Source: www.brooklynpaper.com - Saturday, May 09, 2020
The owner of the iconic Park Slope events venue Grand Prospect Hall, Michael Halkias, died from COVID-19 on Wednesday. He was 82. Halkias’ death sent shockwaves throughout Brooklyn, where community leaders and friends remember him as a passionate, generous figure. “ He was a Brooklyn character for sure in the best sort of way,” said Randy Peers, president and CEO of the Brooklyn Chamber of Commerce. “He was larger than life.” Halkias and his wife Alice bought Grand Prospect Hall in 1984 and turned the extravagant Prospect Avenue building into an opulent catering hall. The space became a New York icon because of the its long-running, popular commercials, where Alice Halkias declares in a Greek accent, “We make your dreams come true!” Saturday Night Live spoofed the famous commercial in February of 2019, and the pair appeared on Jimmy Kimmel Live in October to remake the ad with Mets player Pete Alonso. Grand Prospect Hall, a Victorian banquet hall built in 1892, attracted big names such as dancer Fred Astaire and mafioso Al Capone during its heyday in the early 20th century — and boasted some of the borough’s oldest treasures, such as Brooklyn’s first reported elevator, which functions to this day. But by the 1980s, the landmarked building had fallen into disrepair: its walls had been painted black, molding had been stripped off the walls, and the chandeliers were gone, Halkias told Brooklyn Paper in 2004. The couple spent 20 yea

Students with dyslexia often struggle with math fluency as well, and scholars at a recent conference put a spotlight on some of the possible connections.

The National Math and Science Initiative's new tool aims to help the field look for patterns in STEM data, so educators and policy folks can fill in holes.

At Battle High School in Columbia, Mo., students in geometry class have swapped their compasses and protractors for hammers and hard hats. And they're doing it for a good cause.

If you contracted the coronavirus at work, you may be able to claim for temporary or permanent disability, depending on how you were affected - but you will have to prove that you did, in fact, become ill at work.

If you're shopping for a gamer, especially if you can pin down their preferred platform, these cheap but fun accessories are guaranteed winners.

Valve's tweet describes the upcoming title Half-Life: Alyx as the company's 'flagship VR game.' So you'll probably need a virtual headset to play it. The company will reveal more details on Thursday.

On Thursday, Valve showed off footage for Half-Life: Alyx, which will be set before the events of Half-Life 2. Instead of using a mouse and keyboard, you'll need a VR headset to play it.

The unexpected transition to online classes due to the COVID-19 pandemic has prompted many changes for undergraduate students and their instructors. To understand the magnitude of these impacts and potentially improve digital learning, researchers in the Penn State School of Engineering Design and Professional Programs have received a $196,136 grant from the National Science Foundation.

The National Sustainable Structures Center of Pennsylvania College of Technology, the mid-Atlantic administrator of the Building Operator Certification, will offer two BOC Level I courses at a 75% discount made possible by a grant from the Pennsylvania Department of Environmental Protection.

When can schools use federal funds to help students with disabilities prepare for life after special education? A new resource from the federal education department offers a road map.

Source: www.businessinsider.com - Saturday, May 09, 2020
Many superyacht crew members have been stuck on their vessels after lockdowns and travel bans were instated due to the coronavirus pandemic. We spoke to crew members who felt 'lucky' to be quarantined in such luxury digs — and grateful to still have jobs and secure wages. There is still plenty of work to be done, but workers also described trivia games, sundeck BBQs, and hot tub nights they're using to pass the time and bond with colleagues. Strict new hygiene and sanitation rules have also been put into place. Visit Business Insider's homepage for more stories . In late March, billionaire businessman David Geffen posted a shot on Instagram taken from his 452-foot superyacht Rising Sun. It was hastily deleted — but not before it had raised more than a few eyebrows and stirred discourse around the 1% and their self-isolation privilege. But it's not just the rare billionaire who is bunkering down on their yacht during the COVID-19 pandemic. Here is another group of people for whom this is a new reality: the yacht's crews.  Before this crisis, there were around 80,000 people employed on pleasure craft around the globe, according to Laurence Lewis, CEO of YPI Crew, a yacht recruitment agency. As countries rushed to close their borders, ports were closed — and overnight, many found themselves unable to travel to get to or leave their yachts.  For many, a superyacht sounds like the dream scenario to see out lockdown. But is it?  "Ther

For communities with significant numbers of Latino and immigrant residents, the barriers to an accurate 2020 Census count are high—and so are the stakes for their schools, which could lose hundreds of millions of dollars if counts are inaccurate.

Some educators and advocates fear the rule will dissuade immigrants from seeking certain government benefits, and that further burdens will fall on schools.

The Fujifilm X-Pro3 is a love letter to rangefinder aficionados, and does the best job (this side of Leica) of making the digital experience feel a bit more like film.

The Fujiflim X100 series, now entering its fifth generation, has always wowed with retro chic looks. The latest, the X100V, includes an all-new lens, an improved image sensor, and, for the first time, dust and splash protection for all-weather photography.

Even in its pre-production state, Fujifilm's X-T4 camera looks to be among the company's finest efforts to date.

The Fujifilm X-A7 has a big, swing-out screen, excellent color options, and capable autofocus—but no electronic viewfinder.

Saudi Arabia has begun an internal investigation into the disappearance of a prominent journalist at its Istanbul consulate and could hold people accountable if the evidence warrants it, according to a Saudi official.

An op-ed in Saudi-owned Al Arabiya news has warned of repercussions should the US impose sanctions on Saudi Arabia over the disappearance of journalist Jamal Khashoggi.

Strategic partnerships could be used to create win-win outcomes, says Sifiso Skenjana.

Argentina is a case study in what happens when an economy already on its knees implements an aggressive lockdown, says Mac Margolis.

All is in place for a violent confrontation in Burundi. The failed coup on 13 May has intensified opposition to President Pierre Nkurunziza’s push for a third term in office. After ten years of peace, Burundi is in danger of reopening the fault lines that once led the country into civil war.

Texas has become the first state to have its "alternate assessment aligned to modified academic-achievement standards" pass the U.S. Department of Education's peer-review process.

Federal law requires states to report student test scores in achievement levels, but leaders in the Golden State want to take a different approach.

This article, published ahead of print on 28 July 2008, has been withdrawn by the authors. Although moderate synergy between P2-RANTES and C peptides can be observed with high statistical significance in cell fusion assays, this synergy was not able to be verified in HIV viral assays. The authors regret the overstatement of synergy and will revise the paper for publication at a later date.

Lipid II is an essential precursor of the bacterial cell wall biosynthesis and thereby an important target for various antibiotics. Several lanthionine-containing peptide antibiotics target lipid II with lanthionine-stabilized lipid II-binding motifs. Here, we used the biosynthesis system of the lantibiotic nisin to synthesize a two lipid II binding motifs-containing lantibiotic, termed TL19, which contains the N-terminal lipid II binding motif of nisin and the distinct C-terminal lipid II binding motif of one peptide of the two-component haloduracin (i.e. HalA1). Further characterization demonstrated that (i) TL19 exerts 64-fold stronger antimicrobial activity against E. faecium than nisin (1-22), which has only one lipid II binding site, and (ii) both the N- and C-terminal domains are essential for the potent antimicrobial activity of TL19, as evidenced by mutagenesis of each single and double domains. These results show the feasibility of a new approach to synthesize potent lantibiotics with two different lipid II binding motifs to treat specific antibiotic-resistant pathogens.

Since 2012, single low dose of primaquine (SLDPQ, 0.25mg/kg) has been recommended with artemisinin-based combination therapies, as first-line treatment of acute uncomplicated Plasmodium falciparum malaria, to interrupt its transmission, especially in low transmission settings of multidrug, including artemisinin, resistance. Policy makers in Cambodia have been reluctant to implement this recommendation due to primaquine safety concerns and lack of data on its efficacy.

In this randomized controlled trial, 109 Cambodians with acute uncomplicated P. falciparum malaria received dihydroartemisinin-piperaquine (DP) alone or combined with SLDPQ on the first treatment day. Transmission-blocking efficacy of SLDPQ was evaluated on Days 0, 1, 2, 3, 7, 14, 21, 28 and recrudescence by reverse transcriptase polymerase chain reaction (RT-PCR) (gametocyte prevalence) and membrane-feeding assays with Anopheles minimus mosquitoes (gametocyte infectivity). Without the influence of recrudescent infections, DP+SLDPQ reduced gametocyte carriage 3 fold compared to DP. Of 48 patients tested on Day 0, only three patients were infectious to mosquitoes (~6%). Post-treatment, three patients were infectious: on D14 (3.5%, 1/29), and on the first and seventh day of recrudescence (8.3%, 1/12 for each); this overall low infectivity precluded our ability to assess its transmission blocking efficacy.

Our study confirms effective gametocyte clearance of SLDPQ when combined with DP in multidrug resistant P. falciparum and the negative impact of recrudescent infections due to poor DP efficacy. Artesunate-mefloquine (ASMQ) has replaced DP and ASMQ-SLDPQ has been deployed to treat all P. falciparum symptomatic patients to further support the elimination of multidrug resistant P. falciparum in Cambodia.

The biologic Griffithsin (GRFT) has recently emerged as a candidate to safely prevent sexually transmitted infections (STIs) including human immunodeficiency virus (HIV-1) and herpes simplex virus 2 (HSV-2). However, to date, there are few delivery platforms that are available to effectively deliver biologics to the female reproductive tract (FRT). The goal of this work was to evaluate rapid-release polyethylene oxide (PEO), polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) fibers, that incorporate GRFT, in in vitro (HIV-1 and HSV-2) and in vivo (HSV-2) infection models. GRFT loading was determined via ELISA, and the bioactivity of GRFT fibers was assessed using in vitro HIV-1 pseudovirus and HSV-2 plaque assays. Afterwards, the efficacy of GRFT fibers was assessed in a murine model of lethal HSV-2 infection. Finally, murine reproductive tracts and vaginal lavages were evaluated for histology and cytokine expression, 24 and 72 hr after fiber administration, to determine safety. All rapid-release formulations achieved high levels of GRFT incorporation and were completely efficacious against in vitro HIV-1 and HSV-2 infections. Importantly, all rapid-release GRFT fibers provided potent protection in a murine model of HSV-2 infection. Moreover, histology and cytokine levels, evaluated from collected murine reproductive tissues and vaginal lavages treated with blank fibers, showed no increased cytokine production or histological aberrations, demonstrating the preliminary safety of rapid-release GRFT fibers in vaginal tissue.

Clostridioides difficile, the leading cause of nosocomial infections, is an urgent health threat worldwide. The increased incidence and severity of disease, the high recurrence rates, and the dearth of effective anticlostridial drugs have created an urgent need for new therapeutic agents. In an effort to discover new drugs for treatment of Clostridioides difficile infections (CDIs), we investigated a panel of FDA-approved antiparasitic drugs against C. difficile and identified diiodohydroxyquinoline (DIHQ), an FDA-approved oral antiamoebic drug. DIHQ exhibited potent activity against 39 C. difficile isolates, inhibiting growth of 50% and 90% of these isolates at the concentrations of 0.5 μg/mL and 2 μg/mL, respectively. In a time-kill assay, DIHQ was superior to vancomycin and metronidazole, reducing a high bacterial inoculum by 3-log₁₀ within six hours. Furthermore, DIHQ reacted synergistically with vancomycin and metronidazole against C. difficile in vitro. Moreover, at subinhibitory concentrations, DIHQ was superior to vancomycin and metronidazole in inhibiting two key virulence factors of C. difficile, toxin production and spore formation. Additionally, DIHQ did not inhibit growth of key species that compose the host intestinal microbiota, such as Bacteroides, Bifidobacterium and Lactobacillus spp. Collectively, our results indicate that DIHQ is a promising anticlostridial drug that warrants further investigation as a new therapeutic for CDIs.

Bunyaviruses are significant human pathogens, causing diseases ranging from hemorrhagic fevers to encephalitis. Among these viruses, La Crosse virus (LACV), a member of the California serogroup, circulates in the eastern and midwestern United States. While LACV infection is often asymptomatic, dozens of cases of encephalitis are reported yearly. Unfortunately, no antivirals have been approved to treat LACV infection. Here, we developed a method to rapidly test potential antivirals against LACV infection. From this screen, we identified several potential antiviral molecules, including known antivirals. Additionally, we identified many novel antivirals that exhibited antiviral activity without affecting cellular viability. Valinomycin, a potassium ionophore, was among our top targets. We found that valinomycin exhibited potent anti-LACV activity in multiple cell types in a dose-dependent manner. Valinomycin did not affect particle stability or infectivity, suggesting that it may preclude virus replication by altering cellular potassium ions, a known determinant of LACV entry. We extended these results to other ionophores and found that the antiviral activity of valinomycin extended to other viral families including bunyaviruses (Rift Valley fever virus, Keystone virus), enteroviruses (Coxsackievirus, rhinovirus), flavirivuses (Zika), and coronaviruses (HCoV-229E and MERS-CoV). In all viral infections, we observed significant reductions in virus titer in valinomycin-treated cells. In sum, we demonstrate the importance of potassium ions to virus infection, suggesting a potential therapeutic target to disrupt virus replication.

Importance No antivirals are approved for the treatment of bunyavirus infection. The ability to rapidly screen compounds and identify novel antivirals is one means to accelerate drug discovery for viruses with no approved treatments. We used this approach to screen hundreds of compounds against La Crosse virus, an emerging bunyavirus that causes significant disease, including encephalitis. We identified several known and previously unidentified antivirals. We focused on a potassium ionophore, valinomycin, due to its promising in vitro antiviral activity. We demonstrate that valinomycin, as well as a selection of other ionophores, exhibits activity against La Crosse virus as well as several other distantly related bunyaviruses. We finally observe that valinomycin has activity against a wide array of human viral pathogens, suggesting that disrupting potassium ion homeostasis with valinomycin may be a potent host pathway to target to quell virus infection.

Aspergillus niger, the third species responsible for invasive aspergillosis has been considered as a homogeneous species until DNA-based identification uncovered many cryptic species. These species have been recently reclassified into the Aspergillus section Nigri. However little is yet known among the section Nigri about the species distribution and the antifungal susceptibility pattern of each cryptic species. A total of 112 clinical isolates collected from 5 teaching hospitals in France and phenotypically identified as A. niger were analyzed. Identification to the species level was carried out by nucleotide sequence analysis. The Minimum Inhibitory Concentrations (MICs) of itraconazole, voriconazole, posaconazole, isavuconazole and amphotericin B were determined by both the EUCAST and gradient concentration strips methods. Aspergillus tubingensis (n=51, 45.5%) and A. welwitschiae (n=50, 44.6%) were the most common species while A. niger accounted for only 6.3% (n=7). The MICs of azoles drugs were higher for A. tubingensis than for A. welwitschiae. The MIC of amphotericin B was 2 mg/L or less for all isolates. Importantly, MICs determined by EUCAST showed no correlation with those determined by gradient concentration strips methods, these latter being lower than the former (Spearman's rank correlation tests ranging - depending on the antifungal agent - from 0.01 to 0.25; p>0.4). In conclusion, A. niger should be considered as a minority species in the section Nigri. The differences in MICs between species for different azoles underline the importance of accurate identification. Significant divergences in the determination of MIC between EUCAST and gradient concentration strips methods require further investigation.

Staphylococcus aureus osteomyelitis is a debilitating infection of bone. Treatment of osteomyelitis is impaired by the propensity of invading bacteria to induce pathologic bone remodeling that may limit antibiotic penetration to the infectious focus. The nonsteroidal anti-inflammatory drug diflunisal was previously identified as an osteoprotective adjunctive therapy for osteomyelitis, based on the ability of this compound to inhibit S. aureus quorum sensing and subsequent quorum-dependent toxin production. When delivered locally during experimental osteomyelitis, diflunisal significantly limits bone destruction without affecting bacterial burdens. However, because diflunisal's "quorum-quenching" activity could theoretically increase antibiotic recalcitrance, it is critically important to evaluate this adjunctive therapy in the context of standard of care antibiotics. The objective of this study is to evaluate the efficacy of vancomycin to treat osteomyelitis during local diflunisal treatment. We first determined that systemic vancomycin effectively reduces bacterial burdens in a murine model of osteomyelitis, and identified a dosing regimen that decreases bacterial burdens without eradicating infection. Using this dosing scheme, we found that vancomycin activity is unaffected by the presence of diflunisal in vitro and in vivo. Similarly, locally-delivered diflunisal still potently inhibits osteoblast cytotoxicity in vitro and bone destruction in vivo in the presence of sub-therapeutic vancomycin. However, we also found that the resorbable polyurethane foams used to deliver diflunisal serve as a nidus for infection. Taken together, these data demonstrate that diflunisal does not significantly impact standard of care antibiotic therapy for S. aureus osteomyelitis, but also highlight potential pitfalls encountered with local drug delivery.

One of the reasons for the lengthy tuberculosis (TB) treatment is the difficult to treat non-multiplying mycobacterial subpopulation. In order to assess the ability of (new) TB drugs to target this subpopulation, we need to incorporate dormancy models in our pre-clinical drug development pipeline. In most available dormancy models it takes a long time to create a dormant state and it is difficult to identify and quantify this non-multiplying condition.

The Mycobacterium tuberculosis 18b strain might overcome some of these problems, because it is dependent on streptomycin for growth and becomes non-multiplying after 10 days of streptomycin starvation, but still can be cultured on streptomycin-supplemented culture plates. We developed our 18b dormancy time-kill kinetic model to assess the difference in the activity of isoniazid, rifampicin, moxifloxacin and bedaquiline against log-phase growth compared to the non-multiplying M. tuberculosis subpopulation by CFU counting including a novel AUC-based approach as well as time-to-positivity (TTP) measurements.

We observed that isoniazid and moxifloxacin were relatively more potent against replicating bacteria, while rifampicin and high dose bedaquiline were equally effective against both subpopulations. Moreover, the TTP data suggest that including a liquid culture-based method could be of additional value as it identifies a specific mycobacterial subpopulation that is non-culturable on solid media.

In conclusion, the results of our study underline that the time-kill kinetics 18b dormancy model in its current form is a useful tool to assess TB drug potency and thus has its place in the TB drug development pipeline.

A case of M. leprae rifampicin resistance after irregular anti-leprosy treatments since 1971 is reported. Whole-genome sequencing from four longitudinal samples indicated relapse due to acquired rifampicin resistance and not to reinfection with another strain. A putative compensatory mutation in rpoC was also detected. Clinical improvement was achieved using an alternative therapy.

Many transferable quinolone-resistance mechanisms have been already identified in Gram-negative bacteria. The plasmid-encoded 65 amino-acid long ciprofloxacin-modifying enzyme, namely CrpP, was recently identified in Pseudomonas aeruginosa. We analyzed a collection of 100 clonally-unrelated and multidrug-resistant P. aeruginosa clinical isolates among which 46 (46%) were found positive for crpP-like genes, encoding five CrpP variants conferring variable levels of reduced susceptibility to fluoroquinolones. Those crpP-like genes were chromosomally located, as part of PAGI-like pathogenicity genomic islands.

Drug repositioning is the only feasible option to address the COVID-19 global challenge immediately. We screened a panel of 48 FDA-approved drugs against SARS-CoV-2 which were pre-selected by an assay of SARS-CoV and identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low micromolar IC50s and in particular, two FDA-approved drugs - niclosamide and ciclesonide – were notable in some respects.

"The entire energy market is still on a knife edge," says an economist.

Oil was headed for the longest run of daily gains in more than nine months on signs the worst of the supply glut may be over as production cuts start to take effect.

On the currency market, the rand traded softer against the greenback as it slipped to a session low of R18.77/$.

BACKGROUND:

The ability of the decades-old Boston and Philadelphia criteria to accurately identify infants at low risk for serious bacterial infections has not been recently reevaluated.

Ahead of Matchday 7, UEFA.com looks at some obvious selections and some lesser-owned options.

Elizabeth Stringer Keefe, Becky Shiring, Katie Robinson, Dr. Sonny Magana and Dr. Monica Burns contribute their suggestions on using tech to differentiate instruction.

An AI-powered digital assistant to take notes for you? It’s already happening in the workplace, but classroom note taking could prove harder to automate.

Michelle R. Darnell, associate clinical professor in management and director of honor and integrity at Smeal, has been appointed as the inaugural director of the Tarriff Center for Business Ethics and Social Responsibility.

Students celebrated for athletic and student life achievements during the Finally Finished Fest

If you're buying for someone who lives by the SoulCycle schedule, or wants to get in shape in 2020, this is the gift guide for you.

If you're looking to get the perfect gift for the golfer in your life, here are 19 geeky golf gadgets they will love.