Culture

Researchers at Virginia Commonwealth University and the University of California, Los Angeles have made an important advance that could lead to more energy efficient magnetic memory storage components for computers and other devices.

Magnets are widely used for computer memory because their "up" or "down" polarity -- the magnetic state -- can be "flipped" to write or encode data and store information. Magnetic memory is nonvolatile, so information can be stored on devices without refreshing. However, magnetic memory also requires a lot of energy.

A recently discovered magnetic state called the skyrmion, which is neither "up" nor "down" but flower-shaped, offers a solution. Manipulating the skyrmion state allows for much more efficient, robust data storage for conventional computers and wireless smart devices.

"Our finding demonstrates the possibility of controlling skyrmion states using electric fields, which could ultimately lead to more compact, energy efficient nanomagnetic devices," said Dhritiman Bhattacharya, a doctoral candidate at the VCU College of Engineering and the lead author of the paper, "Creation and annihilation of non-volatile fixed magnetic skyrmions using voltage control of magnetic anisotropy."

The paper published in the June 29 issue of the journal Nature Electronics.

Jayasimha Atulasimha, Ph.D., Qimonda Professor in the VCU Department of Mechanical and Nuclear Engineering, is Bhattachayra's dissertation adviser and corresponding author of the paper. The finding outlined in the paper is "a steppingstone toward ultimately developing commercially viable magnetic memory based on this paradigm," Atulasimha said.

In 2016 and 2018, the VCU researchers showed that using an intermediate skyrmion state to force precise magnetic transitions between the "up" and "down" state could reduce errors in writing information to memory, making devices more robust to material defects and thermal noise. They hold a patent on this idea. The new proof-of-concept experiment presented in Nature Electronics is the first step toward making such a device.

New insight on how four species of seabirds have developed the ability to cruise through both air and water has been published today in the open-access journal eLife.

The study reveals that these birds, from the Alcidae family which includes puffins, murres and their relatives, produce efficient propulsive wakes while flying and swimming. This means that the animals likely spend relatively low amounts of metabolic energy when creating the force they need to move in both air and water. The findings suggest that alcids have been optimised for movement in very different environments through the course of their evolution.

"Birds that use their wings for 'flight' in air and water are expected to fly poorly in both environments compared to those that stick to either air or water only," explains first author Anthony Lapsansky, a PhD candidate at the Field Research Station at Fort Missoula, Division of Biological Sciences, University of Montana, US. "In other words, these jacks-of-all-trades should be the masters of none. Interestingly, however, alcids seem to contradict this notion of a trade-off between aerial and aquatic flight performance, and we wanted to investigate this further."

To gain a better understanding of the potential evolutionary trade-offs between these two types of flight, Lapsansky and his team tested whether alcids exhibit 'efficient Strouhal numbers' when flying in water and air. Animals move in these environments by using oscillating appendages. The Strouhal number describes the frequency at which an animal produces pulses of force with these appendages to power its movement. Only a narrow range of Strouhal numbers are efficient - if a bird flaps its wings too fast or too slow, for a given amplitude and flight speed, then it wastes energy. But most birds have converged on this narrow range of Strouhal numbers, meaning that selection has tuned them to exhibit efficient flapping and swimming movements.

Additionally, Lapsansky and his team were interested to see whether birds that fly in air and water use their muscles in the same way in both environments. "Muscles typically consist of fibers which are tuned for specific activities, but this hardly seems possible when the same muscles are used for movement in two drastically different environments," Lapsansky says. "We hypothesised that alcids maintain efficient Strouhal numbers and consistent stroke velocities across air and water, which would allow them to mitigate the costs of being able to cruise through both environments."

The team used videography to measure the wing movements of four species of alcids that differ substantially in body mass (450g to 1kg) and represent distant branches of the alcid family tree. Their measurements showed that alcids cruise at Strouhal numbers between 0.10 and 0.40 in both air and water, similar to animals that stick to air or water only, but flap their wings approximately 50% slower in water. This suggests that the birds either contract their muscles at inefficient velocities or maintain a two-geared muscle system, highlighting a clear cost to using their wings for movement in air and water.

"Our work provides detailed new insight into how evolution has shaped alcid flight in response to competing environmental demands in air and water," concludes senior author Bret Tobalske, Professor and Director of the Field Research Station at Fort Missoula, Division of Biological Sciences, University of Montana. "Further research is now needed to understand the necessary changes that take place in the flight muscles of these birds to allow them to transition between air and water and back again."

Infant marsupials and monotremes use a connection between their ear and jaw bones shortly after birth to enable them to drink their mothers' milk, new findings in eLife reveal.

This discovery by researchers at King's College London, UK, provides new insights about early development in mammals, and may help scientists better understand how the bones of the middle ear and jaw evolved in mammals and their predecessors.

Marsupials such as opossums, and monotremes such as echidnas, are unusual types of mammals. Both types of animal are born at a very early stage in development, before many bones in the body have started to form. Opossums latch on to their mother's nipple and stay there while they finish developing. Monotremes, which hatch from eggs, lap milk collected near their mother's milk glands as they grow. But how they are able to drink the milk before their jaw joint is fully developed was previously unclear.

"Given the lack of a jaw joint in marsupials and monotremes at birth, scientists have previously suggested that the animals may use a connection between the middle ear bones and jaw bones to allow them to feed," explains lead author Neal Anthwal, Research Associate at the Centre for Craniofacial & Regenerative Biology, at King's College London's Faculty of Dentistry, Oral & Craniofacial Sciences in the UK.

To find out if this is true, Anthwal and his colleagues compared the jaw bones in platypus, short-beaked echidnas, opossums and mice shortly after birth. Their work revealed that, soon after echidnas hatch, their middle ear bones and upper jaw fuse, eventually forming a joint that is similar to the jaws of mammal-like reptile fossils. The team found a similar connection in mouse embryos, but this disappears and the animals are born with functioning jaw joints.

Opossums, by contrast, use connective tissue between their middle ear bones and the base of their skull to create a temporary jaw joint that enables them to nurse shortly after birth. "This all shows that marsupials and monotremes have different strategies for coping with early birth," Anthwal says.

The findings suggest that the connection between the ear and jaw dates back to an early mammal ancestor and persisted when mammals split into subgroups. Marsupials and monotremes continue to use these connections temporarily in early life. In other mammals, such as mice, these connections occur briefly as they develop in the womb but are replaced by a working jaw joint before birth.

"Our work provides novel insight into the evolution of mammals," concludes senior author Abigail Tucker, Principal Investigator and Professor of Development & Evolution at the Centre for Craniofacial & Regenerative Biology, King's College London. "In particular we highlight how structures can change function over evolutionary time but also during development, with the ear bones moving from feeding to hearing. The recent availability of monotreme tissue for molecular analysis, as showcased here, provides an amazing future opportunity to understand the biology of these weird and wonderful mammals, which we are keen to explore."

The study focuses on the effects of Traditional Resistance Training (TRT) and Plyometric Jump Training (PJT) in participants who are sedentary and physically inactive in sports. The aim was to find out important practical applications that can help improve trainings and physical fitness.

The researchers studied the effects of four weeks of Traditional Resistance Training (TRT) versus Plyometric Jump Training (PJT) programs on the muscular fitness of sedentary and physically inactive participants. Baseline and follow-up tests set in the research included the assessment of Squat Jump, Countermovement Jump, elastic index, and maximal strength of the knee extensors. The participants comprised of both males and females with ages between 18 to 29 years. They were randomly assorted into a control group of 11 people, TRT group with 8, and PJT group having 9 participants. The TRT program emphasized slow-speed movements with free weights. The PJT program focused on high-speed jump movements without external loads. Both TRT and PJT sessions were 30-minutes in duration.

The result showed no significant difference, hence it was concluded that in healthy participants who are both physically inactive and sedentary, the routines of Traditional Resistance Training (TRT) and Plyometric Jump Training (PJT) are equally effective in improving the muscular fitness.

Thousands of words, big and small, are crammed inside our memory banks just waiting to be swiftly withdrawn and strung into sentences. In a recent study of epilepsy patients and healthy volunteers, National Institutes of Health researchers found that our brains may withdraw some common words, like "pig," "tank," and "door," much more often than others, including "cat," "street," and "stair." By combining memory tests, brain wave recordings, and surveys of billions of words published in books, news articles and internet encyclopedia pages, the researchers not only showed how our brains may recall words but also memories of our past experiences.

"We found that some words are much more memorable than others. Our results support the idea that our memories are wired into neural networks and that our brains search for these memories, just the way search engines track down information on the internet," said Weizhen (Zane) Xie, Ph.D., a cognitive psychologist and post-doctoral fellow at the NIH's National Institute of Neurological Disorders and Stroke (NINDS), who led the study published in Nature Human Behaviour. "We hope that these results can be used as a roadmap to evaluate the health of a person's memory and brain."

Dr. Xie and his colleagues first spotted these words when they re-analyzed the results of memory tests taken by 30 epilepsy patients who were part of a clinical trial led by Kareem Zaghloul, M.D., Ph.D., a neurosurgeon and senior investigator at NINDS. Dr. Zaghloul's team tries to help patients whose seizures cannot be controlled by drugs, otherwise known as intractable epilepsy. During the observation period, patients spend several days at the NIH's Clinical Center with surgically implanted electrodes designed to detect changes in brain activity.

"Our goal is to find and eliminate the source of these harmful and debilitating seizures," said Dr. Zaghloul. "The monitoring period also provides a rare opportunity to record the neural activity that controls other parts of our lives. With the help of these patient volunteers we have been able to uncover some of the blueprints behind our memories."

The memory tests were originally designed to assess episodic memories, or the associations - the who, what, where and how details - we make with our past experiences. Alzheimer's disease and other forms of dementia often destroys the brain's capacity to make these memories.

Patients were shown pairs of words, such as "hand" and "apple," from a list of 300 common nouns. A few seconds later they were shown one of the words, for instance "hand," and asked to remember its pair, "apple." Dr. Zaghloul's team had used these tests to study how neural circuits in the brain store and replay memories.

When Dr. Xie and his colleagues re-examined the test results, they found that patients successfully recalled some words more often than others, regardless of the way the words were paired. In fact, of the 300 words used, the top five were on average about seven times more likely to be successfully recalled than the bottom five.

At first, Dr. Zaghloul and the team were surprised by the results and even a bit skeptical. For many years scientists have thought that successful recall of a paired word meant that a person's brain made a strong connection between the two words during learning and that a similar process may explain why some experiences are more memorable than others. Also, it was hard to explain why words like "tank," "doll," and "pond" were remembered more often than frequently used words like "street," "couch," and "cloud."

But any doubts were quickly diminished when the team saw very similar results after 2,623 healthy volunteers took an online version of the word pair test that the team posted on the crowdsourcing website Amazon Mechanical Turk.

"We saw that some things - in this case, words - may be inherently easier for our brains to recall than others," said Dr. Zaghloul. "These results also provide the strongest evidence to date that what we discovered about how the brain controls memory in this set of patients may also be true for people outside of the study."

Dr. Xie got the idea for the study at a Christmas party which he attended shortly after his arrival at NIH about two years ago. After spending many years studying how our mental states - our moods, our sleeping habits, and our familiarity with something - can change our memories, Dr. Xie joined Dr. Zaghloul's team to learn more about the inner-workings of the brain.

"Our memories play a fundamental role in who we are and how our brains work. However, one of the biggest challenges of studying memory is that people often remember the same things in different ways, making it difficult for researchers to compare people's performances on memory tests," said Dr. Xie. "For over a century, researchers have called for a unified accounting of this variability. If we can predict what people should remember in advance and understand how our brains do this, then we might be able to develop better ways to evaluate someone's overall brain health."

At the party, he met Wilma Bainbridge, Ph.D., an assistant professor in the department of psychology at the University of Chicago, who, at the time was working as a post-doctoral fellow at the NIH's National Institute of Mental Health (NIMH). She was trying to tackle this same issue by studying whether some things we see are more memorable than others.

For example, in one set of studies of more than 1000 healthy volunteers, Dr. Bainbridge and her colleagues found that some faces are more memorable than others. In these experiments, each volunteer was shown a steady stream of faces and asked to indicate when they recognized one from earlier in the stream.

"Our exciting finding is that there are some images of people or places that are inherently memorable for all people, even though we have each seen different things in our lives," said Dr. Bainbridge. "And if image memorability is so powerful, this means we can know in advance what people are likely to remember or forget."

Nevertheless, these results were limited to understanding how our brains work when we recognize something we see. At the party, Drs. Xie and Bainbridge wondered whether this idea could be applied to the recall of memories that Dr. Zaghloul's team had been studying and if so, what would that tell us about how the brain remembers our past experiences?

In this paper, Dr. Xie proposed that the principles from an established theory, known as the Search for Associative Memory (SAM) model, may help explain their initial findings with the epilepsy patients and the healthy controls.

"We thought one way to understand the results of the word pair tests was to apply network theories for how the brain remembers past experiences. In this case, memories of the words we used look like internet or airport terminal maps, with the more memorable words appearing as big, highly trafficked spots connected to smaller spots representing the less memorable words," said Dr. Xie. "The key to fully understanding this was to figure out what connects the words."

To address this, the researchers wrote a novel computer modeling program that tested whether certain rules for defining how words are connected can predict the memorability results they saw in the study. The rules were based on language studies which had scanned thousands of sentences from books, news articles, and Wikipedia pages.

Initially, they found that seemingly straightforward ideas for connecting words could not explain their results. For instance, the more memorable words did not simply appear more often in sentences than the less memorable ones. Similarly, they could not find a link between the relative "concreteness" of a word's definition and its memorability. A word like "moth" was no more memorable than a word that has more abstract meanings, like "chief."

Instead, their results suggested that the more memorable words were more semantically similar, or more often linked to the meanings of other words used in the English language. This meant, that when the researchers plugged semantic similarity data into the computer model it correctly guessed which words that were memorable from patients and healthy volunteer test. In contrast, this did not happen when they used data on word frequency or concreteness.

Further results supported the idea that the more memorable words represented high trafficked hubs in the brain's memory networks. The epilepsy patients correctly recalled the memorable words faster than others. Meanwhile, electrical recordings of the patients' anterior temporal lobe, a language center, showed that their brains replayed the neural signatures behind those words earlier than the less memorable ones. The researchers saw this trend when they looked at both averages of all results and individual trials, which strongly suggested that the more memorable words are easier for the brain to find.

Moreover, both the patients and the healthy volunteers mistakenly called out the more memorable words more frequently than any other words. Overall, these results supported previous studies which suggested that the brain may visit or pass through these highly connected memories, like the way animals forage for food or a computer searches the internet.

"You know when you type words into a search engine, and it shows you a list of highly relevant guesses? It feels like the search engine is reading your mind. Well, our results suggest that the brains of the subjects in this study did something similar when they tried to recall a paired word, and we think that this may happen when we remember many of our past experiences," said Dr. Xie. "Our results also suggest that the structure of the English language is stored in everyone's brains and we hope that, one day, it is used to overcome the variability doctors face when trying to evaluate the health of a person's memory and brain."

The team is currently exploring ways to incorporate their results and computer model into the development of memory tests for Alzheimer's disease and other forms of dementia.

When the paradise tree snake flies from one tall branch to another, its body ripples with waves like green cursive on a blank pad of blue sky. That movement, aerial undulation, happens in each glide made by members of the Chrysopelea family, the only known limbless vertebrates capable of flight. Scientists have known this, but have yet to fully explain it.

For more than 20 years, Jake Socha, a professor in the Department of Biomedical Engineering and Mechanics at Virginia Tech, has sought to measure and model the biomechanics of snake flight and answer questions about them, like that of aerial undulation's functional role. For a study published by Nature Physics, Socha assembled an interdisciplinary team to develop the first continuous, anatomically-accurate 3D mathematical model of Chrysopelea paradisi in flight.

The team, which included Shane Ross, a professor in the Kevin T. Crofton Department of Aerospace and Ocean Engineering, and Isaac Yeaton, a recent mechanical engineering doctoral graduate and the paper's lead author, developed the 3D model after measuring more than 100 live snake glides. The model factors in frequencies of undulating waves, their direction, forces acting on the body, and mass distribution. With it, the researchers have run virtual experiments to investigate aerial undulation.

In one set of those experiments, to learn why undulation is a part of each glide, they simulated what would happen if it wasn't -- by turning it off. When their virtual flying snake could no longer aerially undulate, its body began to tumble. The test, paired with simulated glides that kept the waves of undulation going, confirmed the team's hypothesis: aerial undulation enhances rotational stability in flying snakes.

Questions of flight and movement fill Socha's lab. The group has fit their work on flying snakes between studies of how frogs leap from water and skitter across it, how blood flows through insects, and how ducks land on ponds. In part, it was important to Socha to probe undulation's functional role in snake glides because it would be easy to assume that it didn't really have one.

"We know that snakes undulate for all kinds of reasons and in all kinds of locomotor contexts," said Socha. "That's their basal program. By program, I mean their neural, muscular program? -- they're receiving specific instructions: fire this muscle now, fire that muscle, fire this muscle. It's ancient. It goes beyond snakes. That pattern of creating undulations is an old one. It's quite possible that a snake gets into the air, then it goes, 'What do I do? I'm a snake. I undulate.'"

But Socha believed there was much more to it. Throughout the paradise tree snake's flight, so many things happen at once, it's difficult to untangle them with the naked eye. Socha described a few steps that take place with each glide ?-- steps that read as intentional.

First, the snake jumps, usually by curving its body into a "J-loop" and springing up and out. As it launches, the snake reconfigures its shape, its muscles shifting to flatten its body out everywhere but the tail. The body becomes a "morphing wing" that produces lift and drag forces when air flows over it, as it accelerates downward under gravity. Socha has examined these aerodynamic properties in multiple studies. With the flattening comes undulation, as the snake sends waves down its body.

At the outset of the study, Socha had a theory for aerial undulation he explained by comparing two types of aircraft: jumbo jets versus fighter jets. Jumbo jets are designed for stability and start to level back out on their own when perturbed, he said, whereas fighters roll out of control.

So which would the snake be?

"Is it like a big jumbo jet, or is it naturally unstable?" Socha said. "Is this undulation potentially a way of it dealing with stability?"

He believed the snake would be more like a fighter jet.

To run tests investigating undulation's importance to stability, the team set out to develop a 3D mathematical model that could produce simulated glides. But first, they needed to measure and analyze what real snakes do when gliding.

In 2015, the researchers collected motion capture data from 131 live glides made by paradise tree snakes. They turned The Cube, a four-story black-box theater at the Moss Arts Center, into an indoor glide arena and used its 23 high-speed cameras to capture the snakes' motion as they jumped from 27 feet up -- from an oak tree branch atop a scissor lift -- and glided down to an artificial tree below, or onto the surrounding soft foam padding the team set out in sheets to cushion their landings.

The cameras put out infrared light, so the snakes were marked with infrared-reflective tape on 11 to 17 points along their bodies, allowing the motion capture system to detect their changing position over time. Finding the number of measurement points has been key to the study; in past experiments, Socha marked the snake at three points, then five, but those numbers didn't provide enough information. The data from fewer video points only provided a coarse understanding, making for choppy and low-fidelity undulation in the resulting models.

The team found a sweet spot in 11 to 17 points, which gave high-resolution data. "With this number, we could get a smooth representation of the snake, and an accurate one," said Socha.

The researchers went on to build the 3D model by digitizing and reproducing the snake's motion while folding in measurements they had previously collected on mass distribution and aerodynamics. An expert in dynamic modeling, Ross guided Yeaton's work on a continuous model by drawing inspiration from work in spacecraft motion.

He had worked with Socha to model flying snakes since 2013, and their previous models treated the snake's body in parts -- first in three parts, as a trunk, a middle, and an end, and then as a bunch of links. "This is the first one that's continuous," said Ross. "It's like a ribbon. It's the most realistic to this point."

In virtual experiments, the model showed that aerial undulation not only kept the snake from tipping over during glides, but it increased the horizontal and vertical distances traveled.

Ross sees an analogy for the snake's undulation in a frisbee's spin: the reciprocating motion increases rotational stability and results in a better glide. By undulating, he said, the snake is able to balance out the lift and drag forces its flattened body produces, rather than being overwhelmed by them and toppling, and it's able to go further.

The experiments also revealed to the team details they hadn't previously been able to visualize. They saw that the snake employed two waves when undulating: a large-amplitude horizontal wave and a newly discovered, smaller-amplitude vertical wave. The waves went side to side and up and down at the same time, and the data showed that the vertical wave went at twice the rate of the horizontal one. "This is really, really freaky," said Socha. These double waves have only been discovered in one other snake, a sidewinder, but its waves go at the same frequency.

"What really makes this study powerful is that we were able to dramatically advance both our understanding of glide kinematics and our ability to model the system," said Yeaton. "Snake flight is complicated, and it's often tricky to get the snakes to cooperate. And there are many intricacies to make the computational model accurate. But it's satisfying to put all of the pieces together."

"In all these years, I think I've seen close to a thousand glides," said Socha. "It's still amazing to see every time. Seeing it in person, there's something a little different about it. It's shocking still. What exactly is this animal doing? Being able to answer the questions I've had since I was a graduate student, many, many years later, is incredibly satisfying."

Socha credits some of the elements that shaped the real and simulated glide experiments to forces out of his control. Chance led him to the indoor glide arena: a few years after the Moss Arts Center opened, Tanner Upthegrove, a media engineer for the Institute for Creativity, Arts, and Technology, or ICAT, asked him if he'd ever thought about working in the Cube.

"What's the Cube?" he asked. When Upthegrove showed him the space, he was floored. It seemed designed for Socha's experiments.

In some ways, it was. "Many projects at ICAT used the advanced technology of the Cube, a studio unlike any other in the world, to reveal that which could normally not be seen," said Ben Knapp, the founding director of ICAT. "Scientists, engineers, artists, and designers join forces here to build, create, and innovate new ways to approach the world's grandest challenges."

In one of the center's featured projects, "Body, Full of Time," media and visual artists used the space to motion capture the body movements of dancers for an immersive performance. Trading dancers for snakes, Socha was able to make the most of the Cube's motion capture system. The team could move cameras around, optimizing their position for the snake's path. They took advantage of latticework at the top of the space to position two cameras pointing down, providing an overhead view of the snake, which they'd never been able to do before.

Socha and Ross see potential for their 3D model to continue exploring snake flight. The team is planning outdoor experiments to gather motion data from longer glides. And one day, they hope to cross the boundaries of biological reality.

Right now, their virtual flying snake always glides down, like the real animal. But what if they could get it to move so that it would actually start to go up? To really fly? That ability could potentially be built into the algorithms of robotic snakes, which have exciting applications in search and rescue and disaster monitoring, Ross said.

"Snakes are just so good at moving through complex environments," said Ross. "If you could add this new modality, it would work not only in a natural setting, but in an urban environment."

"In some ways, Virginia Tech is a hub for bio-inspired engineering," said Socha. "Studies like this one not only provide insight into how nature works, but lay the groundwork for design inspired by nature. Evolution is the ultimate creative tinkerer, and we're excited to continue to discover nature's solutions to problems like this one, extracting flight from a wiggling cylinder."

Researchers from the University of Warwick, Imperial College London, EPFL (Lausanne) and Sciteb Ltd have found a mathematical means of helping regulators and business manage and police Artificial Intelligence systems' biases towards making unethical, and potentially very costly and damaging commercial choices - an ethical eye on AI.

Artificial intelligence (AI) is increasingly deployed in commercial situations. Consider for example using AI to set prices of insurance products to be sold to a particular customer. There are legitimate reasons for setting different prices for different people, but it may also be profitable to 'game' their psychology or willingness to shop around.

The AI has a vast number of potential strategies to choose from, but some are unethical and will incur not just moral cost but a significant potential economic penalty as stakeholders will apply some penalty if they find that such a strategy has been used - regulators may levy significant fines of billions of Dollars, Pounds or Euros and customers may boycott you - or both.

So in an environment in which decisions are increasingly made without human intervention, there is therefore a very strong incentive to know under what circumstances AI systems might adopt an unethical strategy and reduce that risk or eliminate entirely if possible.

Mathematicians and statisticians from University of Warwick, Imperial, EPFL and Sciteb Ltd have come together to help business and regulators creating a new "Unethical Optimization Principle" and provide a simple formula to estimate its impact. They have laid out the full details in a paper bearing the name "An unethical optimization principle", published in Royal Society Open Science on Wednesday 1st July 2020.

The four authors of the paper are Nicholas Beale of Sciteb Ltd; Heather Battey of the Department of Mathematics, Imperial College London; Anthony C. Davison of the Institute of Mathematics, Ecole Polytechnique Fédérale de Lausanne; and Professor Robert MacKay of the Mathematics Institute of the University of Warwick.

Professor Robert MacKay of the Mathematics Institute of the University of Warwick said:

"Our suggested 'Unethical Optimization Principle' can be used to help regulators, compliance staff and others to find problematic strategies that might be hidden in a large strategy space. Optimisation can be expected to choose disproportionately many unethical strategies, inspection of which should show where problems are likely to arise and thus suggest how the AI search algorithm should be modified to avoid them in future.

"The Principle also suggests that it may be necessary to re-think the way AI operates in very large strategy spaces, so that unethical outcomes are explicitly rejected in the optimization/learning process."

An international team of researchers has analysed how SARS-CoV-2, the virus that causes COVID-19, hijacks the proteins in its target cells. The research, published in the journal Cell, shows how the virus shifts the cell's activity to promote its own replication and to infect nearby cells. The scientists also identified seven clinically approved drugs that could disrupt these mechanisms, and recommend that these drugs are immediately tested in clinical trials.

The collaboration included researchers at EMBL's European Bioinformatics Institute (EMBL-EBI), the Quantitative Biosciences Institute's Coronavirus Research Group in the School of Pharmacy at University of California San Francisco (UCSF), the Howard Hughes Medical Institute, the Institut Pasteur, and the Excellence Cluster CIBSS of the University of Freiburg.

Viruses are unable to replicate and spread on their own: they need an organism - their host - to carry, replicate, and transmit them to further hosts. To facilitate this process, viruses need to take control of their host cell's machinery and manipulate it to produce new viral particles. Sometimes, this hijacking interferes with the activity of the host's enzymes and other proteins.

Once a protein is produced, enzymes can change its activity by making chemical modifications to its structure. For example, phosphorylation - the addition of a phosphoryl group to a protein by a type of enzyme called a kinase - plays a pivotal role in the regulation of many cell processes, including cell-to-cell communication, cell growth, and cell death. By altering phosphorylation patterns in the host's proteins, a virus can potentially promote its own transmission to other cells and, eventually, other hosts.

The scientists used mass spectrometry, a tool to analyse the properties of a sample by measuring the mass of its molecules and molecular fragments, to evaluate all host and viral proteins that showed changes in phosphorylation after SARS-CoV-2 infection. They found that 12% of the host proteins that interact with the virus were modified. The researchers also identified the kinases that are most likely to regulate these modifications. Kinases are potential targets for drugs to stop the activity of the virus and treat COVID-19.

The extraordinary behaviour of infected cells

"The virus prevents human cells from dividing, maintaining them at a particular point in the cell cycle. This provides the virus with a relatively stable and adequate environment to keep replicating," explains Pedro Beltrao, Group Leader at EMBL-EBI.

SARS-CoV-2 not only impacts cell division, but also cell shape. One of the key findings from the study is that infected cells exhibit long, branched, arm-like extensions, or filopodia. These structures may help the virus reach nearby cells in the body and advance the infection, but further study is warranted.

"The distinct visualisation of the extensive branching of the filopodia once again elucidates how understanding the biology of virus-host interaction can illuminate possible points of intervention in the disease," says Nevan Krogan, Director of the Quantitative Biosciences Institute at UCSF and Senior Investigator at Gladstone Institutes.

Old drugs, new treatments

"Kinases possess certain structural features that make them good drug targets. Drugs have already been developed to target some of the kinases we identified, so we urge clinical researchers to test the antiviral effects of these drugs in their trials," says Beltrao.

In some patients, COVID-19 causes an overreaction of the immune system, leading to inflammation. An ideal treatment would relieve these exaggerated inflammatory symptoms while stopping the replication of the virus. Existing drugs targeting the activity of kinases may be the solution to both problems.

The researchers identified dozens of drugs approved by the Food and Drug Administration (FDA) or ongoing clinical trials that target the kinases of interest. Seven of these compounds, primarily anticancer and inflammatory disease compounds, demonstrated potent antiviral activity in laboratory experiments.

"Our data-driven approach for drug discovery has identified a new set of drugs that have great potential to fight COVID-19, either by themselves or in combination with other drugs, and we are excited to see if they will help end this pandemic," says Krogan.

"We expect to build upon this work by testing many other kinase inhibitors while identifying both the underlying pathways and additional potential therapeutics that may intervene in COVID-19 effectively," says Kevan Shokat, Professor in the Department of Cellular and Molecular Pharmacology at UCSF.

The growth of cities plays a key role in a region's economic development. Although many factors affecting urban development have been studied extensively, economic research has so far paid little attention to one such factor: ethnolinguistic diversity.

Studies in the area of conflict research have shown that the risk of conflict is increased when various ethnic groups live in close proximity. So far, however, the effect of this factor on urban development had not been examined directly. Professor Kurt Schmidheiny from the University of Basel has now provided the first empirical proof of this relationship in collaboration with colleagues from the University of Lausanne and the London School of Economics.

On the one hand, the researchers based their analysis on a type of world map showing where various language groups lived in 1975. This allowed them to ascertain the degree of ethnolinguistic diversity of 3,540 provinces in 170 countries at that time. On the other hand, they used a new dataset from the EU and OECD that combines satellite data with population data for the year 2015 in order to define cities around the world as contiguous settlement areas and assign population figures to them.

An incentive to remain in rural areas

The coupling of these two geographical datasets showed that, in more ethnically diverse provinces, a lower proportion of the total population lives in cities and the largest city in the province is smaller. In their analysis, the scientists controlled for alternative factors that influence the degree of urbanization, such as population density and topography.

The researchers also went a step further by examining the degree of urbanization already present in 1975. "By controlling for this, we are able to assume with greater certainty that ethnolinguistic diversity influenced urban growth and not vice versa," says Schmidheiny.

According to game theory models, conflicts between ethnolinguistic groups are more costly the more closely the groups live alongside one another. "There are therefore incentives for members of these groups to remain in rural areas. Our analysis confirms this empirically for the first time," says the economist.

Less impact in established democracies and dictatorships

However, Schmidheiny emphasizes that countering ethnic mixing in order to promote urban growth and therefore economic development would be the wrong conclusion to draw in terms of policy. "Diversity is a key driver of innovation in cities in which the various ethnic groups live and work peacefully alongside one another."

Empirical analysis has shown that the influence of ethnolinguistic diversity is less detrimental in mature democracies (and strict autocracies) than in fragile democracies.

"The effect is less pronounced in systems where various ethnic groups have well-established ways of resolving their conflicts and in those where conflicts are suppressed," says Schmidheiny. Fragile democracies are particularly susceptible. "Countries with a well-functioning democracy can take full advantage of the innovation-driving effect of diversity."

A type of anaerobic bacteria responsible for more than 50 percent of nitrogen loss from marine environments has been shown to use solid-state matter present outside their cells for respiration. The finding by KAUST researchers adds to knowledge of the global nitrogen cycle and has important energy-saving potential for wastewater treatment.

Living organisms use oxidation/reduction reactions to harvest the energy they need for survival. This involves the transfer of electrons from an electron donor to an electron acceptor with energy generation. In humans, electrons are released from the food we digest and accepted by soluble oxygen inside our cells. But in many bacteria, other strategies are used for oxidation/reduction, with different types of electron donors and acceptors.

Anammox are anaerobic bacteria found in oxygen-lacking marine and freshwater environments, such as sediments. They derive energy by using ammonium as their electron donor and intracellular soluble nitrite as the acceptor, with the release of nitrogen gas--or so scientists thought.

"We found that freshwater and marine anammox bacteria can also transfer electrons from ammonium to extracellular electron acceptors, like graphene oxide or electrodes in microbial electrolysis cells," says Ph.D. student, Dario Shaw. This novel extracellular electron transfer by anammox bacteria had been conjectured by scientists for more than a decade, but had not been properly explored.

Environmental biotechnologist Pascal Saikaly led a team that found, by looking into the anammox genome, that these bacteria had iron-containing proteins called cytochromes that are also present in types of bacteria known for their ability to transport electrons outside their cells. "We wanted to know if anammox bacteria could also perform extracellular electron transfer," says Saikaly.

They found that electrons were transferred from ammonium inside the bacteria to solid-state matter outside the cell. For this to happen, the electrons crossed three different barriers, starting from inside an anammox cellular organelle called the anammoxosome. "This means that we have demonstrated for the first time a type of bacteria that can transfer electrons through three different membranes," says Saikaly. "This finding challenges our perceptions of cell biology."

"Our findings are a breakthrough in the fields of microbial ecology, bioelectrochemistry and sustainable wastewater treatment," adds Shaw. Anammox bacteria are already used to make wastewater reusable by removing ammonium. They save energy compared to the conventional use of aerobic bacteria, which require oxygen as the electron acceptor for ammonium oxidation. Providing oxygen through an aeration system requires a lot of energy. Anammox bacteria used for wastewater treatment do not need oxygen, but they do currently need nitrite as the electron acceptor. This is provided by another type of bacteria that needs oxygen, and thus energy, to produce it.

The new finding suggests that anammox alone could be used for ammonium removal, while also producing energy in the form of an electric current or energy-rich hydrogen gas in microbial electrolysis cells.

Amsterdam NL, June 29, 2020 - The SARS-CoV-19 virus initially has a limited capability to invade, attacking only one intracellular genetic target, the aryl hydrocarbon receptors (AhRs). Yet it leads to widely diverse clinical symptoms, suggesting multiple pathogenic mechanisms. Writing in Restorative Neurology and Neuroscience, investigators describe how excessive activation of AhRs via the IDO1-kynurenine-AhR signaling pathway, which is used by many pathogens to establish infection, leads to "Systemic AhR Activation Syndrome" (SAAS). The authors also hypothesize that therapies targeting downregulation of AhRs and IDO1 genes should decrease severity of infection.

SAAS underlies inflammation, thromboembolism, and fibrosis that may lead to severe disease and death from COVID-19. When corona virus (CoV) infection persists, it activates IDO1 by massively releasing cytokines. This in turn perpetuates the already extensive viral activation of AhRs, and the self-limiting control mechanisms of the host immune response may derail, triggering the cytokine storm underlying the most severe symptoms of COVID-19.

"The SARS-CoV-19 virus is a living example of viral simplicity complicated by extreme target complexity," explains lead author Waldemar A. Turski, MD, PhD, Department of Experimental and Clinical Pharmacology, Medical University in Lublin, Poland. "Direct activation of AhRs by CoVs may lead to diverse sets of phenotypic disease pictures, depending on time after infection, overall state of health, hormonal balance, age, gender, comorbidities, but also diet and environmental factors modulating AhRs."

The authors demonstrate that CoVs are perfect viruses leaving nothing to chance and show how difficult it is to stop them after cell invasion. They describe how many of the features and symptoms of COVID-19 may be dependent on AhR activation, including thromboembolism, fibrosis, multiple organ injury, and brain damage. They also explore how environmental factors, such as urban dust and diesel fumes, may activate AhRs and make humans more prone to pathogens, including CoV. However, physical exercise plays a positive role in IDO1 function and downregulates AhRs.

The investigators hypothesize that when AhRs remain activated and clinical symptoms are mild, eliminating factors known to increase AhR activation or implementing factors known to suppress AhR activation should decrease the severity of infection. When the disease is fully established and symptoms are severe, IDO1 is believed to be continuously activated in addition to the CoV activation of AhRs. "Such a vicious cycle can only be efficiently interrupted by simultaneous downregulation of both AhR and IDO1. There is currently, however, no licensed medication specifically and simultaneously downregulating the activity of both AhR and IDO1," notes co-author Les Turski, MD, PhD, German Center for Neurodegenerative Diseases, Bonn, Germany.

Co-author Artur Wnorowski, PhD, Department of Biopharmacy, Faculty of Pharmacy, Medical University in Lublin, Poland, undertook an intriguing challenge that yielded surprising results. "I analyzed major databases to identify chemicals that downregulate both AhR and IDO1, or AhR gene expression. I selected 596 molecules and an in-depth analysis of 23,526 experiments involving these molecules identified either a single molecule that repeatedly reduced AhR and IDO1 or AhR gene expression in human cells."

The molecules were dexamethasone for AhR and IDO1, and calcitriol, the active form of vitamin D, which is also known to inhibit the spread of other viral infections, for the AhR gene. Likewise, tocopherol, a form of Vitamin E, might downregulate IDO1 and is known to play a positive role in response to viral infections and inflammation in aging. The authors call for epidemiological studies and prospective trials to determine if calcitriol and tocopherol supplementation should be recommended for the prevention of SARS-CoV-2 infections.

"Our concept is based on 40 years of research experience with the metabolism of tryptophan. Activation of IDO1 in immune cells leads to release of kynurenine, a tryptophan metabolite, activates AhR. IDO1 was the clue that brought us to the AhR-IDO1 axis concept and exposed the role that AhR may play in the pathogenesis of COVID-19," says Dr. Waldemar Turski.

The Editor-in-Chief of Restorative Neurology and Neuroscience, Professor Bernhard Sabel from the University of Magdeburg, Germany, in recognition of novelty of the authors' vision says: "The turning point defined by the authors' concepts requires critical review of our habits, our relationships with the environment, and our education and research in the context of AhR modulation. We seem to be at the very beginning of novel discovery pathways and only see the very tip of an iceberg of unknown size that may critically affect our future."

Because the authors are reporting on changes in gene expression only, their hypotheses need to be tested before claiming that there are benefits of any therapy in modulating the SARs-CoV-2 infection. Randomized controlled trials and large observational studies are needed.

An innovative treatment for patients with Clostridium difficile infection (CDI) which uses transplanted gut bacteria to treat the infection, is a more effective and more cost-efficient treatment than using antibiotics, a new UK study has found.

CDI is an infection of the bowel, which commonly affects people who have recently been treated in hospital, those with underlying conditions and patients over 65. Almost 30 per cent of patients treated for the condition experience at least one recurrence. A recurrence of the condition, has been associated with a higher risk of mortality and is usually treated using antibiotics.

Faecal microbial transplantation (FMT), a treatment pioneered as a licenced medicine by Professor Peter Hawkey and his team at the University of Birmingham, is a method where gut bacteria and other components in faeces are used to treat CDI. The bacteria is taken from a screened healthy donor, processed and screened before being transplanted via a tube passed through the nose into the stomach. Treatment with FMT is associated with higher cure and lower recurrence rates than fidaxomicin or vancomycin- the two most common antibiotics used to treat recurrent CDI (rCDI).

The study, which presents the first decision model for patients with rCDI already hospitalised in the UK, analysed randomised controlled trials, observational studies and expert opinion from the UK, on patients with single or multiple rCDI. Researchers analysed the cost of each of the four treatment options for rCDI for treatment effects, unit costs, resource and health related quality of life to identify which treatment was the most cost-effective and offered the best outcome for patients.

The study showed that both methods for administering FMT were lower in cost compared to standard treatment with antibiotics. FMT via naso-gastric tube was the least costly, with a mean cost of £8,877 per patient, while FMT via colonoscopy was £11,716 per patient. FMT via colonoscopy was also shown to be slightly more effective than treatment via naso-gastric tube, offering patients a higher quality of life. Two other standard antibiotic treatments vancomycin and fidaxomicin were compared in the model but both these treatments were shown to be more costly and less effective than either of the FMT interventions. Moreover, Vancomycin was the most expensive and the least effective treatment.

Professor Peter Hawkey, formerly of the University of Birmingham said, "We at the University of Birmingham pioneered this treatment as the UK's first third party FMT service. FMT is not currently a widespread treatment for this disease but by showing that it not only saves lives, but is also significantly more cost effective, we hope that this could be one of the first steps towards the treatment being accepted more widely."

Professor Tracy Roberts, Head of the University of Birmingham's Health Economics Unit said "As well as being more effective both in terms of cost and benefit to patients, FMT was shown to significantly reduce the amount of days patients were required to be hospitalised which could also provide longer term cost-savings"

Is the basic research that goes into the development of new drugs more efficiently conducted by public-sector scientists, pharmaceutical firms, or independent private laboratories? What role do each of these groups play in determining prices of innovative pharmaceuticals, which have risen steeply over the last years? To answer these questions, economists Francesca Barigozzi, of the University of Bologna, and Izabela Jelovac, of the CNRS,* designed and studied a model inspired by game theory.** In an article recently published in Health Economics, they demonstrate that basic research is most cost-effective when carried out either in a public research laboratory or a pharmaceutical firm. If basic and applied research are highly complementary--where improving the quality of one benefits the other--public research units outperform pharmaceutical companies in the conduct of basic research. Furthermore, the price of new drugs is lowest when basic research takes place in public labs. These findings therefore condition the validity of the economic assumption that greater efficiency in research necessarily results in a more expensive end product.*** In some cases, public-sector basic research is the most efficient and leads to the lowest drug prices.

New research indicates that significant enhancement of secondary aerosol formed in the atmosphere via gas-to-particle conversion, together with long-lasting regional transport, may be the cause of severe haze over China despite a dramatic reduction in emissions during the COVID-19 shutdown. The findings are published in Geophysical Research Letters.

During the Chinese Lunar New Year holiday between January 24 and February 10, 2020, China was in an unprecedented state of shutdown because of COVID-19, with mobility, energy demands, and industrial pollution emissions remaining far below their normal levels. Nevertheless, a high and widespread haze pollution was observed over Eastern China.

To investigate this puzzling occurrence, Yunhua Chang, Professor, of the Nanjing University of Information Science & Technology, Ru-Jin Huang, Professor, of the Chinese Academy of Sciences, and their colleagues analyzed the chemical components of the air in and out of Shanghai before, during, and after the Chinese New Year holidays in 2019 and 2020, and they performed atmospheric transport modeling, a method to track particles and trace gases that are dispersed by atmospheric winds.

The team found that secondary aerosol formation that interacts with long-range transport likely caused the long-lasting haze during the COVID-19 pandemic.

The results highlight the need for joint management efforts and control strategies across large areas to effectively clear China's air.

"We hope our findings can inform future regulatory policies to mitigate China's haze-associated problems," said Dr. Chang.

"Additional studies are needed to pinpoint the role of atmospheric oxidation capacity--which is affected by emission reductions of air pollutants--in the formation of secondary aerosols," added Dr. Huang.

This paper is part of an ongoing special collection of research in AGU journals related to the current pandemic.

Biophysicists from the Moscow Institute of Physics and Technology and their colleagues have proposed a simple way to observe the heart tissue. Besides being relatively uncomplicated, the new method is cheaper and produces results that are more independent, compared with the analogues currently in use. The study came out in Annals of Biomedical Engineering.

The heart tissue is a special kind of muscle. When excitation waves propagate through it, this causes the constituent fibers to contract. The excitation waves coordinate the work of the heart compartments to ensure the organ functions correctly.

Many heart diseases, among them arrhythmias, are associated with disruptions in excitation wave conduction or with some peculiar propagation regimes taking over. This is why fundamental research into the mechanisms of excitation wave propagation in the heart is important. Such studies provide insights into how the heart functions, how arrhythmias arise, and how various drugs and substances affect the processes in the cardiac tissue.

One of the staple methods for observing excitation waves is optical mapping. It involves the use of fluorescent dyes to visualize the propagation of excitations in the heart tissue. The process is monitored with sensitive video cameras, and the resulting data are then subjected to analysis.

Optical mapping has certain drawbacks. For one thing, the dyes and cameras suitable for the technique are fairly expensive. Another disadvantage is that the dye may interact with drugs and thus disturb the experiment. The dyes also affect the cells in the heart tissue sample, reducing their lifetimes.

"We found that if you grow the cardiac tissue culture on an elastic substrate made of polydimethylsiloxane, it is possible to observe wave propagation with a microscope, and no dyes are needed," said Konstantin Guria, a senior researcher at the MIPT Laboratory of the Biophysics of Excitable Systems.

This idea laid the foundation for the new method. In it the heart tissue is cultivated on an elastic substrate. As a result, when an excitation wave propagates across the sample in the experiment, the substrate deforms. This process can be optically registered via oblique illumination. The technique eases camera requirements, because even a GoPro provides sufficient quality.

"We have proposed a method that is simpler and cheaper than conventional mapping. That said, an even greater competitive advantage is being sure that the analyzed substance does not interact with a dye, since it becomes redundant for visualization," commented Konstantin Agladze, who heads the Laboratory of the Biophysics of Excitable Systems at MIPT.

The new method can be used for affordable testing of various processes on tissue cultures grown from stem cells. The process lends itself to automation and is suitable for longer observations than those that rely on regular mapping.

In addition to MIPT staff, this study involved researchers from Vladimirsky Moscow Regional Research and Clinical Institute and the Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences.

The Laboratory of the Biophysics of Excitable Systems is part of the Phystech School of Biological and Medical Physics at MIPT. It uses human cardiac tissue models to conduct experimental research into the fundamental mechanisms behind heart arrhythmias. The head of the laboratory is Konstantin Agladze. You can reach the lab by contacting the secretary, Irina Egorova, at egorova.ia@mipt.ru or by dialing +7 (495) 408-46-45.