Filed under: North America, United States, Hotels and Accommodations

• it's warm and you're not
• former mayor Bob Filner is under house arrest, so there's less of a chance you'll get harassed
• you want to ice skate outside but don't like the cold

Continue reading Because There Aren't Enough Reasons to Visit San Diego in Winter, Now You Can Ice Skate

Because There Aren't Enough Reasons to Visit San Diego in Winter, Now You Can Ice Skate originally appeared on Gadling on Tue, 10 Dec 2013 15:32:00 EST. Please see our terms for use of feeds.

Filed under: Food and Drink, North America, United States

• Regardless of the area's suitability for growing grapes, plop down a vineyard or winery and travelers will come for a taste and buy a sympathy bottle (pro tip: go for the ice wine as it's harder to mess up)
• Ski resorts looking to attract off-season dollars or stale attractions looking to draw media coverage and visitors hook up a zipline

Continue reading Vineyard and Zipline Trends Collide at the Pinot Express

Vineyard and Zipline Trends Collide at the Pinot Express originally appeared on Gadling on Wed, 11 Dec 2013 16:54:00 EST. Please see our terms for use of feeds.

Filed under: North America, United States

Continue reading Sorry Indianapolis, You're No Longer the Sole Location Offering TSA PreCheck Enrollment Background Checks

Sorry Indianapolis, You're No Longer the Sole Location Offering TSA PreCheck Enrollment Background Checks originally appeared on Gadling on Mon, 16 Dec 2013 15:07:00 EST. Please see our terms for use of feeds.

Filed under: Asia, Japan, Airlines, News

Continue reading Another Boeing 787 Dreamliner Has a Battery Problem

Another Boeing 787 Dreamliner Has a Battery Problem originally appeared on Gadling on Tue, 14 Jan 2014 14:57:00 EST. Please see our terms for use of feeds.

Ultimately, there are no easy solutions to reigniting a Covid-19 affected economy. It is evident, however, that addressing the public health crisis is non-negotiable, writes Haroon Bhorat.

The government locked down South Africa without knowing exactly how the virus works. And while there is evidence it helped to "flatten the curve", its time to reopen more of the economy, writes Thabi Leoka.

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

Two more businesses operating in Calgary have been shut down by health officials for violating the province's rules regarding COVID-19.

Frank Soo, the first and only player of Asian heritage to represent England's national football team, has been honoured by Google.

The DML News App offers the best in news reporting.

The post REPORT: National parks visitors should plan for ‘new normal’ appeared first on Dennis Michael Lynch.

The DML News App offers the best in news reporting.

The post VIDEO: Lindsey Graham puts Obama on notice after Justice Department swipe appeared first on Dennis Michael Lynch.

The city says couples can book its Helena Gutteridge Plaza at City Hall for just $85 and bring eight guests to have an outdoor, physically distant wedding ceremony.

The following article, California Sheriff Refuses to Arrest People Defying Stay-at-Home Order: “There cannot be a new normal”, was first published on 100PercentFedUp.com.

Riverside, California Sheriff Chad Bianco spoke to the Riverside Board of Supervisors on May 5th to say that he will not enforce the stay-at-home order in California. He tells people who are afraid of contracting the coronavirus that they should stay home if they want to. Bianco continues with the suggestion that any business owner […]

Continue reading: California Sheriff Refuses to Arrest People Defying Stay-at-Home Order: “There cannot be a new normal” ...

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” ...

8 November 2013

Members Event

Event participants

Professor Shaun Breslin, Associate Fellow, Asia Programme, Chatham House
Professor Jane Duckett, Edward Caird Chair of Politics; Director, Confucius Institute; Director, The Scottish Centre for China Research, University of Glasgow
Professor Christopher Hughes, Head, International Relations Department, LSE
Chair: Rob Gifford, China Editor, 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

Invitation Only Research Event

17 May 2016

14 July 2016

Hidden in the flash. posted a photo:

With a lockdown in place it is against the rules for me to go to places I like to shoot, so I though I would try to create a series called Isolated creativity. The series is not intended to be a diary but a way of documenting thoughts and emotions via photography.

I've felt a bit like Pink Rabbit over the passed few day. I'm not fed up and depressed by the lockdown but by the people who think that it's okay to break the rules. By the tabloid media that run stories that convince people it's okay to go out and about, when it Isn't. By the political points scoring that has started to appear in all forms of media.Lastly I fed up with second home owners that have turned up during lockdown and appear to be going out and about most days.

Just like Pink Rabbit I have the blues.

Iker Merodio | Photography posted a photo:

Martinen dinosaurioa.

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

The White House has halted talks with Congress over any further coronavirus stimulus package as it waits for more information about how U.S. state reopenings affect the economy, White House top economic adviser Larry Kudlow told reporters on Friday. The Senate and House of Representatives have already passed four major bills to address the novel coronavirus outbreak, including three aimed at stabilizing the economy as most Americans have sheltered in place and unemployment has soared.

The former Senate staffer, who is accusing Joe Biden of sexually assaulting her 27 years ago, is being represented by a lawyer who is also a donor to President Trump.

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

The government said it's distributing the promising coronavirus drug, remdesivir, to some hard-hit states. Eventually, all 50 states should get it.

"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."

Attorney General Bill Barr explained that the FBI did not conduct “a bonafide counterintelligence investigation” in the case that led former Trump national security adviser Michael Flynn to plead guilty to federal investigators in 2017.Barr, speaking in an exclusive interview with CBS News after the Justice Department dropped its case against Flynn on Thursday, said that his review of the case found Bureau investigators laid “a perjury trap” for Flynn in a January 2017 White House interview.“They didn’t warn him, the way that would usually be required by the Department, they bypassed the Justice Department, they bypassed the protocols at the White House, and so forth,” Barr stated. “These were things that persuaded me that there was not a legitimate counterintelligence investigation.”Former FBI director James Comey admitted in a December 2018 interview that he “sent” the agents to interview Flynn, adding that it was “something I probably wouldn’t have done or maybe gotten away with in a more organized administration.”In its Thursday court filing, the Justice Department explained that it was “not persuaded” that Flynn’s interview, which led to his guilty plea for lying to FBI agents Peter Strzok and Joe Pientka, had proper predication and was materially relevant.Comey tweeted his disappointment, following the decision, saying "the DOJ has lost its way."> The DOJ has lost its way. But, career people: please stay because America needs you. The country is hungry for honest, competent leadership.> > -- James Comey (@Comey) May 7, 2020Barr pointed to recently-released information that showed the FBI moved to close its surveillance of Flynn after finding “no derogatory information” about the retired general’s contacts with Russians, only for Strzok to keep the case open, leading to the eventual interview.“They were closing the investigation, in December [2016], they started that process and on January 4, they were closing it. When they heard about the phone call, which the FBI had the transcripts to — there was no question as to what was discussed, the FBI knew exactly what was discussed — and General Flynn, being the former director of the DIA, said to them, ‘you listen to everything, you know what was said,’” Barr explained.“So there’s no mystery about the call, but they initially tried some theories of how could open another investigation, which didn’t fly, and then they found out that they had not technically closed the earlier investigation, and they kept it open for the expressed purpose of trying to catch — lay a perjury trap — for General Flynn,” he added. A different filing released last week showed handwritten notes from an FBI official that questioned if the goal of Flynn’s White House interview was “to get him to lie, so we can prosecute him or get him fired.”Barr also did not comment on whether those that sought to entrap Flynn would face criminal charges, pointing to U.S. Attorney John Durham’s probe into the origins of the Trump-Russia investigation and saying his team was “in the middle” of “looking at the whole pattern of conduct.”“I’m going to wait until all the evidence is [in], and I get their recommendations as to what they found and how serious it is. But, if we were to find wrongdoing, in the sense of any criminal act, obviously we would follow through on that,” Barr said. “But again, just because something may even stink to high heaven, and appear to everyone to be bad, we still have to apply the right standard and be convinced that there is a violation of a criminal statute and that we can prove it beyond a reasonable doubt. The same standard applies to everybody.”

Bacterial products such as lipopolysaccharides (or endotoxin) cause systemic inflammation, resulting in a substantial global health burden. The onset, progression, and resolution of the inflammatory response to endotoxin are usually tightly controlled to avoid chronic inflammation. Members of the NF-κB family of transcription factors are key drivers of inflammation that activate sets of genes in response to inflammatory signals. Such responses are typically short-lived and can be suppressed by proteins that act post-translationally, such as the SOCS (suppressor of cytokine signaling) family. Less is known about direct transcriptional regulation of these responses, however. Here, using a combination of in vitro approaches and in vivo animal models, we show that endotoxin treatment induced expression of the well-characterized transcriptional repressor Krüppel-like factor 3 (KLF3), which, in turn, directly repressed the expression of the NF-κB family member RELA/p65. We also observed that KLF3-deficient mice were hypersensitive to endotoxin and exhibited elevated levels of circulating Ly6C+ monocytes and macrophage-derived inflammatory cytokines. These findings reveal that KLF3 is a fundamental suppressor that operates as a feedback inhibitor of RELA/p65 and may be important in facilitating the resolution of inflammation.

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.

Bacterial biofilms are cellular communities that produce an adherent matrix. Exopolysaccharides are key structural components of this matrix and are required for the assembly and architecture of biofilms produced by a wide variety of microorganisms. The human bacterial pathogens Escherichia coli and Salmonella enterica produce a biofilm matrix composed primarily of the exopolysaccharide phosphoethanolamine (pEtN) cellulose. Once thought to be composed of only underivatized cellulose, the pEtN modification present in these matrices has been implicated in the overall architecture and integrity of the biofilm. However, an understanding of the mechanism underlying pEtN derivatization of the cellulose exopolysaccharide remains elusive. The bacterial cellulose synthase subunit G (BcsG) is a predicted inner membrane–localized metalloenzyme that has been proposed to catalyze the transfer of the pEtN group from membrane phospholipids to cellulose. Here we present evidence that the C-terminal domain of BcsG from E. coli (EcBcsGΔN) functions as a phosphoethanolamine transferase in vitro with substrate preference for cellulosic materials. Structural characterization of EcBcsGΔN revealed that it belongs to the alkaline phosphatase superfamily, contains a Zn2+ ion at its active center, and is structurally similar to characterized enzymes that confer colistin resistance in Gram-negative bacteria. Informed by our structural studies, we present a functional complementation experiment in E. coli AR3110, indicating that the activity of the BcsG C-terminal domain is essential for integrity of the pellicular biofilm. Furthermore, our results established a similar but distinct active-site architecture and catalytic mechanism shared between BcsG and the colistin resistance enzymes.

Noncoercive, pay-to-go, voluntary, assisted voluntary, and nonforced returns generally can offer paid travel and/or other financial incentive to encourage unauthorized immigrants to cooperate with immigration officials and leave host countries. A look at three key rationales for governments to choose pay-to-go and other returns.

Drawing on experiences from Asia, Europe, North America, and the Pacific region, this report presents eight strategies that represent best practices developed by immigrant-receiving countries to increase the economic contributions of immigration.

The United States has historically offered unparalleled economic opportunity to successive generations of immigrants and their children, poised to play an increasing role in the U.S. economy. But the lasting impact of job loss and slower growth over the next decade will translate into fewer opportunities for workers—and immigrants may prove the most vulnerable.

THE LAST two months have been two of the worst in the life of former national netball star Nichala Gibson. She lives in New York City, the epicentre for the COVID-19 virus in the United States. Gibson and her sister suffered, then recovered from...

Losses within the entertainment industry are already estimated to be in the billions as the sector continues to reel from the impacts of COVID-19. Major events like Reggae Sumfest, which has already been cancelled this year, had an estimated...

Almost five years ago, lawmakers on a bipartisan committee of Parliament agreed unanimously to amend the law to give the Independent Commission of Investigations (INDECOM) the power to arrest and prosecute cops. That proposed amendment, which was...

May 9 marked a very special day for all Russians as the day of the victory over Nazi Germany in the Great Patriotic war. At 00:16 hours on that day in 1945 Act of Military Surrender was signed by the German military leaders in Berlin. The...

ADVISORY COLUMN: SMALL BUSINESS On Thursday, May 7, the RJR/GLEANER Communications group staged a virtual town hall meeting on Television Jamaica titled “COVID-19...

The coronavirus pandemic (COVID-19) has resulted in many opportunities for the health technology industry. Our usually technophobic population has been embracing technology more and more since the start of the restrictions due to the spread of...

This edited volume from the World Health Organization (WHO), which includes chapters written by MPI researchers, examines country-level responses to the international movement of health-care workers, both before and after adoption of the WHO’s Global Code of Practice on the International Recruitment of Health Personnel.

Millie Small, the first Jamaican vocalist in popular music to make the world stop and look at Jamaica as an emerging musical powerhouse, passed away in London on May 5. She was 72 years old. Speaking to Small by telephone from her home in Shepherd’...

This report provides an overview of several commonly used translation and interpretation technologies. It aims to assist language access practitioners in understanding and identifying which systems would best meet their agency’s language access needs.

A broad consensus exists that the long-term impact of immigration on Americans' average income is small but positive, improving employment, productivity, and income. In the short term, however, immigration may slightly reduce native employment and average income. This report provides an analysis of short- and long-run impacts of immigration over the business cycle.