The islands that make up Japan form a long arc that extends from tropical regions in the south to Palearctic regions in the north. Permafrost has been reported to exist in the Daisetsu Mountains, Mt. Fuji and Mt. Tateyama. The Daisetsu Mountains on the northern island of Hokkaido, which are known to support a variety of alpine plants and animals, are also a valuable natural resource that is visited by numerous climbers every year. However, there is some concern that the thawing of permafrost will have a major impact on this mountain ecosystem. No projections of future permafrost distribution have been undertaken in East Asia, including in Japan, to date.

In this study, by applying the statistical method developed in a previous study for estimating the permafrost distribution to outputs from bias-corrected and downscaled climate model with a 1 km resolution for the area of interest, we investigated the climatic conditions required to sustain permafrost in the Daisetsu Mountains.

Researchers have studied the climate conditions suitable to maintain permafrost in the Daisetsu Mountains. The region of the climate conditions suitable to maintain permafrost starts to decrease significantly in size from around 2000, and under both the low-carbon scenario consistent with Paris target (RCP2.6) and busines-as-usual scenario (RCP8.5). The steep decline in the region at the end of the 20th century occurs because the surface air temperature increases significantly from around the year 2000 onward. The size of the area in the Daisetsu Mountains where climatic conditions were suitable for permafrost were estimated to be approximately 150 km2 in 2010. Under the RCP8.5 scenario, this area is projected to disappear by around 2070. Under the RCP2.6 scenario, the area is projected to decrease to approximately 20 km² by 2100.

The finding that the climatic conditions of the Daisetsu Mountains are projected to shift towards conditions where permafrost will disappear regardless of the climate scenario used, indicates the importance of impact assessments and developing adaptation measures to climate change. Thawing of permafrost can have a significant impact on the surface vegetation and alpine ecosystems. Previous studies have shown that the thawing of permafrost can have a variety of adverse effects, including lowering groundwater levels and replacement of alpine meadows by steppes, extensive desertification such as that in the eastern and western parts of the Tibetan Plateau, and a decrease in species diversity due to warming. Moreover, thawing of the frozen ground reduces the stability of the ground in mountain regions, potentially increasing the frequency and magnitude of rock falls and landslides, which may affect the safety of trekkers that visit the Daisetsu Mountains annually. In order to deal with these problems, it is very important to monitor the environmental changes in mountainous areas. In addition to accurately monitoring changes in mountain environments, providing local governments with appropriate measures to prepare for major future environmental changes, as shown in this study, is an important issue for the future.

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The study findings appear online in 4Open, a journal published by EDP Sciences.

“HCC accounts for nearly 90% of all liver cancers, and current survival rates are between six and 20 months,” said Boris Pasche, M.D., Ph.D., chair of cancer biology and director of Wake Forest Baptist’s Comprehensive Cancer Center. “Currently, there are limited treatment options for patients with this advanced liver cancer.”

For the study researchers used a device called TheraBionic P1, invented by Pasche and Alexandre Barbault of TheraBionic GmbH in Ettlingen, Germany, that works by delivering cancer-specific, amplitude-modulated radiofrequency electromagnetic fields (AM RF EMF) programmed specifically for HCC.

The frequencies used are specific to the patient’s type of cancer as identified through tumor biopsies or blood work, Pasche said.

Pasche and Barbault discovered radio frequencies for 15 different types of cancer, as previously reported in a study published in 2009 in the Journal of Experimental & Clinical Cancer Research.

TheraBionic P1 is a hand-held device that emits radio frequencies via a spoon-shaped antenna, which is placed on the patient’s tongue during treatment and is administered three times a day for one hour to deliver low levels of radiofrequency electromagnetic fields throughout the patient’s body.

In previous studies, the device, which received breakthrough designation from the FDA in 2019, was shown to block the growth of liver cancer cells in the body without damaging healthy cells.

For the current study, 18 patients with advanced HCC participated and received treatment with the device. Researchers also analyzed previously published data on 41 patients from a phase II study and historical controls from earlier clinical trials.

“Our findings show an improvement in overall survival of more than 30% in patients with well-preserved liver function and also in those with more severe disease,” Pasche said.

Researchers also tracked side effects, and no patients stopped TheraBionic P1 treatment because of adverse reactions.

“We’re encouraged by these initial findings,” Pasche said. “Our study shows a benefit in overall survival, and the treatment isn’t associated with any significant side effects.”

Support for this study was provided by TheraBionic Inc. and funds from Wake Forest Baptist’s Comprehensive Cancer Center.

Pasche noted that the study does have several limitations because of the small sample size and “selection bias inherent in the use of historical control data.”

However, two additional clinical trials are underway and are being led by William Blackstock, M.D., chair of radiation oncology at Wake Forest Baptist’s Comprehensive Cancer Center. One is a single-center study to assess the safety and effectiveness of the TheraBionic device in combination with Regorafenib, a chemotherapy drug, as a second-line treatment. Another multicenter, double-blind, randomized study comparing TheraBionic with placebo will assess the safety and effectiveness of the device as a third-line therapy in the treatment of advanced HCC.

Pasche holds stock in TheraBionic Inc. and TheraBionic GmbH. He is chairman of the board and CEO of TheraBionic Inc. and co-CEO of TheraBionic GmbH. He is also a senior editorial board member of Life Sciences-Medicine of 4Open by EDP Sciences. These relationships are being managed per institutional policy by Wake Forest School of Medicine’s Conflict of Interest Review Committee.

Researchers at Columbia Engineering report that they have developed a “green electrospinning” process that addresses many of the challenges to scaling up this fabrication method, from managing the environmental risks of volatile solvent storage and disposal at large volumes to meeting health and safety standards during both fabrication and implementation. The team’s new study, published June 28, 2021, by Biofabrication, details how they have modernized the nanofiber fabrication of widely utilized biological and synthetic polymers (e.g. poly-α-hydroxyesters, collagen), polymer blends, and polymer-ceramic composites.

The study also underscores the superiority of green manufacturing. The group’s “green” fibers exhibited exceptional mechanical properties and preserved growth factor bioactivity relative to traditional fiber counterparts, which is essential for drug delivery and tissue engineering applications.

Regenerative medicine is a $156 billion global industry, one that is growing exponentially. The team of researchers, led by Helen H. Lu, Percy K. and Vida L.W. Hudson Professor of Biomedical Engineering, wanted to address the challenge of establishing scalable green manufacturing practices for biomimetic biomaterials and scaffolds used in regenerative medicine.

“We think this is a paradigm shift in biofabrication, and will accelerate the translation of scalable biomaterials and biomimetic scaffolds for tissue engineering and regenerative medicine,” said Lu, a leader in research on tissue interfaces, particularly the design of biomaterials and therapeutic strategies for recreating the body’s natural synchrony between tissues. “Green electrospinning not only preserves the composition, chemistry, architecture, and biocompatibility of traditionally electrospun fibers, but it also improves their mechanical properties by doubling the ductility of traditional fibers without compromising yield or ultimate tensile strength. Our work provides both a more biocompatible and sustainable solution for scalable nanomaterial fabrication.”

The team, which included several BME doctoral students from Lu’s group, Christopher Mosher PhD’20 and Philip Brudnicki, as well as Theanne Schiros, an expert in eco-conscious textile synthesis who is also a research scientist at Columbia MRSEC and assistant professor at FIT, applied sustainability principles to biomaterial production, and developed a green electrospinning process by systematically testing what the FDA considers as biologically benign solvents (Q3C Class 3).

They identified acetic acid as a green solvent that exhibits low ecological impact (Sustainable Minds® Life Cycle Assessment) and supports a stable electrospinning jet under routine fabrication conditions. By tuning electrospinning parameters, such as needle-plate distance and flow rate, the researchers were able to ameliorate the fabrication of research and industry-standard biomedical polymers, cutting the detrimental manufacturing impacts of the electrospinning process by three to six times.

Green electrospun materials can be used in a broad range of applications. Lu’s team is currently working on further innovating these materials for orthopaedic and dental applications, and expanding this eco-conscious fabrication process for scalable production of regenerative materials.

“Biofabrication has been referred to as the ‘fourth industrial revolution’ following steam engines, electrical power, and the digital age for automating mass production,” noted Mosher, the study’s first author. “This work is an important step towards developing sustainable practices in the next generation of biomaterials manufacturing, which has become paramount amidst the global climate crisis.”

The paper, published today in The Lancet Digital Health, and led by researchers from King’s College London analyses data from the ZOE COVID Symptom Study app between April 20^th to 15^th October 2020. App contributors are invited to get tested as soon as they report any new symptoms, thanks to a joint initiative with the Department of Health and Social Care. The researchers modelled the early signs of COVID-19 infection and successfully detected 80% of cases when using three days of self-reported symptoms.

Researchers compared the ability to predict early signs of COVID-19 infection using current National Health Service UK diagnostic criteria and a Hierarchical Gaussian Process model, a type of machine learning.

This machine learning model was able to incorporate some characteristics about the person affected, such as age, sex, and health conditions, and showed that symptoms of early COVID-19 infection are different among various groups.

18 symptoms were examined, which had different relevance for early detection in different groups. The most important symptoms for earliest detection of COVID-19 overall included loss of smell, chest pain, persistent cough, abdominal pain, blisters on the feet, eye soreness and unusual muscle pain. However, loss of smell lost significance in people over 60 years of age and was not relevant for subjects over 80. Other early symptoms such as diarrhoea were key in older age groups (60-79 and >80). Fever, while a known symptom of disease, was not an early feature of the disease in any age group.

Men were more likely to report shortness of breath, fatigue, chills and shivers, whereas women were more likely to report loss of smell, chest pain and a persistent cough.

While these models were generated in the COVID Symptom study app, models were replicated across time suggesting they would also apply to non-app contributors. Although the models were used on the first strain of the virus and Alpha variants, the key findings suggest the symptoms of the Delta variant and subsequent variants will also differ across population groups.

Lead author, Claire Steves, Reader at King’s College London said: “Its important people know the earliest symptoms are wide-ranging and may look different for each member of a family or household. Testing guidance could be updated to enable cases to be picked up earlier, especially in the face of new variants which are highly transmissible. This could include using widely available lateral flow tests for people with any of these non-core symptoms.”

Dr Liane dos Santos Canas, first author from King’s College London, said: “Currently, in the UK, only a few symptoms are used to recommend self-isolation and further testing. Using a larger number of symptoms and only after a few days of being unwell, using AI, we can better detect COVID-19 positive cases. We hope such a method is used to encourage more people to get tested as early as possible to minimise the risk of spread.”

Dr Marc Modat, Senior Lecturer at King’s College London, said: “As part of our study, we have been able to identify that the profile of symptoms due to COVID-19 differs from one group to another. This suggests that the criteria to encourage people to get tested should be personalised using individuals’ information such as age. Alternatively, a larger set of symptoms could be considered, so the different manifestations of the disease across different groups are taken into account.”

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Research on a newly discovered bird fossil led by The University of Texas at Austin found that a unique brain shape may be why the ancestors of living birds survived the mass extinction that claimed all other known dinosaurs.

“Living birds have brains more complex than any known animals except mammals,” said lead investigator Christopher Torres, who conducted the research while earning a Ph.D. from the UT College of Natural Sciences and is now a National Science Foundation postdoctoral fellow at Ohio University and research associate at the UT Jackson School of Geosciences. “This new fossil finally lets us test the idea that those brains played a major role in their survival.”

The fossil is about 70 million years old and has a nearly complete skull, a rare occurrence in the fossil record that allowed the scientists to compare the ancient bird to birds living today.

The findings were published July 30 in the journal Science Advances.

The fossil is a new specimen of a bird named Ichthyornis, which went extinct at the same time as other nonavian dinosaurs and lived in what is now Kansas during the late Cretaceous Period. Ichthyornis has a blend of avian and nonavian dinosaur-like characteristics — including jaws full of teeth but tipped with a beak. The intact skull let Torres and his collaborators get a closer look at the brain.

Bird skulls wrap tightly around their brains. With CT-imaging data, the researchers used the skull of Ichthyornis like a mold to create a 3D replica of its brain called an endocast. They compared that endocast with ones created for living birds and more distant dinosaurian relatives.

The researchers found that the brain of Ichthyornis had more in common with nonavian dinosaurs than living birds. In particular, the cerebral hemispheres — where higher cognitive functions such as speech, thought and emotion occur in humans — are much bigger in living birds than in Ichthyornis. That pattern suggests that these functions could be connected to surviving the mass extinction.

“If a feature of the brain affected survivorship, we would expect it to be present in the survivors but absent in the casualties, like Ichthyornis,” said Torres. “That’s exactly what we see here.”

The search for skulls from early birds and closely related dinosaurs has been challenging paleontologists for centuries. Bird skeletons are notoriously brittle and rarely survive in the fossil record intact in three dimensions. Well-preserved skulls are particularly rare — but that’s exactly what scientists need in order to understand what their brains were like in life.

“Ichthyornis is key to unraveling that mystery,” said Julia Clarke, a professor at the UT Jackson School of Geosciences and co-author of the study. “This fossil helps bring us much closer to answering some persistent questions concerning living birds and their survivorship among dinosaurs.”

Mark Norell, the curator and division chair of paleontology at the American Museum of Natural History, co-authored the study. This work was funded by the Howard Hughes Medical Institute Science Education Program, the Jackson School of Geosciences and the American Museum of Natural History.

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These diagnostic processes open the door to a better understanding of plasma physics, which could lead to advances in green energy production through methods including fusion, hydrocarbon reforming and hydrogen generation.

Dr. David Staack and Christopher Campbell in the J. Mike Walker ’66 Department of Mechanical Engineering at Texas A&M University are part of the team pioneering this approach to assessing plasma processes. Partners on the project include diagnostics experts from Los Alamos National Laboratories and using the facilities at the Argonne National Laboratory Advanced Photon Source (APS).

The team is working with LTEOIL on patented research into the use of multiphase plasma in carbon-free fuel reforming. The research is supported by the dynamic materials properties campaign (C2) and the advanced diagnostics campaign (C3) at Los Alamos National Laboratories through the Thermonuclear Plasma Physics group (P4) principal investigator, Zhehui (Jeph) Wang.

The research, which was recently published in Physical Review Research, is producing the first-known ultrafast X-ray images of pulsed plasma initiation processes in water. Staack, associate professor and Sallie and Don Davis ’61 Career Development Professor, said these new images provide valuable insight into how plasma behaves in liquid.

“Our lab is working with industry sponsors on patented research into the use of multiphase plasma in carbon-free fuel reforming,” Staack said. “By understanding this plasma physics, we are able to efficiently convert tar and recycled plastics into hydrogen and fuels for automobiles without any greenhouse gas emissions. In the future, these investigations may lead to improvements in inertial confinement fusion energy sources.”

Inertial confinement fusion — in which high temperature, high energy density plasmas are generated — is a specific focus of the project. To better understand the plasma physics involved in this type of fusion, Staack said the team is developing short timescale, high-speed imaging and diagnostic techniques utilizing a simple, low-cost plasma discharge system.

Additionally, they are seeking to better understand the phenomena that occur when plasma is discharged in liquid, causing a rapid release of energy resulting in low-density microfractures in the water that move at over 20 times the speed of sound.

Campbell, a graduate research assistant and Ph.D. candidate, said the team hopes their discoveries can prove to be a valuable contribution to the collective knowledge of their field as researchers seek to develop robust predictive models for how plasma will react in liquid.

“Our goal is to experimentally probe the regions and timescales of interest surrounding this plasma using ultrafast X-ray and visible imaging techniques, thereby contributing new data to the ongoing literature discussion in this area,” said Campbell. “With a complete conceptual model, we could more efficiently learn how to apply these plasmas in new ways and also improve existing applications.”

Although they have made progress, Campbell said current methods are not yet sophisticated enough to collect multiple images of a single plasma event in such a short amount of time — less than 100 nanoseconds.

“Even with the state-of-the-art techniques and fast framerates available at the Advanced Photon Source, we have only been able to image a single frame during the entire event of interest — by the next video frame, most of the fastest plasma processes have concluded,” Campbell said. “This work highlights several resourceful techniques we have developed to make the most of what few images we are able to take of these fastest processes.”

The team is currently working to measure the pressures induced by the rapid phenomena and preparing for a second round of measurements at APS to investigate interacting discharges, discharges in different fluids and processes that may limit confinement of higher energy discharges. They look forward to the opportunity of using even higher-framerate X-ray imaging methods ranging up to 6.7 million frames per second, compared to 271 thousand frames per second in this study.

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The findings upend long-held beliefs about the mechanisms underlying the disease, reinforce the importance of prevention efforts and offer a path forward for investigating the origins of other cancer types.

“Cancers result from DNA mutations that allow defective cells to survive and invade other tissues. However, in most cases, the source of these mutations is not clear, which complicates development of therapies and prevention methods,” said Gerd Pfeifer, Ph.D., a VAI professor and the study’s corresponding author. “In melanoma, we’ve now shown that damage from sunlight primes the DNA by creating ‘premutations’ that then give way to full mutations during DNA replication.”

Melanoma is a serious type of skin cancer that begins in pigment-producing skin cells. Although less common than other types of skin cancer, melanoma is more likely to spread and invade other tissues, which significantly reduces patient survival. Previous large-scale sequencing studies have shown that melanoma has the most DNA mutations of any cancer. Like other skin cancers, melanoma is linked to sun exposure, specifically a type of radiation called UVB. Exposure to UVB damages skin cells as well as the DNA within cells.

Most cancers are thought to begin when DNA damage directly causes a mutation that is then copied into subsequent generations of cells during normal cellular replication. In the case of melanoma, however, Pfeifer and his team found a different mechanism that produces disease-causing mutations — the introduction of a chemical base not normally found in DNA that makes it prone to mutation.

DNA comprises four chemical bases that exist in pairs — adenine (A) and thymine (T), and cytosine (C) and guanine (G). Different sequences of these pairs encode all of the instructions for life. In melanoma, the problem occurs when UVB radiation from the sun hits certain sequences of bases — CC, TT, TC and CT — causing them to chemically link together and become unstable. The resulting instability causes a chemical change to cytosine that transforms it into uracil, a chemical base found in the messenger molecule RNA but not in DNA. This change, called a “premutation,” primes the DNA to mutate during normal cell replication, thereby causing alterations that underlie melanoma.

These mutations may not cause disease right away; instead, they may lay dormant for years. They also can accumulate as time goes on and a person’s lifetime exposure to sunlight increases, resulting in a tough-to-treat cancer that evades many therapeutic options.

“Safe sun practices are very important. In our study, 10-15 minutes of exposure to UVB light was equivalent to what a person would experience at high noon, and was sufficient to cause premutations,” Pfeifer said. “While our cells have built-in safeguards to repair DNA damage, this process occasionally lets something slip by. Protecting the skin is generally the best bet when it comes to melanoma prevention.”

The findings were made possible using a method developed by Pfeifer’s lab called Circle Damage Sequencing, which allows scientists to “break” DNA at each point where damage occurs. They then coax the DNA into circles, which are replicated thousands of times using a technology called PCR. Once they have enough DNA, they use next-generation sequencing to identify which DNA bases are present at the breaks. Going forward, Pfeifer and colleagues plan to use this powerful technique to investigate other types of DNA damage in different kinds of cancer.

Other authors include Seung-Gi Jin, Ph.D., Dean Pettinga, Jennifer Johnson and Peipei Li, Ph.D., of VAI.

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