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Columbus, Ohio - A study led by researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James) described a potential therapeutic anticancer vaccine that frees suppressed cancer-killing immune cells, enabling them to attack and destroy a tumor.

Published in the journal Oncoimmunology, on October 1, 2020, the findings showed that the peptide called PD1-Vaxx, a first checkpoint inhibitor vaccine, was safe and effective in a colon cancer syngeneic animal model.

The vaccine produced polyclonal antibodies that inhibit the programmed cell death receptor, PD-1, on cancer cells. The vaccine mimics the action of the PD-1 inhibitor nivolumab (pronounced nih-VOL-yoo-mab, marketed as Opdivo), but it avoids triggering the innate and acquired resistance associated with that and related agents, the researchers say.

The study found that PD1-Vaxxwas effective in inhibiting tumor growth. It was even more effective when used in combination with a second therapeutic peptide vaccine, one that targets two sites on the HER-2 receptor on colon cancer cells. The combination treatment produced complete responses in nine of 10 animals. That vaccine, called B-Vaxx, was developed earlier by the same research team.

"Our study is important for two key reasons," says first author and vaccine developer Pravin T. P. Kaumaya, PhD, a member of the OSUCCC - James Translational Therapeutics Research Program and professor of medicine at The Ohio State College of Medicine. "First, PD1-Vaxx activates both B- and T-cell functions to promote tumor clearance. Second, the treatment is targeted to block signaling pathways that are crucial for tumor growth and maintenance. By giving this vaccine in combination with an immunotherapy drug, we are essentially super-charging and specifically directing the immune system to target and kill cancer cells."

Like the immune therapy drug nivolumab, PD1-Vaxx is an immune checkpoint inhibitor. Immune checkpoints are proteins that keep immune cells from attacking healthy body cells. PD-1 is a checkpoint protein on killer T cells. PD-L1 is another checkpoint protein that is on healthy cells and on many cancer cells. When PD-1 on T cells binds with PD-L1 on a body cell or a cancer cell, it suppresses the T cell, preventing it from killing the cell.

Nivolumab works by blocking PD-1 from binding with PD-L1, thereby allowing T cells to kill a patient's cancer cells. But while nivolumab consists of anti-PD-1 monoclonal antibodies, which target a single location on the PD-1 protein, the experimental vaccine PD1-Vaxx triggers a range of antibodies - a polyclonal antibody response - that blocks multiple sites on PD-1 and could more effectively inhibit the protein.

For this study, Kaumaya and his colleagues used cell lines and animal models to evaluate four PD-1 B-cell peptide epitopes as vaccine candidates. Of these, the PD-1 epitope sequence 92-110 significantly reduced tumor growth in an animal colon cancer tumor model and was chosen for the PD1-Vaxx inhibitory vaccine.

Key findings:

PD1-Vaxx outperformed the standard anti-mouse PD-1 antibody (mAb 29F.1A12) in an animal model of HER-2 expressing colon carcinoma;

The combination of PD1-Vaxx with combo HER-2 peptide vaccine (B-Vaxx) showed enhanced inhibition of tumor growth in a HER-2-positive colon cancer model;

Both the PD-1 and the combined vaccines were safe with no evidence of toxicity or autoimmunity.

"With additional study," Kaumaya says, "we believe PD1-Vaxx will prove to be safer, more effective and have a lower incidence of resistance than checkpoint-blockade antibodies."

This study was supported by grants from the National Institutes of Health (CA84356, CA13508, CA181115), and by Imugene Ltd. The safety of the vaccine was confirmed in pre-clinical animal studies at OSU and Charles River labs (Ashland, Ohio).

Vaccine Received IND Approval

In November 2020, the U.S. Food and Drug Administration (FDA) granted investigational new drug (IND) approval to Imugene for clinical testing of the investigational vaccine, known as PD1-Vaxx, an important milestone in the research collaboration between Ohio State and Imugene.

A first-in-human, phase1 clinical trial to test the vaccine is expected to open at the OSUCCC James in early 2021 for certain patients with non-small cell lung cancer. Additional U.S. sites may be added to trial at a later date.

"We are excited to begin testing of this vaccine in the United States to offer new hope to patients with lung and other cancers. Reaching this point where we can transition our findings from the lab to the clinic speaks to the perseverance and dedication of Imugene's clinical and research team -- including our research lab staff at Ohio State -- to build on the clinical and commercial potential," said Kaumaya.

Imugene's Chief Executive Officer & Managing Director Leslie Chong, said "the multiple commercial, strategic and clinical benefits of our collaboration with the OSU secures our leadership position in the promising B-cell peptide cancer vaccine sector, and in particular PD-1 checkpoint inhibitors, where OSU's pre-clinical work for a Phase I PD-1 clinical trial was pivotal to our FDA IND approval."

"This collaborative research with Imugene has closely paralleled my personal work over the past two decades, and together we form a strong team driving multiple combination immunotherapy drugs through the clinic targeting lung, breast, gastric and other cancer targets. This collaborative venture with Imugene supports the rapid development to achieving a potential cure for several important cancer targets."

CAMBRIDGE, MA -- Since the coronavirus pandemic began in the spring, many people have only seen their close friends and loved ones during video calls, if at all. A new study from MIT finds that the longings we feel during this kind of social isolation share a neural basis with the food cravings we feel when hungry.

The researchers found that after one day of total isolation, the sight of people having fun together activates the same brain region that lights up when someone who hasn't eaten all day sees a picture of a plate of cheesy pasta.

"People who are forced to be isolated crave social interactions similarly to the way a hungry person craves food. Our finding fits the intuitive idea that positive social interactions are a basic human need, and acute loneliness is an aversive state that motivates people to repair what is lacking, similar to hunger," says Rebecca Saxe, the John W. Jarve Professor of Brain and Cognitive Sciences at MIT, a member of MIT's McGovern Institute for Brain Research, and the senior author of the study.

The research team collected the data for this study in 2018 and 2019, long before the coronavirus pandemic and resulting lockdowns. Their new findings, described today in Nature Neuroscience, are part of a larger research program focusing on how social stress affects people's behavior and motivation.

Former MIT postdoc Livia Tomova, who is now a research associate at Cambridge University, is the lead author of the paper. Other authors include Kimberly Wang, a McGovern Institute research associate; Todd Thompson, a McGovern Institute scientist; Atsushi Takahashi, assistant director of the Martinos Imaging Center; Gillian Matthews, a research scientist at the Salk Institute for Biological Studies; and Kay Tye, a professor at the Salk Institute.

Social craving

The new study was partly inspired by a recent paper from Tye, a former member of MIT's Picower Institute for Learning and Memory. In that 2016 study, she and Matthews, then an MIT postdoc, identified a cluster of neurons in the brains of mice that represent feelings of loneliness and generate a drive for social interaction following isolation. Studies in humans have shown that being deprived of social contact can lead to emotional distress, but the neurological basis of these feelings is not well-known.

"We wanted to see if we could experimentally induce a certain kind of social stress, where we would have control over what the social stress was," Saxe says. "It's a stronger intervention of social isolation than anyone had tried before."

To create that isolation environment, the researchers enlisted healthy volunteers, who were mainly college students, and confined them to a windowless room on MIT's campus for 10 hours. They were not allowed to use their phones, but the room did have a computer that they could use to contact the researchers if necessary.

"There were a whole bunch of interventions we used to make sure that it would really feel strange and different and isolated," Saxe says. "They had to let us know when they were going to the bathroom so we could make sure it was empty. We delivered food to the door and then texted them when it was there so they could go get it. They really were not allowed to see people."

After the 10-hour isolation ended, each participant was scanned in an MRI machine. This posed additional challenges, as the researchers wanted to avoid any social contact during the scanning. Before the isolation period began, each subject was trained on how to get into the machine, so that they could do it by themselves, without any help from the researcher.

"Normally, getting somebody into an MRI machine is actually a really social process. We engage in all kinds of social interactions to make sure people understand what we're asking them, that they feel safe, that they know we're there," Saxe says. "In this case, the subjects had to do it all by themselves, while the researcher, who was gowned and masked, just stood silently by and watched."

Each of the 40 participants also underwent 10 hours of fasting, on a different day. After the 10-hour period of isolation or fasting, the participants were scanned while looking at images of food, images of people interacting, and neutral images such as flowers. The researchers focused on a part of the brain called the substantia nigra, a tiny structure located in the midbrain, which has previously been linked with hunger cravings and drug cravings. The substantia nigra is also believed to share evolutionary origins with a brain region in mice called the dorsal raphe nucleus, which is the area that Tye's lab showed was active following social isolation in their 2016 study.

The researchers hypothesized that when socially isolated subjects saw photos of people enjoying social interactions, the "craving signal" in their substantia nigra would be similar to the signal produced when they saw pictures of food after fasting. This was indeed the case. Furthermore, the amount of activation in the substantia nigra was correlated with how strongly the patients rated their feelings of craving either food or social interaction.

Degrees of loneliness

The researchers also found that people's responses to isolation varied depending on their normal levels of loneliness. People who reported feeling chronically isolated months before the study was done showed weaker cravings for social interaction after the 10-hour isolation period than people who reported a richer social life.

"For people who reported that their lives were really full of satisfying social interactions, this intervention had a bigger effect on their brains and on their self-reports," Saxe says.

The researchers also looked at activation patterns in other parts of the brain, including the striatum and the cortex, and found that hunger and isolation each activated distinct areas of those regions. That suggests that those areas are more specialized to respond to different types of longings, while the substantia nigra produces a more general signal representing a variety of cravings.

Now that the researchers have established that they can observe the effects of social isolation on brain activity, Saxe says they can now try to answer many additional questions. Those questions include how social isolation affect people's behavior, whether virtual social contacts such as video calls help to alleviate cravings for social interaction, and how isolation affects different age groups.

The researchers also hope to study whether the brain responses that they saw in this study could be used to predict how the same participants responded to being isolated during the lockdowns imposed during the early stages of the coronavirus pandemic.

CHAPEL HILL, NC - Strong emotions such as fear and anxiety tend to be accompanied and reinforced by measurable bodily changes including increased blood pressure, heart rate and respiration, and dilation of the eyes' pupils. These so-called "physiological arousal responses" are often abnormally high or low in psychiatric illnesses such as anxiety disorders and depression. Now scientists at the UNC School of Medicine have identified a population of brain cells whose activity appears to drive such arousal responses.

The scientists, whose study is published in Cell Reports, found that artificially forcing the activity of these brain cells in mice produced an arousal response in the form of dilated pupils and faster heart rate, and worsened anxiety-like behaviors.

The finding helps illuminate the neural roots of emotions, and point to the possibility that the human-brain counterpart of the newly identified population of arousal-related neurons might be a target of future treatments for anxiety disorders and other illnesses involving abnormal arousal responses.

"Focusing on arousal responses might offer a new way to intervene in psychiatric disorders," said first author Jose Rodríguez-Romaguera, PhD, assistant professor in the UNC Department of Psychiatry and member of the UNC Neuroscience Center, and co-director of the Carolina Stress Initiative at the UNC School of Medicine.

Rodríguez-Romaguera and co-first author Randall Ung, PhD, an MD-PhD student and adjunct assistant professor in the Department of Psychiatry, led this study when they were members of the UNC laboratory of Garret Stuber, PhD, who is now at the University of Washington.

"This work not only identifies a new population of neurons implicated in arousal and anxiety, but also opens the door for future experiments to systematically examine how molecularly defined cell types contribute to complex emotional and physiological states," Stuber said. "This will be critical going forward for developing new treatments for neuropsychiatric disorders."

Anxiety disorders, depression, and other disorders featuring abnormally high or low arousal responses affect a large fraction of the human population, including tens of millions of adults in the United States alone. Treatments may alleviate symptoms, but many have adverse side effects, and the root causes of these disorders generally remain obscure.

Untangling these roots amid the complexity of the brain has been an enormous challenge, one that laboratory technology has only recently begun to surmount.

Rodríguez-Romaguera, Ung, Stuber and colleagues examined a brain region within the amygdala called the BNST (bed nucleus of the stria terminalis), which has been linked in prior research to fear and anxiety-like behaviors in mice.

Increasingly, scientists view this region as a promising target for future psychiatric drugs. In this case, the researchers zeroed in on a set of BNST neurons that express a neurotransmitter gene, Pnoc, known to be linked to pain sensitivity and more recently to motivation.

The team used a relatively new technique called two-photon microscopy to directly image BNST Pnoc neurons in the brains of mice while the mice were presented with noxious or appealing odors - stimuli that reliably induce fear/anxiety and reward behaviors, respectively, along with the appropriate arousal responses. In this way, the scientists found that activity in these neurons tended to be accompanied by the rapid dilation of the pupils of the mice when the animals were presented with either of these odor stimuli.

The researchers then used another advanced technique called optogenetics - using light to control genetically engineered cells - to artificially drive the activity of the BNST Pnoc neurons. They found that spurring on BNST Pnoc activity triggered a pupillary response, as well as increased heart rate. Optogenetically driving the neurons while the mice underwent an anxiety-inducing maze test (traditionally used to assess anxiety drugs) increased the animals' signs of anxiety, while optogenetically quieting the neurons had the opposite effect.

"Essentially we found that activating these BNST Pnoc neurons drives arousal responses and worsens anxiety-like states," Rodríguez-Romaguera said.

The discovery is mainly a feat of basic neuroscience. But it also suggests that targeting arousal-driving neurons such as BNST Pnoc neurons with future drugs might be a good way to reduce abnormally strong responses to negative stimuli in anxiety disorders, for example, and to boost abnormally weak responses to positive stimuli in depression.

The study uncovered evidence that BNST Pnoc neurons are not all the same but differ in their responses to positive or negative stimuli, and the researchers are now cataloguing these BNST Pnoc neuron sub-groups.

"Even this small part of the amygdala is a complex system with different types of neurons," Ung said. Teasing this apart will help us understand better how this system works."

In the most comprehensive analysis to date of U.S. children tested and treated for COVID-19, an organization representing seven of the nation's largest pediatric medical centers reports that some groups of children are faring significantly worse than children in general during the pandemic.

Findings from the PEDSnet organization--which includes Cincinnati Children's--were published Nov. 23, 2020, in JAMA Pediatrics. The report is based on electronic medical records data from more than 135,000 children who have been tested for infections from the SARS-CoV-2 virus from Jan. 1 through Sept. 8, 2020.

"These findings are important because they improve our understanding of the impact of COVID-19 in the pediatric population," says Nathan Pajor, MD, a pulmonary medicine specialist at Cincinnati Children's and a co-author of the study. "We see that relative to adults, kids are less likely to have severe disease or to die from COVID-19. However, we also notice the disproportionately high rates of infection among Black, Asian and Hispanic children as a clear target of further study."

PEDSnet centers include Children's Hospital of Philadelphia; Cincinnati Children's Hospital Medical Center; Children's Hospital of Colorado; Nationwide Children's Hospital; Nemours Children's Health System; Seattle Children's Hospital; and, St. Louis Children's Hospital. Combined, these centers provide care to about 2.5 million children a year.

Highlights of their analysis include:

Like previous, smaller studies, this data shows that children are less likely to test positive and less likely to suffer severe illness when they do get infected.

Patients of African-American, Hispanic, and Asian race/ethnicity were less likely than white children to be tested. However, they were 2-4 times more likely to test positive.

Teens and young adults were more likely to test positive than younger children.

Children covered by Medicaid and other public programs were more likely to test positive than children from privately insured families.

Underlying cancer, diabetes (types 1 and 2), and other immune-suppressing conditions were indicators of increased risk of severe disease. But children with asthma were not found to be at increased risk of severe illness.

Among the 5,374 children who tested positive, 7% required hospital admissions. Of those hospitalized, 28% required intensive care and 9% required mechanical ventilation. Of the hospitalized children, eight died. (Case fatality rate: 0.2%)

"Further study is needed to understand the causes behind the variations in positivity rates," Pajor says. "How much is related to social determinants of risk, such as exposure to air pollution, housing density, or the likelihood of living with a person who must work at an in-person job? How much reflects differences in disease biology?"

Harnessing the Power of Big Data

The PEDSnet data coordinating center is based in Philadelphia, but the concept behind PEDSnet--launched in 2014--was a national cooperative effort among its co-founders, says Tracy Glauser, MD, Associate Director, Cincinnati Children's Research Foundation.

"Part of the challenge of pediatric research has been that many of our conditions are rare, so that no single institution has enough information by itself to comprehensively tackle certain issues," Glauser says. "The goal of PEDSnet has been to work out ways for institutions to share data to answer questions we cannot address alone."

Cincinnati Children's leaders have invested years of work into launching several data-sharing initiatives, including the Genomics Research and Innovation Network (GRIN) in 2015, becoming the data coordinating center for the Bench to Bassinet (B2B) Program for cardiac research in 2016 and being named the data coordinator for the Rare Diseases Clinical Research Network (RDCRN) in 2019.

Peter Margolis, MD, PhD, chaired the PCORnet Council and serves as the Cincinnati Children's site principal investigator for PEDSnet. Margolis is Co-Director of the James M. Anderson Center for Health System Excellence and has an extensive track record at building networks for health care quality improvement and research.

"PEDSnet provides a national digital architecture that can harness the power of the electronic health record to advance knowledge," Margolis says. "Without PEDSnet, gathering the information we are presenting today would have taken years."

MIS-C Needs Closer Study

While the latest study provides powerful data to address many questions, it also calls attention to the chaotic nature of the early days of the pandemic and how experts dealt with one of the most serious complications affecting children.

Early on children who experienced severe heart-damaging inflammatory reactions were diagnosed with Kawasaki disease, a very rare condition with largely unknown causes. As clinicians noted differences between the new cases and older ones, the diagnosis morphed into Kawasaki-like disease. It has since evolved into "multisystem inflammatory syndrome of childhood" (MIS-C).

The study co-authors say the medical community still has only a partial picture about the impact of MIS-C on children, in part because the rapidly evolving name changes has complicated data gathering. Also, with the pandemic still less than a year old in the U.S., much more study is needed to understand the long-term outcomes of MIS-C.

Much More to Learn

Some of the study's limitations include not including kids who were infected, or potentially killed, by COVID19 due to lack of testing availability. The study likely undercounts the actual numbers of asymptomatic infected children across the country, and does not address what risk those children may have presented to adults in their lives.

The participating medical centers overcame enormous technical challenges to build this tracking system early in the pandemic. Now, the data can be quickly refreshed to allow further, deeper analysis as the pandemic continues.

"Effective response to SARS-CoV-2 will require rapid but robust development of new clinical
and public health practices, based on a better understanding of viral and host biology," the co-authors say. "This knowledge will be critical not only in caring for severely ill patients, but also in constructing sustainable ways to minimize the disease burden caused by SARS-CoV-2."

The savanna tree frog Bokermannohyla ibitiguara is about 4 cm long and is found only in gallery forest along streams in the Serra da Canastra mountain range in the state of Minas Gerais, Southeast Brazil. In this watery forest environment, it can grow, feed, mate, and lay eggs without needing to range very far throughout its life cycle, according to a study published in Diversity and Distributions.

According to the Brazilian and US researchers who conducted the study, topography rather than vegetation is the main factor leading to more or less dispersal of the species in the territory, and this information is even recorded in its DNA.

They analyzed genetic variation among groups of B. ibitiguara living inside and outside the Serra da Canastra National Park, a protected area in the region, discovering that the flatter the terrain, the more genetically diverse is the population.

In areas of highly variable elevation, individuals are genetically similar. In evolutionary terms, this can be harmful to the species, which becomes more susceptible to disease and climate change, for example.

"Genetic analysis and conservation studies typically take land cover into account, among other factors, but the Cerrado [Brazilian savanna] is topographically diverse, including montane regions with high plateaus [chapadões] separated by low areas. We set out to verify whether this variable terrain played a part in the genetic diversity of the species, and found that it did. The vegetation alone didn't explain the genetic differences we identified between sites, or even within the same site. The topography did," said Renato Christensen Nali, first author of the article and a professor at the Federal University of Juiz de Fora's Institute of Biological Sciences (ICB-UFJF) in Minas Gerais, Brazil.

The study was one of the results of Nali's doctoral research, conducted at São Paulo State University's Bioscience Institute (IB-UNESP) in Rio Claro, Brazil, with a scholarship from FAPESP (São Paulo Research Foundation).

The research was part of the project "Reproductive ecology of anuran amphibians: an evolutionary perspective", for which the principal investigator is Cynthia Peralta de Almeida Prado, a co-author of the article. She is a professor at UNESP's School of Agrarian and Veterinary Sciences in Jaboticabal and teaches graduate students in zoology at IB-UNESP in Rio Claro.

The flatter the better

"The findings are very interesting because they bring to light a novel factor for conservation of the Cerrado, among other reasons. Ecological corridors and native forests are rightly considered important for conservation units, but more attention needs to be paid to the type of terrain. The topography should permit dispersal of the animals," said Nali, who heads ICB-UFJF's Amphibian Evolutionary Ecology Laboratory (Lecean).

To arrive at the results, the researchers analyzed 12 populations of B. ibitiguara, six inside Serra da Canastra National Park and six outside. Genetic diversity was much higher among the anurans living in the protected area than among those living outside the park. When the researchers correlated information on the degree of protection of the areas with the state of the vegetation, they found that these factors were less decisive for genetic diversity than the topography.

"The terrain is much more rugged outside the park, whereas inside it there's a large, very even plateau where the anurans can disperse more, find mates in more distant areas, and increase their genetic diversity," Nali said. "Outside the park, the rugged terrain and variable elevation appear to confine them to small areas."

The influence of these factors was evidenced by genetic tests. The researchers used a technique known as macrosatellite marker analysis to examine specific regions of the genome and found higher allele diversity in the populations living in the park. Allele diversity is one of the determinants of genetic integrity and adaptive potential.

In addition, the populations living outside the park displayed a greater loss of heterozygosity. If this loss, which is associated with declining genetic variability, recurs across several generations, it can eventually threaten the population's survival.

The study underscores the importance of topography as a factor to consider in conservation studies, as well as showing how the mere presence of a species in an area cannot ensure that it is not endangered.

"Molecular analysis enables us to find out if a population's genetic status is favorable," Nali said. "An area may have a large number of individuals, but DNA analysis may show that its genetic constitution is unfavorable, with few alleles and low heterozygosity. In practice, therefore, the population's effective size is small."

Although the study focused on only one species, he added, the findings can apply to others as well since the physical characteristics associated with dispersal are similar for other frogs and toads. More species need to be investigated to confirm the applicability of the findings.

The group noted that land cover nevertheless remains an important factor for conservation in the Cerrado, more than 50% of which has been converted into pasture or cropland, while less than 5% is protected by conservation units.

Deep neural networks, multilayered systems built to process images and other data through the use of mathematical modeling, are a cornerstone of artificial intelligence.

They are capable of seemingly sophisticated results, but they can also be fooled in ways that range from relatively harmless - misidentifying one animal as another - to potentially deadly if the network guiding a self-driving car misinterprets a stop sign as one indicating it is safe to proceed.

A philosopher with the University of Houston suggests in a paper published in Nature Machine Intelligence that common assumptions about the cause behind these supposed malfunctions may be mistaken, information that is crucial for evaluating the reliability of these networks.

As machine learning and other forms of artificial intelligence become more embedded in society, used in everything from automated teller machines to cybersecurity systems, Cameron Buckner, associate professor of philosophy at UH, said it is critical to understand the source of apparent failures caused by what researchers call "adversarial examples," when a deep neural network system misjudges images or other data when confronted with information outside the training inputs used to build the network. They're rare and are called "adversarial" because they are often created or discovered by another machine learning network - a sort of brinksmanship in the machine learning world between more sophisticated methods to create adversarial examples and more sophisticated methods to detect and avoid them.

"Some of these adversarial events could instead be artifacts, and we need to better know what they are in order to know how reliable these networks are," Buckner said.

In other words, the misfire could be caused by the interaction between what the network is asked to process and the actual patterns involved. That's not quite the same thing as being completely mistaken.

"Understanding the implications of adversarial examples requires exploring a third possibility: that at least some of these patterns are artifacts," Buckner wrote. " ... Thus, there are presently both costs in simply discarding these patterns and dangers in using them naively."

Adversarial events that cause these machine learning systems to make mistakes aren't necessarily caused by intentional malfeasance, but that's where the highest risk comes in.

"It means malicious actors could fool systems that rely on an otherwise reliable network," Buckner said. "That has security applications."

A security system based upon facial recognition technology could be hacked to allow a breach, for example, or decals could be placed on traffic signs that cause self-driving cars to misinterpret the sign, even though they appear harmless to the human observer.

Previous research has found that, counter to previous assumptions, there are some naturally occurring adversarial examples - times when a machine learning system misinterprets data through an unanticipated interaction rather than through an error in the data. They are rare and can be discovered only through the use of artificial intelligence.

But they are real, and Buckner said that suggests the need to rethink how researchers approach the anomalies, or artifacts.

These artifacts haven't been well understood; Buckner offers the analogy of a lens flare in a photograph - a phenomenon that isn't caused by a defect in the camera lens but is instead produced by the interaction of light with the camera.

The lens flare potentially offers useful information - the location of the sun, for example - if you know how to interpret it. That, he said, raises the question of whether adverse events in machine learning that are caused by an artifact also have useful information to offer.

Equally important, Buckner said, is that this new way of thinking about the way in which artifacts can affect deep neural networks suggests a misreading by the network shouldn't be automatically considered evidence that deep learning isn't valid.

"Some of these adversarial events could be artifacts," he said. "We have to know what these artifacts are so we can know how reliable the networks are."

While respiratory issues continue to be the most common symptom of a COVID-19 infection, new research indicates the disease could also be associated with hypercoagulability, or increased tendency of the blood to clot. In a new study published November 20, 2020 in the journal EClinical Medicine by The Lancet, researchers from UC San Diego Health found that blood clots led to an increased risk of death by 74 percent.

Led by Mahmoud Malas, MD, division chief of Vascular and Endovascular Surgery at UC San Diego Health, researchers reviewed 42 different studies involving more than 8,000 patients diagnosed with COVID-19. Using random models, the team produced summary rates and odds ratios of mortality in COVID-19 patients with thromboembolism, blood clots -- and compared them to patients without these conditions to determine what effect blood clots may have on risk of death.

"We began to notice a really unusual manifestation of venous and arterial thromboembolism in patients with COVID-19," said Malas. "In addition to higher instances of blood clots, the mortality for patients hospitalized for COVID-19 and with thromboembolism was much higher, compared to patients without clots. It's unusual because we have never seen anything like this with other respiratory infections."

Overall, 20 percent of the COVID-19 patients were found to have blood clots in the veins, and among patients in the intensive care unit, that statistic increased to 31 percent.

Blood clots in the vein, or deep vein thrombosis, can reach the lungs and develop into pulmonary embolism, resulting in higher risk of death. Blood clots in the arteries may lead to limb amputation if not treated surgically in a timely fashion.

In the study, Malas and colleagues performed a systemic review through meta-analysis, which is a statistical method that allowed researchers to combine multiple studies to produce a single comprehensive paper.

"The collective experience in the literature as captured in this meta-analysis study brings additional light on the importance of blood vessel clotting events in hospitalized patients with COVID-19," said Bryan Clary, MD, surgeon-in-chief at UC San Diego Health and co-author of the study. "While the frequency of these events is much higher than expected, our study likely underestimates the incidence of thromboembolism in the global population of patients with COVID-19, including non-hospitalized patients."

According to Malas, arterial blood clots developing in people with the flu is extremely rare, and the rate of clotting in patients with COVID-19 is higher than what is reported for other viral pandemics, including the H1N1 influenza of 2009.

Similar symptoms are shared between influenza and SARS-CoV-2, such as fever, cough, shortness of breath, or fatigue. Blood clotting can occur in patients hospitalized with the flu, but only in veins. For patients with COVID-19, blood clots can appear in either veins or arteries.

Typically, clotting in the arteries is caused by health factors, such as atrial fibrillation, high blood pressure, high cholesterol, diabetes, or lifestyle choices like smoking. Patients who are hospitalized for long periods of time are also more at risk for blood clots in the vein due to immobility.

Blood clots in the vein are treated or prevented with prescribed blood thinners. Proactively administering such medications to hospitalized patients can also help prevent clots from forming. Clinical trials are ongoing to determine how blood thinners can reduce the risk of clotting in patients with COVID-19.

"What we can learn from this paper is due diligence," said Malas. "We're still in the process of understanding the pathophysiology of COVID-19, so it's important to have a low index of suspicion when it comes to this infection to ensure we're doing all we can to mitigate the spread and prevent severe outcomes."

The spiral-shaped disc of stars and planets is being pulled, twisted and deformed with extreme violence by the gravitational force of a smaller galaxy - the Large Magellanic Cloud (LMC).

Scientists believe the LMC crossed the Milky Way's boundary around 700 million years ago - recent by cosmological standards - and due to its large dark matter content it strongly upset our galaxy's fabric and motion as it fell in.

The effects are still being witnessed today and should force a revision of how our galaxy evolved, astronomers say.

The LMC, now a satellite galaxy of the Milky Way, is visible as a faint cloud in the southern hemisphere's night skies - as observed by its namesake, the 16th century Portuguese explorer Ferdinand Magellan.

Previous research has revealed that the LMC, like the Milky Way, is surrounded by a halo of dark matter - elusive particles which surround galaxies and do not absorb or emit light but have dramatic gravitational effects on the movement of stars and gas in the universe.

Using a sophisticated statistical model that calculated the speed of the Milky Way's most distant stars, the University of Edinburgh team discovered how the LMC warped our galaxy's motion. The study, published in Nature Astronomy, was funded by UK Science and Technology Facilities Council (STFC).

The researchers found that the enormous attraction of the LMC's dark matter halo is pulling and twisting the Milky Way disc at 32 km/s or 115,200 kilometers per hour towards the constellation Pegasus.

To their surprise they also found that the Milky Way was not moving towards the LMC's current location, as previously thought, but towards a point in its past trajectory.

They believe this is because the LMC, powered by its massive gravitational force, is moving away from the Milky Way at the even faster speed of 370 km/s, around 1.3 million kilometres per hour.

Astronomers say it is as if the Milky Way is trying hard to hit a fast moving target, but not aiming very well.

This discovery will help scientists develop new modelling techniques that capture the strong dynamic interplay between the two galaxies.

Astronomers now intend to find out the direction from which the LMC first fell in to the Milky Way and the exact time it happened. This will reveal the amount and distribution of dark matter in the Milky Way and the LMC with unprecedented detail.

Dr Michael Petersen, lead author and Postdoctoral Research Associate, School of Physics and Astronomy, said:

"Our findings beg for a new generation of Milky Way models, to describe the evolution of our galaxy.

"We were able to show that stars at incredibly large distances, up to 300,000 light-years away, retain a memory of the Milky Way structure before the LMC fell in, and form a backdrop against which we measured the stellar disc flying through space, pulled by the gravitational force of the LMC."

Professor Jorge Peñarrubia, Personal Chair of Gravitational Dynamics, School of Physics and Astronomy, said:

"This discovery definitely breaks the spell that our galaxy is in some sort of equilibrium state. Actually, the recent infall of the LMC is causing violent perturbations onto the Milky Way.

"Understanding these may give us an unparalleled view on the distribution of dark matter in both galaxies."

Changes in climate can increase infectious disease risk in animals, researchers found -- with the possibility that these diseases could spread to humans, they warn.

The study, conducted by scientists at the University of Notre Dame, University of South Florida and University of Wisconsin-Madison, supports a phenomenon known as "thermal mismatch hypothesis," which is the idea that the greatest risk for infectious disease in cold climate-adapted animals - such as polar bears - occurs as temperatures rise, while the risk for animals living in warmer climates occurs as temperatures fall.

The hypothesis proposes that smaller organisms like pathogens function across a wider range of temperatures than larger organisms, such as hosts or animals.

"Understanding how the spread, severity and distribution of animal infectious diseases could change in the future has reached a new level of importance as a result of the global pandemic caused by SARS-CoV-2, a pathogen which appears to have originated from wildlife," said Jason Rohr, co-author of the paper published in Science and the Ludmilla F., Stephen J. and Robert T. Galla College Professor and chair of the Department of Biological Sciences at Notre Dame. "Given that the majority of emerging infectious disease events have a wildlife origin, this is yet another reason to implement mitigation strategies to reduce climate change."

The research team collected data from more than 7,000 surveys of different animal host-parasite systems across all seven continents to provide a diverse representation of animals and their pathogens in both aquatic and terrestrial environments. The study showed that pathogens found at warm locations outperform their animal hosts during cool weather as warm-adapted animals perform poorly. Similarly, pathogens found at cool locations thrive at warm temperatures, while cold-adapted animals are less tolerant of the heat.

Researchers also collected historical temperature and precipitation records at the time and location of each survey, and long-term climate data for each location to understand how temperature affected animal disease risk in different climates, and how these patterns varied depending on traits of animals and pathogens. The study also revealed that cold-blooded animals tended to offer stronger support for the thermal mismatch hypothesis than warm-blooded animals.

Next, they coupled their models to global climate change projections to predict where the risk of animal infectious diseases might change the most. The analysis suggests that global warming will likely shift infectious disease away from the equator, with decreases of animal infectious diseases in the lowland tropics and increases in the highland tropics, temperate and cooler regions of the planet.

"When each pathogen species was given equal weight, the predicted increases in infectious disease at cooler locations outweighed the decreases at warmer locations, potentially suggesting a net increase in animal infectious diseases with climate change," said Rohr, who is also an affiliated member of the Notre Dame Environmental Change Initiative and the Eck Institute for Global Health.

As for next steps, Rohr says the researchers aim to evaluate whether similar patterns exist for human and plant diseases, the latter of which could have implications for food security.

The insulation around nerve cell components in our corneas have unique properties, and little is known about them. But UConn School of Medicine neuroscience professor Royce Mohan believes his lab is on the verge of uncovering a path to better understanding that ultimately could lead to several vision-preserving advances.

Learning more about the cellular environment in the cornea, including what are known as glial cells that wrap around the nerve cell's axons, could have implications for healing after surgeries and corneal transplants, as well as nerve regeneration, not just in the eyes but potentially in other systems of the body.

In a paper published in the Journal of Neuroscience Research, lead author Paola Bargagna-Mohan, assistant professor of neuroscience, details a method of characterizing every cell in the cornea using an approach known as single-cell RNA sequence analysis to answer questions about the cornea's healing process. The study was done through a collaboration with Paul Robson, associate professor and director of single cell biology at The Jackson Laboratory for Genomic Medicine (JAX), which houses state-of-the art facilities for this type of research.

"Going in we knew there would be challenges," says Bargagna-Mohan, a recipient of a UConn Research Excellence Program award. "After several attempts, we were finally able to optimize our experimental approach to our advantage. I was extremely excited to get the funding from the UConn Vice President for Research at this critical time to drive this project."

A material known as myelin insulates axons of nerve fibers and enhances transmission of impulses among neurons. But nature has made the cornea an exception. Myelin in the cornea would interfere with light transmission. Therefore, the non-myelinating corneal Schwann cells, aptly called so because they do not produce myelin, are adapted to maintain corneal transparency, optimizing the focus of light on the retina, a crucial element of our vision.

"This class of glial cells, better known as Schwann cells, have never before been isolated and characterized," Mohan says. "So this is the first big step we took to help this field move forward in trying to repair the nerves of the cornea after surgeries, and also to understand corneal pain."The Mohan Lab's single-cell RNA sequence analysis enables access to these cells to study them to an unprecedented extent.

"All the genes that are expressed in each of the cells can be characterized," Mohan says. "But not all cells are equal, even within a certain cell type, cells are never equal. And so cells that are sitting on the peripheral side of the cornea could be very different from the cells in the middle of the cornea. And by characterizing them, we can actually interpret that information to know what genes are expressed at the corner of the eye versus the one in the middle of the eye."

Mohan, who holds the John A. and Florence Mattern Solomon Endowed Chair in Vision Biology and Eye Research, says this method already has uncovered unique genes that are not expressed in Schwann cells of other tissues, which may eventually solve the mystery of how corneal Schwann cells function without interfering with light transmission.

He has a grant application pending with the National Eye Institute to continue his study of these unique cells and their role in nerve repair and sensory function.

When it comes to corneal transplants - relatively common procedures throughout the world that would be even more common if there were enough donor corneas available to meet demand - one of the associated risks is the recipient doesn't necessarily regain full sensory function of the eye. The corneal nerves' hypersensitivity to foreign bodies is an evolutionary mechanism of injury prevention.

"If you don't get the sensory function, you may accidentally touch your eye and injure your cornea, and that could be very traumatic for someone who's just had a corneal transplant," Mohan says, noting that donor corneas generally can be preserved for several days. "We would be very interested to know how the Schwann cells survive in the existing donor tissue. Is there something we could do to enhance their survival into even higher levels? And, as well, after the operation is done?"

Sensory function is also a consideration for those who undergo laser-assisted in-situ keratomileusis. Commonly known as LASIK, it's a vision correction procedure in which the corneal axons are cut and the Schwann cells are injured.

"They also get some side effects like burning sensation, gritty feeling, and the exact molecular mechanism of what causes it and how to help the tissue heal better is not known," Mohan says.

Another condition that could benefit from a better understanding of Schwann cells' behavior is dry eye. While temporary dry eye is common, for some it can be a chronic condition in which the corneal nerves feel irritated.

"Therapeutics are discovered by knowing which genes have to be activated or which ones have gone berserk that need to be subdued," Mohan says. "What are these genes that are present in the Schwann cell doing when the cornea is injured? And from there, you ask the question, could you support nerve injury healing by either activating a gene or inhibiting something that has gone bad?"

Better understanding of the Schwann cell genes and the proteins they encode could lead to, for example, a topical drop that could support wound healing by inhibiting these targeted proteins.

Physicians and scientists are constantly on the lookout for new disease genes that can help them understand why patients have undiagnosed medical problems. Often the first clues come from genetic testing that reveals a change or mutation in a gene that they see in a child but not their parents. This is exactly what led to a new study published today in the American Journal of Human Genetics.

A multidisciplinary group including researchers at Baylor College of Medicine, Dana-Farber Cancer Institute and other institutions identified the BICRA gene as a new disease gene involved in a neurodevelopmental disorder and found evidence that BICRA functions in neural development in humans and flies. The findings provide answers to families and reveal to physicians and scientists new insights into how BICRA works, allowing for the development of individualized medical plans for patients in the future.

BICRA mutations are associated with human neurodevelopmental disorders

The first patient the researchers identified presented with undiagnosed neurological defects, including neurodevelopmental delay and other features similar, but not identical, to those observed in Coffin-Siris syndrome patients. Genetic studies revealed that the patient carried a mutation in the BICRA gene.

"With the help of the online gene-matching tool GeneMatcher, the researchers found 11 more patients with similar conditions carrying BICRA gene variants," said co-corresponding author, Dr. Hugo Bellen, Distinguished Service Professor of Molecular and Human Genetics at Baylor and member of the Jan and Dan Neurological Research Institute at Texas Children's Hospital.

In all 12 cases, the BICRA mutations were new in the patients; they were not inherited from their parents. Some of the mutations led to loss of function of the BICRA protein.

"Further analyses showed that BICRA mutations can cause disease in a dominant fashion - a mutation of only one of the two copies of the BICRA gene in the genome is sufficient to cause disease," said co-first author Dr. Scott Barish, postdoctoral associate in the Bellen lab.

This work was performed in collaboration with the lab of Dr. Cigall Kadoch at Dana-Farber Cancer Institute and Harvard Medical School.

Zebrafish and fruit flies connect BICRA to neural development

To investigate the potential connection of the BICRA gene with the features observed in the patients, the researchers turned to zebrafish and fruit flies.

"We conducted the work with zebrafish in collaboration with the Undiagnosed Disease Network Zebrafish Core run by Dr. Monte Westerfield and Dr. John Postethwait at the University of Oregon. They made a mutation in the zebrafish version of BICRA that mimicked the mutation in one of the patients," Barish said. "The zebrafish carrying the mutation showed a craniofacial defect that was similar to the facial features observed in the patients."

"In fruit flies, we showed that BICRA is expressed in the nuclei of neurons and glia, both in the larval and adult brain," said Bellen, who also is an investigator at the Howard Hughes Medical Institute at Baylor.

"Identifying BICRA as a disease gene may increase the speed at which other disease genes are identified," said co-corresponding author Dr. Daryl Scott, associate professor of molecular and human genetics at Baylor.

VIRTUAL MEETING (CST), November 22, 2020 -- The rapid spread of COVID-19 overwhelmed hospitals that were unable to contend with the increasing number of patients, many requiring ventilators and other critical care. Such conditions can put medical workers at risk. Now researchers are studying methods to increase hospital safety and efficacy during the pandemic.

A shortage of life-saving ventilators, which typically cost around $30,000 each, hit hospitals particularly hard.

"By building a simple and cheap ventilator, we can help alleviate this burden for the medical staff," said Mohamed Amine Abassi, a PhD student in fluid mechanics.

Based on a prototype designed by his advisor, engineering professor Xiaofeng Liu, Abassi spearheaded an effort with colleagues from San Diego State University and the University of California San Diego to build such a device from readily available parts--plastic tubing, pressure valves, humidifier--and an air supply. Then they tested it.

Preliminary results shared at the 73rd Annual Meeting of the American Physical Society's Division of Fluid Dynamics suggest the ventilator meets essential requirements set by the Food and Drug Administration. It is fully controllable on three parameters--air pressure, inspiration time, and Positive End Expiratory Pressure (PEEP)--with plans for more controls in the works.

Abassi and Liu foresee the ventilators assisting not just overwhelmed hospitals in the United States but also in developing countries and rural areas with limited medical infrastructure. "If they can build it at home, they can use it," said Abassi. "And you can build many of these ventilators in a very short time."

Patients on ventilators who have some pulmonary conditions relevant to COVID-19 with underlying chronic lung diseases will often receive drugs like albuterol through an endotracheal tube. This treatment relaxes the bronchial muscles and improves airflow to the constricted lung airways.

A group from Lehigh University and the University of Arkansas for Medical Sciences sought the most effective methods for administering albuterol via ventilator.

Ariel Berlinski and his group conducted aerosol characterization experiments at the University of Arkansas. Rahul Rajendran at Lehigh used the results to investigate drug delivery through computations.

"The research objective was to evaluate the efficiency of drug delivery when the nebulizer type and its placement were varied in the ventilator circuit," said Arindam Banerjee, a member of the group and a Lehigh professor of mechanical engineering and mechanics.

The researchers found that a vibrating mesh (rather than a jet) nebulizer placed on the dry side of the humidifier delivers the highest dose to the lung. Administering albuterol through intubation works most effectively for smaller particles, while oral administration is more efficient for larger particles.

"Our results are vital for mechanical ventilator based treatment," said Banerjee.

Even in optimal circumstances, healthcare workers still risk contracting COVID-19. A new respiratory apparatus could reduce exhaled aerosols, which are known to transmit the virus that causes the disease.

Researchers from Liberty University and Vapotherm wondered how common respiratory treatments would affect aerosol emissions. So they decided to test a proposed design for a PVC face mask connected to suction, adding a high-velocity nasal insufflation cannula--the kind of tubed device that delivers oxygen to the nose.

Then, with input from medical experts, they modeled a hospital room with two patients and four caregivers using highly sophisticated computational techniques. According to their model, when patients wear the new apparatus, fewer particles reach the healthcare workers.

"It represents an inexpensive way to reduce the spread of airborne contagion using supplies commonly found in hospital rooms already," said engineering PhD candidate Reid Prichard. "This will remain an important tool even after the pandemic is over."

Another group from the University of South Florida, led by mechanical engineering PhD student Anthony Perez, is investigating what happens to any aerosol contaminants that patients do emit into a hospital isolation room--and how quickly the contaminants leave the room.

"As many hospitals are reaching capacity, ensuring a hospital room is safe to enter after an aerosol-generating procedure--or after the removal of a previous patient so hygiene workers can prepare the room--requires significant down time," said Perez.

According to the researchers, the Centers for Disease Control and Prevention ventilation recommendations assume pathogen-containing aerosols are perfectly mixed within a room. Using numerical simulations, the group finds that imperfect mixing conditions significantly affect how quickly ventilation removes pathogens from a room.

"It is both surprising and somewhat concerning that the standard for air sanitization is based on what many would consider a back-of-an-envelope calculation," said Perez.

The simulations suggest aerosol contaminants can linger in "dead zones" for around 10 minutes in a typical hospital isolation room. Meanwhile, "short circuits" expel some packets of contaminants quickly before they can disperse.

"Our research illustrates the need for a more accurate, yet inexpensive, framework for the prediction of aerosol concentrations in an arbitrary hospital room, especially in assessing the level of exposure of healthcare workers," said Perez.

VIRTUAL MEETING (CST), November 22, 2020 -- Mechanical engineer Roberto Zenit spent the summer of 2019 trying to solve a problem that now plagues science departments around the world: How can hands-on fluid dynamics experiments, usually carried out in well-stocked lab rooms, be moved off campus? Since the pandemic hit, leading researchers like Zenit have found creative ways for students to explore flow at home.

Zenit's answer, ultimately, came down to pancakes. He teaches a fluid dynamics lab class at Brown University, and one experiment requires students to measure viscosity, which is often done by measuring how quickly small spheres fall through thick liquids and settle at the bottom. But Zenit realized he didn't have to do it that way. The kitchen is rich with viscous fluids, and all he had to do was pick one.

Why not pancake batter?

This fall, students in his class, wherever they were sequestered, had to mix up pancake batter, pour it on a horizontal surface, and measure how quickly the radius expanded. "By measuring the rate at which this blob grows in time you can back-calculate the viscosity," said Zenit.

Zenit described the experiment during a mini-symposium on kitchen flows at the 73rd Annual Meeting of the American Physical Society's Division of Fluid Dynamics. In addition to his viscosity-through-pancakes project, the symposium included new research on how fluids mix with each other and how they incorporate solid particles (as in batter or dough). Researchers from the University of Cambridge described new findings on hydraulic jumps--those eerily smooth circles of water, surrounded by turbulence, that form directly beneath a running kitchen faucet.

Chemical engineer Endre Mossige, a postdoctoral researcher at Stanford University, organized the symposium. "Kitchen flow experiments are so easy to do," he said. "You need so little equipment to extract such useful information about fluid dynamics."

The kitchen is a natural place to look for inspiration, said Jan Vermant, an engineer at ETH Zurich. "In the kitchen we do a lot with high-interface materials," he said. "You have to mix fluids and air and make emulsions, and work with bubbles. This is a fundamental problem of food projects, and one known by chefs all over the world."

Vermant reported on his group's recent work, which tackled a beer problem by turning it into a fluid dynamics problem. He studies thin films, and in recent research he's been studying the stability of foam in beers and breads. Beermakers, he said, check on the fermentation progress of new brews by looking at the stability of foam. But, he said, the process is very "hand-wavy." When he began looking at beer brewing through the lens of fluid dynamics, he found a rich research environment.

Beer bubbles contain a rich variety of environments: capillary flows, soap films, and protein aggregation. "Basically, they have all the mechanisms one can design as an engineer," he said. His group found, to their surprise, that even though most beers have foam, different beers have different mechanisms behind those foams. Some foams act like soap films; others develop robust protein networks at the surface.

"They each highlight different aspects of the problem nicely," said Vermant. In subsequent work, his group took a similarly close look at interfacial phenomena in breads--and similarly found a variety of behaviors. "They have this rich diversity of mechanisms to stabilize foam structures," he said.

Vermant said the work isn't just about beer and bread; it may also serve as inspiration for new materials. "We can mimic those systems and might make foams using the same principles as beer foams," he said, which could be useful for applications ranging from spray insulation to protective foams for crops.

At Brown, Zenit said not every student successfully completed the experiment. "Some of them took my advice too literally, and did it in a hot pan," he said. Cooking the pancake changed the viscosity--freezing the batter in place--which meant the students don't have usable data. (But they did have breakfast.)

He said turning to pancakes during the pandemic has opened his eyes to different ways to teach fundamental ideas like viscosity. "In the regular experiments, you drop this sphere in a container and measure it," he said. The fluid, he says, is reduced to its measurement. With batter, the student experiences the concept. "With the pancakes, you get to feel the viscosity."

VIRTUAL MEETING (CST), November 22, 2020 --They burst out of toilet bubbles, swim across drinking water, spread through coughs. Tiny infectious microbes--from the virus that causes COVID-19 to waterborne bacteria--kill millions of people around the world each year. Now engineers are studying how zinc oxide surfaces and natural hydrodynamic churning have the power to kill pathogens first.

"Bacterial contamination of common surfaces and of drinking water have been traditionally the main infection routes for transmission of serious diseases, often leading to mortality," said Abinash Tripathy, a researcher in mechanical and process engineering at ETH Zurich. "Our goal was to design a surface that can address both issues."

His group submerged clean zinc in hot water for 24 hours, which formed a zinc oxide surface covered in sharp nanoneedles. Then they introduced E. coli bacteria.

The surface kills almost all bacteria cultured on top of it very efficiently. And the biggest surprise? When sitting in contaminated water, the surface kills all waterborne E. coli within three hours--even bacteria it didn't touch.

This water disinfection at a distance works because the process generates a reactive oxygen species, which damages the cell walls of bacteria. The group from ETH Zurich, IIT Ropar India, and Empa, Switzerland, presented their initial findings at the 73rd Annual Meeting of the American Physical Society's Division of Fluid Dynamics.

In Southeast Asian and African countries where clean drinking water is scarce, current solar water disinfection methods take up to 48 hours and require a minimum intensity of sunlight. The new zinc oxide surface speeds up the disinfection process and does not need light.

"This surface can be used to disinfect water in remote areas at a very low cost," said Tripathy. "The fabrication technique is environmentally friendly, simple, and economical."

Surface and waterborne pathogens aren't the only killers. As the COVID-19 pandemic has reinforced, airborne viruses and bacteria pose a serious global challenge for disinfection.

The very droplets that carry pathogens through the air can play a role in destroying them. In the microseconds that droplets take to form, their fluids rearrange rapidly--stressing the microbes within.

"Think of a bucket with a fish in it. One imagines that if you start churning the fluid in the bucket too quickly, the fish won't be very happy," said Oliver McRae, a mechanical engineer. "It's a similar kind of thing--albeit on a much, much smaller scale--when you have, say, a pathogen in a droplet. Eventually the fluid's going to agitate too much for that bacteria or virus to survive."

McRae and a team from Boston University and the Centers for Disease Control and Prevention were studying how hydrodynamic agitation works when environmental bubbles produce droplets. After the onset of the pandemic, they started modeling droplets similar to those produced by the lungs and respiratory tract.

Using computational fluid dynamics, the team predicted how agitation works during aerosol formation. They discovered that stressors are very sensitive to droplet size. If the droplet shrinks or grows by one order of magnitude, the stressors change by two-and-a-half orders of magnitude.

The research could help explain why pathogens survive in some droplets and not others.

"Our focus has been on quantifying what the stressors are in these droplets," said McRae. "Hopefully this will be used in the future as part of a larger model to predict aerosol-based disease transmission."

Engineering a spaceship is as difficult as it sounds. Modeling plays a large role in the time and effort it takes to create spaceships and other complex engineering systems. It requires extensive physics calculations, sifting through a multitude of different models and tribal knowledge to determine singular parts of a system's design.

Dr. Zohaib Hasnain's research shows that data-driven techniques used in autonomous systems hold the potential to solve these complex modeling problems more accurately and efficiently. Applying high-functioning artificial intelligence to physics-based processes, he aims to "automate" modeling, reducing the time it takes to produce solutions and cutting production costs.

"If I am trying to undertake something along the lines of, say, designing a pencil, there's a process involved in designing that pencil," Hasnain said. "I have a certain set of steps that I would undertake given the knowledge that I have available to me based on what others have done in the past. Anything that can be described by a process or an algorithm on paper can be automated and analyzed in the context of an autonomous system."

An assistant professor in the J. Mike Walker '66 Department of Mechanical Engineering, Hasnain realized while working in the aerospace industry, the delay in projects due to modeling efforts. While conducting traditional modeling processes, scientists and researchers must create various models, many of which require testing. Additionally, filing through individual models takes far too long to produce answers. An example of a traditional modeling for space systems is computer fluid dynamics, or CFD, which uses numerical analysis to determine solutions, resulting in hefty costs computationally, and in human labor for verification.

"I always thought that there was work to be cut out because there are autonomous systems and machines that seemed capable of handling the bottleneck that is modeling," Hasnain said. "My research is a first step in understanding how and when data-driven techniques are beneficial, with the ultimate goal of taking a process that consumes months or weeks to solve, and producing a solution in hours or days."

Hasnain, accompanied by assistant professor Dr. Vinayak R. Krishnamurthy and graduate research assistant Kaustubh Tangsali, conducted a study to understand how commonly used machine-learning architectures such as convolutional neural networks (CNN) and physics informed neural networks (PINN) fare when applied to the problem of fluidic prediction. The data-driven approach uses a pre-existing modeling database to train a model over carefully controlled variations in fundamental physics of the fluid, as well as geometries over which the fluid flows. The model is then used to make a prediction. Their research found that both CNN and PINN have the potential to optimize modeling processes if targeting very specific aspects of the solution process. They are now working on a hybrid learning approach to achieve their final goal of speeding up the design process.

"We're looking at a different set of tools that will replace the old tools," said Hasnain. "We are trying to understand how these new tools behave in the context of applications traditionally governed by first principles-based solution techniques."

The researchers published their findings in the Journal of Mechanical Design. Their article, "Generalizability of Convolutional Encoder-Decoder Networks for Aerodynamic Flow-field Prediction Across Geometric and Physical-Fluidic Variations," focuses on understanding dimensional tools that have the potential of replacing modeling tools that are the current industry standard.

From the research results, Hasnain hopes to build an autonomous infrastructure that pulls from a collection of data to produce modeling solutions through hybrid machine-learning architectures. Through algorithms and pre-existing data, the infrastructure will be a modeling process that can be applied to various systems in real-life applications. Eventually, he plans to share this infrastructure for widespread, free usage.

"I would like this infrastructure to be a community initiative that's offered free to everyone," Hasnain said. "Perhaps more importantly, because it can produce near on-demand solutions as opposed to the current modeling state-of-the-art, which is extremely time-consuming."

The infrastructure is in its early stages of development. Hasnain and his fellow researchers are working to produce a prototype in the near future.