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You searched for subject:(Fkbp12). Showing records 1 – 8 of 8 total matches.
1. Blackburn, Elizabeth Anne. Biophysical studies of protein-ligand interactions and the discovery of FKBP12 inhibitors.
Degree: PhD, 2010, University of Edinburgh
► The principal aim of this study was to discover, through virtual screening, new nonimmunosuppressive inhibitors for the human immunophilin FKBP12, a target of the immunosuppressant… (more)
▼ The principal aim of this study was to discover, through virtual screening, new nonimmunosuppressive inhibitors for the human immunophilin FKBP12, a target of the immunosuppressant drugs rapamycin and FK506. The enzyme acts as peptidyl-prolyl isomerase catalysing protein folding in the cell. Structurally similar isomerase domains are important for molecular recognition in multi-domain chaperone proteins. FKBP inhibitors have been shown to have protective effects against nerve damage and are therefore interesting targets for the treatment of neurodegenerative diseases. Virtual screening has been used to discover novel inhibitors for protein drug targets. Recent advances in computational power and the availability of large virtual libraries, such as the EDULISS database at Edinburgh University, have enhanced the appeal of this approach. X-ray structures of known protein-ligand complexes were examined to obtain an understanding of the key non-covalent interactions in the FKBP12 binding pocket. Virtual screening hits were selected using macromolecular docking and programs that employed a ligand-based approach. The bulk of the virtual screening in this study used Edinburgh University's in-house program LIDAEUS. In the course of this study nearly three hundred compounds were screened in the laboratory using biophysical and biochemical binding assays. Thirty four compounds were found to have an affinity for FKBP12 of less than one hundred micromolar. To test virtual hits, it was necessary to select the most appropriate medium-throughput biophysical assay. The aim was to employ methods with sufficient sensitivity to detect compounds with affinity in the order of one hundred micromolar, coupled with the capacity to screen hundreds of compounds in a week. This study used a wide variety of biophysical techniques, these including: electrospray ionisation mass spectrometry, surface plasmon resonance and isothermal titration calorimetry. There was a particular emphasis on the quality of data from electrospray ionisation mass spectrometry. A correlation was found between the cone voltages that gave 50 % dissociation of the complex with the enthalpic contribution to the free energy of binding. From the careful examination of the differences in charge-state distributions between a pure protein and a protein-ligand mixture, it was possible to determine if a protein-ligand complex had been present in solution prior to dissociation during the electrospray process. This observation provides the basis for an assay that could be of general utility in detecting very weak inhibitors.
Subjects/Keywords: 571.4; FKBP12; Cyclophilin A; immunophilin; electrospray ionisation mass spectrometry
Blackburn, E. A. (2010). Biophysical studies of protein-ligand interactions and the discovery of FKBP12 inhibitors . (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/6504
Blackburn, Elizabeth Anne. "Biophysical studies of protein-ligand interactions and the discovery of FKBP12 inhibitors." 2010. Doctoral Dissertation, University of Edinburgh. Accessed July 16, 2019. http://hdl.handle.net/1842/6504.
Blackburn, Elizabeth Anne. "Biophysical studies of protein-ligand interactions and the discovery of FKBP12 inhibitors." 2010. Web. 16 Jul 2019.
Blackburn EA. Biophysical studies of protein-ligand interactions and the discovery of FKBP12 inhibitors. [Internet] [Doctoral dissertation]. University of Edinburgh; 2010. [cited 2019 Jul 16]. Available from: http://hdl.handle.net/1842/6504.
Blackburn EA. Biophysical studies of protein-ligand interactions and the discovery of FKBP12 inhibitors. [Doctoral Dissertation]. University of Edinburgh; 2010. Available from: http://hdl.handle.net/1842/6504
2. Åström-Olsson, Karin. Myocardial ischemia and reperfusion injury, clinical and experimental studies.
Degree: 2010, University of Gothenburg / Göteborgs Universitet
► Acute myocardial infarction is the consequence of an occluded nutrient coronary artery. Reperfusion reduces infarct size and enhances the rate of survival. But reperfusion may… (more)
▼ Acute myocardial infarction is the consequence of an occluded nutrient coronary artery. Reperfusion reduces infarct size and enhances the rate of survival. But reperfusion may also, in itself, cause reversible injury, stunning and arrhythmias, as well as irreversible lethal reperfusion injury. The aim of this thesis was to gain knowledge about the complex pathophysiology behind myocardial reperfusion injury. Two different patient populations with AMI, treated with primary percutaneous coronary intervention were investigated. Presumptive underlying causes for reperfusion injury such as reactive oxygen species (ROS) production, neutrophil activation, signs of inflammation and myocardial cellular damage were studied. In a part of the patient population, delayed-enhanced magnetic resonance imaging (DE-MRI) was performed to estimate infarct size. An experimental porcine infarction with reperfusion was investigated, in which myocardial microdialysis samples and biopsies were analysed with proteomics, Western Blot and real-time-polymerase chain reaction. Mouse cardiomyocytes (HL-1 cells) were analysed after exposition to hypoxia. The HL-1 cells were further investigated with aspects of FKBP12 and FKBP12.6 release in hypoxia, energy depletion, acidosis, ROS activation and re-establishing of physiologic conditions, simulating ischemia and reperfusion at varying durations. Markers for inflammation increased over time, whereas the markers for ROS production and neutrophil activation were at the maximum level at baseline and during the first day. Biomarkers, showing myocardial injury, were useful for infarct size estimation compared with DE-MRI when obtained correctly. FKBP12 and FKBP12.6, increased during ischemia/hypoxia in both the experimental models. Viability of HL-1 cells matched severity of duration and intensity of ischemia. FKBP12 and FKBP12.6 increased during simulated ischemia, while the mRNA expression was depressed suggesting dissociation from receptors regulating intracellular calcium flows. Clinical symptoms and signs of reperfusion injury may partly be explained by release of FKBP12 and FKBP12.6, this causing disturbance of the intracellular cell contraction. These findings may indicate further important mechanisms in ischemia/hypoxia and reperfusion in the heart.
Subjects/Keywords: myocardium; ischemia; reperfusion injury; FKBP12; FKBP12.6
…located stabilizing 21 proteins FKBP12 and FKBP12.6 and their connection to RyR2. This… …FKBP12 and its homologue FKBP12.6 are cis-trans peptidyl-prolyl isomerases, with a molecular… …subunit of RyR2 binds one FKBP12 alternatively FKBP12.6 unit among several other proteins. The… …function of FKBP12 and FKBP12.6 has been established to be a stabilizing agent of the interaction… …function [Yano 2005]. FKBP12 and FKBP12.6 similarly interacts with another receptor…
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Åström-Olsson, K. (2010). Myocardial ischemia and reperfusion injury, clinical and experimental studies . (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/22192
Åström-Olsson, Karin. "Myocardial ischemia and reperfusion injury, clinical and experimental studies." 2010. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed July 16, 2019. http://hdl.handle.net/2077/22192.
Åström-Olsson, Karin. "Myocardial ischemia and reperfusion injury, clinical and experimental studies." 2010. Web. 16 Jul 2019.
Åström-Olsson K. Myocardial ischemia and reperfusion injury, clinical and experimental studies. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2010. [cited 2019 Jul 16]. Available from: http://hdl.handle.net/2077/22192.
Åström-Olsson K. Myocardial ischemia and reperfusion injury, clinical and experimental studies. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2010. Available from: http://hdl.handle.net/2077/22192
3. Rivero-Castro, Juliette. Towards the Total Synthesis of Antascomicin B. Efforts to Construct the C1-C21 Fragment.
Degree: PhD, 2013, University of Arkansas
URL: https://scholarworks.uark.edu/etd/973
► Antascomicin B is a macrolide isolated from a strain of Micromonospora. It possesses structural similarities to FK506 and rapamycin and exhibits potent binding ability… (more)
▼ Antascomicin B is a macrolide isolated from a strain of Micromonospora. It possesses structural similarities to FK506 and rapamycin and exhibits potent binding ability to FKBP12. Recent reports suggest that small molecule ligands of FKBP12 possess potent neuroprotective and neurodegenerative properties in mouse models of Parkinson's disease. Our approach to the C1-21 fragment of antascomicin B involves an asymmetric amino-Claisen rearrangement originally developed by Tsunoda et al.35 report the scalability of the preparation and rearrangement of an allylic amide possessing a silyloxy group at the terminal position of the alkene. The Tsunoda-Claisen rearrangement uses inexpensive (S)-α-methylbenzylamine as the chiral auxiliary. The allylic amide underwent rearrangement to establish the C14 and C15 stereocenters in high yield and good diastereoselectivity. We found a surprisingly high yielding acid mediated lactonization that was employed to cleave the α-methylbenzyl amide. Details of these studies and further elaboration of the lactone are discussed. We also describe the progress toward the synthesis of the C1-21 fragment of the natural product. Advisors/Committee Members: Matthias C. McIntosh, Neil Allison, Suresh Thallapuranam.
Subjects/Keywords: Pure sciences; Amide bond formation; Amino-claisen rearrangement; Antascomicin B; FKBP12; Ireland-Claisen rearrangement; Ring-closing olefin metathesis; Organic Chemistry
Rivero-Castro, J. (2013). Towards the Total Synthesis of Antascomicin B. Efforts to Construct the C1-C21 Fragment . (Doctoral Dissertation). University of Arkansas. Retrieved from https://scholarworks.uark.edu/etd/973
Rivero-Castro, Juliette. "Towards the Total Synthesis of Antascomicin B. Efforts to Construct the C1-C21 Fragment." 2013. Doctoral Dissertation, University of Arkansas. Accessed July 16, 2019. https://scholarworks.uark.edu/etd/973.
Rivero-Castro, Juliette. "Towards the Total Synthesis of Antascomicin B. Efforts to Construct the C1-C21 Fragment." 2013. Web. 16 Jul 2019.
Rivero-Castro J. Towards the Total Synthesis of Antascomicin B. Efforts to Construct the C1-C21 Fragment. [Internet] [Doctoral dissertation]. University of Arkansas; 2013. [cited 2019 Jul 16]. Available from: https://scholarworks.uark.edu/etd/973.
Rivero-Castro J. Towards the Total Synthesis of Antascomicin B. Efforts to Construct the C1-C21 Fragment. [Doctoral Dissertation]. University of Arkansas; 2013. Available from: https://scholarworks.uark.edu/etd/973
4. Kim, Ju Young. M1 muscarinic acetylcholine receptor regulation of endogenous transient receptor potential-canonical, subtype 6 (TRPC6) channels.
Degree: PhD, Molecular, Cellular, and Developmental Biology, 2005, The Ohio State University
► In this study, we show that activation of M1 mAChRs in neuronal PC12D cells stimulates the formation of a multiprotein complex containing M1 mAChRs, TRPC6… (more)
▼ In this study, we show that activation of M1 mAChRs in neuronal PC12D cells stimulates the formation of a multiprotein complex containing M1 mAChRs, TRPC6 channels and protein kinase C (PKC). TRPC6 channels in this complex are phosphorylated by PKC on a conserved serine residue in the carboxyl terminal domain. The immunophilin FKBP12 binds to the phosphorylated TRPC6 channel and creates a binding site for calcineurin/calmodulin, which dephosphorylates the channels. M1 mAChRs and PKC are transiently associated with TRPC6 channels by binding and dissociating within 5 min, while FKBP12, calcineurin, and calmodulin remain associated with the channels for at least 10 min. Dephophorylation of TRPC6 is required for the dissociation of M1 mAChRs, but PKC from the channels. Prior to receptor activation, M1 mAChRs and TRPC6 channels localize to membrane domains that are soluble in the neutral detergent Triton X-100. Within 2 min after activation of the M1 mAChRs, the receptors and channels move into a detergent-resistant membrane (DRM) fraction that contains PKC and FKBP12. Phosphorylation of the channels by PKC and binding to FKBP12, calcineurin and calmodulin take place in the DRM fraction. The DRM fractionates at low-to-medium density in sucrose density gradients, which are enriched in caveolin-1, an integral membrane protein associated with caveolae. Within 5 min after activation, the M1 mAChRs undergo internalization via a clathrin-dependent pathway and the TRPC6 channels undergo internalization via a non-clathrin pathway. Both the M1 mAChRs and TRPC6 channels recycle to non-DRM fractions in the plasma membrane within 30 min after activation of M1 mAChRs. TRPC6 channels are activated in a non-DRM fraction of the plasma membrane and internalization of the TRPC6 channels functions to uncouple the channels from M1 mAChRs. A TRPC6-centered multiprotein complex also forms in cultured primary hippocampal neurons following activation of endogenous muscarinic acetylcholine receptors. This complex contains the same components detected in PC12D cells: M1 mAChRs, TRPC6 channels, PKC, FKBP12, calcineurin and calmodulin. As observed in PC12D cells, the association of M1 AChRs and PKC with TRPC6 channels is transient, while the association of FKBP12, calcineurin and calmodulin with TRPC6 channels is stable for at least 10 min after exposure to carbachol. Taken together, the results of this study provide new insights into mechanisms by which M1 mAChRs regulate TRPC6 channels. Future studies will build on this foundation to elucidate the molecular mechanisms underlying the activation and inactivation of the TRPC6 channels. The long-term goal of these studies is to elucidate the role of TRPC6 channels in M1 mAChR signaling in neurons and to determine the contribution of these channels to brain functions regulated by M1 mAChRs including memory and cognition. Advisors/Committee Members: Saffen, David (Advisor).
Subjects/Keywords: Biology, Molecular; M1 mAChRs; TRPC6; PKC; cavolin-1; internalization; FKBP12
Kim, J. Y. (2005). M1 muscarinic acetylcholine receptor regulation of endogenous transient receptor potential-canonical, subtype 6 (TRPC6) channels . (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1117570788
Kim, Ju Young. "M1 muscarinic acetylcholine receptor regulation of endogenous transient receptor potential-canonical, subtype 6 (TRPC6) channels." 2005. Doctoral Dissertation, The Ohio State University. Accessed July 16, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1117570788.
Kim, Ju Young. "M1 muscarinic acetylcholine receptor regulation of endogenous transient receptor potential-canonical, subtype 6 (TRPC6) channels." 2005. Web. 16 Jul 2019.
Kim JY. M1 muscarinic acetylcholine receptor regulation of endogenous transient receptor potential-canonical, subtype 6 (TRPC6) channels. [Internet] [Doctoral dissertation]. The Ohio State University; 2005. [cited 2019 Jul 16]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1117570788.
Kim JY. M1 muscarinic acetylcholine receptor regulation of endogenous transient receptor potential-canonical, subtype 6 (TRPC6) channels. [Doctoral Dissertation]. The Ohio State University; 2005. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1117570788
5. Olivieri, Lilian. Recherche et caractérisation par dynamique moléculaire d'états intermédiaires pour la complexation entre la protéine FKBP12 et des ligands de haute affinité : Study of building intermediate states between FKBP12 and high-affinity ligands by molecular dynamics simulations.
Degree: Docteur es, Biologie informatique, 2012, La Réunion
URL: http://www.theses.fr/2012LARE0011
FKBP12 est une protéine ubiquitaire, principalement cytosolique, qui est au carrefour de plusieurs voies signalétiques. Son abondance naturelle dans les tissus nerveux peut être reliée… (more)
FKBP12 est une protéine ubiquitaire, principalement cytosolique, qui est au carrefour de plusieurs voies signalétiques. Son abondance naturelle dans les tissus nerveux peut être reliée à son implication dans les maladies neurodégénératives telles que les maladies d'Alzheimer et de Parkinson ainsi que dans les neuropathies périphériques et diabétiques ou dans des blessures des cordons spinaux. De nombreuses études ont montré que des molécules exogènes (ligands) venant se fixer sur cette protéine permettent la régénération d'un grand nombre de connexions neuronales endommagées. Une difficulté provient cependant du fait que, pour un ligand donné, il n'existe aucune relation claire entre sa structure et sa capacité de liaison à FKBP12. Notre étude vise ainsi à rationaliser la relation entre la structure d'un ligand et son affinité pour cette protéine. Deux complexes modèles, formés entre FKBP12 et chacun des deux ligands 8 et 308, ont été utilisés. Ces deux ligands de haute affinité ont des structures différentes. Notre travail s'est appuyé sur des simulations de dynamique moléculaire pour caractériser l'état intermédiaire qui est formé transitoirement lors du processus de complexation entre la protéine et son ligand. Dans cet état particulier, l'identification des interactions naissantes entre les partenaires a permis (i) de comprendre l'implication des différentes parties du ligand dans le mécanisme de reconnaissance avec FKBP12 et (ii) de rationaliser les affinités de certains ligands apparentés.
FKBP12 is an ubiquitous, mostly cytosolic, protein found at the crossroads of several signaling pathways. Its natural abundance in the nervous tissues can be related to its implication in neurodegenerative diseases like Alzheimer's and Parkinson's as well as in peripheral neuropathies and diabetes or in injuries of the spinal cords. Several studies have demonstrated that exogenous molecules (ligands) that can bind to FKBP12 allow the regeneration of many damaged neuron connections. However, there is no clear relationship between the structure of a ligand and its ability to bind to FKBP12. Our study aims at rationalizing the relationship between the structure of a ligand and its affinity to FKBP12. Two model complexes, formed between FKBP12 and each of the two high-affinity ligands 8 and 308, were studied. These two ligands are structurally different. We used molecular dynamics simulations to characterize the intermediate state that is transiently formed during the binding process between the protein and its ligand. In this state, the analysis of the nascent interactions allowed (i) to unravel the role played by the various ligand moieties in the recognition process with FKBP12 and (ii) to rationalize the affinities of related ligands.
Advisors/Committee Members: Offmann, Bernard (thesis director), Gardebien, Fabrice (thesis director).
Subjects/Keywords: Fkbp12; État intermédiaire de complexation; Reconnaissance moléculaire; Interactions protéine-Ligand; Simulations de dynamique moléculaire; Ligand de haute affinité; Paramétrisation d'un champ de force; Calculs Hartree-Fock; Fkbp12; BÉtat intermédiaire de complexationinding intermediate state; Molecular recognition; Protein-Ligand interactions; Molecular dynamics simulations; High-Affinity ligand; Force field parameterization; Hartree-Fock calculations
Olivieri, L. (2012). Recherche et caractérisation par dynamique moléculaire d'états intermédiaires pour la complexation entre la protéine FKBP12 et des ligands de haute affinité : Study of building intermediate states between FKBP12 and high-affinity ligands by molecular dynamics simulations . (Doctoral Dissertation). La Réunion. Retrieved from http://www.theses.fr/2012LARE0011
Olivieri, Lilian. "Recherche et caractérisation par dynamique moléculaire d'états intermédiaires pour la complexation entre la protéine FKBP12 et des ligands de haute affinité : Study of building intermediate states between FKBP12 and high-affinity ligands by molecular dynamics simulations." 2012. Doctoral Dissertation, La Réunion. Accessed July 16, 2019. http://www.theses.fr/2012LARE0011.
Olivieri, Lilian. "Recherche et caractérisation par dynamique moléculaire d'états intermédiaires pour la complexation entre la protéine FKBP12 et des ligands de haute affinité : Study of building intermediate states between FKBP12 and high-affinity ligands by molecular dynamics simulations." 2012. Web. 16 Jul 2019.
Olivieri L. Recherche et caractérisation par dynamique moléculaire d'états intermédiaires pour la complexation entre la protéine FKBP12 et des ligands de haute affinité : Study of building intermediate states between FKBP12 and high-affinity ligands by molecular dynamics simulations. [Internet] [Doctoral dissertation]. La Réunion; 2012. [cited 2019 Jul 16]. Available from: http://www.theses.fr/2012LARE0011.
Olivieri L. Recherche et caractérisation par dynamique moléculaire d'états intermédiaires pour la complexation entre la protéine FKBP12 et des ligands de haute affinité : Study of building intermediate states between FKBP12 and high-affinity ligands by molecular dynamics simulations. [Doctoral Dissertation]. La Réunion; 2012. Available from: http://www.theses.fr/2012LARE0011
Kyoto University / 京都大学
6. Song, Zhi-Ning. Development of novel affinity-guided catalysts for specific labeling of endogenous proteins in living systems : 生物環境における触媒反応による内在性蛋白質の特異的なラベル化法の開発.
Degree: 博士(工学), 2017, Kyoto University / 京都大学
URL: http://hdl.handle.net/2433/228238  ; http://dx.doi.org/10.14989/doctor.k20764
新制・課程博士
甲第20764号
工博第4416号
Subjects/Keywords: affinity-guided DMAP chemistry; affinity-guided oxime chemistry; endogenous FKBP12 labeling in cells; endogenousAMPA recepter labeling in ive tissues; specific endogenous pretein labeling in living system
Song, Z. (2017). Development of novel affinity-guided catalysts for specific labeling of endogenous proteins in living systems : 生物環境における触媒反応による内在性蛋白質の特異的なラベル化法の開発 . (Thesis). Kyoto University / 京都大学. Retrieved from http://hdl.handle.net/2433/228238 ; http://dx.doi.org/10.14989/doctor.k20764
Song, Zhi-Ning. "Development of novel affinity-guided catalysts for specific labeling of endogenous proteins in living systems : 生物環境における触媒反応による内在性蛋白質の特異的なラベル化法の開発." 2017. Thesis, Kyoto University / 京都大学. Accessed July 16, 2019. http://hdl.handle.net/2433/228238 ; http://dx.doi.org/10.14989/doctor.k20764.
Song, Zhi-Ning. "Development of novel affinity-guided catalysts for specific labeling of endogenous proteins in living systems : 生物環境における触媒反応による内在性蛋白質の特異的なラベル化法の開発." 2017. Web. 16 Jul 2019.
Song Z. Development of novel affinity-guided catalysts for specific labeling of endogenous proteins in living systems : 生物環境における触媒反応による内在性蛋白質の特異的なラベル化法の開発. [Internet] [Thesis]. Kyoto University / 京都大学; 2017. [cited 2019 Jul 16]. Available from: http://hdl.handle.net/2433/228238 ; http://dx.doi.org/10.14989/doctor.k20764.
Song Z. Development of novel affinity-guided catalysts for specific labeling of endogenous proteins in living systems : 生物環境における触媒反応による内在性蛋白質の特異的なラベル化法の開発. [Thesis]. Kyoto University / 京都大学; 2017. Available from: http://hdl.handle.net/2433/228238 ; http://dx.doi.org/10.14989/doctor.k20764
7. Song, Zhi-Ning. Development of novel affinity-guided catalysts for specific labeling of endogenous proteins in living systems .
Degree: 2017, Kyoto University
Song, Z. (2017). Development of novel affinity-guided catalysts for specific labeling of endogenous proteins in living systems . (Thesis). Kyoto University. Retrieved from http://hdl.handle.net/2433/228238
Song, Zhi-Ning. "Development of novel affinity-guided catalysts for specific labeling of endogenous proteins in living systems ." 2017. Thesis, Kyoto University. Accessed July 16, 2019. http://hdl.handle.net/2433/228238.
Song, Zhi-Ning. "Development of novel affinity-guided catalysts for specific labeling of endogenous proteins in living systems ." 2017. Web. 16 Jul 2019.
Song Z. Development of novel affinity-guided catalysts for specific labeling of endogenous proteins in living systems . [Internet] [Thesis]. Kyoto University; 2017. [cited 2019 Jul 16]. Available from: http://hdl.handle.net/2433/228238.
Song Z. Development of novel affinity-guided catalysts for specific labeling of endogenous proteins in living systems . [Thesis]. Kyoto University; 2017. Available from: http://hdl.handle.net/2433/228238
8. S. Chaurasia. IN SILICO STUDY OF PROTEIN PROTEIN INTERACTION STABILIZATION AND MECHANICAL FORCE APPLICATION ON BIOMOLECULES.
Degree: 2014, Università degli Studi di Milano
► Targeting protein-protein interactions is a challenging task in drug discovery process. Despite the challenges, several studies have provided evidences for the development of small molecules… (more)
▼ Targeting protein-protein interactions is a challenging task in drug discovery process. Despite the challenges, several studies have provided evidences for the development of small molecules modulating protein-protein interactions. In Part I, it is demonstrated that how a small molecule can induce the formation of an otherwise unstable protein-protein complex. A study of the stabilization of a FKBP12-FRB complex by a small molecule rapamycin is presented. The stability of the complex is analyzed and its interactions are characterized at the atomic level by performing free energy calculations and computational alanine scanning. It is shown that rapamycin stabilizes the complex by acting as a bridge between the two proteins; and the complex is stable only in the presence of rapamycin. The reported results and the good performance of standard molecular modeling techniques in describing the model system can be interesting not only in the design and development of improved molecules acting as FKBP12–FRB protein interaction stabilizers, but also in the somehow neglected study of protein-protein interactions stabilizers in general. In Part II, studies regarding computational modeling of the application of mechanical force to biomolecules is presented. This part is further divided into two chapters since the investigations have been performed on two biological systems. In the first chapter of Part II (chapter 6), it is described that how the osmolyte molecules affect the mechanical unfolding of a peptide. The mechanical unfolding of peptide has been performed by using Steered Molecular Dynamics. In this study, the effect of four different osmolytes on the free energy difference between the folded and the denatured state have been calculated. The observed trend mirrors the expected behavior of the studied osmolytes and unfolding pathways analysis allows an insight into the mechanism of action of osmolytes. After the successful application of Steered molecular dynamics technique on the β-hairpin peptide, the same is applied on tubulin heterodimers for the in-depth study of the lateral and longitudinal interactions which are responsible for the stability and dynamics of the microtubules. In the other chapter of Part II (chapter 7), these interactions are studied with the help of mechanical dissociation of the tubulin heterodimers. These studies have allowed the identification of the critical interactions responsible for the binding of tubulin heterodimers laterally as well as longitudinally. The observations obtained could be important for the design of compounds that target these interactions and acts as microtubule inhibitors or stabilizers. Advisors/Committee Members: tutor: S. Pieraccini, co-tutor: M. Sironi, coordinator: E. Licandro, PIERACCINI, STEFANO, LICANDRO, EMANUELA.
Subjects/Keywords: protein-protein interactions; FKBP12-rapamycin-FRB; computational alanine scanning; steered molecular dynamics; free energy calculations; microtubules; osmolytes; Settore CHIM/02 - Chimica Fisica
…FKBP12-Rapamycin-FRB Case Study… …_______________________________________________________________________ Figure 5: The structure of the ternary complex of FKBP12-rapamycin-FRB is shown representing… …PPI-stabilization. FKBP12 partner of the complex is represented in cyan whereas FRB partner… …x28;FKBP12) and FKBP12rapamycin-binding domain of FRAP (FRB) with the small…
Chaurasia, S. (2014). IN SILICO STUDY OF PROTEIN PROTEIN INTERACTION STABILIZATION AND MECHANICAL FORCE APPLICATION ON BIOMOLECULES . (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/229253
Chaurasia, S.. "IN SILICO STUDY OF PROTEIN PROTEIN INTERACTION STABILIZATION AND MECHANICAL FORCE APPLICATION ON BIOMOLECULES." 2014. Thesis, Università degli Studi di Milano. Accessed July 16, 2019. http://hdl.handle.net/2434/229253.
Chaurasia, S.. "IN SILICO STUDY OF PROTEIN PROTEIN INTERACTION STABILIZATION AND MECHANICAL FORCE APPLICATION ON BIOMOLECULES." 2014. Web. 16 Jul 2019.
Chaurasia S. IN SILICO STUDY OF PROTEIN PROTEIN INTERACTION STABILIZATION AND MECHANICAL FORCE APPLICATION ON BIOMOLECULES. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2019 Jul 16]. Available from: http://hdl.handle.net/2434/229253.
Chaurasia S. IN SILICO STUDY OF PROTEIN PROTEIN INTERACTION STABILIZATION AND MECHANICAL FORCE APPLICATION ON BIOMOLECULES. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/229253


please someone help me! Simple Controls Gallery's description shows only when mouseover. i want it to show always after the page is loaded! any idea?
thank you very much! And what if i want this with gallery too?
Hmm what do you mean by "with gallery too"?
'till now i liked this site, now i love it! Thank you!
one last question. And what if in the nav panel i son't want to show the "1/4"?


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Déjà Vu (2006)
Posted by Matthew | Dec 2, 2011 | Drama, Sci-Fi, Thrillers | 0 |
Déjà Vu left me very confused. For not one second did I think that the science involved could be possible, but I think it broke its own rules in the process of breaking previous time traveling conventions. By the time it ended, I didn't care much any more, and hoped that I could use the device featured in the film to stop me from getting past the first hour, because that's when the fun stops.
We begin by watching a ferry, and by extension, the people on the ferry. We go around, we see a child lose her doll in the water, and basically just observe life. Then the ship blows up, and all these people die. 543 people are sent to the bottom of the river, if I remember correctly. Enter ATF Special Agent Douglas Carlin (Denzel Washington), who is sent to investigate this explosion. Why him? Well, he's very good at figuring out what should and shouldn't be at a crime scene. Oh, and he's also played by Denzel Washington. That helps too.
The end up discovering a body of a woman named Claire Kuchever (Paula Patton). She has burns on 30% of her body, and her fingers appear to have been severed by shrapnel. There's a problem though: Her body was uncovered before the explosion occurred, and was found in a place going against the current. If that's not suspicious, nothing is. We then decide to focus on her and her assumed murder, with the presumption being that if her killer's found, then so will the person who triggered the explosion. If I was on the case, I'd assume it wasn't just a one-person job, but that thought doesn't seem to cross anyone's mind.
We then enter a facility that contains a mystical technology dubbed "Snow White," which allows our characters to observe events that happened in the past using satellite surveillance. Apparently, satellites actually take 360 degree photos, and are able to capture all sound effects as well. The catch is that you can only view things that happened four and a half days ago, and you can't rewind your footage. What's the reasoning behind that? Apparently it would require too much hard drive space to do that.
We follow Claire around and watch her live her life for a while. After some time, we find out, just as Douglas does, that this machine can also send things back in time, although we're told it can't be anything large or alive, nor will it actually be able to alter the past. If you think you know where the plot is going from here, you're probably right.
It's at this point when I stopped caring. Déjà Vu sets itself up as a mystery film where we get to solve the case of the blown-up ferry, but instead, we end up with a man-on-a-mission story that isn't all that interesting because we've seen it all before. If the technology had just done what we initially thought it could, it would have been more interesting, because that's a unique technology. Bringing time travel into it just gets messy and less interesting the more it's used.
While we open with an explosion, we don't get much action until the final third of the movie, which has many explosions — most of which are implausible — and a couple of high-speed driving sequences. If a car is hit while you're backing up, does it automatically explode? Having never been in an accident, I wouldn't know, but at least three of them do in this movie, and I had a hard time believing that. It also didn't add anything to the plot, and since it came near the end, I wager director Tony Scott found out he was under-budget, and wanted to blow some more things up.
Déjà Vu loses steam way before it ends. Like I said, once the time travel gets involved, I almost completely lost interest. The first hour is an intense mystery movie, while the second is an action movie about a guy wanting to save a girl. He doesn't seem to care much about those 543 people who die in the explosion though. When the movie ends, which it does on a very silly note, I had been ready for the finale for at least 30 minutes.
When Déjà Vu works well, it's because we're not sure what's going on, but we want to find out. When it fails, we're confused but don't care enough to think about how what's going on is possible. There just aren't enough interesting parts to balance out the poor, which left me feeling as if I wasted my time. Parts work, especially early on, but it didn't keep my interest once it brought in time travel and degenerated into an action film.
Denzel Washington is a strong lead, and he gives a solid performance here. So does Paula Patton, someone who gets more screen time than I anticipated she would. Some of the things they're forced to say and do are ridiculous, but coming from them, I could almost buy in. In the end though, I couldn't. What they're forced to do is just too silly to be believable, and even in a movie where time travel exists, I couldn't wrap my head around the logic in this movie.
Déjà Vu is really good for its first hour, and pretty bad for the second, unless you still aren't tired of action movies with the most basic of plots. The science doesn't make a lot of sense, the ending is frustrating, and the mystery ends up taking a back seat to a man trying to change the past, despite being told multiple times that he cannot. There are good moments, but they're pushed aside for the bad and outright ridiculous.
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Gothika (2003)
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Broken: Torture Porn or Psychological Horror?

redpajama_set_name: RedPajamaCommonCrawl


text:
Walt Mossberg agrees that Google Maps is better on iPhone than on Android
Google's new iOS Maps app is universally accepted as the best experience on any mobile platform. First Google told The New York Times columnist David Pogue that it "admits that it's even better than Google Maps for Android phones", which Pogue says has accommodated its evolving feature set "mainly by piling on menus". And now, Pogue's peer over at The Wall Street Journal, Walt Mossberg, seems to agree as he calls Google's iPhone mapping software "better in most respects" on the iPhone than it is on Android phones, where "it looks inelegant by comparison"…
From Mossberg's Google Maps review:
I've been testing the new Google Maps on iPhone for a week or so in the San Francisco and Washington metro areas, and I really like it. It isn't perfect, but I prefer it to any other iPhone Maps app I've used, and to Google Maps on Android. The latter will likely also gain the new design in time, but for now, it looks inelegant by comparison.
Also this (emphasis mine):
However, the biggest news here is that the new iPhone version of Google Maps isn't just better than Apple Maps. For now, at least, Google Maps is better in most respects on the iPhone than it is on Android phones.
It has been redesigned with a cleaner, simpler user interface that makes it easier to use. Google officials say they took the sudden need to build a new iPhone version as an opportunity to rethink the popular app from the ground up.
Pogue also wrote in his review that the two most glaring omission – the lack of native iPad support and offline mode – are likely to be addressed, writing that "goodies like those will be coming soon".
"We believe this delightful new experience is a great starting point—and we'll continue to improve Google Maps for you, every day", the search firm wrote in a blog post.
http://www.youtube.com/watch?v=KEz1sSKCpIc
Of course, Google's been cramming new features into Google Maps for Android by way of adding new options to menus, eventually cluttering the user interface up to the point of confusion. On the iPhone, Google started from scratch and wrote the app from the ground up, with none of the baggage from the past.
It should be noted that the Android version still one-ups that on the iPhone in terms of available features. For example, bicycling directions and interior maps are available on Android, but not on the iPhone. Android users can also cache maps for offline use and receive alerts for nearby offers that show up for some businesses.
According to Mossberg, Google says "these may be added over time". The iPhone version supports other headline features, including Street View and turn-by-turn directions.
People were certainly very eager to try out Google's Maps iOS app.
Currently the App Store's #1 free app, it saw ten million downloads in the first 48 hours of availability.
The program may have even boosted iOS 6 adoption rate, with MoPub seeing a 29 increase in unique iOS 6 users in the five days after Google Maps for iOS was released and a thirteen percent increase from Monday to Wednesday of last week.
Would you agree that Google Maps on the iPhone is better than that on Android?
Tags Apple Apple Maps Google Google Maps Maps NYT WSJ


WONDER WOMAN #41 – Issue 600 arrives in May, if memory serves.
MS MARVEL #50 – Final issue.
Marvel is also releasing issue #4 (of 8) of The Marvelous Land of Oz. I really like the artwork—the series has been surprisingly good.
I'll also be picking up Knights of the Dinner Table #159.
Flash Rebirth number 6!? Hooray!


Quantum machine learning is expected to be one of the first potential general-purpose applications of near-term quantum devices. A major recent breakthrough in classical machine learning is the notion of generative adversarial training, where the gradients of a discriminator model are used to train a separate generative model. In this work and a companion paper, we extend adversarial training to the quantum domain and show how to construct generative adversarial networks using quantum circuits. Furthermore, we also show how to compute gradients -- a key element in generative adversarial network training -- using another quantum circuit. We give an example of a simple practical circuit ansatz to parametrize quantum machine learning models and perform a simple numerical experiment to demonstrate that quantum generative adversarial networks can be trained successfully.


text:
Q: Get file content, rename that file and after that getting the content again fails I have one interesting problem, but I don't know why this happend. Generally I: 1) try get content from file (succesful result) 2) then I rename file in sharepoint (succesful result) 3) try get content of the renamed file (fail)
in code it looks like:
First get content:
public Stream GetFileContent(int fileId)
{
    var item = _list.GetItemById(fileId);
    var fileStream = item.File.OpenBinaryStream();
    _clientContext.ExecuteQuery();
    return fileStream.Value;
}

Then rename:
public void Rename(int id, string newName)
{
    var item = _list.GetItemById(id);
    item["Title"] = newName;
    item["FileLeafRef"] = newName;

    try
    {
        var file = item.File;
        item.Update();
        _clientContext.ExecuteQuery();
    }
    catch (ServerException ex)
    {

    }
}

And for this code after the second call of GetFileContent I have an exception [Microsoft.SharePoint.Client.ServerException] = {"File Not Found."}
==========================================================================
After some investigations I found another way how to rename the file and added Checkout/Checkin commands:
try
        {
        var file = item.File;
        file.CheckOut();
        item.Update();
        file.CheckIn("file name has been changed", CheckinType.MajorCheckIn);
        _clientContext.ExecuteQuery();
    }

But in this case a exception: Message = "The file \"https://my.sharepoint.com/mynewsupersite/Shared Documents/document.docx\" is checked out for editing by i:0#.f|membership|email@email.com"... stuff like that
and renaming doesn't work corrrectly anymore.
I'm new in the sharepoint programming, so can you please explain where I'm wrong and give an idea how to fix it ?
Big thanks

A: Seems like my problem is fixed. I added .Load() for a list item in the Rename method:
try
        {
            item["Title"] = newName;
            item["FileLeafRef"] = newName;
            item.Update();
            _clientContext.Load(
                item,
                i => i,
                i => i.FileSystemObjectType,
                i => i.File,
                i => i.File.ListItemAllFields,
                i => i.File.ListItemAllFields.EffectiveBasePermissions,
                i => i.File.ServerRelativeUrl,
                i => i.Folder,
                i => i.Folder.ListItemAllFields,
                i => i.Folder.ListItemAllFields.EffectiveBasePermissions,
                i => i.Folder.ServerRelativeUrl,
                i => i.Folder.Properties,
                i => i.Folder.Folders
            );
            _clientContext.ExecuteQuery();
        }

redpajama_set_name: RedPajamaStackExchange


text:
Lesson: How Does an Ultrasonic Sensor Work?
Contributed by: GK-12 Program, Computational Neurobiology Center, College of Engineering, University of Missouri
How Does an Ultrasonic Sensor Work?
Time Required: 45 minutes
Lesson Dependency:
What Is a Sensor?
Subject Areas: Biology, Computer Science, Life Science, Science and Technology
Lessons in this Unit:
Lesson Dependency
Lesson dependency indicates that this lesson relies upon the contents of the TeachEngineering document(s) listed.
Print this lesson
Print lesson and its associated curriculum
And, if you provide us with your email address, we may contact you to learn from your experience with this lesson:
How Do Sensors Work?
Robot Sensors and Sound
What Is a Motor and How Does a Rotation Sensor Work?
Master Driver
How Does a Touch Sensor Work?
Music by Touch: Programming Robot Tactile Sensors to Play Sounds
How Does a Sound Sensor Work?
Control Using Sound
How Does a Color Sensor Work?
Follow the Light
Ultrasonic Sensor Robot Design Project: Don't Bump into Me!
body brain distance echo echolocation EV3 human body LEGO MINDSTORMS neuroscience programming radar robot sensor sight sonar sound wave ultrasonic ultrasonic sensor vision
Or, ask a question about this lesson
Worksheets and Attachments
Lesson Closure
Additional Multimedia Support
Bats use echolocation to find and identify objects in their surroundings. To help robots identify objects, engineers have created ultrasonic sensors that operate using the same principles.
Copyright © (left) Wisconsin Department of Natural Resources; (right) LEGO https://shop.lego.com/en-CA/EV3-Ultrasonic-Sensor-45504
Students learn about how ultrasonic sensors work, reinforcing the connection between this sensor and how humans, bats and dolphins estimate distance. They learn the echolocation process—sound waves transmitted, bounced back and received, with the time difference used to calculate the distance of objects. Two mini-activities, which use LEGO® MINDSTORMS® EV3 robots and ultrasonic sensors, give students a chance to experiment with ultrasonic sensors in preparation for the associated activity. A PowerPoint® presentation explains stimulus-to-response pathways, sensor fundamentals, and details about the LEGO ultrasonic sensor. Pre/post quizzes are provided. This lesson and its associated activity enable students to gain a deeper understanding of how robots can take sensor input and use it to make decisions via programming.
Biological engineers and neuroscientists perceive the human body as a functioning, controlled system, similar to a robot. Research findings are showing that mathematical principles similar to those used in robotics are extremely useful or even necessary for a complete understanding of the human body. Through this lesson, students strengthen their understanding of the functioning of each of the human (and bat) senses by relating them to the different sensors used in robots. Ultrasonic sensors are used in medicine to detect shapes and sizes of otherwise unseen internal body parts. For instance, doctors can determine gender of a fetus in the womb of its mother. Ultrasonic sensors are also used to determine wind speed and direction. Sonar and radar technologies are based on the same concepts.
After this lesson, students should be able to:
Describe how ultrasonic sensors work.
Compare the ultrasonic sensor to how humans and bats estimate distance.
Program the LEGO MINDSTORMS EV3 robot with the ultrasonic sensor.
Provide a basic explanation of how sensors are integrated into robots via careful programming.
Use argument supported by evidence for how the body is a system of interacting subsystems composed of groups of cells. (Grades 6 - 8 ) More Details
Use an oral and written argument supported by evidence to support or refute an explanation or a model for a phenomenon.
In multicellular organisms, the body is a system of multiple interacting subsystems. These subsystems are groups of cells that work together to form tissues and organs that are specialized for particular body functions.
Systems may interact with other systems; they may have sub-systems and be a part of larger complex systems.
Scientists and engineers are guided by habits of mind such as intellectual honesty, tolerance of ambiguity, skepticism, and openness to new ideas.
Gather and synthesize information that sensory receptors respond to stimuli by sending messages to the brain for immediate behavior or storage as memories. (Grades 6 - 8 ) More Details
Gather, read, and synthesize information from multiple appropriate sources and assess the credibility, accuracy, and possible bias of each publication and methods used, and describe how they are supported or not supported by evidence.
Each sense receptor responds to different inputs (electromagnetic, mechanical, chemical), transmitting them as signals that travel along nerve cells to the brain. The signals are then processed in the brain, resulting in immediate behaviors or memories.
Cause and effect relationships may be used to predict phenomena in natural systems.
Common Core State Standards - Math
Solve problems involving measurement and conversion of measurements from a larger unit to a smaller unit. (Grade 4 ) More Details
Convert among different-sized standard measurement units within a given measurement system (e.g., convert 5 cm to 0.05 m), and use these conversions in solving multi-step, real world problems. (Grade 5 ) More Details
Various relationships exist between technology and other fields of study. (Grades 3 - 5 ) More Details
Knowledge gained from other fields of study has a direct effect on the development of technological products and systems. (Grades 6 - 8 ) More Details
Missouri - Science
Describe how new technologies have helped scientists make better observations and measurements for investigations (e.g., telescopes, magnifiers, balances, microscopes, computers, stethoscopes, thermometers) (Grade 4 ) More Details
Describe how new technologies have helped scientists make better observations and measurements for investigations (e.g., telescopes, electronic balances, electronic microscopes, x-ray technology, computers, ultrasounds, computer probes such as thermometers) (Grade 5 ) More Details
Explain the interactions between the nervous and muscular systems when an organism responds to a stimulus (Grade 8 ) More Details
How Does the Ultrasonic Sensor Work? Presentation (pptx)
How Does an Ultrasonic Sensor Work? Presentation (pdf)
Ultrasonic Sensor Pre-Quiz (docx)
Ultrasonic Sensor Pre-Quiz (pdf)
Ultrasonic Sensor Pre-Quiz Answer Key (docx)
Ultrasonic Sensor Pre-Quiz Answer Key (pdf)
Ultrasonic Sensor Post-Quiz (docx)
Ultrasonic Sensor Post-Quiz (pdf)
Ultrasonic Sensor Post-Quiz Answer Key (docx)
Ultrasonic Sensor Post-Quiz Answer Key (pdf)
Visit [www.teachengineering.org/lessons/view/umo_sensorswork_lesson06] to print or download.
Students learn about how touch sensors work, while reinforcing their similarities to the human sense of touch. They look at human senses and their electronic imitators, with special focus on the nervous system, skin and touch sensors.
Students learn about electric motors and rotational sensors. They learn that motors convert electrical energy to mechanical energy and typically include rotational sensors to enable distance measuring. Students create a basic program using the LEGO® MINDSTORMS® interface to control a motor to move a...
How Do You Make a Program Wait?
Building on the programming basics learned so far in the unit, students next learn how to program using sensors rather than by specifying exact durations. Working with the LEGO® MINDSTORMS® EV3 robots and software, they learn about wait blocks and how to use them in conjunction with move blocks set ...
Students learn more about how color sensors work, reinforcing their similarities to the human sense of sight. This lesson and its associated activity enable students to gain a deeper understanding of how robots can take sensor input and use it to make decisions via programming.
An understanding of the primary five senses of the human body: sight, hearing, smell, taste and touch.
Completion of the previous units in the series: Humans Are Like Robots (unit 1), Our Bodies Have Computers and Sensors (unit 2), What Is a Computer Program? (unit 3).
Completion of the previous lessons and activities in this unit, especially the What Is a Sensor? lesson.
(Be ready to show students the 19-slide How Does an Ultrasonic Sensor Work? Presentation, a Microsoft® PowerPoint® file, to teach the lesson. In advance, make copies of the Ultrasonic Sensor Pre-Quiz and Ultrasonic Sensor Post-Quiz, one each per student, provided as attachments and slides. For the mini-activities, student pairs use LEGO robot components to experiment with the sensors.)
Today we are investigating another sensor—the ultrasonic sensor. Have you heard of an ultrasonic sensor? This sensor is able to estimate objects in front of it using reflected sound. Does this process sound similar to any other process you know of? (Listen to student ideas. They may mention bats, echolocation, radar or sonar). This process is similar to how bats locate objects in their paths.
Our lesson includes two mini-activities to help us get familiar with the LEGO EV3 ultrasonic sensor. Then in the next class, we will conduct a more-involved activity that gives you the opportunity to program your LEGO robots to move about freely without bumping into LEGO people. To do that, you'll use a LEGO EV3 ultrasonic sensor to detect whether anything is in the way.
(Continue by showing the presentation and delivering the content in the Lesson Background section.)
Lesson Background and Concepts for Teachers
Present the lesson using the content provided in the slide presentation, as described below. The quizzes are embedded in the presentation if you wish to go through them as a class. During the lesson, students engage in two mini-activities (slides 11-12) that require the following items for each student pair:
LEGO MINDSTORMS EV3 robot, such as EV3 Core Set (5003400) for $389.95 at https://education.lego.com/en-us/products/lego-mindstorms-education-EV3-core-set-/5003400
LEGO MINDSTORMS Education EV3 Software 1.2.1, free online, you have to register a LEGO account first; at https://www.lego.com/en-us/mindstorms/downloads/download-software
computer, loaded with EV3 1.2.1 software
paper and pencil, for writing mini-activity observations and programming steps
Note: This activity can also be conducted with the older (and no longer sold) LEGO MINDSTORMS NXT set instead of EV3; see below for those supplies:
LEGO MINDSTORMS NXT Base Set
computer loaded with the NXT 2.1 software
How Does the Ultrasonic Sensor Work? Presentation Outline (Slides 1-19)
Administer the pre-quiz by handing out paper copies; the quiz is also on slide 2. The answers are provided for the teacher on slide 3 for discussion after students have completed the quiz.
(slide 4) Explain the structure of the LEGO EV3 ultrasonic sensor. (Hold up an ultrasonic sensor to show students.) It has two main parts. A transmitter sends out a signal (an ultrasonic wave) that humans cannot hear. And a receiver receives the signal after it has reflected off nearby objects. The sensor times how long it takes for its signals to come back and relays that information to the LEGO brick/computer, which calculates how far away objects are. Ask the students: Does this process sound familiar? Do you know of any animal that are able to sense in a similar way? (Answer: Bats, dolphins, porpoises and some whales use echolocation, sometimes called biosonar.)
(slides 5-7) How does a bat locate its prey in the dark? Explain how bats use echolocation to measure distance and the similar process with a robotic sensor. The time difference between sending and receiving is used to estimate distance.
(slide 8) Provide an overview of robotic sensors to keep emphasizing the big picture.
Measuring distance using the echolocation concept.
Copyright © 2005 Georg Wiora, Wikimedia Commons http://commons.wikimedia.org/wiki/File:Sonar_Principle_EN.svg
(slide 9) Go into the details of the same concepts, but with some specifics on measuring distance. The ultrasonic sensor can measure distances in centimeters and inches. It can measure from 0 to 2.5 meters, with a precision of 3 cm. It provides good readings in sensing large-sized objects with hard surfaces, but has more difficulties reading reflections from soft, curved, thin or small objects.
(slide 10) The ultrasonic sensor sends out sound from one side (one of the "eyes") and receives it back using the sensor on the other side. Together, the ultrasonic sensor's transmitter and receiver look like a pair of eyes, but it is not a sight sensor. Instead, those "eyes" are really more like a speaker and a microphone (a sound sensor).
For the mini-activities, divide the class into pairs and give each pair a LEGO EV3 ultrasonic sensor, motor, intelligent brick and two cables. Direct student pairs to follow the instructions on slides 11-12 to experiment with the EV3 ultrasonic sensor.
(slide 11) In the first activity, they spend ~10 minutes using the ultrasonic sensor connected to the brick to study how the sensor works and what it does. Make sure they do the "Try Me" option and write down their observations from their experimentation.
(slide 12) In the second activity, they add the motor to the setup and spend ~15 minutes programming the LEGO robot so that it plays one music when an object is close to it (less than 10 inches), and keeps the motor turning. If the object is farther than 10 inches, have the program stop. On a separate sheet of paper, have students provide step-by-step explanations describing how the program works. The programming solution is provided for the teacher on slides 13-16.
Administer the post-quiz by handing out paper copies; the quiz is also on slide 17. The answers are provided on slide 18. This concludes the lesson. Slide 19 contains vocabulary terms and definitions. Next, conduct the associated activity Ultrasonic Sensor Robot Design Project: Don't Bump into Me!
Ultrasonic Sensor Robot Design Project: Don't Bump into Me! - Student groups program LEGO robots outfitted with ultrasonic sensors to meet a design challenge: Enable the robot to roam around freely without bumping into the toy people obstacles. They practice and learn programming skills and logic design in parallel, seeing how robots take input from ultrasonic sensors and use it to make decisions to move, similar to echolocation. They iterate their designs to success.
Engineers were inspired by how bats estimate distance to objects in their surroundings to design the ultrasonic sensor. Robots use sensors to make decisions about movement and actions in much the same manner as humans do to control their muscles and bodily functions.
auditory: Related to hearing.
echolocation: Biological sonar used by animals, such as bats and dolphins, in which the animal sends out a call and uses the echo to locate and identify surrounding objects.
peripheral: Surrounding.
sensor: A device that converts one type of signal to another; for instance, the speedometer in a car collects physical data and calculates and displays the speed the car is moving.
transducer: Another term for a sensor.
ultrasonic: A sound that we cannot hear, but bats and dogs can hear.
Pre-Lesson Assessment
Pre-Quiz: Administer the three-question Ultrasonic Sensor Pre-Quiz by handing out paper copies (also on slide 2). Students' answers reveal their base knowledge of ultrasonic sensors, as well as how humans and bats estimate distances. Have students answer as best as they can. Answers are provided in the Ultrasonic Sensor Pre-Quiz Answer Key (and on slide 3).
Post-Introduction Assessment
Hands-On Learning: Observe all students as they engage in the mini-activities described on slides 11-12. Make sure all pairs are following the slide instructions to experiment with the ultrasonic sensor. Question individual students to verify that they understand how the ultrasonic sensor works. Compare groups' programming answers to the teacher solution provided on slides 13-16. Review their written observations and programming answers to gauge their comprehension of the topic and readiness for the associated activity.
Lesson Summary Assessment
Conversion Practice: Have students practice unit conversions as they convert the following example ultrasonic sensor distance readings from centimeters to inches and vice versa:
5 cm = _____ inches (1 cm = ~0.394 inches --> 5 cm x 0.39 = 1.97 inches)
3 cm = _____ inches (1.18 inches)
2 inches = _____ cm (1 inch = 2.54 cm --> 2 in. x 2.54 = 5.08 cm)
4 inches = _____ cm (10.16 cm)
Post-Quiz: Administer the Ultrasonic Sensor Post-Quiz by handing out paper copies (also on slide 17). Review students' answers to assess their understanding, as well as how much they learned during the course of the lesson. Quiz answers are provided on the Ultrasonic Sensor Post-Quiz Answer Key (and on slide 18).
EV3 robots and sensors: http://mindstorms.lego.com/eng/Overview/default.aspx
What is a transducer? http://en.wikipedia.org/wiki/Transducer
What is a sensor? http://en.wikipedia.org/wiki/Sensors
List of sensors http://en.wikipedia.org/wiki/List_of_sensors
Nishant Sinha, Pranit Samarth, Satish S. Nair
© 2013 by Regents of the University of Colorado; original © 2013 Curators of the University of Missouri
GK-12 Program, Computational Neurobiology Center, College of Engineering, University of Missouri
This curriculum was developed under National Science Foundation GK-12 grant no. DGE 0440524. However, these contents do not necessarily represent the policies of the National Science Foundation, and you should not assume endorsement by the federal government.


GMC brand sales declined 8.7% in September with a total of 43,268 vehicles delivered to US customers. Retail sales were down 5.6% at 38,695 units. Five of the seven vehicles in GMC's lineup experienced year-over-year sales increases, but the two vehicles to see declines were down enough to offset those other gains.
Sales of the Sierra were down 8.5% overall at 18,068 units delivered. Despite the hiccup, Sierra sales are up 1.7% year-to-date with a total of 164,440 trucks delivered, and retail sales are the highest they have been since 2006.
Terrain sales fell 48.3% at 5,656 units; year-to-date, sales are down 18.6% at 67,912 units.
Otherwise, September was relatively rosy for GMC. Canyon sales increased 26.5% at 2,949 units delivered; retail sales were up 25%, good for the highest total the truck has ever seen for the month of September. Through nine months, Canyon sales are up 21.3% at 27,205 units, and retail sales are also on pace for a record best.
Yukon sales were up 33.6% at 5,296 units, and Yukon XL sales were up 15.6% at 3,500 units. At retail, the Yukon and Yukon XL both earned their best September performances since 2007 with increases of 24% and 9%, respectively. Sales of the Yukon are up 17.7% through nine months, and Yukon XL sales are up 15.2%; retail-wise, both are experiencing their best first three quarters since 2007.
Acadia sales rose 2.2% at 6,795 units, and Savana sales rose 37.9% at 1,004 units.
Other less visible metrics for success include Denali penetration, which was 28% for September, and a $44,144 ATP that was 45% higher than the industry average and the second highest in brand history.
Through September, GMC's sales are down 4.6% at 391,432 units delivered, and retail sales are down 2.2% at 345,478 units.


text:
Вільям Бромфілд (, також відомий як ; 31 січня 1712 — 24 листопада 1792) — американський і британський хірург та анатом, відкрив у Лондоні першу клініку з лікування венеричних захворювань — госпіталь Lock.

Біографія

Вільям Бромфілд народився 31 січня 1712 року в Лондоні, і після кількох років навчання у хірурга, розпочав власну практику. У 1741 він почав читати курс лекцій з анатомії та хірургії, який відвідувало багато учнів. Кілька років згодом, він сформував з Мартіном Меденом план Лондонської замкової лікарні для лікування венеричного захворювання, на яке він був призначений хірургом. Для театральної вистави на допомогу його фондам він змінив стару комедію, «Міський Матч», написаний в 1639 Джаспаром Меном, який в 1755 діявся на Друрі-Лейн. Він був також обраний одним з хірургів лікарні Св. Георгія.

У 1761 він був призначений одним з набору, щоб супроводити принцесу Мекленбурга на її поїздці до Англії, яка буде пов'язана узами шлюбу з Георгом III, і після шлюбу, він був призначений хірургом на домашнє господарство її величності.

У його пізніших роках він пішов зі своєї професії і проживав у будинку, який він побудував для себе в парку Челсі. Помер 24 листопада 1792 року.

Бібліографія
 An Account of English Nightshades, 1757.
 Narrative of a Physical Transaction with Mr. Aylet, surgeon at Windsor, 1759.
 Thoughts concerning the present peculiar Method of treating persons inoculated for the Small-pox, 1767.
 Chirurgical Cases and Observations, 2 vols., 1773.

Примітки

Посилання
 Ця стаття включає в себе текст з публікації, яка тепер знаходиться у відкритому доступі: Bromfield, William. Dictionary of National Biography.'' London: Smith, Elder & Co. 1885—1900.

redpajama_set_name: RedPajamaWikipedia


I want to give you 3 coupons, for a set I LOVE BERRY CAKES.
I do not have luck to win a kit with you, but I have the coupon. Thank you very much. I am happy because I bought two kits from you and I want even after that. Hugs!
I bought this Kit last weekend and it´s fantastic. I can not stop to make pages with it.
It's a wonderful kit as all your kits are, I just adore The Magic of Childhood, it's at the top of my wish list that's for sure!!
I missed out on the coupon, but just love the new CU!!! obviously as it matchings the Magic of Childhood, lol.
I missed out on the coupon as usual, but I'm off to buy your new CU, thank you for your talent, I just love everything you make.
Oh I bought Designer's CU 15, it's just stunning, but I had a question, in the Deep in the Forest Kit you have an adorable bunny rabbit, I just love him, he is not in the CU, so I was wondering if the rabbit is from a different CU package, and could you tell me which one.


BERNE—The government of Switzerland announced Tuesday that it will appeal a December 17, 2013 decision by the European Court of Human Rights overturning the conviction of Dogu Perinçek for denying the Armenian Genocide.
The decision was made by Switzerland's Federal Office of Justice, which is asking the ECHR Grand Chamber to review the ruling to clarify the scope available to Swiss authorities in applying the Swiss Criminal Code to combat racism. Switzerland created this penal provision, which entered into force in 1995, to close loopholes in its criminal law and enable the country to accede to the UN Convention on the Elimination of All Forms of Racial Discrimination.
"We welcome the Swiss Government's decision to request that the December 17 decision of the European Court of Human Rights be referred to the Grand Chamber for review. By this decision Switzerland is attempting to defend its own legislation, while at the same time is adhering to the expectation of all Armenians to appeal the ECHR December 17 ruling, in order to create the opportunity to rectify the contentious assertions about the Armenian Genocide in that ruling. Of course, this process has several more stages to pass, first of which would be the decision by the Grand Chamber on whether or not to accept the referral," said a statement on the Armenian Revolutionary Federation Political Affairs office.
This is an issue which requires pan-national consensus and the necessity to push for the rectification of the contentious assertions about the Armenian Genocide in the ECHR ruling," added the ARF statement.
Under the provisions of the Swiss law, in 2007, Turkish citizen Doğu Perinçek was convicted for denying the Armenian Genocide. Failing to win two appeals against the judgment, Perincek appealed the ECHR, which on Dec. 17 ruled that the Swiss courts' rulings violated the appellant's right to freedom of expression.
The original case emerged from Perincek's participation in a number of conferences in Switzerland in 2005, during which he publicly denied that the Ottoman Empire had perpetrated the crime of genocide against the Armenian people in 1915.
The Lausanne Police Court found Perincek guilty of racial discrimination on March 9, 2007, based on the Swiss Criminal Code. After a complaint filed by the Switzerland-Armenia Association on July 15, 2005, the court found that Perincek's motives were of a "racist tendency" and did not contribute to the historical debate.
"The Court underlined that the free exercise of the right to openly discuss questions of a sensitive and controversial nature was one of the fundamental aspects of freedom of expression and distinguished a tolerant and pluralistic democratic society from a totalitarian or dictatorial regime," said the official ECHR press release at the time.
"The Court also pointed out that it was not called upon to rule on the legal characterization of the Armenian genocide. The existence of a 'genocide,' which was a precisely defined legal concept, was not easy to prove. The Court doubted that there could be a general consensus as to events such as those at issue, given that historical research was by definition open to discussion and a matter of debate, without necessarily giving rise to final conclusions or to the assertion of objective and absolute truths," added the ECHR release.
"Lastly, the Court observed that those States which had officially recognized the Armenian genocide had not found it necessary to enact laws imposing criminal sanctions on individuals questioning the official view, being mindful that one of the main goals of freedom of expression was to protect minority views capable of contributing to a debate on questions of general interest which were not fully settled," explained the ECHR.
Since the ECHR ruling, many leading Armenian organizations around the world, including the Armenian National Committee offices in Europe, South America, Australia and elsewhere met with Swiss diplomats urging the Swiss government to appeal the ECHR ruling.
sent an open letter to the Swiss government asking that they appeal the case–and that letter made major points about the decision–those scholarly opinions represent a neutral, global perspective.
Bravo to the Swiss government!
I wonder wheather this case was an Strategy to Bring it on and Prove Legally, that, what happened to Armenians between 1914 to 1923 in the Ottoman Empire Turkey, and rule on the legal characterisation of the Armenian genocide, In This Court; while United States, British, France and Germany sitting on the evidences.
We need to learn from the Jewish people to be united and stop backstabbing each other. Armenians should value higher education and it is sad how few Armenians are getting Phd's or getting law degrees and practicing international law where issues of the Armenian Genocide could be addressed. Why is it that many Armenian lawyers are only interested in easy cases to make money rather than serving the community. Look at how many Jewish scientists, engineers and lawyers there are out there in the world. Their culture promotes higher education and that is why they are able to get into top political and academic positions shaping political policies. It seems that the Russian-Armenians in particular are more interested in driving flashy Mercedes Benz cars.


70789 Onua - Master of Earth is a BIONICLE set released in 2015.
This is a description taken from LEGO.com. Please do not modify it. (visit this item's product page) Quarry underground with Onua's earthquake hammer!
Dig deep with Onua – Master of Earth to claim the mystical Golden Mask! This durable, highly posable figure with 4 golden BIONICLE® shells and bashing battle arm is fully geared up for underground combat against the Skull Spider. Burrow underground with the turbo shovelers while evading the evil Skull Spider's efforts to pop off Onua's mask. Then convert his turbo shovelers into a massive earthquake hammer, the only tool powerful enough to break through to the Golden Mask.
Resist the Skull Spider's attempts to pop off Onua's mask!
Combine with 70781 LEGO® BIONICLE® Protector of Earth using building instructions available at LEGO.com/BIONICLE to power up for ultra elemental battle!
Facts about "70789 Onua - Master of Earth"
This page was last edited on 12 January 2016, at 21:22.


Lucas is a young wandering huntsman, paid to track a mysterious and deadly beast.
On his path, he finds long lost friends, rising up painful memories from their childhood and unanswered questions.
@raephium: It's all fixed now ;D!
Is there a reason these last three pages are in... french, I'm guessing?
Hello everyone ! I hope you had a happy Easter if you celebrate it !
This book also contains two exclusive one-shots related to On the Hunt, sketches and bonus drawings !!
This book also contains two exclusive one-shots related to On the Hunt.
I'm here for the comics.
That said, really enjoying the comic; just finding the name amusing.
@Nonny Two years later, and same thing.
Doubling down on Lothan making awful decisions.


This long-awaited book by two of the foremost researchers and writers in the field is the first part of a treatise that covers the subject in breadth and depth, paying special attention to the historical origins, partly in applications, e.g. from geometrical optics, of parts of the theory. A variety of aids to the reader are provided: besides the very detailed table of contents, an introduction to each chapter, section and subsection, an overview of the relevant literature (in Vol. 2) plus the references in the Scholia to each chapter, in the (historical) footnotes, and in the bibliography, and finally an index of the examples used throughout the book. Both individually and collectively these volumes have already become standard references.


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Starting with a blank canvas in Ableton 10, Julian recreates this instant hit from beginning to end, starting with the catchy emotive piano chord progression before moving on to a signature mau5trap pluck.
Using his preferred synth Serum, this course includes Julian's sound design for the groove laden bass lines in both the verse and the awesome drop section, along with clever vocal processing, pad sound creation using resampled reverb tails, and the writing of drum and percussive elements throughout the track.
Julian mixes and arranges as he moves through the course, constantly tweaking and automating so by the time we get to the mixdown and master section everything's already sitting nicely in the mix.
The end result is an sure-fire hit that we guarantee will be stuck in your head after just one play!
Drum Roll.......And this is where things go up a gear!
Sonic Academy have teamed up with Julian to host an exclusive remix competition where the winner has the chance to feature on an up and coming We Are Friends compilation album on mau5trap!
Getting your winning mix out on 'We Are Friends' will gain you unparalleled exposure and will kick start your major career! You can be in with a chance of joining artists such as BlackGummy, No Mana, Rezz, Chris Lake, Noisia, Skrillex and Steve Duda on this illustrious label!
The 'How To Make It Is What It Isn't' Remix Contest is exclusive and only available on Sonic Academy. We're proud to have one of the best music-making communities anywhere, and the level of production skillz coming through the forums is awesome!
So, ourselves and Julian Gray are super excited to see what you guys can come up with - we know you can smash it. You can now download the stems from this awesome tune and start working your magic!
Think we are getting an extended summer here on Sonic Academy after listening to the track... Nice one & an incredible remix-comp again !!
After listening to the playthrough, there are a bunch of sounds that are really good, it will be nice to learn how to play them. The track itself seems like it doesn't go anywhere though, that build in the middle is pretty epic... but then it just drops back to the A part again. I'll give it another listen though, it's probably better and more subtle than what my first reaction told me.
Definitely enlightened - thanks Mr. Gray!
Though Ableton Live stock reverb effect is a decent one, you won't have the same control over early & late reflections as well as the stereo image that you could have with Valhalla Room. There is a lot of 3thrd party reverb plugins out there, with different design and features. An alternative to the Valhalla Room category could be the D16 Group Audio Software "Toraverb" or "Toraverb 2" plugin. Now don't get fooled by the simple Gui design of the Valhalla plugins, the algorithms used by those are really powerful and they are high quality and respected reverb plugins. The company has also a fair pricing policy because each plugin has got a fix price of $50, which is seen as a lowered/discount pricing compare to some crazy price you will see on many other 3thrd party reverb plugins.
Great tutorial and nice track!!
Hi @toango, you seriously cannot go wrong with any of the Valhalla plugins. They are some of the best value reverbs out there. Room is good, but I'd also give Vintage Verb a demo. I have reverbs that cost a lot more and don't sound as good. If you have Ableton Suite, I'd also recommend checking out the Max4Live convolution reverb device.
in tutorial 6 he mentions the Fminor chord is compatible with the A minor scale because F is a relative key. F is in fact a relative key of A minor, it is the relative Lydian. there's no relative minor to an already minor scale, only to other modes.
and in the F Lydian scale, where f is the tonic F is actually a major chord not a minor.
Heeeyyy, finna take his "secrets" with this.
Compelling melody and chord sequence, well arranged. On a theory note: the song is in A minor, of which the relative major is C (not F). The key of F has a B flat, which is never used in this song. As Julian notes, the sequence centers on the F chord, but because F is not the root, the melody never resolves. This gives the song an appropriate brooding, unsettled quality that works perfectly for the mood.
Which preset on the Giant are you using? My Giant sounds very different from yours. Thank you.


The visitors and The Hardships of Escape for Vietnamese Women are two pieces of literature that give an illustration of cultural change and assimilation. The world has become so global that cultural changes are so inevitable. People move from place to place in search of many things. In the first story, Bharati Mukherjee allows the readers to explore the world of a lonely Indian woman whose present home is America. This story is quite typical of events that take place in the world presently. People always acquire traits that prevail in their surrounding- Vinnita is not an exemption. The Vietnamese women also confirm the same trend of events by their adoption of a more liberal lifestyle in America.
The Visitors by Bharati Mukherjee is a story of Vinnita, an Indian woman who migrated into the United States of America from her native Calcutta community. Vinnita had lived in India from the time of her birth. This implies that all her code of conduct was informed by the Indian culture. Life in America was totally strange for this lady who was deeply rooted in the Indian culture. The author gives a picture of a struggling Vinnita. She is a bit confused and torn apart between her Indian way of life and that in America. Vinnita finally gives up and embraces American way of life. She invites people into her house while her husband Kamur is away (Bharati, 2004). Such invitations are totally unacceptable in the Indian culture. Such invites actually display a woman as adulterous.
Van Luu develops a story of how Vietnamese women got assimilated into the American culture. These women left Vietnam to travel to America in search of better life (Luu, 1989). Luu illustrates the hardship faced by these women while in their travelling ship. The women later got transformed from the conservative culture of Vietnam into the liberal American lifestyle. In Vietnam, women are always expected to take a low profile in all matters. On reaching America, the immigrant women became more powerful that men could hardly contain them as before. Luu's illustration of change is slightly different from that of Bharati. The Vietnamese women had to force their way into success while the Indian Vinnitta only got transformed after experiencing pressure in her new home.
The main theme in these two articles is cultural change. I totally agree with the idea that change always occurs due to movement from one place to another. It is true that one can only do exploits to the extent of his or her exposure. This means that nobody can do what they have never known about before. The acquisition of new way of life by the two sets of women is quite typical of the present society. My experience in school is quite synonymous to what Vinnitta and the Vietnamese women faced. Most students come to high school when very naïve and simple. However as high school days go by, most students commonly adopt pop culture. Most of my school colleagues have today adopted the pop culture. They embrace pop music and always talk about girls and night outs.
New acquaintances birth cultural transition. Vinnitta and the Vietnamese women both had a past life that was commonly full of their native way of norms. However as the two sets of women got to new environments, they all changed their way of life. Life in America is typical of free choice in decision. This is what the two authors confirm to us in their stories.


I had the unique opportunity to spend about a week with J.B. Rainsberger (website and second website) and Corey Haines (website), in what proved my best learning experience of the last few years.
During the TDD class, J.B. made a demo of emergent design, called "Architecture without trying". The first thing everyone noticed was how fast he was programming and how he used effectively all the features of the editor (in this case, Eclipse).
How to get there: unplug the mouse and learn fast typing, until the fingers do all the mechanical work.
Refactoring continuously will make the design better. When refactoring, two rules are important: everything (methods/procedures/functions, variables, classes etc.) must be named precisely and duplication must be removed as much as possible. Hint: duplication is also present in names (a1, a2, a3 is duplication – besides being an imprecise name – because the letter 'a' repeats).
For more details, J.B.'s articles on the four elements of simple design and why he names things precisely are wonderful resources.
Martin Fowler's book on refactoring has exercises on how to apply each refactoring method at the end of each chapter. Practicing those exercises is an excellent way to effectively learn refactoring.
I can safely say that I have a lot of experience in refactoring, but what I learned is that it's important to master the "mechanical" side of refactoring, meaning all the small steps one can take such that after each change the code still works. Taking small steps is hard.
TDD is hard. Test First Programming is the natural first step towards TDD. The difference between the two is that for TFP design happens before writing the tests, while in TDD the test drives the design. After a certain time of TFP practice, moving to TDD comes more easily. Another tip is to mock by hand at first. I've made the mistake to try using a mock framework from the beginning, and I soon realized that something was wrong. The typical thing is that it's easy to mock chained calls (first.second.third) in a framework while when doing it by hand is painful – so mocking by hand has a more powerful drive towards refactoring.
The TDD steps are: make an assumption about what should work in the system, write a test that verifies the assumption, write the code that passes the test (thus implements the assumption) and refactor. The key is to go in small steps, such that the assumptions are built incrementally and the code passes only the current assumptions.
The scientific method (explained here) has at its core the following steps: observe a phenomenon and question its cause, create falsifiable hypothesis regarding phenomenon's cause, attempt to falsify hypothesis, if falsified form a new hypothesis, if validated confirm it through other means (more tests, peer review etc.).
The difference between the two is that TDD focuses on obtaining a specific result whereas the scientific method focuses on discovering more about a system. The similarities lie in the way a practitioner must treat the assumptions about the code.
When doing TDD, small steps are the key. Small steps are annoying at first because it seems that programming is much slower than before, but this is only an impression because the work includes some design, writing code and some testing. The rhythm is constant and it's very fulfilling to see that something new is added at each step. After enough practice, the steps that at first seem very slow are performed in a very quick succession (especially after lots of practice using the full capabilities of the tool, keyboard only, and the refactoring patterns).
It's OL not to use TDD. As a professional, I believe you have the duty to try it and see if it works for you. But there are people who may decide it's not useful, and the only thing I'd like to know is why.
I will re-read Martin Fowler's Refactoring book and practice the exercises.
For more information about how you can learn TDD, try looking on the AgileWorks – the Romanian Agile community – website.
I came across your site and found here many interesting posts. I'm sure that i wil come back here soon !


Knowing what you know now...?
I have asked this question often sitting around with friends, and this was before I read this book. Say you could go back... knowing how your life has turned out... are there changes you would make? Different paths you would take knowing that with the "Butterfly Effect," a small change could make dramatic differences in the long run. Not always for the better.
So... if you could go back... would you?
Honestly... I don't think I would... even though I'm broken and might be able to change it. The new path could be a lot shorter and much more painful.
Knowing what I know today, yes, I'd go back. Understanding the concept that "self matters", and put it into play.
I'd hit the GD re-do button so fast and so many times it would most likely break the friggin' thing. Do we have to carry the knowledge we now have with us when we go back or can we wipe that board clean also please? Bring it on, bring it on.
There's an old saying that 'he who regrets nothing learns from everything'...this bugs me. I think regret serves a purpose; it is a type of grieving that hopefully leads to acceptance and avoidance of cyclic mistakes. So, yes, I'm one who'd go back in time. This isn't to say that I wouldn't commit a whole new set of mistakes (and, therefore, new regrets) but it would satisfy that human longing for atonement, a correcting of wrongs, a settling of scores.
Plus, it would be my duty to rid the world of M.C. Hammer parachute pants.
I"d go back. Stick up more for myself. My parents wouldn't have gotten away with being abusive.
I think I was seven. There's wasn't anything to do so I stepped into the pantry and swung my arms, watching myself in miniature in the round silver drawer pulls. Pantry. Summer, but the pantry was cold, designed that way maybe, north side of the house. Windows open, house quiet, and I spot a letter on the shelf, next to the Manhandlers. Yeah, if I could turn back time, as the song has it. You life turns on a dime and that was mine. Everything since has been defined by that moment and even now...even now...as another song has it, all it takes is a glimpse and I'm reeling. O western wind, when wilt thou blow?
If I could stop at high school, I would definitely go back, but to relive my life from birth I'd have to think about that. I suppose I could save my allowance all my life to invest in Microsoft during the 80's.
Let's do it, lol. Surely that would deserve some sort of Medal Of Honor. A selfless act.
Me and you both brother,me and you both.
This post intrigued me. A letter on a shelf? Care to share more? Or maybe you don't want to. I understand.
You're a lovely writer, Walter. I really mean that.
Isn't he? I tried to tell him not too long ago. I think it's even more striking because he doesn't seem to realize it. He has a way with words usually reserved for visionaries and poets.
Back to high school for me.
There was a point in my college football career where one of the coaches told me I had the ability to move on to the pro ranks.. And I just laughed him off.. mainly because he coached the unit I played against every day so he was very hard on us, I didn't think he was being serious. I now realize he was, and I wonder what would have happened if I had applied myself like I should have.. On the reverse, I know for a fact that I have saved some lives at my job that I chose. So if I went back and pursued the football angle, would someone else have saved those lives or would they have died without me there to take action? Interesting question,who knows..


← Join us as we Step Into Christmas!
Announcing our April 2019 Show!
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The production runs from 9th – 13th April 2019.
Tickets are available from the box office at LED Pavilion, Exmouth.


Got attacked by a big fish yesterday!
I have been doing a bit of scuba instructing over the past few days. All straightforward stuff, and the two guys I had with me both turned out to be very good, and had rapidly picked up the basic skills of diving.
It was day two of their open water diving, just their third dive, but they had already pretty much mastered underwater buoyancy to a good standard, and so I was happy to leave the main group of four other trainees, some of whom were still going up and down in the water like yo-yos with their instructor and divemaster, and take my two lads off with me on a gentle swim. On day one of their open water diving the visibility on the second dive of the day was really poor, and so as the visibility at this spot wasn't great but adequate, I got them to do a compass skill exercise. This involves using a compass to swim in a straight line, turn around and come back on a reciprocal course to the start point. I wanted the guys to have a go at this skill on this dive, dive three, rather than leaving it to dive number four as I had a feeling the visibility at the next site was going to be bad again. They both did this quickly and well enough, giving us plenty of time to explore the dive site before having to ascent back to surface.
We have been dropped a fair way off a small island and its surrounding reef that was our dive site for this first dive of the day, and so I decided to take the compass back, set a course myself towards the reef and to swim for ten minutes or so up to the reef and then to turn around and swim back to the boat.
It was as we approached the reef, a few minutes into our swim, that we wandered into the territory of an angry, big trigger fish. This one was a fair size, I would say it was about 40 cms long (15 inches). These large fish are known to be very territorial. Worse still, they have nasty teeth and strong jaws and have been known to take a bite out of a diver's fins, even worse, a chunk of diver's flesh.
To be honest, although I have seen quite a few trigger fish in the past, I wasn't prepared for an attack on myself by one of these rather feisty creatures.
Post event knowledge is a wonderful thing and I have since learnt the thing not to do, but what many divers do end up doing when startled by one of these fish, is to try to swim up and away from an aggressive trigger fish. It appears that they protect a cone-like area above their nest and hence swimming up just makes it look to them as if you are hanging around in their territory longer than necessary.
Fortunately, as much by instinct as anything, I did what turns out to be the best thing to do in a situation like this. I turned on my back, so I could stare into its beady fish eyes as it closed in rapidly, turning on its side and darting back at the last minute like some demented jet fighter pilot. I swam backwards and away from it, staying more or less near the bottom and kicked back at the beast as it went for me with my fins. A bite on the fins is painless, and as they are large and bright, they seem to be the thing these little monsters will go for first. On the other hand, I'm not sure painless could be said if it managed to get a chunk out of my leg.
I didn't think the thing was going to give up, but eventually after a minute or so, it obviously thought I was far enough away from its territory, did a sort of victory roll, and went back to its business of pottering around its favorite bit of coral. I looked around and spotted that the two lads with me had ascended a couple of metres. Maybe the wrong thing to do in the circumstances but as it was solely focused on me, it didn't bother them.
We swam on for another couple of minutes and I spot yet another trigger fish lurking ahead. Needless to say, we gave that one a wide berth. We had then to turn around and to swim back along the same course, so I was more than a little worried that we would run into trigger fish number one again. Fortunately for us, as my underwater navigation skills are far from spot on accurate, and there was a bit of a current, we didn't spot it on the return leg.
We completed dive four with no further fish attacked but as one of my divers had a dodgy tummy, we had to ascend after 30 minutes and abandon the rest of the dive. We got back to the dive shop and completed the paperwork to say the two lads were now certified open water divers and logged their dives. They said they were pretty scared at the time of the trigger fish attack but then again they could have a joke about it; 'On just our third dive, our instructor got attacked by a big fish'. Easy for them to laugh, I must admit I was a bit freaked out at the time.
Re: Got attacked by a big fish yesterday!
Oh goodness what an experience to go through. I have never heard of these fish but do know that lots of strange fish lurk in tropical waters.
Glad you came through it unscathed and can at least talk about the experience as something that not many go through. You did learn something from it and luckily it doesn't put you off from the diving that you enjoy so much.
Rather you than me entering waters with those type of feisty fish around. Glad you are OK.


text:
Arteta urges Arsenal to show courage in intense Athens atmosphere
The sold-out Karaiskakis Stadium is often a difficult place for opposing players.
Last updated: 19 February 2020 - 8.16pm
Arsenal head coach Mikel Arteta has challenged his players to rise above the heated atmosphere expected to greet the Gunners when they take on Olympiacos on Thursday.
Arteta will be keen for his side to put themselves into a strong position to continue their Europa League quest with victory in the opening leg of their round of 32 clash against the Greek champions-elect in Athens.
The sold-out Karaiskakis Stadium is often a difficult place for opposing players and, with Arsenal's side containing a number of youngsters, the evening will be a stern test of their resolve.
Arteta is confident his younger players can handle it and wants to see the same reaction regardless of their experience to date.
Olympiacos is renowned as a tough away trip (Nick Potts/PA)
"It is part of the process," he said.
"You don't know until you expose them. They can have the best intention but they need to go to a stadium like here and when they make a mistake or a bad decision, have the courage to try again and play again.
"And I want to see that in my players, whether they are 17 or 35. That's what I expect from them. If they keep trying, they have my full support.
"If they hide after that, I don't like it. But what I've seen up to now, every time they play on that field they are responding really, really well. That's what I am hoping and I am sure they will do it tomorrow."
While squad rotation in the Europa League has been the order of the day under previous managers Arsene Wenger and Unai Emery, Arteta suggested he make take a different approach.
Arsenal lost to London rivals Chelsea in the final last year and may need to win the competition this time around to return to the Champions League, given they currently sit 10th in the Premier League.
Asked about the intensity of playing Premier League and Europa League games and a potential need to rest players, Arteta added: "That's why we have a big squad and we can rotate the players. But physically in Europe, the game won't be any more demanding than in the Premier League, that's for sure.
"If they have to do that every three days, it can be an issue but as well we have to try to adapt and choose the players that can perform in each game.
"We had a break of 15 days. We played just one game so tomorrow I'm going to send out a team that I think is the best to play. The rest of the game will take care of itself.
Guendouzi is believed to have fallen out with Arteta (Bradley Collyer/PA)
"We cannot control everything. Sometimes you think about resting somebody and in training he gets a little issue or he gets sick.
"So tomorrow we will send out a team that we think is the best to beat Olympiacos and the rest of the teams after that will take care of themselves."
It remains to be seen if Matteo Guendouzi will be involved having been dropped for Sunday's 4-0 win over Newcastle.
Reports suggested the midfielder had fallen out with Arteta during the recent training camp in Dubai, with the head coach adding: "I just do my team selection and the squad in regards to how they train, how they play, how they behave.
"Every week it will be different. One week it will be one reason, one week it will be another reason."
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