Earth

Trapping and controlling electrons in bilayer graphene quantum dots yields a promising platform for quantum information technologies. Researchers at UC Santa Cruz have now achieved the first direct visualization of quantum dots in bilayer graphene, revealing the shape of the quantum wave function of the trapped electrons.

The results, published November 23 in Nano Letters, provide important fundamental knowledge needed to develop quantum information technologies based on bilayer graphene quantum dots.

"There has been a lot of work to develop this system for quantum information science, but we've been missing an understanding of what the electrons look like in these quantum dots," said corresponding author Jairo Velasco Jr., assistant professor of physics at UC Santa Cruz.

While conventional digital technologies encode information in bits represented as either 0 or 1, a quantum bit, or qubit, can represent both states at the same time due to quantum superposition. In theory, technologies based on qubits will enable a massive increase in computing speed and capacity for certain types of calculations.

A variety of systems, based on materials ranging from diamond to gallium arsenide, are being explored as platforms for creating and manipulating qubits. Bilayer graphene (two layers of graphene, which is a two-dimensional arrangement of carbon atoms in a honeycomb lattice) is an attractive material because it is easy to produce and work with, and quantum dots in bilayer graphene have desirable properties.

"These quantum dots are an emergent and promising platform for quantum information technology because of their suppressed spin decoherence, controllable quantum degrees of freedom, and tunability with external control voltages," Velasco said.

Understanding the nature of the quantum dot wave function in bilayer graphene is important because this basic property determines several relevant features for quantum information processing, such as the electron energy spectrum, the interactions between electrons, and the coupling of electrons to their environment.

Velasco's team used a method he had developed previously to create quantum dots in monolayer graphene using a scanning tunneling microscope (STM). With the graphene resting on an insulating hexagonal boron nitride crystal, a large voltage applied with the STM tip creates charges in the boron nitride that serve to electrostatically confine electrons in the bilayer graphene.

"The electric field creates a corral, like an invisible electric fence, that traps the electrons in the quantum dot," Velasco explained.

The researchers then used the scanning tunneling microscope to image the electronic states inside and outside of the corral. In contrast to theoretical predictions, the resulting images showed a broken rotational symmetry, with three peaks instead of the expected concentric rings.

"We see circularly symmetric rings in monolayer graphene, but in bilayer graphene the quantum dot states have a three-fold symmetry," Velasco said. "The peaks represent sites of high amplitude in the wave function. Electrons have a dual wave-particle nature, and we are visualizing the wave properties of the electron in the quantum dot."

This work provides crucial information, such as the energy spectrum of the electrons, needed to develop quantum devices based on this system. "It is advancing the fundamental understanding of the system and its potential for quantum information technologies," Velasco said. "It's a missing piece of the puzzle, and taken together with the work of others, I think we're moving toward making this a useful system."

VIRTUAL MEETING (CST), November 22, 2020 -- Global population and urbanization have boomed over the last few decades. With them came scores of new tall buildings, drones, more energy-efficient ventilation systems, and planned air taxis by Uber and other companies. But these technological advancements must contend with a natural physical phenomenon: wind.

Scientists presented the latest findings on modeling and predicting urban airflow--in the hope of building better buildings, cities, and transportation--at the 73rd Annual Meeting of the American Physical Society's Division of Fluid Dynamics.

The urban skies of the future could teem with autonomous aircraft: air taxis, drones, and other self-flying systems. A team from Oklahoma State University has developed techniques to model environmental hazards these vehicles might encounter so they can safely navigate cities.

"Urban environments present enormous challenges for drone and urban air mobility platforms," said researcher Jamey Jacob, who led the team. "In addition to the challenges of traffic congestion and obstacles, critical technology gaps exist in modeling, detecting, and accommodating the dynamic urban local wind fields as well as in precision navigation through uncertain weather conditions."

Researchers attached sensors to robotic aircraft to take more cohesive measurements of building wakes, or the disturbed airflow around buildings. They combined this data with numerical predictions to get a better picture of the complex wind patterns found in urban environments.

The work could help improve wind and weather forecasting, not only for unmanned aircraft but also for conventional airplanes.

"The potential of outfitting every drone and urban air taxi, as well as other aircraft, with sensors provides a game changing opportunity in our capability to monitor, predict, and report hazardous weather events," said Jacob.

Another group, based at the University of Surrey also investigated building wakes. With an eye toward enhancing air quality in cities, they looked for wake differences between a single tall building and a cluster of tall buildings.

"Understanding how to model the wake of tall buildings is the first step to enable city planners to reduce the heat-island effect as well as improve urban air quality," said Joshua Anthony Minien, a researcher in mechanical engineering.

The team carried out experiments in a wind tunnel, varying the grouping, aspect ratio, and spacing of tall buildings. They were encouraged to see that when measured far enough downstream, a cluster of buildings and an isolated building have similar wake characteristics. Changes to wind direction also seem to significantly affect the wakes of clusters of buildings.

All buildings, tall or not, must be ventilated.

"The ability to predict ventilation flow rates, purging times and flow patterns is important for human comfort and health, as highlighted by the need to prevent the airborne spread of coronavirus," said University of Cambridge researcher Nicholas Wise.

With engineering professor Gary Hunt, Wise found a problem in current models of passive natural ventilation systems. These often use displacement flow--where cooler night air enters a building through one opening and warmer air accumulated during the day exits through another opening.

Their mathematical modeling revealed that displacement flow does not continue during the purge of warm air, as was believed. Instead, the room experiences an "unbalanced exchange flow" which can slow down the purging process.

"Every displacement flow transitions to unbalanced exchange flow," said Wise.

The researchers were surprised at just how much adding a small low-level opening speeds up room cooling, compared to a room with only a high-level opening. Their model will be useful for designers of natural ventilation systems.

Mechanical engineer Michael Gollner and his graduate student, Sriram Bharath Hariharan, from the University of California, Berkeley, recently traveled to NASA's John H. Glenn Research Center in Cleveland, Ohio. There, they dropped burning objects in a deep shaft and study how fire whirls form in microgravity. The Glenn Center hosts a Zero Gravity Research Facility, which includes an experimental drop tower that simulates the experience of being in space.

"You get five seconds of microgravity," said Gollner. The researchers lit a small paraffin wick to generate fire whirls and dropped it, studying the flame all the way down.

Experiments like this, presented at the 73rd Annual Meeting of the American Physical Society's Division of Fluid Dynamics, can help fire scientists answer two kinds of questions. First, they illuminate ways that fire can burn in the absence of gravity--and may even inform protective measures for astronauts. "If something's burning, it could be a very dangerous situation in space," said Gollner. Second, it can help researchers better understand gravity's role in the growth and spread of destructive fires.

The fire burned differently without gravity, said Gollner. The flame was shorter--and wider. "We saw a real slow down of combustion," said Gollner. "We didn't see the same dramatic whirls that we have with ordinary gravity."

Other researchers, including a team from Los Alamos National Laboratory in New Mexico, introduced new developments to a computational fluid dynamics model that can incorporate fuels of varying moisture content. Many existing environmental models average the moisture of all the fuels in an area, but that approach fails to capture the variations found in nature, said chemical engineer Alexander Josephson, a postdoctoral researcher who studies wildfire prediction at Los Alamos. As a result, those models may yield inaccurate predictions in wildfire behavior, he said.

"If you're walking through the forest, you see wood here and grass there, and there's a lot of variation," said Josephson. Dry grasses, wet mosses, and hanging limbs don't have the same water content and burn in different ways. A fire may be evaporating moisture from wet moss, for example, at the same time it's consuming drier limbs. "We wanted to explore how the interaction between those fuels occurs as the fire travels through."

Los Alamos scientists worked to improve their model called FIRETEC (developed by Rod Linn), collaborating with researchers at the University of Alberta in Canada and the Canadian Forest service. Their new developments accommodate variations in moisture content and other characteristics of the simulated fuel types. Researcher Ginny Marshall from the Canadian Forest Service recently began comparing its simulations to real-world data from boreal forests in northern Canada.

During a session on reacting flows, Matthew Bonanni, a graduate student in the lab of engineer Matthias Ihme at Stanford University in California, described a new model for wildfire spread based on a machine learning platform. Predicting where and when fires will burn is a complex process, says Ihme, that's driven by a complex mix of environmental influences.

The goal of Ihme's group was to build a tool that was both accurate and fast, able to be used for risk assessment, early warning systems, and designing mitigation strategies. They built their model on a specialized computer platform called TensorFlow, designed by researchers at Google to run machine learning applications. As the model trains on more physical data, said Ihme, its simulations of heat accumulation and fire-spreading dynamics improve--and get faster.

Ihme said he's excited to see what advanced computational tools bring to wildfire prediction. "It used to be a very empirical research area, based on physical observations, and our community works on more fundamental problems," he said. But adding machine learning to the toolbox, he said, shows how algorithms can improve the fidelity of experiments. "This is a really exciting pathway," he said.

Giving nurse practitioners the authority to prescribe buprenorphine has brought that gold standard treatment for opioid addiction to people who might not have had access to it before, according to a new study led by Tracy Klein, PhD, associate professor at the Washington State University College of Nursing in Vancouver.

Klein and her colleagues Dan Hartung, PharmD, and Jonah Geddes, MPH, used prescription drug monitoring data to look at prescription and dispensing patterns in Oregon before and after nurse practitioners and physician assistants gained the authority to prescribe buprenorphine in 2017. Before that time, only physicians were allowed to prescribe the medication nationally.

Her study found that nurse practitioners almost immediately had an impact on access to buprenorphine in rural Oregon, especially in the sparsely populated areas known as frontier regions - counties with six or fewer people per square mile.

By the end of 2018, nurse practitioners accounted for nearly 1 in 5 buprenorphine prescriptions in rural Oregon, according to the study, published in the Journal of Rural Health. In frontier areas - 10 of Oregon's 36 counties - nurse practitioners accounted for more than a third of buprenorphine prescriptions dispensed, it said.

Nurse practitioners are sometimes the only healthcare provider in these very rural areas, Klein said.

"It's not surprising that having nurse practitioners be able to do this would increase access to buprenorphine in rural areas," she said. "It was surprising the extent to which people were reliant on nurse practitioners for this service and that nurse practitioners were stepping up to the plate and providing it."

Opioid addiction "continues to be an enormous public health crisis that claimed over 46,000 lives in 2018," the study notes.

Implementation of the Comprehensive Addiction and Recovery Act in early 2017 was intended to expand availability of medication-assisted treatment, which includes prescribing buprenorphine in an office or clinic.

Klein said her study "offers a good opportunity to look at whether changing a law has an impact on patient care," especially in little-studied frontier areas.

Said Klein, "This is one of the few studies that's really looked at the impact of nurse practitioners in frontier areas. Most studies look at urban versus rural, but it's important to consider frontier areas that are even more isolated and underserved, and the contribution nurse practitioners make to this very important aspect of health care."

Researchers from Kaunas University of Technology (KTU), Lithuania came up with the idea on how to measure fluctuating blood potassium levels non-invasively, through electrocardiogram. The researchers claim that their method may become a digital biomarker in the future for managing electrolyte levels. This would be a huge step towards preventing potentially life-threatening conditions among people who suffer from chronic kidney disease.

Electrolytes and especially potassium, are paramount in the conduction of the heart's cells. When electrolytes are too low or too high, the heart cannot contract normally, leading to dangerous arrhythmias and potentially sudden cardiac death.

"Electrolyte levels are kept within the healthy range by the kidneys. However, the patients with the last stage of chronic kidney disease, who have no renal function left, rely on hemodialysis to keep their electrolyte levels regulated. This means that they are prone to electrolyte imbalance in a 2-day-long hiatus between hemodialysis sessions", explains Ana Rodrigues, researcher at KTU Biomedical Engineering Institute, one of the authors of the invention.

According to Rodrigues, with today's aging society, it is estimated that the number of people requiring hemodialysis will markedly increase within 10 years. As people age, so do their kidneys. Research shows that up to 50 percent of seniors over the age of 75 can have kidney disease.

Abnormal electrolyte levels disturb the heart's natural rhythm; such abnormalities can be reflected in the electrocardiogram. However, identifying electrolyte imbalance using an electrocardiogram is difficult due to confounding factors that mask these expected changes. The task becomes particularly complicated if electrolyte levels start to fluctuate beyond normal, but not reaching levels that require immediate medical attention.

The method proposed by the team of KTU researchers, tackles the problem through mathematical models that enable to quantify subtle changes that are not visible to the naked eye at the early stages of electrolyte imbalance. The method allows to spot potassium - the most arrhythmogenic electrolyte - induced changes in a certain part of the electrocardiogram.

"The initial results are promising. Our method may become a digital biomarker in the future for the management of electrolyte levels", says Rodrigues.

The method proposed by KTU researchers allows detecting abnormal potassium levels before the onset of life-threatening arrhythmias. Patients could then start hemodialysis sooner, decreasing the chance of hospitalization and even premature death.

Usually, in order to detect the changes in electrolyte balance, a blood sample would be drawn from a patient. However, blood samples are not routinely requested and cannot be drawn outside a clinical environment. Thus, researchers in Lithuania came up with the idea which would allow measuring electrolyte balance noninvasively at home through an electrocardiogram.

"Noninvasive monitoring of electrolyte levels is a very novel concept and is now in its infancy stages. Our paper is one of the first papers published on the topic and, to the best of our knowledge, the first to investigate potassium fluctuations in ambulatory settings between hemodialysis sessions", says Rodrigues.

The research is the outcome of the close collaboration between KTU, Lithuanian University of Health Sciences (LSMU) and the University of Zaragoza, Spain.

At the moment, clinical studies involving 17 patients have been completed. The researchers are planning on continuing clinical trials with more patients in order to validate their findings. Their next goal is to create an algorithm that would include measuring different electrolyte levels, such as calcium.

Later on, the algorithm could be integrated into wearable wrist-worn device capable of acquiring electrocardiograms. Every once in a while, the patient would record a short electrocardiogram signal (roughly 2-min long) using their fingers, and the system would register the electrolyte levels. If electrolytes were at an alarming level, the clinic would be notified, and the patient would be instructed accordingly.

Excessive calcium contributes to harmful inflammation in ischemic stroke, and targeting it may provide doctors with a new way to improve patient outcomes, new research from the University of Virginia School of Medicine suggests.

Petr Tvrdik, PhD, has found that immune cells called microglia are flooded with waves of calcium in the wake of ischemic strokes, which are strokes caused by disruption of blood flow to the brain. These calcium waves, he determined, trigger damaging inflammation that may worsen the stroke's effects.

Blocking the calcium waves, his work suggests, may help control the harmful inflammation and offer doctors a way to reduce the often-debilitating effects of ischemic stroke.

"This publication culminates several years of research on this previously unrecognized aspect of stroke pathology," said Tvrdik, of UVA's Departments of Neurosurgery and Neuroscience. "Our success would not be possible without exceptional contributions of the lead authors on the study, medical students Kathryn Kearns and Lei Liu. A special mention in this regard goes to the support from Medical Summer Research Projects, directed by Dr. Driscoll, which provided a stimulating environment for the students and much-needed help for my lab."

The Answer is Calcium

Scientists have known for almost two decades that the lack of blood flow to the brain during ischemic strokes causes waves of abnormal brain activity, which are called cortical spreading depolarizations, or CSDs. These CSDs are harmful and can set the stage for additional brain damage. In addition to occurring in ischemic stroke, they are also seen in traumatic brain injuries (TBI), migraine and subarachnoid hemorrhages, which are bleeds in the space between the brain and its surrounding membrane.

The new research from Tvrdik and his colleagues sheds light on what is occurring during these CSDs. Working in laboratory mice, the scientists found that ischemic strokes trigger waves of calcium to flood through the brain's defenders, the immune cells known as microglia. This calcium overload "triggers CSDs in a recurring and progressive fashion," the researchers write in a new scientific paper.

"Further research is needed to determine just how harmful these calcium waves are," Tvrdik said. "Our paper received top 5% attention score on social media. We hope that this excitement in the field will translate into more funding for our research."

Promisingly, the researchers were able to use a drug to reduce the calcium waves in their mouse models by more than 25%. This gives them hope that a similar approach could be used to reduce the calcium waves' harmful effects in stroke patients, though more research is needed.

"We are fortunate to collaborate with CalciMedica, a pharmaceutical company who specializes in developing drugs suppressing calcium overload in the immune cells," Tvrdik said. "We share the vison that our research might help to identify an effective drug that will improve the recovery of stroke survivors."

Young children of African ancestry are more at risk of developing obesity if they possess a genetic variant that reduces their ability to produce the hormone leptin. Adults with the variant do not have the same risk, suggesting that leptin plays a role in the development of obesity at a young age but the obesity does not continue into adulthood.

This is one of the findings made in an international study by scientists at the University of Copenhagen, University of Exeter, Icahn School of Medicine at Mount Sinai, and others, who investigated the role of genetics in controlling leptin levels.

"Our findings suggest that young children might be particularly sensitive to the effect of leptin in controlling their body weight," says Associate Professor Tuomas Kilpeläinen from the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen.

Understanding variation in leptin levels through genetics

It has long been established that the hormone leptin is released by the body's fat tissue and tells the brain how much fat is stored on the body - the more body fat a person has, the higher the levels of leptin. The brain uses this information to regulate a person's appetite and food intake.

Leptin levels vary between individuals, however, and around 10 to 20 percent of individuals with obesity have the same leptin levels as individuals with normal weight. This variation raises questions about the role leptin plays in regulating weight.

In the research, published in Diabetes, the scientists screened the genome of more than 55,000 people for genetic variants that affect leptin levels. They identified five new genetic variants that play a role in regulating leptin levels.

Leptin may play a stronger role in weight control in children, than adults.

One of the variations, Vel94Met, which reduces the amount of leptin that the body produces, is only found in individuals of African ancestry. Young people with this variation are more at risk of developing obesity, though this is not true of adults with the variation, who tend to be of similar weight as other adults.

This finding supports the theory that people become less sensitive to leptin with age. Administering leptin to obese adults has proven ineffective at controlling their weight.

"This new knowledge on the impact of leptin in the weight control of young people now needs to be followed up with further studies to uncover the molecular mechanisms that underlie this age-dependent relationship between leptin and BMI," says Associate Professor Tuomas Kilpeläinen.

Palaeontologists at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and the University of Calgary in Canada have provided new proof of parallel evolution: conodonts, early vertebrates from the Permian period, adapted to new habitats in almost identical ways despite living in different geographical regions. The researchers were able to prove that this was the case using fossil teeth found in different geographical locations.

One of the most convincing arguments proving the theory of evolution is that it is fairly easy to predict how animals and plants will evolve to adapt to changes in their habitats. There is no shortage of proof that organisms with a common ancestor evolve in the same way even if they are entirely isolated from each other. One of the most prominent examples is the Midas cichlid in Nicaragua. Approximately 6,000 years ago, individual fish colonised various crater lakes. Interestingly, they developed identical morphologies in their new habitats. One group specialised in catching small shrimps and developed a stocky body with a flat mouth. Another group hunts fish in deeper water and is considerably more streamlined. 'These subspecies are found in each of the crater lakes, although there is no connection whatsoever between the habitats,' says Dr. Emilia Jarochowska from GeoZentrum Nordbayern at FAU. 'This is an example of parallel evolution.'

Fossils from Russia and Bolivia

Emilia Jarochowska's research focuses on evolution in different ecosystems, but rather than studying animals which are still alive today she concentrates on conodonts, organisms which lived in the sea approximately 500 to 200 million years ago and were one of the first vertebrates. The cone-shaped teeth of the eel-like organisms can still be found as micro fossils in sedimentary rocks across the globe. Scientists estimate that there were roughly 3000 different species of conodonts. 'Scientists have suspected for several years now that a certain subspecies known as Conodont Sweetognathus developed several parallel evolutionary adaptations,' says Emilia Jarochowska.

The researchers from Erlangen set out with palaeontologists from the University of Calgary to prove this theory. The Canadian researchers had collected fossilised Sweetognathus teeth from various locations across the world, including Bolivia and Russia. Emilia Jarochowska explains, 'As we now have such a good knowledge of tectonics over the history of the Earth, we can rule out the possibility that organisms from these regions were ever in contact with each other.' The fossils measuring a mere two to three millimetres in length were scanned at GeoZentrum Nordbayern in a scanner with a spatial resolution of four micrometres, which delivers even higher definition pictures than a CT in a hospital. Precise 3D models and mathematical descriptions were made of more than 40 samples.

Parallel evolution confirmed

The painstaking analysis of the morphologies in the dental elements confirmed what scientists have suspected for years: Conodont Sweetognathus adapted repeatedly in response to different food sources after emigrating to new habitats in an almost identical fashion in spite of these habitats being isolated from each other. Comparing samples from a large number of fossils over a number of years has now allowed researchers to confirm without a doubt that the teeth found in Bolivia and Russia come from organisms with a common ancestor. 'We were able to prove that two lineages of Sweetognathus in two different parts of the world followed the same developmental pattern,' Emilia Jarochowska explains. 'That is further proof for the theory of evolution - and for the effectiveness of international collaboration.'

Up to one-quarter of people who suffer child sexual abuse might be passed over for treatment because of current screening procedures, according to UC Riverside psychology researchers.

Their just-published study also finds that whether survivors of child sexual abuse identify themselves as abuse survivors influences the outcomes they experience in young adulthood.

Research has previously shown sexual abuse survivors suffer from increased mental health problems, a poor view of themselves, and are more likely to engage in risk-taking behaviors. The new UCR research looks at the impact of the survivor's perception of the abuse.

Sexual abuse is difficult to define and study. In this study, researchers defined sexual abuse as sexual contact between a minor and a person five or more years older. The study considered how age of onset of abuse, identity of the perpetrator, and degree of force influenced survivor's later psychosocial outcomes and whether the survivor self-defined their experiences as sexual abuse..

The study surveyed 2,195 undergraduate college students, about two-thirds of whom were female. The sample was almost half Asian, about one-fourth Latino; 17% white; 7% Black; and 4% multiracial/other.

Survey questions sought to determine which participants had suffered abuse with questions such as: "Before the age of 17, were you ever touched in a sexual way that made you feel uncomfortable, when you did not want to be, or at a time when you couldn't defend yourself?" and more specific follow-up questions about penetration, force, and identity of the perpetrator. Participants who reported experiences of child abuse survivors were then asked: "To the best of your knowledge, before the age of 17, were you sexually abused?" to identify survivors who self-defined their experiences as sexual abuse and those who did not.

The study found 252, or 11 percent, of those in the study reported experiences of child sexual abuse--similar to percentages researchers have found in the broader population.

Of those 252, 193, or about 77%, identified as sexual abuse survivors, but 59, about 23%, did not self-identify as sexual abuse survivors. Of the remaining group, 1,202 reported no maltreatment, and 741 were excluded because they reported other forms of childhood maltreatment, such as physical abuse or neglect.

"Child sexual abuse survivors who do not acknowledge their experiences as abuse may be employing a protective mechanism wherein the survivor denies the existence of the abuse or takes personal responsibility for the abuse," said Linnea Linde-Krieger, lead author of the paper, which was published this month in the Journal of Child Sexual Abuse.

The results indicated that as child abuse survivors moved into young adulthood, the form and extent of their difficulties were influenced by how they defined their abuse experiences--even though the way they defined those experiences was not related to the severity of the abuse they experienced.

Neither form of identity was more advantageous, the researchers found. When participants identified as abuse survivors, they were more likely to exhibit distress and anger, and had more difficulty regulating their emotions. That group was also more likely to engage in substance abuse, criminal activity, and sexual risk-taking. However, participants who reported experiences of sexual abuse but didn't identify as abuse survivors were more likely to have a poor self-concept.

"Our study shows that survivors who do not acknowledge their experiences as abuse might be protected from some negative outcomes, but they are more likely to have negative beliefs about themselves," said Linde-Krieger, who is a graduate student in the lab of UCR psychology professor Tuppett Yates.

An additional finding: the study authors determined that children abused after the age of 6 were more likely to report that they did not believe they were sexually abused. Researchers said that may be because children are more likely to blame themselves when the age of onset is older.

Linde-Krieger said the research holds implications for organizations and government agencies that assess for adverse experiences in childhood, including for sexual abuse. Often, their questionnaires ask only a single question, such as: "Have you ever been sexually abused?" One-quarter of the survey's abuse survivors would have answered "no" to such a question, Linde-Krieger said.

"Researchers and practitioners must employ multifaceted and behaviorally specific questions to accurately assess a history of child sexual abuse," she said.

(Santa Barbara, Calif.) — Cells move constantly throughout our bodies, performing myriad operations critical to tissue development, immune responses and general wellbeing. This bustle is guided by chemical cues long studied by scientists interested in cellular migration.

To better understand this phenomenon, a team of biologists and physicists, led by UC Santa Barbara’s Distinguished Professor Denise Montell, investigated the effect that the geometry of the biological environment has on cellular movement. Using mathematical models and fruit flies, the group discovered that the physical space holds a lot of sway over cell migration. Namely, tissue geometry can create a path of least resistance, which guides cellular motion. These insights, published in the journal Science, are a triumph for basic research and could find applications in fields as diverse as oncology, neuroscience and developmental biology.

Directed cell migration is an essential feature of biological processes, both normal and pathological. “Without directional cell migration, embryos would not develop, wounds would not heal and the immune and nervous systems would neither form nor function,” said Montell, the Duggan Professor in the Department of Molecular, Cellular, and Developmental Biology. “Yet cell migration also contributes to inflammation and cancer metastasis, so understanding the underlying mechanisms has garnered substantial interest over decades.”

Scientists have known for a long time that cells sense chemical attractants. Many thought a chemo-attractant gradient was all that was necessary for cells to migrate where they were needed. Yet reseachers are now looking increasingly at how the physical environment contributes to the way cells choose their paths. This presents a practical challenge, however, since reconstructing the geometry of a living tissue in an artificial environment is a tall order.

Montell’s team experimented with the ovaries of fruit flies — one of the earliest and best-studied models of cell migration — to tease out the contributions of multiple different factors. Within the ovary are several egg chambers consisting of 15 nurse cells and one oocyte, or developing egg cell, at one end. The nurse cells support the growth of the egg.

Around 850 follicle cells surround the nurse cells and oocyte. Of these, a group of six to eight at the tip of the egg chamber, called border cells, detached and migrate between the nurse cells to the oocyte, where they are critical in the final development of the egg.

Not only does this system provide a perfect model for studying cellular motion in general, the border cell cluster behaves very similarly to metastasizing cancer. “At first, the system might seem very obscure and arcane to pick out of the blue,” Montell admits, “but as it turns out, Mother Nature reuses things, and the mechanisms that these cells use to move are very similar, even in molecular details, to how cancer cells move.”

There are two components to the border cells’ migration. They clearly move from the anterior to the posterior of the egg chamber. However, what was less appreciated until now is that they also stay centrally located rather than moving to the chamber periphery on their journey, despite having roughly 40 different side paths they could take.

The researchers found that the chemo-attractant could not account for the choice of the central path — something else must keep the border cells along their path. In fact, when they knocked out the cells’ ability to detect the chemical signals, the researchers found that the cells still kept to the center of the egg chamber, although they no longer made it all the way to the oocyte at the opposite end.

The egg chamber is filled with many cells, which presents a stacking problem much like packing balls into a crate. Mathematicians have been working on problems like these for centuries and have found that there’s more space in areas where more cells come together. The team confirmed this by dunking the egg chamber into a fluorescent fluid that filled the gaps between the cells.

“It seems that the border cells choose the center because it’s a place where there’s a tiny bit more space,” said Montell. “What was most surprising is that the physical space is really tiny, much smaller than the objects moving through it. It’s this tiny space that makes the difference.”

Co-lead author Wei Dai, a former postdoctoral researcher in Montell’s lab, carefully studied the egg chamber under the microscope and painstakingly recreated the arrangement of cells in a 3D model. This allowed the physicists on the project — Yuansheng Cao and Wouter-Jan Rappel from UC San Diego and Nir Gov from the Weizmann Institute of Science in Israel — to create a mathematical model of the system on which to run simulations.

Montell’s son, a technical director at Pixar Animation Studios, was then able to superimpose the results of the mathematical model onto the 3D recreation of the egg chamber. The results supported the hypothesis that the extra bit of room between cells created an optimal path.

To ascertain that the cellar geometry really was responsible for the border cells’ path, the paper’s other lead author Xiaoran Guo, a doctoral student in Montell’s lab, looked at mutated egg chambers with 31 nurse cells, as opposed to the usual 15. In these more crowded cases, the border cells still chose a path through the area with the most cellular junctions, rather than the physical center of the egg chamber.

“The tissue geometry creates a central path of least resistance, which provides directional information equally important to that provided by chemo-attractants,” said Montell, adding that for 15 years chemical signals were thought to be the sole guidance cues.

She suspects a number of different factors underlie the cells’ behavior. While traveling, the border cells explore their surroundings by extending small projections of the cell membrane, which are about the same scale as the gaps between the nurse cells. Additionally, the nurse cells are zipped together with proteins where they touch. By traveling through the gaps where several cells meet, the border cells don’t need to break all these bonds to slip past.

The study’s results make it apparent that scientists need to consider the influence of the physical environment for all kinds of instances where cells migrate through tight spaces; for example, the development of the brain or the movement of immune cells through lymph nodes and tumors.

“Getting immune cells into the tumor can be a challenge, and maybe part of that is this tissue geometry challenge,” Montell said. “Who would have thought that what we really need to be doing is perhaps loosening up the tumor to help the immune cells get in.

“These findings add a new concept to the way we think about what cells are attracted to and how they move around.”

Scientists from Tomsk Polytechnic University and Saratov State University teamed up with colleagues from Taiwan and proposed to make a laser 'blade' for a medical scalpel with a specified curved shape using a photonic 'hook'. Currently there are laser scalpels only with an axisymmetric focus area, i.e., with a cylindrical blade. According to scientists, changing the shape of the blade will expand the possibilities of using the laser in medicine, while it is about two times thinner than the cylindrical option. The concept and its rationale are published in the Journal of Biophotonics (IF: 3.032; Q1).

A laser scalpel is a surgical instrument used to cut or remove biological tissues by using laser energy. In a limited area of tissue the beam sharply raises the temperature up to 400 °C, thus making the irradiated area to burn out instantly. This way, the laser immediately 'seals' small blood vessels along the edges of an incision. The laser scalpel makes very thin incisions, reduces bleeding, and the radiation itself is absolutely sterile.

"A conventional surgical scalpel has a variety of blade shapes to suit specific applications. Laser scalpels do not have such a variety, or rather, there is only one form of radiation localization - axisymmetric. Therefore, we proposed a simple way to make the tip shape curved using a photonic 'hook'. This is a new type of curved self-accelerating light beam, shaped like a hook. Earlier, we theoretically predicted and experimentally confirmed the existence of such a 'hook'," says Igor Minin, project manager, Professor of the Department of Electronic Engineering at TPU.

An indispensable element of a laser scalpel is the fiber for transmitting laser energy. At its end, a focused laser beam of several wavelengths is formed. With its help, the surgeon performs all necessary manipulations.

"To bend the laser beam, we proposed one of the simplest possible solutions: place an amplitude or phase mask at the end of the fiber. It is a thin plate made of metal or a dielectric material like glass. The mask redistributes the energy flow inside the fiber and forms a curved region of radiation localization at the end of the fiber, that is, a photonic 'hook'.

Through simulation, a curved blade is proved to have a length of up to 3 millimeters and a thickness of about 500 microns (100 microns is the thickness of a human hair - ed.), with a wavelength to be 1,550 nanometers. In other words, we add one small element, without affecting the general design and performance of the device, and get changes in the area of the fiber end alone (at the tip). The shape and thickness of the blade is changing: it is approximately two times thinner than the axisymmetric option," Igor Minin explains.

In the article, the scientists provided a theoretical basis for the concept, and now they are preparing to confirm it experimentally at National Yang-Ming University (Taiwan).

Washington State University scientists have developed a new way to classify the ocean's diverse environments, shedding new light on how marine biomes are defined and changed by nature and humans.

Newly published in Global Ecology and Biogeography, research by Alli Cramer, a 2020 doctoral graduate of WSU's School of the Environment, now at the University of California Santa Cruz, and WSU Professor Stephen Katz revealed a new approach which sorts biomes based on their life-supporting potential and stability of the sea floor.

Cramer and Katz reviewed more than 130 studies to weigh variables such as light, depth, and nutrients across seven biomes incorporating dozens of environments, including coral reefs, kelp beds, ocean ice, and deep abyssal plains.

Analyzing the data inductively, rather than proceeding from an initial hypothesis, they found biomes were most clearly sorted by two strong variables: gross primary production, a measure of the energy in the food web; and substrate mobility, or the movement and composition of the ocean floor.

"This means that energy flow and mobility are common organizing forces across a wide variety of marine ecosystems," Cramer said. "Despite their differences, coral reefs and deep-sea deserts respond to the same processes."

While biomes on land have long been defined by climate, marine biomes have evaded clear categorization.

"The oceans are a big black box," Katz said. "Scientists have traditionally seen depth, temperature, and light as important. But we found that they don't capture every community. The sea's energy economy runs in other ways than just sunlight."

As a doctoral student, Cramer set about developing a more effective way to sort out marine biomes.

After analyzing many variables, "there were really only two that end up revealing the big pattern," Katz said.

Gross primary production measures the energy flowing through a marine community--whether fueled by sunlight, the recycled 'brown food web' of the deeps, or chemicals flowing from hydrothermal vents. Coral reefs, sea ice, and mangrove swamps have high primary production, while the deep, muddy abyssal plains are marine deserts of low productivity.

The other strong variable, substrate mobility, sorted biomes on the nature of their bottom layer--what it is made of, and how much it is moved and stirred by waves and currents. A sandy bottom that's mostly stable defines a different biome from one that's constantly in motion.

"These two axes are important forces in determining the ecosystems in the ocean, and driving their formation," Katz said.

"One of the things that's novel about this classification system is that it's simple-- so simple that nobody bothered," he added. "When we told our colleagues about this, they were surprised that no one had tried it before."

The new method could help scientists, fisheries managers, and conservationists reconsider the richness and diversity of ocean biomes as well as the value of high productivity regions being impacted by humans.

"Previous work has looked at the marine environment on an ecosystem-by-ecosystem basis," Cramer said. "By combining data from many ecosystems, we found the common thread that binds them together. This lets us see the ocean in new ways and highlights some key places where our actions may alter ecosystem function."

A team of researchers has amplified 3D graphene's electrical properties by controlling its curvature.

"Our research showed the conservation and the degradation of the ultra-low dissipative transport of Dirac electrons on the 3D curved surface for the first time," said Yoichi Tanabe, leading author of the study.

Graphene is a 2D atomic-layer material, shaped like honeycombs, which possesses excellent electrical, chemical, thermal, and mechanical properties for a wide range of applications such as semiconductors, electrical batteries, and composites.

Graphene sheets stacked together form graphite which makes up the lead in our pencils. However, packing together graphene tightly means it loses its 2D electronic properties.

One way to overcome this is to separate the graphene sheets with air-filled pores--like a sponge--at the nanometer scale and make it into a three-dimensional structure. This amplifies graphene's properties for practical purposes.

But doing so is not without its challenges; converting 2D graphene into 3D graphene introduces crystal defects and a host of other problems that cause it to lose its desirable characteristics. Little is known about how the curved surface degrades the graphene's electric transport properties and whether this is the reason for graphene losing its Dirac fermions.

The research team sought to investigate this by taking a single, 2D graphene sheet and folding it into a 3D structure with a bicontinuous and open porous structure.

The structure, with a curvature radius down to 25-50 nanometers, retained the basic electronic properties of 2D graphene well. Meanwhile, the motion of electrons on the 3D curvature enhanced electron scattering that had originated from the intrinsic curvature effects. In fact, nanoscale curvature provides a new degree of freedom to manipulate graphene's electronic behaviors for the emergent and unique electrical properties of 3D graphene.

University of Virginia Cancer Center researchers have identified a gene responsible for the spread of triple-negative breast cancer to other parts of the body - a process called metastasis - and developed a potential way to stop it.

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer that accounts for 40,000 deaths in the United States annually. The majority of these deaths result from resistance to chemotherapy and subsequent aggressive metastases. So UVA researchers asked: What causes a primary tumor to become metastatic? This is an important question in cancer biology because patients with metastatic tumors have the highest death rate.

UVA's Sanchita Bhatnagar, PhD, and her team found that the breast cancer oncogene TRIM37 not only causes the cancer to spread but also makes it resistant to chemotherapy. A new approach she and her colleagues have developed could possibly address both, the researchers hope.

"Despite metastasis being the key reason for failure of cancer therapies, it remains poorly understood. We do not clearly understand what drives the metastatic growth in patients," said Bhatnagar, who was the first to identify TRIM37 as a breast cancer oncogene. "In general, several genes are altered during tumorigenesis. However, whether targeting the same genes will prevent metastatic transition remains to be addressed."

Promising research from Bhatnagar's team shows that targeting TRIM37 prevents metastatic lesions in mouse models. Those findings form the foundation of her lab's current work exploring the role of TRIM37 in racial disparities in triple negative breast cancer. Incidence of the disease is disproportionately higher in African-American women compared with other races, with a 5-year survival rate in African-American patients of only 14% compared with 36% in non-African-American women.

Targeting Triple-Negative Breast Cancer

Bhatnagar and UVA's Jogender Tushir-Singh, PhD, have developed a new approach to stop the effects of TRIM37 and, hopefully, prevent or significantly delay the spread of triple-negative breast cancer. This could also lower the disease's defenses against chemotherapy.

Blocking the gene could benefit approximately 80% of triple negative breast cancer patients, the researchers estimate.

Bhatnagar and Tushir-Singh's approach uses nanoparticles - microscopic balls of fat - to deliver treatment to block TRIM37. These nanoparticles are paired with specially engineered antibodies that bind to the cancerous cells but not to healthy cells. "As soon as the antibody finds the triple negative breast cancer cell, it binds to the receptor and is taken up by the cell," explained Tushir-Singh, of UVA's Department of Biochemistry and Molecular Genetics.

"It is a kiss of death," Bhatnagar said, "that selectively reduces the expression of TRIM37 in cancer cells and prevents the spread."

The approach could be used to deliver targeted treatments for many other cancers as well, the researchers report. "That would not only get the treatment where it needs to be but, hopefully, help prevent unwanted side effects. Besides preventing metastases, it adds selectivity," Bhatnagar said.

"A problem in the field is, how will you give [a nanoparticle treatment] to the patients? Most of these nanoparticles are cleared by the liver, so they never have a chance to really do their job," she said. "In this study, researchers bypassed this issue by delivering nanoparticles by nasal route, increasing the rate of uptake in the lungs - one of the most common metastatic target sites in TNBC patients."

The development of the new approach is in its early stages, but tests with lab mice have offered encouraging indications. "The lungs showed dramatic reduction in metastatic lesions after the treatment in comparison to the mice that received no treatment," Bhatnagar said.

Next Steps

To verify that TRIM37 targeting might offer a potential treatment approach, Bhatnagar teamed up with Tushir-Singh, her husband, to test it in the lab. "And we find that our targeted nanoparticles significantly reduce metastatic lesions in the lungs of spontaneous metastatic murine [mouse] models - both immune compromised and immune sufficient," she said. "This is an important proof-of-concept much needed for the bench-to-clinic transition of these important findings."

Clinically, most women in the early stages of breast cancer are treated with surgery, followed by radiation or chemotherapy. However, metastasis remains a challenging medical problem. Bhatnagar's research offers a potential way to target a driver of metastasis that she hopes will prevent or slow metastatic progression and improve overall survival.

Much more work needs to be done, but Bhatnagar's research is being noticed by pharmaceutical companies interested in exploring the approach's potential. "This is a delivery platform, not only for targeting our protein of interest but for many other chemotherapeutic drugs that can be packaged into the nanoparticles and selectively delivered," Bhatnagar said.

Researchers used metal-organic frameworks (MOFs) enhanced with a green tea phytochemical coating to target human prostate cancer cells for the first time.

The new method for deploying the genetic snipping tool directly into target cells is a big step towards more effective, safer and cheaper gene therapy with treatment potential for multiple genetic disorders.

Lead researcher, Associate Professor Ravi Shukla, said MOFs, which are versatile and biocompatible nanomaterials, were a promising alternative to existing viral methods for delivering the gene editing tool CRISPR/Cas9.

"MOFs have the capacity to carry larger genetic loads and as a non-viral option, have the added benefit of being a safer prospect for patients than viral alternatives," he said.

Awarded the 2020 Nobel Prize in Chemistry, CRISPR/Cas9, is widely acknowledged as a breakthrough in genetic editing for its ability to remove and replace defective DNA, however the biggest challenge remains effectively delivering it to cells.

There are currently just 13 approved methods in trial globally and all rely on viral therapies, an approach which is both extremely costly and has associated health risks.

RMIT has partnered with the CSIRO who have previously developed a technology to carry and protect biomolecules with MOFs.

CSIRO Research Team Leader, Dr Cara Doherty, said the CSIRO had also developed technologies to manufacture industrial scale quantities of various MOFs, with the potential to significantly reduce the cost of bringing them to market.

"We're excited to find a novel way in which these materials can address complex biological issues, including targeting specific medicinal purposes like gene therapy," she said.

Cells are not designed to naturally take up foreign genes or DNA material, and the risks associated with introducing a virus into the body have slowed the progress of research into viral approaches to gene therapy.

To further improve the ability of the MOF to enter the host cell, it was coated with a phytochemical found in green tea, called epigallocatechin-gallate (EGCG), known for its antioxidant and anticancer properties.

Co-author Arpita Poddar said the EGCG worked by binding to the surface of the MOF, assisting it to enter the host cell.

"We found an increase in cellular uptake of more than 23% for EGCG coated MOFs compared to uncoated ones," she said.

The latest findings build on previous work by the team who developed a proof of concept for the delivery model late last year.

Next, they will work to further test this technology for its application in targeting several other disease-causing genes.