Culture

In the U.S., someone has a heart attack every 40 seconds, and yet researchers have not had a model that fully mimics what occurs in the human heart after a heart attack.

A team of investigators at the Medical University of South Carolina (MUSC) and Clemson University recently reported in an article in Nature Biomedical Engineering that they have developed human cardiac organoids less than 1 millimeter in diameter that closely resemble the physiological conditions that occur during a heart attack.

The team was led by bioengineer Ying Mei, Ph.D., who holds a joint faculty position at MUSC and Clemson University. He is part of the MUSC Clemson Bioengineering program, which places Clemson bioengineers and bioengineering doctoral students on the MUSC campus so that they can interact with clinicians in need of engineering solutions. The article's lead author, Dylan Richards, Ph.D., is a graduate of the joint program.

"We were essentially able to take that 3D complex nature of a heart attack and then downsize it into a microtissue model," said Richards.

Organoids are three-dimensional multicellular tissues that are less than 1 millimeter in diameter. These organoids, or microtissues, function like their full-size counterparts. In this case, the heart organoids actually beat and contract as the human heart does. This model uses induced pluripotent stem cells, almost like "parent cells," that divide and mature into several types of heart cells that interact and self-assemble to form the organoid.

Traditionally, biologists use cells in a dish or animal models, such as mice or rats, to model diseases being studied. These methods have their own disadvantages that the organoid model overcomes.

Cells in a dish are great for learning things at the cellular level, but it is very unnatural for cells to grow in two dimensions on a flat surface.

Animal models are very useful in taking the next steps toward recapitulating what happens in the human body, but organoids, especially those for the heart, are the closest to recreating what occurs in humans.

"The hearts of rats and mice beat five to 10 times faster than those of humans," Richards explained. "How those mechanisms work physically -the electrophysiology and the pumping action - is just different because of the scale."

In contrast, the cardiac organoid recreates a human version of the heart and closely resembles the tissue dysfunction that takes place after the oxygen shortage caused by a heart attack. Because it is very difficult to obtain a sample immediately after a heart attack occurs, most of what we know about heart attacks comes from observations made long after the initial oxygen shortage. The organoid model fills in this gap, enabling visualization immediately after oxygen deprivation.

"This can help us to understand better how cells respond in the short term and, in turn, how that makes way for long-term damage," said Richards of the organoid model.

This model also enables researchers to test whether heart drugs improve heart attack outcomes.

"It could help us determine whether a drug is effective at preventing some of this damage or preventing a detrimental response to an oxygen shortage," explained Richards.

The model could also provide a way to test whether a drug that is safe in a healthy heart is also safe in a diseased one. Such information could guide physicians in prescribing drugs more appropriately in patients who had preexisting heart conditions at the time of the heart attack.

In short, the model provides researchers with an understanding of the early events of a heart attack that they have not had before. But Mei intends to make the model even better by including immune cells. Immune cells are responsible for cleaning out any dead cells caused by the heart attack, but by doing so, they can determine how immune cells play a role in the restructuring of heart tissue after damage from an oxygen shortage. The Mei lab would like to study how they do so in hopes of preventing the death of damaged but still living areas of the heart.

Mei would also like to examine the effects of patients' genetics on their outcomes. His laboratory is currently working on creating organoids from cells from patients with diverse outcomes. Those organoids can then be used to help us to understand more fully how a patient's specific genetic profile affects his or her recovery.

"We are not the first ones to recapitulate the cellular or even the tissue-level response. I would argue, however, that we are the first ones to recapitulate the organ-level response," said Mei.

Special note: Mei, Richards and their co-authors would like to dedicate this work to their dear friend and co-author Craig Beeson, Ph.D., who was lost to cancer before the publication of their article.

What nitrogen is getting up to in permafrost soils may be much more interesting than researchers have long believed--with potentially significant consequences for our management of climate change.

Nitrogen is a constituent part of nitrous oxide (N2O)--an often overlooked greenhouse gas, and there is a vast amount of nitrogen stored in permafrost soils.

But little is known about N2O emissions from permafrost soils and until recently, it was assumed that releases had to be fairly minimal because of the cold climate.

Decomposition of organic matter is slow in low temperatures. Exacerbating this, there would have to be high competition amongst organisms for what little nitrogen there was in a form that they can use. So there couldn't be much nitrogen left over to contribute to N2O releases.

In recent years however, a growing number of papers have started to hint that there might be very high N2O emissions from such soils, perhaps as much as those from tropical forests or croplands, which suggests that there's a gap in our understanding of what happens to nitrogen in permafrost soils.

To get to the bottom of the issue, Dr. Michael Dannenmann from the Karlsruhe Institute of Technology and Dr. Chunyan Liu from the Institute of Atmospheric Physics at the Chinese Academy of Sciences with their colleagues have established the "NIFROCLIM" project in a high-latitude permafrost region in northeast China that is part of the Eurasian permafrost complex--the world's largest permafrost area.

The profile of "NIFROCLIM" was publsihed on May 23 in Advances in Atmospheric Sciences.

"In contrast to the huge volumes of research into permafrost carbon climate feedbacks, research into permafrost nitrogen climate feedbacks is lagging behind terribly," said by Elisabeth Ramm, the first author of the News & Views article. "We urgently need to better understand what is happening to nitrogen in these soils, especially as the world warms and permafrost thaws."

The researchers are taking high-resolution soil and gas samples down to the upper layers of the permafrost across multiple sites with differing landscape characteristics, from upland forests to lowland bogs, as well as engaging in experiments that simulate varying levels of warming.

Building a scientific outpost on the southern edge of this region is ideal for studying impact of climate change on permafrost as the arctic and subarctic in particular is being hit hard already by global warming.

Temperature increases occur here at more than double the pace of the global average, accelerating permafrost degradation and N transformations.

"If anywhere is going to tell us if we've been getting the math wrong on nitrogen, it's here." said Liu.

CHICAGO (June 12, 2020): A cost-effective strategy for health care systems to offset N95 mask shortages due to the Coronavirus Disease 2019 (COVID-19) pandemic is to switch to reusable elastomeric respirator masks, according to new study results. These long-lasting masks, often used in industry and construction, cost at least 10 times less per month than disinfecting and reusing N95 masks meant to be for single use, say authors of the study, published as an "article in press" on the Journal of the American College of Surgeons website in advance of print.

The study is one of the first to evaluate the cost-effectiveness of using elastomeric masks in a health care setting during the COVID-19 pandemic, said Sricharan Chalikonda, MD, MHA, FACS, lead study author and chief medical operations officer for Pittsburgh-based Allegheny Health Network (AHN), where the study took place.

Disposable N95 masks are the standard face covering when health care providers require high-level respiratory protection, but during the pandemic, providers experienced widespread supply chain shortages and price increases, Dr. Chalikonda said. He said hospitals need a long-term solution.

"We don't know if there will be a shortage of N95s again. We don't know how long the pandemic will last and how often there will be virus surges," he said. "We believe now is the time to invest in an elastomeric mask program."

Dr. Chalikonda said an immediate supply of elastomeric masks in a health care system's stockpile of personal protective equipment is "game changing" given the advantages.

Benefits of elastomeric masks

Elastomeric masks are made of a tight-fitting, flexible, rubber-like material that can adjust to nearly all individuals' faces and can withstand multiple cleanings, Dr. Chalikonda said. These devices, which resemble gas masks, use a replaceable filter. According to the Centers for Disease Control and Prevention (CDC), elastomeric masks offer health care workers equal or better protection from airborne infectious substances compared with N95 masks.1

Like many hospitals during the COVID-19 crisis, AHN was disinfecting and reusing N95 masks for a limited number of uses. However, Dr. Chalikonda said, "Many caregivers felt the N95 masks didn't fit quite as well after disinfection."

At the end of March, AHN began a one-month trial of a half-facepiece elastomeric mask covering the nose and mouth. The mask holds a P100-rated cartridge filter, meaning it filters out almost 100 percent of airborne particles.2

Until AHN could procure more elastomeric masks, the system began its program for P100 elastomeric mask "super-users": those providers who have the most frequent contact with COVID-19 patients. At each of AHN's nine hospitals in Pennsylvania and Western New York, the first providers to receive the new masks were respiratory therapists, anesthesia providers, and emergency department and intensive care unit (ICU) doctors and nurses. Initially, providers shared the reusable masks with workers on other shifts, and the masks underwent decontamination between shifts using vaporized hydrogen peroxide similar to the technique used to sterilize disposable N95 masks.

As more masks became available, workers kept their own mask and disinfected it themselves according to the manufacturer's guidelines. Gradually AHN provided more staff with the new masks.

Among nearly 2,000 health care providers receiving fit testing for an elastomeric mask (as required for any mask to make sure no unfiltered air penetrates it), 94 percent could wear one, the investigators reported. The small number of workers without a proper fit received an alternate type of respirator mask.

After a month of use, no one wearing an elastomeric mask chose to return to an N95 mask, according to the authors. Regarding the elastomeric masks, Dr. Chalikonda said, "Our clinicians were very comfortable with the fit, knowing it was an equivalent if not superior amount of protection, and that these masks were intended to be reused."

Furthermore, patients were receptive to their care providers wearing this type of respirator, he noted.

Cost savings

To determine if the elastomeric masks were cost-effective, the researchers performed a cost-benefit analysis over one month of mask disinfection and reuse comparing the new masks, with the filter replaced monthly, versus N95 masks at one hospital's 18-bed intensive care unit (ICU). Although the elastomeric mask costs about $20 and the filter costs $10 compared with only $3 at that time for an N95 mask, the research team found the elastomeric masks were "conservatively" 10 times less expensive.

The cost savings, Dr. Chalikonda said, increases the longer they use the elastomeric masks, which often can last for years, and these masks can remain in storage for long periods, thus improving the planning and management of the medical supply stockpile for future outbreaks.

He explained the monthly cost is lower because they can disinfect elastomeric masks much more often, multiple caregivers can share the same mask, and, unlike N95s masks, they do not need to waste the mask after a failed fit test.

Another advantage of an elastomeric respirator program, according to Dr. Chalikonda, is it does not require any additional hospital resources to implement if the hospital already has an N95 mask reuse and resterilization program. The AHN elastomeric mask program presented fewer operational challenges than disinfecting N95 masks, he stated.

Emerging evidence suggests that COVID-19 may actually trigger the onset of diabetes in healthy people and also cause severe complications of pre-existing diabetes.

A letter published today in the New England Journal of Medicine and signed by an international group of 17 leading diabetes experts involved in the CoviDiab Registry project, a collaborative international research initiative, announces the establishment of a Global Registry of new cases of diabetes in patients with COVID-19.

The Registry aims to understand the extent and the characteristics of the manifestations of diabetes in patients with COVID-19, and the best strategies for the treatment and monitoring of affected patients, during and after the pandemic.

Clinical observations so far show a bi-directional relationship between COVID-19 and diabetes. On the one hand, diabetes is associated with increased risk of COVID-19 severity and mortality. Between 20 and 30% of patients who died with COVID-19 have been reported to have diabetes. On the other hand, new-onset diabetes and atypical metabolic complications of pre-existing diabetes, including life-threatening ones, have been observed in people with COVID-19.

It is still unclear how SARS-Cov-2, the virus that causes COVID-19, impacts diabetes. Previous research has shown that ACE-2, the protein that binds to SARS-Cov-2 allowing the virus to enter human cells, is not only located in the lungs but also in organs and tissues involved in glucose metabolism such as the pancreas, the small intestine, the fat tissue, the liver and the kidney. Researchers hypothesise that by entering these tissues, the virus may cause multiple and complex dysfunctions of glucose metabolism. It has also been known for many years that virus infections can precipitate type 1 diabetes.

Francesco Rubino, Professor of Metabolic Surgery at King's College London and co-lead investigator of the CoviDiab Registry project, said: "Diabetes is one of the most prevalent chronic diseases and we are now realizing the consequences of the inevitable clash between two pandemics. Given the short period of human contact with this new coronavirus, the exact mechanism by which the virus influences glucose metabolism is still unclear and we don't know whether the acute manifestation of diabetes in these patients represent classic type 1, type 2 or possibly a new form of diabetes".

Paul Zimmet, Professor of Diabetes at Monash University in Melbourne, Honorary President of the International Diabetes Federation and co-lead investigator in the CoviDiab Registry project said: "We don't yet know the magnitude of the new onset diabetes in COVID-19 and if it will persist or resolve after the infection; and if so, whether or not or COVID-19 increases risk of future diabetes. By establishing this Global Registry, we are calling on the international medical community to rapidly share relevant clinical observations that can help answer these questions".

Stephanie Amiel, Professor of Diabetes Research at King's College London and a co-investigator of the CoviDiab Registry project said: "The registry focuses on routinely collected clinical data that will help us examine insulin secretory capacity, insulin resistance and autoimmune antibody status to understand how COVID-19 related diabetes develops, its natural history and best management. Studying COVID-19-related diabetes may uncover novel mechanisms of disease."

Like most galaxies, the Milky Way hosts a supermassive black hole at its center. Called Sagittarius A*, the object has captured astronomers' curiosity for decades. And now there is an effort to image it directly.

Catching a good photo of the celestial beast will require a better understanding of what's going on around it, which has proved challenging due to the vastly different scales involved. "That's the biggest thing we had to overcome," said Sean Ressler, a postdoctoral researcher at UC Santa Barbara's Kavli Institute for Theoretical Physics (KITP), who just published a paper in the Astrophysical Journal Letters, investigating the magnetic properties of the accretion disk surrounding Sagittarius A*.

In the study, Ressler, fellow KITP postdoc Chris White and their colleagues, Eliot Quataert of UC Berkeley and James Stone at the Institute for Advanced Study, sought to determine whether the black hole's magnetic field, which is generated by in-falling matter, can build up to the point where it briefly chokes off this flow, a condition scientists call magnetically arrested. Answering this would require simulating the system all the way out to the closest orbiting stars.

The system in question spans seven orders of magnitude. The black hole's event horizon, or envelope of no return, reaches around 4 to 8 million miles from its center. Meanwhile, the stars orbit around 20 trillion miles away, or about as far as the sun's nearest neighboring star.

"So you have to track the matter falling in from this very large scale all the way down to this very small scale," said Ressler. "And doing that in a single simulation is incredibly challenging, to the point that it's impossible." The smallest events proceed on timescales of seconds while the largest phenomena play out over thousands of years.

This paper connects small scale simulations, which are mostly theory-based, with large-scale simulations that can be constrained by actual observations. To achieve this, Ressler divided the task between models at three overlapping scales.

The first simulation relied on data from Sagittarius A*'s surrounding stars. Fortunately, the black hole's activity is dominated by just 30 or so Wolf-Rayet stars, which blow off tremendous amounts of material. "The mass loss from just one of the stars is larger than the total amount of stuff falling into the black hole during the same time," Ressler said. The stars spend only around 100,000 years in this dynamic phase before transitioning into a more stable stage of life.

Using observational data, Ressler simulated the orbits of these stars over the course of about a thousand years. He then used the results as the starting point for a simulation of medium-range distances, which evolve over shorter time scales. He repeated this for a simulation down to the very edge of the event horizon, where activity takes place in matters of seconds. Rather than stitching together hard overlaps, this approach allowed Ressler to fade the results of the three simulations into one another.

"These are really the first models of the accretion at the smallest scales in [Sagittarius] A* that take into account the reality of the supply of matter coming from orbiting stars," said coauthor White.

And the technique worked splendidly. "It went beyond my expectations," Ressler remarked.

The results indicated that Sagittarius A* can become magnetically arrested. This came as a surprise to the team, since the Milky Way has a relatively quiet galactic center. Usually, magnetically arrested black holes have high-energy jets shooting particles away at relativistic speeds. But so far scientists have seen little evidence for jets around Sagittarius A*.

"The other ingredient that helps create jets is a rapidly spinning black hole," said White, "so this may be telling us something about the spin of Sagittarius A*."

Unfortunately, black hole spin is difficult to determine. Ressler modeled Sagittarius A* as a stationary object. "We don't know anything about the spin," he said. "There's a possibility that it's actually just not spinning."

Ressler and White next plan to model a spinning back hole, which is much more challenging. It immediately introduces a host of new variables, including spin rate, direction and tilt relative to the accretion disc. They will use data from the European Southern Observatory's GRAVITY interferometer to guide these decisions.

The team used the simulations to create images that can be compared to actual observations of the black hole. Scientists at the Event Horizon Telescope collaboration -- which made headlines in April 2019 with the first direct image of a black hole -- have already reached out requesting the simulation data in order to supplement their effort to photograph Sagittarius A*.

The Event Horizon Telescope effectively takes a time average of its observations, which results in a blurry image. This was less of an issue when the observatory had their sights on Messier 87*, because it is around 1,000 times larger than Sagittarius A*, so it changes around 1,000 times more slowly.

"It's like taking a picture of a sloth versus taking a picture of a hummingbird," Ressler explained. Their current and future results should help the consortium interpret their data on our own galactic center.

Ressler's results are a big step forward in our understanding of the activity at the center of the Milky Way. "This is the first time that Sagittarius A* has been modeled over such a large range in radii in 3D simulations, and the first event horizon-scale simulations to employ direct observations of the Wolf-Rayet stars," Ressler said.

Hollings Cancer Center researchers at the Medical University of South Carolina (MUSC) and colleagues assessed the connection between dietary advanced glycation end products (AGEs) and breast cancer risk in a study first published online March 2020 in Cancer Prevention Research.

It supports an increasingly evident link between high levels of AGEs in the body and cancer risk, said principal investigator David Turner, Ph.D., who worked with colleagues Susan Steck, Ph.D., with the University of South Carolina, and Lindsay Peterson, M.D., with Washington University School of Medicine.

The study was part of a larger decade-long prostate, lung, colorectal and ovarian cancer screening trial (PLCO) designed and sponsored by the National Cancer Institute. It included over 78,000 women between the ages of 55 and 74 years who were cancer free at the start of the study. The women completed a food frequency questionnaire at the beginning and again at five years into the study. After an average of 11 ½ years, 1,592 of the women were diagnosed with breast cancer. When the intake of high-AGE food was assessed, based on the questionnaires, increased AGE intake via the diet was associated with an increased risk of in situ and hormone receptor positive breast cancers.

Advanced glycation end products are proteins and lipids (fats) that go through a chemical alteration called glycation when they are exposed to sugars. This process occurs naturally in the body. However, processed foods and foods cooked at high temperatures are extremely high in AGEs, which can lead to a dangerous overabundance in the body.

Turner said AGEs are involved in nearly every chronic disease, in some way. "The study of AGEs in cancer is just starting to get traction. The presence of AGEs has been known for at least 100 years, but the research has been challenging. In order to determine how they work, their mechanism of action, researchers first have to determine a role in various diseases."

Turner said this study is important because it adds to the evidence between high levels of AGEs in the body and cancer risk. Turner and his collaborators are promoting the connection between AGEs and lifestyle choices to help the public make better food choices.

This will become an even more popular area of study as researchers employ new tools to help study AGEs. "A novel device, the AGE reader, is about to change how we look at AGEs in the clinic," Turner said. The AGE reader, made by Diagnoptics, is an easy to use noninvasive device where someone rests their forearm for just 12 seconds. It uses light at certain wavelengths to excite AGE autofluorescence in the human skin tissue.

"This machine actually measures glow from some of the AGEs. The more AGEs that are in the skin, the higher the glow," explained Turner.

While the AGE reader has been used to show strong correlations between AGE levels and Type 2 diabetes, cardiovascular disease and even mortality, Turner is using a cancer center support grant to validate further the AGE reader for use in cancer patients. He and his colleagues plan to investigate whether pigmentation in the skin skews the reading and use the reader as part of a growing community outreach program.

Since a link between AGEs and breast cancer has been shown, the ultimate goal is to test all Hollings Cancer Center patients who are interested at each visit, Turner said. This will provide a huge amount of data about the link between AGEs and a wide variety of cancers. Turner and his collaborators expect that future multicenter grants will come out of this project.

While the connection between high AGE levels and cancer risk might be disconcerting, research is also being done to determine if there is a way to reverse the detrimental effects of AGEs.

Bradley Krisanits, a Ph.D. student in Turner's lab, said that preliminarily, they have seen that physical activity reduces the amount of AGEs in the circulation.

"In our prostate cancer models, we see that physical activity counteracts prostate cancer progression in mice fed a high-AGE diet. This may be occurring due to a reduction in AGEs and changes in the immune system that we need to study more."

Turner hopes that by educating people about AGEs, they can make informed lifestyle decisions and lower their risks for chronic diseases. The top three things that a person can do is learn what AGEs are, avoid processed foods and think about how you cook your food in order to make changes to avoid the highest AGE-inducing cooking methods such as frying, grilling and broiling.

"AGEs build up in a cumulative way. Fats, sugars, everything that is bad for you leads to the accumulation of AGEs. One of our goals at Hollings is to reach out to the community to encourage the public to make healthier choices. Just making small changes in your diet can have a big effect."

Five years before the novel coronavirus ran rampant around the world, saiga antelopes from the steppes of Eurasia experienced their own epidemic.

Millions of these grazing animals--easily recognizable by their oversized snouts--once migrated across what is today Kazakhstan, Mongolia, Georgia and more.

But then, over the span of three weeks in 2015, nearly 200,000, or two-thirds of their existing population, sickened and died from a bacterial infection. Today, the a little more than 100,000 saiga are hanging onto survival in a few pockets of Eurasia.

The decline, and uncertain fate, of the saiga is a story that resonates with Joanna Lambert. She's a conservation biologist at the University of Colorado Boulder and a coauthor of a paper published this week in the journal Frontiers in Ecology and Evolution. The study explores the current state of ungulates, or hoofed animals like the saiga, in the western U.S. and around the world.

Lambert, who has studied ecological communities in both North America and Equatorial Africa, explained that many of these creatures aren't well-known outside of their home regions. But when these animals disappear, entire ecosystems can reshuffle, occasionally beyond recognition.

"We're losing these animals without people ever knowing they were there in the first place," said Lambert, a professor in the Program of Environmental Studies at CU Boulder.

For the researcher, the study's publication marks an opportunity to reflect on how she stays hopeful even amid tremendous losses--and how to talk about the natural world during a period of unprecedented social upheaval.

"I tell my students, 'I have to give you the facts. This is the world you're growing up in, but don't let that paralyze you,'" Lambert said.

Unsung species

The new research was led by Joel Berger of Colorado State University and also included scientists from Bhutan, Argentina and Chile.

The team decided to look at ungulates because--with a few exceptions like rhinos and elephants--they don't usually pop up in brochures for conservation organizations. But, Lambart said, they're still in trouble: Huemel, for example, once roamed across the Patagonia region of South America. Today, a little more than 1,000 of these fluffy deer still live in the wild. The tamaraw, a pint-sized buffalo from the Philippines, is down to just a few hundred individuals.

"The whole world knows the stories of pandas and mountain gorillas, but there are untold numbers of unsung species that come and go without the world's attention," she said.

Their cases also show just how complicated conservation can be.

Lambert has spent years trekking the grasslands and forests of Yellowstone National Park to study wildlife. After federal officials killed all the park's wolves in the 1940s, elk herds there began to multiply--big time. Head counts for these herbivores surged from a few thousand individuals to tens of thousands, and they devoured once-abundant plants like cottonwood and willow trees.

"When you pull one species out of its community, or if you add a new one in, the entire assembly changes," Lambert said. "That has been the history of what humans have done on the planet."

When the park brought wolves back in the 1990s, and elk numbers dropped back down, something unexpected happened: beavers, which had also disappeared from Yellowstone, began reappearing, too. The furry swimmers, it turns out, depend on those same tree species to build their dams.

"In many cases, we don't know what rules these ecosystems followed in the past," she said. "Even when we do know, it doesn't matter because we now have this added element of human tinkering."

Ecological grief

Lambert has also struggled to keep going as a conservation biologist as the wilds around her field sites in Africa and North America dwindled, then vanished entirely.

"As I returned each year from the field, it was taking me longer and longer to recover from a sort of existential depression," she said. "I realized that I have been profoundly impacted by the losses I've seen."

Many of Lambert's students feel similarly hopeless, a phenomenon that psychologists call "ecological grief." She tells them to focus on the success stories, however rare they are. Protected areas like Yellowstone have saved countless animals from extinction and have given others like wolves new chances at survival. Lambert is also providing scientific guidance around proposals to return wolves to Colorado.

And there are still a lot of animals out there--including the few remaining herds of big-nosed saiga.

"We need to fight like hell to keep all that," she said.

Here's some good news for U.S. states trying to spur an economic recovery in the years ahead: The R&D tax credit has a significant effect on entrepreneurship, according to a new study led by an MIT professor.

Moreover, the study finds a striking contrast between two types of tax credits. While the R&D tax credit fuels high-quality new-firm growth, the state-level investment tax credit, which supports general business needs, actually has a slightly negative economic effect on that kind of innovative activity.

The underlying reason for the difference, the study's authors believe, is that R&D tax credits, which are for innovative research and development, help ambitious startup firms flourish. But when states are simply granting investment tax credits, allowing long-established firms to expand, they are supporting businesses with less growth ahead of them, and thus not placing winning policy bets over time.

"What we see is an improvement in the environment for entrepreneurship in general, specifically for those growth-oriented startups that ultimately are the engine of business dynamism," says MIT economist Scott Stern, co-author of a newly published paper detailing the study's results.

"States that introduced R&D tax credits set the table for increased entrepreneurship," says Catherine Fazio MBA '14, a co-author of the study and research affiliate at the MIT Lab for Innovation Science and Policy.

Specifically, the study finds that -- other things being equal, and accounting for existing growth trends -- areas introducing R&D tax credits experience a 20 percent rise in high-quality new-firm-formation over a 10-year period, whereas areas using investment tax credits see a 12 percent drop in high-quality firm growth, also over a 10-year period.

"The investment tax credit arguably reinforces the strength of big business in these states, and that might create a barrier to entry for new firms," Stern explains. "It might harm entrepreneurship. But the R&D tax credit facilitates knowledge, facilitates science, facilitates exactly the sorts of things that can spur new ideas, and spurring new ideas is the key for our entrepreneurial ecosystem."

Indeed, adds Jorge Guzman MBA '11, PhD '17, a management professor and co-author of the study, "States offering both R&D and investment tax credits in an effort to stimulate high-growth entrepreneurship may actually be offering incentives that work at cross purposes to each other."

The paper, "The Impact of State-Level Research and Development Tax Credits on the Quality and Quantity of Entrepreneurship," appears in the latest issue of Economic Development Quarterly. Fazio is also a lecturer at Boston University's Questrom School of Business; Guzman is an assistant professor at the Columbia Business School of Columbia University; and Stern is the David Sarnoff Professor of Management of Technology at the MIT Sloan School of Management.

Third year is the take-off point

The R&D tax credit was introduced in 1981 at the federal level, with states soon adding it to their own policy toolkits. From 1981 through 2006, 32 states have implemented R&D tax credits. At the same time, 20 states granted investment tax credits. Yet no study has specifically examined the impact of state R&D tax credits on new firms.

"A classical question that had previously resisted empirical scrutiny was the impact of the state-level R&D tax credit on entrepreneurship," Stern says. Moreover, he adds, it's reasonable to question how effective the policy might be: "Growth-oriented startups don't pay a lot of taxes upfront, so it's not clear how salient taxes would be for entrepreneurship."

To conduct the study, the researchers used a unique database they have created: the Startup Cartography Project, which features about 30 years of data on business formation and startup quality -- including data showing the likelihood of success for new firms based on their key characteristics. (For instance, firms that seek intellectual property protection, or are organized to attract further equity financing, are more likely to succeed).

The scholars also used the Upjohn Panel Data on Incentives and Taxes, which contain detailed records of state tax policies, collected by Timothy Bartik, a senior economist at the W.J. Upjohn Institute for Employment Research.

By evaluating tax policy changes alongside changes in business activity, the researchers could assess the state-level effects of the R&D tax credit. Crucially, the study not only tallies firm formation, but also analyzes the quality of those startup firms and the development of local innovation ecosystems, to measure the full impact of the policy changes.

Ultimately the study examined 25 states where the two data sets overlapped thoroughly from 1990 to 2010, with the R&D tax credit available to companies in counties within these states 46 percent of the time.

By examining before-and-after data around the introduction of the state-level R&D tax credit, the researchers concluded that the policy change created more startup activity.

Intriguingly, the study found that the third year after the introduction of the R&D tax credit is the real take-off point for entrepreneurship in a state, with a roughly 2 percent annual growth in high-quality firm formation from that year through the 14th year after the policy change.

"It takes a few years for that impact to make its way through the system," Stern says. "If you expect a one-year payoff from this, that's too short."

To be clear, many large businesses have long featured active R&D arms, and may also benefit from the state-level R&D tax credit. Indeed, Stern says, the current study was partly motivated by policymakers' past focus on the benefits of tax credits for major corporations. Those may be real enough, but they are not the sole area of influence for the R&D tax credit.

"The policy discussion has mostly focused on lowering the burden on, and providing incentives for, investment for big business," Stern says. "Right now Amazon, for example, takes a very large R&D tax credit. And it can say, 'Do you like your Amazon Echo or Alexa and your crowdsourcing services? Well, all that came from our R&D.'" At the same time, Stern adds, "If the main policy rationale has always been to help big business, over time, [people in] public policy have discussed if it also helps startups." The study now brings data to that conversation.

The long road ahead

The current study started well before the Covid-19 crisis, which has led to a massive rise in unemployment and severe problems and uncertainty for small businesses. To be clear, Stern observes, any reasonable recovery will require policy tools that extensively reach long-existing types of firms, rather than just depending on new growth.

"In this particular economic crisis, and public health crisis, we're going to need to be restoring Main Street in a really important way," Stern says. That means helping local restaurants, retail stores, and many other traditional small businesses, Stern emphasizes. As part of his ongoing work, he is now examining new business registrations of all kinds this spring, in the midst of the pandemic.

Still, the damage from the recovery has been so vast that efforts to bounce back must take multiple tracks -- including incentives for innovative firms that might fill business needs created by the Covid-19 crisis.

"While no one can predict the future, we know that the actual economic recovery is going to depend on restoring business dynamism," Stern says. "And that means we need to start getting new entrants, and make new entrepreneurship easier and better."

States willing to give R&D tax relief to firms could well see the tactic spurring on part of a larger, eventual recovery.

"The R&D tax credit is one of the few innovation policy instruments that at relatively low administrative cost, can make a big difference for spurring innovation and entrepreneurship within a region," Stern emphasizes. "You have to be committed to it. You have got to be patient. But it does pay off."

Since the discovery of the double helix form of DNA and the hypothesis of DNA mutation induced by proton transfer more than 50 years ago, it has been recognized that proton transfer is crucial to many chemical and biological processes.

As these processes are known to be relevant to biophysics and radiation therapy, a question arises whether a massive ion could be transferred in biochemical processes and lead to fragmentation. Specifically, in a complex bio-environment, does heavy ion transfer play a role?

Published in Nature Communications on June 12, a study reporting a new channel involving heavy N+ ion transfer observed in a charged Van der Waals cluster helps address the above questions.

The study was conducted by a team of researchers from the Institute of Modern Physics (IMP) of the Chinese Academy of Sciences (CAS), the Institute of Applied Physics and Computational Mathematics, and Centre de recherche sur les Ions, les MAtériaux et la Photonique (CIMAP) in France.

"Small van der Waals systems can be employed as experimentally feasible model systems," said Prof. ZHU Xiaolong of IMP, one of the first authors. Van der Waals (vdW) clusters are weakly bound atomic/molecular systems. "They are common in nature and important for understanding microenvironmental chemical phenomena in biosystems."

Interatomic Coulombic decay is a typical process that demonstrates the energy and charge transfer over a large distance between atomic components in a cluster and results in fragmentation, proving that forbidden channels for isolated atoms/molecules may be opened due to the presence of neighboring atoms. Here, the energy and charge transfers are mediated by virtual photon or Coulomb interaction.

In hydrogen-bond clusters, the proton transfer process plays an important role as well. It involves mass and charge migration over large distances within the cluster and results in fragmentation of the latter. Nevertheless, in previous research, this kind of transfer process was limited to hydrogen-bond clusters.

In the current work, the scientists used the neutral vdW cluster N2 Ar as a target in collisions with 1 MeV Ne8+ ions to produce the doubly charged cluster (N2Ar)2+.

Surprisingly, an exotic heavy N+ ion transfer channel (N2 Ar)2+ → N+ + NAr+ was observed. It is the first time that such a heavy-ion transfer process in a vdW cluster has ever been reported and the consequent formation of NAr+ is a novel scenario.

According to the study, this channel originates from the dissociation of the parent doubly charged cluster N22+ Ar generated by the "N2-site" two-electron loss process.

Theoretical calculations show that the polarization interactions between Ar and N22+ lead first to an isomerization process of N22+ Ar from its initial T-shape to a linear shape (N-N-Ar).

In addition, the neighboring neutral Ar atom decreases the N22+ barrier height and width, resulting in significantly shorter lifetimes for the metastable electronic state.

Consequently, the breakup of the covalent N+-N+ bond, the tunneling out of the N+ ion from the N22+ potential well, as well as the formation of the N-Ar+ bound system take place almost simultaneously. Then the Coulomb explosion starts between N+ and NAr+ ion pairs.

"This new mechanism might be general for molecular dimer ions in the presence of a neighboring atom, and be of potential importance in understanding the microdynamics of biological systems," said Prof. MA Xinwen from IMP, one of the corresponding authors of this paper. "For example, it may help us understand the micromechanism of cancer therapy by heavy ion irradiation."

Physicians must be competent collaborators with team members in order to practice medicine effectively. Health professional students have limited opportunities to work and learn together during the course of their medical education. Not only is it important for students to acquire prodigious knowledge, they must also learn how to collaborate well, and the results of their efforts must be evaluated fairly to measure the effectiveness of this collaborative, active learning.

Assistant professor Ikuo Shimizu of Shinshu University School of Medicine and collaborators used a modified Delphi procedure to develop the content validity of the students social interdependence in collaborative learning. Teamwork and collaboration are common goals in all of higher education and the workplace, but not always properly evaluated. It is crucial to come up with a fair assessment that can be utilized for further improvement of techniques and procedures.

Although it was difficult to recruit a diverse panel from abroad, assistant professor Shimizu was able to form a panel of medical students, education experts and medical educators from 8 different countries including Australia, Czech Republic, Japan, Malaysia, the Netherlands, Singapore, Thailand and the United States. The medical educators all had experience on collaborative learning such as problem based learning and team-based learning in health profession education curriculum.

Social interdependence theory, widely applied in educational psychology states that the transformation from self-interest to mutual interest when the outcomes of individuals are affected by their own and other's actions in a positive or negative social interdependence acts as an incentive for collaboration or not. When the common goal can only be achieved by the input of all members and not of just one player, positive social interdependence plays a role in collaborative efforts from all.

In order to execute the study, instrument development was conducted through building consensus among experts in a systematic manner and allowing for multiple feedback rounds and effective implementation. After the instrument development phase, validation of the instrument was performed through evaluating questionnaires. The group was successful in developing a scale for measuring social interdependence in collaborative learning by incorporating the opinions of international stakeholders.

Assistant professor Shimizu expresses, "in medical education, it is important to develop mutual reciprocal interdependence to aim for better practice while bringing out the best in each other's skills. I hope others will utilize this evaluation method in multi-disciplinary cooperative education. By using this evaluation method, active learning practices can hopefully be further improved."

Please read Measuring social interdependence in collaborative learning: instrument development and validation for more information.

Professor Junichiro Shiomi et al. from The University of Tokyo aimed to reduce the thermal conductivity of semiconductor materials by reducing the internal nanostructure, and successfully minimized thermal conductivity by designing, fabricating, and evaluating the optimal nanostructure-multilayer materials through materials informatics (MI), which combines machine learning and molecular simulation. In 2017, this research group developed a method to design an optimal structure that minimizes or maximizes thermal conductivity via MI based on computational science. However, it has not been experimentally demonstrated, and preparation of nano-scale structures and realization of an optimal structure based on property measurements were desired.

Thus, the research group utilized a film deposition method able to regulate, at a molecular level, a superlattice structure wherein two materials were alternately layered at several nm thick, and a measurement method that could assess thermal conductivity of a film at nano-scale, and realized the optimal aperiodic superlattice structure that minimizes thermal conductivity. With the optimal structure, wave interference of the lattice vibration (phonon) that conducts heat was maximized, and thermal conductivity was strongly regulated.

In the present study, using the semiconductor lattice structure as the model, the research group verified the utility of the MI method in design, fabrication, assessment, and mechanism elucidation toward regulation of thermal conductivity. In the future, application of the MI method to various material systems is anticipated. It was also shown that optimization of the aperiodic structure can regulate thermal conductivity by fully controlling the wave property of a phonon at near room temperature. This is expected to contribute to developments in phonon engineering for instance in thermoelectric conversion devices, optical sensors, and gas sensors, where low thermal conductivity is needed while maintaining electric conductivity and mechanical properties.

DURHAM, N.C. -- Duke University researchers have developed an AI tool that can turn blurry, unrecognizable pictures of people's faces into eerily convincing computer-generated portraits, in finer detail than ever before.

Previous methods can scale an image of a face up to eight times its original resolution. But the Duke team has come up with a way to take a handful of pixels and create realistic-looking faces with up to 64 times the resolution, 'imagining' features such as fine lines, eyelashes and stubble that weren't there in the first place.

"Never have super-resolution images been created at this resolution before with this much detail," said Duke computer scientist Cynthia Rudin, who led the team.

The system cannot be used to identify people, the researchers say: It won't turn an out-of-focus, unrecognizable photo from a security camera into a crystal clear image of a real person. Rather, it is capable of generating new faces that don't exist, but look plausibly real.

While the researchers focused on faces as a proof of concept, the same technique could in theory take low-res shots of almost anything and create sharp, realistic-looking pictures, with applications ranging from medicine and microscopy to astronomy and satellite imagery, said co-author Sachit Menon '20, who just graduated from Duke with a double-major in mathematics and computer science.

The researchers will present their method, called PULSE, next week at the 2020 Conference on Computer Vision and Pattern Recognition (CVPR), held virtually from June 14 to June 19.

Traditional approaches take a low-resolution image and 'guess' what extra pixels are needed by trying to get them to match, on average, with corresponding pixels in high-resolution images the computer has seen before. As a result of this averaging, textured areas in hair and skin that might not line up perfectly from one pixel to the next end up looking fuzzy and indistinct.

The Duke team came up with a different approach. Instead of taking a low-resolution image and slowly adding new detail, the system scours AI-generated examples of high-resolution faces, searching for ones that look as much as possible like the input image when shrunk down to the same size.

The team used a tool in machine learning called a "generative adversarial network," or GAN, which are two neural networks trained on the same data set of photos. One network comes up with AI-created human faces that mimic the ones it was trained on, while the other takes this output and decides if it is convincing enough to be mistaken for the real thing. The first network gets better and better with experience, until the second network can't tell the difference.

PULSE can create realistic-looking images from noisy, poor-quality input that other methods can't, Rudin said. From a single blurred image of a face it can spit out any number of uncannily lifelike possibilities, each of which looks subtly like a different person.

Even given pixelated photos where the eyes and mouth are barely recognizable, "our algorithm still manages to do something with it, which is something that traditional approaches can't do," said co-author Alex Damian '20, a Duke math major.

The system can convert a 16x16-pixel image of a face to 1024 x 1024 pixels in a few seconds, adding more than a million pixels, akin to HD resolution. Details such as pores, wrinkles, and wisps of hair that are imperceptible in the low-res photos become crisp and clear in the computer-generated versions.

The researchers asked 40 people to rate 1,440 images generated via PULSE and five other scaling methods on a scale of one to five, and PULSE did the best, scoring almost as high as high-quality photos of actual people.

See the results and upload images for yourself at http://pulse.cs.duke.edu/.

Hamburg/Borstel/Leipzig. The tuberculosis pathogen Mycobacterium tuberculosis can protect itself better when combined and thus stay alive longer in the air. This was the result of a study by the Leibniz Research Alliance INFECTIONS, which was published in the scientific journal Scientific Reports on Monday.

The study examined the biophysical properties of tiny particles in the air (aerosols) that contribute to the spread of the pathogen. A successful human-to-human infection is determined, among other things, by the distance that the pathogen can travel through the air before the infectivity decreases. Conclusion: Although individual mycobacteria form smaller aerosols and can thus travel longer distances in the air, interconnected mycobacteria remain alive for longer. The study is based on earlier results that showed that mycobacteria-infected host cells die necrotic cell death, as occurs in the lungs of tuberculosis patients. It has now been shown that larger aerosol particles from mycobacterial clusters are produced together with components of the dead cells, which are more viable in the air than individual bacteria. Based on these data, computer simulations of airborne dispersal, which take into account the particle size distribution, can be carried out in the future, which will help to find out which aerosol composition may pose an increased risk of infection for humans.

The study was carried out at the Research Center Borstel, Leibniz Lung Center (FZB) in Schleswig-Holstein and the Heinrich Pette Institute (HPI), Leibniz Institute for Experimental Virology in Hamburg. The Leibniz Institute for Tropospheric Research (TROPOS) contributed its expertise in modelling the dispersion of aerosols such as mycobacterial associations floating in the air to the study.

Currently there is a controversial discussion about the importance of the aerosol dispersion of the SARS-CoV-2 virus for the COVID-19 pandemic. Findings on the aerosol spread of pathogens are therefore of particular interest. Whether parts of the new findings on the tuberculosis pathogen can be transferred to the COVID-19 pathogen is, however, currently completely open, since tuberculosis is transmitted by a bacterium that is significantly larger than the SARS-CoV-2 virus. Viruses are considered to be much more sensitive to environmental influences, as they depend on protection by moisture and dry out relatively quickly.

The novel coronavirus SARS-CoV-2 that originated in China has claimed an estimated 100,000 lives in the United States, while a different sort of pandemic is spreading online against Asian Americans, particularly of Chinese descent. A study published in Frontiers in Communication suggests there is a strong relationship between social media use and prejudice.

The authors surveyed nearly 300 people in the United States on their attitudes about China and Chinese people in the wake of the pandemic. They found that "the more an individual believes their most used daily social media is fair, accurate, presents the facts, and is concerned about the public (social media belief), the more that person sees Chinese Americans as a realistic and symbolic threat."

Lead author Dr. Stephen Croucher, a professor of communication at Massey University in New Zealand whose research focuses on the dynamics between majority and minority groups, states that: "This was a big finding for us, as it shows the relationship between a pandemic, social media use and prejudice."

The online questionnaire of 277 white Americans gathered data on demographics, social media use, and various sentiments about Chinese people. The researchers analyzed the results within the framework of Integrated Threat Theory (ITT). ITT examines the components - realistic threats, symbolic threats, intergroup anxiety and negative stereotypes - that lead to prejudice between social groups.

Realistic threats, for example, represent fears related to economic or social power. A sample question on the survey assessing the degree of realistic threat included, ''Because of the presence of Chinese, unemployment will increase.'' Respondents then answered on a scale of one to five, from "strongly disagree" to "strongly agree."

Symbolic threats, on the other hand, relate to concerns about a group's "way of life." Intergroup anxiety refers to negative perceptions that arise from individual interactions between a member of the majority and a minority.

One key finding was that gender plays a significant role in predicting realistic and symbolic threats versus intergroup anxiety among Americans. Women tend to experience realistic or symbolic threats from Chinese Americans, while men experience higher levels of anxiety, according to the study.

"In this case, when faced with a crisis like a pandemic, it just makes sense that men would tend to respond more affectively while women would respond more cognitively - on average," Croucher said.

One head-scratching result from the study found that respondents who identified politically as a Democrat scored higher than Republicans on perceiving Chinese Americans as a symbolic threat.

"The result about political lines really was a surprising result," Croucher said, adding that it would be "really interesting" to further research how political leanings shift when a group is perceived as life threatening.

More than 1,700 incidents of harassment and assaults against Asian Americans have been reported since March 19, according to a website maintained by Asian Pacific Policy and Planning Council, San Francisco State University and Chinese for Affirmative Action.

Until the COVID-19 pandemic, anti-Asian hate crime has been on the decline for at least the past two decades, according to a report in The Washington Post, and the FBI has not reported any anti-Asian-motivated murders since at least 2003.

Croucher said that social media channels, like any media, can also be used effectively for spreading positive messages about Asian Americans. He and his co-authors proposed governments and healthcare industries use social media to combat COVID-19 prejudice.

"In the case of COVID-19, social media, and other media, were and are being used as venues to share and build ideas, values and morals," Croucher said. "Many of these are very positive, but some are not."

The colourful pictures of the whole mouse brain at different ages are the first of their kind and a pivotal step forward in understanding behaviour, scientists say.

Findings - published in the journal Science - could shed light on learning disability and dementia and help to reveal how memories are affected by age.

The images are of synapses - vital connections that carry electrical and chemical messages between brain cells. Synapses store memories and synapse damage is linked to more than 130 brain diseases.

Researchers based at the University of Edinburgh colour-coded the different types of molecules to highlight the range of synapses in mouse brains from birth to old age.

They discovered that the number and molecular makeup of synapses shifts with age in different parts of the brain. This happens at three main phases - childhood, middle and elderly age.

Synapse type shifts with age in patterns unique to areas of the brain, blossoming into a diverse array in midlife.

Images from middle-aged brains burst with colour, illustrating a wide variety of synapses. Both very young and very old brain show less synapses and less complexity.

Researchers say these changes give insights into why genes cause synapse damage at set ages and in set brain areas.

The findings could shed light on why we are more likely to develop brain conditions at certain ages, helping to explain why schizophrenia often starts in adolescence, or why dementia affects older adults.

The study was funded by Wellcome and the European Research Council.

Lead researcher, Professor Seth Grant of the Centre for Clinical Brain Sciences at the University of Edinburgh, said: "The brain is the most complex thing we know of and understanding it at this level of detail is a momentous step forward.

"We believe that these findings will be instrumental to helping understand why the brain is susceptible to disease at different times of life and how the brain changes as we age."