Tech

Most technical functional units are built bit by bit according to a well-designed construction plan. The components are sequentially put in place by humans or machines. Life, however, is based on a different principle. It starts bottom-up with molecular self-assembly. The crystallization of sugar or salt are simple examples of self-assembly processes, where almost perfect crystals form from molecules that randomly move in a solution. To better understand the growth of macroscopic structures from molecules, a research team of physicists and chemists of Kiel University has mimicked such processes with custom-made molecules. As recently reported in the journal Angewandte Chemie they fabricated a variety of patterns over a wide range of sizes including the largest structures reported so far.

The researchers deposited triangular molecules (methyltrioxatriangulenium) on gold and silver surfaces and observed their self-assembly into honeycomb superstructures using a scanning tunneling microscope. The structures are comprised of periodic patterns with controllable sizes. "Our largest fabricated patterns contain subunits of 3.000 molecules each, which is approximately 10 times more than previously reported", says Dr. Manuel Gruber, a physicist from Kiel University. The team also developed a model of the intermolecular forces that drive the self-assembly. "The unique feature of our results is that we can explain, predict and even control their size", Gruber continues.

The detailed understanding of the driving forces controlling the size of the patterns holds promises for nanotechnology applications, and in particular for functionalization of surfaces. It may be envisioned to tune various physical properties like electronic, optical or reactivity to gases of a material by controlling the size of the superstructures on its surface.

At a pivotal moment early in his career, Vittorio Gallo, Ph.D., was accepted to work with Professor Giulio Levi at the Institute for Cell Biology in Rome, a position that leveraged courses Gallo had taken in neurobiology and neurochemistry, and allowed him to work in the top research institute in Italy directed by the Nobel laureate, Professor Rita Levi-Montalcini.

For four years as a student and later as Levi's collaborator, Gallo focused on amino acid neurotransmitters in the brain and mechanisms of glutamate and GABA release from nerve terminals. Those early years cemented a research focus on glutamate neurotransmission that would lead to a number of pivotal publications and research collaborations that have spanned decades.

Now, investigators from around the world who have worked most closely with Gallo penned tributes in the form of manuscripts that were assembled in a special issue of "Neurochemical Research" that honors Gallo "for his contributions to our understanding of glutamatergic and GABAergic transmission during brain development and to his leadership in the field of neural development and regeneration," writes guest editor Arne Schousboe, of the University of Copenhagen in Denmark.

"In spite of news headlines about competition in research and many of the negative things we hear about the research world, this shows that research is also able to create a community around us," says Gallo, chief research officer at Children's National Hospital and scientific director for the Children's National Research Institute.

As just one example, he first met Schousboe 44 years ago when Gallo was a 21-year-old mustachioed graduate student.

"Research can really create a sense of community that we carry on from the time we are in training, nurture as we meet our colleagues at periodic conferences, and continue up to the present. Creating community is bi-directional: influencing people and being influenced by people. People were willing to contribute these 17 articles because they value me," Gallo says. "This is a lot of work for the editor and the people who prepared papers for this special issue."

In addition to Gallo publishing more than 140 peer-reviewed papers, 30 review articles and book chapters, Schousboe notes a number of Gallo's accomplishments, including:

He helped to develop the cerebellar granule cell cultures as a model system to study how electrical activity and voltage-dependent calcium channels modulate granule neuron development and glutamate release.

He developed a biochemical/neuropharmacological assay to monitor the effects of GABA receptor modulators on the activity of GABA chloride channels in living neurons.

He and Maria Usowicz used patch-clamp recording and single channel analysis to demonstrate for the first time that astrocytes express glutamate-activated channels that display functional properties similar to neuronal counterparts.

He characterized one of the spliced isoforms of the AMPA receptor subunit gene Gria4 and demonstrated that this isoform was highly expressed in the cerebellum.

He and his Children's National colleagues demonstrated that glutamate and GABA regulate oligodendrocyte progenitor cell proliferation and differentiation.

Even the image selected to grace the special issue's cover continues the theme of continuity and leaving behind a legacy. That image of Purkinje cells was created by a young scientist who works in Gallo's lab, Aaron Sathyanesan, Ph.D. Gallo began his career working on the cerebellum - a region of the brain important for motor control - and now studies with a team of scientists and clinician-scientists Purkinje cells' role in locomotor adaptive behavior and how that is disrupted after neonatal brain injury.

"These cells are the main players in cerebellar circuitry," Gallo says. "It's a meaningful image because goes back to my roots as a graduate student and is also an image that someone produced in my lab early in his career. It's very meaningful to me that Aaron agreed to provide this image for the cover of the special issue."

Observing Phytoplankton via Satellite

Thanks to a new algorithm, researchers at the AWI can now use satellite data to determine in which parts of the ocean certain types of phytoplankton are dominant. In addition, they can identify toxic algal blooms and assess the effects of global warming on marine plankton, allowing them to draw conclusions regarding water quality and the ramifications for the fishing industry.

The tiny phytoplankton found in the world's oceans are tremendously productive, and create half the oxygen we need to breathe. Just like land-based plants, they use photosynthesis to produce carbohydrate, which they use as an energy source. They grow, divide and produce enormous quantities of biomass, the basis of all marine life. In addition, they are an essential food source for small crustaceans, fish and mussel larvae, which are themselves staples for larger fish. When phytoplankton are in short supply, it jeopardises the food web for all other marine organisms.

There are various groups of phytoplankton around the globe, and they fulfil different functions in marine ecosystems. Some are favourite food sources; others form specific chemical compounds or serve as nutrient fixers in the water, which can have a major influence on marine flora and fauna. On the other hand, certain groups of phytoplankton can grow to dense masses and produce toxic substances; when there are too many of them in the water, it can be lethal for some marine organisms, especially fish. Marine phytoplankton are also extremely important in their role as a CO2 sink. Accordingly, researchers are keen to learn how the populations of the respective phytoplankton groups are developing around the world.

More than chlorophyll

However, until recently it was virtually impossible to estimate these populations in detail. Granted, researchers have been collecting water samples from on board research vessels for decades, in order to identify and quantify the plankton present. But these are only random samplings. And even satellites, which have been scanning the oceans with their sensors for the past three decades, were an imperfect solution at best: though they could certainly be used to gauge the amount of the plant pigment chlorophyll in the water - as an indicator of how high the general concentration of phytoplankton was - distinguishing between the different types of phytoplankton remained extremely difficult. Moreover, there was no way to use satellite data to predict algal growth in specific regions.

But now an international team led by Hongyan Xi and Astrid Bracher from the Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research (AWI) have for the first time managed to glean far more from satellite data: as they report in the journal Remote Sensing of Environment, working in close cooperation with the French company ACRI-ST and with the support of the European-based satellite data provider Copernicus Marine Environment Monitoring Service, they have developed a new algorithm that can be used to distil the data into key information on five main phytoplankton groups.

Reflectance as a key parameter

Satellite sensors register light at various wavelengths; normally, those wavelengths are used which are capable of picking up the colour of the chlorophyll. But Hongyan Xi and her colleagues have found a way to put this wavelength information to better use. More specifically, this involves analysing an aspect known as reflectance (or coefficient of reflection), which represents the amount of sunlight striking the Earth that is reflected back into space. This reflection is due to numerous optical processes: the light is scattered, bent and altered by water molecules and particles in the ocean and atmosphere alike. "And the plankton, which itself contains certain pigments, has an influence on the reflectance," Hongyan Xi explains. "The reflectance can differ, depending on which types of plankton and which pigments are dominant in the water." In fact, each of the five types leaves its own fingerprint on the reflected light - and the new algorithm can recognise them all.

Painstaking comparisons of ship-based and satellite data

This breakthrough was only possible thanks to a tremendous amount of hard work. First the team had to determine which reflectance pattern was characteristic of each plankton type. They then had to compare the satellite readings with plankton samples collected at the same time and place from on board research vessels. Fortunately, the findings of many ship-based expeditions are now available in publicly accessible databases. Thanks to these archives, the experts were able to determine where and when the water samples had been collected, and which species and types of plankton were present. Xi and her colleagues analysed ca. 12,000 of these datasets - and then mapped each and every one to satellite scans taken of the same place at the same time. Doing so allowed them to deduce how the reflectance changed in certain plankton types.

Water quality and toxic algal blooms

Armed with these findings, they were then ready to develop the algorithm. Today, it can be used to determine which types of phytoplankton are dominant in any given marine region worldwide, based on its reflectance information. This is important e.g. to identify toxic "harmful algal blooms" (HABs). The presence of certain types of phytoplankton is also an indicator of water quality; information that is particularly relevant for the fishing industry. According to Hongyan Xi: "In addition, in the future we'll be able to determine whether or not the distribution of phytoplankton is affected by climate change - an important aspect in terms of predicting the impacts on ecosystems."

The study was released in the journal Remote Sensing of Environment under the following original title:
Hongyan Xi, Svetlana N. Losa, Antoine Mangin, Mariana A. Soppa, Philippe Garnesson, Julien Demaria, Yangyang Liu, Odile Hembise Fantond, Astrid Bracher: Global retrieval of phytoplankton functional types based on empirical orthogonal functions using CMEMS GlobColour merged products and further extension to OLCI data, 2020, DOI: 10.1016/j.rse.2020.111704

Someday, underwater robots may so closely mimic creatures like fish that they’ll fool not only the real animals themselves but humans as well. That ability could yield information ranging from the health of fish stocks to the location of foreign watercraft.

Such robots would need to be fast, efficient, highly maneuverable, and acoustically stealthy. In other words, they would have to be very much like bottlenose dolphins or killer whales.

“We’re interested in developing the next generation of underwater vehicles so we’re trying to understand how dolphins and whales swim as efficiently as they do,” says Keith W. Moored, an assistant professor of mechanical engineering and mechanics in Lehigh University’s P.C. Rossin College of Engineering and Applied Science. “We’re studying how these animals are designed and what’s beneficial about that design in terms of their swimming performance, or the fluid mechanics of how they swim.”  

Moored is the principal investigator on a paper recently published in the Journal of the Royal Society Interface that examined the fluid mechanics of cetacean propulsion by numerically simulating their oscillating tail fins. For the first time, Moore and his team were able to develop a model that could quantitatively predict how the motions of the fin should be tailored to its shape to maximize its efficiency. The research was part of a larger project supported by the Office of Naval Research under its Multidisciplinary University Research Initiative program. The project, which received more than $7 million in funding (with $1 million going to Lehigh) over more than five years, also included the University of Virginia, West Chester University, Princeton University, and Harvard University. 

The tail fins of cetaceans (whales and dolphins) come in a wide variety of shapes. The way these animals move their fins, or their kinematics, also varies. Some cetaceans may flap their fins at a greater amplitude, or pitch them at a steeper angle. Moored and his team wanted to better understand this interplay between the two variables to determine if tail fin shape was tailored to a specific set of kinematics.

Using the shape and kinematic data for five cetacean species (with common names of bottlenose dolphin, spotted dolphin, killer whale, false killer whale, and beluga whale), they ran simulations on each of the species to determine its propulsive efficiency. Then they swapped the data around, for example, running a simulation on the fin shape of a killer whale attached to the kinematics of a dolphin.

“We ran 25 of these swapped simulations, and we were really surprised,” says Moored. “The pseudo orca fin shape was always the best, meaning it was the most efficient. It didn’t matter what kinematics we gave it. And the beluga whale kinematics were always the best, regardless of which shape it was attached to. We didn’t expect that, so we started digging into it more and developed this relatively simplistic model of how efficiency scales with different kinematic and shape variables.”

The model worked well to capture the data that Moored and his team had already generated, so they extended their data set to examine any resulting trends. They found that their model  not only predicted efficiency beyond their data set but also revealed that specific shapes were tailored to specific kinematics.

One interesting revelation, says Moored, was the fundamental interplay between circulatory forces and added mass forces that contribute to an animal’s movement. Circulatory forces are those that generate lift, like with aircraft.

“A tail that’s flapping up and down generates forces just like an aircraft, but it also generates added mass forces that have to do with how fast the fluid is being accelerated,” says Moored. “In the past, people didn’t think those added mass forces were that relevant in cetacean swimming. It’s not acknowledged at all in the previous literature. But we found that the accelerations of the fin are integral to predicting the trends of efficiency, and that was fascinating to us. It ultimately gives us a predictive model that’s accurate. Without it, we’d basically be saying that fin shape doesn’t change the efficiency, and that’s not true.” 

Having a model that can predict performance based on shape and kinematics provides a basic design equation of sorts for building an underwater robot that performs like a cetacean. To date, these equations haven’t existed. And the potential for these machines is huge. Fast, efficient, and highly maneuverable fish-shaped robots could help researchers test hypotheses about how the animals swim, and better understand the behavior of fish schools. They could be used to detect submarines and other submersibles. They could also be used to monitor the impact of climate change on fish stock populations.

Moored and his team have already moved on and expanded their scaling model to account for a larger range of variables they then validated with experimental data. Ultimately, they want to build a far more predictive model. One that captures the effects of these variables, and can then predict performance for a range of applications.

“This fish swimming problem is a really exciting problem because it’s so complicated,” he says. “It’s fascinating to take this chaos of variables and see order in it, to see the structure in it, and to understand what’s fundamentally happening.”

Tiny particles composed of metals and semiconductors could serve as light sources in components of future optical computers, as they are able to precisely localize and extremely amplify incident laser light. A team from Germany and Sweden led by Prof. Dr. Christoph Lienau and Dr. Jin-Hui Zhong from the University of Oldenburg has now explained for the first time how this process works. The study is published in the current issue of the journal Nature Communications.

For their study, the team produced hybrid nanomaterials that combine the optical properties of metals and semiconductors. The starting point of the study were sponge-like gold particles with a diameter of several hundred billionths of a metre (nanometres) and pores with a size of around ten nanometres. The material scientists Dr. Dong Wang and Prof. Dr. Peter Schaaf from the Technical University of Ilmenau fabricated these nanosponges and further used advanced nanofabrication techniques to coat the sponges and infiltrate their tiny pores with a thin layer of the semiconductor zinc oxide.

The particles are capable of changing the colour of an optical light beam. For example, if they are irradiated with the light of a red laser, they might emit blue laser light, which has a shorter wavelength. The emitted colour depends on the properties of the material. "Creating such so-called nonlinear optical materials with nanoscale dimensions is one of the grand challenges in current optics research," Lienau reports.

In future optical computers, which might use light instead of electrons for calculations, such nanoparticles could serve as tiny light sources. "You could call such particles nanolasers," adds Zhong, who together with Dr. Jan Vogelsang from Lund University is the lead author of the study. Possible applications include ultrafast optical switches or transistors.

In order to elucidate how nanomaterials convert light of one colour into another, team members led by Prof. Dr. Anne L'Huillier and Prof. Dr. Anders Mikkelsen from Lund University in Sweden used a special microscopic method, ultrafast photoemission electron microscopy. Combining extremely short flashes of light with an electron microscope, they were able to directly show that light is efficiently concentrated in the nanopores - an important prerequisite for its future application.

Prof. Dr. Erich Runge, a physicist from the Technical University of Ilmenau, simulated the properties of the material with theoretical models. As the team reports, nanoparticles composed of metals and semiconductors probably offer new opportunities for adjusting the properties of the emitted light. "Our study provides fundamental new insights into how hybrid metal-semiconductor nanostructures amplify light," says Zhong. In addition, the observations could help develop materials with even better optical properties.

The research group "Ultrafast Nano-Optics" at the University of Oldenburg headed by Prof. Dr. Christoph Lienau specializes in studying processes in the nanoworld with particularly high spatial and temporal resolution. The physicists have already achieved several significant breakthroughs in this field. Only recently, they developed a metallic superlens made of gold with previously unattained optical resolution.

The next time you eat sashimi, nigiri or other forms of raw fish, consider doing a quick check for worms.

A new study led by the University of Washington finds dramatic increases in the abundance of a worm that can be transmitted to humans who eat raw or undercooked seafood. Its 283-fold increase in abundance since the 1970s could have implications for the health of humans and marine mammals, which both can inadvertently eat the worm.

Thousands of papers have looked at the abundance of this parasitic worm, known as Anisakis or "herring worm," in particular places and at particular times. But this is the first study to combine the results of those papers to investigate how the global abundance of these worms has changed through time. The findings were published March 19 in the journal Global Change Biology.

"This study harnesses the power of many studies together to show a global picture of change over a nearly four-decade period," said corresponding author Chelsea Wood, an assistant professor in the UW School of Aquatic and Fishery Sciences. "It's interesting because it shows how risks to both humans and marine mammals are changing over time. That's important to know from a public health standpoint, and for understanding what's going on with marine mammal populations that aren't thriving."

Despite their name, herring worms can be found in a variety of marine fish and squid species. When people eat live herring worms, the parasite can invade the intestinal wall and cause symptoms that mimic those of food poisoning, such as nausea, vomiting and diarrhea. In most cases, the worm dies after a few days and the symptoms disappear. This disease, called anisakiasis or anisakidosis, is rarely diagnosed because most people assume they merely suffered a bad case of food poisoning, Wood explained.

After the worms hatch in the ocean, they first infect small crustaceans, such as bottom-dwelling shrimp or copepods. When small fish eat the infected crustaceans, the worms then transfer to their bodies, and this continues as larger fish eat smaller infected fish.

Humans and marine mammals become infected when they eat a fish that contains worms. The worms can't reproduce or live for more than a few days in a human's intestine, but they can persist and reproduce in marine mammals.

Seafood processors and sushi chefs are well-practiced at spotting the worms in fish and picking them out before they reach customers in grocery stores, seafood markets or sushi bars, Wood explained. The worms can be up to 2 centimeters in length, or about the size of a U.S. 5-cent nickel.

"At every stage of seafood processing and sushi preparation, people are good at finding worms and removing them from fish," Wood said.

Some worms can make it past these screening steps. Still, Wood -- who studies a range of marine parasites -- said she enjoys eating sushi regularly. For sushi consumers who remain concerned about these worms, she recommends cutting each piece in half and looking for worms before eating it.

For the analysis, the study's authors searched the published literature archived online for all mentions of Anisakis worms, as well as another parasitic worm called Pseudoterranova, or "cod worm." They whittled down the studies based on set criteria, ultimately keeping only those studies that presented estimates of the abundance of each worm in fish at a given point in time. While Anisakis worms increased 283-fold over the study period of 1978 to 2015, Pseudoterranova worms did not change in abundance.

Although the health risks of these marine worms are fairly low for humans, scientists think they may be having a big impact on marine mammals such as dolphins, whales and seals. The worms actually reproduce in the intestines of these animals and are released into the ocean via the marine mammals' feces. While scientists don't yet know the physiological impacts of these parasites on marine mammals, the parasites can live in the mammals' bodies for years, which could have detrimental effects, Wood said.

"One of the important implications of this study is that now we know there is this massive, rising health risk to marine mammals," Wood said. "It's not often considered that parasites might be the reason that some marine mammal populations are failing to bounce back. I hope this study encourages people to look at intestinal parasites as a potential cap on the population growth of endangered and threatened marine mammals."

The authors aren't sure what caused the large increase of Anisakis worms over the past several decades, but climate change, more nutrients from fertilizers and runoff, and an increase in marine mammal populations over the same period could all be potential reasons, they said.

Marine mammals have been protected under the Marine Mammal Protection Act since 1972, which has allowed many populations of seals, sea lions, whales and dolphins to grow. Because the worms reproduce inside marine mammals -- and their rise occurred over the same time period as the mammals' increase -- this is the most plausible hypothesis, Wood said.

"It's possible that the recovery of some marine mammal populations has allowed recovery of their Anisakis parasites." Wood said. "So, the increase in parasitic worms actually could be a good thing, a sign that the ecosystem is doing well. But, ironically, if one marine mammal population increases in response to protection and its Anisakis parasites profit from that increase, it could put other, more vulnearble marine mammal populations at risk of increased infection, and that could make it even more difficult for these endangered populations to recover."

The smart watches seen on the wrists of roughly 1 in 5 Americans could be more than just a fun gimmick but a potentially useful research tool to track habitual physical activity levels. People who took more steps daily, as tracked by their watch, had lower blood pressure on average than those taking fewer steps in a study presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC).

The research is part of the Framingham Heart Study, a project focusing on factors affecting heart disease that has been ongoing for more than 70 years. Researchers analyzed data from 638 study participants who were asked to wear an Apple Watch daily and record their blood pressure at home weekly. Over the course of the study, participants' average systolic blood pressure was 122 mm Hg and average diastolic blood pressure was 76 mm Hg, levels that are considered normal to slightly elevated according to the 2017 ACC/AHA High Blood Pressure in Adults guideline.

The study is one of the first to use commercially available wearable devices to track habitual physical activity in a large group of people in the context of daily life outside of a health care setting or research center.

"Measuring habitual physical activity in community-based settings in this way distinguishes our study from prior studies that have looked at either self-reported physical activity or used accelerometers to measure daily activity for only a short amount of time, usually about a week," said Mayank Sardana, MD, a clinical fellow at the University of California, San Francisco, and the study's lead author.

Although the study was observational and does not show cause and effect, the findings align with previous research suggesting that being more physically active can help lower blood pressure. After accounting for demographic factors, the study found participants' systolic blood pressure was about 0.45 points lower for every 1,000 daily steps taken, meaning that a person taking 10,000 steps daily would have a systolic blood pressure 2.25 points lower than a person taking just 5,000 steps daily, on average. Given that study participants had an average systolic blood pressure of 122 mm Hg, this amount could make the difference between blood pressure that is considered normal (less than 120 mm Hg) and elevated (120 mm Hg or higher).

"This study solidifies our understanding of the relationship between physical activity and blood pressure and raises the possibility that obesity or body mass index accounts for a lot of that relationship," Sardana said. "Going forward, it would be useful to look at how smart devices might be leveraged to promote physical activity, reduce the burden of obesity and potentially reduce blood pressure."

Researchers excluded data from the participants with less than 30 days of wear time to ensure participants were accustomed to wearing the watch. They also excluded data from the days on which the watch was worn for less than five hours to ensure the step counts reflected most of a person's daily movements. Over the course of about five months, participants averaged about 7,500 steps per day. Those with a higher daily step count had significantly lower systolic and diastolic blood pressure. In a secondary analysis, the researchers found the association between step count and blood pressure was no longer significant if BMI was taken into account, which suggests BMI might be a mediating factor in the relationship.

However, the study was not designed to discern whether BMI affects step count or the other way around.

"We should look to future studies to answer the question of directionality with a randomized trial or cohort intervention," Sardana said.

Sardana added that the electronic Framingham Heart Study cohort is the largest sample of participants developed leveraging the seminal Framingham Heart Study who are providing continuous data from smart devices for research. Their findings support the role of leveraging the data from wearable devices in epidemiology research to enhance the understanding of the relationship between cardiovascular risk factors and cardiovascular disease.

Nearly half of U.S. adults are estimated to have high blood pressure, and many don't know they have it. Over time, elevated blood pressure can weaken the heart, blood vessels, kidneys and other parts of the body.

We all have stress in our lives--whether it's due to financial woes, work pressures, relationship issues, illness or even natural disasters or health crises like the emerging coronavirus. For some people who survive a heart attack, it seems mental stress--as opposed to physical stress--may be a stronger predictor of a repeat heart attack or dying from heart disease, according to research presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC).

Traditional stress tests, in which someone exercises on a treadmill or takes a medicine that makes the heart beat faster and harder as if the person was actually exercising, have long been used to check blood flow to the heart and gauge the risk of heart problems. Researchers at Emory University sought to investigate whether myocardial ischemia--when blood flow to the heart is reduced such that the heart muscle doesn't get enough oxygen--induced by mental stress was associated with poor outcomes among heart attack survivors and how this type of stress testing compares with conventional stress brought on by exercise.

Among more than 300 young and middle-aged individuals enrolled in the study, those who endured myocardial ischemia with mental stress had a two-fold higher likelihood of having another heart attack or dying from heart disease compared with those who did not have cardiac ischemia induced by mental stress.

"In our study, myocardial ischemia provoked by mental stress was a better risk indicator than what we were able to see with conventional stress testing," said Viola Vaccarino, MD, PhD, Wilton Looney Professor of Cardiovascular Research in the department of epidemiology at Emory University Rollins School of Public Health in Atlanta, and the study's principal investigator, adding that this is the only study of its kind in this relatively young adult population of heart attack survivors. "These data point to the important effect that psychological stress can have on the heart and on the prognosis of patients with heart disease. It gives us tangible proof of how psychological stress, which is not specifically addressed in current clinical guidelines, can actually affect outcomes."

She added that taking into account patients' psychological stress may help clinicians better evaluate the risk of recurrent heart attacks or death seen in some patients surviving a heart attack. These results also underscore the need for strategies to identify the best stress management interventions for these patients.

The investigators studied 306 adults aged 61 years or younger (50 years on average and ranging from 22-61 years), who had been in the hospital for a heart attack in the previous eight months. Participants were recruited in the Atlanta metro area and represented a diverse group of patients; half were women and 65% were African American. All participants underwent two types of "stress" testing to examine blood flow to the heart: mental stress testing (provoked by giving one speech with emotional content in front of an intimidating, seemingly disinterested audience followed by myocardial perfusion imaging), and conventional stress testing (pharmacologic or exercise). Patients were followed for a median of three years for the primary endpoint, which included a combination of either the occurrence of a repeat heart attack or cardiovascular death. These were adjudicated through an independent medical record review and examination of death records. Ischemia was defined as a new or worsening disruption in adequate blood flow to the heart and was assessed using cardiac nuclear imaging scans.

Overall, mental stress induced myocardial ischemia occurred in 16% of patients and conventional ischemia in 35%, suggesting that traditional ischemia due to exercise or drug-induced stress is more common. Over a three-year follow-up, 10% of patients (28 individuals) had another heart attack and two died of heart-related problems. The incidence of heart attack or cardiovascular-related death was more than doubled in patients with mental stress induced ischemia compared with those without mental stress ischemia, occurring in 10 (20%) and 20 (8%) patients, respectively. The relationship between acute mental stress and heart attack or death remained even after adjusting for clinical risk factors and symptoms of depression. In contrast, conventional stress ischemia was not significantly related to the primary endpoint.

"Patients who developed ischemia with mental stress had more than two times the risk of having a repeat heart attack or dying from heart disease compared with those who did not develop ischemia during mental stress," Vaccarino said. "What this means is that the propensity to have a reduction in blood flow to the heart during acute psychological stress poses substantial future risk to these patients."

Such reduction in blood flow, when it occurs in real life, could trigger a heart attack or serious heart rhythm problems, she said. Another interesting finding, according to Vaccarino, is that ischemia with mental stress and with conventional stress were not strongly related to each other, suggesting that they occur through different pathways.

"This points to the fact that stress provoked by emotions has a distinct mechanism of risk for heart disease and its complications compared with physical stress," she said.

Vaccarino and her team plan to expand this research using a larger sample size and a longer follow-up time to determine if there are specific subgroups of patients that are especially at risk of adverse outcomes when they develop ischemia from mental stress. Because of the relatively small sample size, the investigators were not able to determine if such risk differs by sex or race, for example, or whether past exposures to social stressors or trauma play a role. Furthermore, the investigators plan to examine whether myocardial ischemia induced by mental stress in the lab reflects enhanced physiological responses to stress in real life.

PHILADELPHIA - The protein peptidyl arginine deiminase 4 (PAD4), which enables some immune cells to trap bacteria, promoted breast cancer metastasis in mice when expressed in cancer cells, according to data published in Molecular Cancer Research, a journal of the American Association for Cancer Research.

"Breast cancer is a leading cause of cancer-related death among women. Patients with metastatic breast cancer have a high risk of death," said Yanming Wang, PhD, professor at the Henan University in Kaifeng, China. "The purpose of our study was to understand cellular factors that may contribute to metastasis."

Wang, a former graduate student Lai Shi, PhD, and their colleagues examined the role of PAD4, a protein that can modify DNA-compacting proteins called histones, thereby loosening DNA compaction. PAD4 is highly enriched in neutrophils, a type of immune cell, where its effect on DNA compaction leads to the formation of DNA and protein networks outside the cell called neutrophil extracellular traps (NETs). The normal role of NETs is to trap invading microbes, but studies have shown that NETs released by neutrophils can also facilitate cancer metastasis. Moreover, another study showed that high expression of PAD4 was sufficient to cause cells other than neutrophils to form similar structures.

"In addition to its high expression in neutrophils, PAD4 is highly expressed in malignant tumors of various cell types; however, the role of PAD4 in breast cancer cells has been elusive," said Wang. "We were interested in learning if PAD4 expression in breast cancer cells could affect cancer biology, such as tumor growth and metastasis."

To understand PAD4 expression levels in breast cancer cells, Wang and colleagues performed a meta-analysis of gene expression profiles from The Cancer Genome Atlas and the Oncomine database. Results from the meta-analysis showed that human breast cancer cells were more likely than normal cells to have increased PAD4 expression. Consistent with this finding, a mouse breast cancer cell line called 4T1 had higher PAD4 levels than cell lines from other cancer types.

Due to PAD4's known roles in DNA compaction and NET formation, Wang and colleagues examined how PAD4 expression in breast cancer cells impacts the structure of DNA-protein networks known as chromatin. They found that activation of PAD4 in 4T1 cells led to the modification of histones and the release of chromatin fibers outside the cell. The released chromatin fibers formed NET-like structures, which the authors referred to as cancer extracellular chromatin networks (CECNs).

Further experiments demonstrated that PAD4 was required for the formation of CECNs, both in cell culture and in allograft tumors in mice. By comparing the growth and spread of allograft tumors that did or did not express PAD4, the authors observed that PAD4-expressing tumors grew significantly faster in mice and had significantly more metastases in the lungs, which are the usual site of 4T1 metastasis. Further experimentation revealed that PAD4 promoted the growth of metastatic tumors after cancer cells had reached the lungs.

"Together, our results demonstrate that PAD4 expression in breast cancer cells promotes CECN formation, primary tumor growth, and lung metastasis in mice," said Wang. "The exact mechanism by which PAD4 exerts these effects is something we are actively investigating." Understanding how PAD4 promotes tumor growth and metastasis could help researchers develop drugs to target this process, explained Wang.

"While further investigation is needed, it is interesting to consider the possibility that PAD4 or CECNs could potentially be used as biomarkers to predict disease progression. Furthermore, therapies to inhibit PAD4 or eliminate CECNs could be explored as a method to reduce the risk of metastasis in patients with breast cancer," Wang added. Wang and colleagues are also interested in investigating if PAD4 contributes to progression or metastasis of other cancers.

A limitation of the study is that it was performed using a single cell line. Thus, studying additional cell types and human breast cancer samples will be needed to understand the prevalence of CECN formation and PAD4's role in the process, Wang noted.

A research team consisting of Ryota Kondo (Ph.D. candidate), Yamato Tani (Graduate student), and Professor Michiteru Kitazaki from Toyohashi University of Technology, Associate Professor Maki Sugimoto and Professor Kouta Minamizawa from Keio University, and Professor Masahiko Inami from The University of Tokyo has revealed that a re-association of the right thumb with the virtual left arm can be induced by visuo-motor synchronization in a virtual environment; however, this re-association may be weaker than the natural association. This study contributes to the expanding perspectives on body schemes of augmented humans and understanding their limitations. Body-part re-association can be applied to developing functional prosthesis and embodied tools in future. This research was published in the open access journal Frontiers in Robotics and AI in 19th March 2020.

Illusory body ownership can be induced by visuo-motor synchrony; It appears as if a virtual body is one's own body if the virtual body moves synchronously with one's movements. It is possible to have illusory body ownership to various bodies with different appearances, including a transparent body (Kondo, et al., Scientific Reports, 2018). However, in most studies, virtual body parts were associated with the corresponding actual body parts. For example, the virtual left arm was synchronously moved with the actual left arm.

The research team focused on the difference in correspondence between the actual and virtual body parts. In 2017, Sasaki, Inami et al. (SIGGRAPH 2017) created two additional robot arms by controlling them with left and right foot movements ('MetaLimbs'). However, the sense of ownership to the robotic arms has not been investigated in detail. The team aimed to investigate whether the illusory body ownership can be induced by body-part re-association at different levels of the human body hierarchy: a virtual left arm and the actual right thumb.

Twenty participants moved the right thumb voluntarily when they observed a virtual left arm through a head-mounted display for 5 minutes. The virtual left arm was moved either synchronized or asynchronized with the right thumb. It was found that participants felt as if their right thumb had become the left arm and the virtual left arm was a part of their own body in the synchronous condition. However, the sense of ownership was not very strong, suggesting that the re-association of different body parts may be weaker than the natural association. This may be because the re-association was performed for only 5 minutes in the experiment.

This study contributes to expanding perspectives on human body or body scheme and offers the means to investigate potentials and limitations of augmented humans. The body-part re-association may be applied to developing functional prosthesis and embodied tools in future.

While Rancho La Brea, commonly known as the La Brea Tar Pits, is famous for its thousands of bones of large extinct mammals, big insights are coming from small fossils, thanks to new excavation and chemical techniques.

Today, a team of researchers from La Brea Tar Pits, the University of Oklahoma and the University of California Irvine report the first coprolites - or fossil feces - ever discovered in an asphaltic - or tar pit - context. These hundreds of fossilized rodent pellets were found during the excavation of a parking garage for the Los Angeles County Museum of Art in Hancock Park in 2016, which had also yielded the more traditional La Brea fossils, such as extinct mammoths, dire wolves and saber-toothed cats.

Alexis Mychajliw, a postdoctoral research associate at OU, is the lead author of the study. The details of the research team's findings were published today in Scientific Reports.

"It's incredible that after more than a century of excavation and study, we are still unearthing new types of fossils from La Brea's treasure trove of deposits," said Emily Lindsey, assistant curator at La Brea Tar Pits. "These tiny finds may lead to big discoveries about the climate and ecosystems of Ice Age Los Angeles."

Researchers were skeptical at first, given the abundance of urban rats in the area.

"We noted the occasional rodent fecal pellet in the processed matrix before, but it was easy to explain it away as modern contamination," said Laura Tewksbury, senior preparator at La Brea Tar Pits.

But, with more and more pellets appearing encased in asphalt, Tewksbury recalled, "We stared at the sheer number of pellets in silence for a minute, before looking at each other and stating, 'There's just no way that much is contamination.'"

Indeed, radiocarbon dates generated at UC Irvine would confirm the pellets were ~50,000 years old.

Rancho La Brea has been associated with the image of big animals getting stuck in "tar pits," or shallow, sticky asphalt pools, with carnivores attracted en masse by struggling herbivore prey. But these coprolites tell a new story of how fossils can be preserved at Rancho La Brea.

"The intact nature and density of the fossils require a taphonomic explanation other than entrapment. The preservation is more likely the result of an asphalt seep overtaking an existing rodent nest," noted Karin Rice, preparator at La Brea Tar Pits.

Using a suite of cutting-edge tools, including stable isotope analysis and scanning electron microscopy, the researchers demonstrated that the fecal pellets were associated with beautifully preserved twigs, leaves, and seeds, apparently as part of an intact nest made by a woodrat. Woodrats - also known as packrats - are well-known in the paleontological community for their hoarding behavior that produces massive nests that can be preserved for thousands of years. Slices of plant material from these nests, in turn, represent snapshots of vegetation and climate conditions of the past.

"This nest provides an unparalleled view of what was beneath the feet of Rancho La Brea's famous megafauna," Mychajliw said. "And to me, it emphasizes the importance of studying small mammals, too. Woodrats survived the Ice Age and still build nests in local urban green spaces like Griffith Park! By studying these nests, we have a direct line from the past to the present through which to trace human impacts on Los Angeles' nature over time."

In the past decade, on-chip nanophotonics has attracted increasing attention for the realization of integrated photonic circuits with faster operation, broader bandwidth, lower power consumption and higher compactness. While a number of on-chip nanophotonic devices and circuits have been successfully fabricated using a complementary metal-oxide semiconductor (CMOS) -compatible technique, on-chip light sources remain challenging. On the other hand, bottom-up grown semiconductor nanowires have long been used for nanoscale waveguide lasers. In recent years, increasing attention has been paid to the integration of active nanowires with on-chip planar waveguides for on-chip light sources. However, due to the large discrepancy in fabrication techniques, refractive index and geometric compatibility between a freestanding nanowire and an on-chip planar waveguide, a variety of issues, including a relatively low coupling efficiency, ineffective mode selection and low reproductivity, have yet to be addressed.

In a new paper published in Light Science & Application, scientists from the State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, Zhejiang University, China demonstrated an on-chip single-mode CdS nanowire laser with high coupling efficiency. The mode selection is realized using a Mach-Zehnder interferometer (MZI) structure. When the pumping intensity exceeds the lasing threshold of 4.9 kW/cm2, on-chip single-mode lasing at approximately 518.9 nm is achieved with a linewidth of 0.1 nm and a side-mode suppression ratio of 20 (13 dB). The output of the nanowire laser is channelled into an on-chip SiN waveguide with high efficiency (up to 58%) by evanescent coupling, and the directional coupling ratio between the two output ports can be varied from 90% to 10% by predesigning the coupling length of the SiN waveguide. Benefitting from the great diversity of the available nanowire materials and high flexibility for bandgap engineering, the on-chip integration scheme demonstrated here can be readily extended to realize on-chip nanolasers from the ultraviolet to near-infrared ranges, which may offer new opportunities for both semiconductor nanowires and on-chip photonic devices.

These scientists summarize the fabrication and operational principle of the laser:

"We use micromanipulation under an optical microscope to integrate a CdS nanowire onto a SiN chip and form a hybrid MZI structure with excellent reproducibility. By using the MZI for mode selection, we operate the laser in single mode. We can also change the output ratios between the two ports of the lasing MZI by using different coupling lengths of the waveguide bends."

"The overall size of the hybrid MZI structure is kept below 100 μm. Fibre-to-chip grating couplers are designed at both ends of the SiN waveguide, which couple the laser signal from the on-chip SiN waveguide into standard optical fibres for optical characterization." "By comparing the lasing output intensities from the nanowire end and the grating area, we estimate the fractional power channelled into the SiN waveguide to be approximately 58%, much higher than previous results obtained in chip integrated nanowire lasers, and can be further improved by optimizing the coupling efficiency between the nanowire and the SiN waveguide." they added.

"Benefitting from the great diversity of the available nanowire materials and high flexibility for bandgap engineering, the on-chip integration scheme demonstrated here can be readily extended to realize on-chip nanolasers from the ultraviolet to near-infrared ranges, and the on-chip single-mode nanowire laser may thus offer an opportunity to develop on-chip physical and biochemical optical sensors with higher stability and compactness. " the scientists forecast.

In a new publication from Cardiovascular Innovations and Applications; DOI https://doi.org/10.15212/CVIA.2019.0569, Lutfu Askin, Kader Eliz Uzel, Okan Tanriverdi and Serdar Turkmen from the Department of Cardiology, Adiyaman Education and Research Hospital, Adiyaman, Turkey consider serum irisin pathogenesis and clinical research in cardiovascular diseases.

The authors summarize studies on the role of serum irisin levels in the process of atherosclerosis and other cardiovascular events in cardiovascular diseases. Irisin is a recently discovered molecule produced by muscles. It has been shown to be associated with different metabolic markers. Current studies suggest that irisin is a promising therapeutic agent in diseases such as DM, metabolic syndrome, and CVDs.

The discovery of new topological states of matter has become a vital goal in fundamental physics and material science. A three-dimensional (3D) Dirac semimetal (DSM), accommodating many exotic transport properties such as anomalous magnetoresistance and ultrahigh mobility, is an exceptional platform for exploring topological phase transitions and other novel topological quantum states. It is also of fundamental interest to serve as a solid-state realization of a (3+1)-dimensional Dirac vacuum. So far the realized Dirac points always come in pairs and could be eliminated by their merger and pairwise annihilation through the continuous tuning of parameters that preserve the symmetry of the system.

In a new paper published in Light Science & Application, scientists from the Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education and School of Physics and Technology, Wuhan University, China, we report an experimental realization of a 3D phononic crystal that hosts symmetry-enforced Dirac points at the Brillouin zone corners. Markedly different from the existed DSMs, the occurrence of Dirac points is an unavoidable result of the nonsymmorphic space group of the material, which cannot be removed without changing the crystal symmetry. In addition to the Dirac points identified directly by angle-resolved transmission measurements, highly intricate quad-helicoid surface states are unveiled by our surface measurements and associated Fourier spectra. Specifically, the surface states are composed of four gaplessly crossed spiral branches and thus are strikingly different than the double Fermi arc surface states observed recently in electronic and photonic systems.

"This study may open up new manners for controlling sound, such as realizing unusual sound scattering and radiation, considering the conical dispersion and vanishing density of states around the Dirac points. The dispersion around the Dirac point is isotropic, and thus, our macroscopic system serves as a good platform to simulate relativistic Dirac physics." the scientists forecast.

In a new paper published in Light Science & Application, researchers from Tsinghua University and Arizona State University report their results on studying the fundamental physics of excitons, trions, and related complexes. Excitons are quasi-particles formed by an electron and a void called hole left when an electron is excited in a semiconductor. Such an exciton can be charged, to form a so called trion when it further binds with another electron or a hole. The team discovered an interesting process that gives optical gain, a prerequisite for signal amplification or lasing in a semiconductor, by exploring the intricate balance and conversion of excitons, electrons, holes, and trions. Interestingly the required level of input power to realize such optical gain is extremely low, 4 to 5 orders of magnitude lower than in a conventional semiconductor such as GaAs or InP, which are the workhorse materials for optoelectronic devices currently.

The distribution of these exciton-related complexes and their dynamical mutual conversion are at the very heart of solid state physics for many decades. There are still unresolved issues as to how these excitons form more complex particles and eventually transform into an ionized conducting phase of charged particles as we introduce more and more of them into a semiconductor. This process is called the Mott transition, after Sir Nevill Francis Mott, the celebrated British Nobel winning physicist. Conventional theory for the occurrence of optical gain says that free excitons cannot produce optical gain before the Mott transition in a semiconductor with freely moving charges. Optical gain occurs after electron density exceeds the so-called Mott density, typically a very high level of density on the orders of trillions of particles per centimeter squared. Such an extremely high density requires a high level of injection of electrical current, or electrical power. Most of our current semiconductor lasers that power our internet, data centers, and many other applications are based on such semiconductors.

Exploring the relationship between occurrence of optical gain and Mott transition, especially searching for new mechanisms of optical gain at low densities before the Mott transition is thus not only an issue of fundamental importance in solid state physics, it is also of importance in device applications in photonics. If optical gain can be achieved with excitonic complexes below the Mott transition at low levels of power input, future amplifiers and lasers could be made that would require small amount of driving power. This is obviously of great current interest for energy efficient photonic devices or green photonics. But unfortunately, such issues could not be fully and systematically explored in a conventional semiconductor, because excitons themselves are not very stable and the chance of pursuing higher excitonic complexes is limited.

The recent emergence of atomically thin layered materials made such study possible and more meaningful. These materials comprise of only a few layers of atoms. Because of the thinness of the materials, electrons and holes attract each other 100s times stronger than in conventional semiconductors. Such strong charge interactions make excitons and trions very stable even at room temperature. This was the reason why the authors could explore such intricate balance and carefully control their mutual conversion to achieve optical gain. By creating excitons through optical pumping by a laser, excitons form trions with part of electrons whose number is controlled by a gate voltage. When more electrons are in the trion state than electron state, a condition called population inversion occurs. More photons can be emitted than absorbed, leading to a process called stimulated emission and optical amplification or gain.

"Another motivation for this study was the apparent contradiction between a few high profile experiments in the field in recent years. There have been a few experiments reporting laser demonstrations using 2D materials as gain media. There lasers required very low level of pumping when excitons are dominant light emission mechanism. But the only existing experiment that proved the existence of optical gain in such materials requires much higher level of pumping", said Ning, who leads the research team. Ning noticed the densities in the laser experiments are smaller than the Mott density by 3 to 5 orders of magnitude, while optical gain was only observed after the Mott transition. Since laser operation requires the existence of optical gain, Ning asked "where does optical gain come from in those laser experiments?" or "what is the mechanisms of optical gain at such a lower level of optical pumping? Or more generally, are there any possible new gain mechanisms before Mott transition?" These questions led to their experimental investigation started several years ago.

"We have systematically pursued this issue experimentally for 2-3 years. We bounced a beam of light of a broad spectrum off 2D molybdenum ditelluride and carefully watch if the reflected signal is larger or smaller than the incident beam to look for any sign of light amplification," said Hao Sun, who is a lead author of this paper in charge of optical measurement.

"To be sure, similar trion gain experiment was conducted in 1990s with conventional semiconductors", noticed Ning. "But the excitons and trions were so unstable, both experimental observation and, especially, utilization of this optical gain for real devices are extremely difficult." "Since the excitons and trions are much more stable in the 2D materials, there are new opportunities to make real-world devices out of this observation", pointed out Ning. "For the moment, this result belongs to basic physics research, but as for all the important observations in semiconductors, they could eventually be applied to making real lasers," commented Ning.