Culture

These mysterious earthquakes originate between 400 and 700 kilometers below the surface of the Earth and have been recorded with magnitudes up to 8.3 on the Richter scale.

Xanthippi Markenscoff, a distinguished professor in the Department of Mechanical and Aerospace Engineering at the UC San Diego Jacobs School of Engineering, is the person who solved this mystery. Her paper "Volume collapse instabilities in deep earthquakes: a shear source nucleated and driven by pressure" appears in the Journal of the Mechanics and Physics of Solids.

The term deep-focus earthquake refers to the fact that this type of earthquake originates deep within the Earth's mantle where pressure forces are very high. Since deep-focus earthquakes were first identified in 1929, researchers had been trying to understand what processes cause them. Researchers thought that the high pressures would produce an implosion which would intuitively produce pressure waves. However, they had not been able to connect the dots between the high pressure and the specific kind of seismic waves -- called shear (or distortional) seismic waves -- produced by deep-focus earthquakes. (You can feel distortional energy if you hold your forearm and then twist it.)

In her new paper, Markenscoff completes her explanation of this mystery that occurs under ultra-high pressures. She unraveled the mystery in a string of papers beginning in 2019. In addition, her solution gives insight into many other phenomena such as planetary impacts and planetary formation that share similar geophysical processes.

"This is a perfect example of how deep mathematical modeling rigorously rooted in mechanics and physics can help us solve mysteries in nature. Professor Markenscoff's work can have profound impact not only on how we understand deep-focus earthquakes, but also on how we might controllably use dynamic phase transformations in engineering materials to our benefit," said Huajian Gao, a Distinguished University Professor in Singapore's Nanyang Technological University and the Editor of the Journal of the Mechanics and Physics of Solids where Markenscoff's paper appears.

From transforming rock to earthquake

It has been well recognized that the high pressures that exist between 400 and 700 kilometers below the surface of the earth can cause olivine rock to undergo a phase transformation into a denser type of rock called spinel. This is analogous to how coal can transform into diamond, which also happens deep in Earth's mantle.

Going from olivine to denser spinel leads to reductions in volume of rock as atoms move closer to each other under great pressure. This can be called "volume collapse." This volume collapse and the associated "transformational faulting" has been considered the predominant cause for deep-focus earthquakes. However, until now, there was no model based on volume collapse that predicted the shear (distortional) seismic waves that actually arrive at the earth's surface during deep-focus earthquakes. For this reason other models were also considered, and the state of affairs remained stagnant.

Markenscoff has now solved this mystery using fundamental mathematical physics and mechanics by discovering instabilities that occur at very high pressures. One instability concerns the shape of the expanding region of transforming rock and the other instability concerns its growth.

For the expanding regions of this phase transformation from olivine to spinel to grow large, these transforming regions with large densification will assume a flattened "pancake-like" shape that minimizes the energy required for the densified region to propagate in the untransformed medium as it grows large. This is a symmetry breaking mode which can occur under the very high pressures that exist where deep-focus earthquakes originate, and it is this symmetry breaking that creates the shear deformation responsible for the shear waves that reach Earth's surface. Previously, researchers assumed symmetry-preserving spherical expansion, which would not result in the shear seismic waves. They did not know that symmetry would be allowed to be broken.

"Breaking the spherical symmetry of the shape of the transforming rock minimizes the energy required for the propagating region of phase transformation to grow large," said Markenscoff. "You do not spend energy to move the surface of a large sphere, but only the perimeter."

In addition, Markenscoff explained that inside the expanding region of phase transformation of rock, there is no particle motion and no kinetic energy (it is a "lacuna"), and, thus, the energy that radiates out is maximized. This explains why the seismic waves can get to the surface, rather than much of the energy dissipating in the interior of the Earth.

Markenscoff's analytical model for the deformation fields of the expanding seismic source is based on the dynamic generalization of the seminal Eshelby (1957) inclusion which satisfies the lacuna theorem (Atiya et al, 1970). The energetics of the expanding region of phase transformation are governed by Noether's (1918) theorem of theoretical physics through which she obtained the instabilities that create a growing and fast moving avalanche of collapsing volume under pressure. This is the second discovered instability (regarding growth): once an arbitrarily small densified flattened region has been triggered, under a critical pressure it will continue to grow without needing further energy. (It just keeps collapsing "like a house of cards".) Thus, the mystery is resolved: although it is a shear source, what drives deep-focus earthquake propagation is the pressure acting on the change in volume.

When asked to reflect on her discovery that deep-focus earthquakes could be described with the theorems that are the bedrock of mathematical physics, she said, "I feel like I have bonded to nature. I have discovered the beauty of how nature works. It's the first time in my life. Before it was putting a little step on someone else's steps. I felt this immense joy."

Relevant discovery

The deep-focus earthquakes are only one of the phenomena in which these instabilities manifest themselves. They also occur in other phenomena of dynamic phase transformations under high pressures, such as planetary impacts and amorphization. Today, there are new experimental facilities such as the National Ignition Facility (NIF) managed by Lawrence Liver National Laboratory in which researchers are able to study materials under extremely high pressures that were impossible to test before.

The new work from Markenscoff provides an important demonstration and reminder that gaining deeper understanding of the mysteries of nature often requires the insights that can be gained by harnessing the fundamentals of mathematical physics together with experimental research done in extreme conditions.

In fact, Markenscoff co-organized two National Science Foundation (NSF) funded workshops at UC San Diego in 2016 and 2019 which brought together geophysicists and seismologists with mechanicians to ensure that these research communities remain aware of the methodologies and techniques developed in mechanics.

"Our education systems should continue to invest in the teaching of the fundamentals of science as the pillars for the advancement of knowledge, which can be achieved by interdisciplinary convergence of theory, experiments and data science," said Markenscoff.

She also noted the importance of the research support she has received over the years from the US National Science Foundation (NSF).

"Knowing that my NSF program manager believed that it was possible to solve this 'mystery' and funded me, bolstered both my confidence and my determination to persevere", said Markenscoff. "I point this out as a reminder for all of us. It's also critical that we give thoughtful and considered encouragement to our students and colleagues. Knowing that people whom you respect believe in you and your work can be very powerful."

ARLINGTON HEIGHTS, IL (April 27, 2021) - The American Society of Plastic Surgeons (ASPS) - the world's largest plastic surgery organization, representing nearly 8,000 members - today released the 2020 results of the organization's annual procedure survey coupled with national consumer research reflecting trends during the COVID-19 era to help predict what 2021 will bring.

The Society's board-certified plastic surgeons reported they stopped performing elective surgical procedures for an average of 8.1 weeks in 2020 due to COVID-19, or 15 percent of the year, which mirrors the decline in the total number of procedures performed last year.

ASPS Survey Finds Americans Have More Positive Attitude Toward Plastic Surgery During COVID-19

ASPS recently gauged Americans' perceptions of plastic surgery more than a year into the COVID-19 pandemic, analyzing responses from more than 1,000 women in a national survey fielded by market firm Equation Research, providing insights into how consumers feel about the category, top treatments and their likelihood to pursue a plastic surgery procedure.

During the pandemic, 11% of women surveyed indicated they are more interested in cosmetic plastic surgery or non-surgical procedures now than before COVID-19, and the figure is even higher among women who have already had surgery or a procedure - 24%, respectively. Also, 35% of women who have previously had at least one cosmetic surgical procedure or minimally invasive procedure plan to spend significantly or somewhat more on treatments in 2021 than in 2020.

"For more than a year, COVID-19 has largely confined people to their homes during quarantine and significantly impacted nearly every aspect of their lives," says Lynn Jeffers, MD, MBA, FACS. "The pandemic isn't over, but thanks to vaccines, a new normal is starting to define itself - and some surgeons' offices that were closed or offered only limited services within the last year are seeing higher demand."

Upping the Ante on Body Enhancement

While the first wave of pandemic demand saw a rush on facial procedures in response to a significant surge in Zoom calls and downtime for discreet recovery at home, the national survey results show that tummy tucks (22%) and liposuction (17%) are among the top procedures that women who are extremely or very likely to consider procedures within six months are seeking. The reason is attributed to weight fluctuation during quarantine, and more time to consider procedures long delayed due to time or cost.

ASPS 2020 Top Procedures

Top 5 Cosmetic Surgical Procedures

While ASPS saw an overall 15% decrease in total number of cosmetic procedures in 2020 due to the COVID-19 pandemic, the dip is largely on par with the amount of time practices were closed - and three of the top 5 procedures focused on the face.

The Top 5 cosmetic surgical procedures performed in 2020 were:

1. Nose reshaping (352,555 procedures)

2. Eyelid surgery (352,112 procedures)

3. Facelift (234,374 procedures)

4. Liposuction (211,067 procedures)

5. Breast augmentation (193,073 procedures)

Top 5 Cosmetic Minimally Invasive Procedures

In 2020, minimally invasive cosmetic procedures decreased slightly more than surgical procedures (16% vs. 14%) during stay-at-home orders, dropping for the first time in four years.

Injectables continued to be the most sought-after treatments in 2020. ASPS member surgeons cited a significant uptick in demand during the coronavirus pandemic with current patients eager to reschedule missed neurotoxin and filler appointments, and new patients motivated for the first time to pursue the minimally invasive facial treatments they'd been considering - some even before last March.

Among the 13.3 million cosmetic minimally invasive procedures performed in 2020, the top 5 were:

1. Botulinum toxin type A (4.4 million procedures)

2. Soft tissue fillers (3.4 million procedures)

3. Laser skin resurfacing (997,245 procedures)

4. Chemical peel (931,473 procedures)

5. Intense Pulsed Light (IPL) treatment (827,409 procedures)

Top 5 Reconstructive Procedures

Nearly 7 million reconstructive procedures were performed in 2020, up 3% overall compared to 2019, despite the global pandemic's impact on elective surgeries. Tumor removal is by far the most common reconstructive plastic surgery procedure with approximately 5.2 million procedures performed.

The Top 5 reconstructive procedures performed in 2020 were:

1. Tumor removal (5.2 million procedures)

2. Laceration repair (386,710 procedures)

3. Scar revision (263,643 procedures)

4. Maxillofacial surgery (256,085 procedures)

5. Hand surgery (206,928 procedures)

"While many reconstructive procedures were prioritized as COVID-19 restrictions eased across the country, I'm encouraged that the Society's members were able to quickly attend to patients in need of these surgeries - ranging from burn and wound care to migraine to pediatric craniofacial procedures - to improve their quality of life," says ASPS President Joseph E. Losee, MD, FACS, FAAP.

Although not within the top five, breast reconstruction (137,808 procedures) saw a significant 29 percent year-over-year jump, a greater increase than any of the top five reconstructive procedures.

"A major concern at the onset of the COVID-19 pandemic was continuing care for reconstructive patients," said Dr. Losee. "Despite the year's challenges, patients and care teams were not only able to move forward with procedure plans when deemed safe to do so, but, in terms of breast reconstruction, more women than ever are benefiting from today's technologies and treatments."

Visit plasticsurgery.org/connect for patient safety tips, procedure information, to find a surgeon and book a consultation.

Tokyo, Japan - Human T-cell lymphotropic virus type-1 (HTLV-1) is a retrovirus similar to human immunodeficiency virus (HIV) and has mostly been thought to be transmitted vertically (mother-to-child), or horizontally (sexually or parenterally (e.g. via blood transfusion)). The spread of this infection in metropolitan areas such as Tokyo is presumed to be due to horizontal transmission, especially sexual transmission.HTLV-1-associated diseases are thought to be caused mainly through vertical transmission. In a new study, clinicians from Tokyo Medical and Dental University (TMDU) describe that horizontal transmission route is responsible for HTLV-1 associated disease, i.e. HTLV-1 uveitis.

The clinicians saw a 57-year-old woman who presented with sudden blurred vision. An eye examination revealed profound pathologies in different anatomical locations of her eyes. Most prominent were cellular infiltrates and opacity in the vitreous body, a large gel-like substance between the lens and the back of the eye. Because the pathologies were consistent with uveitis and an inflammation of the eyes, and given the patient's age, the clinicians tested her for the presence of several autoimmune diseases, such as rheumatoid arthritis and sarcoidosis, because uveitis can be a result of those. The tests didn't reveal anything, so the clinicians tested the patient for a number of infectious diseases, such as HTLV-1 and HIV, that can also cause uveitis. When the HTLV-1 test came back positive, the clinicians made their diagnosis of HTLV-1 uveitis.

"HTLV-1 can cause adult T-cell lymphoma, myelopathy and uveitis, among other disorders," says senior author of the study Kyoko Ohno-Matsui. "Although we started the patient on the proper treatment, an unanswered question was how did the patient get infected with the virus in the first place."

Because there's no targeted therapy for HTLV-1 infections, the clinicians had to weaken the patient's immune system with corticosteroids, because an over-reacting immune system is thought to cause harm to the patient. The clinicians started the patient on corticosteroid therapy systemically as well as with topical eye drops over 6 weeks. Over the course of the next several months, the patient suffered from several recurrences, so the clinicians started her on a maintenance corticosteroid therapy, i.e. treatment over the course of 8 months. While no recurrences happened in this time period, 18 months after the start of the maintenance therapy, the patient presented with another recurrence, including a retinal detachment, which could lead to permanent blindness. This detachment was managed by ophthalmic surgery and the patient was again started on corticosteroids, this time for 4 years. No recurrences have happened since then and the patients has remained symptom-free.

Interestingly, during follow-up the patient's mother underwent cataract surgery at the same clinic site. Testing for HTLV-1 revealed no infection of the mother, ruling out vertical transmission to the patient. Of note, HTLV-1 can become symptomatic even decades after initial infection.

"In the current environment of increasing HTLV-1 incidence, the existence of horizontal transmission causing HTLV-1 uveitis should be acknowledged as it can result in more severe inflammation than vertical transmission. Thus, physicians should take the route of infection into consideration when providing medical care to patients with HTLV-1-associated diseases." says first / corresponding author of the study Koju Kamoi.

Most conventional molecular diagnostics usually detect only a single disease-related biomarker. Great examples are the PCR tests currently used to diagnose COVID-19 by detecting a specific sequence from SARS-CoV-2. Such so-called singleplex methods provide reliable results because they are "calibrated" to a single biomarker. However, determining whether a patient is infected with a new SARS-CoV-2 variant or a completely different pathogen requires probing for many different biomarkers at one time.

Scientists from the Helmholtz Institute for RNA-based Infection Research (HIRI) and the Julius Maximilians University (JMU) in Würzburg have now paved the way for a completely new diagnostic platform with LEOPARD. It is a CRISPR-based method that is highly multiplexable, with the potential to detect a variety of disease-related biomarkers in just one test.

How LEOPARD works

LEOPARD, which stands for "Leveraging Engineered tracrRNAs and On-target DNAs for PArallel RNA Detection," is based on the finding that DNA cutting by Cas9 could be linked to the presence of a specific ribonucleic acid (RNA). This link allows LEOPARD to detect many RNAs at once, opening opportunities for the simultaneous detection of RNAs from viruses and other pathogens in a patient sample.

The study published today in "Science" was initiated by Chase Beisel, professor at JMU and research group leader at HIRI, and Professor Cynthia Sharma from JMU's Institute of Molecular Infection Biology (IMIB). "With LEOPARD, we succeeded in detecting RNA fragments from nine different viruses,' says Beisel. "We were also able to differentiate SARS-CoV-2 and one of its variants in a patient sample while confirming that each sample was correctly collected from the patient."

Background

CRISPR-Cas9 is principally known as a biomolecular tool for genome editing. Here, CRISPR-Cas9 function as molecular scissors that cut specific DNA sequences. These same scissors are naturally used by bacteria to cut DNA associated with invading viruses. Whether editing genomes or eliminating viruses, Cas9 cutting is directed by guide RNAs. The guide RNAs found in bacteria must pair with a separate RNA called the tracrRNA. The RNA couple then can work with Cas9 to direct DNA cutting.

An unexpected discovery

The tracrRNA was thought to only pair with guide RNAs coming from the antiviral system. However, the Würzburg scientists discovered that the tracrRNA was pairing with other RNAs, turning them into guide RNAs. Cynthia Sharma, Chair of Molecular Infection Biology II at the IMIB and spokesperson of the Research Center for Infection Diseases (ZINF) at JMU was astounded by this discovery: "When we searched for RNAs binding to Cas9 in our model organism Campylobacter, we surprisingly found that we detected not only guide RNAs, but also other RNA fragments in the cell that looked like guide RNAs. The tracrRNA was pairing with these RNAs, resulting in "non-canonical" guide RNAs that could direct DNA cutting by Cas9."

The LEOPARD diagnostic platform builds on this discovery. "We figured out how to reprogram the tracrRNAs to decide which RNAs become guide RNAs," says Beisel. "By monitoring a set of matching DNAs, we can determine which RNAs were present in a sample based on which DNAs get cut. As part of the ongoing pandemic, LEOPARD could allow a doctor to figure out whether the patient is infected with SARS-CoV-2, if it's a unique variant, and whether the sample was correctly taken or needs to be repeated--all in one test."

In the future, LEOPARD's performance could dwarf even multiplexed PCR tests and other methods. "The technology has the potential to revolutionize medical diagnostics not only for infectious diseases and antibiotic resistances, but also for cancer and rare genetic diseases," says Oliver Kurzai, director of JMU's Institute of Hygiene and Microbiology, which provided patient samples for the study.

"The work highlights the excellent collaborative and interdisciplinary research taking place here in Würzburg," says Jörg Vogel, director of IMIB and HIRI, a joint facility of JMU with the Helmholtz Center for Infection Research in Braunschweig. "LEOPARD impressively demonstrates that we can cover the full spectrum of complementary cutting-edge research in Würzburg, from the fundamentals of RNA research to clinical applications."

A combination of remdesivir, a drug currently approved in the United States for treating COVID-19 patients, and repurposed drugs for hepatitis C virus (HCV) was 10 times more effective at inhibiting SARS-CoV-2, the virus that causes COVID-19.

The combination therapy points a way toward a treatment for unvaccinated people who become infected, as well as for vaccinated people whose immunity has waned, for example due to the emergence of virus variants that escape this immune protection.

Four HCV drugs--simeprevir, vaniprevir, paritaprevir, and grazoprevir--in combination with remdesivir boosted the efficacy of remdesivir by as much as 10-fold, the researchers reported today in Cell Reports. The research team included scientists from Icahn School of Medicine at Mount Sinai, the University of Texas at Austin, and Rensselaer Polytechnic Institute (RPI).

Remdesivir targets a range of viruses and was originally developed over a decade ago to treat hepatitis C and a cold-like virus called respiratory syncytial virus (RSV). During the Ebola outbreak, Remdesivir was tested in clinical trials and found to be safe and effective for patients. Early in the pandemic, it was seen as a good therapy for COVID-19 but did not live up to its early promise in studies.

The research team performed protein binding and viral replication studies on SARS-CoV-2, the virus that causes COVID-19, using remdesivir and 10 hepatitis C drugs, some of which are already approved by the Food and Drug Administration.

RPI team had previously identified "striking similarity" between protease structures, or enzymes that are essential for coronaviral replication, in SARS-CoV-2 and HCV. The similarity raised the possibility that existing drugs which bind to and block the hepatitis C protease would have the same effect against SARS-CoV-2.

Using a supercomputer to model how drugs bind to viral proteins, the RPI researchers predicted that the 10 HCV drugs could bind snugly to the SARS-CoV-2 Main protease, named Mpro. In addition, they showed that seven of these drugs actually inhibited the SARS-CoV-2 protease. The research team at Icahn Mount Sinai then tested whether these seven drugs would inhibit SARS-CoV-2 virus replication in monkey and human cells grown in culture. In subsequent experiments the researchers were surprised to find that the four HCV drugs inhibited a different SARS-CoV-2 protease, known as PLpro. This observation proved to be very important. When each of the seven HCV drugs were tested in combination with remdesivir, only the four drugs that unexpectedly targeted PLpro boosted the efficacy of remdesivir, by as much as 10-fold.

Adolfo Garcia-Sastre, PhD, one of the authors on the paper, Irene and Dr. Arthur M. Fishberg Professor of Medicine. and Director of the Global Health and Emerging Pathogens Institute at Icahn Mount Sinai, said, "Combined use of remdesivir with PLpro inhibitors for the treatment of COVID-19 could be a game changer for patients with COVID-19 who are not vaccinated. It could also reduce the possibility of selecting SARS-CoV-2-resistant viruses."

"The identification of PLpro as an antiviral target that has a synergistic effect in combination with remdesivir is a very important finding. We hope this work will encourage the development of specific SARS-CoV-2 PLpro inhibitors for inclusion in combination therapies to produce a highly effective antiviral cocktail that may potentially prevent the rise of resistance mutations," said Kris White, PhD, Assistant Professor of Microbiology at Icahn Mount Sinai.

"Because these HCV drugs are already approved for use and their potential side effects are known, such a combination therapy could be tested in humans more quickly than for a new drug," said Robert M. Krug, PhD, Professor Emeritus of Molecular Biosciences at The University of Texas at Austin and co-corresponding author of the paper.

One big drawback of remdesivir is that it must be administered intravenously, limiting its use to patients already admitted to the hospital. "Our goal is to develop a combination of oral drugs that can be administered to outpatients before they are sick enough to require hospitalization," said Krug. "The HCV drugs that enhance remdesivir's antiviral activity are oral drugs. It is important to identify oral drugs that inhibit the SARS-CoV-2 polymerase in order to develop an effective outpatient treatment."

"Nearly 3 million people have died worldwide from COVID-19. There are situations where the vaccine isn't the best option and it would be helpful to have orally available antivirals," said Gaetano Montelione, PhD, a member of the Rensselaer Center for Biotechnology and Interdisciplinary Studies (CBIS). "Here we see a promising synergy that, if confirmed through additional research and clinical trials, could provide a new antiviral to combat COVID-19."

The research was conducted at the Department of Food Science at the University of Copenhagen (UCPH FOOD) with professor emeritus Lars Munck as coordinator and builds on earlier work since 1963 at Svaloef Plant Breeding Institute and the Carlsberg Laboratory.

A complete picture of the organism

The research shows how, with the help of a fast, non-destructive and green analysis method, near-infrared spectroscopy (NIRS), we can obtain a global overview that mirrors how the entire chemical composition of nutrients in a barley grain is changed, for example, by a mutation in a single gene. This is in contrast to current conventional plant breeding, where you do not have an overview of all the changes that the barley grain undergoes when a single gene is modified.

Lars Munck and his team have studied barley grains from different barley lines using near-infrared spectroscopy (NIRS). In a split second, this method can provide a "chemical fingerprint" (read more about Near-infrared spectroscopy below) of the barley grains, which describes the chemical-physical composition of the grains, including the nutrients. The researchers analysed the resulting intact spectra by comparing and calibrating them to barley lines of known composition using mathematics (chemometrics).

"We were surprised by the precision that characterises the chemical fingerprints of the grains from the NIRS spectra. At the same time, it surprised us to find that we got the same classification result if we instead used the secondary nutrients/metabolites determined by a more complicated measurement method called gas chromatography mass spectrometry as the chemical fingerprint. Using two different types of analysis with completely different focuses, we arrived at the same classification result," explains Lars Munck and continues:

"This is coherence in a nutshell - all local fingerprints are part of the plant's self-organising network and affect the plant's overall global chemical-physical fingerprints."

One of the barley lines examined was found to have a higher content of the essential amino acid lysine compared to a normal barley. The high content of lysine gives good growth in feeding studies with pigs, but the yield in the field was horrible and with a low starch content.

"By analysing the high-lysine barley lines that were crossed with high starch barley lines bringing high yield, we could use measurements of NIRS fingerprints to select lines with a high content of both lysine and starch, which thus gave higher yields. At the same time, global coherence also allowed us to gain knowledge about the optimal combination of genetic traits for a specific quality purpose," explains Lars Munck, who believes that this is a radical advancement compared to today's plant breeding that is focused on one gene-chemical trait combination at a time.

"With a more holistic approach, allowed by the NIRS method - we can instead examine the chemical fingerprint totality of the different plant lines, and quickly obtain an overview of what material is available and thus target and select lines from the variable crossing pool that are high quality by calibrating to interesting marker lines" says Lars Munck.

Global coherence - the inner self-organisation of the plant

In the discipline of plant breeding, people speak of the genotype, which describes the plant's genetic material, and the phenotype, which describes the traits that can be observed directly or can be measured chemically and thus may be characterised using NIRS.

The approach when using NIRS phenotyping is to change the order of the plant breeding procedure to start by screening the different barley lines for all of their chemical properties represented by fingerprints. This is done by calibrating to known barley lines that have one or more of the desired chemical properties (e.g., high starch content). Only at the end when you have selected the optimal barley line, you make an in-depth determination of the genes that are changed. When searching for an expression for the whole organism, using NIRS fingerprints provides a far more nuanced result, allowing you to examine the overall chemistry of an organism rather than examining each individual gene combination separately. Because coherence guarantees that all fingerprint aspects of an individual communicate you can manage the global composition from very different fingerprint positions.

"With the new method, we have closed the large knowledge gap that exists in the genetics between genotype and phenotype. Now molecular biology will finally have an outlet for its impressive library of primary gene functions, where the result of total contribution of changed genes to a functioning plant can be studied as a whole," says Lars Munck and continues:

"Molecular biology has come up with crucial solutions for genetic diseases, resistance and vaccinations against diseases. But in this success story, we have forgotten that it is not the gene that is the biological unit, but that it is the self-organised individual that uses its inner "calculator" to organize the internal interaction coherence precisely and reproducibly," says Lars Munck.

The researchers call this interaction, which is shown in barley grains using NIRS fingerprints and which they believe can be transferred to all living organisms, global coherence.

"When change occurs in a single or in several of the plant's genes or in the environment, the chemistry and the implicite morphology of the whole organism changes as the plant reorganises itself to obtain a new coherent balance point. This unifying force, coherence, was previously defined in the physics between light beams and atoms in non-living matter and we have now discovered coherence in biology as a macroscopic chemical fingerprint, that we call global coherence. It explains how living matter can replicate itself into recognizable individuals," explains Lars Munck.

The importance of the introduction of macroscopic chemical fingerprint coherence in biology that coordinates physical morphological structures with chemical is a fundamental discovery and highly simplifying complement to molecular genetic indepth understand to gene expression.

Muscle weakness in patients with Becker disease is caused by unusual electrical activity in muscle fibres termed 'plateau potentials' that make them temporarily inactive, says a study published today in eLife.

An understanding of these mechanisms and the ion channels involved may help the search for more effective therapies for weakness in Becker disease and other muscle diseases, and help understand how electrical activity is regulated in muscles.

Recessive myotonia congenita, also known as Becker disease, is a heritable skeletal muscle disease caused by mutated chloride channels in the muscles that do not work properly. People with the condition experience a phenomenon called myotonia whereby the muscles are hyperexcitable, meaning they are more sensitive than usual to activation. This results in stiff muscles that struggle to relax after being used.

After moving, patients can also suffer debilitating bouts of weakness that can last from seconds to minutes. "The mechanism underlying this weakness has remained a mystery since its initial description almost 50 years ago," explains first author Jessica Myers, a researcher at the Department of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine. "There are hints that weakness is due to hypoexcitability, or reduced sensitivity, of muscle fibres, but this conclusion is at odds with the discovery that muscle in Becker disease is hyperexcitable."

Myers and colleagues sought to uncover the mechanisms behind muscle weakness in patients by studying models of Becker disease in mice. They mimicked the disease by inactivating chloride channels either by genetically modifying them or by blocking them with a drug. They then measured how much force the muscles produced and the electrical activity within the muscle cells to see whether weakness was a result of hypo- or hyperexcitability.

The team found that the weakness was caused by temporary depolarisation of the muscle cells which they termed 'plateau potential'. At rest, muscle cells carry a negative electrical charge of -70 to -90 millivolts (mV) relative to their surroundings. When depolarised during a plateau potential, the charge reduces to a less negative state of between -30 and -45 mV which can last up to 100 seconds. Plateau potentials leave muscle fibres inexcitable, making them essentially inactive.

These results suggest that muscle affected by Becker disease rapidly cycles between hyper- and hypoexcitability as individual fibers switch from experiencing myotonia (causing stiffness) to the generation of plateau potentials (causing weakness), respectively. The state depends on the strength of the signal experienced by the muscle fibres: mild depolarisation triggers myotonia and more severe depolarisation triggers the generation of a plateau potential.

The team also demonstrated that both calcium and sodium ion channels are involved in creating a plateau potential, finding that sodium channels trigger this state while calcium channels are responsible for maintaining it. Moreover, blocking a subset of sodium channels with the drug ranolazine prevented the development of plateau potentials and eliminated the temporary muscle weakness.

"Further study is needed to identify all the ion channels involved in the generation of plateau potentials," concludes senior author Mark Rich, Professor at the Department of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine. "Doing so could lead to the development of novel therapies for weakness in Becker disease as well as similar diseases including periodic paralysis."

WASHINGTON, April 27, 2021 -- If a base station in a local area network tries to use a directional beam to transmit a signal to a user trying to connect to the network -- instead of using a wide area network broadcast, as base stations commonly do -- how does it know which direction to send the beam?

Researchers from Rice University and Brown University developed a link discovery method in 2020 using terahertz radiation, with high-frequency waves above 100 gigahertz. For this work, they deferred the question of what would happen if a wall or other reflector nearby creates a non-line-of-sight (NLOS) path from the base station to the receiver and focused on the simpler situation where the only existing path was along the line-of-sight (LOS).

In APL Photonics, from AIP Publishing, those same researchers address this question by considering two different generic types of transmitters and exploring how their characteristics can be used to determine whether an NLOS path contributes to the signal received by the receiver.

"One type of transmitter sends all frequencies more or less in the same direction," said Daniel Mittleman, co-author and an engineering professor at Brown, "while the other type sends different frequencies in different directions, exhibiting strong angular dispersion. The situation is quite different in these two different cases."

The researchers' work shows that the transmitter sending different frequencies in different directions has distinct advantages in its ability to detect the NLOS path and distinguish them from the LOS path.

"A well-designed receiver would be able to detect both frequencies and use their properties to recognize the two paths and tell them apart," Mittleman said.

Many recent reports within academic literature have focused on various challenges involved in using terahertz signals for wireless communications. Indeed, the term 6G has become a buzzword to encompass future generations of wireless systems that use these ultrahigh-frequency signals.

"For terahertz signals to be used for wireless communications, many challenges must be overcome, and one of the biggest is how to detect and exploit NLOS paths," said Mittleman.

This work is among the first to provide a quantitative consideration of how to detect and exploit NLOS paths, as well as a comparison of the behavior of different transmitters within this context.

"For most realistic indoor scenarios we can envision for an above-100 gigahertz wireless network, the issue of NLOS path is definitely going to require careful consideration," said Mittleman. "We need to know how to exploit these link opportunities to maintain connectivity."

If, for example, the LOS path is blocked by something, an NLOS path can be used to maintain the link between the base station and receiver.

"Interestingly, with a transmitter creating strong angular dispersion, sometimes an NLOS link can provide even faster connectivity than the LOS link," said Yasaman Ghasempour, co-author formerly at Rice University and currently an assistant professor at Princeton University. "But you can't take advantage of such opportunities if you don't know the NLOS path exists or how to find it."

Abu Dhabi, UAE, April 27, 2021: As people around the world increasingly get their news from social media, online misinformation has emerged as an area of great concern. To improve news literacy and reduce the spread of misinformation, NYUAD Center for Cybersecurity researcher and lead author Nicholas Micallef is part of a team that designed Fakey, a game that emulates a social media news feed and prompts players to use available signals to recognize and scrutinize suspicious content and focus on credible information. Players can share, like, or fact-check individual articles.

In a new study, Fakey: A Game Intervention to Improve News Literacy on Social Media published in the ACM Digital Library, Micallef and his colleagues Mihai Avram, Filippo Menczer, and Sameer Patil from the Luddy School of Informatics, Computing, and Engineering, Indiana University, present the analysis of interactions with Fakey, which was released to the general public as a web and mobile app with data procured after 19 months of use. Interviews were conducted to verify player understanding of the game elements. The researchers found that the more players interacted with articles in the game, the better their skills at spotting credible content became. However, playing the game did not affect players' ability to recognize questionable content. Further research will help determine how much gameplay would be necessary to be able to distinguish between legitimate and questionable content.

Games like Fakey, which was designed and developed by researchers at Indiana University, could be offered as a tool to social media users. For example, social media platforms could conduct regular exercises (akin to 'phishing drills' used in organizations for employee security training) wherein users practice identifying questionable articles. Or, the researchers say, such games could be integrated into media literacy curricula in schools. "The impact of misinformation could be substantially reduced if people were given tools to help them recognize and ignore such content," said Micallef. "The principles and mechanisms used by Fakey can inform the design of social media functionality in a way that empowers people to distinguish between credible and fake content in their news feeds and increase their digital literacy."

Aerosol products used in the home now emit more harmful volatile organic compound (VOC) air pollution than all the vehicles in the UK, new research shows.

A new study by the University of York and the National Centre for Atmospheric Science reveals that the picture is damaging globally with the world's population now using huge numbers of disposable aerosols - more than 25 billion cans per year.

This is estimated to lead to the release of more than 1.3 million tonnes of VOC air pollution each year, and could rise to 2.2 million tonnes by 2050.

The chemicals now used in compressed aerosols are predominantly volatile organic compounds (VOCs), chemicals which are also released from cars and fuels. The report says the VOCs currently being used in aerosols are less damaging than the ozone-depleting CFCs they replaced in the 1980's. However, in the 80's when key international policy decisions were made, no-one foresaw such a large rise in global consumption.

In the presence of sunlight, VOCs combine with a second pollutant, nitrogen oxides, to cause photochemical smog which is harmful to human health and damages crops and plants.

In the 1990s and 2000s by far the largest source of VOC pollution in the UK was gasoline cars and fuel, but these emissions have reduced dramatically in recent years through controls such as catalytic converters on vehicles and fuel vapour recovery at filling stations.

Researchers found that on average in high-income countries 10 cans of aerosol are used per person per year with the largest contributor being personal care products. The global amount emitted from aerosols every year is surging as lower and middle-income economies grow and people in these countries buy more.

The report authors are calling on international policymakers to reduce the use of VOCs in compressed aerosols, either by encouraging less damaging propellants like nitrogen, or advocating the use of non-aerosol versions of products. At present VOCs are used in around 93 per cent of aerosol cans.

Professor Alastair Lewis from the Department of Chemistry and a Director of the National Centre for Atmospheric Science said: "Virtually all aerosol based consumer products can be delivered in non-aerosol form, for example as dry or roll-on deodorants, bars of polish not spray. Making just small changes in what we buy could have a major impact on both outdoor and indoor air quality, and have relatively little impact on our lives.

"The widespread switching of aerosol propellant with non-VOC alternatives would lead to potentially meaningful reductions in surface ozone.

"Given the contribution of VOCs to ground-level pollution, international policy revision is required and the continued support of VOCs as a preferred replacement for halocarbons is potentially not sustainable for aerosol products longer term."

The report says there are already non-aerosol alternatives that can be easily be applied in their liquid or solid forms, for example, as roll-on deodorant, hair gel, solid furniture polish, bronzing lotion, and room fragrance.

Study authors conclude that the continued use of aerosols when non-aerosol alternatives exist is often down to the continuation of past consumer habits. And that the role played by aerosol VOC emissions in air pollution needs to be much more clearly articulated in messaging on air pollution and its management to the public.

Professor Lewis added: "Labelling of consumer products as high VOC emitting--and clearly linking this to poor indoor and outdoor air quality--may drive change away from aerosols to their alternatives, as has been seen previously with the successful labelling of paints and varnishes."

Amber Yeoman, a PhD student from the Wolfson Atmospheric Chemistry Laboratories was a co-author of the study which used data from industry and regulatory bodies from around the world.

Arum Han, professor in the Department of Electrical and Computer Engineering at Texas A&M University, and his collaborators have designed an experimental system that shows exposure of coronavirus to a very high temperature, even if applied for less than a second, can be sufficient to neutralize the virus so that it can no longer infect another human host.

Applying heat to neutralize COVID-19 has been demonstrated before, but in previous studies temperatures were applied from anywhere from one to 20 minutes. This length of time is not a practical solution, as applying heat for a long period of time is both difficult and costly. Han and his team have now demonstrated that heat treatment for less than a second completely inactivates the coronavirus -- providing a possible solution to mitigating the ongoing spread of COVID-19, particularly through long-range airborne transmission.

The Medistar Corporation approached leadership and researchers from the College of Engineering in the spring of 2020 to collaborate and explore the possibility of applying heat for a short amount of time to kill COVID-19. Soon after, Han and his team got to work, and built a system to investigate the feasibility of such a procedure.

Their process works by heating one section of a stainless-steel tube, through which the coronavirus-containing solution is run, to a high temperature and then cooling the section immediately afterward. This experimental setup allows the coronavirus running through the tube to be heated only for a very short period of time. Through this rapid thermal process, the team found the virus to be completely neutralized in a significantly shorter time than previously thought possible. Their initial results were released within two months of proof-of-concept experiments.

Han said if the solution is heated to nearly 72 degrees Celsius for about half a second, it can reduce the virus titer, or quantity of the virus in the solution, by 100,000 times which is sufficient to neutralize the virus and prevent transmission.

"The potential impact is huge," Han said. "I was curious of how high of temperatures we can apply in how short of a time frame and to see whether we can indeed heat-inactivate the coronavirus with only a very short time. And, whether such a temperature-based coronavirus neutralization strategy would work or not from a practical standpoint. The biggest driver was, 'Can we do something that can mitigate the situation with the coronavirus?'"

Their research was featured on the cover of the May issue of the journal Biotechnology and Bioengineering.

Not only is this sub-second heat treatment a more efficient and practical solution to stopping the spread of COVID-19 through the air, but it also allows for the implementation of this method in existing systems, such as heating, ventilation and air conditioning systems.

It also can lead to potential applications with other viruses, such as the influenza virus, that are also spread through the air. Han and his collaborators expect that this heat-inactivation method can be broadly applied and have a true global impact.

"Influenza is less dangerous but still proves deadly each year, so if this can lead to the development of an air purification system, that would be a huge deal, not just with the coronavirus, but for other airborne viruses in general," Han said.

In their future work, the investigators will build a microfluidic-scale testing chip that will allow them to heat-treat viruses for much shorter periods of time, for example, tens of milliseconds, with the hope of identifying a temperature that will allow the virus to be inactivated even with such a short exposure time.

The Marcellus Formation straddles the New York State and Pennsylvania border, a region that shares similar geography and population demographics. However, on one side of the state line unconventional natural gas development - or fracking - is banned, while on the other side it represents a multi-billion dollar industry. New research takes advantage of this 'natural experiment' to examine the health impacts of fracking and found that people who live in areas with a high concentration of wells are at higher risk for heart attacks.

"Fracking is associated with increased acute myocardial infarction hospitalization rates among middle-aged men, older men and older women as well as with increased heart attack-related mortality among middle-aged men," said Elaine Hill, Ph.D., an associate professor in the University of Rochester Medical Center (URMC) Department of Public Health Sciences, and senior author of the study that appears in the journal Environmental Research. "Our findings lend support for increased awareness about cardiovascular risks of unconventional natural gas development and scaled-up heart attack prevention, as well as suggest that bans on hydraulic fracturing can be protective for public health."

Natural gas extraction, including hydraulic fracking, is a well-known contributor to air pollution. Fracking wells operate around the clock and the process of drilling, gas extraction, and flaring - the burning off of natural gas byproducts - release organic compounds, nitrogen oxide, and other chemicals and particulates into the air. Additionally, each well requires the constant transportation of equipment, water, and chemicals, as well as the removal of waste water from the fracking process, further contributing to air pollution levels. Fracking wells remain in operation for several years, prolonging exposure to people who work at the wells sites and those who live nearby.

Instead of the typical single source of industrial air pollution, such as a factory or power plant, fracking entails multiple well sites spread across a large, and often rural, geographic area. In 2014, there were more than 8,000 fracking well sites in Pennsylvania. Some areas of the state have a dense population of fracking wells - three Pennsylvania counties have more than 1,000 sites. Contrast that with New York State, which has essentially banned the process of hydraulic fracking since 2010.

Exposure to air pollution is recognized as a significant risk factor for cardiovascular disease. Other research has shown that the intensity of oil and gas development and production is positively associated with diminished vascular function, blood pressure, and inflammatory markers associated with stress and short-term air pollution exposure. Light and noise pollution from the continuous operation of the wells are also associated with increasing stress, which is another contributor to cardiovascular disease.

The research team decided to measure the impact of fracking on cardiovascular health by studying heart attack hospitalization and death rates in 47 counties on either side of the New York and Pennsylvania state line. Using data from 2005 to 2014, they observed that heart attack rates were 1.4 to 2.8 percent higher in Pennsylvania, depending upon the age group and level of fracking activity in a given county.

The associations between fracking and heart attack hospitalization and death were most consistent among men aged 45-54, a group most likely to be in the unconventional gas industry workforce and probably the most exposed to fracking-related air pollutants and stressors. Heart attack deaths also increase in this age group by 5.4 percent or more in counties with high concentrations of well sites. Hospitalization and mortality rates also jumped significantly in women over the age of 65.

Fracking is more concentrated in rural communities, which the authors speculate may further compromise cardiovascular heath due to the trend of rural hospital closures. People who suffer from cardiovascular disease in these areas may be at increased risk of adverse health outcomes, including death, due to less access to care. The authors suggest that more should be done to raise awareness about fracking-related risks for cardiovascular disease and physicians should keep a closer eye on high risk patients who reside in areas with fracking activity. They also contend that the study should inform policymakers about the tradeoffs between public health and the economic activity generated by the industry.

"These findings contribute to the growing body of evidence on the adverse health impact of fracking," said Alina Denham, a Ph.D. candidate in Health Policy at the University of Rochester School of Medicine and Dentistry and first author of the study. "Several states, including New York, have taken the precaution of prohibiting hydraulic fracturing until more is known about the health and environmental consequences. If causal mechanisms behind our findings are ascertained, our findings would suggest that bans on hydraulic fracturing can be protective for human health."

A team of engineering researchers at the Georgia Institute of Technology hopes to uncover new ways to diagnose and treat brain ailments, from tumors and stroke to Parkinson's disease, leveraging vibrations and ultrasound waves.

The five-year, $2 million National Science Foundation (NSF) project initiated in 2019 already has resulted in several published journal articles that offer promising new methods to focus ultrasound waves through the skull, which could lead to broader use of ultrasound imaging -- considered safer and less expensive than magnetic resonance imaging (MRI) technology.

Specifically, the team is researching a broad range of frequencies, spanning low frequency vibrations (audio frequency range) and moderate frequency guided waves (100 kHz to 1 MHz) to high frequencies employed in brain imaging and therapy (in the MHz range).

"We're coming up with a unique framework that incorporates different research perspectives to address how you use sound and vibration to treat and diagnose brain diseases," explained Costas Arvanitis, an assistant professor in Georgia Tech's George W. Woodruff School of Mechanical Engineering and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. "Each researcher is bringing their own expertise to explore how vibrations and waves across a range of frequencies could either extract information from the brain or focus energy on the brain."

Accessing the Brain Is a Tough Challenge

While it is possible to treat some tumors and other brain diseases non-invasively if they are near the center of the brain, many other conditions are harder to access, the researchers say.

"The center part of the brain is most accessible; however, even if you are able to target the part of the brain away from the center, you still have to go through the skull," Arvanitis said.

He added that moving just 1 millimeter in the brain constitutes "a huge distance" from a diagnostic perspective. The science community widely acknowledges the brain's complexity, each part associated with a different function and brain cells differing from one to the other.

According to Brooks Lindsey, a biomedical engineering assistant professor at Georgia Tech and Emory, there is a reason why brain imaging or therapy works well in some people but not in others.

"It depends on the individual patient's skull characteristics," he said, noting that some people have slightly more trabecular bone - the spongy, porous part of the bone - that makes it more difficult to treat.

Using ultrasound waves, the researchers are tackling the challenge on multiple levels. Lindsey's lab uses ultrasound imaging to assess skull properties for effective imaging and therapy. He said his team conducted the first investigation that uses ultrasound imaging to measure the effects of bone microstructure -- specifically, the degree of porosity in the inner, trabecular bone layer of the skull.

"By understanding transmission of acoustic waves through microstructure in an individual's skull, non-invasive ultrasound imaging of the brain and delivery of therapy could be possible in a greater number of people," he said, explaining one potential application would be to image blood flow in the brain following a stroke.

Refocusing Ultrasound Beams on the Fly

Arvanitis' lab recently found a new way to focus ultrasound through the skull and into the brain, which is "100-fold faster than any other method," Arvanitis said. His team's work in adaptive focusing techniques would allow clinicians to adjust the ultrasound on the fly to focus it better.

"Current systems rely a lot on MRIs, which are big, bulky, and extremely expensive," he said. "This method lets you adapt and refocus the beam. In the future this could allow us to design less costly, simpler systems, which would make the technology available to a wider population, as well as be able to treat different parts of the brain."

Using 'Guided Waves' to Access Periphery Brain Areas

Another research cohort, led by Alper Erturk, Woodruff Professor of Mechanical Engineering at Georgia Tech, and former Georgia Tech colleague Massimo Ruzzene, Slade Professor of Mechanical Engineering at the University of Colorado Boulder, performs high-fidelity modeling of skull bone mechanics along with vibration-based elastic parameter identification. They also leverage guided ultrasonic waves in the skull to expand the treatment envelope in the brain. Erturk and Ruzzene are mechanical engineers by background, which makes their exploration of vibrations and guided waves in difficult-to-reach brain areas especially fascinating.

Erturk noted that guided waves are used in other applications such as aerospace and civil structures for damage detection. "Accurate modeling of the complex bone geometry and microstructure, combined with rigorous experiments for parameter identification, is crucial for a fundamental understanding to expand the accessible region of the brain," he said.

Ruzzene compared the brain and skull to the Earth's core and crust, with the cranial guided waves acting as an earthquake. Just as geophysicists use earthquake data on the Earth's surface to understand the Earth's core, so are Erturk and Ruzzene using the guided waves to generate tiny, high frequency "earthquakes" on the external surface of the skull to characterize what comprises the cranial bone.

Trying to access the brain periphery via conventional ultrasound poses added risks from the skull heating up. Fortunately, advances such as cranial leaky Lamb waves increasingly are recognized for transmitting wave energy to that region of the brain.

These cranial guided waves could complement focused ultrasound applications to monitor changes in the cranial bone marrow from health disorders, or to efficiently transmit acoustic signals through the skull barrier, which could help access metastases and treat neurological conditions in currently inaccessible regions of the brain.

Ultimately, the four researchers hope their work will make full brain imaging feasible while stimulating new medical imaging and therapy techniques. In addition to transforming diagnosis and treatment of brain diseases, the techniques could better detect traumas and skull-related defects, map the brain function, and enable neurostimulation. Researchers also see the potential for uncovering ultrasound-based blood-brain barrier openings for drug delivery for managing and treating diseases such as Alzheimer's.

DALLAS (SMU) - An international team of paleontologists has identified a new genus and species of hadrosaur or duck-billed dinosaur, Yamatosaurus izanagii, on one of Japan's southern islands.

The fossilized discovery yields new information about hadrosaur migration, suggesting that the herbivors migrated from Asia to North America instead of vice versa. The discovery also illustrates an evolutionary step as the giant creatures evolved from walking upright to walking on all fours. Most of all, the discovery provides new information and asks new questions about dinosaurs in Japan.

The research, "A New Basal Hadrosaurid (Dinosauria: Ornithischia) From the latest Cretaceous Kita-ama Formation in Japan implies the origin of Hadrosaurids," was recently published in Scientific Reports. Authors include Yoshitsugu Kobayashi of Hokkaido University Museum, Ryuji Takasaki of Okayama University of Science, Katsuhiro Kubota of Museum of Nature and Human Activities, Hyogo and Anthony R. Fiorillo of Southern Methodist University.

Hadrosaurs, known for their broad, flattened snouts, are the most commonly found of all dinosaurs. The plant-eating dinosaurs lived in the Late Cretaceous period more than 65 million years ago and their fossilized remains have been found in North America, Europe, Africa and Asia.

Uniquely adapted to chewing, hadrosaurs had hundreds of closely spaced teeth in their cheeks. As their teeth wore down and fell out, new teeth in the dental battery, or rows of teeth below existing teeth, grew in as replacements. Hadrosaurs' efficient ability to chew vegetation is among the factors that led to its diversity, abundance and widespread population, researchers say.

The Yamatosaurus' dental structure distinguishes it from known hadrosaurs, says Fiorillo, senior fellow at SMU's Institute for the Study of Earth and Man. Unlike other hadrosaurs, he explains, the new hadrosaur has just one functional tooth in several battery positions and no branched ridges on the chewing surfaces, suggesting that it evolved to devour different types of vegetation than other hadrosaurs.

Yamatosaurus also is distinguished by the development of its shoulder and forelimbs, an evolutionary step in hadrosaurid's gait change from a bipedal to a quadrupedal dinosaur, he says.

"In the far north, where much of our work occurs, hadrosaurs are known as the caribou of the Cretaceous," says Fiorillo. They most likely used the Bering Land Bridge to cross from Asia to present-day Alaska and then spread across North America as far east as Appalachia, he says. When hadrosaurs roamed Japan, the island country was attached to the eastern coast of Asia. Tectonic activity separated the islands from the mainland about 15 million years ago, long after dinosaurs became extinct.

The partial specimen of the Yamatosaurus was discovered in 2004 by an amateur fossil hunter in an approximately 71- to 72-million-year-old layer of sediment in a cement quarry on Japan's Awaji Island. The preserved lower jaw, teeth, neck vertebrae, shoulder bone and tail vertebra were found by Mr. Shingo Kishimoto and given to Japan's Museum of Nature and Human Activities in the Hyogo Prefecture, where they were stored until studied by the team.

"Japan is mostly covered with vegetation with few outcrops for fossil-hunting," says Yoshitsugu Kobayashi, professor at Hokkaido University Museum. "The help of amateur fossil-hunters has been very important."

Kobayashi has worked with SMU paleontologist Tony Fiorillo since 1999 when he studied under Fiorillo as a Ph.D. student. They have collaborated to study hadrosaurs and other dinosaurs in Alaska, Mongolia and Japan. Together they created their latest discovery's name. Yamato is the ancient name for Japan and Izanagi is a god from Japanese mythology who created the Japanese islands, beginning with Awaji Island, where Yamatosaurus was found.

Yamatosaurus is the second new species of hadrosaurid that Kobayashi and Fiorillo have identified in Japan. In 2019 they reported the discovery of the largest dinosaur skeleton found in Japan, another hadrosaurid, Kamuysaurus, discovered on the northern Japanese island of Hokkaido.

"These are the first dinosaurs discovered in Japan from the late Cretaceous period," Kobayashi says. "Until now, we had no idea what dinosaurs lived in Japan at the end of the dinosaur age," he says. "The discovery of these Japanese dinosaurs will help us to fill a piece of our bigger vision of how dinosaurs migrated between these two continents," Kobayashi says.

Researchers at the Pritzker School of Molecular Engineering (PME) at the University of Chicago have designed a completely novel potential treatment for COVID-19: nanoparticles that capture SARS-CoV-2 viruses within the body and then use the body's own immune system to destroy it.

These "Nanotraps" attract the virus by mimicking the target cells the virus infects. When the virus binds to the Nanotraps, the traps then sequester the virus from other cells and target it for destruction by the immune system.

In theory, these Nanotraps could also be used on variants of the virus, leading to a potential new way to inhibit the virus going forward. Though the therapy remains in early stages of testing, the researchers envision it could be administered via a nasal spray as a treatment for COVID-19.

The results were published April 19 in the journal Matter.

"Since the pandemic began, our research team has been developing this new way to treat COVID-19," said Asst. Prof. Jun Huang, whose lab led the research. "We have done rigorous testing to prove that these Nanotraps work, and we are excited about their potential."

Designing the perfect trap

To design the Nanotrap, the research team - led by postdoctoral scholar Min Chen and graduate student Jill Rosenberg - looked into the mechanism SARS-CoV-2 uses to bind to cells: a spike-like protein on its surface that binds to a human cell's ACE2 receptor protein.

To create a trap that would bind to the virus in the same way, they designed nanoparticles with a high density of ACE2 proteins on their surface. Similarly, they designed other nanoparticles with neutralizing antibodies on their surfaces. (These antibodies are created inside the body when someone is infected and are designed to latch onto the coronavirus in various ways).

Both ACE2 proteins and neutralizing antibodies have been used in treatments for COVID-19, but by attaching them to nanoparticles, the researchers created an even more robust system for trapping and eliminating the virus.

Made of FDA-approved polymers and phospholipids, the nanoparticles are about 500 nanometers in diameter - much smaller than a cell. That means the Nanotraps can reach more areas inside the body and more effectively trap the virus.

The researchers tested the safety of the system in a mouse model and found no toxicity. They then tested the Nanotraps against a pseudovirus - a less potent model of a virus that doesn't replicate - in human lung cells in tissue culture plates and found that they completely blocked entry into the cells.

Once the pseudovirus bound itself to the nanoparticle - which in tests took about 10 minutes after injection - the nanoparticles used a molecule that calls the body's macrophages to engulf and degrade the Nanotrap. Macrophages will generally eat nanoparticles within the body, but the Nanotrap molecule speeds up the process. The nanoparticles were cleared and degraded within 48 hours.

The researchers also tested the nanoparticles with a pseudovirus in an ex vivo lung perfusion system - a pair of donated lungs that is kept alive with a ventilator - and found that they completely blocked infection in the lungs.

They also collaborated with researchers at Argonne National Laboratory to test the Nanotraps with a live virus (rather than a pseudovirus) in an in vitro system. They found that their system inhibited the virus 10 times better than neutralizing antibodies or soluble ACE2 alone.

A potential future treatment for COVID-19 and beyond

Next the researchers hope to further test the system, including more tests with a live virus and on the many virus variants.

"That's what is so powerful about this Nanotrap," Rosenberg said. "It's easily modulated. We can switch out different antibodies or proteins or target different immune cells, based on what we need with new variants."

The Nanotraps can be stored in a standard freezer and could ultimately be given via an intranasal spray, which would place them directly in the respiratory system and make them most effective.

The researchers say it is also possible to serve as a vaccine by optimizing the Nanotrap formulation, creating an ultimate therapeutic system for the virus.

"This is the starting point," Huang said. "We want to do something to help the world."

The research involved collaborators across departments, including chemistry, biology, and medicine.