Culture

Functional polymers to improve thermal stability of bioplastics

image: Synthesis of tetrapropanolamide derivatives of thiacalixarene, i: M2CO3 (M = Na, K, Cs for cone, partial cone, 1,3-alternate stereoisomers, correspondingly), BrCH2C(O)OEt, acetone, reflux; ii H2NCH2CH2CH2OH, methanol/toluene, reflux

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Kazan Federal University

One of the key objectives for contemporary chemistry is to improve thermomechanical properties of polymers, in particular, thermostability of bioplastics.

In this paper, the team concentrated on researching oligomer and polymer materials with macrocyclic compounds characterized by enhanced thermostability. "Such products have lower vitrification temperatures, which makes them more malleable in comparison with commercial polylactic acid," says co-author, Research Associate Pavel Padnya.

Polycondensation products of lactic acid (poly- and oligolactides) are of great interest for targeted drug delivery and implant design. A width of the range of their applications is due to a number of practically important properties, such as biocompatibility and biodegradability, non-toxicity and mechanical strength.

"Modification of the obtained polymers with various additives can improve their properties and expand possible applications. One of the strategies to increase the stability of materials in biological media and to make drug loading possible is to obtain branched, or, as they are called, star-shaped polymers," explains Padnya.

"We've been working on this topic for five years thanks to Russian Science Foundation's funding. We have had some non-trivial results for biodegradable polymers," adds team leader, Professor Ivan Stoikov.

In the course of the study, new functional star-shaped polymers of lactic acid were obtained. Researchers chose macrocyclic compounds, thiacalixarenes, as the "crosslinking units" of polymer chains. An important result of this work is that the dependence of the structure of the obtained oligo- and polymer products on the synthesis temperature and the nature of the solvents used, as well as on the spatial structures selected for the "crosslinking" of chains of macrocyclic compounds, was established.

This development can have a significant impact on the use of polymers in medicine: it turned out that the obtained compounds have an affinity for a certain type of xanthene dyes - a means for medical diagnostics and the study of biochemical processes in cells.

Credit: 
Kazan Federal University

First global map of rockfalls on the Moon

image: A falling boulder has left a clear trace on the lunar surface.

Image: 
NASA/GSFC/ASU

In October 2015, a spectacular rockfall occurred in the Swiss Alps: in the late morning hours, a large, snow-covered block with a volume of more than 1500 cubic meters suddenly detached from the summit of Mel de la Niva. It fell apart on its way downslope, but a number of boulders continued their journey into the valley. One of the large boulders came to a halt at the foot of the summit next to a mountain hut, after travelling more than 1.4 kilometers and cutting through woods and meadows.

On the Moon, time and again boulders and blocks of rock travel downslope, leaving behind impressive tracks, a phenomenon that has been observed since the first unmanned flights to the Moon in the 1960s. During the Apollo missions, astronauts examined a few such tracks on site and returned displaced rock block samples to Earth. However, until a few years ago, it remained difficult to gain an overview of how widespread such rock movements are and where exactly they occur.

Researchers at the Max Planck Institute for Solar System Research (MPS) in Germany and ETH Zurich have analyzed an archive of more than two million images of the lunar surface and present the first global map of rockfalls on the Moon in today's edition of Nature Communications.

"The vast majority of displaced boulders on the Moon have a diameter of between seven and ten meters," explains Valentin Bickel of MPS and ETH Zurich, first author of the new study. "Earlier space probes that have studied the Moon were unable to detect such small features on a global scale," he adds. It was not until 2010, with the launch of NASA's Lunar Reconnaissance Orbiter, that imagery of the entire lunar surface, with the necessary spatial resolution and coverage, has been available.

The result is a map of the lunar surface between 80 degrees northern and southern latitude that shows 136,610 rockfalls with diameters of more than two and a half meters. "For the first time, this map enables us to systematically analyze the occurrence and causes of rockfalls on another celestial body", says Dr. Urs Mall from MPS.

Previously, scientists had assumed that lunar quakes in particular were responsible for the displacement of boulders. The new global map of rockfalls indicates that impacts from asteroids may play a much more important role. They are apparently - directly or indirectly - responsible for more than 80 percent of all observed rockfalls.

"Most of the rockfalls are found near crater walls," says Prof. Dr. Simon Loew of ETH Zurich. Some of the boulders are displaced soon after the impact, others much later. The researchers hypothesize that impacts cause a network of cracks that extend in the underlying bedrock. Parts of the surface can thus become unstable even after very long periods of time.

Surprisingly, even in the oldest lunar landscapes, which formed up to 4 billion years ago or even earlier, traces of rockfall events can be found. Since such imprints would typically disappear after a few million years, these surfaces are apparently still subject to erosion through rockfall, even billions of years after they were formed.

"Apparently, impacts influence and modify the geology of a region over very, very long time scales," says Bickel. The results also suggest that very old surfaces on other airless bodies such as Mercury or the large asteroid Vesta may still be evolving as well.

Credit: 
ETH Zurich

Heart injury among hospitalized COVID-19 patients associated with higher risk of death

image: Myocardial injury reflected by troponin concentrations above the upper reference limit (URL) of normal (>0.03ng/mL) was present in 36% of patients hospitalized with COVID-19.

Troponin levels among patients hospitalized with COVID-19 were generally under 1.0 ng/mL.(low levels)

Even small amounts of myocardial injury (e.g. troponin I 0.03-0.09 ng/mL, n=455, 16.6%) were associated with higher risk of death (adjusted HR: 1.75, 95% CI 1.37-2.24) while greater amounts (e.g. troponin I>0.09 ng/dL, n=530, 19.4%) were associated with more pronounced risk for death (adjusted HR 3.03, 95% CI 2.42-3.80; P

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Mount Sinai Health System

Mount Sinai researchers have found that myocardial injury (heart damage) is prevalent among patients hospitalized with COVID-19 and is associated with higher risk of mortality. More specifically, a serious myocardial injury can triple the risk of death. The results were published in the June 5 issue of the Journal of the American College of Cardiology.

“There has been a lot of speculation about how COVID-19 affects the heart and blood vessels, and with what frequency. Our observational study may help to shed some light on this. We found that 36 percent of patients who were hospitalized with COVID-19 had elevated troponin levels—which represents heart injury—and were at higher risk of death,” says lead author Anu Lala, MD, Assistant Professor of Medicine (Cardiology) at the Icahn School of Medicine at Mount Sinai. “These findings, which are consistent with reports from China and Europe, are important for clinicians. If COVID-19-positive patients arrive in the emergency room and their initial test results show troponin levels are elevated, doctors may be able to better triage these patients and watch over them more closely, but this remains a testable hypothesis.”

A team of investigators analyzed electronic health records of nearly 3,000 adult patients with confirmed positive COVID-19 admitted to five New York City hospitals within the Mount Sinai Health System between February 27 and April 12, 2020 (The Mount Sinai Hospital, Mount Sinai West, Mount Sinai Morningside, Mount Sinai Queens, and Mount Sinai Brooklyn). The median age for patients analyzed was 66, and roughly 60 percent were male. One-quarter of all patients self-identified as African American, and 27 percent self-identified as Hispanic or Latino. Roughly 25 percent of the patients had a history of heart disease (including coronary artery disease, atrial fibrillation and heart failure) and roughly 25 percent had cardiovascular disease risk factors (including diabetes or hypertension).

Mount Sinai researchers found that 36 percent of hospitalized COVID-19 patients had myocardial injury. For those with substantial injury, their risk of death was three times higher than COVID-19-positive patients without myocardial injury.

To get this information, researchers focused on the patients’ levels of troponin—proteins that are released when the heart muscle becomes damaged—and their outcomes. (Higher troponin levels mean greater heart damage.) All patients had a blood test for this within 24 hours of admission and were grouped into three categories: 64 percent were in the normal range (0.00-0.03 ng/mL); 17 percent had mild elevation (between one and three times the upper limit of normal, or >0.03-0.09 ng/mL), and 19 percent had higher elevation (more than three times the upper limit of normal, or >0.09 ng/mL). Higher troponin levels were more prevalent in patients who were over 70 years old and had previously known conditions including diabetes, high blood pressure, atrial fibrillation, coronary artery disease and heart failure. Researchers made adjustments for these factors in the analysis.

Then, they analyzed the associated risk of death after adjusting for factors including age, sex, body mass index, history of cardiovascular disease, medication, and illness at hospital admission. They found patients with milder forms of myocardial injury were associated with lower likelihood of hospital discharge and a 75 percent higher risk of death compared to patients with normal levels. Patients with higher troponin concentrations were associated with a three times higher risk of death compared to those with normal levels. Additionally, when adjusting for relevant factors including heart disease, diabetes and high blood pressure, troponin was independently associated with risk of death. More specifically, heart injury seems to be a more important indicator in predicting risk of death than a history of heart disease.

“The study concludes that myocardial injury is common among patients hospitalized with COVID -19 but is more often mild and associated with low-level troponin elevation. Despite low levels, even small amounts of heart injury could be linked to a pronounced risk of death, and COVID-19 patients with a history of cardiovascular disease are more likely to have myocardial injury when compared to patients without heart disease,” explains Dr. Lala.

“Myocardial injury is frequent in COVID-19 patients, but the question is what is the main etiology? Is this by direct effect of the virus into the myocardium, or is it an indirect effect of the cytokine storm also into the myocardium, or a procoagulant causing coronary thrombotic ischemia? These are questions that need to be addressed in future studies,” says senior author Valentin Fuster, MD, PhD, Director of Mount Sinai Heart and Physician-in-Chief of The Mount Sinai Hospital. “Additionally, we now need to follow COVID-19 patients with myocardial injury to learn more about the consequences.”

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The Mount Sinai Hospital / Mount Sinai School of Medicine

Research team to study food resilience in the face of catastrophic global events

image: A collection of microgreens that are being tested for robust growth and nutritional properties in one of Penn State's greenhouses.

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Francesco Di Gioia, Penn State

UNIVERSITY PARK, Pa. -- In the midst of the COVID-19 pandemic, we have all become aware of how a global crisis can affect our access to food. But imagine the food security impacts of an even worse scenario -- an all-out nuclear war, a large asteroid strike or a supervolcano eruption. Such catastrophes could block out sunlight, alter rainfall patterns and contaminate water supplies, which could drastically affect our food systems. An interdisciplinary team of Penn State professors has received $3 million from Open Philanthropy to study food resilience in the face of such catastrophic global events.

"Although they are infrequent in Earth's history, global catastrophes have caused massive extinction events," said Charles Anderson, an associate professor of biology and the lead investigator on the project. "For example, the Cretaceous-Paleogene extinction event is thought to have been caused by an asteroid impact near the Yucatan peninsula, possibly in combination with increased volcanic eruptions. Over the last century, the invention and stockpiling of nuclear weapons has raised the specter of a nuclear conflict that would kill many people outright, but could also cause massive firestorms that would loft soot high into the atmosphere, blocking sunlight and causing global famine during a 'nuclear winter' lasting more than a decade. Under these conditions, the ability to grow, produce, process, distribute and store food could well become limiting factor for the survival of humanity."

In a pilot study leading up to their new project, the researchers discovered that existing food reserves and seed banks are inadequate to ensure human survival after a major global catastrophe; that the breakdown of global transportation, communication, and economic networks following a catastrophe would decimate long-distance food trade and distribution, and that limited crop production might remain possible in certain locations post-catastrophe, but would need to be supplemented by alternative methods of food generation, such as converting inedible plant materials like wood into food.

With the four-year grant from Open Philanthropy, the team will expand upon these findings; develop, test and optimize strategies for emergency food resilience; and produce recommendations for prudent planning for post-catastrophic food resilience. The project will comprise several focus areas, including:

Predicting and testing the environmental limits of some of our most important cold-tolerant crop plants, such as barley, wheat, rye and potato.

Creating a detailed global inventory of available edible food resources and feedstocks for food production with a focus on "emergency" foods, such as tree leaves that can be used as vegetables; bark from birch and pine trees; and edible cones, seeds, gums, resin and pollen.

Developing a soilless "Emergency Greens Growing Box" that in the immediate aftermath of a catastrophe could allow survivors to grow nutrient-dense microgreens for essential nutrients.

Investigating the efficacy of growing edible aquatic plants on a mix of sugars derived from woody plants and wastewater, converting two inedible feedstocks into a food source.

Examining long-term storage of existing and newly produced food, such as hot-air drying and freeze drying.

Investigating behavioral responses to global catastrophes; for example, "panicky" responses such as runs on bottled water, bread or canned goods.

"Our goal is to determine ways to significantly improve the food security, probability of survival and quality of life for as many people as possible following a global catastrophe," said Anderson. "If successful, our project will accurately predict how much food could be produced in limiting environments using conventional agricultural methods and provide novel strategies for supporting human nutrition."

The team's findings could also potentially be adapted to other types of global disturbances, such as the current COVID-19 pandemic and climate change, as well as to novel environments, such as space or other planets.

"Despite the current capability of our global food systems to produce enough calories for everyone, socioeconomic inequities and challenges in food distribution and storage already cause hunger for millions of people, and the current COVID-19 crisis has unfortunately placed many more people at risk of malnutrition and starvation," said Anderson. "This is especially damaging for children, whose brain development can be permanently affected by malnutrition. Even in the United States, the wealthiest country on Earth, one in six families with children are currently facing food insecurity. By thinking innovatively about how to ensure human nutrition under extremely challenging conditions, we hope to make discoveries that will improve food security under many different conditions and raise the prospects for healthy development and economic productivity for everyone."

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Penn State

Specific kidney proximal tubular injury caused by SARS-CoV-2

SARS-CoV-2-associated acute kidney injury (AKI) is one of the more frequently encountered organ involvements in COVID-19 - in as many as 80% of critically ill patients, according to a recent study [2]. The virus infects the cells of the renal tubule system (proximal tubule cells), inter alia, because tubular cells express the ACE2 cell surface receptor that SARS-CoV-2 uses to invade host cells. The proximal tubular cells normally ensure (by reabsorption into blood) that important substances are not excreted in urine and are thus lost to the body (e.g., glucose, bicarbonate, potassium, phosphate, amino acids/proteins). Proximal tubule injury can cause renal Fanconi syndrome, a disease in which said substances are lost in urine. The consequences or symptoms are disorders of mineral balance, accompanied by a reduction in bone density due to phosphate loss, bone pain, hyperacidity of the blood (acidosis, i.e., lowered pH), frequent urination (polyuria), dehydration, increased thirst, physical weakness (loss of cellular energy due to phosphate deficiency).

A study conducted in Nancy, France, investigated the hypothesis that, depending on the severity of SARS-CoV-2 infection, Fanconi syndrome might occur as an indication of renal tubule involvement. Data from 42 hospitalized COVID-19 patients (all with positive throat swab) who had no previous kidney disease were analyzed retrospectively. The mean follow-up was 19.7 (±12) days. It was found that a total of 75% of the patients had (incomplete) Fanconi syndrome (at least two tubular abnormalities). The most frequently presented features were proteinuria (88%, n=35), phosphate loss in urine (55%, n=22), increased uric acid excretion (43%, n=17) and glycosuria (30%, n=12). Intensive care patients were more frequently affected (96% vs. 62%) and were also more severely affected by proteinuria (protein in urine 844±43 vs. 350±221 mg/g) and by AKI. A noteworthy finding was that Fanconi syndrome preceded severe AKI in 7/8 (88%) of the patients. Five of the AKI patients required dialysis; two died (after 13 and 27 days); one patient was dialysis-free after one week and two patients were still on dialysis at the end of the follow-up. A total of 7/42 patients died (including six intensive care patients with AKI), 24/42 could be discharged (including 12 intensive care patients) and 11/42 patients were treated as in-patients for a further 34 (±4.3) days. Clinical improvement of patients was also accompanied by a reversal of renal Fanconi symptom.

"The proximal renal tubules seem to be a specific target of SARS-CoV-2 because of their ACE2 receptors, and we see verification of our hypothesis that this is the cause of the tubular disorders and AKI that so many of our COVID-19 patients have developed", explains Dr. Raphaël Kormann. "Although by no means all COVID-19 patients with Fanconi syndrome developed AKI, we believe that the four markers (increased urinary excretion of protein, phosphate, uric acid and glucose), if a new occurrence, indicate specific proximal-tubular injury from which AKI can develop", says Kormann. "This should be subjected to further systematic investigation - with regard to the significance of Fanconi syndrome as a biomarker of tubular cell infection and as a potential predictive prognostic marker."

"It must also be assumed that there is an increased risk of subsequent kidney disease after SARS-CoV-2-associated Fanconi syndrome, as is also the case after acute kidney injury", added Professor Alberto Ortiz, Editor-in-Chief of the CKJ. "For that reason, patients should always be followed-up nephrologically so that associated conditions are detected in time."

Credit: 
ERA – European Renal Association

Switching from aluminum to zinc alloys could improve sustainability of automotive parts

image: Professor Mark Jolly, Director of Manufacturing at Cranfield University,

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Cranfield University

A new study reveals that switching from aluminum to zinc alloys in the production of automotive parts could greatly enhance their longevity and sustainability.

The study, conducted by Cranfield University's Sustainable Manufacturing Systems Centre, compared three different alloys (Aluminium-A380, Magnesium-AZ91D and Zinc-ZA8). Over recent years aluminum alloys have been favoured by the automotive manufacturing industry for their lightweight properties and lower cost.

The study, published in the 'International Journal of Sustainable Manufacturing', suggests that aluminum is frequently chosen ahead of other alloys because of a failure to fully factor the sustainability of the end-product into consideration. When examining sustainability alongside traditional factors such as time, cost and flexibility, Cranfield's research demonstrated that the zinc rather than the aluminum or magnesium alloys offered the better choice for automotive manufacturers.

The zinc alloy proved to be a more sustainable and higher performing option, when considering measures such as the environmental impact caused by the extraction of the metal and the quality of the parts it produces. Despite the aluminum alloy being a lower cost option, the study found that the zinc alloy also offered better value for money as the parts it creates are likely to have a much longer life than the other alloys.

Previous Cranfield research has demonstrated that the automotive industry's focus on increasingly lighter weight cars to increase fuel efficiency, often through lightweight aluminum, may not actually be a more environmentally sustainable option.

Professor Konstantinos Salonitis, Head of Sustainable Manufacturing Systems Centre at Cranfield University, said: "Aluminum has become the favoured material of the automotive industry for its lightweight properties and comparatively low cost. However, our study which looked in depth at sustainability, alongside traditional factors such as time, cost and flexibilty, showed that actually a zinc alloy can be better value for money as well as being more sustainable."

Professor Mark Jolly, Director of Manufacturing at Cranfield University, added: "With the pressing climate crisis and consumers becoming ever more interested in the impact that the products they purchase have on the environment, manufacturers need to have a greater understanding of not just how they keep costs down but how they find the more sustainable option."

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Cranfield University

Indirect effects of SARS-CoV-2 on the kidneys: beware of the genetic background

SARS-CoV-2-associated acute kidney injury is not uncommon. Many hospitalized COVID-19 patients - as many as 80% of critically ill COVID-19 patients, according to a current study [2] - develop acute kidney injury, but without requiring dialysis in most cases. Proteinuria and hematuria are present in about half the cases. Examinations of renal tissue from deceased patients show injury to the renal corpuscles (glomeruli) or filter membrane (podocytes), and to the renal tubules (tubular cells). Given that SARS-CoV-2 uses the ACE2 receptor to infect cells, and that tubular cells and podocytes express ACE2, it is clear that the kidney can be a specific tissue targeted by the virus.

The current study, published in Clinical Kidney Journal (CKJ), reports on two COVID-19 patients with injury to both these renal structures. Both patients were over 50 years of age and were known to have high blood pressure; one had cardiac insufficiency, the other hepatitis B. Both had been complaining of coughing for four days; one of them also had a fever. On admission, they had pulmonary CT findings typical of COVID-19 and differently elevated creatinine levels indicating reduced renal function (acute kidney injury). Within a few days, one patient required ventilation, whereas the other only needed oxygen; dialysis was not required in either case. Both recovered their pulmonary function within one to two weeks (extubation on day 14). Kidney function also improved, but they both had persistent, high proteinuria. Kidney biopsies were therefore performed. These showed capillary collapse in the glomeruli ("collapsing glomerulopathy/FSGS"), podocyte swelling and glomerular deposits of immunoglobulins (IgM and complement factor C3). Tubule injury (tubulointerstitial lesions), partly with tubule atrophy and necrosis, as well as inflammatory cells (monocytes, macrophages) were also found.

Although both patients had positive virus detection from the throat swab, SARS-CoV-2 was not detected in blood, urine or in kidney tissue, despite highly sensitive RT-PCR testing. Molecular genetic analysis showed variants in the APOL1 gene (homozygous G1 polymorphism and G1/G2 heterozygosity), which are known to be associated with a predisposition (increased risk) for kidney disease.

"The histological findings and the negative PCR results do not definitively rule out direct viral infection of the kidneys, but it seems probable that the injury was not in fact caused directly by the viral infection, but rather by a SARS-CoV-2-induced inflammatory reaction," explains the study's corresponding author, Professor Ziad Massy, Paris/France. "Particularly in the context of genetic APOL1 risk variants, SARS-CoV-2 might have triggered the 'collapsing FSGS' in accordance with the 'second hit' hypothesis."

"SARS-CoV-2 has meanwhile arrived in every country in the world. This means that we will be confronted very often with SARS-CoV-2-induced kidney injury in those regions where the APOL1 gene variants G1/G2 are common," added Professor Alberto Ortiz, Editor-in-Chief of the CKJ. "People of African-American descent, in particular, often express APOL1 risk variants, so in addition to lung problems, renal complications and associated conditions, especially, can be expected in the U.S.A., among other countries."

Credit: 
ERA – European Renal Association

Red tape may have a silver lining for micro businesses -- new study

Small business owners who complain about excessive regulation may be overlooking the business benefits it brings, according to a new study from the University of Bath.

Often perceived as a costly burden that hinders success, the reputation of regulation may have suffered from research that has failed to give businesses the chance to reflect on the positive effects that exist alongside the costs.

Researchers from the Centre for Governance, Regulation, and Industrial Strategy in the University's School of Management questioned over 700 micro firms (of 0 to 9 employees) in the English holiday accommodation sector and found that for these small businesses, success requires a more rounded analysis than just financial performance.

When the burden and benefits of regulation are explored independently, the researchers suggest that regulation may trigger significant benefits, which could include new business opportunities and strategies; protection of existing markets for small businesses by acting as a barrier to new start-ups; and ensuring a level playing field across the industry.

"Regulation is generally thought to benefit society at the direct cost of the small business owner, but it can bring positives too, particularly as many of these businesses are measuring success not just by financial performance, but very personal measures derived from a desired lifestyle," explained Dr Marc Betton, researcher at the University of Bath.

"There is a more complex relationship between regulation and micro firm performance when broader goal-based measures are included - and that requires more exploration," said Betton, who helps to run a family caravan park business in the south west.

Research to date has focused on the financial impact of regulation on micro firms - the cost of acquiring and installing regulatory required equipment, changes to processes following regulatory change, and the time diverted to researching and understanding regulation - all of which are felt to disproportionately affect micro firms with fewer resources than larger firms.

"Small businesses are enduring hardship and face an uncertain future in the face of Covid-19 closure and the ensuing recession, and we can only empathise with the many business owners who are already losing their livelihoods. For those businesses that survive and can hopefully soon re-open, there will be a new slew of regulation to make their business Covid ready that will likely come at a cost, not least the likelihood of running below capacity to enable social distancing," said Dr Rob Branston, Senior Lecturer in Business Economics at the University.

"Our previous research shows many small businesses can struggle to access and correctly interpret guidance, and that must be extra difficult at the moment when announcements are made without the detail. But they may find their struggle with regulation and red tape pays off in the long run."

Seventy percent of businesses focused on English holiday accommodation are micro firms, including B&Bs, self-catering, and caravan parks, and they operate in a highly regulated sector.

Regulation - designed to ensure that businesses comply with minimal standards in the public interest - covers everything from who can be employed and on what terms, to the way buildings are designed and constructed, to how food is prepared, grown, and sold.

Despite accounting for 96 per cent of all businesses in the UK economy micro-firms are often overlooked or deliberately excluded from business studies on regulation in favour of those with a greater number of employees. Yet, according to Branston, these firms are the backbone of the economy and are vital to restoring its health through the Covid crisis.

Credit: 
University of Bath

Rice team makes tiny, magnetically powered neural stimulator

image: A sample of Rice University's 'magnetoelectric' film atop a bed of uncooked rice. Rice neuroengineers created the bi-layered film to power implantable neural stimulators that are approximately the size of a grain of rice. The film converts energy from a magnetic field directly into an electrical voltage, eliminating the need for a battery or wired power connection.

Image: 
Jeff Fitlow/Rice University

HOUSTON -- (June 8, 2020) -- Rice University neuroengineers have created a tiny surgical implant that can electrically stimulate the brain and nervous system without using a battery or wired power supply.

The neural stimulator draws its power from magnetic energy and is about the size of a grain of rice. It is the first magnetically powered neural stimulator that produces the same kind of high-frequency signals as clinically approved, battery-powered implants that are used to treat epilepsy, Parkinson's disease, chronic pain and other conditions.

The research is available online today in the journal Neuron.

The implant's key ingredient is a thin film of "magnetoelectric" material that converts magnetic energy directly into an electrical voltage. The method avoids the drawbacks of radio waves, ultrasound, light and even magnetic coils, all of which have been proposed for powering tiny wireless implants and have been shown to suffer from interference with living tissue or produce harmful amounts of heat.

To demonstrate the viability of the magnetoelectric technology, the researchers showed the implants worked in rodents that were fully awake and free to roam about their enclosures.

"Doing that proof-of-principle demonstration is really important, because it's a huge technological leap to go from a benchtop demonstration to something that might be actually useful for treating people," said Jacob Robinson, corresponding author of the study and a member of the Rice Neuroengineering Initiative. "Our results suggest that using magnetoelectric materials for wireless power delivery is more than a novel idea. These materials are excellent candidates for clinical-grade, wireless bioelectronics."

Tiny implants capable of modulating activity of the brain and nervous system could have wide-ranging implications. While battery-powered implants are frequently used to treat epilepsy and reduce tremors in patients with Parkinson's disease, research has shown that neural stimulation could be useful for treating depression, obsessive-compulsive disorders and more than a third of those who suffer from chronic, intractable pain that often leads to anxiety, depression and opioid addiction.

Robinson said the miniaturization by study lead author and graduate student Amanda Singer is important because the key to making neural stimulation therapy more widely available is creating battery-free, wireless devices that are small enough to be implanted without major surgery. Devices about the size of a grain of rice could be implanted almost anywhere in the body with a minimally invasive procedure similar to the one used to place stents in blocked arteries, he said.

Study co-author and neuroengineering initiative member Caleb Kemere said, "When you have to develop something that can be implanted subcutaneously on the skull of small animals, your design constraints change significantly. Getting this to work on a rodent in a constraint-free environment really forced Amanda to push down the size and volume to the minimum possible scale."

For the rodent tests, devices were placed beneath the skin of rodents that were free to roam throughout their enclosures. The rodents preferred to be in portions of the enclosures where a magnetic field activated the stimulator and provided a small voltage to the reward center of their brains.

Singer, an applied physics student in Robinson's lab, solved the wireless power problem by joining layers of two very different materials in a single film. The first layer, a magnetostrictive foil of iron, boron, silicon and carbon, vibrates at a molecular level when it's placed in a magnetic field. The second, a piezoelectric crystal, converts mechanical stress directly into an electric voltage.

"The magnetic field generates stress in the magnetostrictive material," Singer said. "It doesn't make the material get visibly bigger and smaller, but it generates acoustic waves and some of those are at a resonant frequency that creates a particular mode we use called an acoustic resonant mode."

Acoustic resonance in magnetostrictive materials is what causes large electrical transformers to audibly hum. In Singer's implants, the acoustic reverberations activate the piezoelectric half of the film.

Robinson said the magnetoelectric films harvest plenty of power but operate at a frequency that's too high to affect brain cells.

"A major piece of engineering that Amanda solved was creating the circuitry to modulate that activity at a lower frequency that the cells would respond to," Robinson said. "It's similar to the way AM radio works. You have these very high-frequency waves, but they're modulated at a low frequency that you can hear."

Singer said creating a modulated biphasic signal that could stimulate neurons without harming them was a challenge, as was miniaturization.

"When we first submitted this paper, we didn't have the miniature implanted version," she said. "Up to that point, the biggest thing was figuring out how to actually get that biphasic signal that we stimulate with, what circuit elements we needed to do that.

"When we got the reviews back after that first submission, the comments were like, 'OK, you say you can make it small. So, make it small,'" Singer said. "So, we spent another a year or so making it small and showing that it really works. That was probably the biggest hurdle. Making small devices that worked was difficult, at first."

All told, the study took more than five years, largely because Singer had to make virtually everything from scratch, Robinson said.

"There is no infrastructure for this power-transfer technology," he said. "If you're using radio frequency (RF), you can buy RF antennas and RF signal generators. If you're using ultrasound, it's not like somebody says, 'Oh, by the way, first you have to build the ultrasound machine.'

"Amanda had to build the entire system, from the device that generates the magnetic field to the layered films that convert the magnetic field into voltage and the circuit elements that modulate that and turn it into something that's clinically useful. She had to fabricate all of it, package it, put it in an animal, create the test environments and fixtures for the in vivo experiments and perform those experiments. Aside from the magnetostrictive foil and the piezoelectric crystals, there wasn't anything in this project that could be purchased from a vendor."

Credit: 
Rice University

Case Western Reserve-led research uncovers connections between psoriasis and joint disease

image: Nicole Ward, professor of nutrition and dermatology at the Case Western Reserve University School of Medicine

Image: 
Case Western Reserve University

CLEVELAND--A team led by Case Western Reserve University School of Medicine researchers has made two major discoveries involving psoriasis, a chronic and debilitating skin disease with no known cure.

The researchers found that an overabundance of a protein known as KLK6 can produce and worsen the skin inflammation characteristic of psoriasis, and--even more significant--that KLK6 can play a key role in damaging the joints and bones of people with the disorder.

The research also revealed that normalizing the level of KLK6 can eliminate skin inflammation and lessen the arthritis-like damage. The research, which used mouse models and patient skin samples, appeared this spring in The Journal of Clinical Investigation.

While scientists had known that about a third of people diagnosed with psoriasis also develop psoriatic arthritis (PsA), the reason wasn't clear.

"To discover that turning down KLK6 eliminated the skin inflammation and even improved the arthritis-like changes--that was unbelievable," said Nicole Ward, the study's principal investigator and a professor of nutrition and dermatology at the medical school. "This suggests that clinicians need to aggressively treat patients with psoriasis to prevent the arthritis changes, which generally occur after the skin disease presents itself. Since the joint and bone damage are largely irreversible in patients, prevention becomes critical."

Study co-authors included an interdisciplinary team of 20 researchers from Cleveland Clinic Lerner Research Institute, the University of Michigan and New York University.

Psoriasis is characterized by red, scaly patches that are itchy and painful; it is chronic, incurable and affects 2% to 3% of the population worldwide. The associated psoriatic arthritis can cause disabling damage to bones and joints. Because that damage also is irreversible, study researchers said it is critical to identify patients with psoriatic arthritis early to prevent further destruction to their bones, tendons and joints.

The study is the latest in a series Ward and her colleagues have conducted involving psoriasis and Kallikrein-related peptidase 6, or KLK6.

They undertook the current research to understand how the cellular and molecular mechanisms of KLK6 and another protein, known as protease-activated receptors (PAR)1, promote skin inflammation. Ward said that until now, little was known about the connections between KLK6 and psoriasis or psoriatic arthritis, and even less was known about PAR1 and psoriasis.

KLK6 controls reactions within--and sometimes even outside--cells. Increasing scientific evidence suggests it also may have a role in certain inflammatory skin diseases as well as cancer, multiple sclerosis and Parkinson's and Alzheimer's diseases.

PAR1 is a receptor protein, meaning it receives chemical signals from outside a cell, such as from KLK6. When such signals activate the receptor, they cause cellular/tissue responses, including inflammation.

Previously, Ward and colleagues found the skin of psoriasis patients contained as much as six times more KLK6 than normal. They also found that the PAR1 receptor was overproduced in skin and immune cells. Based on that, they theorized that KLK6 might drive inflammation by signaling through PAR1.

To address the latest question, genetic engineering was used to overproduce KLK6, which resulted in the development of a psoriasis-like skin disease as well as bone and joint disease. They also found that "knocking out," or deleting, PAR1 led to a reduction in skin inflammation and, "more profoundly," Ward said, a significant improvement in bone and joint problems. "These findings suggest that chronic inflammation originating in the skin has the capacity to cause distant joint and bone destruction seen in arthritis."

The researchers then took psoriasis skin from patients, treated it with an FDA-approved PAR1 antagonist in a petri dish and showed significant decreases in several psoriasis markers.

Next, the researchers aim to study how skin inflammation causes arthritis-like damage and translate those findings to benefit patients. They also plan to study and compare models that do and don't develop arthritis to identify biomarkers that can predict the development of psoriatic arthritis.

"If successful, this would be paradigm-shifting and would lead to a more personalized method for identifying which psoriasis patient will go on to develop PsA so we can modify their treatment accordingly," Ward said.

Credit: 
Case Western Reserve University

Addressing sexual violence in sport: American Medical Society for Sports Medicine issues position statement

June 8, 2020 - Sexual violence is a serious problem with potentially severe and lasting negative effects on the physical, psychological, and social well-being of victims - including athletes. A new American Medical Society for Sports Medicine (AMSSM) Position Statement on sexual violence in sport was published simultaneously in four leading sports medicine journals, including Current Sports Medicine Reports (CSMR), official journal of the American College of Sports Medicine (ACSM); and the Clinical Journal of Sports Medicine (CJSM), official journal of the AMSSM. Both CSMR and CJSM are published in the Lippincott portfolio by Wolters Kluwer.

"The objective of this position statement is to raise awareness of this critical issue among sports medicine physicians and to declare a commitment to engage in collaborative, multidisciplinary solutions to reduce sexual violence in sport," according to the new document, developed by an expert Task Force following a formal consensus-building process. The lead author is Jennifer Scott Koontz, MD, PMH, of University of Kansas School of Medicine, Wichita. The Position Statement also appears in British Journal of Sports Medicine and the Journal of Sports Health.

The Position Statement defines sexual violence as "an egregious violation of an athlete's right to safety." It encompasses sexual harassment, defined as "any unwanted and unwelcome conduct of a sexual nature, whether verbal, nonverbal, or physical"; and sexual abuse, referring to "any conduct of a sexual nature, whether noncontact, contact, or penetrative, where consent is coerced/manipulated or is not or cannot be given."

The statement outlines key principles related to sexual violence, including other settings of nonaccidental violence in which it may occur. The Task Force writes: "AMSSM condemns the actions of sports medicine physicians and other health care providers or individuals who perpetrate sexual violence or passively facilitate sexual violence through inaction."

Other principles include:

Mandated reporting of incidents involving minors, as well as safe and confidential reporting procedures for adult victims of sexual violence
An active role of sports medicine physicians in developing policies to reduce sexual violence within their organization, as well as developing their own competencies in recognizing and managing sexual violence.
The need for sexual violence training and education for all athletes, coaches, administrators, health care providers and other members of sports teams and organizations.
Background checks and other mechanisms to prevent perpetrators from moving from one sport organization to another.

The Position Statement also affirms AMSSM's commitment to reducing sexual violence in sport. A set of educational resources targeting sports medicine physicians and trainees is under development, comprising policies aimed at effective prevention, recognition, and treatment of sexual violence, as well as responses to disclosure of sexual violence by athletes. The Task Force concludes: "AMSSM is committed to developing a long-term plan to work collaboratively with other health care providers and all stakeholders to reduce sexual violence in sport."

"Current Sports Medicine Reports is grateful for the opportunity to co-publish this very important AMSSM Position Statement," said CSMR Editor-in-Chief Shawn F. Kane, MD. "Sexual violence is unacceptable and we are all in agreement that it needs to be aggressively addressed and prevented. Our hope is that this statement serves as a catalyst for change."

Credit: 
Wolters Kluwer Health

Kawasaki-like syndrome linked to COVID-19 in children is a new condition

A study on children suffering from severe inflammatory symptoms shows the condition is new and distinct from Kawasaki disease.

In April, researchers in the UK and several European countries with high numbers of COVID-19 cases recognised a new inflammatory syndrome in children that was similar to Kawasaki disease, a rare syndrome known to affect young children.

Now in a paper published today in the Journal of the American Medical Association researchers have identified the main symptoms and clinical markers of the new syndrome. This will help clinicians diagnose and treat the condition and researchers to understand it further and find new treatments.

The study, led by Imperial College Academic Health Science Centre (AHSC) researchers, involved clinicians and academic partners in hospitals across England, including Great Ormond Street Hospital (GOSH) and the Evelina London Children's Hospital, as well the Kawasaki Disease Research Center at the University of California San Diego.

The condition, which the researchers have named Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS), was studied in 58 children admitted to eight hospitals in England.

The condition is believed to be extremely rare, but there are concerns about long-lasting coronary damage. Less than 200 cases have been reported in England with a range of symptoms and severity and most children have already recovered.

Lead author Dr Elizabeth Whittaker, from the Department of Infectious Disease at Imperial College London and a consultant in paediatric infectious diseases and immunology at Imperial College Healthcare NHS Trust, said: "The new condition, PIMS-TS, is extremely rare but it can make a child very ill, so it's important to characterise the disease properly so we can provide close monitoring and the best treatment.

"For any parents worried about their children, I would urge them to follow their usual instincts - whatever would normally prompt you to visit your GP or A&E with your child still applies here."

Dr Julia Kenny, consultant in paediatric infectious diseases and immunology at Evelina London, said: "Our analysis has shown that this is indeed a new condition. Untreated, there is a risk of severe complications in very unwell children, but with early identification and treatment the outcome is excellent, with the children we are reviewing after discharge completely well.

"For clinicians, it's important that we build collaborative research to quickly improve our understanding of the condition and provide the best evidence-based treatment for our patients."

PIMS-TS appears to be more likely to affect older children than Kawasaki disease (average nine years old versus four years old respectively) and presents more often with abdominal pains and diarrhoea alongside the common features such as persistent fever. It also appears to affect a higher proportion of Black and Asian patients.

Blood tests also show different results, with PIMS-TS patients showing more markers of inflammation and cardiac enzymes, which suggest the heart is under strain.

Kawasaki disease is known to damage the coronary artery in such a way that as the child grows the artery does not, leading to a reduction in the amount of blood that can reach the heart. Immune therapy is known to help alleviate these problems, so has been used on patients with PIMS-TS as well, although the team say differences in the two diseases mean this needs to be investigated further and treatment should be carefully monitored.

Lead researcher Professor Michael Levin, from the Department of Infectious Disease at Imperial College London, said: "The new disease presents in a number of ways and can have serious complications. However, the more we learn the better prepared we are to intervene and prevent worse outcomes. For example, patients who develop shock and cardiac failure have a different pattern of blood tests that may help to identify the at-risk group for targeted treatment."

While the team cannot say for certain that PIMS-TS is caused by COVID-19, 45 of the 58 children had evidence of current or past COVID-19 infection, and the researchers say the emergence of a new inflammatory condition during a pandemic is unlikely to be a coincidence.

The majority of children with indications of infection had antibodies for the new coronavirus, suggesting PIMS-TS happens after infection, potentially as a result of an immune system overreaction.

For this reason, the researchers also say understanding more about PIMS-TS could help a more general understanding of COVID-19 and its effects, even in adults. Because PIMS-TS is so distinct, it is easy to study individuals with high inflammation, which may be harder to identify in the general population.

The researchers are collaborating with teams across Europe and the USA that are also studying the new condition in the hopes of rapidly learning more about PIMS-TS and COVID-19. For example, if the condition is caused by an immune system overreaction, this could have implications for the use of vaccines.

Dr Alasdair Bamford, consultant and specialty lead in paediatric infectious diseases at Great Ormond Street Hospital, said: "An important next step will be to review this data in the context of other studies being published from around the world. This will help inform management guidelines and to further refine the case definition. Recruitment of children into observational studies and clinical trials will be key to creating an evidence base for the best treatment."

This research is an example of the work carried out by Imperial College Academic Health Science Centre, a joint initiative between Imperial College London and three NHS hospital trusts. It aims to transform healthcare by turning scientific discoveries into medical advances to benefit local, national and global populations in as fast a timeframe as possible.

Credit: 
Imperial College London

Researchers shed light on new enzymatic reaction

image: Huang, CABBI postdoc at the University of Illinois at Urbana-Champaign, led a study which blended bio- & photocatalysis to expand an enzyme's synthetic repertoire.

Image: 
CABBI Communications Staff

Researchers have identified key ingredients for producing high-value chemical compounds in an environmentally friendly fashion: repurposed enzymes, curiosity, and a little bit of light.

A paper published in Nature describes a study led by Xiaoqiang Huang (pictured), a postdoctoral researcher in the University of Illinois at Urbana-Champaign's Department of Chemical and Biomolecular Engineering (ChBE) and the Carl R. Woese Institute for Genomic Biology (IGB). Huang works in the lab of ChBE Professor Huimin Zhao, Conversion Theme Leader at the Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), a U.S. Department of Energy-funded Bioenergy Research Center (BRC).

Catalysts are substances used to speed up chemical reactions; in living organisms, protein molecules called enzymes catalyze reactions in a process called biocatalysis.

Biocatalysis is rapidly emerging as a nuanced, agile way to synthesize valuable compounds. Scientists are investigating the ability of enzymes to catalyze diverse reactions, and for good reason: biocatalytic reactions are highly selective, meaning that scientists can use enzymes to act on specific substrates and create target products.

Enzymatic reactions are also highly sustainable as they are relatively inexpensive, consume low levels of energy, and do minimal damage to the environment: while chemical catalysts typically require organic solvents, heat, and high pressure to function, biocatalysts work in aqueous solutions, operating at room-temperature and normal-pressure conditions.

Despite their value to science and sustainability, enzymes can be complicated to work with. Reactions enzymes can catalyze are limited to those found in nature; this means that scientists often struggle to track down the perfect biocatalyst to meet their need.

The process is similar to mixing paint: How can an artist creatively combine the colors already on a palette to produce the right shade? In the language of a chemical reaction: How can scientists leverage enzymes already existing in nature to create the products they need?

The research team developed a solution: a visible-light-induced reaction that uses the enzyme family ene-reductase (ER) as a biocatalyst and can produce high yields of valuable chiral carbonyl compounds.

"Our solution might be considered 'repurposing.' We take known enzymes that occur in nature, and repurpose them for a novel reaction," Zhao said.

In other words, the researchers didn't need to add a new kind of paint to the palette -- they discovered an artful way to combine what was already there.

These "repurposed" enzymatic reactions are not only economically and environmentally efficient, but highly desirable: chiral carbonyl compounds have potential applications in the pharmaceutical industry to be used for drug production.

The team's solution is particularly unique in that it merges biocatalysis with photocatalysis -- wherein light is used as a renewable source of activation energy -- in a novel, photoenzymatic reaction.

Over the course of the study, researchers tested a variety of substrates (i.e., the substance on which the catalyst acts), documenting the ER enzymes' reactivity in response to each. This process is comparable to baking a chemical chocolate-chip cookie: by keeping light levels constant and tweaking the "ingredients" (i.e. ERs and substrates), the team was able to gradually circle in on a desired reaction.

Using chemical insights and clever design to synthesize value-added products is characteristic of CABBI's Conversion theme.

"Creating novel enzyme function is one of CABBI's major scientific challenges," Zhao said. "This study addresses that challenge by uncovering novel uses for enzymes and showing what they're capable of."

The substrates used in this study (hydrocarbon compounds known as alkenes) also align with CABBI's mission to investigate applications of plant biomass. In principle, fatty acids from crops like miscanthus, sorghum, and sugarcane can be converted into alkenes, which can then be used in place of petroleum-based substrates to produce valuable compounds.

By blending bio- and photocatalysis and experimenting with various reactionary "ingredients," this study expanded the ER enzyme's repertoire to synthesize high-value, high-quantity compounds.

But merging light with enzymes is just the beginning.

"We are by no means limited to creating chiral carbonyl compounds," Huang said. "Hopefully, this research will inspire scientists to combine several types of enzymes and explore new options for reactivity."

In the future, researchers can build on this study to create an even more diverse portfolio of products -- and further expand upon the economic and environmental benefits of enzymes.

Credit: 
University of Illinois at Urbana-Champaign Institute for Sustainability, Energy, and Environment

COVID-19: Are we handling this the right way?

COVID-19 Reflections: Severe lockdowns and Stay-at-Home orders have been hallmark of the national and global response to this Pandemic. They have been imposed with little precedent and scant evidence of their effectiveness as opposed to less restrictive social distancing measures.

Given the widely acknowledged negative medical and socioeconomic impacts of these interventions their assessment is critical. Over the two months since their imposition, US cases have soared to some 1.5 million and deaths have exceeded 100, thousand and the epidemiological curve has only recently begun to drop even with an infectious disease that has an average incubation period of 5 days. The reasons for this are explored as well as implications for going forward.

Given the unrelenting march of this Pandemic and a safe and effective vaccine probably at least a year away, if at all, Herd Immunity needs to be looked at as a reasonable strategy. The issues of transmission, and individual and population susceptibility are addressed as well as what the realistic level of Herd Immunity required might be.

Importantly, Herd Immunity is not an all or none figure; any increase in the number of non-susceptibles in the population will decrease transmission and truly help "flatten the curve."

Credit: 
Society for Disaster Medicine and Public Health, Inc.

Research team builds better rock models

image: A figure illustrating how CT-scan slices allow detailed visualization and investigation of rock sample grains.

Image: 
Eric Goldfarb

Once you crush, cut or fracture a rock, there are no do-overs. It's a fact that means geoscientists have to be particularly careful about which rock samples they can sacrifice to physics experiments versus which ones should stay on the shelf.

A team of geoscience researchers from The University of Texas at Austin is working to change that with a new method for creating digital replicas of rock samples that is more accurate and simpler to use than other techniques.

The digital replicas can take the place of the real thing in certain experiments, allowing scientists to learn about rock samples without having to touch them. They also allow scientists to collect data from samples that are too small to run certain experiments on, such as cuttings brought up when drilling for oil.

"Now we don't have to take a rock into the lab," said Ken Ikeda, a graduate student at the UT Jackson School of Geosciences. "We don't have to risk a sample, there's no way to ruin it."

Ikeda is the lead author of a paper published in the Journal of Geophysical Research - Solid Earth on April 14, 2020, that describes the new method. The research was conducted entirely by Jackson School researchers in the Department of Geological Sciences, with the other two authors being graduate student Eric Goldfarb, and Nicola Tisato, an assistant professor in the Jackson School's Department of Geological Sciences.

In their study, the researchers tested their method against two others, comparing how the three techniques fared at calculating how fast seismic waves could move through a sample. The new method came closest to the speeds measured in the actual sample, with the calculation being off by 4.5%. The other methods were off by 4.7% and 29%.

Seismic velocity data is a fundamental tool used by geoscientists to learn about rock formations underground. But the researchers said that their method could be used for calculating a number of other important rock properties, such as permeability or electrical conductivity.

All digital rock replicas are built using data collected from a CT scan of a rock sample, which provides a high-resolution record of how the rock interacts with X-rays. By analyzing that information, researchers can determine physical properties about the sample.

The other two methods came with processing trade offs. One of these methods can account for pores and fractures in the rock sample - features that have a big influence on overall elasticity - but requires a target, a pure sample of the mineral that makes up the majority of the rock, to be scanned at the same time as the rock. The other method doesn't require a target, but can't account for the pores and fractures.

The new technique gets around these trade-offs by sampling itself for targets, using extremes in the X-ray data to find bits of pure mineral--something the researchers call a "pseudotarget"--as well as fractures and pores.

"A rock has certain areas that are pristine, grains of quartz that are pristine, and space, pores, that are totally empty," Tisato said. "So if you find those points, you have calibration points."

With no need for a pure mineral target to accompany a sample, the technique simplifies the CT scanning process. The study also shows that, when it comes to calculating seismic speed, the technique is more accurate than the other two methods.

Gary Mavko, a professor emeritus in geophysics at Stanford University who did not take part in the research, said that the study helps advance research in a rapidly growing field.

"This work represents a promising new approach for elastic digital rock physics -- the much studied problem of predicting effective elastic properties of porous Earth materials from high-resolution CT image," he said.

Currently, the new technique can only be applied to samples that are made mostly of a single mineral - such as the Berea Sandstone core used in the study. Nevertheless, there are plenty of fascinating rocks that fit the bill. Goldfarb said he has applied the technique to three Mars meteorites, samples currently being studied by fellow Jackson School graduate student Scott Eckley.

The meteorite example highlights the value of the technique as a way to make rare specimens more accessible for research, Goldfarb said. A high-quality rock replica means you don't need a meteorite in your lab to be able to study one.

Credit: 
University of Texas at Austin