Here's another one: ?Our tax system greatly advantages employer-provided health-care coverage, and Obamacare places health-care provision obligations onto large employers. ?But with the other Obamacare reforms protecting those with existing conditions (why we typically say "pre-existing" I'm not sure), isn't it time to put employer- and self-paid health care coverage on the same tax footing and to remove mandatory coverage rules?
London:The Guardian newspaper says its Twitter accounts have come under a cyberattack, and it said the Syrian Electronic Army claimed responsibility for the same. The British paper reported on its website Monday that several of its Twitter feeds were broken into over the weekend.
It said it has since discovered that the attack apparently originated from Internet protocol addresses within Syria. The paper said the Syrian Electronic Army, which has claimed responsibility for attacks on other media targets including The Associated Press, accused The Guardian of spreading ?lies and slander about Syria?.
The Guardian said it first recognized it was being targeted when suspect emails were sent to staff members. Some of The Guardian?s Twitter accounts, including those focusing on books and film, were suspended Monday.
It's a busy life we lead?most of us, anyway. And between work, play, family time, rest, secret-other-family time, whatever it may be that you've got going on, making sure you're distributing your time evenly can be a challenge. The simple Android fix Jiffy is here to help.
What does it do?
Lets you track up to three activities in the free version as many as you can handle in the $2, premium version. The main screen lists all your running tasks, letting you tap the one you're about to begin and automatically stopping whichever came before. As time goes on, you can look at summaries by day, week, month in all sorts of fun, brightly colored charts - all of which can be saved as a backup.
Why do we like it?
The app's UI couldn't suit its purpose better: a simplified app to try and break down a complicated life. And if you're more worried about keeping time than you are about reminding yourself to move on, you can set work times so the app stops tracking at a certain point whether you remember to flip it off or not. One of the most practical features, though, is its ability to export a CSV file of all your time-kept data, which you can then use in invoices, web apps, alibis, etc.
Dodgers prospect Yasiel Puig was arrested by police in Chattanooga, Tenn., early Sunday and charged with speeding, reckless driving and driving without proof of insurance.
A spokesman for the Hamilton County jail confirmed that Puig was booked Sunday morning and released a short time later. He has a hearing scheduled for the afternoon of May 14 in Hamilton County court.
Puig, rated the #47 overall prospect by Baseball America going into the season, was hitting .333 with a 1.010 OPS in 52 plate appearances with Double-A Chattanooga. The Dodgers signed the 22-year-old Cuban on June 27 last year on a seven-year, $42 million contract. Puig seemed to be on the fast track to the Majors. His arrest this morning is his first bump in the road.
Frequently used biologic agents might cause acute liver injuryPublic release date: 29-Apr-2013 [ | E-mail | Share ]
Contact: Rachel Steigerwald media@gastro.org 301-272-1603 American Gastroenterological Association
Bethesda, MD (April 29, 2013) A commonly used class of biologic response modifying drugs can cause acute liver injury with elevated liver enzymes, according to a new study in Clinical Gastroenterology and Hepatology, the official clinical practice journal of the American Gastroenterological Association. Patients with inflammatory diseases such as Chron's disease or ulcerative colitis often are prescribed tumor necrosis factor-alpha (TNF-?) antagonists, which modify the body's response to infection. Patients with inflammatory arthropathies and selected dermatological diseases are also candidates to receive such compounds.
"TNF-? antagonists are extremely beneficial as therapies for several bowel, joint and skin inflammatory conditions," said Maurizio Bonacini, MD, AGAF, study author and associate clinical professor, University of California, San Francisco. "However, gastroenterologists, internists, rheumatologists and dermatologists all need to be aware of this potential complication and know how to diagnose it. They should conduct tests for autoimmunity early upon diagnosis of abnormalities to determine the proper path of care."
Researchers searched the U.S. Drug-Induced Liver Injury Network database and identified six well-characterized cases of drug-induced liver injury (DILI) in the setting of TNF-? antagonist therapy. Additionally, they reviewed 28 additional cases identified in PubMed. The researchers found acute liver injury in all cases, most frequently autoimmunity and hepatocellular injury, but mixed non-autoimmune patterns and cholestasis (blocked flow of bile from the liver) also occurred. No deaths were attributed to the liver injury; one patient required a liver transplant, which was attributed to pre-existing cirrhosis with superimposed DILI.
Of the TNF-? antagonists, infliximab-associated liver injury has been the best documented, most likely because of its earlier approval and more wide-spread clinical use. Etanercept and adalimumab have also been linked to drug-induced liver injury. So far, there are no published cases found to be linked to natalizumab, golimumab or certolizumab.
The researchers found that liver damage was typically resolved following drug discontinuation, although some patients did benefit from a course of corticosteroids. Importantly, patients treated with an alternative TNF-? after resolution of their liver injury appeared to tolerate the drugs without recurrence.
"If patients who are taking these biologic agents experience symptoms such as abdominal pain, nausea and fatigue, physicians should check liver enzyme levels to determine if the symptoms are a result of these drugs," added Dr. Bonacini.
###
About the AGA Institute
The American Gastroenterological Association is the trusted voice of the GI community. Founded in 1897, the AGA has grown to include 17,000 members from around the globe who are involved in all aspects of the science, practice and advancement of gastroenterology. The AGA Institute administers the practice, research and educational programs of the organization. http://www.gastro.org.
About Clinical Gastroenterology and Hepatology
The mission of Clinical Gastroenterology and Hepatology is to provide readers with a broad spectrum of themes in clinical gastroenterology and hepatology. This monthly peer-reviewed journal includes original articles as well as scholarly reviews, with the goal that all articles published will be immediately relevant to the practice of gastroenterology and hepatology. For more information, visit http://www.cghjournal.org.
Like AGA (https://www.facebook.com/AmerGastroAssn) and Clinical Gastroenterology and Hepatology (http://www.facebook.com/cghjournal) on Facebook.
Join AGA on LinkedIn (http://www.linkedin.com/groups?mostPopular=&gid=915257).
Follow us on Twitter @AmerGastroAssn (http://www.twitter.com/amergastroassn).
Check out our videos on YouTube (http://www.youtube.com/amergastroassn).
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Frequently used biologic agents might cause acute liver injuryPublic release date: 29-Apr-2013 [ | E-mail | Share ]
Contact: Rachel Steigerwald media@gastro.org 301-272-1603 American Gastroenterological Association
Bethesda, MD (April 29, 2013) A commonly used class of biologic response modifying drugs can cause acute liver injury with elevated liver enzymes, according to a new study in Clinical Gastroenterology and Hepatology, the official clinical practice journal of the American Gastroenterological Association. Patients with inflammatory diseases such as Chron's disease or ulcerative colitis often are prescribed tumor necrosis factor-alpha (TNF-?) antagonists, which modify the body's response to infection. Patients with inflammatory arthropathies and selected dermatological diseases are also candidates to receive such compounds.
"TNF-? antagonists are extremely beneficial as therapies for several bowel, joint and skin inflammatory conditions," said Maurizio Bonacini, MD, AGAF, study author and associate clinical professor, University of California, San Francisco. "However, gastroenterologists, internists, rheumatologists and dermatologists all need to be aware of this potential complication and know how to diagnose it. They should conduct tests for autoimmunity early upon diagnosis of abnormalities to determine the proper path of care."
Researchers searched the U.S. Drug-Induced Liver Injury Network database and identified six well-characterized cases of drug-induced liver injury (DILI) in the setting of TNF-? antagonist therapy. Additionally, they reviewed 28 additional cases identified in PubMed. The researchers found acute liver injury in all cases, most frequently autoimmunity and hepatocellular injury, but mixed non-autoimmune patterns and cholestasis (blocked flow of bile from the liver) also occurred. No deaths were attributed to the liver injury; one patient required a liver transplant, which was attributed to pre-existing cirrhosis with superimposed DILI.
Of the TNF-? antagonists, infliximab-associated liver injury has been the best documented, most likely because of its earlier approval and more wide-spread clinical use. Etanercept and adalimumab have also been linked to drug-induced liver injury. So far, there are no published cases found to be linked to natalizumab, golimumab or certolizumab.
The researchers found that liver damage was typically resolved following drug discontinuation, although some patients did benefit from a course of corticosteroids. Importantly, patients treated with an alternative TNF-? after resolution of their liver injury appeared to tolerate the drugs without recurrence.
"If patients who are taking these biologic agents experience symptoms such as abdominal pain, nausea and fatigue, physicians should check liver enzyme levels to determine if the symptoms are a result of these drugs," added Dr. Bonacini.
###
About the AGA Institute
The American Gastroenterological Association is the trusted voice of the GI community. Founded in 1897, the AGA has grown to include 17,000 members from around the globe who are involved in all aspects of the science, practice and advancement of gastroenterology. The AGA Institute administers the practice, research and educational programs of the organization. http://www.gastro.org.
About Clinical Gastroenterology and Hepatology
The mission of Clinical Gastroenterology and Hepatology is to provide readers with a broad spectrum of themes in clinical gastroenterology and hepatology. This monthly peer-reviewed journal includes original articles as well as scholarly reviews, with the goal that all articles published will be immediately relevant to the practice of gastroenterology and hepatology. For more information, visit http://www.cghjournal.org.
Like AGA (https://www.facebook.com/AmerGastroAssn) and Clinical Gastroenterology and Hepatology (http://www.facebook.com/cghjournal) on Facebook.
Join AGA on LinkedIn (http://www.linkedin.com/groups?mostPopular=&gid=915257).
Follow us on Twitter @AmerGastroAssn (http://www.twitter.com/amergastroassn).
Check out our videos on YouTube (http://www.youtube.com/amergastroassn).
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
When it comes to major news, we didn't expect to hear much from Google in the run-up to I/O, but clearly, the company just couldn't wait that long. Google Now, a service that Android users have enjoyed for a year, just became available on iOS devices in the form of an update to the Google Search app, confirming those leaked videos we saw a few weeks ago. It won't have integration with notifications or alerts at launch -- it may come in a future update, but the company wasn't willing to divulge its future plans -- so you'll need to enter the app and swipe up to refresh your list of cards. The iOS version won't have every type of card that you'll find on Android, either: boarding passes, activity summary, events, concerts, Fandango and Zillow aren't included this go-round. Improvements and additional features will likely trickle in over time, but it's certainly better than nothing for iOS fans who've looked at Jelly Bean users with a slightly jealous eye. We've included Google's blog post in its entirety below, and you can jump to More Coverage to download the app.
As advanced as multitasking gets on smartphones, many times you're still left to completely switch between apps. Paranoid Android is looking to set things into overdrive with in-app, multiple-window multitasking for its skin of Android, going beyond the similar (but limited) functionality seen in the likes of Samsung's basked-in Galaxy apps. PA's Paul Henschel recently posted a demo to YouTube highlighting the feature working with various apps on both an Android tablet and a Nexus smartphone, with a post to Google+ saying it shows less than 10 percent of the planned functionality. If that weren't enough, the post further clarifies PA's drive to build out its version stating: "We think these [Samsung, Cyanogen & Cornerstone] implementations suck and we want to get it right this time." Thirsty for more info? Hit the source link and the video after the break, while we eagerly wait further updates.
>>tonight in the
boston
bombings investigation involving the car used by the suspects and what investigators are now saying about their mother. we'll get the latest from
michelle franzen
from
boston
.
>> reporter: nbc news has learned that although early accounts focus largely on the stolen
suv
, investigators are also focusing on a second vehicle. a green honda used by the suspects on the day of the man hunt and fatal shooting of m.i.t. officer sean collier in cambridge. federal authorities say the suspects carjacked a vehicle. police say a mercedes
suv
, following the shooting when they were riding together during the chase that ended in watertown, but in paragraphs, a green honda was also spotted at the scene in watertown along with the black
suv
. in nearby bedford friday, investigators also searcheded a landfill. police say they were looking for dzhokhar's laptop and receipts for fireworks used to make the bombs. overseas, more details on the brothers' family. tsarnaev's mother was placed on the
u.s. government
terrorist database because of her son, tamerlan, 18 months before the
boston
bombings. russian authorities passed along information to the cia, stating both tamerlan and his mother were saying signs of increasing radicalization, accusations the mother denied this week. cnbc obtained these photos posted on the mother's
web page
on a russian
social media
website in
2010
. back in
boston
, copely square was packed with visitors.
>>to help us get through it, we need to be able to live it a little bit, to see what happened and how we're remembering the people who were affected.
>>in nearby dorchester, martin richard's team paid tribute to the 8-year-old who died in the bombing. his name painted on the field and his jersey draping the fence. a fitting remembrance for the boy who loved to play ball. and crowds continue to gather here tonight leaving messages, flowers and all along
boylston street
, businesses are reopening and we're getting an update on the people injured. there are still 30 victims that remain in
boston
hospitals.
The Focusrite Forte ($749.99 list) is one of a host of portable, higher-end audio interfaces that have appeared in the wake of Apogee's now-iconic original Duet. It one-ups the Apogee lineup in that it works with PCs as well as Macs?helping not just PC users, but also musicians and engineers, like myself, who use both Macs and PCs on a regular basis, and don't want to be restricted to a specific platform for a particular piece of gear. That said, there are a few limitations with the Forte you should be aware of before purchase, such as its AC power requirement when using phantom power, and sound quality that, while very good, doesn't quite catch Apogee. But overall, it's a top-quality piece of audio gear that's easily worth its high entry price.
Design, Display, and Connectivity The Forte gets its name from the company's original recording console, which was based on famed engineer Rupert Neve's designs for George Martin's AIR studios. At least physically, if an audio interface can be beautiful, the Forte certainly is, with its solid aluminum enclosure, colorful OLED display, and oversized volume and control knob. The small display shows individual track levels with fat meters that turn green, yellow, and red depending on signal level.
Below the display are four touch-sensitive mode buttons for selecting input level (which alternates between input 1 and input 2 when you press it again), speaker volume, headphone volume, and DAW mode for controlling a software transport. The multi-function encoder knob spins around smoothly, but with a lightweight feeling to it, unlike the Apogee Duet for iPad & Mac's knob, which clicks ever so slightly as you turn it. As with the Duet, to make selections, you push the Forte's knob down.
A ?-inch headphone socket sits on the front edge; two would have been better at this price, as many engineers and musicians tend to work with another person simultaneously. (The MOTU Track16, which we haven't tested yet, is the only similar unit on the market with two headphone outputs, although one is 1/4-inch sized and the other is a consumer-level 3.5mm jack.)
Around back, you get a power input, a USB 2.0 port, an input socket for the breakout cable, and a pair of TRS line outputs?meaning that if you're not recording, you don't need to attach the breakout cable even when listening over speakers, unlike the Duet. The "loom connector," as Focusrite calls the breakout cable, contains a pair of XLR microphone inputs and a pair of TRS line/instrument-level inputs, so you can connect two mics and two instruments at the same time and leave them all hooked up; the Duet, by comparison, combines the inputs together, which is fine in most cases but could become inconvenient if you do a lot of stereo miking.
However, chances are that if you're attaching the Forte's breakout cable to record, you'll also need to plug in the AC adapter, as it's required whenever you record microphones that require phantom power. For most people recording at home or on the go, that's pretty much all of the time, since both small- and large-diaphragm condenser mics need phantom power. In addition, when running without the AC adapter, the speaker and headphone outputs are limited to -18dB?not as big a deal, but something to note if you're monitoring over headphones with a high impedance and you're recording at a noisy venue; I certainly noticed it with several different pairs of closed-back headphones, all of which could have gone a little louder than the -18dB point without discomfort.
Setup, Performance, and Conclusions Setting up the Forte is a snap; you register on the company site, download the drivers and bundled Midnight Plug-in Suite software, install everything, and then connect the Forte via USB. A reboot is required after installing the software, even on a Mac, which isn't true of the Apogee Duet. The bundled Forte Control software (pictured above) offers low-latency monitoring and level control.
I?tested the Focusrite Forte with an Apple MacBook Pro running OS X 10.8.3 (Mountain Lion), a quad-core Xeon-based Mac Pro running OS X 10.7.5 (Lion), and a Lenovo ThinkPad L420 running Windows 7 Professional 64-bit. In all three cases, I tested recording and playback using Avid Pro Tools 10, which worked perfectly, and at acceptably low latencies. The Focusrite Forte records at 24-bit and 192kHz, thanks to its built-in D/A converters. The two mic preamps are the same ones from the company's RedNet range of pro audio interfaces, and offer 75dB of gain range.
As I expected from a higher-end Focusrite interface, sound quality was sublime for both recording and playback. I didn't hear quite as much detail in the upper midrange to high-end as I did on the Duet; recordings made through a Rode NT-1A mic sounded a little more present, with less of a thin veil over the result, with the Duet, although the Forte sounded just as warm and full otherwise. ?The Forte's preamp also sounded a bit cleaner than the Avid Mbox Mini's, although I'd argue you could make excellent recordings with any of these interfaces. Still, the differences are there.
The same goes for playback; listening to Dave Matthews Band's "Funny the Way It Is," I heard a clean, smooth, and well-separated presentation through the Forte, although the Duet lent a little more presence and clarity to specific details in the recording that didn't jump out at me quite as much with the Forte.?Both exhibited exceptionally tight and extended bass response.
All told, the Focusrite Forte sets out what it's designed to do, and unlike some of the competition, it works on both PCs and Macs. You can also leave the cable loom detached except when you're recording. That said, it's not exactly equivalent to the Apogee Duet, as it sounds a bit different, and requires the AC adapter to be attached most of the time. The Apogee Duet is probably a better choice if you're exclusively on the Mac platform, as it integrates a bit better, and its iPad connectivity is second to none in its simplicity.
Other options: Propellerhead Reason fans can save a bit of cash by looking at the clean-sounding Propellerhead Balance interface, which integrates better with that company' software, while the Editors' Choice Focusrite iTrack Solo brings clear recording to PCs, Macs, and iPads at a budget price.
KHARTOUM (Reuters) - Rebels from Sudan's Darfur region launched a dawn attack on the city of Um Rawaba on Saturday, taking their fight closer to the capital Khartoum, witnesses said.
The attack marks the biggest push by a rebel alliance that is seeking to topple President Omar Hassan al-Bashir. Fighting had hitherto been limited mainly to remote regions of Darfur and South Kordofan and Blue Nile states, which border South Sudan.
The Justice and Equality Movement (JEM), which launched an unprecedented assault on Khartoum in 2008, said the rebel alliance stormed Um Rawaba in North Kordofan state, around 500 km (300 miles) south of the capital.
Sudan's army said late in the evening it had restored security in the state's second largest city. It accused insurgents of destroying a power plant, petrol stations and a telecommunications tower.
"The defeated rebels have withdrawn, and the army is continuing to expel elements of the rebels who have run away in different directions," army spokesman al-Sawarmi Khalid told state news agency SUNA.
JEM spokesman Gibril Adam said forces from the group had only withdrawn from the center of Um Rawaba to the outskirts after Sudanese warplanes had launched air strikes.
The rebels arrived at dawn with 20 trucks in Um Rawaba, an important market for a major Sudanese agricultural export product, gum arabic, residents said.
"People are in a state of panic," said one Um Rawaba resident, asking not to be named.
The rebels then opened fire into the air and looted a market and several commercial banks. JEM's spokesman denied any pillaging by rebels.
"The goal of this attack is to weaken the government to realize our strategic plan to topple the regime," JEM spokesman Adam said.
ROAD REOPENED
The government later said it had reopened the key road between Khartoum and the North Kordofan state capital El-Obeid, which had been blocked by fighting, state governor Mutassim Mirghani Zaki Uddi told the state-linked Sudanese Media Center.
On a separate front, the SPLM-North which is part of the rebel movement attacking Um Rawaba, said it had seized four villages east of Kadugli, capital of South Kordofan state. There was no immediate comment from the army on the statement.
Events outside Khartoum are difficult to verify in the vast African country. Um Rawaba is a two-hour drive from Kosti, Sudan's biggest Nile river port.
JEM forces drove across hundreds of miles of desert to attack the Khartoum suburb of Omdurman in May 2008 and were stopped just short of the presidential palace and army headquarters.
The group was one of two main rebel forces that took up arms against Sudan's government in 2003, demanding better representation for Darfur and accusing Khartoum of neglecting its development.
Khartoum mobilized militias to crush the uprising, unleashing a campaign that Washington and activists described as genocide. Sudan's government denies the charge and accuses the Western media of exaggerating the conflict.
In 2011, JEM teamed up with two other Darfuri groups and the Sudan People's Liberation Movement-North (SPLM-North) which took up arms in South Kordofan and Blue Nile states around the time of South Sudan's secession.
They formed the "Sudanese Revolutionary Front", which says it fights to topple Bashir to secure a fairer share of government in a country dominated by three Arab tribes.
Fighters of the SPLM-North sided with southern Sudan during decades of civil war that ended with a peace deal in 2005, which paved the way for South Sudan's formal breakaway in July 2011.
Sudan on Wednesday started peace talks with the SPLM-North after a thaw in relations with South Sudan.
(Writing by Ulf Laessing; Editing by Mark Heinrich and Mike Collett-White)
Every week, a new and interesting human being tackles our decidedly geeky take on the Proustian Q&A. This is the Engadget Questionnaire.
Oculus VR founder and designer Palmer Luckey has a go at our weekly set of questions while chatting perception modification and the importance of a meatspace presence. Join us beyond the jump in order to peruse the full collection of responses.
KANDAHAR, Afghanistan (AP) ? A bus collided on Friday with the wreckage of a truck that had been attacked by Taliban insurgents in southern Afghanistan, killing 45 people aboard the bus in a fiery crash, officials said.
The battered oil tanker had been left in the middle of a narrow road near the border of Kandahar and Helmand provinces for several days after insurgents attacked it. Police considered the area too dangerous to enter, the officials said.
Before sunrise Friday, the bus smashed into the truck and burst into flames, said Abdul Razaq, the provincial police chief of Kandahar.
Police, soldiers and ambulances rushed to the crash site in a desolate area. Many of the victims were burned beyond recognition and it will be difficult to establish their identities, Razaq said.
One survivor, Mohammad Habib, cried as he searched for his brother.
"I don't care about my belongings and money that were burned inside the bus, but please help me find my brother, dead or alive," he told AP Television News. "How will I face my mother without him?"
Forty-five people were killed and 10 injured, said Javeed Faisal, the spokesman for the governor of Kandahar province. He spoke to The Associated Press at Mirwais Hospital in Kandahar city where many of the victims, including men, women and children, were taken.
The bus began its journey in the capital of Helmand province and was to stop in Kandahar city, then travel north to Kabul, the Afghan capital, Razaq said.
Traffic accidents are common in Afghanistan, where rules of the road are often ignored by a chaotic mix of cars, trucks, bicycles, pedestrians and animals. Roads outside the capital are often poorly maintained and travelers are subject to roadside bombs and highway robberies.
Last September, a bus and truck collided and burst into flames on a highway in the eastern province of Ghazni, killing at least 51 people.
Also Friday, the U.S.-led international military coalition said Afghan and foreign forces arrested about 10 insurgents in the past two days in four provinces, including several Taliban fighters in Kandahar.
___
AP writers Thomas Wagner and Amir Shah in Kabul contributed.
Apr. 25, 2013 ? Exciting new data presented today at the International Liver Congress? 2013 include results from early in vitro and in vivo studies targeting covalently closed circular DNA (cccDNA), which may form the basis of a cure for chronic hepatitis B virus (HBV) infection.
HBV cccDNA is organized into mini-chromosomes within the nucleus of infected cells by histone and non-histone proteins. Despite the availability of efficient therapies against HBV, long-term persistence of cccDNA necessitates life-long treatments to suppress the virus. The following three experimental studies demonstrate effective HBV-cccDNA targeting/depletion using novel therapeutic approaches which offer the potential of a cure.
Liver regeneration induces strong reduction of viral replication and cccDNA levels, but not complete cccDNA eradication; without antiviral treatment, de novo HBV infection can be re-established.
Key findings of research in HBV-infected human hepatocytes using the uPA/SCID chimeric mouse system show that liver regeneration induces strong reduction of viral replication and cccDNA levels, with rapid formation of cccDNA-free hepatocytes. However, because complete cccDNA eradication is not achieved, in the absence of antiviral treatment, de novo HBV infection could be re-established in quiescent (non-dividing) human hepatocytes. This suggests that induction of hepatocyte turn-over together with antiviral drugs inducing viral suppression, such as nucleoside analogues and IFN, or blocking cell entry, may accelerate the clearance of the viral minichromosome.
Targeting epigenetic control of nuclear cccDNA minichromosome to suppress HBV transcription and replication may form basis for other therapeutic approaches to curing chronic HBV infection.
In the infected liver cell the rate of replication of HBV is regulated by the acetylation or methylation of histone proteins which surround the cccDNA minichromosome -- so called epigenetic regulation. In a separate innovative study, the suppression of HBV transcription and replication by small molecules that target the epigenetic control of nuclear cccDNA minichromosome was investigated. The different classes of small molecules studied included: Class I, II and III histone deacetylase inhibitors (HDACi); p300 and PCAF histone acetyltransferases (HAT) inhibitors; hSirt1 activators; JMJD3 histone demethylase inhibitors.
The combined inhibition of p300 and PCAF HATs resulted in an evident reduction of HBV replication which mirrored the decrease of pgRNA transcription. The hSirt1/2 activator MC2791 and the JMJD3 inhibitor MC3119, albeit with different efficiency, inhibited both HBV replication and cccDNA transcription. Results represent a proof of concept that activation of hSirt1 and Ezh2 (through the inhibition of its functional antagonist JMJD3) by small molecules can induce an active epigenetic suppression of HBV cccDNA minichromosome similar to that observed with IFN?, and lead to persistent cccDNA silencing.
Lymphtoxin beta receptor (LTbR) agonisation represents basis for novel alternative therapeutic approach to curing chronic HBV infection.
The final study demonstrated that stimulating the lymphtoxin beta receptor (LTbR) provides an effective, long lasting and non-cytopathic mechanism for achieving effective HBV-cccDNA depletion in infected hepatocytes. Cell culture models including HBV-infected HepaRG cells and primary human hepatocytes were used to test the effect of antibodies stimulating human LTbR (BS1 or CBE11). Results show that a strong and dose-dependent anti-HBV effect was achieved by activation of the LTbR. All HBV replication markers were decreased with this treatment, including cccDNA in cells where HBV infection was already established.
Hepatitis B is the most prevalent cause of chronic viral hepatitis and a major global health problem. Prof. Fabien Zoulim, EASL Educational Councillor commented on the exciting new data: "In chronic hepatitis B infection, the viral genome forms a stable minichromosome -- the covalently closed circular DNA (cccDNA) -- which can persist throughout the lifespan of the hepatocyte."
"Current treatments focus on suppression of HBV and discovery of compounds directly targeting cccDNA has been one of the major challenges to curing HBV infection; but these preliminary data show novel therapeutic approaches can be applied to successfully target cccDNA with the long-term aspiration of finding a cure" added Prof. Fabien Zoulim.
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Amazon is rectifying the long wait for a Kindle for Android update today with a version 4.0 refresh that carries with it a major UI redesign. The library view looks very different: instead of a basic grid, recently read items are presented in a rotating carousel at the top of the home screen, while the navigation panel has been expanded to provide quicker access to books, documents and periodicals. The actual reading pane remains untouched, so whether you're using a smartphone or a tablet, your e-copy of War and Peace should still look the same. To have a peek at the Kindle app makeover, Android users can go ahead and download the new version from the source.
Battery of tests on cancer cells shows them as 'squishy,' yet tactically strongPublic release date: 26-Apr-2013 [ | E-mail | Share ]
Contact: Skip Derra skip.derra@asu.edu 480-965-4823 Arizona State University
Student researchers get a new view of the dynamics of cancer cells as they metastasize
TEMPE, Ariz. A team of student researchers and their professors from 20 laboratories around the country have gotten a new view of cancer cells. The work could shed light on the transforming physical properties of these cells as they metastasize, said Jack R. Staunton, a Ph.D. candidate at Arizona State University in the lab of Prof. Robert Ros, and the lead author of a paper reporting on the topic.
Metastasis is a critical step in the progression of cancer. It is when the cancer spreads from one organ or part to another. While much is known about metastasis, it remains an incomplete understanding of the physical biology of the transition.
To get a better understanding of metastasis, more than 95 graduate students, post docs and professors in a variety of laboratories across the U.S. subjected two cell lines to a battery of high-tech tests and measurements. Their results, outlined in the paper "A physical sciences network characterization of non-tumorigenic and metastatic cells," were published today (April 26, 2013) in Scientific Reports.
The researchers performed coordinated molecular and biophysical studies of non-malignant and metastatic breast cell lines to learn more about what happens to a cell when it transitions to a metastatic state.
Each laboratory is part of the National Cancer Institute's Physical Sciences Oncology Center (PSOC), a network of 12 centers devoted to understanding the physical sciences of cancer. ASU's center, the Center for the Convergence of Physical Science and Cancer Biology, is led by Prof. Paul Davies.
Each PS-OC was supplied with identical cell lines and common reagents, and considerable effort was made to ensure that all the conditions were standardized and documented at regular intervals. Staunton said the ASU group made three contributions to the study.
Other ASU researchers involved in the project and co-authors on the paper are: Alexander Fuhrmann, Vivek Nandakumar, Laimonas Kelbauskas, Patti Senechal, Courtney Hemphill, Roger H. Johnson and Deirdre Meldrum.
"We compared the stiffness of normal breast cells and highly metastatic breast cancer cells, and found the cancer cells to be significantly more 'squishy' or deformable," Staunton said. "This makes sense because in order for a cell to metastasize, it has to squeeze through tight passages in the lymphatics and microvasculature, so being squishy helps cancer cells spread through the body."
"We also looked at the morphology of their nuclei," he added. "The cancer cell nuclei were found to have a characteristic 'crushed beach-ball' shape that might correspond to the abnormal chromosomal rearrangements associated with cancer."
"Finally, we took individual cells, put each one in an airtight chamber, and measured how much oxygen they consumed," Staunton said. "This tells us about their metabolism. We found the cancer cells use less oxygen, relying more on glycolysis, kind of like what bacteria and yeast do."
Taken together, researchers at the 12 PSOC's used some 20 distinct techniques, including atomic force microscopy, ballistic intracellular nano-rheology, cell surface receptor expression levels, differential interference contrast microscopy, micro-patterning and extracellular matrix secretion, and traction force microscopy.
The work has enabled a comprehensive cataloging and comparison of the physical characteristics of non-malignant and metastatic cells, and the molecular signatures associated with those characteristics. This made it possible to identify unique relationships between observations, Staunton said.
"We were surprised that even though the cancer cells are softer, they are able to exert more contractile forces on the fibers surrounding them which was determined at the Cornell University PSOC by a method called traction force microscopy. This pair of characteristics is somewhat contradictory from a purely physical perspective, but it makes sense for a cancer cell, since both traits improve their chances of metastasizing. Understanding why is still an active area of research," explained Staunton, who is working towards his doctorate in physics.
"Another interesting finding was that a protein called CD44, which doubles as a cancer stem cell marker and as a molecule that helps the cell stick to certain fibers in the extracellular matrix, is equally abundant in the normal and cancer cells. But in the cancer cells the proteins don't make it to the cell surface," he added.
"For some reason they stay inside the cytoplasm, so the cancer cells are not as sticky," added Staunton whose hometown is Buffalo, N.Y. "This is another trait that contributes to their ability to spread through the body."
The PSOC network went to great lengths to have all of the studies performed under comparable conditions. While the cell lines studied are well understood, part of the effort for the network was to prove they could consistently coordinate the research.
Staunton, who has been involved in ASU's center since its inception, says the experience has helped his growth as a researcher.
"It is the perfect habitat for budding scientists and for transdisciplinary collaborations," he said.
###
Source:
Jack "Rory" Staunton, (480) 809-7212
Media contact:
Skip Derra, (480) 965-4823; skip.derra@asu.edu
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Battery of tests on cancer cells shows them as 'squishy,' yet tactically strongPublic release date: 26-Apr-2013 [ | E-mail | Share ]
Contact: Skip Derra skip.derra@asu.edu 480-965-4823 Arizona State University
Student researchers get a new view of the dynamics of cancer cells as they metastasize
TEMPE, Ariz. A team of student researchers and their professors from 20 laboratories around the country have gotten a new view of cancer cells. The work could shed light on the transforming physical properties of these cells as they metastasize, said Jack R. Staunton, a Ph.D. candidate at Arizona State University in the lab of Prof. Robert Ros, and the lead author of a paper reporting on the topic.
Metastasis is a critical step in the progression of cancer. It is when the cancer spreads from one organ or part to another. While much is known about metastasis, it remains an incomplete understanding of the physical biology of the transition.
To get a better understanding of metastasis, more than 95 graduate students, post docs and professors in a variety of laboratories across the U.S. subjected two cell lines to a battery of high-tech tests and measurements. Their results, outlined in the paper "A physical sciences network characterization of non-tumorigenic and metastatic cells," were published today (April 26, 2013) in Scientific Reports.
The researchers performed coordinated molecular and biophysical studies of non-malignant and metastatic breast cell lines to learn more about what happens to a cell when it transitions to a metastatic state.
Each laboratory is part of the National Cancer Institute's Physical Sciences Oncology Center (PSOC), a network of 12 centers devoted to understanding the physical sciences of cancer. ASU's center, the Center for the Convergence of Physical Science and Cancer Biology, is led by Prof. Paul Davies.
Each PS-OC was supplied with identical cell lines and common reagents, and considerable effort was made to ensure that all the conditions were standardized and documented at regular intervals. Staunton said the ASU group made three contributions to the study.
Other ASU researchers involved in the project and co-authors on the paper are: Alexander Fuhrmann, Vivek Nandakumar, Laimonas Kelbauskas, Patti Senechal, Courtney Hemphill, Roger H. Johnson and Deirdre Meldrum.
"We compared the stiffness of normal breast cells and highly metastatic breast cancer cells, and found the cancer cells to be significantly more 'squishy' or deformable," Staunton said. "This makes sense because in order for a cell to metastasize, it has to squeeze through tight passages in the lymphatics and microvasculature, so being squishy helps cancer cells spread through the body."
"We also looked at the morphology of their nuclei," he added. "The cancer cell nuclei were found to have a characteristic 'crushed beach-ball' shape that might correspond to the abnormal chromosomal rearrangements associated with cancer."
"Finally, we took individual cells, put each one in an airtight chamber, and measured how much oxygen they consumed," Staunton said. "This tells us about their metabolism. We found the cancer cells use less oxygen, relying more on glycolysis, kind of like what bacteria and yeast do."
Taken together, researchers at the 12 PSOC's used some 20 distinct techniques, including atomic force microscopy, ballistic intracellular nano-rheology, cell surface receptor expression levels, differential interference contrast microscopy, micro-patterning and extracellular matrix secretion, and traction force microscopy.
The work has enabled a comprehensive cataloging and comparison of the physical characteristics of non-malignant and metastatic cells, and the molecular signatures associated with those characteristics. This made it possible to identify unique relationships between observations, Staunton said.
"We were surprised that even though the cancer cells are softer, they are able to exert more contractile forces on the fibers surrounding them which was determined at the Cornell University PSOC by a method called traction force microscopy. This pair of characteristics is somewhat contradictory from a purely physical perspective, but it makes sense for a cancer cell, since both traits improve their chances of metastasizing. Understanding why is still an active area of research," explained Staunton, who is working towards his doctorate in physics.
"Another interesting finding was that a protein called CD44, which doubles as a cancer stem cell marker and as a molecule that helps the cell stick to certain fibers in the extracellular matrix, is equally abundant in the normal and cancer cells. But in the cancer cells the proteins don't make it to the cell surface," he added.
"For some reason they stay inside the cytoplasm, so the cancer cells are not as sticky," added Staunton whose hometown is Buffalo, N.Y. "This is another trait that contributes to their ability to spread through the body."
The PSOC network went to great lengths to have all of the studies performed under comparable conditions. While the cell lines studied are well understood, part of the effort for the network was to prove they could consistently coordinate the research.
Staunton, who has been involved in ASU's center since its inception, says the experience has helped his growth as a researcher.
"It is the perfect habitat for budding scientists and for transdisciplinary collaborations," he said.
###
Source:
Jack "Rory" Staunton, (480) 809-7212
Media contact:
Skip Derra, (480) 965-4823; skip.derra@asu.edu
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
For local youth seeking ways to improve their skateboarding skills, the town?s Parks and Recreation Department will come to the rescue this spring and summer.
The department has announced that there is still space available in its Skateboarding Clinics this spring. The classes will meet after school for children six to 12 years of age. Each clinic will meet four consecutive Tuesdays, Wednesdays, or Thursdays from 4:15 to 5:15 p.m. and began on April 23.
The fee for the four sessions is $65 for annual members and $95 for non members. The price includes free practice skate time before or after the lesson until the park closes. For more information or to sign up call the Skatepark at 203-496-9876 or visit greenwichct.org.
The department also announced that registration has begun for its summer Skate Park Ramp Camps starting June 25. The Ramp Camp is for skateboarders between the ages of six and 14. Weekly sessions take place the weeks of June 25 to 28; July 8 to 12; Aug. 5 to 9; Aug. 12 to 16, and Aug. 19 to 23. Camp time will be spent teaching skaters new tricks, playing games and skating at this unique park.
The program runs weekly Monday to Friday, from 9 a.m. to noon. The cost for the weekly Ramp Camp program is $190 for the week for non members? $140 for the week for members.
There are also Pee Wee clinics for skateboarders six to nine years of age that run for one hour from 6:30 to 7:30 p.m. Monday to Thursday with a rain date on Friday. These weekly clinics will meet the weeks of July 15 to 18; July 22 to 25; and July 29 to Aug. 1. The cost for the Pee Wee clinics is $95 for non members and $65 for members.
For more information, call Frank Gabriele at 203-532-1259, stop by the Parks and Recreation Department, or visit greenwichct.org.
WASHINGTON (AP) ? Investigators say Eric Justin Toth's five-year run as a fugitive began when he was fired from his teaching job at a prestigious private school in Washington after being confronted about images of child pornography taken with a school camera in the man's possession.
It ended over the weekend when Nicaraguan authorities, acting on a tip, found him living in that Central American country ? with phony passports, driver's licenses and credit cards, authorities said. The FBI is investigating why Toth was living there and has previously said he may have been advertising as a nanny or tutor while on the lam.
Now, investigators are trying to piece together how he avoided capture even after he was added to the FBI's Most Wanted list, a notorious designation reserved for those considered dangerous criminals and that has featured the likes of Osama bin Laden and Whitey Bulger. Prosecutors are encouraging any other abuse victims to come forward as they proceed with a federal child pornography case against the 31-year-old Toth, who was ordered held without bond during a brief court appearance Tuesday.
"The fact that he is a known child predator and that he's been on the run for five years, we assume that there's potentially other victims in other places that he's been over the past five years," said Valerie Parlave, the head of the FBI's Washington field office.
A federal public defender assigned to Toth didn't immediately return a call seeking comment. Phone listings for possible relatives of Toth either declined to comment or did not return phone messages.
The arrest on Saturday, in a city near Nicaragua's border with Honduras, ended a frustrating international manhunt for the computer-savvy third-grade teacher and former camp counselor.
There were tantalizing clues along the way ? a fake suicide note in Minnesota, an apparent sighting at a shelter in Arizona, a tip that led agents on an extensive search of South America. Yet Toth continued to elude authorities, even as pictures of his bespectacled and sometimes bearded face were featured on news programs, billboards around the country and the FBI's list.
The big break came from a tip last week after a female tourist who encountered Toth in a social setting recognized him and contacted authorities, said FBI spokeswoman Jacqueline Maguire.
Toth first arrived in Nicaragua in October and appeared to have spent at least part of his time there creating false identities and ID documents, police said. When his house was raided, police found passports, driver's licenses and credit cards from three banks, under different names, suggesting he was preparing new false identities to use, said national Police Chief Aminta Granera. Toth was living under an assumed name, authorities said, and the FBI used records of a recent purchase to pinpoint his whereabouts.
Federal prosecutors unsealed a criminal complaint Tuesday charging Toth with possessing and producing child pornography, charges that together carry a maximum 50-year prison sentence. Toth wore a blue jail jumpsuit, his hair considerably longer than in the photographs the FBI had made public, and he spoke softly in response to a judge's perfunctory questions.
Prosecutors revealed no new details of their case in court. But according to the complaint, multiple images of child pornography ? including one video in which Toth allegedly appeared alongside an undressed young boy ? were located in June 2008 on a media card found inside his classroom at Beauvoir, a private elementary school on the grounds of the Washington National Cathedral.
Although "not the most socially adept guy," he was an engaged teacher who helped students think outside the box in math and logic and who even incorporated lessons on why people do or don't do the right things, recalled Michele Booth Cole, whose daughter was in one of Toth's classes.
"He wasn't teaching from the textbook. It was really much more creative and thought-provoking for the kids," said Cole, executive director of Safe Shores ? the DC Children's Advocacy Center, which helps abused children.
The media card with the pornographic images was found in in a box addressed to Toth at the school's address, the complaint says. Although some of the images showed children laughing and playing, others were every parent's nightmare, said Ron Machen, the U.S. Attorney for the District of Columbia.
Those include photographs and videos showing the hand of an adult male fondling a boy, the complaint says. Another video, taken in what appears to be a classroom at the school, shows a man investigators believe to be Toth with an undressed prepubescent boy.
Toth was fired after the images were discovered by fellow school employees and escorted from the school. He disappeared immediately, long before anyone could arrest him.
But there were soon clues that would set agents in motion.
His car was found later that summer in a long-term parking lot at the Minneapolis airport along with a fake suicide note inside that claimed he was going to kill himself in a nearby lake. But no body was found, and investigators concluded it was a ruse.
"Clearly he was trying to throw investigators off at that point," said FBI Special Agent Kyle Loven, an agency spokesman in Minneapolis.
He was believed to have been sighted in Phoenix in 2009, apparently working as a quasi-counselor at a shelter under an assumed name, the FBI has said. He was gone before agents could get to him.
Authorities also believe Toth, who is from the Midwest, traveled while on the run to Illinois, Indiana, Wisconsin and Minnesota.
In April 2012, the FBI, concerned that the trail was going cold and that Toth's experience in interacting with children and earning their trust might be putting other kids at risk, announced that it was adding him to the bureau's Most Wanted fugitives list, where he filled a slot left vacant by the death of bin Laden.
Ron Hosko, then the special agent in charge of the criminal division of the FBI's Washington field office, said at the time, "This is a dangerous person because of his nature, because he is a child predator, because of his ability to groom both adults and potentially these children to develop some sorts of bond of trust."
___
Associated Press researcher Rhonda Shafner in New York and writers Luis Manuel Galeano in Managua, Nicaragua, and Steve Karnowski in Minneapolis contributed to this report.
___
Follow Tucker on Twitter at http://twitter.com/etuckerAP
Apr. 24, 2013 ? Researchers from the U.S. Department of Energy's (DOE) SLAC National Accelerator Laboratory and Stanford University have designed a low-cost, long-life battery that could enable solar and wind energy to become major suppliers to the electrical grid.
"For solar and wind power to be used in a significant way, we need a battery made of economical materials that are easy to scale and still efficient," said Yi Cui, a Stanford associate professor of materials science and engineering and a member of the Stanford Institute for Materials and Energy Sciences, a SLAC/Stanford joint institute. "We believe our new battery may be the best yet designed to regulate the natural fluctuations of these alternative energies."
Cui and colleagues report their research results, some of the earliest supported by the DOE's new Joint Center for Energy Storage Research battery hub, in the May issue of Energy & Environmental Science.
Currently the electrical grid cannot tolerate large and sudden power fluctuations caused by wide swings in sunlight and wind. As solar and wind's combined contributions to an electrical grid approach 20 percent, energy storage systems must be available to smooth out the peaks and valleys of this "intermittent" power -- storing excess energy and discharging when input drops.
Among the most promising batteries for intermittent grid storage today are "flow" batteries, because it's relatively simple to scale their tanks, pumps and pipes to the sizes needed to handle large capacities of energy. The new flow battery developed by Cui's group has a simplified, less expensive design that presents a potentially viable solution for large-scale production.
Today's flow batteries pump two different liquids through an interaction chamber where dissolved molecules undergo chemical reactions that store or give up energy. The chamber contains a membrane that only allows ions not involved in reactions to pass between the liquids while keeping the active ions physically separated. This battery design has two major drawbacks: the high cost of liquids containing rare materials such as vanadium -- especially in the huge quantities needed for grid storage -- and the membrane, which is also very expensive and requires frequent maintenance.
The new Stanford/SLAC battery design uses only one stream of molecules and does not need a membrane at all. Its molecules mostly consist of the relatively inexpensive elements lithium and sulfur, which interact with a piece of lithium metal coated with a barrier that permits electrons to pass without degrading the metal. When discharging, the molecules, called lithium polysulfides, absorb lithium ions; when charging, they lose them back into the liquid. The entire molecular stream is dissolved in an organic solvent, which doesn't have the corrosion issues of water-based flow batteries.
"In initial lab tests, the new battery also retained excellent energy-storage performance through more than 2,000 charges and discharges, equivalent to more than 5.5 years of daily cycles," Cui said.
To demonstrate their concept, the researchers created a miniature system using simple glassware. Adding a lithium polysulfide solution to the flask immediately produces electricity that lights an LED.
A utility version of the new battery would be scaled up to store many megawatt-hours of energy.
In the future, Cui's group plans to make a laboratory-scale system to optimize its energy storage process and identify potential engineering issues, and to start discussions with potential hosts for a full-scale field-demonstration unit.
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The above story is reprinted from materials provided by DOE/SLAC National Accelerator Laboratory.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
Yuan Yang, Guangyuan Zheng, Yi Cui. A membrane-free lithium/polysulfide semi-liquid battery for large-scale energy storage. Energy & Environmental Science, 2013; DOI: 10.1039/C3EE00072A
Note: If no author is given, the source is cited instead.
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Public release date: 29-Apr-2013
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