Tech

Facial deformity in royal dynasty was linked to inbreeding, scientists confirm

image: King Charles II of Spain was the last in the Habsburg line and one of the most afflicted with the facial deformity

Image: 
Don Juan Carreño de Miranda

The "Habsburg jaw", a facial condition of the Habsburg dynasty of Spanish and Austrian kings and their wives, can be attributed to inbreeding, according to new results published in the Annals of Human Biology.

The new study combined diagnosis of facial deformities using historical portraits with genetic analysis of the degree of relatedness to determine whether there was a direct link. The researchers also investigated the genetic basis of the relationship.

Generations of intermarriage secured the family's influence across a European empire including Spain and Austria for more than 200 years but led to its demise when the final Habsburg monarch was unable to produce an heir. However, until now no studies have confirmed whether the distinct chin known as "Habsburg jaw" was a result of inbreeding.

"The Habsburg dynasty was one of the most influential in Europe, but became renowned for inbreeding, which was its eventual downfall. We show for the first time that there is a clear positive relationship between inbreeding and appearance of the Habsburg jaw," says lead researcher Professor Roman Vilas from the University of Santiago de Compostela.

The researchers recruited 10 maxillofacial surgeons to diagnose facial deformity in 66 portraits of 15 members of the Habsburg dynasty. Despite differences in artistic style, the portraits are characterised by a realistic approach to the human face. The surgeons were asked to diagnose 11 features of mandibular prognathism, otherwise known as "Habsburg jaw", as well as seven features of maxillary deficiency, the most recognisable of which are a prominent lower lip and an overhanging nasal tip.

The portraits, which can be viewed online, are preserved by some of the most important art museums in the world, including the Kunsthistorisches Museum in Vienna and the Prado Museum in Madrid.

The surgeons gave scores for the degree of mandibular prognathism and maxillary deficiency in each member of the Habsburg family. Mary of Burgundy, who married into the family in 1477, showed the least degree of both traits. Mandibular prognathism was most pronounced in Philip IV, King of Spain and Portugal from 1621 to 1640. Maxillary deficiency was diagnosed to the greatest degree in five members of the family: Maximilian I (regent from 1493), his daughter Margaret of Austria, his nephew Charles I of Spain, Charles' great-grandson Philip IV and the last in the Habsburg line, Charles II.

The study authors detected a correlation between the two conditions, suggesting that "Habsburg jaw" is in fact characterised by them both and that they share a common genetic basis. The extent of inbreeding was calculated from a large-scale family tree, including more than 6,000 individuals belonging to more than 20 generations. Analysis was carried out to determine if it was connected to the degree of facial deformity. The researchers detected a strong relationship between the degree of inbreeding and the degree of mandibular prognathism. The relationship to maxillary deficiency was also positive, but it was only statistically significant in two of the seven features diagnosed.

The causes of the relationship between inbreeding and facial deformity remain unclear, but the authors suggest it's because the main effect of mating between relatives is an increase in the chances of offspring inheriting identical forms of a gene from both parents, known as genetic homozygosity. This reduces people's genetic fitness, so "Habsburg jaw" should be considered a recessive condition.

However, the authors note that the study involves only a small number of individuals so it's possible that the prevalence of Habsburg jaw is due to the chance appearance of traits, or genetic drift. They suggest this scenario is unlikely, but can't rule it out.

"While our study is based on historical figures, inbreeding is still common in some geographical regions and among some religious and ethnic groups, so it's important today to investigate the effects," says Vilas. "The Habsburg dynasty serves as a kind of human laboratory for researchers to do so, because the range of inbreeding is so high."

Credit: 
Taylor & Francis Group

New principle for activation of cancer genes discovered

image: This is Anita Göndör's research group at the Department of Oncology-Pathology at Karolinska Institutet in Sweden.

Image: 
Stefan Zimmerman

Researchers have long known that some genes can cause cancer when overactive, but exactly what happens inside the cell nucleus when the cancer grows has so far remained enigmatic. Now, researchers at Karolinska Institutet in Sweden have found a new mechanism that renders one canonical driver of cancer overactive. The findings, published in Nature Genetics, create conditions for brand new strategies to fight cancer.

One gene that is called MYC is central for normal cell growth. However, if the gene mutates and/or becomes overactive, it could lead to abnormal cell growth and cancer. It is previously known that so-called super-enhancers, large regions in the DNA that develop near cancer genes, could somehow make the MYC gene overactive.

The current study increases our understanding of how this process takes place by highlighting how environmental cues can conspire with the architecture of the cell nucleus to cause overexpression. With the help of new laboratory techniques and computer models, the researchers show how the activation of the pathway of the signal-molecule WNT charges the super-enhancer with proteins that lures the MYC gene to the cell nucleus pores. The pores are situated on the membrane of the cell nucleus and control the flow of information between the cell nucleus and the cytoplasm.

When the MYC gene is anchored to the nuclear pores and copied into so-called messenger RNA (mRNA), it significantly increases the likelihood that its mRNA is exported from the cell nucleus to the cytoplasm. mRNA works as a template for the formation of the MYC protein that controls the cell's ability to grow. Since MYC mRNA doesn't break down quite as effective in the cytoplasm as in the cell nucleus, this mechanism gradually leads to abnormally high levels of the MYC protein and thereby uncontrolled cancer growth.

By using pharmaceuticals that knocked out WNT-signaling, the research team was able to prevent the super-enhancer from transporting and anchoring the MYC gene to the nuclear pores. This resulted in normal levels of the MYC protein in the cytoplasm without affecting the rate of mRNA formation in the nucleus.

"Our results offer a completely new perspective on how cancer genes may become overactive," says Anita Göndör, researcher at the Department of Oncology-Pathology at Karolinska Institutet who led the study together with Rolf Ohlsson at the same department. "Since the principle is specific for cancer cells, this opens the possibility of new targeted drugs that do not harm normal cells."

The next step will be to identify new drugs that interrupts different parts of the process. The researchers hope the findings could open up for a new generation of cancer treatments that are less harmful than for example radiation and chemotherapy, which knock out many normally growing cells and have negative side-effects.

"The strength of our study is the identification of a previously unknown process that increases the possibility of finding combinatorial drug treatments and thereby pave the way for a significantly more effective therapy of cancer patients," says Rolf Ohlsson.

Credit: 
Karolinska Institutet

How ancient microbes created massive ore deposits, set the stage for early life on Earth

image: Bacteria cultured from an iron-rich lake in Democratic Republic of Congo are helping researchers solve two of the early Earth's biggest mysteries.

Image: 
University of British Columbia

New research in Science Advances is uncovering the vital role that Precambrian-eon microbes may have played in two of the early Earth's biggest mysteries.

University of British Columbia (UBC) researchers, and collaborators from the universities of Alberta, Tübingen, Autònoma de Barcelona and the Georgia Institute of Technology, found that ancestors of modern bacteria cultured from an iron-rich lake in Democratic Republic of Congo could have been key to keeping Earth's dimly lit early climate warm, and in forming the world's largest iron ore deposits billions of years ago.

The bacteria have special chemical and physical features that in the complete absence of oxygen allow them to convert energy from sunlight into rusty iron minerals and into cellular biomass. The biomass ultimately causes the production of the potent greenhouse gas methane by other microbes.

"Using modern geomicrobiological techniques, we found that certain bacteria have surfaces which allow them to expel iron minerals, making it possible for them to export these minerals to the seafloor to make ore deposits," said Katharine Thompson, lead author of the study and PhD student in the department of microbiology and immunology.

"Separated from their rusty mineral products, these bacteria then go on to feed other microbes that make methane. That methane is what likely kept Earth's early atmosphere warm, even though the sun was much less bright than today."

This is a possible explanation to the 'faint-young-sun' paradox, originated by astronomer Carl Sagan. The paradox is that there were liquid oceans on early Earth, yet heat budgets calculated from the early Sun's luminosity and modern atmospheric chemistry imply Earth should have been entirely frozen. A frozen Earth would not have supported very much life. A methane-rich atmosphere formed in connection to large-scale iron ore deposits and life was initially proposed by University of Michigan atmospheric scientist James Walker in 1987. The new study provides strong physical evidence to support the theory and finds that microscale bacterial-mineral interactions were likely responsible.

"The fundamental knowledge we're gaining from studies using modern geomicrobiological tools and techniques is transforming our view of Earth's early history and the processes that led to a planet habitable by complex life including humans," said senior author of the paper, Sean Crowe, Canada Research Chair in Geomicrobiology and associate professor at UBC.

"This knowledge of the chemical and physical processes through which bacteria interact with their surroundings can also be used to develop and design new processes for resource recovery, novel building and construction materials, and new approaches to treating disease."

In the future, such geo-microbiological information will likely be invaluable to large-scale geoengineering efforts that might be used to remove from CO2 from the atmosphere for carbon capture and storage, and again influence climate through bacterial mineral interactions.

Credit: 
University of British Columbia

Predicting molecular bond energy by artificial intelligence

image: This is a neural network protocol for predicting molecular bond energy.

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©Science China Press

Theoretical prediction of molecular bond energy is of key importance for understanding molecular properties. For instance, information of chemical reaction pathways can be inferred from a numerical analysis of the bond energies involved. A well-accepted way is to calculate the difference in values of molecular energies before and after chemical bond rupture using quantum chemistry tools. However, for complicated chemical reactions, a large number of chemical bonds need to be analyzed, requiring many repeated quantum mechanics calculations that consume heavy computing resources. Other ways such as mapping method are unreliable and limited. Developing an efficient solution for quickly and accurately predicting bond energies remain an open challenge.

Recently, data-driven research paradigm based on big data and artificial intelligence (AI) techniques is increasingly important in chemistry. Especially, neural networks ---- a class of algorithms featured by learning characters of data, is deemed a promising AI approach that can significantly reduce the computation cost of complex problems with well-defined rules yet high-dimensional data. "Inspired by this," Prof. Jiang Jun introduced, a research group leader at Hefei National Laboratory for Physical Science at the Microscale of University of Science and Technology of China, "we have employed neural networks to predict the molecular bond energies. In addition, we found that the combination of artificial intelligence and theoretical calculations of quantum chemistry provides an efficient tool for accurately and quickly predicting molecular bond energy."

"Recent years, our group has devoted ourselves to the development of the application of machine learning technology in the field of quantification, and has tried to make it an important tool for solving quantitative problems", Jiang said, "in this work, we first obtained 8,000 sets of bond energy data based on quantum chemical calculations. Through the random forest method, the appropriate descriptors are selected from the basic information (e.g. geometry and charge) of molecules, and the 8,000 sets of quantum chemical data are iteratively learned through the neural network, and the neural network model between the molecular bond energy and its basic state information is established. This model successfully predicted the molecular bond energy."

In addition, the performance of neural network models with different kinds of atomic charge distributions is also compared. This work proves the feasibility and advantages of machine learning in molecular bond energy simulation, and provides a reasonable solution for predicting molecular bond energy in complex systems.

Credit: 
Science China Press

Virtual reality becomes more real

Scientists from Skoltech ADASE (Advanced Data Analytics in Science and Engineering) lab have found a way to enhance depth map resolution, which should make virtual reality and computer graphics more realistic. They presented their research results at the prestigious International Conference on Computer Vision 2019 in Korea.

When taking a photo, we capture visual information about objects around us, with the different pixels in the image containing the colors of the respective parts of the object. Depth maps are photos that capture spatial information and their pixels contain the distances from the camera to the respective points in space. Applications such as computer graphics and augmented or virtual reality use spatial information to reconstruct a 3D object's shape and, for instance, display it on a computer screen.

One of the issues of depth cameras is that their resolution, that is, the spatial frequency of distance measurements, is insufficient for restoration of high quality object's shape, making the virtual reconstructions look all but unrealistic.

The researchers are faced with the challenge of finding a way to obtain high-resolution depth maps from low-resolution depth maps.
Scientists from Skoltech ADASE lab have proposed to assess the reconstruction quality using a novel method closely related to human perception. Training an artificial neural network with this quality assessment technique produces a depth map super-resolution method that largely outperforms the existing methods in the visual quality of the result.

"When dealing with super-resolved depth maps, one should assess the quality of the result, first, to compare the performance of different methods, and second, to use it as feedback for further improvements. The easiest way is to compare the result to some reference. The overwhelming majority of works on depth map super-resolution use for this purpose mean difference between super-resolved and reference depth values. By no means does this method reflect the visual quality of the 3D reconstruction obtained from the super-resolved depth map," explains the first author of the study, Oleg Voynov.

"We propose an altogether different method which leverages the human perception of the difference between visualizations of the 3D reconstructions obtained from super-resolved and reference depth maps. The graphics you obtain with this method looks highly realistic. We hope that our method will find extensive use," says one of the developers, Alexey Artemov.

Credit: 
Skolkovo Institute of Science and Technology (Skoltech)

TU Dresden biologists examine sperm quality on the basis of their metabolism

image: This is bovine sperm in bright-field microscopy with differential interference contrast.

Image: 
Copyright: Dr. Veronika Magdanz

Thanks to the advanced possibilities, in vitro fertilization is part of everyday medical practice. The so-called swim-up method is a sperm purification method that is being used daily in andrology labs around the world as a simple step for in vitro sperm selection. This method accumulates the most motile sperm in the upper fraction and leaves sperm with low or no motility in the lower fraction by adding them to a culture medium. The reasons for the different sperm qualities are still poorly understood.

A team of biologists from TU Dresden has now compared bovine sperm from the upper and lower layers with regard to their metabolic rate, their motility and sperm tail length. In their study, they identified clear connections: the faster sperm selected by swim-up show higher metabolic rates and longer driving flagella than non-selected cells.

Dr. Veronika Magdanz, head of the study, explains the results as follows: "However, it is not quite as easy as that these sperm simply metabolize more. The stored energy is also lower in the selected sperm, which shows that they consume more energy reserves. Understanding the metabolism of the selected spermatozoa is important because certain metabolic pathways can also have a detrimental effect on the spermatozoa. For example, cell respiration in the mitochondria, one of the possible metabolic pathways, produces harmful oxygen radicals that affect the genetic integrity and cell functions of the sperm."

The results of the study are the first to provide a metabolic explanation for why the swim-up method selects sperm that appear to be functionally superior. These findings can be applied to all human and animal sperm and provide valuable new insights into the origins of life.

Credit: 
Technische Universität Dresden

Disclaimers on retouched photos don't solve problem of negative body image

TORONTO, November 28, 2019 -Labels that warn an image has been altered or enhanced do nothing to mitigate women's negative perceptions of their appearance, according to a study published in Body Image this week. More importantly, some disclaimers heightened and even harmed body dissatisfaction in at-risk women, the study showed.

"Disclaimers aren't helpful. Once that image hits the brain, it has a profound effect on the way a woman thinks about how her body should look, says Jennifer Mills, associate professor in the Department of Psychology and senior author on the study. "Telling people that the image is not real doesn't change the fact that that image becomes internalized."

Mills and Sarah McComb, a Ph.D. student in Mills' lab and first author of the study, conducted a systematic review of 15 experimental studies and found that disclaimers were ineffective at reducing women's body dissatisfaction following exposure to thin-ideal images.

The goal of the study was to determine the effectiveness of media disclaimers in protecting women's body image and mood after exposure to thin-ideal media. The keywords "warning*" or "disclaimer*" and "body image" or "body dissatisfaction" were searched in the PsycINFO and MEDLINE/PubMed databases.

Researchers looked at several types of commonly used disclaimers on photos in the study. The 'specific' disclaimer tells the viewer which body part has been altered, the 'warning or consequence' disclaimer explains that the photo can be bad for body image or your health, the 'generic' disclaimer lets consumers know "This image has been digitally altered" and the 'information' disclaimer says the model is underweight.

"We found that specific disclaimers and warning disclaimers were harmful to women who were already very dissatisfied with their bodies - the disclaimers seemed to trigger their already negative feelings about their bodies," says McComb. "The warning disclaimer was especially harmful, because it also had negative impacts on women's eating habits. Women who already had restrictive eating habits and who saw an image of a model with a warning label were actually found to eat less calories than when they saw the image without the disclaimer."

Overall, 11 studies found that disclaimers were ineffective at mitigating body dissatisfaction after exposure to thin-ideal images (relative to no disclaimer), three studies found medium effects that disclaimers were effective at mitigating increased body dissatisfaction, and one study found a small-medium effect that disclaimers actually heightened body dissatisfaction.

"If the disclaimer is too specific it draws the person's attention to parts of the body on a model that are unattainable or unrealistic," says Mills. "Individuals still want to look like the model despite knowing there is a disclaimer, because it draws our attention to the unrealistic body part. People tend to want what they cannot have."

Credit: 
York University

Harvard Wyss Institute researchers demonstrate machine-guided engineering of AAV capsids

image: In this photo Sam Sinai, George Church, Eric Kelsic, and Pierce Ogden are holden small models of the AVVs capsid in their hands.

Image: 
Wyss Institute at Harvard University

(BOSTON) -- Adeno-associated viruses (AAVs) have become the go-to vehicle for delivering therapeutic gene cargo to target tissues for the recent wave of gene therapies that are in development in academic and biotechnology laboratories. However, natural AAVs do not specifically target diseased cells and tissues, and they can be recognized by the immune system in ways that limit therapeutic success. To improve AAVs, synthetic biologists have been taking a "directed evolution" approach in which they randomly mutate specific amino acid building blocks of the capsid proteins that form the shell of the virus and directly contact target cells. By evaluating which changes can route the virus to target tissues and successively layering mutations on top of each other in an arduous iterative process, they aim to improve desirable AAV traits.

Now scientists at Harvard's Wyss Institute for Biologically Inspired Engineering and Harvard Medical School (HMS) report an approach to speed up the process of making such enhanced AAV capsids, and to develop even better viruses.

Taking a different, more systematic approach to the capsid protein-engineering problem, the team mutated one by one each of the 735 amino acids within the AAV2 capsid, the best-known member of the AAV family, including all possible codon substitutions, insertions and deletions at each position. They generated a virus library containing about 200,000 variants and identified capsid changes that both maintained AAV2's viability and improved its "homing" potential (tropism) to specific organs in mice. Unexpectedly, the team also discovered a new accessory protein hidden within the capsid-encoding DNA sequence that binds to the membrane of target cells. Their findings are reported in Science.

The team led by Wyss Core Faculty member George Church, Ph.D., and his former postdoctoral fellow Eric Kelsic, Ph.D., deployed an advanced synthetic biology armamentarium including next-generation DNA-synthesis, barcoding, and DNA sequencing capabilities for constructing one of the most comprehensive AAV capsid libraries to date. "With the information generated by this library, we were also able to design capsids with more mutations than previous natural or synthetic variants, and furthermore with efficiencies of generating viable capsids that far exceed those of AAV created by random mutagenesis approaches" said Church, who is a Lead of the Wyss Institute's Synthetic Biology platform, and also the Robert Winthrop Professor of Genetics at HMS and Professor of Health Sciences and Technology at Harvard University and the Massachusetts Institute of Technology (MIT).

"These high-throughput technologies paired with machine-guided design lay the foundation for engineering superior and highly tailored AAV variants for future gene therapies", said co-first author Eric Kelsic, Ph.D., who is now CEO of Dyno Therapeutics. "Past approaches such as rational design or random mutagenesis each had their drawbacks, either being limited in the library size or being low in quality, respectively. Machine-guided design is a data-driven approach to protein engineering. Here we show that even a simple mathematical model, powered by enough data, can successfully generate viable synthetic capsids. This iterative and empirical approach to protein engineering enables us to get the best of both worlds and generate large numbers of high quality capsid variants."

"Unexpectedly, the high-resolution data we generated enabled us to spot a new protein encoded by a different reading frame within the capsid's DNA sequence - which had escaped notice despite decades of intense research on the virus," said co-first author Pierce Ogden, Ph.D., a former graduate student and now postdoctoral fellow working with Church. "Membrane-associated accessory protein (MAAP), as we named it, exists in all of the most popular AAV serotypes and we believe that it plays a role in the virus' natural life cycle. Studying how MAAP functions will be an exciting area for future research and could potentially lead to a better understanding of how to better produce and engineer AAV gene therapies."

According to co-author Sam Sinai, Ph.D., a former graduate student of Church, now a Machine Learning Scientist at Dyno Therapeutics, "This reveals the promise of data-driven protein engineering, in particular for proteins like the AAV capsid that are difficult to model with current computational approaches. Our results are highly encouraging but also only a first step. Using this data and those from future experiments, we will be building machine learning models to optimize capsids and address a wide variety of gene therapy challenges."

Kelsic, Sinai and Church are co-founders of Dyno Therapeutics Inc., and all hold equity in the company.

"This study is a landmark in the Wyss Institute's Synthetic Biology platform's effort to advance AAV technology to the next level. This work is also a great example of how we are beginning to integrate machine learning and artificial intelligence approaches into our therapeutics pipeline," said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS, the Vascular Biology Program at Boston Children's Hospital, and Professor of Bioengineering at Harvard's John A. Paulson School of Engineering and Applied Sciences (SEAS).

Credit: 
Wyss Institute for Biologically Inspired Engineering at Harvard

Growing nano-tailored surfaces using micellar brushes

Growing nanoscale polymer brushes on materials' surfaces overcomes a key challenge in surface chemistry, researchers report, creating a new way to fabricate a diverse array of materials that could hold advanced uses in catalysis or chemical separation applications, for example. Their approach represents a crucial step forward in the search for simple and general techniques to create functional surfaces with tailor-made chemical properties, writes Alejandro Presa Soto in a related Perspective; "Pandora's box is now open, and the limits of this approach are only restricted by the imagination and skills of the scientific community." As technology advances, the ability to create advanced materials with specific surface properties and functionalities is becoming critically significant in a wide variety of areas including chemical engineering and biomedicine. One recently developed approach for creating functionalized surfaces makes use of polymer chains, grafted to surfaces in brush-like patches. However limited, the method allows for tailoring of the surface chemistry at the molecular level. Similar approaches using nano- or micron-scale structures hold great promise for greatly expanded functionality and applications; however, the precise fabrication of these surfaces remains a prohibitive challenge. Jiandon Cai and colleagues address this by growing nanoscale micellar brushes directly on a material's surface. Cai et al. attached small crystalline micelle-seeds on a variety of surfaces, including silicon wafers, graphene oxide nanosheets and gold nanoparticles. Unimers are used to initiate the crystallization-driven growth of well-defined cylindrical nanostructures over the seed-coated surface. The approach allows for the precise control over the density, length and chemistry of the micellar brushes, which can further be outfitted with other functional molecules and nanoparticles to enable a variety of catalysis and antibacterial and chemical separation applications.

Credit: 
American Association for the Advancement of Science (AAAS)

Additive manufacturing and NI/TI metal bolster cooling technology

Scientists at the University of Maryland (UMD) have developed a novel elastocaloric cooling material, comprised of a nickel (Ni)-titanium (Ti) alloy and sculpted using additive technology, that is highly efficient, eco-friendly and easily scaled-up for commercial use. The study was published in the journal Science on November 29.

Cooling technology, used in refrigeration and HVAC systems around the globe, is a multi-billion dollar business. Vapor compression cooling, which has dominated the market for over 150 years, has not only plateaued where efficiency is concerned, but also uses chemical refrigerants with high global-warming potential (GWP). Solid-state elastocaloric cooling, where stress is applied to materials to release and absorb (latent) heat, has been under development for the last decade and is a front-runner in the so-called alternative cooling technologies. Shape-memory alloys (SMAs) are found to display a significant elastocaloric cooling effect; however, presence of hysteresis - work lost in each cycle and cause of materials fatigue and eventual failure - remains a challenge.

To that end, an international team of collaborators led by UMD A. James Clark School of Engineering Professor Ichiro Takeuchi has developed an improved elastocaloric cooling material using a blend of nickel and titanium metals, forged using a 3D printer, that is not only potentially more efficient than current technology, but is completely 'green.' Moreover, it can be quickly scaled up for use in larger devices.

"In this field of alternative cooling technologies, it's very important to work on both the materials end, as well as the systems end - we are fortunate to have a highly-qualified team of experts at UMD College Park to work on both ends," said Professor Takeuchi. "It's only when these two efforts closely align that you make rapid progress, which our team was able to do."

Comparatively speaking, there are three classes of caloric cooling technology - magnetocaloric, electrocaloric and elastocaloric - all of which are 'green' and vapor-less. Magnetocaloric, the oldest of the three, has been under development for 40 years and is just now on the verge of being commercialized.

"The need for additive technology, otherwise known as 3D printing, in this field is particularly acute because these materials also act as heat exchangers, delivering cooling to a medium such as water," said Takeuchi.

Takeuchi has been developing this technology for almost a decade - he received the UMD Outstanding Invention of the Year for this research in 2010, and the DOE ranked elastocaloric cooling, also known as thermoelastic cooling, #1 as the 'most promising' of alternative cooling technology in 2014 - and it is one step closer to commercialization.

"The key to this innovation that is fundamental, but not often discussed, is that materials fatigue - they wear out," said Takeuchi. "This is a problem when people expect their refrigerators to last for a decade, or longer. So, we addressed the problem in our study."

The team tested their creation heavily - the material underwent one million cycles over a four-month period and still maintained its integrity. "Some known elastocaloric materials start showing degradation in cooling behavior after just hundreds of cycles. To our surprise, the new material we synthesized showed no change after one million cycles," said Hou, the first author of the work. The metal additive manufacturing which uses a laser to melt and then mix metals in powder form. By controlling the powder feed, the team was able to produce nanocomposites which gave rise to the robust mechanical integrity in the material.

Credit: 
University of Maryland

Home urine test for prostate cancer could revolutionize diagnosis

A simple urine test under development for prostate cancer detection can now use urine samples collected at home - according to new research from University of East Anglia and the Norfolk and Norwich University Hospital.

Scientists pioneered the test which diagnoses aggressive prostate cancer and predicts whether patients will require treatment up to five years earlier than standard clinical methods.

Their latest study shows how the 'PUR' test (Prostate Urine Risk) could be performed on samples collected at home, so men don't have to come into the clinic to provide a urine sample - or have to undergo an uncomfortable rectal examination.

This is an important step forward, because the first urination of the day provides biomarker levels from the prostate that are much higher and more consistent. And the research team hope that the introduction of the 'At-Home Collection Kit' could revolutionise diagnosis of the disease.

Lead researcher Dr Jeremy Clark, from UEA's Norwich Medical School, said: "Prostate cancer is the most common cancer in men in the UK. It usually develops slowly and the majority of cancers will not require treatment in a man's lifetime. However, doctors struggle to predict which tumours will become aggressive, making it hard to decide on treatment for many men.

"The most commonly used tests for prostate cancer include blood tests, a physical examination known as a digital rectal examination (DRE), an MRI scan or a biopsy.

"We developed the PUR test, which looks at gene expression in urine samples and provides vital information about whether a cancer is aggressive or 'low risk'.

"Because the prostate is constantly secreting, the collection of urine from men's first urination of the day means that the biomarker levels from the prostate are much higher and more consistent, so this is a great improvement.

"Being able to simply provide a urine sample at home and post a sample off for analysis could really revolutionise diagnosis.

"It means that men would not have to undergo a digital rectal examination, so it would be much less stressful and should result in a lot more patients being tested."

The research team provided 14 participants with an At Home Collection Kit, and instructions. They then compared the results of their home urine samples, taken first thing in the morning, with samples collected after a digital rectal examination.

"We found that the urine samples taken at home showed the biomarkers for prostate cancer much more clearly than after a rectal examination. And feedback from the participants showed that the at home test was preferable.

"Using our At Home test could in future revolutionise how those on 'active surveillance' are monitored for disease progression, with men only having to visit the clinic for a positive urine result. This is in contrast to the current situation where men are recalled to the clinic every six to 12 months for painful and expensive biopsies.

"Because the PUR test accurately predicts aggressive prostate cancer, and predicts whether patients will require treatment up to five years earlier than standard clinical methods - it means that a negative test could enable men to only be retested every two to three years, relieving stress to the patient and reducing hospital workload."

The Norfolk and Norwich University Hospital receives more than 800 referrals a year to investigate and treat potential prostate cancers. Prostate cancer usually develops slowly and the majority of cancers will not require treatment in a man's lifetime.

Robert Mills, Consultant Surgeon in Urology at the Norfolk and Norwich University Hospital, said: "This is a very exciting development as this test gives us the possibility of differentiating those who do from those who do not have prostate cancer so avoiding putting a lot of men through unnecessary investigations.

"When we do diagnose prostate cancer, the urine test has the potential to differentiate those who need to have treatment from those who do not need treatment, which would be invaluable. These patients go on to an active surveillance programme following the diagnosis which may involve repeat biopsies and MRI scans which is quite intrusive. This urine test has the potential to tell us whether we needed to intervene with these patients."

The research team say that their findings could also help pioneer the development of home-collection tests for bladder or kidney cancer.

'Methodology for the At-Home Collection of Urine Samples for Prostate Cancer Detection' is published in the journal BioTechniques.

Credit: 
University of East Anglia

Toward more efficient computing, with magnetic waves

MIT researchers have devised a novel circuit design that enables precise control of computing with magnetic waves -- with no electricity needed. The advance takes a step toward practical magnetic-based devices, which have the potential to compute far more efficiently than electronics.

Classical computers rely on massive amounts of electricity for computing and data storage, and generate a lot of wasted heat. In search of more efficient alternatives, researchers have started designing magnetic-based "spintronic" devices, which use relatively little electricity and generate practically no heat.

Spintronic devices leverage the "spin wave" -- a quantum property of electrons -- in magnetic materials with a lattice structure. This approach involves modulating the spin wave properties to produce some measurable output that can be correlated to computation. Until now, modulating spin waves has required injected electrical currents using bulky components that can cause signal noise and effectively negate any inherent performance gains.

The MIT researchers developed a circuit architecture that uses only a nanometer-wide domain wall in layered nanofilms of magnetic material to modulate a passing spin wave, without any extra components or electrical current. In turn, the spin wave can be tuned to control the location of the wall, as needed. This provides precise control of two changing spin wave states, which correspond to the 1s and 0s used in classical computing.

In the future, pairs of spin waves could be fed into the circuit through dual channels, modulated for different properties, and combined to generate some measurable quantum interference -- similar to how photon wave interference is used for quantum computing. Researchers hypothesize that such interference-based spintronic devices, like quantum computers, could execute highly complex tasks that conventional computers struggle with.

"People are beginning to look for computing beyond silicon. Wave computing is a promising alternative," says Luqiao Liu, a professor in the Department of Electrical Engineering and Computer Science (EECS) and principal investigator of the Spintronic Material and Device Group in the Research Laboratory of Electronics. "By using this narrow domain wall, we can modulate the spin wave and create these two separate states, without any real energy costs. We just rely on spin waves and intrinsic magnetic material."

Joining Liu on the paper are Jiahao Han, Pengxiang Zhang, and Justin T. Hou, three graduate students in the Spintronic Material and Device Group; and EECS postdoc Saima A. Siddiqui.

Flipping magnons

Spin waves are ripples of energy with small wavelengths. Chunks of the spin wave, which are essentially the collective spin of many electrons, are called magnons. While magnons are not true particles, like individual electrons, they can be measured similarly for computing applications.

In their work, the researchers utilized a customized "magnetic domain wall," a nanometer-sized barrier between two neighboring magnetic structures. They layered a pattern of cobalt/nickel nanofilms -- each a few atoms thick -- with certain desirable magnetic properties that can handle a high volume of spin waves. Then they placed the wall in the middle of a magnetic material with a special lattice structure, and incorporated the system into a circuit.

On one side of the circuit, the researchers excited constant spin waves in the material. As the wave passes through the wall, its magnons immediately spin in the opposite direction: Magnons in the first region spin north, while those in the second region -- past the wall -- spin south. This causes the dramatic shift in the wave's phase (angle) and slight decrease in magnitude (power).

In experiments, the researchers placed a separate antenna on the opposite side of the circuit, that detects and transmits an output signal. Results indicated that, at its output state, the phase of the input wave flipped 180 degrees. The wave's magnitude -- measured from highest to lowest peak -- had also decreased by a significant amount.

Adding some torque

Then, the researchers discovered a mutual interaction between spin wave and domain wall that enabled them to efficiently toggle between two states. Without the domain wall, the circuit would be uniformly magnetized; with the domain wall, the circuit has a split, modulated wave.

By controlling the spin wave, they found they could control the position of the domain wall. This relies on a phenomenon called, "spin-transfer torque," which is when spinning electrons essentially jolt a magnetic material to flip its magnetic orientation.

In the researchers' work, they boosted the power of injected spin waves to induce a certain spin of the magnons. This actually draws the wall toward the boosted wave source. In doing so, the wall gets jammed under the antenna -- effectively making it unable to modulate waves and ensuring uniform magnetization in this state.

Using a special magnetic microscope, they showed that this method causes a micrometer-size shift in the wall, which is enough to position it anywhere along the material block. Notably, the mechanism of magnon spin-transfer torque was proposed, but not demonstrated, a few years ago. "There was good reason to think this would happen," Liu says. "But our experiments prove what will actually occur under these conditions."

The whole circuit is like a water pipe, Liu says. The valve (domain wall) controls how the water (spin wave) flows through the pipe (material). "But you can also imagine making water pressure so high, it breaks the valve off and pushes it downstream," Liu says. "If we apply a strong enough spin wave, we can move the position of domain wall -- except it moves slightly upstream, not downstream."

Such innovations could enable practical wave-based computing for specific tasks, such as the signal-processing technique, called "fast Fourier transform." Next, the researchers hope to build a working wave circuit that can execute basic computations. Among other things, they have to optimize materials, reduce potential signal noise, and further study how fast they can switch between states by moving around the domain wall. "That's next on our to-do list," Liu says.

Credit: 
Massachusetts Institute of Technology

Imaging uncovers secrets of medicine's mysterious ivory manikins

image: This is an ivory figurine reclining on its 'bed' with all organs placed inside.

Image: 
Study author and RSNA

CHICAGO - Little is known about the origins of manikins--small anatomical sculptures thought to be used by doctors four centuries ago--but now advanced imaging techniques have offered a revealing glimpse inside these captivating ivory dolls. Researchers using micro-CT successfully identified the material composition and components of several ancient ivory manikins, according to a new study being presented next week at the annual meeting of the Radiological Society of North America (RSNA).

Ivory manikins are typically thought to have been carved in Germany in the late 17th century. They are reclining human figurines, 4-8 inches long, generally female, which open to reveal removable organs and sometimes a fetus attached with a fabric "umbilical" cord. The manikins have intricately carved features, and some even have pillows beneath their heads. It is believed that they were used for the study of medical anatomy or perhaps as a teaching aid for pregnancy and childbirth. By the 18th century, they had been replaced by more realistic teaching tools, such as wax models and cadavers. The manikins then became objects of curiosity and luxury status symbols in private collections.

Duke University in Durham, N.C., holds the world's largest collection of manikins (22 out of 180 known manikins worldwide). Most of the manikins in the Duke collection were purchased in the 1930s and 1940s by Duke thoracic surgeon Josiah Trent, M.D., and his wife Mary Duke Biddle Trent, prior to the 1989 ivory trade ban. The researchers noted that after being donated to the university by Trent's granddaughters, the manikins have spent most of their time in archival storage boxes or behind display glass, as they are too fragile for regular handling.

"They are usually stored in a library vault and occasionally rotated into a special display unit in the Duke Medical Library for visitors to appreciate," said Fides R. Schwartz, M.D., research fellow in the Department of Radiology at Duke.

Non-destructive imaging with X-rays and CT has been used in the past to examine fragile artwork and ancient artifacts. Imaging of relics has been extremely beneficial to the fields of archaeology and paleopathology--the study of ancient diseases.

Micro-CT is an imaging technique with greatly increased resolution, compared to standard CT. It not only allows visualization of internal features, it noninvasively provides volumetric information about an object's microstructure.

Dr. Schwartz and colleagues hoped that through micro-CT imaging they could determine the ivory type used in the Duke manikins, discover any repairs or alterations that were not visible to the naked eye, and allow a more precise estimation of their age.

"The advantage of micro-CT in the evaluation of these manikins enables us to analyze the microstructure of the material used," she said. "Specifically, it allows us to distinguish between 'true' ivory obtained from elephants or mammoths and 'imitation' ivory, such as deer antler or whale bone."

The research team scanned all 22 manikins with micro-CT and found that 20 out of the 22 manikins were composed of true ivory alone, though materials like antler might have been less expensive in that time. They discovered that one manikin was made entirely of antler bone, and one manikin contained both ivory and whale bone components.

Metallic components were found in four of the manikins, and fibers in two. Twelve manikins contained hinging mechanisms or internal repairs with ivory pins, and one manikin contained a long detachable pin disguised as a hairpiece.

The most established trade routes in the 17th and 18th centuries sourced ivory from Africa, leading the researchers to believe that since nearly all of the manikins were made from true ivory, it is likely that the ivory obtained to craft the manikins was acquired from the African region.

"This may assist in further narrowing down the most probable production period for the manikins," Dr. Schwartz said. "Once historical trade routes are more thoroughly understood, it might become clear that the German region of origin had access to elephant ivory only for a limited time during the 17th and 18th century, for example, from 1650 to 1700 A.D."

Additionally, identifying non-ivory components in the manikins may provide more accessibility to carbon dating, allowing the researchers to more accurately estimate the age of some of the manikins without damage to the fragile pieces.

The researchers also hope to acquire 3D scans to create digital renderings and enable subsequent 3D printed models.

"This is potentially valuable to scientific, historic and artistic communities, as it would allow display and further study of these objects while protecting the fragile originals," Dr. Schwartz said. "Digitizing and 3D printing them will give visitors more access and opportunity to interact with the manikins and may also allow investigators to learn more about their history."

Credit: 
Radiological Society of North America

On balance, some neonicotinoid pesticides could benefit bees

image: A buff-tailed bumblebee collects pollen and nectar from a red clover flower.

Image: 
American Chemical Society

The story of neonicotinoids is growing more nuanced. Europe has banned outdoor use of three of these insecticides to protect bee populations. Two other neonicotinoids are still permitted, but little is known about their impact on bees. New research reported in ACS' Environmental Science & Technology on one of the permitted neonicotinoids indicates it effectively controls pests and might even help bees.

Neonicotinoids are widely used to defend crops from insects that can destroy them. Some of these crops benefit from pollination, but pesticide treatment can expose bees and other beneficial insects to residues in pollen and nectar. The exposure can kill bees or impair them -- for example, by diminishing their foraging abilities -- contributing to declines in bee populations. This outcome led to the ban of three high-risk neonicotinoid insecticides in Europe. Maj Rundlöf and Ola Lundin wanted to know if bees and the flowering crops they use for food would be better off with or without the use of one of the less-harmful neonicotinoids.

In a field study, the researchers found that applying the neonicotinoid thiacloprid on red clover had no observable negative effects on bumblebees. The thiacloprid treatment effectively controlled pests and increased bumblebee crop visitation. However, if this neonicotinoid weren't available, farmers might replace red clover with other nonflowering crops less sensitive to pest infestations, the researchers reasoned. So the team also examined bee performance in landscapes lacking red clover. They found that bumblebee colonies near thiacloprid-treated red clover fields grew heavier (with more larvae, bees and food stores in them) compared to colonies in landscapes without red clover. According to the researchers, the study indicates that certain neonicotinoid insecticides still permitted in the European Union might benefit bumblebees by presenting a low risk to the bees while protecting flowering crops as an important food source. The researchers also say that neonicotinoid insecticides should not be considered as a homogeneous group when conducting risk assessments.

Credit: 
American Chemical Society

Bad news for Nemo

image: If high-quality anemones remain healthy, the clownfish population will persist. However, if the anemones and coral reefs they call home are impacted by climate warming, clownfish are in trouble.

Image: 
(Photo by Simon Thorrold, Woods Hole Oceanographic Institution)

The beloved anemone fish popularized by the movies "Finding Nemo" and "Finding Dory" don't have the genetic capacity to adapt to rapid changes in their environment, according to a new study by France's National Centre for Scientific Research (CNRS), Woods Hole Oceanographic Institution (WHOI) and colleagues. Their findings published Nov. 27, 2019, in the journal Ecology Letters.

An international team of researchers monitored clownfish in the lagoons of Kimbe Bay--a biodiversity hot spot in Papua New Guinea--for more than a decade. Using genetic analysis of the population's DNA, the researchers were able to calculate their potential to adapt to habitat changes and renew their population. They found that big families of clownfish that extended over many generations were linked to high-quality habitats, rather than to shared genes.

"The findings reported here were made possible by a huge sampling and DNA sequencing effort that had not been attempted for any marine species before," says WHOI biologist Simon Thorrold, a coauthor of the paper. "The biggest surprise to us was also the most troubling: conservation efforts cannot rely on genetic adaptation to protect clownfish from the effects of climate change. It seems that Nemo won't be able to save himself."

The quality of the anemone that provides a home to clownfish contributes significantly--on average 50 percent--to its ability to survive and renew its population. If high-quality anemones remain healthy, the clownfish population will persist. However, if the anemones and coral reefs they call home are impacted by climate warming, the clownfish are in trouble.

"Nemo is thus at the mercy of a habitat that is degrading more and more every year," says Benoit Pujol, an evolutionary geneticist at CNRS. To expect a clownfish to genetically adapt at pace which would allow it to persist in the lagoons would be unreasonable, and thus the ability of these fish to remain in the lagoons over time will depend on our ability to maintain the quality of its habitat."

Credit: 
Woods Hole Oceanographic Institution