Culture

A breakthrough astrophysics code, named Octo-Tiger, simulates the evolution of self-gravitating and rotating systems of arbitrary geometry using adaptive mesh refinement and a new method to parallelize the code to achieve superior speeds.

This new code to model stellar collisions is more expeditious than the established code used for numerical simulations. The research came from a unique collaboration between experimental computer scientists and astrophysicists in the Louisiana State University Department of Physics & Astronomy, the LSU Center for Computation & Technology, Indiana University Kokomo and Macquarie University, Australia, culminating in over of a year of benchmark testing and scientific simulations, supported by multiple NSF grants, including one specifically designed to break the barrier between computer science and astrophysics.

"Thanks to a significant effort across this collaboration, we now have a reliable computational framework to simulate stellar mergers," said Patrick Motl, professor of physics at Indiana University Kokomo. "By substantially reducing the computational time to complete a simulation, we can begin to ask new questions that could not be addressed when a single-merger simulation was precious and very time consuming. We can explore more parameter space, examine a simulation at very high spatial resolution or for longer times after a merger, and we can extend the simulations to include more complete physical models by incorporating radiative transfer, for example."

Recently published in Monthly Notices of the Royal Astronomical Society, "Octo-Tiger: A New, 3D Hydrodynamic Code for Stellar Mergers That Uses HPX Parallelisation," investigates the code performance and precision through benchmark testing. The authors, Dominic C. Marcello, postdoctoral researcher; Sagiv Shiber, postdoctoral researcher; Juhan Frank, professor; Geoffrey C. Clayton, professor; Patrick Diehl, research scientist; and Hartmut Kaiser, research scientist, all at Louisiana State University--together with collaborators Orsola De Marco, professor at Macquarie University and Patrick M. Motl, professor at Indiana University Kokomo--compared their results to analytic solutions, when known and other grid-based codes, such as the popular FLASH. In addition, they computed the interaction between two white dwarfs from the early mass transfer through to the merger and compared the results with past simulations of similar systems.

"A test on Australia's fastest supercomputer, Gadi (#25 in the World's Top 500 list), showed that Octo-Tiger, running on a core count over 80,000, displays excellent performance for large models of merging stars," De Marco said. "With Octo-Tiger, we cannot only reduce the wait time dramatically, but our models can answer many more of the questions we care to ask."

Octo-Tiger is currently optimized to simulate the merger of well-resolved stars that can be approximated by barotropic structures, such as white dwarfs or main sequence stars. The gravity solver conserves angular momentum to machine precision, thanks to a correction algorithm. This code uses HPX parallelization, allowing the overlap of work and communication and leading to excellent scaling properties to solve large problems in shorter time frames.

"This paper demonstrates how an asynchronous task-based runtime system can be used as a practical alternative to Message Passing Interface to support an important astrophysical problem," Diehl said.

The research outlines the current and planned areas of development aimed at tackling a number of physical phenomena connected to observations of transients.

"While our particular research interest is in stellar mergers and their aftermath, there are a variety of problems in computational astrophysics that Octo-Tiger can address with its basic infrastructure for self-gravitating fluids," Motl said.

The animation (https://www.youtube.com/watch?v=hg9MQNLLJw4) was prepared by Shiber, who says: "Octo-Tiger shows remarkable performance both in the accuracy of the solutions and in scaling to tens of thousands of cores. These results demonstrate Octo-Tiger as an ideal code for modeling mass transfer in binary systems and in simulating stellar mergers."

Anyone with children knows that while controlling one child can be hard, controlling many at once can be nearly impossible. Getting swarms of robots to work collectively can be equally challenging, unless researchers carefully choreograph their interactions -- like planes in formation -- using increasingly sophisticated components and algorithms. But what can be reliably accomplished when the robots on hand are simple, inconsistent, and lack sophisticated programming for coordinated behavior?

A team of researchers led by Dana Randall, ADVANCE Professor of Computing and Daniel Goldman, Dunn Family Professor of Physics, both at Georgia Institute of Technology, sought to show that even the simplest of robots can still accomplish tasks well beyond the capabilities of one, or even a few, of them. The goal of accomplishing these tasks with what the team dubbed "dumb robots" (essentially mobile granular particles) exceeded their expectations, and the researchers report being able to remove all sensors, communication, memory and computation -- and instead accomplishing a set of tasks through leveraging the robots' physical characteristics, a trait that the team terms "task embodiment."

The team's BOBbots, or "behaving, organizing, buzzing bots" that were named for granular physics pioneer Bob Behringer, are "about as dumb as they get," explains Randall. "Their cylindrical chassis have vibrating brushes underneath and loose magnets on their periphery, causing them to spend more time at locations with more neighbors." The experimental platform was supplemented by precise computer simulations led by Georgia Tech physics student Shengkai Li, as a way to study aspects of the system inconvenient to study in the lab.

Despite the simplicity of the BOBbots, the researchers discovered that, as the robots move and bump into each other, "compact aggregates form that are capable of collectively clearing debris that is too heavy for one alone to move," according to Goldman. "While most people build increasingly complex and expensive robots to guarantee coordination, we wanted to see what complex tasks could be accomplished with very simple robots."

Their work, as reported April 23, 2021 in the journal Science Advances, was inspired by a theoretical model of particles moving around on a chessboard. A theoretical abstraction known as a self-organizing particle system was developed to rigorously study a mathematical model of the BOBbots. Using ideas from probability theory, statistical physics and stochastic algorithms, the researchers were able to prove that the theoretical model undergoes a phase change as the magnetic interactions increase -- abruptly changing from dispersed to aggregating in large, compact clusters, similar to phase changes we see in common everyday systems, like water and ice.

"The rigorous analysis not only showed us how to build the BOBbots, but also revealed an inherent robustness of our algorithm that allowed some of the robots to be faulty or unpredictable," notes Randall, who also serves as a professor of computer science and adjunct professor of mathematics at Georgia Tech.

Osaka, Japan - Scientists at Osaka University, in cooperation with JOANNEUM RESEARCH (Weiz, Austria), introduced wireless health monitoring patches that use embedded piezoelectric nanogenerators to power themselves with harvested biomechanical energy. This work may lead to new autonomous health sensors as well as battery-less wearable electronic devices.

As wearable technology and smart sensors become increasingly popular, the problem of providing power to all of these devices become more relevant. While the energy requirements of each component may be modest, the need for wires or even batteries become burdensome and inconvenient. That is why new energy harvesting methods are needed. Also, the ability for integrated health monitors to use ambient motion to both power and activate sensors will help accelerate their adoption in doctor's offices.

Now, an international team of researchers from Japan and Austria has invented new ultraflexible patches with a ferroelectric polymer that can not only sense a patient's pulse and blood pressure, but also power themselves from normal movements. The key was starting with a substrate just one micron thick. Using a strong electric field, ferroelectric crystalline domains in a copolymer were aligned so that the sample had a large electric dipole moment. Based on the piezoelectric effect, which is very efficient in converting natural motion into small electric voltages, the device responds rapidly to strain or pressure changes. These voltages can be transduced either into signals for the medical sensors or to directly harvest the energy. "Our e-health patches may be employed as part of screening for lifestyle-related diseases such as heart disorders, signs of stress, and sleep apnea," first-author Andreas Petritz says.

The authors estimate that multilayer patches can harvest up to 200 millijoules per day from biomechanical motions if placed on joints, like knees or elbows. This is enough to monitor cardiovascular parameters several times a day. And the patches are so thin that they are barely perceptible thus making a necessary evil for many patients—daily health monitoring—less unpleasant.

"We expect that our findings will assist in the development of other sheet-type sensor systems that can perform precise biomonitoring when affixed to the skin surface," senior author Tsuyoshi Sekitani says. Additional modules allow other features, such as wireless communication with a smartphone or computer.

Sophia Antipolis - 23 April 2021: A study of 2.4 million hospitalised cannabis users has found that those with an arrhythmia were 4.5 times more likely to die while in hospital than those without. The research is presented at EHRA 2021, an online scientific congress of the European Society of Cardiology (ESC).1

"People should be aware of this devastating outcome and be careful when using cannabis if they have a concomitant heart problem," said study author Dr. Sittinun Thangjui of Bassett Healthcare Network, Cooperstown, US.

Marijuana or cannabis is the most commonly used psychoactive substance worldwide.2 However, there is limited knowledge about safety of the drug in people with cardiac arrhythmias. This study examined the burden of arrhythmias in drug users admitted to hospital. It also compared length of hospital stay and deaths in hospital between those with and without an arrhythmia.

The study was conducted using the National Inpatient Sample database, which covers 97% of the US population. The study included 2,457,544 adult cannabis users admitted to hospital in 2016 to 2018. Of those, 187,825 (7.6%) patients had an arrhythmia. Atrial fibrillation was the most common, followed by abnormally slow heart rate and abnormally fast heart rate.

Patients in arrhythmia group were older: the average age was 50.5 years compared to 38.3 years for those without an arrhythmia. Those with arrhythmias also had more co-existing health conditions.

The researchers compared deaths between the two groups after adjusting for factors that could influence the relationship including age, sex, race, income, diabetes, heart failure, chronic kidney disease, obesity, and hospital location. Cannabis users with an arrhythmia had a 4.5 times higher odds of in-hospital mortality compared to those without an arrhythmia. Patients with an arrhythmia had a longer length of hospital stay (5.7 days) compared to those without (5.1 days).

Dr. Thangjui said: "Our study highlights that heart rhythm disorders may be a warning sign for an increased risk of death in people who use cannabis. More studies are needed to confirm our results. In the meantime, it seems sensible to screen these patients for arrhythmias if they present to hospital so that those with a heart rhythm problem can be closely monitored."

Among the first lessons any grade school science student learns is that white light is not white at all, but rather a composite of many photons, those little droplets of energy that make up light, from every color of the rainbow - red, orange, yellow, green, blue, indigo, violet.

Now, researchers at Stanford University have developed an optical device that allows engineers to change and fine-tune the frequencies of each individual photon in a stream of light to virtually any mixture of colors they want. The result, published April 23 in Nature Communication, is a new photonic architecture that could transform fields ranging from digital communications and artificial intelligence to cutting-edge quantum computing.

"This powerful new tool puts a degree of control in the engineer's hands not previously possible," said Shanhui Fan, a professor of electrical engineering at Stanford and senior author of the paper.

The clover-leaf effect

The structure consists of a low-loss wire for light carrying a stream of photons that pass by like so many cars on a busy throughway. The photons then enter a series of rings, like the off-ramps in a highway cloverleaf. Each ring has a modulator that transforms the frequency of the passing photons - frequencies which our eyes see as color. There can be as many rings as necessary, and engineers can finely control the modulators to dial in the desired frequency transformation.

Among the applications that the researchers envision include optical neural networks for artificial intelligence that perform neural computations using light instead of electrons. Existing methods that accomplish optical neural networks do not actually change the frequencies of the photons, but simply reroute photons of a single frequency. Performing such neural computations through frequency manipulation could lead to much more compact devices, say the researchers.

"Our device is a significant departure from existing methods with a small footprint and yet offering tremendous new engineering flexibility," said Avik Dutt, a post-doctoral scholar in Fan's lab and second author of the paper.

Seeing the light

The color of a photon is determined by the frequency at which the photon resonates, which, in turn, is a factor of its wavelength. A red photon has a relatively slow frequency and a wavelength of about 650 nanometers. At the other end of the spectrum, blue light has a much faster frequency with a wavelength of about 450 nanometers.

A simple transformation might involve shifting a photon from a frequency of 500 nanometers to, say, 510 nanometers - or, as the human eye would register it, a change from cyan to green. The power of the Stanford team's architecture is that it can perform these simple transformations, but also much more sophisticated ones with fine control.

To further explain, Fan offers an example of an incoming light stream comprised of 20 percent photons in the 500-nanometer range and 80 percent at 510 nanometers. Using this new device, an engineer could fine-tune that ratio to 73 percent at 500 nanometers and 27 percent at 510 nanometers, if so desired, all while preserving the total number of photons. Or the ratio could 37 and 63 percent, for that matter. This ability to set the ratio is what makes this device new and promising. Moreover, in the quantum world, a single photon can have multiple colors. In that circumstance, the new device actually allows changing of the ratio of different colors for a single photon.

"We say this device allows for 'arbitrary' transformation but that does not mean 'random,'" said Siddharth Buddhiraju, who was a graduate student in Fan's lab during the research and is first author of the paper and who now works at Facebook Reality Labs. "Instead, we mean that we can achieve any linear transformation that the engineer requires. There is a great amount of engineering control here."

"It's very versatile. The engineer can control the frequencies and proportions very accurately and a wide variety of transformations are possible," Fan added. "It puts new power in the engineer's hands. How they will use it is up to them."

Sugar is not just something we eat. On the contrary. Sugar is one of the most naturally occurring molecules, and all cells in the body are covered by a thick layer of sugar that protects the cells from bacteria and virus attacks. In fact, close to 80 per cent of all viruses and bacteria bind to the sugars on the outside of our cells.

Sugar is such an important element that scientists refer to it as the third building block of life - after DNA and protein. And last autumn, a group of researchers found that the spike protein in corona virus needs a particular sugar to bind to our cells efficiently.

Now the same group of researchers have completed a new study that further digs into the cell receptors to which sugars and thus bacteria and virus bind.

'We have established how the sugars bind to and activate the so-called Siglec receptors that regulate immunity. These receptors play a major role, as they tell the immune system to decrease or increase activities. This is an important mechanism in connection with autoimmune diseases', says the first author of the study, Postdoc Christian Büll from the Copenhagen Center for Glycomics (CCG) at the University of Copenhagen.

The unique sugar language

When the immune system receives wrong signals, it can lead to autoimmune diseases, which is when the immune system attacks itself. The Siglec receptors receive signals via the sialic acid sugar, a carbohydrate that typically closes the sugar chains on the surface of our cells. When Siglec receptors meet the right sugar chains, the immune system is told to dampen or activate.

'As part of the new study, we have created a cell library that can be used to study how various sugars bind to and interact with receptors. We have done this by creating tens of thousands of cells each containing a bit of the unique sugar language, which enables us to distinguish them from one another and to study their individual effect and process. This knowledge can help us develop better treatment options in the future', says Associate Professor Yoshiki Narimatsu from CCG, who also contributed to the study.

'The surface of the cells in the library is the same as the one found on cells in their natural environment. This means that we can study the sugars in an environment with the natural occurrence of e.g. proteins and other sugars, and we can thus study the cells in the form in which virus and bacteria find them', Yoshiki Narimatsu explains.

Important discovery for Alzheimer's

Working on the new study, the researchers identified the sugars that bind to the specific receptor that plays a main role in the development of Alzheimer's disease.

'Our main finding concerns the Siglec-3 receptor. Mutations in the Siglec-3 receptor is already known to play a role in connection with Alzheimer's, but we did not know what the receptor specifically binds to. Our method has now identified a potential natural sugar that binds specifically to the Siglec-3 receptor. This knowledge represents an important step forwards in understanding the genetic defects that cause a person to develop the disease', says Christian Büll.

It is 2,250 kilometers long, but only 355 kilometers wide at its widest point - on a world map, the Red Sea hardly resembles an ocean. But this is deceptive. A new, albeit still narrow, ocean basin is actually forming between Africa and the Arabian Peninsula. Exactly how young it is and whether it can really be compared with other young oceans in Earth's history has been a matter of dispute in the geosciences for decades. The problem is that the newly formed oceanic crust along the narrow, north-south aligned rift is widely buried under a thick blanket of salt and sediments. This complicates direct investigations.

In the international journal Nature Communications, scientists from GEOMAR Helmholtz Centre for Ocean Research Kiel, King Abdullah University for Science and Technology in Thuwal (Saudi Arabia) and the University of Iceland have now published a study that makes a good case for the Red Sea being quite mature and having an almost classical oceanic evolution. "Using a combination of different methods, we can show for the first time that the structures in the Red Sea are typical for a young but already fully developed ocean basin." says Dr. Nico Augustin from GEOMAR, lead author of the study.

In addition to information from high-resolution seafloor maps and chemical investigations of rock samples, the team primarily used gravity and earthquake data to develop a new tectonic model of the Red Sea basin. Gravity anomalies have already helped to detect hidden seafloor structures such as rift axes, transform faults and deep-sea mountains in other regions, for example in the Gulf of Mexico, the Labrador Sea or the Andaman Sea.

The authors of the current study compared gravity patterns of the Red Sea axis with comparable mid-ocean ridges and found more similarities than differences. For example, they identified positive gravity anomalies running perpendicular to the rift axis, which are caused by variations in crustal thickness running along the axis. "These so-called 'off-axis segmentation trails' are very typical features of oceanic crust originating from magmatically more active, thicker and thus, heavier areas along the axis. However, this observation is new for the Red Sea," says Dr. Nico Augustin.

Bathymetric maps as well as earthquake data also support the idea of an almost continuous rift valley throughout the Red Sea basin. This is also confirmed by geochemical analyses of rock samples from the few areas that are not overlain by salt masses. "All the samples we have from the Red Sea rift have geochemical fingerprints of normal oceanic crust," says Dr. Froukje van der Zwan, co-author of the study.

With this new analysis of gravity and earthquake data, the team constrains the onset of ocean expansion in the Red Sea to about 13 million years ago. "That's more than twice the generally accepted age," Dr. Augustin says. That means the Red Sea is no longer a baby ocean, but a young adult with a structure similar to the young southern Atlantic some 120 million years ago.

The model now presented is, of course, still being debated in the scientific community, says the lead author, "but it is the most straightforward interpretation of what we observe in the Red Sea. Many details in salt- and sediment-covered areas that were previously difficult to explain suddenly make sense with our model." While it has thus been able to answer some questions about the Red Sea, the model also raises many new ones that inspire further research in the Red Sea from a whole new scientific perspective.

Tsukuba, Japan - Blood vessels can be injured by the build-up of atherosclerosis and long-standing hypertension, among other conditions. As a consequence, blood vessels may undergo a process called remodeling, whereby their walls thicken and cause blockages (known as occlusion). In a new study, researchers from the University of Tsukuba discovered how cells marked by platelet-derived growth factor receptor alpha (PDGFRa+) residing predominantly in the most outer layer of blood vessels contribute to their remodeling.

Blood vessels comprise three layers, each of which fulfills a unique role in the function and stability of blood vessels: The innermost layer (the intima) is lined with endothelial cells that regulate the exchange between the blood and tissues; the medial layer (the media) consists of smooth muscle cells that regulate the tone of the blood vessel; and the outermost layer (the adventitia) contains various cell types and connective tissue to provide structural integrity and stability to the blood vessels. The intima is highly sensitive to pathologic conditions, such as atherosclerosis and hypertension, but also vascular occlusion due to stent implantation (also called in-stent restenosis). When the intima is damaged, the blood vessel undergoes remodeling, whereby smooth muscle cells in the media multiply and result in the blocking of the vessel wall. While adventitial cells are also known to contribute to this process, how and to what extent they do so remains unknown.

"Neointima formation is a major complication of vascular disorders and stent implantations," says lead author of the study Assistant Professor Kenichi Kimura. "Because they contribute to the overall morbidity and mortality of patients, it's important to understand the mechanism leading to neointima formation, so we can provide a therapeutic approach to patients. The role of the media in neointima formation has been heavily studied in the past. Therefore, in this study we wanted to understand how adventitial cells may contribute to it."

To achieve their goal, the researchers used lineage tracing and marked PDGFRa+ cells of mice with a fluorescent protein. By doing so, they were able to identify and track cell populations and their progeny over time. To understand how PDGFRa+ cells contribute to neointima formation, the researchers applied three different types of injury to blood vessels of mice: Carotid artery ligation (tying off the major blood vessel in the neck), denudation (using a wire to injure the blood vessel from within) and pressure overload (tying off the aorta to increase the blood pressure in the vessels arising from the aorta).

Intriguingly, the researchers found that the responses of the PDGFRa+ cells differed depending on the type of injury. While these cells populated the neointima slowly and developed into immature vessel muscle cells after carotid artery ligation, this process was accelerated in the case of denudation injury and PDGFRa+ cells developed into mature vessel smooth muscle cells. Furthermore, after pressure overload injury, PDGFRa+ cells proliferated in the adventitia and produced connective tissue there.

"These are striking results that show how PDGFRa+ cells exhibit a context-dependent response to vascular injuries. We hope that our findings may help provide a new therapeutic avenue for patients affected by neointima formation and vessel occlusion," says Professor Hiromi Yanagisawa.

Networks offer a powerful way to visualize and analyze complex systems. However, depending on the size and complexity of the network, many visualizations are limited. Protein interactions in the human body constitute such a complex system that can hardly be visualized. Jörg Menche, Adjunct Principal Investigator at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Professor at the University of Vienna and research group leader at Max Perutz Labs (Uni Wien/MedUni), and his team developed an immersive virtual reality (VR) platform that solves this problem. With the help of VR visualization of protein interactions, it will be possible in the future to better recognize correlations and identify those genetic aberrations that are responsible for rare diseases.

The larger and more complex networks are, the more difficult their visualization on the screen becomes. Conventional computer programs quickly reach their limits. This challenge was addressed by network scientist Jörg Menche and his research group at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences. They developed a VR platform for exploring huge amounts of data and their complex interplay in a uniquely intuitive fashion.

The body as a network

The representation of complex data can be particularly important in the search for the cause of rare diseases, because the human body, with its approximately 20,000 proteins that are encoded in the human genome and interact with each other, represents a huge complex network. Whether movement or digestion - at the molecular level, all biological processes are based on the interaction between proteins. If the protein interactions are illustrated in a network, a barely representable picture of about 18,000 dots - proteins - and about 300,000 lines between these dots will be created. Menche and his research group used the virtual reality (VR) platform they developed to make this image "readable" and, in collaboration with St. Anna Children's Cancer Research, succeeded in making the entirety of protein interactions visible for the first time. This makes it possible to interactively explore the vast and complex network.

Approaching the cause of rare immune diseases

For their study, published in Nature Communications, first author Sebastian Pirch and Menche's research group identified connection patterns between different protein complexes in the human body and linked them to their biological functions. In addition, the scientists used global databases to identify specific protein complexes associated with a particular disease. "While conventional forms of representation would look like a proverbial 'hairball', the 3-dimensional representation enables the precise analysis and observation of the different protein complexes and their interactions," says study author Pirch. This can be particularly important in the identification of rare genetic defects and crucial for therapeutic measures. "On the one hand, our study represents an important proof of concept of our VR platform; on the other hand, it directly demonstrates the enormous potential of visualizing molecular networks," says project leader Menche. "Especially in rare diseases, severe immune diseases, protein complexes associated with specific clinical symptoms can be analyzed in more detail to develop hypotheses about their respective pathobiological mechanisms. This facilitates the approach to disease causes and subsequently the search for targeted therapeutic measures."

About the VR platform

The platform developed by Menche's research group is designed for maximum flexibility and extensibility. Key features include the import of user-defined code for data analysis, easy integration of external databases, and a high degree of design freedom for arbitrary elements of user interfaces. The researchers were able to draw on technology normally used in the development of 3D computer games, such as the globally popular game Fortnite. By publishing the source code, the researchers hope to convince other developers of the potential of virtual reality for analyzing scientific data.

How can I prepare myself for something I do not yet know? Scientists from the Fritz Haber Institute in Berlin and from the Technical University of Munich have addressed this almost philosophical question in the context of machine learning. Learning is no more than drawing on prior experience. In order to deal with a new situation, one needs to have dealt with roughly similar situations before. In machine learning, this correspondingly means that a learning algorithm needs to have been exposed to roughly similar data. But what can we do if there is a nearly infinite amount of possibilities so that it is simply impossible to generate data that covers all situations?

This problem comes up a lot when dealing with an endless number of possible candidate molecules. Organic semiconductors enable important future technologies such as portable solar cells or rollable displays. For such applications, improved organic molecules - which make up these materials - need to be discovered. Tasks of this nature are increasingly using methods of machine learning, while training on data from computer simulations or experiments. The number of potentially possible small organic molecules is, however, estimated to be on the order of 1033. This overwhelming number of possibilities makes it practically impossible to generate enough data to reflect such a large material diversity. In addition, many of those molecules are not even suitable for organic semiconductors. One is essentially looking for the proverbial needle in a haystack.

In their work published recently in Nature Communications the team around Prof. Karsten Reuter, Director of the Theory Department at the Fritz-Haber-Institute, addressed this problem using so-called active learning. Instead of learning from existing data, the machine learning algorithm iteratively decides for itself which data it actually needs to learn about the problem. The scientists first carry out simulations on a few smaller molecules, and obtain data related to the molecules' electrical conductivity - a measure of their usefulness when looking at possible solar cell materials. Based on this data, the algorithm decides if small modifications to these molecules could already lead to useful properties or whether it is uncertain due to a lack of similar data. In both cases, it automatically requests new simulations, improves itself through the newly generated data, considers new molecules, and goes on to repeat this procedure. In their work, the scientists show how new and promising molecules can efficiently be identified this way, while the algorithm continues its exploration into the vast molecular space, even now, at this very moment. Every week new molecules are being proposed that could usher in the next generation of solar cells and the algorithm just keeps getting better and better.

In the brain, more than a hundred molecular substances act as transmitters that control communication pathways between nerve cells via thousands of different receptor types. In a review article, an international research team discusses how the activation of certain nerve cell receptors affects neuronal networks in the brain. The authors from Ruhr-Universität Bochum (RUB), Pompeu Fabra University in Barcelona and Oxford University present concepts to quantify receptor-specific modulations of brain states. They have also developed a computer model that can predict the impact of individual receptor types on brain activity.

In addition, the researchers show how the predictions obtained in the computer can be verified and refined by experimental methods. They hope this will lead to new ways of diagnosing and treating mental disorders. They report on their work and the current state of research in a State-of-the-Art Review in the FEBS Journal, published by the Federation of European Biochemical Societies in April 2021.

Simulating dynamics of brain states in a computer model

Much is already known about the molecular structure of neuronal receptors. But researchers know little about how individual receptor types modify holistic dynamics in the brain's networks. To simulate this in a computer model, the research team compiled data from three different imaging techniques: information on the anatomical connectivity in the brain, recorded with diffusion-weighted magnetic resonance imaging; information about resting-state activity of participants, obtained from measurements using functional magnetic resonance imaging, fMRI for short; and the distributions of receptor types, recorded with positron emission tomography. Using this input, the researchers were able to create an individual receptome for each subject reflecting the overall distribution of receptor types in the brain.

This enabled the researchers to simulate interactions between neurons dependent on activations of individual receptor types in the computer model. For example, they virtually activated the serotonin receptor 5-HT2A and observed the following changes in the in-silico model brain. "Activity patterns were surprisingly similar to those observed in the scanner after human subjects had been administered psilocybin or LSD - both psychedelic substances that specifically bind to the 5-HT2A receptor," explains Associate Professor Dr. Dirk Jancke, Head of the Bochum Optical Imaging Lab, lead author of the review article. The computer model was thus able to predict changes in the overall dynamics of the brain after activation of a single receptor type.

Testing predictions in experiments

Pharmacological substances are usually not specific to only one type of receptor; another drawback is that they can't be used to activate neurons locally in a targeted manner. This means that more complex predictions and tests on human subjects are only possible to a limited extent.

The authors therefore propose to refine their hypotheses by using optogenetic methods and to test them in animal experiments. The research group led by co-author Professor Stefan Herlitze from the Department of General Zoology and Neurobiology at RUB is one of the pioneers of this technique. Viral vectors are used to instruct cells to produce certain proteins. With this technique, gene-modified mice can, for example, be made to produce light-activated receptors and proteins that fluoresce when nerve cells are active.

In previous studies, the authors used the method for the first time to show how serotonin affects visual information processing. "Our results suggest that the 5-HT2A receptor suppresses current visual inputs," explains Dirk Jancke. "External stimuli thus become less important for the brain and, at the same time, internally occurring processes are relatively amplified. Hallucinations could have their cause in the fact that this imbalance has become too strong."

Prognosis, diagnosis and therapeutic potential

Mental illnesses are often based on dysfunctions of transmitter systems and, consequently, on changes in the activation of various receptors in the receptome. This is associated with specific modulations of brain states, which can manifest themselves in subtle changes in the dynamics of wide-spread and entangled neuronal networks in the brain. Through their research, the scientists hope to initiate new concepts using biomarkers to better diagnose and more specifically treat mental disorders. "Conceivable are specific pharmacological therapies and stimulation techniques in combination with concomitant psychiatric treatments, which help to learn new contexts to rebalance pathological brain states," says Jancke.

How primates get from A to B gives vital information about their cognitive evolution, say researchers in a new study looking at the travel paths of animals in the wild. Using data from 164 wild primate populations, the global survey examines the mental abilities that primates, including ourselves, use to know where and when to travel in the most efficient way.

A birds eye view

Co-author Miguel de Guinea, expert in Evolutionary Anthropology at Oxford Brookes University commented: "Imagine looking down on a huge outdoor market from high in the sky, perhaps from a drone hovering quietly above. The people below move in different ways. Some wander haphazardly among the stalls: they are learning what's available but are clearly not busy. Others take bee-line routes across the market to a destination they obviously wanted to reach, then, after buying what they need, head back in much the same way.

"If you could distinguish individuals, and watch them on many occasions, these patterns are likely to change, sometimes dependent on fruit and vegetables in season. We would also begin to learn about social aspects, as networks of repeated contacts show who is friendly with whom. We can get a good idea of people's knowledge, their needs, their ability to think ahead and how they learn over time - just from watching their travel paths. The same observations have been made by the research team using data from GPS devices and in-field studies of wild primates, giving us fascinating information about their development."

Travel decision-making adds to picture

The original data was gathered from small GPS devices, used routinely in primate fieldwork: sometimes these are attached to the animals themselves, but in many studies a researcher follows the animals, usually noting a rich variety of background information on what they are doing and for how long.

The international team developed a conceptual framework to highlight ways in which these data can be analysed. Currently, primate cognition is studied by comparing measures such as brain size, or conducting experiments with artificial problems to primates in captivity. The evidence from travel decision-making amongst wild populations will enhance these approaches and give a fuller picture of the cognitive development of these species.

An urgent vision for primate research

Lead-author Karline Janmaat from the University of Amsterdam said: "Our ultimate dream is to set up a consortium to support data sharing and collaboration among primatologists. Hopefully this attracts MSc and PhD students from around the world to share and compare their collected data to these existing datasets."

The researchers say that further research is urgent, because so many species are now threatened with extinction in the wild. Since 1970, two-thirds of all vertebrate populations have been lost, and large, day-living animals like primates have been significantly impacted.

Miguel de Guinea stressed: "Time is fast running out - if we don't act now we may never be able to understand the drivers of cognitive evolution. By applying our research methodology and findings we can make use of previously collected valuable data from wild populations and apply that to our understanding of the cognitive evolution of primate species."

The research Using natural travel paths to infer and compare primate cognition in the wild is published in iScience.

An evolutionary biologist from the University of Bonn brought a new octopus species to light from depths of more than 4,000 meters in the North Pacific Ocean. The sensational discovery made waves in the media a few years ago. Researchers in Bonn have now published the species description and named the animal "Emperor dumbo" (Grimpoteuthis imperator). Just as unusual as the organism is the researchers' approach: in order to describe the new species, they did not dissect the rare creature, but instead used non-destructive imaging techniques. The results have now been published in the prestigious journal BMC Biology.

In the summer of 2016, Dr. Alexander Ziegler from the Institute of Evolutionary Biology and Ecology at the University of Bonn spent several months in the North Pacific aboard the research vessel SONNE. The crew lowered the steel basket to the seabed around 150 times in order to retrieve rocks, sediments, and living creatures. One organism in particular caused a media stir: a dumbo octopus. The animal, about 30 centimeters in size, was found in waters more than 4,000 meters deep. However, the octopus could not be recovered alive: "The deep-sea organism is not adapted to the environmental conditions of the ocean surface," Ziegler explains.

Dumbo octopuses are a group of deep-sea-dwelling octopuses that includes 45 species. The name is based on the flying elephant from the Walt Disney movie of the same name, who is made fun of because of his unusually large ears - the fins of the dumbo octopuses, which are on the sides of the head resemble these elephant ears. However, the dumbo on the research vessel SONNE differed significantly from the known octopus species. "It was clear to me straight away that we had caught something very special," the biologist reports. So Ziegler immediately photographed the unusual animal, took a small tissue sample for DNA analysis, and then preserved the octopus in formalin.

Together with his former master's student Christina Sagorny, Ziegler has now published a description of the previously unknown species. Just as unusual as the octopus was the methodology used. The animals are usually dissected by zoologists, as the internal organs are also important for the description of a new species. "However, as this octopus is very valuable, we were looking for a non-destructive method," explains the researcher.

High-field MRI instead of scalpel

The eight-armed cephalopod therefore did not end up under the scalpel, but in the high-field magnetic resonance imaging system of the German Center for Neurodegenerative Diseases (DZNE) in Bonn. This device is routinely used to image test persons' brains. Thankfully, Dr. Eberhard D. Pracht from the DZNE agreed to conduct a high-resolution scan of the dumbo octopus in 3D. As part of her master's thesis, Christina Sagorny then investigated whether high-field MRI can be used to study internal organs and other soft tissues just as well as through conventional dissection. "The quality is actually even better," Ziegler says.

One of the few exceptions: the beak and rasping tongue (radula) of the cephalopod are made of hard chitin that does not image well using MRI. The biologists therefore also consulted the micro-computed tomography system of the paleontologists at the University of Bonn. This technique showed the beak and radula razor-sharp and in 3D. "These hard part structures are an integral part of the species description of octopuses," Ziegler explains. The researchers also decoded the animal's genetic material to reconstruct the family relationships. Ziegler: "The DNA showed beyond a doubt that we were looking at a species of the genus Grimpoteuthis."

Examination of the reproductive organs revealed the dumbo octopus to be an adult male. Compared to other species of this genus, it displays several special characteristics. For example, an average of 71 suckers were detected on each arm, which the animal needs to catch prey and which reflect body size. The length of the cirri, which are small appendages on the arms that the deep-sea animals presumably use to sense their prey, also differs from species already known.

The web that stretches between the arms, with which the dumbo slowly floats down in the water column, catching worms and crustaceans as if in a bell, also only reaches just over halfway from the mouth down the arms. "The web is much longer in dumbo octopus species that mainly float freely in the water column," Ziegler says. This would indicate that the new species lives close to the seafloor, because otherwise the web would be a hindrance to movements on the bottom.

As the species-describing researchers, Sagorny and Ziegler had the privilege of naming the new species: they decided on Grimpoteuthis imperator - in English "Emperor dumbo". Background: the animal was discovered not far from Japan in an underwater mountain range whose peaks are named after Japanese emperors.

Digital copy of the organism

The combination of non-destructive methods produced a crisp digital copy of the animal. Anybody interested can download it from the online database "MorphoBank" for further research and learning purposes. The preserved octopus itself is kept in the archives of the Museum für Naturkunde in Berlin, Germany. "There, it can then still be analyzed 100 years from now, for example when more modern investigation methods or new questions arise," Ziegler explains. "Our non-destructive approach could set a precedent, especially for rare and valuable animals," said the Bonn-based evolutionary biologist.

There are many different types of cancer, but they all have one thing in common: errors in the signals that control normal cell behaviour can cause uncontrolled cell growth and cell division, leading to a tumour. An enzyme called SHP2 plays a key role in this regard. SHP2 is a signalling molecule that in its activated state stimulates cell proliferation. In a normal healthy body, the rates of cell proliferation and cell death are balanced and tumours do not develop. However, if SHP2 becomes too active, the number of cells being created outweighs the number that die, which can lead to the formation of dangerous tumours. Enhanced SHP2 activity resulting from genetic mutations has been shown to play a central role in a number of types of leukaemia.

'It would be of immense value if we could effectively inhibit the SHP2 protein. But if you want to inhibit something, you first have to find out how it is activated,' says Jochen Hub, explaining the issue at the core of this long-standing scientific puzzle. Hub, Professor of Theoretical Physics at Saarland University, specializes in molecular dynamics simulations and his group develops computer models of biological processes. Hub and his research colleague Dr. Massimiliano Anselmi, who is the lead author of the research paper, have been able to simulate the SHP2 activation mechanism.

The two researchers made a surprising discovery: 'Over the last twenty years, there has been a consensus amongst experts that SHP2 is activated when a closed binding pocket on the SHP2 protein opens when a peptide docks onto this binding site.' A simple comparison would be opening a closed door (the 'binding pocket' or 'binding cleft' as it is also known) with a key (the peptide). However, no one has managed to produce clear experimental evidence that confirms this theoretical conjecture.

'We've now been able to show that the model simply isn't right', explains Jochen Hub. 'It turns out that the binding pocket is not actually closed, and so cannot be opened by the peptide.' The sophisticated simulations carried out by the Saarbrücken research team show that it is in fact other structures in the SHP2 molecule that open in the presence of the peptide. These flexible structures, known as beta sheets, play the role that scientists had for so long erroneously attributed to the binding pocket. When the peptide 'key' is 'inserted', the beta sheets open, changing the shape of the SHP2 molecule and thus causing it to become activated.

'This finding is of considerable significance. Because we now know that the binding pocket is not the crucial site for SHP2 activation, it may be possible to develop much more targeted agents that can prevent the activation of SHP2,' says Jochen Hub when describing the consequences of decoding the activation mechanism. As a result of this research work, Hub and particularly Massimiliano Anselmi have now opened the door for novel therapeutic approaches to treating certain forms of cancer. The Saarbrücken simulation specialists are hoping to collaborate with experimental teams to corroborate their findings.

Researchers at the University of Cincinnati say a regulatory protein found in skeletal muscle fiber may play an important role in the body's fight or flight response when encountering stressful situations.

The protein, fast skeletal myosin binding protein-C (fMyBP-C), plays a foundational role in the proper regulation of contractile structure and function in the body's fast twitch muscles -- these muscles produce sudden bursts of power to sprint into action, jump or lift heavy objects. Fast skeletal myosin binding protein-C modulates the speed and force of fast skeletal muscle contraction.

"This response is very critical for the higher animal and human survival. Just imagine, you are walking through a forest and suddenly you see a tiger in front of you," says Sakthivel Sadayappan, PhD, a professor in the UC Division of Cardiovascular Health and Disease. "You will immediately act, either to fight or run away from the animal. For that action, fast muscle is essential, and fast myosin binding protein-C is the key molecule to regulate the speed of action."

Myosin-binding protein-C is a thick filament regulatory protein found in striated muscle in both the heart and skeletal system. The protein performs different functions in the two organs, regulating contractility in the heart and playing a role in the development of fast and slow muscle fibers in skeletal muscle tissue.

Sadayappan along with researchers at UC College of Medicine, Florida State University, the University of Massachusetts Medical School and the Illinois Institute of Technology published research in the scholarly journal PNAS to further the understanding of the protein in skeletal function and regulation. Their findings are available online.

The study's lead author is Taejeong Song, PhD, a postdoctoral fellow in the Sadayappan Lab at the UC College of Medicine.

Song says that research examined the role of the protein in fast-twitch muscles by generating a knockout mouse--an animal in which researchers have either inactivated, replaced or disrupted the existing fast myosin binding protein-C gene to study its impact.

"We found that knockout mice demonstrated a reduced ability to exercise, showed less maximal muscle force and a diminished ability for muscle to recover from injury," explains Sadayappan. "Our study concludes that fast myosin binding protein-C is essential in regulating the force generation and speed of contraction of fast muscles."

Song says advancing the knowledge of fast myosin binding protein-C may someday assist in addressing skeletal muscular disorders.

"Individuals lose their ability of muscle force generation for various reasons," says Song. "They may be extremely inactive or hospitalized for long periods of time. Aging may also be the cause for some. We also think if we can manipulate the workings of fast myosin binding protein-C in skeletal muscle that we can prevent or at least slow down the loss of muscle function in genetic muscle disease such as distal arthrogryposis. Our research is trying to figure out this problem in human health."