Tech

Energy demands limit our brains' information processing capacity

Our brains have an upper limit on how much they can process at once due to a constant but limited energy supply, according to a new UCL study using a brain imaging method that measures cellular metabolism.

The study, published in the Journal of Neuroscience, found that paying attention can change how the brain allocates its limited energy; as the brain uses more energy in processing what we attend to, less energy is supplied to processing outside our attention focus.

Explaining the research, senior author Professor Nilli Lavie (UCL Institute of Cognitive Neuroscience) said: "It takes a lot of energy to run the human brain. We know that the brain constantly uses around 20% of our metabolic energy, even while we rest our mind, and yet it's widely believed that this constant but limited supply of energy does not increase when there is more for our mind to process.

"If there's a hard limit on energy supply to the brain, we suspected that the brain may handle challenging tasks by diverting energy away from other functions, and prioritising the focus of our attention.

"Our findings suggest that the brain does indeed allocate less energy to the neurons that respond to information outside the focus of our attention when our task becomes harder. This explains why we experience inattentional blindness and deafness even to critical information that we really want to be aware of."

The research team of cognitive neuroscientists and biomedical engineers measured cerebral metabolism with a non-invasive optical imaging method. In this way they could see how much energy brain regions use as people focus attention on a task, and how that changes when the task becomes more mentally demanding. They used broadband near-infrared spectroscopy to measure the oxidation levels of an enzyme involved in energy metabolism in brain cells' mitochondria, the energy generators that power each cell's biochemical reactions.

The researchers employed their technique to measure brain metabolism in different regions of the visual cortex in the brains of 18 people as they carried out visual search tasks that were either complex or simple, while sometimes also presented with a visual distraction that was irrelevant to the task.

They identified elevated cellular metabolism in the brain areas responsive to the attended task stimuli as the task was more complex, and these increases were directly mirrored with reduced cellular metabolism levels in areas responding to unattended stimuli. This push-pull pattern was closely synchronised, showing a trade-off of limited energy supply between attended and unattended processing.

Co-author Professor Ilias Tachtsidis (UCL Medical Physics & Biomedical Engineering) said: "By using our in-house developed broadband near-infrared spectroscopy, an optical brain monitoring technology we developed at UCL, we were better able to measure an enzyme in the mitochondria (the power factory of the cells) that plays an integral part in metabolism."

First author, PhD student Merit Bruckmaier (UCL Institute of Cognitive Neuroscience) said: "Using these methods, our conclusions about brain energy usage are more direct and telling than in past studies using fMRI imaging methods that measure cerebral blood oxygenation levels instead of an intracellular marker of metabolism."

Professor Lavie said: "In this way, we have managed to connect people's experience of brain overload to what's going on inside their neurons, as high energy demands for one purpose are balanced out by reduced energy use related to any other purpose. If we try to process too much information we may feel the strain of overload because of the hard limit on our brain capacity.

"During recent months, we've heard from a lot of people who say they're feeling overwhelmed, with constant news updates and new challenges to overcome. When your brain is at capacity, you are likely to fail to process some information. You might not even notice an important email come in because your child was speaking to you, or you might miss the oven timer go off because you received an unexpected work call. Our findings may explain these often-frustrating experiences of inattentional blindness or deafness."

Credit: 
University College London

Four-stranded DNA structures found to play role in breast cancer

Four stranded DNA structures - known as G-quadruplexes - have been shown to play a role in certain types of breast cancer for the first time, providing a potential new target for personalised medicine, say scientists at the University of Cambridge.

In 1953, Cambridge researchers Francis Crick and James Watson co-authored a study published in the journal Nature which showed that DNA in our cells has an intertwined, 'double helix' structure. Sixty years later, a team led by Professor Sir Shankar Balasubramanian and Professor Steve Jackson, also at Cambridge, found that an unusual four-stranded configuration of DNA can occur across the human genome in living cells.

These structures form in regions of DNA that are rich in one of its building blocks, guanine (G), when a single strand of the double-stranded DNA loops out and doubles back on itself, forming a four-stranded 'handle' in the genome. As a result, these structures are called G-quadruplexes.

Professor Balasubramanian and colleagues have previously developed sequencing technologies and approaches capable of detecting G-quadruplexes in DNA and in chromatin (a substance comprised of DNA and proteins). They have previously shown that G-quadruplexes play a role in transcription, a key step in reading the genetic code and creating proteins from DNA. Crucially, their work also showed that G-quadruplexes are more likely to occur in genes of cells that are rapidly dividing, such as cancer cells.

Now, for the first time, the team has discovered where G-quadruplexes form in preserved tumour tissue/biopsies of breast cancer. Details of their study are published today in the journal Nature Genetics.

The Cambridge team led by Professor Balasubramanian and Professor Caldas used their quantitative sequencing technology to study G-quadruplex DNA structures in 22 model tumours. These models had been generated by taking biopsies from patients at Addenbrooke's Hospital, Cambridge University Hospital NHS Foundation Trust, then transplanting and growing the tumours in mice.

During the process of DNA replication and cell division that occurs in cancer, large regions of the genome can be erroneously duplicated several times leading to so-called copy number aberrations (CNAs). The researchers found that G-quadruplexes are prevalent within these CNAs, particularly within genes and genetic regions that play an active role in transcription and hence in driving the tumour's growth.

Professor Balasubramanian said: "We're all familiar with the idea of DNA's two-stranded, double helix structure, but over the past decade it's become increasingly clear that DNA can also exist in four-stranded structures and that these play an important role in human biology. They are found in particularly high levels in cells that are rapidly dividing, such as cancer cells. This study is the first time that we've found them in breast cancer cells."

"The abundance and location of G-quadruplexes in these biopsies gives us a clue to their importance in cancer biology and to the heterogeneity of these breast cancers," added Dr Robert Hänsel-Hertsch who is now at the Center for Molecular Medicine Cologne, University of Cologne, and is first author on the publication.

"Importantly, it highlights another potential weak spot that we might use against the breast tumour to develop better treatments for our patients."

There are thought to be at least 11 subtypes of breast cancer, and the team found that each has a different pattern - or 'landscape' - of G-quadruplexes that is unique to the transcriptional programmes driving that particular subtype.

Professor Carlos Caldas from the Cancer Research UK Cambridge Institute, said: "While we often think of breast cancer as one disease, there are actually at least 11 known subtypes, each of which may respond in different ways to different drugs.

"Identifying a tumour's particular pattern of G-quadruplexes could help us pinpoint a woman's breast cancer subtype, enabling us to offer her a more personalised, targeted treatment."

By targeting the G-quadruplexes with synthetic molecules, it may be possible to prevent cells from replicating their DNA and so block cell division, halting the runaway cell proliferation at the root of cancer. The team identified two such molecules - one known as pyridostatin and a second compound, CX-5461, which has previously been tested in a phase I trial against BRCA2-deficient breast cancer.

Credit: 
University of Cambridge

Iron-mediated cancer cell activity: A new regulation mechanism

image: Mesenchymal stem cells (on the right) are associated with metastatic dissemination, resistance to conventional chemotherapy and to relapses. During the transition to this state, the protein CD44 takes over from transferrin and its TfR1 receptor and ensures the majority of the iron endocytosis. This leads to a significant increase in cellular ion concentration. In the nucleus, iron operates as a chemical catalyst for oxidative demethylation and "releases" genes whose expression is reprimed by methylated histone proteins, in particular those involved in metastatic dissemination. Accordingly, CD44 regulates the epigenetic plasticity and expression of these genes by iron mediation.

Image: 
© Raphaël Rodriguez/Nature

CNRS researchers at the Institut Curie have recently shown that cancer cells use a membrane protein that has been known for several decades to internalise iron. Published in Nature Chemistry (August 3rd, 2020), this work shows that the absorbed iron allows cancer cells to acquire metastatic properties.

Biologists knew CD44 well, but didn't know the major biological function that it fulfils. CD44 is a glycoprotein found on the surface of many cells, in various organs, that is also involved in several biological processes: immune response, inflammation and cancer, among others. For the first time, a research team has shown that it participated in these phenomena by allowing iron to enter cells through endocytosis.

Scientists at the Laboratoire Chimie et Biologie du Cancer (CNRS/INSERM/Institut Curie) and their colleagues (1) reached this conclusion by studying CD44's activity in cancer cells, and the resulting changes to metabolism and genetic expression.

Their results show that CD44 can internalise iron bound to hyaluronic acid. For cancer cells, the iron then fulfils two roles: it supplies the mitochondria so that it can produce metabolites necessary for the cell to pass into a metastatic state and epigenetically "unlocks" certain genes that are also necessary to the metastatic process. In that state, CD44 even becomes the main pathway for iron to enter cells.

These observations explain why CD44 was already known for its association with the appearance of metastases and relapses. But they are also surprising because until now biologists thought that a different mechanism was involved in iron endocytosis, involving transferrin and its TfR1 receptor. The research team now hopes to develop molecules capable of blocking cellular iron traffic to eliminate cells with high metastatic potential.

Credit: 
CNRS

Immunotherapy biomarker discovery could benefit thousands with Type 1 diabetes

Scientists at UCL have discovered new biomarkers, which may identify those people with Type 1 diabetes who would benefit from the immunotherapy drug Abatacept, a finding which could eventually help thousands manage the disease more effectively.

Type 1 diabetes is an autoimmune disease, which means it is caused by the body's own immune system attacking healthy body tissues. People with the condition are unable to produce the hormone insulin, which is essential to control and use glucose as energy.

Abatacept is an immunosuppressive drug that subdues the aberrant immune response in people with autoimmune diseases, and identifying a biomarker will enable clinicians to give the drug to those who would positively respond.

The research group, led by Professor Lucy Walker (UCL Institute of Immunity & Transplantation), built on their discovery in 2014, which found that certain immune cells, known as 'follicular helper T cells' (Tfh), can cause Type 1 diabetes by triggering the destruction of insulin-producing cells in the pancreas.

In this latest study, published in Nature Immunology, researchers at UCL in collaboration with scientists from King's College London and AstraZeneca, wanted to find out why some people with Type 1 diabetes responded well to Abatacept, while others did not.

Explaining the study's focus, Professor Walker said: "Abatacept is already widely used to treat other autoimmune conditions, including rheumatoid arthritis.

"Early tests in people with Type 1 diabetes have found the drug is not suitable for routine use because the response is very variable - some people benefit a lot, while others not at all.
"Being able to tell in advance who is likely to respond may reignite interest in this therapy for those with diabetes."

For the study, blood samples from people with Type 1 diabetes, who had taken part in a clinical trial of Abatacept were studied. The team discovered that the numbers of Tfh cells were reduced by Abatacept treatment and the cells' phenotype (biochemical characteristics) had been changed.

Machine learning was then used to compare blood samples from people who showed a good response to Abatacept with those who showed a poor response.

To the team's surprise, the machine learning algorithm was able to detect differences in the profile of the Tfh cells, even before treatment, which could be used as biomarkers to establish whether someone was likely to respond to Abatacept.

Professor Walker said: "Our new work suggests that by analysing these T cells, and looking at the markers they express, we can make predictions about how well people will respond to Abatacept.

"The next step will be to test this in more people and explore whether it works for other therapies and other autoimmune diseases.
"New improved versions of Abatacept have now been developed and it will be particularly exciting to see if the biomarker approach is applicable to these."

In the UK, there are around 400,000 people with the Type 1 diabetes, including 29,000 children. As those with the condition cannot produce insulin, glucose builds up in the bloodstream, and over time can cause serious kidney, heart and eye damage.

In 1999, Professor Walker identified signals that controlled 'follicular helper T cell' behaviour, and later found that these cells appear in high numbers in those people with Type 1 diabetes.

She added: "The project has been years in the making and has relied heavily on collaboration between researchers, clinicians, bioinformaticians and industry partners."

Professor Walker's research team are part of the UCL Institute of Immunity & Transplantation, based at the Royal Free hospital, London. The project received funding from Diabetes UK, AstraZeneca, the Medical Research Council and the Rosetrees Trust.

Credit: 
University College London

Study calls for urgent plan to manage invasive weed which threatens livelihoods in Africa

image: Mimosa diplotricha is already present in a number of countries in eastern and southern Africa and likely to expand its range, exacerbating biodiversity loss and further reducing crop yields and rangeland productivity.

Image: 
Arne Witt

CABI scientists have conducted research which is calling for an urgent integrated management strategy, including biological control, to fight the invasive weed Mimosa diplotricha which is threatening livelihoods in eastern and southern Africa

Dr Arne Witt, lead author of the study published in the journal Bothalia, said that over half of farmers surveyed in the Karonga District of Malawi believe that M. diplotricha significantly reduces crop yields; more than 40 years ago it was already considered to be one of the 76 worst weeds in the world,

The CABI scientists, including Tim Beale and Winnie Nunda working with Dr Lilian Chimphepo of the Malawian Government's Environmental Affairs Department, sought to establish the current distribution of M. diplotricha in eastern and southern Africa and its impacts on livelihoods in northern Malawi.

Current distribution was based on roadside surveys, literature reviews and herbarium data. The researchers also conducted surveys among 151 households in 32 villages across Karonga District - all areas affected by the devastating weed - to determine its impacts on local livelihoods.

Dr Witt said, "Mimosa diplotricha is an emerging or established weed in many parts of the world, including many countries in Africa, where it is impacting on biodiversity, crop and pasture production, and driving socio-ecological change.

"We found that it is abundant in western Ethiopia, southern Tanzania,
and northern and south eastern Malawi with isolated populations in western
Rwanda, Burundi, Mozambique, and on the northern shores of Lake Victoria in
Uganda.

"Most respondents said that M. diplotricha invasions were reducing the
amount of grass and shrubs in rangelands, with over half saying it reduced crop
yields. This invasive plant is also reducing the availability of medicinal plants and
other natural resources."

Dr Witt added that M. diplotricha has the potential to significantly expand its
range in eastern Africa and parts of southern Africa and as such there is an urgent
need to develop and implement an integrated management strategy, including
biological control, to reduce the negative effects of this invasive plant on local
livelihoods.

"All respondents said that M. diplotricha hampered the movement of people and livestock. In addition, the majority of those interviewed said that invasions reduced
the abundance of grasses and shrubs, while 50% of respondents said that it had a negative impact on trees," he said. "To inhibit its further spread, it is imperative that communities be informed as to its negative impacts and best management practices which include the use of appropriate biological controls."

Credit: 
CABI

Cannabinoids may affect activity of other pharmaceuticals

Hershey, Pa. -- Cannabinoid-containing products may alter the effects of some prescription drugs, according to Penn State College of Medicine researchers. They published information that could help medical professionals make safe prescribing choices for their patients who use prescription, over-the-counter or illicit cannabinoid products.

Kent Vrana, professor and chair of pharmacology at the College of Medicine, and Paul Kocis, a pharmacist at Penn State Health Milton S. Hershey Medical Center, compiled a list of 57 medications that may not function as intended when used with medical cannabinoids, CBD oil (hemp oil) and medical or recreational marijuana. The list was published in the journal Medical Cannabis and Cannabinoids.

The medications on the list have a narrow therapeutic index, meaning they are prescribed at specific doses - enough to be effective, but not enough to cause harm. Vrana says it's important for medical professionals to consider the list when prescribing medical cannabinoids and how it may affect other medications a patient is taking.

To develop the list, the researchers looked at the prescribing information for four prescription cannabinoid medications. This information included a list of enzymes in the body that process the active ingredients in those medications, which can include delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). They compared this information against prescribing information from common medications using information available from regulatory agencies like the U.S. Food and Drug Administration to identify where there may be overlap, called a drug-drug interaction.

The list contains a variety of drugs from heart medications to antibiotics and antifungals. As one example, researchers identified warfarin, a common anticoagulant that prevents harmful blood clots from forming, as having a potential drug-drug interaction with cannabinoid products. Often prescribed for patients with atrial fibrillation or following cardiac valve replacement, the drug has a narrow therapeutic index, and Vrana cautions that medical professionals consider this potential drug-drug interaction both when prescribing warfarin to patients on prescription cannabinoids or prescribing cannabinoids to a patient taking warfarin.

The researchers say that medical professionals should also consider patient use of CBD oil products and medical and recreational marijuana when using or prescribing drugs on the identified list. Most of those products lack government regulation and there is little to no prescribing or drug-drug interaction information for those products.

"Unregulated products often contain the same active ingredients as medical cannabinoids, though they may be present in different concentrations," Vrana said. "The drug-drug interaction information from medical cannabinoids may be useful as medical professionals consider the potential impact of over-the-counter or illicit cannabinoid products."

Vrana advises that patients be honest with their health care providers about their use of cannabinoid products - from over-the-counter products to recreational marijuana. He says that doing so can help ensure the safe and effective use of prescribed medications.

In addition to the identified list of 57 prescription medications with a narrow therapeutic index that is potentially impacted by concomitant cannabinoid use, a comprehensive list of 139 medications that could have a potential drug-drug interaction with a cannabinoid is available online. Vrana and Kocis plan to routinely update this drug-drug interaction list as newer medications are approved and real-world evidence accumulates.

Kent Vrana received a sponsored research agreement from PA Options for Wellness, a medical cannabis provider and clinical registrant in Pennsylvania, and this research was supported in part by the agreement. The College of Medicine and PA Options for Wellness have a 10-year research agreement designed to help physicians and patients make better informed clinical decisions related to cannabinoids.

Credit: 
Penn State

Transferrin identified as potential contributor to COVID-19 severity

The University of Kent's School of Biosciences and the Institute of Medical Virology at Goethe-University, Frankfurt am Main, have identified that a glycoprotein known as transferrin may critically contribute to severe forms of COVID-19.

SARS-CoV-2 is the coronavirus that causes COVID-19. It is currently not known why some individuals develop only mild or no symptoms when infected, whilst others experience severe, life-threatening forms of the disease. However, it is known that the risk of COVID-19 becoming severe increases with age and is higher in males than in females. Many severe COVID-19 cases are characterised by increased blood clotting and thrombosis formation.

The team combined existing data on gene expression in humans and infected cells to search for molecules involved in blood coagulation that differ between females and males, change with age, and are regulated in response to SARS-CoV-2 infection.

Out of more than 200 candidate factors, researchers identified a glycoprotein called transferrin to be a procoagulant (a cause of blood clotting) that increases with age, is higher in males than in females, and is higher in SARS-CoV-2-infected cells. Hence, transferrin may have potential as a biomarker for the early identification of COVID-19 patients at high risk of severe disease.

Katie-May McLaughlin, the first author of the study said: 'It is very exciting to be involved in such an important study that may improve therapies for COVID-19 in its most severe form'.

Credit: 
University of Kent

A blood test could predict who benefits from immunotherapy

video: Dr. Lillian Siu checks Mr. Azim Jamal in a clinic visit at Princess Margaret. Mr. Jamal was part of a Princess Margaret Cancer Centre study showing which patients can benefit from immunotherapy with a specially designed blood test based on each individual’s tumour tissue.

Image: 
Princess Margaret Cancer Centre, UHN

A test which detects changing levels of tumour fragments in the blood may be an easy, non-invasive and quick way to predict who will benefit from immunotherapy, a treatment option for advanced cancers.

Although immunotherapy has been shown to shrink tumours and prolong survival for patients for whom other treatments have failed, about 20-30% of patients benefit from it. Clinicians don't yet know ahead of time who this subset of patients is.

Understanding this is crucial, since immunotherapy can have severe side effects in a small percentage of patients, and knowing whether to begin or continue would be helpful for patients weighing different treatment options.

A team of Princess Margaret Cancer Centre scientists and clinicians addressed this question with a novel study evaluating various cancer patients' response to a specific immunotherapy drug via a customized test based on each patient's tumour profile.

They found that individual response to treatment can be predicted within weeks, based on increasing or decreasing levels of DNA fragments which are shed from the tumour into the blood.

Genomic testing with powerful new technologies can detect the same genetic mutations in the fragments circulating in the blood as in the actual tumour. These fragments are called circulating DNA or ctDNA.

Specifically, the study found that a decrease in these circulating tumour DNA fragments at six - seven weeks after treatment with the immunotherapy drug pembrolizumab was associated with a beneficial response to the drug and longer survival.

The study, "Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab", is published in Nature Cancer, August 3, 2020.

Dr. Lillian Siu, a Senior Scientist and medical oncologist at the Princess Margaret, BMO Chair in Precision Cancer Genomics, and a co-senior author, noted that the study is one of the first studies across a broad spectrum of tumours to show that measuring levels of ctDNA could be useful as a predictor of who responds well to immunotherapy.

"It's like a molecular CT scan that gives us a molecular dimension, an added layer of information to know whether a tumour is growing or not, " she says, "That's why this is so exciting. It helps to predict early on what may happen over time.

"Although important, computerized tomography (CT) and other scans alone will not tell us what we need to know quickly or accurately enough."

Dr. Scott Bratman, who is first author and a radiation oncologist and Senior Scientist at Princess Margaret and Associate Professor of Radiation Oncology and Medical Biophysics, University of Toronto, points out that it may take many months to detect whether a tumour is shrinking with various imaging scans.

"New next-generation sequencing technologies can detect and measure these tiny bits of cellular debris floating in the blood stream accurately and sensitively, allowing us to pinpoint quite quickly whether the cancer is active."

The prospective study analyzed the change in ctDNA from 74 patients, with different types of advanced cancers, being treated with pembrolizumab.

In order to customize or personalize the test, all the genes from the tumour biopsy tissue of each patient were sequenced or decoded at Princess Margaret, with specific attention to the mutations that occur in cancer. These cancer mutations ranged from dozens to tens of thousands of mutations per tissue sample, differing according to cancer type.

Sixteen genetic mutations for each patient were then selected for a specific test to be developed and customized to detect personalized ctDNA of each patient via a simple blood sample.

"When we looked at all 20,000 genes in each cancer, the range of mutations in different individuals was huge due to the many different cancer types in the study," says Dr. Trevor Pugh, a co-senior author, Senior Scientist at Princess Margaret and Associate Professor, Dept. of Medical Biophysics, University of Toronto, and Director of Genomics, Ontario Institute for Cancer Research.

"The novelty is that, rather than taking a one-size-fits-all approach, we designed a personalized blood test for each person based on their own cancer's mutation list."

Of the 74 patients, 33 had a decrease in ctDNA levels from their original baseline levels to week six to seven after treatment with the drug. These patients had better treatment responses and longer survival. Even more striking was that all 12 patients who had clearance of the ctDNA to undetectable levels during treatment were still alive at a median follow-up of 25 months.

Conversely, a rise in ctDNA levels was linked to a rapid disease progression in most patients, and poor survival.

"Few studies have used a clinical biomarker across different types of cancers," says Dr. Siu, who is also the Clinical Lead for the Tumor Immunotherapy Program at the Princess Margaret and Professor of Medicine, University of Toronto, adding that "the observation that ctDNA clearance during treatment and its link to long-term survival is novel and provocative, suggesting that this biological marker can have broad clinical impact."

Mr. Azim Jamal, 71, was part of the study, and one of the patients who benefited from immunotherapy. He was diagnosed with throat cancer in 2016, and received radiation and targeted molecular therapy.

With limited response and the cancer spreading to his lungs, he then received immunotherapy over two years, beginning in 2017. As of July 2020, his disease is in remission, with no evidence of progression.

"It was a last resort, but I said yes immediately," he says when asked if he would like to participate in the immunotherapy clinical trial. "I want to enjoy life, I want to see my grandchildren, participate in my community and church. And I also appreciate the opportunity to participate in important research that could help others."

Serena Jamal-Esmail, his daughter who is also a nurse, says that seeing her father respond so well to the immunotherapy was "like a light...It had been so emotional, so scary. My kids will be able to remember their granddad. I can breathe again."

The prospective study is part of a larger flagship clinical trial, INSPIRE, which has enrolled more than 100 patients with head and neck, breast, ovarian, melanoma and other advanced solid tumours. Launched at Princess Margaret in 2016, the trial follows and tests patients at various stages of their treatment to pembrolizumab, a commonly used type of immunotherapy.

It also brings together researchers from many disciplines to investigate if specific genomic and immune biomarkers in patients may predict for response or resistance to the drug.

Credit: 
University Health Network

Analyzing pros and cons of two composite manufacturing methods

image: Comparing bulk and frontal polymerization.

Image: 
P. H. Geubelle, Grainger Engineering

Airplane wings, wind turbine blades, and other large parts are typically created using bulk polymerization in composite manufacturing facilities. They are heated and cured in enormous autoclaves and heated molds as big as the finished part. Frontal polymerization is a new out-of-autoclave method for composite manufacturing that doesn't require a large facility investment. Researchers at the University of Illinois Urbana-Champaign conducted a study pitting one process against the other to discover the pros and cons of each.

"Frontal polymerization doesn't use an autoclave at all, so it doesn't require that huge upfront investment," said Bliss Professor Philippe Geubelle in the Department of Aerospace Engineering at the U of I. "It's a chemical reaction sustained by the release of heat as the front propagates. It can save a lot of energy and it generates much less carbon dioxide, so that's an environmental benefit."

Geubelle said they began comparing the two methods by looking at the thermo-chemical equations in order to model the two polymerization processes. In that way, they could compare the methods for a variety of composite materials, and particularly, the time duration each method takes to manufacture the same part.

"The key contribution from the theoretical point of view is that we've rewritten the reaction-diffusion equations to extract the two most important nondimensional parameters," Geubelle said. "Using just these two parameters allowed us to look at a wide range of chemical parameters, such as the activation energy and the heat of reaction, and at the impact of the initial temperature of the resin."

Geubelle said this method helped to compare the composite manufacturing processes based on bulk and frontal polymerization in terms of the time it takes to manufacture a part. The study found that there were instances when one or the other was faster.

"Imagine you want to make something that is one meter long. Frontal polymerization will be able to do complete the task before bulk polymerization starts to kick in," Geubelle said. "On the other hand, if you want to make something that is 10 meters long, then bulk polymerization may actually take place before the front reaches the other end of the part. It's the competition between these two processes that we analyzed in this study."

He went on to say there are several ways to speed up the process for frontal polymerization: start the front at both ends so it goes twice as fast, or heat it from the bottom by using a heated panel beneath it. "That process is so fast, we refer to it as flash curing," Geubelle said, "but it does use more energy than for a single front."

Manufacturing composite parts using frontal polymerization instead of bulk polymerization has a lot of advantages.

"With frontal polymerization, you don't need the large capital investment of the autoclave, making it a very attractive option," Geubelle said. "The time it takes to cure a composite part is also much shorter and the environmental impact is substantially reduced."

Credit: 
University of Illinois Grainger College of Engineering

NASA finds an eye and a giant 'tail' in Typhoon Hagupit

image: NASA-NOAA's Suomi NPP satellite provided forecasters with a visible image of Typhoon Hagupit on Aug. 3 as it moved through the Northwestern Pacific Ocean, just northeast of Taiwan.

Image: 
NASA Worldview, Earth Observing System Data and Information System (EOSDIS)

NASA-NOAA's Suomi NPP satellite provided forecasters with a visible image of Typhoon Hagupit in the Northwestern Pacific Ocean that showed the development of an eye as it quickly intensified. Imagery also showed a thick band of thunderstorms that resembled a giant tail, spiraling into the powerful storm.

Tropical Depression 03W formed northeast of Luzon, Philippines on August 1 and was renamed Hagupit when it strengthened to a tropical storm on Aug. 2. By Aug. 3, Hagupit had quickly intensified into a typhoon.

On Aug. 3, the Visible Infrared Imaging Radiometer Suite (VIIRS) instrument aboard Suomi NPP revealed that the storm had developed an eye, although it appeared somewhat obscured by high clouds. VIIRS showed that powerful bands of thunderstorms had circled the eye. A large, thick band of thunderstorms that extended south-southeast of the center looked like a giant tail on the VIIRS imagery. Hagupit was northeast of Taiwan at the time Suomi NPP passed overhead.

At 5 a.m. EDT (0900 UTC) on Aug. 3, the Joint Typhoon Warning Center (JTWC) noted that Hagupit had maximum sustained winds near 65 knots (75 mph/120 kph), making it a Category 1 hurricane on the Saffir-Simpson Hurricane Wind Scale. The center of Hagupit was located near latitude 26.8 degrees north and longitude 122.2 degrees east. It was centered about 285 nautical miles west of Kadena Air Base, Okinawa, Japan. Hagupit was moving northwest.

Hagupit is forecast to make landfall later today, Aug. 3, south of Shanghai and curve north then northeast. The center of the storm is expected to pass to the west of Shanghai and then re-emerge into the East China Sea.

Credit: 
NASA/Goddard Space Flight Center

NASA puts visible and water vapor eyes on Tropical Storm Isaias

image: NASA's Aqua satellite provided a visible image to forecasters of Tropical Storm Isaias of Florida's east coast on Aug. 2 at 1:30 p.m. EDT.

Image: 
Image Courtesy: NASA Worldview, Earth Observing System Data and Information System (EOSDIS).

NASA's Aqua satellite obtained visible and water vapor imagery as Tropical Storm Isaias continued moving along the east coast of Florida. On Aug. 3, Warnings and Watches stretched from Florida to Maine.

NASA Satellite View: Isaiah's Organization

The Moderate Resolution Imaging Spectroradiometer or MODIS instrument that flies aboard NASA's Aqua satellite captured a visible image of Tropical Storm Isaias on Aug. 2 at 1:30 p.m. EDT. There was no visible eye in the storm at the time of the imagery. The satellite image was created using NASA's Worldview product at NASA's Goddard Space Flight Center in Greenbelt, Md.

Water Vapor Imagery Shows Location of Heaviest Rain

NASA's Aqua satellite passed over Isaias on Aug. 3 at 3:45 a.m. EDT (0745 UTC) when it was off the coast of northeastern Florida and found highest concentrations of water vapor and coldest cloud top temperatures were offshore and mostly north and northeast of the center.

NHC noted, "Isaias continues to produce an area of vigorous convection near and to the northeast of its low-level center.  Overnight radar data from Melbourne and Jacksonville have shown a transient mid-level eye feature that is located northeast of the low-level center."

Coldest cloud top temperatures were as cold as or colder than minus 70 degrees Fahrenheit (minus 56.6 degrees Celsius) in those storms. Storms with cloud top temperatures that cold have the capability to produce heavy rainfall.

Water vapor analysis of tropical cyclones tells forecasters how much potential a storm has to develop. Water vapor releases latent heat as it condenses into liquid. That liquid becomes clouds and thunderstorms that make up a tropical cyclone. Temperature is important when trying to understand how strong storms can be. The higher the cloud tops, the colder and stronger they are.

The heavy rain potential in the storm is in the forecast as Isaias makes landfall and moves northeast along the U.S. East Coast. The National Hurricane Center (NHC) noted, "Heavy rainfall will result in flash and urban flooding, some of which may be significant in the eastern Carolinas and the mid-Atlantic, through midweek along and near the path of Isaias across the East Coast of the United States. Widespread minor to moderate river flooding is possible across portions of the Carolinas and the mid-Atlantic. Additionally, quick-responding rivers in the southern Appalachians and Northeast will be susceptible to minor river flooding."

Warnings and Watches Posted All Along U.S. East Coast

On Aug. 3, 2020, the National Hurricane Center posted watches and warnings along the U.S. East coast from Florida to Maine.

A Storm Surge Warning is in effect for Edisto Beach, South Carolina to Cape Fear, North Carolina. A Storm Surge Watch is in effect for Cape Fear to Duck, North Carolina and the Pamlico and Albemarle Sounds. A Hurricane Warning is in effect for South Santee River, South Carolina to Surf City, North Carolina. A Tropical Storm Warning is in effect for Flagler/Volusia County Line, Florida to South Santee River, South Carolina; north of Surf City, North Carolina to west of Watch Hill, Rhode Island; Chesapeake Bay south of North Beach; Tidal Potomac River south of Cobb Island; Delaware Bay; Long Island and Long Island Sound; Pamlico and Albemarle Sounds. A Tropical Storm Watch is in effect for Watch Hill, Rhode Island to Stonington, Maine and for Martha's Vineyard, Nantucket, and Block Island.

Tropical Storm Isaias on Aug. 3

At 8 a.m. EDT (1200 UTC) on Aug. 3, the center of Tropical Storm Isaias was located by an Air Force Reserve reconnaissance aircraft and NOAA Doppler weather radars near latitude 30.2 degrees north and longitude 80.1 degrees west. That is about 100 miles (155 km) east-southeast of Jacksonville, Fla. and about 250 miles (400 km) south-southwest of Myrtle Beach, So. Carolina. The estimated minimum central pressure is 994 millibars.

Isaias is moving toward the north near 13 mph (20 kph).  A turn toward the north and north-northeast along with an increase in forward speed is expected later today and Tuesday, Aug. 4. Maximum sustained winds are near 70 mph (110 kph) with higher gusts. Some strengthening is anticipated today, and Isaias is forecast to regain hurricane strength before it reaches the coast of northeastern South Carolina or southern North Carolina tonight. Slow weakening is forecast after Isaias makes landfall in the Carolinas and moves across the U.S. mid-Atlantic region tonight and Tuesday.

 An 8 a.m. EDT Florida Observation on Aug. 3

During the 7 a.m. hour a wind gust to 40 mph (65 kph) was observed at the St, Augustine Pier, Florida, and a sustained wind of 34 mph (55 kph) and a gust to 40 mph (65 kph) were measured by a Weatherflow station at the Jacksonville Beach Pier, Florida.

Isaias' Forecast and Track  

The NHC Discussion at 8 a.m. EDT on Aug. 3 noted that the vertical wind shear that has been plaguing Isaias is forecast to abate slightly today as the storm turns north-northeastward. All of the intensity models shows some slight strengthening during the next 12 hours, and the global models also indicate some deepening. As a result, the updated NHC intensity forecast calls for Isaias to regain hurricane status before the system moves over the coast of  the Carolinas.

 The NHC noted, "On the forecast track, the center of Isaias will pass well east of the Georgia coast through this morning.  The center of Isaias will then approach the coast of northeastern South Carolina and southern North Carolina within the hurricane warning area later today.  The center will then move inland over eastern North Carolina tonight, and move along the coast of the mid-Atlantic states on Tuesday and into the northeastern United States by Tuesday night."

Credit: 
NASA/Goddard Space Flight Center

A framework for the future

As the population grows, and the global standard of living improves, humanity's appetite for seafood is increasing. In 2020 seafood consumption reached an all-time high, with an average of 20kg consumed annually by every person on the planet.

Up to now most of this was caught in the world's freshwaters and oceans. But things are changing, and today half of all seafood consumed comes from farmed sources, called aquaculture. The sector is expected to double by 2050 to supply the increasing global demand.

UC Santa Barbara Assistant Professor Halley E. Froehlich has contributed to an evaluation of the complex interactions between human, environmental and animal health parameters of this budding industry, a view scientists call the One Health framework. The study, published in the journal Nature Food, brings together a diverse team of scientists, economists, sociologists and policy specialists led by the Centre for Sustainable Aquaculture Futures -- a joint initiative between the University of Exeter and the United Kingdom's Centre for Environment, Fisheries and Aquaculture Science.

"Aquaculture is now being more widely recognized as an important part of our global food system," said Froehlich, a faculty member in the departments of environmental studies and of ecology, evolution, and marine biology. "And it will continue to grow. So the question is, how do we plot that course in a more sustainable way?"

Aquaculture has played a major role in lifting millions of people out of poverty in many low and middle-income nations, but it faces a range of sustainability challenges. These include environmental degradation, overuse of antibiotics, release of disease agents and the requirement of wild-caught fish meal and fish oil to produce feed. Parts of the industry also engage in poor labor practices and gender inequality.

Negative societal impressions created by such examples mask aquaculture's potentially significant benefits. Farming cold-blooded animals is very efficient from a nutrient perspective. Many species, such as oysters, don't even require feeding. In addition, aquaculture can operate on a smaller footprint than many other forms of food production.

The new paper uses the One Health framework to lay out a set of metrics to include in national aquaculture strategies across the globe to improve sustainability as the industry expands. These include concepts like access to nutritious food and quality employment, the health of wild fish stocks and ecosystems and maintaining a small environmental footprint and resilience to climate change.

Communication, cooperation and coordination will be critical to the sustainable development of aquaculture as the sector grows. "If you don't have that knowledge transfer -- for instance, from scientists to policy-makers or farmers to scientists -- these types of framework structures won't go anywhere," Froehlich said.

With that in mind, the authors collaborated widely on this report. "The paper results from extensive interaction between a wide range of academic experts in aquaculture, health, environmental and social sciences, economists, industry stakeholders and policy groups," said senior co-author Charles Tyler from the University of Exeter.

The paper presents a strategy for developing aquiculture as well as the benchmarks to which we will measure its sustainability and success. "This is an important paper," said lead author, Grant Stentiford of the Centre for Environment, Fisheries and Aquaculture Science, "acknowledging that aquaculture is set to deliver most of our seafood by 2050, but also that sustainability must be designed-in at every level."

The One Health approach offers a tool for governments to consider when designing policies. "I hope it will become a blueprint for how government and industry interact on these issues in the future," Stentiford added. "Most importantly, it considers aquaculture's evolution from a subject studied by specialists to an important food sector -- requiring now a much broader interaction with policy and society than arguably has occurred in the past."

Some of these principles are already being applied in the European Union and in Norway, according to Froehlich, who has begun shifting her focus toward the industry in the United States, especially California. She is currently in the middle of a Sea Grant project collecting the most comprehensive dataset of marine aquaculture information from across all coastal states in the U.S. This includes practices, policies, and the hidden interactions with fisheries that influence how aquaculture is conducted in each state.

"Aquaculture is everywhere and nowhere at the same time," Froehlich said. "People don't realize how integrated it is into so many facets of marine ecology, conservation biology, and fisheries."

Credit: 
University of California - Santa Barbara

Mathematical modeling revealed how chitinase, a molecular monorail, obeys a one-way sign

image: Fig. 2. (A) Unidirectional motion observed by single-molecule imaging of chitinase. (B) Chemical-state-dependent free energy profiles estimated from the imaging data.

Image: 
NINS/IMS

Biomolecular motors in cells generate unidirectional motion, consuming chemical energy gained by, for example, hydrolysis of ATP. Elucidation of the operation principle of such molecular motors, which are nature-made nanomachines composed of proteins, has attracted much attention. Single-molecule imaging, which can directly capture the motion of molecular motors, is a promising technique toward understanding the operation principle of molecular motors. However, it is still unclear how the consumption of chemical energy, i.e., change in chemical states of such motor proteins, gives rise to the unidirectional motion of the entire motors. Researchers at Institute for Molecular Science and Shizuoka University have found the change of the shapes of free energy profiles along the motion of a molecular motor triggered by chemical state changes of the motor.

The researchers first tried to establish a computational model to describe the motion of the molecular motors. The motion of a motor can be regarded as diffusive motion on free energy profiles that switch according to the chemical states of molecules which consist of the motor. More specifically, as shown in Fig. 1A, the motor first moves on the free energy surface of chemical state 1 (red) of the motor molecules, and then moves on the free energy surface of chemical state 2 (blue). However, this chemical state switching is not usually observed in single-molecule imaging. The researchers treated the transition between the chemical states using a hidden Markov model in which the chemical states are regarded as "hidden" states (Fig. 1B).

Using this hidden Markov model, it is possible to calculate "likelihood", which evaluates the probability to show how well the model explains the trajectory of the actual single-molecule motion. It is also possible to incorporate knowledge of the free energy profiles as prior probabilities. The researchers have developed a method for estimating chemical-state-dependent free energy profiles, diffusion coefficients on each profile, and rate constants of transitions between these states within the Bayesian inference framework by Monte Carlo sampling using posterior probabilities expressed as a product of the likelihood and the prior probabilities.

Then, the method developed in the present study was applied to analyze the motion of chitinase, a linear molecular motor, observed by single-molecule imaging. Analyzing trajectory data of unidirectional motion of chitinase with degrading a chitin chain revealed the characteristic free energy profiles which govern the motion (Fig. 2). Results of the analysis showed that a chitinase gets on a rail of chitin chain over a relatively low free energy barrier by Brownian motion. Then, the unidirectional motion is achieved by switching chemical states through the hydrolysis reaction of the chitin chain and dissociation of the reaction products. The present study provides a physical basis for the "burnt-bridge" Brownian ratchet mechanism* that the researchers have previously reported.

"We will apply our method developed in this study to various molecular motors and hope to clarify the similarities and differences in the mechanisms of the molecular motors. We believe that new findings will be obtained by our method in the future and give us a clue to the general operation principles of molecular motors. Studies using our method will pave the way for designing new artificial molecular motors," said Okazaki.

* "Burnt-bridge" Brownian ratchet mechanism:

A mechanism to explain how to achieve unidirectional motion of a molecular motor using nondirectional Brownian motion due to thermal fluctuations as driving force. In this mechanism the backward motion is prevented by removing the rail behind the molecular motor. (Akihiko Nakamura et al. in Nature Communications (2018) DOI: 10.1038/s41467-018-06362-3. See also EurekAlert! Research News URL: https://www.eurekalert.org/pub_releases/2018-09/nion-ca091818.php)

Credit: 
National Institutes of Natural Sciences

Exploring the sustainability of the Indian sugar industry

Generations of political support for sugar cultivation have helped India become the second-largest producer of sugar worldwide. Now, the country’s commitment to renewable energy could create additional benefits, like conserving natural resources and providing better nutrition to the poor.

Stanford researchers conducted the first comprehensive analysis of India’s sugar industry and its impact on water, food and energy resources through the lens of its political economy – that is, how entrenched political interests in sugar production threaten food, water and energy security over time. The results show that a national biofuel policy encouraging production of ethanol made directly from sugarcane juice may make India’s water and energy resources more sustainable. Using sugarcane juice instead of molasses would also free up land and irrigation water for growing nutrient-rich foods. The research was published July 24 in Environmental Research Letters.

“There are spillover effects between sectors, unintended consequences,” said co-author Rosamond Naylor, a food security expert and the William Wrigley Professor in Stanford’s School of Earth, Energy & Environmental Sciences (Stanford Earth). “It’s very instructive to think about the connection between food, water and energy because the solution may not be in the sector you’re focusing on.”

Moving toward renewables

Somewhat analogous to the corn industry in the U.S., which has shifted about 40 percent of its output to ethanol production in recent years, policymakers in India – many of whom benefit financially from the sugar industry – are currently exploring how to use sugarcane to increase energy independence and shift toward renewable energy use.

The Indian government has set a goal to increase the ethanol-to-gasoline blending rate from its current rate of about 6 percent to 20 percent by 2030 and introduced several policies to promote production of ethanol from sugarcane. The increased blending rate is a “desirable goal for improved energy security,” the researchers write. However, its effects on human health and the environment will largely depend on which sugar product ends up being the main feedstock: juice extracted from crushed sugarcane, or molasses, a by-product from sugar processing.

India’s national policy on biofuels only recently began allowing use of sugarcane juice in ethanol production, in addition to molasses.

“If the energy industry continues to use molasses as the bioethanol feedstock to meet its target, it would require additional water and land resources and result in the production of extra sugar,” said co-author Anjuli Jain Figueroa, a postdoctoral researcher in Earth system science. “In contrast, if the industry used the sugarcane juice to produce ethanol, the target could be met without requiring additional water and land beyond current levels.”

Using sugarcane juice to create ethanol could also help alleviate government spending to subsidize sugar and sell it below cost in its public distribution system.

Entrenched incentives

The public distribution system of sugar in India dates to the 1950s, when frequent famines plagued the country. Back then, sugar helped to meet basic calorie requirements. But today – with micronutrient deficiency leading to illness, disabilities and even death – the Indian government is more concerned with nutrition.

“In India right now, even poor populations have met their basic calorie needs,” said Naylor, who is also a senior fellow at the Stanford Woods Institute for the Environment. “They have been able to buy sugar at subsidized prices, but meanwhile they don’t have access to adequate protein and micronutrients for cognitive growth and for physical well-being.”

Sugarcane cultivation in India has expanded in part because of policies that incentivize production, including a minimum price, guaranteed sales of sugarcane and public distribution of sugar. These regulations have become entrenched over many generations, making the crop highly profitable to the 6 million farmers in the country, but the empty-calorie crop reduces the amount of resources available for micronutrient-rich foods.

“Using scarce natural resources to produce a crop that doesn’t fulfill nutritional needs for the second most populated country in the world can place pressure on the global food system if more and more food imports are required to meet the rising demand in India,” Naylor said.

Balancing act

The researchers focused their analysis on Maharashtra in western India, one of the country’s largest sugarcane-producing states. Sugarcane cultivation in Maharashtra has increased sevenfold in the past 50 years to become the dominant user of irrigation water. The study found that in 2010-11, sugarcane occupied only 4 percent of Maharashtra’s total cropped areas but used 61 percent of the state’s irrigation water. Meanwhile, irrigation for other nutritious food crops remained lower than the national averages.

“Irrigation of sugarcane in our study region is about four times that of all other crops and has doubled from 2000 to 2010. This resulted in about a 50 percent reduction of river flow over that period,” said co-author Steven Gorelick, the Cyrus Fisher Tolman Professor at Stanford Earth. “Given that this region is susceptible to significant drought, future water management is likely to be quite challenging.”

As part of continued efforts to examine the Indian sugar industry and its impacts, lead author Ju Young Lee, a PhD student in Earth system science, also developed satellite imagery analyses to identify sugarcane from space.

“Despite the importance of sugarcane in the water, food and energy sectors in India, there are no reliable sugarcane maps for recent years and in time series,” Lee said. “Using remote sensing data, I am developing current time-series sugarcane maps in Maharashtra – an important step forward.”

Scarcity or abundance?

The agricultural area of Maharashtra is considered drought-ridden, and yet in September 2019, the region experienced major floods that killed 21 people and caused 28,000 residents of Pune city to evacuate.

While the researchers started the FUSE project in Maharashtra with an explicit focus on drought management, their objectives expanded to include flooding after witnessing the devastation of Pune during their research period, presenting “a far more difficult water management problem,” according to co-author Steven Gorelick.

“Climate projections over the next 40 to 80 years suggest maybe a 10 percent increase in rainfall, but much greater variability – and that variability is what worries me the most, in terms of future management of both floods and droughts,” Gorelick said.

Credit: 
Stanford's School of Earth, Energy & Environmental Sciences

Promises found to reduce cheating in large study of adolescents

The study, of 640 10 to 14-year-olds in India, was designed in a way that meant it was impossible to tell who had and had not kept their promise - suggesting it is not just the fear of social retaliation that makes people stick to their word.

The team of researchers included two newly appointed members of the School of Psychology at the University of Plymouth, and the study is published in the Journal of Behavioral Decision Making.

Cheating and dishonesty, even on a small scale, can undermine trust and lead to costs for others, and society at large. Cheating in academic settings is a problem worldwide. As of 2018, 20% of the world's adolescents - about 250 million individuals - lived in India and the country's highly competitive educational system means academic cheating is a concern. To the best of the research team's knowledge, there are no previous experimental studies into the effect of promises on cheating rates in Indian adolescents.

The research used a series of experiments to test the effectiveness of inviting participants to promise to be truthful, with points that would later be converted into prizes as an incentive. For example, participants played a game in which they mentally chose a location in a box with 16 dice, shook the box and recorded the number of the die falling in their chosen position. Prizes were proportional to their total reported scores across fifteen rounds. As the initial choice was private, opportunistic and unobservable switching to a higher scoring die was possible.

Before the task, the adolescents received a choice to promise to be truthful or not. To make promising attractive for participants, those who did so received extra points. This gave even potentially dishonest participants an incentive to choose to promise. Control groups of participants could choose between the same incentives but did not have to promise.

The authors were able to measure the degree of dishonesty by comparing participants' reported results to what would be statistically expected. Compared to control groups, promises in the study systematically lowered cheating rates, and the authors conclude that they could be a simple tool to reduce dishonest behaviour.

The study's first author, Dr Patricia Kanngiesser, who is an Associate Professor in Psychology at the University, commented: "Promises are what we call 'speech acts' and create commitments by merely saying specific words. So one would think that they have very little binding power. In contrast, research has shown over and over again that many people do keep their word, even at a personal cost.

"This study provides more evidence of that, and suggests promises could be a powerful way of encouraging and sustaining honest behaviour in an academic context.

"The study also exemplifies the benefits of global cooperation and diverse perspectives in research: we were conducting online studies with adults on promise keeping when our collaborator, Dr Jahnavi Sunderarajan, suggested applying this in academic contexts in India, where there is a lot of competition and educators are worried about cheating, but few empirical studies exist. As a result we have been able to expand our research into a new area and make progress towards addressing an important problem."

Credit: 
University of Plymouth