Culture

Scientists at UNSW Sydney, together with collaborators from Western Sydney University and The Netherlands, were surprised to find that dihydrogen phosphate anions - vital inorganic ions for cellular activity - bind with other dihydrogen phosphate anions despite being negatively charged.

The same team also made a molecule that could 'grab' these dihydrogen phosphate anions and depending on what coloured light was shone on them, either increase or inhibit their movement in solution.

The research, which was published recently in The Journal of the American Chemical Society, provides new insight into molecular interactions that occur during biochemical processes, while introducing new methods for controlling the transport of molecules in solution.

Associate Professor Jon Beves from UNSW's School of Chemistry says chemists have always known dihydrogen phosphate was 'a bit weird' and hard to study in solution, but until now nobody knew what was really happening.

"Our work shows that these negatively charged anions are actually bound together, even in dilute solutions where hydrogen bonds are thought to be extremely weak," he says.

"The hydrogen bonds between dihydrogen phosphate anions seem to be surprisingly strong. They're strong enough to overcome like-charge repulsion, and strong enough to hold the anion clusters together even when dissolved in hydrogen-bonding solvents that we expected would tear them apart."

A/Prof. Beves says the new understanding could also go some way towards explaining the structure of biological membranes, or how RNA or DNA are attracted to one another in solution, since these interactions all involve phosphate groups. And being able to control the movement of these molecules in solution by using light raises some interesting ideas about how this could be applied in biological or environmental situations.

"Mixed liquid solutions are made up of lots of molecules all moving and tumbling at random," A/Prof. Beves says.

"This makes it really hard to do things like extract valuable or polluting metals from dilute solutions, or deliver drug molecules where they need to go in a human body. If we could control the movement of some of those molecules and tell them where to go, it could make those tasks much more achievable."

But A/Prof. Beves stresses that such applications would be a long way down the track requiring much more research. For now, he's excited about doing important work in a poorly understood area of fundamental chemistry.

He says the work his team carried out used an organic solvent called dimethyl sulfoxide and he imagines future studies would look at whether phosphate behaves in the same way in water, where all biological chemistry takes place.

But for the next step, his team is looking at exploring how molecules can be actively transported in solution.

"Our next goals will be to use these types of interactions to actively drive the transport of molecules using light - for example, using a laser pointer to direct molecules to move."

In recent decades China has built over 1,400 large industrial parks, a massive investment accounting for over 40 percent of the country's manufacturing jobs. However, some of these projects are more successful than others. Now, a study co-authored by an MIT professor suggests that some industrial parks appear to have been developed due to networks of political ties -- and those parks distinctly underperform their counterparts.

The finding adds nuance and detail to the big-picture story of China's explosive economic growth over the last thirty-plus years. The research outlines the broad success of China's industrial policy and new cities, while revealing the dynamics behind some less-successful economic choices and "ghost towns."

Specifically, the study finds that when provincial political leaders have preexisting ties to city leaders, those cities are more likely to acquire new industrial parks -- but those sites produce 5.2 percent less GDP per capita than their counterparts in other cities, which lack the same political connections but have stronger economic fundamentals.

"We call it the price of the friendship," says MIT Professor Siqi Zheng, an expert on urban growth in China and co-author of a new paper detailing the study's findings. "That price is about 5 percent less GDP per capita than if you made the decision based on economic fundamentals."

The study also shows that about a quarter of China's provincial-level party secretaries have had significant workplace connections to city-level party secretaries in the period under study, providing a strong set of ties that can influence economic decisions.

The study's results are described in a newly published paper, "Do Political Connections Help or Hinder Economic Growth? Evidence from 1,400 Industrial Parks in China," appearing in the December issue of the Journal of Urban Economics.

The co-authors of the paper are Zheng, who is the Samuel Tak Lee Professor of Urban and Real Estate Sustainability in MIT's Department of Urban Studies and Planning, as well as the faculty director for the MIT Center for Real Estate and the faculty director for the MIT Sustainable Urbanization Lab; Matthew E. Kahn, a professor of economics and business, and director of the 21st Century Cities Initiative at Johns Hopkins University; Weizeng Sun, an associate professor of economics at the Central University of Finance and Economics in Beijing; and Jianfeng Wu, an associate professor of economics at Fudan University.

In recent decades, China has built 1,417 large industrial parks in and around 276 cities, with the earlier projects mostly located in the more-developed eastern part of the country near the coast, and the later ones moving toward the less-developed inland areas. The goods and services situated in these industrial parks account for 10 percent of China's GDP while occupying just 0.1 percent of its land. Past studies have shown that two years after the construction of an industrial park, employment is 47 percent higher than it otherwise would have been in the area, and local economic output rises by 55 percent.

However, a 2017 study co-authored by Zheng also showed that in eight cities with 110 industrial parks, 30 percent of those parks did not add extra economic value, indicating that the outcomes of this kind of targeted industrial expansion can vary significantly.

China's economic policy provides a significant measure of autonomy for local and regional decision-making, including matters such as place-based industrial policy and subsidies. Provincial leaders have the authority to develop new industrial parks, with city officials often vying to have the parks situated in their locales.

To conduct the study, the scholars used economic data from China's National Bureau of Statistics as well as industrial park information from the Ministry of Land and Resources, and built their own data set about the careers and connections of political leaders. To establish whether or not political leaders had preexisting ties with each other, the scholars looked at four factors: their past workplaces, birthplaces, university and college backgrounds, and ties involving political associations or groups in China, such as the Communist Youth League.

The dataset about political leaders covered the years 1987-2008 and yielded useful insights. For instance: When provincial-level and city-level leaders have past ties, those cities are 7.4 percent more likely to have industrial parks awarded to them in the first place.

"Mayors all want parks because they know it will potentially boost their cities' local economies," Zheng says. At the same times, she notes, "If the park can stimulate the economy, this is also good for the local provincial leader. But the other consideration is friendship -- a provincial leader might reward his friend in return for loyalty and political support."

In the research, which began eight years ago and now had yielded multiple published papers, the scholars worked carefully to account for other factors affecting the placement and performance of industrial parks throughout China, until ultimately they believed they could make an apples-to-apples comparison of parks built in cities with connected local officials, and those built elsewhere.

There have been multiple waves of industrial park-building in China; from their previous research, Zheng and her colleagues have concluded that the most economically successful industrial parks capitalize on synergies with existing firms, such as relationship between suppliers and manufacturers, to produce positive outcomes.

When industrial parks are developed in places without logical synergies in existence, Zheng ultimately concludes, "The political connections cause problems of misallocation."

Comprehensive identification of viral proteins encoded by viral genes is required to understand the pathophysiology of viral infections. A research team led by Professor Yasushi Kawaguchi of the Institute of Medical Science, the University of Tokyo, conducted mass spectrometry specialized for novel synthetic proteins of viruses, and developed a new decoding method for viral genes that can easily and quickly obtain even non-canonical genetic information.

Using this new decoding method, they identified nine novel proteins encoded by herpes simplex virus type 1(HSV-1) (*1) and found that one of them, piUL49, is a pathogenic factor that specifically controls the onset of herpes encephalitis (*2).

These results were published in Nature Communications on September 29, 2020.

Protein piUL49 is involved in brain-specific viral proliferation and the onset mechanism of viral encephalitis

It is difficult to decipher the whole picture of diverse and complex genetic information hidden in the viral genome with conventional technology, and the development of a new method has been required for decoding viral genes, especially those encoding non-canonical translational elements.

Many viruses are known to shut-off new synthesis of host proteins. Focusing on this property, the research team purified newly synthesized proteins by the BONCAT method (*3) and performed high-sensitivity mass spectrometry.

They found that most of the peptides obtained were derived from HSV-1, including peptides from viral proteins encoded by nine novel HSV-1 genes. All the newly identified HSV-1 genes encode non-canonical translational products.

They named one of these novel viral proteins piUL49. Using analysis of a mouse model of HSV-1 infection, they clarified that piUL49 is involved in brain-specific viral proliferation and the onset mechanism of viral encephalitis. For details of the research, please see the paper.

Expected to lead to the development of new treatments for HSV encephalitis

The entire base sequence of the HSV-1 genome was determined about 20 years ago, and it is thought that the decoding of the viral genes encoding canonical translational elements has already been completed. However, information on the decoding of viral genes encoding non-canonical translational elements has been limited.

It is of great academic significance to discover nearly 10 new HSV genes and to clarify that one of them encodes piUL49, which is involved in the development of viral encephalitis.

Professor Kawaguchi, the lead scientist of this research, stressed the importance of their finding as follows. "Elucidation of the onset mechanism of encephalitis through piUL49 will greatly contribute to the understanding of the high central nervous system orientation of HSV-1. We hope that the results will lead to the development of new treatments for HSV-1 encephalitis.

An area in the Olympic Peninsula's Hoh Rain Forest in Washington state for years held the distinction as one of the quietest places in the world. Deep within the diverse, lush, rainy landscape the sounds of human disturbance were noticeably absent.

But in recent years, the U.S. Navy switched to a more powerful aircraft and increased training flights from its nearby base on Whidbey Island, contributing to more noise pollution on the peninsula -- and notably over what used to be the quietest place in the continental U.S. While local residents and visitors have noticed more aircraft noise, no comprehensive analysis has been done to measure the amount of noise disturbance, or the impact it has on people and wildlife.

Now, as the Navy is set to implement another increase in flight activities, a University of Washington study provides the first look at how much noise pollution is impacting the Olympic Peninsula. The paper found that aircraft were audible across a large swath of the peninsula at least 20% of weekday hours, or for about one hour during a six-hour period. About 88% of all audible aircraft in the pre-pandemic study were military planes.

"I think there is a huge gap between what the Navy is telling people -- that its aircraft are not substantially louder and operations haven't changed -- and what people are noticing on the ground," said lead author Lauren Kuehne, who completed the work as a research scientist at the UW School of Aquatic and Fishery Sciences and is now an independent consultant. "Our project was designed to try and measure noise in the ways that reflect what people are actually experiencing."

The study was published Nov. 25 in the journal Northwest Science.

The Navy is set to implement a 75% increase in air activities over the Olympic Peninsula, a place that is historically, culturally and ecologically significant. Eight American Indian tribes call the peninsula home, while Olympic National Park receives more than 3 million visitors a year and is a UNESCO World Heritage Site. More than two dozen animal species are found only on the peninsula, and multiple species are listed as threatened or endangered under the federal Endangered Species Act.

"The Olympic Peninsula is a renowned hotspot for wildlife, home for people of many different cultures and a playground for outdoor enthusiasts," said co-author Julian Olden, professor at the UW School of Aquatic and Fishery Sciences.

The researchers chose three primary sites on the Olympic Peninsula to monitor the soundscape during four seasonal periods from June 2017 to May 2018. Two sites, at Third Beach and Hoh Watershed, were near the coast, while the third site was inland on the Hoh River Trail. They placed recorders at each site to capture sound continuously for 10 days at time, then recruited and trained volunteers to help process the nearly 3,000 hours of recorded audio.

"This data is very accessible -- you can hear and see it, and it's not rocket science," Kuehne said. "I wanted people to feel like they could really own the process of analyzing it."

From their analysis, the researchers identified nearly 5,800 flight events across all monitoring locations and periods. Of these, 88% were military aircraft, 6% were propeller planes, 5% were commercial airplanes and less than 1% were helicopters. Three-quarters of all recorded military aircraft noise occurred between 9 a.m. and 5 p.m. on weekdays. Most of the military aircraft were Growlers, or Boeing EA-18G jets that are used for electronic warfare -- drills that resemble "hide and seek" with a target.

The researchers found that most of the aircraft noise was intermittent, detectible across all the sites that were monitored simultaneously, and followed no set pattern. The noise mostly registered between 45 and 60 decibels, which is comparable to the air traffic sounds in Seattle, Kuehne said. Occasionally, the sound level would hit 80 decibels or more, which is akin to the persistent noise when walking under Seattle's former waterfront viaduct.

Conversations with local residents also revealed a majority who notice the low-level jet noise, the researchers said. The chronic and unpredictable nature of the noise is especially tiresome for residents, and some report difficulty sleeping, learning in school and even interference with hearing aids.

Previous research has shown that loudness is only one aspect of how sound can impact human health. Studies have found that the duration of noise, unpredictable patterns and the inability to control exposure all contribute to stress, annoyance, sleep disturbance and interference with learning.

Noise impacts on wildlife are less studied, but some research has shown it can prompt physiological stress and impact animals' ability to reproduce successfully. Noise can also interfere with how animals communicate and find prey.

"The deafening sound of anthropogenic noise not only threatens wildlife but may also deter people from visiting in the future," Olden said. "Why travel to the Olympic Peninsula to only experience noise comparable to Seattle?"

The researchers hope these results will prompt follow-up assessments of how chronic aircraft noise impacts residents on the peninsula. They also hope the Navy will publicly acknowledge the extent of its noise pollution and consider changing its operations near the peninsula.

"My wildest-dream scenario is that this would allow the Navy to take seriously people's requests that they move at least some of the training elsewhere, to other military operations areas," Kuehne said.

The white of paper and the white of monitor can be precisely the same color values, yet they appear fundamentally different. That disparity may not lie in the mode of display, but rather how the colors are constructed, according to a research team at Yokohama National University in Japan.

They published their findings on October 27 in Scientific Reports, a Nature Research journal.

"We experimentally showed that the reason why color appearance between surface color and self-luminous color cannot be matched is the difference of spectral distributions, not the difference of devices," said paper author Katsunori Okajima, professor in the Faculty of Environment and Information Sciences at Yokohama National University.

Surface colors are those that humans see by light bouncing off a solid media, such as paper, wood or fabric. Self-luminous colors are seen via a light that emits directly from the color itself, such as those displayed on computer monitors or phone screens.

"Theoretically, the color appearance of lights that have equal colorimetric values should match regardless of their spectral distributions," Okajima said. "However, the color appearances of objects with the same colorimetric values on a monitor and a paper are mostly mismatched, even under conditions where not only the tristimulus values of the targets but also those of the surrounding environment and observation environment are identical."

Tristimulus values are standardized assessments of red, green and blue that account for color as well as how humans visually perceive the color. According to Okajima, previous studies in the field of color science have not been able to solve the underlying problem of mismatch between cross-media because they have not rigorously examined the physical effects of color perception.

"In other words, the physical and psychological factors cannot be made independent, and as a fundamental problem, it cannot be denied that the difference in physical luminescence also affects the color appearance," Okajima said. "Therefore, we need to determine whether we can match the color appearance when we compare isomeric color-matching conditions that have the same spectral distributions between cross-media. Such an isomeric condition has one more advantage in that we do not have to consider the individual difference between observers."

To achieve isomeric, or identical, color-matching conditions, the researchers designed an experiment that allowed participants to view surface and self-luminous colors with exactly the same spectral distributions. The researchers also prepared conditions in which the color values matched identically, but not the spectral distribution of light.

The researchers found that the 12 out of 13 participants could not match the color appearances under metameric conditions, yet they were able to match colors more than 90% of the time under identical spectral distributions. One outlier participant had high matches in both categories, leading the researches to guess that person may be a standard observer, meaning they can naturally precisely perceive colors.

"These results show the difference in the physical mechanism does not affect the color appearance problem," Okajima said. "They further suggest the differences in spectral distributions cause mismatch of color appearance in cross-media color reproduction. If the spectral distributions are matched, color matching is possible in any color appearance mode."

The researchers will next work to clarify how the cells in the eye that send light to the brain may affect color appearance.

"Our results are significant not only for color science, but also for industry, and lead to the importance of multispectral displays for recreating color images precisely," Okajima said.

While many people are now enjoying longer, healthier lives, current retirement ages are posing challenges for both policymakers and retirees. A new study looked into whether there is potential to increase the retirement age based on the relationship between working life expectancy and health aspects important for work ability for women and men in Europe.

Life expectancy has steadily been increasing in many countries around the world due to, among others, advances in healthcare and people adopting healthier lifestyles. At the same time, fertility has been declining or stabilized at low levels, leading to a marked increase in the share of older adults in these populations. This situation poses a risk to financial sustainability in several areas of social security systems, one of them being pension systems, as most European countries provide public pensions to their citizens. Retirement ages and measures to support longer working lives are being widely discussed at the country, as well as the European Union level, and many countries have already initiated and passed policy changes to gradually increase the official retirement age. One pertinent question that has however surfaced in this context is how large the potential is to increase working lives further given people's health status.

In their study published in the European Journal of Aging, IIASA researcher Daniela Weber and Elke Loichinger from the Federal Institute for Population Research in Germany investigated whether there is potential to generally increase the retirement age. They based their analysis on the relationship between working life expectancy and three health expectancies that represent health aspects important for work ability and employability between ages 50 and 59, as well as ages 60 and 69 for women and men in Europe.

"There are several studies on the relationship between retirement and health on the individual level, but studies on the population level are rare and we were surprised to find that differences in health and working life expectancies had not been quantified before. We wanted to see how large the potential is to increase working lives further, given people's health status and also how this potential differs between men and women for different age groups and between different socioeconomic groups," explains Loichinger.

To this end, the researchers analyzed the relationship between working life expectancy and health expectancy, differentiating between three health dimensions, namely physical health, cognitive health, and general health. Moreover, they analyzed heterogeneity in working life expectancy and all three health outcomes by education. The analysis specifically focused on age groups 50-59 and 60-69 as those are, and will continue to be, most affected by future increases in retirement ages.

The findings indicate that, overall, there is potential to increase the expected number of economically active years for both men and women between the ages 60 and 69. An education-specific analysis however revealed large differences between socioeconomic subgroups of the population when it comes to the size of this potential. For instance, 60-year old men in Sweden with low education can expect to work 4.2 more years. This increases to six more years when they have a tertiary-level education. With regard to their physical health, men with a low level of educational attainment can expect 8.4 years in good health and 8.7 years when they have a tertiary-level education. In Bulgaria, men of the same age with a tertiary level of education can expect to work 4.5 more years while expecting 5.7 more years in good physical health. Their counterparts with a low level of educational attainment can expect only 2.7 years in good physical health, during which they are also expected to work.

"The heterogeneity between education groups in terms of health and the ability to work beyond currently observed labor market exit ages has to be taken into account when working lives are being extended. Our results indicate potential to extend working lives beyond current levels. However, significant differences in the expected number of years in good health between persons with different levels of education require policies that account for this heterogeneity," Weber concludes.

Nearly three percent of the world's population is at risk of developing an intracranial aneurysm, a localized dilation of a blood vessel forming a fragile pocket. Rupture of this aneurysm results in extremely severe, and, in one-third of cases, fatal haemorrhage. In the framework of the International Stroke Genetics Consortium, a team led by the University of Geneva (UNIGE), the University Hospitals of Geneva (HUG) and the University of Utrecht is studying the genetic determinants of aneurysms in order to better understand the different forms of the disease and to assess individual risk. Through the examination of the genome of more than 10,000 people suffering from aneurysms compared to that of 300,000 healthy volunteers, 17 genetic abnormalities have been identified that are notably involved in the functioning of the vascular endothelium, the inner lining of blood vessels. In addition, the scientists discovered a potential link between these genetic markers and anti-epileptic drugs, making it possible to consider the use of certain drugs in the management of the disease. These results, to be read in the journal Nature Genetics, also highlight how the wise use of large databases containing genomic and phenotypic information can advance research.

Every year, five out of every 100,000 people experience a rupture of an intracranial aneurysm - as many as those injured in road accidents. And only very rapid and highly specialized surgical management can hope to save their lives. &laquoIt is therefore essential to better understand the genetic basis - inherited or otherwise - governing the risk of developing the disease, but also to distinguish between the different forms of the disease and its severity. This will allow us to detect people at risk and offer them the most appropriate treatment,» explains Philippe Bijlenga, Assistant Professor in the Department of Clinical Neurosciences at UNIGE Faculty of Medicine and Senior Consultant at HUG Division of Neurosurgery, who led the Swiss part of this study. This multipronged disease, whose evolution depends on genetic, congenital and environmental factors, is indeed complex to apprehend. &laquoThe tiny variations that make it up must therefore be deciphered,» he adds.

A study of unprecedented scope

The work carried out in Geneva and Utrecht is the largest genetic study in the world in the field of intracranial aneurysms. The DNA of more than 10,000 patients was examined and compared with that of 300,000 volunteers: eleven new regions of the genome - compared with six previously - were found to be associated with the disease. &laquoEach of these DNA variations causes a slight increase in the risk of an intracranial aneurysm,» says Ynte Ruigrok, neurologist and associate professor at the University Medical Center of Utrecht University, who co-led the study. &laquoThus, their accumulation can, together, constitute a significant risk."

Most of these genetic abnormalities appear to be related to the functioning of the endothelial cells that line the inside of blood vessels and usually make them robust. "These cells have long been suspected of being responsible for aneurysms,» says Philippe Bijlenga. &laquoWe now have evidence that leads us to work on possible markers of instability that could indicate whether the aneurysm is stable, healed, or at high risk of adverse outcomes."

In addition, this research shows that a genetic predisposition to high blood pressure and smoking play an important role in the development of an intracranial aneurysm. If these risk factors were already known from a clinical and epidemiological point of view, we now have the genetic evidence.

The scientists also made a surprising discovery: &laquoIt appears that the protein structures of some of the genes we identified are linked to antiepileptic drugs. We do not yet know whether this effect is positive or negative, but it opens up the possibility for pharmacological treatments, potentially less invasive than the surgical approaches we are currently using,» says Philippe Bijlenga. The scientists will now work on modelling the disease, both biologically and therapeutically, to offer physicians a medical decision support system that will help determine potential management protocols based on each person's genetic data.

Scientific advances and data protection

To carry out these studies, the research teams must have access to a very large number of patients, and therefore work in international consortia. &laquoTo achieve this, we have set up tools to standardize complex data. We had to find a common language, unify clinical evaluation criteria, imaging methods and their computer processing, and establish exchange structures while guaranteeing the protection of personal data,» reports Philippe Bijlenga, who supervised this work on data.

The consortium has set up a structure capable of collecting, harmonizing and securing huge amounts of data. The Swiss Institute of Bioinformatics (SIB) manages the phenotypic data, while the University of Utrecht stores the genomic data. Both datasets are accessible through an approval process to research teams around the world. &laquoHowever, proper use must be demonstrated. Our system allows scientific advances, but with protection of personal data,» the authors conclude.

At some point in life, most people have stood over a rolled-out slab of cookie dough and pondered just how to best cut out cookies with as little waste as possible. Now, even math experts have given up on finding a computer algorithm to answer this type of geometric problem.

How can we maximize dough while cutting out Christmas cookies? How do we pack a suitcase or fill a kitchen cabinet while making the best use of space? One may have thought, "there must be a best way to do this." Pondering such questions too deeply now appears to be a complete waste of time. The science is now here to support that it is impossible, for the time being, to figure out what works best for more than four or five spicy gingerbread men or Christmas tree cookies.

Assistant Professor Mikkel Abrahamsen of the Department of Computer Science and two research colleagues studied how difficult it is to figure out the optimal way to pack objects in two dimensions without overlap -- a conundrum that computer scientists have plugged away at for decades.

"While algorithms let us solve seriously complex problems, this is one that remains too much of a mouthful for today's computers. For now, it isn't possible to pack more than 5-10 objects optimally. And, our result suggests that this number probably won't increase much for the time being," explains Mikkel Abrahamsen.

Packing things optimally isn't just an occasional problem at home, but in a variety of industries, including clothing manufacturing and metal processing. In each case, it is important to cut out materials with as little waste possible. In shipping, it applies to the packing of containers.

Only four gingerbread cookies

We know the size of the smallest square container in which we can pack up to 10 square 1x1 meter pallets. But by simply adding one additional pallet, it becomes impossible to calculate the optimal size of the container. Abrahamsen explains:

"As more pallets are added, the calculation time increases beyond exponentially. Not even the best computers can keep up. Theoretically it's possible. But based upon the speed at which computing power is growing, it will probably take millions of years before we are able to optimize the handling of a few additional objects."

Furthermore, if one is working with more complicated shapes, like Christmas tree-shaped gingerbread, Mikkel Abrahamsen says that optimal solutions can only be found for up to four objects today.

An infinite number of options

What makes it so difficult? Abrahamsen explains that the problem is similar to solving equations of degree five or higher, and with many unknowns. Here, it is known that such a solution cannot always be written down using regular arithmetic operations.

"Our study proves that the problem has a nature that we in mathematics refer to as continuous -- which in a nutshell, means that one must know all of the coordinates at which the cookies can be placed and all of the angles at which they can be rotated," explains Abrahamsen.

As the possible combinations are infinite, there is no way to create a list of all the locations needed to try in order to find an optimal packing solution. Instead, algorithms that solve packing problems optimally need to be more analytical, which is time consuming. This contrasts with many other known algorithmic problems, where one can try a limited number of combinations before finding one that is optimal. Thus, packing problems are much more difficult.

So in practice, there are no better solutions to packing problems than the ones we humans can come up with.

"In both industry and over the kitchen counter we must continue to be satisfied with our less-than-optimal solutions and rest assured that we humans are still better than computers for these types of tasks -- for the time being," concludes Mikkel Abrahamsen.

The mangrove forests on Java's north coast are slowly suffocating in plastic waste. The plastic problem in northeast Asia is huge and a growing threat to the region's mangroves; a natural alley against coastal erosion. Based on fieldwork published in Science of the Total Environment, NIOZ researcher Celine van Bijsterveldt shows that restoration of this green protection belt is impossible without better waste management

Plastic trap

Van Bijsterveldt has monitored the accumulation of plastic waste in Indonesian mangroves over years. Most of it includes household litter, carried from the inland to the coastal area by local rivers. Ultimately, the waste gets stuck in the last stronghold between land and sea. Van Bijsterveldt: 'Mangroves form a perfect plastic trap.' For the mangrove tree, this trap can become quite lethal. The most common mangrove tree on Java's coast, the grey mangrove, has upward-growing roots to get oxygen flowing during high tide. 'You can look at these roots as snorkels,' says Van Bijsterveldt. 'When plastic waste accumulates in these forests, the snorkels are blocked.' In areas completely covered by plastic, trees suffocate.

On the forest floor of mangroves along the north coast, it is hard to find a square metre without plastic. 'On average, we found 27 plastic items per square metre,' recounts Van Bijsterveldt. At several locations, plastic covered half of the forest floor. The problem isn't only the plastic on the surface. The team found plastics buried as deep as 35 cm inside the sediment. Plastic, stuck in these upper layers further decreases the trees access to oxygen. Still, Van Bijsterveldt was impressed by the trees' resilience. 'The roots change course when they are obstructed. They grow around the plastic. When half of the forest floor is covered, the tree still gets enough oxygen to keep its leaves.' However, the prospect of survival gets much gloomier once the threshold of 75 % is reached and plastic in the sediment pushes it towards 100%. 'We've seen roots stuck inside plastic bags. Trying to find a way out, they just grow in circles. Eventually trees that cannot outgrow the plastic die.'

Battling erosion and breaking waves
In cooperation with NGO's and local communities, Van Bijsterveldt works on mangrove restoration projects to prevent further erosion. Over the years many mangrove forests had to make way for rice paddies and later aquaculture ponds. A business model that brings fast profits but lacks in sustainability as it accelerates erosion. Not a small problem in a region threatened by coastal loss and rapid subsidence, and no financial means to build high-cost and high-maintenance solutions like dykes. Van Bijsterveldt: 'Mangroves form a low-cost, natural defence for the coastal communities. They act like wave breakers and can prevent erosion by trapping sediment from the water.'

Restoration brings more benefits. Healthy mangroves mean healthy fish populations and a sustainably fishing economy. The tourism industry is also discovering the forests as a growing attraction that boosts the local economy. The Indonesian government is investing in mangrove restoration in an attempt to re-create a green-belt along the coast. But restoration is slow and existing forests are stressed. Van Bijsterveldt, saw attempts of planting new mangroves fail: 'There is so much focus on increasing the initial number of mangrove seedlings, that the challenges posed by plastic waste on the actual survival of young trees is overlooked'. Replanting mangroves without tackling the plastic problem is like trying to try to empty the ocean with a thimble. Successful restoration needs to go hand in hand with sustainable waste management.'

Some useful drugs consist of peptides acting on their protein targets. To make them more efficient and stable, scientists have found a way to replace crucial segments of the peptides with ureido units. These oligoureas, which are composed of urea-based units, fold into a structure similar to that of peptides. Oligourea-based "fake" peptides enhance the options for rational drug design, concludes the study published in the journal Angewandte Chemie.

Several drugs are peptides that inhibit or activate the actions of certain proteins. To enhance their efficiency, scientists are investigating peptide mimics. Peptide mimics contain strands of small organic units that resemble amino acids--the building blocks of peptides--but are not identical to them. The rationale is that proteolytic enzymes will less likely attack such fake peptide strands, so the drugs would be more effective.

However, the synthetic strands--called oligomers--must fold into the structure of the original peptide to bind to its target protein properly. Gilles Guichard and his team from CNRS, University of Bordeaux, and colleagues from the University of Strasbourg and Ureka Pharma, Mulhouse, France, have explored oligomers made of ureido units, which are derivatives of urea. These oligoureas fold into a helix, one of the hallmark structures of peptides. However, there are slight differences. "Oligourea helices have fewer residues per turn, a smaller rise per turn, and a larger diameter than the original peptide alpha-helix," says Guichard.

To determine whether oligoureas could mimic real peptide structures, the researchers prepared peptide-oligourea hybrids and investigated their binding to target proteins. One of the targets, MDM2, is a natural regulator of the tumor suppressor protein p53. The other one, VDR, is a protein required in the regulation of cell growth, immunity, and other biological functions.

For the MDM2-binding peptide mimic, the researchers prepared hybrids by replacing three terminal key amino acids with ureido units. For the VDR-binding peptide mimic, they replaced the middle amino acid segment with ureido units. After some rounds of optimization, the authors found hybrid structures with high binding affinities.

The binding affinities were similar to those of the original peptides. Moreover, X-ray analysis revealed that the hybrid structures adopted a regular helical structure. However, the helices were still a bit wider and had larger spaces between the side chains along the oligourea backbone than those of natural peptides.

Peptide-oligourea hybrids are expected to resist proteolytic degradation, an important goal in medicinal chemistry. Another advantage is that they allow more modifications. "Alpha amino acids can be substituted at two positions, but ureido units have one site more," says Guichard. This means that hybrid peptide-oligourea drugs offer more options for optimization.

Guangzhou, December 5, 2020: New journal BIO Integration (BIOI) publishes its third issue, volume 1, issue 3 which is a themed issue on the integration of artificial intelligence (AI) in medicine and biomedicine. BIOI is a peer-reviewed, open access, international journal, which is dedicated to spreading multidisciplinary views driving the advancement of modern medicine. Aimed at bridging the gap between the laboratory, clinic, and biotechnology industries, it will offer a cross-disciplinary platform devoted to communicating advances in the biomedical research field and offering insights into different areas of life science, in order to encourage cooperation and exchange among scientists, clinical researchers, and health care providers.

Featured papers in this issue:

The first featured article in this issue is an opinion article entitled "New Roles for Clinicians in the Age of Artificial Intelligence" by authors Fengyi Zeng, Xiaowen Liang and Zhiyi Chen. Artificial intelligence (AI) has been widely applied in the medical field. Barely a day goes by without a claim that AI techniques are poised to replace most of today's professionals. The integration of AI in medicine has necessitated the exploration of new roles for clinicians in the age of AI.

The second featured article in this issue is a review article entitled "Artificial Intelligence (AI)-aided Disease Prediction" by Chenxi Liu, Dian Jiao and Zhe Liu. Artificial intelligence (AI) used in clinical medicine is witnessing increasing innovations in the fields of AI-aided image analysis, AI-aided lesion determination and AI-assisted healthcare management. This review article focuses on the emerging applications of AI-related medicine and AI-assisted visualized medicine, including novel diagnostic approaches, metadata analytical methods, and versatile AI-aided treatment applications in preclinical and clinical uses, and also looks at future perspectives of AI-aided disease prediction.

The third featured article in this issue is a review article entitled "A Survey on Artificial Intelligence in Chest Imaging of COVID-19" by Yun Chen, Gongfa Jiang, Yue Li, Yutao Tang, Yanfang Xu, Siqi Ding, Yanqi Xin and Yao Lu. Chest imaging techniques including computed tomography and X-ray scans are indispensable tools in COVID-19 diagnosis and its management. The strong infectiousness of this disease brings a huge burden for radiologists. In order to overcome the difficulty and improve accuracy of the diagnosis, artificial intelligence (AI)-based imaging analysis methods are explored. This survey focuses on the development of chest imaging analysis methods based on AI for COVID-19 in the past few months. Imaging analysis methods of two typical viral pneumonias are reviewed, which can provide a reference for studying the disease on chest images.

Other articles published in the issue include:

Editorial

An Integrated Approach to Ultrasound Imaging in Medicine and Biology
Pingtong Huang

Original Article

Scale-aware Auto-context-guided Fetal US Segmentation with Structured Random Forests
Xin Yang, Haoming Li, Li Liu and Dong Ni

News and Views

BIOI Virtual Academic Series PART 2: Frontiers and Multidisciplinarity in Nanomedicine
Phei Er Saw

As the global population grows and ages, so does their need for eye care. But according to two new studies published in The Lancet Global Health, these needs aren't being met relative to international targets to reduce avoidable vision loss.

As 2020 comes to a close, an international group of researchers set out to provide updated estimates on the number of people that are blind or visually impaired across the globe, to identify the predominant causes, and to illustrate epidemiological trends over the last 30 years.

"This is important because when we think about setting a public health agenda, knowing the prevalence of an impairment, what causes it, and where in the world it's most common informs the actions that key decision makers like the WHO and ministries of health take to allocate limited resources," says Joshua Ehrlich, M.D., M.P.H., a study author and ophthalmologist at Kellogg Eye Center.

The study team assesses a collection of secondary data every five years, undertaking a meta-analysis of population-based surveys of eye disease assembled by the Vision Loss Expert Group and spanning from 1980 to 2018.

Creating a blueprint

A study like this poses challenges since regional populations vary in age.

"For example, the population in some Asian and European countries is much older on average than the population in many African nations. Many populations are also growing older over time. A direct comparison of the percentage of the population with blindness or vision impairment wouldn't paint a complete picture" says Ehrlich, who is also a member of University of Michigan's Institute for Healthcare Policy and Innovation, explains.

To address this issue, the study looked at age-standardized prevalence, accomplished by adjusting regional populations to fit a standard age structure.

"We found that the age-standardized prevalence is decreasing around the world, which tells us eye care systems and quality of care are getting better," says study author Monte A. Del Monte, M.D., a pediatric ophthalmologist at Kellogg Eye Center. "However, as populations age, a larger number of people are being affected by serious vision impairment, suggesting we need to improve accessibility to care and further develop human resources to provide care."

In fact, the researchers found that there wasn't any significant reduction in the number of people with treatable vision loss in the last ten years, which paled in comparison to the World Health Assembly Global Action Plan target of a 25% global reduction of avoidable vision loss in this same time frame.

Although findings varied by region globally, cataracts and the unmet need for glasses were the most prevalent causes of moderate to severe vision impairment. Approximately 45% of the 33.6 million cases of global blindness were caused by cataracts, which can be treated with surgery.

Refractive error, which causes a blurred image resulting from an abnormal shape of the cornea and lens not bending light correctly, accounted for vision loss in 86 million people across the globe. This largest contributor to moderate or severely impaired vision can be easily treated with glasses.

Also important, vision impairment due to diabetic retinopathy, a complication of diabetes that affects eyesight, was found to have increased in global prevalence.

"This is another condition in which we can prevent vision loss with early screenings and intervention," says study author Alan L. Robin, M.D., a collaborating ophthalmologist at Kellogg Eye Center and professor at Johns Hopkins Medicine. "As diabetes becomes more common across the globe, this condition may begin to affect younger populations, as well."

Looking to 2050

"Working as a global eye care community, we need to now look at the next 30 years," Ehrlich says. "We hope to take these findings and create implementable strategies with our global partners through our Kellogg Eye Center for International Ophthalmology so fewer people go blind unnecessarily."

In an effort to contribute to the WHO initiative VISION 2020: The Right to Sight, the researchers updated estimates of the global burden of vision loss and provided predictions for what the year 2050 may look like.

They found that the majority of the 43.9 million people blind globally are women. Women also make up the majority of the 295 million people who have moderate to severe vision loss, the 163 million who have mild vision loss and the 510 million who have visual impairments related to the unmet need for glasses, specifically poor near vision.

By 2050, Ehrlich, Del Monte, and Robin predict 61 million people will be blind, 474 million will have moderate and severe vision loss, 360 million will have mild vision loss and 866 million will have visual impairments related to farsightedness.

"Eliminating preventable blindness globally isn't keeping pace with the global population's needs," Ehrlich says. "We face enormous challenges in treating and preventing vision impairment as the global population grows and ages, but I'm optimistic of a future where we will succeed because of the measures we take now to make a difference."

NORFOLK, Va. -- After more than three years in development, a team of U.S. Army researchers and industry partners completed the construction of a testbed that will help to inform the design of future Army rotorcraft.

The team plans to test the TiltRotor Aeroelastic Stability Testbed, or TRAST, in a massive wind tunnel at the NASA Langley Research Center to gauge the effectiveness of modern tiltrotor stability models.

"This research effort is to gain confidence in Future Vertical Lift vehicles that are aimed at a tiltrotor configuration," said Andrew Kreshock, an Army aerospace engineer at the U.S. Army Combat Capabilities Development Command, now known as DEVCOM, Army Research Laboratory. "Since future vehicles are being developed without wind tunnel testing, this puts more pressure for accurate stability predictions."

Tiltrotors offer enormous potential for the Army in terms of speed and vertical lift capability. Unlike most aircraft, they can hover in the air like a helicopter or fly forward at great speeds like an airplane depending on the orientation of their rotors.

The ability to transition between the two modes allows tiltrotors to capitalize on the advantages of both rotorcraft and fixed-wing aircraft depending on the situation.

"Currently, the max speed of conventional helicopters is around 160 to 180 knots," Kreshock said. "Tiltrotors can achieve 300 knots. We're looking at almost doubling the speed of our current fleet and thus increasing our range by almost twice as much in the same flight time."

But despite its versatility, tiltrotors face severe stability issues due to the placement of incredibly heavy engines with large rotors on the end of the wings.

The interaction between the propellers and the wings can generate a dangerous phenomenon known as whirl flutter, where strong aerodynamic forces cause the airframe structure to shake violently and even fail.

As a result, tiltrotors are difficult to construct properly, and researchers continue to validate tools necessary to predict how different tiltrotor configurations will fare against whirl flutter.

According to Kreshock, TRAST serves to help researchers develop state-of-the-art analysis software that open the possibilities for new tiltrotor designs.

"Helicopters have gone through many generations from when they were first built to now, but the only tiltrotor in production is the V-22 Osprey," Kreshock said. "And the tools developed for predicting stability in the V-22 were made in the 1960s and 1970s. Because we have better computers now, we can model as many degrees of freedom as we need compared to the tools from decades ago."

In order to predict whirl flutter behavior in TRAST, Kreshock and his team employed different analysis codes for different parts of the tiltrotor structure.

They used a structural code called NASA Structure Analysis, or NASTRAN, to model the aerodynamics of the wing and two different programs--the Comprehensive Analytical Model of Rotorcraft Aerodynamics, or CAMRAD, and the Rotorcraft Comprehensive Analysis System, RCAS--to model the rotorcraft.

Through the combination of these three programs, the team isolated the aerodynamic behavior of individual aircraft components and then used this information to estimate the stability boundaries of the TRAST model.

Once the researchers test the TRAST model in the wind tunnel, they can compare how well the predictions generated by the analysis codes match the actual behavior of TRAST in the face of extreme whirl flutter.

"We want to measure the stability boundary without actually breaking the model," Kreshock said. "It's tricky because as you start getting closer to the stability boundary, you can watch the model vibrate and become more unstable. As we watch this model shake from the window, we have to make sure to keep one finger on the switch to shut down the wind tunnel before the model actually breaks."

According to Kreshock, present tiltrotors like the V-22 Osprey handle the issue of whirl flutter through reinforced airframes and thick airfoils, which severely increase the weight of the aircraft.

He believes that TRAST may help the Army explore new design possibilities for tiltrotors that resolve the whirl flutter problem in different ways, such as wing extensions.

"Compared to civilian aircraft, the Army always pushes their aircraft to the limit," Kreshock said. "In order to meet this demand, we need to improve the stability predictions so that we not only have more efficient aircraft but also be able to test new technology in the future."

Each and every biological organism has an important function in creating a healthy ecosystem, which is why conservationists everywhere encourage protecting biodiversity. However, monitoring wildlife health is an ongoing challenge. A new article in Environmental Toxicology and Chemistry explores the use of a simple, inexpensive, and minimally invasive technique referred to as "micronuclei detection" to assess genetic toxicity (genotoxicity) in free-ranging bats in areas of varying agricultural activity.

Bats play a vital role in our ecosystems and economies as natural pest control agents, seed dispersers, and pollinators. Bats are susceptible to pesticide exposure, especially if they forage near agricultural lands and prey on contaminated pests. Additionally, pesticide applications often take place at dusk when bats are most active.

To evaluate the potential effects of pesticides on bats, Author Natalia Ivone Sandoval Herrera and colleagues collected blood samples from 35 bats* across three roosting caves in Mexico that were surrounded by different levels of agricultural activity. They examined the occurrence and magnitude of damage to genetic material (genotoxicity) in bat cells by measuring the frequencies of micronuclei in the bats. Micronuclei frequency is an index of accumulated genetic damage during the life span of the cells, so higher frequency levels would be expected in bat populations inhabiting areas with more intensive agriculture. In fact, that is exactly what the authors found. The bats roosting in sites surrounded by agricultural lands presented higher frequency of micronuclei compared with bats inhabiting sites with lower agricultural activity. The work showed that this testing method can have wide applications as an inexpensive and minimally invasive technique to evaluate genotoxicity in animals and monitor wildlife health.

Biodiversity is decreasing world-wide, and it is likely due to anthropogenic activities. It is critical to have methods to monitor wildlife population health, because protective and remedial measures are better for maintaining biodiversity than post-mortem assessments. Micronucleus testing does not require expensive equipment and training. Additionally, while there are more sophisticated methods to evaluate genotoxicity, they are not necessarily more sensitive. When asked why we should be paying attention to this testing method, Sandoval Herrera said, "Access to resources might be limited for institutions with less financial support such as conservation NGOs and researchers in developing countries. The use of early warning biomarkers such as genotoxic effects are most needed in these regions, where the use of pesticides is extensive and there is high biodiversity. This test as a logistically simple, sensitive, and robust method for biomonitoring genotoxic effects in wild bat populations."

In a recent study, Alexander von Humboldt Professor Jijie Chai at the University of Cologne and his team together with MPIPZ researchers have succeeded for the first time in reconstructing the sequence of molecular events that activate an inactive plant immune receptor and thus mediate the death of the host cell. The researchers' discoveries are of great importance for understanding how these critical plant immune molecules protect their hosts from infections. The configuration adopted by the activated protein is similar to that of other plant and mammal receptors, including humans. This suggests that these receptors are based on a common structural principle to trigger intracellular immune signals and cell death in different areas of life.

The scientists describe their results in the article 'Direct pathogen-induced assembly of an NLR immune receptor complex to form a holoenzyme' in Science.

Although separated by millions of years of evolution, plants and animals have independently developed similar immune strategies to protect themselves against microbial infections. In both kingdoms of life, immune receptors called nucleotide-binding/leucine-rich repeat proteins (NLR proteins) form an important defence layer within cells against pathogen attack. NLRs are complex devices consisting of several modules. These modules recognize the molecules (effectors) of invading microbes. Effectors trigger the immune response of the plant - they activate receptors, resistance and cell death pathways to limit infection. Based on different structural and signalling characteristics, plant NLRs are divided into two main classes: those that contain coiled-coiled (CC) modules (CNL proteins) and those that contain toll/interleukin-1 receptor/resistance (TIR) modules (TNL proteins).

The scientists conducted their research on the model organism Arabidopsis thaliana, or thale cress. Jijie Chai, together with the MPIPZ research group leader Jane Parker and MPIPZ dirctor Paul Schulze-Lefert, determined the structural and biochemical features underlying the activation of a specific receptor: the so-called TNL type NLR Receptor of Peronospora parasitica 1 (RPP1). It protects the model plant against infection with the fungus Hyaloperonospora arabidopsidis (Hpa).

To understand how RPP1 protects plants on the molecular level from Hpa infection, the team generated RPP1 protein together with the known Hpa effector ATR1 . The RPP1 receptor activated in this way is an enzyme that breaks down nicotinamide adenine dinucleotide (NAD+), which is important for defence signalling.

By isolating RPP1-ATR1 complexes and subjecting them to cryo electron microscopy, the authors have answered two open questions of NLR biology: first, how direct binding of the effector to the NLR receptor induces the activation of a receptor. Secondly, they determined that the TNL receptor in this case organizes itself as a so-called tetramer, a molecule consisting of four tightly packed receptor molecules. Tetramers belong to the group of oligomeric molecules, which are all structurally made up of similar units. The observed tetramer creates a unique surface within a part of the receptor, which is necessary for the cleavage of NAD+ to trigger defence signals.

The effector ATR1 induces tetramerization at one end of RPP1 and simultaneously forces the above-mentioned four TIR modules at the opposite end of the molecule to form two asymmetric TIR pairs that degrade NAD+.

Strikingly, the results of the groups around Eva Nogales and Brian Staskawicz at the University of California, Berkeley, on another NLR of the TNL type, Roq1 from the tobacco relative Nicotiana benthamiana, also show that TNL activation involves direct effector recognition and adoption of a similar tetrameric structure. The effector recognized by Roq1 is produced by a bacterial pathogen and the activated Roq1 receptor complex provides resistance to bacterial infections. Therefore, the discoveries of Jijie Chai, his team and the MPIPZ researchers seem to be of great importance for understanding how these critical plant immune molecules protect their hosts from infections. More generally, the oligomeric configurations adopted by active RPP1 and Roq1 resemble the induced oligomeric scaffolds of other plant and mammalian NLR receptor proteins, including human innate immune receptors. This suggests that these receptors are based on a common structural principle to trigger intracellular immune signals and cell death in different kingdoms of life.