text:
Nitric oxide differentially modulates ON and OFF responses of retinal ganglion cells
Guo Yong Wang, Lauren C. Liets, Leo M. Chalupa
Several lines of evidence suggest that nitric oxide (NO) can regulate diverse retinal functions, but whether this gas is capable of modulating the visual responses of retinal output neurons has not been established. In the present study the effects of NO on rod-driven responses of retinal ganglion cells were tested by making whole cell patch-clamp recordings from morphologically identified ganglion cells in the isolated ferret retina. Bath application of L-arginine, the substrate of nitric oxide synthase, and S-nitroso-N-acetylpenicillamine, the NO donor, was found to differentially affect ON and OFF discharge patterns. The introduction of these drugs significantly decreased visual responses of retinal ganglion cells, but the effects were more pronounced on OFF than on ON discharges. The peak discharge rates of ON responses were usually reduced by about 40%, but not completely blocked. In contrast, OFF responses were completely blocked in most cells. These differential effects were observed in ON-OFF cells as well as in cells that yielded just ON or OFF discharges. The OFF responses that were blocked by NO were also blocked by DL-2-amino-phosphonobutyric acid (APB) and strychnine, suggesting the involvement of the APB-sensitive rod pathway.
Journal of neurophysiology
https://doi.org/10.1152/jn.00243.2003
10.1152/jn.00243.2003
Dive into the research topics of 'Nitric oxide differentially modulates ON and OFF responses of retinal ganglion cells'. Together they form a unique fingerprint.
Retinal Ganglion Cells Medicine & Life Sciences 100%
Nitric Oxide Medicine & Life Sciences 70%
S-Nitroso-N-Acetylpenicillamine Medicine & Life Sciences 26%
Amino Acids Medicine & Life Sciences 24%
Retinal Neurons Medicine & Life Sciences 23%
Strychnine Medicine & Life Sciences 23%
Ferrets Medicine & Life Sciences 22%
Nitric Oxide Donors Medicine & Life Sciences 20%
Wang, G. Y., Liets, L. C., & Chalupa, L. M. (2003). Nitric oxide differentially modulates ON and OFF responses of retinal ganglion cells. Journal of neurophysiology, 90(2), 1304-1313. https://doi.org/10.1152/jn.00243.2003
Nitric oxide differentially modulates ON and OFF responses of retinal ganglion cells. / Wang, Guo Yong; Liets, Lauren C.; Chalupa, Leo M.
In: Journal of neurophysiology, Vol. 90, No. 2, 01.08.2003, p. 1304-1313.
Wang, GY, Liets, LC & Chalupa, LM 2003, 'Nitric oxide differentially modulates ON and OFF responses of retinal ganglion cells', Journal of neurophysiology, vol. 90, no. 2, pp. 1304-1313. https://doi.org/10.1152/jn.00243.2003
Wang GY, Liets LC, Chalupa LM. Nitric oxide differentially modulates ON and OFF responses of retinal ganglion cells. Journal of neurophysiology. 2003 Aug 1;90(2):1304-1313. https://doi.org/10.1152/jn.00243.2003
Wang, Guo Yong ; Liets, Lauren C. ; Chalupa, Leo M. / Nitric oxide differentially modulates ON and OFF responses of retinal ganglion cells. In: Journal of neurophysiology. 2003 ; Vol. 90, No. 2. pp. 1304-1313.
@article{4d69ad600f534eab9c5b8d8188c0494f,
title = "Nitric oxide differentially modulates ON and OFF responses of retinal ganglion cells",
abstract = "Several lines of evidence suggest that nitric oxide (NO) can regulate diverse retinal functions, but whether this gas is capable of modulating the visual responses of retinal output neurons has not been established. In the present study the effects of NO on rod-driven responses of retinal ganglion cells were tested by making whole cell patch-clamp recordings from morphologically identified ganglion cells in the isolated ferret retina. Bath application of L-arginine, the substrate of nitric oxide synthase, and S-nitroso-N-acetylpenicillamine, the NO donor, was found to differentially affect ON and OFF discharge patterns. The introduction of these drugs significantly decreased visual responses of retinal ganglion cells, but the effects were more pronounced on OFF than on ON discharges. The peak discharge rates of ON responses were usually reduced by about 40%, but not completely blocked. In contrast, OFF responses were completely blocked in most cells. These differential effects were observed in ON-OFF cells as well as in cells that yielded just ON or OFF discharges. The OFF responses that were blocked by NO were also blocked by DL-2-amino-phosphonobutyric acid (APB) and strychnine, suggesting the involvement of the APB-sensitive rod pathway.",
author = "Wang, {Guo Yong} and Liets, {Lauren C.} and Chalupa, {Leo M.}",
doi = "10.1152/jn.00243.2003",
journal = "Journal of Neurophysiology",
T1 - Nitric oxide differentially modulates ON and OFF responses of retinal ganglion cells
AU - Wang, Guo Yong
AU - Liets, Lauren C.
AU - Chalupa, Leo M.
N2 - Several lines of evidence suggest that nitric oxide (NO) can regulate diverse retinal functions, but whether this gas is capable of modulating the visual responses of retinal output neurons has not been established. In the present study the effects of NO on rod-driven responses of retinal ganglion cells were tested by making whole cell patch-clamp recordings from morphologically identified ganglion cells in the isolated ferret retina. Bath application of L-arginine, the substrate of nitric oxide synthase, and S-nitroso-N-acetylpenicillamine, the NO donor, was found to differentially affect ON and OFF discharge patterns. The introduction of these drugs significantly decreased visual responses of retinal ganglion cells, but the effects were more pronounced on OFF than on ON discharges. The peak discharge rates of ON responses were usually reduced by about 40%, but not completely blocked. In contrast, OFF responses were completely blocked in most cells. These differential effects were observed in ON-OFF cells as well as in cells that yielded just ON or OFF discharges. The OFF responses that were blocked by NO were also blocked by DL-2-amino-phosphonobutyric acid (APB) and strychnine, suggesting the involvement of the APB-sensitive rod pathway.
AB - Several lines of evidence suggest that nitric oxide (NO) can regulate diverse retinal functions, but whether this gas is capable of modulating the visual responses of retinal output neurons has not been established. In the present study the effects of NO on rod-driven responses of retinal ganglion cells were tested by making whole cell patch-clamp recordings from morphologically identified ganglion cells in the isolated ferret retina. Bath application of L-arginine, the substrate of nitric oxide synthase, and S-nitroso-N-acetylpenicillamine, the NO donor, was found to differentially affect ON and OFF discharge patterns. The introduction of these drugs significantly decreased visual responses of retinal ganglion cells, but the effects were more pronounced on OFF than on ON discharges. The peak discharge rates of ON responses were usually reduced by about 40%, but not completely blocked. In contrast, OFF responses were completely blocked in most cells. These differential effects were observed in ON-OFF cells as well as in cells that yielded just ON or OFF discharges. The OFF responses that were blocked by NO were also blocked by DL-2-amino-phosphonobutyric acid (APB) and strychnine, suggesting the involvement of the APB-sensitive rod pathway.
U2 - 10.1152/jn.00243.2003
DO - 10.1152/jn.00243.2003
JO - Journal of Neurophysiology
JF - Journal of Neurophysiology


Quaife ATB Helical LSD for the Audi R8's rear differential. A direct replacement for the standard Audi R8 open differential, the Quaife ATB differential transforms your car's performance.
The Audi R8 ATB differential never locks harshly with a set pre-load of wheel slip across the driven axle, like a conventional LSD. Rather, it automatically biases the torque away from the spinning wheel across the axle, to a constantly varying degree, and never locks.


"KBRA subjected MAC's insured portfolio to rigorous statistical modeling and concluded that MAC's claims-paying resources are able to withstand KBRA stress losses at a AAA rating level with a comfortable balance remaining"
NEW YORK--(BUSINESS WIRE)--Kroll Bond Rating Agency (KBRA) affirmed its insurance financial strength rating of AA+, with a Stable Outlook, for Municipal Assurance Corp. (MAC), a financial guaranty subsidiary of Assured Guaranty Ltd. (together with its subsidiaries, Assured Guaranty)(NYSE:AGO) on July 14, 2017.
Strong claims-paying resources which can withstand KBRA stress losses in a run-off scenario with a comfortable balance remaining.
Diverse, high quality insured portfolio; no exposure to Puerto Rico.
Skilled and disciplined management and staff with deep expertise and market experience.
A mature and high-functioning operating platform supported by strong governance and risk management systems.
"Once again, KBRA has affirmed MAC's strong AA+ stable rating, reflecting the high level of protection available to investors in MAC-insured bonds," said Dominic Frederico, President and CEO of Assured Guaranty. "KBRA subjected MAC's insured portfolio to rigorous statistical modeling and concluded that MAC's claims-paying resources are able to withstand KBRA stress losses at a AAA rating level with a comfortable balance remaining," he added.
MAC is licensed to insure municipal bonds in all 50 states and the District of Columbia. MAC was launched on July 22, 2013 to guarantee only U.S. municipal bonds in the most well understood bond sectors such as general obligations and tax-backed issues for cities, counties and school districts, and public electric, water, sewer and transportation revenue bonds. At March 31, 2017, MAC had $1.4 billion of claims-paying resources and a $52.8* billion direct and assumed insured portfolio. Its highly diversified insured portfolio generates predictable future revenue from its embedded $284* million net unearned premium reserve, which is part of MAC's $1.1 billion investment portfolio.
In addition to the KBRA rating, MAC's financial strength is rated AA with a Stable Outlook by Standard & Poor's Ratings Services.
*Based on Generally Accepted Accounting Principles (GAAP) reporting.
Any forward-looking statements made in this press release reflect Assured Guaranty's current views with respect to future events and are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such statements involve risks and uncertainties that may cause actual results to differ materially from those set forth in these statements. These risks and uncertainties include, but are not limited to, those resulting from changes in rating agency models or opinions, adverse credit developments in MAC's insured portfolio and the impact of those developments on rating agency models and opinions, other risks and uncertainties that have not been identified at this time, management's response to these factors, and other risk factors identified in Assured Guaranty's filings with the Securities and Exchange Commission. Readers are cautioned not to place undue reliance on these forward-looking statements, which are made as of July 17, 2017. Assured Guaranty undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.
MAC is a New York insurance company and a subsidiary of Assured Guaranty Ltd., which is a publicly traded (NYSE: AGO) Bermuda-based holding company. The operating subsidiaries of Assured Guaranty Ltd. provide credit enhancement products to the U.S. and international public finance, infrastructure and structured finance markets. More information on Assured Guaranty Ltd. and its subsidiaries, including MAC, can be found at AssuredGuaranty.com.


We hope you can find everything you need. AAA CHECKER is focused on providing high-quality service and - we will do everything we can to meet your expectations.
Airport Pickup/Drop off to Newark, JFK, Philadelphia airports, also provides local and long distances. Sight seeing to Washington D.C, Niagara Falls and New York city .


Get the women's fragrance that suits you. Be it a DKNY or Chloé perfume, at PerfectHair.ch you will find the best women's fragrances. Explore our fragrance range for women and buy your perfume affordably online. We have Love from Chloé, Dot and Honey from Marc Jacobs, Be Delicious from DKNY, CK One from Calvin Klein, Cool Water from Davidoff, Cavalli Signature from Roberto Cavalli and many more.


text:
Darren Taggart
guitarist music technology specialist
Welcome to the website for Darren Taggart, a UK based Musician and Teacher of Music and Production.
With more than 20 years playing experience, Darren has appeared across the UK, Europe, United States of America and Canada to crowds exceeding 50,000. Career highlights include sharing stages with Billy Idol, Newton Faulkner, James Blunt, Lightning Seeds, A-ha, The Wonderstuff, Gary Numan, The Stranglers, Matt Terry (X Factor) and Lee Latchford Evans (Steps) as well as live sessions for regional and national radio stations. Darren is also an experienced backline technician and sound engineer, with past clients including The Australian Pink Floyd Show, Pete Docherty, Toby Jepson (Little Angels), Dean Howard (Cats in Space), Diversity, Simon Webb (Blue), Alabama 3, Bez (Happy Mondays), Babyshambles, The Horrors and The Sonics.
In addition to extensive live and studio experience, Darren holds certification from Apple (UK), Qualified Teacher Status and is currently studying a PhD in Music at Canterbury Christ Church University.
Darren is currently the Guitarist in The Neotones (award winning covers band featured on BBC Radio) and part of the backing band for Aid Lewis (critically acclaimed singer/songwriter also featured on BBC Radio). He is available for live and studio sessions as well as private lessons in guitar, music theory and music technology.

redpajama_set_name: RedPajamaCommonCrawl


17-sai, Kiss to Dilemma 5 - Read 17-sai, Kiss to Dilemma Chapter 5 Online 17-sai, Kiss to Dilemma 5 Online Reader Tip: Click on the 17-sai, Kiss to Dilemma manga image or use left-right keyboard arrow keys to go to the next page. MangaHere is your best place to read 17-sai, Kiss to Dilemma 5 Chapter online. You can also go mangalist to read other series or check latest manga updates for new releases 17-sai, Kiss to Dilemma 5 released in mangahere fastest, recommend your friends to read 17-sai, Kiss to Dilemma 5 now!
How to Make Your Data Pretty? Utilize These Data Visualization Tools Tired of showcasing the same old boring tables to your management? A spice of colors and layout brings life to data representation. If you need to understand million rows of data and you are short on time. The data might be coming from different sources and you may need to compile it to get a holistic view to make a decision on it. In order to make the meaning of the information effectively, Data Visualization is an important answer.Data Visualization is an art for visual communication which enhances the expression of data in to one collective graphic for anyone to digest and action upon. The best of the data visualizations explain something complex in a digestible format and expose something underlying which cannot be visible to the naked eye.
QwikSlides: Presentation creator from ClassTools.net Qwikslides lets you create a multimedia presentation in a few seconds!


Prepare the skewers alternating the salmon and pineapple. Squeeze lime juice over them, salt and pepper. Let stand for 10 minutes.
Heat the grill and cook for a few minutes on each side. It's okay if the inside of the salmon is a little undercooked.


text:
// we use a nightwatch.conf.js file so we can include comments and helper functions
module.exports = {
  "src_folders": [
    "test/e2e"// Where you are storing your Nightwatch e2e tests
  ],
  "output_folder": "./reports", // reports (test outcome) output by nightwatch
  "selenium": { // downloaded by selenium-download module (see readme)
    "start_process": true, // tells nightwatch to start/stop the selenium process
    "server_path": "./node_modules/nightwatch/bin/selenium.jar",
    "host": "127.0.0.1",
    "port": 4444, // standard selenium port
    "cli_args": { // chromedriver is downloaded by selenium-download (see readme)
      "webdriver.chrome.driver" : "./node_modules/nightwatch/bin/chromedriver"
    }
  },
  "test_settings": {
    "default": {
      "screenshots": {
        "enabled": true, // if you want to keep screenshots
        "path": './screenshots' // save screenshots here
      },
      "globals": {
        "waitForConditionTimeout": 5000 // sometimes internet is slow so wait.
      },
      "desiredCapabilities": { // use Chrome as the default browser for tests
        "browserName": "chrome"
      }
    },
    "chrome": {
      "desiredCapabilities": {
        "browserName": "chrome",
        "javascriptEnabled": true // turn off to test progressive enhancement
      }
    }
  }
}

/**
 * selenium-download does exactly what it's name suggests;
 * downloads (or updates) the version of Selenium (& chromedriver)
 * on your localhost where it will be used by Nightwatch.
 */
var BINPATH = './node_modules/nightwatch/bin/';
require('fs').stat(BINPATH + 'selenium.jar', function (err, stat) { // got it?
  if (err || !stat || stat.size < 1) {
    require('selenium-download').ensure(BINPATH, function(error) {
      if (error) throw new Error(error); // no point continuing so exit!
      console.log('✔ Selenium & Chromedriver downloaded to:', BINPATH);
    });
  }
});

redpajama_set_name: RedPajamaGithub


China's Mobile Economy: Opportunities in the Largest and Fastest Information Consumption Boom is a cutting-edge text that spotlights the digital transformation in China. Organised into three major areas of the digital economy within China, this ground-breaking book explores the surge in e-commerce of consumer goods, the way in which multi-screen and mobile Internet use has increased in popularity, and the cultural emphasis on the mobile Internet as a source of lifestyle- and entertainment-based content. Targeted at the global business community, this lucid and engaging text guides business leaders, investors, investment banking professionals, corporate advisors, and consultants in grasping the challenges and opportunities created by China's emerging mobile economy, and its debut onto the global stage.
The development of China's mobile economy is one of the most important trends that will reshape the future of business, technology and society both in China and the world. China's Mobile Economy: Opportunities in the Largest and Fastest Information Consumption Boom introduces you to the digital transformation in China, and explains how this transformation has the potential to transform both China and the global consumer landscape.


text:
[Tribeca 2020] ASIA -- An Effectively Emotional Melodrama
The directorial debut of Ruthy Pribar, Asia is a new Israeli character drama that addresses some unexpected topics. And even though the film's syncretism of different genres doesn't always pay off, there are some really interesting things happening here that make it a very involving and compelling watch.
The movie follows a young mother and her teenage daughter as they are drawn closer together when the daughter experiences medical issues that send her on a journey of self-discovery. A blend of coming-of-age tropes and tear-jerking "sick kid" clichés, the film barely treads the line between touching and overly sentimental.
Without a doubt, the first half act of the movie is far more interesting than the second and third. Pribar's script becomes a lot more conventional as it progresses, and while it still has some emotional impact towards the end, the middle section falls flat more often than not. A few of the character arcs that are set up in the beginning of the film don't pay off by the end.
Perhaps the most disappointing thing about the movie is that it doesn't fully develop its protagonist. Her daughter has the much more interesting arc in the film, but there was even more potential in regards to her story as a young mother experiencing these issues with her daughter at the age she was when she had her.
That said, the relationship between the two characters is very interesting, although there could have been more development in this department as well. Unfortunately, the direction that this arc takes in the final third is one of the more frustrating things about the movie, as it counteracts a lot of the emotional substance from earlier.
Alena Yiv and Shira Haas both give excellent performances and have superb chemistry together. Yiv is perhaps the more impressive of the two, bringing a lot to the table in terms of empathy. Haas's performance is also surprisingly grounded given the tricky material she was given.
Stylistically, the film has a very down-to-earth feel to it and that helps it counteract some of the melodrama of the script. The cinematography and production design are both very muted, giving the movie an understated but admirably realistic feel that makes it hit all the more on an emotional level.
Asia does feel a tad bit underbaked at times, but thanks to strong performances and interesting ideas, it's consistently very interesting. It's a very effective and crowd-pleasing film that may struggle to find eyes in the changing cinema landscape.
Asia was set to debut at the 2020 Tribeca Film Festival. It is currently seeking distribution.


text:
angle-left angle-right angle-down angle-up
Free Invoice Audit
How is Stagnant Brand Value Growth Affecting FedEx and UPS
by Nick Nowaczyk — Vice President, Phoenix
What Does This Mean for Other Parcel Carriers?
For years, FedEx and UPS have pretty much had a duopoly on the logistics shipping industry. Both companies are enormously valuable: in 2017, analysts estimated that the UPS brand was worth $22 billion, and FedEx, $18.2 billion.
But brand value growth is stagnating for traditional carriers worldwide. The top six logistics brands that includes FedEx and UPS, grew only 0.2% in aggregate in 2017. UPS's value shrunk by 1%.
The reason for stagnant growth is simple: vastly increased competition from disruptors and legacy companies alike is slowing down the values of long-established brands.
Who's Competing with FedEx and UPS?
Customer service is increasingly important to shippers. Often, they're more satisfied with regional carriers than they are with corporate giants. Larger traditional carriers like DHL continue to introduce cutting-edge services in an effort to eat into the market share of FedEx and UPS.
Public agencies are breaking through, as well. The U.S. Postal Service continues to get higher and higher ratings from shippers, especially as small and medium-sized sellers rely on its flat-rate Priority Mail service. In Europe in 2017, Poste Italiane's brand grew 20% in 2018, and Deutsche Post grew 29%. The former reorganized and began collecting a greater share of revenue from financial services, and the latter added additional parcel services.
The brand of the year may have been MTR, Hong Kong's public transport agency, according to the American Journal of Transportation. As an author wrote in March:
"MTR operates one of the most efficient rapid transit systems on the planet, with 99.9% of passengers arriving within 5 minutes of the scheduled time. Its focus on high-quality services is attractive to customers, and protects the brand amongst key stakeholders."
Finally, of course, there's the name in the back of every logistics-focused mind: Amazon.
Its forthcoming shipping service, Shipping with Amazon would be a courier-reliant service that moves products from Amazon sellers to warehouses, according to news reports. The company hasn't yet confirmed that it is developing this program. After reaching Amazon fulfillment centers, parcels would join Amazon's existing distribution network, which (for now) relies on traditional carriers.
Amazon has enormous market reach. According to some reports, the company captures half of all American dollars spent online. Analysts are mixed on whether it can grow enough to truly challenge FedEx and UPS, but it will certainly eat into their market share.
What Does Stagnant Brand Value Growth Mean for Other Parcel Carriers?
FedEx and UPS have long been the world's most valuable shipping brands. For four years, UPS has held the top spot. Strategy consulting firm, Brand Finance estimates its brand value at $22 billion. This is down 1% from the previous year as profits dipped.
FedEx's brand value actually grew 6% last year, bringing it to $18.2 billion. Analysts chalked that growth up to its acquisition of TNT Express, a Netherlands-based courier service that primarily serves markets outside the U.S.
All told, the top six brands in shipping right now — UPS, FedEx, Japan Railways, DHL, Union Pacific and McLane Co. — saw aggregate brand value growth of just 0.2% last year.
These big global brands, analysts say, are trying to serve retailers who want to offer customers free shipping and negotiate hard for lower prices from carriers. In this competitive environment, regional and alternative carriers are increasingly able to undercut the giants. That pulls business from FedEx, UPS and DHL, who must then lower prices even more, and the cycle continues.
This doesn't mean shipping is getting less valuable overall. It means the market is diversifying. In a time of disruption, smaller companies may have more opportunity to break into the logistics space than they've had in years.
This is good news for companies that rely on shipping to do business. FedEx and UPS can no longer count on retailers as customers. They have to offer better prices, expanded services or better customer service to secure it. UPS, for example, is in the process of implementing ORION, a new navigation system that will offer real-time updates to drivers' routes. ORION is projected to save the company about $400 million annually, while promising to increase delivery speed and reliability.
Are you taking advantage of this competitive market to secure better shipping rates? If not, contact Reveel today to get localized insights into your shipping budget and talk about what items in your carrier invoice to target in your next contract negotiation.
Carriers Need to Develop Distinct Brands
As brand value growth stagnates among traditional industry leaders, there is more pressure than ever among carriers to differentiate their services. It's essential to stay relevant, and to mitigate the impacts of a future loss of market share to Shipping With Amazon and other newcomers.
Some public agencies, like the U.S. Postal Service and Deutsche Post, have added additional services and kept prices flat, serving a growing audience of online sellers with ongoing routine shipping needs. MTR, Hong Kong's public transit agency, is growing in popularity as it proves its reliability and commitment to environmental preservation.
At the same time, private innovators like Amazon have sought to bring more shipping in-house, reducing their costs but also taking business away from traditional carriers. And while UPS and FedEx have experimented with last-mile delivery innovations, these venture-funded companies have a lot more room to play with cutting-edge technologies like drones.
As Richard Haigh, Managing Director of consulting firm, Brand Finance told the American Journal of Transportation:
"As Amazon prepares to launch 'Shipping with Amazon,' having a strong brand can help protect incumbents from this new competition. Powerful brands alone will not be enough to prevent Amazon from gaining a foothold in the industry; however, they will allow breathing room for the existing brands to riposte and limit their loss of market share."
Ready to leverage the power of Shipping Intelligence for your company? Contact us today to schedule a consultation.
Find out just how much you can save with a complimentary preview of our Invoice Auditing service.
Carrier Price Increases
Reveel Services
Shipping Industry News
Nisolo Saves 22% on Shipping and Offsets Carbon Emissions
Access the 2021 Shipping Rate Increase Guide
FedEx Raises Surcharges on Int'l Shipments for Some Countries—One by 350%
Gunner Kennels and Reveel Partner for Savings
UPS' 2021 General Rate Increase: What You Need to Know
About Reveel®
Our dedicated team gives you unmatched local knowledge with complete transparency and exceptional service.
Subscribe to Reveel®
Shipping insights directly affect your bottom line. Sign up now to receive updates from Reveel.
"When I was first approached by Josh and Chad, I was skeptical, to say the least. Many 'money-saving' schemes come across my desk and most of them fall short of their promises. Not so with Reveel! They showed us real savings!"
Robert NorVelle Publisher/Vice President – Cycle News Publications
About Reveel
Since 2006, Reveel has been dedicated to providing Shipping Intelligence for the smartest business decisions possible. Founded by former DHL sales executives, Reveel was created to level the shipping playing field.
© 2020 Reveel. Privacy Policy
We use cookies to help make Reveel better. By visiting this site, you agree to our privacy policy


John Lambert • A wonderfull and inspirational collection of work and a very professional web site. You understand and have an empathy with the food and drinks industry and your work in this regard is outstanding. Your portrait and travel images are of an equally outstanding quality.
I just love your work, you made me smile today because I could really appreciate and enjoy the visual delight and energy within so many of your compositions.
Arnold is an excellent photographer to work with, and he has consistently produced quality results for restaurant 'Het Bosch' over the years. Highly recommendable to anyone in the restaurant/hotel business.
Founder at In Serious Business | With a passion for (training and coaching) people and happy to add value to your team!
Arnold van West is a true professional: easy to get along with, and able to take the desired shots without disturbing the proceedings. The results are stunning.
"Wij werken al een kleine 10 jaar met Arnold.
Een geweldig gedreven en flexibele vakman!


text:
O Infomaniac é um personagem ficcional LEGO da linha LEGO Island.

Caracterização
É um personagem muito falador, mas às vezes esquece as coisas e perde-se na sua linha de raciocínio. Vive no "Centro de Informações" em LEGO Island. Foi ele quem construiu a ilha, por isso sabe muito sobre ela. Ele também foi o responsável pela criação do Brickster, personagem que se tornou o vilão de LEGO Island.

Participações em jogos para computador
Em LEGO Island, o Infomaniac ajuda o personagem Pepper Roni em sua cruzada para derrotar o Brickster.
Em LEGO Island 2: The Brickster's Revenge, o Infomaniac ajuda novamente Pepper, falando com ele sob a forma de um holograma por meio de uma antena no chapéu de Pepper.
Em LEGO Island Xtreme Stunts, o Infomaniac é feito refém pelo Brickster, sendo salvo por Pepper.

A minifig
Uma minifig do Infomaniac foi distribuída promocionalmente com as primeiras cópias do jogo LEGO Island. Com óculos e uma barba, ele reflete a imagem de seu criador, Wes Jenkins, designer do jogo, e seu diretor artístico.

Posteriormente, a minifig foi incluída no conjunto "Xtreme Tower" (código 6740 do tema LEGO Xtreme Stunts), que também apresentava uma versão totalmente nova do "Centro de Informações" de LEGO Island.

Lego

redpajama_set_name: RedPajamaWikipedia


text:
SSA testing Microsoft HealthVault
The goal is to get digital records to improve disability determinations
By Alice Lipowicz
The Social Security Administration has entered into an agreement to test the use of the Microsoft HealthVault software for SSA's disability determination process.
SSA has been trying out several ways to collect electronically the health records of people applying for disability income. SSA currently requests about 15 million to 20 million medical records a year in a process that is labor- and paper-intensive.
HealthVault is a free online personal health record service in which patients are encouraged to collect and store their health information in a single location.
The SSA said Aug. 27 that it and Microsoft are developing a technical prototype connecting the two organizations that will be available later this year. SSA also will collaborate with Microsoft to study current personal health record standards, gaps in those standards, and options for filling those gaps.
"The use of personal health records holds great promise for ensuring that the medical information we collect from someone applying for disability benefits is accurate and complete," SSA Commissioner Michael Astrue said in a news release.
"Combined with other advancements in health information technology, our use of HealthVault should result in faster decisions for disability applicants," he said.
SSA has been using the Health and Human Service Department's Nationwide Health Information Network to link with providers for the purpose of getting the disability records.
The agency recently issued a Request for Information asking vendors to propose how to link more providers' records through the NHIN. SSA also is working with MedVirginia to test sharing of digital patient records in that state.
Alice Lipowicz is a staff writer covering government 2.0, homeland security and other IT policies for Federal Computer Week.


text:
Q: insert images in 7 by 3 grid view I am trying to put images in a simple 7 X 3 table /grid view.
But I am not getting the desired result..
Probably I am looking at very wrong place.
I dont want to create a viewer or anything..
Just show the images in 7 X 3 grid view..
.floated_img
{
    margin-left: 10px
    width:140px; /* you can use % */
    height: auto;

}

....

Is there any template i can quickly download and use it to just put my images in it.
I have the images.. I just want to align them in a clean table view and just take a screen shot of it..

A: If you don't want to deal with table you can put your images in LI:
ul {
    line-height: 0;
    font-size: 0;
}
li {
    display: inline-block;
    width: 14.28%; /* 100%/7 */
}
li img {
    display: inline-block;
    max-width: 100%;
}

http://jsfiddle.net/NnrEv/

A: If you are looking for a floating solution check this http://jsfiddle.net/fSzxb/1/
.floater {
    float:left;
    ...
}
.floater.first {clear:both;}

/*clearfix*/
.cf:before,.cf:after {content: " "; display: table;}
.cf:after {clear: both;}
.cf {*zoom: 1;}

and your html

Of course you can use some more semantic class names, instead of floater and cf

redpajama_set_name: RedPajamaStackExchange


The Bernard Controls ST range of multi turn IP68 electric actuators are available from 60Nm to 20,000Nm and available as modulating / positioning.
The ST range of multi turn IP68 electric actuators from Bernard Controls provides direct multi turn torques from 60Nm to 20,000Nm. Features include asynchronous motor with high starting spring loaded torque, on / off operation: 30% duty rating, Modulating class 3: 50% duty rating. The watertight IP68 and NEMA housing can withstand a submersion of 5 Metres for 72+ hours. Integrated Intelli controls available.


text:
Humour and Jokes
Make a selection: Critical Discourse Analysis Linguistic Relativity Transcription Cazden, Courtney Conversation Analysis Prosopography Sensitizing Concepts Indexicality Translation in Qualitative Methods Belonging Whorf, Benjamin Lee Humour and Jokes Labov, William Hymes, Dell Hathaway
Part of Series: Language and Qualitative Research
Critical Discourse Analysis
Linguistic Relativity
Cazden, Courtney
Sensitizing Concepts
Indexicality
Translation in Qualitative Methods
Whorf, Benjamin Lee
Labov, William
Hymes, Dell Hathaway
Social structures
By:Daniel R. Smith | Edited by: Paul Atkinson, Sara Delamont, Alexandru Cernat, Joseph W. Sakshaug & Richard A.Williams
Discipline: Sociology, Anthropology, Political Science and International Relations
Methods: Social structures, Ontology
Smith, D. R., (2019). Humour and Jokes, In P. Atkinson, S. Delamont, A. Cernat, J.W. Sakshaug, & R.A. Williams (Eds.), SAGE Research Methods Foundations. https://dx.doi.org/10.4135/9781526421036847997
Smith, Daniel R.. "Humour and Jokes." In SAGE Research Methods Foundations, edited by Paul Atkinson, Sara Delamont, Alexandru Cernat, Joseph W. Sakshaug, and Richard A. Williams. London: SAGE Publications Ltd, 2019. https://dx.doi.org/10.4135/9781526421036847997.
Smith, D. R., 2019. Humour and Jokes. In: Paul Atkinson, ed., SAGE Research Methods Foundations. London: SAGE Publications Ltd. Available at: <https://dx.doi.org/10.4135/9781526421036847997> [Accessed 30 Jan 2023].
Smith, Daniel R.. "Humour and Jokes" SAGE Research Methods Foundations, Edited by Paul Atkinson, et al. London: SAGE Publications Ltd, 2019. SAGE Research Methods. 30 Jan 2023, doi: https://dx.doi.org/10.4135/9781526421036847997
Smith, Daniel R. (2019). In P. Atkinson, S. Delamont, A. Cernat, J.W. Sakshaug, & R.A. Williams (Eds.), SAGE Research Methods Foundations. https://dx.doi.org/10.4135/9781526421036847997
https://methods.sagepub.com/foundations/humour-and-jokes


text:
La Polonia partecipò ai X Giochi olimpici invernali, svoltisi a Grenoble, Francia, dal 6 al 18 febbraio 1968, con una delegazione di 31 atleti impegnati in sette discipline.

Risultati

Altri progetti

Collegamenti esterni

1968
Polonia


text:
Expression and significance of histone H3K27 demethylases in renal cell carcinoma
Yongqing Shen1,5,
Xiaoqiang Guo1,2,
Yuejia Wang1,
Wei Qiu4,
Yanzhong Chang1,
Aili Zhang3 &
Xianglin Duan1
The histone H3K27 demethylases UTX and JMJD3 are important regulatory factors that modulate gene expression by altering the physical state of chromatin. Previous studies have indicated an abnormal H3K27 methylation status in carcinogenesis. We therefore investigated the expression patterns of UTX and JMJD3 in renal cell carcinoma (RCC) and their roles in cancer development.
The mRNA expression levels of the UTX and JMJD3 genes were determined in cancer tissues and adjacent normal tissues in 36 patients with primary RCC, using quantitative real-time-polymerase chain reaction. The UTX and JMJD3 protein contents were measured by western blotting and immunohistochemical analysis.
UTX and JMJD3 transcripts were significantly increased in cancer tissues compared to normal tissues (P < 0.05). mRNA levels of the inhibitor of cyclin-dependent kinases 4 and 6 p16INK4a were also increased in cancer tissues (P < 0.001). Western blotting indicated that levels of both demethylases were increased in cancer tissues. The level of tri-methylated H3K27 (H3K27me3) was lower in cancer tissues compared to normal tissues, but expression of the H3K27 methyltransferase EZH2 was increased (P < 0.05). These results suggest that the two H3K27 demethylases may play critical roles in the regulation of H3K27 methylation status in RCC. Immunohistochemical analysis confirmed that UTX and JMJD3 expression were upregulated in cancer tissues compared to adjacent tissues.
This study demonstrated that UTX and JMJD3 were upregulated in cancer tissues, suggesting that they may be involved in the development of primary RCC. The potential roles of H3K27 demethylases as biomarkers in the early diagnosis of RCC need to be further explored.
Kidney cancer is the third most common urological malignancy and is responsible for an estimated 120,000 deaths per year worldwide [1]. The incidence of kidney cancer has increased significantly over the past 20 years [2], and accounts for nearly 3% of all cancer cases in Europe [3]. The two most common types of kidney cancer are renal cell carcinoma (RCC) and urothelial cell carcinoma. RCC is the most common kidney cancer in adults, and is generally resistant to chemotherapy and radiation therapy [4, 5]. Radical or partial nephrectomy of the tumor at a localized stage remains the mainstay of curative therapy [6]. Unfortunately, however, distant metastases are present at the time of initial diagnosis in approximately one third of patients, and the tumor will recur in a further third, even after nephrectomy with curative intent [7, 8]. In addition, there is lack of specific diagnostic markers for RCC, which is an important contributory factor in its poor prognosis [9]. A better understanding of the molecular basis of RCC has facilitated the development of novel and more selective diagnostic and therapeutic approaches.
Many studies have shown that epigenetic modification plays an important role in cancer development [10]. Histone methylation is essentially a post-translational and epigenetic modification, which is miswritten, misinterpreted and incorrectly erased in many human cancers, including RCC [11]. Histone methylation can occur at certain amino acids including lysine (K) and arginine (R) in the N-terminus of histones H3 and H4, by the addition of one, two, or three methyl groups. H3K27 methylation is a reversible process that can be catalyzed by histone lysine methyltransferase 6 (KMT6, also known as EZH2), and the demethylases 6A (KDM6A, also known as ubiquitously-transcribed TPR gene on the X chromosome, UTX) and 6B (KDM6B, also known as jumonji domain-containing protein 3, JMJD3) [12]. Tri-methylated histone H3K27 (H3K27me3) is a suppressor marker that inhibits the expression of specific target genes by altering the physical state of chromatin. EZH2 (enhancer of zeste homolog 2) can be regarded as an oncogene and is frequently overexpressed in a wide variety of cancers [13], including RCC [14, 15]. Several studies have identified UTX and JMJD3 as H3K27-specific demethylases that contribute to gene activation [16–20]. Both UTX and JMJD3 are considered as tumor suppressors, and inactivating somatic mutations of UTX are frequently observed in several tumor types, including RCC [21]. However, the relationship between the expression of these two enzymes and cancer development is largely unknown. In this study, we therefore investigated the gene and protein expression levels of UTX and JMJD3 and their clinical significance in RCC.
Patients and tissue specimens
Sixty-three patients were diagnosed with clear cell RCC by computed tomography (CT) combined with clinical symptoms, and the diagnoses were confirmed by clinicopathological examination at the Fourth Clinical Medical College of Hebei Medical University (Shijiazhuang, China). All cancer tissues and paired adjacent tissues were obtained through radical nephrectomy. Written informed consent was obtained from all patients before surgery and the study was approved by the Human Research Ethics Committee of The Fourth Clinical Medical College of Hebei Medical University. Histological classification (Additional file 1: Figure S1) was performed according to the standard provided by Fuhrman et al. [22] and postoperative pathological staging was performed in all cases (Table 1).
Table 1 Demographics of patients and tumor characteristics of radical nephrectomy specimens
Quantitative real-time-polymerase chain reaction (qRT-PCR)
Total RNA was extracted from cancer tissues and adjacent tissues with Trizol reagent (Invitrogen, Carlsbad, CA, USA) according to the manufacturer's protocol. The total RNA concentration was determined using a NanoDrop ND-1000 spectrophotometer (Thermo Scientific, Wilmington, DE, USA). cDNA was synthesized from 2 μg of total RNA using a RT system, according to the manufacturer's instructions (Invitrogen). The mRNA expression levels of UTX, JMJD3, EZH2 and p16INK4a were analyzed using SYBR green PCR Mix (Tiangen, Beijing, China), with 18S rRNA as an internal reference. qRT-PCR was performed using a 7500 RealTime PCR System (Applied Biosystems, Foster City, CA, USA). Primer sequences were synthesized by Sangon (Shanghai, China) and included: UTX forward 5'- TTTGTCAATTAGGTCACTTCAACCTC −3' and UTX reverse 5'- AAAAAGGCAGCATTCTTCCAGTAGTC −3', JMJD3 forward 5'- GGAGGCCACACGCTGCTAC −3' and JMJD3 reverse 5'- GCCAGTATGAAAGTTCCAGAGCTG-3', EZH2 (isoforms 1–5) forward 5'- GGGACAGTAAAAATGTGTCCTGC-3' and EZH2 reverse 5'-TGCCAGCAATAGATGCTTTTTG-3', INK4A (isoforms 1/2) forward 5'- GAAGGTCCCTCAGACATCCCC −3' and INK4A reverse 5'- CCCTGTAGGACCTTCGGTGAC −3', 18S rRNA forward 5'-CGGCGGCTTT GGTGACTCTAG-3' and 18S rRNA reverse 5'-CCGTTTCTCAGGCTCCCTCTCC-3'. Relative expression levels of the four genes were normalized to the internal reference 18S RNA. Data were analyzed using the comparative threshold cycle (2-ΔCT) method.
Cancer tissues and adjacent normal tissues from all 63 patients were homogenized in radioimmunoprecipitation assay buffer containing the protease inhibitors phenylmethylsulfonyl fluoride (100 μg/mL), NaVO3 (1 mmol/L) and dithiothreitol (0.5 mmol/L). Homogenates were centrifuged and supernatants were collected. Protein concentrations were determined using a NanoDrop ND-1000 and corrected appropriately. A total of 50 μg of protein from each sample was resolved by reducing loading buffer and separated by 8% sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by electrophoretic transfer to a nitrocellulose (NC) membrane. The NC membrane was saturated with 5% skim milk in TBST (50 mM Tris–HCl, 150 mM NaCl, 0.1% Tween-20) for 2 h and then incubated with primary antibodies at 4°C overnight. The primary antibodies used included rabbit polyclonal antibodies to UTX (1:1,000, Abcam, Hong Kong, China), JMJD3 (1:1500, Abcam), EZH2 (1:500, Santa Cruz Biotechnology, Hong Kong, China), H3K27me3 (1:1,500, Epigentek, Brooklyn, USA), H3 (1:2,000, Sigma-Aldrich, St Louis, USA) and actin (1:2,500, Sigma, St Louis, USA). NC membranes were incubated with 1:5,000-diluted peroxidase-coupled goat anti-rabbit immunoglobulin G (IgG) (secondary antibody, Sigma) for 1 h, after washing three times with TBST (5 min/time) at room temperature. After further washing with TBST four times, the NC membranes were exposed to enhanced chemiluminescence substrate (Pierce, Rockford, USA) for 5 min and detection was performed using a Fujifilm LAS-4000 imaging system (GE Healthcare, Bucks, UK).
Immunohistochemical analysis
After fixation in 4% formalin, cancer tissues and adjacent normal tissues from the 63 RCC patients were dehydrated through an ascending series of graded ethanols, embedded in paraffin wax, and cut into 5-μm sections using a microtome. The endogenous peroxidase activity of sections was inhibited by treatment with 3% H2O2/methanol. Antigen retrieval was performed on xylene-deparaffinized and dehydrated sections by heating the slides for 10 min in 0.01 M citrate buffer (pH 6.0). Non-specific binding was blocked by incubating sections with 5% BSA in a humidified chamber. Sections were then incubated overnight at 4°C with 1:100 dilution of anti-UTX or anti-JMJD3 primary polyclonal rabbit antibodies (Abcam). After washing twice in PBS, sections were treated with peroxidase-conjugated AffiniPure goat anti-rabbit IgG (ZSGB Bio, Beijing, China) at room temperature for 30 min, followed by diaminobenzidine (ZSGB Bio) as a chromogen to visualize the peroxidase activity. A negative immunohistochemical control was provided by replacement of the primary antibodies by antibody diluents.
The protein expression scores for both UTX and JMJD3 were quantitated according to Wu et al. [23]. Briefly, the proportions of UTX/JMJD3-expressing tumor cells were scored as follows: 0, no positive cells; 1, <5%; 2, 6–25%; 3, 26–50%; 4, 51–75%; and 5, >75%. Staining intensity was graded according to the mean optical density: 0, no staining; 1, weak staining (light yellow); 2, moderate staining (yellow-brown); and 3, strong staining (brown). The staining index was calculated as the product of the staining intensity score and the proportion of UTX/JMJD3-positive tumor cells.
Statistical analysis was carried out using the SPSS 17.0 statistical software package. qRT-PCR and immunohistochemical data were analyzed by two-tailed paired-sample t-tests and Mann–Whitney U tests (α = 0.05). A P value of ≤ 0.05 was considered to indicate a statistically significant difference between cancer tissues and adjacent normal tissues.
Patient clinical characteristics
A total of 63 samples of cancer tissues and paired adjacent normal tissues were available from patients with RCC who had undergone surgery. All the patients were treated by radical nephrectomy and received no preoperative radiation or chemotherapy y. Most patients (56/63) were at an early stage (stages 1 and 2), and no lymph node metastasis was present in any patients. The overall 5-year survival rate was 100%, suggesting that early diagnosis and surgical removal of the cancer tissue resulted in a good prognosis. The clinical data are shown in Table 1.
mRNA expression levels of UTX and JMJD3 in cancer tissues and adjacent normal tissues in RCC patients
The transcription levels of the two H3K27 demethylase genes, UTX and JMJD3, the H3K27 methyltransferase EZH2 and the CDK4/CDK6 inhibitor p16INK4a were determined by qRT-PCR in cancer tissues and adjacent normal tissues from 36 RCC patients. The mRNA levels of UTX, JMJD3 and EZH2 were significantly increased in cancer tissues compared to the adjacent tissues (P < 0.05, Figure 1), while the expression of p16INK4a mRNA was highly significantly upregulated in cancer tissues (P < 0.001, Figure 1).
Real-time qRT-PCR analysis of the H3K27 demethylases UTX and JMJD3 , the H3K27 methyltransferase EZH2 and the CDK4/CDK6 inhibitor p16INK4a. Relative mRNA expression levels of UTX, JMJD3 and EZH2 were higher in RCC cancer tissues than in paired adjacent normal tissues (n = 36; all P < 0.05). The mRNA level of p16INK4a was also upregulated in cancer tissues compared to adjacent normal tissues (P < 0.001).
Levels of UTX and JMJD3 proteins in cancer tissues and adjacent normal tissues in RCC patients
To support the changes in mRNA levels of UTX and JMJD3, the protein contents of the two H3K27 demethylases were measured by western blotting. Levels of UTX and JMJD3 proteins were obviously increased in cancer tissues compared to adjacent normal tissues (Figure 2), while the level of H3K27me3 was reduced and H3K27 methyltransferase EZH2 was upregulated (Figure 2).
Western blotting analysis of H3K27 methylation-modifying enzymes and H3K27me3 levels. The protein expression levels of the H3K27 demethylases UTX and JMJD3 were higher in RCC cancer tissues (C) than in paired adjacent normal tissues (A). The H3K27me3 level was lower in RCC cancer tissues, although the protein level of the H3K27 methyltransferase EZH2 was increased.
Changes in UTX and JMJD3 expression in cancer tissues and adjacent normal tissues in RCC patients analyzed by immunohistochemistry
The expression and subcellular localization of the two H3K27 demethylases UTX and JMJD3 were further determined by immunohistochemical analysis in 63 paraffin-embedded RCC cancer tissues and paired adjacent tissues. The H3K27 demethylases were localized mainly in the nucleus in renal tissue. UTX and JMJD3 protein contents were higher in cancer tissues than in adjacent normal tissues (P < 0.01, Figures 3, 4, and 5).
Changes in UTX and JMJD3 protein expression levels in RCC. Levels of UTX and JMJD3 proteins were higher in RCC cancer tissue samples (C) than in paired adjacent normal tissue samples (A) (n = 63, P < 0.05).
Immunohistochemical analysis of UTX expression. UTX protein expression was obviously higher in cancer tissues (C and D) than in adjacent normal tissues (A and B). Magnifications × 200 (A and C) and × 400 (B and D).
Immunohistochemical analysis of JMJD3 expression. JMJD3 protein expression was obviously higher in cancer tissues (C and D) than in adjacent normal tissues (A and B). Magnifications × 200 (A and C) and × 400 (B and D).
Histone demethylases are known to be closely related to tumor formation [24] and several studies have also indicated an association between the H3K9 demethylase JMJD1A and RCC [25, 26]. The role of histone demethylases in RCC is thus worthy of further investigation. Both UTX and JMJD3 are H3K27me3 demethylases and are essential for the expression of many genes, including HOX, through decreasing the levels of H3K27me3 [16, 17]. Inactivating somatic mutations of UTX and reduced expression of JMJD3 have been demonstrated in many cancers [21, 27]. Both UTX and JMJD3 can be considered as candidate tumor suppressors [28, 29], and may be involved in tumor suppression via an oncogene-induced senescence (OIS) mechanism.
The human tumor suppressor genes INK4b-ARF-INK4a are located on chromosome 9p21 and encode the proteins p16INK4a, p15INK4b and p14ARF. p16INK4a/p15INK4b are CDK4/CDK6 inhibitors and block retinoblastoma protein (Rb) phosphorylation and inactivation, which enhances the pRB-E2F signaling pathway. p14ARF inhibits the activity of p53-specific ubiquitin ligase murine double minute 2 (MDM2), which increases expression of p53 protein [30]. These three proteins are involved in senescence regulation and induction of cell cycle arrest at the G0/G1 phase, leading to cell senescence [31]. Cellular senescence causes irreversible growth arrest, while OIS is an important preventive mechanism for pre-cancerous damage [32] and can effectively block uncontrolled cell proliferation induced by DNA damage or oncogenic stimuli. Imbalance of OIS can lead to unlimited cell proliferation and eventually to cancer development [33].
The INK4b-ARF-INK4a locus is regulated by many factors, including histone modification [34]. The polycomb repressive complex 2 (PRC2) containing EZH2 can bind the INK4b-ARF-INK4a locus and silence their gene expressions through increasing local H3K27me3 content, which in turn promotes cell proliferation and reduces cell senescence [35, 36]. In contrast, JMJD3 binding to the INK4b-ARF-INK4a locus can inhibit PRC2 occupancy and decrease H3K27me3 content, resulting in the increased expressions of these three proteins and promotion of cell senescence [29]. In primary Hodgkin's lymphoma, JMJD3 is over-expressed and induced by the Epstein-Barr virus oncogene [37]. The results of our study revealed that H3K27me3 levels were lower in cancer tissues compared to adjacent normal tissues, accompanied by increased JMJD3 expression. Consistent with the strong decrease in H3K27me3 levels, p16INK4a gene expression was obviously higher in cancer tissues compared to normal tissues. Previous research indicated that homozygous deletions of the INK4a/ARF locus contributed to tumor progression in RCC [38]. These results suggest that inactivation or down-regulation of p16INK4a is a later event in RCC progression.
UTX also plays an important role in cell senescence in tumor suppression. The tumor suppressor Rb and its binding proteins are regulated by UTX-catalyzed H3K27me3 demethylation [39]. UTX can occupy the promoter region of Rb and the related gene Rbl2 (retinoblastoma-like protein 2) and increase their expression, thus reducing cell proliferation and increasing cell senescence [40]. In Drosophila, UTX-mutant cells showed tumor-like growth characteristics accompanied by reduced Rb expression [41]. In the current study, UTX expression was obviously higher in cancerous tissues at both the mRNA and protein levels. Although all three of these proteins are upregulated in RCC, the reduction in H3K27me3 level implies that the H3K27 demethylases UTX and JMJD3 play more important roles than the H3K27 methyltransferase EZH2 in regulating p16INK4a expression.
Previous studies demonstrated that abnormal H3K27 levels or EZH2 expression were associated with cancer development and prognosis [14, 42]. This study also demonstrated that upregulated expression of the H3K27 demethylases UTX and JMJD3 was relevant to tumor suppression. Previous studies found evidence for JMJD3 regulation in tissues from many cancers, including prostate cancer and primary Hodgkin's lymphoma [20, 37]. Further studies of the relationship between histone demethylases and cancer development will improve our understanding of the molecular mechanisms involved, and potentially aid in the development of new therapies for RCC [43, 44]. The possible roles of UTX and JMJD3 in RCC can be summarized as follows: oncogene activation leads to increased binding of JMJD3 to the p16INK4a promoter and subsequent transcriptional induction through demethylation of H3K27me3 at the INK4A-ARF locus [31]. p16INK4a then inhibits RCC development via induction of cell cycle arrest. However, our understanding of the mechanism underlying cell senescence in tumor suppression is currently limited, and further studies are needed to clarify the roles of UTX and JMJD3 in RCC.
In summary, this study revealed that upregulated expression levels of UTX and JMJD3 are common in cancer tissues in early stage RCC patients with a good prognosis. These H3K27 demethylases may inhibit cell proliferation in primary RCC through OIS. The results also imply that identification of the genes regulated by UTX and JMJD3 during RCC development will improve our understanding of the carcinogenesis and screening strategies in RCC. The potential roles of H3K27 demethylases as biomarker(s) for the early diagnosis of RCC and for prognostic evaluation need to be investigated.
Rini BI, Campbell SC, Escudier B: Renal cell carcinoma. Lancet. 2009, 373: 1119-1132. 10.1016/S0140-6736(09)60229-4.
Giubellino A, Linehan WM, Bottaro DP: Targeting the Met signaling pathway in renal cancer. Expert Rev Anticancer Ther. 2009, 9: 785-793. 10.1586/era.09.43.
Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P: Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol. 2007, 18: 581-592.
Basu B, Eisen T: Perspectives in drug development for metastatic renal cell cancer. Target Oncol. 2010, 5: 139-156. 10.1007/s11523-010-0149-2.
Suárez C, Morales R, Muñoz E, Rodón J, Valverde CM, Carles J: Molecular basis for the treatment of renal cell carcinoma. Clin Transl Oncol. 2010, 12: 15-21. 10.1007/s12094-010-0461-4.
Banumathy G, Cairns P: Signaling pathways in renal cell carcinoma. Cancer Biol Ther. 2010, 10: 658-864. 10.4161/cbt.10.7.13247.
Mohammed A, Shergill I, Little B: Management of metastatic renal cell carcinoma: current trends. Expert Rev Mol Diagn. 2009, 9: 75-83. 10.1586/14737159.9.1.75.
Chin AI, Lam JS, Figlin RA, Belldegrun AS: Surveillance strategies for renal cell carcinoma patients following nephrectomy. Rev Urol. 2006, 8: 1-7.
Eichelberg C, Junker K, Ljungberg B, Moch H: Diagnostic and prognostic molecular markers for renal cell carcinoma: a critical appraisal of the current state of research and clinical applicability. Eur Urol. 2009, 55: 851-863. 10.1016/j.eururo.2009.01.003.
Hatziapostolou M, Iliopoulos D: Epigenetic aberrations during oncogenesis. Cell Mol Life Sci. 2011, 68: 1681-1702. 10.1007/s00018-010-0624-z.
Chi P, Allis CD, Wang GG: Covalent histone modifications–miswritten, misinterpreted and mis-erased in human cancers. Nat Rev Cancer. 2010, 10: 457-469. 10.1038/nrc2876.
Hübner MR, Spector DL: Role of H3K27 demethylases Jmjd3 and UTX in transcriptional regulation. Cold Spring Harb Symp Quant Biol. 2010, 75: 43-49.
Simon JA, Lange CA: Roles of the EZH2 histone methyltransferase in cancer epigenetics. Mutat Res. 2008, 647: 21-29. 10.1016/j.mrfmmm.2008.07.010.
Wagener N, Macher-Goeppinger S, Pritsch M, Hüsing J, Hoppe-Seyler K, Schirmacher P, Pfitzenmaier J, Haferkamp A, Hoppe-Seyler F, Hohenfellner M: Enhancer of zeste homolog 2 (EZH2) expression is an independent prognostic factor in renal cell carcinoma. BMC Cancer. 2010, 10: 524-10.1186/1471-2407-10-524.
Hinz S, Weikert S, Magheli A, Hoffmann M, Engers R, Miller K, Kempkensteffen C: Expression profile of the polycomb group protein enhancer of Zeste homologue 2 and its prognostic relevance in renal cell carcinoma. J Urol. 2009, 182: 2920-2925. 10.1016/j.juro.2009.08.014.
Swigut T, Wysocka J: H3K27 demethylases, at long last. Cell. 2007, 131: 29-32. 10.1016/j.cell.2007.09.026.
Agger K, Cloos PA, Christensen J, Pasini D, Rose S, Rappsilber J, Issaeva I, Canaani E, Salcini AE, Helin K: UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature. 2007, 449: 731-7314. 10.1038/nature06145.
Lee MG, Villa R, Trojer P, Norman J, Yan KP, Reinberg D, Di Croce L, Shiekhattar R: Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination. Science. 2007, 318: 447-450. 10.1126/science.1149042.
Lan F, Bayliss PE, Rinn JL, Whetstine JR, Wang JK, Chen S, Iwase S, Alpatov R, Issaeva I, Canaani E, Roberts TM, Chang HY, Shi Y: A histone H3 lysine 27 demethylase regulates animal posterior development. Nature. 2007, 449: 689-694. 10.1038/nature06192.
Xiang Y, Zhu Z, Han G, Lin H, Xu L, Chen CD: JMJD3 is a histone H3K27 demethylase. Cell Res. 2007, 17: 850-857. 10.1038/cr.2007.83.
van Haaften G, Dalgliesh GL, Davies H, Chen L, Bignell G, Greenman C, Edkins S, Hardy C, O'Meara S, Teague J, Butler A, Hinton J, Latimer C, Andrews J, Barthorpe S, Beare D, Buck G, Campbell PJ, Cole J, Forbes S, Jia M, Jones D, Kok CY, Leroy C, Lin ML, McBride DJ, Maddison M, Maquire S, McLay K, Menzies A, Mironenko T, Mulderrig L, Mudie L, Pleasance E, Shepherd R, Smith R, Stebbings L, Stephens P, Tang G, Tarpey PS, Turner R, Turrell K, Varian J, West S, Widaa S, Wray P, Collins VP, Ichimura K, Law S, Wong J, Yuen ST, Leung SY, Tonon G, DePinho RA, Tai YT, Anderson KC, Kahnoski RJ, Massie A, Khoo SK, Teh BT, Stratton MR, Futreal PA: Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat Genet. 2009, 41: 521-523. 10.1038/ng.349.
Fuhrman SA, Lasky LC, Limas C: Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol. 1982, 6: 655-663. 10.1097/00000478-198210000-00007.
Wu S, Wang Y, Sun L, Zhang Z, Jiang Z, Qin Z, Han H, Liu Z, Li X, Tang A, Gui Y, Cai Z, Zhou F: Decreased expression of dual-specificity phosphatase 9 is associated with poor prognosis in clear cell renal cell carcinoma. BMC Cancer. 2011, 11: 413-10.1186/1471-2407-11-413.
Kampranis SC, Tsichlis PN: Histone demethylases and cancer. Adv Cancer Res. 2009, 102: 103-169.
Guo X, Shi M, Sun L, Wang Y, Gui Y, Cai Z, Duan X: The expression of histone demethylase JMJD1A in renal cell carcinoma. Neoplasma. 2011, 58: 153-157. 10.4149/neo_2011_02_153.
Krieg AJ, Rankin EB, Chan D, Razorenova O, Fernandez S, Giaccia AJ: Regulation of the histone demethylase JMJD1A by hypoxia-inducible factor 1 alpha enhances hypoxic gene expression and tumor growth. Mol Cell Biol. 2010, 30: 344-353. 10.1128/MCB.00444-09.
Agger K, Cloos PA, Rudkjaer L, Williams K, Andersen G, Christensen J, Helin K: The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence. Genes Dev. 2009, 23: 1171-1176. 10.1101/gad.510809.
Tsai MC, Wang JK, Chang HY: Tumor suppression by the histone demethylase UTX. Cell Cycle. 2010, 9: 2043-2044. 10.4161/cc.9.11.11845.
Barradas M, Anderton E, Acosta JC, Li S, Banito A, Rodriguez-Niedenführ M, Maertens G, Banck M, Zhou MM, Walsh MJ, Peters G, Gil J: Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS. Genes Dev. 2009, 23: 1177-1182. 10.1101/gad.511109.
Campisi J: Cancer and ageing: rival demons?. Nat Rev Cancer. 2003, 3: 339-349. 10.1038/nrc1073.
Gil J, Peters G: Regulation of the INK4b–ARF–INK4a tumour suppressor locus: All for one or one for all. Nat Rev Mol Cell Biol. 2006, 7: 667-677.
Collado M, Serrano M: The power and the promise of oncogene induced senescence markers. Nat Rev Cancer. 2006, 6: 472-476. 10.1038/nrc1884.
Campisi J, D'Adda Di Fagagna F: Cellular senescence: When bad things happen to good cells. Nat Rev Mol Cell Biol. 2007, 8: 729-740.
Popov N, Gil J: Epigenetic regulation of the INK4b-ARF-INK4a locus: In sickness and in health. Epigenetics. 2010, 5: 685-690. 10.4161/epi.5.8.12996.
Kotake Y, Cao R, Viatour P, Sage J, Zhang Y, Xiong Y: pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4alpha tumor suppressor gene. Genes Dev. 2007, 21: 49-54. 10.1101/gad.1499407.
Bracken AP, Kleine-Kohlbrecher D, Dietrich N, Pasini D, Gargiulo G, Beekman C, Theilgaard-Mönch K, Minucci S, Porse BT, Marine JC, Hansen KH, Helin K: The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev. 2007, 21: 525-530. 10.1101/gad.415507.
Anderton JA, Bose S, Vockerodt M, Vrzalikova K, Wei W, Kuo M, Helin K, Christensen J, Rowe M, Murray PG, Woodman CB: The H3K27me3 demethylase, KDM6B, is induced by Epstein-Barr virus and over-expressed in Hodgkin's Lymphoma. Oncogene. 2011, 30: 2037-2043. 10.1038/onc.2010.579.
Kasahara T, Bilim V, Hara N, Takahashi K, Tomita Y: Homozygous deletions of the INK4a/ARF locus in renal cell cancer. Anticancer Res. 2006, 26: 4299-4305.
Wang JK, Tsai MC, Poulin G, Adler AS, Chen S, Liu H, Shi Y, Chang HY: The histone demethylase UTX enables RB-dependent cell fate control. Genes Dev. 2010, 24: 327-332. 10.1101/gad.1882610.
Terashima M, Ishimura A, Yoshida M, Suzuki Y, Sugano S, Suzuki T: The tumor suppressor Rb and its related Rbl2 genes are regulated by Utx histone demethylase. Biochem Biophys Res Commun. 2010, 399: 238-244. 10.1016/j.bbrc.2010.07.061.
Herz HM, Madden LD, Chen Z, Bolduc C, Buff E, Gupta R, Davuluri R, Shilatifard A, Hariharan IK, Bergmann A: The H3K27me3 demethylase dUTX is a suppressor of Notch- and Rb-dependent tumors in Drosophila. Mol Cell Biol. 2010, 30: 2485-2497. 10.1128/MCB.01633-09.
He LR, Liu MZ, Li BK, Rao HL, Liao YJ, Guan XY, Zeng YX, Xie D: Prognostic impact of H3K27me3 expression on locoregional progression after chemoradiotherapy in esophageal squamous cell carcinoma. BMC Cancer. 2009, 9: 461-10.1186/1471-2407-9-461.
Varier RA, Timmers HT: Histone lysine methylation and demethylation pathways in cancer. Biochim Biophys Acta. 2011, 1815: 75-89.
Rotili D, Mai A: Targeting histone demethylases: a new avenue for the fight against cancer. Genes Cancer. 2011, 2: 663-679. 10.1177/1947601911417976.
This project was supported by the National Natural Science Foundation of China (No. 30870265) and Natural Science Foundation of Hebei Province (No. C2010000410).
Laboratory of Iron Metabolism and Molecular Biology, College of Life Science, Hebei Normal University, Shijiazhuang, 050016, China
Yongqing Shen
, Xiaoqiang Guo
, Yuejia Wang
, Yanzhong Chang
& Xianglin Duan
Department of Biochemistry, Bethune Military Medical College, Shijiazhuang, 050081, China
Xiaoqiang Guo
Department of Urology, The Fourth Hospital, Hebei Medical University, Shijiazhuang, 050011, China
Aili Zhang
Department of Urology, Peking University First Hospital, Beijing, 100034, China
Wei Qiu
Xishan College, Hebei Medical University, Shijiazhuang, 050011, China
Search for Yongqing Shen in:
Search for Xiaoqiang Guo in:
Search for Yuejia Wang in:
Search for Wei Qiu in:
Search for Yanzhong Chang in:
Search for Aili Zhang in:
Search for Xianglin Duan in:
Correspondence to Aili Zhang or Xianglin Duan.
XG, YC, AZ and XD were responsible for experimental design, data analysis and writing of manuscript. YS, XG and YW conducted the experiments including qRT-PCR, western blotting and immunohistochemical analysis. YS, WQ and AZ were responsible for collection and histological classification of clinical specimens. All authors have read and approved the final manuscript.
Yongqing Shen, Xiaoqiang Guo contributed equally to this work.
Additional file 1: Figure S1. The pathological stage of RCC. The A~D represents grade 1~4 of RCC according to the standard presented by Fuhrman et al [22]. (TIFF 1 MB)
Shen, Y., Guo, X., Wang, Y. et al. Expression and significance of histone H3K27 demethylases in renal cell carcinoma. BMC Cancer 12, 470 (2012) doi:10.1186/1471-2407-12-470
Histone H3K27 demethylase
UTX
JMJD3


text:
Home / World Tourism / United States closes borders to travellers from Schengen area
The United States will introduce wide-ranging new restrictions on travellers from Europe as the country battles the coronavirus outbreak.
In a televised address earlier, president Donald Trump said the move was "strong but necessary".
Travellers from the 26 countries in the Schengen border-free travel zone will be barred from entering the United States for 30 days from tomorrow.
This includes arrivals from Austria, Germany, Italy, France, the Netherlands and Portugal, among others.
"To keep new cases from entering our shores, we will be suspending all travel from Europe," Trump said from the Oval Office on Wednesday evening.
"The new rules will go into effect Friday at midnight," he added.
A presidential proclamation also specified the ban would apply to anyone who had been in the Schengen area in the 14 days before their arrival in the United States.
There are 1,135 confirmed cases of the virus across the US, with 38 deaths so far.
The travel order does not apply to US citizens.
The United Kingdom and Ireland, which are outside the travel-free zone, will also be unaffected.
Trump added the European Union had "failed to take the same precautions" as the United States in fighting the virus.
As of Wednesday, the number of cases of the coronavirus in the Schengen area totalled 17,442, with 711 deaths.
According to health officials, the area also shows high continuous growth in infection rates.
The United States president initially said the suspension would also "apply to the tremendous amount of trade and cargo" coming from Europe into the country.
He later backtracked, tweeting to say that trade would "in no way be affected".
In response to the ban, the European Commission issued a scathing statement.
"The coronavirus is a global crisis, not limited to any continent and it requires cooperation rather than unilateral action," it said.
"The European Union disapproves of the fact that the United States decision to impose a travel ban was taken unilaterally and without consultation."
Dylan Travis/ABACA/ABACA/PA Images
Previous Gathy to lead development of Amaala Island
Next WTTC warns 50 million tourism jobs could go in coronavirus outbreak
Gathy to lead development of Amaala Island
5 Tips for Visiting Kennedy Space Center with Kids
More Americans -including Millennials- seeking the expertise of travel agents
Sushisamba coming to the Palm Tower, Palm Jumeirah


text:
Tag: AOC
LG 27UD58-B 27″ 4K Widescreen FreeSync LED Monitor for $219.00 Shipped
LG 27UD58-B 27″ 4K Widescreen FreeSync LED Monitor for $219.00 shipped. Here is a screenshot for reference. It features a 3840 x 2160 resolution, FreeSync technology, and inputs for HDMI and DisplayPort. Most places have it for about $299.
Report Deal Status Awesome deal. Thanks! Deal not valid anymore! :(
AOC U2879VF 28″ 4K Widescreen FreeSync LCD Monitor for $199.98 Shipped
AOC U2879VF 28″ 4K Widescreen FreeSync LCD Monitor for $199.98 shipped. Here is a screenshot for reference. It features a 3840 x 2160 resolution, FreeSync technology, and inputs for VGA, DVI, HDMI, and DisplayPort.
AOC U2879VF 28″ 4K Widescreen LCD Monitor for $280.98 Shipped
AOC U2879VF 28″ 4K Widescreen LCD Monitor for $279.99 after promo code MPGAMER16 with MasterPass checkout. Shipping is $0.99 for a total of $280.98 shipped. Here is a screenshot for reference. It features a 3840 x 2160 resolution, and inputs for VGA, DVI, HDMI, and DisplayPort.
AOC E2752VH 27″ 1080p LED-Backlit LCD Monitor for $129.99 Shipped
AOC E2752VH 27″ 1080p LED-Backlit Monitor for $129.99 shipped. Here is a screenshot for reference. It features a 1920 x 1080 resolution, built-in speakers, and inputs for HDMI and VGA. Most places have this LED-backlit LCD monitor for over $175.
AOC E2752VH 27″ 1080p LED-Backlit Monitor for $149.99 shipped. Here is a screenshot for your reference. It features a 1920 x 1080 resolution, built-in speakers, and inputs for HDMI and VGA. Most places have this LED-backlit LCD monitor for about $180.
AOC E2425SWD 23.6″ 1080p LED-Backlit LCD Monitor for $99.99 Shipped
AOC E2425SWD 23.6″ 1080p LED-Backlit LCD Monitor for $99.99 shipped. Here is a screenshot for reference. This monitor features LED back-lighting, a 1920 x 1080 resolution, 20,000,00:1 dynamic contrast ratio, and inputs for both DVI and VGA. Most places have this LCD monitor for over $125.
AOC e2752She 27″ 1080p LED-Backlit Monitor for $149.99 Shipped
AOC e2752She 27″ 1080p LED-Backlit Monitor for $149.99 shipped. Here is a screenshot for reference. This monitor features a 1920 x 1080 resolution, and inputs for 2 HDMI and VGA. Most places have this LED-backlit LCD monitor for over $200.
AOC 27″ 1080p LED-Backlit Monitor for $179.99 Shipped
AOC E2752SHE 27″ 1080p LED-Backlit Monitor for $179.99 shipped. Here is a screenshot for your reference. This monitor features a 1920 x 1080 resolution, and inputs for HDMI and VGA. Most places have this LED-backlit LCD monitor for about $215.
AOC E2470 23.6″ 1080p LED-Backlit Monitor for $99.99 Shipped
AOC E2470 23.6″ 1080p LED-Backlit Monitor for $99.99 shipped. Here is a screenshot for reference. This monitor features a 1920 x 1080 resolution, and inputs for HDMI and VGA.
AOC E2470 23.6″ 1080p LED-Backlit Monitor for $99.99 shipped. Here is a screenshot for your reference. This monitor features a 1920 x 1080 resolution, and inputs for HDMI and VGA.
AOC e2752She 27″ 1080p LED-Backlit Monitor for $179.99 shipped. Here is a screenshot for your reference. Alternatively, it is available at B&H for $184.60 with free expedited shipping as shown here. This monitor features a 1920 x 1080 resolution, and inputs for HDMI and VGA. Most places have this LED-backlit LCD monitor for about $219.
AOC e2752She 27″ 1080p LED-Backlit Monitor for $152.99 shipped when you combine it with this deal. Here is a screenshot before the 10% off through this deal. It features a 1920 x 1080 resolution, and 2 inputs for HDMI and 1 for VGA. Most places have this LED-backlit LCD monitor for about $199.
AOC E1649FWU 15.6″ USB Portable LED-Backlit LCD Monitor for $69.99 Shipped
AOC E1649FWU 15.6″ USB Portable LED-Backlit LCD Monitor for $69.99 shipped after promo code BFLGJLMNQT76. Here is a screenshot for your reference. It features a 1366 x 768 resolution, 90° horizontal and 50° vertical viewing angles, and USB interface. Most places have this portable LCD monitor for about $88 or more.
AOC E2425SWD 23.6″ 1080p LED-Backlit LCD Monitor for $109.99 Shipped
AOC E2425SWD 23.6″ 1080p LED-Backlit LCD Monitor for $109.99 shipped after promo code SAVINGS10. Here is a screenshot for your reference. This monitor features LED back-lighting, a 1920 x 1080 resolution, 20,000,00:1 dynamic contrast ratio, and inputs for both DVI and VGA. Most places have this LCD monitor for about $134 or more.
Originally posted earlier, this post has been revised.
AOC E2425SWD 23.6″ 1080p LED-Backlit LCD Monitor for $119.99 shipped. Here is a screenshot for your reference. This monitor features LED backlighting, a 1920 x 1080 resolution, 20,000,00:1 dynamic contrast ratio, and inputs for both DVI and VGA. Most places have this LCD monitor for about $139.
AOC e2752She 27″ 1080p LED-Backlit Monitor for $199.99 shipped. Here is a screenshot for your reference. Alternatively, it is available at Amazon for $199.99 shipped. It features a 1920 x 1080 resolution, and 2 inputs for HDMI and 1 for VGA. Most places have this LED-backlit LCD monitor for about $229 or more.
AOC e2752She 27″ 1080p LED-Backlit Monitor for $199.99 shipped. Here is a screenshot for your reference. It features a 1920 x 1080 resolution, and 2 inputs for HDMI and 1 for VGA. Most places have this LED-backlit LCD monitor for about $244.
AOC E2351F 23″ 1080p LED-Backlit LCD Monitor for $99.90 Shipped
AOC E2351F 23″ 1080p LED-Backlit LCD Monitor for $99.90 shipped. Here is a screenshot for your reference. Note that availability varies by locations but appears to be available at most places. This monitor features LED backlighting, a 1920 x 1080 resolution, 20,000,00:1 dynamic contrast ratio, and inputs for both DVI and VGA. As a comparison, Best Buy currently has this LCD monitor for about $169.
AOC E1649FWU 15.6″ USB Portable LED-Backlit LCD Monitor for $69.99 shipped. Here is a screenshot for your reference. It features a 1366 x 768 resolution, 90° horizontal and 50° vertical viewing angles, and USB interface. Most places have this portable LCD monitor for over $91 or more.
AOC E2752VH 27″ 1080p LED-Backlit Monitor for $199.99 shipped. Here is a screenshot for your reference. It features a 1920 x 1080 resolution, built-in speakers, and inputs for HDMI and VGA. Most places have this LED-backlit LCD monitor for over $250.
AOC E950SW 18.5″ LED-Backlit LCD Monitor for $55.24 Shipped
AOC E950SW 18.5″ LED-Backlit LCD Monitor for $55.24 shipped after code NATURE15. Here is a screenshot for your reference. This monitor features LED backlighting, a 1366 x 768 resolution, 20,000,00:1 dynamic contrast ratio, and input options for both VGA and DVI.
AOC E2060SWD 19.5″ LED HD Monitor for $79.99 Shipped
AOC E2060SWD 19.5″ LED HD Monitor for $79.99 shipped. Here is a screenshot for your reference. It features a 1600 x 900 resolution, 20,000,000:1 dynamic contrast ratio, and inputs for VGA and DVI with HDCP support.
AOC E2460SWD 24″ 1080p LED-Backlit LCD Monitor for $129.99 Shipped
AOC E2460SWD 24″ 1080p LED-Backlit LCD Monitor for $129.99 shipped. Here is a screenshot for your reference. This monitor features LED backlighting, a 1920 x 1080 resolution, 20,000,00:1 dynamic contrast ratio, and inputs for both DVI and VGA. Most places have this LCD monitor for about $169.
AOC E2243FWK 21.5″ LED HD Monitor for $99.99 Shipped
AOC E2243FWK 22″ LED-Backlit LCD Monitor for $99.99 shipped. Here is a screenshot for your reference. IT features a 1920 x 1080 resolution, 50,000,000:1 dynamic contrast ratio, and inputs for VGA and DVI with HDCP support. Most places have this 21.5″ LED-backlit LCD monitor for about $141.
AOC E2352PHZ 23″ 1080p 3D LED-Backlit Monitor for $168.70 Shipped
AOC E2352PHZ 23″ 1080p 3D LED-Backlit Monitor for $168.70 shipped. Here is a screenshot for your reference. It features a 1920 x 1080 resolution, 3D capable, built-in stereo speakers, 20,000,000:1 dynamic contrast ratio, and inputs for VGA, DVI-D with HDCP and HDMI 1.4a. Most places have it for about $200.
AOC E2243FWK 22″ LED-Backlit LCD Monitor for $99.99 shipped. Here is a screenshot for your reference. IT features a 1920 x 1080 resolution, 50,000,000:1 dynamic contrast ratio, and inputs for VGA and DVI with HDCP support. Most places have this 22″ LED-backlit LCD monitor for over $145.
AOC E2243FWK 22″ LED-Backlit LCD Monitor for $99.99 shipped. Here is a screenshot for your reference. IT features a 1920 x 1080 resolution, 50,000,000:1 dynamic contrast ratio, and inputs for VGA and DVI with HDCP support. Most places have this 22″ widescreen LED-backlit LCD monitor for about $149.
AOC E2351F 23″ 1080p LED-Backlit LCD Monitor for $104.99 Shipped
AOC E2351F 23″ 1080p LED-Backlit LCD Monitor for $104.99 shipped. Here is a screenshot for your reference. This monitor features LED backlighting, a 1920 x 1080 resolution, 20,000,00:1 dynamic contrast ratio, and inputs for both DVI and VGA. Most places have this LCD monitor for about $129.
AOC E2350SF 24″ 1080p LED-Backlit LCD Monitor for $139.99 Shipped
AOC E2350SF 24″ 1080p LED-Backlit LCD Monitor for $139.99 shipped. Here is a screenshot for your reference. This monitor features LED backlighting, a 1920 x 1080 resolution, 20,000,00:1 dynamic contrast ratio, and inputs for both DVI and VGA. Most places have this LCD monitor for about $189.
AOC E2051SN 20″ LED-Backlit LCD Monitor for $89.99 Shipped
AOC E2051SN 20″ LED-Backlit LCD Monitor for $89.99 shipped. Here is a screenshot for your reference. Alternatively, it is available at Amazon for $99.99 shipped. This monitor features LED backlighting, a 1600 x 900 resolution, 20,000,00:1 dynamic contrast ratio, and VGA input.
AOC 2436V 24″ 1080p Widescreen LCD Monitor for $129.00 or $133.97 Shipped
AOC 2436V 24″ 1080p Widescreen LCD Monitor for $129.99. Select free site-to-store for in-store pickup at Walmart to save on shipping. Otherwise, shipping is $4.97 for a total of $133.97 shipped. Here is a screenshot for your reference. It features a 1920 x 1080 (1080p) resolution, and inputs for VGA and DVI with HDCP support. Most places have it for about $169.
AOC E2043FK 20″ LED-Backlit Monitor for $92.00 Shipped
AOC E2043FK 20″ LED-Backlit Monitor for $92.99 shipped. Here is a screenshot for your reference. This LCD monitor features a 1600 x 900 resolution, LED backlight, 5ms response time, 50,000,000:1 dynamic contrast ratio, and inputs for VGA and DVI. Most places have this LED-backlit monitor for about $119.
AOC 2436V 24″ 1080p Widescreen LCD Monitor for $133.97 Shipped
AOC 2436V 24″ 1080p Widescreen LCD Monitor for $129.99. Select free site-to-store for in-store pickup at Walmart to save on shipping. Otherwise, shipping is $4.97 for a total of $133.97 shipped. Here is a screenshot for your reference. Alternatively, it is available at TigerDirect for $139.99 shipped. It features a 1920 x 1080 (1080p) resolution, and inputs for VGA and DVI with HDCP support. Most places have it for about $169.
AOC E1649FWU 15.6″ USB Portable LED-Backlit LCD Monitor for $99.99 shipped. Here is a screenshot for your reference. Alternatively, it is available at Best Buy for $99.99 shipped. It features a 1366 x 768 resolution, 90° horizontal and 50° vertical viewing angles, and USB interface. Most places have this portable LCD monitor for over $115.
AOC E2250SWD 22″ 1080p LED-Backlit Monitor for $109.99 Shipped
AOC E2250SWD 22″ 1080p LED-Backlit Monitor for $109.99 shipped. Here is a screenshot for your reference. It features a 1920 x 1080 resolution, 5ms response time, and inputs for VGA and DVI. Most places have it for about $128.
AOC 2436V 24″ 1080p Widescreen LCD Monitor for $129.99 shipped. Here is a screenshot for your reference. It features a 1920 x 1080 (1080p) resolution, and inputs for VGA and DVI with HDCP support. Most places have LCD monitor for over $170.
AOC E2043F 20″ LED-Backlit Monitor for $89.99 Shipped
AOC E2043F 20″ LED-Backlit Monitor for $89.99 shipped. Here is a screenshot for your reference. This LCD monitor features a 1600 x 900 resolution, LED backlight, 5ms response time, 50,000,000:1 dynamic contrast ratio, and inputs for VGA and DVI. Most places have this LED-backlit monitor for about $114 or more.
AOC 2436VW 24″ 1080p Widescreen LCD Monitor for $129.00 Shipped
AOC 2436VW 24″ 1080p Widescreen LCD Monitor for $129.00 shipped. Here is a screenshot for your reference. It features a 1920 x 1080 (1080p) resolution, and inputs for VGA and DVI with HDCP support. Most places have LCD monitor for over $160.
AOC 2436VH 24″ 1080p HD LCD Monitor for $140.34 Shipped
AOC 2436VH 24″ 1080p HD LCD Monitor for $129.99. Shipping is $10.35 for a total of $140.34 shipped. Here is a screenshot for your reference. It features a 1920 x 1080 resolution, built-in speakers, and input options for HDMI and VGA. Most places have this HD LCD monitor for about $149.
AOC 2436VW 24″ 1080p Widescreen LCD Monitor for $129.00 or $133.97 Shipped
AOC 2436VW 24″ 1080p Widescreen LCD Monitor for $129.00. Select free site-to-store for in-store pickup at Walmart to save on shipping. Otherwise, shipping is $4.97 for a total of $133.97 shipped. Here is a screenshot for your reference. It features a 1920 x 1080 (1080p) resolution, and inputs for VGA and DVI with HDCP support. Most places have LCD monitor for over $165.
AOC 2236VW 22″ 1080p LCD Monitor for $99.99 or $103.97 Shipped
AOC 2236VW 22″ 1080p Widescreen LCD Monitor for $99.99. Select free site-to-store for in-store pickup at Walmart to save on shipping. Otherwise, shipping is $4.97 for a total of $103.97 shipped. Here is a screenshot for your reference. It features a 1920 x 1080 (1080p) resolution, and inputs for VGA and DVI with HDCP support. Most places have this AOC 22″ LCD monitor for over $135.
AOC 2770VH1 27″ 1080p Widescreen LCD Monitor for $229.99 Shipped
AOC 2770VH1 27″ 1080p Widescreen LCD Monitor for $229.99 shipped. Here is a screenshot for your reference. It features a 1920 x 1080 (1080p) resolution, and inputs for VGA, DVI, and HDMI. Most places have it for about $270.
AOC E2243FWK 22″ LED-Backlit Monitor for $109.99 Shipped
AOC E2243FWK 22″ LED-Backlit Monitor for $109.99 shipped. Here is a screenshot for your reference. IT features a 1920 x 1080 resolution, 50,000,000:1 dynamic contrast ratio, and inputs for VGA and DVI with HDCP support. Most places have this 22″ widescreen LED-backlit LCD monitor for about $139.
AOC 2436VW 24″ 1080p Widescreen LCD Monitor for $139.99 shipped. Here is a screenshot for your reference. It features a 1920 x 1080 (1080p) resolution, and inputs for VGA and DVI with HDCP support. Most places have it for over $170.
AOC E2043FK 20″ LED-Backlit Monitor for $99.99 shipped. Here is a screenshot for your reference. IT features a 1600 x 900 resolution, 50,000,000:1 dynamic contrast ratio, and inputs for VGA and DVI with HDCP support. Most places have this LED-backlit LCD monitor for about $115 or more


text:
2018 Man Booker Prize Longlist
Random Thoughts /
The 2018 Man Booker Prize for Fiction Longlist
The Man Booker Prize has announced their baker's dozen of longlisted titles! An intriguing list, The Guardian has said it contains "new voices (is less global), but more diverse" and for the first time in Man Booker history, a graphic novel appears on its longlist.
Author (country/territory) Title (imprint)
Belinda Bauer (UK) Snap (Bantam Press)
Anna Burns (UK) Milkman (Faber & Faber)
Nick Drnaso (USA) Sabrina (Granta Books)
Esi Edugyan (Canada) Washington Black (Serpent's Tail)
Guy Gunaratne (UK) In Our Mad And Furious City (Tinder Press)
Daisy Johnson (UK) Everything Under (Jonathan Cape)
Rachel Kushner (USA) The Mars Room (Jonathan Cape)
Sophie Mackintosh (UK) The Water Cure (Hamish Hamilton)
Michael Ondaatje (Canada) Warlight (Jonathan Cape)
Richard Powers (USA) The Overstory (William Heinemann)
Robin Robertson (UK) The Long Take (Picador)
Sally Rooney (Ireland) Normal People (Faber & Faber)
Donal Ryan (Ireland) From A Low And Quiet Sea (Doubleday Ireland)
An interesting one that I will try my best to track down because this sounds so intriguing to read, to see how it is structured, to see how the poetry is used, or if there is any prose component as this one is categorized as poetry:
The Long Take by Robin Roberston.
"Walker, a young Canadian recently demobilised after war and his active service in the Normandy landings and subsequent European operations. Suffering from post-traumatic stress disorder, and unable to face a return to his family home in rural Nova Scotia, he goes in search of freedom, change, anonymity and repair. We follow Walker through a sequence of poems as he moves through post-war American cities of New York, Los Angles and San Francisco."
I've added almost all of the books to my TBR, but some were already on there before the list was announced. It's a good list I think!? Makes me long for the days when we were a part of BookerMarks and we could spend the next couple of months reading and debating our favourites. 🙂
This is a longlist where I am very encouraged to read almost all of the books listed. Many are very new to me titles. What do you think of the list? Are there any books that you thought were a sure bet to be here, but you don't see? Which one do you think you'll read first? (Some of these aren't yet published, but don't come with a lengthy wait like sometimes happened in past years.) Two books are Canadian, and one (The Long Take) is set in Canada!
The shortlist of six books will be announced on Thursday 20 September.
The 2018 winner will then be announced on Tuesday 16 October (in London's Guildhall at a black-tie dinner, one of the highlights of the publishing year. The ceremony will be broadcast by the BBC.)
Happy start to Book Award Season! I can't believe it's already starting! The announcement of the Man Booker gets me excited because it means Giller Prize time is almost upon us too!
I'm really behind in reading online because the heat this summer has been atrocious (as you know very well)! The only one here I've read is Warlight, which I wholly enjoyed and I'm almost afraid to look very closely at the ones I don't recognize because I will probably have the same response that you've had (adding them ALL to Mount TBR). And, yes, it's hard to believe that Giller season is almost here. I'm trying to clear the decks but it's always a challenge this time of year.
The only one I've read has been The Overstory which was wonderful. Like you, No Time! to read anything else! All those books need reading and we're less than a month away for Giller titles! Panic. Thanks for commenting because I see I've made a silly mistake in the post's title – Man Book. I'm off to correct that! Oops.


HELP THE WEED TO BE FREE IN 2003!
NORTHAMPTON, Mass. (AP) Police confiscated $50,000 in cash from a Vermont couple who had come to bail their daughter out of jail, because the money smelled like marijuana and was thought to be the proceeds of drug deals.
NEW ZEALAND –Documents obtained under the Official Information Act show police investigated and wanted to arrest Green Party MP Nandor Tanczos, based on no other evidence than his public statements about his use of cannabis.
BRITISH COLUMBIA — A Canadian man is accused of helping dump three hockey bags filled with marijuana from a rented single-engine Cessna into a remote gravel pit in Northern Washington on Nov. 25. Inside the bags, authorities found two avalanche beacons, used by rescuers to locate skiers buried under snow.
When local officials defended the police for going through people's garbage to obtain evidence, two courageous journalists responded by collecting garbage from the mayor and sheriff and then publishing the contents in the local paper.


I went through many different trials and builds trying to find one that worked well for the sort of Nemesis I played and wanted to play. In the end, this build came to be. She's quick to chase after enemies and quick to run away, with her attacks swinging in a furious blur. I do warn she is a bit squishy (not much health and little protections against physical and magical attacks) especially in the beginning. But if you keep the order of items as I have them, once you get the 4th thing, and even more so the 5th and 6th, you'll start killing people with a full bar of health in seconds flat (because of that be careful as well. Enemy teams are likely to try and gank you, casting any and all traps and slows to get rid of you). I personally found this order of items to be the best, based off of the prices of some and also what I wanted to come earlier than others to start dealing better damage in the game. In terms of skill leveling order I don't touch them, use to and not minding how the auto leveler does it. Otherwise I hope whoever tries the full build out finds her just as fun and powerful as I.
1. Boots, in my opinion, should come first for any build and I went with the Ninja Tabi for Nemesis. Yes the physical damage isn't as good, but getting that extra attack speed for an assassin in general is a big difference.
2. The Hastened Fatalis doesn't necessarily have to be second, but if you're a strong player and your team is really pushing the other back or an enemy God strayed too far, it let's you chase after them and still attack without slowing down thanks to its passive ability--and I wanted to be able to chase down wounded runaway enemy Gods as soon as possible.
3. Now, I decided I wanted Rage to be the third instead of Qin's Sais or even The Executioner because I wanted to start building and getting criticals early. This build's key is the attack speed and the high critical chance and damage that wipes out anything you attack. Your crit chance will start to build, and thanks to your first two items with your high attack speed, you should see critical hits popping up fairly often.
4. Qin's Sais just boots your physical damage and you'll see a big increase in your attack speed as well, and because of it's passive, you'll really start to hurt enemy Gods and creatures even more so now. Once you get the Sais, that's when the kills start rolling in.
5. The Executioner is very similar to Qin's Sais, as both give you a boost to physical power and attack speed. The buying order of the Sais and The Exectioner can easily be flipped if you want to save some money (as The Executioner is less money than Qin's Sais) and the build should still be relatively the same. Once you get The Executioner into play, your attack speed is even greater now, and because of Rage, you're bound to see critical hits every 3-4 hits about. Normally after getting the Sais and killing a few Gods or nearly killing them before they escape or get help, your enemies see your power. But once you get The Executioner, there is little hope that even a God who has a full bar of health will make it out alive. Usually around the time of getting the Sais and/or The Executioner, enemy Gods will back away or flat out turn and run at the sight of your Nemesis coming near.
6. If you get enough money to reach the full final item, Deathbringer is just icing on the cake. With another huge boost to physical power, the extra crit chance on top of your Rage stacks, plus it's passive, you'll be mowing down Gods even more.
I´ve been trying the build and its pretty good, but it feels very squishy. Interesting choice of rage being the third item I´ll try that and see how it goes. Nemesis is my favorite god but I can´t really play her that well.
108838 ReneJMR I´ve been trying the build and its pretty good, but it feels very squishy. Interesting choice of rage being the third item I´ll try that and see how it goes. Nemesis is my favorite god but I can´t really play her that well.
No I totally agree she is pretty squishy. Two of her abilities are good at helping to get away when your health gets too low or you start to get surrounded and whatnot, so I don't mind that she's squishy because she has such good getaways. Plus I didn't want to subtract a damage or speed item for a defense item that might not have a big affect. I also forgot to put in the relics I use for her, biggest assister is the one that makes you immune to crowd control stuff because those are the things that ruin her being able to run away--highly recommended.
109002 Seeoshu No I totally agree she is pretty squishy. Two of her abilities are good at helping to get away when your health gets too low or you start to get surrounded and whatnot, so I don't mind that she's squishy because she has such good getaways. Plus I didn't want to subtract a damage or speed item for a defense item that might not have a big affect. I also forgot to put in the relics I use for her, biggest assister is the one that makes you immune to crowd control stuff because those are the things that ruin her being able to run away--highly recommended.


text:
Pensioner jailed over £32,000 benefit fraud
A pensioner who dishonestly claimed £32,000 in benefits over a four-year period has been sent to prison.
William Pearson, 68, was jailed for six months over the deception after a court heard how he lied to authorities about his wife's employment status in order to claim pension credits.
Leeds Crown Court heard Pearson, of Woodend, Allerton Bywater, retired in 2009 after being made redundant from his job in the construction industry.
He told the Department of Work and Pensions that he was married and received no other form of income other than his wife's claim for Jobseeker's Allowance.
Michael Jowett, prosecuting, said Pearson's wife began working for a catering company in 2010 but he failed to declare it to the DWP.
Pearson continued to claim the money despite regularly receiving leaflets from the DWP informing him that he must notify them of any change in his circumstances which may affect his entitlement to benefits.
Pearson was interviewed after the offences came to light in December 2014 and initially claimed that his wife did not have a job.
He then claimed he thought he was entitled to the money on an unconditional basis.
Pearson pleaded guilty to failing to notify a change in circumstances affecting the entitlement to social security benefit.
Anne-Marie Hutton, mitigating, said Pearson had worked hard all his life until being made redundant and had no previous convictions.
Miss Hutton said Pearson was sorry for what he had done and was in poor health as he suffered from heart and lung problems.
The lawyer said Pearson did not have any debts and was now repaying the money he illegally claimed.
Judge Tom Bayliss, QC, told Pearson: "You engaged in a persistent fraud against the Department of Work and Pensions. It was not a moment's thoughtlessness.
Arrests after 'bollards thrown' from top of Ridings Shopping Centre car park
"It was deliberate dishonesty over a period of four years and it netted you a significant amount of money to which you were not entitled.
"I take into account your previous good character and that you were a hard working man and are voluntarily making repayments.
"But those like you who cheat the benefits system out of considerable amounts of money over a considerable period of time must be deterred."
Castleford Tigers coach Daryl Powell weighing up his options for Warrington game
Jake Trueman: We need to give Castleford Tigers fans something back in Wakefield derby
Castleford Tigers' recent record against Wakefield Trinity is irrelevant says Daryl Powell
'Pavement trip' man in court after trying to con Wakefield Council out of £150k
Man jailed after urinating on Pinderfields Hospital floor and abusing NHS staff
More from Hemsworth and South Elmsall Express