Tech

MISSOULA - Only an anthropologist would treasure millennia-old human feces found in dry caves.

Just ask Dr. Meradeth Snow, a University of Montana researcher and co-chair of UM's Department of Anthropology. She is part of an international team, led by the Harvard Medical School-affiliated Joslin Diabetes Center, that used human "paleofeces" to discover that ancient people had far different microorganisms living in their guts than we do in modern times.

Snow said studying the gut microbes found in the ancient fecal material may offer clues to combat diseases like diabetes that afflict people living in today's industrialized societies.

"We need to have some specific microorganisms in the right ratios for our bodies to operate effectively," Snow said. "It's a symbiotic relationship. But when we study people today - anywhere on the planet - we know that their gut microbiomes have been influenced by our modern world, either through diet, chemicals, antibiotics or a host of other things. So understanding what the gut microbiome looked like before industrialization happened helps us understand what's different in today's guts."

This new research was published May 12 in the prestigious journal Nature. The article is titled "Reconstruction of ancient microbial genomes from the human gut." Snow and UM graduate student Tre Blohm are among the 28 authors of the piece, who hail from institutions around the globe.

Snow said the feces they studied came from dry caves in Utah and northern Mexico. So what does the 1,000-year-old human excrement look like?

"The caves these paleofeces came from are known for their amazing preservation," she said. "Things that would normally degrade over time look almost brand new. So the paleofeces looked like, well, feces that are very dried out."

Snow and Blohm worked hands-on with the precious specimens, suiting up in a clean-room laboratory at UM to avoid contamination from the environment or any other microorganisms - not an easy task when the tiny creatures are literally in and on everything. They would carefully collect a small portion that allowed them to separate out the DNA from the rest of the material. Blohm then used the sequenced DNA to confirm the paleofeces came from ancient people.

The senior author of the Nature paper is Aleksandar Kostic of the Joslin Diabetes Center. In previous studies of children living in Finland and Russia, he and his partners revealed that kids living in industrialized areas - who are much more likely to develop Type 1 diabetes than those in non-industrialized areas - have very different gut microbiomes.

"We were able to identify specific microbes and microbial products that we believe hampered a proper immune education in early life," Kostic said. "And this leads later on to higher incidents of not just Type 1 diabetes, but other autoimmune and allergic diseases."

Kostic wanted to find a healthy human microbiome without the effects of modern industrialization, but he became convinced that couldn't happen with any modern living people, pointing out that even tribes in the remote Amazon are contracting COVID-19.

So that's when the researchers turned to samples collected from arid environments in the North American Southwest. The DNA from eight well-preserved ancient gut samples were compared with the DNA of 789 modern samples. Half the modern samples came from people eating diets where most food comes from grocery stores, and the remainder came from people consuming non-industrialized foods mostly grown in their own communities.

The differences between microbiome populations were striking. For instance, a bacterium known as Treponema succinifaciens wasn't in a single "industrialized" population's microbiome the team analyzed, but it was in every single one of the eight ancient microbiomes. But researchers found the ancient microbiomes did match up more closely with modern non-industrialized population's microbiomes.

The scientists found that almost 40% of the ancient microbial species had never been seen before. Kostic speculated on what caused the high genetic variability:

"In ancient cultures, the foods you're eating are very diverse and can support a more eclectic collection of microbes," Kostic said. "But as you move toward industrialization and more of a grocery-store diet, you lose a lot of nutrients that help to support a more diverse microbiome."

Moreover, the ancient microbial populations incorporated fewer genes related to antibiotic resistance. The ancient samples also featured lower numbers of genes that produce proteins that degrade the intestinal mucus layer, which then can produce inflammation that is linked with various diseases.

Snow and several coauthors and museum collection managers also led a project to ensure the inclusion of Indigenous perspectives in the research.

"This was a really vital part of the work that had to accompany this kind of research," she said. "Initially, we sent out multiple letters and emails and called the tribal historic preservation officers of the all the recognized tribes in the Southwest region. Then we met with anyone who was interested, doing short presentations and answering questions and following up with interested parties.

"The feedback we received was noteworthy, in that we needed to keep in mind that these paleofeces have to ties their ancestors, and we needed to be - and hopefully have been - as respectful as possible about them," she said.

"There is a long history of misuse of genetic data from Indigenous communities, and we strove to be mindful of this by meeting and speaking with as many people as possible to obtain their insights and perspectives. We hope that this will set a precedent for us as scientists and others working with genetic material from Indigenous communities past and present."

Snow said the research overall revealed some fascinating things.

"The biggest finding is that the gut microbiome in the past was far more diverse than today - and this loss of diversity is something we are seeing in humans around the world," she said. "It's really important that we learn more about these little microorganisms and what they do for us in our symbiotic relationships.

"In the end, it could make us all healthier."

Scientists are exploring a number of ways for people with disabilities to communicate with their thoughts. The newest and fastest turns back to a vintage means for expressing oneself: handwriting.

For the first time, researchers have deciphered the brain activity associated with trying to write letters by hand. Working with a participant with paralysis who has sensors implanted in his brain, the team used an algorithm to identify letters as he attempted to write them. Then, the system displayed the text on a screen - in real time.

The innovation could, with further development, let people with paralysis rapidly type without using their hands, says study coauthor Krishna Shenoy, a Howard Hughes Medical Institute Investigator at Stanford University who jointly supervised the work with Jaimie Henderson, a Stanford neurosurgeon.

By attempting handwriting, the study participant typed 90 characters per minute - more than double the previous record for typing with such a "brain-computer interface," Shenoy and his colleagues report in the journal Nature on May 12, 2021.

This technology and others like it have the potential to help people with all sorts of disabilities, says Jose Carmena, a neural engineer at the University of California, Berkeley, who was not involved in the study. Though the findings are preliminary, he says, "it's a big advancement in the field."

Brain-computer interfaces convert thought into action, Carmena says. "This paper is a perfect example: the interface decodes the thought of writing and produces the action."

Thought-powered communication

When an injury or disease robs a person of the ability to move, the brain's neural activity for walking, grabbing a cup of coffee, or speaking a sentence remain. Researchers can tap into this activity to help people with paralysis or amputations regain lost abilities.

The need varies with the nature of the disability. Some people who have lost the use of their hands can still use a computer with speech recognition and other software. For those who have difficulty speaking, scientists have been developing other ways to help people communicate.

In recent years, Shenoy's team has decoded the neural activity associated with speech in the hopes of reproducing it. They have also devised a way for participants with implanted sensors to use their thoughts associated with attempted arm movements to move a cursor on a screen. Pointing at and clicking on letters in this way let people type about 40 characters per minute, the previous speed record for typing with a brain computer interface (BCI).

No one, however, had looked at handwriting. Frank Willett, a neuroscientist in Shenoy's group, wondered if it might be possible to harness the brain signals evoked by putting pen to paper. "We want to find new ways of letting people communicate faster," he says. He was also motivated by the opportunity to try something different.

The team worked with a participant enrolled in a clinical trial called BrainGate2, which is testing the safety of BCIs that relay information directly from a participant's brain to a computer. (The trial's director is Leigh Hochberg, a neurologist and neuroscientist at Massachusetts General Hospital, Brown University, and the Providence VA Medical Center.) Henderson implanted two tiny sensors into the part of the brain that controls the hand and arm, making it possible for the person to, for example, move a robotic arm or a cursor on a screen by attempting to move their own paralyzed arm.

The participant, who was 65 years old at the time of the research, had a spinal cord injury that left him paralyzed from the neck down. Using signals the sensors picked up from individual neurons when the man imagined writing, a machine learning algorithm recognized the patterns his brain produced with each letter. With this system, the man could copy sentences and answer questions at a rate similar to that of someone his age typing on a smartphone.

This so-called "Brain-to-Text" BCI is so fast because each letter elicits a highly distinctive activity pattern, making it relatively easy for the algorithm to distinguish one from another, Willett says.

A new system

Shenoy's team envisions using attempted handwriting for text entry as part of a more comprehensive system that also includes point-and-click navigation, much like that used on current smartphones, and even attempted speech decoding. "Having those two or three modes and switching between them is something we naturally do," he says.

Next, Shenoy says, the team intends to work with a participant who cannot speak, such as someone with amyotrophic lateral sclerosis, a degenerative neurological disorder that results in the loss of movement and speech.

The new system could potentially help those suffering from paralysis caused by a number of conditions, Henderson adds. Those include brain stem stroke, which afflicted Jean-Dominique Bauby, the author of the book The Diving Bell and the Butterfly. "He was able to write this moving and beautiful book by selecting characters painstakingly, one at a time, using eye movement," Henderson says. "Imagine what he could have done with Frank's handwriting interface!"

What The Study Did: This survey study estimated the number of children and adolescents in the United States who have received medical care as a result of assault, abuse or exposure to violence.

Authors: David Finkelhor, Ph.D., of the University of New Hampshire in Durham, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.9250)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

HOUSTON - The mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) plays an important and previously unknown role in blocking a form of cell death called ferroptosis, according to a new study published today in Nature by researchers at The University of Texas MD Anderson Cancer Center. Preclinical findings suggest that targeting DHODH can restore ferroptosis-driven cell death, pointing to new therapeutic strategies that may be used to induce ferroptosis and inhibit tumor growth.

"By understanding ferroptosis and how cells defend against it, we can develop therapeutic strategies to block those defense mechanisms and trigger cell death," said senior author Boyi Gan, Ph.D., associate professor of Experimental Radiation Oncology. "We have discovered that DHODH plays a key role in defending against ferroptosis and shown that we can exploit this vulnerability with clinically tested therapies."

Ferroptosis is a recently identified form of controlled cell death triggered by the toxic accumulation of lipid peroxides in the cell. Because lipid peroxides are generated through normal metabolic activities, cells also have mechanisms in place to defend against ferroptosis. Glutathione peroxidase 4 (GPX4) is one of the key defense mechanisms identified to date.

In this study, the researchers used GPX4 inhibitors to block its activity and to identify new defense mechanisms. Metabolic analyses pointed them to DHODH, a mitochondrial enzyme that normally is involved in the pyrimidine biosynthesis pathway.

In cells with low GPX4 expression, loss of DHODH activity led to the accumulation of lipid peroxides in mitochondria and the activation of ferroptosis. By contrast, cells with high GPX4 expression were able to continue blocking ferroptosis activity in the absence of DHODH. The findings suggest that DHODH and GPX4 work as redundant defense mechanisms in the mitochondria to prevent ferroptosis.

The researchers further clarified DHODH's role in regulating ferroptosis and then investigated the therapeutic potential of targeting this enzyme in cancer cells. Using extensive preclinical models, they evaluated the DHODH inhibitor brequinar, which has been tested in multiple clinical trials for other indications.

In GPX4-low cancers, brequinar effectively induced ferroptosis and suppressed tumor growth, but the effects were not seen in GPX4-high cancers. However, the combination of brequinar and sulfasalazine, an FDA-approved ferroptosis inducer, resulted in a synergistic effect to overcome high GPX4 expression and to block tumor growth.

"We were able to leverage our understanding of a new ferroptosis defense mechanism into a novel therapeutic strategy that appears promising in preclinical studies," Gan said. "Because ferroptosis is active across cancer types, we believe this could have broad implications, particularly in cancers with low expression of GPX4."

Long-lasting, quick-charging batteries are essential to the expansion of the electric vehicle market, but today's lithium-ion batteries fall short of what's needed -- they're too heavy, too expensive and take too long to charge.

For decades, researchers have tried to harness the potential of solid-state, lithium-metal batteries, which hold substantially more energy in the same volume and charge in a fraction of the time compared to traditional lithium-ion batteries.

"A lithium-metal battery is considered the holy grail for battery chemistry because of its high capacity and energy density," said Xin Li, Associate Professor of Materials Science at the Harvard John A. Paulson School of Engineering and Applied Science (SEAS). "But the stability of these batteries has always been poor."

Now, Li and his team have designed a stable, lithium-metal solid state battery that can be charged and discharged at least 10,000 times -- far more cycles than have been previously demonstrated --- at a high current density. The researchers paired the new design with a commercial high energy density cathode material.

This battery technology could increase the lifetime of electric vehicles to that of the gasoline cars -- 10 to 15 years -- without the need to replace the battery. With its high current density, the battery could pave the way for electric vehicles that can fully charge within 10 to 20 minutes.

The research is published in Nature.

"Our research shows that the solid-state battery could be fundamentally different from the commercial liquid electrolyte lithium-ion battery," said Li. "By studying their fundamental thermodynamics, we can unlock superior performance and harness their abundant opportunities."

The big challenge with lithium-metal batteries has always been chemistry. Lithium batteries move lithium ions from the cathode to the anode during charging. When the anode is made of lithium metal, needle-like structures called dendrites form on the surface. These structures grow like roots into the electrolyte and pierce the barrier separating the anode and cathode, causing the battery to short or even catch fire.

To overcome this challenge, Li and his team designed a multilayer battery that sandwiches different materials of varying stabilities between the anode and cathode. This multilayer, multimaterial battery prevents the penetration of lithium dendrites not by stopping them altogether but rather by controlling and containing them.

Think of the battery like a BLT sandwich. First comes the bread -- the lithium metal anode -- followed by lettuce -- a coating of graphite. Next, a layer of tomatoes -- the first electrolyte -- and a layer of bacon -- the second electrolyte. Finish it off with another layer of tomatoes and the last piece of bread -- the cathode.

The first electrolyte (chemical name Li5.5PS4.5Cl1.5 or LPSCI) is more stable with lithium but prone to dendrite penetration. The second electrolyte, (Li10Ge1P2S12 or LGPS) is less stable with lithium but appears immune to dendrites. In this design, dendrites are allowed to grow through the graphite and first electrolyte but are stopped when they reach the second. In other words, the dendrites grow through the lettuce and tomato but stop at the bacon. The bacon barrier stops the dendrites from pushing through and shorting the battery.

"Our strategy of incorporating instability in order to stabilize the battery feels counterintuitive but just like an anchor can guide and control a screw going into a wall, so too can our multilayer design guide and control the growth of dendrites," said Luhan Ye, co-author of the paper and graduate student at SEAS. "The difference is that our anchor quickly becomes too tight for the dendrite to drill through, so the dendrite growth is stopped," Li added.

The battery is also self-healing; its chemistry allows it to backfill holes created by the dendrites.

"This proof-of-concept design shows that lithium-metal solid-state batteries could be competitive with commercial lithium-ion batteries," said Li. "And the flexibility and versatility of our multilayer design makes it potentially compatible with mass production procedures in the battery industry. Scaling it up to the commercial battery wont' be easy and there are still some practical challenges, but we believe they will be overcome."

The human brain is a vast network of billions of biological cells called Neurons which fires electrical signals that process information, resulting in our sense and thoughts. The ion channels of atomic scale in each neuron cell membrane plays a key role in such firings that opens and closes the ion flow in an individual cell by the electrical voltage applied across the cell membrane, acting as a "biological transistor" similar to electronic transistors in computers. For decades, scientists have learned that biological ion channels are life's transistors capable to gate extremely fast and precisely selective permeation of ions through the atomic-scale selectivity filters to maintain vital living functions. However, it remains a grand challenge to date to produce artificial structures to mimic such biological systems for fundamental understanding and practical applications.

Researchers led by Professor Xiang Zhang, the President of the University of Hong Kong (HKU), have developed an atomic-scale ion transistor based on electrically gated graphene channels of around 3 angstrom width which demonstrated highly selective ion transport. They also found that ions move a hundred times faster in such a tiny channel than they do in bulk water.

This breakthrough, recently reported in Science, not only provides fundamental understanding of fast ion sieving in atomic scale, but also leads to highly switchable ultrafast ion transport that can find important applications in electrochemical and biomedical applications.

"This innovative ion transistor demonstrates electrically switching of ultrafast and simultaneously selective ion transport through atomic-scale channels like biological ion channels functioning in our brain," said principle investigator Professor Xiang Zhang. "It deepens our fundamental understanding of ion transport at ultrasmall limit and will significantly impact important applications such as sea water desalination and medical dialysis."

The development of artificial ion channels using traditional pore structures has been hindered by the trade-off between permeability and selectivity for ion transport. Pore sizes exceeding the diameters of hydrated ions render ion selectivity largely vanished. Elevated selectivity of monovalent metal ions can be achieved with precisely controlled channel dimension at the angstrom scale. However, these angstrom-scale channels significantly preclude the fast diffusion due to steric resistance for hydrated ions to enter narrower channel space.

"We observed ultrafast selective ion transport through the atomic scale graphene channel with an effective diffusion coefficient as high as Deff ? 2.0´10-7 m2/s." said study lead author Yahui Xue, a former postdoctoral researcher in Professor Zhang's group. "To the best of our knowledge, this is the fastest diffusion observed in concentration-driven ion permeation through artificial membranes and even surpasses the intrinsic diffusion coefficient observed in biological channels."

Scientists from Hong Kong and UC Berkeley first used gate voltage to control the surface potential of graphene channels and realized ultrahigh density of charge packing inside these channels. The neighboring charges exhibit strong electrostatic interaction with each other. This results in a dynamic charging equilibrium state so that the insertion of one charge from one end of the channel would lead to the ejection of another at the other end. The resultant concerted charge movement greatly enhances the overall transport speed and efficiency.

"Our in situ optical measurements revealed a charge density as high as 1.8´1014 /cm2 at the largest applied gate voltage." said Yang Xia, a former PhD student in Professor Zhang's group. "It is surprisingly high, and our mean field theoretical modeling suggests the ultrafast ion transport is attributed to highly dense packing of ions and their concerted movement inside the graphene channels."

The atomic-scale ion transistor has also demonstrated superior switching capability, similar to that in biological channels, originating from a threshold behavior induced by the critical energy barrier for hydrated ion insertion. The smaller channel size than the hydration diameters of alkali metal ions creates an intrinsic energy barrier that forbids ion entry in the open circuit condition. By applying gating electric potential, the hydration shell could be distorted or partially striped off to overcome the ion-entry energy barrier, enabling ion intercalation and eventually permeable ion transport beyond a percolation threshold.

The atomic scale graphene channel was made of a single flake of reduced graphene oxide flake. This configuration has the advantage of intact layer structures for fundamental property investigation and also preserves large flexibility for scaling-up fabrication in the future.

The selection sequence of alkali metal ions through the atomic-scale ion transistor was found to resemble that of biological potassium channels. This also implies a controlling mechanism similar to biological systems, which combines ion dehydration and electrostatic interaction.

This work is a fundamental breakthrough in the study of ion transport through atomic scale solid pores. The integration of the atomic-scale ion transistors into large-scale networks can even make it possible to produce exciting artificial neural systems and even brain-like computers.

Strawberry production is one of the driving forces in the Spanish agriculture sector, as strawberries are highly valued for their organoleptic characteristics and health benefits. These two factors, their economic relevance, and the value that consumers assign them, make this fruit an object of scientific research from multiple perspectives, including that of food safety. A research project headed by Liliana Pérez-Lavalle, Elena Carrasco, Pedro Vallesquino-Laguna, Manuel Cejudo, Guiomar Denisse Posada and Antonio Valero has aimed to evaluate whether the Salmonella Thompson bacteria, one of the pathogens that can contaminate the fruit through sewage and/or the soil, could penetrate through the roots of strawberry plants (specifically, the 'San Andreas' variety) and reach the fruit.

For the study, several groups of strawberries were subjected to water contaminated with the pathogen at different levels of inoculation. The roots, leaves and fruits were then analysed, finding a very low proportion even in those that had received the greatest amount of contaminated water. In this way it was determined that access from the root to the edible zone is not a significant entry route for the pathogen. It was also determined that drip irrigation is more effective in preventing contamination than sprinkler irrigation, as the former prevents direct contact between the water and fruit, thus tending to avert both product contamination and deterioration. "An excess of humidity in the fruit due to contact with water can cause the proliferation of mould, resulting in rotting", explained the group's researchers.

The reason why the Salmonella bacterium was researched is its high degree of survival in products made from strawberries and its durability, being able to exist in wastewater and soil for periods of more than eight months. It has a great capacity to adapt to different conditions of environmental stress, such as the acidic pH of some fruits.

The research group concluded that there is also a greater possibility of surface contamination of strawberries, which can occur during harvesting, when workers do not comply with the corresponding hygienic measures, or due to the fruit coming into contact with contaminated surfaces. They stress that most strawberries are not washed, in order to prevent deterioration due to mould, which is why it is particularly important that consumers, as the last link in the chain, make sure that they do wash this fruit prior to consumption.

Central to any technological progress is the enrichment of human life. The internet and wireless connectivity have done that by allowing not only virtually anyone anywhere to connect real time, but by making possible connections between humans and a range of intelligent devices both indoors and outdoors, putting smart cities on the horizon.

One key aspect of realizing smart cities is "smart vehicles", the latest development in intelligent transportation systems (ITS), which involve the integration of communication, mapping, positioning, network, and sensor technologies to ensure cooperative, efficient, intelligent, safe, and economical transportation.

For decades, research on bringing to the streets smart vehicles that operate successfully as part of smart city infrastructure has focused on improving computing paradigms for vehicular network connectivity. Over the past 30 years, vehicular ad-hoc network (VANET), a framework where vehicles self-organize themselves to provide essential services related to road safety, has been in stable development. However, with the advent of 5G networks, VANET is soon giving way to the internet of vehicles (IoV), a novel vehicular environment with more powerful infrastructures.

"VANET was primarily conceived to inform drivers about harsh conditions or emergencies happening nearby. IoV, on the other hand, uses artificial intelligence (AI) technology to provide higher-level services such as information about traffic jams based on user location and personal preferences," explains Dr. Naercio Magaia of the University of Lisbon, Portugal, who works on computer networks and AI, and who with a global team, has recently scoped out computing paradigms that are shaping emerging vehicular environments. Their research is published in IEEE/CAA Journal of Automatica Sinica.

IoV is in the nascent stages and there are certain crucial aspects to consider. For instance, how many different services and devices can be included in an IoV framework? How can we ensure that a user can access information most relevant to them with the least delay? And of course, how to secure a heterogeneous network with a variety of devices?

In their analysis, Dr. Magaia and team find that to naturally solve these problems, broadly, two main types of computing paradigms must be integrated and improved upon: 1) vehicular cloud computing (VCC), which is similar to cloud computing (delivery of computing services, including servers, storage, databases, networking, software, and intelligence, over the internet or "cloud"), except here, the vehicles function as the "cloud" or a "computational cluster"; and 2) vehicular fog computing (VFC), in which the computing entities (nodes) are either distributed as roadside units (RSU)--infrastructures deployed to extend vehicle coverage and network performance--or the vehicles themselves.

There are advantages and disadvantages to both these paradigms. While VCC has all the benefits of general cloud computing and is good for traffic jam situations, it is costly to apply and suffers from high network delay due to the fact that the location of the overall system is remote, making it inadequate for real-time applications. VFC, on the other hand, is cost-effective and allows real-time services because the nodes are close to the user where the service is required. It is also adaptable to a variety of requirements but lacks adequate security and convenient wireless protocols.

Dr. Magaia and team argue that for intelligent vehicular networks to be truly integrated with smart cities in real-time applications, these two paradigms must complement one another. For instance, during a traffic congestion, the vehicles can from a cloud while performing fog node computations simultaneously. Moreover, the union of next generation technological elements such as software-defined networking, 6G mobile networks, and serverless computing, with these paradigms is where the future lies.

"We believe that by 2050, with such research, billions of devices will form an internet-of-everything (IoE)," says Dr. Magaia, speaking of his vision. "Future safer driving is imperative. This kind of research is expected to revolutionize how the driver and traffic relationship around the world works. Vehicles will be "smarter", giving more comfort to the driver and passengers. From a social perspective, vehicles become an extension of the drivers' individuality, embedded in everyday life just as smartphones are after almost 12 years of existence as we know them."

These times that Dr. Magaia envisions may not be too far!

The field of magnonics offers a new type of low-power information processing, in which magnons, the quanta of spin waves, carry and process data instead of electrons. The end goal of this field is to create magnonic circuits, which would be smaller and more energy-efficient than current electronic ones.

Until recently, the development of a functional magnonic device could take years of trial-and-error. Researchers from the University of Vienna and the TU Kaiserslautern have developed a new computational method to design new devices in a considerably shorter time. Moreover, the efficiency added through this novel inverse design method helps overcome a traditional problem with such devices: they were just suitable for one function only. Now, thanks to the proposed new concept, a primary device could, in principle, be easily modified to perform any function.

Qi Wang, the first author of the study published in Nature Communications, suggested adopting a method that had been used in the field of photonics to magnonics, where the approach has proven to work even better. Three basic principles help to explain the process, as is shown in the figure. First the researchers decide on the functionalities of the device they want to design e.g. a Y-circulator, one of the most common components for separating signal directions in systems engineering. This device guides spin waves from one port into another port according to the circulation condition: wave from port 1 should go into port 2, wave from port 2 into port 3 and from port 3 into port 1. Second, this "task" is translated into a computer language. Finally, the computer generates random structures and optimizes them step-by-step to reach the required functionality. This trial-and-error process is carried out at a very high speed and attains the best solution thanks to an intelligent algorithm. The end result is a design of a working device with the functionalities envisaged by the researchers. This, as Wang from the University of Vienna puts it: "[...] opens the door to large scale magnonic integrated circuits, with any functionality and a high level of complexity".

The proposed approach overcomes the hurdle of designing through experimentation and, instead, emphasizes the importance of researchers' imagination, who fix the parameters and objectives for the computer-designed devices. An example of this creative process comes from Philipp Pirro, scientist at the TU Kaiserslautern: "With inverse-design one could develop neurons like the ones in our brain, but made out of magnonic elements instead."

The excitement about the possibilities of this approach comes from its capacity to create different functionalities. In their article, the scientists describe how they created a set of different devices. Thus, besides the mentioned Y-circulator, they realized a "multiplexer" that separates a wave with a specific frequency into one channel and a wave of another frequency into another channel. This kind of devices is used in our everyday life to get fast internet. The final demonstrated device is a "non-linear switch" that separates spin waves of different energies: it sends a wave of low power to one output and a wave of high power to another. However, Andrii Chumak, head of the research group at the University of Vienna, points out: "Our study opens the new field of inversed design magnonics with great perspectives. This approach, for now, has been demonstrated numerically only. The next big challenge is to implement it in experiments."

Reflecting on the potential of their findings, Qi Wang jokes: "If I would have had the inverse design approach at the beginning of my studies, I would have finished my PhD way faster!"

The multiplexing capability of fluorescence microscopy is severely limited by the broad fluorescence spectral width. Spectral imaging offers potential solutions, yet typical approaches to disperse the local emission spectra notably impede the attainable throughput and place substantial constraints on temporal resolution. Tunable bandpass filters provide a possibility to scan through the emission wavelength in the wide field. However, applying narrow bandpasses to the fluorescence emission results in inefficient use of the scarce signal.

In a new paper published in Light: Science & Application, a team of scientists, led by Professor Ke Xu from College of Chemistry, University of California, Berkeley, USA have demonstrated that using a single, fixed fluorescence emission detection band, through frame-synchronized fast scanning of the excitation wavelength from a white lamp via an acousto-optic tunable filter (AOTF), up to 6 subcellular targets, labeled by common fluorophores of substantial spectral overlap, can be simultaneously imaged in live cells with low (~1%) crosstalks and high temporal resolutions (down to ~10 ms). The demonstrated capability to quantify the abundances of different fluorophores in the same sample through unmixing the excitation spectra next enabled them to devise novel, quantitative imaging schemes for both bi-state and FRET (Förster resonance energy transfer) fluorescent biosensors in live cells. They thus achieved full-frame high sensitivities and spatiotemporal resolutions in quantifying the mitochondrial matrix pH and the intracellular macromolecular crowding. They thus unveiled significant spatial heterogeneities in both parameters, including spontaneous sudden jumps in the mitochondrial matrix pH accompanied by dramatic mitochondrial shape changes. They further demonstrated, for the first time, the multiplexing of absolute pH imaging with three additional target organelles/proteins to elucidate the complex, Parkin-mediated mitophagy pathway.

"The potential extension of our approach to even more fluorophores may be achieved by further increasing the number of excitation wavelengths or integrating emission dispersion" "Whereas in this work we focused on a facile system based on a lamp-operated epifluorescence microscope, the fast multi-fluorophore and quantitative biosensor imaging capabilities we demonstrated here should be readily extendable to other systems, including light-sheet fluorescence microscopy and structured illumination microscopy" the scientists discussed.

Together, these results "unveil the exceptional opportunities excitation spectral microscopy provides for highly multiplexed fluorescence imaging." "The prospect of acquiring fast spectral images in the wide-field without the need for fluorescence dispersion or the care for the spectral response of the detector offers tremendous potential."

A researcher at University of Limerick has developed a low-cost, environmentally friendly sensor that can detect damage in pipelines and could save water as a result.

The damage detection sensor uses highly sensitive, eco-friendly crystals that generate an electrical signal in response to a leak.

It is the first validation of these biological crystals for real world applications, according to Dr Sarah Guerin, a postdoctoral researcher at the Department of Physics and the Bernal Institute in UL, who has been developing amino acid crystal devices since 2017.

An Irish research collaboration between the Bernal Institute at UL and the Dynamical Systems and Risk Laboratory in University College Dublin has validated the crystal-based sensor.

The journal Cell Reports Physical Science has just published a study on the findings of the innovative research.

"The sensor is made of crystallised amino acids that are sensitive enough to detect leaks as small as 2mm," said Dr Guerin.

"Computer simulations show that they generate electricity in response to a force - such as strain or vibration - known as the piezoelectric effect.

"Biomolecular piezoelectric materials such as these offer an inexpensive, non-toxic and renewable alternative to current commercial piezoelectric devices, which rely on toxic heavy elements or require heavy processing," she explained.

Leak detection in fluid-carrying pipes is crucial for sustainable water access, and vibration-based techniques have proven to be effective at early detection of leak onset. Current commercial solutions are either battery powered, or if piezoelectric, very costly.

In addition, most commercial accelerometers have rigid structures, making them unsuitable for bonding to curved pipes, explained the UL researcher.

"This sensor has a number of advantages over current technologies," said Dr Guerin.

"It is flexible, cheap to make, and outperforms ceramics and polymers that are used in these structural health monitoring applications. The fabrication process is suitable for mass production of these devices," she added.

Professor Vikram Pakrashi of UCD, a senior author on the study who has developed extensive testing facilities for validating materials for structural health monitoring that simulate infrastructural damage in for example buildings and pipelines, said the findings of the research were significant.

"These amino-acid-based sensors will provide real-time sensing of pipe degradation, allowing for data-driven decision making on repair and maintenance, aiding in the global challenge of equitable water access," he explained.

"This is the first time such materials have been applied for real engineering problems and it has addressed one of the core challenges of our time - water," added Dr Favour Okosun of UCD, whose doctoral research created the application of this sensor.

In mathematics, simple equations can generate a complex evolution in time and intriguing patterns in space. One famous example of this is the Mandelbrot set, named after the French-American mathematician of Polish origin, Benoit B. Mandelbrot (1924-2010), the most studied fractal. This set is based on a single quadratic equation with only one parameter and one variable. The fascinating fractal patterns of the Mandelbrot set have attracted attention far beyond mathematics.

An article by Ralph Andrzejak, entitled "Chimeras confined by fractal boundaries in the complex plane", forms part of a special edition of the journal Chaos in memory of Russian professor Vadim S. Anishchenko, (1943-2020), published on 3 May 2021. Andrzejak is head of the Nonlinear Time Series Analysis Group at the UPF Department of Information and Communication Technologies (DTIC). The work generalizes the Mandelbrot set for four quadratic equations. The figure shown above is an example of the patterns generated through this approach.

A journey through many orders of magnitude

Andrzejak notes that "the complexity of fractal patterns can be seen when we get closer to increasingly small details", which the author illustrates in the image below. He explains the image by saying that "globally, the pattern shown in the top left panel of the figure resembles Mandelbrot's classic set. However, as soon as we inspect the details, we can see patterns that cannot be found in the Mandelbrot set. To see these details better, we magnify the square to produce the next panel".

"Iterative zoom in fractal patterns. From left to right and top to bottom, subsequent panels magnify the squares of the corresponding previous panels. The first figure above appears again, here as the fifth step in magnification.

The author uses a comparison to emphasize that these patterns are indeed at many orders of magnitude. He states that "the zoom applied to the twelve panels that make up the image corresponds to blowing up an atom to the size of an SUV car". "As we zoom in, increasing the size of the image, we see that there is a rich variety of aesthetically intriguing forms and shapes. The patterns we have discovered may seem less filigree and less ordered, but they can be more varied than those found in the Mandelbrot set".

Interaction of fractals and synchronization

But there is more than fractal patterns to approach Andrzejak's proposal. As the author uses four equations instead of one, he has also been able to study synchronization within these fractal patterns. How can we understand this? Andrzejak explains by saying "the Mandelbrot set is based on one equation with one parameter and one variable. We can imagine this variable as a small ball moving on the surface of a large round table. What happens to this ball depends on the parameter of the equation. For some values of this parameter, the ball moves and is always on the table. The set of all these parameter values for which the ball remains on the table is what defines the Mandelbrot set. On the contrary, for the remaining parameter values, the ball falls from the table at some point in time".

"If we study the basic mechanisms of partial synchronization in very simple models, this can help understand how it is established and how it can be kept stable in such complex systems as the human brain"

Andrzejak continues by saying that "one might think that the four equations we are using describe the movement of not only one, but four balls on the table surface. Since the equations are connected, the balls cannot move freely. However, they attract each other, like the sun, Earth and moon attract each other through gravity". The researcher adds that "as a result of this attraction, the four balls can show various forms of synchronization. The two extremes are: The four balls move together along the same paths or each ball follows its own path". Andrzejak then stresses that "most importantly, beyond these extremes, is finding so-called partial synchronization. For example, two balls can move in sync together, while the other two balls remain unsynchronized from this movement. This particular state of partial synchronization is called the chimera state", hence the title of the article.

A matter of great importance for the dynamics of the real world

If we ask ourselves whether the mathematical model in question can be relevant to the dynamics of the real world, Andrzejak responds "Yes. Absolutely. The best example is the brain. If all our neurons synchronized or went out of sync, our brain could no longer do its job. Our brain can only work properly if some neurons synchronize while other neurons remain out of sync. Partial synchronization is essential for the brain to work properly". The author relates this to his work saying: "we demonstrate how it is possible to establish partial synchronization in a very simple model and, moreover, we show how this partial synchronization is confined within the fractal limits through full synchronization and desynchronization". The author concludes: "If we study the basic mechanisms of partial synchronization in very simple models, this can help understand how it is established and how it can be kept stable in such complex systems as the human brain"

AdaptiFont has recently been presented at CHI, the leading Conference on Human Factors in Computing.

Language is without doubt the most pervasive medium for exchanging knowledge between humans. However, spoken language or abstract text need to be made visible in order to be read, be it in print or on screen.

How does the way a text looks affect its readability, that is, how it is being read, processed, and understood? A team at TU Darmstadt's Centre for Cognitive Science investigated this question at the intersection of perceptual science, cognitive science, and linguistics. Electronic text is even more complex. Texts are read on different devices under different external conditions. And although any digital text is formatted initially, users might resize it on screen, change brightness and contrast of the display, or even select a different font when reading text on the web.

The team of researchers from TU Darmstadt now developed a system that leaves font design to the user's visual system. First, they needed to come up with a way of synthesizing new fonts. This was achieved by using a machine learning algorithm, which learned the structure of fonts analysing 25 popular and classic typefaces. The system is capable of creating an infinite number of new fonts that are any intermediate form of others - for example, visually halfway between Helvetica and Times New Roman.

Since some fonts may make it more difficult to read the text, they may slow the reader down. Other fonts may help the user read more fluently. Measuring reading speed, a second algorithm can now generate more typefaces that increase the reading speed.

In a laboratory experiment, in which users read texts over one hour, the research team showed that their algorithm indeed generates new fonts that increase individual user's reading speed. Interestingly all readers had their own personalized font that made reading especially easy for them. However: This individual favorite typeface does not necessarily fit in all situations. "AdaptiFont therefore can be understood as a system which creates fonts for an individual dynamically and continuously while reading, which maximizes the reading speed at the time of use. This may depend on the content of the text, whether you are tired, or perhaps are using different display devices," explains Professor Constantin A. Rothkopf, Centre for Cognitive Science und head of the institute of Psychology of Information Processing at TU Darmstadt.

The AdaptiFont system was recently presented to the scientific community at the Conference on Human Factors in Computing Systems (CHI). A patent application has been filed. Future possible applications are with all electronic devices on which text is read.

Experts in virtual reality locomotion have developed a new resource that analyses all the different possibilities of locomotion currently available.

Moving around in a virtual reality world can be very different to walking or employing a vehicle in the real world and new approaches and techniques are continually being developed to meet the challenges of different applications.

Called Locomotion Vault, the project was developed by researchers at the Universities of Birmingham, Copenhagen, and Microsoft Research. It aims to provide a central, freely-available resource to analyse the numerous locomotion techniques currently available.

The aim is to make it easier for developers to make informed decisions about the appropriate technique for their application and researchers to study which methods are best. By cataloguing available techniques in the Locomotion Vault, the project will also give creators and designers a head-start on identifying gaps where future investigation might be necessary. The database is an interactive resource, so it can be expanded through contributions from researchers and practitioners.

Researcher Massimiliano Di Luca, of the University of Birmingham, said: "Locomotion is an essential part of virtual reality environments, but there are many challenges. A fundamental question, for example, is whether there should be a unique 'best' approach, or instead whether the tactics and methods used should be selected according to the application being designed or the idiosyncrasies of the available hardware. Locomotion Vault will help developers with these decisions."

The database also aims to address vital questions of accessibility and inclusivity. Both of these attributes were assessed in relation to each technique included in the Vault.

Co-researcher, Mar Gonzalez-Franco, of Microsoft Research, said: "As new and existing technologies progress and become a more regular part of our lives, new challenges and opportunities around accessibility and inclusivity will present themselves. Virtual reality is a great example. We need to consider how VR can be designed to accommodate the variety of capabilities represented by those who want to use it."

The research team are presenting Locomotion Vault this week at the online Conference on Human Factors in Computing Systems (CHI 2021).

"This is an area of constant and rapid innovation," says co-author Hasti Seifi, of the University of Copenhagen. "Locomotion Vault is designed to help researchers tackle the challenges they face right now, but also to help support future discoveries in this exciting field."

How to predict the sound produced by a tonewood block once carved into the shape of a violin plate? What is the best shape for the best sound? Artificial Intelligence offer answers to these questions.

These are the conclusions that researchers of the Musical Acoustics Lab of Politecnico di Milano presented in a study that was recently published in Scientific Reports.

In the article "A Data-Driven Approach to Violinmaking" the Chilean physicist and luthier Sebastian Gonzalez (post-doc researcher) and the professional mandolin player Davide Salvi (PhD student) show how a simple and effective neural network is able to predict the vibrational be-havior of violin plates. This prediction is obtained from a limited set of geometric and mechanical parameters of the plate.

The ability to predict the sound of a violin design, can truly be a game changer for violin makers, as not only will it help them do better than the "grand masters", but it will also help them explore the potential of new designs and materials. This research allowed us to take the first steps in this direction, showing how Artificial Intelligence, physical simulation and craftsmanship can all join forces to shed light on the art of violin making.

Violins are extremely complex objects, and their geometry is defined by their outline, arching on the horizontal and vertical sections. The inspira-tion of this study came from a historical drawing on display at the "Museo del Violino" in Cremona. Politecnico di Milano researchers developed a model that describes the violin's outline as the conjunction of arcs of nine circles. Thanks to this representation and an effi-cient model of the curvature of the plate, based on the renowned "Messi-ah" violin by Stradivarius, researchers were able to draw a violin plate as a function of 35 parameters.

By randomly changing such parameters, such as radii and center position of the circles, arching, thickness, mechanical characteristics of the wood, etc., they built a dataset of violins, which includes shapes that are very similar to those used in violin making, but also designs that had never been seen before. Such shapes constituted the input for the neural network.

Advanced tools for the modeling of vibrations were used for characterizing the acoustic behavior of each violin in the dataset.

The next step was to understand if a simple neural network would be able to predict the acoustic behavior of a violin plate, starting from its parame-ters. The answer turned out to be positive, with an accuracy that came close to 98%, exceeding any expectations.

This work offers an innovative and promising tool in the hands of Cremona violin makers and, in perspective, of the international community. By using a neural network, it will enable luthiers to predict how a tone-wood block will "sound" once carved into a plate. But it can also be used to design two violins with matching acoustic behavior even if built with different wood. In the future this research will allow us to select the best wood to be used for a particular violin, something that today is still based on purely aesthetic considerations.

The full-text version of the article is available here: https://www.nature.com/articles/s41598-021-88931-z