Culture

Edge Localised Modes, ELMs for short, are one of the disturbances of the plasma confinement that are caused by the interaction between the charged plasma particles and the confining magnetic field cage. During ELM events, the edge plasma loses its confinement for a short time and periodically throws plasma particles and energy outwards onto the vessel walls. Typically, one tenth of the total energy content can thus be ejected abruptly. While the present generation of medium-sized fusion devices can cope with this, large devices such as ITER or a future power plant would not be able to withstand this strain.

Experimental methods to attenuate, suppress or avoid ELMs have already been successfully developed in current fusion devices (see PI 3/2020). After extensive previous work, it has now been possible for the first time by means of computational simulations to identify the trigger responsible for the explosive onset of these edge instabilities and to reconstruct the course of several ELM cycles - in good agreement with experimentally observed values. A publication accepted in the scientific journal Nuclear Fusion explains this important prerequisite for predicting and avoiding ELM instabilities in future fusion devices.

The ELM instability builds up after a quiet phase of about 5 to 20 milliseconds - depending on the external conditions - until in half a millisecond between 5 and 15 percent of the energy stored in the plasma is flung onto the walls. Then the equilibrium is restored until the next ELM eruption follows.

The plasma theorists around first author Andres Cathey of IPP, who come from several laboratories of the European fusion programme EUROfusion, were able to describe and explain the complex physical processes behind this phenomenon in detail: as a non-linear interplay between destabilising effects - the steep rise in plasma pressure at the plasma edge and the increase in current density - and the stabilising plasma flow. If the heating power fed into the plasma is changed in the simulation, the calculated result shows the same effect on the repetition rate of the ELMs, i.e. the frequency, as an increase of the heating power in a plasma experiment at ASDEX Upgrade tokamak: experiment and simulation are in Agreement.

Although the processes take place in a very short time, their simulation requires a great deal of computing effort. This is because the simulation must resolve into small calculation steps both the short ELM crash and the long development phase between two ELMs - a calculation problem that could only be solved with one of the fastest supercomputers currently available.

For the simulations the JOREK code was used, a non-linear code for the calculation of tokamak plasmas in realistic geometry, which is being developed in European and international cooperation with strong contributions from IPP.

Hitting a specific point on a screen with a laser pointer during a presentation isn't easy - even the tiniest nervous shaking of the hand becomes one big scrawl at a distance. Now imagine having to do that with several laser pointers at once. That is exactly the problem faced by physicists who try to build quantum computers using individual trapped atoms. They, too, need to aim laser beams - hundreds or even thousands of them in the same apparatus - precisely over several metres such as to hit regions only a few micrometres in size that contain the atoms. Any unwanted vibration will severely disturb the operation of the quantum computer.

At ETH in Zurich, Jonathan Home and his co-workers at the Institute for Quantum Electronics have now demonstrated a new method that allows them to deliver multiple laser beams precisely to the right locations from within a chip in such a stable manner that even the most delicate quantum operations on the atoms can be carried out.

Aiming for the quantum computer

To build quantum computers has been an ambitious goal of physicists for more than thirty years. Electrically charged atoms - ions - trapped in electric fields have turned out to be ideal candidates for the quantum bits or qubits, which quantum computers use for their calculations. So far, mini computers containing around a dozen qubits could be realized in this way. "However, if you want to build quantum computers with several thousand qubits, which will probably be necessary for practically relevant applications, current implementations present some major hurdles," says Karan Mehta, a postdoc in Home's laboratory and first author of the study recently published in the scientific journal "Nature". Essentially, the problem is how to send laser beams over several metres from the laser into a vacuum apparatus and eventually hit the bull's eye inside a cryostat, in which the ion traps are cooled down to just a few degrees above absolute zero in order to minimize thermal disturbances.

Optical setup as an obstacle

"Already in current small-scale systems, conventional optics are a significant source of noise and errors - and that gets much harder to manage when trying to scale up", Mehta explains. The more qubits one adds, the more complex the optics for the laser beams becomes which is needed for controlling the qubits. "This is where our approach comes in", adds Chi Zhang, a PhD student in Home's group: "By integrating tiny waveguides into the chips that contain the electrodes for trapping the ions, we can send the light directly to those ions. In this way, vibrations of the cryostat or other parts of the apparatus produce far less disturbance."

The researchers commissioned a commercial foundry to produce chips which contain both gold electrodes for the ion traps and, in a deeper layer, waveguides for laser light. At one end of the chips, optical fibres feed the light into the waveguides, which are only 100 nanometres thick, effectively forming optical wiring within the chips. Each of those waveguides leads to a specific point on the chip, where the light is eventually deflected towards the trapped ions on the surface.

Work from a few years ago (by some of the authors of the present study, together with researchers at MIT and MIT Lincoln Laboratory) had demonstrated that this approach works in principle. Now the ETH group has developed and refined the technique to the point where it is also possible to use it for implementing low-error quantum logic gates between different atoms, an important prerequisite for building quantum computers.

High-fidelity logic gates

In a conventional computer chip, logic gates are used to carry out logic operations such as AND or NOR. To build a quantum computer, one has make sure that it can to carry out such logic operations on the qubits. The problem with this is that logic gates acting on two or more qubits are particularly sensitive to disturbances. This is because they create fragile quantum mechanical states in which two ions are simultaneously in a superposition, also known as entangled states.

In such a superposition, a measurement of one ion influences the result of a measurement on the other ion, without the two being in direct contact. How well the production of those superposition states works, and thus how good the logic gates are, is expressed by the so-called fidelity. "With the new chip we were able to carry out two-qubit logic gates and use them to produce entangled states with a fidelity that up to now could only be achieved in the very best conventional experiments", says Maciej Malinowski, who was also involved in the experiment as a PhD student.

The researchers have thus shown that their approach is interesting for future ion trap quantum computers as it is not just extremely stable, but also scalable. They are currently working with different chips that are intended to control up to ten qubits at a time. Furthermore, they are pursuing new designs for fast and precise quantum operations that are made possible by the optical wiring.

About half of the people with multiple sclerosis have the HLA-DR15 gene variant. A study led by the University of Zurich has now shown how this genetic predisposition contributes to the development of the autoimmune disease multiple sclerosis in combination with environmental factors. The decisive factor is the shaping of a repertoire of immune cells which - although they are effective in fighting off pathogens such as Epstein-Barr virus - also attack brain tissue.

Multiple sclerosis is an autoimmune disease that damages the brain and the spinal cord and often severely limits a person's quality of life. It affects about 2.5 million people worldwide, most of them young adults. The cause of the disease is a complex interaction between genetic factors and environmental influences such as smoking or infections.

Genetic variation and viruses as risk factors

For almost 50 years now, it has been known that a gene variant called HLA-DR15 is strongly associated with multiple sclerosis (MS). This gene variant is responsible for up to 60 percent of genetic risk. If carriers of this common gene (about a quarter of the healthy population is HLA-DR15 positive) are also infected with the Epstein-Barr virus and have a symptomatic course of infection called Pfeiffer's disease (also known as glandular fever or infectious mononucleosis), the risk of MS increases 15-fold.

UZH Professor Roland Martin, Head of the Department of Neuroimmunology and MS Research at the University Hospital Zurich, says: "There are therefore clear indications that the interaction between HLA-DR15 and infectious agents such as Epstein-Barr virus is significant for the development of the disease, even though the exact mechanisms behind this have not been understood until now."

An interdisciplinary, international study led by Martin has now shown that the immune cells of people with HLA-DR15 recognize certain microbes - such as the Epstein-Barr virus - very effectively, but that this "fitness" can also lead to an undesired immune reaction against the person's own brain tissue.

Individual training for immune cells

The gene products of HLA-DR15 control how the adaptive immune system shapes an immune repertoire that allows the body to recognize and fight pathogens. One of the locations of HLA-DR15 molecules is on the surface of white blood cells. There, they present protein fragments from bacteria, viruses and body cells to the T lymphocytes of the immune system.

The T lymphocytes - which later control the immune response - learn to distinguish between foreign proteins and the body's own tissue. This individual training of immune cells takes place first in the thymus and then in the blood. Since there are many more possible pathogens than T lymphocytes, each T lymphocyte must be able to respond to many different antigens and probably also many different pathogens.

Identifying the fragments presented

The researchers first investigated which fragments HLA-DR15 captured and presented to the immune cells. To do this, they used two novel antibodies that recognize the two variants of HLA-DR15 that occur in MS patients with a very high level of specificity. They found that the HLA-DR15 molecules in the thymus mainly present fragments of themselves. This is new information that was not previously known.

The T lymphocytes that have been trained in this way then migrate into the blood. There, they also learn to recognize fragments of the Epstein-Barr virus if the carrier of the genetic variant becomes infected with it. The fragments from the virus have a much stronger activating effect than the HLA-DR15 fragments.

As a result, the T lymphocytes not only keep virus-infected cells in check, but can also migrate to the brain and react with the body's own proteins that trigger an autoimmune reaction in the case of MS. Nearly 100 percent of people with MS are infected with the Epstein-Barr virus. It is the greatest environmental risk factor for MS. The researchers also often found a reaction to fragments of the intestinal bacterium Akkermansia muciniphila, which occurs in abnormally high numbers in MS patients.

Good immune defenses come with a risk of MS

Summarizing, Martin states that "The most important genetic risk factor for MS therefore shapes a repertoire of T lymphocytes that responds very well to certain infectious agents such as Epstein-Barr virus and intestinal bacteria." However, as the experiments have shown, this group of T lymphocytes also reacts to proteins found in the brain by way of a kind of cross-reactivity. "The disadvantage of this fitness is therefore that those affected also become susceptible to an immune response against their own brain tissue, which can lead to multiple sclerosis."

Therefore, these results have for the first time illustrated how the combination of genetic predisposition and certain environmental factors can trigger an autoimmune disease. "Our work has shed light on mechanisms that are likely to play a role in a number of other autoimmune diseases," says Martin. "In addition to improving our understanding of underlying causes of the disease, this could also lead to the development of new treatments".

The March 2014 landslide in Oso, Washington, about 55 miles northeast of Seattle, became the deadliest landslide event in United States history. Forty-three people died and 49 homes and structures were destroyed.

A University of Washington engineer who analyzed the event's aftermath began to investigate the circumstances that can make landslides so deadly. The resulting study shows that certain human actions increase the chance of surviving a devastating event, and suggests simple behavioral changes could save more lives than expensive engineering solutions.

The open-access study, published in the October issue of GeoHealth, suggests key actions that range from opening doors and windows to continuing to move and make noise if you do get buried.

"There are in fact some really simple, cost-effective measures that can be taken that can dramatically improve the likelihood that one will survive a landslide," said senior author Joseph Wartman, a UW professor of civil and environmental engineering.

Worldwide, landslides cause on average more than 4,000 deaths a year recently, with about 25 to 50 of those deaths occurring each year in the U.S. These events may become more frequent as wildfires fueled by warmer temperatures can leave slopes bare and more vulnerable to slides.

Wartman and a UW graduate student compiled and analyzed records of 38 landslides that affected occupied buildings. Most of the data came from the U.S., but it included landslides from around the world for which there were detailed records.

The authors recorded the geologic details of each landslide, as well as the reports from survivors of the events. They used newspaper articles, scientific papers, medical examiner reports and other documents to produce a detailed catalog of fatalities caused by landslides hitting occupied buildings. The events, spanning from 1881 to 2019, included the Oso mudslide and the 2018 mudslide in Southern California, as well as events in Bangladesh, Philippines, China, Malaysia, Australia and New Zealand.

Their analysis showed behavioral factors, such as a having an awareness of local landslide hazards and moving to a higher floor of a building during an event, had the strongest association with survival.

"Simply by being on an upper floor, an individual can increase their odds of survival by up to a factor of twelve. This is a powerful finding that we need to consider when we design the layout and vertical access routes in homes," said first author William Pollock, who did the work for his UW doctorate in civil and environmental engineering and is now a lecturer in the department.

The analysis showed many things they predicted would be important, including the size or the intensity of landslide events, made little difference to the death toll for landslides below about 20 feet depth. Similarly, the distance between a building and the landslide slope, or an inhabitant's age and gender, didn't make a big difference to their survival.

But the researchers found some behaviors, despite being performed by only a small number of people, often save lives. According to their results, those actions are:

Before an event

Be informed about potential hazards, from hazard maps or other sources

Talk to people who have experienced these events

Move areas of high occupancy, such as bedrooms, upstairs or to the downhill side of a building

During an event

Move away from the threat -- don't approach an active landslide

Escape vertically by moving upstairs or even on countertops to avoid being swept away

Identify and relocate to interior, ideally unfurnished, areas of a building that offer more protection

Open downhill doors and windows to let debris escape

After an event

If caught in landslide debris, continue to move and make noise to alert rescuers

The results suggest practical ways to lower the number of lives lost to landslides in the United States, Wartman said. He hopes the information can be incorporated in education and community awareness programs.

"This is a message of hope," Wartman said. "What this work suggests is that a modest investment put toward social science, policy and education could have a very marked effect in protecting people from landslides."

Residents who want to know if they are vulnerable to landslides can contact a local agency, such as the Washington State Department of Natural Resources, to learn more about local risks. Federal legislation is pending to make this information more easily accessible across the United States, Wartman said.

Ravens, crows, magpies and their relatives are known for their exceptional intelligence, which allows them to solve complex problems, use tools or outsmart their conspecifics. One capability, however, that we humans value highly, seems to be missing from their behavioral repertoire: generosity. Only very few species within the crow family have so far been found to act generously in experimental paradigms, while the highly intelligent ravens, for example, have demonstrated their egoistic tendencies in multiple studies. Lisa Horn of the of the Department of Behavioral and Cognitive Biology of the University of Vienna could now demonstrate, together with Jorg Massen of Utrecht University and an international team of researchers, that the social life of corvids is a crucial factor for whether the birds benefit their group members or not.

"Spontaneous generosity, without immediately expecting something in return, is a cornerstone of human society whose evolutionary foundations are still not fully understood. One hypothesis postulates that raising offspring cooperatively may have promoted the emergence of a tendency to willingly benefit group members in early human groups. Another hypothesis speculates that only increased tolerance towards group members and a reduced level of aggression made such generous behavior possible. While researchers found evidence for both hypotheses when investigating other non-human primates, results from other animal taxa have so far been missing", explains lead author Lisa Horn.

That is why Horn and her colleagues tested generous behavior in multiple species from the crow family. Some of the tested species raise their offspring cooperatively, while others do not. Additionally, some of the species nest in close proximity with their conspecifics, thereby demonstrating their high levels of tolerance, while other species jealously guard their territories against other members of their own species. In the experiment, the birds operated a seesaw mechanism by landing on a perch, which brought food into reach of their group members. If the birds wanted to grab the food themselves, they would have had to leave the perch and the seesaw would tilt back, thereby moving the food out of reach again. Since the birds thus could not get anything for themselves the authors argued that only truly generous birds would continue to deliver food to their group members throughout multiple experimental sessions.

Raising offspring cooperatively and high tolerance as driving factors for generosity

It became evident that this behavior was displayed most strongly by these corvid species that work together to raise their offspring cooperatively. Among male birds, the researchers also found evidence for the hypothesis that high tolerance towards conspecifics is important for the emergence of generous behavior. Males from species that commonly nest in very close proximity to each other were particularly generous. These results seem to support the hypotheses that raising offspring cooperatively and increased levels of tolerance may have promoted the emergence of generous tendencies not only in humans, but also in other animals. "What fascinates me the most is that in animals that are so different from us evolutionary mechanisms very similar to the ones in our human ancestors seem to have promoted the emergence of generous behavior", concludes Horn. More studies with different bird species, like the similarly intelligent parrots, or other animal taxa are, however, needed to further investigate these connections.

It is probably the immune response to, rather than the virus in itself, that causes sudden confusion and other symptoms from the nervous system in some patients with COVID-19. This is shown by a study of cases involving six Swedish patients, now published in the journal Neurology.

With accumulated experience of the disease, it has become evident that symptoms and signs from the nervous system is common in patients suffering from COVID-19.

Symptoms reported in the acute phase of the disease have included, for example, delirium, personality changes, and memory problems, all of which are signs of brain impairment or failure. These signs occur more frequently in more severe cases, and are usually temporary.

To date, it remains unclear whether SARS-CoV-2, the virus causing COVID-19, has the capacity to infect the brain and central nervous system directly. The current study from the University of Gothenburg indicates that, more likely, the patient's immune response is what may underlie the effects on the nervous system.

In the study, cerebrospinal fluid (CSF) samples were taken from six hospitalized patients at Sahlgrenska University Hospital in Gothenburg with moderate or severe COVID-19 and signs of brain impairment. The samples were analyzed for biomarkers that reflect how the brain is reacting to infections.

Every patient exhibited markedly elevated levels of the inflammation (immune activation) markers neopterin and beta-2-microglobulin, suggesting substantial activation of the brain's immune cells. In two cases, an increase in the protein neurofilament light (NfL), a marker that is sensitive to nerve-cell damage, was also seen.

On the other hand, no impact was observed on markers for damage to the blood-brain barrier, local antibody production or a raised white blood-cell count, which are otherwise common in virus infections in the central nervous system.

As for proof of actual SARS-CoV-2 invasion, the results from the analysis were uncertain, but most indications are that no virus was present in the cerebrospinal fluid, at least not to any significant degree.

Magnus Gisslén, Professor of Infectious Diseases at Sahlgrenska Academy, University of Gothenburg, and Chief Physician at the Department of Infectious Diseases, Sahlgrenska University Hospital, heads the Academy's clinical research on COVID-19.

"Overall, we see an unusual picture with marked inflammation and sometimes nerve-cell injury, but without a recruitment of immune-system cells from the bloodstream, detectable virus or damage to the blood-brain barrier, which are usually found in viral infections in the brain," he says.

The researchers emphasize that the mechanisms behind the symptoms seem to diverge from those of other viral infections. The first author of the study is Arvid Edén, PhD in Infectious Diseases at Sahlgrenska Academy, University of Gothenburg, and senior consultant at the Department of Infectious Diseases, Sahlgrenska University Hospital.

"It's an urgent priority for us to learn more about how COVID-19 affects the nervous system, not least so that we can determine which types of treatment may be suitable to counteract or mitigate the effects of infection with SARS-CoV-2 on the brain, both in the acute phase and in the longer term," Edén says.

Every cell in our body constantly divides to form new cells. This happens without us even thinking about it. However, every single time a cell divides, a complicated process has to unfold just the right way for our cells to avoid sickness and death.

The most essential step in this process is DNA replication, where the DNA in a mother cell is copied into its two daughter cells. Here, many molecules have to work together in order to assemble two new, identical DNA strings.

Writing for a prestigious international journal Nature, researchers from the University of Copenhagen have discovered how MCM proteins ensure that DNA replication proceeds at the right pace and thus avoids unnecessary molecular collisions, which could damage their genomes.

Even more importantly, the new findings explain how mother cells manage to instruct their daughters to keep the pace of their DNA replication within physiological limits. In simple terms, the new findings discovered nothing less than how an essential skill required for life continuation is preserved in cell's memory.

'We have quite many of these MCM proteins inside our cells. We can see them in the microscope, but for decades, scientists did not know what the vast majority of them actually do. From an evolutionary standpoint, it did not make sense to maintain a huge surplus of proteins only as back up, with no other important function. We have now solved this "MCM paradox" by finding that all those many MCM proteins in our cells actually have a defined function', says first author Hana Sedlackova, PhD student at the Novo Nordisk Foundation Center for Protein Research.

Exploiting cancer weaknesses

To explain the new finding by an analogy, researchers found that the excess of young MCM proteins is used by cells to slow down the DNA replication by adding "speed bumps" ahead of their older siblings, that 'drive' the DNA replication engine. And while it may seem impractical to slow down this process, the body has a very good reason to do so.

'These new results show that most of MCM proteins work a bit like speed bumps on a busy street. If they were not there, the traffic would go too fast and accidents could easily happen. Our study shows that the same thing happens in the cell: If the newly born MCM proteins cannot be passed by other cells on to their daughters, DNA is replicated too quickly, and this can be fatal for the cell. Just like a car, the DNA replication engine loses its maneuverability when it goes too fast'," explains professor Jiri Lukas, Executive Director at the Novo Nordisk Foundation Center for Protein Research.

The researchers suggest that their findings could potentially help exploit the weaknesses of cancer cells.

"During our work, we have also found that the young MCM proteins require a 'molecular babysitter' (a protein called MCMBP), which protects them and escorts them to DNA, where they can be useful. Without such protection, molecular roadblocks that slow down DNA replication cannot be made. While DNA in normal cell can be viewed as a nice new highway that allows reasonably fast speed, DNA in cancer cells is riddled by 'potholes', where every fast car (or a molecular motor that replicates DNA) is bound to crash. Based on our new findings, we are currently testing the idea that genetic of pharmacological removal of the MCMBP, and the resulting high speed of DNA replication, can be tolerated by normal cells but lethal to cancer cells" says Jiri Lukas.

The researchers managed to map the proteins and find their function using a variety of high-tech equipment such as CRISPR-Cas9 and HaloTag. Using 4D imaging, they were then able to label native MCM proteins and observe how they are born in the mother cells, how they are inherited by their daughters, and how their functions are changed in the absence of MCMBP the 'MCM babysitter'.

A new way of producing an enzyme called fucosyltransferase VI (FTVI) in the lab could help enhance the therapeutic potential of cord blood transplants.

Cord blood is currently used to treat more than 80 life-threatening conditions, ranging from cancer and immune deficiency to metabolic and genetic disorders. The therapy is predicated on the idea that stem cells in the cord blood will traffic to the bone marrow, where they can help rebuild a healthy blood and immune system that has been damaged by disease. But cord blood stem cells are not naturally adept at this process--which is why several drugmakers have turned to FTVI as a way of enhancing the cells' homing ability.

FTVI is an enzyme involved in tagging cells with sugar molecules in a way that alters migration patterns in the body. In clinical trials, cord blood stem cells treated with FTVI showed enhanced engraftment following infusion into cancer patients. Yet most commercial sources of FTVI available today have only limited enzymatic activity. Plus, they tend to be made using various expression systems that either produce enzymes with low activity or are costly and generate low yields.

Seeking a better manufacturing platform, a team led by Jasmeen Merzaban at KAUST engineered yeast cells and silkworm larvae to express the human version of FTVI. Working with collaborators in Japan, KAUST researchers from several teams came together to devise a purification scheme for obtaining the enzyme at high yields; they then tested how efficiently the end-product could alter human stem cells.

The researchers showed that their yeast- and silkworm-derived FTVI far outperformed commercial sources of the enzyme made in standard expression systems. "Now, these enzymes can be used ex vivo on stem cells to enhance their migration toward the bone marrow during a transplant," Merzaban says.

Alternatively, researchers could take advantage of the new yeast- and silkworm-produced FTVI for drug screening efforts. First author of the study, Asma Al-Amoodi, points out that many metastatic cancers exhibit enhanced activity of FTVI and similar enzymes. "We could envision using such enzymes to screen for small molecule inhibitors that block metastasis," she says.

The outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly across the globe at an alarming pace, causing considerable anxiety and fear among the general public. In response to the growing number of new cases, many countries have imposed lockdown measures to slow the spread of coronavirus. However, nearly every individual, community, business, and economy has been adversely affected by lockdown measures - an impact to society that cannot be ignored.

The health and well-being of the population will be affected if the community is kept open, but the lockdown strategy also incurs economic and financial impacts. Each strategy on its own will increase the total 'cost' to society. Can both losing strategies be combined in a manner that leads to a winning outcome? That is the question that researchers from the Singapore University of Technology and Design (SUTD) set out to answer in a recent paper published in Advanced Science.

The team, led by Assistant Professor Kang Hao Cheong from SUTD, seeks to answer this question by modeling the population using Parrondo's paradox with a view to relieve the cost of the epidemic by means of a switching strategy. The model takes into account the health and well-being of the population, as well as economic impacts and describes the interaction and flow between the different population compartments during the COVID-19 epidemic.

The researchers were inspired by a phenomenon called Parrondo's paradox. The paradox states that it is possible to alternate between a pair of losing strategies and still end up winning. Their results represent one of the first studies to focus on the lockdown exit strategy. It is also one of the first to link Parrondo's paradox to epidemiology.

From this study, the researchers show that keeping the community open results in a large number of infected individuals and a sharp increase in the number of deaths over time, so naturally the 'cost' increases. At the same time, a lockdown strategy reduces the possibility of infection, but has an adverse effect on the socio-economic cost.

"This means that each strategy cannot individually result in a decline to the 'cost' in the long-term during an epidemic. Such rising 'cost' allows us to classify them as losing strategies," explained Tao Wen, a research student from SUTD and a co-author of the study.

"When one switches between the losing strategies in accordance with any of the proposed alternating strategies, the 'cost' per day will decline. This, in itself, is a winning strategy to control the loss caused by COVID-19," he added.

This is a manifestation of the game theory Parrondo's paradox: two losing strategies can be combined into an outcome that wins.

The researchers have introduced three different switching rules. They are the time-based switching, result-based switching, and random switching schemes. Each switching rule comes with its own strengths and is applicable across a wide range of real-world scenarios.

"Such novel strategies can be implemented to curb the spread of COVID-19 or future epidemics, and have the potential to alleviate suffering, preserve and promote health and well-being among the population," observed Assistant Professor Kang Hao Cheong, the principal investigator for this study from SUTD.

"COVID-19 is a complex of medical conditions and not a cause. The ultimate causative agent is not a virus in isolation, but a virus in complexity with particular social factors -- the Four Horsemen: a) overpopulation, b)globalization, c) hyperconnectivity, and d) extreme centralization and increasing fragility of supply chains," cautioned Assistant Professor Cheong.

Most diseases are caused by aberrant cell signaling processes and basic research in cell signaling is needed to identify targets for future therapeutic approaches, especially in cases where no cures or effective treatments are currently available.

Cellular optogenetics uses light to precisely control cell signaling in space and over time, making it an invaluable technique for disease research. However, this potentially revolutionary method has been difficult for many researchers to use as, over long periods of time, the used light can itself have adverse effects on biological systems and the optogenetic tools can inactivate unexpectedly rapidly.

Now, researchers from the University of Turku in Finland, in collaboration with Frankfurt University Hospital in Germany, have developed a novel way to harness the quantum mechanical phenomenon of resonance energy transfer to design optogenetic tools that are more sensitive to light. The new method also informs the user exactly when an optogenetic tool is going to inactivate in cells. If continued activity is required, just the right amount of additional light can then be re-applied to re-activate the tool.

Combining these advances with existing tools and knowledge, the researchers were able to design and build more efficient optogenetic tools to investigate signaling pathways. With the improved tools, they studied two common chemotherapy drugs known to cause side effects on neurons and cause neuropathic pain. The new tools revealed how both activatory and inhibitory pathways contribute to the actions of these drugs on the investigated disease-associated pathway.

"Now we can develop more powerful tools to understand precisely how harmful conditions disrupt signaling in living cells. This information is likely to help us in identifying targets and designing better therapeutic compounds for conditions such as chemotherapy-induced neuropathic pain," says Lili Li, the lead author of the study and Postdoctoral Researcher at the Turku Bioscience Centre.

"There is still considerable potential to further exploit these quantum mechanical phenomena to devise even better quantitative and informative methods in biology and medicine, which could support the future discovery of new therapeutic approaches," adds senior author of the study Michael Courtney.

Millions of years ago, several species of crocodiles of different genera and characteristics inhabited Europe and sometimes even coexisted. But among all these species, it was thought unlikely that crocodiles of the genus Crocodylus, of African origin, had ever lived in the Mediterranean basin. The remains found in the Italian regions of Gargano, Tuscany and Scontrone over the last few decades confirm that they did.

Now, a study published in the Journal of Paleontology corroborates this with the fossils of two crocodiles measuring about three metres in length that were discovered in the Valencian Venta del Moro site -excavated by researchers from the University of Valencia between 1995 and 2006-, and which were ascribed at the time to the Crocodylus checchiai species . This new work describes the remains more than 14 years after they were found for the first time.

"Our comparisons indicate that this material clearly does not belong to the Diplocynodon genera -an extinct genus of alligatoroid, similar to today's caimans- or Tomistoma -similar to gavials-, the only other two crocodilians described so far for the late European Miocene," as Ángel Hernández Luján, a palaeontologist at the Miquel Crusafont Catalan Institute of Palaeontology (ICP) and co-author of the work, has explained to Sinc.

However, as the remains are too fragmented, an analysis of the cranial bones, isolated teeth and osteoderms (bone plaque on the skin) suggests that they could belong to the C. checchiai species, as assigned at the time of their discovery, but their taxonomy is still not completely clear and hinders a more precise specific identification. In any case, "the morphology of the Venta del Moro crocodile remains is congruent with the Crocodylus genus," the researcher states.

Swimming from Africa to Europe

The fossil remains of this Valencian site, which are the first Crocodylus in the Iberian Peninsula, "unequivocally" support the non-occasional dispersion of this genus from Africa to Europe during the late Miocene, according to palaeontologists. The discovery of two partial individuals, instead of just one, could indicate that a whole population was present in this area.

During their "colonisation", these reptiles spread more significantly in the southern areas of Mediterranean Europe, as suggested by the Italian and Spanish areas where the fossils have been found. "All European localities with late Miocene crocodilians, including Venta del Moro, were at that time close to the northern Mediterranean coast and therefore easily accessible thanks to specimens that became scattered in the seawater," the authors stress in the study.

"What is most certain is that it would have also inhabited the coasts of Murcia and Andalusia, although we cannot rule out that it would also have become dispersed along the coast of Catalonia and the Balearic Islands," Hernández Luján has pointed out to SINC. But how could they have got there from the African coasts?

The researchers' hypothesis is that these crocodiles swam from one continent to another in the sea before a land connection was established between Africa and Europe. This idea would be supported by the behaviour of modern crocodiles, which are good swimmers and can even reach 32 km/h in the water.

An example of this is the current saltwater crocodile (Crocodylus porosus), which can make significant forays into the open sea to colonise other islands or other continents between Oceania and South-East Asia. "You only have to look at how easily it moves in the open sea to be seen in the waters of the Solomon Islands or even in French Polynesia," says the palaeontologist.

But there are more examples that reinforce this hypothesis. Because of its anatomical similarity to American crocodiles, the extinct species Crocodylus checchiai, which originated in Libya and Kenya, could well be its ancestor. This suggests that crocodiles were able to cross the Atlantic Ocean during the Miocene, which would explain the appearance of the genus in America.

Therefore, in the case of the specimens found in Venta del Moro, swimming from the African to the European continent "must not have meant a great effort for them before they reached the Peninsula," the researcher concludes.

CHAMPAIGN, Ill. -- A multidisciplinary group that studies the physical and chemical properties of insect wings has demonstrated the ability to reproduce the nanostructures that help cicada wings repel water and prevent bacteria from establishing on the surface. The new technique - which uses commercial nail polish - is economical and straightforward, and the researchers said it will help fabricate future high-tech waterproof materials.

The team used a simplified version of a fabrication process - called nanoimprinting lithography - to make a template of the complex pillar-shaped nanostructures on the wings of Neotibicen pruinosus, an annual cicada found in the central region of the United States. The templates are fully dissolvable and produce replicas that average 94.4% of the pillar height and 106% of the original wing, or master structure's pillar diameter, the researchers said.

The results of the study are published in the journal Nano Letters.

"We chose to work with wings of this species of cicada because our past work demonstrates how the complex nanostructures on their wings provide an outstanding ability to repel water. That is a highly desirable property that will be useful in many materials engineering applications, from aircraft wings to medical equipment," said Marianne Alleyne, an entomology professor at the University of Illinois at Urbana-Champaign, who co-led the study with Donald Cropek, of the U.S. Army Corps of Engineers' Construction Engineering Research Laboratory, and Nenad Miljkovic, a professor of mechanical science and engineering at Illinois.

Nanoimprinting lithography is not new but can be labor-intensive and expensive, the researchers said. Some approaches use toxic materials that can damage the original copied object, like a delicate cicada wing. Others require high temperatures that are not compatible with biological samples such as plants or insects.

"Our process allows us to do this in an open lab at room temperature and atmospheric pressure," Cropek said. "We use nail polish and rubbing alcohol, which does not inflict any damage to the delicate wing nanostructures."

In the lab, the team applies a quick-drying nail polish directly to a cicada wing, which is then left to cure at room temperature.

"It was not easy to find the right formula of nail polish because we want to avoid one that will warp or stretch the template during removal," Alleyne said. Once completed, the template can be coated with a polymer or metal then dissolved away, leaving only the replica metal or polymer.

To show the versatility of the new method, the team experimented with two very different replica materials: copper metal and a flexible silicon-based organic polymer called PDMS.

"We showed that the technique is compatible with physical vapor deposition and electrochemical deposition of metals, oxides or ceramics, as well as chemical vapor deposition and spin coating of softer materials like polymers," Miljkovic said.

"Copper is particularly interesting to us because of its inherent antimicrobial properties, and our past work indicates that some cicada species display antimicrobial properties on their wings," Alleyne said. "We don't know if it is the chemicals on the wing's surface or the physical nanostructures, or a combination of both chemistry and topography, that produce the bactericidal activity, but being able to produce materials with different chemistries and structures will help us answer that fundamental question. This new, relatively simple fabrication method will ultimately help us design multifunctional engineered materials."

Based on digital endocranial cast models the canine brain does not increase proportionally with body size. Researchers at ELTE Eötvös Loránd and Kaposvár University in Hungary reconstructed the surface morphology of 28 canine brains, including various dog breeds, wolves, coyotes, and jackals. The shortening of the facial skeleton greatly influences the ratio of certain brain regions, primarily the olfactory bulb and the frontal lobe. These changes might have profound implications for olfactory and problem-solving abilities.

Reconstructing the brain based on the internal surface patterns of a skull is a well-known method among archeologists studying the brains of extinct species, e.g. dinosaurs, mammoths and even cavemen. One way to achieve a model of the brain is to fill the endocranial space with specific gradually hardening fluids, and after the solidifying of the material the bones can be removed to reveal the cast, which reflects the surface of the brain with high fidelity. These are called endocranial casts, or endocasts.

Skull and endocast of a beagle. Video created by dr. Kálmán Czeibert: https://youtu.be/R7k-b-soVN4

Nowadays, rather than utilising endocasts, invasive process diagnostic imaging techniques are highly preferred. Computer tomography (CT) is the best and easiest way to visualize the bones, with all of their external and internal structures and composition. Using CT is also advantageous in endocranial analysis, as researchers can create virtual endocasts based on the digitized skulls. This allows for a higher freedom during examinations, because these virtual models can be rotated, colorized, cut, and completed. They can be shown not only on mobile phones, tablets or computers, but with the help of 3D-printing technology one can replicate them in the requested number and scale as well.

This digital endocasting technique was used by researchers from ELTE who scanned skulls from the collection of dr. Tibor Csörg? (ELTE, Department of Anatomy, Cell and Developmental Biology), which comprises almost 400 dog skulls from 152 canine breeds. "Due to the high resolution scanning, detailed 3D models could be created. This means that not only the main convolutions, that is, the cerebral gyri, can be recognized on the final model, but the location of the major blood vessels can also be seen on the surface." - explains dr. Kálmán Czeibert, veterinarian and postdoctoral researcher at the Senior Family Dog Project, first author of the publication. "We compared the shape, volume and surface features of the endocasts from 28 specimens in our recent study in Frontiers in Veterinary Science. These models clearly show how the shortening of the facial part of the skull affected the morphology of the brain, distorting the olfactory bulb, which is pushed back and underneath the frontal lobe in certain breeds (like the French bulldog or pug), changing the ratio between the cerebral areas."

In order to clarify how this change affects dogs' olfactory and cognitive performance, further imaging and behavioral investigations are needed. The new collection is part of the Canine Brain and Tissue Bank at ELTE, funded by a European Research Council (ERC) grant. The bank will help researchers to link the brain with behaviour. "In some areas, where volume has diminished, neuronal density and the relationship with other brain regions may act to counteract these changes. To further examine these speculations, behavioural testing, diagnostic imaging (like CT, MR or EEG), and histological and molecular assessment will be needed." - said dr. Eniko Kubinyi, senior researcher at ELTE, principal investigator of the research group.

"One of our primary aims was the widespread dissemination of scientific knowledge.' - adds dr. Czeibert. "How dog skulls and brains vary is striking. For example, despite the 30-fold difference in body weight between a Neapolitan mastiff and a chihuahua, their endocasts' volumes have only a 2-fold difference." The researchers from ELTE plan to increase the number of skulls by digitizing more specimens for microevolutionary studies in the framework of an international cooperation.

OCTOBER 22, 2020 - Nutley, NJ - A more efficient and much faster method to assess high levels of neutralizing antibodies to COVID-19 could point the way to better understanding and treatment of the disease, according to new published findings by scientists from the Hackensack Meridian Center for Discovery and Innovation (CDI) and the University of Michigan (U-M).

A new portable "lab on a chip," developed by the U-M scientists and demonstrated with help of the CDI, can identify the presence of COVID-19 antibodies in blood donors with greater speed and efficiency than the current standard "enzyme-linked immunosorbent assay" or ELISA technology.

Together, the CDI and U-M researchers have shown the device can identify COVID-19 antibodies in human blood in 15 minutes - much shorter than the few days the process normally takes. The test can also be done with smaller amounts of blood.

The work could have particular value for the validation of convalescent plasma as a treatment for COVID-19. A paper on the findings is published in Biosensors and Bioelectronics.

"Convalescent plasma is a treatment that can be very effective - but for it to have the best chance to work, it needs to have rigorous standards, which include assessing the presence of high-titer neutralizing antibodies," said David Perlin, Ph.D., chief scientific officer and senior vice president of the Hackensack Meridian Center for Discovery and Innovation, and one of the new study's authors. "This paper shows how the antibody thresholds can mean a better potential COVID-19 treatment - and also better outcomes."

"This research shows what an important role microfluidics can play in both saving lives and costs during the COVID-19 pandemic," said Xudong (Sherman) Fan, U-M biomedical engineering professor and co-founder of Optofluidic Bioassay.

The U-M device detects the presence and amount of neutralizing immunoglobulin--antibodies created by the immune system within seven to 10 days of a COVID-19 infection. Only donors with high levels are likely to provide samples that could be effective in treatment, such as convalescent plasma therapy.

The treatment involves taking plasma - the liquid portion of the blood that contains antibodies - from survivors and infusing it into sick patients to boost their immune response.

Thousands of patients nationally have been administered convalescent plasma through a program overseen by the Mayo Clinic. Hackensack University Medical Center also has its own clinical trial underway involving high-titer (levels) of antibodies.

The lab-on-a-chip approach developed by U-M analyzes on-site and requires just a finger prick's worth of blood--8 microliters. The traditional ELISA methods require 100 microliters to do its work. The U-M system is contained in a device the size of a portable 3D printer.

A new discovery about how the body transports dexamethasone, a drug that can increase the survival chances of patients with severe COVID-19, suggests diabetes and other factors may reduce its potentially lifesaving effectiveness. Based on their findings, the researchers say doctors may need to rethink how they dose the drug for certain groups of patients.

The team of scientists, based at the University of Virginia School of Medicine, the University of South Carolina, and in Poland, has determined how a protein in our blood called serum albumin picks up dexamethasone and takes it where it is needed. Low serum albumin levels are already considered a major risk factor for severe COVID-19, as is diabetes.

The new research suggests diabetes or low albumin levels may make it difficult for patients to get the benefits of dexamethasone, a corticosteroid that calms the hyperactive immune response that can lead to death in severe COVID-19.

Diabetes is associated with high blood sugar levels, which results in a modification of albumin that may alter the binding site for dexamethasone. Other drugs may also compete with dexamethasone for the limited space in serum albumin's cargo holds. Albumin's cargo capacity is also naturally decreased when there is a low albumin level in the blood.

"At this point, we do not have a readily available treatment better than dexamethasone for severe COVID-19 cases, but, like COVID-19 itself, its effectiveness is somewhat unpredictable," said lead researcher Wladek Minor, PhD, of UVA's Department of Molecular Physiology and Biological Physics. "In order to provide a comprehensive picture, this research was conducted in collaboration among structural biologists, computer scientists and clinicians. So, every author of this paper had to step out of the box to combine medical data with structural biology results in order to suggest possible modifications of the treatment that could potentially save more human lives."

Researcher Ivan Shabalin, PhD, the first author of a new paper outlining the findings, added: "Working on this interdisciplinary team and seeing how our research in fundamental science may save lives in the current pandemic felt extremely rewarding."

Dexamethasone and COVID-19

For the first time, Minor and his colleagues have demonstrated exactly how serum albumin binds with dexamethasone so that the drug can be distributed through our bodies.

Serum albumin binds with dexamethasone the same way it binds with the hormone testosterone, suggesting that the two could compete with each other, the researchers report. More men die of COVID-19 than women, and low testosterone levels have already been associated with worse outcomes. The authors of the study hypothesized that high dexamethasone levels might affect testosterone transport by competing for the same drug site on albumin.

Serum albumin also uses the same binding dock to pick up several common nonsteroidal anti-inflammatory drugs, so doctors may need to consider the potential for competition in deciding COVID-19 treatment plans, the research suggests.

That said, it's not as simple as increasing the dexamethasone dose for patients with diabetes or low serum albumin. Too much dexamethasone can be harmful or have unwanted side effects. More research is needed to determine the best dosing in various patient populations, particularly for people with diabetes or low albumin levels, the researchers say.

To better understand serum albumin's role in COVID-19, the researchers analyzed data from 373 patients at a hospital in Wuhan, China, that treated many severe cases of the disease. The scientists found that patients who died had lower albumin levels than those who survived. Those who died also had higher levels of blood sugar. That aligned with the researchers' conclusion that high blood sugar could affect serum albumin's ability to carry its cargo.

"In order to provide rapid response to emerging biomedical challenges and threats like COVID-19, we need to analyze medical data in the context of other in-vitro and in-vivo results," Minor said. "Five years ago, I wrote in Expert Opinion in Drug Discovery that, 'The use of recent advancements in biochemical, spectroscopy and bioinformatics methods may revolutionize drug discovery, albeit only when these data are combined and analyzed with effective data management systems. Accurate and complete data management is crucial for developing experimental procedures that are robust and reproducible.' This assessment is still valid, and, clearly, not enough progress has been made, because it is mistakenly not recognized as a grand challenge for biomedical sciences."

"Until a vaccine or new drugs are widely available, we have to make the best use of the drugs we know can help fight COVID-19," added team member Dariusz Brzezinski, PhD.