Culture

When someone is suspected of criminal activity, one of the most important questions they are asked is if they have a credible alibi. Playing back past events in our minds, however, is not like playing back a video recording. Recollections of locations, dates, and companions can become muddled with the passage of time. If a suspect's memories are out of line with documented events, a once-plausible alibi can crumble and may be seen as evidence of guilt.

To put people's memories of past whereabouts to the test, a team of researchers tracked the locations of 51 volunteers for one month and found that their recollections were wrong approximately 36% of the time.

"This is the first study to examine memory for where an event happened," said Simon J. Dennis, director of the Complex Human Data Hub at the University of Melbourne's School of Psychological Sciences and lead author of the study, which was published in the journal Psychological Science. "We were able to use experience-sampling methods to actually examine people's memories and analyze what is affecting memory error in their everyday life."

In the study, an app on the participants' smartphones continuously (and securely) recorded their locations and surroundings via GPS. The app also made sound recordings of the environment every 10 minutes. Participants had the freedom to turn off the app or to delete events--a mechanism designed to protect privacy.

At the end of the month, the participants received a memory test in which they were given a time and date and then asked to select one of four markers on Google Maps to show where they had been at that moment.

The results revealed that participants tended to confuse days across weeks. They also often confused weeks in general and hours across days. The participants had the poorest recall when memories of one event become entwined with memories of a similar experience, such as filling up a car with gas at a different location of the same gas-station chain.

Additionally, the researchers found that people tended to confuse places they had visited at similar times or locations, such as multiple bars visited in one evening. People also made mistakes--although less frequently--when events involved similar sounds or movement patterns, such as when they had walked through town on different days while listening to their favorite music.

"This has implications for alibi generation, as jurors tend to assume that a suspect who is wrong is lying," said Dennis. "These results can alert investigators to the questions they should ask in order to catch the memory errors that suspects are likely to make."

The protein actin is ubiquitous and essential for life. In mammals, every cell expresses two of its forms, beta-actin and gamma-nonmuscle-actin. Despite having distinct roles, the two forms are nearly identical, sharing 99% of their amino acid sequence.

Research by Anna Kashina of Penn's School of Veterinary Medicine and colleagues has shown that, contrary to scientific dogma, it's not the slight differences in amino acid sequence that govern these proteins' discrete functions in the cell. Rather, their nucleotide sequences--the "letters" that make up their DNA coding sequence, which differ by roughly 13% between the two forms--are responsible for their individual roles in organisms' survival and cell migration.

And in a new study the researchers offer an explanation for why: Beta-actin mRNA is translated into protein faster than gamma-actin. Both forms help cells move, but beta-actin's faster rate seems to cause cell to affix to a substrate more strongly, slowing down cell movement.

"On a global, philosophical level, this expands our understanding of genetic code," says Kashina, a professor of biochemistry at Penn Vet and the senior author on the study, which was published in the journal eLife. "We used to believe that the role of the nucleotides was to encode amino acids, but now we see that, actually, proteins with the same amino acid sequence have different translation rates, and that makes a difference in their function."

Kashina uses the term "silent code" to refer to the influence of these nucleotide differences. In earlier work, her team showed that, in mice, editing the amino acid sequence but maintaining the silent nucleotide code could cause gamma-actin to behave like beta-actin in the body. Normally, mice lacking beta-actin would die before birth, but the researchers showed that performing gene editing to the beta-actin gene so it had the same amino acid sequence as gamma-actin kept mice alive thanks to the nucleotide differences.

A finding from an earlier paper, also published in eLife, motivated the new work. In that earlier study the researchers found that beta-actin RNA had a much higher density of ribosomes than that of gamma-actin. Ribosomes are crucial to the synthesis of protein from RNA, leading the scientists to hypothesize that this difference in protein translation rate could be responsible for the different functions between gamma and beta-actin.

To test their idea, they used cell lines to express only the coding sections of beta- and gamma-actin in mouse cells, as well as their edited versions: the beta-actin that had been edited to have the same amino acid sequence as gamma-actin and vice versa for gamma-actin.

When put to the test in a wound-healing experiment, the researchers found that the nucleotide sequence was paramount in determining the speed at which actin facilitated cell movement. Cells expressing only the typical beta-actin migrated at typical rates, but gamma-actin-expressing cells moved twice as fast. The cells containing edited versions of actin proved that this difference is nucleotide-sequence dependent. Beta-actin edited to have the amino acid sequence of gamma moved like gamma-actin-expressing cells, and those with gamma-actin edited to have the amino acid sequence of beta-actin moved at the rate of beta-actin-expressing cells.

These results surprised the researchers since they expected the higher density of ribosomes in beta-actin mRNA could support faster translation and thus faster movement. And, indeed, when they measured the rate of translation on a single-molecule level, they found that translation occurs about twice as fast for beta-actin as for gamma-actin.

"We expected that faster translation would mean faster movement," Kashina says, "and that's not what we found. It took us a long time to explain why."

What they eventually discovered, was that although the subunits of beta-actin could be supplied faster than those of gamma-actin, that speed worked to the detriment of cell migration speed.

"We found that the faster you supply it, the better the cell attaches to the substrate," Kashina says. "It creates proper traction, which is essential for normal migration. And if you don't supply it fast enough the cell can't attach properly and starts sliding. So that explained our seemingly counterintuitive results."

Kashina and colleagues plan to continue to probe the role of the nucleotide sequence, including why evolutionary forces led to the production of such similar forms of actin and whether the "silent code" is at work in other proteins.

"We think this is part of a bigger story," Kashina says. "We believe actins are not the only proteins that behave this way. There are a number of protein families in the human genome that contain highly similar proteins encoded by different genes. This silent code could be at play in those families as well."

Researchers have produced vaccine-like immune responses to a dangerous bacterium by colonizing 26 healthy volunteers with a related, but harmless, commensal bacterial species. The first-in-human, controlled infection study showed the strategy was safe, as no side effects were reported and the volunteers didn't transmit the commensal bacteria to bedroom-sharers over the 90-day study. Neisseria lactamica is a member of the microbiome that usually resides in the upper airways of children but can also safely colonize the airways of adults. Some researchers theorize that these bacteria could serve as vehicles for immunization, by delivering molecules from more dangerous bacteria to the respiratory system. But commensal bacteria are usually tolerated by the immune system, and it has been difficult to genetically engineer N. lactamica to deliver bacterial antigens. However, Jay Laver and colleagues successfully engineered N. lactamica to express Neisseria Adhesin A as a vaccine antigen. Neisseria Adhesin A is a protein from a related species named Neisseria meningitidis, which can cause meningitis. The team intranasally inoculated 26 adult volunteers with the engineered N. lactamica, which persisted in 86% of the subjects for 90 days. The colonization produced immune responses against Neisseria Adhesin A from both plasma cells and memory B cells within 28 days, and the B cells persisted for at least 90 days after colonization. There were no adverse effects in the volunteers, none of them transmitted the N. lactamica to any contacts who shared the same bed, and the bacteria could be eradicated after 90 days with antibiotics. Laver et al. conclude their delivery system could be used in other applications, such as manipulating the respiratory microbiome or inducing immune tolerance to allergens.

The measures taken during the COVID-19 pandemic limited the access of citizens to natural objects. It is still unexplored, what consequences this had for the residents and what conclusions should be drawn for more effective urban planning. RUDN University scientists with colleagues from Australia and Germany studied how the restrictions associated with COVID-19 affected the use of blue and green infrastructure by citizens in Moscow (Russia) and Perth (Australia), and what consequences this had for their health. In the article "Human Dimensions of Urban Blue and Green Infrastructure during a Pandemic. The Case Study of Moscow (Russia) and Perth (Australia)", published in Sustainability, they presented the results of a study on the importance of green and blue infrastructure for the physical and mental health of the citizens. The results give a basis for developing a balanced strategy for landscape design and urban space planning based on the development of green infrastructure that allows effectively maintaining the well-being and health of citizens, especially during a crisis such as that caused by COVID-19.

The significant challenges caused by the COVID-19 pandemic emphasized that the concept and features of the modern environmentally balanced cities development should consider not only the implementation of economic and social urban strategies, but also functional urban design, related to the urban spaces planning and the development of green infrastructure. Using the results of a web questionnaire survey conducted in May-July 2020 in Moscow (Russia) and Perth (Australia), the article presents an analysis of the significance of contact with nature and various objects of green and blue infrastructure of cities, as well as their changes during and after the COVID-19 restrictions. In order to identify the way people relate to green and blue urban objects and what role they play in providing a comfortable environment, as well as how the general restrictions associated with COVID-19 affected the nature of their interaction with natural infrastructure, they developed a questionnaire of 25 questions, which became the basis of an online study.

216 Muscovites and 110 residents of Perth took part in the survey. The results were analysed statistically. The survey data collected during the isolation period provided information about access to green and blue urban spaces, inequalities in access, as well as changes in the development of urban green infrastructure that are necessary from the respondents' point of view. Scientists analysed the social aspects of citizens' perception of natural objects of the urban and emphasized the importance of contact with nature for maintaining physical and mental health, socio-cultural identification, and socialization (the importance of green and blue objects as social and multicultural spaces). In both cities, measures taken during the COVID-19 restricted people's access to green spaces and water bodies, which negatively affected their mental and physical health and well-being. The survey results showed that the quality, functionality, and location of open natural spaces illustrate the inequality in their distribution and accessibility to the population. In some cases, it was noted that residents of certain areas of cities suffered from limited access to natural objects.

"The COVID-19 circumstances, when access to natural urban facilities was limited for millions of people around the world, highlighted that in extraordinary situations, urban nature can play an essential role in contributing to human well-being and shaping human-nature relationships. Studies have confirmed that public green and blue spaces play a key role not only in maintaining a comfortable environmental situation, but also in restoring mental and physical health during and after an emergency. owever, the issues of how these differential impacts could influence future urban development that will make the cities sustainable and resilient towards addressing challenges, such as those associated with the COVID-19 pandemic and climate change, need to be better understood. In this sense, the comparison of experiences from cities in different countries could be very valuable," says Diana Dushkova, PhD, associate professor at the RUDN University and senior researcher at The Helmholtz-Centre for Environmental Research

The researchers compared Moscow and Perth as two cities with different approaches to the organization of natural objects and landscaping strategies. In Moscow, most of the green areas and water bodies are open to public. In Perth, more than half of the city's green infrastructure facilities are located on private territories. It turned out that residents of Perth and Moscow consider access to nature equally important, even though cities differ in size, climatic conditions, and planning approaches. In both cities, more than 60% of residents said that the opportunity of contact with nature is important or extremely important for physical and mental health. Among the main values of contact with nature, citizens noted fresh air (82.9% in Perth and 51.6% in Moscow), a sense of unity with nature (89.5% in Perth and 71.2% in Moscow), the scenic beauty (89.5% in Perth and 71.2% in Moscow). The differences in the responses of residents of the two cities are noticeable in questions that relate to the specifics of the restrictions adopted in the pandemic. Changes in visiting natural spaces before and during the pandemic are especially noticeable in Moscow, where strict restrictions were introduced. 56.9% of Muscovites visited green and water zones less often. In Perth, parks and other natural recreation areas remained open, and 59.4% of residents did not visit urban natural spaces less often, and 26.7% even began to do it even more often.

"Our results showed that urban residents are aware of the value of green and blue spaces and emphasize their important role in maintaining health and well-being, especially during the COVID-19 pandemic. This is new convincing evidence that the issues of accessibility of natural objects and their balanced distribution in urban areas should be considered in the development strategy of a modern city, which considers the new requirements of the modern world in ensuring safe and comfortable life and maintaining human health. In addition, it indicates that access to nature and public rights to use green spaces determine the overall resilience of cities to the crisis. The obtained results obtained provide the basis for further research in the development of modern approaches to landscape design and planning of urban green and water zones and allow us to see how effectively they can ensure and maintain the well-being and health of citizens, especially during a crisis such as that caused by COVID --19," says Diana Dushkova.

Astronomers have designed and trained a computer program which can classify tens of thousands of galaxies in just a few seconds, a task that usually takes months to accomplish.

In research published today, astrophysicists from Australia have used machine learning to speed up a process that is often done manually by astronomers and citizen scientists around the world.

"Galaxies come in different shapes and sizes" said lead author Mitchell Cavanagh, a PhD candidate based at The University of Western Australia node of the International Centre for Radio Astronomy Research (ICRAR).

"Classifying the shapes of galaxies is an important step in understanding their formation and evolution, and can even shed light on the nature of the Universe itself."

Mr Cavanagh said that with larger surveys of the sky happening all the time, astronomers are collecting too many galaxies to look at and classify on their own.

"We're talking several million galaxies over the next few years. Sometimes citizen scientists are recruited to help classify galaxy shapes in projects like Galaxy Zoo, but this still takes time."

This is where convolutional neural networks, or CNNs, come in. In today's high-tech world, these kinds of computer programs are everywhere, used in everything from medical imaging, stock markets and data analytics, to how Netflix generates recommendations based on your viewing history.

In recent years, CNNs have begun to see wider adoption in astronomy. Most of the existing CNNs that astronomers use are binary - is this a spiral galaxy or not? - but this new CNN uses multiclass classification - is this an elliptical, lenticular, spiral, or irregular galaxy? - with more accuracy than the existing binary networks.

Mr Cavanagh said that machine learning is becoming more widespread in astronomy.

"The massive advantage of neural networks is speed. Survey images that would otherwise have taken months to be classified by humans can instead be classified in mere minutes."

"Using a standard graphics card, we can classify 14,000 galaxies in less than 3 seconds."

"These neural networks are not necessarily going to be better than people because they're trained by people, but they're getting close with more than 80% accuracy, and up to 97% when classifying between ellipticals and spirals."

"If you place a group of astronomers into a room and ask them to classify a bunch of images, there will almost certainly be disagreements. This inherent uncertainty is the limiting factor in any AI model trained on labelled data."

One great advantage of this new AI is that the researchers will be able to classify more than 100,000,000 galaxies at different distances (or redshifts) from Earth and in different environments (groups, clusters etc). This will help them understand how galaxies are being transformed over time, and why it might happen in particular environments.

The CNNs that Mr Cavanagh has developed aren't just for astronomy. They can be repurposed for use in many other fields, as long as they have a large enough dataset to train with.

"CNNs will play an increasingly important role in the future of data processing, especially as fields like astronomy grapple with the challenges of big data," he said

A new screening method that can test the effectiveness of therapeutic molecules designed to 'glue' proteins together in the body has been developed by researchers at the University of Birmingham and the University of Leicester.

The research paves the way for drug developers to screen large numbers of potential new drug compounds to discover new treatments for diseases such as breast cancer and Parkinson's disease.

The ways in which proteins interact with each other are fundamental to all cell functions. These interactions underpin every function of a healthy body, with any slight change in these interactions resulting in disease.

A handful of drugs have been designed that can break apart these interactions, and this serves to disrupt the progress of the disease. However, in some diseases, the problem is caused by protein interactions not happening, or not happening in the right way. So new drugs that work by 'gluing' these proteins together would be highly effective, but finding them is not straightforward.

In this study, Chemical Science, researchers in the University of Birmingham's School of Biosciences have designed a system that uses mass spectrometry to measure the precise mass of a pair of proteins, plus the 'glue', to identify which 'glue' is the strongest and thus will likely be the most successful in treating the disease.

Lead author Dr Aneika Leney said: "A healthy body depends very much on the cells' proteins being able to signal effectively. Any wrong signal can lead to disease and that could be the wrong proteins sticking together - or proteins not joining up as they should. We want a drug that corrects for this. Our methods provides a 'snapshot' of what is happening to the proteins when we add a potential drug so we can see quickly whether the 'glue' is working"

The team worked with chemical biologists at the University of Leicester to test the method on therapeutic compounds being studied by co-lead author Dr Richard Doveston and his team.

Dr Doveston says: Looking for molecules that act as glues is not easy because things are complicated by having two proteins in the mix. At the early stage of development we often just want to find molecules that are good starting points for development, so they might not be that good as glues at this stage. The current high-throughput screening methods available to us are usually not very effective in this context. The mass spectrometry method is great because we can learn so much from the data and it can be gathered relatively easily and quickly.

Because the glue compounds are highly specific to the identified proteins, interactions with other proteins are rare, so the therapy is unlikely to produce any unlooked-for effects."

Dr Leney adds: "We hope our approach will be taken up by pharmaceutical companies and used to rapidly screen and test promising drug compounds that can bind proteins together to deliver a therapeutic benefit."

CLEVELAND, Ohio (July 7, 2021)--Estrogen has been thought to play a role in a woman's risk of developing Alzheimer disease (AD). A new study has taken a different approach to identifying risk factors for AD by examining the association between a woman's reproductive life span as an indicator of endogenous estrogen exposure and levels of cerebrospinal fluid biomarkers. Study results are published online in Menopause, the journal of The North American Menopause Society (NAMS).

Alzheimer disease represents 60% to 70% of all dementia diagnoses, making it the most common form of dementia. Approximately two-thirds of those with AD are women. This is not surprising, because age is the greatest known risk factor for AD, and women tend to live longer than men.

The incidence of AD is rising quickly because of the aging population, so multiple studies have been undertaken to identify other risk factors, especially those that may explain any sex differences. Prior studies have shown a link between both higher and lower estradiol blood levels and risk of dementia, whereas others have identified no associations. Some studies have shown that hormone therapy after menopause can increase the risk of dementia, but others have documented a decreased risk. Similarly, cognitive decline has been linked with both longer and shorter reproductive periods.

Despite all the conflicting evidence, few, if any, studies have examined the association between estrogen and biomarkers for AD in cerebrospinal fluid, the clear body fluid found within the tissues surrounding the brain and spinal cord. In this new study, a small sampling of women who were free of dementia and underwent natural menopause were followed for 25 years. Based on the results from the cerebrospinal fluid samples, researchers concluded that a longer reproductive life was associated with increased levels of AD biomarkers in the preclinical phase of the disease; however, they suggested that larger studies should be conducted to confirm these findings.

Study results appear in the article "Reproductive period and preclinical cerebrospinal fluid markers for Alzheimer disease: a 25-year study."

"This small population-based study showed an association between duration of the reproductive life span (a surrogate marker for exposure to endogenous estrogen) and biomarkers of Alzheimer disease in the cerebrospinal fluid of women without dementia. This finding needs to be confirmed in larger studies but may be another factor contributing to the increased burden of Alzheimer disease in women that, at least in part, likely relates to aging and the longer life expectancy in women compared with men," says Dr. Stephanie Faubion, NAMS medical director.

A new study in the Journal of the European Economic Association, published by Oxford University Press, finds that electoral districts with a larger gender pay gaps show favoritism toward male political candidates in Parliamentary elections, with fewer female candidates on the ballot.

The researchers here gathered data for seven parliamentary elections in France between 1988 and 2017. Researchers studied candidates from the Left and Right political coalitions, which account for 80% of elected members of Parliament. The researchers consulted administrative and web data on candidates and electoral outcomes, survey data on voters' attitude towards gender, as well as census data on earnings, and voters' demographics across electoral districts.

Analysis found that female candidates made up approximately 15% of all Parliamentary candidates in the 1980s and 1990s. The figure doubled to nearly 30% following the implementation of the Parity Law in 2000, which stipulated that each party should have an equal fraction of male and female candidates across electoral districts in Parliamentary elections. Noncompliance with the parity rule results in a financial penalty to the public funding provided to political parties.

Researchers analyzed local gender pay gaps compared to voting support for male and female candidates in the same electoral districts. Researchers found a positive and strong correlation between gender earnings gaps and electoral gaps across municipalities of the same electoral district: a 150 euros increase in gender monthly earnings gap leads to an increase by 0.6 percentage points in vote shares between male and female candidates. Researchers concluded that female candidates obtain lower votes in areas with less favorable attitudes towards women, including significant gender pay gaps, and thus women are less likely to run for elections in these areas.

Indeed researchers found that voters' attitudes towards gender are strongly associated with the gender distribution of candidates across electoral districts within France. A 10 percentage points increase in survey respondents who thought that men were better political leaders than women correlated with a 2.3 percentage points decrease in the share of female candidates.

Researchers concluded that in districts with strongest electoral competition, the electoral cost of selecting women outweighs the cost of the financial penalty under the Parity Law. When voters are biased against female candidates, electoral competition limits the effectiveness of "soft" quota rules on candidates. In the last Parliamentary election (17 years after the Parity rule was introduced) the two main political parties still selected an average of 40% of female candidates, significantly below the 50% objective of the Parity Law.

"Overall we find that parties allocate female candidates across districts strategically," Thomas Le BarBanchon, Bocconi University, said. "This is very clear after the introduction of the Parity Law. Then parties avoid putting women on the ballot of the most contested districts. In such districts, voters biased against female politicians may lead women to lose the few votes that matter for winning the close race, and parties internalize this competitive disadvantage."

A research team consisting of Tsutomu Kobayashi, Ichiro Hasuo, Fuyuki Ishikawa, and Shinya Katsumata at the National Institute of Informatics (NII, Japan) and Rick Salay and Krzysztof Czarnecki at University of Waterloo (Canada) developed a method that automatically transforms models of controller software into models that satisfy safety requirements even when there is uncertainty in sensing the state of the environment. In addition to the transformation, the method generates formulas that represent the degree of uncertainty that the controller software can tolerate. The method can be applied to various controller systems that interact with the external environment, including autonomous vehicles.

This research was conducted under the ERATO MMSD Project (*1) funded by the Japan Science and Technology Agency (JST, Japan). The findings were presented at the 13th NASA Formal Methods Symposium (online) on May 26th, 2021.

Background

Controller systems such as drones and autonomous vehicles are vital in society. These systems must be able to function as safely as possible because many of them are intended for use in the real world. Approaches involving mathematical modeling of the systems and verifying their safety are effective for guaranteeing safety.

The controller software in such systems determines its actions in response to the state of the environment, which is perceived with sensors. In reality, however, the systems may perceive values that differ from the true values (perceptual uncertainty). This can cause safety violations if the controller software behaves in response to the incorrectly perceived values. For instance, if the sensor of an autonomous vehicle can misperceive the positions of other cars up to 1 m, it should operate with a safety margin of at least 1 m (Figure 1 (a)).

Designing such uncertainty-aware and safe controller software is quite complicated because developers need to verify that safety is guaranteed for every possible behavior of the system while taking into consideration differences between true values and perceived values (Figure 1 (b)). In addition, it is difficult to estimate the degree of the uncertainty. For example, perceptual uncertainty depends on the situation in which the controller system is deployed, such as whether or not it is foggy. Therefore, rather than specifying concrete perceptual uncertainty in models, constructing uncertainty-unaware controller models and calculating the degree of uncertainty the constructed controllers can tolerate are more suitable for flexible analysis. However, obtaining this limit as a formula proved to be difficult.

Methods and Results

In this study, we propose a method that automatically transforms a model of an uncertainty-unaware controller into a model of a robustified controller, that is, a new controller that safely behaves even under uncertainty (Figure 2).

The method consists of two steps.

The first step (uncertainty injection) is to transform an input model of an uncertainty-unaware controller into an intermediate model of an uncertainty-aware controller. Note that the behavior of the intermediate model is the same as that of the input model so it is unsafe.

Then the next step (robustification) is to transform the intermediate model into one that is uncertainty-aware and safe. The behavior of the resulting controller is updated so that it operates safely even under uncertainty.

In addition, the method generates a formula that represents the degree of uncertainty that the output controller can tolerate.

In the first step (uncertainty injection), variables of perceived values, which can differ from true values, are introduced. Moreover, while the input model is specified under an ideal assumption that the controller can refer to the true value when it determines an action, the intermediate controller refers to the perceived value to reflect the reality of the perception. Although the intermediate controller determines its actions in response to perceived values, safety is not guaranteed because its behavior is the same as that of the input controller. For example, an autonomous vehicle may misperceive the distance to another car as 5 m when it is only 4 m, resulting in a collision.

In the second step (robustification), the case distinction of the state of the environment is calculated. For instance, in some situations, an autonomous vehicle may be unsure of whether it should cruise or brake due to perceptual uncertainty about the distance between itself and a car ahead. The robustification method exhaustively lists such uncertain cases so that they are considered separately. In addition, the behavior of the controller is updated so that safety will be guaranteed even under perceptual uncertainty. The method considers all possibilities of the true value estimated from the perceived value and calculates behavior that is safe for every possibility.

Constraints on the behavior of the generated controller are specified so that it is guaranteed to operate safely even under uncertainty. However, whether such constraints are satisfiable depends on the uncertainty. As an extreme example, if a sensor misperceives the positions of other cars up to 100 km, then guaranteeing safety is impossible in many situations. This raises the question of how much uncertainty the generated controller can tolerate. Where is the limit?

To answer this, the proposed approach also generates the limit as a formula of uncertainty. Developers can choose appropriate sensors from a given catalog by using the formula as the criterion. In addition, the formula can be used to analyze uncertainty, such as how the uncertainty will be propagated if the controller is combined with other components.

The method makes the construction of uncertainty-aware and safe controllers more systematic and effortless. Moreover, it enables developers to flexibly analyze various situations of perceptual uncertainty. Thus, the method improves the overall safety of the real world in which controller systems are implemented ubiquitously.

Future outlook

In addition to autonomous vehicles, the proposed method can also be applied to various other controller systems that interact with external environments. In future work, we intend to generalize the method so that it will be able to deal with a broader range of uncertainty. For instance, we will tackle misclassification problems such as an object classifier module classifying an object as a wrong object class.

Comments from Tsutomu Kobayashi

"Controller systems are crucial because most software systems' usefulness is due to their interactions with external environments. This research aims to help developers apply formal modeling approaches to realistic software by addressing the inevitable problem of controller systems regarding the gap between the perception and reality. Thus, developers can focus on the essence of controller behavior. We believe that the method is valuable and can be extended in various ways. We will continue working towards the systematic and easy application of rigorous mathematical methods to ensure a safe environment for everyone."

Information on Paper

Title

: Robustifying Controller Specifications of Cyber-Physical Systems Against Perceptual Uncertainty

Authors

: Tsutomu Kobayashi, Rick Salay, Ichiro Hasuo, Krzysztof Czarnecki, Fuyuki Ishikawa, Shin-ya Katsumata

Conference

: The 13th NASA Formal Methods Symposium https://shemesh.larc.nasa.gov/nfm2021/

Date of Presentation

: May 26th, 2021 (US Eastern Time)

(*1) ERATO Hasuo Metamathematics for Systems Design Project (ERATO-MMSD): a project funded in the Exploratory Research for Advanced Technology (ERATO) scheme of the Japan Science and Technology Agency (JST). The project conducts academic research for quality assurance of cyber-physical systems as the core of Society 5.0. The project specifically focuses on automated driving systems and investigates reliability techniques for modeling, formal verification, testing, and holistic, practical V&V techniques including all of them. This challenge requires tight collaboration of different academic areas such as software science and engineering, control theory and engineering, and artificial intelligence. Therefore, the project also focuses on (meta)mathematical theories. https://www.jst.go.jp/erato/hasuo/en/

Philadelphia, July 7, 2021 - Tourette syndrome, a neurodevelopmental disorder, causes motor and phonic "tics" or uncontrollable repeated behaviors and vocalizations. People affected by Tourette syndrome can often suppress these tics for some time before the urges become overwhelming, and researchers have long wondered at the neural underpinnings of the suppression effort.

Now, in a new study using a non-invasive technique to measure brain activity called high-density electroencephalography (hdEEG), researchers at Yale School of Medicine have assessed the impact of tic suppression on functional connectivity between brain regions.

The study appears in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier.

"Tic suppression is an important feature of Tourette syndrome. Understanding how someone may temporarily gain control over their tics may inform several research areas in Tourette syndrome. Yet, brain correlates of tic suppression have not been studied extensively, especially in children," said Denis Sukhodolsky, PhD, senior author of the study, and Associate Professor at the Yale Child Study Center at the Yale School of Medicine, New Haven, CT, USA.

Cameron Carter, MD, Editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, said of the study, "Understanding brain mechanisms associated with successful coping in disorders such as Tourette syndrome opens up opportunities for developing targeted treatments to enhance the innate self-control that normally emerges as the brain matures."

The team led by Dr. Sukhodolsky recorded the brain activity of 72 children, aged 8 to 16 years old, with Tourette syndrome using hdEEG, while they were ticcing freely and while they were suppressing their tics. The researchers then assessed connectivity between the different regions in the brain.

The authors found that connectivity between multiple brain regions was increased while children suppressed their tics. "Some of these regions are part of the default mode network, an array of brain regions engaged during internal thought processes such as daydreaming," explained first author Simon Morand-Beaulieu, PhD.

Additionally, the researchers reported that functional brain connectivity during tic suppression was positively correlated with age, suggesting that the brain networks of tic suppression undergo developmental changes in response to the experience of tics. "This increase in functional connectivity as children mature is consistent with increasing tic suppression capacities developing into adolescence as well as a better awareness of the sensory phenomena accompanying tics," said Dr. Morand-Beaulieu.

The study highlights the brain mechanism involved in a temporary decrease in tic frequency, which could have therapeutic implications. "It will be important to assess whether the same mechanism plays a role in a more structured intervention to decrease tic severity, such as behavioral therapy for Tourette syndrome," said Dr. Sukhodolsky.

Researchers at Karolinska Institutet in Sweden publish new findings in the journal Cancer Discovery showing how pharmacological activation of the protein p53 boosts the immune response against tumours. The results can be of significance to the development of new combination therapies that will give more cancer patients access to immunotherapy.

Given its ability to react to damage to cellular DNA and the key part it is thought to play in preventing tumour growth, the protein p53 has been dubbed the "guardian of the genome". Half of all tumours have mutations in the gene that codes for the protein, and in many other tumours, p53 is disabled by another protein, MDM2.

It has long been known that p53 is able to silence certain sequences in our genome called endogenous retroviruses (i.e. DNA elements evolutionarily inherited from viruses), thus preventing genome instability. The researchers now show that the protein can also activate these sequences in cancer cells, leading to anti-tumour immune response.

"This was an astonishing discovery. When we blocked the suppressor MDM2, p53 activated endogenous retroviruses which induced antiviral response and boosted the production of immune-activating interferons," says lead investigator Galina Selivanova, Professor at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.

The results were obtained when the researchers blocked MDM2 in mouse models using a substance coded as ALRN-6924 from the US company Aileron Therapeutics. The increase of interferon response was also seen in tumour samples from two patients taking part in the company's clinical trials of ALRN-6924.

"This shows that there are synergies that should be exploited between substances that block MDM2 and modern immunotherapies," Professor Selivanova continues. "A combination of these can be particularly important for patients who don't respond to immunotherapy."

Immunotherapy, or immuno-oncology, is described as a revolution in modern cancer treatment in the way it triggers the body's immune system to fight cancer cells. However, it does not work with all patients, and the presence of interferons could be a biomarker for whether or not immunotherapy will prove efficacious.

"If we can increase the level of interferons, we can therefore increase the chances that the immunotherapy will succeed."

Professor Selivanova is a pioneer in research on how mutated p53 can be re-activated using special molecules, one of which, APR-246, is undergoing clinical studies under the name Eprenetapopt at Aprea Therapeutics, a company that she co-founded.

"We now want to examine if Eprenetapopt produces the same interferon boost and can have the same potential to increase access to immunotherapy for patients with severe forms of cancer," she says.

The Mid-infrared lasers (MIR) with high peak power and high repetition rate operating in the range of 2.7~3 μm have important application in laser surgery and optical parametric oscillator (OPO).

A recent study conducted by SUN Dunlu's research group at the Hefei Institutes of Physical Science(HFIPS) of the Chinese Academy of Sciences (CAS) achieved high power, high efficiency and quasi-continuous mid-infrared laser in the free running and langasite [La3 Ga5 SiO14 (LGS)] Q-switched modes by using the Er3+ ions-doped YAP crystals as laser gain medium.

Based on their previous research work on laser, the researchers further improved the laser performance of Er:YAP laser crystal by laser-diode (LD) side-pumping method, a Er:YAP crystal rod with concave end-faces was used to compensate the thermal lensing effect. The maximum output powers of 26.75 W were achieved at 250 Hz, and 13.18 W at 1000 Hz, which is the highest working frequency in all the LD side- pumped Er-doped MIR laser so far.

In addition, they demonstrated a LD side-pumped and electro-optical Q-switched Er,Pr:YAP laser with emission at 2.7 μm. A giant pulse laser was obtained with pulse energy of 20.5 mJ, pulse width of 61.4 ns, and peak power of 0.33 MW at the highest working frequency of 150 Hz.

These results indicate that the Er3+-doped YAP crystals are promising candidate for the high power and high frequency mid-infrared laser device, which possess great potential for the application of dental ablation surgery and OPO pump source.

In 2016, researchers from the EDDyLab - Evolution & Diversity Dynamics Lab - at the University of Liège (Belgium) proposed a new definition of the geological boundary between the Devonian and Carboniferous periods (359 million years). This new definition has been tested by hundreds of researchers around the world and the results are now compiled in a special issue of the journal Palaeodiversity & Palaeoenvironments.

Geological time is divided into periods (Cambrian, Carboniferous, Jurassic, etc.), together covering the 4.6 billion year history of the Earth. The many climatic, environmental and biological changes that have punctuated this history are recorded in the rock layers, forming an incredibly rich archive of the Earth's past. "The study of these successive layers allows us to recognise the boundaries between these different periods, each boundary being defined by a specific event or 'marker', such as an extinction event or a change in climate," explains Julien Denayer, a palaeontologist at the EDDyLab and first author of the article. A locality is then designated, making the rocky successions of this particular place the international reference for this transition. "It was in Belgium, in the 19th century, that numerous divisions of the time scale were defined, such as the Frasnian, Tournaisian, Viséian, Namurian, etc... These references are still used today on an international scale.

The boundary between the so-called Devonian and Carboniferous geological periods (359 million years ago) was the first to be formally defined in 1927. The fossils marking the boundary were too rare in the rocks, so this definition was of little use. A second attempt was proposed fifty years later, but was also invalidated by the International Commission of Stratigraphy, the scientific body that establishes and validates the subdivision of geological time, again because of the scarcity of boundary fossils.

For the past ten years or so, palaeontologists and geologists specialising in the Devonian and Carboniferous periods have been working on redefining this boundary," says Cyrille Prestianni, palaeontologist at ULiège and co-author of the article. In 2016, we proposed a new definition, this time based on several contemporary phenomena, well recorded in the rocky successions of Wallonia. "According to the ULiège researchers, the boundary between these two periods is defined by the so-called Hangenberg Sandstone event - an episode of abrupt fall in sea level - which is also marked by a major extinction that decimated typical Devonian ecosystems such as coastal marshes and reefs. In ecological terms, this extinction was greater than the extinction of the dinosaurs at the end of the Cretaceous!

Since then, researchers around the world have tested the applicability of this criterion for defining the boundary. The results of these years of research are now compiled in a special volume of the journal Palaeodiversity & Palaeoenvironments. The EDDy Lab researchers publish an exhaustive review of the geological and palaeontological knowledge of the Devonian-Carboniferous boundary in Wallonia and the surrounding regions. In this publication, the members of the EDDy Lab were able to propose a scenario explaining the ecological and climatic crisis that caused the extinction of the Devonian fauna and flora. Our work is not yet finished," says Julien Denayer, "the next step is to select a new type locality. Several Walloon sites are now being studied using state-of-the-art techniques with a view to being proposed to become the world reference for the Devonian-Carboniferous boundary! »

Scientists from Tohoku University and the University of Maryland have pinpointed the strong magnetic field of the early sun as the reason behind the radial variation of rock and metal in rocky planets' cores. This magnetic field, which pulled small iron grains inward, explains Mercury's big iron core and why Mars has so little iron in its core.

The details of their research were published in the journal Progress in Earth and Planetary Science on July 5, 2021.

Planets have iron cores surrounded by a rocky shell, mostly made up of mantle and a thin skin of crust. The four inner planets of our Solar System, Mercury, Venus, Earth, and Mars have their own distinctive size and density. These differences have long since puzzled scientists.

Mercury has a metallic core making up about 3/4 of its mass, with the remaining 1/4 being a rocky silicate shell. The cores of Earth and Venus possess a metallic core of only 1/3 of their mass, with the rest being rock. Mars has a measly core comprising only 1/4 of its mass.

These radical changes in metal content offer clues about what controlled the distribution of raw materials in the early formation of the solar system.

During this period, swirling gas and dust cloud drew matter into the Solar System's center, thus forming the Sun. The rapid delivery to the center caused many collisions and heated the inner region of the Solar System. When the Sun was big enough to have its own internal gravity, it caused its proton-rich core to ignite its nuclear fuel, brightly turning on the Sun. Following this, the Sun's core began convecting, creating a dynamo generating a strong magnetic field.

The high temperatures of the inner Solar System turned elements into a vapor state. As the element cloud cooled down it rained out mineral compounds. Evidence from primitive meteorites reveals the compounds precipitated were either silicates or metals. The sun's magnetic field pulled the metal particles inwards.

The composition of inner rocky planets is remarkably similar to primitive meteorites. Also known as chondrites, these meteorites are jumbled mixtures of rock and metal in different proportions. Unlike rocky planets, they do not have cores.

The raw materials making up the rocky planets are just four unevenly distributed elements: oxygen, iron, magnesium, and silicon. This represents about 93% of a rocky planet's mass. Around 70% of that is equal measure oxygen and iron, whilst the rest consists of equal measure magnesium and silicon.

"Planetary cores are a big deal," proclaims coauthor of the study Bill McDonough. "They control where elements end up in the planet." McDonough points to the Earth's abundance of the nutrient phosphorus concentrated in its core as an example. "Planetary habitability also depends upon the size and compositions of its core in addition to the lifetime of its dynamo."

The core's dynamo generates a magnetic shield that protects us from cancer-causing cosmic rays. Once Mars lost its core dynamo, its surface water disappeared quickly thereafter.

Early on in Solar System formation, a cloudy disc of gas and dust surrounded the Sun and planets, serving as a conduit for the Sun's magnetic field. The strength of the magnetic field weakened as it got further away from the Sun. Mercury formed in the prime location - close to where the Sun's magnetic field was strongest, thus explaining its large iron core.

The study is the first on epidemiology and causes of traumatic brain injury in over 20 years. The research team reports in the journal BMJ Open of 4 June 2021.

Falling and cycling without a helmet are common causes

From a minor fall on a bicycle to a serious road traffic accident: The causes of a traumatic brain injury are manifold. About 90 percent of the approximately 270,000 cases per year are classified as mild, ten percent as moderate or severe. Current findings show that traumatic brain injury is increasing in the age group of over-65s. The research team at BG Kliniken in Bochum, Hamburg, Berlin, Halle, Frankfurt, Ludwigshafen and Murnau found that there has been a shift in the age group most frequently affected and that there is a discernible correlation between the severity of a traumatic brain injury, age and cause.

The study shows that the most frequent causes of traumatic brain injury are falls and no longer road traffic accidents. There has also been a shift with regard to road traffic accidents: The largest group here is no longer car occupants, but cyclists without helmets.

"We are registering a clear shift in the majority of the affected age group towards the older generation. This phenomenon can be observed in almost all industrialised countries," explains Professor Peter Schwenkreis, senior physician at the Neurological Clinic at Bergmannsheil. A link with the age of those affected is also discernible. Falls are the most common cause, especially among older women and men. "Older people are significantly more prone to falls and thus suffer a traumatic brain injury more quickly than other age groups. In addition, the severity of the injury is higher in these patients", Schwenkreis specifies. "This also explains why we are seeing an increase in deaths caused by such an injury in this age group."

Study with over 3,500 participants

For the study, a neuroscientific research group of the BG Kliniken observed and evaluated the development, treatment and impact for patients with traumatic brain injury. A total of 3,514 patients were included in the study. All of them were treated at one of the participating BG Kliniken between 1 October 2014 and 30 September 2015. The prerequisite was that the medical care had taken place within the first 24 hours after suffering the traumatic brain injury.

The results were collected using two different methods: Evaluation of documentation forms from initial care to rehabilitation on the one hand, and standardised telephone interviews with the affected persons three and twelve months after they suffered the trauma on the other hand. A study of this magnitude on the epidemiology of traumatic brain injury has not been published in Germany since 2000/2001.

Simple measures can have a big impact

As moderate to severe traumatic brain injuries occur more frequently in older people, the research group identifies a specific need for more prevention work here. "Training measures for safe walking, training in the use of walking aids or redesigning the home by removing tripping hazards are conceivable. As simple as these measures sound, they can prevent serious injuries", says Peter Schwenkreis. "The advances in passenger protection in cars have had a clearly demonstrable effect", he explains further. "Now it is important to implement the protection of pedestrians and cyclists as part of the emerging shift in mobility."

Traumatic brain injury

A traumatic brain injury is any injury to the skull, with or without fracture, that involves damage to the brain. Just like the causes, the symptoms can also be very diverse. They range from headaches, dizziness and lightheadedness to amnesia or impaired consciousness. However, even minor injuries to the skull can cause bleeding or swelling the brain, which is why a traumatic brain injury should be assessed immediately after an accident.