Convection is buoyancy-driven flow resulting from unstable density stratification in the presence of a gravitational field. Beyond convection’s central role in myriad engineering heat transfer applications, it underlies many of nature’s dynamical designs on larger-than-human scales. For example, solar heating of Earth’s surface generates buoyancy forces that cause the winds...

Merkel cell carcinoma (MCC) is often caused by persistent expression of Merkel cell polyomavirus (MCPyV) T-antigen (T-Ag). These non-self proteins comprise about 400 amino acids (AA). Clinical responses to immune checkpoint inhibitors, seen in about half of patients, may relate to T-Ag–specific T cells. Strategies to increase CD8⁺ T-cell number, breadth, or function could augment checkpoint inhibition, but vaccines to augment immunity must avoid delivery of oncogenic T-antigen domains. We probed MCC tumor-infiltrating lymphocytes (TIL) with an artificial antigen-presenting cell (aAPC) system and confirmed T-Ag recognition with synthetic peptides, HLA-peptide tetramers, and dendritic cells (DC). TILs from 9 of 12 (75%) subjects contained CD8⁺ T cells recognizing 1–8 MCPyV epitopes per person. Analysis of 16 MCPyV CD8⁺ TIL epitopes and prior TIL data indicated that 97% of patients with MCPyV⁺ MCC had HLA alleles with the genetic potential that restrict CD8⁺ T-cell responses to MCPyV T-Ag. The LT AA 70–110 region was epitope rich, whereas the oncogenic domains of T-Ag were not commonly recognized. Specific recognition of T-Ag–expressing DCs was documented. Recovery of MCPyV oncoprotein–specific CD8⁺ TILs from most tumors indicated that antigen indifference was unlikely to be a major cause of checkpoint inhibition failure. The myriad of epitopes restricted by diverse HLA alleles indicates that vaccination can be a rational component of immunotherapy if tumor immune suppression can be overcome, and the oncogenic regions of T-Ag can be modified without impacting immunogenicity.

Hypervirulent Klebsiella pneumoniae strains are the major cause of liver abscesses throughout East Asia, and these strains are usually antibiotic susceptible. Recently, multidrug-resistant and hypervirulent (MDR-HV) K. pneumoniae strains have emerged due to hypervirulent strains acquiring antimicrobial resistance determinants or the transfer of a virulence plasmid into a classic MDR strain. In this study, we characterized the clinical and microbiological properties of K. pneumoniae liver abscess (KPLA) caused by MDR-HV strains in Taiwan. Patients with community onset KPLA were retrospectively identified at Taipei Veterans General Hospital during January 2013 to May 2018. Antimicrobial resistance mechanisms, capsular types, and sequence types were determined. MDR-HV strains and their parental antimicrobial-susceptible strains further underwent whole-genome sequencing (WGS) and in vivo mice lethality tests. Thirteen MDR-HV strains were identified from a total of 218 KPLA episodes. MDR-HV strains resulted in similar outcomes to antimicrobial-susceptible strains. All MDR-HV strains were traditional hypervirulent clones carrying virulence capsular types. The major resistance mechanisms were the overexpression of efflux pumps and/or the acquisition of ESBL or AmpC β-lactamase genes. WGS revealed that two hypervirulent strains had evolved to an MDR phenotype due to mutation in the ramR gene and the acquisition of an SHV-12-bearing plasmid, respectively. Both these MDR-HV strains retained high virulence compared to their parental strains. The spread of MDR-HV K. pneumoniae strains in the community raises significant public concerns, and measures should be taken to prevent the further acquisition of carbapenemase and other resistance genes among these strains in order to avoid the occurrence of untreatable KPLA.

Although they are usually not considered to be diabetes complications, musculoskeletal disorders (MSKDs) are common in individuals with type 1 or type 2 diabetes and can strongly interfere with daily diabetes care, especially in people using diabetes technologies. The authors of this retrospective study in a population of 140 patients with type 1 diabetes report the distribution of subtypes of MSKDs and speculate about the mechanisms involved. The authors emphasize the need for multidisciplinary care involving not only the diabetes care team but also orthopedic surgeons. This report should lead to large, prospective studies to increase knowledge about these under-studied complications.

Real estate insiders and experts said it is essential to develop strict penalties to combat those operating fraudulent property businesses to protect the legitimate rights of consumers and legitimate enterprises.

The makers of Blair Witch, Observer and Layers of Fear today announced a new psychological horror game - The Medium.

An international team of paleontologists from the University of Plymouth, the University of Kansas and the Forge Fossils has found a specimen of the squid-like cephalopod Clarkeiteuthis montefiorei preserved with the herring-like fish Dorsetichthys bechei in its two arms; the bones in the head of the fish are broken in a manner that suggests a [...]

Israel exports ready-to-eat fully cooked and not shelf-stable poultry products to the United States. And those exports may continue, according to a report by the USDA’s Food Safety and Inspection Service. That’s because Israel has passed its latest foreign equivalency audit by the United States. The audit did not turn up any deficiencies that might... Continue Reading

Read our live coronavirus updates HERE Coronavirus: The symptoms

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Follow our live coronavirus updates HERE Coronavirus: The symptoms

Defiant US healthcare workers have been praised after silently blocking cars during coronavirus anti-lockdown demonstrations in Colorado.

Millions of Britons fell silent at 11am today in memory of the healthcare heroes and key workers who have died fighting coronavirus.

The UK will fall silent on Tuesday in tribute to key workers who have died during the coronavirus pandemic.

Bus drivers paid their respects to a colleague who died with coronavirus symptoms as his funeral cortege passed through the depot where he had worked for almost 20 years.

The Budd family hopes to raise £20,000 for charities including The Felix Project You can donate at virginmoneygiving.com/fund/FoodforLondonNOW

A number of police officers have been injured after responding to reports that men were "acting suspiciously" in Finsbury Park.

The team behind The Artist will have spent the first day of the rest of their lives conforming to the grandest, and most lucrative, of Hollywood traditions.

'Covid-19 gave me a beating physically and mentally'

Around the 19-minute mark, I noticed something odd; it wasn’t that I felt any less out of breath than normal, but I felt detached

Mindfulness is the last thing I want to practise while running. When I’m really up against a wall (which is to say, after four minutes), the only thing that keeps me going is listening to Maniac and imagining I’m that gorilla in a paddling pool. So I approached this with a closed mind, and discarded a lot of podcasts because they were too woo-hoo, or because you had to listen to them before you run (“no headphones” is a typical mindful runner’s instruction), or because the person had an annoying voice. Finally, I settled on The Milestone Pursuit podcast, by a likable blokey Londoner, Steve Hobbs. He didn’t sound at all spiritual; he sounded like a person who would help you with your bike if your chain came off.

He has one mindful episode that I’ve listened to seven or eight times. Total convert. But full disclosure: I’ve never got to the end. It lasts 36 minutes, and I still don’t run for that long. So it’s partly suspense that keeps me going back.

April 29th, 2020, Toronto: In response to the impact on the lives of artists and their teams caused by COVID-19, Canada’s major record companies, Sony Music Entertainment Canada, Universal Music Canada and Warner Music Canada have announced direct financial support for the Unison Benevolent Fund, Canada’s leading music community support program. Unison is a non-profit, […]

The post Canada’s major record companies announce support for Unison Benevolent Fund appeared first on Music Canada.

Maurizio Sarri has revealed how he shared a "conflicted relationship" with his Chelsea squad but admits he misses the Premier League, describing it as "extraordinary".

Aston Villa assistant manager and former Chelsea defender John Terry insists Manchester United target Jack Grealish is destined for greatness, likening him to ex team-mate Eden Hazard.

Chelsea are no longer the best place for English youngsters to go as Manchester City establish themselves as an attractive option, Training Ground Guru has found.

Whenever baseball returns after the delay caused by the coronavirus pandemic, there’s an element that might come into play like never before: the sound of silence.

Apartment: A Separated Place is an interactive tale about moving on.

Corrie's Geoff's violent past with women was brought to light at last by a suspicious police officer, as Alya raised Sally's concerns

Britain's Got Talent's choir D Day Juniors sang a moving original song to thank WWII veterans for giving their lives

EXCLUSIVE: Tonight's episode of Britain's Got Talent on ITV features inspiring children's choir D-Day Juniors who remember the heroes of generations past

A 25-year-old man has been arrested on suspicion of section 18 assault

New research has shown that the key to implementing successful reform in low-performing schools is hiring and retaining effective principals and teachers.

Temperatures will reach highs of 23 Celsius (73F) and it will feel noticeably warmer along North Sea coasts.

The 77-year old is never going to be an electrifying nominee, but Joe Biden has a lot to feel good about seven months out from election day.

Some companies are selling fraudulent products with claims to prevent, treat, mitigate, diagnose, or cure coronavirus.
Medscape Medical News

Britain's Got Talent has been giving us perfect entertainment for the whole family to...

En 2017, je me suis plongée dans la peau d’une préposée aux bénéficiaires. Cette fois, le travail est le même, mais le contexte est bien différent.

A new generation of female footy players is beginning to hit the AFLW, with coaches saying their talent is "really quite scary" and could change the game in the next few years.

The star gave his support to five-year-old Christian Kilduff, who is raising money for the NHS

The former vice president of reinsurance of American International Group Inc. (AIG), was sentenced today to four years in prison for his role in a fraudulent scheme to manipulate AIG’s financial statements.

DaJuan Jackson, a former tax return preparer in District Heights, Md., was sentenced to 51 months in prison by U.S. District Judge Roger W. Titus for preparing false tax returns for customers.

Rodrick Williams, a former tax return preparer from District Heights, Md., was sentenced to 24 months in prison by U.S. District Judge Roger W. Titus for preparing false tax returns for customers.

A federal grand jury in Lubbock, Texas, has charged 17 members and associates of the violent gang known as the Almighty Latin King and Queen Nation (ALKQN) with various charges related to their alleged narcotics and weapons trafficking violations, a well as a variety of alleged violent crimes throughout Texas.

The United States has sued tax return preparers in Placerville, Calif., and Columbia, S.C., seeking to bar them from preparing federal tax returns for others. According to the government complaints in the two cases, Teresa Marty of Pollock Pines, Calif., and Winston Able of Blythewood, S.C., prepare federal income tax returns for their customers that claim fraudulent tax refunds.

Jerry R. Williamson, a promoter of the American Rights Litigators/Guiding Light of God Ministries (ARL) formerly based in Florida, pleaded guilty today to mail fraud. Williamson appeared today before Judge Henry H. Kennedy Jr. in Washington, D.C., and admitted that he that he sent a fictitious “Bill of Exchange” purporting to be drawn upon the U.S. Treasury to the Bureau of Land Management of the Department of the Interior.

A Miami federal grand jury has charged two South Florida men with conspiracy, mail and wire fraud in connection with the operation of a fraudulent ATM business opportunity. The criminal charges are part of the government’s continued nationwide crackdown on business opportunity fraud.

Todd Gongwer of Dublin, Ohio; Lance Parker of Dublin, Ohio; and Joel Lee, of Galena, Ohio, pleaded guilty today to conspiracy to commit bank fraud. Gongwer, a licensed real estate agent, also pleaded guilty to tax evasion in the hearing before Judge Michael H. Watson in Columbus, Ohio. Parker also pleaded guilty to illegally structuring cash transactions.

The Department has filed suit against convicted tax fraud promoter Daniel Andersen to enjoin him from promoting fraudulent tax schemes. The government’s complaint alleges that Andersen directed the activities of both the Institute for Global Prosperity (between 1996 and 2002) and the Stratia Corporation (between 2002 and 2004). The lawsuit states that Andersen used these organizations to promote the fraudulent tax schemes sold by others in a series of audio recordings and at offshore conferences.

The owner of a Costa Rica-based telemarketing call center and two employees of another Costa Rica call center were sentenced for their roles in schemes that targeted and defrauded thousands of American victims of more than $10 million.