Tech

New algorithm to help process biological images

image: At train-time, we embed each pixel of the ground truth image SI as the mean of predefined guide functions f over instance pixels it belongs to, resuling in embeddings e(S, Ψ). We then train the neural network E to reproduce the ground truth embedding given the input image I. To simplify learning, guide functions f are inputed into intermediate representations of the network using SinConv layers. The learning process uses a simple pixelwise L1-Loss between ground truth embed- ding e(S,Ψ) and the neural network prediction E(I,θ) as a learning objective. At test time instances are retrieved from the predicted embedding E(I, θ) using mean shift clustering.

Image: 
Skoltech

Skoltech researchers have presented a new biological image processing method that accurately picks out specific biological objects in complex images. Their results will be presented as an oral talk at the high-profile computer vision conference, CVPR 2020.

Biologists get a wealth of information in the form of biological images, which makes their automatic processing a formidable task. Researchers often have to handle images with a large number of objects, which is especially hard when it comes to microscopy images with overlapping objects and poor image quality and sharpness.

Machine Learning (ML) helps train the computer to process biological images, making data analysis much faster, more accurate and consistent across experiments.

Skoltech Computer Vision Laboratory of the Skoltech Center for Computational and Data-Intensive Science and Engineering (CDISE) put forward a new method for segmenting biological objects, such as individual cells, organisms and parts of plants, in complex images. The first author of the study was Victor Kulikov, who worked as a research scientist under the supervision of Skoltech professor Victor Lempitsky. The new method reduces the challenging object separation task to a simpler regression problem. This is achieved by introducing additional "harmonic" signals into the neural network's input layers and automatically tuning the signals' parameters to the typical size and arrangement of the objects to be isolated.

The scientists used four types of images: photos of plants, pictures with a large number of C. Elegants worms, microscopic images of E. Coli bacteria, and HeLa cancer cell culture images. Their two-step neural network training algorithm coped brilliantly with the task: trained for a selected image type, the neural networks outperformed other methods in isolating plant leaves, worms, cancer cells, and individual bacteria. The new method can be employed in scientific research and healthcare applications.

"A major advantage of the new method is that it can learn even from small datasets. We hope that our algorithm will find use in both biological research and other fields where labeled training images are hard to obtain," Lempitsky said.

Credit: 
Skolkovo Institute of Science and Technology (Skoltech)

Organic memory devices show promise for flexible, wearable, personalized computing

image: The device structure at a molecular level. The gold nanoparticles on the bottom electrode enhance the field enabling an ultra-low energy operation of the molecular device.

Image: 
Sreetosh Goswami, Sreebrata Goswami and Thirumalai Venky Venkatesan

WASHINGTON, April 21, 2020 -- The advent of artificial intelligence, machine learning and the internet of things is expected to change modern electronics and bring forth the fourth Industrial Revolution. The pressing question for many researchers is how to handle this technological revolution.

"It is important for us to understand that the computing platforms of today will not be able to sustain at-scale implementations of AI algorithms on massive datasets," said Thirumalai Venkatesan, one of the authors of a paper published in Applied Physics Reviews, from AIP Publishing.

"Today's computing is way too energy-intensive to handle big data. We need to rethink our approaches to computation on all levels: materials, devices and architecture that can enable ultralow energy computing."

Brain-inspired electronics with organic memristors could offer a functionally promising and cost- effective platform, according to Venkatesan. Memristive devices are electronic devices with an inherent memory that are capable of both storing data and performing computation. Since memristors are functionally analogous to the operation of neurons, the computing units in the brain, they are optimal candidates for brain-inspired computing platforms.

Until now, oxides have been the leading candidate as the optimum material for memristors. Different material systems have been proposed but none have been successful so far.

"Over the last 20 years, there have been several attempts to come up with organic memristors, but none of those have shown any promise," said Sreetosh Goswami, lead author on the paper. "The primary reason behind this failure is their lack of stability, reproducibility and ambiguity in mechanistic understanding. At a device level, we are now able to solve most of these problems,"

This new generation of organic memristors is developed based on metal azo complex devices, which are the brainchild of Sreebata Goswami, a professor at the Indian Association for the Cultivation of Science in Kolkata and another author on the paper.

"In thin films, the molecules are so robust and stable that these devices can eventually be the right choice for many wearable and implantable technologies or a body net, because these could be bendable and stretchable," said Sreebata Goswami. A body net is a series of wireless sensors that stick to the skin and track health.

The next challenge will be to produce these organic memristors at scale, said Venkatesan.

"Now we are making individual devices in the laboratory. We need to make circuits for large-scale functional implementation of these devices."

Credit: 
American Institute of Physics

New insight into how a genetic change increases the risk of schizophrenia

image: A genetic change increases the risk of developing schizophrenia

Image: 
Lancaster University

A genetic change increases the risk of developing schizophrenia and highlights new opportunities for drug treatment say researchers.

The collaborative research by a team from Lancaster, Glasgow and Strathclyde Universities was funded by the Medical Research Council.

In the human genome, small sections of DNA have been found to be duplicated (copied) or deleted in a small number of people, a phenomenon known as Copy Number Variation. Some of these genetic changes are linked to an increased risk of developing neurodevelopmental disorders, such as schizophrenia and autism, but the disease mechanisms involved remain largely unknown. For example, people with a DNA duplication at chromosome 16p11.2, that results in having extra copies of around 30 different genes, are approximately 15 times more likely to develop schizophrenia than people without the duplication. Why this should be the case is very poorly understood.

For the first time, research reported by the team in the journal Cell Reports, has shown that the 16p11.2 duplication impacts on a number of different inhibitory neuron types, neurons that use the neurotransmitter GABA, in brain areas dysfunctional in schizophrenia. These brain areas include the prefrontal cortex, hippocampus and amygdala. The researchers also show that these GABA neuron changes are accompanied by impaired functional communication between the same brain regions. Importantly, the researchers found that 16p11.2 duplication also results in cognitive and social deficits. These deficits not only parallel those seen in patients with schizophrenia, but are also known to involve the brain regions identified as being dysfunctional as a result of 16p11.2 duplication.

Dr Neil Dawson, the lead researcher from Lancaster University said: "Our data give new insight into how 16p11.2 duplication increases the risk of developing schizophrenia and the mechanisms involved. A key finding is the observation of disrupted connectivity between brain regions that are known to be dysfunctional in schizophrenia. We can now test the ability of drugs to restore these changes as part of ongoing research to develop better treatments for the disorder".

Professor Judith Pratt, the lead research from Strathclyde University, also highlighted the potential opportunity for drug development given these findings. "The current drug treatment options available for people with schizophrenia are limited, only effective for some patients and often involve severe side effects. Drugs to help patients with their cognitive and social problems are particularly urgently needed, as these symptoms dramatically impact on their quality of life. Our findings highlight the potential of drugs targeting the GABA neurons and provide a range of translational biomarker measures against which we can test the potential therapeutic efficacy of these and other drugs for schizophrenia".

Professor Brian Morris, the lead researcher from Glasgow University adds: "The finding of disturbed GABA neuron function as a consequence of 16p11.2 duplication is particularly intriguing, given that we know these cell types are dysfunctional in the brains of people with schizophrenia. This suggests that we are now closer to pinpointing the genes that regulate GABA cell function, and hence in the future to a potential approach to help people with schizophrenia".

Credit: 
Lancaster University

Study: Football offensive linemen should start plays upright to avoid hits to the head

WEST LAFAYETTE, Ind. -- Repetitive hits to the head can cause brain damage without actually leading to a concussion, past studies have suggested.

Just a simple change to the starting stance of players on the offensive line in American football might reduce this burden, a study conducted by Purdue University and Stanford University researchers now shows.

The study found that offensive linemen experienced at least 40% fewer hits to the head if they started a play standing up, rather than with their fingers touching the ground. The slight positional change could eliminate a significant number of hits without affecting the game, the researchers say.

Offensive linemen are known to take on more head impacts than any other player in the game.

"An offensive lineman tends to start off in a three-point stance, which means that one hand remains in contact with the ground until the start of the play, similar to sprinter fashion. The first move is always to come up, and most players tend to lead with their head," said Eric Nauman, a Purdue professor of mechanical engineering and basic medical sciences.

"If you're required to be in a two-point stance, meaning standing up with no hands on the ground, then you're already up a little bit. You've already got your hands in a good position and it's harder, actually, to lead with your head."

The study, published in the Clinical Journal of Sport Medicine, observed players participating in The Spring League, a professional football developmental league.

The findings back a rule change suggested by Paul Auerbach, the Redlich Family Professor Emeritus in the Department of Emergency Medicine at the Stanford University School of Medicine. He is an adjunct professor of military and emergency medicine at the F. Edward Hébert School of Medicine of the Uniformed Services University of the Health Sciences.

Based on his experience as a physician for football teams at the high-school, collegiate and professional levels, Auerbach had a hunch that eliminating the "down lineman" would reduce hits to the head. He wrote a letter suggesting this rule change in 2016, which is published in the Journal of the American Medical Association (JAMA). He repeated his suggestion in a 2018 opinion editorial that appeared in the Wall Street Journal.

"It seemed logical that if something could be done to lessen the number of potentially injurious blows to the heads of linemen, that this would be desired by people who care about making the game safer. So, I was delighted when I was contacted by Brian Woods, CEO of The Spring League, who inquired what he might do to help figure this out," Auerbach said.

Auerbach and a team led by Nauman and Thomas Talavage, a professor of electrical and computer engineering and biomedical engineering at Purdue, set out to investigate this suggested rule change in an observational pilot study of three Spring League practice sessions and one exhibition game in July 2018 in San Diego.

The researchers glued sensors behind the ears of 78 participating athletes each time that they played. The sensors allowed the researchers to record the number of hits and how hard they were. The participating athletes represented all positions on the team.

Video footage indicated which players were on the field for each play and whether players positioned on the offensive line were in a two-point stance or a three- or four-point stance.

The researchers found that offensive and defensive linemen collectively took on the greatest number of hits to the head in a game: 98 hits for offensive linemen and 52 hits for defensive linemen.

Linebackers and tight ends, however, experienced the hardest hits - many of which were greater than 60 times the force of gravity. Nauman and Talavage have previously seen that hits greater than 50 times the force of gravity start to affect brain chemistry.

Offensive linemen in a two-point stance sustained fewer hits than those in a three- or four-point stance, which led to at least a 40% reduction in hits.

"If nothing else, this study suggests that you can actually make a big difference with rule changes that quite honestly, at least from our perspective, didn't affect the game play in any meaningful way. In fact, if you make everybody start in a two-point stance, it's harder to tell if it's a run or pass play," Nauman said.

According to the researchers, this study is the first to look at a specific intervention for American football and see an effect on real plays.

While the study was small, the researchers believe that there are enough data to advocate for a rule change.

"Forty percent fewer hits would translate to both games and practices. The next step is to improve coaching and blocking and tackling techniques, which could lead to reducing even more hits to the head," Talavage said.

Purdue researchers are currently developing helmet sensors that would help referees to better call when players try to "spear," or use their heads as weapons.

Credit: 
Purdue University

New macrolactone database could aid drug discovery, research

Researchers from North Carolina State University and Collaborations Pharmaceuticals have created a free-to-use database of 14,000 known macrolactones - large molecules used in drug development - which contains information about the molecular characteristics, chemical diversity and biological activities of this structural class. The database, called MacrolactoneDB, fills a knowledge gap concerning these molecules and could serve as a useful tool for future drug discovery.

Macrolactones are molecules with at least 12 atoms composing their ring-like structure. Among many useful characteristics, macrolactones' ability to bind to difficult protein targets makes them suitable for antiviral, antibiotic, antifungal and antiparasitic drugs. However, their size and complicated structure make them difficult to synthesize.

"Macrolactones are titanic molecules - their size presents challenges to researchers who may want to work with them," says Sean Ekins, CEO of Collaborations Pharmaceuticals, member of NC State's Comparative Medicine Institute, entrepreneur in residence at UNC-Chapel Hill's Eshelman School of Pharmacy and corresponding author of the research. "We wanted to address that issue by creating a publicly available database of these molecules and their properties."

NC State graduate student and first author of the paper Phyo Phyo Zin mined 13 public databases for 14,000 known macrolactones, compiling them into MacrolactoneDB. Only 20% of the macrolactone compounds she curated had biological data associated with them.

Zin, Ekins, and NC State Associate Professor of Chemistry Gavin Williams conducted cheminformatics analyses of the macrolactones' molecular properties and developed 91 descriptors to better characterize the molecules. The researchers then looked at three targets of interest for some of the macrolactones - specifically malaria, hepatitis C and T cells - and used machine-learning techniques to understand the structure-activity relationship between the macrolactones and these targets.

"We know that macrolactone drugs are effective, but there's a lot we don't know about what makes a good one," Williams says. "That's why we set out to do this research. We found that it is possible to utilize machine learning with these molecules, and improving our analysis and description of macrolactones will improve prediction models going forward."

"Anyone interested in these molecules or in drug development utilizing macrolactones now has a user-friendly database where everything is accessible and in one location," Ekins says. "Researchers can ask questions about what makes a particular macrolactone molecule well-suited for a particular biological application.

"Hopefully MacrolactoneDB will help us to understand this diverse class of molecules, and move forward in creating new ones."

Credit: 
North Carolina State University

Terahertz science discloses the ultrafast photocarrier dynamics in carbon nanotubes

image: Comparison of computed peak values of THz emission and photocurrent with experimental data.

Image: 
@2020 American Chemical Society

A team of researchers from Osaka University, TU Wien, Nanyang Technological University, Rice University, University of Alberta and Southern Illinois University-Carbondale comes closer to unraveling the physics of quasiparticles in carbon nanotubes.

Carbon nanotubes (CNTs), a model one-dimensional (1D) material made up entirely of carbon atoms, have attracted considerable attention ever since their discovery because of the unique properties arising from quantum confinement effects. CNTs have been labeled as one of the materials for next-generation optoelectronic devices. Critical towards this advancement is understanding how quasiparticles - theoretical particles used to describe observable phenomena in solids - behave and interact with each other in a 1D system. This requires a fundamentally different model compared to a conventional 3D material like silicon as a consequence of the reduced dimensionality in CNTs.

"It was difficult to develop a terahertz radiation device with an external high electric field in a specific direction to CNT," says corresponding author Masayoshi Tonouchi.

By combining different experimental techniques, the team was able to directly probe the creation of free charge carriers in CNTs at different time scales after photoexcitation. Very complex interactions that involve different quasiparticles occur after the initial photoexcitation. These processes change over time, and being able to probe one of the quasiparticles makes it easier to understand the whole process.

Together with state-of-the-art simulations, the team was able to identify two key mechanisms that explain their data and helped them develop a detailed microscopic model describing quasiparticle interactions in a strong electric field in CNTs.

"We proposed a model in which electron-hole bound quasiparticles excited in the high energy E22 exciton band diverge to the low energy band and play a role in ultrafast electrical conduction. This model successfully explained the experimental facts and led to the clarification of the physical properties of CNTs."

Their results shed light on a number of long-standing issues in CNT ultrafast dynamics, moving us closer towards the realization of advanced optoelectronics based on CNTs and other low-dimensional materials.

Credit: 
Osaka University

Modelling wrinkling and buckling in materials that form the basis of flexible electronics

Flexible circuits have become a highly desirable commodity in modern technology, with applications in biotechnology, electronics, monitors and screens, being of particular importance. A new paper authored by John F. Niven, Department of Physics & Astronomy, McMaster University, Hamilton, Ontario, published in EPJ E, aims to understand how materials used in flexible electronics behave under stress and strain, particularly, how they wrinkle and buckle.

The design of flexible circuits generally involves a thin rigid capping layer - ?a metallic or polymeric film - ?placed upon a thick flexible substrate - ?a soft and stretchable elastomer. Compressing this rigid capping layer can lead to local buckling with a sinusoidal wrinkling pattern that allows its excess surface area to be accommodated by the compressed substrate.

When designing biomedical devices and wearable electronics, mechanical-induced buckling is the most plausible mechanism. Thus, for such applications, it is vital to understand mechanical instabilities and how they depend on the geometry and material properties of the individual layers. The ultimate aim being avoiding a loss of binding between layers and the development of voids.

Niven and his colleagues conducted an experiment to determine the geometrical parameters that dictate how a free-standing bilayer of film transitions into global or local buckling. The experiment also measured the effect of varying characteristics of the capping film and substrate layers such as their relative thickness. Stress was placed on the material - Elastosil sheets - ?biaxially by shifting the well-adhered layers in different directions, whilst leaving the perpendicular direction of the material fixed.

The result of the team's experiments was a force balance model that allows researchers to better understand the behaviour of such systems as the thickness ratio between the film layer and the substrate is adjusted, and quantify the amount and nature of wrinkling and buckling in materials that could form the basis of the next generation of electronics.

Credit: 
Springer

Charismatic invasive species have an easier time settling into new habitats

image: Pontic rhododendron is an example of an invasive species.

Image: 
University of Córdoba

Charisma can launch professional success and improve leadership skills. It can make a difference in a debate, make people become the center of attention and even be a factor in winning an election. However, humans do not have the monopoly on this inherent magnetism for triumph studied in so many coaching textbooks. It can also turn into an ally for certain living things in order to make their homes in a new ecosystem. Charismatic species have an easier time.

At least this is the main conclusion of an international study performed by the Biology Centre of the Czech Academy of Sciences in the Czech Republic and the Leibniz-Institute of Freshwater Ecology and Inland Fisheries, and on which University of Cordoba researcher Pablo González also collaborated. The study assessed the influence of charisma on the management of invasive species and concluded that this capacity that some living things have to fascinate can hinder controlling them and condition how they spread. "Charismatic species such as decorative plants, aquarium fish and exotic pets are more likely to be deliberately brought in by humans", explains Pablo González.

According to the literature, as this concept has been studied for years, charisma in exotic species is defined as "attractiveness that affects perceptions and produces positive responses from human beings". Research has shown that body size, emitting certain sounds or nice smells, distinctive coloring and furriness are some of the main features that contribute to this attraction. One example is raccoons, an exotic species in Japan that has spread throughout practically the entire country. Their facial features and funny behavior, such as dipping food in water before eating it, have made them one of Japan's most popular pets.

Though to the human eye a lizard does not provoke the same likeability as a panda bear, invasive species, regardless of their attractiveness, "can cause serious problems in their new habitats when competing for food or being disease carriers", explains Professor Jonathan Jeschke, one of the study's authors.

The study, in which Spanish researcher Ana Novoa also participated, analyzed several cases when charisma also influenced the language used by the media. It is no coincidence that some plant species are called "weeds", whereas other decorative plants with long flowering periods have a better reputation. The gray squirrel in Italy, an invasive species native to North America, is a prime example. A campaign defending animal rights that portrayed these squirrels as likeable cartoon characters played a part in the failure of removal programs. "The fact that a problematic species is seen as being adorable can make managing the situation difficult when the public objects", points out Ivan Jaric, lead author of the paper.

According to the study, the social perception of these species also depends on a cultural component. Echium plantagomieum, a European weed introduced in Australia, is known in some places as "Paterson's curse", while in others its nickname is "Salvation Jane". This poisonous plant kills everything that grows around it, but on the other hand it provides large areas of purple flowers that are pleasant to look at.

Effects of charisma on research programs

Scientific research programs and funding programs can also fall for this. According to the study, research into charismatic invasive species usually receives more funding and greater interest from the research community. "This can create gaps in scientific knowledge and make managing invasive species with greater social interest a priority but they are not necessarily the ones that actually make the greatest impact", highlights researcher Ana Novoa.

To do so, the team in charge of the study reminds us of the importance of awareness of charisma's influence over the treatment that these living things receive. Some species can cause severe problems when settling into an ecosystem that is not used to them, no matter how adorable they are. As the saying goes, all that glitters is not gold. It is what is on the inside that counts.

Credit: 
University of Córdoba

Children face three times more air pollution during the school run

Children face a worrying threefold increase in air pollution during the daily school runs, causing air quality experts to call for restrictions on the use of cars during those periods.

In a study published by the journal Science of the Total Environment, experts from the University of Surrey's world-renowned Global Centre for Clean Air Research (GCARE) partnered with a local school and the local community in Guildford to investigate the impact cars have on air quality in and around schools during drop-off and pick-up times.

In a school of around 420 pupils, the research team installed air quality sensor kits in five key areas around the school - including drop-off points where cars often sit idling in queues, the playground which is located near a main road, and a classroom. The team investigated the concentration of fine (PM2.5) and coarse particulate matter, as well as carbon dioxide in the morning (7:30am until 9:30am) and the evenings (2pm until 4pm).

The study discovered that dangerous PM2.5 from vehicles lining up to drop off children were the main source of air pollution around the school. The team also found that PM2.5 levels were nearly three times higher during morning drop-off periods than the afternoon pick-up or active school periods. This is due to the fact that pick-ups were conducted from off-site parking areas and a large number of pupils took part in after school activities.

The team also found that PM2.5 levels rose slightly within the classrooms closest to the road during drop-off and pick-up times. Researchers speculated that this could be because of the classroom's dependence on natural ventilation (open windows) which brings in unfiltered air.

The study also found that the playground's close proximity to the main road, a characteristic similar to many of the country's schools, resulted in the playground having consistently high PM2.5 levels at key times in the school day.

The researchers from GCARE have recommended that schools provide safe and accessible off-site parking drop-off points to help reduce levels of air pollution. The team has also recommended the use of green hedges as physical barriers to prevent air pollutants reaching children from cars at drop-off points and the main road.

Professor Prashant Kumar, Director of GCARE at the University of Surrey, said: "This is work of global significance, but we are also proud to collaborate with our local community on this work - employing smart sensing technology and a citizen science approach. The findings will be of great concern to parents locally and further afield. It goes without saying that our children's health and wellbeing is of the highest priority in society and that is why we must protect them from the dangers of air pollution, including where the school run can now be seen to be directly impacting the school environment.

"Every school is different. However, many have characteristics that will mean that children are exposed to hotspots of air pollution in school premises. We have found that the use of cars during the school run is increasing the number of dangerous particles our children breath in, even during playtime long after they have been dropped off."

Mr Neil Lewin, the Headteacher of St Thomas of Canterbury Catholic Primary School in Guildford, said: "Minimising air pollution exposure in and around the school has to be at the top of our agenda and we need to find practical but effective ways to reduce this exposure to air pollution in our school environment. This co-designed study has been an excellent experience for our children (especially our eco-warriors) giving them hands-on real science experience, and I hope will be very influential in compelling our parents to think again about their journeys to and from school to ensure the safest environment for their children."

Mr Andrew Strawson, the Chairman of Merrow Residents' Association in Guildford, said: "This is a rare and welcome opportunity for direct community involvement in the co-creation and co-design of a scientific study aimed at addressing important local and national issues. We thank Professor Kumar and his team for their continuing involvement with this community programme. His team promotes excellent guidance on green infrastructure initiatives. He has now taken this further and enabled this joint project which provides key data and strategies for use in helping to protect our children from air pollution at school."

Credit: 
University of Surrey

Milestone for the early detection of sepsis

image: A team led by Christoph W. Sensen (right), head of the Institute of Computational Biotechnology at TU Graz, has succeeded in using biomarkers to diagnose sepsis 2 to 3 days before the first clinical symptoms appear.

Image: 
© Lunghammer - TU Graz

Whether activating or silencing genes, breaking down defective cells or building new tissue, our body is constantly working to repair itself, even in cases of illness. To fight a disease, our body sends out signals, often long before we ourselves notice the disease. Such signals are, for example, DNA molecules that are released from the body's own cells, circulate in the blood and are most likely recognised by other cells as a message to stimulate a defence reaction.

Researchers at TU Graz's Institute of Computational Biotechnology have identified messengers and together with scientists from the Austrian Centre of Industrial Biotechnology (acib), the Medical University of Graz and CNA Diagnostics GmbH (Grambach, Styria), have developed a ground-breaking method: using these endogenous signals (biomarkers), sepsis can be diagnosed with high accuracy two to three days before the first clinical symptoms occur. The test based on this method could significantly increase the chance of survival of sepsis patients and lower the negative side effects for sepsis survivors. The researchers have now published details on this in the two papers "Evaluation of host-based molecular markers for the early detection of human sepsis" and "Circulating cell-free DNA is predominantly composed of retrotransposable elements and non-telomeric satellite DNA" in Journal of Biotechnology (Elsevier).

Classification algorithms serve as a basis

"Our team has identified 24 biomarkers with which bacterial- or fungal-induced sepsis can be detected at an earlier stage when compared to the currently used tests, using classification newly developed algorithms," explains Christoph W. Sensen, head of the Institute of Computational Biotechnology at TU Graz.

For their work, the bioinformaticians used sequencing data derived from anonymised plasma samples provided by the research groups led by Robert Krause, co-director of BioTechMed-Graz, and Peter Neumeister at the Medical University of Graz. The samples came from persons diagnosed with sepsis caused by bacteria or fungi, respectively, (in whose blood these pathogens were detected), influenza (a disease with symptoms partly similar to sepsis) or lymphoma, as well as from healthy individuals. The sequencing data formed the basis for the development of the algorithms that were used to identify the markers, thus creating an unprecedented set of markers. "This data set can be used to distinguish people in the early stages of sepsis and those with early clinical signs from healthy people and from people with other diseases." Sensen continues: "Within the patient group for which the markers were developed, the diagnostic accuracy was almost 90 percent in the period from two days before the first clinical signs until two days after diagnosis with the currently used diagnostic methods. In blind studies with patient groups that were not included in the marker development, the accuracy was still up to 81 percent." With the help of this method, sepsis can therefore be diagnosed much earlier than with any other diagnostic method.

Host-based test procedure, approval procedure already underway

In the course of their studies, the researchers also developed a new form of quantitative real-time PCR test. PCR stands for Polymerase Chain Reaction, a method for amplifying nucleic acids. PCR-based tests are already in use in clinics, for example for the detection of the covid-19 virus in patients. These kind of tests are often used to amplify the DNA or RNA of an infectious agent in a blood, plasma or serum sample, e.g. allowing the direct detection of bacteria or fungi in sepsis patients. In view of the large number of possible pathogen species which might case sepsis however, this is only possible to a very limited extent for sepsis patients and is therefore very imprecise. The newly developed test of the Graz group, on the other hand, focuses on the body's own signals, which are representative for the onset of sepsis for all bacterial and fungal cases. These can therefore be measured with much higher accuracy and also 2-3 days earlier than the direct detection of pathogens would allow.

Approval in the United States at the U.S. Food and Drug Administration (FDA) in Washington has already been applied for via the 510k approval process and the clinical trial has begun. The work for approval in Europe is just starting. Christoph W. Sensen hopes that the tests will soon be used on a large scale. "However, the corona pandemic is putting our timetable somewhat on the back burner, as US hospitals will of course not be able to supply plasma samples for some time due to the current situation."

Bernd Nidetzky, CSO of the Austrian Centre of Industrial Biotechnology (acib), comments: "The development of fast and efficient diagnostic procedures, such as the method for early detection of sepsis presented here, is a new field within acib, which we are establishing in the current funding phase of our competence center. We are delighted that this work has reached the clinical trial phase so quickly!"

Further plasma samples sought

In the meantime, data from China shows that even covid-19 patients with severe end-stage disease often had sepsis as a secondary disease. Sensen and his team are all the more interested in cooperating with biobanks such as BBMRI-ERIC and hospitals that are able to provide the team in Graz with plasma samples from Covid-19 patients. Because, according to Sensen: "On the basis of the sepsis early-detection research programme, we should be able to develop diagnostic tools for the faster identification of high-risk patients and a strategy for early intervention at the first signs of sepsis, which can be used in future pandemics to reduce the consequences of the infection for those affected."

This research project is anchored in the Fields of Expertise Human & Biotechnology and Information, Communication & Computing, two of the five strategic foci of Graz University of Technology. The participating researchers are part of BioTechMed-Graz - the research cooperation between Med Uni Graz, TU Graz and Graz University of Technology in the field of life sciences.

Credit: 
Graz University of Technology

Water replaces toxins: Green production of plastics

image: 1L steel reactor in the laboratory of Miriam Unterlass.

Image: 
TU Wien

Many materials that we use every day are not sustainable. Some are harmful to plants or animals, others contain rare elements that will not always be as readily available as they are today. A great hope for the future is to achieve different material properties by using novel organic molecules. Organic high-performance materials containing only common elements such as carbon, hydrogen or oxygen could solve our resource problem - but their preparation is usually anything but environmentally friendly. Often very toxic substances are used during the synthesis of such materials, even if the end product itself is non-toxic.

At TU Wien a different approach is taken: In the research group for organic high-performance materials, led by Prof. Miriam Unterlass at the Faculty of Technical Chemistry at TU Wien, a completely different synthetic method is employed. Instead of toxic additives, only hot water is used. A decisive breakthrough has now been achieved: two important classes of polymers could be generated using the new process - an important step towards industrial application of the new method. The results have now been published in the renowned journal Angewandte Chemie.

High pressure and high temperature

"We are investigating so-called hydrothermal synthetic processes," says Miriam Unterlass. "We are working at high pressure and high temperature in the order of 17 bar and 200 °C. As it turns out, under such extreme conditions it is possible to avoid using toxic solvents that would otherwise be necessary for producing these polymers. The term "green chemistry" refers to those methods that allow to render not only the end products but also the synthetic processes in the chemical industry more environmentally friendly.

Already several years ago, Miriam Unterlass achieved first positive results with this technology. "We succeeded, for example, in producing organic dyes, or polyimides - plastics that are indispensable in the aviation and electronics industries. This also generated a great deal of interest from the industry," says Unterlass. "But now we have taken an important step forward: We were able to synthesize different polymer examples from two highly interesting classes of plastics - polybenzimidazoles and pyrron polymers."

New preparation processes for super-plastics

Polybenzimidazoles are, for example, nowadays used as membranes in fuel cells since they are acid-resistant even at high temperatures and can also conduct protons. Polybenzimidazole fibers are also found in fireproof clothing such as the protective suits of firefighters. " That already shows that they are real super-plastics," says Unterlass.

Pyrron polymers, on the other hand, have particularly interesting electronic properties in addition to their excellent stability. Therefore, they are suitable for applications such as field-effect transistors or as powerful and highly resistant electrode material in batteries.

"The fact that these polymers can be prepared using our hydrothermal process is remarkable since under usual conditions the chemical reactions for generating these plastics are sensitive to water", says Miriam Unterlass. "This shows how promising our method is for a wide range of applications."

The new fabrication method for the two new material classes has already been patented, with the assistance of the research and transfer support of the TU Wien. The electrochemical analysis of the products was carried out in cooperation with Imperial College London.

Credit: 
Vienna University of Technology

How do our cells respond to stress?

image: Model representing the behavior of the protein G3BP under stress: RNA molecules bind to G3BP, allowing multiple interactions that promote the clustering of G3BP and the assembly of dynamic stress granules (SG). The image on the left shows a cell in which stress granules were labeled with a fluorescent dye. The schematic on the right gives insight into the molecular structure and organization of stress granules.

Image: 
(c) BIOTEC

Cells are often exposed to stressful conditions that can be life threatening, such as high temperatures or toxins. Fortunately, our cells are masters of stress management with a powerful response program: they cease to grow, produce stress-protective factors, and form large structures, which are called stress granules. Scientists at the Biotechnology Center (BIOTEC) of the TU Dresden and the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), together with partners in Heidelberg and St. Louis (USA) have investigated how these mysterious structures assemble and dissolve, and what may cause their transition into a pathological state as observed in neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis). Their results were published in the renowned scientific journal Cell.

ALS is a hitherto incurable disease of the central nervous system in which the motor neurons - nerve cells responsible for the muscles movement - gradually die. Do stress granules play a role in this process?

Stress granules are formed in the cytoplasm of the cell and assemble from a large number of macromolecular components such as messenger RNAs and RNA-binding proteins. Stress granules usually disassemble when the stress subsides, a process which is promoted by the dynamic nature of stress granules. However, a hallmark of ALS is the presence of non-dynamic, persistent forms of stress granules.

"In ALS, patients suffer from muscle weakness and paralysis. Stress granule-containing motor neurons slowly degenerate, causing a progressive loss of motor functions. We need to better understand the complex biology of stress granules in order to design and develop future therapeutic strategies that counteract the course of the disease. But the complex environment of the cells within an organism makes this difficult," explains Dr. Titus Franzmann, one of the senior authors of the publication.

In order to systematically test their hypotheses about the assembly of stress granules and the pathology causing molecular changes, the scientists developed a controlled environment using an in vitro system with purified components that allowed the recreation of stress granules in a test tube. They observed stress granule assembly step by step and characterized the critical factors underlying their dynamics.

"Stress granules have a very complex structure. Nevertheless, their formation depends primarily on the behavior of a single protein - the RNA-binding protein G3BP," says Dr. Jordina Guillén-Boixet, one of the first authors of the study. "This protein undergoes a critical structural change: Under non-stress conditions G3BP adopts a compact state that does not allow stress granules to assemble. But under stress, RNA molecules bind to G3BP allowing multiple interactions that promote the assembly of dynamic stress granules. The subsequent transition from dynamic into non-dynamic state, which may be caused for example by prolonged stress, may trigger the death of the motor neurons, as we can observe in the disease ALS."

The research project was initiated in 2015 and led by the Alberti research group at TU Dresden´s BIOTEC. The close co-operation of 23 scientists from the TU Dresden, the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, the European Molecular Biology Laboratory in Heidelberg and the Washington University in St. Louis (USA) was central for the success of the project. Prof. Simon Alberti: "There is a number of remaining questions. Our experimental system at BIOTEC is now available for further testing and will be central to developing new diagnostics and therapeutics to combat neurodegenerative diseases such as ALS."

Credit: 
Technische Universität Dresden

High-performance electrolyte solves battery puzzle

COLLEGE PARK, Md. - Lithium ion batteries have already become an integral part of our everyday life. However, our energy-hungry society demands longer life, faster charging, and lighter batteries for a variety of applications from electric vehicles to portable electronics, including lightening the load a soldier carries as numerous electronics become adopted by the Army.

Can we get closer to such lighter and faster-charging batteries? The current generation of lithium ion batteries uses graphite as an anode, which has a relatively low capacity, and could be replaced with a silicon anode with high capacity and low environmental impact. This is a highly promising direction for research - yet elusive, as batteries with silicon anodes with a large particle size tend to have shorter lives, generally less than 50 cycles. When researchers tried using nanoparticles of silicon, aluminum, and bismuth, they found that these nano-sized alloy anodes still suffer short cycle life and high cost. Chunsheng Wang and his colleagues may have found a new direction for fixing this degradation problem: the electrolyte.

The team from the University of Maryland and the Army Research Laboratory have made an electrolyte that forms a protective layer on silicon, which is stable and resists the swelling that occurs in silicon anode particles. The new electrolyte - rationally designed with underlying principles in place - gives the anode particles room for Si to swell insight the protected layer. The results were published in the journal Nature Energy on April 20, 2020.

Dr. Ji Chen, a lead author of the paper from the Department of Chemical and Biomolecular Engineering at the University of Maryland, said, "Our research proves that it is practical and possible to stably cycle silicon, aluminum, and bismuth particles as lithium ion battery anodes, simply with a rationally designed electrolyte, which has been regarded as unachievable before."

"The energy density of the battery is determined by the electrodes, while the performance of the battery is critically controlled by the electrolytes. The designed electrolytes enable the use of micro-sized alloy anodes, which will significantly enhance the energy density of the battery, " said Dr. Xiulin Fan, a co-first author from the University of Maryland, and now a professor in Zhejiang University, China.

"Current efforts by combination of molecular modeling and experimental provided a clear path to a new direction to rationally design the electrolytes that enable long cycle life for high capacity silicon anodes opening a path to developing high energy batteries for a warfighter, " said Dr. Oleg Borodin, a collaborator from the Army Research Laboratory.

Current electrolyte design for siliconi anodes aims to form a uniform polymer layer called the solid electrolyte interface or SEI that is flexible and strongly bonds with silicon. However, the strong bonding between polymer SEI and silicon forces the SEI to have the same volume change as the anode particles, so both the particles and the SEI crack during battery operation.

"After extensive research on silicon electrodes, the battery community has reached a consensus that the micro-sized silicon anodes cannot be used in commercial lithium-ion batteries," said Chunsheng Wang, a professor of Chemical and Biomolecular Engineering at the University of Maryland. "We successfully avoided the SEI damage by forming a ceramic SEI that has a low affinity to the lithiated silicon particles, so that the lithiated silicon can relocate at the interface during volume change without damaging the SEI. The electrolyte design principle is universal for all alloy anodes, and opens a new opportunity to develop high energy batteries."

Challenges still remain for the commercialization of the electrolyte, the voltage window of 4.2V still needs to be expanded, Wang said.

Credit: 
University of Maryland

New hybrid material improves the performance of silicon in Li-ion batteries

image: SEM image of hybrid anode material. Mesoporous silicon microparticles are bound together with carbon nanotubes at multiple points.

Image: 
Timo Ikonen

Researchers at the University of Eastern Finland have developed a new hybrid material of mesoporous silicon microparticles and carbon nanotubes that can improve the performance of silicon in Li-ion batteries. Advances in battery technology are essential for sustainable development and for achieving climate neutrality.

States and companies worldwide are eagerly looking for new and sustainable technologies to achieve climate neutrality in every sector of society, ranging from transportation and production of consumables to energy production. Once green energy is produced, it needs to be stored before it can be used in portable applications. In this step, battery technology plays an essential role in making the consumption of green energy a viable alternative.

In the future, silicon will gradually replace carbon as the anode material in Li-ion batteries (LIBs). This development is driven by the fact that the capacity of silicon is ten times higher than the capacity of graphite, which is nowadays used as the anode material in LIBs. Using silicon in the anode makes it possible to even double the capacity of the total battery cell. However, silicon is facing severe challenges in battery technology due to its unstable material properties. Moreover, there is no technology available so far to produce feasible anodes solely from silicon.

To minimise the reducing effect of high charging rates on the capacity of silicon anodes, researchers from the University of Eastern Finland have developed a hybrid material of mesoporous silicon (PSi) microparticles and carbon nanotubes (CNTs). According to the researchers, the hybrid material needs to be realised through chemical conjugation of PSi and CNTs with the right polarity so as to not hinder the diffusion of lithium ions into silicon. With the right type of conjugation, also the electrical conductivity and mechanical durability of the material was improved. Further, the PSi microparticles used in the hybrid material were produced from barley husk ash to minimise the carbon footprint of the anode material and to support its sustainability. Silicon was produced through a simple magnesiothermic reduction process applied to the phytoliths that are amorphous porous silica structures found in abundance in husk ash. The findings were published in Scientific Reports and Materials Chemistry and Physics.

Next, the researchers are aiming to produce a full silicon anode with a solid electrolyte to address the challenges related to the safety of LIBs and to the unstable solid electrolyte interface (SEI).

"The progress of the LIB research is very exciting, and we want to contribute to the field with our know-how related to mesoporous structures of silicon. Hopefully, the EU will invest more in the basic research of batteries to pave the wave for high performance batteries and to support the competitiveness of Europe in this field. The Battery 2030+ roadmap would be essential in supporting this progress," Professor Vesa-Pekka Lehto from the University of Eastern Finland notes.

Credit: 
University of Eastern Finland

Present-day dogs defy the domestication syndrome

Does the domestication syndrome exist? New research reveals that this does not seem to be the case in present-day dogs.

Across a wide range of domesticated animals the same morphological, physiological and behavioural traits appear to change together in a non-random way. For instance, many domesticated animals have white patterns in their coat and floppy ears, and most are more docile and tame than their wild ancestors. This phenomenon where traits change together in domesticated species, compared to their wild ancestors, is known as the domestication syndrome. However, recently a scientific discussion of the mechanism and even the existence of this syndrome has caught on.

A group of researchers from Stockholm University, lead by Dr. Christina Hansen Wheat, have now added to this discussion with a study published in Evolution Letters on April 11th 2020. Using 78 different dog breeds, Dr. Hansen Wheat and colleagues formally tested whether there is evidence for the domestication syndrome in dogs. Specifically, they quantified whether the look of different dog breeds (floppy ears, curly tails and white pigmentation) predicts how those breeds behave (playfulness, sociability, fearfulness, aggression). Because the domestication syndrome has been argued to arise from a singular mechanism, all of these traits are expected to change together within dog breeds. However, no such covariation among these traits was observed, thereby contradicting earlier hypotheses that the domestication syndrome originates from a single mechanism. But more importantly, the study also calls into question if we are currently viewing the effects of domestication in the right way.

"For dogs, the issue is that we are trying to infer what happened when we domesticated the species at least 15,000 years ago by looking at the dogs we have today", says Dr. Christina Hansen Wheat, "but the dogs we have today are not likely to be representative of the early dogs our forefathers domesticated".

Present day dogs are bred for very specific purposes and breed requirements vary drastically in terms of both appearance (i.e. morphology) and behaviour. This has resulted in an extreme variation among dog breeds - just picture a Chihuahua, a Labrador Retriever, and a Great Dane standing next to each other. They look dramatically different, and if you throw a stick, one breed is more likely to respond than others. For most dog owners, the researchers results, finding that morphology and behaviour do not covary among modern day dog breeds, will perhaps not be particularly surprising. However, it is nevertheless the first time that this has been formally tested and it adds valuable information to the discussion about the domestication syndrome, our expectations to the alterations that we see in domesticated animals and which traits are even relevant for this discussion.

Dogs, and other domesticated species, have experienced extensive artificial selection to create breeds with certain traits enhanced for greater production yield, functionality or esthetics. "These improvement traits likely have little to do with the traits that were important during early stages of domestication. Unfortunately, because dog domestication happened such a long time ago, we do not have any records of what the first dogs looked or behaved like", says Christina Hansen Wheat. "This is problematic when forming hypotheses about the domestication process, because when we base our theories on the dogs we see today, we are primarily looking at improvement traits and not actual domestication traits. Recognizing and identifying the difference between domestication traits and improvement traits is important, but can also be challenging".

Looking forward, the researchers now wonder whether the lack of covariance between morphology and behaviour in dogs is due to a decoupling of independent domestication traits, these traits never having covaried, or whether it is because we are applying a domestication syndrome hypothesis to traits that are not actual domestication traits, but rather improvement traits.

Credit: 
Stockholm University