AUTO CHINA 2015, SHANGHAI – HARMAN, the premier audio, infotainment and software services company (NYSE:HAR), continues to make strides in China’s fast-growing auto market with new business wins and market roll-outs of infotainment and audio solutions with regional OEMs.

You heard it here first: in 2018, HARMAN received a record-breaking 53 product design and technology awards, bringing our six-year-total to more than 300 awards for 190 different products.   This unprecedented number is a direct reflection of our...

Graphene particles that seed ice formation in water only need to be 8 square nanometres to kick-start the freezing process – any smaller and they can stop ice forming

The 2020 Abel prize was awarded to mathematicians Hillel Furstenberg and Gregory Margulis for their use of probability and dynamics in group theory, number theory and combinatorics

Wine tears – the drops that form inside a glass after wine is swirled in a glass – are caused by the formation of an unstable shock wave

STAMFORD, CT - HARMAN, the premium global audio and infotainment group (NYSE:HAR), has been awarded two Plus X Awards in the categories Innovation and High Quality for their ground-breaking sound solutions QuantumLogic Surround 3D and Clari-Fi. In addition, Clari-Fi also received the Plus X Award for “Best Audio Software of the Year”. The awards have been presented earlier today at the German Bundestag in Bonn. The Plus X Award honors manufacturers for new and innovative technologies, extraordinary design and intelligent and easy to use operating systems. With an international and independent panel of judges from 25 industries, the Plus X Award is the world’s largest competition for technology, sports and lifestyle.

As Thailand's capital cautiously reopens many restaurants shuttered over coronavirus fears, the feline "employees" of the Caturday Cafe are back at work.

Self-educated ice sage James Croll cracked the conundrum of why Earth periodically freezes over. He was feted in his time, so why did the world forget him?

A valley longer than the Grand Canyon hidden beneath the Greenland ice sheet may carry running water. How quickly it flows may affect how the ice melts

The Atacama Desert is one of the most hostile places on Earth, but new microbes arrive there every day on dust grains carried by the wind

From Etna to Vesuvius, Santorini to Stromboli, volcanoes have long been linked to excellent wines. New book Volcanoes and Wine explores this unlikely terroir

Ancient humans in Africa mixed far more than we thought, according to new findings revealed by sequencing the genomes of a diverse group of people from across the world

U.S. President Donald Trump said on Wednesday his White House coronavirus task force would remain in place but with a focus on medical treatments and easing restrictions on businesses and social life and perhaps with different advisers. This report produced by Chris Dignam.

London's High Court on Friday threw out part of a claim brought by Meghan, Britain's Duchess of Sussex, against a tabloid newspaper for breaching her privacy, ruling that it had not acted dishonestly. Lauren Anthony reports.

Expensive, risky and involving scores of people, live theater may be the last form of entertainment to come back - and will likely look very different when the curtain raises.

Justin Bieber and his wife Hailey Baldwin are opening up in an intimate series for Facebook Watch in which they discuss their marriage, their problems and their lives together.

Britain's Tate Modern gallery in London reveals additional building called the 'Switch House' which will open to the public on June 17.

A 3D printed grate can be used to make a smart window that blocks heat from sunlight out in the summer while letting it through in the winter, conserving energy

Payne Capital Management's Courtney Dominguez says the high level of investor pessimism indicates the markets may have bottomed. She says savings could make their way into stocks.

Title: Asthma Sufferers Win When Coal Plants Shut Down
Category: Health News
Created: 4/16/2020 12:00:00 AM
Last Editorial Review: 4/17/2020 12:00:00 AM

Title: Is Drinking Wine a Key to Antiaging?
Category: Health News
Created: 4/28/2010 9:36:00 AM
Last Editorial Review: 4/28/2010 9:36:34 AM

Title: Chewing Khat Linked to Severe Liver Damage
Category: Health News
Created: 4/28/2010 6:10:00 PM
Last Editorial Review: 4/29/2010 12:00:00 AM

Title: Twins Study Points to Environmental Cause for MS
Category: Health News
Created: 4/28/2010 2:10:00 PM
Last Editorial Review: 4/29/2010 12:00:00 AM

Title: Wine, Salt, and Your Heart: Confusion Abounds
Category: Health News
Created: 4/27/2011 11:00:00 AM
Last Editorial Review: 4/27/2011 12:00:00 AM

Title: How That Glass of Red Wine Might Help You Live Longer
Category: Health News
Created: 5/1/2012 2:06:00 PM
Last Editorial Review: 5/2/2012 12:00:00 AM

Title: Could Blowing Your Horn Cut Your Odds for Sleep Apnea?
Category: Health News
Created: 4/24/2015 12:00:00 AM
Last Editorial Review: 4/27/2015 12:00:00 AM

Title: Coffee, Wine Good for Healthy Gut, Sodas May Be Bad
Category: Health News
Created: 4/28/2016 12:00:00 AM
Last Editorial Review: 4/29/2016 12:00:00 AM

Title: Two Genes May Raise Odds for Fraternal Twin Pregnancies
Category: Health News
Created: 4/28/2016 12:00:00 AM
Last Editorial Review: 4/29/2016 12:00:00 AM

Title: 1 in 3 Americans May Have Had Warning Stroke Without Knowing It
Category: Health News
Created: 5/1/2017 12:00:00 AM
Last Editorial Review: 5/2/2017 12:00:00 AM

Title: Red Wine Antioxidant Might Help Diabetics' Arteries
Category: Health News
Created: 5/4/2017 12:00:00 AM
Last Editorial Review: 5/5/2017 12:00:00 AM

Title: Why You Should Unwind After a Tough Day at Work
Category: Health News
Created: 5/1/2018 12:00:00 AM
Last Editorial Review: 5/2/2018 12:00:00 AM

Title: What Drives Millennials to Tan, Knowing the Risks?
Category: Health News
Created: 5/2/2018 12:00:00 AM
Last Editorial Review: 5/3/2018 12:00:00 AM

Title: Pain Is a Growing Threat to the Nation's Surgeons, New Research Reveals
Category: Health News
Created: 4/1/2020 12:00:00 AM
Last Editorial Review: 4/2/2020 12:00:00 AM

Title: Will a Jolt of Java Get Your Creative Juices Flowing?
Category: Health News
Created: 3/9/2020 12:00:00 AM
Last Editorial Review: 3/9/2020 12:00:00 AM

Title: Health Tip: Coping With Winter Nosebleeds
Category: Health News
Created: 1/10/2020 12:00:00 AM
Last Editorial Review: 1/10/2020 12:00:00 AM

Title: Could the Weather Swings of Climate Change Make Flu Seasons Worse?
Category: Health News
Created: 2/20/2020 12:00:00 AM
Last Editorial Review: 2/21/2020 12:00:00 AM

Title: Flu Vaccine Making a Strong Showing This Season
Category: Health News
Created: 2/20/2020 12:00:00 AM
Last Editorial Review: 2/21/2020 12:00:00 AM

Title: Swine Flu
Category: Diseases and Conditions
Created: 4/21/2009 12:00:00 AM
Last Editorial Review: 2/24/2020 12:00:00 AM

There is a need to develop novel approaches to improve the balance between efficacy and toxicity for transcription factor–targeted therapies. In this study, we exploit context-dependent differences in RNA polymerase II processivity as an approach to improve the activity and limit the toxicity of the EWS-FLI1–targeted small molecule, mithramycin, for Ewing sarcoma. The clinical activity of mithramycin for Ewing sarcoma is limited by off-target liver toxicity that restricts the serum concentration to levels insufficient to inhibit EWS-FLI1. In this study, we perform an siRNA screen of the druggable genome followed by a matrix drug screen to identify mithramycin potentiators and a synergistic "class" effect with cyclin-dependent kinase 9 (CDK9) inhibitors. These CDK9 inhibitors enhanced the mithramycin-mediated suppression of the EWS-FLI1 transcriptional program leading to a shift in the IC₅₀ and striking regressions of Ewing sarcoma xenografts. To determine whether these compounds may also be liver protective, we performed a qPCR screen of all known liver toxicity genes in HepG2 cells to identify mithramycin-driven transcriptional changes that contribute to the liver toxicity. Mithramycin induces expression of the BTG2 gene in HepG2 but not Ewing sarcoma cells, which leads to a liver-specific accumulation of reactive oxygen species (ROS). siRNA silencing of BTG2 rescues the induction of ROS and the cytotoxicity of mithramycin in these cells. Furthermore, CDK9 inhibition blocked the induction of BTG2 to limit cytotoxicity in HepG2, but not Ewing sarcoma cells. These studies provide the basis for a synergistic and less toxic EWS-FLI1–targeted combination therapy for Ewing sarcoma.

Teams fail when they cannot achieve a common goal. They also fail when they do not have one. In baseball, different goals between players and staff are unusual. Everyone wants to win. In neurology, where teams may be loosely defined and comprise people from many disciplines, goals differ. A win for you may not be a win for me.

African swine fever (ASF) is a highly contagious hemorrhagic viral disease of domestic and wild pigs that is responsible for serious economic and production losses. It is caused by the African swine fever virus (ASFV), a large and complex icosahedral DNA virus of the Asfarviridae family. Currently, there is no effective treatment or approved vaccine against the ASFV. pS273R, a specific SUMO-1 cysteine protease, catalyzes the maturation of the pp220 and pp62 polyprotein precursors into core-shell proteins. Here, we present the crystal structure of the ASFV pS273R protease at a resolution of 2.3 Å. The overall structure of the pS273R protease is represented by two domains named the "core domain" and the N-terminal "arm domain." The "arm domain" contains the residues from M1 to N83, and the "core domain" contains the residues from N84 to A273. A structure analysis reveals that the "core domain" shares a high degree of structural similarity with chlamydial deubiquitinating enzyme, sentrin-specific protease, and adenovirus protease, while the "arm domain" is unique to ASFV. Further, experiments indicated that the "arm domain" plays an important role in maintaining the enzyme activity of ASFV pS273R. Moreover, based on the structural information of pS273R, we designed and synthesized several peptidomimetic aldehyde compounds at a submolar 50% inhibitory concentration, which paves the way for the design of inhibitors to target this severe pathogen.

IMPORTANCE African swine fever virus, a large and complex icosahedral DNA virus, causes a deadly infection in domestic pigs. In addition to Africa and Europe, countries in Asia, including China, Vietnam, and Mongolia, were negatively affected by the hazards posed by ASFV outbreaks in 2018 and 2019, at which time more than 30 million pigs were culled. Until now, there has been no vaccine for protection against ASFV infection or effective treatments to cure ASF. Here, we solved the high-resolution crystal structure of the ASFV pS273R protease. The pS273R protease has a two-domain structure that distinguishes it from other members of the SUMO protease family, while the unique "arm domain" has been proven to be essential for its hydrolytic activity. Moreover, the peptidomimetic aldehyde compounds designed to target the substrate binding pocket exert prominent inhibitory effects and can thus be used in a potential lead for anti-ASFV drug development.

Simian-human immunodeficiency virus (SHIV) infection of rhesus monkeys is an important preclinical model for human immunodeficiency virus type 1 (HIV-1) vaccines, therapeutics, and cure strategies. SHIVs have been optimized by incorporating HIV-1 Env residue 375 mutations that mimic the bulky or hydrophobic residues typically found in simian immunodeficiency virus (SIV) Env to improve rhesus CD4 binding. We applied this strategy to three SHIV challenge stocks (SHIV-SF162p3, SHIV-AE16, and SHIV-325c) and observed three distinct outcomes. We constructed six Env375 variants (M, H, W, Y, F, and S) for each SHIV, and we performed a pool competition study in rhesus monkeys to define the optimal variant for each SHIV prior to generating large-scale challenge stocks. We identified SHIV-SF162p3S/wild type, SHIV-AE16W, and SHIV-325cH as the optimal variants. SHIV-SF162p3S could not be improved, as it already contained the optimal Env375 residue. SHIV-AE16W exhibited a similar replicative capacity to the parental SHIV-AE16 stock. In contrast, SHIV-325cH demonstrated a 2.6-log higher peak and 1.6-log higher setpoint viral loads than the parental SHIV-325c stock. These data demonstrate the diversity of potential outcomes following Env375 modification in SHIVs. Moreover, the clade C SHIV-325cH challenge stock may prove useful for evaluating prophylactic or therapeutic interventions against clade C HIV-1.

IMPORTANCE We sought to enhance the infectivity of three SHIV stocks by optimization of a key residue in human immunodeficiency virus type 1 (HIV-1) Env (Env375). We developed the following three new simian-human immunodeficiency virus (SHIV) stocks: SHIV-SF162p3S/wild type, SHIV-AE16W, and SHIV-325cH. SHIV-SF162p3S could not be optimized, SHIV-AE16W proved comparable to the parental virus, and SHIV-325cH demonstrated markedly enhanced replicative capacity compared with the parental virus.

Synesthesia is a neurologic trait in which specific inducers, such as sounds, automatically elicit additional idiosyncratic percepts, such as color (thus “colored hearing”). One explanation for this trait—and the one tested here—is that synesthesia results from unusually weak pruning of cortical synaptic hyperconnectivity during early perceptual development. We tested the...

Grasses are among the most resilient plants, and some can survive prolonged desiccation in semiarid regions with seasonal rainfall. However, the genetic elements that distinguish grasses that are sensitive versus tolerant to extreme drying are largely unknown. Here, we leveraged comparative genomic approaches with the desiccation-tolerant grass Eragrostis nindensis and...

HIV-1 persists in cellular reservoirs that can reignite viremia if antiretroviral therapy (ART) is interrupted. Therefore, insight into the nature of those reservoirs may be revealed from the composition of recrudescing viremia following treatment cessation. A minor population of macrophage-tropic (M-tropic) viruses was identified in a library of recombinant viruses...

Aerosol–radiation interaction (ARI) plays a significant role in the accumulation of fine particulate matter (PM2.5) by stabilizing the planetary boundary layer and thus deteriorating air quality during haze events. However, modification of photolysis by aerosol scattering or absorbing solar radiation (aerosol–photolysis interaction or API) alters the atmospheric oxidizing capacity, decreases...

In 2006, the New York City-based Vilcek Foundation created an annual prize program for foreign-born biomedical scientists who have made major contributions to their fields while living and working in the United States. The founders, themselves immigrants from Czechoslovakia, established the program to raise public awareness of the indispensable role...

Kathryn Knight

Andreas Nord, Arne Hegemann, and Lars P. Folkow

Animals in seasonal environments must prudently manage energy expenditure to survive the winter. This may be achieved through reductions in the allocation of energy for various purposes (e.g. thermoregulation, locomotion, etc.). We studied whether such trade-offs also include suppression of the innate immune response, by subjecting captive male Svalbard ptarmigan (Lagopus muta hyperborea) to bacterial lipopolysaccharide (LPS) during exposure to either mild temperature (0°C) or cold snaps (acute exposure to –20°C), in constant winter darkness when birds were in energy-conserving mode, and in constant daylight in spring. The innate immune response was mostly unaffected by temperature. However, energy expenditure was below baseline when birds were immune challenged in winter, but significantly above baseline in spring. This suggests that the energetic component of the innate immune response was reduced in winter, possibly contributing to energy conservation. Immunological parameters decreased (agglutination, lysis, bacteriostatic capacity) or did not change (haptoglobin/PIT54) after the challenge, and behavioural modifications (anorexia, mass loss) were lengthy (9 days). While we did not study the mechanisms explaining these weak, or slow, responses, it is tempting to speculate they may reflect the consequences of having evolved in an environment where pathogen transmission rate is presumably low for most of the year. This is an important consideration if climate change and increased exploitation of the Arctic would alter pathogen communities at a pace outwith counter-adaption in wildlife.

Maria Stager, Nathan R. Senner, Bret W. Tobalske, and Zachary A. Cheviron

Flexibility in heat generation and dissipation mechanisms provides endotherms the ability to match their thermoregulatory strategy with external demands. However, the degree to which these two mechanisms account for seasonal changes in body temperature regulation is little explored. Here we present novel data on the regulation of avian body temperature to investigate how birds alter mechanisms of heat production and heat conservation to deal with variation in ambient conditions. We subjected Dark-eyed Juncos (Junco hyemalis) to chronic cold acclimations of varying duration and subsequently quantified their metabolic rates, thermal conductance, and ability to maintain normothermia. Cold-acclimated birds adjusted traits related to both heat generation (increased summit metabolic rate) and heat conservation (decreased conductance) to improve their body temperature regulation. Increases in summit metabolic rate occurred rapidly, but plateaued after one week of cold exposure. In contrast, changes to conductance occurred only after nine weeks of cold exposure. Thus, the ability to maintain body temperature continued to improve throughout the experiment, but the mechanisms underlying this improvement changed through time. Our results demonstrate the ability of birds to adjust thermoregulatory strategies in response to thermal cues and reveal that birds may combine multiple responses to meet the specific demands of their environments.