Tech

New microcarrier, or particle used in bioreactor-based cell manufacturing, offers significantly higher harvest of cells grown with over 90% harvest rate compared to 50-60% rate seen in current standards

Homogenous microcarrier dimensions facilitate uniform environmental conditions for controlling consistent cell numbers per microcarrier

Facilitates expansion of mesenchymal stromal cells used to treat various ailments such as heart attacks, bone defects and immune system rejection of cell therapies

Singapore, 29 October 2020 - Researchers from Singapore-MIT Alliance for Research and Technology (SMART), MIT's research enterprise in Singapore, have developed a novel microcarrier for large-scale cell production and expansion that offers higher yield and cost-effectiveness compared to traditional methods, and reduces steps required in the cell retrieval process. Microcarriers are particles used in bioreactor-based cell manufacturing of anchorage-dependent cells.

SMART's newly developed dissolvable gelatin-based microcarrier has proven useful for expansion of mesenchymal stromal cells (MSCs), a cell type of great current interest as they can be isolated from adult tissues and further expanded to treat various ailments such as bone and cartilage defects and the body's rejection of foreign bone-marrow and cells (called graft vs. host disease). This dissolvability of the microcarriers also eliminates an additional separation step to retrieve the cells from the microcarriers. This reduces the complexity of cell manufacturing and increasing the ease with which the therapeutic cells can be harvested to make the product for patients.

SMART's Critical Analytics for Manufacturing Personalized-Medicine (CAMP) Interdisciplinary Research Group (IRG) discovered that gelatin microcarriers, which fully dissolves in enzymatic treatment, can be useful in the cell recovery step - one of the current bottlenecks faced in 3D microcarrier culture. The novel gelatin microcarrier showed higher yield and reduced cell loss at the cell harvesting step compared to commercial microcarriers, with comparable cell attachment efficiency and proliferation rate.

Their discovery is explained in a paper titled "Dissolvable gelatin-based microcarriers generated through droplet microfluidics for expansion and culture of mesenchymal stromal cells" published in Biotechnology Journal and co-authored by researchers from SMART CAMP, Massachusetts Institute of Technology (MIT), National University of Singapore (NUS) and City University of Hong Kong (CityU).

"Our study achieved over 90% harvest rate of cells grown on the gelatin microcarriers, which is significantly higher than the 50-60% harvest rate seen in current standards," said Dr. Ee Xien Ng, lead author of the paper and CAMP alumnus. "Using gelatin microcarriers also achieved tight control over microcarrier dimensions (for example, microcarrier diameter and stiffness) that facilitate uniform environmental conditions for controlling consistent cell numbers per microcarrier."

The research also showed that MSCs cultured by gelatin microcarriers retain critical quality attributes of retrieved cells, such as a higher degree of trilineage multipotency with more balanced differentiation performance compared to commercial microcarriers. Most commercial microcarriers showed similar trends in adipogenic differentiation efficiency, while losing some degrees of chondrogenic and osteogenic differentiation capability.

"Innovations in microcarriers will aid in the scalability of certain cell types such as mesenchymal stromal cells for cell-based therapy, including for regenerative medicine applications," says Professor Krystyn J. Van Vliet, co-author of the paper as well as Lead Principal Investigator at CAMP and Professor of Materials Science and Engineering and Biological Engineering at MIT. "Developing a microcarrier platform for MSC culture has been a key part for SMART CAMP's understanding and managing the critical quality attributes of these cell therapy products. We hope our findings help bring about better, more efficient and scalable cell therapies with predictable therapeutic outcomes for multiple patient needs, and high harvesting efficiency of those potent cells."

While the study focused on whether gelatin microcarriers are suitable for MSC culture and expansion, the team's research could potentially be extended for other types of anchorage-dependent cells.

The research is carried out by SMART and supported by the National Research Foundation (NRF) Singapore under its Campus for Research Excellence And Technological Enterprise (CREATE) programme.

In 2009, the European Union's Renewable Energy Directive (EU RED) established goals to produce more energy from renewable sources, triggering exponential growth in the solid biomass trade. By 2018, the EU was trading over 18 million tons of wood pellets, with a third imported from the southeastern United States.

But what effect does this large, new industry have on southeastern US forests? Until now, European policymakers could only infer that the region's wood pellet industry was compliant with EU RED rules through case studies, land use projections, and literature reviews. This first-of-its-kind study gives a more definite confirmation of compliance.

From 2005 to 2017, an international team conducted a systemic assessment of 123 areas where wood pellet mills managed vast swaths of forest. Composed of researchers from the Swedish University of Agricultural Sciences, University of Missouri, and Resources for the Future, the team found the following trends:

Overall, there was a net expansion in the amount of carbon stored in southeastern forests--which means that current production is compliant with EU trade requirements calling for the preservation of carbon stocks in biomass sourcing areas.

The amount of carbon stored in the soil of southeastern forests decreased with each year of milling operations.
There were no significant changes in the amount of carbon stored in live or standing-dead trees, but the carbon was concentrated in fewer but larger trees.

There was a downward trend in the number of standing-dead trees.

"All in all, our analysis suggests some positive areas but possible concerns if some trends were to continue. We examined 12 years of data, but that is only a small window of time to assess sustainable forestry," lead author Francisco Aguilar said. "Monitoring using the best-available data shall continue. And it must be observant of other co-localized factors that can significantly alter forest conditions. For instance, systematic assessments must also take into consideration population changes, expansion in wood fibre demand from other competing sectors, and extreme weather."

The researchers also note that the US Department of Energy suggests a 21% increase in domestic electricity generation using wood by 2030 may also signal a further increase in demand--and that future monitoring is warranted.

"This research provides the first comprehensive assessment of changes to US timberlands induced by demand in the EU for pelletized wood for energy production," coauthor and RFF Darius Gaskins Senior Fellow Dallas Burtraw said. "The findings provide cautious support for the sustainability of US forests, with ongoing monitoring, as demand for wood pellets is likely to increase."

Researchers from Skoltech and their US colleagues have designed a new machine learning-based approach for detecting atrial fibrillation drivers, small patches of the heart muscle that are hypothesized to cause this most common type of cardiac arrhythmia. This approach may lead to more efficient targeted medical interventions to treat the condition that is estimated to affect more than 33 million people worldwide, according to the American Heart Association. The recent paper was published in the journal Circulation: Arrhythmia and Electrophysiology.

The mechanism behind atrial fibrillation (AF), a type of abnormal heart rhythm that is associated with increased risk of heart failure and stroke, is yet unclear. Research suggests it may be caused and maintained by what's called reentrant AF drivers, highly localized sources of repetitive rotational activity that lead to irregular heart rhythm. These drivers can be burnt via a surgical procedure, which can mitigate the condition or even restore the normal functioning of the heart.

To locate these reentrant AF drivers for subsequent destruction, doctors use multi-electrode mapping, a technique that allows them to record multiple electrograms inside the heart (this is done with a catheter) and build a map of electrical activity within the atria. However, clinical applications of this technique often produce a lot of false negatives, when an existing AF driver is not found, and false positives, when a driver is detected where there really is none.

Recently, researchers have tapped machine learning algorithms for the task of interpreting ECGs to look for atrial fibrillation; however, these algorithms require labeled data with the true location of the driver, and the accuracy of multi-electrode mapping is insufficient. The authors of the new study, co-led by Dmitry Dylov from the Skoltech Center of Computational and Data-Intensive Science and Engineering (CDISE) and Vadim Fedorov from the Ohio State University, used high-resolution near-infrared optical mapping (NIOM) to locate AF drivers and stuck with it as a reference for training.

"NIOM is based on well-penetrating infrared optical signals and therefore can record the electrical activity from within the heart muscle, whereas conventional clinical electrodes can only measure the signals on the surface. Add to this trait the excellent optical resolution, and the optical mapping becomes a no-brainer modality if you want to visualize and understand the electrical signal propagation through the heart tissue," says Dmitry Dylov.

The team tested their approach on eleven explanted human hearts, all donated posthumously for research purposes. Researchers performed the simultaneous optical and multi-electrode mapping of AF episodes induced in the hearts. ML model can indeed efficiently interpret electrograms from multielectrode mapping to locate AF drivers, with an accuracy of up to 81%. They believe that larger training datasets, validated by NIOM, can improve machine learning-based algorithms enough for them to become complementary tools in clinical practice.

"The dataset of recording from 11 human hearts is both extremely priceless and too small. We realized that clinical translation would require a much larger sample size for representative sampling, yet we had to make sure we extracted every piece of available information from the still-beating explanted human hearts. Dedication and scrutiny of two of our PhD students must be acknowledged here: Sasha Zolotarev spent several months on the academic mobility trip to Fedorov's lab understanding the specifics of the imaging workflow and present the pilot study at the HRS conference - the biggest arrhythmology meeting in the world, and Katya Ivanova partook in the frequency and visualization analysis from within the walls of Skoltech. These two young researchers have squeezed out everything one possibly could, to train the machine learning model using optical measurements," Dylov notes.

Foxes are considered to be particularly adaptable and suited to life in large cities. A team of scientists from the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW) in cooperation with the Berlin-Brandenburg State Laboratory has now deciphered an important aspect of these adaptations. Using stable isotope analysis, they showed that individual red foxes (Vulpes vulpes) have a much narrower diet than might be expected from their omnivorous habits. The population of country foxes had a much broader diet than their urban conspecifics, whose diet differed little between individuals. The diet of urban and country foxes showed little overlap. This combination of specialisation and flexibility is a key to this omnivore's adaptability, according to a paper published in the scientific journal Ecology and Evolution.

The diet is crucial to the survival of any animal. Using stable isotope analysis, the team led by first author Carolin Scholz (Leibniz-IZW) has now decoded the dietary spectrum of individual foxes in urban and rural areas. The results confirmed that red foxes are omnivorous and can feed on a wide variety of different animals and plants. At the same time, the results showed two different sets of specialisations: "Firstly, the diet of country foxes was much more varied than that of urban foxes", explains Scholz. "We detected a broad diet in foxes in unsealed habitats, ranging from plants, molluscs and insects to larger prey items. In contrast, urban foxes probably take advantage of the benefits of big city life and mainly fed on food items with increased δ13C values, an indication of food thrown away by people." Secondly, the isotope analyses confirmed that every fox is picky and specialises on particular food items, whether in the city or in the country. So, although the population of country foxes has a broad diet, each country fox follows quite a one-sided diet. City foxes celebrate a double monotony at the dinner table: both individuals and the population as a whole very often eat (different kinds of) discarded food.

The red fox's ability to eat almost anything is certainly a key to success in conquering urban habitats. The fact that urban foxes all eat more or less the same food probably also indicates that there is plenty for all of them, says Scholz. "Obviously there is enough for everyone. We city dwellers set their table abundantly - with leftover food, waste, compost and pet food."

For over a century, scientists have been puzzled by the electrification of water when it is brought in contact with water-repellent or "hydrophobic" materials, such as paraffin wax, oils, air bubbles and perfluorinated membranes and sheets. Underlying mechanisms remain hotly debated. Now, a team of KAUST engineers has untangled the roles of water, hydrophobicity and environmental factors in this process. This fundamental contribution could support development of better devices for microfluidics and nanofluidics and for generating clean energy.

"Hydrophobic surfaces are quite common," notes Jamilya Nauruzbayeva, Ph.D. student and lead author of the study. "For instance, polypropylene and perfluorinated pipettes, tubes, coatings and membranes are hydrophobic surfaces used for many basic sciences and engineering applications. Thus, it is important to understand which mechanisms are at play to improve them and develop new ones."

Himanshu Mishra, who conceived and led this study, says that he has been thinking about this problem for over five years. "Probing the surface of water is an excruciatingly difficult undertaking because the thickness of interfaces is down to the molecular scale, which no experimental techniques can probe unambiguously," Mishra explains.

"This is an electrifying subject at water conferences; over the years, through experiment and theory, several competing factors and mechanisms have been proposed," says Mishra. These include, for instance, the dipolar nature of the water molecule; the instantaneous charge transfer between interfacial water molecules and hydrophobes; the dissolution of atmospheric CO2 in water; and the interfacial accumulation of intrinsic ions of water (i.e., hydroxide and hydronium ions).

Mishra and his students teamed up with Carlos Santamarina to design elemental experiments to unentangle the role of water, its ions and pH, hydrophobicity of surfaces, and environmental factors, such as relative humidity and CO2 content.

Using a parallel plate capacitor, they exposed "pendant" droplets formed from hydrophobic capillaries respond to uniform electric fields. The competition between their weight and the electrical force tilted the pendant droplets, which revealed their charge.

Next, they utilized an electrometer--capable of measuring charges down to a few electrons--to measure the charge of the water reservoirs from where the droplets were withdrawn. They discovered that as a water droplet is withdrawn using a hydrophobic capillary, the water reservoir acquires an equal and opposite negative charge. This is not the case when you use a glass capillary.

"From these experimental results, we could deduce that these hydrophobic surfaces carried negative surface charge, even in air, which is quite counterintuitive," explains Nauruzbayeva. "When the surface is inserted in water, positive ions are attracted toward it and negative ions are repelled. Hydrophobicity ensures that the liquid departs from the surface without leaving a film behind."

"This discovery was born out of a deep understanding of the science concepts coupled with simple scientific elegance," says Santamarina. Mishra agrees by concluding that "the strength of our contribution lies in its simplicity."

CHAMPAIGN, Ill. -- Vestal Grove in the Somme Prairie Grove forest preserve in Cook County, Illinois, looks nothing like the scrubby, buckthorn-choked tangle that confronted restoration ecologists 37 years ago. Thanks to the efforts of a dedicated team that focused on rooting up invasive plants and periodically burning, seeding native plants and culling deer, the forest again resembles its ancient self, researchers report in the journal PLOS ONE.

Now, shooting stars and wild hyacinths bloom at the base of mature oak trees each spring. Appalachian brown butterflies and other native insects, salamanders, birds and reptiles have returned to reclaim the territory. Native plant biodiversity is comparable to the region's best remnant woodlands that were not as degraded by overgrazing of deer or lack of fire.

The level of success achieved in this 7-acre woodland is rare in restoration ecology, the scientists say. Most such efforts are hamstrung by limited financial resources, expertise, personnel and time. Many plant restoration interventions focus on only one technique - such as brush removal or burning to kill invasive plants - and fail to address the other factors that can undermine their efforts.

"Even very expensive vegetation restoration projects fail to meet their conservation goals more often than not," the researchers write. "In addition, long-term studies of management impacts are rare."

"We feel like we don't have a minute to spare from our stewardship, so it's hard to take time to collect data," said study co-author Karen Glennemeier, an ecologist with Habitat Research LLC. "But monitoring the ecosystem is essential for understanding the impacts of our management."

"Once we destroy a natural area, it has proved disturbingly difficult and expensive to bring it back," said study co-author Greg Spyreas, a research scientist at the Illinois Natural History Survey who focuses on plant ecology and botany. "This study shows you how to do it."

"Collaboration was key to this success," said study co-author Stephen Packard, a restoration ecologist and land steward of Somme Prairie Grove. "The Cook County Forest Preserve District, which owns the land, assembled a team of staff, contractors, volunteers and a variety of research and conservation organizations."

This team slashed and burned a dense thicket of buckthorn trees, thinned native tree density to give the oaks a chance to reproduce, harvested seed from native plants and scattered that seed in autumn for many years. Dozens of "citizen-science" volunteers led the most detailed work while hundreds of recreational conservationists joined the effort each year.

"Staff, contractors and volunteers all helped burn the woods, on average, once every two years," Packard said. The volunteers hand-weeded invasive garlic mustard, but didn't bother with most other weeds. The thinning of trees and ground vegetation allowed more sunlight to penetrate to the forest floor and promoted the restoration of natural woodland grasses and wildflowers.

"We initially feared that alien species might be impossible to control over large areas," Packard said. "Instead, with regular controlled burns and reseeding of diverse species, most of the nonnative species dropped out by themselves. They couldn't compete against the natural richness that we had thought of as so fragile."

The researchers used several measures of ecosystem health to assess the quality of the restoration. Most reflected positive changes over time. One of the metrics, known as the cover-weighted Floristic Quality Index, was very responsive to changes in ecological health.

The restoration work began in 1983 but was halted from September 1996 to July 2003 as a result of political wrangling over management of the property. The FQI showed steady improvement in the health and biodiversity of the woods until the hiatus, when the property began to revert to its degraded state.

"The effects were immediate," Packard said. "Years of work on the site could be seen slipping back into nonnative species dominance, and diversity and native plant community health crashed rapidly."

When the restoration work resumed in 2003, the recovery began again. Biodiversity and the conservation quality of the surviving flora increased, surpassing previous levels.

"Today, many people love to stroll through these restored woodlands, enchanted by their diversity and beauty," Packard said. "Because of what we've learned from this and similar experiments, much larger areas are now being restored more quickly and at less expense."

"The opportunity to walk around these woods give you a sense of what Illinois once looked and felt like," Spyreas said. "That, to me, is priceless."

Anti-NMDAR encephalitis is an autoimmune brain illness that is often mistaken by a psychiatric disorder since it causes psychoses and other behaviour alterations. Despite having these similarities, the illness does not respond to common antipsychotic treatments.

A new study by the University of Barcelona (UB) and the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) shows these symptoms would be caused by alterations in the quantity of dopaminergic receptors D1R and D2R in the hippocampal area of the brain. These results, published in the journal Annals of Neurology, shed light on the biological base of psychotic symptoms in this and other autoimmune psychoses and they could ease the development of new drugs in the future.

The study results from the bachelor's degree final project of the former student of the Faculty of Medicine and Health Sciences of the UB Marc Carceles-Cordon and it is co-led by Josep Dalmau, ICREA professor, director of the Program on Clinical and Experimental Neuroimmunology at IDIBAPS-Hospital Clínic and UB, and lecturer of Neurology at the University of Pennsylvania (Philadelphia, United States) and Jesús Planagumà, researcher at IDIBAPS. Other participants in the study are the UB and IDIBAPS researchers Francesco Mannara, Esther Aguilar and Aida Castellanos.

Schizophrenia-like symptoms

The objective of the study was to improve the understanding of the molecular origins of the psychotic symptoms in anti-NMDAR encephalitis, the most representative example for autoimmune encephalitis. These are a series of inflammatory brain diseases caused due to the generation of antibodies that attack proteins found in the surface of the neurons of the affected patients. In this illness, found by Professor Dalmau in 2007, the antibodies affect the NMDA receptor, one of the most important ones in synaptic transmission, causing alterations in behaviour and neuropsychiatric symptoms that are similar to those from schizophrenia. Given these similarities, researchers considered the hypothesis that there could be a converging mechanism between autoimmune psychosis and this psychiatric disorder. "Since the dopaminergic system of schizophrenia is altered, we focused on the analysis of the levels of dopaminergic receptors in cell cultures and in one animal model of anti-NMDAR encephalitis", notes Marc Carceles-Cordon.

This model, carried out by the research group of the UB, administers mice the cerebrospinal fluid that contains pathological antibodies from patients with anti-NMDAR encephalitis. Then, mice develop similar symptoms to those seen in patients, which are molecularly correlated to what occurs in the brain of those affected. The new study adopted the pre-existing model, which has been used successfully in other projefcts, to study psychotic symptoms in depth.

A first step towards potential treatments

The results show that giving cerebrospinal fluid from patients with anti-NMDAR encephalitis produces several changes in the levels of D1r and D2R in neuron brain cultures and similar alterations in the animal model of the disease. These changes cause memory deficits and psychotic behaviour in mice. Last, they observed that all of this reverts when stopping the administration of antibodies to patients.

According to the researchers, these results help understand the biological base of the psychiatric symptoms of anti-NMDAR encephalitis, and the autoimmune psychosis, with important implications in the design of new treatments. "In the future, these data can provide us with the development of antipsychotic drugs that consider the molecular base of this symptom and are more efficient than current antipsychotics -which have been used for decades-, which are not useful and can even be counter-productive when trying to control psychotic symptoms of anti-NMDAR encephalitis", notes Marc Carceles Cordon.

Moreover, the study can help understand other types of psychosis, a symptom that affects different mental disorders. "For a long time, we regarded this symptom as a part of schizophrenia, but psychosis is present in many mental illnesses (depression, dementia, etc.), and understanding its underlaying mechanisms can, in the future, guide treatments aimed at reducing the pain of the patients", concludes the researcher.

During photosynthesis, plants take in CO2 from the environment and, with the help of sunlight, convert it into energy-rich sugars. CO2 uptake is regulated via the opening and closing of small pores on the leaf known as stomata. However, when stomata are open, water is lost from the plant through transpiration. Therefore, a balance must be struck between water loss and CO2 uptake. In C3 photosynthesis, the stomata open during the day when sunlight is available. This is energetically efficient, but results in significant water loss in environments with high daytime temperatures and low humidity. As an alternative, some plants can perform Crassulacean acid metabolism (CAM) photosynthesis, in which they open their stomata and temporarily fix CO2 at night when temperatures are lower and humidity is higher. They then release the fixed CO2 and refix it for sugar synthesis during the day while keeping the stomata closed. CAM photosynthesis is water-saving but less efficient.

To answer the question whether full CAM or alternative water-saving modes would be more productive in the environments typically experienced by C3 crops, the researchers coupled a day-night model of leaf metabolism and a gas-exchange model and performed simulations for a wide range of environments. Their results have recently been published in Plant Cell magazine.

"We found that, by running a partial CAM cycle, the plant could save more than 50% of its water while maintaining 80% of its maximum productivity in a temperate climate", says Dr. Nadine Töpfer, head of the independent research group "Metabolic Systems Interactions" at IPK.

Moreover, the model identified an alternative CAM cycle involving the mitochondrial enzyme isocitrate dehydrogenase (ICDH) as a potential contributor to initial carbon fixation at night. "The additional water-saving effect of carbon fixation by ICDH can reach 11% of the total water saving for the conditions tested", says Dr. Nadine Töpfer. "We also found that the CO2 storage capacity in the leaf vacuoles had a major effect on the extent of CAM and would need to be increased to establish a CAM cycle in C3 crops."

In conclusion, the study demonstrates the water-saving potential of introducing CAM-like metabolism into C3 plants under a wide range of environmental conditions and suggests environment-specific engineering targets for improved drought resistance. Dr. Nadine Töpfer, who started the work during the tenure of a Marie-Curie Postdoctoral Fellowship in Professor Lee Sweetlove's group in Oxford and completed it at IPK, says: "Modelling is a powerful tool for exploring complex systems and it provides insights that can guide lab and field-based work. I believe that our results will provide encouragement and ideas for the researchers who aim to transfer the water-conserving trait of CAM plants into other species."

When living cells are bombarded with fast, heavy ions, their interactions with water molecules can produce randomly scattered 'secondary' electrons with a wide range of energies. These electrons can then go on to trigger potentially damaging reactions in nearby biological molecules, producing electrically charged fragments. So far, however, researchers have yet to determine the precise energies at which secondary electrons produce certain fragments. In a new study published in EPJ D, researchers in Japan led by Hidetsugu Tsuchida at Kyoto University define for the first time the precise exact ranges in which positively and negatively charged fragments can be produced.

Through a better understanding of how biomolecules such as DNA are damaged by ionising radiation, researchers could make important new advances towards more effective cancer therapies. Like molecular bullets, heavy ions will leave behind nanometre-scale tracks as they pass through water; scattering secondary electrons as they deposit their energy. These electrons may then either attach themselves to nearby molecules if they have lower energies, potentially causing them to fragment afterwards; or they may trigger more direct fragmentation if they have higher energies. Since water comprises 70% of all molecules in living cells, this effect is particularly pronounced in biological tissues.

In their previous research, Tsuchida's team bombarded liquid droplets containing the amino acid glycine with fast, heavy carbon ions, then identified the resulting fragments using mass spectrometry. Drawing on these results, the researchers have now used computer models incorporating random sampling methods to simulate secondary electron scattering along a carbon ion's water track. This allowed them to calculate the precise energy spectra of secondary electrons produced during ion bombardment; revealing how they related to the different types of glycine fragment produced. Through this approach, Tsuchida and colleagues showed that while electrons with energies lower 13 electronvolts (eV) went on to produce negatively charged fragments including ionised cyanide and formate, those in the range between 13eV and 100eV created positive fragments such as methylene amine.

TROY, N.Y. -- A small energy harvesting device that can transform subtle mechanical vibrations into electrical energy could be used to power wireless sensors and actuators for use in anything from temperature and occupancy monitoring in smart environments, to biosensing within the human body.

In research recently published online in the Journal of Micromechanics and Microengineering, engineers at Rensselaer Polytechnic Institute developed a predictive model for such a device, which will allow researchers to better understand and optimize its functionalities.

"Sooner or later these harvesters will replace batteries, reducing associated environmentally hazardous waste and maintenance costs," said Diana-Andra Borca-Tasciuc, a professor of mechanical, aerospace, and nuclear engineering at Rensselaer, who led this research effort.

She was joined by John Tichy, a professor of mechanical, aerospace, and nuclear engineering at Rensselaer, and Jinglun Li, a graduate student in mechanical engineering who designed the model.

This most recent work builds upon research that Borca-Tasciuc's lab published in the Journal of Micromechanics and Microengineering in 2016. At that time, the team created and tested an energy harvesting device made of silicon both in the lab and on a vibrating HVAC duct. The device was able to convert mechanical energy into electricity, as hoped, but at the time, the team wasn't able to fully explain its experimental results, which exceeded expectations. This new model answers those questions and will allow the researchers to optimize the device in order to generate more power.

A key finding, Borca-Tasciuc said, was when Li realized that parts of the device deform after mechanical impact -- which is triggered by vibrations. Li then created a predictive model using a series of equations that represent the dynamics of the device by modeling its mass coupled with the movement of a series of springs. These motion equations were critical to determining how vibrational motion translates to voltage. According to this paper, the predictions shown by the model were consistent with experimental results that the team previously gathered.

"This model laid a solid foundation for parametric study and helps to push the boundaries of output power through design optimization," Li said. "The high-power device developed by our group, together with its accurate analytical model, is an advancement of energy harvesting and will enable silicon-based autonomous green power supply at a microscale in the near future."

Washington, October 29, 2020--A study published today in Educational Researcher, a peer-reviewed journal of the American Educational Research Association, provides preliminary projections of the impact of COVID-19-related school closures in spring 2020 on student learning. The study authors found that compared to a typical year, students likely did not gain as much academically during the truncated 2019-20 school year and likely lost more of those gains due to extended time out of school.

Watch study coauthor Megan Kuhfeld discuss major findings and implications: https://youtu.be/8n4njJXbOqg

Using a model that assumed that school closures functioned as an extended summer break, the authors estimated that returning students likely started school this fall with approximately 63 percent to 68 percent of the typical annual learning gains in reading and 37 percent to 50 percent of the typical annual learning gains in math. However, they projected that losing ground during the school closures was not universal, with the top third of students potentially making gains in reading.

The projections imply that educators and policymakers will need to address that many students are substantially behind academically as a result of extended school closures, particularly if many schools remain disrupted throughout periods of the 2020-21 school year.

"It will be important to identify students who are struggling and fallen behind academically and provide those students with extra supports, such as high dosage tutoring and additional structural time," said study coauthor Megan Kuhfeld, senior research scientist at NWEA.

"Inequalities that have existed in our education system prior to COVID are getting worse at the same time school districts are facing massive budget shortages," added Kuhfeld. "We need additional investments from the federal government to prevent looming school budget cuts."

BOSTON - A key step in the immune system's response to allergens has been uncovered by researchers at Massachusetts General Hospital (MGH). They have shown that a neuropeptide called Substance P is released by certain neurons in the skin when they detect allergens, and that this substance is essential in the development of allergen-induced immune responses. This research could lead to the development of new and better methods to treat and prevent allergies.

How allergens are detected by the immune system had not been known. "The focus has been on dendritic cells and T cells, which play a major role both in allergies and in protecting the body from pathogens, such as viruses, bacteria or fungi," says Caroline Sokol, MD, PhD, investigator at MGH's Center for Immunology and Inflammatory Diseases and lead author of the study, which appears in Immunity. "Now we know that sensory nerves link allergen exposure to immune activation."

While the steps in the immune system's response to pathogens are well understood, there has been less certainty about how that system responds to allergens, such as pollen, dust mites or animal fur. Dendritic cells activate T cells that are necessary for that immune response, but until now, scientists did not know all the steps from exposure to an allergen to the development of itching. Sokol's team has filled in a key blank in that process.

"Allergy-triggering dendritic cells are located next to allergen-responsive neurons in the skin. We found that when exposed to an allergen, these neurons release Substance P," says Sokol. "Substance P then directly induces migration of those dendritic cells to the lymph nodes, where they, in turn, activate T cells. Those T cells then marshal the attack against the allergen invader." Those allergic-response triggering dendritic cells are called CD301b+ DCs.

Sokol and her colleagues studied this chain of events in both isolated cells and living systems. "We saw that something was happening in living systems that doesn't happen in cultured dendritic cells," Sokol explains. "So we hypothesized that in living systems there must be some intermediate step between exposure to the allergen and activation of the dendritic cells."

Their experiments support that idea. First, they showed that sensory neurons detect allergens both in isolated cells and in mice. Next they demonstrated that CD301b+ dendritic cells can be found close to sensory neurons in the skin. Taken together, these findings suggested that sensory neurons play a major role in immune cell activation in response to allergens.

Further studies demonstrated that by chemically blocking allergy-sensing neurons in mice, the researchers could interrupt the activation of an allergic response. They also showed that Substance P is released by allergen-activated neurons in both cultured cells and living systems and that Substance P, on its own, can activate the specific types of dendritic cells needed to in turn activate the T cells and complete the allergic response. Further, they showed that blocking sensory neuron function inhibited the activation of T cells associated with the allergic response.

This breakthrough discovery not only broadens understanding of the immune system, but also opens new avenues for the development of therapies to treat allergies. "This sensory-neuron-dependent pathway, and Substance P, are necessary to trigger an immune response to allergens," says Sokol. "If we can interrupt that we can possibly stop the allergic immune response."

(Philadelphia, PA) - Like a key, SARS-CoV-2 - the virus that causes coronavirus disease 2019 (COVID-19) - attaches to specific molecules on the host cell surface, opening gateways into the cell interior. Viral entry into host cells triggers a prodigious immune response. Much of this battle is waged within the lungs, which explains why many patients hospitalized with COVID-19 have severe respiratory symptoms.

Respiratory symptoms, however, are only part of the story. Increasing evidence points toward blood vessel inflammation as having a crucial impact on the severity of COVID-19. In addition, anywhere from 30 to 80 percent of patients experience neurological symptoms, including dizziness, headache, nausea, and loss of concentration. These symptoms suggest that SARS-CoV-2 also affects cells of the central nervous system.

While there is no evidence yet that the virus invades the brain, new work by scientists at the Lewis Katz School of Medicine at Temple University shows that the spike proteins that extrude from SARS-CoV-2 promote inflammatory responses on the endothelial cells that form the blood-brain barrier. The study, published in the December print issue of the journal Neurobiology of Disease, is the first to show that SARS-CoV-2 spike proteins can cause this barrier to become "leaky," potentially disrupting the delicate neural networks within the brain.

"Previous studies have shown that SARS-CoV-2 infects host cells by using its spike proteins to bind to the angiotensin converting enzyme 2 (ACE2) on the host cell surface," explained Servio H. Ramirez, PhD, Professor of Pathology and Laboratory Medicine at the Lewis Katz School of Medicine at Temple University and principal investigator on the new study.

ACE2 is expressed on endothelial cells, which form the inner lining of blood vessels, and serves a central role in mediating different functions of the cardiovascular system. According to Dr. Ramirez, "since ACE2 is a major binding target for SARS-CoV-2 in the lungs and vasculature of other organs in the body, tissues that are behind the vasculature, that receive blood from affected vessels, are at risk of damage from the virus."

It has been unclear, however, whether ACE2 is also present in the brain vasculature or whether its expression changes in health conditions that worsen COVID-19, such as high blood pressure (hypertension). To find out, the team began by examining postmortem human brain tissue for vascular ACE2 expression, using tissues from individuals without underlying health conditions and from individuals in whom hypertension and dementia had been established. Analyses showed that ACE2 is in fact expressed throughout blood vessels in the frontal cortex of the brain and is significantly increased in the brain vasculature of persons with a history of hypertension or dementia.

The researchers then investigated the effects of the SARS-CoV-2 spike protein on brain endothelial cells in cell culture models. Introduction of the spike protein, particularly a portion designated subunit 1, produced substantial changes in endothelial barrier function that led to declines in barrier integrity. The researchers also uncovered evidence that subunit 2 of the SARS-CoV-2 spike protein can directly impact blood-brain barrier function. "This is of importance because unlike subunit 1, subunit 2 of the spike protein doesn't bind to ACE2, meaning that a breach to the blood-brain barrier could occur in a manner that is independent of ACE2," explained postdoctoral fellow and first author on the new report Tetyana P. Buzhdygan, PhD.

Dr. Ramirez's team further investigated the effects of SARS-CoV-2 spike proteins on tissue-engineered microfluidic constructs designed to mimic a human brain capillary. "The tissue-engineered microfluidic models allow recapitulation of the 3D cyto-architecture and mechanical forces caused by fluid movement, which the vasculature is continuously exposed to," said Allison M. Andrews, PhD, Assistant Professor in the Department of Pathology & Laboratory Medicine at LKSOM and a co-author on the report. Experiments showed that binding of spike protein subunit 1 increased barrier permeability in the engineered vessel-like constructs.

"Our findings support the implication that SARS-CoV-2, or its shed spike proteins circulating in the blood stream, could cause destabilization of the blood-brain barrier in key brain regions," Dr. Ramirez said. "Altered function of this barrier, which normally keeps harmful agents out of the brain, greatly increases the possibility of neuroinvasion by this pathogen, offering an explanation for the neurological manifestations experienced by COVID-19 patients."

The long-lasting effects of altered blood-brain barrier function in the presence of SARS-CoV-2 are unknown. Moreover, as Dr. Buzhdygan explained, "the brain vasculature is extremely branched, so even a small amount of neuroinflammation can be very damaging." Based on the team's observations of ACE2 expression in the brain, this neurological damage could be extensive in COVID-19 patients with pre-existing health conditions in which the vasculature has already suffered some amount of injury.

It also remains unknown whether the virus can actually get inside neurons or glial cells that lie beyond the barrier. "The viral genome has not been found yet in the specific cell types of the brain," Dr. Ramirez noted. "The next steps in our work are to look for genomic viral copies in different parts of the brain using autopsy material from COVID-19 cases and to investigate the pathogen's ability to neuroinvade using different cell culture and tissue-engineered constructs."

Boulder, Colo., USA: Per-/poly-fluroalkyl substances, or PFAS, are everywhere. They are used in firefighting foam, car wax, and even fast-food wrappers. They're one of the most toxic substances ever identified--harmful at concentrations in the parts per trillion--yet very little is known about them. PFAS, which is a class of over 3000 compounds, are only regulated at the state level, so while some states are working to aggressively tackle the problem, other states have chosen to ignore PFAS completely, leaving concentrations unknown and health risks unexplored.

Tomorrow from 10 a.m. to 2 p.m. EDT at the Geological Society of America's 2020 Annual Meeting, a technical session will help bring PFAS to national attention. Presentations will discuss how PFAS are released into the environment, transported through groundwater, river, and soils, and partially remediated. PFAS have been produced in the U.S. for decades, primarily for industrial use. Matt Reeves, a professor at Western Michigan University and lead author of one of the presentations, says PFAS have been labelled "forever chemicals" because they have bonds that are "among the strongest in all of chemistry."

"It's almost like armor...we don't have any evidence of degradation of these compounds," he says.

The health risks from PFAS bioaccumulation are heightened because of their toxicity at extremely low concentrations. At the federal advisory level, which is non-enforceable and was set in 2016, the EPA has deemed just 70 parts per trillion (ppt) safe; that's like a few grains of sand in an Olympic-size swimming pool. Compare that to arsenic, a toxic element whose safe limit is 10 parts per billion--much higher than the PFAS limit. Due to bioaccumulation, fish in southeastern Michigan were found with PFAS concentrations in the parts per billion--far exceeding safe limits and prompting "do not eat the fish" signs to be posted along rivers and lakes. Health effects from PFAS are still being studied, but they potentially include increased rates of some types of cancer, hormonal disruption, and immune responses.

Michigan is receiving special attention because in July of this year, the state government enacted strict regulations for seven compounds in the PFAS family. For one compound, the highest safe limit is just 6 ppt--far lower than the EPA's guidelines. "Michigan is the most proactive state of the nation in characterizing and studying PFAS, and with their legislation," Reeves says. His talk highlights the PFAS cycle on land and complications with site remediation.

"Notice we don't call it a 'life cycle,'" he says. "It's a perpetual cycle. We cannot break down these compounds, so there's no 'death.'"

Even once a PFAS source is identified, remediation is difficult. North Carolina, like Michigan, has legacy PFAS contamination from industries past. Marie-Amélie Pétré, a postdoc at NCSU, is studying how quickly PFAS are flushed from groundwater to streams. This flushing is a critical part of the water cycle that determines when residents can expect their drinking water to be safe. "Quantifying the timescale for PFAS flushing from groundwater can help predict downriver concentrations in the future," Pétré says. "We're the first to quantify PFAS transport... between groundwater and streams using field data. It's such a rapidly evolving field. This ongoing discharge isn't included in remediation plans."

At the University of Arizona, Mark Brusseau and Bo Guo are studying PFAS in soils, which serve as a PFAS repository between groundwater and surface waters. "Concentrations of PFAS in the soil can be orders of magnitude higher than they are in the groundwater at the same location," Brusseau says. Despite differences in state regulation, one thread is clear: PFAS are everywhere. His talk examines over 30,000 soil samples from around the world. "PFAS were found to be present at almost every site that was sampled, whether it was a metropolitan area, near an industrial source, or out in a rural area," he says. "[They are] even in some very remote mountain areas."

"PFAS don't discriminate," Steve Sliver, a co-author on Reeves' talk and lead of Michigan's PFAS response team, says. "The sources are pretty much everywhere."

Highlighted presentations from this session include:

255-2 - Observations and Considerations On the Fate, Transport, and Bioaccumulation of PFAS in the Environment
10:15-10:30 a.m. EDT
Abstract link: https://gsa.confex.com/gsa/2020AM/meetingapp.cgi/Paper/355477
Contact: Donald M. (Matt) ReevesWestern Michigan Universitymatt.reeves@wmich.edu

255-7 - Per- and polyfluroalkyl substance (PFAS) transport from groundwater to streams near a PFAS manufacturing facility in North Carolina, USA
11:30-11:45 a.m. EDT
Abstract link: https://gsa.confex.com/gsa/2020AM/meetingapp.cgi/Paper/358242
Contact: Marie-Amelie PetreNorth Carolina State Universitymcpetre@ncsu.edu

255-10 - PFAS retention and leaching in soils & the vadose zone
12:15-12:30 p.m. EDT
Abstract link: https://gsa.confex.com/gsa/2020AM/meetingapp.cgi/Paper/356072
Contact: Mark BrusseauUniversity of Arizonabrusseau@arizona.edu and Bo GuoUniversity of Arizonaboguo@arizona.edu

Session 255-T181 Fate and Transport of PFAS in the Geologic Landscape
Friday, 30 October: 10 a.m.-2 p.m. EDT
Session Link: https://gsa.confex.com/gsa/2020AM/meetingapp.cgi/Session/49997
Contact: Timothy Schroedertschroeder@bennington.eduBennington College (lead session convener)
Donald M. (Matt) ReevesWestern Michigan Universitymatt.reeves@wmich.edu
Marie-Amelie PetreNorth Carolina State Universitymcpetre@ncsu.edu
Mark BrusseauUniversity of Arizonabrusseau@arizona.edu and Bo GuoUniversity of Arizonaboguo@arizona.edu

Silicon does not have to be crystalline, but can also be produced as an amorphous thin film. In such amorphous films, the atomic structure is disordered like in a liquid or glass. If additional hydrogen is incorporated during the production of these thin layers, so-called a-Si:H layers are formed. "Such a-Si:H thin films have been known for decades and are used for various applications, for example as contact layers in world record tandem solar cells made of perovskite and silicon, recently developed by HZB" explains Prof. Klaus Lips from HZB. "With this study, we show that the a-Si:H is by no means a homogeneously amorphous material. The amorphous matrix is interspersed with nanometre-sized areas of varying local density, from cavities to areas of extremely high order," the physicist comments.

In cooperation with the Technical Universities of Eindhoven and Delft, Lips and his team have succeeded for the first time in experimentally observing and quantitatively measuring these inhomogeneities in differently produced a-Si:H thin films. To do this, they combined the results of complementary analytical methods to form an overall picture.

"We find a nanoscopic order in the disorder of the a-Si:H layers by x-ray scattering measurements performed at BESSY II. We were then able to determine the distribution of the hydrogen atoms in the amorphous network by neutron scattering at the former research reactor BER II at the HZB site Wannsee", says Eike Gericke, PhD student and first author of the paper. Further insights were provided by the electron microscopy performed at the CCMS Corelab and measurements of electron spin resonance (ESR).

"We were able to discover nanometer-sized voids, which are created by slightly more than 10 missing atoms. These voids arrange themselves into clusters with a recurrent distance of about 1.6 nanometres to each other," explains Gericke. These voids are found in increased concentrations when the a-Si:H layer has been deposited at a very high rate.

The researchers also found nanometre-sized regions with higher order compared to the surrounding disordered material. These densely ordered domains (DOD) contain hardly any hydrogen. "The DODs form aggregates of up to 15 nanometres in diameter and are found in all the a-Si:H materials considered here," explains Gericke.

"The DOD regions have been theoretically predicted in 2012 and are able to reduce mechanical stress in the material and thus contribute to the stability of the a-Si:H thin film. The voids on the other hand, can promote electronic degradation of the semiconductor layers as indicated by ESR measurements," says Klaus Lips.

Targeted optimization of manufacturing processes with regard to the substructures now discovered could enable new applications such as optical waveguides for programmable photonic systems or a future silicon battery technology. Last but not least, the findings will also help to finally unravel the microscopic mechanism of light-induced degradation of a-Si:H solar cells, one of the puzzles the scientific community is trying to solve since more than 40 years.