The fiancee of murdered journalist Jamal Khashoggi says Newcastle United and the Premier League must put moral values ahead of financial gains.

Apple India Website Puts Siri in Silent Mode

Create a Time-Lapse Movie with Google Street View

Google Street View - Time Lapse Movie

The Most Useful Websites - self published using Amazon KDP.

Bollywood Movies on Zero Dollar Movies

She created Mother's Day out of love for her own mother but was shocked by how it became commercialised.

The fiancee of murdered journalist Jamal Khashoggi says Newcastle United and the Premier League must put moral values ahead of financial gains.

As millions of people have their salaries cut, will mortgage providers lend based on reduced salary?

Tesla boss Elon Musk has threatened to pull the firm's headquarters and only US car factory out of California after local officials stopped the company from reopening the electric vehicle plant.

Filed under: Asia, Thailand

Not only are tourists still coming, but they've been arriving in increasing numbers in recent years, according to government data.

Continue reading Demonstrations in Thailand? No Problem, Travelers Say.

Demonstrations in Thailand? No Problem, Travelers Say. originally appeared on Gadling on Mon, 02 Dec 2013 11:26:00 EST. Please see our terms for use of feeds.

Filed under: Europe, North America, France, United Kingdom, United States

Continue reading London, Rome, Paris Top TripAdvisor's Most-Reviewed Cities List

London, Rome, Paris Top TripAdvisor's Most-Reviewed Cities List originally appeared on Gadling on Tue, 17 Dec 2013 14:11:00 EST. Please see our terms for use of feeds.

• This week's most popular movies on Netflix include its original thriller "Dangerous Lies" and "Den of Thieves."
• Netflix introduced daily top lists of the most popular titles on the service in February.
• Streaming search engine Reelgood keeps track of the lists and provides Business Insider with a rundown of the week's most popular movies on Netflix every Friday.
• Visit Business Insider's homepage for more stories.

The Netflix action movie "Extraction" is pacing to be the streaming giant's biggest movie premiere ever, but it was dethroned this week as the service's most popular movie. Another Netflix original, "Dangerous Lies," stole the crown.

Netflix introduced daily top 10 lists of its most viewed movies and TV shows in February (it counts a view if an account watches at least two minutes of a title).

Every week, the streaming search engine Reelgood compiles for Business Insider a list of which movies have been most prominent on Netflix's daily lists that week. On Reelgood, users can browse Netflix's entire movie library and sort by IMDb or Rotten Tomatoes ratings.

This week's list also includes "Den of Thieves," another movie starring Gerard Butler after his "Angel Has Fallen" enjoyed a few weeks on the list.

But the real winner this week is Netflix itself, as five of the seven movies on the list are Netflix originals. 

SEE ALSO: Insiders say major questions hang over DC Universe as its parent company prepares to launch Netflix rival HBO Max

7. "The Willoughbys" (2020 — Netflix original)

Netflix description: "Four siblings with horribly selfish parents hatch a plan to get rid of them for good and form a perfectly imperfect family of their own."

Rotten Tomatoes critic score: 89%

What critics said: "Though the film-makers are indebted to Edward Gorey and Lemony Snicket — and pay musical homage to Mark Mothersbaugh's work on The Royal Tenenbaums — they find their own voice, when it counts." — London Evening Standard

6. "Murder to Mercy: The Cyntoia Brown Story" (2020 — Netflix original)

Netflix description: "After 16-year-old Cyntoia Brown is sentenced to life in prison, questions about her past, physiology and the law itself call her guilt into question."

Rotten Tomatoes critic score: 75%

What critics said: "A moving reflection of what criminal justice reform means in personal terms." — New York Times

5. "Arctic Dogs" (2019)

Netflix description: "When he stumbles upon evil Otto Von Walrus's scheme to melt the Arctic, ambitious delivery fox Swifty assembles a ragtag crew to protect the planet."

Rotten Tomatoes critic score: 13%

What critics said: "There's really not much to recommend about this film: the animation lacks texture, the score is overwrought, the plotting is scattershot, and the character design is uninspired." — AV Club

4. "Den of Thieves" (2018)

Netflix description: "A highly skilled crew of bank robbers plotting a heist at the supposedly impenetrable Federal Reserve faces off against an elite unit of L.A. cops."

Rotten Tomatoes critic score: 41%

What critics said: "It often resembles a men's rights bonding weekend more than it does a movie." — Guardian

3. "Extraction" (2020 — Netflix original)

Netflix description: "A hardened mercenary's mission becomes a soul-searching race to survive when he's sent into Bangladesh to rescue a drug lord's kidnapped son."

Rotten Tomatoes critic score: 68%

What critics said: "Illustrates an important principle in escapist entertainment: you don't have to one-up your predecessors. Sometimes, it's enough to replicate what made them successful." — Newsday

2. "All Day and a Night" (2020 — Netflix original)

Netflix description: "While serving life in prison, a young man looks back at the people, the circumstances and the system that set him on the path toward his crime."

Rotten Tomatoes critic score: 56%

What critics said: "'All Day and a Night' lingers and sometimes meanders in that gray zone, where the story can accrue texture and feeling and emerge as more than the sum of its plot mechanics." — Los Angeles Times

1. "Dangerous Lies" (2020 — Netflix original)

Netflix description: "A broke caregiver unexpectedly inherits her patient's estate, but dark secrets swirl around her newfound wealth, tangling her in deceit and danger."

Rotten Tomatoes critic score: 39%

What critics said: "Looks like it cost the amount of your monthly Netflix subscription and is as satisfying to watch as it is paying that particular bill." — Globe and Mail

A bodyguard of Eastern Cape Social Development MEC Siphokazi Mani-Lusithi has been arrested with four others by the Green Scorpions for illegal hunting on a private farm outside East London, as well as for breaking Covid-19 lockdown regulations.

Four minutes and 28 seconds. That is how long it took a News24 reporter to find cigarettes – meant to be banned under Level 4 lockdown regulations – which were available for purchase at one of many places in South Africa.

While the phased-in reopening of schools in South Africa in the midst of Covid-19 remains provisional and sensitive, the Western Cape Education Department has advised principals and school management teams to wait a few more days before returning.

Messages to mothers and words of support were front and centre as Edmontonians cruised by MacTaggart Place retirement residence on Saturday afternoon.

Dozens of protesters descended on the legislature Saturday afternoon, calling for a quicker reopening of the Alberta economy.

Some kids took advantage of the opportunity to show their appreciation for their moms on Saturday afternoon at the Love You Mama event.

Several local food trucks held a pop-up drive-thru at the Southgate Mall parking lot on Saturday.

Soon after CTV News Edmonton aired a story about a local wood carver who had one of his carvings stolen, he got a knock on his door.

A man is dead after a single-vehicle motorcycle crash in southeast Calgary.

Two-time women's World Cup winner Alex Morgan and husband Servando Carrasco have welcomed a new player to their team.

SuperSport United winger Aubrey Modiba says a conversation with club CEO Stanley Matthews convinced him to stay despite interest from Mamelodi Sundowns.

Former New Zealand head coach and current England defence chief John Mitchell believes some good may come for rugby union from the coronavirus.

It seemed like such a great idea at the time. You wanted to put together a video for a loved one, including all their family and friends singing their praises, making their life look as epic as a Hollywood production.

Oh, it was a Hollywood production, all right. Contributors showed up late and sent weird file formats, editing took forever, the music wasn’t right...and on it went. Before you know it, a simple tribute video you thought might take an hour or two consumed multiple nights and had you cursing the day you ever thought of the idea.

Video montages take work. But by enlisting Tribute to help you assemble your message of love, It’s all a lot more manageable.

In fact, the Tribute process is so easy that you probably won’t have to do more than a few minutes of work to produce a high-quality tribute video that brings tears of joy. No, seriously...Tribute swears 80 percent of their videos elicit actual tears of joy. Of course, there’s no way of knowing their metrics for judging the results of their 500,000 Tribute videos so far...but if they’re close, your odds for an emotional testament to your subject are pretty darn high.

With Tribute, you just enter the emails for all the people you’d like to contribute to the video. Tribute emails your participants, explains the project, and guides your subjects through how to shoot and submit their segment for the finished video.

Once all your videos are in, Tribute will compile all your clips into a touching, polished montage. Read the rest

Canadians working aboard two cruise ships who weren't allowed to come to shore because of concerns about COVID-19 are finally able to return home.

Dr. Bonnie Henry announced 15 new confirmed cases of the virus in the province, bringing the total number of positive tests since the pandemic began to 2,330.

The manager of a Vancouver barber shop warns that once many B.C. salons are back open, they may have to implement a price increase for their services.

Police and City of Vancouver park rangers escorted the last person living in Oppenheimer Park out of the tent city Saturday afternoon, moments before crews with excavators moved in to clean up the mountains of trash left behind.

The following article, Professor Who Mocked Barron Trump During Senate Hearings Gets Censorship Position at Facebook, was first published on 100PercentFedUp.com.

Facebook just announced a 20 person board of oversight that will assist with content moderation. One of the people selected for the board, a professor at Stanford Law School, was announced as a member of the board and is raising eyebrows because of her snarky comment about Barron Trump during Senate Impeachment Hearings. Pamela Karlan, […]

Continue reading: Professor Who Mocked Barron Trump During Senate Hearings Gets Censorship Position at Facebook ...

The following article, Rep. Ilhan Omar Asks For Contributions To Her Campaign To Help MN Food Bank…Food Bank Director Says Omar Has Nothing To Do With Project: “I have no idea where this money is going”, was first published on 100PercentFedUp.com.

Ilhan Omar is a lot of things. First, and foremost, she’s deceitful. David Steinberg of PJ Media was one of the first investigative journalists to break the story about the anti-Semitic, freshman lawmaker’s marriage to her immigrant brother while she was still married to her first husband, who she has since divorced after having an […]

Continue reading: Rep. Ilhan Omar Asks For Contributions To Her Campaign To Help MN Food Bank…Food Bank Director Says Omar Has Nothing To Do With Project: “I have no idea where this money is going” ...

Members Event

Event participants

Richard Heald, CEO, UK India Business Council (UKIBC)
Manoj Ladwa, Communications Director, Narendra Modi for Prime Minister Campaign
Dr Gareth Price, Senior Research Fellow, Asia Programme, Chatham House

Chair: Adam Roberts, South Asia Bureau Chief, Delhi, The Economist

Invitation Only Research Event

Event participants

Dr Leena Koni Hoffmann, Centre for Population, Poverty and Public Policy Studies; Author, Who Speaks for the North? Politics and Influence in Northern Nigeria; ERANDA Junior Research Fellow, Africa Programme, Chatham House (2013)
Chair: Elizabeth Donnelly, Assistant Head, Africa Programme, Chatham House

23 February 2015

Members Event

Event participants

Dr Mukulika Banerjee, Director, South Asia Centre, London School of Economics
Nandan Nilekani, Co-founder and Chairman, EkStep; Chairman, Unique Identification Authority of India (UIAI) (2009-14)
Dr Gareth Price, Senior Research Fellow, Asia Programme, Chatham House
Mihir Swarup Sharma, India Columnist, Bloomberg View; Senior Fellow, Observer Research Foundation, New Delhi
Chair: James Crabtree, Contributing Editor, Financial Times; Senior Visiting Fellow, Lee Kuan Yew School of Public Policy

ridureyu1 posted a photo:

A thematic interpretation of Scream: Curse of Carnage, using the new NECA Rhino Alien as a stand-in for Grendel's Mother. Like I said, thematic.

South Dakota Governor Kristi Noem sent letters to two Sioux tribes demanding they remove COVID-19 checkpoints because they interfere with traffic.

"I think it's always important to think about suicide as individual vulnerabilities and context," Eric Caine said.

China's National Health Commission reported 14 new confirmed coronavirus cases on May 9, the highest number since April 28, including the first for more than a month in the city of Wuhan where the outbreak was first detected late last year. While China had officially designated all areas of the country as low-risk last Thursday, the new cases according to data published on Sunday represent a jump from the single case reported for the day before. The new Wuhan case, the first reported in the epicentre of China's outbreak since April 3, was previously asymptomatic, according to the health commission.

Prime Minister Justin Trudeau called Saturday for caution and expressed concern about loosening lockdown measures in Montreal, the epicenter of Canada's coronavirus outbreak. While several Canadian provinces, including Quebec, are preparing reopening measures and a gradual revival of their economies, Trudeau stressed prudence and said that the country is not yet out of danger. Quebec is the worst-hit province in Canada, with more than half of both the country's 67,000 cases of coronavirus and 4,700 deaths.

"Passing along a message from Mother Nature," the National Weather Service in Binghamton, New York, tweeted alongside a photo of a car covered in light snow. "Happy Mother's Day Weekend."

Lethal infections by strains of the highly-pathogenic avian influenza virus (HPAIV) H5N1 pose serious threats to both the poultry industry and public health worldwide. A lack of confirmed HPAIV epitopes recognized by cytotoxic T lymphocytes (CTLs) has hindered the utilization of CD8+ T-cell–mediated immunity and has precluded the development of effectively diversified epitope-based vaccination approaches. In particular, an HPAIV H5N1 CTL-recognized epitope based on the peptide MHC-I–β2m (pMHC-I) complex has not yet been designed. Here, screening a collection of selected peptides of several HPAIV strains against a specific pathogen-free pMHC-I (pBF2*1501), we identified a highly-conserved HPAIV H5N1 CTL epitope, named HPAIV–PA123–130. We determined the structure of the BF2*1501–PA123–130 complex at 2.1 Å resolution to elucidate the molecular mechanisms of a preferential presentation of the highly-conserved PA123–130 epitope in the chicken B15 lineage. Conformational characteristics of the PA123–130 epitope with a protruding Tyr-7 residue indicated that this epitope has great potential to be recognized by specific TCRs. Moreover, significantly increased numbers of CD8+ T cells specific for the HPAIV–PA123–130 epitope in peptide-immunized chickens indicated that a repertoire of CD8+ T cells can specifically respond to this epitope. We anticipate that the identification and structural characterization of the PA123–130 epitope reported here could enable further studies of CTL immunity against HPAIV H5N1. Such studies may aid in the development of vaccine development strategies using well-conserved internal viral antigens in chickens.

Although a robust inflammatory response is needed to combat infection, this response must ultimately be terminated to prevent chronic inflammation. One mechanism that terminates inflammatory signaling is the production of alternative mRNA splice forms in the Toll-like receptor (TLR) signaling pathway. Whereas most genes in the TLR pathway encode positive mediators of inflammatory signaling, several, including that encoding the MyD88 signaling adaptor, also produce alternative spliced mRNA isoforms that encode dominant-negative inhibitors of the response. Production of these negatively acting alternatively spliced isoforms is induced by stimulation with the TLR4 agonist lipopolysaccharide (LPS); thus, this alternative pre-mRNA splicing represents a negative feedback loop that terminates TLR signaling and prevents chronic inflammation. In the current study, we investigated the mechanisms regulating the LPS-induced alternative pre-mRNA splicing of the MyD88 transcript in murine macrophages. We found that 1) the induction of the alternatively spliced MyD88 form is due to alternative pre-mRNA splicing and not caused by another RNA regulatory mechanism, 2) MyD88 splicing is regulated by both the MyD88- and TRIF-dependent arms of the TLR signaling pathway, 3) MyD88 splicing is regulated by the NF-κB transcription factor, and 4) NF-κB likely regulates MyD88 alternative pre-mRNA splicing per se rather than regulating splicing indirectly by altering MyD88 transcription. We conclude that alternative splicing of MyD88 may provide a sensitive mechanism that ensures robust termination of inflammation for tissue repair and restoration of normal tissue homeostasis once an infection is controlled.

Antibodies are widely used as cancer therapeutics, but their current use is limited by the low number of antigens restricted to cancer cells. A receptor tyrosine kinase, receptor tyrosine kinase-like orphan receptor 2 (ROR2), is normally expressed only during embryogenesis and is tightly down-regulated in postnatal healthy tissues. However, it is up-regulated in a diverse set of hematologic and solid malignancies, thus ROR2 represents a candidate antigen for antibody-based cancer therapy. Here we describe the affinity maturation and humanization of a rabbit mAb that binds human and mouse ROR2 but not human ROR1 or other human cell-surface antigens. Co-crystallization of the parental rabbit mAb in complex with the human ROR2 kringle domain (hROR2-Kr) guided affinity maturation by heavy-chain complementarity-determining region 3 (HCDR3)-focused mutagenesis and selection. The affinity-matured rabbit mAb was then humanized by complementarity-determining region (CDR) grafting and framework fine tuning and again co-crystallized with hROR2-Kr. We show that the affinity-matured and humanized mAb retains strong affinity and specificity to ROR2 and, following conversion to a T cell–engaging bispecific antibody, has potent cytotoxicity toward ROR2-expressing cells. We anticipate that this humanized affinity-matured mAb will find application for antibody-based cancer therapy of ROR2-expressing neoplasms.

Protease-activated receptor 2 (PAR-2) is activated by secreted proteases from immune cells or fungi. PAR-2 is normally expressed basolaterally in differentiated nasal ciliated cells. We hypothesized that epithelial remodeling during diseases characterized by cilial loss and squamous metaplasia may alter PAR-2 polarization. Here, using a fluorescent arrestin assay, we confirmed that the common fungal airway pathogen Aspergillus fumigatus activates heterologously-expressed PAR-2. Endogenous PAR-2 activation in submerged airway RPMI 2650 or NCI–H520 squamous cells increased intracellular calcium levels and granulocyte macrophage–colony-stimulating factor, tumor necrosis factor α, and interleukin (IL)-6 secretion. RPMI 2650 cells cultured at an air–liquid interface (ALI) responded to apically or basolaterally applied PAR-2 agonists. However, well-differentiated primary nasal epithelial ALIs responded only to basolateral PAR-2 stimulation, indicated by calcium elevation, increased cilia beat frequency, and increased fluid and cytokine secretion. We exposed primary cells to disease-related modifiers that alter epithelial morphology, including IL-13, cigarette smoke condensate, and retinoic acid deficiency, at concentrations and times that altered epithelial morphology without causing breakdown of the epithelial barrier to model early disease states. These altered primary cultures responded to both apical and basolateral PAR-2 stimulation. Imaging nasal polyps and control middle turbinate explants, we found that nasal polyps, but not turbinates, exhibit apical calcium responses to PAR-2 stimulation. However, isolated ciliated cells from both polyps and turbinates maintained basolateral PAR-2 polarization, suggesting that the calcium responses originated from nonciliated cells. Altered PAR-2 polarization in disease-remodeled epithelia may enhance apical responses and increase sensitivity to inhaled proteases.

β-1,3-d-Glucan is a ubiquitous glucose polymer produced by plants, bacteria, and most fungi. It has been used as a diagnostic tool in patients with invasive mycoses via a highly-sensitive reagent consisting of the blood coagulation system of horseshoe crab. However, no method is currently available for measuring β-1,6-glucan, another primary β-glucan structure of fungal polysaccharides. Herein, we describe the development of an economical and highly-sensitive and specific assay for β-1,6-glucan using a modified recombinant endo-β-1,6-glucanase having diminished glucan hydrolase activity. The purified β-1,6-glucanase derivative bound to the β-1,6-glucan pustulan with a KD of 16.4 nm. We validated the specificity of this β-1,6-glucan probe by demonstrating its ability to detect cell wall β-1,6-glucan from both yeast and hyphal forms of the opportunistic fungal pathogen Candida albicans, without any detectable binding to glucan lacking the long β-1,6-glucan branch. We developed a sandwich ELISA-like assay with a low limit of quantification for pustulan (1.5 pg/ml), and we successfully employed this assay in the quantification of extracellular β-1,6-glucan released by >250 patient-derived strains of different Candida species (including Candida auris) in culture supernatant in vitro. We also used this assay to measure β-1,6-glucan in vivo in the serum and in several organs in a mouse model of systemic candidiasis. Our work describes a reliable method for β-1,6-glucan detection, which may prove useful for the diagnosis of invasive fungal infections.

Actinobacillus pleuropneumoniae (App) is the etiological agent of acute porcine pneumonia and responsible for severe economic losses worldwide. The capsule polymer of App serotype 1 (App1) consists of [4)-GlcNAc-β(1,6)-Gal-α-1-(PO4-] repeating units that are O-acetylated at O-6 of the GlcNAc. It is a major virulence factor and was used in previous studies in the successful generation of an experimental glycoconjugate vaccine. However, the application of glycoconjugate vaccines in the animal health sector is limited, presumably because of the high costs associated with harvesting the polymer from pathogen culture. Consequently, here we exploited the capsule polymerase Cps1B of App1 as an in vitro synthesis tool and an alternative for capsule polymer provision. Cps1B consists of two catalytic domains, as well as a domain rich in tetratricopeptide repeats (TPRs). We compared the elongation mechanism of Cps1B with that of a ΔTPR truncation (Cps1B-ΔTPR). Interestingly, the product profiles displayed by Cps1B suggested processive elongation of the nascent polymer, whereas Cps1B-ΔTPR appeared to work in a more distributive manner. The dispersity of the synthesized products could be reduced by generating single-action transferases and immobilizing them on individual columns, separating the two catalytic activities. Furthermore, we identified the O-acetyltransferase Cps1D of App1 and used it to modify the polymers produced by Cps1B. Two-dimensional NMR analyses of the products revealed O-acetylation levels identical to those of polymer harvested from App1 culture supernatants. In conclusion, we have established a protocol for the pathogen-free in vitro synthesis of tailored, nature-identical App1 capsule polymers.