Capsid assembly is a critical step in the hepatitis B virus (HBV) life cycle, mediated by the core protein. Core is a potential target for new antiviral therapies, the capsid assembly modulators (CAMs). JNJ-56136379 (JNJ-6379) is a novel and potent CAM currently in phase II trials. We evaluated the mechanisms of action (MOAs) and antiviral properties of JNJ-6379 in vitro. Size exclusion chromatography and electron microscopy studies demonstrated that JNJ-6379 induced the formation of morphologically intact viral capsids devoid of genomic material (primary MOA). JNJ-6379 accelerated the rate and extent of HBV capsid assembly in vitro. JNJ-6379 specifically and potently inhibited HBV replication; its median 50% effective concentration (EC₅₀) was 54 nM (HepG2.117 cells). In HBV-infected primary human hepatocytes (PHHs), JNJ-6379, when added with the viral inoculum, dose-dependently reduced extracellular HBV DNA levels (median EC₅₀ of 93 nM) and prevented covalently closed circular DNA (cccDNA) formation, leading to a dose-dependent reduction of intracellular HBV RNA levels (median EC₅₀ of 876 nM) and reduced antigen levels (secondary MOA). Adding JNJ-6379 to PHHs 4 or 5 days postinfection reduced extracellular HBV DNA and did not prevent cccDNA formation. Time-of-addition PHH studies revealed that JNJ-6379 most likely interfered with postentry processes. Collectively, these data demonstrate that JNJ-6379 has dual MOAs in the early and late steps of the HBV life cycle, which is different from the MOA of nucleos(t)ide analogues. JNJ-6379 is in development for chronic hepatitis B treatment and may translate into higher HBV functional cure rates.

Mismatch repair (MMR)–deficient tumors exhibit proteome-wide protein instability and aggregation.

This protocol describes a simple single-step column purification (SSCP) of rAAV2 by gravity flow based on its affinity to heparin, without ultracentrifugation.

Hepatitis C virus (HCV) is an important and underreported infectious disease, causing chronic infection in ~71 million people worldwide. The limited host range of HCV, which robustly infects only humans and chimpanzees, has made studying this virus in vivo challenging and hampered the development of a desperately needed vaccine. The restrictions and ethical concerns surrounding biomedical research in chimpanzees has made the search for an animal model all the more important. In this review, we discuss different approaches that are being pursued toward creating small animal models for HCV infection. Although efforts to use a nonhuman primate species besides chimpanzees have proven challenging, important advances have been achieved in a variety of humanized mouse models. However, such models still fall short of the overarching goal to have an immunocompetent, inheritably susceptible in vivo platform in which the immunopathology of HCV could be studied and putative vaccines development. Alternatives to overcome this include virus adaptation, such as murine-tropic HCV strains, or the use of related hepaciviruses, of which many have been recently identified. Of the latter, the rodent/rat hepacivirus from Rattus norvegicus species-1 (RHV-rn1) holds promise as a surrogate virus in fully immunocompetent rats that can inform our understanding of the interaction between the immune response and viral outcomes (i.e., clearance vs. persistence). However, further characterization of these animal models is necessary before their use for gaining new insights into the immunopathogenesis of HCV and for conceptualizing HCV vaccines.

It all boils down to how resilient the region is, says an urban planner and designer based in Manila.

You are preparing your home for sale? Don’t forget to make some small repairs since they can make a big difference both in terms of interest levels and offer prices for the home.

Just after the prosecutor assigned to the case resigned on Thursday, the Department of Justice announced that it dropped the charges against Michael Flynn, the former national security advisor who’d already pleaded guilty to lying to the FBI about his contacts with Russia. 

President Trump forecast this before it happened. Last week, he insisted that Flynn had been exonerated.  Apparently referring to his pardon power, Trump suggested that if the court did not do something he would use “a different kind of power.”

And now it’s happened. While the president has the broad power to pardon, he should not control individual prosecutorial decisions, especially those concerning a political ally. It is extremely unusual for the government to dismiss charges after a guilty plea. This is a sign that the historic independence of the Justice Department has been compromised. 

Read more at The Daily Beast.

For the past two months, Katie Holliday has been cooped up alone in her Brooklyn apartment thinking longingly about an unlikely erogenous zone: the lower half of a stranger’s face. 

“I remember joking to my friend before all of this started, ‘Imagine if someone’s face becomes their most coveted body part?’” Holliday, who is 31, told The Daily Beast. “‘When someone removes their mask, is it a sign of trust? Is it like letting someone see you naked?’ I was kidding back then, but now it’s reality.”

Holliday doesn’t know exactly when it will be safe to start seeing people like she did before the pandemic began, but she’ll return to a singles scene unlike any other in history. “I’m picturing walking into a bar where everyone’s wearing masks,” she said. “I’ll meet someone whose face is covered. Are they cute or not? I don’t know!” 

Read more at The Daily Beast.

Roboticists share what they've learned so far from DARPA's Subterranean Challenge, and how they readied their bots for the next event—the Tunnel Circuit

Cerebras aims to speed deep learning at supercomputing centers

Whether for maintenance or augmentation, robots that can use tools on themselves are more independent and capable

Fast-growing Melbourne payments company PromisePay is ramping its growth plans in the global platform economy.

The B.C. Lions made sure to count every last penny when announcing a new contract for free-agent quarterback Mike Reilly ahead of the 2019 Canadian Football League season. Reilly, who had ...

The White House is making "contingency plans" for a second wave of coronavirus after emails reportedly contradict their claims that Centers for Disease Control and Prevention guidelines to safely reopen the economy were set aside because medical experts did not approve of them.

Noida Police Commissioner has written to national carrier Air India, requesting the airline to ensure that pilots and crew involved in repatriation flights should stay back in Delhi.

Around 250 Indian students and tourists were seen queuing with their luggage at the airport as they prepared for the journey home.

The infection is being eliminated as a public health threat by countries that introduce widespread testing and treatment for those at risk

Welsh plan to reopen stores offers hope for UK-wide industry closed in prime sales season

Garden centres are preparing for a surge in plant and flower sales that could help salvage a catastrophic year for the horticulture industry.

The UK’s 2,000 garden centres and nurseries were forced to close in March because, unlike DIY chains such as B&Q and Homebase, they were not granted “essential” retailer status. The shutdown came at a critical time of year, with 70% of sales rung up in spring, forcing devastated growers to throw away millions of plants.

Vanessa Bryant, the widow of late NBA star Kobe Bryant, filed a legal claim Friday against the Los Angeles County Sheriff’s Department over graphic photos that deputies allegedly took and shared of the helicopter crash scene where her husband, 13-year-old daughter, Gigi, and seven others were killed in late January.

Future Navy SEALs will conduct combat scenarios six-feet apart, emulate high-risk combat scenarios, study in smaller classrooms and be directed by megaphones at farther distances, because more candidates for the special operations unit are again competing, training and preparing for war following temporary delays caused by COVID 19.

Siemens is preparing for a prolonged economic trough triggered by the COVID-19 pandemic, Chief Executive Joe Kaeser told CNBC on Friday after releasing fiscal second-quarter results.

Coronavirus: the symptoms Read our LIVE updates on the coronavirus here

Read our live updates on coronavirus HERE Coronavirus: The symptoms

In today's Diary: how Whitehall's cats are coping with coronavirus / Russell Crowe sideswipes Oliver Reed / Angela Scanlon on the glory of cheese / Michael Fabricant vows to wear pink shorts

From being "too slow" to act on testing, PPE and the lockdown, to care home deaths and Boris Johnson's attendance at meetings, ministers are caught in a storm.

Ministers were reportedly warned to prepare for a pandemic virus last year, according to a leaked document.

Bosses at John Lewis have started talks on which department stores should keep their doors permanently closed once the coronavirus lockdown ends, according to sources.

Tributes have been paid to Ken and Betty Hill, who were together for more than 40 years

Boris Johnson is preparing a plan for the UK's escape from lockdown after declaring the nation has "past the peak" of its coronavirus outbreak.

Boris Johnson wants people in the UK to be back at work by the end of May if coronavirus cases are low enough, it has been reported.

Boris Johnson has said doctors prepared to announce his death as he battled coronavirus in intensive care.

The Royal Hospital Chelsea today revealed that nine of its residents had died from the coronavirus.

The first changes to the UK's coronavirus lockdown will be "small" and "very carefully monitored" when the Prime Minister reveals his "roadmap" on Sunday.

The UK was ill-prepared to deal with a health pandemic, according to a secret Whitehall document produced years before the coronavirus outbreak.

The nation is preparing to celebrate the 75th anniversary of Victory in Europe (VE) Day , with the Queen set to make a historic address to mark the occasion.

Cabinet Secretary Oliver Dowden admitted on Friday morning that the lockdown is facing a major test from the sunny weekend ahead.

Living on a 10-acre plot of land 100 kilometres outside Toronto, David Stevens thought he and his family were well prepared to ride out the COVID-19 quarantine. But after a call from his mother, he learned that even the best laid plans can go wrong.

The mother of a newborn wants to see her own mother cuddle the baby, while adult children must rely on virtual connections with their elderly mother. COVID-19 proves challenging physically and emotionally for many this Mother's Day.

https://www.ebay.com/itm/Microsoft-Xbox-One-X-1TB-Black-Console-as-is-for-repair-or-parts-only/264227168298

YMMV obviously--I ordered two of these a month ago and they have been running fine for me.  All I had to do was reinstall the newest system update and they have both been fine with no issues.  One system's issue noted was "freezes" and the other was "no video". 

It says he has only 2 in stock, but I bought two a while back and the listing has remained active for the entire time with stock available, so he probably leaves the number low to keep demand going. This is probably a bulk buyer who doesn't extensively troubleshoot the systems.  I am not affiliated with the seller.  Cosmetically, the systems are nice enough to trade in without taking a refurb fee when stores re-open for business.

John Nichols

The post The Labor Department Is Sacrificing Workers on the Altar of ‘Reopening’ appeared first on The Nation.

An elephant figurine gifted by the then HM LK Advani to US Secretary of State Colin Powell in 2002, has made its way to the State Department hall.

Fate and politics have rewarded decisions made by the former national security adviser and his legal team, ultimately delivering him from legal jeopardy after a years-long odyssey.

Nintendo is no longer repairing the Wii video game console, which was released in 2006 and let players swing controllers to impact action on screen.

• State auditor says Favre will repay money for no-show speeches
• Hall of Fame quarterback faces no criminal charges after report

Former NFL quarterback Brett Favre is repaying $1.1m in welfare money that he received for multiple speeches where he did not show up, the Mississippi state auditor said Wednesday.

Auditor Shad White said his office received $500,000 from Favre on Wednesday, plus a commitment that Favre will repay the other $600,000 in installments over the next few months.

Related: NFL tells teams to have facility reopening protocols in place by next week