Tech

Kirigami/origami: Unfolding the new regime of advanced 3D micro-/nanofabrication with 'folding'

image: (a) Schematic illustrations of folding, bending, and twisting in kirigami/origami techniques. (b) Graphene kirigami. (c) Graphene origami. (d) Scale and type of stimuli employed in reported 3D micro-/nanoscale kirigami/origami techniques.

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by Shanshan Chen, Jianfeng Chen, Xiangdong Zhang, Zhi-Yuan Li, and Jiafang Li

3D micro-/nanofabrication holds the key to build a large variety of micro-/nanoscale materials, structures, devices, and systems with unique properties that do not manifest in their 2D planar counterparts. Recently, scientists have explored some very different 3D fabrication strategies such as kirigami and origami that make use of the science of cutting and folding 2D materials/structures to create versatile 3D shapes. Such new methodologies enable continuous and direct 2D-to-3D transformations through folding, bending and twisting, with which the occupied space can vary "nonlinearly" by several orders of magnitude compared to the conventional 3D fabrications. More importantly, these new-concept kirigami/origami techniques provide an extra degree of freedom in creating unprecedented 3D micro-/nanogeometries beyond the imaginable designs of conventional subtractive and additive fabrication.

In a new paper published in Light: Science & Applications, Chinese scientists from Beijing Institute of Technology and South China University of Technology made a comprehensive review on some of the latest progress in kirigami/origami in micro-/nanoscale. Aiming to unfold this new regime of advanced 3D micro-/nanofabrication, they introduced and discussed various stimuli of kirigami/origami, including capillary force, residual stress, mechanical stress, responsive force and focused-ion-beam irradiation induced stress, and their working principles in the micro-/nanoscale region. The focused-ion-beam based nano-kirigami, as a prominent example coined in 2018 by the team, was highlighted particularly as an instant and direct 2D-to-3D transformation technique. In this method, the focused ion beam was employed to cut the 2D nanopatterns like "knives/scissors" and gradually "pull" the nanopatterns into complex 3D shapes like "hands". By utilizing the topography-guided stress within the nanopatterns, versatile 3D shape transformations such as upward buckling, downward bending, complex rotation and twisting of nanostructures were precisely achieved.

As discussed in this review, the unprecedented micro-/nanoscale geometries created by kirigami/origami have brought about extensive potentials for the reshaping of 2D materials, as well as in biological, optical, and reconfigurable applications. Moreover, 3D transformations of emerging 2D materials (such as graphene, MoS2, MoS2, WSe2 and PtSe2), for example, were briefly introduced and the associated new electrical and mechanical properties were uncovered.

"Advanced kirigami/origami provides an easily accessible approach for the modulation of mechanical, electrical, magnetic and optical properties of existing materials, with remarkable flexibility, diversity, functionality, generality and reconfigurability", they said. "These key features clearly differentiate the facile kirigami/origami from other complicated 3D nanofabrication techniques, and make this new paradigm technique unique and promising for solving many difficult problems in practical applications of micro/nano-devices."

Furthermore, they discussed the current challenges in kirigami/origami-based 3D micro-/nanofabrication, such as the limited strategies of stimuli and reconfigurations, and the difficulties in on-chip and large-scale integration. "When these challenges are met and the advantages are fully adopted," they envisioned, "micro-/nanoscale kirigami/origami will greatly innovate the regime of 3D micro-/nanofabrication. Unprecedented physical characteristics and extensive functional applications can be achieved in wide areas of optics, physics, biology, chemistry and engineering. These new-concept technologies, with breakthrough prototypes, could provide useful solutions for novel LIDAR/LADAR systems, high-resolution spatial light modulators, integrated optical reconfigurations, ultra-sensitive biomedical sensors, on-chip biomedical diagnosis and the emerging nano-opto-electro-mechanical systems."

Credit: 
Light Publishing Center, Changchun Institute of Optics, Fine Mechanics And Physics, CAS

The analysis of copper levels in blood facilitates diagnosis of Alzheimer's disease

image: This is Peep Palumaa, professor at TalTech Division of Gene Technology.

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TalTech

In biology it is well-known that every living organism is triggered by the hereditary material or DNA that encodes various protein molecules, which in turn perform all the necessary biological functions and it might seem that nothing else is needed to sustain the life of an organism.

However, we are struggling to find an answer when a question arises where and how the energy required to synthesize complex molecules or for example to maintain the body temperature of complex organisms comes from. It is known that the human body needs oxygen to produce energy, but the fact that all organisms need the trace element copper as a catalyst for safe consumption of oxygen is less known.

Head of the Research Group of Metalloproteomics, Professor Peep Palumaa says, "Scientists, more specifically biochemists, have known about the importance of copper in human body for a long time, but even they do not know, for example, how this element reaches from our food to the right destinations, i.e. various copper enzymes."

This pathway is not safe, because if copper ions (as effective catalysts) are uncontrolled, dangerous radical side reactions can be triggered in the presence of oxygen derivatives like superoxide and hydrogen peroxide, leading to oxidative stress and related diseases (the frightening examples include atherosclerosis, various forms of cancer and neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, etc.) Oxidative stress can lead also to accelerated ageing of an organism.

An important environment, where copper ions are transported in the body is blood. The primary function of blood is to transport various molecules and ions from the digestive tract to the tissues. The reverse process occurs in blood when excessive amounts of substances accumulate in the tissues that can become toxic to the body. There are many transport proteins that could presumably transport copper in blood, but data on real transporters and their copper-binding affinities have been very controversial so far.

The scientists of the Research Group of Metalloproteomics from TalTech Department of Chemistry and Biotechnology in cooperation with the Swedish pharmaceutical company Wilson Therapeutics AB investigated the proteins and ligands transporting copper ions in blood and their binding affinity. To this end, the research group developed a new and innovative liquid chromatography and ICP MS (a trace element analysis technique) based approach. The study showed that copper ions are primarily bound to only two proteins in the blood - about 75% to ceruloplasmin, which binds copper ions very strongly, almost irreversibly, and about 25% to serum albumin, which binds copper ions with picomolar affinity. In addition to proteins, a small proportion of copper ions are also bound to histidine and other free amino acids in the blood. The results of the study demonstrated also that the previously presumed copper transporter alpha-2 macroglobulin does not bind copper ions.

"The research findings can be used for various applications. First, they help to understand the normal copper metabolism in the body, which has a direct diagnostic value. Second, these results also help to identify disturbances in the body's copper metabolism. The latter occur in several genetic diseases, such as Wilson and Menkes diseases as well as the most common neurodegenerative disease - Alzheimer's disease. In addition to specific diagnoses, the effect of pharmaceuticals normalizing copper metabolism that are used for the treatment of the abovementioned diseases can also be monitored through copper equilibrium in blood," Professor Palumaa says.

Credit: 
Estonian Research Council

New method for capturing carbon via root exudates in wild forest

image: Root Exudate Collection using the glass-fiber filter method

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Naoki Makita Ph.D., Faculty of Science, Shinshu University

It is well known that plants use carbon dioxide obtained from the air in photosynthesis to use as energy and grow bigger. Naoki Makita and Maiko Akatsuki of Shinshu University confirmed that a large amount of this carbon is expelled into the soil through root exudates. It had previously been confirmed that plants exude organic compounds in liquid form from their root systems in hydroponics and seedlings grown under the lab experiments. However, measurements of root systems of trees growing in the wild had been rarely performed due to technical problems. It was necessary to develop a new measurement method to elucidate the belowground carbon allocation in forest ecosystems to confirm exudates of trees in the natural environment. This method, for the small scale finer root systems needed to be convenient for on-site work.

When the root system is dug up from the soil, the roots dry out immediately and its bioactivity is significantly reduced. The researchers had to dig very carefully not to damage the roots in order to evaluate them accurately. The amount of exudate taken at a time was very small, so there was no room for any dirt or other contaminants. They needed to develop a method that is quick, easy and gentle on the fine scale roots. Makita and Akatsuki developed this new method by working through a lot of trial and error for the best method of digging, measurement time, size and material of the filter. It was very difficult to dig up the roots without damaging them. However, with their diligent effort they were finally able to detect and measure the exudates of the small scale fine roots with short measurement time. In the beginning, they were unable to record the exudate because the amount fell below the detection limit of the measuring device. By adjusting the measurement time and sample size, they succeeded in detecting the exudates.

Carbon is often said to be the building block of life, and in this research, Makita and Akatsuki were able to show that a large amount of this carbon is released from the root system of trees as exudates. It was also found that not all root parts are equal. Thinner, finer roots exude more than thicker roots. The surrounding microbial symbiotic groups, such as ectomycorrhiza and arbuscular mycorrihiza form a strong relationship with tree roots, and play a significant role in the chemistry and morphology of the root exudation.

Roots release exudates which include amino acids, organic acids, sugars, phenolics and other secondary metabolites. They have an allelopathic effect, demonstrating inhibitory or stimulatory on microorganisms and other creatures that thrive around the root system. Exudates inhibit the growth of competitive plants while promoting the growth and colonization of similar plants. By chemically and physically changing the properties of the rhizosphere soil near the exuding root system, they are able to change the number and activity of microorganisms which in turn effect the priming and decomposition rate of fallen leaves, branches and dead roots through the availability of inorganic ions. The fine roots at the extremity of trees exert such effects and make a great contribution to the material cycle of the forest ecosystem.

Dr. Makita would like to continue to measure root exudates of many tree species using this new method. With this study, it became clear that the release characteristics of exudates differ according to the type of mycorrhizal fungus that coexists with roots, but the sample species was very limited. By being able to accurately measure how much carbon a type of ecosystem of tree and its symbiotic microbial associations exudes from its roots into the soil, more precise estimates of the carbon cycle on a local and global scale can be made. This area of study is still in its infancy, so the hope is that other researchers too can learn this method and collect more data to get a better understanding of exudates and the role they play in the forest carbon cycle.

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Shinshu University

Metal collector made of bacteria

image: Dirk Tischler was invited to write a review article about metal-binding substances.

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© RUB, Marquard

How to extract metals from the environment

Microorganisms such as fungi and bacteria as well as plants generate a wide range of chemical substances that are not absolutely necessary for their survival. Such so-called secondary metabolites are usually formed in response to current environmental conditions. They include metal-binding molecules called chelators. The best described group of chelators are the iron-binding siderophores. They are relevant for many metabolic processes, as iron is an essential component of many enzymes and signalling pathways. For example, pathogenic bacteria use siderophores to extract iron from their host for their metabolism. The host might then suffer from iron deficiency. But siderophores are also used by bacteria living in soil that thus get access to iron and, as a result, gain an advantage over other organisms in the same habitat. In addition to iron-specific chelators, there are a number of others for various metals and metalloids such as zinc, vanadium, molybdenum or even uranium oxides.

Many potential applications

"Such chelators have many potential applications," explains Dirk Tischler. "They can be used, for example, to remediate floors, selectively extract or separate raw materials, or in biosensorics or medicine." In medical applications, siderophores are used to treat iron overload in the body, a disorder known as "iron storage disease".

Over the last few years, his research group, together with other teams, has identified further strains that form chelators and described new structures. They have also successfully deciphered the genetic information for the formation of these substances and introduced them into easy-to-handle organisms such as Escherichia coli bacteria. These bacteria then serve as producers of the required natural substances or of modified substances. "This is how we can create semi-artificial compounds," says Dirk Tischler.

Biosynthesis of precursors

In the review article, he describes the different natural chelators and their ability to bind metals and metalloids and explores current and potential future applications. "At present, we are using the knowledge we've gained so far to create artificial biosynthetic pathways that enable us to generate and characterise precursors of siderophores," concludes Tischler. These precursors will subsequently be chemically modified in order to gain access to new drug classes.

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Ruhr-University Bochum

Controlling angular dispersions in optical metasurfaces

image: (a) By controlling the coupling between meta-atoms (upper inset) and the radiation properties of constituent meta-atoms (lower inset), one can realize angle-dependent multifunctional meta-devices with wave-control functionalities that change as the incident angle of the excitation light varies. (b) TE-TM reflection-phase difference as function of incident angle, illustrating the incident-angle-dependent polarization controllability of meta-design shown in the inset. (c) Schematics of angle-multiplexed wave-front meta-controller based on reflective metasurfaces combining with angular dispersion manipulations.

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by Xiyue Zhang, Qi Li, Feifei Liu, Meng Qiu, Shulin Sun, Qiong He, Lei Zhou

Despite of impressive successes already achieved on metasurfaces, most fascinating light-manipulation effects were only demonstrated under normal-incidence excitations. The angular dispersions of the devices, that the responses of such metasurfaces can sensitively depend on the impinging angle, were often overlooked. Obviously, angular dispersion is a critical issue that must be carefully addressed in different application scenarios. Unfortunately, meta-devices realized so far usually exhibit uncontrolled angular dispersions, which were only known after (rather than before) the devices were designed.

In a new paper published in Light Science & Application, scientists from the State Key Laboratory of Surface Physics, Physics Department of Fudan University, China, established a general strategy to guide design optical metasurfaces with fully controlled angular dispersions. They first theoretically and experimentally demonstrated that angular dispersions of metasurfaces are collectively determined by the near-field couplings between meta-atoms and the radiation pattern of a single constitutional meta-atom. Such a complete picture helps the authors to further experimentally realize a series of meta-devices in the near infrared freqeuncy regime, including one meta-polarizer with polarization-control functionality depending on the incident angle, two meta-absorber that can either selectively absorb light at a particular incident angle or absorb light at all incident angles. Finally, the authors numerically demonstrated an angle-multiplexed functional meta-device that can exhibit different controllabilities on the wave-front of light depending on the incident angle. The reported findings establish a new platform for achieving angle-multiplexed functional meta-devices, significantly expanding the wave-manipulation capabilities of optical metasurfaces.

The authors summarized the key scientific achievements of their work as:

"Our findings not only revealed the underlying physics governing the angular dispersions in optical metasurfaces, but more importantly, also significantly expand the capabilities of metasurface in manipulating EM waves by using "angle" as an additional degree of freedom."

"Our strategy to control angular dispersions is general enough, which can be applied to both transmissive and reflective metasurfaces, and to realize angle-multiplexed meta-devices with arbitrary intendent phase profiles for different incident angles, as long as one can design a set of meta-atoms exhibiting incident-angle-dependent phases covering a whole range of at the desired frequencies."

"Our finding has explored the angle as a new degree of freedom to control the EM response of metasurfaces. The combination of the angular dispersion control and the gradient metasurfaces design provide much more possibilities to achieve angle-multiplexed functional meta-devices", the authors forecast.

Credit: 
Light Publishing Center, Changchun Institute of Optics, Fine Mechanics And Physics, CAS

Circadian oscillation of a cyanobacterium doesn't need all three Kai proteins to keep going

image: Inactivating KaiA does not stop but damps circadian oscillations of the cyanobacterial' circadian clock (A). The amplitude of the damped oscillation is elevated by resonance with external cycles (B).

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Iwasaki Laboratory, Waseda University

Circadian rhythms are driven by a highly autonomous, self-sustaining circadian clock in our cells, telling us when to sleep or wake up in a 24-hour cycle.

This mechanism can also be found in other organisms, including in primitive, photosynthetic bacteria known as cyanobacteria. In cyanobacteria, three types of proteins known as KaiA, KaiB, and KaiC work together like gears of a clock to create the rhythms. According to previous studies, all three Kai proteins are required for the circadian clock of cyanobacteria to function, and lacking KaiA could abolish oscillations.

However, in a recent study published in Nature Communications, scientists from Waseda University, Kyushu University, and Ritsumeikan University presented an observation of damped, low-amplitude (damped) circadian oscillations in the absence of KaiA in the cyanobacterium Synechococcus elongatus.

Hideo Iwasaki, professor of cell biology at Waseda University and the corresponding author of this study, actually recorded such weak circadian rhythms during an experiment conducted more than 20 years ago retrospectively, but at the time, it was dismissed as a discrepancy and overlooked. However, when a graduate student from his laboratory pointed out the same subtle oscillations while they were observing gene expression patterns of a genomic variant of cyanobacteria lacking KaiA, Iwasaki knew something was going on.

"We spent much time and energy in conducting experiments, such as monitoring rhythms with a technique called the bioluminescence reporter, to understand physiological importance and molecular mechanisms of the damp circadian oscillations, as well as to establish our theoretical perspective because we had a hunch that our findings would overturn conventional knowledge," Iwasaki says. "Our findings are the results of efforts made by the graduate student who noticed the oscillations, who is the first author of this paper, and by the talented researchers we collaborated with. I would like to thank everyone involved for their dedication and hard work."

Iwasaki adds, "We also found that the damped rhythms resonate with external cycles with a period of 24 to 26 hours, meaning that its natural frequency is similar to that of a circadian clock. So, in a day-night altered environment, low-amplitude oscillations could theoretically act as a circadian clock to regulate various activities within cells and adapt to change in the cyclic environment."

Though much research has been done on the circadian clock, there has been a tendency for researchers to shy away from studying damped circadian oscillations because of the difficulty in analyzing them and their phenotypes being not particularly intriguing, but Iwasaki believes that there needs to be more focus on the topic.

"Based on our results, we could hypothesize that the circadian clock did not become autonomous and self-sustaining all the sudden but instead gradually evolved from low-amplitude oscillations," says Iwasaki. "From the evidence that some cyanobacteria in the natural environment do not possess KaiA, perhaps obtaining and losing KaiA happened multiple times along its evolution, and it could be that some cyanobacteria do not have KaiA for good reasons. Through further studies on damp circadian oscillations, we could be unveiling a great mystery with physiological and evolutionary significance."

Iwasaki and his team are interested in further investigating the roles that damp circadian oscillations play. If similar circadian mechanisms can be observed among higher plants and mammals, it may be able to manipulate our circadian rhythms more accurately by applying damped circadian oscillations and resonation.

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Waseda University

The prevention of childhood obesity would require stricter advertising regulations

Spain ranks fifth among European countries for childhood obesity. Sugar-sweetened beverages and soft drinks are consumed by 81% of Spanish children weekly. Mireia Montaña and Mònika Jiménez, researchers of the Open University of Catalonia and the UPF Department of Communication, respectively, have performed a study based on the assumption that advertising is one of the factors that contributes to the obesogenic environment.

This study, published in May in the International Journal of Environmental Research and Public Health, correlated longitudinally the nutritional values of sugar-sweetened beverages and soft drinks and advertising discursive strategies between 2013 and 2018 for all Spanish advertising media.

"The aim of this study is to find associations between advertisements for sugar-sweetened beverages and soft drinks in different media (TV, leaflets, radio, Internet, etc.), the language used, and the products' low nutritional value. To do so, we selected campaigns carried out by the top 10 companies in these categories between 2013 and 2018 in Spain", the authors state.

The authors applied a mixed-methods approach that included a quantitative analysis of advertising spend data, a content analysis and a study of the discursive strategies used in advertisements. In addition, the Nutri-score system was used to determine the nutritional quality of the beverages. Nutri-score classifies products into colours ranging from red to green, depending on their nutritional value. Red is for low nutritional value products, orange is for medium nutritional value foods and beverages, while green is for products of high nutritional value. Spain approved the application of the Nutri-score system in 2018.

The results were analysed considering the PAOS strategy, which is the standard for the prevention of childhood obesity that regulates advertising aimed at children under twelve. The main results point to an association between low nutritional value beverage advertisements and a discourse based on hedonistic elements. Happiness, the ability to make friends and to stand out from the rest of the group are some of the discursive elements used in advertising.

In addition, the results indicate that none of the advertisements analysed refer to the product's intrinsic properties, as determined by the regulatory framework established by the PAOS strategy. The analysis also determines that the companies supporting the PAOS code, and showing an initial commitment to respecting the regulatory framework contained therein, constantly violate it in their advertising.

The study concludes that in order to reduce and prevent childhood obesity in Spain, there is a need for tighter advertising regulation, especially with regard to the language used to present products and celebrity endorsements.

Credit: 
Universitat Pompeu Fabra - Barcelona

Ultrafast optical response and ablation mechanisms of molybdenum disulfide

image: a Optical images of the final structures and comparison with the transient reflectivity image at a 100 ps delay time. b Comparison of the XPS Mo 3d spectra of pristine and laser-treated MoS2. c Schematic of ablation processes in different fluence cases.

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by Changji Pan, Lan Jiang, Jingya Sun, Qingsong Wang, Feifei Wang, Kai Wang, Yongfeng Lu, Yeliang Wang, Liangti Qu and Tianhong Cui

Molybdenum disulfide (MoS2) has attracted considerable attention because of its potential applications in field-effect transistors, optoelectronic devices, and electrocatalysts, among others. For successful application of MoS2 in optoelectronics, it is necessary to understand the electron dynamics, which is known to determine the electronic transport and optical properties of semiconductors. In addition to its importance in optoelectronics applications, the ultrafast electron dynamics also plays a vital role in the laser fabrication of MoS2. Numerous valuable studies on the electron dynamics have already focused on the attractive properties of MoS2; however, they all investigated the free electron density below the damage level. At a laser fluence above the damage threshold, the electron dynamics may differ from that under lower-energy excitation. Therefore, it is necessary to provide deeper insights into the electron dynamics when an ultrafast intense laser pulse is applied.

In a new paper published in Light Science & Application, scientists from the Laser Micro/Nano-Fabrication Laboratory, School of Mechanical Engineering, Beijing Institute of Technology, Beijing 100081, PR China, in cooperation with a scientist at the University of Minnesota, predicted and examined what happens to molybdenum disulfide on the electron and lattice level under irradiation by intense femtosecond laser pulses. A theoretical model was first developed for MoS2 to simulate electron dynamics during femtosecond laser ablation processes. Simultaneously, a pump-probe setup was constructed to detect the ultrafast optical response of MoS2 under irradiation by intense femtosecond laser pulses. The results revealed two types of ablation mechanisms, which led to two distinct types of electron dynamics and final ablation morphology. At a higher fluence, the emergence of a superheated liquid induced a dramatic change in the transient reflectivity and micro-honeycomb structures. At a lower fluence, the material was just removed by sublimation, and the ablation structure was relatively flat. To further examine the ablated surface, X-ray photoelectron spectroscopy (XPS) measurement was performed. The results demonstrated that thermal decomposition occurred only at the higher fluence. According to the simulation results, under a higher fluence, the lattice temperature was much higher than the melting point of MoS2, whereas under a lower fluence, the lattice temperature was just below the melting point. The simulation results were in good agreement with the XPS results, as well as pump-probe detection.

The simulated and experimental results revealed the behaviour of electrons and the lattice during femtosecond laser ablation of MoS2, which enabled the manufacturing processes to be presented from electron level. This method and theoretical model provide a new perspective for understanding the mechanism of femtosecond laser processing, and even the control of the patterns and properties of materials. These scientists summarise their simulated and experimental work:

"We built up a theoretical model for MoS2 to account for several complex physical processes during femtosecond laser ablation, including (1) photoionisation, (2) free electron heating, (3) impact ionisation, (4) electron-lattice coupling, and (5) free electron recombination."

"We constructed a pump-probe setup to directly detect the ultrafast optical response of MoS2 under irradiation by intense femtosecond pulses. This detection system can detect the evolution of the electron dynamics with high spatial and temporal resolution."

"Our simulation results are in good agreement with the detection results, which indicates that the model is valid for predicting the interaction between a femtosecond laser and MoS2, and further provides more detailed information on the ultrafast electron dynamics during ablation processes."

Credit: 
Light Publishing Center, Changchun Institute of Optics, Fine Mechanics And Physics, CAS

A clinical decision system to predict trauma patient outcome

Chinese researchers from Trauma Center, Peking University People's Hospital and National Institute of Health Data Science of Peking University are using big data to help identify trauma patients who could experience potential adverse health events in the emergency department through the aid of a clinical decision support system. It was developed using a novel real-world evidence mining and evidence-based inference method, driven by improved information storage and electronic medical records.

The researchers published their results online on February 7 in IEEE Transactions on Systems, Man, and Cybernetics: Systems, a journal of the Institute of Electrical and Electronics Engineers. This is the first clinical decision support systems developed using evidential reasoning in an emergency department setting.

"Appropriate use of information technologies, particularly clinical decision support systems, may aid clinicians to make better clinical decisions and reduce the rate of medical errors," said the corresponding author Baoguo Jiang, Director at theTrauma Center, Peking University People's Hospital. "By inputting clinical data of a patient, combined with available historical data, our proposed clinical decision support system outputs a predicted belief degree of severe trauma, including ICU admission and in-hospital death."

"The clinical variable signs and symptoms may be interrelated and lead to a clinical outcome. For example, a patient may have low level of consciousness because of the location of the injury, or it might be related to the high body temperature". In developing their clinical decision support system, the first author Dr. Guilan Kong used a trauma dataset from the emergency department at Kailuan Hospital in China, a hospital that has a close research collaboration with the Trauma Center, Peking University People's Hospital. Through the dataset, the researchers obtained the data of 1,299 trauma patients. The degree of interdependence between clinical signs and symptoms can be calculated from historical patient data. In the proposed clinical decision support system, the emergency room physician supplies information about the patient, including blood pressure, pulse rate, respiration rate, consciousness level, body temperature, age, comorbidities, mechanism and location of injury. These clinical signs and symptoms are then processed using an evidential reasoning rule, which compares each piece against the evidence mined from real-world data to predict the probability of adverse events and to optimally manage trauma patients and help them achieve ideal outcomes, trauma patients with a high probability of being admitted to the intensive care unit or dying in hospital need to be identified quickly and accurately upon their arrival at a hospital.

The team found that not only did their model prove especially useful in cases without prior expert knowledge or clinical experiences, but that the clinical decision support system also allowed for more accurate identification of trauma patients with adverse events compared to other systems with traditional machine learning models. Furthermore, the clinical decision support system works in a real-time fashion. From a physician's input of a patient's data to generating appropriate advices, the system works almost without any delay, which in turn helps buy trauma patients valuable time.

Next, the researchers plan to finetune their system and to generalize it for use in other clinical areas and non-emergent department settings.

Credit: 
National Center for Trauma Medicine

Exchange of arms between chromosomes using molecular scissors

image: For the first time, chromosomes of the thale cress model plant were recombined with the help of the Cas9 protein. (Figure. Angelina Schindele, KIT)

Image: 
Angelina Schindele, KIT

The CRISPR/Cas molecular scissors work like a fine surgical instrument and can be used to modify genetic information in plants. The research teams of Professor Holger Puchta of Karlsruhe Institute of Technology (KIT) and Professor Andreas Houben from the Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) in Gatersleben have now been the first to not only exchange single genes, but to recombine entire chromosomes with the CRISPR/Cas technology. In this way, desired properties can be combined in crops. Their work using the thale cress model plant is reported in Nature Plants. (DOI: https://doi.org/10.1038/s41477-020-0663-x External Link)

For thousands of years, humans have taken advantage of the fact that the genetic material of organisms changes by evolution. They cultivate crops that produce high yields, are aromatic or resistant against diseases, pests, and extreme climatic conditions. For this purpose, they choose plants with various favorable properties and crossbreed them. This approach, however, is very time-consuming. Moreover, it is impossible to prevent disadvantageous traits from entering the plants.

Molecular biologist Professor Holger Puchta studies how plants can be cultivated more quickly and more precisely. For his CRISBREED project, he received an Advanced Grant of the European Research Council (ERC) in the amount of EUR 2.5 million. Holger Puchta is considered a pioneer of genome editing. He uses molecular scissors to specifically modify the DNA (deoxyribonucleic acid) that carries the genetic information in crops. With the help of this CRISPR/Cas technology, genes can be removed, inserted, or exchanged easily. CRISPR/Cas stands for a certain section on the DNA (CRISPR – Clustered Regularly Interspaced Short Palindromic Repeats) and an enzyme (Cas) that recognizes this section and cuts the DNA precisely at this point. Crops produced by genome editing do not contain any DNA, which is why they are not to be equated with classical genetically modified organisms.

First Exchange of Arms between Chromosomes

Within CRISBREED, researchers of the Chair for Molecular Biology and Biochemistry of KIT’s Botanical Institute headed by Professor Holger Puchta, in cooperation with Professor Andreas Houben from IPK, Gatersleben, have now achieved first decisive progress in using the molecular CRISPR/Cas scissors: For the first time, they have exchanged arms between chromosomes of the thale cress model plant (Arabidopsis thaliana) with the help of the Cas9 protein originating from the Staphylococcus aureus bacterium. “The genome consists of a certain number of chromosomes, on which the individual genes are arranged in fixed order,” Puchta explains. “So far, CRISPR/Cas has enabled modifications of single genes only. Now, we can modify and recombine entire chromosomes.” These novel chromosomes are then heritable.

The findings presented in Nature Plants promise to result in major advantages for crop cultivation: It is generally difficult to combine positive properties and eliminate negative properties at the same time, because the decisive genes often are arranged in very close proximity on the same chromosome and transmitted together. By the exchange of arms between chromosomes, these properties can now be separated. “We now have the possibility to specifically control the modification of chromosomes and to strengthen or loosen the links between properties,” Puchta explains. “This controlled restructuring of the genome will revolutionize future crop cultivation.”

Original Publication:

Natalja Beying, Carla Schmidt, Michael Pacher, Andreas Houben, and Holger Puchta: CRISPR/Cas9-mediated induction of heritable chromosomal translocations in Arabidopsis. Nature Plants, 2020. (DOI: https://doi.org/10.1038/s41477-020-0663-x External Link)

Abstract at https://www.nature.com/articles/s41477-020-0663-x External Link

Being “The Research University in the Helmholtz Association”, KIT creates and imparts knowledge for the society and the environment. It is the objective to make significant contributions to the global challenges in the fields of energy, mobility, and information. For this, about 9,300 employees cooperate in a broad range of disciplines in natural sciences, engineering sciences, economics, and the humanities and social sciences. KIT prepares its 24,400 students for responsible tasks in society, industry, and science by offering research-based study programs. Innovation efforts at KIT build a bridge between important scientific findings and their application for the benefit of society, economic prosperity, and the preservation of our natural basis of life. KIT is one of the German universities of excellence.

Credit: 
Karlsruher Institut für Technologie (KIT)

Nanoneedles to increase the capacity and robustness of digital memories

image: Some samples of FeRh metamagnetic material, ready to be analysed at the ALBA Synchrotron

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ICMAB-CSIC

Some memory devices where information from smartphones and computers is stored are based on a very precise control of the magnetic properties, at nanoscopic scale. The more precise this control is, the more storage capacity and speed they can have. In certain cases, the combination of ferromagnetism (where the magnetism of all the atoms in the material points in the same direction) and antiferromagnetism (where the magnetism of the atoms in the material points alternately in opposite directions) is used to store the information. One of the materials that can show these two arrangements is the alloy of iron and rhodium (FeRh), because it shows a metamagnetic transition between these two phases at a temperature very close to room temperature. In particular, it can change state from antiferromagnetic to ferromagnetic simply when heated. The antiferromagnetic state is more robust and secure than the ferromagnetic one, since it is not easily altered by the presence of magnets in its proximity, i.e. an external magnetic field cannot erase the information easily.

A team of researchers from the UAB, the ICMAB, and the ALBA Synchrotron, along with scientists from the UB and the ICN2, have used mechanical pressure to modify this transition and stabilize the antiferromagnetic state. The researchers have observed that pressing the surface of the iron-rhodium alloy with a nanometer-sized needle causes the magnetic state to change in a simple and localized way. By pressing on different areas of the material, the researchers have managed to generate antiferromagnetic nano-islands embedded in a ferromagnetic matrix, a very difficult task with the current techniques available. If the process is repeated over the entire surface of the alloy, the new technique can induce this change across large areas of the material drawing patterns with nanoscopic resolution with areas with different magnetic properties, generating structures as small as those that can currently be achieved using more complex methods.

Improvement to miniaturize magnetic devices

This is a major improvement to miniaturize the patterns that can be built with magnetic materials, an improvement in the resolution of the tools that engineers use to design the magnetic devices of the technology we use daily. "The idea is very simple," explains Ignasi Fina, researcher at the Institute of Materials Science of Barcelona (ICMAB-CSIC), "in phase transitions, everything you do to the material has a great impact on the other properties. Our alloy has a magnetic phase transition. With a nanometer-sized needle we change the magnetic order just by pressing the material. Specifically, it changes from ferromagnetic to antiferromagnetic. And since the needle is nanometric, the change is at the nanoscale. "

"The new technique based on the application of pressure using nanoneedles can allow the construction of magnetic nanometric devices with much smaller structures and much more robust and safe than the current ones, facilitating the manufacture of magnetic memories with different architectures that improve their capacities", says ICREA researcher from the Department of Physics at the UAB, Jordi Sort.

There are other techniques based on the application of voltage or intense magnetic fields to increase the stability of the antiferromagnetic phase of the alloy, but they cause large-scale changes in the entire material, which limit its control and miniaturization capacity. Applying pressure in a very localised manner offers unprecedented accuracy, affecting only small local areas at the nanometric scale. When pressing, the transition temperature of the alloy increases, the temperature at which its state changes, which involves the change in its magnetization.

In order to resolve the magnetic changes around an individual indentation on the nanoscale, the work used the Photoemission Electron Microscopy combined with X -ray magnetic circular dichroism at the CIRCE-PEEM beamline of the ALBA Synchrotron. "Our synchrotron light-based techniques make possible to resolve the changes on a really small scale", explains Michael Foerster, beamline scientist at ALBA.

Applications in other fields

The possible applications go beyond magnetic materials. The fact of modifying the properties of a material by applying pressure, i.e., by modifying the cell volume of its crystalline structure, can be extrapolated to other types of materials. Researchers believe that this technique opens the door to a new way of nanostructuring the physical and functional properties of materials, and of implementing new architectures in other types of non-magnetic nanodevices and microdevices.

Credit: 
Universitat Autonoma de Barcelona

Terrestrial bacteria can grow on nutrients from space

Interest in space exploration is increasing again. In the past decade, there has been renewed thinking about missions to the moon, perhaps even to Mars. As inevitable fellow travellers on the bodies of astronauts, spaceships, or equipment, terrestrial microorganisms will undoubtedly come into contact with extraterrestrial environments. Researchers from the Radboudumc describe in an article in Astrobiology that bacteria can survive on an 'extraterrestrial diet', which affected their pathogenic potential.

No matter how well astronauts and material are decontaminated, co-travelling microorganisms into space cannot be prevented. Given the enormous adaptability potential of bacteria, it is conceivable that they will sometimes survive space travel and be able to settle in an extraterrestrial environment.

For this study, four non-fastidious environment-derived bacterial species with pathogenic features were selected, including Klebsiella pneumoniae and Pseudomonas aeruginosa. A minimal 'diet' based on nitrogen, phosphorus, sulphur, iron and water to which carbohydrates found in carbonaceous meteorites were added was made to determine whether extraterrestrial survival and growth were possible. The four bacterial species were shown to survive and multiply on this minimal 'diet'.

In follow-up experiments, the team of researchers observed that the adaptation of bacteria, especially in the case of K. pneumoniae, caused changes in the cell membrane - the shell of the cell - as a result of which the immune system reacted more strongly to the bacteria. In short, the bacteria become more immunogenic. Research in cell culture, but also in mice, showed that the bacteria survive on extraterrestrial nutrients and become less virulent as a result of this necessary adaptation. At the same time, this research shows that bacteria can survive under these conditions, which means that the risk of infection among space travellers remains, precisely because - as other researchers have shown - a space journey has negative effects on the functioning of the immune system, making astronauts more susceptible to infections.

Credit: 
Radboud University Medical Center

Can e-learning help stem the threat of invasive alien species such as Japanese Knotweed?

image: Invasive Pennywort in Leeds, UK

Image: 
Stephanie Bradbeer

E-learning could be a crucial tool in the biosecurity fight against invasive alien species such as Japanese Knotweed, Zebra Mussels and Signal Crayfish according to a new study published in the academic journal 'Biological Invasions'.

According to previous studies, the cost of invasive alien species is estimated to be £1.7billion per annum. Governments across the UK have launched regular public awareness campaigns aimed such as 'Check Clean Dry' which was aimed at increasing awareness of biosecurity measures among people such as anglers and recreational boaters.

In the study, led by Cranfield University's Dr Caitriona Shannon, over 600 field workers and researcher were surveyed before, and six months after undertaking an e-learning course on invasive alien species and biosecurity practices. The study was carried out at the University of Leeds and funded by the Natural Environment Research Council (NERC).

After following the 'Better Biosecurity' e-Learning course, the participants showed not only a much greater knowledge of the risk of accidentally spreading invasive species through their work, but they also demonstrated an increase in biosecurity behaviour and cleaning practices.

The paper is the first to evaluate the effectiveness of e-learning as a tool to increase awareness, risk perception and biosecurity behaviour in relation to invasive alien species among individuals conducting work activities or research (fieldwork) in the field.

Dr Caitriona Shannon, Research Fellow in Perceptions & Behaviour at Cranfield University, said: "Invasive alien species do tremendous damage to the UK's natural environment and costs the economy billions of pounds a year. Often the spread of these species is accidental and caused by a low level of biosecurity knowledge and poor cleaning practices. This study shows the effectiveness of the role e-learning can play in improving the nation's biosecurity levels and safeguarding our indigenous species.

"As we all adapt to new ways of working, such as delivering teaching online, this study also illustrates just how effective e-learning can be as an educational tool."

Credit: 
Cranfield University

Novel electric impulses relieve the pain

image: The device creating the electrical pulses to stimulate the vagus nerve.

Image: 
TU Wien

The vagus nerve plays an important role in our body. It consists of various fibres, some of which connect to the internal organs, but the vagus nerve can also be found in the ear. It is of great importance for various body functions, including the perception of pain. Therefore, a lot of research has been focussing on how the vagus nerve can be stimulated effectively and gently with special electrodes.

An important step forward has now been achieved through a cooperation between the TU Wien (Vienna) and MedUni Vienna: the microanatomy of the vagus nerve branches in the human ear, in relation to auricular blood vessels, has been studied with a precision on a micrometer scale. Then a 3D computer model was created to calculate the optimal stimulation of nerve branches using tiny needle-shaped electrodes. These results were then tested on patients. This way, a novel stimulation pattern could be determined, which stimulates the vagus nerve in the ear particularly well.

Tiny electrodes directly on the ear

The team of the electrical engineer Prof. Eugenijus Kaniusas (Institute for Microwave and Circuit Engineering, TU Wien) in cooperation with the Medical University of Vienna has already conducted several studies in which chronic pain or even peripheral circulatory disorders were treated with electrical stimulation of the vagus nerve in the ear. In this process, small electrodes are inserted directly into the ear, which then - controlled by a small portable device worn on the neck - create specific electrical pulses.

A major challenge, however, is to attach the electrodes in exactly the right place. "It is important not to hit any blood vessels, and the electrodes have to be placed at exactly the right distance from the nerve," explains Eugenijus Kaniusas. "If the electrode is too far away, the nerve is not stimulated at all. If it is too close, the signal is too strong, leading to blockage of the nerve. The nerve can become 'tired' over time and eventually stop sending signals to the brain."

Until now, medical doctors had to rely on experience when positioning the electrodes in the ear. Now, for the first time, a microanatomical study has been carried out to investigate in great detail spatial arrangements of the nerve fibres and blood vessels in the ear. For this purpose, sectional images of tissue samples were photographed in high resolution and then combined into a three-dimensional model on the computer by Babak Dabiri Razlighi, a researcher in Eugenijus Kaniusas' team.

"The blood vessels can be made clearly visible in patients by shining light through the ear", says Prof. Wolfgang J. Weninger from MedUni Vienna. "The nerves, however, cannot be seen. Our microanatomical measurements on donated human bodies now tell us exactly where the nerves run in relation to blood vessels, as well as the average distance between blood vessels and nerves at certain important positions of the ear. This helps us to find the correct spot for placing the stimulation electrodes."

Three-phase signal for optimal stimulation

The computer model can also be used to calculate which electrical signals should be used. Not only the strength of the signal is important, but also its shape: "In our computer simulation, it was shown for the first time that from a biophysical point of view, a triphasic signal pattern should be helpful, similar to what is known from power engineering - only with much lower magnitude," reports Kaniusas. "Three different electrodes each deliver oscillating electrical pulses, but these pulses are not in synch, there needs to be a specific time delay."

This type of stimulation was tested on people suffering from chronic pain - and the experiments showed that indeed the triphasic stimulation pattern is particularly effective.

"Vagus nerve stimulation is a promising technique, the effect of which has been validated with our new findings and is now being further improved," says Eugenijus Kaniusas. "Vagus nerve stimulation is often a lifesaving option, especially for people with chronic pain who have already been treated with other methods and do not respond to medication anymore."

Credit: 
Vienna University of Technology

Honeybees: Pesticides disrupt nursing behavior and larval development

image: side view of the construction and camera view of the brood area. The brood area of the bees was filmed with a camera (green) through a dome lighting (grey). The specially designed hive (brown) was only 2.4 cm wide, so that the bees would raise young as quickly as possible (right)

Image: 
Paul Siefert/Bee Research Institute Oberursel/Goethe University Frankfurt

A newly developed video technique has allowed scientists at Goethe University Frankfurt at the Bee Research Institute of the Polytechnical Society to record the complete development of a honey bee in its hive for the first time. It also led to the discovery that certain pesticides - neonicotinoids - changed the behaviour of the nurse bees: researchers determined that they fed the larvae less often. Larval development took up to 10 hours longer. A longer development period in the hive can foster infestation by parasites such as the Varroa mite (Scientific Reports, DOI 10.1038/s41598-020-65425-y).

Honey bees have very complex breeding behaviour: a cleaning bee cleans an empty comb (brood cell) of the remains of the previous brood before the queen bee lays an egg inside it. Once the bee larva has hatched, a nurse bee feeds it for six days. Then the nurse bees caps the brood cell with wax. The larva spins a cocoon and goes through metamorphosis, changing the shape of its body and developing a head, wings and legs. Three weeks after the egg was laid, the fully-grown bee hatches from the cocoon and leaves the brood cell.

Using a new video technique, scientists at Goethe University Frankfurt have now succeeded for the first time in recording the complete development of a honey bee in a bee colony at the Bee Research Institute of the Polytechnical Society. The researchers built a bee hive with a glass pane and were thus able to film a total of four bee colonies simultaneously over several weeks with a special camera set-up. They used deep red light so that the bees were not disturbed, and recorded all the movements of the bees in the brood cells.

The researchers were particularly interested in the nursing behaviour of the nurse bees, to whose food (a sugar syrup) they added small amounts of pesticides known as neonicotinoids. Neonicotinoids are highly effective insecticides that are frequently used in agriculture. In natural environments, neonicotinoids arrive in bee colonies through nectar and pollen collected by the bees. It is already known that these substances disturb the navigational abilities and learning behaviour of bees. In a measure criticised by the agricultural industry, the European Union has prohibited the use of some neonicotinoids in crop cultivation.

Using machine learning algorithms developed by the scientists together with colleagues at the Centre for Cognition and Computation at Goethe University, they were able to evaluate and quantify the nursing behaviour of the nurse bees semi-automatically. The result: even small doses of the neonicotinoids Thiacloprid or Clothianidin led to the nurse bees feeding the larva during the 6-day larval development less frequently, and consequently for a shorter daily period. Some of the bees nursed in this manner required up to10 hours longer until the cell was capped with wax.

"Neonicotinoids affect the bees' nervous systems by blocking the receptors for the neurotransmitter acetylcholine," explains Dr Paul Siefert, who carried out the experiments in Professor Bernd Grünewald's work group at the Bee Research Institute Oberursel. Siefert: "For the first time, we were able to demonstrate that neonicotinoids also change the social behaviour of bees. This could point to the disruptions in nursing behaviour due to neonicotinoids described by other scientists." Furthermore, parasites such as the feared Varroa mite (Varroa destructor) profit from an extended development period, since the mites lay their eggs in the brood cells shortly before they are capped: if they remain closed for a longer period, the young mites can develop and multiply without interruption.

However, according to Siefert, it still remains to be clarified whether the delay in the larval development is caused by the behavioural disturbance of the nurse bee, or whether the larvae develop more slowly because of the altered jelly. The nurse bees produce the jelly and feed it to the larvae. "From other studies in our work group, we know that the concentration of acetylcholine in the jelly is reduced by neonicotinoids," says Siefert. "On the other hand, we have observed that with higher dosages, the early embryonal development in the egg is also extended - during a period in which feeding does not yet occur." Additional studies are needed to determine which factors are working together in these instances.

In any case, the new video technique and the evaluation algorithms offer great potential for future research projects. In addition to feeding, behaviours for heating and construction were also able to be reliably identified. Siefert: "Our innovative technology makes it possible to gain fundamental scientific insights into social interactions in bee colonies, the biology of parasites, and the safety of pesticides."

Credit: 
Goethe University Frankfurt