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Understanding the inner workings of the human heart

Researchers have investigated the function of a complex mesh of muscle fibers that line the inner surface of the heart. The study, published in the journal Nature, sheds light on questions asked by Leonardo da Vinci 500 years ago, and shows how the shape of these muscles impacts heart performance and heart failure.

In humans, the heart is the first functional organ to develop and starts beating spontaneously only four weeks after conception. Early in development, the heart grows an intricate network of muscle fibers — called trabeculae — that form geometric patterns on the heart’s inner surface. These are thought to help oxygenate the developing heart, but their function in adults has remained an unsolved puzzle since the 16th century.

“Our work significantly advanced our understanding of the importance of myocardial trabeculae,” explains Hannah Meyer, a Cold Spring Harbor Laboratory Fellow. “Perhaps even more importantly, we also showed the value of a truly multidisciplinary team of researchers. Only the combination of genetics, clinical research, and bioengineering led us to discover the unexpected role of myocardial trabeculae in the function of the adult heart.”

To understand the roles and development of trabeculae, an international team of researchers used artificial intelligence to analyse 25,000 magnetic resonance imaging (MRI) scans of the heart, along with associated heart morphology and genetic data. The study reveals how trabeculae work and develop, and how their shape can influence heart disease. UK Biobank has made the study data openly available.

Leonardo da Vinci was the first to sketch trabeculae and their snowflake-like fractal patterns in the 16th century. He speculated that they warm the blood as it flows through the heart, but their true importance has not been recognized until now.

“Our findings answer very old questions in basic human biology. As large-scale genetic analyses and artificial intelligence progress, we’re rebooting our understanding of physiology to an unprecedented scale,” says Ewan Birney, deputy director general of EMBL.

The research suggests that the rough surface of the heart ventricles allows blood to flow more efficiently during each heartbeat, just like the dimples on a golf ball reduce air resistance and help the ball travel further.

The study also highlights six regions in human DNA that affect how the fractal patterns in these muscle fibers develop. Intriguingly, the researchers found that two of these regions also regulate branching of nerve cells, suggesting a similar mechanism may be at work in the developing brain.

The researchers discovered that the shape of trabeculae affects the performance of the heart, suggesting a potential link to heart disease. To confirm this, they analyzed genetic data from 50,000 patients and found that different fractal patterns in these muscle fibers affected the risk of developing heart failure. Nearly five million Americans suffer from congestive heart failure.

Further research on trabeculae may help scientists better understand how common heart diseases develop and explore new approaches to treatment.

“Leonardo da Vinci sketched these intricate muscles inside the heart 500 years ago, and it’s only now that we’re beginning to understand how important they are to human health. This work offers an exciting new direction for research into heart failure,” says Declan O’Regan, clinical scientist and consultant radiologist at the MRC London Institute of Medical Sciences. This project included collaborators at Cold Spring Harbor Laboratory, EMBL’s European Bioinformatics Institute (EMBL-EBI), the MRC London Institute of Medical Sciences, Heidelberg University, and the Politecnico di Milano.

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Exploring the impacts of climate change on hydropower production

A new study by researchers from IIASA and China investigated the impacts of different levels of global warming on hydropower potential and found that this type of electricity generation benefits more from a 1.5°C than a 2°C climate scenario.

In a sustainable and less carbon-intensive future, hydropower will play an increasingly crucial role as an important source of renewable and clean energy in the world’s overall energy supply. In fact, hydropower generation has doubled over the last three decades and is projected to double again from the present level by 2050. Global warming is however threatening the world’s water supplies, posing a significant threat to hydropower generation, which is a problem in light of the continuous increase in energy demand due to global population growth and socioeconomic development.

The study, undertaken by researchers from IIASA in collaboration with colleagues at several Chinese institutions and published in the journal Water Resources Research, employed a coupled hydrological and techno-economic model framework to identify optimal locations for hydropower plants under global warming levels of 1.5°C and 2°C, while also considering gross hydropower potential, power consumption, and economic factors. According to the authors, while determining the effects of different levels of global warming has become a hot topic in water resources research, there are still relatively few studies on the impacts of different global warming levels on hydropower potential.

The researchers specifically looked at the potential for hydropower production under the two different levels of warming in Sumatra, one of the Sunda Islands of western Indonesia. Sumatra was chosen as it is vulnerable to global warming because of sea level rise, and the island’s environmental conditions make it an ideal location for developing and utilizing hydropower resources. They also modeled and visualized optimal locations of hydropower plants using the IIASA BeWhere model, and discussed hydropower production based on selected hydropower plants and the reduction in carbon emissions that would result from using hydropower instead of fossil fuels.

The results show that global warming levels of both 1.5°C and 2°C will have a positive impact on the hydropower production of Sumatra relative to the historical period. The ratio of hydropower production to power demand provided by 1.5°C of global warming is however greater than that provided by 2°C of global warming under a scenario that assumes stabilization without overshooting the target after 2100. This is due to a decrease in precipitation and the fact that the south east of Indonesia observes the highest discharge decrease under this scenario. In addition, the reduction in CO2 emissions under global warming of 1.5°C is greater than that achieved under global warming of 2°C, which reveals that global warming decreases the benefits necessary to relieve global warming levels. The findings also illustrate the tension between greenhouse gas-related goals and ecosystem conservation-related goals by considering the trade-off between the protected areas and hydropower plant expansion.

“Our study could significantly contribute to establishing a basis for decision making on energy security under 1.5°C and 2°C global warming scenarios. Our findings can also potentially be an important basis for a large range of follow-up studies to, for instance, investigate the trade-off between forest conservancy and hydropower development, to contribute to the achievement of countries’ Nationally Determined Contributions under the Paris Agreement,” concludes study lead author Ying Meng, who started work on this project as a participant of the 2018 IIASA Young Scientists Summer Program (YSSP). She is currently affiliated with the School of Environment at the Harbin Institute of Technology in China.

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Utilizing relativistic effects for laser fusion: A new approach for clean power

A team of researchers at Osaka University has investigated a new method for generating nuclear fusion power, showing that the relativistic effect of ultra-intense laser light improves upon current “fast ignition” methods in laser-fusion research to heat the fuel long enough to generate electrical power. These findings could provide a spark for laser fusion, ushering in a new era of carbonless energy production.

Current nuclear power uses the fission of heavy isotopes, such as uranium, into lighter elements to produce power. Yet, this fission power has major concerns, such as spent fuel disposal and the risk of meltdowns. A promising alternative to fission is nuclear fusion. Like all stars, our sun is powered by the fusion of light isotopes, notably hydrogen, into heavier elements. Fusion has many advantages over fission, including the lack of hazardous waste or risk of uncontrolled nuclear reactions.

However, getting more energy out of a fusion reaction than was put into it has remained an elusive goal. This is because hydrogen nuclei strongly repel each other, and fusion requires extreme heat and pressure conditions — like those found in the interior of the sun, for instance — to squeeze them together. One method, called “inertial confinement” uses extremely high-energy laser pulses to heat and compress a fuel pellet before it gets the chance to be blown apart. Unfortunately, this technique requires extremely precise control of the laser’s energy so that the compression shock waves all arrive at the center simultaneously.

Now, a team led by Osaka University has developed a modified method for inertial confinement that can be performed more consistently using a second laser shot. In “super-penetration” fast ignition, the directly irradiated second laser produces fast-moving electrons in dense plasma that heat the core during compression to trigger fusion. “By utilizing the relativistic behavior of the high-intensity laser, the energy can be reliably delivered to fuel in the imploded plasma aiming the ignition,” first author Tao Gong says.

The fuel for this method, which is usually a mix of the hydrogen isotopes deuterium and tritium, is easier to obtain than uranium, and becomes harmless helium after fusion. “This result is an important step towards the realization of laser fusion energy, as well as for other applications of high-energy density physics, including medical treatment,” explains senior author Kazuo Tanaka.

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Bioprinting: Living cells in a 3D printer

Tissue growth and the behavior of cells can be controlled and investigated particularly well by embedding the cells in a delicate 3D framework. This is achieved using additive 3D printing methods — so called “bioprinting” techniques. However, this involves a number of challenges: Some methods are very imprecise or only allow a very short time window in which the cells can be processed without being damaged. In addition, the materials used must be cell-friendly during and after the 3D biopriting process. This restricts the variety of possible materials.

A high-resolution bioprinting process with completely new materials has now been developed at TU Wien (Vienna): Thanks to a special “bio ink” for the 3D printer, cells can now be embedded in a 3D matrix printed with micrometer precision — at a printing speed of one meter per second, orders of magnitude faster than previously possible.

The environment matters

“The behavior of a cell behaves depends crucially on the mechanical, chemical and geometric properties of its environment,” says Prof. Aleksandr Ovsianikov, head of the 3D Printing and Biofabrication research group at the Institute of Materials Science and Technology (TU Wien). “The structures in which the cells are embedded must be permeable to nutrients so that the cells can survive and multiply. But it is also important whether the structures are stiff or flexible, whether they are stable or degrade over time.”

It is possible to first produce suitable structures and then colonise them with living cells — but this approach can make it difficult to place the cells deep inside the scaffold, and it is hardly possible to achieve a homogeneous cell distribution that way. The much better option is to embed the living cells directly into the 3D structure during the production of the structure — this technique is known as “bioprinting.”

Printing microscopically fine 3D objects is no longer a problem today. However, the use of living cells presents science with completely new challenges: “Until now, there has simply been a lack of suitable chemical substances,” says Aleksandr Ovsianikov. “You need liquids or gels that solidify precisely where you illuminate them with a focused laser beam. However, these materials must not be harmful to the cells, and the whole process has to happen extremely quickly.”

Two photons at once

In order to achieve an extremely high resolution, two-photon polymerization methods have been used at TU Wien for years. This method uses a chemical reaction that is only initiated when a molecule of the material simultaneously absorbs two photons of the laser beam. This is only possible where the laser beam has a particularly high intensity. At these points the substance hardens, while it remains liquid everywhere else. Therefore, this two-photon method is best suited to produce extremely fine structures with high precision.

However, these high resolution techniques usually have the disadvantage of being very slow — often in the range of micrometers or a few millimeters per second. At TU Wien, however, cell-friendly materials can be processed at a speed of more than one meter per second — a decisive step forward. Only if the entire process can be completed within a few hours is there a good chance of the cells surviving and developing further.

Numerous new options

“Our method provides many possibilities to adapt the environment of the cells,” says Aleksandr Ovsianikov. Depending on how the structure is built, it can be made stiffer or softer. Even fine, continuous gradients are possible. In this way, it is possible to define exactly how the structure should look in order to allow the desired kind of cell growth and cell migration. The laser intensity can also be used to determine how easily the structure will be degraded over time.

Ovsianikov is convinced that this is an important step forward for cell research: “Using these 3D scaffolds, it is possible to investigate the behavior of cells with previously unattainable accuracy. It is possible to study the spread of diseases, and if stem cells are used, it is even possible to produce tailor-made tissue in this way.”

The research project is an international and interdisciplinary cooperation in which three different institutes of the TU Vienna were involved: Ovsianikov’s research group was responsible for the printing technology itself, the Institute of Applied Synthesic Chemistry developed fast and cell friendly photoinitiators (the substances that initiate the hardening process when illuminated) and the Institute of Lightweight Structures and Structural Biomechanics analyzed the mechanical properties of the printed structures.

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Watching energy transport through biomimetic nanotubes

Scientists from the University of Groningen (the Netherlands) and the University of Würzburg (Germany) have investigated a simple biomimetic light-harvesting system using advanced spectroscopy combined with a microfluidic platform. The double-walled nanotubes work very efficiently at low light intensities, while they are able to get rid of excess energy at high intensities. These properties are useful in the design of novel materials for the harvesting and transport of photon energy. The results were published in the journal Nature Communications on 10 October.

The remarkable ability of natural photosynthetic complexes to efficiently harness sunlight — even in dark environments — has sparked widespread interest in deciphering their functionality. Understanding energy transport on the nanoscale is key for a range of potential applications in the field of (opto)electronics. The overwhelming complexity of natural photosynthetic systems, consisting of many hierarchically arranged sub-units, led scientists to turn their attention to biomimetic analogs, which are structured like their natural counterparts but can be more easily controlled.

Ligh-harvesting molecules

The Optical Condensed Matter Science group and the Theory of Condensed Matter group (both at the Zernike Institute for Advanced Materials, University of Groningen) have joined forces with colleagues from the University of Würzburg (Germany) to gain a comprehensive picture of energy transport in an artificial light-harvesting complex. They used a new spectroscopic lab-on-a-chip approach, which combines advanced time-resolved multidimensional spectroscopy, microfluidics, and extensive theoretical modeling.

The scientists investigated an artificial light-harvesting device, inspired by the multi-walled tubular antenna network of photosynthetic bacteria found in nature. The biomimetic device consists of nanotubes made out of light-harvesting molecules, self-assembled into a double-walled nanotube. ‘However, even this system is rather complex,’ explains Maxim Pshenichnikov, professor of ultrafast spectroscopy at the University of Groningen. His group devised a microfluidic system, in which the outer wall of the tube can be selectively dissolved and, thus, switched off. ‘This is not stable, but in the flow system, it can be studied.’ In this way, the scientists could study both the inner tube and the complete system.

Adapting

At low light intensity, the system absorbs photons in both walls, creating excitations or excitons. ‘Due to the different sizes of the walls, they absorb photons of different wavelengths,’ Pshenichnikov explains. ‘This increases the efficiency.’ At high light intensity, a large number of photons are absorbed, creating a huge number of excitons. ‘We observed that, when two excitons meet, one of them actually ceases to exist.’ This effect acts as a kind of safety valve, as high numbers of excitons could damage the nanotubes.

Thus, the scientists also demonstrated that the double-walled molecular nanotube is capable of adapting to changing illumination conditions. They mimic the essential functional elements of nature’s design toolbox at low light conditions by acting as highly sensitive antennas but get rid of excess energy at high intensities when there is too much light — a situation that would not normally occur in nature. Both these properties pave the way for better control of the transport of energy through complex molecular materials.

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Curved nanochannels allow independent tuning of charge and spin currents

To increase the efficiency of microchips, 3D structures are now being investigated. However, spintronic components, which rely on electron spin rather than charge, are always flat. To investigate how to connect these to 3D electronics, University of Groningen physicist Dr. Kumar Sourav Das created curved spin transport channels. Together with his colleagues, he discovered that this new geometry makes it possible to independently tune charge and spin currents. The results were published online by the journal Nano Letters on 13 September 2019.

Das started with two main questions: how to tune spin current using geometry, and how to create spin transport in a 3D nanostructure. Electron spin is a quantum mechanical property, a magnetic moment that can be used to transfer or store information. Spin is already used in memory storage, and could also be used in logic circuits.

Curved architecture

‘So far, most spintronic devices have been based on a flat structure. We wanted to find out how the spin currents behave in a curved channel’, says Das. Using silicon oxide substrates with trenches created by an ion beam, designed at the HZDR in Dresden by Dr. Denys Makarov, Das grew aluminum nanochannels that crossed the trenches. In this curved architecture, the thickness of the aluminum varies at nanoscale dimensions, shorter than the spin relaxation length.

Das used different sized trenches and measured both spin resistance and charge currents. ‘What we discovered is that variations in the trench size affect spin and charge transport in the channel differently’, Das explains. ‘We were therefore able to independently tune both spin and charge currents based on the channel geometry.’

Novel functionalities

His colleague Dr. Carmine Ortix from Utrecht University created a theoretical model describing this phenomenon. ‘Our theory clearly demonstrates that it is possible to independently tune the spin and charge characteristics using the shape of the materials alone. This possibility overcomes the existing technological hurdles for the applicability of spintronics in modern electronics’, says Dr. Ortix. ‘Extending low-dimensional structures into the three-dimensional space can provide the means to modify conventional functionalities or even launch completely novel functionalities by suitably tailoring the shape of real materials.’

‘This discovery is important because it allows us to tune spintronic components to match both the spin current and the charge current of electronic circuits’, says Das. ‘It enables the efficient integration of spin injectors and detectors or spin transistors into modern 3D circuitry.’ This could help to create more energy-efficient electronics, as spintronics is an attractive way of creating low-power devices. ‘And we can now use our model to purpose-design channels.’

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