database, DAD), within the province. The NACRS and DAD contain hospital records with diagnoses 35 , among other personal and environmental data, which are indicated by entries under the ICD-10 Canadian Enhancement (ICD-10-CA) 36 . Study design and big data An observational study was conducted using health administrative data of all patients discharged from the ED or acute care in the province between the fiscal years 2007/08 and 2015/16 with a diagnostic code for TBI 37 (ICD-10- CA codes S02.0, S02.1, S02.3, S02.7, S02.8, S02.9, S04.0, S07.1, and S06). Personal, clinical, and environmental data for each patient were stored at the ICES; data collected five years prior to each TBI event was extracted for each patient and used in the analysis. A 10% random sample of patients discharged from the ED or acute care during the same study period for a reason other than TBI, individually", "role": "user" }, { "content": "University of Toronto researchers used a novel data-mining approach to uncover the most common medical problems affecting people in the time before they suffered a traumatic brain injury (TBI). The results can be used to better predict and prevent these life-altering incidents. Professor Michael Escobar, a biostatistician at the Dalla Lana School of Public Health, and researchers from the Faculty of Medicine and University Health Network, looked at the health records of almost 240,000 Ontario residents who fell, were struck by or against objects, were assaulted, got into a motor vehicle collision or otherwise suffered brain injuries. The researchers sliced and diced the data, studying different time periods, including the five years before injury, and found some interesting patterns in health status that distinguish people with TBI from those who entered health-care services for reasons other than brain injury. Patients studied were individually matched based on age, sex, income level and place of residence. \"I was amazed at the numbers of people that had environmental exposure to gases and fumes, electrical currents, sharp objects, machinery and the cold in the five years before their traumatic brain injury,\" says lead author Tatyana Mollayeva, a post-doctoral researcher in the Acquired Brain Injury Lab at U of T and the Toronto Rehabilitation Institute-UHN. \"Our results bring attention to the link between exposure to occupational and other environmental hazards and subsequent critical injuries.\" Neurotoxicity from prescription drugs was another important link to brain injury, says Mollayeva. \"Neurotoxic effects can mimic TBI symptoms, especially in the milder spectrum of severity, which adds complexity to the diagnosis of TBI.\" Research shows two of the most common groups to suffer serious brain injury are older adults who fall and young people, who are at an overall greater risk of injury because of heightened risk-taking behaviours. The research bolstered a long-held hypothesis that the factors associated with injury are multiple, complex and interdependent. \"TBI is a curious injury because it's very heterogeneous,\" notes Escobar. \"It affects elderly women who fall, young hockey players, all kinds of people who get into car crashes. So we need a lot of data, and very sophisticated means of analyzing it to help identify the range of people at risk. In this study, we used an interesting variety of tools, from psychometrics to classical epidemiology to genomics to machine learning.\" The team's results were published in Nature's open-access journal Scientific Reports earler this month. The researchers hope their findings, and tools such as big data, contribute to the use of precision medicine to identify and intervene those at high risk for a traumatic brain injury. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The use of precision medicine is poised to increase in complex injuries such as traumatic brain injury (TBI), whose multifaceted comorbidities and personal circumstances create significant challenges in the domains of surveillance, management, and environmental mapping. Population-wide health administrative data remains a rather unexplored, but accessible data source for identifying clinical associations and environmental patterns that could lead to a better understanding of TBIs. However, the amount of data structured and coded by the International Classification of Disease poses a challenge to its successful interpretation. The emerging field of data mining can be instrumental in helping to meet the daunting challenges faced by the TBI community. The report outlines novel areas for data mining relevant to TBI, and offers insight into how the above approach can be applied to solve pressing healthcare problems. Future work should focus on confirmatory analyses, which subsequently can guide precision medicine and preventive frameworks. Introduction With the enormous progress in the consolidation of large clinical datasets and national registries in modern healthcare 1 , 2 , vast amounts of personal, clinical, and environmental data are increasingly becoming available for research 3 . This presents an opportunity to identify novel associations and complex patterns of patient morbidity, personal circumstances, treatment seeking behaviours, and care over time, promoting scientific advancements in personalized medicine for the most complex disorders and injuries 3 , 4 , 5 . Traumatic brain injury (TBI), defined as structural and/or physiological disruption of brain function as a result of an external force 6 , is rapidly becoming a major challenge faced by healthcare systems worldwide 7 . When internationally reported numbers are extrapolated, it is estimated that 50–60 million individuals are affected each year, and it is predicted that close to 50% of the world’s population will sustain a TBI in their lifetime 8 . The clinical view of TBI has shifted in the last decade from that of an injury event, to a chronic disorder with lifelong effects on both morbidity and mortality 9 , which expedites development of new clinical entities (comorbidities) over time, bringing complexity to its management 10 . Recently, TBI has been recognized as a consequence of multiple comorbid disorders which can potentiate or modify the risks associated with falls or adverse behaviors (e.g., assault and domestic abuse), including but not limited to depressive and substance-use disorders, epilepsy, vascular disease, psychosis, and medication effects 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 . Adding to this complexity, any single known adverse determinant of health (e.g. advanced age, socioeconomic deprivation, and gender inequality) 21 can be implicated in the development of multiple comorbid disorders, thus increasing vulnerability to injury as a result of decreased physical and cognitive reserves 22 . The World Health Organization (WHO) identified the prevention of injuries as a priority given the projected 40% increase in global deaths due to injury between 2002 and 2030 23 . Likewise, the United States Congress, through Public Law 110–252 24 , highlighted injury surveillance as a federal priority given drastic increase in emergency department visits and hospitalizations for TBI over the past decades 25 . Primary prevention efforts are those designed to prevent the initial injury 26 . Although several studies describe medical and environmental factors associated with an increased risk of TBI including low socioeconomic status, youngest and oldest age groups, male sex, and place of residence 27 , 28 , 29 , 30 , these studies are not population-based, and their results may impose a ceiling effect based on the research hypotheses, selected populations with a wide variety of providers and specialists, as well as researcher knowledge and expertise. Based on the fundamental assumption that causal factors of TBI can be identified through the systematic examination of different populations, or of subgroups within populations 31 , successful prevention of TBI is theoretically possible with comprehensive concurrent evaluation of personal, clinical, and environmental contexts in the period prior to TBI 32 in populations and population subgroups. Here we describe exploratory research utilizing a data mining non-hypothesis driven approach used in genomics 33 , 34 applied to a population which used emergency and acute care resources following TBI, and comparing them to a matched population (individually matched based on age, sex, income level, and place of residence) who used emergency and acute care resources for reasons other than TBI. The focus of this research is not only the data mining methodology, but also the results obtained through data mining approach sequencing more than 70,000 diagnosis codes within the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes within the five years preceding TBI event. Methods Data sources Residents of Ontario, Canada’s largest province, have universal public health insurance covering all medically necessary services. The Institute for Clinical Evaluative Sciences (ICES) 35 houses high quality health administrative data on a wide variety of publicly funded services provided to residents, including but not limited to individual-level information on emergency departments (ED) (identified in the National Ambulatory Care Reporting System, NACRS), and acute care visits (identified in the Discharge Abstract Database, DAD), within the province. The NACRS and DAD contain hospital records with diagnoses 35 , among other personal and environmental data, which are indicated by entries under the ICD-10 Canadian Enhancement (ICD-10-CA) 36 . Study design and big data An observational study was conducted using health administrative data of all patients discharged from the ED or acute care in the province between the fiscal years 2007/08 and 2015/16 with a diagnostic code for TBI 37 (ICD-10- CA codes S02.0, S02.1, S02.3, S02.7, S02.8, S02.9, S04.0, S07.1, and S06). Personal, clinical, and environmental data for each patient were stored at the ICES; data collected five years prior to each TBI event was extracted for each patient and used in the analysis. A 10% random sample of patients discharged from the ED or acute care during the same study period for a reason other than TBI, individually<|im_end|> <|im_start|>assistant University of Toronto researchers used a novel data-mining approach to uncover the most common medical problems affecting people in the time before they suffered a traumatic brain injury (TBI). The results can be used to better predict and prevent these life-altering incidents. Professor Michael Escobar, a biostatistician at the Dalla Lana School of Public Health, and researchers from the Faculty of Medicine and University Health Network, looked at the health records of almost 240,000 Ontario residents who fell, were struck by or against objects, were assaulted, got into a motor vehicle collision or otherwise suffered brain injuries. The researchers sliced and diced the data, studying different time periods, including the five years before injury, and found some interesting patterns in health status that distinguish people with TBI from those who entered health-care services for reasons other than brain injury. Patients studied were individually matched based on age, sex, income level and place of residence. "I was amazed at the numbers of people that had environmental exposure to gases and fumes, electrical currents, sharp objects, machinery and the cold in the five years before their traumatic brain injury," says lead author Tatyana Mollayeva, a post-doctoral researcher in the Acquired Brain Injury Lab at U of T and the Toronto Rehabilitation Institute-UHN. "Our results bring attention to the link between exposure to occupational and other environmental hazards and subsequent critical injuries." Neurotoxicity from prescription drugs was another important link to brain injury, says Mollayeva. "Neurotoxic effects can mimic TBI symptoms, especially in the milder spectrum of severity, which adds complexity to the diagnosis of TBI." Research shows two of the most common groups to suffer serious brain injury are older adults who fall and young people, who are at an overall greater risk of injury because of heightened risk-taking behaviours. The research bolstered a long-held hypothesis that the factors associated with injury are multiple, complex and interdependent. "TBI is a curious injury because it's very heterogeneous," notes Escobar. "It affects elderly women who fall, young hockey players, all kinds of people who get into car crashes. So we need a lot of data, and very sophisticated means of analyzing it to help identify the range of people at risk. In this study, we used an interesting variety of tools, from psychometrics to classical epidemiology to genomics to machine learning." The team's results were published in Nature's open-access journal Scientific Reports earler this month. The researchers hope their findings, and tools such as big data, contribute to the use of precision medicine to identify and intervene those at high risk for a traumatic brain injury. <|im_end|>

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304, 4173, 24203, 220, 1644, 1174, 220, 1958, 9435, 311, 264, 7187, 902, 1511, 13147, 323, 30883, 2512, 5070, 2768, 350, 8768, 11, 323, 27393, 1124, 311, 264, 18545, 7187, 320, 485, 65023, 1870, 18545, 3196, 389, 4325, 11, 1877, 11, 8070, 2237, 11, 323, 2035, 315, 22423, 8, 889, 1511, 13147, 323, 30883, 2512, 5070, 369, 8125, 1023, 1109, 350, 8768, 13, 578, 5357, 315, 420, 3495, 374, 539, 1193, 279, 828, 11935, 38152, 11, 719, 1101, 279, 3135, 12457, 1555, 828, 11935, 5603, 62119, 810, 1109, 220, 2031, 11, 931, 23842, 14236, 2949, 279, 7327, 66794, 55982, 315, 70674, 323, 25368, 6401, 45635, 11, 350, 21341, 27893, 320, 1341, 35, 12, 605, 8, 14236, 2949, 279, 4330, 1667, 38846, 350, 8768, 1567, 13, 19331, 2956, 8336, 64348, 315, 21193, 11, 7008, 753, 7928, 17271, 11, 617, 20789, 586, 2890, 8276, 18702, 682, 78269, 5995, 3600, 13, 578, 10181, 369, 33135, 76198, 1413, 23199, 320, 16213, 8, 220, 1758, 15316, 1579, 4367, 2890, 23541, 828, 389, 264, 7029, 8205, 315, 17880, 24853, 3600, 3984, 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13, 330, 8140, 3135, 4546, 6666, 311, 279, 2723, 1990, 14675, 311, 65195, 323, 1023, 12434, 52642, 323, 17876, 9200, 15319, 1210, 32359, 998, 14668, 488, 505, 22866, 11217, 574, 2500, 3062, 2723, 311, 8271, 11134, 11, 2795, 386, 980, 352, 74518, 13, 330, 8989, 2868, 998, 14668, 6372, 649, 56459, 350, 8768, 13803, 11, 5423, 304, 279, 296, 21439, 20326, 315, 31020, 11, 902, 11621, 23965, 311, 279, 23842, 315, 350, 8768, 1210, 8483, 5039, 1403, 315, 279, 1455, 4279, 5315, 311, 7831, 6129, 8271, 11134, 527, 9191, 12884, 889, 4498, 323, 3995, 1274, 11, 889, 527, 520, 459, 8244, 7191, 5326, 315, 11134, 1606, 315, 60487, 5326, 80671, 71177, 13, 578, 3495, 48227, 291, 264, 1317, 58606, 31178, 430, 279, 9547, 5938, 449, 11134, 527, 5361, 11, 6485, 323, 958, 38655, 13, 330, 51, 8768, 374, 264, 22999, 11134, 1606, 433, 596, 1633, 98882, 1359, 8554, 15917, 32493, 13, 330, 2181, 22223, 29920, 3278, 889, 4498, 11, 3995, 28051, 4311, 11, 682, 13124, 315, 1274, 889, 636, 1139, 1841, 37237, 13, 2100, 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1,859

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The 4th Industrial Revolution (4IR henceforth) is fundamentally reshaping the way we live and work. Each industrial revolution has evolved to solve major problems in society. This study views unmatched demand and oversupply as the major problems in the fashion industry and posits that 4IR technologies are being deployed to solve these problems by addressing three prime goals—hyper-personalization, environmental sustainability, and productivity. Based on a literature review and analyses of global industry cases, this study examines what, why, and how the 4IR technologies address these three prime goals. By comparing successful cases that do not utilize the 4IR technologies with those that do, this study highlights that innovative business models that address the unmet needs of the consumers are more important than technology adoption per se. Drawn from ample global cases, the findings can offer strategic directions for fashion firms preparing for unforeseeable changes that are further being accelerated by the Covid-19 pandemic. This study concludes with insights into how 4IR is shaping the fashion industry and raises thought-provoking questions for the industry and academia. Introduction The 4th Industrial Revolution (4IR henceforth) is fundamentally reshaping the way we live and work. In each industrial revolution, inventions and new technologies contributed to the enhancement of industries and human lives through mechanization during the 1st Industrial Revolution, mass production and electricity during the 2nd, and IT systems and automation during the 3rd. As with the previous industrial revolutions, numerous technologies have enabled the 4th Industrial Revolution: robotics, intelligent manufacturing, augmented and virtual reality, and artificial intelligence, to name a few. The focus of every industrial revolution in history was never the development of technologies itself. Rather, it was about enhancing the quality of human life through enhanced productivity, which was made possible by inventions and innovative technologies. Then, what are the aims of the 4th Industrial Revolution in the context of the fashion industry, which includes a wide range of product categories, from apparel and footwear, jewelry, to bags and accessories? With the 4IR technologies, what is the fashion industry seeking to achieve? Given that the ultimate goal of technology development is solving industry challenges to better serve human needs (Schwab, 2016 ), it is logical to first identify unique challenges in the fashion industry and then to discuss how technologies are being applied to address them. Yet, a comprehensive review of what, why, and how the 4IR technologies are being applied in the fashion industry is limited. Prior research has primarily focused on a single technology, whether it be robotics and intelligent manufacturing (Acaccia et al., 2003 ; Michelini & Razzoli, 2013 ), 3D printing (Perry, 2018 ; Sun & Zhao, 2017 ; Vanderploeg et al., 2017 ), virtual and augmented reality (Kim & Forsythe, 2008 ; Park et al., 2018 ; Shim & Lee, 2011 ), or artificial intelligence (Guo et al., 2011 ; Liang et al., 2019 ). While there are a few studies that offer a comprehensive overview of the technology’s implications for the fashion industry, they are still limited in scope (Bertola & Teunissen, 2018 ; Braglia et al., 2020 ). They mainly discuss benefits for companies as opposed to consumers, such as improving efficiency in the supply chain and staff training (Braglia et al., 2020 ), or lack a thorough discussion on the role of business models (Bertola & Teunissen, 2018 ), despite their central role in determining the commercial value of a technology (Chesbrough, 2010 ). To better understand the role of the 4IR technologies in the global fashion industry, this study examines what, why, and how these technologies are being applied to address major challenges in the industry from a macro perspective. This study posits that these technologies are being deployed to solve three prime concerns of both the industry and consumers—productivity, environmental sustainability, and hyper-personalization. Further, this study posits that these concerns can also be addressed with non-technology based innovations, such as business model innovations. This study begins with a brief overview of former industrial revolutions, focusing on their impact on the industry. Following an analysis of major challenges in the industry, three prime industry and consumer concerns (i.e., productivity, environmental sustainability, and hyper-personalization) are proposed to examine what, why, and how the 4IR technologies fulfill the concerns. Furthermore, this study identifies different types of fashion companies that fulfill the prime concerns without relying heavily on 4IR technologies. Those companies are largely DTC (direct to consumer) start-ups that sell to consumers directly via online without any intermediaries, such as wholesalers and retailers (Jin & Shin, 2020 ). Their success in fulfilling the prime concerns is fundamentally driven by business model innovations. By contrasting the two types of successful cases (i.e., those that capitalize on the 4IR technologies and those whose success is driven by business model innovations), this study highlights that developing an innovative business model that addresses major industry concerns is more crucial than adopting an emerging technology per se. While advanced technologies play a critical role, as they allow companies to deliver new customer values at scale, they are not a prerequisite for market disruptions. This study concludes with insights into how 4IR is shaping the fashion industry and raises thought-provoking questions for the industry and academia. Literature review Brief overview and prime aim of industrial revolutions Each industrial revolution radically transformed economic systems and social structures (Schwab, 2016 ). The fashion industry was no exception. Between 1760 and 1840, the 1st industrial revolution ushered in mechanical production, powered by water and steam. Between the late 1800s and early 1900s, the 2nd industrial revolution enabled mass production, powered by electricity and the assembly line. The prime goal of the first two industrial revolutions was to enhance production productivity through mechanization and automation. Following a series of inventions, such as the spinning jenny, spinning mule, and assembly line, fashion production has moved away from the traditional system of craft-based production (Duarte et al., 2018 ). The 3rd Industrial Revolution, which occurred in the mid twentieth century, focused on maximizing already enhanced", "role": "user" }, { "content": "After each season, clothing retailers offer deep discounts to lure in consumers to buy leftover, unsold products. But what if they could do a better job predicting what consumers will want, in what size and in the right quantity to increase profits, and reduce textile waste? In a recent article, Byoungho Ellie Jin, Albert Myers Distinguished Professor of Textile Economics and Management at NC State, explored the role that technologies like artificial intelligence (AI), virtual reality (VR) and 3D printing could play in addressing industry problems like oversupply. She suggested technology could help the industry become more sustainable, deliver more personalized goods and become more productive. The Abstract: What technologies define the fourth industrial revolution? Byoungho Ellie Jin: There are multiple technological advancements happening in the fourth industrial revolution including augmented reality, VR, big data, AI, and robotics. I was very curious how these technologies could impact the apparel and retail industry. I found they will help the industry with three themes: personalization, sustainability and productivity. TA: How are new technologies addressing unmatched demand in fashion? Jin: Demand is so unpredictable in the fashion industry. We don't know who will buy what, in what size, in what color and in what material. The biggest variable in the fashion industry is size. Even if you like the style and color, if it doesn't fit, you don't buy it. Apparel companies have to try to predict all of that. That means there are tons of leftover products after each season, and there are tons of markdowns to get rid of all the production that's done. That means huge losses for the industry. If they can anticipate demand better, the industry could become more profitable. Now, with AI analysis, we can make predictions in real time. We can analyze what consumers will buy, and what size they want. AI can anticipate and analyze it, and based on that information, we can develop sizes, lengths, color, and styles consumers would like to buy. TA: You also talk about how AI will also help fulfill one of the industry's goals—to personalize apparel. Why is personalization important to the industry? Jin: People are tired of choosing what has already been produced for the mass market. We want something that was created to suit our own personal needs. Before the industrial revolution, moms would often make clothes for their children. They knew their children's sizes, colors they like, designs they like. Through the second and third industrial revolutions, there is mass production. There are more products, but they are limited. Our tastes, real preferences and real needs are not satisfied. Now, personalization is possible. Through AI analyses, retailers know all our purchases. They know what I need. 3D printing and 3D knitting are also good for personalization. They can increase productivity, and create the opportunity for printing on demand. They could also potentially help with environmental sustainability as well. TA: How can these technologies make the industry more environmentally sustainable? You write about how the textile industry is a major environmental polluter. Jin: Every year, the industry produces tons of leftover products. After the 70%markdown, where do the unsold products go? We donate them, and then unsold items are shipped in bulk to developing countries. A lot of it ends up in landfills. The cotton and the silk, those natural fibers will biodegrade. But polyester and nylon, they're there forever. That's a huge environmental problem. If we produce the right amount with accurate demand forecasting, we can reduce environmental pollution. AI could be important to accurate foresting. Also, 3D printing and knitting leads to less production waste, with less fabric left over in the production stage. TA: How are retailers using virtual and augmented reality technologies? Jin: Experiential retail is a keyword in the industry right now. A store is not just a place to buy something. We can buy something anytime. People want to have an experience. If we apply/utilize VR or AR technologies in the store, people perceive that as a fun experience. Some retailers are testing it out, but it's not heavily utilized right now. In a recent study we did at NC State, we compared consumers' experience of browsing a website to their experience using VR goggles to look through a boutique in downtown Raleigh. We rented a camera and used it to take a video of the store. Large retailers have tons and tons of stores across the country. They have nice websites. It's harder for a small boutique to increase store awareness. To help them, we asked: Why don't they utilize VR, and put that on their websites so people can experience the store virtually? Consumers might be more interested in their products and store, and more likely to visit. We thought we can help them promote their store and increase awareness. The results of our experiment showed that with VR, consumers who experienced the 360-degree videos of the store reported positive emotions, and increased perceptions of the store's attractiveness. Their pleasure increased. Initially, we thought we should have those goggles in consumers' hands to see the store environment. But now, there is also an app you can download. Even without wearing goggles, you feel you like are in the store. That means that without investments from the consumer side, it's still possible. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The 4th Industrial Revolution (4IR henceforth) is fundamentally reshaping the way we live and work. Each industrial revolution has evolved to solve major problems in society. This study views unmatched demand and oversupply as the major problems in the fashion industry and posits that 4IR technologies are being deployed to solve these problems by addressing three prime goals—hyper-personalization, environmental sustainability, and productivity. Based on a literature review and analyses of global industry cases, this study examines what, why, and how the 4IR technologies address these three prime goals. By comparing successful cases that do not utilize the 4IR technologies with those that do, this study highlights that innovative business models that address the unmet needs of the consumers are more important than technology adoption per se. Drawn from ample global cases, the findings can offer strategic directions for fashion firms preparing for unforeseeable changes that are further being accelerated by the Covid-19 pandemic. This study concludes with insights into how 4IR is shaping the fashion industry and raises thought-provoking questions for the industry and academia. Introduction The 4th Industrial Revolution (4IR henceforth) is fundamentally reshaping the way we live and work. In each industrial revolution, inventions and new technologies contributed to the enhancement of industries and human lives through mechanization during the 1st Industrial Revolution, mass production and electricity during the 2nd, and IT systems and automation during the 3rd. As with the previous industrial revolutions, numerous technologies have enabled the 4th Industrial Revolution: robotics, intelligent manufacturing, augmented and virtual reality, and artificial intelligence, to name a few. The focus of every industrial revolution in history was never the development of technologies itself. Rather, it was about enhancing the quality of human life through enhanced productivity, which was made possible by inventions and innovative technologies. Then, what are the aims of the 4th Industrial Revolution in the context of the fashion industry, which includes a wide range of product categories, from apparel and footwear, jewelry, to bags and accessories? With the 4IR technologies, what is the fashion industry seeking to achieve? Given that the ultimate goal of technology development is solving industry challenges to better serve human needs (Schwab, 2016 ), it is logical to first identify unique challenges in the fashion industry and then to discuss how technologies are being applied to address them. Yet, a comprehensive review of what, why, and how the 4IR technologies are being applied in the fashion industry is limited. Prior research has primarily focused on a single technology, whether it be robotics and intelligent manufacturing (Acaccia et al., 2003 ; Michelini & Razzoli, 2013 ), 3D printing (Perry, 2018 ; Sun & Zhao, 2017 ; Vanderploeg et al., 2017 ), virtual and augmented reality (Kim & Forsythe, 2008 ; Park et al., 2018 ; Shim & Lee, 2011 ), or artificial intelligence (Guo et al., 2011 ; Liang et al., 2019 ). While there are a few studies that offer a comprehensive overview of the technology’s implications for the fashion industry, they are still limited in scope (Bertola & Teunissen, 2018 ; Braglia et al., 2020 ). They mainly discuss benefits for companies as opposed to consumers, such as improving efficiency in the supply chain and staff training (Braglia et al., 2020 ), or lack a thorough discussion on the role of business models (Bertola & Teunissen, 2018 ), despite their central role in determining the commercial value of a technology (Chesbrough, 2010 ). To better understand the role of the 4IR technologies in the global fashion industry, this study examines what, why, and how these technologies are being applied to address major challenges in the industry from a macro perspective. This study posits that these technologies are being deployed to solve three prime concerns of both the industry and consumers—productivity, environmental sustainability, and hyper-personalization. Further, this study posits that these concerns can also be addressed with non-technology based innovations, such as business model innovations. This study begins with a brief overview of former industrial revolutions, focusing on their impact on the industry. Following an analysis of major challenges in the industry, three prime industry and consumer concerns (i.e., productivity, environmental sustainability, and hyper-personalization) are proposed to examine what, why, and how the 4IR technologies fulfill the concerns. Furthermore, this study identifies different types of fashion companies that fulfill the prime concerns without relying heavily on 4IR technologies. Those companies are largely DTC (direct to consumer) start-ups that sell to consumers directly via online without any intermediaries, such as wholesalers and retailers (Jin & Shin, 2020 ). Their success in fulfilling the prime concerns is fundamentally driven by business model innovations. By contrasting the two types of successful cases (i.e., those that capitalize on the 4IR technologies and those whose success is driven by business model innovations), this study highlights that developing an innovative business model that addresses major industry concerns is more crucial than adopting an emerging technology per se. While advanced technologies play a critical role, as they allow companies to deliver new customer values at scale, they are not a prerequisite for market disruptions. This study concludes with insights into how 4IR is shaping the fashion industry and raises thought-provoking questions for the industry and academia. Literature review Brief overview and prime aim of industrial revolutions Each industrial revolution radically transformed economic systems and social structures (Schwab, 2016 ). The fashion industry was no exception. Between 1760 and 1840, the 1st industrial revolution ushered in mechanical production, powered by water and steam. Between the late 1800s and early 1900s, the 2nd industrial revolution enabled mass production, powered by electricity and the assembly line. The prime goal of the first two industrial revolutions was to enhance production productivity through mechanization and automation. Following a series of inventions, such as the spinning jenny, spinning mule, and assembly line, fashion production has moved away from the traditional system of craft-based production (Duarte et al., 2018 ). The 3rd Industrial Revolution, which occurred in the mid twentieth century, focused on maximizing already enhanced<|im_end|> <|im_start|>assistant After each season, clothing retailers offer deep discounts to lure in consumers to buy leftover, unsold products. But what if they could do a better job predicting what consumers will want, in what size and in the right quantity to increase profits, and reduce textile waste? In a recent article, Byoungho Ellie Jin, Albert Myers Distinguished Professor of Textile Economics and Management at NC State, explored the role that technologies like artificial intelligence (AI), virtual reality (VR) and 3D printing could play in addressing industry problems like oversupply. She suggested technology could help the industry become more sustainable, deliver more personalized goods and become more productive. The Abstract: What technologies define the fourth industrial revolution? Byoungho Ellie Jin: There are multiple technological advancements happening in the fourth industrial revolution including augmented reality, VR, big data, AI, and robotics. I was very curious how these technologies could impact the apparel and retail industry. I found they will help the industry with three themes: personalization, sustainability and productivity. TA: How are new technologies addressing unmatched demand in fashion? Jin: Demand is so unpredictable in the fashion industry. We don't know who will buy what, in what size, in what color and in what material. The biggest variable in the fashion industry is size. Even if you like the style and color, if it doesn't fit, you don't buy it. Apparel companies have to try to predict all of that. That means there are tons of leftover products after each season, and there are tons of markdowns to get rid of all the production that's done. That means huge losses for the industry. If they can anticipate demand better, the industry could become more profitable. Now, with AI analysis, we can make predictions in real time. We can analyze what consumers will buy, and what size they want. AI can anticipate and analyze it, and based on that information, we can develop sizes, lengths, color, and styles consumers would like to buy. TA: You also talk about how AI will also help fulfill one of the industry's goals—to personalize apparel. Why is personalization important to the industry? Jin: People are tired of choosing what has already been produced for the mass market. We want something that was created to suit our own personal needs. Before the industrial revolution, moms would often make clothes for their children. They knew their children's sizes, colors they like, designs they like. Through the second and third industrial revolutions, there is mass production. There are more products, but they are limited. Our tastes, real preferences and real needs are not satisfied. Now, personalization is possible. Through AI analyses, retailers know all our purchases. They know what I need. 3D printing and 3D knitting are also good for personalization. They can increase productivity, and create the opportunity for printing on demand. They could also potentially help with environmental sustainability as well. TA: How can these technologies make the industry more environmentally sustainable? You write about how the textile industry is a major environmental polluter. Jin: Every year, the industry produces tons of leftover products. After the 70%markdown, where do the unsold products go? We donate them, and then unsold items are shipped in bulk to developing countries. A lot of it ends up in landfills. The cotton and the silk, those natural fibers will biodegrade. But polyester and nylon, they're there forever. That's a huge environmental problem. If we produce the right amount with accurate demand forecasting, we can reduce environmental pollution. AI could be important to accurate foresting. Also, 3D printing and knitting leads to less production waste, with less fabric left over in the production stage. TA: How are retailers using virtual and augmented reality technologies? Jin: Experiential retail is a keyword in the industry right now. A store is not just a place to buy something. We can buy something anytime. People want to have an experience. If we apply/utilize VR or AR technologies in the store, people perceive that as a fun experience. Some retailers are testing it out, but it's not heavily utilized right now. In a recent study we did at NC State, we compared consumers' experience of browsing a website to their experience using VR goggles to look through a boutique in downtown Raleigh. We rented a camera and used it to take a video of the store. Large retailers have tons and tons of stores across the country. They have nice websites. It's harder for a small boutique to increase store awareness. To help them, we asked: Why don't they utilize VR, and put that on their websites so people can experience the store virtually? Consumers might be more interested in their products and store, and more likely to visit. We thought we can help them promote their store and increase awareness. The results of our experiment showed that with VR, consumers who experienced the 360-degree videos of the store reported positive emotions, and increased perceptions of the store's attractiveness. Their pleasure increased. Initially, we thought we should have those goggles in consumers' hands to see the store environment. But now, there is also an app you can download. Even without wearing goggles, you feel you like are in the store. That means that without investments from the consumer side, it's still possible. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Hybrid quantum systems with inherently distinct degrees of freedom have a key role in many physical phenomena. Well-known examples include cavity quantum electrodynamics 1 , trapped ions 2 , and electrons and phonons in the solid state. In those systems, strong coupling makes the constituents lose their individual character and form dressed states, which represent a collective form of dynamics. As well as having fundamental importance, hybrid systems also have practical applications, notably in the emerging field of quantum information control. A promising approach is to combine long-lived atomic states 2 , 3 with the accessible electrical degrees of freedom in superconducting cavities and quantum bits 4 , 5 (qubits). Here we integrate circuit cavity quantum electrodynamics 6 , 7 with phonons. Apart from coupling to a microwave cavity, our superconducting transmon qubit 8 , consisting of tunnel junctions and a capacitor, interacts with a phonon mode in a micromechanical resonator, and thus acts like an atom coupled to two different cavities. We measure the phonon Stark shift, as well as the splitting of the qubit spectral line into motional sidebands, which feature transitions between the dressed electromechanical states. In the time domain, we observe coherent conversion of qubit excitation to phonons as sideband Rabi oscillations. This is a model system with potential for a quantum interface, which may allow for storage of quantum information in long-lived phonon states, coupling to optical photons or for investigations of strongly coupled quantum systems near the classical limit. Main Superconducting qubits based on Josephson junctions 5 have offered an unparalleled testing ground for quantum mechanics in relatively large systems. At the same time, Josephson devices constitute a promising implementation for quantum information processing. Basic quantum algorithms have been recently demonstrated with phase 9 and transmon 10 , 11 , 12 qubits. The latter operate in the framework of circuit cavity quantum electrodynamics (QED), in which the qubits couple to an on-chip 6 or three-dimensional microwave cavity resonator 13 . The circuit cavity QED set-up, which enables coupling of qubits and non-destructive measurements of quantum states, can be regarded as the most feasible platform for quantum information. The forthcoming challenges in circuit cavity QED include the construction of an interface for the storage and retrieval of qubit states in a long-lived quantum memory, as well as quantum communication 14 between spatially separated superconducting qubits. Hybrid quantum systems show promise for these purposes because in principle the specific assets of each ingredient can be combined. The merger of macroscopic qubits with spin ensembles is intriguing owing to the long lifetime of the latter 15 , 16 , but the scheme has the disadvantage of a small coupling at the level of a single atomic degree of freedom. The quantum regime of micromechanical resonators was first reached only very recently 17 , 18 . They have been suggested as a plausible interfacial medium for Josephson junction qubits 19 , 20 , 21 , with the potential to achieve the aforementioned results. The first experiment of this kind demonstrated the interaction between a charge qubit and a beam resonating at the frequency ω m /2π ≈ 60 MHz (ref. 22 ). This experiment, using a read-out via the micromechanical device, did not allow for time-resolved measurements, which is a prerequisite for coherent state transfer. The resonant coupling was recently demonstrated using a microwave-regime piezoelectric device 23 , with ω m /2π ≈ 6.2 GHz, but the energy decay times were short owing to the high mechanical frequency and special materials required. Our approach to improving on these issues is to use a membrane-type micromechanical resonator embedded in a complete circuit cavity QED device. This allows access to all the techniques of circuit cavity QED. Notwithstanding that our mechanical resonator can be understood classically, our aim is also to further the understanding of the emergence of ultrastrong coupling of a micromechanical phonon degree of freedom, representing matter, to microwave-frequency light. On the conceptual level, our device is analogous to an optical cavity QED system where a two-level atom is coupled to two cavities with different frequencies ( Fig. 1a ). We use a superconducting transmon qubit 8 with capacitance C q , single-electron charging energy and Josephson energy E J as an artificial two-level system. It is coupled to a highly detuned phononic cavity, formed by a suspended aluminium membrane ( Fig. 1d ) with flexural-mode resonant frequency ω m /2π ≈ 72 MHz, by means of a position-dependent capacitance C g ( x ), as well as to a nearly resonant photonic cavity realized as an on-chip coplanar waveguide microwave resonator with frequency ω c . Figure 1: Hybrid cavity QED set-up. a , Illustration of a cavity QED system consisting of an atom (green) coupled to two cavities. The (photonic) microwave resonator is coloured blue and the (phononic) lower-frequency mechanical resonator is coloured red. b , Circuit schematics of an analogous electromechanical tripartite system, measured using a microwave cavity with a probe tone at frequency ω c . c , Optical image of the chip. Shown is the quarter-wave microwave cavity, the superconducting transmon qubit playing the part of the atom, the mechanical resonator with its external control, a flux control line (orange) and the ground plane (magenta). d , Scanning electron micrograph showing the 5-μm-long and 4-μm-wide bridge-type mechanical resonator (dashed box) suspended above the qubit island. PowerPoint slide Full size image The equivalent electrical circuit ( Fig. 1b ) for the two-resonator circuit cavity QED system allows the Hamiltonian to be written where is the qubit Hamiltonian ( Supplementary Information , equation (17)), and are the annihilation operators of the microwave cavity and of the mechanical resonator, respectively, and are the corresponding creation operators, is the number operator of Cooper pairs on the transmon island and is Planck’s constant divided by 2π. The interaction between the qubit and the mechanical resonator is given by the electromechanical coupling energy, . Here x zp ≈ 4 fm is defined as the mechanical zero-point motion, V", "role": "user" }, { "content": "(Phys.org)—Aalto University researchers in Finland have successfully connected a superconducting quantum bit, or qubit, with a micrometer-sized drum head. Thus they transferred information from the qubit to the resonator and back again. - This work represents the first step towards creating exotic mechanical quantum states. For example, the transfer makes it possible to create a state in which the resonator simultaneously vibrates and doesn't vibrate, says professor Mika Sillanpää from Aalto University, who runs the research group. A qubit is the quantum-mechanical equivalent of the bits we know from computers. A traditional bit can be in a state of 0 or 1, while a qubit can be in both states at the same time. In theory, this inconceivable situation allows for a quantum calculation in which the operations are performed simultaneously for all possible numbers. In the case of a single qubit, this means zero and one, but as the number of qubits increases, the amount of possible numbers and simultaneous calculations grows exponentially. The quantum state of a qubit is very fragile and easily disturbed between and during the operations. The key to successful quantum calculation is being able to protect the qubit state from disturbances in the environment. - In this case, the qubit state can be stored as vibration, thus preserving the state for much longer than the qubit itself. The resonator also functions as a mechanical quantum memory, which is something that an ordinary memory can't do, explains Juha Pirkkalainen from Aalto University, who is doing his dissertation on the topic. The work combines the achievements of two Nobel Prize winners The work combined the achievements of both winners of this year's Nobel Prize for Physics. The qubit state was measured using a superconducting cavity in the same way that Serge Haroche measured atoms, and the qubit state was also linked to mechanical movement as in David Wineland's experiments. In contrast to these larger-scale measurement arrangements, the experiment at the O.V. Lounasmaa Laboratory was prepared for a tiny silicon microchip. This made it possible to cool the sample to near absolute zero temperatures and then use microwaves. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Hybrid quantum systems with inherently distinct degrees of freedom have a key role in many physical phenomena. Well-known examples include cavity quantum electrodynamics 1 , trapped ions 2 , and electrons and phonons in the solid state. In those systems, strong coupling makes the constituents lose their individual character and form dressed states, which represent a collective form of dynamics. As well as having fundamental importance, hybrid systems also have practical applications, notably in the emerging field of quantum information control. A promising approach is to combine long-lived atomic states 2 , 3 with the accessible electrical degrees of freedom in superconducting cavities and quantum bits 4 , 5 (qubits). Here we integrate circuit cavity quantum electrodynamics 6 , 7 with phonons. Apart from coupling to a microwave cavity, our superconducting transmon qubit 8 , consisting of tunnel junctions and a capacitor, interacts with a phonon mode in a micromechanical resonator, and thus acts like an atom coupled to two different cavities. We measure the phonon Stark shift, as well as the splitting of the qubit spectral line into motional sidebands, which feature transitions between the dressed electromechanical states. In the time domain, we observe coherent conversion of qubit excitation to phonons as sideband Rabi oscillations. This is a model system with potential for a quantum interface, which may allow for storage of quantum information in long-lived phonon states, coupling to optical photons or for investigations of strongly coupled quantum systems near the classical limit. Main Superconducting qubits based on Josephson junctions 5 have offered an unparalleled testing ground for quantum mechanics in relatively large systems. At the same time, Josephson devices constitute a promising implementation for quantum information processing. Basic quantum algorithms have been recently demonstrated with phase 9 and transmon 10 , 11 , 12 qubits. The latter operate in the framework of circuit cavity quantum electrodynamics (QED), in which the qubits couple to an on-chip 6 or three-dimensional microwave cavity resonator 13 . The circuit cavity QED set-up, which enables coupling of qubits and non-destructive measurements of quantum states, can be regarded as the most feasible platform for quantum information. The forthcoming challenges in circuit cavity QED include the construction of an interface for the storage and retrieval of qubit states in a long-lived quantum memory, as well as quantum communication 14 between spatially separated superconducting qubits. Hybrid quantum systems show promise for these purposes because in principle the specific assets of each ingredient can be combined. The merger of macroscopic qubits with spin ensembles is intriguing owing to the long lifetime of the latter 15 , 16 , but the scheme has the disadvantage of a small coupling at the level of a single atomic degree of freedom. The quantum regime of micromechanical resonators was first reached only very recently 17 , 18 . They have been suggested as a plausible interfacial medium for Josephson junction qubits 19 , 20 , 21 , with the potential to achieve the aforementioned results. The first experiment of this kind demonstrated the interaction between a charge qubit and a beam resonating at the frequency ω m /2π ≈ 60 MHz (ref. 22 ). This experiment, using a read-out via the micromechanical device, did not allow for time-resolved measurements, which is a prerequisite for coherent state transfer. The resonant coupling was recently demonstrated using a microwave-regime piezoelectric device 23 , with ω m /2π ≈ 6.2 GHz, but the energy decay times were short owing to the high mechanical frequency and special materials required. Our approach to improving on these issues is to use a membrane-type micromechanical resonator embedded in a complete circuit cavity QED device. This allows access to all the techniques of circuit cavity QED. Notwithstanding that our mechanical resonator can be understood classically, our aim is also to further the understanding of the emergence of ultrastrong coupling of a micromechanical phonon degree of freedom, representing matter, to microwave-frequency light. On the conceptual level, our device is analogous to an optical cavity QED system where a two-level atom is coupled to two cavities with different frequencies ( Fig. 1a ). We use a superconducting transmon qubit 8 with capacitance C q , single-electron charging energy and Josephson energy E J as an artificial two-level system. It is coupled to a highly detuned phononic cavity, formed by a suspended aluminium membrane ( Fig. 1d ) with flexural-mode resonant frequency ω m /2π ≈ 72 MHz, by means of a position-dependent capacitance C g ( x ), as well as to a nearly resonant photonic cavity realized as an on-chip coplanar waveguide microwave resonator with frequency ω c . Figure 1: Hybrid cavity QED set-up. a , Illustration of a cavity QED system consisting of an atom (green) coupled to two cavities. The (photonic) microwave resonator is coloured blue and the (phononic) lower-frequency mechanical resonator is coloured red. b , Circuit schematics of an analogous electromechanical tripartite system, measured using a microwave cavity with a probe tone at frequency ω c . c , Optical image of the chip. Shown is the quarter-wave microwave cavity, the superconducting transmon qubit playing the part of the atom, the mechanical resonator with its external control, a flux control line (orange) and the ground plane (magenta). d , Scanning electron micrograph showing the 5-μm-long and 4-μm-wide bridge-type mechanical resonator (dashed box) suspended above the qubit island. PowerPoint slide Full size image The equivalent electrical circuit ( Fig. 1b ) for the two-resonator circuit cavity QED system allows the Hamiltonian to be written where is the qubit Hamiltonian ( Supplementary Information , equation (17)), and are the annihilation operators of the microwave cavity and of the mechanical resonator, respectively, and are the corresponding creation operators, is the number operator of Cooper pairs on the transmon island and is Planck’s constant divided by 2π. The interaction between the qubit and the mechanical resonator is given by the electromechanical coupling energy, . Here x zp ≈ 4 fm is defined as the mechanical zero-point motion, V<|im_end|> <|im_start|>assistant (Phys.org)—Aalto University researchers in Finland have successfully connected a superconducting quantum bit, or qubit, with a micrometer-sized drum head. Thus they transferred information from the qubit to the resonator and back again. - This work represents the first step towards creating exotic mechanical quantum states. For example, the transfer makes it possible to create a state in which the resonator simultaneously vibrates and doesn't vibrate, says professor Mika Sillanpää from Aalto University, who runs the research group. A qubit is the quantum-mechanical equivalent of the bits we know from computers. A traditional bit can be in a state of 0 or 1, while a qubit can be in both states at the same time. In theory, this inconceivable situation allows for a quantum calculation in which the operations are performed simultaneously for all possible numbers. In the case of a single qubit, this means zero and one, but as the number of qubits increases, the amount of possible numbers and simultaneous calculations grows exponentially. The quantum state of a qubit is very fragile and easily disturbed between and during the operations. The key to successful quantum calculation is being able to protect the qubit state from disturbances in the environment. - In this case, the qubit state can be stored as vibration, thus preserving the state for much longer than the qubit itself. The resonator also functions as a mechanical quantum memory, which is something that an ordinary memory can't do, explains Juha Pirkkalainen from Aalto University, who is doing his dissertation on the topic. The work combines the achievements of two Nobel Prize winners The work combined the achievements of both winners of this year's Nobel Prize for Physics. The qubit state was measured using a superconducting cavity in the same way that Serge Haroche measured atoms, and the qubit state was also linked to mechanical movement as in David Wineland's experiments. In contrast to these larger-scale measurement arrangements, the experiment at the O.V. Lounasmaa Laboratory was prepared for a tiny silicon microchip. This made it possible to cool the sample to near absolute zero temperatures and then use microwaves. <|im_end|>

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1,812

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Detection of pathogens in food processing facilities by routine environmental monitoring (EM) is essential to reduce the risk of foodborne illness but is complicated by the complexity of equipment and environment surfaces. To optimize design of EM programs, we developed EnABLe (“ En vironmental monitoring with an A gent- B ased Model of L ist e ria ”), a detailed and customizable agent-based simulation of a built environment. EnABLe is presented here in a model system, tracing Listeria spp. (LS) (an indicator for conditions that allow the presence of the foodborne pathogen Listeria monocytogenes ) on equipment and environment surfaces in a cold-smoked salmon facility. EnABLe was parameterized by existing literature and expert elicitation and validated with historical data. Simulations revealed different contamination dynamics and risks among equipment surfaces in terms of the presence, level and persistence of LS. Grouping of surfaces by their LS contamination dynamics identified connectivity and sanitary design as predictors of contamination, indicating that these features should be considered in the design of EM programs to detect LS. The EnABLe modeling approach is particularly timely for the frozen food industry, seeking science-based recommendations for EM, and may also be relevant to other complex environments where pathogen contamination presents risks for direct or indirect human exposure. Introduction Listeria monocytogenes (LM) is an opportunistic foodborne pathogen that has been estimated to cause more than 23,000 illnesses and nearly 5,500 deaths worldwide each year 1 . Illness- and recall-associated costs to American consumers and food companies are estimated to exceed $4 billion annually 2 . LM can be present in a variety of environments and is typically associated with soiled and moist conditions, not uncommon in food production facilities 3 , 4 , 5 , 6 . Although the risk of foodborne illness due to LM can be reduced through heat treatment and/or the addition of antimicrobial ingredients or processes, numerous food products are exposed to the processing environment after heat treatment and may not undergo a cook step by the consumer prior to consumption (known as ready-to-eat or RTE, e.g., deli meats, ice cream, many cheeses, frozen fruits and vegetables used in smoothies) or are never exposed to lethal treatments during processing (e.g., fresh-cut produce and frozen fruit). Contaminated products have been traced back to events of environmental recontamination during processing 7 , 8 , thus highlighting the impact of LM in processing facilities on product safety and foodborne illness. Identification of LM sources in the facility via routine environmental monitoring (EM) is an essential practice to inform the corrective actions necessary for elimination of LM and prevention of recontamination. EM involves routine collection of swab samples from equipment, tools, personnel, and the facility environment. While LM is the only human pathogen in the genus Listeria , environmental samples are often evaluated to detect the presence of Listeria spp. (LS) as a conservative approach to identifying conditions that will allow for LM presence. In general, previous experience in the facility and industry guidance are used, over statistically-based and random sampling approaches, when determining the number and location of samples taken for both routine EM programs and investigations into potential Listeria harborage sites 9 , 10 , 11 , 12 , 13 , 14 . Areas of a facility are often prioritized according to levels of required hygienic care (also known as hygienic zoning) and surfaces within each area may be designated into zones (also known as zoning) according to different levels of LM control and their proximity to food products, for example. These areas and surfaces are monitored with different frequencies or intensities to detect a loss of control and indicate the risk of product recontamination during processing 9 , 12 . The complexity of the processing equipment and environment, coupled with the heterogeneous distribution of contamination, present major challenges when designing EM programs and evaluating results. Despite the numerous publications on Listeria in food processing facilities, a recent extensive scoping review concluded that there is a need for individual facility-specific techniques to scientifically support alternative designs and implementation of EM programs 15 . Simulation and risk assessment models are useful for EM decision-making, especially where experimental approaches would not be feasible or ethical and where empirical data are difficult to obtain. Quantitative risk assessment (QRA) models, employing discrete-event simulation, for management of LM during food processing and handling have previously considered processing equipment and environment compartments as potential sources of contamination of soft cheese and retail delicatessen products 16 , 17 . While these QRA models have improved understanding of LM cross-contamination and recontamination and the resulting consumer exposure to LM, both acknowledged gaps in modeling the growth and behavior of Listeria under specific environmental conditions and on equipment surfaces prior to contaminating food products. Agent-based modeling (ABM) is a complementary approach towards addressing this gap, sharing many features with a QRA (as it is also a simulation tool), that utilizes spatially explicit and rule-based computation to represent in detailed granularity the real-world components and day-to-day features of a system 18 , in order to preserve natural heterogeneity within and among facility environments and practices. The individuals, or agents, that make up an agent-based model are unique in their characteristics and autonomous in their interactions with each other and their environment 18 . Modeled continuously over time, the collective interactions of agents and their environment reveal both causes and consequences of emerging patterns. Thus, application of ABM in food processing facilities allows for simulation of microbial behavior under complex and dynamic environmental conditions and on surfaces that could not otherwise be modeled by analytically tractable mathematical models or experimented on using other methods. En vironmental monitoring with an A gent- B ased Model of L ist e ria ( EnABLe ) is an in silico approach to simulate the behavior of LS in food processing environments in order to evaluate features and characteristics relevant for designing EM programs. EnABLe was implemented in this study to recreate the complex environment of a cold-smoked salmon processing facility and", "role": "user" }, { "content": "An innovative computer program could be a big help for food safety professionals working to keep production facilities free of food-borne pathogens. Cornell University scientists have developed a computer program, Environmental Monitoring With an Agent-Based Model of Listeria (EnABLe), to simulate the most likely locations in a processing facility where the deadly food-borne pathogen Listeria monocytogenes might be found. Food safety managers may then test those areas for the bacteria's presence, adding an important tool to prevent food contamination and human exposure to the pathogen through tainted food. The computer model, which is described in the Jan. 24 issue of Scientific Reports, has the potential to be modified for a wide range of microbes and locations. \"The goal is to build a decision-support tool for control of any pathogen in any complex environment,\" said Renata Ivanek, associate professor in the Department of Population Medicine and Diagnostic Sciences and senior author of the paper. The study was funded by the Frozen Food Foundation through a grant to Martin Wiedmann, professor of food science, who is also a co-author of the paper. The researchers, including first author Claire Zoellner, a postdoctoral research associate in Ivanek's lab, want to eventually apply the framework to identifying contamination from pathogens that cause hospital-acquired infections in veterinary hospitals or E. coli bacteria in fruit and vegetable processing plants. Food safety professionals at processing facilities keep regular schedules for pathogen testing. They rely on their own expertise and knowledge of the building to determine where to swab for samples. \"Whenever we have an environment that is complex, we always have to rely on expert opinion and general rules for this system, or this company, but what we're trying to offer is a way to make this more quantitative and systematic by creating this digital reality,\" Ivanek said. For the system to work, Zoellner, Ivanek and colleagues entered all relevant data into the model—including historical perspectives, expert feedback, details of the equipment used and its cleaning schedule, the jobs people do, and materials and people who enter from outside the facility. \"A computer model like EnABLe connects those data to help answer questions related to changes in contamination risks, potential sources of contamination and approaches for risk mitigation and management,\" Zoellner said. \"A single person could never keep track of all that information, but if we run this model on a computer, we can have in one iteration a distribution of Listeria across equipment after one week. And every time you run it, it will be different and collectively predict a range of possible outcomes,\" Ivanek said. The paper describes a model system that traces Listeria species on equipment and surfaces in a cold-smoked salmon facility. Simulations revealed contamination dynamics and risks for Listeria contamination on equipment surfaces. Furthermore, the insights gained from seeing patterns in the areas where Listeria is predicted can inform the design of food processing plants and Listeria-monitoring programs. In the future, the model will be applied to frozen food facilities. Food-borne Listeria monocytogenes infects about 1,600 people in the U.S. each year with flu-like symptoms, with about one in five of those infections ending in death. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Detection of pathogens in food processing facilities by routine environmental monitoring (EM) is essential to reduce the risk of foodborne illness but is complicated by the complexity of equipment and environment surfaces. To optimize design of EM programs, we developed EnABLe (“ En vironmental monitoring with an A gent- B ased Model of L ist e ria ”), a detailed and customizable agent-based simulation of a built environment. EnABLe is presented here in a model system, tracing Listeria spp. (LS) (an indicator for conditions that allow the presence of the foodborne pathogen Listeria monocytogenes ) on equipment and environment surfaces in a cold-smoked salmon facility. EnABLe was parameterized by existing literature and expert elicitation and validated with historical data. Simulations revealed different contamination dynamics and risks among equipment surfaces in terms of the presence, level and persistence of LS. Grouping of surfaces by their LS contamination dynamics identified connectivity and sanitary design as predictors of contamination, indicating that these features should be considered in the design of EM programs to detect LS. The EnABLe modeling approach is particularly timely for the frozen food industry, seeking science-based recommendations for EM, and may also be relevant to other complex environments where pathogen contamination presents risks for direct or indirect human exposure. Introduction Listeria monocytogenes (LM) is an opportunistic foodborne pathogen that has been estimated to cause more than 23,000 illnesses and nearly 5,500 deaths worldwide each year 1 . Illness- and recall-associated costs to American consumers and food companies are estimated to exceed $4 billion annually 2 . LM can be present in a variety of environments and is typically associated with soiled and moist conditions, not uncommon in food production facilities 3 , 4 , 5 , 6 . Although the risk of foodborne illness due to LM can be reduced through heat treatment and/or the addition of antimicrobial ingredients or processes, numerous food products are exposed to the processing environment after heat treatment and may not undergo a cook step by the consumer prior to consumption (known as ready-to-eat or RTE, e.g., deli meats, ice cream, many cheeses, frozen fruits and vegetables used in smoothies) or are never exposed to lethal treatments during processing (e.g., fresh-cut produce and frozen fruit). Contaminated products have been traced back to events of environmental recontamination during processing 7 , 8 , thus highlighting the impact of LM in processing facilities on product safety and foodborne illness. Identification of LM sources in the facility via routine environmental monitoring (EM) is an essential practice to inform the corrective actions necessary for elimination of LM and prevention of recontamination. EM involves routine collection of swab samples from equipment, tools, personnel, and the facility environment. While LM is the only human pathogen in the genus Listeria , environmental samples are often evaluated to detect the presence of Listeria spp. (LS) as a conservative approach to identifying conditions that will allow for LM presence. In general, previous experience in the facility and industry guidance are used, over statistically-based and random sampling approaches, when determining the number and location of samples taken for both routine EM programs and investigations into potential Listeria harborage sites 9 , 10 , 11 , 12 , 13 , 14 . Areas of a facility are often prioritized according to levels of required hygienic care (also known as hygienic zoning) and surfaces within each area may be designated into zones (also known as zoning) according to different levels of LM control and their proximity to food products, for example. These areas and surfaces are monitored with different frequencies or intensities to detect a loss of control and indicate the risk of product recontamination during processing 9 , 12 . The complexity of the processing equipment and environment, coupled with the heterogeneous distribution of contamination, present major challenges when designing EM programs and evaluating results. Despite the numerous publications on Listeria in food processing facilities, a recent extensive scoping review concluded that there is a need for individual facility-specific techniques to scientifically support alternative designs and implementation of EM programs 15 . Simulation and risk assessment models are useful for EM decision-making, especially where experimental approaches would not be feasible or ethical and where empirical data are difficult to obtain. Quantitative risk assessment (QRA) models, employing discrete-event simulation, for management of LM during food processing and handling have previously considered processing equipment and environment compartments as potential sources of contamination of soft cheese and retail delicatessen products 16 , 17 . While these QRA models have improved understanding of LM cross-contamination and recontamination and the resulting consumer exposure to LM, both acknowledged gaps in modeling the growth and behavior of Listeria under specific environmental conditions and on equipment surfaces prior to contaminating food products. Agent-based modeling (ABM) is a complementary approach towards addressing this gap, sharing many features with a QRA (as it is also a simulation tool), that utilizes spatially explicit and rule-based computation to represent in detailed granularity the real-world components and day-to-day features of a system 18 , in order to preserve natural heterogeneity within and among facility environments and practices. The individuals, or agents, that make up an agent-based model are unique in their characteristics and autonomous in their interactions with each other and their environment 18 . Modeled continuously over time, the collective interactions of agents and their environment reveal both causes and consequences of emerging patterns. Thus, application of ABM in food processing facilities allows for simulation of microbial behavior under complex and dynamic environmental conditions and on surfaces that could not otherwise be modeled by analytically tractable mathematical models or experimented on using other methods. En vironmental monitoring with an A gent- B ased Model of L ist e ria ( EnABLe ) is an in silico approach to simulate the behavior of LS in food processing environments in order to evaluate features and characteristics relevant for designing EM programs. EnABLe was implemented in this study to recreate the complex environment of a cold-smoked salmon processing facility and<|im_end|> <|im_start|>assistant An innovative computer program could be a big help for food safety professionals working to keep production facilities free of food-borne pathogens. Cornell University scientists have developed a computer program, Environmental Monitoring With an Agent-Based Model of Listeria (EnABLe), to simulate the most likely locations in a processing facility where the deadly food-borne pathogen Listeria monocytogenes might be found. Food safety managers may then test those areas for the bacteria's presence, adding an important tool to prevent food contamination and human exposure to the pathogen through tainted food. The computer model, which is described in the Jan. 24 issue of Scientific Reports, has the potential to be modified for a wide range of microbes and locations. "The goal is to build a decision-support tool for control of any pathogen in any complex environment," said Renata Ivanek, associate professor in the Department of Population Medicine and Diagnostic Sciences and senior author of the paper. The study was funded by the Frozen Food Foundation through a grant to Martin Wiedmann, professor of food science, who is also a co-author of the paper. The researchers, including first author Claire Zoellner, a postdoctoral research associate in Ivanek's lab, want to eventually apply the framework to identifying contamination from pathogens that cause hospital-acquired infections in veterinary hospitals or E. coli bacteria in fruit and vegetable processing plants. Food safety professionals at processing facilities keep regular schedules for pathogen testing. They rely on their own expertise and knowledge of the building to determine where to swab for samples. "Whenever we have an environment that is complex, we always have to rely on expert opinion and general rules for this system, or this company, but what we're trying to offer is a way to make this more quantitative and systematic by creating this digital reality," Ivanek said. For the system to work, Zoellner, Ivanek and colleagues entered all relevant data into the model—including historical perspectives, expert feedback, details of the equipment used and its cleaning schedule, the jobs people do, and materials and people who enter from outside the facility. "A computer model like EnABLe connects those data to help answer questions related to changes in contamination risks, potential sources of contamination and approaches for risk mitigation and management," Zoellner said. "A single person could never keep track of all that information, but if we run this model on a computer, we can have in one iteration a distribution of Listeria across equipment after one week. And every time you run it, it will be different and collectively predict a range of possible outcomes," Ivanek said. The paper describes a model system that traces Listeria species on equipment and surfaces in a cold-smoked salmon facility. Simulations revealed contamination dynamics and risks for Listeria contamination on equipment surfaces. Furthermore, the insights gained from seeing patterns in the areas where Listeria is predicted can inform the design of food processing plants and Listeria-monitoring programs. In the future, the model will be applied to frozen food facilities. Food-borne Listeria monocytogenes infects about 1,600 people in the U.S. each year with flu-like symptoms, with about one in five of those infections ending in death. <|im_end|>

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1,929

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The structural connectivity of the brain has been addressed by various imaging techniques such as diffusion weighted magnetic resonance imaging (DWMRI) or specific microscopic approaches based on histological staining or label-free using polarized light (e.g., three-dimensional Polarized Light Imaging (3D-PLI), Optical Coherence Tomography (OCT)). These methods are sensitive to different properties of the fiber enwrapping myelin sheaths i.e. the distribution of myelin basic protein (histology), the apparent diffusion coefficient of water molecules restricted in their movements by the myelin sheath (DWMRI), and the birefringence of the oriented myelin lipid bilayers (3D-PLI, OCT). We show that the orientation and distribution of nerve fibers as well as myelin in thin brain sections can be determined using scanning small angle neutron scattering (sSANS). Neutrons are scattered from the fiber assembly causing anisotropic diffuse small-angle scattering and Bragg peaks related to the highly ordered periodic myelin multilayer structure. The scattering anisotropy, intensity, and angular position of the Bragg peaks can be mapped across the entire brain section. This enables mapping of the fiber and myelin distribution and their orientation in a thin brain section, which was validated by 3D-PLI. The experiments became possible by optimizing the neutron beam collimation to highest flux and enhancing the myelin contrast by deuteration. This method is very sensitive to small microstructures of biological tissue and can directly extract information on the average fiber orientation and even myelin membrane thickness. The present results pave the way toward bio-imaging for detecting structural aberrations causing neurological diseases in future. Introduction The brain serves as the center of our nervous system and consists of gray and white matter. White matter accounts for around 40% of the human brain 1 . It is composed of fiber bundles of mostly myelinated axons that allow rapid transmission of action potentials to distant brain areas including the spinal cord. The myelin sheath surrounding the axon electrically insulates the axonal membrane to allow fast saltatory signal transduction. Injury to the myelinated white matter or diseases leading to the loss of myelination severely deteriorate brain and body functions such as in multiple sclerosis (MS), causing serious neurodegenerative diseases and psychological disorders 2 , 3 . Therefore, there is great interest in the development of methods to study the myelinated axon fiber distribution in the brain. The investigation of the fiber distribution has received increasing attention in recent years, because the three-dimensional fiber network structure of the brain reveals the connectivity of the axonal network (connectome) that is necessary to understand dysfunctions of the brain 4 . Hence, methods that provide accurate local information on the myelin structure and orientation have become important tools in brain research. Established methods to determine local fiber structure and orientation are diffusion weighted MRI (DWMRI), 3D Polarized Light Imaging (3D-PLI), Optical Coherence Tomography (OCT) and confocal laser scanning microscopy (CLSM) to name only a few. DWMRI provides orientation-based/tractography-modelled descriptions of nerve fiber pathways in the entire brain at the millimeter scale in case of in vivo measurements 5 , down to a few hundred microns in the post mortem case 6 . It probes the diffusion length of water molecules as a function of the spatial direction 5 , 6 , 7 , 8 . Due to the concentric wrapping of the myelin sheath around the axon, water molecules within the myelin sheath can diffuse over large distances parallel to the axon 9 , whereas long-distance diffusion normal to the axon direction is strongly hindered by multiple myelin bilayer membranes 10 , 11 . Recent MRI studies demonstrated the ability to extract the myelin distribution across the human brain 12 . Note, the measured MRI/DWMRI signal is sensitive to myelin, but also to other tissue components and microstructures, which makes a clear disentanglement of the myelin difficult. 3D-PLI probes the birefringence originating from the optical anisotropy of the rod-shaped lipid molecules constituting the myelin bilayer membrane 13 , 14 , 15 , 16 , Because of the molecular optical anisotropy, there is a difference between the refractive index parallel to the bilayer membrane compared to the value perpendicular to the membrane 17 , 18 . In recent years, 3D-PLI demonstrated in various applications to different species its benefit in determining the local fiber axis direction at a few micrometer resolution 19 . Optical coherence tomography (OCT) delivers depth-resolved cross-sectional images of microstructures in the biological tissue with micrometer scale resolution 20 . Using birefringence properties of myelin, this technique can be used to differentiate white matter from gray and to determine fiber orientations in ex-vivo brain 21 , 22 , 23 . Confocal laser scanning microscopy (CLSM) can be applied to image fluorescently stained thin brain section 24 . Myelin staining can provide 3D information about the local nerve fiber distribution by 3D volume reconstruction of a series of brain sections. CLSM achieves 0.2 μm in-plane resolution 25 . Myelin immunostaining can further reveal differences in the myelination pattern between healthy and diseased brains 26 . As each method has specific limitations due to the lack of spatial resolution, sensitivity to non-axonal signal contributions and uncertainty concerning signal pre-factors, comparisons between these methods have been conducted to verify the 3D fiber orientation distributions. This has been done e.g. with confocal microscopy vs. DWMRI 27 or DWMRI vs. PLI 28 . Recently, small angle X-ray scattering (SAXS) has been introduced as a further method to probe the myelin structure as well as its 3D orientational distribution 29 . SAXS provides the Bragg diffraction peaks resulting from the periodic concentric arrangement of the lipid bilayers in the myelin sheath 30 , 31 , 32 , 33 . As the azimuthal position of the Bragg peaks on the detector depends on the 3D-orientation of the myelinated axons, a series of data with different inclination angles allows to quantitatively reconstruct the 3D orientational distribution 32 , 34 , 35 , 36 , 37 . It was possible to quantitatively correlate the 3D fiber orientation distribution function (fODF) with DWMRI. A method that can provide valuable complementary", "role": "user" }, { "content": "The brain can be divided into so-called gray matter and white matter. The white matter contains the axons that transmit stimuli. For faster stimulus transmission, the axons are wrapped in an insulating layer of myelin, in the same way as a cable is wrapped in rubber insulation to ensure that no electricity is lost along the way. If the myelin sheath is damaged or degraded, this leads to impaired brain and body functions. In multiple sclerosis, for example, the insulating myelin layer is severely impaired. However, the exact causes of the disease are still unclear. Researchers at the Jülich Institute of Neuroscience and Medicine and the Jülich Centre for Neutron Science have developed a new imaging method at the small-angle scattering facility KWS-1 at the MLZ to map the density, structure, and spatial orientation of nerve fibers and myelin. New method complements previous procedures \"For a long time now, it has been possible to determine the spatial orientation of nerve fibers in brain slices using light microscopy and polarization,\" explains Dr. Heinrich Frielinghaus from the JCNS, head of the KWS-1 group, \"but the exact structure and orientation of the myelin on the molecular scale cannot be detected using light.\" With the help of neutrons, the researchers can now for the first time determine both structure and orientation, and correlate these with polarization measurements. Schematic diagram of the experimental setup at the small-angle scattering instrument. The neutron beam hits a brain section (\"sample\"). A detector records the scattering. Credit: Forschungszentrum Jülich The special feature of this new method is that it allows scientists to image the axons bundled into nerve fibers at the same time as the insulating myelin sheath. \"With our neutron-based method, we can confirm the results of previous methods and provide additional information,\" says Frielinghaus. Applications in medicine \"Since we work with brain slices, it is of course not a diagnostic procedure,\" explains Frielinghaus. With their new method, the researchers hope to better understand the causes of neurological diseases in the future by being able to visualize structural changes in the brain more completely. The resolution of the new method is still in the millimeter range. However, Frielinghaus and his colleagues expect that measurements precise to the micrometer will be possible in the future. This will enable them to study even the smallest structures in biological tissues. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The structural connectivity of the brain has been addressed by various imaging techniques such as diffusion weighted magnetic resonance imaging (DWMRI) or specific microscopic approaches based on histological staining or label-free using polarized light (e.g., three-dimensional Polarized Light Imaging (3D-PLI), Optical Coherence Tomography (OCT)). These methods are sensitive to different properties of the fiber enwrapping myelin sheaths i.e. the distribution of myelin basic protein (histology), the apparent diffusion coefficient of water molecules restricted in their movements by the myelin sheath (DWMRI), and the birefringence of the oriented myelin lipid bilayers (3D-PLI, OCT). We show that the orientation and distribution of nerve fibers as well as myelin in thin brain sections can be determined using scanning small angle neutron scattering (sSANS). Neutrons are scattered from the fiber assembly causing anisotropic diffuse small-angle scattering and Bragg peaks related to the highly ordered periodic myelin multilayer structure. The scattering anisotropy, intensity, and angular position of the Bragg peaks can be mapped across the entire brain section. This enables mapping of the fiber and myelin distribution and their orientation in a thin brain section, which was validated by 3D-PLI. The experiments became possible by optimizing the neutron beam collimation to highest flux and enhancing the myelin contrast by deuteration. This method is very sensitive to small microstructures of biological tissue and can directly extract information on the average fiber orientation and even myelin membrane thickness. The present results pave the way toward bio-imaging for detecting structural aberrations causing neurological diseases in future. Introduction The brain serves as the center of our nervous system and consists of gray and white matter. White matter accounts for around 40% of the human brain 1 . It is composed of fiber bundles of mostly myelinated axons that allow rapid transmission of action potentials to distant brain areas including the spinal cord. The myelin sheath surrounding the axon electrically insulates the axonal membrane to allow fast saltatory signal transduction. Injury to the myelinated white matter or diseases leading to the loss of myelination severely deteriorate brain and body functions such as in multiple sclerosis (MS), causing serious neurodegenerative diseases and psychological disorders 2 , 3 . Therefore, there is great interest in the development of methods to study the myelinated axon fiber distribution in the brain. The investigation of the fiber distribution has received increasing attention in recent years, because the three-dimensional fiber network structure of the brain reveals the connectivity of the axonal network (connectome) that is necessary to understand dysfunctions of the brain 4 . Hence, methods that provide accurate local information on the myelin structure and orientation have become important tools in brain research. Established methods to determine local fiber structure and orientation are diffusion weighted MRI (DWMRI), 3D Polarized Light Imaging (3D-PLI), Optical Coherence Tomography (OCT) and confocal laser scanning microscopy (CLSM) to name only a few. DWMRI provides orientation-based/tractography-modelled descriptions of nerve fiber pathways in the entire brain at the millimeter scale in case of in vivo measurements 5 , down to a few hundred microns in the post mortem case 6 . It probes the diffusion length of water molecules as a function of the spatial direction 5 , 6 , 7 , 8 . Due to the concentric wrapping of the myelin sheath around the axon, water molecules within the myelin sheath can diffuse over large distances parallel to the axon 9 , whereas long-distance diffusion normal to the axon direction is strongly hindered by multiple myelin bilayer membranes 10 , 11 . Recent MRI studies demonstrated the ability to extract the myelin distribution across the human brain 12 . Note, the measured MRI/DWMRI signal is sensitive to myelin, but also to other tissue components and microstructures, which makes a clear disentanglement of the myelin difficult. 3D-PLI probes the birefringence originating from the optical anisotropy of the rod-shaped lipid molecules constituting the myelin bilayer membrane 13 , 14 , 15 , 16 , Because of the molecular optical anisotropy, there is a difference between the refractive index parallel to the bilayer membrane compared to the value perpendicular to the membrane 17 , 18 . In recent years, 3D-PLI demonstrated in various applications to different species its benefit in determining the local fiber axis direction at a few micrometer resolution 19 . Optical coherence tomography (OCT) delivers depth-resolved cross-sectional images of microstructures in the biological tissue with micrometer scale resolution 20 . Using birefringence properties of myelin, this technique can be used to differentiate white matter from gray and to determine fiber orientations in ex-vivo brain 21 , 22 , 23 . Confocal laser scanning microscopy (CLSM) can be applied to image fluorescently stained thin brain section 24 . Myelin staining can provide 3D information about the local nerve fiber distribution by 3D volume reconstruction of a series of brain sections. CLSM achieves 0.2 μm in-plane resolution 25 . Myelin immunostaining can further reveal differences in the myelination pattern between healthy and diseased brains 26 . As each method has specific limitations due to the lack of spatial resolution, sensitivity to non-axonal signal contributions and uncertainty concerning signal pre-factors, comparisons between these methods have been conducted to verify the 3D fiber orientation distributions. This has been done e.g. with confocal microscopy vs. DWMRI 27 or DWMRI vs. PLI 28 . Recently, small angle X-ray scattering (SAXS) has been introduced as a further method to probe the myelin structure as well as its 3D orientational distribution 29 . SAXS provides the Bragg diffraction peaks resulting from the periodic concentric arrangement of the lipid bilayers in the myelin sheath 30 , 31 , 32 , 33 . As the azimuthal position of the Bragg peaks on the detector depends on the 3D-orientation of the myelinated axons, a series of data with different inclination angles allows to quantitatively reconstruct the 3D orientational distribution 32 , 34 , 35 , 36 , 37 . It was possible to quantitatively correlate the 3D fiber orientation distribution function (fODF) with DWMRI. A method that can provide valuable complementary<|im_end|> <|im_start|>assistant The brain can be divided into so-called gray matter and white matter. The white matter contains the axons that transmit stimuli. For faster stimulus transmission, the axons are wrapped in an insulating layer of myelin, in the same way as a cable is wrapped in rubber insulation to ensure that no electricity is lost along the way. If the myelin sheath is damaged or degraded, this leads to impaired brain and body functions. In multiple sclerosis, for example, the insulating myelin layer is severely impaired. However, the exact causes of the disease are still unclear. Researchers at the Jülich Institute of Neuroscience and Medicine and the Jülich Centre for Neutron Science have developed a new imaging method at the small-angle scattering facility KWS-1 at the MLZ to map the density, structure, and spatial orientation of nerve fibers and myelin. New method complements previous procedures "For a long time now, it has been possible to determine the spatial orientation of nerve fibers in brain slices using light microscopy and polarization," explains Dr. Heinrich Frielinghaus from the JCNS, head of the KWS-1 group, "but the exact structure and orientation of the myelin on the molecular scale cannot be detected using light." With the help of neutrons, the researchers can now for the first time determine both structure and orientation, and correlate these with polarization measurements. Schematic diagram of the experimental setup at the small-angle scattering instrument. The neutron beam hits a brain section ("sample"). A detector records the scattering. Credit: Forschungszentrum Jülich The special feature of this new method is that it allows scientists to image the axons bundled into nerve fibers at the same time as the insulating myelin sheath. "With our neutron-based method, we can confirm the results of previous methods and provide additional information," says Frielinghaus. Applications in medicine "Since we work with brain slices, it is of course not a diagnostic procedure," explains Frielinghaus. With their new method, the researchers hope to better understand the causes of neurological diseases in the future by being able to visualize structural changes in the brain more completely. The resolution of the new method is still in the millimeter range. However, Frielinghaus and his colleagues expect that measurements precise to the micrometer will be possible in the future. This will enable them to study even the smallest structures in biological tissues. <|im_end|>

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2989, 40, 63610, 279, 293, 556, 1658, 287, 768, 71373, 505, 279, 29393, 459, 285, 354, 18237, 315, 279, 21236, 35831, 68700, 35715, 9129, 10831, 279, 856, 33830, 20934, 1155, 39654, 220, 1032, 1174, 220, 975, 1174, 220, 868, 1174, 220, 845, 1174, 9393, 315, 279, 31206, 29393, 459, 285, 354, 18237, 11, 1070, 374, 264, 6811, 1990, 279, 19914, 3104, 1963, 15638, 311, 279, 20934, 1155, 39654, 7863, 311, 279, 907, 77933, 311, 279, 39654, 220, 1114, 1174, 220, 972, 662, 763, 3293, 1667, 11, 220, 18, 35, 12, 2989, 40, 21091, 304, 5370, 8522, 311, 2204, 9606, 1202, 8935, 304, 26679, 279, 2254, 24722, 8183, 5216, 520, 264, 2478, 19748, 88371, 11175, 220, 777, 662, 75939, 78925, 10390, 5814, 320, 46, 1182, 8, 28421, 8149, 11849, 8905, 5425, 97319, 5448, 315, 8162, 47194, 304, 279, 24156, 20438, 449, 19748, 88371, 5569, 11175, 220, 508, 662, 12362, 293, 556, 1658, 287, 768, 6012, 315, 856, 33830, 11, 420, 15105, 649, 387, 1511, 311, 54263, 4251, 5030, 505, 18004, 323, 311, 8417, 24722, 89935, 304, 506, 8437, 6632, 8271, 220, 1691, 1174, 220, 1313, 1174, 220, 1419, 662, 15323, 3768, 21120, 36201, 92914, 320, 3218, 9691, 8, 649, 387, 9435, 311, 2217, 74864, 398, 61152, 15792, 8271, 3857, 220, 1187, 662, 3092, 33830, 88896, 649, 3493, 220, 18, 35, 2038, 922, 279, 2254, 32015, 24722, 8141, 555, 220, 18, 35, 8286, 43738, 315, 264, 4101, 315, 8271, 14491, 13, 7121, 9691, 83691, 220, 15, 13, 17, 33983, 76, 304, 90649, 11175, 220, 914, 662, 3092, 33830, 33119, 537, 2101, 649, 4726, 16805, 12062, 304, 279, 856, 301, 2617, 5497, 1990, 9498, 323, 6759, 1503, 35202, 220, 1627, 662, 1666, 1855, 1749, 706, 3230, 9669, 4245, 311, 279, 6996, 315, 29079, 11175, 11, 27541, 311, 2536, 12, 710, 25180, 8450, 19564, 323, 27924, 18815, 8450, 864, 2269, 21846, 11, 36595, 1990, 1521, 5528, 617, 1027, 13375, 311, 10356, 279, 220, 18, 35, 24722, 17140, 43785, 13, 1115, 706, 1027, 2884, 384, 1326, 13, 449, 2389, 3768, 92914, 6296, 13, 423, 15565, 4403, 220, 1544, 477, 423, 15565, 4403, 6296, 13, 10528, 40, 220, 1591, 662, 42096, 11, 2678, 9392, 1630, 30630, 72916, 320, 50, 3027, 50, 8, 706, 1027, 11784, 439, 264, 4726, 1749, 311, 22477, 279, 856, 33830, 6070, 439, 1664, 439, 1202, 220, 18, 35, 11744, 1697, 8141, 220, 1682, 662, 75326, 50, 5825, 279, 3320, 16094, 3722, 16597, 40035, 13239, 505, 279, 39445, 10219, 2265, 27204, 315, 279, 68700, 20934, 5184, 304, 279, 856, 33830, 1364, 589, 220, 966, 1174, 220, 2148, 1174, 220, 843, 1174, 220, 1644, 662, 1666, 279, 93060, 278, 2361, 315, 279, 3320, 16094, 40035, 389, 279, 32314, 14117, 389, 279, 220, 18, 35, 12, 25280, 315, 279, 856, 301, 15846, 3944, 2439, 11, 264, 4101, 315, 828, 449, 2204, 77004, 27030, 6276, 311, 10484, 275, 8046, 44928, 279, 220, 18, 35, 11744, 1697, 8141, 220, 843, 1174, 220, 1958, 1174, 220, 1758, 1174, 220, 1927, 1174, 220, 1806, 662, 1102, 574, 3284, 311, 10484, 275, 8046, 81584, 279, 220, 18, 35, 24722, 17140, 8141, 734, 320, 69, 2114, 37, 8, 449, 423, 15565, 4403, 13, 362, 1749, 430, 649, 3493, 15525, 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49774, 323, 856, 33830, 13, 1561, 1749, 1946, 1392, 3766, 16346, 330, 2520, 264, 1317, 892, 1457, 11, 433, 706, 1027, 3284, 311, 8417, 279, 29079, 17140, 315, 32015, 49774, 304, 8271, 35354, 1701, 3177, 92914, 323, 83245, 1359, 15100, 2999, 13, 64782, 14172, 31502, 20659, 32651, 505, 279, 61683, 2507, 11, 2010, 315, 279, 735, 7585, 12, 16, 1912, 11, 330, 8248, 279, 4839, 6070, 323, 17140, 315, 279, 856, 33830, 389, 279, 31206, 5569, 4250, 387, 16914, 1701, 3177, 1210, 3161, 279, 1520, 315, 26878, 26692, 11, 279, 12074, 649, 1457, 369, 279, 1176, 892, 8417, 2225, 6070, 323, 17140, 11, 323, 81584, 1521, 449, 83245, 22323, 13, 328, 82149, 13861, 315, 279, 22772, 6642, 520, 279, 2678, 35481, 72916, 14473, 13, 578, 73404, 24310, 13280, 264, 8271, 3857, 3573, 13925, 1865, 362, 32314, 7576, 279, 72916, 13, 16666, 25, 50990, 331, 2234, 14694, 306, 10952, 622, 2448, 6915, 578, 3361, 4668, 315, 420, 502, 1749, 374, 430, 433, 6276, 14248, 311, 2217, 279, 3944, 2439, 52550, 1139, 32015, 49774, 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1,895

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Rapid, simple, inexpensive, accurate, and sensitive point-of-care (POC) detection of viral pathogens in bodily fluids is a vital component of controlling the spread of infectious diseases. The predominant laboratory-based methods for sample processing and nucleic acid detection face limitations that prevent them from gaining wide adoption for POC applications in low-resource settings and self-testing scenarios. Here, we report the design and characterization of an integrated system for rapid sample-to-answer detection of a viral pathogen in a droplet of whole blood comprised of a 2-stage microfluidic cartridge for sample processing and nucleic acid amplification, and a clip-on detection instrument that interfaces with the image sensor of a smartphone. The cartridge is designed to release viral RNA from Zika virus in whole blood using chemical lysis, followed by mixing with the assay buffer for performing reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) reactions in six parallel microfluidic compartments. The battery-powered handheld detection instrument uniformly heats the compartments from below, and an array of LEDs illuminates from above, while the generation of fluorescent reporters in the compartments is kinetically monitored by collecting a series of smartphone images. We characterize the assay time and detection limits for detecting Zika RNA and gamma ray-deactivated Zika virus spiked into buffer and whole blood and compare the performance of the same assay when conducted in conventional PCR tubes. Our approach for kinetic monitoring of the fluorescence-generating process in the microfluidic compartments enables spatial analysis of early fluorescent “bloom” events for positive samples, in an approach called “Spatial LAMP” (S-LAMP). We show that S-LAMP image analysis reduces the time required to designate an assay as a positive test, compared to conventional analysis of the average fluorescent intensity of the entire compartment. S-LAMP enables the RT-LAMP process to be as short as 22 minutes, resulting in a total sample-to-answer time in the range of 17–32 minutes to distinguish positive from negative samples, while demonstrating a viral RNA detection as low as 2.70 × 10 2 copies per μl, and a gamma-irradiated virus of 10 3 virus particles in a single 12.5 μl droplet blood sample. This article is part of the themed collections: Analyst HOT Articles 2022 and Smartphone-based sensors 1. Introduction Zika virus (ZIKV) is a flavivirus that was first isolated in Uganda, Africa in 1947 and is known to cause fetal microcephaly, a developmental disorder of newborn babies that is a consequence of mothers becoming infected during early pregnancy. 1–3 ZIKV is transmitted mostly by the bites of infected Aedes aegypti mosquitos, but sexual, perinatal, and blood-transfusion transmission have also been documented. 4–9 Although its presence was of little concern at first as the virus spread sporadically within the countries of continental South America and Asia, the 2015 ZIKV epidemic in Brazil progressed quickly, raising global awareness of the infectious disease, leading to a declaration of global health emergency by the World Health Organization in early 2016. 10 Now, ZIKV has become one of the neurotropic viruses that circulate in more than 87 countries, still actively infecting thousands of people annually. 11 In 2020, a total of 22 923 cases were reported worldwide among which 18 941 cases were from Brazil and 2215 cases were from countries in Central America. 12 Given the wealth of evidence indicating the apparent danger posed by the ZIKV, immediate action must be taken to stop the propagation of the virus and prevent future outbreaks. Controlling and monitoring ZIKV and other insect-borne viral pathogens have been particularly challenging since most infection cases are asymptomatic, while even the symptomatic infections have been reported to show non-specific acute febrile illness with symptoms that are identical to that of other common viral infections such as Dengue virus and Chikungunya virus. 13–15 All these viruses result in diseases that present clinically with similar symptoms, including fever, fatigue, headache, rash, arthralgia, myalgia, and conjunctivitis. 16 As a result of these characteristics, viral containment and early detection have been especially difficult in underdeveloped countries where limited access to testing facilities, shortage of trained personnel, and under-funded medical infrastructures have hindered patients from receiving a proper diagnosis and prompt effective treatment. This disproportionate distribution of the burden of infectious diseases is most prominent in the poorest countries and regions, motivating the development of more portable and cost-effective POC diagnosing tools for viral detection that can provide equivalent sensitivity and accuracy as conventional laboratory-based methods. 17 Various technologies are currently available for ZIKV detection but have limitations that hinder their application to POC scenarios. The gold standard molecular testing method, quantitative reverse transcription PCR (RT-qPCR) has been extensively exploited to detect the presence of genomic contents of ZIKV through the utilization of the reverse transcriptase enzyme to amplify viral RNA copies from patient samples, including blood, 18,19 urine, 20–22 saliva, 20 semen, 23,24 and amniotic fluid. 25 Although PCR-based nucleic acid amplification provides detection limits as low as 190 copies per μl when detecting extracted ZIKA RNA spiked in whole blood, 26 the assays require sample preparation and instruments in laboratory settings, using protocols that require benchtop instrumentation, highly trained personnel to perform sample purification, viral isolation, complex genome extractions, and interpretation of complex time-resolved calibration curves. 27 Moreover, due to the necessity for precise thermal control, the acquisition of bulky and/or expensive equipment is not optional, making the method unsuitable for POC testing. 28–32 An alternative to nucleic acid testing is enzyme-linked immunosorbent assay (ELISA), which detects viral proteins, such as antigens or antibodies. Recognized as being sensitive and robust, ELISA has been used in several studies for detecting low concentrations of Zika-specific proteins. 33,34 However, ELISA also requires benchtop instrumentation, complex workflow, and suffers from cross-reactivity, long sample-to-answer time (∼4 h.), washing steps, and stringent sample preparation procedures, resulting in an assay that is difficult to deploy in resource-limited environments. Further, the antibody reagents for ELISA require careful handling and strict storage conditions to preserve their function against denaturation and aggregation. 35 For these reasons, nucleic acid tests using isothermal amplification such as Loop-Mediated Isothermal Amplification (LAMP) have recently", "role": "user" }, { "content": "As seen with the COVID-19 pandemic, detection methods that are rapid, simple, accurate, and sensitive are vital for detecting viral pathogens and for controlling the spread of infectious diseases. Unfortunately, laboratory-based methods often require trained personnel and involve complex procedures. In a new study, researchers at the University of Illinois Urbana-Champaign have combined their efforts to develop an instrument that can be clipped on to a smartphone to rapidly test for Zika virus in a single droplet of blood. Zika virus is primarily transmitted through Aedes aegypti mosquitoes. Although the disease is largely asymptomatic or results in mild symptoms in adults, it causes developmental disorders in newborn babies if their mothers are infected during early pregnancy. Currently, the virus is circulating in more than 87 countries, infecting thousands of people annually, necessitating better testing and control measures. \"Mosquito-borne viruses cause serious diseases, but they have similar symptoms. If you have Zika, malaria, dengue, or chikungunya, you just might show up to the doctor with a fever and they won't know why,\" said Brian Cunningham (CGD Director/MMG), the Intel Alumni Endowed Chair of Electrical and Computer Engineering. \"But it's important to know whether it's Zika, especially if the patient is a pregnant woman, because the consequences to a developing fetus are really severe.\" Zika virus infections are currently detected through polymerase chain reaction tests performed in a laboratory, which can amplify the genetic material of the virus, allowing scientists to detect it. In the new study, researchers used Loop-Mediated Isothermal Amplification to detect the virus in the blood samples using an approach suitable for point-of-care clinics. While PCR requires 20-40 repeated temperature shifts to amplify the genetic material, LAMP only requires one temperature—65 °C—making it easier to control. Additionally, PCR tests are very sensitive to the presence of contaminants, especially the other components in a blood sample. As a result, the sample is first purified before it can be used. On the other hand, LAMP does not require any such purification step. A cartridge, that contains reagents required to detect the virus, is inserted into the instrument to perform the test while the instrument is clipped onto a smartphone. Once the patient adds a drop of blood, one set of chemicals break open the viruses and the blood cells within five minutes. A heater below the cartridge heats it up to 65 °C. A second set of chemicals then amplifies the viral genetic material, and the liquid inside the cartridge fluoresces bright green if the blood sample contains the Zika virus. The entire process takes 25 minutes. \"The other cool aspect is that we're doing the readout with a smartphone,\" Cunningham said. \"We've designed a clip-on device so that the smartphone's rear camera is looking at the cartridge while the amplification occurs. When there's a positive reaction, you see little green blooms of fluorescence that eventually fill up the entire cartridge with green light.\" The researchers are now developing similar devices to simultaneously detect other mosquito-borne viruses and are working on making the devices even smaller. \"Although our clip-on detector is pretty small, a lot of the space is taken up by the batteries. In the next version, it will be powered by the phone's battery,\" Cunningham said. The study \"Smartphone clip-on instrument and microfluidic processor for rapid sample-to-answer detection of Zika virus in whole blood using spatial RT-LAMP\" was published in the journal Analyst. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Rapid, simple, inexpensive, accurate, and sensitive point-of-care (POC) detection of viral pathogens in bodily fluids is a vital component of controlling the spread of infectious diseases. The predominant laboratory-based methods for sample processing and nucleic acid detection face limitations that prevent them from gaining wide adoption for POC applications in low-resource settings and self-testing scenarios. Here, we report the design and characterization of an integrated system for rapid sample-to-answer detection of a viral pathogen in a droplet of whole blood comprised of a 2-stage microfluidic cartridge for sample processing and nucleic acid amplification, and a clip-on detection instrument that interfaces with the image sensor of a smartphone. The cartridge is designed to release viral RNA from Zika virus in whole blood using chemical lysis, followed by mixing with the assay buffer for performing reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) reactions in six parallel microfluidic compartments. The battery-powered handheld detection instrument uniformly heats the compartments from below, and an array of LEDs illuminates from above, while the generation of fluorescent reporters in the compartments is kinetically monitored by collecting a series of smartphone images. We characterize the assay time and detection limits for detecting Zika RNA and gamma ray-deactivated Zika virus spiked into buffer and whole blood and compare the performance of the same assay when conducted in conventional PCR tubes. Our approach for kinetic monitoring of the fluorescence-generating process in the microfluidic compartments enables spatial analysis of early fluorescent “bloom” events for positive samples, in an approach called “Spatial LAMP” (S-LAMP). We show that S-LAMP image analysis reduces the time required to designate an assay as a positive test, compared to conventional analysis of the average fluorescent intensity of the entire compartment. S-LAMP enables the RT-LAMP process to be as short as 22 minutes, resulting in a total sample-to-answer time in the range of 17–32 minutes to distinguish positive from negative samples, while demonstrating a viral RNA detection as low as 2.70 × 10 2 copies per μl, and a gamma-irradiated virus of 10 3 virus particles in a single 12.5 μl droplet blood sample. This article is part of the themed collections: Analyst HOT Articles 2022 and Smartphone-based sensors 1. Introduction Zika virus (ZIKV) is a flavivirus that was first isolated in Uganda, Africa in 1947 and is known to cause fetal microcephaly, a developmental disorder of newborn babies that is a consequence of mothers becoming infected during early pregnancy. 1–3 ZIKV is transmitted mostly by the bites of infected Aedes aegypti mosquitos, but sexual, perinatal, and blood-transfusion transmission have also been documented. 4–9 Although its presence was of little concern at first as the virus spread sporadically within the countries of continental South America and Asia, the 2015 ZIKV epidemic in Brazil progressed quickly, raising global awareness of the infectious disease, leading to a declaration of global health emergency by the World Health Organization in early 2016. 10 Now, ZIKV has become one of the neurotropic viruses that circulate in more than 87 countries, still actively infecting thousands of people annually. 11 In 2020, a total of 22 923 cases were reported worldwide among which 18 941 cases were from Brazil and 2215 cases were from countries in Central America. 12 Given the wealth of evidence indicating the apparent danger posed by the ZIKV, immediate action must be taken to stop the propagation of the virus and prevent future outbreaks. Controlling and monitoring ZIKV and other insect-borne viral pathogens have been particularly challenging since most infection cases are asymptomatic, while even the symptomatic infections have been reported to show non-specific acute febrile illness with symptoms that are identical to that of other common viral infections such as Dengue virus and Chikungunya virus. 13–15 All these viruses result in diseases that present clinically with similar symptoms, including fever, fatigue, headache, rash, arthralgia, myalgia, and conjunctivitis. 16 As a result of these characteristics, viral containment and early detection have been especially difficult in underdeveloped countries where limited access to testing facilities, shortage of trained personnel, and under-funded medical infrastructures have hindered patients from receiving a proper diagnosis and prompt effective treatment. This disproportionate distribution of the burden of infectious diseases is most prominent in the poorest countries and regions, motivating the development of more portable and cost-effective POC diagnosing tools for viral detection that can provide equivalent sensitivity and accuracy as conventional laboratory-based methods. 17 Various technologies are currently available for ZIKV detection but have limitations that hinder their application to POC scenarios. The gold standard molecular testing method, quantitative reverse transcription PCR (RT-qPCR) has been extensively exploited to detect the presence of genomic contents of ZIKV through the utilization of the reverse transcriptase enzyme to amplify viral RNA copies from patient samples, including blood, 18,19 urine, 20–22 saliva, 20 semen, 23,24 and amniotic fluid. 25 Although PCR-based nucleic acid amplification provides detection limits as low as 190 copies per μl when detecting extracted ZIKA RNA spiked in whole blood, 26 the assays require sample preparation and instruments in laboratory settings, using protocols that require benchtop instrumentation, highly trained personnel to perform sample purification, viral isolation, complex genome extractions, and interpretation of complex time-resolved calibration curves. 27 Moreover, due to the necessity for precise thermal control, the acquisition of bulky and/or expensive equipment is not optional, making the method unsuitable for POC testing. 28–32 An alternative to nucleic acid testing is enzyme-linked immunosorbent assay (ELISA), which detects viral proteins, such as antigens or antibodies. Recognized as being sensitive and robust, ELISA has been used in several studies for detecting low concentrations of Zika-specific proteins. 33,34 However, ELISA also requires benchtop instrumentation, complex workflow, and suffers from cross-reactivity, long sample-to-answer time (∼4 h.), washing steps, and stringent sample preparation procedures, resulting in an assay that is difficult to deploy in resource-limited environments. Further, the antibody reagents for ELISA require careful handling and strict storage conditions to preserve their function against denaturation and aggregation. 35 For these reasons, nucleic acid tests using isothermal amplification such as Loop-Mediated Isothermal Amplification (LAMP) have recently<|im_end|> <|im_start|>assistant As seen with the COVID-19 pandemic, detection methods that are rapid, simple, accurate, and sensitive are vital for detecting viral pathogens and for controlling the spread of infectious diseases. Unfortunately, laboratory-based methods often require trained personnel and involve complex procedures. In a new study, researchers at the University of Illinois Urbana-Champaign have combined their efforts to develop an instrument that can be clipped on to a smartphone to rapidly test for Zika virus in a single droplet of blood. Zika virus is primarily transmitted through Aedes aegypti mosquitoes. Although the disease is largely asymptomatic or results in mild symptoms in adults, it causes developmental disorders in newborn babies if their mothers are infected during early pregnancy. Currently, the virus is circulating in more than 87 countries, infecting thousands of people annually, necessitating better testing and control measures. "Mosquito-borne viruses cause serious diseases, but they have similar symptoms. If you have Zika, malaria, dengue, or chikungunya, you just might show up to the doctor with a fever and they won't know why," said Brian Cunningham (CGD Director/MMG), the Intel Alumni Endowed Chair of Electrical and Computer Engineering. "But it's important to know whether it's Zika, especially if the patient is a pregnant woman, because the consequences to a developing fetus are really severe." Zika virus infections are currently detected through polymerase chain reaction tests performed in a laboratory, which can amplify the genetic material of the virus, allowing scientists to detect it. In the new study, researchers used Loop-Mediated Isothermal Amplification to detect the virus in the blood samples using an approach suitable for point-of-care clinics. While PCR requires 20-40 repeated temperature shifts to amplify the genetic material, LAMP only requires one temperature—65 °C—making it easier to control. Additionally, PCR tests are very sensitive to the presence of contaminants, especially the other components in a blood sample. As a result, the sample is first purified before it can be used. On the other hand, LAMP does not require any such purification step. A cartridge, that contains reagents required to detect the virus, is inserted into the instrument to perform the test while the instrument is clipped onto a smartphone. Once the patient adds a drop of blood, one set of chemicals break open the viruses and the blood cells within five minutes. A heater below the cartridge heats it up to 65 °C. A second set of chemicals then amplifies the viral genetic material, and the liquid inside the cartridge fluoresces bright green if the blood sample contains the Zika virus. The entire process takes 25 minutes. "The other cool aspect is that we're doing the readout with a smartphone," Cunningham said. "We've designed a clip-on device so that the smartphone's rear camera is looking at the cartridge while the amplification occurs. When there's a positive reaction, you see little green blooms of fluorescence that eventually fill up the entire cartridge with green light." The researchers are now developing similar devices to simultaneously detect other mosquito-borne viruses and are working on making the devices even smaller. "Although our clip-on detector is pretty small, a lot of the space is taken up by the batteries. In the next version, it will be powered by the phone's battery," Cunningham said. The study "Smartphone clip-on instrument and microfluidic processor for rapid sample-to-answer detection of Zika virus in whole blood using spatial RT-LAMP" was published in the journal Analyst. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Using carbon dioxide (CO 2 ) as a feedstock for commodity synthesis is an attractive means of reducing greenhouse gas emissions and a possible stepping-stone towards renewable synthetic fuels 1 , 2 . A major impediment to synthesizing compounds from CO 2 is the difficulty of forming carbon–carbon (C–C) bonds efficiently: although CO 2 reacts readily with carbon-centred nucleophiles, generating these intermediates requires high-energy reagents (such as highly reducing metals or strong organic bases), carbon–heteroatom bonds or relatively acidic carbon–hydrogen (C–H) bonds 3 , 4 , 5 . These requirements negate the environmental benefit of using CO 2 as a substrate and limit the chemistry to low-volume targets. Here we show that intermediate-temperature (200 to 350 degrees Celsius) molten salts containing caesium or potassium cations enable carbonate ions (CO 3 2– ) to deprotonate very weakly acidic C–H bonds (p K a > 40), generating carbon-centred nucleophiles that react with CO 2 to form carboxylates. To illustrate a potential application, we use C–H carboxylation followed by protonation to convert 2-furoic acid into furan-2,5-dicarboxylic acid (FDCA)—a highly desirable bio-based feedstock 6 with numerous applications, including the synthesis of polyethylene furandicarboxylate (PEF), which is a potential large-scale substitute for petroleum-derived polyethylene terephthalate (PET) 7 , 8 . Since 2-furoic acid can readily be made from lignocellulose 9 , CO 3 2– -promoted C–H carboxylation thus reveals a way to transform inedible biomass and CO 2 into a valuable feedstock chemical. Our results provide a new strategy for using CO 2 in the synthesis of multi-carbon compounds. Main The chemistry described here is inspired by ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), which effects C–C bond formation in the Calvin cycle by deprotonating a C–H bond of ribulose-1,5-bisphosphate and exposing the resulting carbon-centred nucleophile to CO 2 to form a carboxylate (C–CO 2 – ) 10 . Emulating this strategy synthetically requires deprotonating un-activated C–H bonds using a simple base that does not have a large CO 2 footprint. To meet these requirements, we envisioned a CO 3 2– -promoted C–H carboxylation reaction, wherein CO 3 2– reversibly deprotonates a C–H bond to generate HCO 3 – and a carbon-centred nucleophile that reacts with CO 2 to form C–CO 2 – ( Fig. 1a ). HCO 3 – decomposition results in a net consumption of one-half equivalents of CO 3 2– and CO 2 per C–CO 2 – produced. The cycle could be closed by protonating C–CO 2 – with strong acid and using electrodialysis to regenerate the acid and base 11 , 12 , effecting a net transformation of C–H and CO 2 into C–CO 2 H without using any other stoichiometric reagents. Alternatively, CO 2 -promoted esterification could be used to convert the carboxylate into an ester (C–CO 2 R) and regenerate CO 3 2– directly 13 . Previously, researchers have shown that Cs 2 CO 3 can deprotonate alkynyl 14 , allylic 15 , and activated heteroaryl C–H bonds with p K a values of up to 27 (ref. 16 ) in organic solvents at elevated temperature (where p K a is the negative base-10 logarithm of the acid dissociation constant). However, using CO 3 2– -promoted C–H carboxylation for commodity synthesis requires deprotonating C–H bonds that are considerably less acidic. Figure 1: CO 2 utilization cycle. a , C–H deprotonation by CO 3 2– forms a carbon-centred nucleophile (C – ) that reacts with CO 2 to form a C–C bond (red box and arrows). Protonation and electrodialysis (black box and arrows) produces a carboxylic acid. Alternatively, CO 2 -promoted esterification (grey box and arrows) produces an ester. Net transformations are shown in the blue box. b , Potential application for FDCA synthesis from lignocellulose. Current approaches rely on converting lignocellulose into HMF, a difficult reaction that has not been commercialized. C–H carboxylation enables the use of furfural, which has been produced industrially from lignocellulose for many decades. M, metal; R, alkyl group. PowerPoint slide Full size image Carbonate-promoted C–H carboxylation is particularly desirable for the synthesis of polymer units from biomass. A longstanding goal of renewable polymer chemistry is a scalable synthesis of FDCA from lignocellulose to replace petroleum-derived terephthalic acid for polyester synthesis ( Fig. 1b ) 6 . In particular, PEF has been reported to have superior physical properties to PET, a polymer produced at 50 megatons a year as an industrial commodity 8 . Current approaches to FDCA synthesis use dehydration processes to convert hexose sugars into hydroxymethyl furfural (HMF), which is then oxidized to form FDCA 17 . Recent work has improved the efficiency of converting fructose to HMF 8 , 18 and it has been estimated that PEF production from fructose would emit 50% less CO 2 than the established process for PET production 7 . However, producing FDCA on a scale commensurate with terephthalic acid and achieving maximal reduction in CO 2 emissions will require using lignocellulose as the feedstock. Converting lignocellulose into HMF is very challenging because the hexoses are incorporated into intractable cellulose fibres 17 . Researchers have recently reported a high-yielding conversion of lignocellulose to HMF in ionic liquids 19 , 20 and an efficient process that converts lignocellulose into sugar monomers 21 . Despite these advances, an economical, large-scale lignocellulose-to-HMF process has not been demonstrated 17 , 22 . In contrast, the conversion of lignocellulose to furfural is a decades-old industrial process that is currently performed on a scale of about 400 kilotons a year 9 , 22 . Furthermore, several methods are available for oxidizing furfural to 2-furoic acid 23 , 24 . At present, however, the available methods for converting 2-furoic acid into FDCA are inefficient, unselective, and consume stoichiometric amounts of energy-intensive reagents 25 , 26 . CO 3 2– -promoted C–H carboxylation could be used to convert 2-furoic acid into FDCA and thereby open a new route to PEF using a lignocellulose-derived monomer that is already produced industrially. The CO 3 2– -promoted C–H carboxylation reaction required for FDCA synthesis is the conversion of furan-2-carboxylate into furan-2,5-dicarboxylate", "role": "user" }, { "content": "Stanford scientists have discovered a novel way to make plastic from carbon dioxide (CO2) and inedible plant material, such as agricultural waste and grasses. Researchers say the new technology could provide a low-carbon alternative to plastic bottles and other items currently made from petroleum. \"Our goal is to replace petroleum-derived products with plastic made from CO2,\" said Matthew Kanan, an assistant professor of chemistry at Stanford. \"If you could do that without using a lot of non-renewable energy, you could dramatically lower the carbon footprint of the plastics industry.\" Kanan and his Stanford colleagues described their results in the March 9 online edition of the journal Nature. Changing the plastic formula Many plastic products today are made from a polymer called polyethylene terephthalate (PET), also known as polyester. Worldwide, about 50 million tons of PET are produced each year for items such as fabrics, electronics, recyclable beverage containers and personal-care products. PET is made from two components, terephthalic acid and ethylene glycol, which are derived from refined petroleum and natural gas. Manufacturing PET produces significant amounts of CO2, a greenhouse gas that contributes to global warming. \"The use of fossil-fuel feedstocks, combined with the energy required to manufacture PET, generates more than four tons of CO2 for every ton of PET that's produced,\" Kanan said. For the Nature study, he and his co-workers focused on a promising alternative to PET called polyethylene furandicarboxylate (PEF). PEF is made from ethylene glycol and a compound called 2-5-Furandicarboxylic acid (FDCA). \"PEF is an attractive replacement for PET, because FDCA can be sourced from biomass instead of petroleum,\" Kanan said. \"PEF is also superior to PET at sealing out oxygen, which is useful for bottling applications.\" Despite the many desirable attributes of PEF, the plastics industry has yet to find a low-cost way to manufacture it at scale. The bottleneck has been figuring out a commercially viable way to produce FDCA sustainably. One approach is to convert fructose from corn syrup into FDCA. The Dutch firm, Avantium, has been developing that technology in partnership with Coca Cola and other companies. But growing crops for industry requires lots of land, energy, fertilizer and water. \"Using fructose is problematic, because fructose production has a substantial carbon footprint, and, ultimately, you'll be competing with food production,\" Kanan said. \"It would be much better to make FDCA from inedible biomass, like grasses or waste material left over after harvest.\" Turning plant waste into plastic Instead of using sugar from corn to make FDCA, the Stanford team has been experimenting with furfural, a compound made from agricultural waste that has been widely used for decades. About 400,000 tons are produced annually for use in resins, solvents and other products. But making FDCA from furfural and CO2 typically requires hazardous chemicals that are expensive and energy-intensive to make. \"That really defeats the purpose of what we're trying to do,\" Kanan said. The Stanford team solved the problem using a far more benign compound: carbonate. Graduate student Aanindeeta Banerjee, lead author of the Nature study, combined carbonate with CO2 and furoic acid, a derivative of furfural. She then heated the mixture to about 392 degrees Fahrenheit (200 degrees Celsius) to form a molten salt. The results were dramatic. After five hours, 89 percent of the molten-salt mixture had been converted to FDCA. The next step, transforming FDCA into PEF plastic, is a straightforward process that has been worked out by other researchers, Kanan said. Recycled carbon The Stanford team's approach has the potential to significantly reduce greenhouse emissions, Kanan said, because the CO2 required to make PEF could be obtained from fossil-fuel power plant emissions or other industrial sites. Products made of PEF can also be recycled or converted back to atmospheric CO2 by incineration. Eventually, that CO2 will be taken up by grass, weeds and other renewable plants, which can then be used to make more PEF. \"We believe that our chemistry can unlock the promise of PEF that has yet to be realized,\" Kanan said. \"This is just the first step. We need to do a lot of work to see if it's viable at scale and to quantify the carbon footprint.\" Kanan and colleagues have also begun to apply their new chemistry to the production of renewable fuels and other compounds from hydrogen and CO2. \"That's the most exciting new application that we're working on now,\" he said. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Using carbon dioxide (CO 2 ) as a feedstock for commodity synthesis is an attractive means of reducing greenhouse gas emissions and a possible stepping-stone towards renewable synthetic fuels 1 , 2 . A major impediment to synthesizing compounds from CO 2 is the difficulty of forming carbon–carbon (C–C) bonds efficiently: although CO 2 reacts readily with carbon-centred nucleophiles, generating these intermediates requires high-energy reagents (such as highly reducing metals or strong organic bases), carbon–heteroatom bonds or relatively acidic carbon–hydrogen (C–H) bonds 3 , 4 , 5 . These requirements negate the environmental benefit of using CO 2 as a substrate and limit the chemistry to low-volume targets. Here we show that intermediate-temperature (200 to 350 degrees Celsius) molten salts containing caesium or potassium cations enable carbonate ions (CO 3 2– ) to deprotonate very weakly acidic C–H bonds (p K a > 40), generating carbon-centred nucleophiles that react with CO 2 to form carboxylates. To illustrate a potential application, we use C–H carboxylation followed by protonation to convert 2-furoic acid into furan-2,5-dicarboxylic acid (FDCA)—a highly desirable bio-based feedstock 6 with numerous applications, including the synthesis of polyethylene furandicarboxylate (PEF), which is a potential large-scale substitute for petroleum-derived polyethylene terephthalate (PET) 7 , 8 . Since 2-furoic acid can readily be made from lignocellulose 9 , CO 3 2– -promoted C–H carboxylation thus reveals a way to transform inedible biomass and CO 2 into a valuable feedstock chemical. Our results provide a new strategy for using CO 2 in the synthesis of multi-carbon compounds. Main The chemistry described here is inspired by ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), which effects C–C bond formation in the Calvin cycle by deprotonating a C–H bond of ribulose-1,5-bisphosphate and exposing the resulting carbon-centred nucleophile to CO 2 to form a carboxylate (C–CO 2 – ) 10 . Emulating this strategy synthetically requires deprotonating un-activated C–H bonds using a simple base that does not have a large CO 2 footprint. To meet these requirements, we envisioned a CO 3 2– -promoted C–H carboxylation reaction, wherein CO 3 2– reversibly deprotonates a C–H bond to generate HCO 3 – and a carbon-centred nucleophile that reacts with CO 2 to form C–CO 2 – ( Fig. 1a ). HCO 3 – decomposition results in a net consumption of one-half equivalents of CO 3 2– and CO 2 per C–CO 2 – produced. The cycle could be closed by protonating C–CO 2 – with strong acid and using electrodialysis to regenerate the acid and base 11 , 12 , effecting a net transformation of C–H and CO 2 into C–CO 2 H without using any other stoichiometric reagents. Alternatively, CO 2 -promoted esterification could be used to convert the carboxylate into an ester (C–CO 2 R) and regenerate CO 3 2– directly 13 . Previously, researchers have shown that Cs 2 CO 3 can deprotonate alkynyl 14 , allylic 15 , and activated heteroaryl C–H bonds with p K a values of up to 27 (ref. 16 ) in organic solvents at elevated temperature (where p K a is the negative base-10 logarithm of the acid dissociation constant). However, using CO 3 2– -promoted C–H carboxylation for commodity synthesis requires deprotonating C–H bonds that are considerably less acidic. Figure 1: CO 2 utilization cycle. a , C–H deprotonation by CO 3 2– forms a carbon-centred nucleophile (C – ) that reacts with CO 2 to form a C–C bond (red box and arrows). Protonation and electrodialysis (black box and arrows) produces a carboxylic acid. Alternatively, CO 2 -promoted esterification (grey box and arrows) produces an ester. Net transformations are shown in the blue box. b , Potential application for FDCA synthesis from lignocellulose. Current approaches rely on converting lignocellulose into HMF, a difficult reaction that has not been commercialized. C–H carboxylation enables the use of furfural, which has been produced industrially from lignocellulose for many decades. M, metal; R, alkyl group. PowerPoint slide Full size image Carbonate-promoted C–H carboxylation is particularly desirable for the synthesis of polymer units from biomass. A longstanding goal of renewable polymer chemistry is a scalable synthesis of FDCA from lignocellulose to replace petroleum-derived terephthalic acid for polyester synthesis ( Fig. 1b ) 6 . In particular, PEF has been reported to have superior physical properties to PET, a polymer produced at 50 megatons a year as an industrial commodity 8 . Current approaches to FDCA synthesis use dehydration processes to convert hexose sugars into hydroxymethyl furfural (HMF), which is then oxidized to form FDCA 17 . Recent work has improved the efficiency of converting fructose to HMF 8 , 18 and it has been estimated that PEF production from fructose would emit 50% less CO 2 than the established process for PET production 7 . However, producing FDCA on a scale commensurate with terephthalic acid and achieving maximal reduction in CO 2 emissions will require using lignocellulose as the feedstock. Converting lignocellulose into HMF is very challenging because the hexoses are incorporated into intractable cellulose fibres 17 . Researchers have recently reported a high-yielding conversion of lignocellulose to HMF in ionic liquids 19 , 20 and an efficient process that converts lignocellulose into sugar monomers 21 . Despite these advances, an economical, large-scale lignocellulose-to-HMF process has not been demonstrated 17 , 22 . In contrast, the conversion of lignocellulose to furfural is a decades-old industrial process that is currently performed on a scale of about 400 kilotons a year 9 , 22 . Furthermore, several methods are available for oxidizing furfural to 2-furoic acid 23 , 24 . At present, however, the available methods for converting 2-furoic acid into FDCA are inefficient, unselective, and consume stoichiometric amounts of energy-intensive reagents 25 , 26 . CO 3 2– -promoted C–H carboxylation could be used to convert 2-furoic acid into FDCA and thereby open a new route to PEF using a lignocellulose-derived monomer that is already produced industrially. The CO 3 2– -promoted C–H carboxylation reaction required for FDCA synthesis is the conversion of furan-2-carboxylate into furan-2,5-dicarboxylate<|im_end|> <|im_start|>assistant Stanford scientists have discovered a novel way to make plastic from carbon dioxide (CO2) and inedible plant material, such as agricultural waste and grasses. Researchers say the new technology could provide a low-carbon alternative to plastic bottles and other items currently made from petroleum. "Our goal is to replace petroleum-derived products with plastic made from CO2," said Matthew Kanan, an assistant professor of chemistry at Stanford. "If you could do that without using a lot of non-renewable energy, you could dramatically lower the carbon footprint of the plastics industry." Kanan and his Stanford colleagues described their results in the March 9 online edition of the journal Nature. Changing the plastic formula Many plastic products today are made from a polymer called polyethylene terephthalate (PET), also known as polyester. Worldwide, about 50 million tons of PET are produced each year for items such as fabrics, electronics, recyclable beverage containers and personal-care products. PET is made from two components, terephthalic acid and ethylene glycol, which are derived from refined petroleum and natural gas. Manufacturing PET produces significant amounts of CO2, a greenhouse gas that contributes to global warming. "The use of fossil-fuel feedstocks, combined with the energy required to manufacture PET, generates more than four tons of CO2 for every ton of PET that's produced," Kanan said. For the Nature study, he and his co-workers focused on a promising alternative to PET called polyethylene furandicarboxylate (PEF). PEF is made from ethylene glycol and a compound called 2-5-Furandicarboxylic acid (FDCA). "PEF is an attractive replacement for PET, because FDCA can be sourced from biomass instead of petroleum," Kanan said. "PEF is also superior to PET at sealing out oxygen, which is useful for bottling applications." Despite the many desirable attributes of PEF, the plastics industry has yet to find a low-cost way to manufacture it at scale. The bottleneck has been figuring out a commercially viable way to produce FDCA sustainably. One approach is to convert fructose from corn syrup into FDCA. The Dutch firm, Avantium, has been developing that technology in partnership with Coca Cola and other companies. But growing crops for industry requires lots of land, energy, fertilizer and water. "Using fructose is problematic, because fructose production has a substantial carbon footprint, and, ultimately, you'll be competing with food production," Kanan said. "It would be much better to make FDCA from inedible biomass, like grasses or waste material left over after harvest." Turning plant waste into plastic Instead of using sugar from corn to make FDCA, the Stanford team has been experimenting with furfural, a compound made from agricultural waste that has been widely used for decades. About 400,000 tons are produced annually for use in resins, solvents and other products. But making FDCA from furfural and CO2 typically requires hazardous chemicals that are expensive and energy-intensive to make. "That really defeats the purpose of what we're trying to do," Kanan said. The Stanford team solved the problem using a far more benign compound: carbonate. Graduate student Aanindeeta Banerjee, lead author of the Nature study, combined carbonate with CO2 and furoic acid, a derivative of furfural. She then heated the mixture to about 392 degrees Fahrenheit (200 degrees Celsius) to form a molten salt. The results were dramatic. After five hours, 89 percent of the molten-salt mixture had been converted to FDCA. The next step, transforming FDCA into PEF plastic, is a straightforward process that has been worked out by other researchers, Kanan said. Recycled carbon The Stanford team's approach has the potential to significantly reduce greenhouse emissions, Kanan said, because the CO2 required to make PEF could be obtained from fossil-fuel power plant emissions or other industrial sites. Products made of PEF can also be recycled or converted back to atmospheric CO2 by incineration. Eventually, that CO2 will be taken up by grass, weeds and other renewable plants, which can then be used to make more PEF. "We believe that our chemistry can unlock the promise of PEF that has yet to be realized," Kanan said. "This is just the first step. We need to do a lot of work to see if it's viable at scale and to quantify the carbon footprint." Kanan and colleagues have also begun to apply their new chemistry to the production of renewable fuels and other compounds from hydrogen and CO2. "That's the most exciting new application that we're working on now," he said. <|im_end|>

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2,623

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Organic agriculture is proposed as a promising approach to achieving sustainable food systems, but its feasibility is also contested. We use a food systems model that addresses agronomic characteristics of organic agriculture to analyze the role that organic agriculture could play in sustainable food systems. Here we show that a 100% conversion to organic agriculture needs more land than conventional agriculture but reduces N-surplus and pesticide use. However, in combination with reductions of food wastage and food-competing feed from arable land, with correspondingly reduced production and consumption of animal products, land use under organic agriculture remains below the reference scenario. Other indicators such as greenhouse gas emissions also improve, but adequate nitrogen supply is challenging. Besides focusing on production, sustainable food systems need to address waste, crop–grass–livestock interdependencies and human consumption. None of the corresponding strategies needs full implementation and their combined partial implementation delivers a more sustainable food future. Introduction Intensification of agriculture has greatly increased food availability over recent decades. However, this has led to considerable adverse environmental impacts, such as increases in reactive nitrogen over-supply, eutrophication of land and water bodies, greenhouse gas (GHG) emissions and biodiversity losses 1 , 2 , 3 , 4 , 5 , 6 . It is commonly assumed that by 2050, agricultural output will have to further increase by 50% to feed the projected global population of over 9 billion 7 . This challenge is further exacerbated by changing dietary patterns. It is, therefore, crucial to curb the negative environmental impacts of agriculture, while ensuring that the same quantity of food can be delivered. There are many proposals for achieving this goal, such as further increasing efficiency in production and resource use, or adopting holistic approaches such as agroecology and organic production, or reducing consumption of animal products and food wastage 8 , 9 , 10 , 11 . Organic agriculture is one concrete, but controversial, suggestion for improving the sustainability of food systems. It refrains from using synthetic fertilizers and pesticides, promotes crop rotations and focuses on soil fertility and closed nutrient cycles 4 , 12 . The positive performance of organic agriculture when measured against a range of environmental indicators has been widely reported 13 , 14 , 15 , 16 . However, organic systems produce lower yields 17 and thus require larger land areas to produce the same output as conventional production systems. In consequence, environmental benefits of organic agriculture are less pronounced or even absent if measured per unit of product than per unit of area 14 , 18 . Furthermore, abandoning synthetic N-fertilizers could lead to nutrient undersupply, even with increased legume cropping 19 . As a consequence, the ability of organic agriculture to feed the world sustainably has been challenged 19 , 20 . Some authors contribute to the discussion on lower yields in organic agriculture by considering nutrient availability, but none of these provide a robust analysis of nutrient availability in organic production systems 19 , 20 , 21 . In addition, these studies do not pursue a detailed food systems approach, and do not address the role that animal feeding regimes, consumption trends and food wastage (i.e. food loss and waste) may play—all of which represent factors for strategies that could substantially reduce land demand, while alleviating environmental impacts and contributing to global food availability 2 , 10 , 22 , 23 , 24 , 25 , 26 . We address this research gap by taking a food systems approach that goes beyond a focus on production, yields and environmental impacts per unit output of specific commodities. We first investigate the impacts of a conversion to organic agriculture on a range of environmental and production indicators. We then complement this scenario of organic conversion with two additional changes to the food system, namely (a) reductions of livestock feed from arable land (i.e. food-competing feed) with corresponding reductions in animal numbers and products supply (and thus human consumption) and in related natural resource use and environmental impacts 25 , 26 ; and (b) reductions of food wastage, with correspondingly reduced production levels and impacts 10 . Our leading research question is whether producing a certain total amount of food, in terms of protein and calories, with organic agriculture would lead to higher, or lower, impacts than producing the same amount of food with conventional agriculture. We then assess whether, and to which extent a combination of organic agriculture with the two other strategies mentioned above may contribute to mitigating potential adverse effects of a conversion to organic production. We thus assess the contexts in terms of complementary food system changes in which a conversion to organic agriculture may contribute to more sustainable food systems. Despite the availability of a number of global models to assess various aspects of food production and consumption, few are able to consider organic production 22 , 27 and so far, none have captured the main agronomic characteristics of organic agriculture in a systematic way. We apply the SOL-model 26 which is able to simulate important aspects of organic agriculture, such as increased legume shares, absence of synthetic fertilizers, lower yields (the ‘yield gap’) and lower use of food-competing feed components, such as grain legumes or cereals. The SOL-model is a mass-flow model of the global food system, which is built to cover physical and biological aspects at country level for a large number of commodities, thus allowing assessment and comparison of the physical viability and impacts of different scenarios. The SOL-model explicitly does not cover decisions of farmers and consumers, and price and market effects in an economic sense. The purpose is rather to examine the option space spanned by combining a number of food-system level strategies for increased sustainability, and to assess the potential and contribution of these strategies, and their combinations, towards increased sustainability in food systems. This assessment is undertaken with and without impacts of climate change on yields, to also assess the performance of these strategies under climate change (we refer to the Methods", "role": "user" }, { "content": "Agriculture could go organic worldwide if we slashed food waste and stopped using so much cropland to feed livestock, a new study finds. The analysis, published in the journal Nature Communications, shows that it will take several strategies operating at once to feed the growing human population in a more sustainable way - and some of those strategies may require people to shift their dietary patterns, too. The world's population is expected to hit 9.8 billion by 2050, which means an extra 2 billion or so mouths to feed. This will require increasing agricultural output by an additional 50 percent, the study authors wrote - which is made an even greater challenge as dietary patterns have been changing and the demand for meat has been rising. (Raising livestock leaves a large carbon and water footprint relative to growing plant-based foods.) All of this puts an additional strain on an already taxed environment. \"It is, therefore, crucial to curb the negative environmental impacts of agriculture, while ensuring that the same quantity of food can be delivered,\" the study authors wrote. Experts have thrown out several strategies to deal with the impending food security problem, without coming to a clear agreement on which one would be best. Among the options: improving efficiencies in producing crops and using resources; reducing food waste; cutting down the animal products we eat; or resorting to more organic agriculture. \"Organic agriculture is one concrete, but controversial, suggestion for improving the sustainability of food systems,\" the study authors wrote. \"It refrains from using synthetic fertilizers and pesticides, promotes crop rotations and focuses on soil fertility and closed nutrient cycles.\" Regardless of whether organic fruits, vegetables and other crops are better for you, there's evidence showing they may be better for the environment. Since organically grown crops can't use synthetic nitrogen fertilizer, it means that less excess nitrogen acidifies the soil and ends up in waterways, or escapes into the air as a greenhouse gas. It also means no man-made pesticides, meaning fewer chemicals in the local environment and less risk to insect biodiversity - which is important because many insects are crucial players in their local ecosystems. But those benefits are offset somewhat by what's known as the yield gap: the idea that organic crops require more land because their yields are lower than the fertilizer-fed, pesticide-protected conventional crops - potentially resulting in some extra deforestation. Still, could organic crops allow future food needs to be met with less environmental impact? \"Because of the yield gap, there are opposing voices that say it's not possible ... (and) there are proponents that say this yield gap is not really important and one could overcome it,\" said lead author Adrian Muller, an environmental systems scientist at the Research Institute of Organic Agriculture in Switzerland. \"We just wanted to look at it from a food-systems perspective, because we think only looking at the yield gap is not enough. It is important to really look at production and consumption together and to see what organic agriculture can contribute on such a food-systems level.\" To find out, Muller and colleagues developed models based on data from the Food and Agriculture Organization of the United Nations, looking at the effects that going organic would have under different scenarios, modulating the severity of climate change, the amount of food waste and the share of crops used to feed livestock instead of people, for example. The researchers found that the human population's needs could be fully met by all-organic agriculture - but only if food waste was cut in half and the competing feed sources for livestock were eliminated altogether. Since that would seriously scale back the amount of livestock, that might be a hard sell with today's meat-filled diets. Muller said a more feasible solution might be one where organic crops make up about 50 percent of crops, food waste is cut by half, and the competing feed sources are cut by half (allowing for more acreage to grow human food). \"We need to utilize all the potential strategies we have, without supporting one extreme and leaving out other approaches,\" he said. Getting to that point may still be a challenge. Organic crops make up a tiny fraction of agriculture overall, nowhere near that 50 percent target. But there are some things that can be done now, Muller pointed out, such as putting an extra \"nitrogen tax\" on producers so that the environmental cost of excess fertilizer becomes an economic one. \"I think we are moving in the right direction,\" Muller said, \"and as an optimist I think, yeah, somehow, it will work.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Organic agriculture is proposed as a promising approach to achieving sustainable food systems, but its feasibility is also contested. We use a food systems model that addresses agronomic characteristics of organic agriculture to analyze the role that organic agriculture could play in sustainable food systems. Here we show that a 100% conversion to organic agriculture needs more land than conventional agriculture but reduces N-surplus and pesticide use. However, in combination with reductions of food wastage and food-competing feed from arable land, with correspondingly reduced production and consumption of animal products, land use under organic agriculture remains below the reference scenario. Other indicators such as greenhouse gas emissions also improve, but adequate nitrogen supply is challenging. Besides focusing on production, sustainable food systems need to address waste, crop–grass–livestock interdependencies and human consumption. None of the corresponding strategies needs full implementation and their combined partial implementation delivers a more sustainable food future. Introduction Intensification of agriculture has greatly increased food availability over recent decades. However, this has led to considerable adverse environmental impacts, such as increases in reactive nitrogen over-supply, eutrophication of land and water bodies, greenhouse gas (GHG) emissions and biodiversity losses 1 , 2 , 3 , 4 , 5 , 6 . It is commonly assumed that by 2050, agricultural output will have to further increase by 50% to feed the projected global population of over 9 billion 7 . This challenge is further exacerbated by changing dietary patterns. It is, therefore, crucial to curb the negative environmental impacts of agriculture, while ensuring that the same quantity of food can be delivered. There are many proposals for achieving this goal, such as further increasing efficiency in production and resource use, or adopting holistic approaches such as agroecology and organic production, or reducing consumption of animal products and food wastage 8 , 9 , 10 , 11 . Organic agriculture is one concrete, but controversial, suggestion for improving the sustainability of food systems. It refrains from using synthetic fertilizers and pesticides, promotes crop rotations and focuses on soil fertility and closed nutrient cycles 4 , 12 . The positive performance of organic agriculture when measured against a range of environmental indicators has been widely reported 13 , 14 , 15 , 16 . However, organic systems produce lower yields 17 and thus require larger land areas to produce the same output as conventional production systems. In consequence, environmental benefits of organic agriculture are less pronounced or even absent if measured per unit of product than per unit of area 14 , 18 . Furthermore, abandoning synthetic N-fertilizers could lead to nutrient undersupply, even with increased legume cropping 19 . As a consequence, the ability of organic agriculture to feed the world sustainably has been challenged 19 , 20 . Some authors contribute to the discussion on lower yields in organic agriculture by considering nutrient availability, but none of these provide a robust analysis of nutrient availability in organic production systems 19 , 20 , 21 . In addition, these studies do not pursue a detailed food systems approach, and do not address the role that animal feeding regimes, consumption trends and food wastage (i.e. food loss and waste) may play—all of which represent factors for strategies that could substantially reduce land demand, while alleviating environmental impacts and contributing to global food availability 2 , 10 , 22 , 23 , 24 , 25 , 26 . We address this research gap by taking a food systems approach that goes beyond a focus on production, yields and environmental impacts per unit output of specific commodities. We first investigate the impacts of a conversion to organic agriculture on a range of environmental and production indicators. We then complement this scenario of organic conversion with two additional changes to the food system, namely (a) reductions of livestock feed from arable land (i.e. food-competing feed) with corresponding reductions in animal numbers and products supply (and thus human consumption) and in related natural resource use and environmental impacts 25 , 26 ; and (b) reductions of food wastage, with correspondingly reduced production levels and impacts 10 . Our leading research question is whether producing a certain total amount of food, in terms of protein and calories, with organic agriculture would lead to higher, or lower, impacts than producing the same amount of food with conventional agriculture. We then assess whether, and to which extent a combination of organic agriculture with the two other strategies mentioned above may contribute to mitigating potential adverse effects of a conversion to organic production. We thus assess the contexts in terms of complementary food system changes in which a conversion to organic agriculture may contribute to more sustainable food systems. Despite the availability of a number of global models to assess various aspects of food production and consumption, few are able to consider organic production 22 , 27 and so far, none have captured the main agronomic characteristics of organic agriculture in a systematic way. We apply the SOL-model 26 which is able to simulate important aspects of organic agriculture, such as increased legume shares, absence of synthetic fertilizers, lower yields (the ‘yield gap’) and lower use of food-competing feed components, such as grain legumes or cereals. The SOL-model is a mass-flow model of the global food system, which is built to cover physical and biological aspects at country level for a large number of commodities, thus allowing assessment and comparison of the physical viability and impacts of different scenarios. The SOL-model explicitly does not cover decisions of farmers and consumers, and price and market effects in an economic sense. The purpose is rather to examine the option space spanned by combining a number of food-system level strategies for increased sustainability, and to assess the potential and contribution of these strategies, and their combinations, towards increased sustainability in food systems. This assessment is undertaken with and without impacts of climate change on yields, to also assess the performance of these strategies under climate change (we refer to the Methods<|im_end|> <|im_start|>assistant Agriculture could go organic worldwide if we slashed food waste and stopped using so much cropland to feed livestock, a new study finds. The analysis, published in the journal Nature Communications, shows that it will take several strategies operating at once to feed the growing human population in a more sustainable way - and some of those strategies may require people to shift their dietary patterns, too. The world's population is expected to hit 9.8 billion by 2050, which means an extra 2 billion or so mouths to feed. This will require increasing agricultural output by an additional 50 percent, the study authors wrote - which is made an even greater challenge as dietary patterns have been changing and the demand for meat has been rising. (Raising livestock leaves a large carbon and water footprint relative to growing plant-based foods.) All of this puts an additional strain on an already taxed environment. "It is, therefore, crucial to curb the negative environmental impacts of agriculture, while ensuring that the same quantity of food can be delivered," the study authors wrote. Experts have thrown out several strategies to deal with the impending food security problem, without coming to a clear agreement on which one would be best. Among the options: improving efficiencies in producing crops and using resources; reducing food waste; cutting down the animal products we eat; or resorting to more organic agriculture. "Organic agriculture is one concrete, but controversial, suggestion for improving the sustainability of food systems," the study authors wrote. "It refrains from using synthetic fertilizers and pesticides, promotes crop rotations and focuses on soil fertility and closed nutrient cycles." Regardless of whether organic fruits, vegetables and other crops are better for you, there's evidence showing they may be better for the environment. Since organically grown crops can't use synthetic nitrogen fertilizer, it means that less excess nitrogen acidifies the soil and ends up in waterways, or escapes into the air as a greenhouse gas. It also means no man-made pesticides, meaning fewer chemicals in the local environment and less risk to insect biodiversity - which is important because many insects are crucial players in their local ecosystems. But those benefits are offset somewhat by what's known as the yield gap: the idea that organic crops require more land because their yields are lower than the fertilizer-fed, pesticide-protected conventional crops - potentially resulting in some extra deforestation. Still, could organic crops allow future food needs to be met with less environmental impact? "Because of the yield gap, there are opposing voices that say it's not possible ... (and) there are proponents that say this yield gap is not really important and one could overcome it," said lead author Adrian Muller, an environmental systems scientist at the Research Institute of Organic Agriculture in Switzerland. "We just wanted to look at it from a food-systems perspective, because we think only looking at the yield gap is not enough. It is important to really look at production and consumption together and to see what organic agriculture can contribute on such a food-systems level." To find out, Muller and colleagues developed models based on data from the Food and Agriculture Organization of the United Nations, looking at the effects that going organic would have under different scenarios, modulating the severity of climate change, the amount of food waste and the share of crops used to feed livestock instead of people, for example. The researchers found that the human population's needs could be fully met by all-organic agriculture - but only if food waste was cut in half and the competing feed sources for livestock were eliminated altogether. Since that would seriously scale back the amount of livestock, that might be a hard sell with today's meat-filled diets. Muller said a more feasible solution might be one where organic crops make up about 50 percent of crops, food waste is cut by half, and the competing feed sources are cut by half (allowing for more acreage to grow human food). "We need to utilize all the potential strategies we have, without supporting one extreme and leaving out other approaches," he said. Getting to that point may still be a challenge. Organic crops make up a tiny fraction of agriculture overall, nowhere near that 50 percent target. But there are some things that can be done now, Muller pointed out, such as putting an extra "nitrogen tax" on producers so that the environmental cost of excess fertilizer becomes an economic one. "I think we are moving in the right direction," Muller said, "and as an optimist I think, yeah, somehow, it will work." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Aggregation of amyloid-β peptides into fibrils or other self-assembled states is central to the pathogenesis of Alzheimer’s disease. Fibrils formed in vitro by 40- and 42-residue amyloid-β peptides (Aβ40 and Aβ42) are polymorphic, with variations in molecular structure that depend on fibril growth conditions 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 . Recent experiments 1 , 13 , 14 , 15 , 16 suggest that variations in amyloid-β fibril structure in vivo may correlate with variations in Alzheimer’s disease phenotype, in analogy to distinct prion strains that are associated with different clinical and pathological phenotypes 17 , 18 , 19 . Here we investigate correlations between structural variation and Alzheimer’s disease phenotype using solid-state nuclear magnetic resonance (ssNMR) measurements on Aβ40 and Aβ42 fibrils prepared by seeded growth from extracts of Alzheimer’s disease brain cortex. We compared two atypical Alzheimer’s disease clinical subtypes—the rapidly progressive form (r-AD) and the posterior cortical atrophy variant (PCA-AD)—with a typical prolonged-duration form (t-AD). On the basis of ssNMR data from 37 cortical tissue samples from 18 individuals, we find that a single Aβ40 fibril structure is most abundant in samples from patients with t-AD and PCA-AD, whereas Aβ40 fibrils from r-AD samples exhibit a significantly greater proportion of additional structures. Data for Aβ42 fibrils indicate structural heterogeneity in most samples from all patient categories, with at least two prevalent structures. These results demonstrate the existence of a specific predominant Aβ40 fibril structure in t-AD and PCA-AD, suggest that r-AD may relate to additional fibril structures and indicate that there is a qualitative difference between Aβ40 and Aβ42 aggregates in the brain tissue of patients with Alzheimer’s disease. Main There is a range of evidence that amyloid-β fibril polymorphism may correlate with variations in clinical and pathological features of Alzheimer’s disease. First, Aβ40 fibrils with different molecular structures exhibit different levels of toxicity in primary neuronal cell cultures 1 . Second, patterns of amyloid deposition in transgenic mice, induced by exogenous amyloid-containing biological material, vary with the source of this material 13 , 14 . Third, the size and composition of amyloid plaques induced in transgenic mice by synthetic Aβ42 fibrils depend on the morphology and growth conditions of these fibrils 15 . Fourth, the size distributions and resistance to chemical denaturation of Aβ42 aggregates in brain tissue differ between patients with rapidly progressing and slowly progressing Alzheimer’s disease 16 . Improved characterization of the structures of neurotoxic amyloid-β assemblies in Alzheimer’s disease and of correlations between structure and disease phenotype would have a major impact on our understanding of pathogenesis, on the development of appropriate diagnostic and therapeutic biomarkers, and on drug development. Data from ssNMR are particularly sensitive to structural variations, allowing 2D 13 C– 13 C and 15 N– 13 C ssNMR spectra to be used as ‘fingerprints’ of specific fibril polymorphs 1 , 4 , 20 , 21 . Since ssNMR requires milligram-scale quantities of isotopically labelled fibrils, we amplified and labelled structures in brain tissue by seeded growth, using brain tissue as the source of fibril seeds, as described previously 4 . In prion diseases, different strains produce different durations of illness, preferentially target different brain regions and are associated with conformational differences in disease-related prion proteins 17 , 18 , 19 , 22 . By analogy, we selected tissue samples from patients from two unusual Alzheimer’s disease subtypes: PCA-AD, which is associated with disruption of visual processing 23 ; and r-AD, in which neurodegeneration occurs within months and which clinically resembles Creutzfeldt–Jakob disease 24 . We also included tissue from three individuals who died without dementia but who were nevertheless found to have amyloid-β deposition at autopsy. We prepared Aβ40 and Aβ42 fibrils separately by seeded growth from amyloid-enriched cortical extracts. Transmission electron microscope (TEM) images were acquired and ssNMR measurements attempted for all fibril samples, although in some cases the signal-to-noise ratios in ssNMR data were insufficient for acquisition or subsequent analysis of 2D spectra. Table 1 summarizes the tissue samples, patient categories, and ssNMR measurements. Examples of TEM images and full sets of 2D spectra are given in Extended Data Figs 1 , 2 , 3 . Control experiments using cortical extracts from a patient without Alzheimer’s disease or substantial amyloid-β deposition are described in the Supplementary Discussion and Extended Data Fig. 4 . Table 1 Summary of brain tissue samples and 2D ssNMR data Full size table Figure 1 shows representative data for Aβ40 fibrils. In TEM images ( Fig. 1a and Extended Data Fig. 1 ), certain fibrils exhibit modulations of their apparent width with a period of 107 ± 20 nm (mean ± s.d. from 65 measurements). This fibril morphology may be more abundant in images of Aβ40 fibrils derived from t-AD and PCA-AD tissue samples. However, quantification of the relative populations of fibril polymorphs from the TEM images is not possible because only a small subset of the fibrils can be visualized clearly. By contrast, all fibrils contribute to the 2D ssNMR spectra. Most 2D spectra of brain-seeded Aβ40 fibrils contain the same set of strong cross-peak signals, indicated by assignments to the isotopically labelled residues in Fig. 1b, c , although spectra of certain samples contain additional cross-peak signals with varying intensities. Figure 1: Representative TEM images and 2D ssNMR spectra of brain-seeded Aβ40 fibrils. a , Images of negatively-stained fibrils derived from t-AD3f, PCA1o, and r-AD1f tissue, recorded 4 h after initiation of seeded fibril growth (representative of 37 fibril samples). Single-headed arrows indicate the periodic modulation of apparent fibril width in a common Aβ40 fibril morphology. Double-headed arrows indicate an additional morphology. b , Aliphatic regions of 2D 13 C– 13 C spectra of the same samples (colour-coded as in a ), with assignments of cross-peak signals to isotopically labelled residues shown in the 2D spectrum of t-AD3f fibrils. Aβ40 was uniformly 15 N– 13 C-labelled at residues F19, V24, G25, S26, A30,", "role": "user" }, { "content": "(Medical Xpress)—A team of researchers working at the National Institutes of Health in the U.S. and the University College London Institute of Neurology in the U.K. has found what appears to be a correlation between fibril formation types in the brain and Alzheimer's subtypes. In their paper published in the journal Nature, the team describes their examination of the brains of deceased Alzheimer's patients and what they found by comparing amyloid-beta peptide deposits with progression types. One of the physical hallmarks of Alzheimer's disease is the development of amyloid-beta peptide deposits in brain tissue leading to the creation of fibrils. Prior research has shown that such fibrils in patients can vary in shape and size between people to the degree that subtypes have been identified. In this new effort, the researchers sought to find out if certain subtypes could be associated with certain types of disease progression—in this case, rapidly progressive and posterior cortical atrophy, which causes problems with visual processing. To learn more, the researchers obtained 37 brain samples from 18 deceased Alzheimer's patients, some of whom had been diagnosed with typical symptoms, some with rapid progression and some with posterior cortical atrophy, and then compared the types of fibrils found (using solid-state NMR spectroscopy) with the three progression types—a very labor intensive, year-long process, which is why the sample numbers were low. In so doing, they found that patients with typical symptoms and those with posterior cortical atrophy had similar fibril formations in their brains, whereas those with rapidly progressive Alzheimer's had fibrils that were not only different from those with typical symptoms, but from others with the same progressive condition. The researchers suggest their findings indicate that fibril subtypes can be correlated with progression types in patients with Alzheimer's disease, and that there might be different processes involved in fibril formation. However, they note the mechanism responsible for the differences is still unknown. They also suggest that as more is learned about Alzheimer's subtypes, new customized diagnostic tests and therapies might be developed to target specific kinds of fibril formations, helping to slow the progression of the still incurable disease for patients regardless of their progression type. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Aggregation of amyloid-β peptides into fibrils or other self-assembled states is central to the pathogenesis of Alzheimer’s disease. Fibrils formed in vitro by 40- and 42-residue amyloid-β peptides (Aβ40 and Aβ42) are polymorphic, with variations in molecular structure that depend on fibril growth conditions 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 . Recent experiments 1 , 13 , 14 , 15 , 16 suggest that variations in amyloid-β fibril structure in vivo may correlate with variations in Alzheimer’s disease phenotype, in analogy to distinct prion strains that are associated with different clinical and pathological phenotypes 17 , 18 , 19 . Here we investigate correlations between structural variation and Alzheimer’s disease phenotype using solid-state nuclear magnetic resonance (ssNMR) measurements on Aβ40 and Aβ42 fibrils prepared by seeded growth from extracts of Alzheimer’s disease brain cortex. We compared two atypical Alzheimer’s disease clinical subtypes—the rapidly progressive form (r-AD) and the posterior cortical atrophy variant (PCA-AD)—with a typical prolonged-duration form (t-AD). On the basis of ssNMR data from 37 cortical tissue samples from 18 individuals, we find that a single Aβ40 fibril structure is most abundant in samples from patients with t-AD and PCA-AD, whereas Aβ40 fibrils from r-AD samples exhibit a significantly greater proportion of additional structures. Data for Aβ42 fibrils indicate structural heterogeneity in most samples from all patient categories, with at least two prevalent structures. These results demonstrate the existence of a specific predominant Aβ40 fibril structure in t-AD and PCA-AD, suggest that r-AD may relate to additional fibril structures and indicate that there is a qualitative difference between Aβ40 and Aβ42 aggregates in the brain tissue of patients with Alzheimer’s disease. Main There is a range of evidence that amyloid-β fibril polymorphism may correlate with variations in clinical and pathological features of Alzheimer’s disease. First, Aβ40 fibrils with different molecular structures exhibit different levels of toxicity in primary neuronal cell cultures 1 . Second, patterns of amyloid deposition in transgenic mice, induced by exogenous amyloid-containing biological material, vary with the source of this material 13 , 14 . Third, the size and composition of amyloid plaques induced in transgenic mice by synthetic Aβ42 fibrils depend on the morphology and growth conditions of these fibrils 15 . Fourth, the size distributions and resistance to chemical denaturation of Aβ42 aggregates in brain tissue differ between patients with rapidly progressing and slowly progressing Alzheimer’s disease 16 . Improved characterization of the structures of neurotoxic amyloid-β assemblies in Alzheimer’s disease and of correlations between structure and disease phenotype would have a major impact on our understanding of pathogenesis, on the development of appropriate diagnostic and therapeutic biomarkers, and on drug development. Data from ssNMR are particularly sensitive to structural variations, allowing 2D 13 C– 13 C and 15 N– 13 C ssNMR spectra to be used as ‘fingerprints’ of specific fibril polymorphs 1 , 4 , 20 , 21 . Since ssNMR requires milligram-scale quantities of isotopically labelled fibrils, we amplified and labelled structures in brain tissue by seeded growth, using brain tissue as the source of fibril seeds, as described previously 4 . In prion diseases, different strains produce different durations of illness, preferentially target different brain regions and are associated with conformational differences in disease-related prion proteins 17 , 18 , 19 , 22 . By analogy, we selected tissue samples from patients from two unusual Alzheimer’s disease subtypes: PCA-AD, which is associated with disruption of visual processing 23 ; and r-AD, in which neurodegeneration occurs within months and which clinically resembles Creutzfeldt–Jakob disease 24 . We also included tissue from three individuals who died without dementia but who were nevertheless found to have amyloid-β deposition at autopsy. We prepared Aβ40 and Aβ42 fibrils separately by seeded growth from amyloid-enriched cortical extracts. Transmission electron microscope (TEM) images were acquired and ssNMR measurements attempted for all fibril samples, although in some cases the signal-to-noise ratios in ssNMR data were insufficient for acquisition or subsequent analysis of 2D spectra. Table 1 summarizes the tissue samples, patient categories, and ssNMR measurements. Examples of TEM images and full sets of 2D spectra are given in Extended Data Figs 1 , 2 , 3 . Control experiments using cortical extracts from a patient without Alzheimer’s disease or substantial amyloid-β deposition are described in the Supplementary Discussion and Extended Data Fig. 4 . Table 1 Summary of brain tissue samples and 2D ssNMR data Full size table Figure 1 shows representative data for Aβ40 fibrils. In TEM images ( Fig. 1a and Extended Data Fig. 1 ), certain fibrils exhibit modulations of their apparent width with a period of 107 ± 20 nm (mean ± s.d. from 65 measurements). This fibril morphology may be more abundant in images of Aβ40 fibrils derived from t-AD and PCA-AD tissue samples. However, quantification of the relative populations of fibril polymorphs from the TEM images is not possible because only a small subset of the fibrils can be visualized clearly. By contrast, all fibrils contribute to the 2D ssNMR spectra. Most 2D spectra of brain-seeded Aβ40 fibrils contain the same set of strong cross-peak signals, indicated by assignments to the isotopically labelled residues in Fig. 1b, c , although spectra of certain samples contain additional cross-peak signals with varying intensities. Figure 1: Representative TEM images and 2D ssNMR spectra of brain-seeded Aβ40 fibrils. a , Images of negatively-stained fibrils derived from t-AD3f, PCA1o, and r-AD1f tissue, recorded 4 h after initiation of seeded fibril growth (representative of 37 fibril samples). Single-headed arrows indicate the periodic modulation of apparent fibril width in a common Aβ40 fibril morphology. Double-headed arrows indicate an additional morphology. b , Aliphatic regions of 2D 13 C– 13 C spectra of the same samples (colour-coded as in a ), with assignments of cross-peak signals to isotopically labelled residues shown in the 2D spectrum of t-AD3f fibrils. Aβ40 was uniformly 15 N– 13 C-labelled at residues F19, V24, G25, S26, A30,<|im_end|> <|im_start|>assistant (Medical Xpress)—A team of researchers working at the National Institutes of Health in the U.S. and the University College London Institute of Neurology in the U.K. has found what appears to be a correlation between fibril formation types in the brain and Alzheimer's subtypes. In their paper published in the journal Nature, the team describes their examination of the brains of deceased Alzheimer's patients and what they found by comparing amyloid-beta peptide deposits with progression types. One of the physical hallmarks of Alzheimer's disease is the development of amyloid-beta peptide deposits in brain tissue leading to the creation of fibrils. Prior research has shown that such fibrils in patients can vary in shape and size between people to the degree that subtypes have been identified. In this new effort, the researchers sought to find out if certain subtypes could be associated with certain types of disease progression—in this case, rapidly progressive and posterior cortical atrophy, which causes problems with visual processing. To learn more, the researchers obtained 37 brain samples from 18 deceased Alzheimer's patients, some of whom had been diagnosed with typical symptoms, some with rapid progression and some with posterior cortical atrophy, and then compared the types of fibrils found (using solid-state NMR spectroscopy) with the three progression types—a very labor intensive, year-long process, which is why the sample numbers were low. In so doing, they found that patients with typical symptoms and those with posterior cortical atrophy had similar fibril formations in their brains, whereas those with rapidly progressive Alzheimer's had fibrils that were not only different from those with typical symptoms, but from others with the same progressive condition. The researchers suggest their findings indicate that fibril subtypes can be correlated with progression types in patients with Alzheimer's disease, and that there might be different processes involved in fibril formation. However, they note the mechanism responsible for the differences is still unknown. They also suggest that as more is learned about Alzheimer's subtypes, new customized diagnostic tests and therapies might be developed to target specific kinds of fibril formations, helping to slow the progression of the still incurable disease for patients regardless of their progression type. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract If crystallization can be avoided during cooling, a liquid will display a substantial increase of its viscosity, and will form a glass that behaves as a solid with a relaxation time that grows exponentially with decreasing temperature. Given this ‘off-equilibrium’ nature, a hysteresis loop appears when a cooling/heating cycle is performed across the glass transition. Here we report on molecular dynamics simulations of densified glass-forming liquids that follow this kind of cycle. Over a finite pressure interval, minuscule thermal changes are found, revealing glasses of ‘thermally reversible’ character with optimal volumetric or enthalpic recovery. By analysing the topology of the atomic network structure, we find that corresponding liquids adapt under the pressure-induced increasing stress by experiencing larger bond-angle excursions. The analysis of the dynamic behaviour reveals that the structural relaxation time is substantially reduced in these adaptive liquids, and also drives the reversible character of the glass transition. Ultimately, the results substantiate the notion of stress-free (Maxwell isostatic) rigidity in disordered molecular systems, while also revealing new implications for the topological engineering of complex materials. Introduction Certain materials, when cooled fast enough through their melting point, can remain in a metastable supercooled state and, upon further cooling, can eventually freeze into a glass at a reference temperature T g , which is usually associated 1 , 2 with a viscosity of 10 12 Pa s or a relaxation time of 100 s. As the temperature of the liquid is lowered, viscosity and the relaxation time towards thermodynamic equilibrium will increase markedly. However, even in the obtained glassy state, the material will continue to relax to a lower energy state but on timescales that exceed the laboratory timescale by several orders of magnitude. To track such subtle effects, one conventionally uses calorimetry to measure the heat capacity of the glass and the liquid, and with heating a hysteresis loop appears 3 , 4 , causing a heat capacity overshoot at the glass transition. This endotherm peak simply reveals that previously frozen degrees of freedom during the quench are now excited, so that the overshoot is a direct manifestation of the relaxation taking place between room temperature and T g . Here we show by using molecular dynamics (MD) simulations that for a fixed cooling/heating rate this hysteresis can be minuscule under certain thermodynamic conditions, and defines a calorimetric reversibility window (RW) and a volume recovery window, while also underscoring an obvious anomalous relaxation behaviour that is characterized. A direct connection is made with the softening of bond angles at the molecular level, which adapt under the pressure-driven increasing stress leading to a growth of the atomic coordination numbers, and network connectivity. It is found that such ‘thermally reversible’ glasses are stress-free, and bear striking similarities with calorimetric anomalies in modified glassy alloys, while also satisfying the well-known Maxwell stability criterion of isostatic mechanical structures 5 , 6 , and displaying anomalous relaxation dynamics in the supercooled regime. These findings open the possibility to use stress-free rigidity for the design of a variety of functionalities in disordered materials, an original perspective that is directly derived from basic findings, and which has inspired the recent development of topological engineering of commercial glasses. Results Glass transition cycle To establish our conclusions, we use as a target system a densified sodium silicate liquid (2SiO 2 –Na 2 O or NS2) that is investigated by MD in ( N , V , T ) and ( N , P , T ) ensembles (see Methods Summary in refs 7 , 8 , 9 ). These materials are made of SiO 4/2 tetrahedra that are connected by bridging oxygens (BOs) whereas sodium cations create in their immediate vicinity so-called non-BOs (NBO), which contribute to the depolymerization of the network structure ( Fig. 1 ) 10 . Figure 1: Structure of a densified silicate. Snapshot of a sodium disilicate (2SiO 2 –Na 2 O, NS2) glass at room temperature. The structure is composed of network-forming species Si (yellow) and O (red), and cations (Na, blue spheres). Full size image We systematically perform isobaric/isochoric cycles, and start from an equilibrated liquid configuration at 3,000 K, and then cool the system at a rate of 1 K ps −1 to 300 K. The simulations reproduce the phenomenology of the glass transition temperature ( Fig. 2 , and Methods), that is, a slower cooling (from 10 to 0.1 K ps −1 ) leads to lower glass energies and a fictive temperature (the temperature at which the system deviates from its equilibrium line) that is lower. The crossover between the low-temperature and high-temperature linear expansion permits one to determine a fictive temperature, in very much the same fashion as in experiments. Once in the glassy state, we subsequently anneal the system back to the initial temperature at the same rate. The same procedure is then repeated at different pressures/volumes. Figure 3a shows the behaviour of the volume for selected pressures (0, 8 and 16 GPa) during the MD cycle (see also Fig. 2b ). Because of the off-equilibrium nature of glasses, one usually obtains a hysteretic behaviour for volume or enthalpy driven by the relaxation, and this is, in fact, recovered in the simulation. However, for certain pressures (for example, 8 GPa) this hysteresis becomes minuscule, and the cooling/heating curves nearly overlap. When the area A H ( A V ) of the enthalpy (volume) hysteresis is followed as a function of pressure ( Fig. 3b ), a deep minimum is found, indicating that glasses in that pressure range must display a quite different relaxation behaviour that leads to a RW. Figure 2: A numerical glass transition cycle. ( a ) Evolution in ( N , V , T ) ensemble ( ρ =3.2 g cm −3 ) of the liquid potential energy E* ( T ) with temperature for different cooling rates. All are represented after subtraction of 9 RT /2 to account for the harmonic motions in the glassy state upon cooling. The inset shows a typical cooling/heating cycle", "role": "user" }, { "content": "Researchers at the UCLA Henry Samueli School of Engineering and Applied Science and the Université Pierre et Marie Curie in Paris have identified a method for manufacturing longer-lasting and stronger forms of glass. The research could lead to more durable display screens, fiber optic cables, windows and other materials, including cement. Glasses are liquids that are cooled in the manufacturing process to reach a stable \"frozen liquid\" state. However, as glass ages and is exposed to temperature variations, it continues to flow or \"relax,\" causing it to change shape. This means that over time, windows and digital screens can deform, eventually becoming unusable. In the case of cement, which has a molecular structure similar to that of glass, relaxation eventually leads to cracking and, in bridges and tall buildings, a loss of structural integrity. Mathieu Bauchy, an assistant professor of civil and environmental engineering at UCLA, and Matthieu Micoulaut, a professor of materials science at the Université Pierre et Marie Curie, have identified optimal conditions for developing more durable glass and cement. By performing computer simulations to test the molecular dynamics of materials commonly used to make glass, the researchers identified a range of pressures that are best for achieving \"thermal reversibility,\" in which a material will retain the same properties it had when it was produced, even if it has been exposed over time to variations in temperature. The research was published March 9 in Nature Communications. \"The key finding is that if you use specific conditions to form glass—the right pressure and the right composition of the material—you can design reversible glasses that show little or no aging over time,\" Bauchy said. Bauchy said the molecular structure of glass is analogous to the metal framework of the Eiffel Tower. Strength and rigidity are partially a result of the angles at which beams and crossbeams connect. The researchers' new process improves the angles at which molecular bonds occur, making the material stronger. The research could also have a significant impact in slowing the production of greenhouse gases. The manufacture of cement and concrete results in approximately 5 percent of all greenhouse gas production, according to the American Ceramic Society. \"The smaller the quantity of material we use to rebuild deteriorating structures, the better it is for the environment,\" said Bauchy, whose research focuses on forging stronger ties between fundamental physics and engineering to design better, more sustainable materials. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract If crystallization can be avoided during cooling, a liquid will display a substantial increase of its viscosity, and will form a glass that behaves as a solid with a relaxation time that grows exponentially with decreasing temperature. Given this ‘off-equilibrium’ nature, a hysteresis loop appears when a cooling/heating cycle is performed across the glass transition. Here we report on molecular dynamics simulations of densified glass-forming liquids that follow this kind of cycle. Over a finite pressure interval, minuscule thermal changes are found, revealing glasses of ‘thermally reversible’ character with optimal volumetric or enthalpic recovery. By analysing the topology of the atomic network structure, we find that corresponding liquids adapt under the pressure-induced increasing stress by experiencing larger bond-angle excursions. The analysis of the dynamic behaviour reveals that the structural relaxation time is substantially reduced in these adaptive liquids, and also drives the reversible character of the glass transition. Ultimately, the results substantiate the notion of stress-free (Maxwell isostatic) rigidity in disordered molecular systems, while also revealing new implications for the topological engineering of complex materials. Introduction Certain materials, when cooled fast enough through their melting point, can remain in a metastable supercooled state and, upon further cooling, can eventually freeze into a glass at a reference temperature T g , which is usually associated 1 , 2 with a viscosity of 10 12 Pa s or a relaxation time of 100 s. As the temperature of the liquid is lowered, viscosity and the relaxation time towards thermodynamic equilibrium will increase markedly. However, even in the obtained glassy state, the material will continue to relax to a lower energy state but on timescales that exceed the laboratory timescale by several orders of magnitude. To track such subtle effects, one conventionally uses calorimetry to measure the heat capacity of the glass and the liquid, and with heating a hysteresis loop appears 3 , 4 , causing a heat capacity overshoot at the glass transition. This endotherm peak simply reveals that previously frozen degrees of freedom during the quench are now excited, so that the overshoot is a direct manifestation of the relaxation taking place between room temperature and T g . Here we show by using molecular dynamics (MD) simulations that for a fixed cooling/heating rate this hysteresis can be minuscule under certain thermodynamic conditions, and defines a calorimetric reversibility window (RW) and a volume recovery window, while also underscoring an obvious anomalous relaxation behaviour that is characterized. A direct connection is made with the softening of bond angles at the molecular level, which adapt under the pressure-driven increasing stress leading to a growth of the atomic coordination numbers, and network connectivity. It is found that such ‘thermally reversible’ glasses are stress-free, and bear striking similarities with calorimetric anomalies in modified glassy alloys, while also satisfying the well-known Maxwell stability criterion of isostatic mechanical structures 5 , 6 , and displaying anomalous relaxation dynamics in the supercooled regime. These findings open the possibility to use stress-free rigidity for the design of a variety of functionalities in disordered materials, an original perspective that is directly derived from basic findings, and which has inspired the recent development of topological engineering of commercial glasses. Results Glass transition cycle To establish our conclusions, we use as a target system a densified sodium silicate liquid (2SiO 2 –Na 2 O or NS2) that is investigated by MD in ( N , V , T ) and ( N , P , T ) ensembles (see Methods Summary in refs 7 , 8 , 9 ). These materials are made of SiO 4/2 tetrahedra that are connected by bridging oxygens (BOs) whereas sodium cations create in their immediate vicinity so-called non-BOs (NBO), which contribute to the depolymerization of the network structure ( Fig. 1 ) 10 . Figure 1: Structure of a densified silicate. Snapshot of a sodium disilicate (2SiO 2 –Na 2 O, NS2) glass at room temperature. The structure is composed of network-forming species Si (yellow) and O (red), and cations (Na, blue spheres). Full size image We systematically perform isobaric/isochoric cycles, and start from an equilibrated liquid configuration at 3,000 K, and then cool the system at a rate of 1 K ps −1 to 300 K. The simulations reproduce the phenomenology of the glass transition temperature ( Fig. 2 , and Methods), that is, a slower cooling (from 10 to 0.1 K ps −1 ) leads to lower glass energies and a fictive temperature (the temperature at which the system deviates from its equilibrium line) that is lower. The crossover between the low-temperature and high-temperature linear expansion permits one to determine a fictive temperature, in very much the same fashion as in experiments. Once in the glassy state, we subsequently anneal the system back to the initial temperature at the same rate. The same procedure is then repeated at different pressures/volumes. Figure 3a shows the behaviour of the volume for selected pressures (0, 8 and 16 GPa) during the MD cycle (see also Fig. 2b ). Because of the off-equilibrium nature of glasses, one usually obtains a hysteretic behaviour for volume or enthalpy driven by the relaxation, and this is, in fact, recovered in the simulation. However, for certain pressures (for example, 8 GPa) this hysteresis becomes minuscule, and the cooling/heating curves nearly overlap. When the area A H ( A V ) of the enthalpy (volume) hysteresis is followed as a function of pressure ( Fig. 3b ), a deep minimum is found, indicating that glasses in that pressure range must display a quite different relaxation behaviour that leads to a RW. Figure 2: A numerical glass transition cycle. ( a ) Evolution in ( N , V , T ) ensemble ( ρ =3.2 g cm −3 ) of the liquid potential energy E* ( T ) with temperature for different cooling rates. All are represented after subtraction of 9 RT /2 to account for the harmonic motions in the glassy state upon cooling. The inset shows a typical cooling/heating cycle<|im_end|> <|im_start|>assistant Researchers at the UCLA Henry Samueli School of Engineering and Applied Science and the Université Pierre et Marie Curie in Paris have identified a method for manufacturing longer-lasting and stronger forms of glass. The research could lead to more durable display screens, fiber optic cables, windows and other materials, including cement. Glasses are liquids that are cooled in the manufacturing process to reach a stable "frozen liquid" state. However, as glass ages and is exposed to temperature variations, it continues to flow or "relax," causing it to change shape. This means that over time, windows and digital screens can deform, eventually becoming unusable. In the case of cement, which has a molecular structure similar to that of glass, relaxation eventually leads to cracking and, in bridges and tall buildings, a loss of structural integrity. Mathieu Bauchy, an assistant professor of civil and environmental engineering at UCLA, and Matthieu Micoulaut, a professor of materials science at the Université Pierre et Marie Curie, have identified optimal conditions for developing more durable glass and cement. By performing computer simulations to test the molecular dynamics of materials commonly used to make glass, the researchers identified a range of pressures that are best for achieving "thermal reversibility," in which a material will retain the same properties it had when it was produced, even if it has been exposed over time to variations in temperature. The research was published March 9 in Nature Communications. "The key finding is that if you use specific conditions to form glass—the right pressure and the right composition of the material—you can design reversible glasses that show little or no aging over time," Bauchy said. Bauchy said the molecular structure of glass is analogous to the metal framework of the Eiffel Tower. Strength and rigidity are partially a result of the angles at which beams and crossbeams connect. The researchers' new process improves the angles at which molecular bonds occur, making the material stronger. The research could also have a significant impact in slowing the production of greenhouse gases. The manufacture of cement and concrete results in approximately 5 percent of all greenhouse gas production, according to the American Ceramic Society. "The smaller the quantity of material we use to rebuild deteriorating structures, the better it is for the environment," said Bauchy, whose research focuses on forging stronger ties between fundamental physics and engineering to design better, more sustainable materials. <|im_end|>

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1,844

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The microbiota modulates gut immune homeostasis. Bacteria influence the development and function of host immune cells, including T helper cells expressing interleukin-17A (T H 17 cells). We previously reported that the bile acid metabolite 3-oxolithocholic acid (3-oxoLCA) inhibits T H 17 cell differentiation 1 . Although it was suggested that gut-residing bacteria produce 3-oxoLCA, the identity of such bacteria was unknown, and it was unclear whether 3-oxoLCA and other immunomodulatory bile acids are associated with inflammatory pathologies in humans. Here we identify human gut bacteria and corresponding enzymes that convert the secondary bile acid lithocholic acid into 3-oxoLCA as well as the abundant gut metabolite isolithocholic acid (isoLCA). Similar to 3-oxoLCA, isoLCA suppressed T H 17 cell differentiation by inhibiting retinoic acid receptor-related orphan nuclear receptor-γt, a key T H 17-cell-promoting transcription factor. The levels of both 3-oxoLCA and isoLCA and the 3α-hydroxysteroid dehydrogenase genes that are required for their biosynthesis were significantly reduced in patients with inflammatory bowel disease. Moreover, the levels of these bile acids were inversely correlated with the expression of T H 17-cell-associated genes. Overall, our data suggest that bacterially produced bile acids inhibit T H 17 cell function, an activity that may be relevant to the pathophysiology of inflammatory disorders such as inflammatory bowel disease. Main Bile acids (BAs) are steroidal natural products that are secreted into the gastrointestinal tract postprandially, where they act as detergents that aid in digestion and as ligands for host receptors 2 , 3 . In the gut, host-derived primary BAs are metabolized by resident microbes to form a large group of compounds called secondary BAs 3 . Both primary and secondary BAs regulate host metabolism 2 , 4 and immune responses 5 , 6 , 7 , 8 . BAs modulate the differentiation and function of T cells, including inflammatory T H 17 cells and anti-inflammatory regulatory T (T reg ) cells, which help to protect against extracellular pathogens and maintain host immune tolerance, respectively 9 , 10 , 11 , 12 , 13 . Specifically, secondary BAs such as isoallolithocholic acid (isoalloLCA) and isodeoxycholic acid (isoDCA) modulate the differentiation of T reg cells 1 , 14 , 15 . Furthermore, 3-oxoLCA inhibits T H 17 cell differentiation by blocking the function of the nuclear hormone receptor retinoic-acid-receptor-related orphan nuclear receptor-γt (RORγt) 1 , 16 , 17 . 3-OxoLCA is absent from the caeca of germ-free (GF) C57BL/6 mice 1 , indicating that gut bacteria may synthesize 3-oxoLCA. However, it is unknown which commensal bacteria and bacterial enzymes produce 3-oxoLCA (Fig. 1a ) and whether this compound or additional secondary BAs that modulate T H 17 cell responses are implicated in the pathogenesis of inflammatory bowel disease (IBD). Fig. 1: Human gut bacteria produce 3-oxoLCA, a T H 17-cell-modulating BA metabolite. a , Bacterial conversion of host-produced BAs. C. scindens , Clostridium scindens . R′, taurine or glycine. b , Representative ultra-performance liquid chromatography coupled with mass spectrometry (UPLC–MS) traces (left) and the percentage production of 3-oxoLCA (right) by human bacterial isolates. Total ion chromatograms are shown. An unknown peak of m / z 375.2 (#; retention time 5.7 min) was later identified as isoLCA (Extended Data Fig. 2c ). n = 3 biological replicates per group. Data are mean ± s.e.m. The full results are provided in Supplementary Table 2 . c , d , Supernatants from E. lenta DSM2243 cultured with LCA inhibited T H 17 cell differentiation in vitro. Representative fluorescence-activated cell sorting (FACS) plots ( c ) and population frequencies ( d ) of mouse T cells activated and expanded in vitro are shown. Naive CD4 + T cells from wild-type C57BL/6J mice were cultured under T H 17 cell polarizing conditions for 3 days and bacterial supernatants were added 18 h after T cell receptor (TCR) activation. n = 3 biologically independent samples per group. Data are mean ± s.e.m. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by Tukey’s multiple-comparison test. Source data Full size image Here we used a screen of human isolates to identify gut bacteria that produce 3-oxoLCA as well as an abundant gut metabolite, isolithocholic acid (isoLCA), which we demonstrate inhibits T H 17 cell differentiation. Multi-omics analyses of two IBD registries revealed that 3-oxoLCA and isoLCA as well as the bacterial genes responsible for their production are negatively associated with IBD and T H 17-cell-related host gene expression. Together, our data suggest that bacterial production of 3-oxoLCA and isoLCA may contribute to gut immune homeostasis in humans. Screen for 3-oxoLCA-producing bacteria We screened strains isolated from human stool samples for their ability to convert LCA into 3-oxoLCA. LCA is present in high concentrations in human caecal contents (mean, ~160 μM) 18 and we reasoned that gut bacteria might be able to oxidize the C3-hydroxyl group of LCA to produce 3-oxoLCA (Fig. 1a ). After testing stool from 15 individuals, we used the two samples that contained the highest 3-oxoLCA levels in the screen (Extended Data Fig. 1a (P3 and P27)). We established a library of 990 culturable isolates comprising a diverse array of bacteria, representing members from all of the major gut phyla ( Methods and Extended Data Fig. 1b–d ). A total of 238 bacterial isolates converted LCA into 3-oxoLCA after 48 h. These producers belonged to 12 genera (Supplementary Table 2 ). Among these, the top producers included Gordonibacter pamelaeae P7-E3, Eggerthella lenta P7-G7, Raoultibacter massiliensis P7-A2, Collinsella intestinalis P8-C1, Adlercreutzia equolifaciens P11-C8 and Clostridium citroniae P2-B6 (Fig. 1b ). Consistent with our findings, an early study showed that isolates of Eubacterium lentum (which was later reclassified as Eggerthella lenta ) could produce small amounts of 3-oxoLCA in anaerobic resting cell culture 19 . The type strains of a subset of these organisms produced a comparable amount of 3-oxoLCA in vitro (Extended Data Fig. 1e ). Taken together, these data indicate that human gut bacteria from an array of families within the Actinobacteria and Firmicutes phyla produce 3-oxoLCA. Supernatant from E. lenta", "role": "user" }, { "content": "Bile acids made by the liver have long been known for their critical role in helping to absorb the food we ingest. But, according to a series of new studies from Harvard Medical School, these fat- and vitamin-dissolving substances are also important players in gut immunity and inflammation because they regulate the activity of key immune cells linked to a range of inflammatory bowel conditions, such as ulcerative colitis and Crohn's disease. An initial report in 2020 mapped out the effects of bile acids on mouse gut immunity, but left some key questions unanswered: First, just how do bile acids get gut immune cells to perform their immune-regulatory work? Second, which bacteria and bacterial enzymes produce these bile acids? Third, do these bile acids play a role in human intestinal inflammation? Now, two studies led by the same team of investigators—one published March 16 in Nature and one published in Cell Host & Microbe in 2021—answer these questions and add further clarity to the initial observations. The research, conducted at the intersection of chemical biology, microbiology, and immunology, was co-led by Sloan Devlin, assistant professor of biological chemistry and molecular pharmacology, and Jun Huh, associate professor of immunology at HMS. The studies identify three bile acid metabolites and corresponding bacterial genes that produce molecules that affect the activity of inflammation-regulating immune cells. The work also demonstrates that the presence and activity of these bacteria and the immune molecules they produce are notably reduced in patients with inflammatory bowel disease (IBD). \"We carry trillions of bacteria in and on our bodies, and a growing body of research indicates that gut bacteria can affect host immune responses,\" Huh said. \"Our findings provide a novel mechanistic insight into how these bacteria work to mediate immune regulation in the gut.\" The findings, based on experiments in mice and human stool samples, reveal the identity of three critical microbial players in this cascade and the bacterial genes that regulate bile acid modification. Furthermore, they show that intestinal samples from patients with conditions such as ulcerative colitis or Crohn's disease have markedly lower levels of both the anti-inflammatory molecules and the bacterial genes responsible for their production. The findings bring scientists a step closer to developing small-molecule treatments and live bacterial therapeutics that regulate intestinal inflammation. \"All three molecules and the bacterial genes that we discovered that produce these molecules are reduced in patients with IBD,\" Devlin said. \"Restoring the presence of either the compounds or the bacteria that make them offers a possible therapeutic avenue to treat a range of inflammatory diseases marked by these deficiencies and affecting millions of people worldwide.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The microbiota modulates gut immune homeostasis. Bacteria influence the development and function of host immune cells, including T helper cells expressing interleukin-17A (T H 17 cells). We previously reported that the bile acid metabolite 3-oxolithocholic acid (3-oxoLCA) inhibits T H 17 cell differentiation 1 . Although it was suggested that gut-residing bacteria produce 3-oxoLCA, the identity of such bacteria was unknown, and it was unclear whether 3-oxoLCA and other immunomodulatory bile acids are associated with inflammatory pathologies in humans. Here we identify human gut bacteria and corresponding enzymes that convert the secondary bile acid lithocholic acid into 3-oxoLCA as well as the abundant gut metabolite isolithocholic acid (isoLCA). Similar to 3-oxoLCA, isoLCA suppressed T H 17 cell differentiation by inhibiting retinoic acid receptor-related orphan nuclear receptor-γt, a key T H 17-cell-promoting transcription factor. The levels of both 3-oxoLCA and isoLCA and the 3α-hydroxysteroid dehydrogenase genes that are required for their biosynthesis were significantly reduced in patients with inflammatory bowel disease. Moreover, the levels of these bile acids were inversely correlated with the expression of T H 17-cell-associated genes. Overall, our data suggest that bacterially produced bile acids inhibit T H 17 cell function, an activity that may be relevant to the pathophysiology of inflammatory disorders such as inflammatory bowel disease. Main Bile acids (BAs) are steroidal natural products that are secreted into the gastrointestinal tract postprandially, where they act as detergents that aid in digestion and as ligands for host receptors 2 , 3 . In the gut, host-derived primary BAs are metabolized by resident microbes to form a large group of compounds called secondary BAs 3 . Both primary and secondary BAs regulate host metabolism 2 , 4 and immune responses 5 , 6 , 7 , 8 . BAs modulate the differentiation and function of T cells, including inflammatory T H 17 cells and anti-inflammatory regulatory T (T reg ) cells, which help to protect against extracellular pathogens and maintain host immune tolerance, respectively 9 , 10 , 11 , 12 , 13 . Specifically, secondary BAs such as isoallolithocholic acid (isoalloLCA) and isodeoxycholic acid (isoDCA) modulate the differentiation of T reg cells 1 , 14 , 15 . Furthermore, 3-oxoLCA inhibits T H 17 cell differentiation by blocking the function of the nuclear hormone receptor retinoic-acid-receptor-related orphan nuclear receptor-γt (RORγt) 1 , 16 , 17 . 3-OxoLCA is absent from the caeca of germ-free (GF) C57BL/6 mice 1 , indicating that gut bacteria may synthesize 3-oxoLCA. However, it is unknown which commensal bacteria and bacterial enzymes produce 3-oxoLCA (Fig. 1a ) and whether this compound or additional secondary BAs that modulate T H 17 cell responses are implicated in the pathogenesis of inflammatory bowel disease (IBD). Fig. 1: Human gut bacteria produce 3-oxoLCA, a T H 17-cell-modulating BA metabolite. a , Bacterial conversion of host-produced BAs. C. scindens , Clostridium scindens . R′, taurine or glycine. b , Representative ultra-performance liquid chromatography coupled with mass spectrometry (UPLC–MS) traces (left) and the percentage production of 3-oxoLCA (right) by human bacterial isolates. Total ion chromatograms are shown. An unknown peak of m / z 375.2 (#; retention time 5.7 min) was later identified as isoLCA (Extended Data Fig. 2c ). n = 3 biological replicates per group. Data are mean ± s.e.m. The full results are provided in Supplementary Table 2 . c , d , Supernatants from E. lenta DSM2243 cultured with LCA inhibited T H 17 cell differentiation in vitro. Representative fluorescence-activated cell sorting (FACS) plots ( c ) and population frequencies ( d ) of mouse T cells activated and expanded in vitro are shown. Naive CD4 + T cells from wild-type C57BL/6J mice were cultured under T H 17 cell polarizing conditions for 3 days and bacterial supernatants were added 18 h after T cell receptor (TCR) activation. n = 3 biologically independent samples per group. Data are mean ± s.e.m. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by Tukey’s multiple-comparison test. Source data Full size image Here we used a screen of human isolates to identify gut bacteria that produce 3-oxoLCA as well as an abundant gut metabolite, isolithocholic acid (isoLCA), which we demonstrate inhibits T H 17 cell differentiation. Multi-omics analyses of two IBD registries revealed that 3-oxoLCA and isoLCA as well as the bacterial genes responsible for their production are negatively associated with IBD and T H 17-cell-related host gene expression. Together, our data suggest that bacterial production of 3-oxoLCA and isoLCA may contribute to gut immune homeostasis in humans. Screen for 3-oxoLCA-producing bacteria We screened strains isolated from human stool samples for their ability to convert LCA into 3-oxoLCA. LCA is present in high concentrations in human caecal contents (mean, ~160 μM) 18 and we reasoned that gut bacteria might be able to oxidize the C3-hydroxyl group of LCA to produce 3-oxoLCA (Fig. 1a ). After testing stool from 15 individuals, we used the two samples that contained the highest 3-oxoLCA levels in the screen (Extended Data Fig. 1a (P3 and P27)). We established a library of 990 culturable isolates comprising a diverse array of bacteria, representing members from all of the major gut phyla ( Methods and Extended Data Fig. 1b–d ). A total of 238 bacterial isolates converted LCA into 3-oxoLCA after 48 h. These producers belonged to 12 genera (Supplementary Table 2 ). Among these, the top producers included Gordonibacter pamelaeae P7-E3, Eggerthella lenta P7-G7, Raoultibacter massiliensis P7-A2, Collinsella intestinalis P8-C1, Adlercreutzia equolifaciens P11-C8 and Clostridium citroniae P2-B6 (Fig. 1b ). Consistent with our findings, an early study showed that isolates of Eubacterium lentum (which was later reclassified as Eggerthella lenta ) could produce small amounts of 3-oxoLCA in anaerobic resting cell culture 19 . The type strains of a subset of these organisms produced a comparable amount of 3-oxoLCA in vitro (Extended Data Fig. 1e ). Taken together, these data indicate that human gut bacteria from an array of families within the Actinobacteria and Firmicutes phyla produce 3-oxoLCA. Supernatant from E. lenta<|im_end|> <|im_start|>assistant Bile acids made by the liver have long been known for their critical role in helping to absorb the food we ingest. But, according to a series of new studies from Harvard Medical School, these fat- and vitamin-dissolving substances are also important players in gut immunity and inflammation because they regulate the activity of key immune cells linked to a range of inflammatory bowel conditions, such as ulcerative colitis and Crohn's disease. An initial report in 2020 mapped out the effects of bile acids on mouse gut immunity, but left some key questions unanswered: First, just how do bile acids get gut immune cells to perform their immune-regulatory work? Second, which bacteria and bacterial enzymes produce these bile acids? Third, do these bile acids play a role in human intestinal inflammation? Now, two studies led by the same team of investigators—one published March 16 in Nature and one published in Cell Host & Microbe in 2021—answer these questions and add further clarity to the initial observations. The research, conducted at the intersection of chemical biology, microbiology, and immunology, was co-led by Sloan Devlin, assistant professor of biological chemistry and molecular pharmacology, and Jun Huh, associate professor of immunology at HMS. The studies identify three bile acid metabolites and corresponding bacterial genes that produce molecules that affect the activity of inflammation-regulating immune cells. The work also demonstrates that the presence and activity of these bacteria and the immune molecules they produce are notably reduced in patients with inflammatory bowel disease (IBD). "We carry trillions of bacteria in and on our bodies, and a growing body of research indicates that gut bacteria can affect host immune responses," Huh said. "Our findings provide a novel mechanistic insight into how these bacteria work to mediate immune regulation in the gut." The findings, based on experiments in mice and human stool samples, reveal the identity of three critical microbial players in this cascade and the bacterial genes that regulate bile acid modification. Furthermore, they show that intestinal samples from patients with conditions such as ulcerative colitis or Crohn's disease have markedly lower levels of both the anti-inflammatory molecules and the bacterial genes responsible for their production. The findings bring scientists a step closer to developing small-molecule treatments and live bacterial therapeutics that regulate intestinal inflammation. "All three molecules and the bacterial genes that we discovered that produce these molecules are reduced in patients with IBD," Devlin said. "Restoring the presence of either the compounds or the bacteria that make them offers a possible therapeutic avenue to treat a range of inflammatory diseases marked by these deficiencies and affecting millions of people worldwide." <|im_end|>

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2,188

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Electrical currents in a quantum spin Hall insulator are confined to the boundary of the system. The charge carriers behave as massless relativistic particles whose spin and momentum are coupled to each other. Although the helical character of those states is already established by experiments, there is an open question regarding how those edge states interact with each other when they are brought into close spatial proximity. We employ an inverted HgTe quantum well to guide edge channels from opposite sides of a device into a quasi-one-dimensional constriction. Our transport measurements show that, apart from the expected quantization in integer steps of 2 e 2 / h , we find an additional plateau at e 2 / h . We combine band structure calculations and repulsive electron–electron interaction effects captured within the Tomonaga–Luttinger liquid model and Rashba spin–orbit coupling to explain our observation in terms of the opening of a spin gap. These results may have direct implications for the study of one-dimensional helical electron quantum optics, and for understanding Majorana and para fermions. Main The discovery of the quantum spin Hall effect 1 , 2 , 3 in HgTe quantum wells 4 was the first landmark in the physics of topological materials. Such quantum wells boast an inverted band structure for well widths d QW larger than a critical thickness d c = 6.3 nm. The quantum spin Hall phase was subsequently also observed in other material systems such as InAs/GaSb double quantum wells 5 and in monolayers of WTe 2 and bismuthene 6 , 7 . The defining property of this state is the emergence of topologically protected helical edge channels, while the bulk is insulating. Non-local edge transport and spin polarization of these edge channels has already been demonstrated in HgTe quantum wells 8 , 9 . Here, we investigate the open question of how helical edge states interact with each other. A quantum point contact (QPC) can be used to guide edge channels from opposite boundaries of the sample into a constriction. Such a device allows for studies of charge and spin transfer mechanisms, for example, by adjusting the overlap of the edge states 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 . Besides the general interest in the study of transport processes in such a device, the appropriate model to describe the essential physics and to capture interaction effects of helical edge states is still unclear. We present the realization of a QPC based on HgTe quantum wells, as evidenced by the observation of the expected conductance steps in integer values of G 0 . Our lithographic process allows the fabrication of sophisticated nanostructures based on topological materials without lowering the material quality. Depending on the QPC width W QPC and quantum well thickness d QW , we observe a fractional plateau at 0.5 G 0 in the absence of an applied magnetic field. We label this phenomenon the 0.5 anomaly, in analogy with the 0.7 anomaly frequently observed in QPCs fabricated in more conventional semiconductors 21 . Self-consistent k ⋅ p calculations allow us to identify the most plausible transport mechanism. Using the theory of helical Tomonaga–Luttinger liquids, we associate the experimental results with the presence of a spin gap. The bias and temperature dependencies of the 0.5 anomaly are in agreement with such a gap. Furthermore, we identify an indicator of the conventional 0.7 anomaly in our devices when increasing the applied bias voltage. This observation is in qualitative agreement with our theory and the explanation given for the 0.7 anomaly in ref. 22 . Realization of a quantum spin Hall QPC Figure 1a,b shows a scanning electron micrograph (SEM) image of a HgTe QPC and a schematic of the device. A constriction is formed by wet chemical etching of the HgTe heterostructure 23 and a top-gate electrode is used to tune the chemical potential. The thickness of the HgTe layer, if not explicitly stated otherwise, is d QW = 10.5 nm. Details about the device fabrication are presented in the Methods and material parameters are provided in Supplementary Section I . Fig. 1: Realization of a topological QPC. a , SEM image of a typical device. A narrow channel is defined in the HgTe mesa with width W QPC and length L QPC . A metallic gate electrode is separated from the mesa by a HfO 2 dielectric. b , Schematic of the QPC design and measurement set-up. The gate electrode is depicted in yellow and the ohmic contacts in orange. The inset shows the epitaxially grown layer stack on a commercially available Cd 0.96 Zn 0.04 Te substrate. c , Gate voltage dependence of the conductance of QPC-III ( W QPC ≈ 150 nm) measured at 1.4 K. The conductance is divided into three regimes separated by vertical dashed lines. In the QPC regime, integer steps up to 14 e 2 / h are observed. The pure quantum spin Hall regime is defined by a conductance of 2 e 2 / h (indicated as the QSH regime in c ). In the 0.5 anomaly regime, an interaction-driven gap opens, leading to a quantized conductance of e 2 / h . The inset shows an enlarged view of the 0.5 anomaly regime. Full size image The conductance G of a representative QPC as a function of applied gate voltage V G is depicted in Fig. 1c . Three regimes can be identified. For gate voltages V G ≥ −0.75 V, we observe conventional QPC behaviour. Conductance plateaux develop at integer multiples of G 0 and the quality of quantization can be improved by applying a small magnetic field (shown in red). For gate voltages in the range −0.75 V > V G > −1.2 V the QPC is in the quantum spin Hall regime. A long plateau around G 0 is assigned to two helical edge channels. For still more negative gate voltages V G ≤ −1.2 V,", "role": "user" }, { "content": "Topological insulators are materials with astonishing properties: Electric current flows only along their surfaces or edges, whereas the interior of the material behaves as an insulator. In 2007, Professor Laurens Molenkamp at Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany, was the first to experimentally demonstrate the existence of such topological states. His team achieved this seminal work with quantum wells based on mercury and tellurium (HgTe). Since then, these novel materials have been the hope for a fundamentally new generation of components that, for example, promise innovations for information technology. Physicists at JMU have now succeeded for the first time in constructing an essential element for such components—a Quantum Point Contact (QPC). They present this achievement in a recent publication in the journal Nature Physics. Confinement for topological states Quantum point contacts are quasi one-dimensional constrictions in otherwise two-dimensional structures that are only a few atomic layers thin. In topological HgTe quantum wells, in which the conducting states are located exclusively at the edges, these edge states are spatially merged at the QPC. This proximity makes it possible to investigate potential interactions between the edge states. \"This experiment could only work because of a breakthrough in our lithographic methods. It has enabled us to create incredibly small structures without damaging the topological material. I am convinced that this technology will enable us to find impressive, novel effects in topological nanostructures in the near future,\" said Molenkamp. Anomalous conductance behavior through interaction Using a sophisticated manufacturing process, the JMU physicists have succeeded in structuring the bottleneck precisely and gently. This technological progress allowed them to functionalize the topological properties of the system. In this context, the team led by Professors Laurens Molenkamp and Björn Trauzettel was able to demonstrate for the first time ever interaction effects between the different topological states of a system using anomalous conductance signatures. The Würzburg researchers attribute this particular behaviour of the analyzed topological QPCs to the physics of one-dimensional electronic systems. Interacting electrons in one dimension If electronic correlations are analysed in one spatial dimension, electrons move—unlike in two or three spatial dimensions—in a well-ordered manner because there is no possibility of \"overtaking\" the leading electron. Pictorially speaking, the electrons in this case behave like pearls on a chain. This special property of one-dimensional systems leads to interesting physical phenomena. Trauzettel says: \"The interplay of strong Coulomb interaction and spin orbit coupling is rare in nature. I therefore expect this system to yield fundamental discoveries in the coming years.\" Outlook for future research Topological QPCs are an elementary component for many applications that have been predicted in theory in recent years. A particularly prominent example of this kind is the possible realization of Majorana fermions, which the Italian physicist Ettore Majorana predicted back in 1937. A promising application potential in connection with topological quantum computers is attributed to these excitations. For this purpose, it is of great importance not only to detect Majorana fermions, but also to be able to control and manipulate them at will. The topological QPC, first implemented at JMU Würzburg, offers an exciting perspective in this respect. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Electrical currents in a quantum spin Hall insulator are confined to the boundary of the system. The charge carriers behave as massless relativistic particles whose spin and momentum are coupled to each other. Although the helical character of those states is already established by experiments, there is an open question regarding how those edge states interact with each other when they are brought into close spatial proximity. We employ an inverted HgTe quantum well to guide edge channels from opposite sides of a device into a quasi-one-dimensional constriction. Our transport measurements show that, apart from the expected quantization in integer steps of 2 e 2 / h , we find an additional plateau at e 2 / h . We combine band structure calculations and repulsive electron–electron interaction effects captured within the Tomonaga–Luttinger liquid model and Rashba spin–orbit coupling to explain our observation in terms of the opening of a spin gap. These results may have direct implications for the study of one-dimensional helical electron quantum optics, and for understanding Majorana and para fermions. Main The discovery of the quantum spin Hall effect 1 , 2 , 3 in HgTe quantum wells 4 was the first landmark in the physics of topological materials. Such quantum wells boast an inverted band structure for well widths d QW larger than a critical thickness d c = 6.3 nm. The quantum spin Hall phase was subsequently also observed in other material systems such as InAs/GaSb double quantum wells 5 and in monolayers of WTe 2 and bismuthene 6 , 7 . The defining property of this state is the emergence of topologically protected helical edge channels, while the bulk is insulating. Non-local edge transport and spin polarization of these edge channels has already been demonstrated in HgTe quantum wells 8 , 9 . Here, we investigate the open question of how helical edge states interact with each other. A quantum point contact (QPC) can be used to guide edge channels from opposite boundaries of the sample into a constriction. Such a device allows for studies of charge and spin transfer mechanisms, for example, by adjusting the overlap of the edge states 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 . Besides the general interest in the study of transport processes in such a device, the appropriate model to describe the essential physics and to capture interaction effects of helical edge states is still unclear. We present the realization of a QPC based on HgTe quantum wells, as evidenced by the observation of the expected conductance steps in integer values of G 0 . Our lithographic process allows the fabrication of sophisticated nanostructures based on topological materials without lowering the material quality. Depending on the QPC width W QPC and quantum well thickness d QW , we observe a fractional plateau at 0.5 G 0 in the absence of an applied magnetic field. We label this phenomenon the 0.5 anomaly, in analogy with the 0.7 anomaly frequently observed in QPCs fabricated in more conventional semiconductors 21 . Self-consistent k ⋅ p calculations allow us to identify the most plausible transport mechanism. Using the theory of helical Tomonaga–Luttinger liquids, we associate the experimental results with the presence of a spin gap. The bias and temperature dependencies of the 0.5 anomaly are in agreement with such a gap. Furthermore, we identify an indicator of the conventional 0.7 anomaly in our devices when increasing the applied bias voltage. This observation is in qualitative agreement with our theory and the explanation given for the 0.7 anomaly in ref. 22 . Realization of a quantum spin Hall QPC Figure 1a,b shows a scanning electron micrograph (SEM) image of a HgTe QPC and a schematic of the device. A constriction is formed by wet chemical etching of the HgTe heterostructure 23 and a top-gate electrode is used to tune the chemical potential. The thickness of the HgTe layer, if not explicitly stated otherwise, is d QW = 10.5 nm. Details about the device fabrication are presented in the Methods and material parameters are provided in Supplementary Section I . Fig. 1: Realization of a topological QPC. a , SEM image of a typical device. A narrow channel is defined in the HgTe mesa with width W QPC and length L QPC . A metallic gate electrode is separated from the mesa by a HfO 2 dielectric. b , Schematic of the QPC design and measurement set-up. The gate electrode is depicted in yellow and the ohmic contacts in orange. The inset shows the epitaxially grown layer stack on a commercially available Cd 0.96 Zn 0.04 Te substrate. c , Gate voltage dependence of the conductance of QPC-III ( W QPC ≈ 150 nm) measured at 1.4 K. The conductance is divided into three regimes separated by vertical dashed lines. In the QPC regime, integer steps up to 14 e 2 / h are observed. The pure quantum spin Hall regime is defined by a conductance of 2 e 2 / h (indicated as the QSH regime in c ). In the 0.5 anomaly regime, an interaction-driven gap opens, leading to a quantized conductance of e 2 / h . The inset shows an enlarged view of the 0.5 anomaly regime. Full size image The conductance G of a representative QPC as a function of applied gate voltage V G is depicted in Fig. 1c . Three regimes can be identified. For gate voltages V G ≥ −0.75 V, we observe conventional QPC behaviour. Conductance plateaux develop at integer multiples of G 0 and the quality of quantization can be improved by applying a small magnetic field (shown in red). For gate voltages in the range −0.75 V > V G > −1.2 V the QPC is in the quantum spin Hall regime. A long plateau around G 0 is assigned to two helical edge channels. For still more negative gate voltages V G ≤ −1.2 V,<|im_end|> <|im_start|>assistant Topological insulators are materials with astonishing properties: Electric current flows only along their surfaces or edges, whereas the interior of the material behaves as an insulator. In 2007, Professor Laurens Molenkamp at Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany, was the first to experimentally demonstrate the existence of such topological states. His team achieved this seminal work with quantum wells based on mercury and tellurium (HgTe). Since then, these novel materials have been the hope for a fundamentally new generation of components that, for example, promise innovations for information technology. Physicists at JMU have now succeeded for the first time in constructing an essential element for such components—a Quantum Point Contact (QPC). They present this achievement in a recent publication in the journal Nature Physics. Confinement for topological states Quantum point contacts are quasi one-dimensional constrictions in otherwise two-dimensional structures that are only a few atomic layers thin. In topological HgTe quantum wells, in which the conducting states are located exclusively at the edges, these edge states are spatially merged at the QPC. This proximity makes it possible to investigate potential interactions between the edge states. "This experiment could only work because of a breakthrough in our lithographic methods. It has enabled us to create incredibly small structures without damaging the topological material. I am convinced that this technology will enable us to find impressive, novel effects in topological nanostructures in the near future," said Molenkamp. Anomalous conductance behavior through interaction Using a sophisticated manufacturing process, the JMU physicists have succeeded in structuring the bottleneck precisely and gently. This technological progress allowed them to functionalize the topological properties of the system. In this context, the team led by Professors Laurens Molenkamp and Björn Trauzettel was able to demonstrate for the first time ever interaction effects between the different topological states of a system using anomalous conductance signatures. The Würzburg researchers attribute this particular behaviour of the analyzed topological QPCs to the physics of one-dimensional electronic systems. Interacting electrons in one dimension If electronic correlations are analysed in one spatial dimension, electrons move—unlike in two or three spatial dimensions—in a well-ordered manner because there is no possibility of "overtaking" the leading electron. Pictorially speaking, the electrons in this case behave like pearls on a chain. This special property of one-dimensional systems leads to interesting physical phenomena. Trauzettel says: "The interplay of strong Coulomb interaction and spin orbit coupling is rare in nature. I therefore expect this system to yield fundamental discoveries in the coming years." Outlook for future research Topological QPCs are an elementary component for many applications that have been predicted in theory in recent years. A particularly prominent example of this kind is the possible realization of Majorana fermions, which the Italian physicist Ettore Majorana predicted back in 1937. A promising application potential in connection with topological quantum computers is attributed to these excitations. For this purpose, it is of great importance not only to detect Majorana fermions, but also to be able to control and manipulate them at will. The topological QPC, first implemented at JMU Würzburg, offers an exciting perspective in this respect. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Active wound dressings are attracting extensive attention in soft tissue repair and regeneration, including bacteria-infected skin wound healing. As the wide use of antibiotics leads to drug resistance we present here a new concept of wound dressings based on the polycaprolactone nanofiber scaffold (NANO) releasing second generation lipophosphonoxin (LPPO) as antibacterial agent. Firstly, we demonstrated in vitro that LPPO released from NANO exerted antibacterial activity while not impairing proliferation/differentiation of fibroblasts and keratinocytes. Secondly, using a mouse model we showed that NANO loaded with LPPO significantly reduced the Staphylococcus aureus counts in infected wounds as evaluated 7 days post-surgery. Furthermore, the rate of degradation and subsequent LPPO release in infected wounds was also facilitated by lytic enzymes secreted by inoculated bacteria. Finally, LPPO displayed negligible to no systemic absorption. In conclusion, the composite antibacterial NANO-LPPO-based dressing reduces the bacterial load and promotes skin repair, with the potential to treat wounds in clinical settings. Introduction Systemic use of antibiotics is currently the hallmark of treating (burn) wound infections, but it may result in harmful side-effects either through direct toxicity or by contributing to the emergence of resistant microorganisms 1 , 2 . Furthermore, many of the currently used topical antimicrobial agents exert cytotoxic effects on keratinocytes and fibroblasts, which may delay wound healing 3 . From this point of view, an efficient topical antimicrobial agent must act at a delicate balance between the need to control microbial growth in the wound bed and the potential risk that the agent impairs wound healing. Previously, we reported the synthesis of novel compounds termed lipophosphonoxins (LPPO) exhibiting significant antibacterial activities against a wide range of bacteria, including multidrug-resistant strains, with no cytotoxicity on human cells at bactericidal concentrations 4 , 5 , 6 . LPPO act through permeabilization of the bacterial membrane leading to its disruption and cell death. So far, we have synthesized and tested two generations of LPPOs. The first LPPO generation 4 displayed significant antibacterial activities against Gram-positive pathogens. Further modifications led to the second LPPO generation with improved antibacterial activities against both Gram-positive and Gram-negative bacteria 6 . Consequently, selected second generation LPPO have been successfully evaluated as antibacterial additives to bone cement 7 . Conventional wound dressings such as gauze, polymer bandage or cotton wool, cannot prevent wound beds from drying and bacterial infection, and need to be replaced, which often results in damage of the healing tissue. Therefore, the development of an active antibacterial and repair/regeneration promoting (e.g. by stem/progenitor cells or growth factor), ideally biodegradable wound dressing is the key for further therapy towards normal healing in a fully controlled manner 8 , 9 , 10 , 11 . Faced with enormous quantities of clinically approved wound dressings it is tempting to find those with the most reliable clinically-relevant properties 12 . In this context, the polycaprolactone (PCL)-based nanofibrous scaffold wound dressing produced by electrospinning is one of the most promising materials as it mimics the original architecture of the native extracellular matrix (ECM) and is biodegradable, degraded into naturally occurring metabolite 6-hydroxyhexanoic acid. It also maintains appropriate moisture and supports gas exchange at the injury site 13 . Moreover, the PCL scaffold has been approved by the American Food and Drug Administration (FDA) for biomedical applications, such as a surgical suture and/or endodontic material 14 , 15 . Microorganisms can develop resistance to conventional antimicrobial drugs. However, based on the structure and underlying mechanism of action, different from that of clinically used antibiotics, it is less likely that microbes will develop cross-resistance to LPPO 6 . Since electrospun nanofibrous scaffolds are potentially useful in medical applications such as wound healing and drug delivery 16 , we loaded the PCL-based wound dressing with LPPO to open new horizons towards novel approaches controlling wound infection. Our new concept was validated on a modified mice model of Staphylococcus aureus impaired wound healing and a series of in vitro experiments conducted on keratinocytes and fibroblasts. Results Wound dressing preparation and morphology PCL-based nanofibrous wound dressings were prepared by blending electrospinning technology 17 , 18 , with the addition of increasing concentrations (0, 2, 5, and 10 wt%) of LPPO DR-6180 (hereafter LPPO). LPPO was selected for its strong antibacterial properties and low cytotoxicity and was synthesized according to the procedure published previously 6 . The quality of the prepared nanofibrous materials was assessed by scanning electron microscopy (SEM). SEM of scaffolds with subsequent basic image analysis of fiber diameters revealed comparable morphology of prepared materials (Fig. 1 ). Histograms show that the fiber diameters were 579 ± 60 nm for PCL, 469 ± 44 nm for NANO-LPPO2%, 664 ± 56 nm for NANO-LPPO5%, and 608 ± 70 nm for PCL-LPPO10%. Figure 1 Representative photomicrographs from scanning electron microscope ( A – H ) and corresponding fiber diameter analysis (histograms, mean ± 95% confidence interval, n = 300) of electrospun PCL material ( I – L ) containing different amount of LPPO: 0% ( A , E , I ), 2% ( B , F , J ), 5% ( C , G , K ) and 10% ( D , H , L ). Scale bar top panel—10 µm (magnification 5000×), bottom panel—50 µm (magnification 1000×). Full size image LPPO release in PBS and LPPO release during enzymatically catalyzed degradation For the antibiotic function of the NANO-LPPO wound covers to be effective, controlled release of the active compound, LPPO, is necessary. Figure 2 A shows a weight loss of NANO-LPPO samples incubated in PBS in the presence or absence of lipase. In a phosphate-buffered saline environment, only the material with the highest concentration of LPPO (NANO-LPPO10%) showed a strong release of LPPO (Fig. 2 B). The LPPO release from NANO-LPPO10% occurred gradually, in the first 24 h 2.9 mg was released rapidly. This is the so-called burst release, which is typical for drugs incorporated using blending electrospinning technology 17 , 18 . Then the release continued more slowly and after 7 days the total amount of LPPO released was", "role": "user" }, { "content": "Researchers at the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague) and the Technical University of Liberec in collaboration with researchers from the Institute of Microbiology of the CAS, the Department of Burns Medicine of the Third Faculty of Medicine at Charles University (Czech Republic), and P. J. Šafárik University in Košice (Slovakia) have developed a novel antibacterial material combining nonwoven nanotextile and unique compounds with antibacterial properties. Called NANO-LPPO, the new material can fulfill a wide range of applications as a dressing for wounds, such as burn injuries, by preventing infection and thus facilitating treatment and healing. Because the number of bacterial strains resistant to common antibiotics is steadily increasing, there is a growing need for new substances with antibacterial properties. A very promising class of substances are the so-called lipophosphonoxins (LPPO) developed by the team of Dominik Rejman of IOCB Prague in collaboration with Libor Krásný of the Institute of Microbiology of the CAS. \"Lipophosphonoxins hold considerable promise as a new generation of antibiotics. They don't have to penetrate the bacteria but instead act on the surface, where they disrupt the bacterial cell membrane. That makes them very efficient at destroying bacteria,\" says Rejman. \"A big advantage of LPPO is the limited ability of bacteria to develop resistance to them. In an experiment lasting several weeks, we failed to find a bacteria resistant to these substances, while resistance to well-known antibiotics developed relatively easily,\" explains Krásný. The potential of LPPO is especially evident in situations requiring immediate targeted intervention, such as skin infections. Here, however, the substances must be combined with a suitable material that ensures their topical efficacy without the need to enter the circulatory system. This reduces the burden to the body and facilitates use. Dr. Dominik Rejman, head of the Antimicrobial Compounds Group at IOCB Prague (Czech Republic). Credit: Tomáš Belloň / IOCB Prague One such suitable material is a polymer nanofiber developed by the team of David Lukáš of the Faculty of Science, Humanities and Education at the Technical University of Liberec. The researchers combined it with LPPO to prepare a new type of dressing material for bacteria-infected skin wounds. The material's main benefit is that the antibacterial LPPO are released from it gradually and in relation to the presence and extent of infection. \"The research and development of the material NANO-LPPO is a continuation of the work carried out in a clinical trial on the NANOTARDIS medical device, which we recently successfully completed in collaboration with Regional Hospital Liberec, University Hospital Královské Vinohrady, and Bulovka University Hospital. With its morphological and physical-chemical properties, the device promotes the healing of clean acute wounds,\" says Lukáš. \"This collaboration with colleagues from IOCB Prague is really advancing the possibilities for use of functionalized nanofiber materials in the areas of chronic and infected wounds.\" \"Enzymes decompose the nanomaterial into harmless molecules. The LPPO are an integral component of the material and are primarily released from it during this decomposition. Moreover, the process is greatly accelerated by the presence of bacteria, which produce lytic enzymes. This means that the more bacteria there are in the wound, the faster the material decomposes, which in turn releases more of the active substances into the affected site to promote healing and regeneration of soft tissues,\" says Rejman in describing the action of the material. Nonwoven nanotextile NANOTARDIS. With its morphological and physical-chemical properties, the device promotes the healing of clean acute wounds. Credit: Technical University of Liberec \"Our experiments on mice confirmed the ability of NANO-LPPO to prevent infection in the wound and thus accelerate healing and regeneration. There was practically no spread of infection where we used the material. If clinical trials go well, this could be a breakthrough in the treatment of burns and other serious injuries where infection poses an acute threat and complication to treatment,\" explains wound care specialist Peter Gál of the Department of Burns Medicine at Charles University's Third Faculty of Medicine, the Faculty of Medicine at P. J. Šafárik University in Košice, and the East Slovak Institute for Cardiovascular Diseases. Nonwoven nanotextile NANOTARDIS. With its morphological and physical-chemical properties, the device promotes the healing of clean acute wounds. Credit: Technical University of Liberec In terms of applications, NANO-LPPO is an interesting material for manufacturers of medicinal products and medical devices. Its commercialization is being coordinated through a collaborative effort between IOCB TECH, a subsidiary of IOCB Prague, and Charles University Innovations Prague, a subsidiary of Charles University, both of which were created for the purpose of transferring results of academic research to practice. The companies are currently seeking a suitable commercial partner. The findings of the interdisciplinary study were published in Scientific Reports. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Active wound dressings are attracting extensive attention in soft tissue repair and regeneration, including bacteria-infected skin wound healing. As the wide use of antibiotics leads to drug resistance we present here a new concept of wound dressings based on the polycaprolactone nanofiber scaffold (NANO) releasing second generation lipophosphonoxin (LPPO) as antibacterial agent. Firstly, we demonstrated in vitro that LPPO released from NANO exerted antibacterial activity while not impairing proliferation/differentiation of fibroblasts and keratinocytes. Secondly, using a mouse model we showed that NANO loaded with LPPO significantly reduced the Staphylococcus aureus counts in infected wounds as evaluated 7 days post-surgery. Furthermore, the rate of degradation and subsequent LPPO release in infected wounds was also facilitated by lytic enzymes secreted by inoculated bacteria. Finally, LPPO displayed negligible to no systemic absorption. In conclusion, the composite antibacterial NANO-LPPO-based dressing reduces the bacterial load and promotes skin repair, with the potential to treat wounds in clinical settings. Introduction Systemic use of antibiotics is currently the hallmark of treating (burn) wound infections, but it may result in harmful side-effects either through direct toxicity or by contributing to the emergence of resistant microorganisms 1 , 2 . Furthermore, many of the currently used topical antimicrobial agents exert cytotoxic effects on keratinocytes and fibroblasts, which may delay wound healing 3 . From this point of view, an efficient topical antimicrobial agent must act at a delicate balance between the need to control microbial growth in the wound bed and the potential risk that the agent impairs wound healing. Previously, we reported the synthesis of novel compounds termed lipophosphonoxins (LPPO) exhibiting significant antibacterial activities against a wide range of bacteria, including multidrug-resistant strains, with no cytotoxicity on human cells at bactericidal concentrations 4 , 5 , 6 . LPPO act through permeabilization of the bacterial membrane leading to its disruption and cell death. So far, we have synthesized and tested two generations of LPPOs. The first LPPO generation 4 displayed significant antibacterial activities against Gram-positive pathogens. Further modifications led to the second LPPO generation with improved antibacterial activities against both Gram-positive and Gram-negative bacteria 6 . Consequently, selected second generation LPPO have been successfully evaluated as antibacterial additives to bone cement 7 . Conventional wound dressings such as gauze, polymer bandage or cotton wool, cannot prevent wound beds from drying and bacterial infection, and need to be replaced, which often results in damage of the healing tissue. Therefore, the development of an active antibacterial and repair/regeneration promoting (e.g. by stem/progenitor cells or growth factor), ideally biodegradable wound dressing is the key for further therapy towards normal healing in a fully controlled manner 8 , 9 , 10 , 11 . Faced with enormous quantities of clinically approved wound dressings it is tempting to find those with the most reliable clinically-relevant properties 12 . In this context, the polycaprolactone (PCL)-based nanofibrous scaffold wound dressing produced by electrospinning is one of the most promising materials as it mimics the original architecture of the native extracellular matrix (ECM) and is biodegradable, degraded into naturally occurring metabolite 6-hydroxyhexanoic acid. It also maintains appropriate moisture and supports gas exchange at the injury site 13 . Moreover, the PCL scaffold has been approved by the American Food and Drug Administration (FDA) for biomedical applications, such as a surgical suture and/or endodontic material 14 , 15 . Microorganisms can develop resistance to conventional antimicrobial drugs. However, based on the structure and underlying mechanism of action, different from that of clinically used antibiotics, it is less likely that microbes will develop cross-resistance to LPPO 6 . Since electrospun nanofibrous scaffolds are potentially useful in medical applications such as wound healing and drug delivery 16 , we loaded the PCL-based wound dressing with LPPO to open new horizons towards novel approaches controlling wound infection. Our new concept was validated on a modified mice model of Staphylococcus aureus impaired wound healing and a series of in vitro experiments conducted on keratinocytes and fibroblasts. Results Wound dressing preparation and morphology PCL-based nanofibrous wound dressings were prepared by blending electrospinning technology 17 , 18 , with the addition of increasing concentrations (0, 2, 5, and 10 wt%) of LPPO DR-6180 (hereafter LPPO). LPPO was selected for its strong antibacterial properties and low cytotoxicity and was synthesized according to the procedure published previously 6 . The quality of the prepared nanofibrous materials was assessed by scanning electron microscopy (SEM). SEM of scaffolds with subsequent basic image analysis of fiber diameters revealed comparable morphology of prepared materials (Fig. 1 ). Histograms show that the fiber diameters were 579 ± 60 nm for PCL, 469 ± 44 nm for NANO-LPPO2%, 664 ± 56 nm for NANO-LPPO5%, and 608 ± 70 nm for PCL-LPPO10%. Figure 1 Representative photomicrographs from scanning electron microscope ( A – H ) and corresponding fiber diameter analysis (histograms, mean ± 95% confidence interval, n = 300) of electrospun PCL material ( I – L ) containing different amount of LPPO: 0% ( A , E , I ), 2% ( B , F , J ), 5% ( C , G , K ) and 10% ( D , H , L ). Scale bar top panel—10 µm (magnification 5000×), bottom panel—50 µm (magnification 1000×). Full size image LPPO release in PBS and LPPO release during enzymatically catalyzed degradation For the antibiotic function of the NANO-LPPO wound covers to be effective, controlled release of the active compound, LPPO, is necessary. Figure 2 A shows a weight loss of NANO-LPPO samples incubated in PBS in the presence or absence of lipase. In a phosphate-buffered saline environment, only the material with the highest concentration of LPPO (NANO-LPPO10%) showed a strong release of LPPO (Fig. 2 B). The LPPO release from NANO-LPPO10% occurred gradually, in the first 24 h 2.9 mg was released rapidly. This is the so-called burst release, which is typical for drugs incorporated using blending electrospinning technology 17 , 18 . Then the release continued more slowly and after 7 days the total amount of LPPO released was<|im_end|> <|im_start|>assistant Researchers at the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague) and the Technical University of Liberec in collaboration with researchers from the Institute of Microbiology of the CAS, the Department of Burns Medicine of the Third Faculty of Medicine at Charles University (Czech Republic), and P. J. Šafárik University in Košice (Slovakia) have developed a novel antibacterial material combining nonwoven nanotextile and unique compounds with antibacterial properties. Called NANO-LPPO, the new material can fulfill a wide range of applications as a dressing for wounds, such as burn injuries, by preventing infection and thus facilitating treatment and healing. Because the number of bacterial strains resistant to common antibiotics is steadily increasing, there is a growing need for new substances with antibacterial properties. A very promising class of substances are the so-called lipophosphonoxins (LPPO) developed by the team of Dominik Rejman of IOCB Prague in collaboration with Libor Krásný of the Institute of Microbiology of the CAS. "Lipophosphonoxins hold considerable promise as a new generation of antibiotics. They don't have to penetrate the bacteria but instead act on the surface, where they disrupt the bacterial cell membrane. That makes them very efficient at destroying bacteria," says Rejman. "A big advantage of LPPO is the limited ability of bacteria to develop resistance to them. In an experiment lasting several weeks, we failed to find a bacteria resistant to these substances, while resistance to well-known antibiotics developed relatively easily," explains Krásný. The potential of LPPO is especially evident in situations requiring immediate targeted intervention, such as skin infections. Here, however, the substances must be combined with a suitable material that ensures their topical efficacy without the need to enter the circulatory system. This reduces the burden to the body and facilitates use. Dr. Dominik Rejman, head of the Antimicrobial Compounds Group at IOCB Prague (Czech Republic). Credit: Tomáš Belloň / IOCB Prague One such suitable material is a polymer nanofiber developed by the team of David Lukáš of the Faculty of Science, Humanities and Education at the Technical University of Liberec. The researchers combined it with LPPO to prepare a new type of dressing material for bacteria-infected skin wounds. The material's main benefit is that the antibacterial LPPO are released from it gradually and in relation to the presence and extent of infection. "The research and development of the material NANO-LPPO is a continuation of the work carried out in a clinical trial on the NANOTARDIS medical device, which we recently successfully completed in collaboration with Regional Hospital Liberec, University Hospital Královské Vinohrady, and Bulovka University Hospital. With its morphological and physical-chemical properties, the device promotes the healing of clean acute wounds," says Lukáš. "This collaboration with colleagues from IOCB Prague is really advancing the possibilities for use of functionalized nanofiber materials in the areas of chronic and infected wounds." "Enzymes decompose the nanomaterial into harmless molecules. The LPPO are an integral component of the material and are primarily released from it during this decomposition. Moreover, the process is greatly accelerated by the presence of bacteria, which produce lytic enzymes. This means that the more bacteria there are in the wound, the faster the material decomposes, which in turn releases more of the active substances into the affected site to promote healing and regeneration of soft tissues," says Rejman in describing the action of the material. Nonwoven nanotextile NANOTARDIS. With its morphological and physical-chemical properties, the device promotes the healing of clean acute wounds. Credit: Technical University of Liberec "Our experiments on mice confirmed the ability of NANO-LPPO to prevent infection in the wound and thus accelerate healing and regeneration. There was practically no spread of infection where we used the material. If clinical trials go well, this could be a breakthrough in the treatment of burns and other serious injuries where infection poses an acute threat and complication to treatment," explains wound care specialist Peter Gál of the Department of Burns Medicine at Charles University's Third Faculty of Medicine, the Faculty of Medicine at P. J. Šafárik University in Košice, and the East Slovak Institute for Cardiovascular Diseases. Nonwoven nanotextile NANOTARDIS. With its morphological and physical-chemical properties, the device promotes the healing of clean acute wounds. Credit: Technical University of Liberec In terms of applications, NANO-LPPO is an interesting material for manufacturers of medicinal products and medical devices. Its commercialization is being coordinated through a collaborative effort between IOCB TECH, a subsidiary of IOCB Prague, and Charles University Innovations Prague, a subsidiary of Charles University, both of which were created for the purpose of transferring results of academic research to practice. The companies are currently seeking a suitable commercial partner. The findings of the interdisciplinary study were published in Scientific Reports. <|im_end|>

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2,495

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Ensembles of trapped atoms interacting with on-chip microwave resonators are considered as promising systems for the realization of quantum memories, novel quantum gates, and interfaces between the microwave and optical regime. Here, we demonstrate coupling of magnetically trapped ultracold Rb ground-state atoms to a coherently driven superconducting coplanar resonator on an integrated atom chip. When the cavity is driven off-resonance from the atomic transition, the microwave field strength in the cavity can be measured through observation of the AC shift of the atomic hyperfine transition frequency. When driving the cavity in resonance with the atoms, we observe Rabi oscillations between hyperfine states, demonstrating coherent control of the atomic states through the cavity field. These observations enable the preparation of coherent atomic superposition states, which are required for the implementation of an atomic quantum memory. Introduction Hybrid quantum systems of superconductors and atomic spin ensembles have been proposed 1 , 2 , 3 for quantum information processing to overcome the limited coherence of superconducting qubits 4 , 5 . In the envisioned hybrid system, information is processed by fast superconducting circuits and stored in a cloud of cold atoms, which serves as a quantum memory 6 , 7 , 8 . Information is transferred between the two quantum systems using a superconducting coplanar waveguide resonator as a quantum bus. In recent years, coupling between superconducting structures and spin systems such as nitrogen vacancy centers 9 , 10 , 11 , 12 , 13 and ions in solid-state systems 14 , 15 has been observed. Cold atoms coupled to superconducting resonators would, furthermore, enable the implementation of novel quantum gates 16 , 17 , 18 , 19 , the realization of a microwave-to-optical transducer 20 , 21 , and on-chip micromasers 22 . The interaction between Rydberg atoms and three-dimensional superconducting microwave resonators has been a rich research topic, especially with regard to atom–photon interactions on the fundamental level 23 . Research on planar superconducting structures, however, holds the promise of switchable interactions between the subsystems, integration with scalable solid-state circuitry 24 , 25 , 26 , and long information storage times in the atomic ensemble. While long coherence times in cold atoms have been studied extensively 27 , 28 , 29 , 30 , 31 and trapping and manipulation of atoms in the vicinity of superconducting chips has been demonstrated in a series of experiments 32 , 33 , 34 , 35 , 36 , 37 , coupling between trapped atoms and planar superconducting resonators has not been shown yet. In this article, we demonstrate magnetic coupling of ultracold magnetically trapped atoms to a superconducting coplanar waveguide resonator operated at temperatures around 6 K. The cavity is near resonant with the atomic hyperfine splitting of 87 Rb and coherently driven by an external microwave synthesizer. We investigate both the dispersive and the resonant coupling regime. By driving the cavity off-resonantly with respect to the atoms, the atomic states reveal an AC-Zeeman shift under the influence of the microwave (MW) field 38 . This leads to a shift of the atomic transition frequency, which is measured by Ramsey interferometry. We use the AC-Zeeman shift to reconstruct the microwave intensity in the coplanar resonator. In contrast, when the cavity is driven at a frequency corresponding to an atomic transition, Rabi oscillations between atomic hyperfine states are observed. Our measurements present a vital step toward the realization of an atom–superconductor hybrid system, paving the way toward the implementation of an atomic quantum memory coupled to a superconducting quantum circuit and the realization of microwave-to-optical transducers. Results Atomic ensembles trapped in a coplanar waveguide resonator For our experiments, we magnetically trap an ensemble of ultracold 87 Rb atoms in the state 5 S 1/2 F = 1, \$m_F = - 1: = \\left| {1, - 1} \\right\\rangle\$ close to a coplanar microwave resonator on an integrated atom chip. The chip comprises two essential structures: i) a Z-shaped wire for magnetic trapping of neutral atoms and ii) a superconducting coplanar waveguide (CPW) resonator (Fig. 1a, b ). Fig. 1 A superconducting atom chip for coupling ultracold atoms to a coplanar resonator. a Schematic top view of the superconducting atom chip, comprising a Z-shaped trapping wire and a coplanar microwave resonator (center conductor marked in red). Parts of the niobium ground planes have been replaced by gold to circumvent the Meissner effect and facilitate magnetic trapping. The slit in the lower ground plane prevents the formation of a closed superconducting loop. b Optical microscope image of the trapping region with the position of the atoms trapped close to the antinode of the resonator. During the measurements, trapping is purely provided by persistent supercurrents around the upper cavity gap and external fields. c Microscope image of the coupling inductances at the output of the resonator and d at the input of the resonator. e Scheme of the measurement setup. Atoms are coupled to a driven coplanar waveguide resonator and detected by state-selective absorption imaging. For Ramsey experiments in the dispersive regime, additional external microwave fields are used to manipulate the atoms. f Simulated coupling strength g /2 π (Hz) between a single ground-state atom and a single photon in the cavity, resonant to the |1, −1〉 → |2, 0〉 transition. The white lines indicate positions of equal density for an atomic cloud of temperature T at = 800 nK in the trap, corresponding to 20, 40, 60, and 80% of the density in the center Full size image The CPW resonator is an inductively coupled half-wavelength cavity 39 with a fundamental mode resonance frequency of ω Res ≈ 2 π · 6.84 GHz and a linewidth of κ ≈ 2 π · 3 MHz corresponding to a quality factor of Q ≈ 2200 in the temperature range ( T = 6–7 K) relevant for the experiments described here. By varying the temperature of the atom chip, the resonance frequency of the microwave cavity can be tuned by about 30 MHz, where the atomic hyperfine transition frequency ω", "role": "user" }, { "content": "Today's quantum technologies are set to revolutionize information processing, communications, and sensor technology in the coming decades. The basic building blocks of future quantum processors are, for example, atoms, superconducting quantum electronic circuits, spin crystals in diamonds, and photons. In recent years it has become clear that none of these quantum building blocks is able to meet all the requirements such as receiving and storing quantum signals, processing and transmitting them. A research group headed by Professors József Fortágh, Reinhold Kleiner and Dieter Kölle of the University of Tübingen Institute of Physics has succeeded in linking magnetically-stored atoms on a chip with a superconducting microwave resonator. The linking of these two building blocks is a significant step towards the construction of a hybrid quantum system of atoms and superconductors which will enable the further development of quantum processors and quantum networks. The study has been published in the latest Nature Communications. Quantum states allow especially efficient algorithms which far outstrip the conventional options to date. Quantum communications protocols enable, in principle, unhackable data exchange. Quantum sensors yield the most precise physical measurement data. \"To apply these new technologies in everyday life, we have to develop fundamentally new hardware components,\" Fortágh says. Instead of the conventional signals used in today's technology – bits – which can only be a one or a zero, the new hardware will have to process far more complex quantum entangled states. \"We can only achieve full functionality via the combination of different quantum building blocks,\" Fortágh explains. In this way, fast calculations can be made using superconducting circuits; however storage is only possible on very short time scales. Neutral atoms hovering over a chip's surface, due to their low strength for interactions with their environment, are ideal for quantum storage, and as emitters of photons for signal transmission. For this reason, the researchers connected two components to make a hybrid in their latest study. The hybrid quantum system combines nature's smallest quantum electronic building blocks – atoms – with artificial circuits – the superconducting microwave resonators. \"We use the functionality and advantages of both components,\" says the study's lead author, Dr. Helge Hattermann, \"The combination of the two unequal quantum systems could enable us to create a real quantum processor with superconducting quantum lattices, atomic quantum storage, and photonic qubits.\" Qubits are – analogous to bits in conventional computing – the smallest unit of quantum signals. The new hybrid system for future quantum processors and their networks forms a parallel with today's technology, which is also a hybrid, as a look at your computer hardware shows: Calculations are made by microelectronic circuits; information is stored on magnetic media, and data is carried through fiber-optic cables via the internet. \"Future quantum computers and their networks will operate on this analogy – requiring a hybrid approach and interdisciplinary research and development for full functionality,\" Fortágh says. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Ensembles of trapped atoms interacting with on-chip microwave resonators are considered as promising systems for the realization of quantum memories, novel quantum gates, and interfaces between the microwave and optical regime. Here, we demonstrate coupling of magnetically trapped ultracold Rb ground-state atoms to a coherently driven superconducting coplanar resonator on an integrated atom chip. When the cavity is driven off-resonance from the atomic transition, the microwave field strength in the cavity can be measured through observation of the AC shift of the atomic hyperfine transition frequency. When driving the cavity in resonance with the atoms, we observe Rabi oscillations between hyperfine states, demonstrating coherent control of the atomic states through the cavity field. These observations enable the preparation of coherent atomic superposition states, which are required for the implementation of an atomic quantum memory. Introduction Hybrid quantum systems of superconductors and atomic spin ensembles have been proposed 1 , 2 , 3 for quantum information processing to overcome the limited coherence of superconducting qubits 4 , 5 . In the envisioned hybrid system, information is processed by fast superconducting circuits and stored in a cloud of cold atoms, which serves as a quantum memory 6 , 7 , 8 . Information is transferred between the two quantum systems using a superconducting coplanar waveguide resonator as a quantum bus. In recent years, coupling between superconducting structures and spin systems such as nitrogen vacancy centers 9 , 10 , 11 , 12 , 13 and ions in solid-state systems 14 , 15 has been observed. Cold atoms coupled to superconducting resonators would, furthermore, enable the implementation of novel quantum gates 16 , 17 , 18 , 19 , the realization of a microwave-to-optical transducer 20 , 21 , and on-chip micromasers 22 . The interaction between Rydberg atoms and three-dimensional superconducting microwave resonators has been a rich research topic, especially with regard to atom–photon interactions on the fundamental level 23 . Research on planar superconducting structures, however, holds the promise of switchable interactions between the subsystems, integration with scalable solid-state circuitry 24 , 25 , 26 , and long information storage times in the atomic ensemble. While long coherence times in cold atoms have been studied extensively 27 , 28 , 29 , 30 , 31 and trapping and manipulation of atoms in the vicinity of superconducting chips has been demonstrated in a series of experiments 32 , 33 , 34 , 35 , 36 , 37 , coupling between trapped atoms and planar superconducting resonators has not been shown yet. In this article, we demonstrate magnetic coupling of ultracold magnetically trapped atoms to a superconducting coplanar waveguide resonator operated at temperatures around 6 K. The cavity is near resonant with the atomic hyperfine splitting of 87 Rb and coherently driven by an external microwave synthesizer. We investigate both the dispersive and the resonant coupling regime. By driving the cavity off-resonantly with respect to the atoms, the atomic states reveal an AC-Zeeman shift under the influence of the microwave (MW) field 38 . This leads to a shift of the atomic transition frequency, which is measured by Ramsey interferometry. We use the AC-Zeeman shift to reconstruct the microwave intensity in the coplanar resonator. In contrast, when the cavity is driven at a frequency corresponding to an atomic transition, Rabi oscillations between atomic hyperfine states are observed. Our measurements present a vital step toward the realization of an atom–superconductor hybrid system, paving the way toward the implementation of an atomic quantum memory coupled to a superconducting quantum circuit and the realization of microwave-to-optical transducers. Results Atomic ensembles trapped in a coplanar waveguide resonator For our experiments, we magnetically trap an ensemble of ultracold 87 Rb atoms in the state 5 S 1/2 F = 1, $m_F = - 1: = \left| {1, - 1} \right\rangle$ close to a coplanar microwave resonator on an integrated atom chip. The chip comprises two essential structures: i) a Z-shaped wire for magnetic trapping of neutral atoms and ii) a superconducting coplanar waveguide (CPW) resonator (Fig. 1a, b ). Fig. 1 A superconducting atom chip for coupling ultracold atoms to a coplanar resonator. a Schematic top view of the superconducting atom chip, comprising a Z-shaped trapping wire and a coplanar microwave resonator (center conductor marked in red). Parts of the niobium ground planes have been replaced by gold to circumvent the Meissner effect and facilitate magnetic trapping. The slit in the lower ground plane prevents the formation of a closed superconducting loop. b Optical microscope image of the trapping region with the position of the atoms trapped close to the antinode of the resonator. During the measurements, trapping is purely provided by persistent supercurrents around the upper cavity gap and external fields. c Microscope image of the coupling inductances at the output of the resonator and d at the input of the resonator. e Scheme of the measurement setup. Atoms are coupled to a driven coplanar waveguide resonator and detected by state-selective absorption imaging. For Ramsey experiments in the dispersive regime, additional external microwave fields are used to manipulate the atoms. f Simulated coupling strength g /2 π (Hz) between a single ground-state atom and a single photon in the cavity, resonant to the |1, −1〉 → |2, 0〉 transition. The white lines indicate positions of equal density for an atomic cloud of temperature T at = 800 nK in the trap, corresponding to 20, 40, 60, and 80% of the density in the center Full size image The CPW resonator is an inductively coupled half-wavelength cavity 39 with a fundamental mode resonance frequency of ω Res ≈ 2 π · 6.84 GHz and a linewidth of κ ≈ 2 π · 3 MHz corresponding to a quality factor of Q ≈ 2200 in the temperature range ( T = 6–7 K) relevant for the experiments described here. By varying the temperature of the atom chip, the resonance frequency of the microwave cavity can be tuned by about 30 MHz, where the atomic hyperfine transition frequency ω<|im_end|> <|im_start|>assistant Today's quantum technologies are set to revolutionize information processing, communications, and sensor technology in the coming decades. The basic building blocks of future quantum processors are, for example, atoms, superconducting quantum electronic circuits, spin crystals in diamonds, and photons. In recent years it has become clear that none of these quantum building blocks is able to meet all the requirements such as receiving and storing quantum signals, processing and transmitting them. A research group headed by Professors József Fortágh, Reinhold Kleiner and Dieter Kölle of the University of Tübingen Institute of Physics has succeeded in linking magnetically-stored atoms on a chip with a superconducting microwave resonator. The linking of these two building blocks is a significant step towards the construction of a hybrid quantum system of atoms and superconductors which will enable the further development of quantum processors and quantum networks. The study has been published in the latest Nature Communications. Quantum states allow especially efficient algorithms which far outstrip the conventional options to date. Quantum communications protocols enable, in principle, unhackable data exchange. Quantum sensors yield the most precise physical measurement data. "To apply these new technologies in everyday life, we have to develop fundamentally new hardware components," Fortágh says. Instead of the conventional signals used in today's technology – bits – which can only be a one or a zero, the new hardware will have to process far more complex quantum entangled states. "We can only achieve full functionality via the combination of different quantum building blocks," Fortágh explains. In this way, fast calculations can be made using superconducting circuits; however storage is only possible on very short time scales. Neutral atoms hovering over a chip's surface, due to their low strength for interactions with their environment, are ideal for quantum storage, and as emitters of photons for signal transmission. For this reason, the researchers connected two components to make a hybrid in their latest study. The hybrid quantum system combines nature's smallest quantum electronic building blocks – atoms – with artificial circuits – the superconducting microwave resonators. "We use the functionality and advantages of both components," says the study's lead author, Dr. Helge Hattermann, "The combination of the two unequal quantum systems could enable us to create a real quantum processor with superconducting quantum lattices, atomic quantum storage, and photonic qubits." Qubits are – analogous to bits in conventional computing – the smallest unit of quantum signals. The new hybrid system for future quantum processors and their networks forms a parallel with today's technology, which is also a hybrid, as a look at your computer hardware shows: Calculations are made by microelectronic circuits; information is stored on magnetic media, and data is carried through fiber-optic cables via the internet. "Future quantum computers and their networks will operate on this analogy – requiring a hybrid approach and interdisciplinary research and development for full functionality," Fortágh says. <|im_end|>

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1,995