Culture

Boston, Mass. - The development of a safe and effective vaccine will likely be required to end the COVID-19 pandemic. A group of scientists, led by Beth Israel Deaconess Medical Center (BIDMC) immunologist Dan H. Barouch, MD, PhD, now report that a leading candidate COVID-19 vaccine developed at BIDMC in collaboration with Johnson & Johnson raised neutralizing antibodies and robustly protected non-human primates (NHPs) against SARS-CoV-2, the virus that causes COVID-19. This study builds on the team's previous results and is published in the journal Nature.

"This vaccine led to robust protection against SARS-CoV-2 in rhesus macaques and is now being evaluated in humans," said Barouch, who is Director of BIDMC's Center for Virology and Vaccine Research.

The vaccine uses a common cold virus, called adenovirus serotype 26 (Ad26), to deliver the SARS-CoV-2 spike protein into host cells, where it stimulates the body to raise immune responses against the coronavirus. Barouch has been working on the development of a COVID-19 vaccine since January, when Chinese scientists released the SARS-CoV-2 genome. Barouch's group, in collaboration with Johnson & Johnson, developed a series of vaccine candidates designed to express different variants of the SARS-CoV-2 spike protein, which is the major target for neutralizing antibodies.

Barouch and colleagues conducted a study in 52 NHPs, immunizing 32 adult rhesus macaques with a single dose of one of seven different versions of the Ad26-based vaccine, and giving 20 animals sham vaccines as placebo controls. All vaccinated animals developed neutralizing antibodies following immunization. Six weeks after the immunization, all animals were exposed to SARS-CoV-2. All 20 animals that received the sham vaccine became infected and showed high levels of virus in their lungs and nasal swabs. Of the six animals that received the optimal vaccine candidate, Ad26.COV2.S, none showed virus in their lungs, and only one animal showed low levels of virus in nasal swabs.

Moreover, neutralizing antibody responses correlated with protection, suggesting that this biomarker will be useful in the clinical development of COVID-19 vaccines for use in humans.

"Our data show that a single immunization with Ad26.COV2.S robustly protected rhesus macaques against SARS-CoV-2 challenge," said Barouch, who is also the William Bosworth Castle Professor of Medicine at Harvard Medical School, a member of the Ragon Institute of MGH, MIT, and Harvard, and a co-leader of the vaccine working group of the Massachusetts Consortium on Pathogen Readiness. "A single-shot immunization has practical and logistical advantages over a two-shot regimen for global deployment and pandemic control, but a two-shot vaccine will likely be more immunogenic, and thus both regimens are being evaluated in clinical trials. We look forward to the results of the clinical trials that will determine the safety and immunogenicity, and ultimately the efficacy, of the Ad26.COV2.S vaccine in humans."

Investigators at Beth Israel Deaconess Medical Center (BIDMC) and other institutions have initiated a first-in-human Phase 1/2 clinical trial of the Ad26.COV2.S vaccine in healthy volunteers. Kathryn E. Stephenson, MD, MPH, is the principal investigator for the trial at BIDMC, which is funded by Janssen Vaccines & Prevention, B.V., a pharmaceutical research arm of Johnson & Johnson.

Pending clinical trial outcomes, the Ad26.COV2.S vaccine is on track to start a phase 3 efficacy trial in 30,000 participants in September.

To fight viruses, cells can deploy defence enzymes that progressively destroy viral genome strands starting from one of the two strand ends. However, this degradation mechanism is not effective against epidemic viruses such as Zika. In fact, the defence enzyme jams at precise points of the viral genome, which put up a strenuous resistance by assuming "defensive" conformation. This is how the virus succeeds at protecting important pieces of its RNA inside infected cells, as demonstrated by a recent study coordinated by SISSA of Trieste and published in the journal Nature Communications. Although the capability of some viruses, such as those responsible for Zika infection, dengue or yellow fever, to generate RNAs resistant to the attack from the cellular machinery was already known, the scientists have discovered and explained in this study the mechanistic rationale behind the phenomenon using computer simulations. Some parts of the viral RNA strand react to the progressive enzymatic degradation, which starts from one particular end of the strand, by assuming an extremely compact form. The degradation process is thus blocked and eluded. At the same time, if the same RNA strand is approached from the other end, the one engaged by the enzymes that copy it, the molecule does not oppose as strongly, allowing the virus to replicate itself efficiently. The defence mechanism, in short, starts where the attack begins.

The new study opens new perspectives for the use of computer simulations to discover heretofore unimagined properties of viral RNAs and thus providing, in perspective, possible mechanistic clues for novel therapeutic approaches.

Furthermore, the unusual properties found in Zika RNA, which are the product of the long evolutionary race between the virus and the infected organisms, could be exploitable for designing new meta-materials endowed with directional mechanical resistance.

Virtual experiments to study viral genome resistance

"Lab experiments had already discovered that sizeable portions of the Zika genome could successfully resist to the attack of degrading enzymes. How exactly this occurred, however, was unclear and beyond reach of direct probing with current experimental techniques", explains Cristian Micheletti of SISSA, who coordinated the study. To shed light on the issue, the scientists have used computer simulations, reproducing in a sort of virtual experiment what happens inside the cell when the viral RNA is engaged at its two ends. "The research has allowed us to understand how the degradation resistance of these viral RNA is encoded in their intricate structure and how the latter, in turn, causes the mechanical resistance to be so different at the two ends. The uncovered mechanical rationale is as simple as it is elegant and at the same time very efficient."

Like an automatic umbrella

Micheletti explains it using the metaphor of an automatic umbrella: "if we put our automatic umbrella into the holder and we inadvertently press the button, the umbrella will get stuck and will resist our attempts to pull it out. This is more or less what happens when the defence enzymes interact with special spots of the viral RNA strand: they trigger a tightening process of the strand which prevents them from proceeding any further". By contrast, the enzymes that read or copy the same viral RNA work from the opposite end of the strand, and do not trigger a significant resistance, allowing the pathogen to replicate and spread the infection. In short, by taking the umbrella from the other end, there is no risk of triggering the switch.

From biology to nanotechnology: new research perspectives

Antonio Suma, lead author of the study, explains: "By using modelling and simulations we have shed light on the unusual mechanical properties of Zika genome and complemented experiments by providing a detailed description of the underpinning atomistic processes."

"It will be very interesting" continues Micheletti, "to investigate whether these surprising mechanical properties can be found in other viral and non-viral RNA. We also hope our findings will inspire the realization of new types of meta-materials, for example supra-molecular strands that, thanks to a judicious design of their conformation, might acquire the same directional mechanical strength found in Zika RNA."

A new study has revealed that tumours can evade the immune system by telling immune cells to produce immunosuppressive steroids. Researchers from the Wellcome Sanger Institute, Department of Pathology, University of Cambridge, and MRC Cancer Unit, discovered that immune T cells from mouse skin and breast tumours secrete steroids, and that preventing this steroid production reduced growth of tumours in mice. The study found that either removing a key steroid-producing gene, or switching it off with a drug, dramatically slowed the formation or progression of cancers.

Reported in Nature Communications, the mouse study revealed this steroid signalling pathway contained potential drug targets for developing new types of cancer immunotherapy, although further human studies are needed.

The immune system is extremely complex. While immune cells protect the body from tumours and infections, some chemicals produced in the body can dampen down the immune system. This makes it much harder for the body to fight against cancer, and cancer immunotherapies that restore the activity of the immune system are urgently needed.

A previous study* had revealed that some immune cells, known as T cells, produced steroids after an infection had passed, to reduce their activity back to low levels again. The researchers wanted to find out if tumour T cells could behave in the same way.

The team tested T cells from melanoma and breast tumours in mice, using single cell RNA sequencing to see exactly which genes were switched on in each individual cell. The researchers discovered that T cells from tumours did produce steroids, which could potentially reduce their effectiveness at battling the tumour.

Dr Bidesh Mahata, the lead author from the University of Cambridge and the Wellcome Sanger Institute, said: "For the first time, we could see that mouse tumour T cells were producing immunosuppressive steroids, even though T cells from healthy mice didn't. It appears that tumours could be instructing their T cells to produce steroids, which would then allow the tumours to evade the immune system and continue growing. This is a really exciting discovery as it means there might be a way of switching the steroid production off again to treat cancer. This is a new hope in cancer, particularly for those tumours that use this trick to suppress anti-tumour immunity."

To test switching off the steroid production, the researchers worked with mice that were missing a key steroid-synthesis gene - Cyp11a1 - from their T cells. They discovered that whereas tumours developed rapidly in normal, wild-type mice, tumour growth was inhibited in these knockout mice with any tumours being much smaller and slower to grow. They also showed that a drug that inactivates the Cyp11a1 protein, aminoglutethimide, also reduced the tumours in normal mice.

Dr Jacqui Shields from the MRC Cancer Unit Cambridge, said: "Using mouse models, we showed that preventing T cells from producing steroids made a huge difference to tumour growth, reducing it dramatically. We found that either removing the key gene, or preventing it from functioning with drugs, stimulated anti-tumour immunity. This suggests the steroid-production pathway could be a real contender in the search for drug targets for designing cancer immunotherapies, to help treat cancer patients."

Dr Sarah Teichmann, a senior author from the Wellcome Sanger Institute, said: "This study may pave the way for new hope in cancer immunotherapy. While these results are from mice, preliminary data from human tissues suggests that the same tumour defence may happen in people and we now need further research to show direct evidence in human cancer. If this is confirmed, in the future, it might be possible to target this immunosuppressive pathway, to create new treatments to switch the immune system back on, and help save lives."

Resembling a butterfly with its symmetrical structure, beautiful colours, and intricate patterns, this striking bubble of gas — known as NGC 2899 — appears to float and flutter across the sky in this new picture from ESO’s Very Large Telescope (VLT). This object has never before been imaged in such striking detail, with even the faint outer edges of the planetary nebula glowing over the background stars.

NGC 2899’s vast swathes of gas extend up to a maximum of two light-years from its centre, glowing brightly in front of the stars of the Milky Way as the gas reaches temperatures upwards of ten thousand degrees. The high temperatures are due to the large amount of radiation from the nebula’s parent star, which causes the hydrogen gas in the nebula to glow in a reddish halo around the oxygen gas, in blue.

This object, located between 3000 and 6500 light-years away in the Southern constellation of Vela (The Sails), has two central stars, which are believed to give it its nearly symmetric appearance. After one star reached the end of its life and cast off its outer layers, the other star now interferes with the flow of gas, forming the two-lobed shape seen here. Only about 10–20% of planetary nebulae [1] display this type of bipolar shape.

Astronomers were able to capture this highly detailed image of NGC 2899 using the FORS instrument installed on UT1 (Antu), one of the four 8.2-metre telescopes that make up ESO’s VLT in Chile. Standing for FOcal Reducer and low dispersion Spectrograph, this high-resolution instrument was one of the first to be installed on ESO’s VLT and is behind numerous beautiful images and discoveries from ESO. FORS has contributed to observations of light from a gravitational wave source, has researched the first known interstellar asteroid, and has been used to study in depth the physics behind the formation of complex planetary nebulae.

This image was created under the ESO Cosmic Gems programme, an outreach initiative to produce images of interesting, intriguing or visually attractive objects using ESO telescopes, for the purposes of education and public outreach. The programme makes use of telescope time that cannot be used for science observations. All data collected may also be suitable for scientific purposes, and are made available to astronomers through ESO’s science archive.

Irvine, Calif., July 30, 2020 -- The first landmark study using next-generation technology to comprehensively examine contaminants in oysters in Myanmar reveals alarming findings: the widespread presence of human bacterial pathogens and human-derived microdebris materials, including plastics, kerosene, paint, talc and milk supplement powders.

The study -- led by scientists from the University of California, Irvine, in collaboration with Environmental Defense Fund, Cornell University and the University of Queensland -- was conducted in the eastern Andaman Sea through partnerships with local researchers in Myanmar in the densely populated but still rural Tanintharyi region. The study concludes that coastal urbanization and lack of sewage treatment increases contamination in seafood and can cause potential health risks to humans, even large distances from pollution sources.

Study results appear in Science of the Total Environment. (Link to study: https://doi.org/10.1016/j.scitotenv.2020.139081)

The area covered by the study spanned nine coral reefs off Myanmar's Mergui Archipelago, situated roughly 40 miles from Myeik, a city with a population of over 250,000 people. The study examined contaminants in seawater and in oysters using next-generation DNA sequencing to reveal 5,459 potential human pathogens belonging to 87 species of bacteria. More than half of these pathogens are considered detrimental to human health. In addition, the scientists used infrared spectroscopy to examine individual microdebris particles found in the oysters. Of the 1,225 individual microdebris particles examined, 78 different types of contaminant materials were found.

"While 48 percent of the microparticles were microplastics - a finding representative across numerous ocean ecosystems - many other particles were not plastic and originated from a variety of human-derived materials that are constituents of fuels, paints and cosmetics," said senior author Joleah Lamb, assistant professor of ecology & evolutionary biology at UCI. "We were particularly surprised to find three different brands of milk powder formula, which comprised 14 percent of the microdebris contaminants."

Both types of contaminants - pathogens and microparticles - reflect the pervasive presence of sewage and runoff from human and animal sources. The implications for other coastal regions are significant, since coastal marine environments worldwide are being increasingly subjected to reduced water quality from urbanization that could be leading to the contamination of important fishery species on a global scale.

Implications for human health are also significant. Oysters in this region and elsewhere are part of the local diet and typically consumed raw and whole. The contaminants found in this study indicate that even the Mergui Archipelago in largely rural Myanmar has significant and widespread pollution from runoff of agricultural and human waste that can affect downstream food sources over a wide area far from urban centers.

Today more than half of seafood exports by value originate in developing countries, raising more general concerns about local food safety and food security worldwide.

"It's important to keep in mind that much of our seafood is imported from overseas, from places that may be contaminated, emphasizing the importance of both adequate testing and improvements to coastal water quality worldwide," said lead author Raechel Littman, a postdoctoral scholar in ecology & evolutionary biology at UCI.

Apart from human bacterial pathogens, the predominance of microplastics and other types of microparticles present in seafood could have implications for both the environment and human health.

"Scientists are only beginning to explore the human health consequences from consuming microplastics," said Lamb.

Many plastic particles can carry toxins, such as persistent organic pollutants, or POPs, like dichlorodiphenyltrichloroethane (DDT), polychlorinated biphenyls (PCBs) and bisphenol A (BPA), that subsequently enter the ocean and marine food webs, and can eventually be transferred to people through food. Therefore, the uptake of microplastics in the marine environment could have far-reaching consequences for human consumption of seafood and can be an emerging risk to public health globally.

Also concerning is that over half of the microdebris contaminants detected in the Myanmar oyster tissues were composed of non-polymer materials that can be harmful to human health if ingested, such as kerosene, saponin and talc. Moreover, the prominence of milk supplement detected suggests a direct fecal-oral link between human waste and sewage making its way back into the food chain, thereby elevating the risk of contamination or disease transmission.

"This study in important in its global implications. There is strong evidence of transferability of the findings from Myanmar to other seafood sources around the world," said Douglas Rader, chief scientist for the EDF Oceans program and collaborator on this study. "These findings highlight both the risks of coastal urbanization and the importance of adequate wastewater and stormwater management. It also shows clearly the need for better science related to the potential impacts of these contaminants, and the need for better testing programs so that seafood consumers can rely on its wholesomeness.

COVID-19 has changed the lives of millions and even billions of people around the world. The disease is caused by SARS coronavirus 2 (SARS-CoV-2), an RNA virus, i.e. a virus that uses RNA to store its genetic information. In order to confront it, we must have a detailed understanding of the structure and function of its individual proteins.

One of the mechanisms that the coronavirus uses to try and outsmart our immunity and convince our cells that the viral RNA is harmless is the installation of so-called caps, special structures at the beginning of the RNA, thanks to which the viral RNA imitates human RNA, allowing the virus to infect the human body and multiply within it.

The cap installation process catalyzes the Nsp16 coronavirus protein with involvement from another viral protein, Nsp10. Headed by Dr. Evžen Bou?a and Dr. Radim Nencka, a group of researchers at the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences used X-ray crystallography to determine and analyze the precise structure of the complex of these two proteins.

This allowed the researchers to identify several fundamental characteristics of the Nsp16 and Nsp10 protein complex, namely a deep canyon on the surface of the protein complex where binding of the viral RNA occurs and a cap is installed. This canyon can be targeted by inhibitors that suppress the activity of the Nsp16 and Nsp10 protein complex and thus of the entire cap installation process and may, in the future, serve as drugs to combat many coronaviruses.

"Hundreds of research teams tried to shed light on how the COVID-19 virus is able to hide its RNA from cellular immunity. In the end, two American teams and we here in Prague were the ones who succeeded," explains Evzen Boura, head of the Structural Membrane Biology group. "We used X-ray analysis to determine the structure of the responsible viral enzyme with inhibitor."

Two teams of astronomers have made a compelling case in the 33-year-old mystery surrounding Supernova 1987A. Based on observations of the Atacama Large Millimeter/submillimeter Array (ALMA) and a theoretical follow-up study, the scientists provide new insight for the argument that a neutron star is hiding deep inside the remains of the exploded star. This would be the youngest neutron star known to date.

Ever since astronomers witnessed one of the brightest explosions of a star in the night sky, creating Supernova 1987A (SN 1987A), they have been searching for a compact object that should have formed in the leftovers from the blast.

Because particles known as neutrinos were detected on Earth on the day of the explosion (23 February 1987), astronomers expected that a neutron star had formed in the collapsed center of the star. But when scientists could not find any evidence for that star, they started to wonder whether it subsequently collapsed into a black hole instead. For decades the scientific community has been eagerly awaiting a signal from this object that has been hiding behind a very thick cloud of dust.

The "blob"

Recently, observations from the ALMA radio telescope provided the first indication of the missing neutron star after the explosion. Extremely high-resolution images revealed a hot "blob" in the dusty core of SN 1987A, which is brighter than its surroundings and matches the suspected location of the neutron star.

"We were very surprised to see this warm blob made by a thick cloud of dust in the supernova remnant," said Mikako Matsuura from Cardiff University and a member of the team that found the blob with ALMA. "There has to be something in the cloud that has heated up the dust and which makes it shine. That's why we suggested that there is a neutron star hiding inside the dust cloud."

Even though Matsuura and her team were excited about this result, they wondered about the brightness of the blob. "We thought that the neutron star might be too bright to exist, but then Dany Page and his team published a study that indicated that the neutron star can indeed be this bright because it is so very young," said Matsuura.

Dany Page is an astrophysicist at the National Autonomous University of Mexico, who has been studying SN 1987A from the start. "I was halfway through my PhD when the supernova happened," he said, "it was one of the biggest events in my life that made me change the course of my career to try to solve this mystery. It was like a modern holy grail."

The theoretical study by Page and his team, published today in The Astrophysical Journal, strongly supports the suggestion made by the ALMA team that a neutron star is powering the dust blob. "In spite of the supreme complexity of a supernova explosion and the extreme conditions reigning in the interior of a neutron star, the detection of a warm blob of dust is a confirmation of several predictions," Page explained.

These predictions were the location and the temperature of the neutron star. According to supernova computer models, the explosion has "kicked away" the neutron star from its birthplace with a speed of hundreds of kilometers per second (tens of times faster than the fastest rocket). The blob is exactly at the place where astronomers think the neutron star would be today. And the temperature of the neutron star, which was predicted to be around 5 million degrees Celsius, provides enough energy to explain the brightness of the blob.

Not a pulsar or a black hole

Contrary to common expectations, the neutron star is likely not a pulsar. "A pulsar's power depends on how fast it spins and on its magnetic field strength, both of which would need to have very finely tuned values to match the observations," said Page, "while the thermal energy emitted by the hot surface of the young neutron star naturally fits the data."

"The neutron star behaves exactly like we expected," added James Lattimer of Stony Brook University in New York, and a member of Page's research team. Lattimer has also followed SN 1987A closely, having published prior to SN 1987A predictions of a supernova's neutrino signal that subsequently matched the observations. "Those neutrinos suggested that a black hole never formed, and moreover it seems difficult for a black hole to explain the observed brightness of the blob. We compared all possibilities and concluded that a hot neutron star is the most likely explanation."

This neutron star is a 25 km wide, extremely hot ball of ultra-dense matter. A teaspoon of its material would weigh more than all the buildings within New York City combined. Because it can only be 33 years old, it would be the youngest neutron star ever found. The second youngest neutron star that we know of is located in the supernova remnant Cassiopeia A and is 330 years old.

Only a direct picture of the neutron star would give definite proof that it exists, but for that astronomers may need to wait a few more decades until the dust and gas in the supernova remnant become more transparent.

Detailed ALMA images

Even though many telescopes have made images of SN 1987A, none of them have been able to observe its core with such high precision as ALMA. Earlier (3-D) observations with ALMA already showed the types of molecules found in the supernova remnant and confirmed that it produced massive amounts of dust.

"This discovery builds upon years of ALMA observations, showing the core of the supernova in more and more detail thanks to the continuing improvements to the telescope and data processing," said Remy Indebetouw of the National Radio Astronomy Observatory and the University of Virginia, who has been a part of the ALMA imaging team.

Global warming will modify the distribution and abundance of fish worldwide, with effects on the structure and dynamics of food networks. However, making precise predictions on the consequences of this global phenomenon is hard without having a wide historical perspective.

A study carried out at the University of Barcelona and the Southern Centre for Scientific Research (CADIC-CONICET, Argentina), analysed the potential implications in the distribution of the Argentinian hake (Merluccius hubbsi), caused by the warming of marine waters. The study is based on the analysis of the structure of the marine ecosystems from 6,000 to 500 years ago, when temperatures were warmer than now. The results show this species could expand towards south and reach the coast of the South America extreme southern area, like it happened in the past. According to the researchers, this approach allows researchers to make predictions on the transformations to be caused by the climate change in the marine environment with important ecogical and economic implications.

The study, published in the journal Oecologia, is part of the doctoral thesis by the researcher Maria Bas, member of CADIC-CONICET and the Biodiversity Research Institute (IRBio) of the University of Barcelona, co-supervised by the tenure-track 2 lecturer Lluís Cardona, from the Research Groups on Large Marine Vertebrates at the Department of Evolutionary Biology, Ecology and Environmental Sciences of the Faculty of Biology and IRBio, and by the expert Ivan Briz i Godino, from CADIC-CONICET. York University (United Kingdom) and British Columbia University (Canada) have also taken part in the study.

The Middle Holocene, a plausible view of the future

Researchers focused on the Atlantic coast of Isla Grande in Tierra del Fuego, in the extreme south of Argentina, where the hake is a key species for industrial fisheries. They collected samples from two archaeological sites dating from the Middle Holocene, that is, between 6,000 and 500 years ago, a period when temperatures would be analogous to those we are heading to in the future -according to climate models. "Remains from fish that lived in the warmest periods of the Holocene are specially interesting since they offer a plausible view of the future in the context of global warming. At the moment, the average annual temperature of the sea surface in Tierra del Fuego is about 7ºC, but during the Middle Holocene it reached 11 and 12ºC. Therefore, data on the biology of the hake during this period can provide information on the distribution of this species in a near future", note the authors.

The presence of remains from other models of hake in the archaeological site Río Chico 1, in the north of Tierra del Fuego (Argentina), show the existence of a large population of hake in the northern east of Tierra del Fuego during the Middle Holocene. Since then, this population disappeared due to the cooling temperatures and their habitat was unknown.

Changes in the distribution of the Argentinian hake

In order to discover the habitat of these fish, the first step in the study was to identify the remains through the mitochondrial DNA analysis and make a reconstruction of the size of old models. Then, researchers used the technique of carbon and nitrogen stable isotope analysis to study changes in the trophic position and the use of the habitat over time. This technique enables researchers to get information on the food intake, and the environment of the species that lived in a recent past, since the information is registered in the bone isotopic signal.

Results show that Argentinian hake that lived in the Atlantic coast of Tierra del Fuego during the Middle Holocene had a broader isotopic niche and fed in more coastal habitats compared to those in current times. "This information, combined with strong winds and currents of the region, together with the lack of sailing technology during the Middle Holocene suggest that groups of aboriginal hunter-fisher-gatherers were likely to fish in the shore", note the authors. If the environmental conditions of a warmer world coincide with what prevails in the Middle Holocene, the Argentinian hake could be more abundant in the continental Argentinian platform of Tierra del Fuego. "From a fishing perspective, this situation suggests a potential increase of resources in shallow waters regarding Tierra del Fuego with important changes in the fishing industry in this region", highlights Lluís Cardona.

According to the researchers, this methodology can be used with other species and in other areas of the planet. "In the future, we would like to know the changes that have taken place in the distribution and ecological niche of the hake and the cod in European waters", concludes the researcher.

RESEARCH TRIANGLE PARK, N.C. -- An Army-funded project marks a turning point in the field of scalable quantum processors, producing the largest quantum chip of its type using diamond-based qubits and quantum photonics.

Millions of quantum processors will be needed to build quantum computers, and new research at MIT and Sandia National Laboratories, funded and managed in part by the U.S. Army Combat Capability Development's Command's Army Research Laboratory's Center for Distributed Quantum Information, demonstrates a viable way to scale-up processor production.

"Building large scale quantum devices will entail both the assembly of large numbers of high-quality qubits and the creation of reliable circuits for transmitting and manipulating quantum information between them," said Dr. Fredrik Fatemi, Army researcher and CDQI co-manager. "Here, the research team has demonstrated exceptional progress toward reliably manufacturing complex quantum chips with both critical elements."

Unlike classical computers, which process and store information using bits represented by either 0s and 1s, quantum computers operate using quantum bits, or qubits, which can represent 0, 1, or both at the same time. This strange property allows quantum computers to simultaneously perform multiple calculations, solving problems that would be intractable for classical computers.

The qubits in the new chip are artificial atoms made from defects in the diamond, which can be prodded with visible light and microwaves to emit photons that carry quantum information. The process, which the researchers describe in the peer-reviewed journal Nature, is a hybrid approach, in which carefully selected quantum micro-chiplets containing multiple diamond-based qubits are placed on an aluminum nitride photonic integrated circuit.

"In the past 20 years of quantum engineering, it has been the ultimate vision to manufacture such artificial qubit systems at volumes comparable to integrated electronics," said Dirk Englund, an associate professor in MIT's Department of Electrical Engineering and Computer Science. "Although there has been remarkable progress in this very active area of research, fabrication and materials complications have thus far yielded just two to three emitters per photonic system."

Using their hybrid method, the researchers were able to build a 128-qubit system -- the largest integrated artificial atom-photonics chip yet.

The artificial atoms in the chiplets consist of color centers in diamonds, defects in diamond's carbon lattice where adjacent carbon atoms are missing, with their spaces either filled by a different element or left vacant. In the chiplets, the replacement elements are germanium and silicon. Each center functions as an atom-like emitter whose spin states can form a qubit. The artificial atoms emit colored particles of light, or photons, that carry the quantum information represented by the qubit.

Diamond color centers make good solid-state qubits, but "the bottleneck with this platform is actually building a system and device architecture that can scale to thousands and millions of qubits," said Noel Wan, MIT research and the paper's coauthor. "Artificial atoms are in a solid crystal, and unwanted contamination can affect important quantum properties such as coherence times. Furthermore, variations within the crystal can cause the qubits to be different from one another, and that makes it difficult to scale these systems."

Instead of trying to build a large quantum chip entirely in diamond, the researchers decided to take a modular and hybrid approach.

"We use semiconductor fabrication techniques to make these small chiplets of diamond, from which we select only the highest quality qubit modules," Wan said. "Then we integrate those chiplets piece-by-piece into another chip that wires the chiplets together into a larger device."

The integration takes place on a photonic integrated circuit, which is analogous to an electronic integrated circuit but uses photons rather than electrons to carry information. Photonics provides the underlying architecture to route and switch photons between modules in the circuit with low loss. The circuit platform is aluminum nitride, rather than the traditional silicon of some integrated circuits.

Using this hybrid approach of photonic circuits and diamond chiplets, the researchers were able to connect 128 qubits on one platform. The qubits are stable and long-lived, and their emissions can be tuned within the circuit to produce spectrally indistinguishable photons, according to the researchers.

While the platform offers a scalable process to produce artificial atom-photonics chips, the next step will be to test its processing skills.

"This is a proof of concept that solid-state qubit emitters are very scalable quantum technologies," Wan said. "In order to process quantum information, the next step would be to control these large numbers of qubits and also induce interactions between them."

The qubits in this type of chip design wouldn't necessarily have to be these particular diamond color centers. Other chip designers might choose other types of diamond color centers, atomic defects in other semiconductor crystals like silicon carbide, certain semiconductor quantum dots, or rare-earth ions in crystals.

"Because the integration technique is hybrid and modular, we can choose the best material suitable for each component, rather than relying on natural properties of only one material, thus allowing us to combine the best properties of each disparate material into one system," said Tsung-Ju Lu, MIT researcher and the paper's co-author.

Finding a way to automate the process and demonstrate further integration with optoelectronic components such as modulators and detectors will be necessary to build even bigger chips necessary for modular quantum computers and multichannel quantum repeaters that transport qubits over long distances, the researchers said.

"The team has made an incredible advance toward the large-scale integration of artificial atoms and photonics and, looking forward, we are very excited for increasingly complex testing of the devices," said Dr. Sara Gamble, program manager at the Army Research Office, an element of CCDC ARL, and CDQI co-manager. "The modular approach so far successfully demonstrated by the team has enormous promise for the future quantum computers and quantum networks of high interest to the Army."

Washington, DC - Before the era of COVID-19, research suggested that premature deaths among white Americans were rising. Even before the era of COVID-19, these findings were surprising. As Dr. Cooley explains, "These trends were puzzling to us because white people, on average, have more wealth than other racial groups and are generally privileged in our society." As a result, Cooley and colleagues questioned whether factors other than income and education, known as objective indicators of status, may not buy happiness for white people. Instead, they investigated the role of social comparisons - or the desire to "keep up with the Joneses."

Their research indicates that white Americans tend to compare their own status to other white Americans--people they perceive as much wealthier than their selves; and, the greater the perceived disparity, the worse they feel--psychologically and physically--regardless of their objective status.

In one study, white and Black Americans (490 white people and 519 Black people) were asked to rank their own status on a ladder--selecting higher ladder rungs if they felt high status and lower rungs if they felt low status. Next, participants were asked to rank "the majority of their racial group" (i.e., white or Black people) on the same scale. The researchers followed with questions about participants' health, emotions, and wellbeing. A second study replicated their findings.

"Results revealed that white Americans tended to make upward status comparisons - in other words, they most often compared their status to other white people--people who they perceived as having higher status than the self" says Erin Cooley, one of the study's co-lead authors. "In contrast, Black Americans most often compared their status to other Black people--people who they perceived as doing worse than the self." And, among white Americans, larger upward comparisons were associated with feeling fewer positive emotions and having worse physical health.

Interestingly, these data suggest that it is exactly because of this belief that white = wealth, that many white people feel as if they are falling behind.

Although their work illuminates psychological processes that may harm the health of white Americans, the authors also urge readers to consider two points: (1) these data were collected before the worldwide COVID-19 pandemic, and (2) as clearly revealed by the pandemic, minority racial/ethnic groups - particularly African Americans and Latinx Americans - are disproportionately impacted by poor health outcomes and economic downturns.

"Due to racism and persistent racial inequities, there are many health disparities experienced by people of color in the United States including rates of heart disease and diabetes," says Jazmin Brown-Iannuzzi, also a co-lead author of the research. Thus, while the authors think the current work represents an interesting psychological mechanism for white Americans, this work should not detract from the fact that structural racism in this country creates health and wealth inequalities along racial lines.

Leesburg, VA, July 30, 2020--An open-access article published in ARRS' American Journal of Roentgenology (AJR) investigating the association between coronavirus disease (COVID-19) and stroke subtypes determined that patients with COVID-19 presenting with acute neurologic symptoms warrant a lower threshold for suspicion of large vessel occlusion (LVO) stroke, thus necessitating prompt workup.

"To our knowledge, this is the first study to describe an association between COVID-19 and large vessel strokes," wrote lead investigator Shingo Kihira of the Icahn School of Medicine at Mount Sinai.

This retrospective case-control study included patients for whom a code for stroke was activated during March 16 to April 30, 2020 at a single system of six hospitals across the New York City boroughs of Manhattan, Queens, and Brooklyn. Demographic data (age, sex, and race or ethnicity), COVID-19 status, stroke-related risk factors, as well as clinical and imaging findings pertaining to stroke were collected from the electronic medical record.

Among the 329 patients (175 [53.2%] men, 154 [46.8%] women; mean age, 66.9 years) in the study sample, 35.3% (116) had acute ischemic stroke confirmed with imaging; 21.6% (71) had LVO stroke; and 14.6% (48) had small vessel occlusion (SVO) stroke.

The most commonly observed LVO [62.0% (44/71)] was middle cerebral artery segment M1-M2 occlusion. Meanwhile, multifocal LVOs were observed in only 9.9% (7/71) of patients with LVO stroke.

With COVID-19 present in 38.3% (126/329) of patients, the 61.7% (203/329) of patients without COVID-19 formed the negative control group. LVO stroke was present in 31.7% of patients with COVID-19, compared with 15.3% of patients without COVID-19 (p = 0.001). SVO stroke was present in 15.9% of patients with COVID-19 and 13.8% of patients without COVID-19 (p = 0.632).

As Kihira et al. explained: "In multivariate analysis controlled for race and ethnicity, presence of COVID-19 had a significant independent association with LVO stroke (odds ratio, 2.4) compared with absence of COVID-19 (p = 0.011)."

After stratification for race and ethnicity, the results from this AJR study indicate that the risk of large vessel stroke among patients with COVID-19 was 2.4 times as high as that among patients without COVID-19.

"Although the incidence of SARS-CoV-2 infection in New York City is declining, a large population of patients continue to present with COVID-19," Kihira and colleagues noted. Clarifying that COVID-19 is associated with LVO stroke--but not with SVO stroke--the authors of this AJR article reiterated the lower threshold of suspicion for large vessel stroke in COVID-19 patients who present with acute neurologic symptoms.

In medicine, men generally earn more than women for similar work, but a new study published July 30 in BMJ finds that the income gap between genders shrinks substantially in practices with more equal gender distributions of staff physicians.

The analysis showed that in nonsurgical specialty practices with at least as many women as men, men earn 12 percent more than women. However, that gap nearly doubles--to 20 percent--for practices with more than 90 percent male physicians on staff.

In absolute terms, this means that in nonsurgical specialty practices with 90 percent male representation, female physicians earn as much as $91,000 less per year than their male peers.

The study's senior author, Anupam Jena, the Ruth L. Newhouse Associate Professor of Health Care Policy in the Blavatnik Institute at Harvard Medical School collaborated with researchers from the Rand Corporation, the University of California, Berkeley, and Doximity.

The findings offer important evidence supporting the notion that diversity in the workplace may have a positive effect on reducing earnings gaps and other inequities, the researchers said.

"There are many good reasons to have greater diversity in our workplaces, including the idea that if you make a workplace more diverse, some of the pay inequities we see will go away," Jena said. "This is exciting evidence that diversity can improve equity, not just in terms of representation, but in very tangible economic terms."

The researchers analyzed data from a national survey of physician salaries in the United States from 2014-18 that included 18,802 physicians from 9,848 group practices. They compared earnings across practices with different proportions of male and female physicians, adjusting for physician specialty, years of experience, hours worked, measures of clinical workload, practice type and geography.

Research into workplace diversity and income equity has been scant at best, the study authors said, in part because it is difficult to combine information about an individual's income and demographic information about their workplace. This survey assigned each doctor a unique practitioner identifier number, which allowed the researchers to compare information about respondents' individual incomes against demographic information about the practices where they work. Doximity conducted the survey and owns the database containing practice demographic information.

The researchers found that among 11,490 nonsurgical specialists, the absolute adjusted difference in annual income between men and women was $36,604 for practices with less than 50 percent male physicians compared with $91,669 for practices with at least 90 percent male physicians.

They found a similar distribution of incomes among 3,483 surgical specialists, with absolute adjusted gender differences of $46,503 in annual income for practices with less than 50 percent male physicians compared with $149,460 for practices with at least 90 percent male physicians. The relative difference in pay for surgical specialists was 10 percent in the practices with the most women compared to 27 percent in practices with more than 90 percent men.

Incomes were not affected by gender representation among primary care practitioners. Among the 3,829 primary care physicians in the sample, differences in income for men and women did not vary according to the proportion of male physicians in a practice. The researchers said that this was likely because there is less variation in income among primary care physicians. Primary care is among the specialties with the highest proportion of female physicians.

The researchers said that one likely explanation for greater equity in practices with more women was that the experience of working with women might change some of the implicit and explicit biases that many people hold about women in the workplace. They also said that women who were hired by practices with more female physicians might face less difficulty negotiating parameters such as how long they are allowed to spend with each patient, how long it will take to become a partner and other factors that impact earnings over the long term.

"For a woman negotiating the initial terms of her employment with a new practice, there might be a real difference if you're sitting at the table with five men compared to if there are three men and two women," said Christopher Whaley, the study's lead author and policy researcher at the Rand Corporation.

Whaley said that the wage gap would fall by about 20 percent if practices had more equal gender representation.

"Our findings suggest that increasing the gender diversity of specialty practices would do a lot to close the pay gap between men and women in medicine," Whaley said. "Yet another reason to push for greater diversity."

Compounds tested for their potential as antibiotics have demonstrated promising activity against one of the deadliest infectious diseases - tuberculosis (TB).

Researchers from the John Innes Centre evaluated two compounds with antibacterial properties, which had been produced by the company Redx Pharma as antibiotic candidates, particularly against TB.

TB, which is caused by the bacterium Mycobacterium tuberculosis, is often thought of as a disease of the past. But in recent years it has been increasing due, in part, to rising resistance to treatments and decreasing efficacy of vaccines.

One strategy in the search for new treatments is to find compounds that exploit well-known existing targets for drugs such as the bacterial enzyme DNA gyrase. This member of the DNA topoisomerase family of enzymes is required for bacterial DNA functionality, so compounds that inhibit its activity are much sought after as antibiotic candidates.

Using X-ray crystallography, the team elucidated the molecular details of the action of the compounds against their target.

Surprisingly, a very common mutation in DNA gyrase that causes bacteria to be resistant to a related group of antibiotics, the aminocoumarins, did not lead to resistance to the compounds under scrutiny here.

"We hope that companies and academic groups working to develop new antibiotics will find this study useful. It opens the way for further synthesis and investigation of compounds that interact with this target," says Professor Tony Maxwell one of the authors of the study which appears in the Journal of Antimicrobial Chemotherapy.

To date, efforts to develop new treatments for TB have been unsuccessful, with current treatments having been used for over 50 years.

World Health Organisation (WHO) figures reveal that each day over 4000 people die from TB and 300,000 people fall ill from the disease. Nearly 500,000 people fell ill with drug-resistant TB in 2018.

Professor Maxwell says: "Antimicrobial resistance (AMR) is now well-recognised as one of the biggest problems facing us in the in the 21st Century. If we don't find solutions to it soon, we could be looking at epidemics of bacterial disease going forward. People know about the bubonic plague and other such terrible pestilence through studying history but it's not overstating the case that bacterial diseases of this sort could reemerge if we do not have effective antibiotics. We must find a way of bringing together expertise from the academic and business sector towards decisive action."

BLOOMINGTON, Ind. -- The list of companies that have filed for bankruptcy during the first half of 2020 reads like a "who's who" of major retailers and recognized brands. Consumers may know J.C. Penney, Hertz, Neiman Marcus, J. Crew and Pier 1, but the carnage also includes tech firms previously seen to have much potential.

With the recent rise in bankruptcies, suppliers and partners of these companies are being forced to make a difficult decision: Should they bet on the bankrupt customer or partner to survive by continuing to invest in the relationship? Or should they bet that the bankrupt customer or partner will not survive by cutting off their investments so they can minimize losses and redeploy resources?

New research from the Indiana University Kelley School of Business found that when a company is in bankruptcy, its advertising and research and development investments can cut both ways. They increase the odds of surviving for some bankrupt companies and decrease the odds for others.

"This difference hinges on the influence that the bankrupt company's suppliers have in the bankruptcy process," said Niket Jindal, assistant professor of marketing and the study's author. "Advertising and R&D increase bankruptcy survival when suppliers have high influence, whereas they decrease bankruptcy survival when suppliers have low influence."

His article, "The Impact of Advertising and R&D on Bankruptcy Survival: A Double-Edged Sword," appears in the current issue of the Journal of Marketing.

Jindal studied whether a company's past investments in intangible assets -- specifically investments in advertising and R&D -- can help suppliers and partners make a decision on whether to bet on the bankrupt company. He analyzed 1,672 bankruptcy cases filed in U.S. bankruptcy courts from 1996 to 2019 and found that managers could substantially improve their odds of correctly predicting whether a bankrupt customer or partner will survive by considering the company's past advertising and R&D investments, in addition to the usual financial predictors.

He found that by considering a bankrupt company's advertising and R&D, managers can increase the accuracy of predicting whether that company will survive by 11 percent.

Specifically, the results show that a bankrupt company's advertising increases the odds of its survival when at least 38 percent of the company's debt has been borrowed from suppliers. For R&D, the cutoff point is when at least 21 percent of the company's debt has been borrowed from suppliers.

"A losing bet can be catastrophic for a supplier or partner," Jindal said. "If the company bets on a bankrupt customer or partner to survive and they do not survive, investments in the relationship will be lost, and the company will have fewer resources and time to try to attract other customers and partners to make up for the lost sales. On the other hand, if the company bets against the bankrupt customer or partner and they do survive, the relationship will be soured and will put future sales from them at risk."

Jindal said that suppliers and partners should be careful when including a bankrupt firm's advertising and R&D investments in their decision-making process.

"The key is to look at the portion of the bankrupt company's debt that is due to suppliers versus banks, because this shows the influence that the bankrupt company's suppliers will have, relative to other creditors, in the bankruptcy process," he said.

Suppliers have greater noncontractual revenue and generally do not require collateral, while banks have less noncontractual revenue and generally do require collateral. The impact of advertising and R&D on the value that is received if the bankrupt firm survives versus gets liquidated differs for suppliers versus banks.

Women receiving standard treatment in New York City for ovarian, uterine, and cervical cancers are not at increased risk of being hospitalized for or dying from COVID-19 due to their cancer, a new study shows. The researchers found that neither having cancer nor receiving treatment for it, which can come with its own toxicities, worsened COVID-19 disease outcomes.

Led by researchers at NYU Langone's Perlmutter Cancer Center and NYU Grossman School of Medicine, the study showed that 121 women, ages 51 to 63, who were receiving standard treatments for such malignancies and who contracted the pandemic coronavirus had similar rates of hospitalization and death as those who only had COVID-19.

Publishing in the journal Cancer online July 31, the study showed that 54 percent of the women (66 of 121) required hospitalization and among these, 25 percent (17 of 66) died, for an overall death rate of 14 percent. This is comparable to the results of another study, which showed a 21 percent death rate among all 5,700 hospitalized patients with COVID-19 in the city, who were mostly male (60 percent) and at greater risk of the disease, researchers say.

Having late-stage gynecologic cancer, cancer surgery, or high-dose chemotherapy also did not increase a woman's risk of dying from COVID-19.

Importantly, the work also found that 75 percent of gynecologic cancer patients with COVID-19 had a mild form of the disease and recovered from their infection.

"Our study should be reassuring for women with gynecologic cancers who are worried that having cancer increases their risk of becoming seriously ill if they go to the hospital because of COVID-19," says study lead investigator Olivia Lara, MD, an oncology fellow in the Department of Obstetrics and Gynecology at Perlmutter. These patients already contend with increased inflammation and imbalanced immune systems that, in theory, coronavirus infection could make worse.

"Women with gynecologic cancers have the same risk factors for dying from COVID-19 as women without these cancers," says study senior investigator Bhavana Pothuri, MD, MS, a professor in the Department of Obstetrics and Gynecology at Perlmutter.

These shared risk factors, she says, which overall double women's risk of dying from COVID-19, are being African-American or having two or more underlying health conditions, such as hypertension, obesity, and diabetes.

As part of the study, researchers reviewed the medical records of women treated for both COVID-19 and gynecologic cancer at area hospitals between March 1 and April 22, 2020. These included NYU Langone's Perlmutter Cancer Center, NYC Health + Hospitals Bellevue Hospital, Memorial Sloan-Kettering Cancer Center, Columbia University Medical Center, SUNY Downstate Medical Center, and the Montefiore Medical System.

Another study finding was that a small number (eight of 121) of participants receiving immunotherapy, drugs that harness the immune system to attack cancer cells, were three times more likely to die than women who were receiving standard radiation, surgery, chemotherapy, or a combination of these therapies. However, Pothuri cautions that the number of women receiving immunotherapy was not large enough to lead to any firm recommendations about clinical care. (or to result in any firm conclusions about clinical care)

Pothuri says the team has plans to analyze patient records for further insights into any factors that might lessen the impact of these underlying risk factors for COVID-19 on women with cancer, including how best to communicate with local community groups.

For now, Pothuri says, women should definitely not put off screening, diagnosis, or treatment of new cancers out of any additional fear they have about the risks from COVID-19. "The basic rules of cancer care have not changed during the pandemic," she says. "Early detection, screening, and care lead to more people surviving what remains a leading cause of death among American women."