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A new method developed by Northwestern Engineering's Manijeh Razeghi has greatly reduced a type of image distortion caused by the presence of spectral cross-talk between dual-band long-wavelength photodetectors.

The work opens the door for a new generation of high spectral-contrast infrared imaging devices with applications in medicine, defense and security, planetary sciences, and art preservation.

"Dual-band photodetectors offer many benefits in infrared imaging, including higher quality images and more available data for image processing algorithms," said Razeghi, Walter P. Murphy Professor of Electrical and Computer Engineering in the McCormick School of Engineering. "However, performance can be limited by spectral cross-talk interference between the two channels, which leads to poor spectral contrast and prevents infrared camera technology from reaching its true potential."

A paper outlining her work, titled "Suppressing Spectral Crosstalk in Dual-Band Long- Wavelength Infrared Photodetectors with Monolithically Integrated Air-Gapped Distributed Bragg Reflectors," was recently published in the IEEE Journal of Quantum Electronics.

Dual-band imaging allows for objects to be seen in multiple wavelength channels through a single infrared camera. The use of dual-band detection in night-vision cameras, for example, can help the wearer better distinguish between moving targets and objects in the background.

Spectral cross-talk is a type of distortion that occurs when a portion of the light from one wavelength channel is absorbed by the second channel. The issue becomes more severe as the detection wavelengths get longer.

To suppress that, Razeghi and her group in the Center for Quantum Devices developed a novel version of a distributed Bragg re?ector (DBR), a highly-refractive, layered material placed between channels that separates the two wavelengths.

While DBRs have been widely used as optical filters to reflect target wavelengths, Razeghi's team is the first to adapt the structure to divide two channels in an antimonide type-II superlattice photodetector, an important element of night-vision cameras that the researchers previously studied.

To test their design, the team compared the quantum efficiency levels of two long-wavelength infrared photodetectors with and without the air-gapped DBR. They found notable spectral suppression, with quantum efficiency levels as low as ten percent, when using the air-gapped DBR. The results were conrmed using theoretical calculations and numerical simulation.

She weighs less than one ten-thousandth of an ounce and her top speed is less than two miles per hour. Nonetheless, the female mosquito is one of the most dangerous animals on the planet. For as she flies from person to person, biting us to draw the blood she needs to lay her eggs, this tiny creature transmits microbes that sicken and kill millions of people every year.

Recently, however, scientists in the lab of Leslie B. Vosshall have shown that female mosquitoes can be persuaded not to bite at all. Their work, which appears in the journal Cell, illuminates the biology underlying the host-seeking and blood-feeding behaviors that make these insects such a menace--and could lead to new ways of shutting those behaviors down.

A bloated mosquito is a safe mosquito

The researchers conducted their experiments on Aedes aegypti mosquitoes, the species responsible for spreading dengue, Zika, chikungunya, and yellow fever.

Female Aedes are fiercely attracted to human beings, whose blood contains the protein they need to produce their eggs. Yet once they have fed, that attraction declines precipitously, and the bloated mosquitoes show little interest in seeking another blood meal for several days.

"It's like the ultimate Thanksgiving dinner," says Laura Duvall, the postdoctoral fellow who led the project.

Scientists can reproduce that long-term postprandial effect by injecting female mosquitoes with large doses of small protein-like molecules called neuropeptides, which activate specialized receptors. But the list of possible neuropeptide-receptor combinations is long, and better tools were needed to develop compounds that could more efficiently suppress a female's feeding behaviors without having other, unwanted effects.

Fortunately, similar receptors regulate feeding behavior in many species, including our own. And that shared evolutionary inheritance provided Duvall and her colleagues with the clue they needed to solve the mystery of the mosquito's missing appetite.

Appetite suppressant

In humans, so-called Neuropeptide Y or NPY receptors regulate food intake, and the pharmaceutical industry has developed anti-obesity drugs that both activate and inhibit them.

Duvall and her colleagues reckoned the same drugs might affect the mosquitoes' NPY-like receptors, as well. And they were right.

When the researchers fed female mosquitoes saline solution doped with drugs that activate human NPY receptors, the insects' attraction to a human host--as measured by their willingness to fly towards a bit of nylon stocking that Duvall had worn long enough to absorb the bodily odors that scream "mealtime" to mosquitoes--plummeted just as if they had had a blood meal. Alternately, when the researchers fed the mosquitoes blood doped with a drug that inhibits the same receptors, they behaved as if they had not eaten at all.

To pinpoint the particular receptor that the human drugs were acting upon, the team used their knowledge of the mosquito genome to clone all 49 of the species' possible neuropeptide receptors and exposed them to the same compounds. Only one, an NPY-like receptor known as NPYLR7, responded to all the human drugs that had affected the mosquitoes.

"We were impressed and amazed that drugs designed to affect human appetite worked perfectly to suppress mosquito appetite," said Vosshall, Robin Chemers Neustein Professor.

What's more, when the team fed blood to mutant Ae. Aegypti that had been genetically engineered to lack proper NPYLR7 receptors, those mosquitoes remained as interested as ever in their next meal--confirming that NPYLR7 was indeed the receptor they had been looking for.

Use only as directed

At that point, the researchers knew that NPYLR7 might be what they have long sought: a means of preventing mosquitoes from biting people. But the human drugs they used to manipulate the receptor in the lab wouldn't be suitable for use in the wild, where they might affect people as well as mosquitoes.

Instead, they began searching for molecules that would selectively activate NPYLR7 without triggering human NPY receptors. Starting with an initial list of more than 250,000 candidates, the team ultimately settled on "compound 18"--a molecule that suppressed Aedes' host-seeking behavior with no off-target effects.

Demonstrating that a drug will cause female mosquitoes to turn up their noses at a piece of tasty-smelling nylon is one thing, however. Proving that it will prevent them from biting a living, breathing host when it is laid out in front of them like a Thanksgiving turkey is another.

So for their final test, the researchers let the mosquitoes loose on a live mouse. (While Aedes prefer humans, they will make do with other mammals when necessary.) Much to their satisfaction, mosquitoes that were fed compound 18 were as disinterested in feeding on the rodent as mosquitoes that had enjoyed a full-blown blood meal.

A bite-free future?

The team's findings have far-reaching implications, both for future research and for vector control.

Now that the researchers know which receptor is responsible for switching off Ae. Aegypti's host-seeking and biting behaviors, they can begin to identify where it is produced in the insect's body, and when it might be naturally activated by chemicals that the mosquitoes produce themselves. (Although they still do not know exactly which naturally occurring neuropeptides activate NPYLR7, Duvall and her colleagues now have a list of nine possible candidates.) That, in turn, will help them trace the larger neural circuits that govern the mosquito's feeding behavior.

At the same time, their results suggest a new strategy for reducing the transmission of mosquito-borne diseases--and perhaps ailments spread by other insects, as well.

With a bit of luck, medicinal chemists could refine compound 18 to produce an even more potent molecule that could be delivered to female mosquitoes in the wild through baited traps, or through the semen of male mosquitoes that have been genetically modified to produce it themselves.

Muzzling Ae. Aegypti would be a boon in and of itself. But other blood-feeding, disease-carrying arthropods, including the mosquitoes that spread malaria and the ticks that transmit Lyme disease, also possess NPY-like receptors. It seems likely that a compound that suppresses Ae. Aegypti's feeding behaviors would suppress theirs, too.
And that would take a significant bite out of the global disease burden imposed by these pernicious blood-suckers.

A massive release of passive-surveillance satellite data of nighttime lights could help researchers in fields ranging from agriculture to epidemiology. Researchers at Penn State and the University of Southampton in the UK have provided open access to detailed satellite data on brightness for five cities in Niger and Nigeria from 2000 to 2005, as well as detailed methods for analyzing the data to track seasonal population movements. A paper describing the data and methods, which can be applied to other populations and other similar data sets, is available in the online, open-access journal Scientific Data.

"This type of data set has never been released before," said Nita Bharti, assistant professor of biology at Penn State and lead author of the paper. "We initially used it to track seasonal changes in population sizes to help vaccination campaigns achieve higher coverage levels in areas where diseases like measles still pose a large threat. We later received a lot of inquiries for access to these data from researchers in diverse fields. The data and associated code in 'R'--an open-source statistical computing software--are now openly available on 'ScholarSphere,' Penn State's open-access, online data repository."

The data originate from the Defense Meteorological Satellite Program (DMSP), which is a U.S. Department of Defense program run by the Air Force Space Command that is largely focused on cloud and other meteorological observations. The DMSP satellites capture thermal infrared images, which are used to study cloud cover, and visual images of the earth. Photographs are taken daily during the day and at night. By choosing only nighttime images, researchers can measure anthropogenic--related to human activity--light to address a variety of research questions.

"No one was really using the visual images until DMSP started to release annual composites of the Earth at night," said Bharti. "But the annual composites are only really useful if you are looking at annual or longer-scale changes. We decided to dig into the archives to pull out and process the daily images. We can then look for differences between the images on shorter time-scales and see things like seasonal changes in populations, which are really important for infectious diseases and public health interventions. Without this imagery, it would be incredibly difficult and require a massive amount of work on the ground to see detailed population changes across six years."

In addition to the data release, the researchers also provide detailed methods for analyzing this type of data, which could be applied to other similar data sets for different time periods and different locations.

"One of the things we wanted to get across is the value of this type of passive-surveillance data," said Bharti. "Satellites have been collecting this type of data for decades and even though these particular images were initially collected to study cloud cover, we can use them to address lots of different research questions. It's unconventional, but it's out there and is reasonably easy to access and it's underutilized, maybe because people don't know quite what to do with it or how to get it. That's why we published these methods as a sort of road map."

Warren Dick has worked with gypsum for more than two decades. You'd think he'd be an expert on drywall and plastering because both are made from gypsum. But the use of gypsum that Dick studies might be unfamiliar to you: on farmland.

"Gypsum is a good source of both calcium and sulfur, which crops need for good yields," says Dick. "We also found that it improves many other soil characteristics. Gypsum helps soil better absorb water and reduces erosion. It also cuts down on phosphorus movement from soils to lakes and streams and improves the quality of various fruits and vegetables, among other benefits."

Gypsum is a mineral that is naturally found concentrated in various places and can be mined out of the ground. But Dick's research focuses on gypsum recovered from coal-fired electricity generating power plants.

Gypsum that comes from coal plants is called flue-gas desulfurization gypsum, as it comes from the process that 'scrubs' sulfur out of the smoke stacks to reduce air pollution. "The gypsum that is recovered has good quality," says Dick. "The gypsum particles are small and uniform in size making them quite reactive. This can be a real benefit in agriculture. We also determined that it is safe for agricultural use through many studies. Reusing it for agricultural purposes, instead of putting it in landfills, provides multiple wins."

Gypsum is high in both calcium and sulfur. In addition, the chemical formula of gypsum makes those nutrients more available to plants than some other common sources of these nutrients. Chemically speaking, gypsum is calcium sulfate. Its use is often confused with that of lime, which is calcium carbonate.

Gypsum will change soil pH very slightly, yet it can promote better root development of crops, especially in acid soils, even without a big pH change. This is because the gypsum counteracts the toxic effect of soluble aluminum on root development. Aluminum occurs naturally in soil and often isn't a problem for crops. But when soil becomes acidic, the aluminum is available to plants--and it can stunt or kill them.

Another bonus of gypsum is that it is a moderately-soluble mineral. This means the calcium can move further down into the soil than the calcium from lime (calcium carbonate). This can inhibit aluminum uptake at depth and promote deeper rooting of plants. When roots are more abundant and can grow deeper into the soil profile, they can take up more water and nutrients, even during the drier periods of a growing season.

Although moderately soluble, gypsum can be an excellent source of sulfur over several growing seasons. Research found that the sulfur is available not only in the year applied, but can continue to supply sulfur for one or two years after, depending on the initial application rate. Gypsum as a sulfur fertilizer has benefitted corn, soybean, canola, and alfalfa.

Gypsum can also help improve soil structure. Many of us look at soil as a uniform, static substance. In reality, soil is a mixture of inorganic particles, organic particles, and a complex mixture of pore spaces, water, and soil microbes. Its composition changes through weather events like rainstorms, by tillage, or as plants pull nutrients for growth. Farmers have to manage their soil well in order to maintain good crop yields year after year.

Improving soil structure helps farmers with some common agricultural problems. Adding gypsum to the soil reduces erosion by increasing the ability of soil to soak up water after precipitation, thus reducing runoff. Gypsum application also improves soil aeration and water percolation through the soil profile. A recent study showed the benefit of gypsum application to improve movement of water through the profile to tile drains. It also reduces phosphorus movement out of the field.

No matter what solutions farmers are trying to implement when using gypsum, they have several options for application. Of course, the type of application method will be determined by the reasons to use gypsum. Finely crushed gypsum can be dissolved in irrigation water and applied that way. Farmers can take gypsum and apply it to the topsoil prior to planting or right after harvest. It can also be applied to hay fields after hay cutting. If tilling is needed (again, dependent on the soil conditions), gypsum can be worked into the soil with the tilling equipment.

Although gypsum has been used in agriculture for more than 250 years, the benefits it provides are still being studied. In addition, the re-use of gypsum by-products from coal power plants reduces the need to mine gypsum from geologic deposits. It also saves landfill space. Gypsum can't solve every agricultural problem, but it is a proven resource to add nutrients and improve soil structure.

"It's a great example of recycling a waste product and using it in a beneficial way," Dick says.

Dick, Professor Emeritus at The Ohio State University, presented "Crop and Environmental Benefits of Gypsum as a Soil Amendment" at the November 2018 meeting of the American Society of Agronomy and the Crop Science Society of America. The meeting abstract and recorded presentation can be found here. Research funding was obtained from a variety of federal, state, and commercial sources.

MYC, a gene with high cancer-initiating potential, is overexpressed in over 40% of breast cancers. While MYC programs breast cancer cells to build more macromolecules (anabolic metabolism) it also creates a metabolic vulnerability by making them more sensitive to a type of cell death known as apoptosis. Research Director Juha Klefstrom, PhD, University of Helsinki, Finland, has worked for a long time to exploit this apoptosis-sensitizing effect of MYC in the battle against the cancer.

Klefstrom and his research group found that, because of this vulnerability, cancer cells can be attacked with a "drug cocktail" that includes the diabetes drug metformin and venetoclax, a BCL-2 protein inhibitor that can induce apoptosis in cancer cells. The group identified metformin in a search for drugs that could boost the apoptosis-inducing action of venetoclax. Venetoclax has been approved to treat certain leukemias but not yet for the treatment of breast cancer.

"This drug combo exploits specific metabolic vulnerabilities that high levels of MYC creates in tumor cells. Metformin and venetoclax, when given together, killed breast tumor cells in culture and blocked tumor growth in breast cancer animal models. Furthermore, the drugs efficiently killed authentic breast cancer tissue donated by breast cancer patients. The breast cancer samples were obtained fresh from surgeries performed in Helsinki University Hospital", Dr. Klefstrom says.

However, the researchers soon discovered that the metformin plus venetoclax treatment only held tumors in check as long as the mice with implanted breast tumors were actively being treated with the drugs; once the treatment was stopped, the tumors grew back. The study shows that tumors were initially filled with tumor-killing lymphocytes; however, after the treatment they largely vanished and the remaining killer cells expressed PD-1, a marker of immune cell exhaustion.

To help the immune cells better fight the tumor, the researchers developed a new treatment strategy. First, they hit breast tumors with apoptosis-inducing drugs metformin and venetoclax to reduce the tumor size and to wake up killer lymphocytes. After the primary tumors were surgically removed, the mice were then treated with a triple combination: metformin, venetoclax and a PD-1-targeted antibody, which is used in immunotherapies to keep killer cells active long-term.

"With this combination the survival of mice carrying implanted tumors was extended dramatically in comparison to mice that were treated with only single or double combinations", Klefstrom states.

Klefstrom highlights that this is a wonderful example of a translational study fundamentally aimed at taking research from bench to bedside. The key people from the University of Helsinki and Helsinki University Hospital (HUS) - basic researchers, pathologists, surgeons and oncologists - were all involved at the earliest stages of the study.

The first author of the study Dr Heidi Haikala notes: "It's quite amazing how we've been able to bring a discovery from the lab bench all the way to the doors of the cancer clinics within the time frame of one PhD project. We are very excited about our findings and hope that they will translate to benefit breast cancer patients."

"This is a great example of how scientists in academia, leveraging highly specialized tumor models and applying their unique insights, can contribute to the discovery of potential new treatments for people with cancer. It is also a testament to the great research being done in smaller countries like Finland," states Joel Leverson, Ph.D., a Senior Scientific Director at AbbVie and one of the senior authors in the study.

"We finally have a drug combination that efficiently exploits MYC's apoptotic function and most importantly, these drugs can be tested in the clinic in real patients. We are currently working hard towards this next step.", Klefstrom concludes.

A new Personal Relationships study documents how the quality of a person's romantic relationship and the life stress he or she experiences at two key points in early adulthood (at age 23 and 32) are related to sleep quality and quantity in middle adulthood (at age 37).

Investigators found that people who have positive relationship experiences in early adulthood experience fewer, less disruptive stressful life events at age 32, which in turn predicts better sleep quality at age 37. Sleep is a shared behavior in many romantic relationships, and it is a strong contender for how relationships "get under the skin" to affect long-term health. The study's findings add to a growing body of literature showing that one of the important ways in which relationships impact individuals is by reducing the occurrence and severity of life stress.

"Although a large body of evidence shows that relationships are important for health, we are just beginning to understand how the characteristics of people's close relationships affect health behaviors, such as sleep," said lead author Chloe Huelsnitz, a PhD candidate at the University of Minnesota. "The findings of our study suggest that one way that relationships affect health behavior is through their effects on individuals' stress."

Children who have more conflict in relationships with their mothers during early years of elementary school may find it more difficult to find a sense of purpose in life as they reach adulthood, suggests new research from Washington University in St. Louis.

"One of the biggest takeaway messages from these findings is that the path to a purposeful life starts very early, well before we start to consider different goals for life," said Patrick Hill, associate professor of psychological and brain sciences in Arts & Sciences and co-author of the study.

"This research shows that it's the child's perspective of conflict that has the greatest effect on later sense of purpose and what matters most in this equation is the child's relationship with his or her mother," he said.

As defined by the study, a sense of purpose involves having the belief that one has a stable, far-reaching aim that organizes and stimulates behaviors and goals to promote progress toward that objective.

While having a sense of purpose is important to setting goals and picking careers, studies show it also plays a key role in motivating children to develop the life skills necessary for independence -- learning how to cook, stick to a budget, buy insurance and a host of other day-to-day survival skills that millennials now refer to as "adulting."

The study is one of the first to show long-term associations between a child's reports of early life experiences and whether that child feels purposeful later in life.

Children who reported conflicted early relations with fathers were negatively influenced by the experience, but the negative impact on sense of purpose was not nearly as strong as it was found to be among children who reported early conflicts with mothers. Childhood reports of conflicts with fathers also predicted less life satisfaction in emerging adulthood.

Again, only the child's perspective seemed to matter.

Parental reports of troubled relations with their young offspring turned out to be poor predictors of a child's later sense of purpose, the study found.

The study, finally published in January 2019 print issue of the Journal of Youth and Adolescence, is based on data from a long-running Oregon study of 1,074 students (50 percent female) and their parents, all of whom self-reported on levels of parent-child conflict in their families during grades 1–5. This study was first made available online in August 2018.

Children and parents were asked to respond to true-or-false statements about their interactions, such as "We joke around often," "We never have fun together," or "We enjoy the talks we have." Other questions asked whether "We get angry at each other" at least once a day, three times a week, or "a lot."

Follow-up surveys, which included questions on life satisfaction and perceived stress were repeated until the students reached early adulthood (ages 21-23 years).

Sense of purpose was scored based on responses to statements such as "There is a direction in my life," "My plans for the future match with my true interests and values," "I know which direction I am going to follow in my life," and "My life is guided by a set of clear commitments."

Other questions focused on life satisfaction and perceived stress: In the past month, how often have you felt that you were unable to control the important things in your life, confident about your ability to handle your personal problems, that things were going your way, or that difficulties were piling up so high that you could not overcome them?

Hill and his colleagues utilized this rich data set to link what children thought of their relationships with their parents to their attitudes about purpose in life as they were starting to enter adulthood. His co-authors include Joshua Jackson, the Saul and Louise Rosenzweig Associate Professor in Personality Science at Washington University; Leah Schultz, doctoral student in psychological and brain sciences at Washington University; and Judy Andrews, senior scientist at Oregon Research Institute in Eugene, Ore.

"A growing body of literature shows that having a sense of purpose is clearly something beyond just being satisfied with your life or not feeling stressed," Schultz said. "With our design, we were able to disentangle these outcomes and see the direct relationship between parent conflict and sense of purpose."

Schultz studies the development of individual differences such as personality traits and vocational interests across the lifespan. She is particularly interested in how individuals navigate these differences in their daily lives, how they select into the environments that fit them best, and what implications better person-environment fit may have for a variety of life outcomes.

"In this study, we were able to look at factors of the parent-child relationship, like how much parents and children experience conflict," Schultz said. "But it will be important for researchers to understand, specifically, how are parents demonstrating the value of a purposeful life? How are they helping children to define and pursue their own purposeful paths? Understanding the content of those conversations can help us all understand how conversations matter to the children in our lives."

Rockville, Md. (February 5, 2019)--Research in mice suggests that fermentation of flaxseed fibers in the gut changes the microbiota to improve metabolic health and protect against diet-induced obesity. The study, published ahead of print in the American Journal of Physiology--Endocrinology and Metabolism, was chosen as an APSselect article for February.

The organisms that live in the digestive tract (gut microbiota) play a role in regulating weight and the way the body processes sugar (glucose tolerance). The breakdown of dietary fiber in the gut--a process called fermentation--can produce favorable changes in the digestive system, such as an increase in beneficial fatty acids, which may reduce the production of fat tissue in the body and improve immune function. Flaxseed is a fiber-rich plant that has been shown to improve cholesterol levels and inflammation in the colon. However, there is little research on the fermentability of flaxseed and how flaxseed fiber affects gut microbiota.

Researchers studied mice assigned to four different diets:

a standard diet that contained 4.6 percent soy-based fiber ("control");

a high-fat diet that contained no fiber ("high-fat");

a high-fat diet that contained 10 percent indigestible cellulose fiber ("cellulose"); and

a high-fat diet that contained 10 percent flaxseed fiber ("flaxseed").

The research team measured the amount of oxygen the mice used, carbon dioxide produced, food and water consumed and energy expended. Glucose tolerance was also measured near the end of the trial. At the end of 12 weeks, the researchers examined the animals' cecal contents--bacteria and other biological materials in the pouch that forms the beginning of the large intestine (cecum).

The high-fat group had fewer bacteria associated with improved metabolic health, lower levels of beneficial fatty acids and more of a bacterium linked to obesity when compared to the other groups. Bacteria levels in both the cellulose and flaxseed groups returned to healthier levels when compared to the high-fat group. The flaxseed group was more physically active and had less weight gain than the other high-fat diet groups. The mice that received flaxseed supplements also had better glucose control and levels of beneficial fatty acids that were comparable to the healthy control group. When examining the cecal contents, the research team found evidence that the bacteria present ferment fibers from the thick, glue-like layer of the flaxseed shell. The bacteria that perform fermentation then produce more beneficial fatty acids.

"Our data suggest that flaxseed fiber supplementation affects host metabolism by increasing energy expenditure and reducing obesity as well as by improving glucose tolerance. Future research should be directed to understand relative contribution of the different microbes and delineate underlying mechanisms for how flaxseed fibers affect host metabolism," the researchers wrote.

Today, thousands of databases with biological data are publicly available. They include data on gene and protein sequences and detailed measurements of different cellular parameters, such as the exact quantities of all proteins produced and degraded by a given cell in various experimental conditions. Brazilian researchers explored mRNA and protein public databases and found out how gene sequence choice can predict different aspects of protein synthesis, such as protein production efficiency. The study, published in Nucleic Acids Research, could help the development of new biotechnological applications of genes and proteins.

The genetic information contained in the cell nucleus in the form of DNA is copied in messenger RNAs (mRNAs). Different from the DNA, mRNAs are dynamic and unstable molecules that leave the nucleus and are translated by the ribosomes, the molecular machines able to convert a sequence of nucleotides that make RNA (and DNA) into a sequence of amino acids that form proteins. Each amino acid corresponds to one or more combinations of 3 nucleotides - or codon. Because the same amino acid can be translated from different codons, the genetic code is described as degenerate (or redundant).

Scientists already know that even though the same protein can be produced from alternative gene sequences, some combinations result in higher protein yields. They also know that optimal codons and non-optimal codons can decrease or enhance mRNA degradation, respectively. Different groups have measured mRNA production and degradation rates, but, surprisingly, there are many deviations in the data.

Brazilian scientists synthesized apparently disparate pieces of data and extended our knowledge of how gene sequence choice can predict different aspects of protein synthesis, such as mRNA stability and production efficiency. A research group led by Fernando Palhano and Tatiana Domitrovic at the Federal University of Rio de Janeiro used a metric derived from mRNA codon composition to compare the existing data to different cellular parameters. They found that this metric correlated well with protein abundance and protein production efficiency, indicating the most coherent mRNA decay datasets. Their work reiterated that mRNA degradation is somehow connected to protein production efficiency. "Even proteins needed in high levels under specific conditions, such as stress response, have their gene sequence optimized for efficient translation", says Fernando Palhano.

Fernando and Tatiana worked with Rodolfo Carneiro and other colleagues, who identified a group of low abundance proteins coded by a non-optimal subset of codons. As they show in their paper published in Nucleic Acids Research, codon choice is vital not only to guarantee high protein production but also to tune down the output of proteins that should be produced in minimum amounts, such as regulatory proteins.

The amount of protein produced in a cell is crucial to maintaining the organism function - "Many human diseases are caused by inefficient or unbalanced protein production, such as cystic fibrosis and cancer", says Tatiana. She adds that "from a practical perspective, understanding the relationship between the genetic sequence and protein production can have a profound effect both on medicine and bioengineering".

The authors note that many "silent" DNA mutations, that is, mutations that alter the codon sequence, but not the coded amino acid, can lead to significant modifications on protein production rates, which could lead to disease. By carefully selecting the gene sequence one can finely tune the protein production and boost biotechnological applications of genes and proteins.

Although it has been ranked as the cutest creature in US National Parks, the American pika is tough, at home in loose alpine rocks in windswept mountain regions. Related to rabbits and hares, pikas live in cold, wet climates and high terrain, spending winters in snowy homes living off of stored grasses and other forage they have gathered, only venturing out for more when weather permits.

Unfortunately for these adorable little mammals, they have a fairly severe sensitivity to overheating - they die if they are exposed to temperatures above 77°F for longer than six hours. Due to their lethal threshold for heat stress, pikas are indicators of how changing environmental conditions can affect mountain-dwelling species.

It might appear that the danger for pikas lies mostly with increasing temperatures and summer heat extremes. In some cases, however, decreased snowpack and lower air moisture may threaten pikas more.

Vapor-pressure deficit (VPD) can be likened to air's aridity - higher VPD is drier. VPD governs the growth of many plants that pikas depend on for food, and controls cloud formation and snow. If VPD becomes higher, it will inhibit the growth of plants that pikas depend on for food, and will shrink snow packs which they use for insulation against extreme temperature. The snowpack also stores water until springtime, when it provides water for forage plants that pikas eat.

A team of researchers lead by Aaron N. Johnston of the U.S. Geological Survey sought to understand how climate change, specifically changes in snowpack and VPD, is affecting pikas. In a paper published recently in the Ecological Society of America's journal Ecology, they related population abundances to weather and snowpack dynamics in the North Cascades National Park Service Complex in Washington state. In the Pacific Northwest, a place with mild summers and prevailing cool, moist conditions, pikas occur at unusually low elevations including near sea level.

The study period included a year with record-low snowpack and high VPD (very dry air) in winter of 2014-2015, a data point that provided valuable observations of these variables' influences on the ecosystem. The researchers further studied the dynamics across differing elevations - low, middle, and high.

The results were surprisingly variable, with different dynamics acting over different elevations.

"We expected snowpack to be an important factor because it has many important ecological functions for pikas," said Johnston. "The effect of VPD in winter was a big surprise."

At the lowest elevations, populations declined markedly. Unusually high VPD during the snow drought dried up forage plant species accustomed to moist conditions, and lack of food may have prompted malnourished pikas to forgo reproduction. Cold exposure did not appear to affect these pikas, where absence of snowpack is common because of generally warm temperatures.

At middle elevations, it was cold stress, not dry air, that had the biggest effect. Along a narrow elevation band, about 1200-1500 meters, pika populations lacked a strong snowpack in which to seek shelter and insulation from extreme cold. However, it was a dip in reproduction the following year, not pika mortality in a single winter, that caused the population abundance to drop. Pikas may have even resorbed fetuses in response to the cold stress of the snow drought.

At high elevations, where snow often persists for up to 7-9 months, forage came back into play as the important driver of abundances. Populations increased, having had sufficient snow cover for insulation despite a snow drought, and having benefitting from increased forage availability due to earlier snowmelt and a longer growth season for food. Pikas were able to consume and collect enough food to increase their health and ability to produce many offspring over the following winter.

Given the pervasive influence of moisture on the physiology of plants and animals, the authors find the lack of previous studies on animal responses to VPD surprising.

"Moisture is distinct from climatic factors of temperature and precipitation that are commonly used to explain animal distributions," Johnston stated. "Incorporating moisture into species distribution models should improve ecological understanding of species and their responses to climate change."

Climate-indicator species like pikas provide a number of ecosystem services and play an important role in biodiversity. Pikas serve as a food source for a number of predators, including weasels, coyotes, and birds of prey. They are also ecosystem engineers - their foraging helps promote the diversity and distribution of various plant species and nutrients. Consequently, pika die-offs could have many lasting dire consequences for the environment and serve as a harbinger in forecasting potential climate change impacts on animal and plant life across the greater continental US.

As extreme events like snow drought continue to increase in frequency, how these events and their interactions with VPD will affect animal species remains largely unexplored. Support for continued research into climate indicator species such as the pika is critically important.

A new approach to defining opioid-related auto fatalities provides insight into the nature and distribution of opioid-involved deaths in the state of Maryland, say the authors of a new study led by researchers at the Johns Hopkins Bloomberg School of Public Health.

In their study, which appeared online Jan. 24 in the journal Accident Analysis and Prevention, researchers examined opioid-related auto fatalities in Maryland from 2006 through 2017. During the study period, opioid-involved crash deaths accounted for 10 percent of all driver deaths. In one analysis, the researchers used data on drivers with an opioid-positive toxicology report, which included those who received opioid treatment--possibly for crash-related injuries--hours or even days after the accident and subsequently died but who may not have had opioids in their system at the time of the crash. In this analysis, the researchers found that the number of opioid-involved fatal crashes increased from 8.3 percent of all crashes in 2006 to 14.1 percent in 2017.

Yet in a second analysis that only counted driver deaths at the scene and one positive toxicology report, there was no significant change from 2006 to 2017. In 2006, seven percent of drivers dead on the scene tested positive for opioids, increasing to nine percent of drivers in 2017. The statistical analysis shows the prevalence of fatal opioid-involved car accidents in Maryland has not significantly increased over time as had been previously thought.

"When we just looked at all drivers who died with opioids in their system, we saw an increase, but when we looked at people who died on the scene and did not receive medical intervention, there was no increasing trend," says Johnathon Ehsani, PhD, Leon S. Robertson Faculty Development Chair and assistant professor in the Bloomberg School's Department of Health Policy and Management and the study lead. "A new case definition is what we want to see with these kinds of analyses. No one has used this strict of a definition before and it changes the picture."

It is common practice for Emergency Medical Services (EMS) and first responders to use opioids to quickly treat pain for severely injured drivers at the scene of a crash. A positive toxicology test indicates the driver has opioids in his/her system at the time, but does not necessarily mean the driver was impaired by the drug at the time of the crash. Previous studies may have misrepresented the number of opioid-related auto fatalities by not differentiating between those who died on the scene and those who died hours or days later from crash-related injuries, but received opioids administered by a medical professional.

"When determining the prevalence of opioid use in a population, it can be tricky to untangle the two circumstances," says Ehsani. "Thinking differently about the way in which researchers count cases has implications that can offer policymakers and public health professionals more meaningful results."

For their study, the researchers used data from Maryland's Chief Medical Examiner supplemented with information from the U.S. Census, the Maryland Highway Safety Office and the Centers for Disease Control and Prevention (CDC) databases from 2006 to 2017.

The research team originally undertook the study to explore the demographics of drivers involved in opioid-related crashes, trends of opioid use in driver fatalities over time and geographical differences of opioid-related crashes in the state of Maryland.

Other results from the study align with national opioid research. Not only were opioid-involved crashes significantly higher among Caucasian drivers than African American or Hispanic drivers, there was statistical significance found in the presence of opioids in drivers aged 50 to 54.

Geographically, the presence of opioids was higher in drivers with fatal accidents occurring in rural counties. Maryland counties with higher opioid-involved driver deaths corresponded to counties with a higher prevalence of opioid overdoses and opioid use. After adjusting the analysis, Maryland's rural counties have the highest rates of opioid-involved crash fatalities, similar to rural counties across the nation.

"Our demographic and geographic findings build on the existing evidence: middle-aged, white, populations are more likely to be using opioids," says Ehsani. "Part of the story we told in this study is simply a reflection of broader societal trends in opioid use and overdose risk in the country."

Changing the way researchers think about and define opioid-related deaths has important implications for the future. "Having no significant increase in opioid-involved crash deaths in Maryland suggests that our focus should remain fixed on other road safety issues, like alcohol, as it is the primary substance involved in crash deaths in Maryland and across the country," says Ehsani.

MORGANTOWN, W.Va.--A field trip to Namibia to study volcanic rocks led to an unexpected discovery by West Virginia University geologists Graham Andrews and Sarah Brown.

While exploring the desert country in southern Africa, they stumbled upon a peculiar land formation--flat desert scattered with hundreds of long, steep hills. They quickly realized the bumpy landscape was shaped by drumlins, a type of hill often found in places once covered in glaciers, an abnormal characteristic for desert landscapes.

"We quickly realized what we were looking at because we both grew up in areas of the world that had been under glaciers, me in Northern Ireland and Sarah in northern Illinois," said Andrews, an assistant professor of geology. "It's not like anything we see in West Virginia where we're used to flat areas and then gorges and steep-sided valleys down into hollows."

After returning home from the trip, Andrews began researching the origins of the Namibian drumlins, only to learn they had never been studied.

"The last rocks we were shown on the trip are from a time period when southern Africa was covered by ice," Andrews said. "People obviously knew that part of the world had been covered in ice at one time, but no one had ever mentioned anything about how the drumlins formed or that they were even there at all."

Andrews teamed up with WVU geology senior Andy McGrady to use morphometrics, or measurements of shapes, to determine if the drumlins showed any patterns that would reflect regular behaviors as the ice carved them.

While normal glaciers have sequential patterns of growing and melting, they do not move much, Andrews explained. However, they determined that the drumlins featured large grooves, which showed that the ice had to be moving at a fast pace to carve the grooves.

These grooves demonstrated the first evidence of an ice stream in southern Africa in the late Paleozoic Age, which occurred about 300 million years ago.

"The ice carved big, long grooves in the rock as it moved," Andrews said. "It wasn't just that there was ice there, but there was an ice stream. It was an area where the ice was really moving fast."

McGrady used freely available information from Google Earth and Google Maps to measure their length, width and height.

"This work is very important because not much has been published on these glacial features in Namibia," said McGrady, a senior geology student from Hamlin. "It's interesting to think that this was pioneer work in a sense, that this is one of the first papers to cover the characteristics of these features and gives some insight into how they were formed."

Their findings also confirm that southern Africa was located over the South Pole during this period.

"These features provide yet another tie between southern Africa and south America to show they were once joined," Andrews said.

The study, "First description of subglacial megalineations from the late Paleozoic ice age in southern Africa" is published in the Public Library of Science's PLOS ONE journal.

"This is a great example of a fundamental discovery and new insights into the climatic history of our world that remain to be discovered," said Tim Carr, chair of the Department of Geology and Geography.

Children born after assisted reproductive technology (ART) do not appear to be at greater risk of developing cancer than other children, according to the first study to look at the long-term cancer risk in ART children compared to those in the general population or who were naturally conceived by subfertile women.

The study of 47,690 children is published today (Monday) in Human Reproduction, one of the world's leading reproductive medicine journals, and is important because, until now, there has been conflicting evidence about whether or not ART children have an increased risk of cancer. The children in this study were followed for a median average of 21 years, which makes it the first study to compare outcomes in these children over such a long period of time.

Lead researcher, Professor Flora van Leeuwen, Head of the Department of Epidemiology in The Netherlands Cancer Institute, Amsterdam (The Netherlands), said: "This study, with a median follow-up of 21 years, is especially important because it includes a comparison group of naturally conceived children born to subfertile women; these women are different from the general population and it is possible that difficulty in conceiving could be a factor that influences the risk of cancer in their offspring."

The first author of the study, Ms Mandy Spaan, a PhD student in the Department of Epidemiology, said: "We found that of the 47,690 children included in the analysis, 231 developed cancer. After adjusting for factors that could confound the results such as age and the parental cause of subfertility, the overall long-term risk for cancer was neither increased in the ART-conceived children compared with naturally conceived children from subfertile women, nor when compared with the general population.

"However, cancer risk was somewhat increased, although not statistically significantly so, in children conceived after intracytoplasmic sperm injection [ICSI] or from embryos that had been frozen before being thawed and used for fertility treatment. These are two types of fertility treatments that are used more often nowadays. We also found a slightly increased, statistically insignificant risk of lymphoblastic leukaemia and melanoma. As the numbers of cancers in these groups were small, these findings may be due to chance and must be interpreted with caution."

Researchers analysed data from a large, nationwide study of subfertile women (the OMEGA study) who were treated in one of 12 Dutch fertility clinics between 1980 and 2001. They also collected data on the offspring and the information was linked to data on the incidence of cancer from The Netherlands Cancer Registry between January 1989 and November 2016. Information on the method of conception and any confounding factors, such as the cause of the parents' subfertility, the mother's age, the child's birth year, birth weight, duration of pregnancy, and whether they were single or multiple births, was also collected from the mothers' completed questionnaires and medical records.

Of the 47,690 children born alive, 24,269 were conceived by ART, 13,761 were naturally conceived and 9,660 were conceived naturally or with the help of fertility drugs, such as ovarian stimulation medication, but not by ART.

Of the 231 cases of cancer occurring among all the offspring, there were 31 cases of lymphoblastic leukaemia and 26 cases of melanoma.

Ms Spaan said: "There is no clear explanation for why there should be higher numbers of these cancers. It could be that some fertility treatments might induce heritable alterations in certain genes that increase the risk of melanoma and leukaemia; however, more research with larger numbers is needed to clarify this finding."

Prof van Leeuwen concluded: "These results provide reassuring evidence that children conceived as a result of fertility treatments do not have an increased risk of cancer after a median follow-up of 21 years. They will enable physicians to better inform couples considering fertility treatment about its long-term safety for their children.

"However, as ever more children are born through ICSI and cryopreservation of embryos, the long-term cancer risk should be investigated in larger numbers of children born as a result of these techniques.

"We are currently expanding our study to include more than 30,000 ART-conceived children born in more recent years. It will include children born after ICSI and/or embryo cryopreservation of the embryo. We hope this will provide more evidence about the possible long-term risk of cancer for these children."

Cancer in children and young adults is rare, occurring in less than one per cent worldwide, and so a limitation of this study is that the small number of cancers makes it difficult to produce reliable results from subgroup analyses. In addition, the method of conception could not be identified in 12% of children from the information in the mothers' questionnaires and medical records. A strength of the study is its large size, the long and complete follow-up, the comparison with naturally conceived children from subfertile women as well as the general population, and the detailed information on potential confounding factors.

Spectrally pure lasers lie at the heart of precision high-end scientific and commercial applications, thanks to their ability to produce near-perfect single-color light. A laser's capacity to do so is measured in terms of its linewidth, or coherence, which is the ability to emit a constant frequency over a certain period of time before that frequency changes.

In practice, researchers go to great lengths to build highly coherent, near-single-frequency lasers for high-end systems such as atomic clocks. Today, however, because these lasers are large and occupy racks full of equipment, they are relegated to applications based on bench tops in the laboratory.

There is a push to move the performance of high-end lasers onto photonic micro-chips, dramatically reducing cost and size while making the technology available to a wide range of applications including spectroscopy, navigation, quantum computation and optical communications. Achieving such performance at the chip scale would also go a long way to address the challenge posed by the internet's exploding data-capacity requirements and the resulting increase in worldwide energy consumption of data centers and their fiber-optic interconnects.

In the cover article of the January 2019 issue of Nature Photonics, researchers at UC Santa Barbara and their collaborators at Honeywell, Yale and Northern Arizona University, describe a significant milestone in this pursuit: a chip-scale laser capable of emitting light with a fundamental linewidth of less than 1 Hz -- quiet enough to move demanding scientific applications to the chip scale. The project was funded under the Defense Advanced Research Project Agency's (DARPA) OwlG initiative.

To be impactful, these low-linewidth lasers must be incorporated into photonic integrated circuits (PICs) -- the equivalents of computer micro-chips for light -- that can be fabricated at wafer-scale in commercial micro-chip foundries. "To date, there hasn't been a method for making a quiet laser with this level of coherence and narrow linewidth at the photonic-chip scale," said co-author and team lead Dan Blumenthal, a professor in the Department of Electrical and Computer Engineering at UC Santa Barbara. The current generation of chip-scale lasers are inherently noisy and have relatively large linewidth. New innovations have been needed that function within the fundamental physics associated with miniaturizing these high-quality lasers.

Specifically, DARPA was interested in creating a chip-scale laser optical gyroscope. Important for its ability to maintain knowledge of position without GPS, optical gyroscopes are used for precision positioning and navigation, including in most commercial airliners.

The laser optical gyroscope has a length-scale sensitivity on par with that of the gravitational wave detector, one of the most precise measuring instruments ever made. But current systems that achieve this sensitivity incorporate bulky coils of optical fiber. The goal of the OwlG project was to realize an ultra-quiet (narrow-linewidth) laser on the chip to replace the fiber as the rotation-sensing element and allow further integration with other components of the optical gyroscope.

According to Blumenthal, there are two possible ways to build such a laser. One is to tether a laser to an optical reference that must be environmentally isolated and contained in a vacuum, as is done today with atomic clocks. The reference cavity plus an electronic feedback loop together act as an anchor to quiet the laser. Such systems, however, are large, costly, power-consuming and sensitive to environment disturbances.

The other approach is to make an external-cavity laser whose cavity satisfies the fundamental physical requirements for a narrow linewidth laser, including the ability to hold billions of photons for a long time and support very high internal optical power levels. Traditionally, such cavities are large (to hold enough photons), and although they have been used to achieve high performance, integrating them on-chip with linewidths approaching those of lasers stabilized by reference cavities has proved elusive.

To overcome these limitations, the research team leveraged a physical phenomenon known as stimulated Brillouin scattering to build the lasers.

"Our approach uses this process of light-matter interaction in which the light actually produces sound, or acoustic, waves inside a material," Blumenthal noted. "Brillouin lasers are well known for producing extremely quiet light. They do so by utilizing photons from a noisy 'pump' laser to produce acoustic waves, which, in turn, act as cushions to produce new quiet, low-linewidth output light. The Brillouin process is highly effective, reducing the linewidth of an input pump laser by a factor of up to a million."

The drawback is that bulky optical fiber setups or miniature optical resonators traditionally used to make Brillouin lasers are sensitive to environmental conditions and difficult to fabricate using chip-foundry methods.

"The key to making our sub-Hz Brillouin laser on a photonic integrated chip was to use a technology developed at UC Santa Barbara -- photonic integrated circuits built with waveguides that are extremely low loss, on par with the optical fiber," Blumenthal explained. "These low-loss waveguides, formed into a Brillouin laser ring cavity on the chip, have all the right ingredients for success: They can store an extremely large number of photons on the chip, handle extremely high levels of optical power inside the optical cavity and guide photons along the waveguide much as a rail guides a monorail train."

A combination of low-loss optical waveguides and rapidly decaying acoustic waves removes the need to guide the acoustic waves. This innovation is key to the success of this approach.

Since being completed, this research has led to multiple new funded projects both in Blumenthal's group and in those of his collaborators.

Transplanted pancreatic islets in diabetic animals can survive for a long period of time if the animals are treated with short anti-rejection therapy around the time of the transplant. This has been shown by researchers at Karolinska Institutet, Sweden, and the Diabetes Research Institute, University of Miami Miller School of Medicine, USA, in a new study published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]). The results might have a significant impact on clinical islet transplantation in the treatment of type 1 diabetes.

Transplantation of pancreatic islets with their insulin-secreting cells is a promising therapy in type 1 diabetes. However, one complication is that anti-rejection therapy, in the form of generalised immune suppression, is required to ensure the survival and function of the transplanted islets by preventing the immune system from attacking the transplants.

It is well known that extended use of generalised immune suppression might have serious side effects that harm the transplanted patient. Moreover, immune attack against the transplanted islets can still occur despite continued immune suppression. Therefore, the transplantation field has been looking for new ways to ensure the long-term survival and function of transplanted islets with little or even no immune suppression.

This new study demonstrates the potential for achieving long-term survival and function of transplanted pancreatic islets with short-term anti-rejection therapy around the time of the transplant. In transplanted mice and monkeys, this strategy resulted in immune tolerance that enabled survival of the transplanted islets long after the anti-rejection treatment was stopped.

"These findings support the establishment of immune tolerance towards the transplanted islets and thereby their long-term protection from an immune attack in the transplanted patient after stopping the use of anti-rejection therapy," says first author Dr Midhat H Abdulreda at the Diabetes Research Institute.

This new way of achieving immune tolerance might minimise the need for life-long immune suppression, which raises hope for an effective treatment of type 1 diabetes with fewer side effects.

"If these findings are repeated in humans, this approach may serve as a game changer and positively impact on the success of islet transplantation for future treatment of type 1 diabetes," says senior author Professor Per-Olof Berggren at the Rolf Luft Research Center for Diabetes and Endocrinology at Karolinska Institutet.

The research was supported by funds from the Diabetes Research Institute Foundation (DRIF) and the Diabetes Wellness Foundation and by grants from the Stanley J. Glaser Foundation Research Award, the NIH/NIDDK/NIAID, the Swedish Diabetes Association Fund, the Swedish Research Council, Novo Nordisk Foundation, the Family Erling-Persson Foundation, the Strategic Research Program in Diabetes at Karolinska Institutet, the ERC-2013-AdG 338936-BetaImage, the Knut and Alice Wallenberg Foundation, Skandia Insurance Company Ltd, the Diabetes and Wellness Foundation, the Berth von Kantzow Foundation, and the Stichting af Jochnick Foundation.

Per-Olof Berggren is cofounder and CEO of Biocrine, an unlisted biotech company that is using the approach of cell transplant in the anterior chamber of the eye as a research tool. Midhat H Abdulreda is a consultant for the same company. More information about the technique can be found in the scientific article.