Tech

Holography is best known for its ability to produce 3D images (holograms) by recording an interference pattern of light scattered by an object with some reference wave. This simple optical experiment records the amplitude as well as the normally invisible phase of the underlying electric field. Once known, this information can be used to simultaneously localize many individual particles in all 3 dimensions.

In biology though holography is less common, as the most suitable technique, combining sensitivity, resolution and specificity, is fluorescence imaging which is widely used in live cell imaging. It would be fantastic if one could combine fluorescence microscopy with holography and thus retrieve the full 3D distribution of fluorescently labeled entities inside a cell. Unfortunately, fluorescence is incoherent, with a very short path-length and phase memory, complicating the creation of a reference wave for any fluorescence interference and hence holography.

Now holographic fluorescence imaging is presented by ICFO researchers Matz Liebel and Jaime Ortega-Arroyo, working the groups of ICREA professors at ICFO Niek van Hulst and Romain Quidant. They implemented a scheme that eliminates the need for a reference wave. Instead, they used the intrinsic phase information of each individual photon to access its phase via a technique called lateral shearing-interferometry. In essence, rather than directly measuring the phase they measured the position-dependent phase change in wide-field using a CMOS camera. Next, they computationally integrated this information to recover the full electric field of fluorescent light with single-molecule sensitivity. The novel scheme expands the principle of digital holography to fast fluorescent detection by eliminating the need for phase cycling and enables 3D-tracking of individual nanoparticles with an in-plane resolution of 15 nm and a z-range of 8 micrometer.

Liebel and Ortega-Arroyo then teamed up with the group of Hakho Lee at the Massachusetts General Hospital in Boston, to image and track the 3D motion of extracellular vesicles (EVs) inside live cells. They resolved both near-isotropic 3D diffusion as well as directional transport. Interestingly, for extended observation windows, they observed a transition toward anisotropic motion with the EVs being transported over long distances in the axial plane, confined in the horizontal dimension.

The fluorescence holography is directly compatible with present-day super-resolution modalities and equally well suited for other volumetric imaging challenges, such as tracking in tissue or calcium imaging. The work was recently published in Science Advances.

Raman spectroscopy is widely used in analytical sciences to identify molecules via their structural fingerprint. In the biological context the Raman response provides a valuable label-free specific contrast that allows distinguishing different cellular and tissue contents. Unfortunately, spontaneous Raman scattering is very weak, over ten orders of magnitude weaker than fluorescence. Unsurprisingly, fluorescence microscopy is often the preferred choice for applications such as live cell imaging. Luckily, Raman can be enhanced dramatically on metal surfaces or in metallic nanogaps and this surface enhanced Raman scattering (SERS) can even overcome the fluorescence response. Nanometric SERS probes are thus promising candidates for biological sensing applications, preserving the intrinsic molecular specificity. Still, the effectiveness of SERS probes depends critically on the particle size, stability and brightness, and, so far, SERS-probe based imaging is rarely applied.

Now ICFO researchers Matz Liebel and Nicolas Pazos-Perez, working in the groups of ICREA professors Niek van Hulst (ICFO) and Ramon Alvarez-Puebla (Univ. Rovira i Virgili) have presented "holographic Raman microscopy". First, they synthesized plasmonic superclusters from small nanoparticle building blocks, to generate very strong electric fields in a restricted cluster size. These extremely bright SERS nanoprobes require very low illumination light exposure in the near-infrared, thus reducing potential photo-damage of live cells to a minimum, and allow wide-field Raman imaging. Second, they took advantage of the bright SERS probes to realize 3D holographic imaging, using the scheme for incoherent holographic microscopy developed by Liebel and team in a study in Science Advances (Link). Remarkably, the incoherent Raman scattering is made to "self-interfere" to achieve Raman holography for the first time.

Liebel and Pazos-Perez demonstrated Fourier transform Raman spectroscopy of the wide-field Raman images and were able to localize single-SERS-particles in 3D volumes from one single-shot. The authors then used these capabilities to identify and track single SERS nanoparticles inside living cells in three dimensions.

The results, published in Nature Nanotechnology represent an important step towards multiplexed single-shot three-dimensional concentration mapping in many different scenarios, including live cell and tissue interrogation and possibly anti-counterfeiting applications.

A team of chemists from RUDN University suggested a universal method to synthesize thienoindolizine derivatives. Because of their special properties, these substances can be used to manufacture antibacterial and antitumor drugs, as well as new materials for optoelectronics. The results of the study were published in the Chemistry Select journal.

Thienoindolizines are tricyclic compounds containing sulfur and nitrogen heteroatoms. Thienoindolizines are combinations of two structural elements: thiophene and indolizine. Both these substances have many important biological characteristics, such as antitumor and antibacterial properties. Thienoindolizines are used not only in biomedicine but also in optoelectronics to create new materials. However, the existing synthesis methods work only for a small group of initial substances and are unable to secure the presence of any functional atom groups in the product. A team of chemists from RUDN University was the first to suggest a universal approach to the synthesis of thienoindolizines based on two- and three-component thienopyridine reactions.

"Currently, there are no universal methods for the synthesis of thienoindolizine derivatives that would not only form the framework of a compound but also allow for the addition of different functional substituents. Therefore, researchers focus on affordable and mild approaches to the creation of thienoindolizine structures from simple precursors," explained Alexander Titov, PhD, and a senior lecturer at the Department of Organic Chemistry, RUDN University.

The team based the synthesis reaction on compounds from the group of heterocycles with sulfur and nitrogen atoms - thienopyridine derivatives. For them to turn into thienoindolizines, they required one more cycle and several functional groups to be added to them. The scientists studied the reactions of thienopyridine derivatives with substances from six different groups: alkynes, aldehydes, alcohols, and other organic compounds.

The RUDN team tried different reaction conditions for different reagents: microwave radiation, inert atmosphere, solvents, catalysts, different temperatures within the 140-150°C range, and different reaction times--from 10 minutes to several hours. As a result, they managed to obtain 28 thienoindolizine derivatives. For some of them, the team identified optimal synthesis conditions that ensured a high yield of 70% or more. Without the catalysts and proper conditions, the yield remained at the level of 10-20%.

Seven of the obtained compounds were tested for their ability to kill tumor cells or cytotoxicity. Compared to existing chemotherapy drugs, the activity of these substances was insignificant. However, three of them had cytotoxic properties and required further research. The study of the antibacterial activity of the obtained compounds led to similar results: one out of six tested substances turned out to be efficient against hay bacillus and Candida fungi.

"The synthetic and biological aspects of thienoindolizines remain largely understudied. We believe that a combination of two biologically active substances in one molecule must have its advantages. We will continue to develop new methods to synthesize these substances and control their characteristics. In the future, we expect to develop a family of heterocyclic compounds with known antitumor, antibacterial, and painkilling properties," added Alexander Titov, PhD, and a senior lecturer at the Department of Organic Chemistry, RUDN University.

Warming waters and oxygen depletion in the Red Sea could slow the flow of organic carbon from the surface into the deep ocean where it can be stored, out of reach of the atmosphere. A KAUST team has used an underwater robot to investigate the little-studied mesopelagic, or "twilight," zone, at depths of between 100 and 1000 meters.

The oceans absorb billions of tons of carbon dioxide (CO2) from the atmosphere each year that either dissolves or is transformed into organic carbon by plants and phytoplankton in the sunlit shallows (0 - 100m). Most of this organic carbon is converted back into CO2 by microorganisms as it falls through the mesopelagic zone, but some of it eventually sinks into the deep ocean, where it can remain for centuries.

Understanding what controls the fate of organic carbon at different depths could help scientists predict how the oceans will absorb and store atmospheric CO2 in the future. Malika Kheireddine and her team used an underwater robot equipped with bio-optical sensors to measure particulate organic carbon (POC) variations between the surface and the bottom of the mesopelagic zone in the northern Red Sea, where sea temperatures are rising particularly fast. "The Red Sea offers unrivalled opportunities as a natural laboratory for studying the impact of climate change on the fate of organic carbon," says Kheireddine.

Throughout 2016, the device also measured water temperature, salinity, density and oxygen concentrations. "Our observations allowed us to estimate the rates at which POC is converted back into CO2 by marine microorganisms," explains Giorgio Dall'Olmo, a co-author from the UK National Centre for Earth Observation, "and how these microorganisms are affected by temperature and oxygen levels."

In the Red Sea's warm and oxygen-starved waters, the conversion occurred mainly in the shallowest, most productive layer of the mesopelagic zone; only 10 percent of POC sank below 350 meters. "The conversion rates could be expressed as a function of temperature and oxygen concentration," adds Kheireddine, "which could help us predict how climate change will affect these rates in the future."

The team was surprised to find that more than 85 percent of POC was broken down within a few days of entering the mesopelagic zone, whereas the rest drifted for weeks to months before being consumed. There are multiple drivers of organic carbon transfer and transformation in tropical seas.

"Underwater gliders in the Red Sea are collecting continuous data that could reveal the effects of physical processes, such as eddies and coastal currents, on these biogeochemical processes," says group leader Burton Jones, a marine scientist at KAUST.

"The fate of organic carbon in the oceans affects the global climate," says Kheireddine. "Our findings will help refine models showing whether the amount of carbon sinking in the ocean is increasing or decreasing." The deeper organic carbon sinks before it is converted to CO2, the longer it is likely to remain there, locked away from the atmosphere.

Scientists of Tomsk Polytechnic University, in cooperation with the Czech colleagues have developed a new hydrogel for agriculture. It is meant to retain moisture and fertilizers in soil. The difference of the new hydrogel from other formulations is that it is made entirely of natural components and degrades in soil into nontoxic products to humans, animals, and plants. The research results are published in the Journal of Cleaner Production (IF: 7, 246; Q1).

Hydrogels are used in agriculture and forestry to retain moisture in soil, which directly affects germination. They are also used in combination with fertilizers as hydrogels reduce volatilization of fertilizers and therefore control fertilizer release.

"Due to the hydrogels, plants require less watering and fertilization. On the one hand, it is important for fresh water conservation on the planet, on the other hand, it reduces the harmful effect of fertilizers to the soil. Most of the hydrogels available on the market are made of polyacrylamide and polyacrinolintrile. They are not fully biodegradable, that is why they are considered potential soil contaminants. Even though the components themselves are not toxic, their commercial formulations contain residual amounts of acrylamide, which is a neurotoxic and carcinogen substance. We used whey protein and alginic acid as primary components in our research work. These are affordable, natural and completely non-toxic components. This is the main advantage of our hydrogel," Antonio Di Martino, one of the article authors, associate professor of the TPU Research School of Chemistry & Applied Biomedical Sciences, says.

The process of obtaining the hydrogel suggested by the authors of the research is simple: the primary components must be mixed in a solution, dried, and compressed into a tablet. In contact with liquids, the substance swells and becomes gel-like.

"We also added urea in the mixture which is a well-known fertilizer. Over time, the hydrogel degrades in soil gradually and evenly releasing the fertilizer. Moreover, the hydrogel itself degrades into carbon and nitrogen over time, while nitrogen is a widely used macronutrient in agriculture and an essential structural material for plants. The laboratory experiments showed that the hydrogel can be used a few more times after a full release of moisture," Antonio Di Martino notes.

In the future, the scientists will continue experimenting and searching for new materials for a controlled application of fertilizers in soil.

Researchers from the Centre for Audio, Acoustics and Vibration at the University of Technology Sydney are exploring technology for those wanting a quieter life!

Reporting in the journal Scientific Reports (a Nature Springer publication), the team of Tong Xiao, Xiaojun Qiu and Benjamin Halkon highlight the positive impacts for health and wellbeing of their 'virtual Active Noise Control/Cancellation (ANC) headphone' and its enhanced ability to reduce ambient noise.

By integrating laser-based technology - which can deal with high frequencies - into headrests they eliminate the need for users to wear head/ear phones or buds.

So, in an open plan or home office, you can cancel out colleagues' chatter, ringing phones, the neigbour's mower, the dog barking, and the kettle whistling while you work without the discomfort / inconvenience of a set of headphones...

And, in enclosed spaces such as cars and aircraft, the virtual headset can significantly reduce all the extraneous noises that can enter the environment, decreasing distractions and making work/rest easier. For machinery and equipment operators, it provides a solution that reduces fatigue often caused by enclosed wearable headphones.

"What we achieved for this ANC headrest/chair is that the ANC performance is significantly improved over the current state-of-the-art result. In particular, some of the high-pitched noise, previously difficult to cancel out, can now be reduced," said Tong Xiao.

Attempts to deliver a practical ANC headset have been decades in progress.

The system they describe is a remote acoustic approach using a laser Doppler vibrometer (LDV) and a small, lightweight and retro-reflective membrane pick-up placed in the cavum concha of a user's ear.

LDVs typically have very high sensitivity with commercially available instruments able to resolve vibration displacements down to pm and velocities down to nm/s resolution. The membrane pick-up can be designed to be small and lightweight and have a wide dynamic range.

"The results show that more than 10 dB sound attenuation can be
obtained for an ultra-broadband frequency range up to 6 kHz in the ears for multiple sound sources and for various types of common environmental noise," said Xiao.

"This virtual ANC headphone system has significantly better performance than any other virtual error sensing solution in the published literature thus far."

A new University of Wollongong study overcomes a major challenge of thermoelectric materials, which can convert heat into electricity and vice versa, improving conversion efficiency by more than 60%.

Current and potential future applications range from low-maintenance, solid-state refrigeration to compact, zero-carbon power generation, which could include small, personal devices powered by the body’s own heat.

“The decoupling of electronic (electron-based) and thermal (phonon-based) transport will be a game-changer in this industry,” says the UOW’s Prof Xiaolin Wang.

Thermoelectric applications and challenges

Bismuth telluride-based materials (Bi2Te3, Sb2Te3 and their alloys) are the most successful commercially-available thermoelectric materials, with current and future applications falling into two categories: converting electricity into heat, and vice versa:

Converting electricity into heat: reliable, low-maintenance solid-state refrigeration (heat pump) with no moving parts, no noise, and no vibration.
Converting heat into electricity including fossil-free power generation from a wide range of heat sources or powering micro-devices ‘for free’, using ambient or body temperature.

Heat ‘harvesting’ takes advantage of the free, plentiful heat sources provided by body heat, automobiles, everyday living, and industrial process. Without the need for batteries or a power supply, thermoelectric materials could be used to power intelligent sensors in remote, inaccessible locations.

An ongoing challenge of thermoelectric materials is the balance of electrical and thermal properties: In most cases, an improvement in a material’s electrical properties (higher electrical conductivity) means a worsening of thermal properties (higher thermal conductivity), and vice versa.

“The key is to decouple thermal transport and electrical transport”, says lead author, PhD student Guangsai Yang.

Better efficiency through decoupling

The team added a small amount of amorphous nano-boron particles to bismuth telluride-based thermoelectric materials, using nano-defect engineering and structural design.

Amorphous nano boron particles were introduced using the spark plasma sintering (SPS) method.

“This reduces the thermal conductivity of the material, and at the same time increases its electron transmission”, explains corresponding author Prof Xiaolin Wang.

“The secret of thermoelectric materials engineering is manipulating the phonon and electron transport,” explains Professor Wang.

Because electrons both carry heat and conduct electricity, material engineering based on electron transport alone is prone to the perennial tradeoff between thermal and electrical properties.

Phonons, on the other hand, only carry heat. Therefore, blocking phonon transport reduces thermal conductivity induced by lattice vibrations, without affecting electronic properties.

“The key to improving thermoelectric efficiency is to minimize the heat flow via phonon blocking, and maximize electron flow via (electron transmitting),” says Guangsai Yang. “This is the origin of the record-high thermoelectric efficiency in our materials.”

The result is record-high conversion efficiency of 11.3%, which is 60% better than commercially-available materials prepared by the zone melting method.

As well as being the most successful commercially-available thermoelectric materials, bismuth telluride-based materials are also typical topological insulators.

The study

Ultra-High Thermoelectric Performance in Bulk BiSbTe/Amorphous Boron Composites with Nano-Defect Architectures was published in Advanced Energy Materials in September 2020, and selected as the cover story for the November edition. DOI 10.1002/aenm.202000757

As well as support from the Australian Research Council (Future Fellowship, Centre of Excellence and Linkage Infrastructure Equipment and Facilities programs) funding was received from the China Scholarship Council and National Natural Science Foundation of China.

Experimentation facilities included the University of Wollongong Electron Microscopy Centre, with technical support from the Australian Centre for Microscopy and Microanalysis (ACMM) at the University of Sydney.

Novel material studies at FLEET

The properties of novel and atomically-thin materials are studied at FLEET, an Australian Research Council Centre of Excellence, within the Centre’s Enabling technology A.

The Centre for Future Low-Energy Electronics Technologies (FLEET) is a collaboration of over a hundred researchers, seeking to develop ultra-low energy electronics to face the challenge of energy use in computation, which already consumes 8% of global electricity, and is doubling each decade.

Project leader and co-author Prof Xiaolin Wang leads FLEET’s University of Wollongong node, as well as leading the Enabling Technology team developing the novel and atomically thin materials underpinning FLEET’s search for ultra-low energy electronics, managing synthesis and characterisation of novel 2D materials at the University of Wollongong

Journal

Advanced Energy Materials

DOI

10.1002/aenm.202000757

A material that mimics human skin in strength, stretchability and sensitivity could be used to collect biological data in real time. Electronic skin, or e-skin, may play an important role in next-generation prosthetics, personalized medicine, soft robotics and artificial intelligence.

"The ideal e-skin will mimic the many natural functions of human skin, such as sensing temperature and touch, accurately and in real time," says KAUST postdoc Yichen Cai. However, making suitably flexible electronics that can perform such delicate tasks while also enduring the bumps and scrapes of everyday life is challenging, and each material involved must be carefully engineered.

Most e-skins are made by layering an active nanomaterial (the sensor) on a stretchy surface that attaches to human skin. However, the connection between these layers is often too weak, which reduces the durability and sensitivity of the material; alternatively, if it is too strong, flexibility becomes limited, making it more likely to crack and break the circuit.

"The landscape of skin electronics keeps shifting at a spectacular pace," says Cai. "The emergence of 2D sensors has accelerated efforts to integrate these atomically thin, mechanically strong materials into functional, durable artificial skins."

A team led by Cai and colleague Jie Shen has now created a durable e-skin using a hydrogel reinforced with silica nanoparticles as a strong and stretchy substrate and a 2D titanium carbide MXene as the sensing layer, bound together with highly conductive nanowires.

"Hydrogels are more than 70 percent water, making them very compatible with human skin tissues," explains Shen. By prestretching the hydrogel in all directions, applying a layer of nanowires, and then carefully controlling its release, the researchers created conductive pathways to the sensor layer that remained intact even when the material was stretched to 28 times its original size.

Their prototype e-skin could sense objects from 20 centimeters away, respond to stimuli in less than one tenth of a second, and when used as a pressure sensor, could distinguish handwriting written upon it. It continued to work well after 5,000 deformations, recovering in about a quarter of a second each time. "It is a striking achievement for an e-skin to maintain toughness after repeated use," says Shen, "which mimics the elasticity and rapid recovery of human skin."

Such e-skins could monitor a range of biological information, such as changes in blood pressure, which can be detected from vibrations in the arteries to movements of large limbs and joints. This data can then be shared and stored on the cloud via Wi-Fi.

"One remaining obstacle to the widespread use of e-skins lies in scaling up of high-resolution sensors," adds group leader Vincent Tung; "however, laser-assisted additive manufacturing offers new promise."

"We envisage a future for this technology beyond biology," adds Cai. "Stretchable sensor tape could one day monitor the structural health of inanimate objects, such as furniture and aircraft."

Kanazawa, Japan - Pharmaceuticals, plastics, and many other chemical products have transformed human life. To prepare these products, chemists often use a catalyst--frequently based on rare metals--at various points in their syntheses. Although rare-metal catalysts are incredibly useful, their limited supply means that their use is unsustainable in the long term. Synthetic chemists need an alternative.

In a study recently published in Angewandte Chemie, researchers from Kanazawa University report such an alternative. Their research on a broad class of chemical reactions that are common in pharmaceutical and other syntheses will pave the way to a more sustainable chemical industry.

The 2010 Nobel Prize in Chemistry went to researchers who used catalysts based on palladium metal to perform a common type of chemical reaction known as cross-coupling. Such catalysts work very well for synthesizing what are known as congested quaternary carbon centers, which are common in molecules used in agriculture and medicine. However, for long-term sustainability, researchers need an alternative to rare-metal catalysts.

"We used benzylic organoborates to perform tertiary alkylative cross-coupling of aryl or alkyl electrophiles," says Hirohisa Ohmiya, corresponding author of the study. "Our procedure does not use rare elements and is a straightforward route to quaternary carbon centers."

The researchers' initial studies consisted of a tertiary benzylboronate that is first activated by a potassium alkoxide base to become a benzyl anion. This anion then undergoes a cross-coupling reaction with a secondary alkyl chloride electrophile.

"The reaction has broad scope," explains corresponding author Hirohisa Ohmiya. "For example, replacing the phenyl group of the boronate with various aromatic rings was successful, and the electrophile can be a wide range of rings and linear chains."

Subsequent studies replaced the secondary alkyl chloride with various aryl nitriles, aryl ethers, and aryl fluorides. Many of these reactions were successful, such as those with 4-cyanopyridine and 4-fluorophenylbenzene.

A comment in Nature on November 19 indicates that the COVID-19 pandemic has disrupted supply chains to various rare metals that are pertinent to the chemical industry. Hundreds of mines and factories have been closed, and many national borders are more restricted than before the pandemic. A long-term solution to supply chain disruptions is to develop synthetic protocols that don't use rare metals. The research described here is an important part of that effort and will help make chemical syntheses more sustainable for future generations.

Scientists have developed a new biomaterial that helps bones heal faster by enhancing adults' stem cell regenerative ability.

The study, led by researchers from RCSI University of Medicine and Health Sciences and CHI at Temple Street, is published in the current edition of Biomaterials, the highest ranked journal in the field of biomaterials science.

The researchers had previously discovered a molecule called JNK3, which is a key driver of children's stem cells being more sensitive to their environment and regenerating better than adults'. This explains, at least partially, why children's bones are able to heal more quickly. Building on this knowledge, they created a biomaterial that mimics the structure of bone tissue and incorporates nanoparticles that activate JNK3.

When tested in a pre-clinical model, the biomaterial quickly repaired large bone defects and reduced inflammation after a month of use. The biomaterial also proved to be safer and as effective as other drug-loaded biomaterials for bone repair whose use has been controversially associated with dangerous side-effects, including cancer, infection or off-site bone formation.

"While more testing is needed before we can begin clinical trials, these results are very promising," said Professor Fergal O'Brien, the study's principal investigator and RCSI's Director of Research and Innovation.

"This study has shown that understanding stem cell mechanobiology can help identify alternative therapeutic molecules for repairing large defects in bone, and potentially other body tissues. In a broader sense, this project is a great example of how growing our understanding of mechanobiology can identify new treatments that directly benefit patients - a key goal of what we do here at RCSI."

The work was carried out by researchers from the Tissue Engineering Research Group (TERG) and SFI AMBER Centre based at RCSI in collaboration with a team from Children's Health Ireland (CHI) at Temple Street Hospital. The CHI at Temple Street team was led by Mr Dylan Murray, a lead consultant craniofacial, plastic and reconstructive surgeon at the National Paediatric Craniofacial Centre (NPCC), who has collaborated with the RCSI team for a number of years.

"It is very exciting to be part of this translational project in which the participation and consent of the patients of the NPCC at Temple Street -whom donated harvested bone cells- have contributed immensely to this success," said Mr Murray.

The research was funded by the Children's Health Foundation Temple Street (RPAC-2013-06), Health Research Board of Ireland under the Health Research Awards - Patient-Oriented Research scheme (HRA-POR-2014-569), European Research Council (ERC) under Horizon 2020 (ReCaP project #788753) and Science Foundation Ireland (SFI) through the Advanced Materials and Bioengineering Research (AMBER) Centre (SFI/12/RC/2278).

"We have now proven that identifying mechanobiology-inspired therapeutic targets can be used to engineer smart biomaterials that recreate children's superior healing capacity in adults' stem cells," said Dr Arlyng Gonzalez Vazquez, the study's first author and a research fellow in TERG.

"We are using the same strategy to develop a novel biomaterial for cartilage repair in adults. A follow-up project recently funded by Children's Health Foundation Temple Street is also aiming to utilise a similar scientific approach to identify if the molecular mechanisms found in children diagnosed with craniosynostosis (a condition where the skull fuses to early and in his brain growth) could be used to develop a therapeutic biomaterial that accelerates bone formation and bone healing in adults."

In a paper published in NANO, researchers study the role of memristors in neuromorphic computing. This novel fundamental electronic component supports the cloning of bio-neural system with low cost and power.

Contemporary computing systems are unable to deal with critical challenges of size reduction and computing speed in the big data era. The Von Neumann bottleneck is referred to as a hindrance in data transfer through the bus connecting processor and memory cell. This gives an opportunity to create alternative architectures based on a biological neuron model. Neuromorphic computing is one of such alternative architectures that mimic neuro-biological brain architectures.

The humanoid neural brain system comprises approximately 100 billion neurons and numerous synapses of connectivity. An efficient circuit device is therefore essential for the construction of a neural network that mimics the human brain. The development of a basic electrical component, the memristor, with several distinctive features such as scalability, in-memory processing and CMOS compatibility, has significantly facilitated the implementation of neural network hardware.

The memristor was introduced as a "memory-like resistor" where the background of the applied inputs would alter the resistance status of the device. It is a capable electronic component that can memorise the current in order to effectively reduce the size of the device and increase processing speed in neural networks. Parallel calculations, as in the human nervous system, are made with the support of memristor devices in a novel computing architecture.

System instability and uncertainty have been described as current problems for most memory-based applications. This is the opposite of the biological process. Despite noise, nonlinearity, variability and volatility, biological systems work well. It is still unclear, however, that the e?ectiveness of biological systems actually depends on these obstacles. Neural modeling is sometimes avoided because it is not easy to model and study. The possibility of exploiting these properties is therefore, of course, a critical path to success in the achievement of arti?cial and biological systems.

By analyzing the gene expression of single cells, algorithms are able to not only reconstruct their original location in the tissue, but also to determine details about their function. Teams led by Kai Schmidt-Ott and Nikolaus Rajewsky have published their findings in JASN, using the kidney as an example.

To find out exactly what happens when in a particular cell, scientists look at its transcriptome - the totality of all genes that are expressed and transcribed into RNA at a specific point in time. Today, single-cell RNA sequencing allows the expression profiles of many thousands of cells to be analyzed simultaneously. But this method requires the cells to first be detached from their cell aggregate, which causes information on the cell's original location in the tissue to be lost.

Nevertheless, gene expression enables this information to be reconstructed bioinformatically. "We wanted to know whether, in addition to providing a reconstruction of the cells' spatial arrangement, algorithms could also be used to gain functional information from single-cell sequencing - for example, about the environmental conditions of kidney cells," says Dr. Christian Hinze from Charite - Universitaetsmedizin Berlin and the Molecular and Translational Kidney Research Lab at the Max Delbrueck Center for Molecular Medicine in the Helmholtz Association (MDC). He is the first author of the study, which has now been published in the Journal of the American Society of Nephrology (JASN).

A heterogeneous organ

Spatially speaking, the kidneys of mammals are very heterogeneous. The two bean-shaped organs consist of a renal cortex and an outer and inner renal medulla. The inner renal medulla is where highly concentrated urine forms after undergoing various filtering processes, and is then excreted via the ureter and bladder. "Over 15 different cell types are found in a mouse kidney, for example - and some are present in all three kidney regions," says Hinze. Think it sounds like an impossible puzzle? Actually, it's not. Because the microenvironment in which a cell lives is also reflected in its gene expression.

Back in 2019, the team led by Professor Nikolaus Rajewsky, Scientific Director of the MDC's Berlin Institute for Medical Systems Biology (BIMSB) and one of the current study's last authors, developed the program NovoSpaRc, which allows the spatial arrangement of cells within an organ to be reconstructed based on gene expression. In initial studies, the researchers found that cells that are arranged close to each other also resemble one another in terms of the activity of certain genes. "This is because they have to function in the same environment," explains Hinze. "In the inner renal medulla, for example, conditions are much more severe than in the renal cortex. This is because the osmolality of the environment - i.e., the concentration of dissolved substances in the cell's surroundings - increases drastically from the outside to the inside of the organ."

An algorithm solves the 3D puzzle

For their current study, the researchers concentrated primarily on a specific cell type in the kidney known as principal cells. These cells play an important role in the reabsorption of blood salts and water and are distributed throughout the entire organ. Thanks to the particular gene expression of this cell type, they were able to extract these cells from the single-cell data of mouse kidneys. They then subjected the cells to the NovoSpaRc algorithm, which organized the expression data by comparing more than 800 selected genes for similarities. "NovoSpaRc works like someone doing a jigsaw puzzle," explains bioinformatician Dr. Nikos Karaiskos from the Rajewsky Lab. "It tries to bring the different parts, which are the cells, together in such a way that the end result makes sense." Karaiskos is also co-developer of NovoSpaRc and leading the DFG-funded "Unbiased Single-Cell Spatial Transcriptomics" project.

And the algorithm succeeded in completing the puzzle. "The gene expression analysis confirmed that osmolality in the tissue greatly increases along the axis from the renal cortex to the inner medulla," says Hinze. "At higher salt concentrations, the cell switches on certain protective genes so that it can survive in this environment." The researchers verified their results by carrying out comparative tests on tissue from genetically modified mice, in which the normal salt gradient had been disrupted.

An atlas of gene expression in the kidney

So, to what extent does spatial single-cell analysis actually advance kidney research? "We are now able to more accurately predict the spatial gene expression in the kidney, and thus also to make deductions about functions or malfunctions in certain regions of the kidney," explains Professor Kai Schmidt-Ott, a nephrologist at the MDC and Charite and co-last author of the study. "We were already able to take a first step and create a high-resolution spatial atlas of the gene expression of healthy mouse kidneys, which we are now making available online to the scientific community."

Previous data analyses are limited to healthy and genetically modified kidneys from animal models. Now, the researchers want to turn their attention to sick kidneys. "We believe that the new methods can also give us a better understanding of the regional molecular processes in kidney disease," says Schmidt-Ott.

Reconstructed in seconds

Combining single-cell RNA sequencing with bioinformatic tissue reconstruction has a number of benefits. For one, several experiments are usually necessary to study different regions of an organ. "Now, we can simply cut up the entire kidney, sequence it, and determine all sorts of information from the transcriptomes - which saves a lot of time and money on research," Hinze emphasizes. It can be used to investigate practically everything that is reflected in the gene expression of a cell - complete with spatial resolution. This includes the oxygen or nutrient supply of the tissue, or, as is the case here, the osmolality. What is particularly exciting, however, is that existing archived data sets can be used to answer new research questions - even if samples of the corresponding cells have long since ceased to exist.

And one last benefit: It takes practically no time for the expression data puzzle to be completed. "In one minute, the algorithm scans the data of a couple of thousand cells," says Karaiskos. "And for a full reconstruction of the small mouse kidney, it only needed a few seconds."

Scientists have conducted a 'molecular dissection' of a part of the virus that causes foot-and-mouth disease, to try and understand why the pathogen is so infectious.

Foot-and-mouth disease is a highly contagious infection of cloven-hoofed animals, which impacts on agricultural production and herd fertility. Global economic losses due to the disease have been estimated at between $6.5 billion and $22.5 billion each year, with the world's poorest farmers hit the hardest.

A team of scientists from the University of Leeds and University of Ilorin, in Nigeria, has investigated the significance of the unusual way the virus's genome - or genetic blueprint - codes for the manufacture of a protein called 3B. The protein is involved in the replication of the virus.

Researchers have known for some time that the virus's genetic blueprint contains three separate codes or instructions for the manufacture of 3B. Each code produces a similar but not identical copy of 3B. Up to now, scientists have not been able to explain the significance of having three different forms of the protein.

In a paper published in the Federation of American Societies for Experimental Biology Journal, the researchers reveal the results of a series of laboratory experiments which has demonstrated that having multiple forms of 3B gives the virus a competitive advantage, increasing its chances of survival.

The paper can be accessed by clicking on the following link: http://dx.doi.org/10.1096/fj.202001473RR

Dr Oluwapelumi Adeyemi, formerly a researcher at Leeds and now with the University of Ilorin and one of the paper's lead authors, said: "Our experiments have shown that having three forms of 3B gives the virus an advantage and that probably plays a role in why the virus is so successful in infecting its hosts.

"It is not as straightforward as saying because there are three forms of 3B - it is going to be three times as competitive. There is a more nuanced interplay going on which needs further investigation."

The paper describes how the scientists manipulated the genetic code, creating viral fragments with one form of 3B, two different forms of 3B and all three forms of 3B. Each was then measured to see how well they replicated.

They found there was a competitive advantage - greater replication - in those samples that had more than one copy of 3B.

Dr Joe Ward, post-doctoral researcher at Leeds and second co-lead author of the study, said: "The results of the data analysis were clear in that having multiple copies of the 3B protein gives the virus a competitive advantage. In terms of future research, the focus will be on why is that the case, and how the virus uses these multiple copies to its advantage.

"If we can begin to answer that question, then there is a real possibility we will identify interventions that could control this virus."

The study involved using harmless viral fragments and replicons, fragments of RNA molecules, the chemical that make up the virus's genetic code.

Anew study from the UPF and WEHI (the Walter and Eliza Hall Institute of Medical Research) in Melbourne, Australia, has described the role of p53 target gene Zmat3 in lymphoma and lung cancer development. The study, conducted in pre-clinical mice models, has been led by Ana Janic, laboratory head of the Cancer Biology group at UPF and Kate Sutherland, laboratory head in the Cancer Biology and Stem Cells Division at WEHI. The findings have been published in the journal Cell Death & Disease.

The gene p53 is known as the "guardian of the genome" due to its role in protecting cells from cancer by repairing DNA or by killing cells if they have irreparable damage. More than half the cancers in the world involve mutations in the p53 gene, but how it performs its role remains poorly understood. Importantly, p53 works in combination with other genes, and thus the characterisation of its target genes is essential to contribute to the cancer battle.

Zmat3, one of the p53 target genes, was identified more than 10 years ago and it has been shown to be altered in human cancers. The purpose of this research was to examine whether this protein could have critical functions that p53 uses to prevent cancer. To answer this question, the researchers eliminated Zmat3 to disable the p53-Zmat3 pathway in pre-clinical mice models of lymphomas and lung cancer in which p53 is known to have critical function.

Ana Janic explains that, to their surprise: "we found that removing ZMAT3 had little impact on the tumor development or severity of malignant disease. Our findings have shifted the focus of how Zmat3 could function in tumor development". She adds that "it is likely that at least in some types of blood and lung cancers, it is not Zmat3 protein alone but several proteins that work together to prevent cancer formation". Further research to identify these proteins and how their functions are integrated will be an important step towards understanding the tumour-suppressing function of p53. "Ultimately, this knowledge will have therapeutic impact on the identification of novel strategies to restore p53 function in tumors." Ana Janic concludes.

Most studies on transportation noise and cardiovascular mortality have focused on long-term exposure to noise. These studies demonstrated that chronic noise exposure is a risk factor for cardiovascular mortality. Across Europe, 48,000 cases of ischemic heart disease per year can be attributed to noise exposure, in particular to road traffic noise.

For the first time, a study led by researchers at Swiss TPH found that acute noise from airplanes during the night can trigger cardiovascular deaths within two hours of aircraft noise exposure. The study published today in the peer-reviewed European Heart Journal found that the risk of a cardiovascular death increases by 33% for night-time noise levels between 40 and 50 decibels and 44% for levels above 55 decibels.

"We found that aircraft noise contributed to about 800 out of 25,000 cardiovascular deaths that occurred between 2000 and 2015 in the vicinity of Zurich airport. This represents three percent of all observed cardiovascular deaths," said Martin Röösli, corresponding author of the study and Head of the Environmental Exposures and Health unit at Swiss TPH.

According to Röösli, the results are similar to the effects that emotions such as anger or excitement have on cardiovascular mortality. "This is not so surprising, as we know night-time noise causes stress and affects sleep," he added. The night-time noise effect was more pronounced in quiet areas with little railway and road traffic background noise and for people living in older houses, which often have less insulation and are thus more noise-prone.

The Zurich airport has a flight curfew from 23:30 to 6:00. "Based on our study results, we can deduce that this night-time flight ban prevents additional cardiovascular deaths," said Röösli.

Innovative study design to exclude confounding factors

The study used a case-crossover design to evaluate whether aircraft noise exposure at the time of a death was unusually high compared to randomly chosen control time periods. "This study design is very useful to study acute effects of noise exposure with high day-to-day variability such as for airplane noise, given changing weather conditions or flight delays," said Apolline Saucy, first author of the study and PhD student at Swiss TPH. "With this temporal analysis approach, we can isolate the effect of unusually high or low levels of noise on mortality from other factors. Lifestyle characteristics such as smoking or diet cannot be a bias in this study design."

Noise exposure was modelled using a list of all aircraft movements at Zurich Airport between 2000 and 2015 and linking with pre-existing outdoor aircraft noise exposure calculations, specific for aircraft type, air route, time of day and year.