Culture

Could a small ringlike structure made of plastic and copper amplify the already powerful imaging capabilities of a magnetic resonance imaging (MRI) machine? Xin Zhang, Stephan Anderson, and their team at the Boston University Photonics Center can clearly picture such a feat. With their combined expertise in engineering, materials science, and medical imaging, Zhang and Anderson, along with Guangwu Duan and Xiaoguang Zhao, designed a new magnetic metamaterial, reported in Communications Physics, that can improve MRI quality and cut scan time in half.

Zhang and Anderson say that their magnetic metamaterial could be used as an additive technology to increase the imaging power of lower-strength MRI machines, increasing the number of patients seen by clinics and decreasing associated costs, without any of the risks that come with using higher-strength magnetic fields. They even envision the metamaterial being used with ultra-low field MRI, which uses magnetic fields that are thousands of times lower than the standard machines currently in use. This would open the door for MRI technology to become widely available around the world.

"This [magnetic metamaterial] creates a clearer image that may be produced at more than double the speed" of a current MRI scan, says Anderson, a School of Medicine professor of radiology and vice chairman of research in Boston Medical Center's radiology department.

MRI uses magnetic fields and radio waves to create images of organs and tissues in the human body, helping doctors diagnose potential problems or diseases. Doctors use MRI to identify abnormalities or diseases in vital organs, as well as many other types of body tissue, including the spinal cord and joints. "[MRI] is one of the most complex systems invented by human beings," says Zhang, a College of Engineering professor of mechanical engineering, electrical and computer engineering, biomedical engineering, materials science and engineering, and a professor at the Photonics Center.

Depending on what part of the body is being analyzed and how many images are required, an MRI scan can take up to an hour or more. Patients can face long wait times when scheduling an examination and, for the healthcare system, operating the machines is time-consuming and costly. Strengthening MRI from 1.5 T (the symbol for tesla, the measurement for magnetic field strength) to 7.0 T can definitely "turn up the volume" of images, as Anderson and Zhang describe. But although higher-power MRIs can be done using stronger magnetic fields, they come with a host of safety risks and even higher costs to medical clinics. The magnetic field of an MRI machine is so strong that chairs and objects from across the room can be sucked toward the machine--posing dangers to operators and patients alike.

The magnetic metamaterial designed by the Boston University researchers is made up of an array of units called helical resonators--three-centimeter-tall structures created from 3-D-printed plastic and coils of thin copper wire--materials that aren't too fancy on their own. But put together, helical resonators can be grouped in a flexible array, pliable enough to cover a person's kneecap, abdomen, head, or any part of the body in need of imaging. When the array is placed near the body, the resonators interact with the magnetic field of the machine, boosting the signal-to-noise ratio (SNR) of the MRI, "turning up the volume of the image" as Anderson says.

"A lot of people are surprised by its simplicity," says Zhang. "It's not some magic material. The 'magical' part is the design and the idea."

To test the magnetic array, the team scanned chicken legs, tomatoes, and grapes using a 1.5 T machine. They found that the magnetic metamaterial yielded a 4.2 fold increase in the SNR, a radical improvement, which could mean that lower magnetic fields could be used to take clearer images than currently possible.

Now, Zhang and Anderson hope to partner with industry collaborators so that their magnetic metamaterial can be smoothly adapted for real-world clinical applications.

"If you are able to deliver something that can increase SNR by a significant margin, we can start to think about possibilities that didn't exist before," says Anderson, such as the possibility of having MRI near battlefields or in other remote locations. "Being able to simplify this advanced technology is very appealing," he says.

A team of researchers from the NYU Silver School of Social Work has found that bureaucratic barriers rather than personal intransigence lead many street homeless people in New York City to refuse outreach workers' offers of shelter.

The qualitative study of 43 people living unsheltered in Manhattan was led by Silver School Professor Deborah Padgett with the assistance of PhD student Lynden Bond, MSW student Anna Nathanson (a May '19 graduate of the school), and research assistant Christina Wusinich of the non-profit homeless advocacy organization Human.nyc. For the past three years, Padgett has been working closely with Human.nyc, which was founded by alumni from NYU's Stern School of Business.

For six months beginning in September 2017, members of Padgett's team randomly sampled and interviewed 33 men and 10 women living on the streets in Manhattan neighborhoods with high concentrations of street homelessness. Interviewers asked participants about barriers they faced in obtaining housing and accessing services, their interactions with outreach workers, and any experiences with the New York City shelter system.

When New York City announced expanded homeless outreach efforts in January 2018, Mayor Bill de Blasio said, "It can take dozens or more contacts to convince homeless New Yorkers to come in off the streets and into permanent housing." In fact, Padgett said, "Our research indicates that if people were really being offered permanent housing, they would take it without hesitation. The allure of living on the streets is a myth."

Dr. Padgett, who is the co-lead of the Grand Challenges for Social Work's End Homelessness Challenge, noted that the process of gaining access to permanent housing is lengthy and confusing. As illustrated on the Human.nyc website, eligibility is dependent on being seen bedded down in the same location multiple times by outreach teams and living on the streets for at least nine months. Gathering all the required documentation, such as a birth certificate, can be time-consuming and costly, delaying a move forward in the housing process. Once a person is deemed eligible, the search for transitional or permanent housing can take months or years due to a scarcity of available units in a market where supply is exceeded by demand.

Unsurprisingly, many study participants were left frustrated and uncertain about their future. These barriers are exacerbated by their reasonable aversion to shelters seen as over-crowded and unsafe. "In the process of trying to secure safe, permanent housing there is almost no light at the end of the tunnel and little to be gained by cooperation when the results are so disappointing. In this context, homeless people are not 'service resistant,' they are rational actors all too familiar with un-kept promises," Padgett said.

The researchers found other barriers, including the exclusion of pets from city shelters and a lack of accommodations for homeless people with physical disabilities. "Given the prevalence of disabilities and complex healthcare needs among people living on the street, it is shocking how few options are open to them, leaving them no alternative to a hospital emergency room," said Professor Padgett.

Study participants told the researchers that they survived by using soup kitchens, drop-in centers and panhandling. Their safety was most at risk at night, leading many to seek out the subways or busy areas where they might be left alone. Simple daily tasks such as bathing and using a toilet remained major challenges and theft of their belongings was a constant risk. Passersby could be exceedingly generous or hostile--living outdoors left them vulnerable at all times.

Findings from the NYU Silver study were vividly illustrated by 40 videotaped testimonials Human.nyc gathered from people living unsheltered across the five boroughs. Co-Founder Josh Dean, who earned his BS at NYU Stern in 2016, said, "New York City leaders say their goal is to reduce street homelessness, but the city's own process makes it remarkably difficult for street homeless New Yorkers to secure housing. For those who understandably avoid shelters, the best case scenario is moving into transitional housing after nine months, but even that timeline is rarely met. We believe that we can do better for our fellow New Yorkers."

Human.nyc, recently proposed ways to expedite the street-to-home journey. Their recommendations include streamlining the process to secure case management services, maximizing the usage of faith-based respite sites, designating a number of shelter and transitional housing sites as pet-friendly, and strengthening initiatives to increase permanent affordable and supportive housing.

The organization's recommendations align with Dr. Padgett's advocacy for the evidence-based "Housing First" approach, which rejects prerequisites and moves homeless individuals directly into permanent housing with support services. Dr. Padgett, who co-authored the book Housing First: Ending Homelessness, Changing Systems and Transforming Lives (2016, Oxford University Press) said, "While smaller, less restrictive safe havens are better than large shelters, the lasting solution is Housing First along with the expansion of affordable housing. HF is a policy priority in the U.S. and many other nations; it is humane and also saves money compared to shelters and other alternatives. Diverting a portion of the $2 billion spent annually by the City's Department of Homeless Services to increased investment in rental assistance and support services could end homelessness for thousands of New Yorkers."

For a copy of the report, or to speak with Deborah Padgett and her co-authors, please contact the NYU Press Officer listed with this release.

Pill testing services at music festivals may be most effective in reducing harm for people trying ecstasy for the first time, but less so for prior users.

The new Edith Cowan University (ECU) research also found:

Experienced ecstasy users are no more knowledgeable than novices when it comes to safe dosage amounts and harmful ingredients.

Festival attendees would be willing to pay an average $12 subsidy to fund pill testing services.

The study led by Dr Ross Hollett, from the School of Arts and Humanities, looked at ecstasy-using intentions following different pill test scenarios to determine the factors that predict subsequent risky behaviour.

Over 250 music festival attendees were presented with three hypothetical pill test scenarios and reported their risk intentions, ecstasy use history and sensation seeking.

"The findings from the study suggest that people who attend a festival and might be looking to try ecstasy for the first time are most cautious after a pill test, regardless of the outcome of the test," Dr Hollett said.

"For prior ecstasy users (60 per cent of the sample), they were only more likely to reduce their harm intentions if the ecstasy contained a toxic contaminant, not if the test revealed a high dose or an inconclusive result.

"This finding is important because some of the recent ecstasy-related deaths at festivals in Australia have been linked to high doses of ecstasy," Dr Hollett said.

"Additionally, if the participant was a prior ecstasy user who was also high in sensation seeking, then they were at the greatest risk of harm, even after participating in the pill test," he said.

More education needed

Dr Hollett said introducing counselling and drug education services alongside formal pill testing could further reduce the risk of harm.

"People who had previously used ecstasy were no more knowledgeable than people who had never used ecstasy in terms of sensible doses and harmful contaminants," he said.

Festival attendees in favour of pill testing

Festival attendees surveyed indicated they would be willing to pay $12 on average to support the provision of pill testing services.

"Almost 50 per cent of ecstasy users reported they did not know or trust their supplier.

"These findings suggest that the provision of a pill checking service would greatly improve some people's ability to manage risk," Dr Hollett said.

Trichoplax is one of the simplest animals one can imagine, and looks like a shapeless little blob. Senior author Nicole Dubilier says it reminds her of a potato chip. Trichoplax lives in warm coastal waters around the world, where it grazes on microscopic algae that cover sand and rocks. Although most aquarists may not know it, Trichoplax can also be found in almost any saltwater aquarium with corals.

Trichoplax, together with sponges and jellyfish, belongs to one of the most basal lineages of the animal kingdom. Until the 70ies, it was not even clear if Trichoplax is a proper, fully-grown animal or just the juvenile stage of a jellyfish. Only about a half a millimetre in diameter, these animals lack a mouth, gut and any other organs, and are made up of only six different kinds of cells. Its simplicity makes it a popular model organism for biologists.

Scientists from the Max Planck Institute for Marine Microbiology in Bremen, Germany, the University of Hawaii and North Carolina State University have now discovered that Trichoplax is not as simple as it looks. It lives in a remarkably sophisticated symbiosis with highly unusual bacteria.

Simple is beautiful

The first observation of bacteria in Trichoplax was nearly 50 years ago by the German zoologist Karl Grell. But no one has really taken a closer look since then. An international group of scientists around Harald Gruber-Vodicka, Niko Leisch and Nicole Dubilier from the Max Planck Institute for Marine Microbiology, and Michael Hadfield from the University of Hawaii have now investigated the bacterial tenants of Trichoplax by sequencing their genomes and using high-resolution microscopy to see where they live. "Despite being so simple, Trichoplax harbors two very different and highly unusual bacterial symbionts in its cells," says Gruber-Vodicka. "Both symbionts are very picky - or cell-specific, as we call it. Each symbiont lives in only one type of host cell."

Grellia - the first known symbiont to live in the endoplasmic reticulum

One symbiont, named Grellia after the zoologist Karl Grell, lives inside the endoplasmic reticulum (ER) of Trichoplax, and is the first symbiont known to permanently live in an animal's ER. The ER plays a central role in protein and membrane production. Proving that Grellia is truly in the ER was challenging. "We reconstructed a detailed three-dimensional model of the ER to show that Grellia lives inside of it, supported by the electron microscopy facility of the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden," Niko Leisch explains. "Other parasitic bacteria imitate the structure of the ER to trick the hosts into thinking they are not harmful. However, our imaging data clearly showed that Grellia lives inside its host's ER." Intriguingly, Grellia, although closely related to parasites, doesn't appear to be harmful for Trichoplax. "Although it has genes that would allow it to steal energy from its host, it does not use them," Leisch continues.

Ruthmannia - seeing microbial dark matter

The second symbiont of Trichoplax, Ruthmannia, belongs to a group of bacteria that were only recently discovered, the Margulisbacteria. "Before our study, Margulisbacteria were part of the so-called microbial dark matter - the vast majority of microbial organisms that biologists find through sequencing, but are unable to culture," explains Harald Gruber-Vodicka. "We have never actually seen them, even though their genetic traces were found in aquatic samples all over the globe." Now Gruber-Vodicka and Leisch took the first images of a Margulisbacteria. "It's the first time we could see a member of this group. For us, observing this microbial dark matter was just as exciting as imaging black holes." This symbiont lives in cells that Trichoplax uses to digest its algal food. "Ruthmannia appears to only eat the fats and other lipids of the algae, and leaves the rest to its host. In return, we think Ruthmannia may provide Trichoplax with vitamins and amino acids." With Trichoplax thriving in the lab cellars of the Max Planck Institute for Marine Microbiology, the authors now have continuous access to this enigmatic group of bacteria.

What's next

"In this study, we focused on the symbiotic partners of a single Trichoplax species," says Nicole Dubilier, Director at the Max Planck Institute for Marine Microbiology. "However, at least 20 more species have been described, and our first results indicate that each host species has its own, very specific set of symbionts. We are excited about taking a closer look at this remarkable diversity and how it evolved. These tiny animals not only look like potato chips, they also pack a crunch when it comes to what's inside them."

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Plant scientists at the Universities of Cambridge and Bordeaux have discovered a gene that they hope can be used to widen a nutrient trafficking bottleneck and potentially increase crop yields.

Plant scientists around the world are working on a number of different strategies to sustainably increase crop yields. Increasing the efficiency of how plants transport sugars, proteins and other organic nutrients between different parts of the plant is one of the approaches that could contribute to this next Green Revolution.

Having an understanding of factors that affect local and long distance transport within a plant could enable plant biotechnologists to breed more productive crops in the future. Ultimately, it might be possible to direct transport of organic nutrients to specific parts of the plant that are harvested (seeds, fruits and storage tubers).

Professor Yrjö Helariutta's research team at the Sainsbury Laboratory Cambridge University (SLCU) and Dr Emmanuelle Bayer's team at the University of Bordeaux/CNRS have brought this goal a step closer by discovering Phloem Unloading Modulator (PLM), a novel gene that affects nutrient trafficking by altering the channels connecting neighbouring plant cells called plasmodesmata. These nanoscale membrane-lined channels traverse the cell wall barrier to link plant cells together and enable the transfer of essential substances (see notes).

The study, published today in Nature Plants, shows that Arabidopsis thaliana mutant plants missing the PLM gene were found to release more substances from the phloem (a specialised tissue for long distance transport) at the tips of their roots. Using a fluorescent protein as a proxy for macromolecules, the scientists could see that the PLM gene was having a clear controlling effect on the amount of phloem unloading. To find out how the gene was doing this, they looked at what was happening at different cell interfaces in the roots of seedling plants.

Lead author, Dr Dawei Yan, from Cambridge's Sainsbury Laboratory, explains: "We found that mutating PLM relieves a trafficking bottleneck, that was previously reducing the outward movement of nutrients from the vascular system to the rapidly growing tissues in the roots.

PLM is specifically acting at the interface between the phloem pole pericycle (PPP) and endodermal cells, an interface important for the radial movement of substances after unloading. Removing PLM gene activity could enable plants to more rapidly and efficiently transport nutrients to where they are needed."

As a result of the increased unloading, the roots in the mutant plants grew faster and longer.

Further molecular and genetic investigations also revealed that PLM is involved in the biosynthesis of sphingolipids, which are a class of lipids associated with plant development and response to environment. While Dr Bayer's team had previously shown that the membranes of plasmodesmata are enriched with sphingolipids, this is the first study to link sphingolipids to plasmodesmata function.

The next step was to determine how PLM was affecting cell-to-cell conductivity. The team looked at whether PLM was influencing plasmodesmata density - it wasn't. The team also confirmed that PLM was not modifying callose accumulation, which was the only well-known regulator of plasmodesmata permeability.

Second author and PhD student in the Helariutta group, Andrea Paterlini, went to France to work with Dr Bayer to take a closer look at whether PLM was instead affecting the plasmodesmata structure. They used electron tomography to create a 3D map of the channels at the nanometre scale.

Paterlini says: "This allowed us to detect fine alterations to the plasmodesmal architecture. We found equal proportions of simple and branched plasmodesmata in both the plm mutant and wild type plants. However, plants without PLM only had Type I plasmodesmata (see notes), rather than the two types normally found.

"Previous models have assumed that the size of the cytoplasmic sleeve (the spacing between endoplasmic reticulum and plasma membranes in plasmodesmata) would positively correlate with transport capacity. The results of our paper challenge this and show that Type I plasmodesmata, those with a very narrow cytoplasmic sleeve, are actually more conductive than Type II plasmodesmata, which have an open cytoplasmic sleeve."

Professor Helariutta says: "The correlation between the gene function (lipid biosynthesis) and the alteration in plasmodesmata ultrastructure is likely to be the result of a defect in the organisation of the tethers that separate the plasma membrane from the endoplasmic reticulum within plasmodesmata: This results in the majority of the plasmodesmata lacking visible cytoplasmic sleeves in the plants with a mutated PLM gene.

"There are still many new questions to be answered for future research, such as, how and why plasmodesmata that lack cytoplasmic sleeves have higher rates of trafficking and how the metabolism of sphingolipids is mechanistically related to the function of PLM.

"However, this research has advanced our understanding of the factors regulating plant nutrient transport. There is an urgent need to develop crops with increased nutrient efficiency, both to reduce the use of fertilisers and to increase the yield of crops. We may eventually be able to use this information about nutrient transport to more efficiently partition nutrients between various organs and direct nutrients from stems and leaves to fruit and storage organs."

In a study published in Nature on June 10, researchers from Dr. YANG Hui's Lab at the Institute of Neuroscience of the Chinese Academy of Sciences (CAS), and collaborators from the CAS-MPG Partner Institute for Computational Biology of CAS and Sichuan University demonstrated that DNA base editors generated tens of thousands of off-target RNA single nucleotide variants (SNVs) and these off-target SNVs could be eliminated by introducing point mutations to the deaminases.

This study revealed a previously overlooked aspect of the risk of DNA base editors and further provided a solution to the problem by engineering deaminases.

DNA base-editing methods have enabled direct point mutation correction in genomic DNA without generating any double-strand breaks (DSBs), but the potential off-target effects have limited the application of these methods. Adeno-associated viruses (AAV) are the most common delivery system for DNA editing gene therapies. Since these viruses can sustain long-term gene expression in vivo, the extent of potential RNA off-target effects induced by DNA base editors is of great concern for their clinical application.

Several previous studies have evaluated off-target mutations in genomic DNA by DNA base editors. Meanwhile, the deaminases integral to commonly used DNA base editors often exhibit RNA binding activities. For example, the cytosine deaminase APOBEC1 used in cytosine base editors (CBEs) was found to target both DNA and RNA, and the adenine deaminase TadA used in adenine base editors (ABEs) was found to induce site-specific inosine formation on RNA. However, any potential RNA mutations caused by DNA base editors had not been evaluated.

In order to evaluate the off-target effect of DNA base editors at the level of RNA, the researchers counted the off-target RNA SNVs in each replicate of CBE- or ABE-treated cells, and then explored the possibility of eliminating the off-target RNA SNVs by engineering deaminases of DNA base editors.

They transfected one type of CBE, BE3 (APOBEC1-nCas9-UGI), or ABE, ABE7.10 (TadA-TadA*-nCas9), together with GFP and with or without single-guide RNA (sgRNA), into HEK293T-cultured cells. After validating the high on-target efficiency of DNA editing by both BE3 and ABE7.10 in these HEK293T cells, they performed RNA-seq at an average depth of 125X on these samples and quantitively evaluated the RNA SNVs in each replicate.

The on-target editing efficiency was evaluated in each replicate of the CBE- or ABE-treated cells to guarantee efficient editing. Then the number of off-target RNA SNVs in CBE- and ABE-treated groups was compared with the GFP-only control group. They found strikingly higher numbers of RNA SNVs in DNA base editor-treated cells.

Furthermore, the researchers found that the mutation bias in BE3- or ABE7.10-treated cells was the same as that of APOBEC1 or TadA, respectively, indicating the off-target effects were caused by the overexpression of DNA base editors. They also identified CBE- and ABE-specific motifs and genetic regions of these off-target RNA SNVs.

To eliminate the RNA off-target activity of base editors, they examined the effect of introducing point mutations on APOBEC1 or TadA. Three high-fidelity variants, BE3W90Y+R126E, BE3 (hA3AR128A) and BE3 (hA3AY130F), reduced RNA off-target SNVs to the base level. Similarly, an ABE variant ABE7.10F148A also showed complete elimination of off-target effects.

This study obtained both high-fidelity variants for both CBEs and ABEs by introducing point mutations to the deaminases and provided a proposed method using rational engineering to increase the specificity of base editors.

Viruses, spread through mosquito bites, cause human illnesses such as dengue fever, Zika and yellow fever. A new control technique harnesses a naturally occurring bacterium called Wolbachia that blocks replication of viruses and breaks the cycle of mosquito-borne disease, according to an international team of researchers.

"Wolbachia is present in around 50 percent of all insects," said Beth McGraw, professor and Huck Scholar in Entomology at Penn State, who did this research while at Monash University. "Interestingly it is not present in some of the major mosquito vectors (insects that transmit pathogens). After researchers put Wolbachia into mosquitoes, they found that, quite excitingly, Wolbachia effectively vaccinates mosquitoes, preventing viruses from replicating."

Spread by Aedes aegypti mosquitoes, dengue virus affects millions of people each year. Symptoms include fever, body aches and nausea, although a more severe version, known as dengue hemorrhagic fever, can be fatal.

In the tropics and subtropics where Ae. aegypti resides, several large releases of Wolbachia are underway to test whether Wolbachia can reduce the incidence of human disease.

In a paper published today in Virus Evolution, McGraw and her team report that dengue virus failed to evolve resistance to Wolbachia in controlled lab-based experiments. These findings show promise for the long-term efficacy of Wolbachia following field release.

"I am continually surprised by Wolbachia," said McGraw. "I thought we would get dengue variants that would evolve resistance. Wolbachia is doing a better job than I expected at controlling virus replication in cells."

The researchers took dengue virus and infected mosquito cells that either had Wolbachia or were free of bacteria. After five days, they collected the viruses that had been released from the cells and used them to infect fresh cells.

"Dengue takes over the machinery of the host cells, makes lots of copies of itself, and then it buds or burst out of the cell," explained McGraw.

After nine rounds of passaging the virus through mosquito cells, the team found that the amount of virus released was stable in the Wolbachia-free cells. However, in the presence of Wolbachia, virus levels crashed -- and in some cases, disappeared completely.

Dengue viruses grown with Wolbachia were also less effective at infecting mosquito cells and had reduced ability to replicate, compared to viruses grown without the bacterium.

Although this is good news for the control of dengue and other mosquito-transmitted diseases, the researchers note the study has limitations. The researchers used mosquito cells -- which may not reflect what happens within the whole insect. And outside the lab, where mosquito populations are much larger, there may be more opportunities for the virus to develop resistance to Wolbachia.

"I think our study suggests that the evolution of resistance to Wolbachia in the virus is challenging," said McGraw. "I don't think it's a guarantee that the virus is not going to evolve under field conditions because the natural system is much more complex. The real experiment is being done in the field right now, because Wolbachia has been released into communities in Australia, Indonesia and Brazil, among others. Monitoring in release areas will be needed to test for the emergence of resistance in the virus."

Other control methods for dengue have largely been unsuccessful. Because Ae. aegypti is active during the day, bed nets are ineffective at reducing mosquito bites. Spraying of insecticides to control the mosquito and removing standing-water breeding sites have also been difficult to implement in urban environments where the mosquito thrives.

Wolbachia is an attractive control option because it blocks the replication of many disease-causing viruses. It is also self-spreading because of a curious effect, where Wolbachia-containing male mosquitoes cannot reproduce successfully with Wolbachia-free females. According to McGraw, this means that these males prevent Wolbachia-free females from reproducing. Because the bacterium is transmitted from mother to offspring, each generation has successively more mosquitoes containing Wolbachia.

Researchers are still unsure exactly how Wolbachia reduces virus replication in the mosquito.

"We think it might have to do with competition between Wolbachia and the virus for physical space (inside the cell) or for nutrition they both need from the mosquito," said McGraw. "Or it could be that Wolbachia is increasing the immune capacity of the mosquito. There are a whole range of theories, none of which are entirely satisfying."

A team of researchers led by a member of the University of Colorado School of Medicine faculty at the Anschutz Medical Campus examined post-advisory financial relationships between U.S. physicians who advised FDA committees during dermatological drug approval processes. Critics of these industry-physician relationships claim these types of payments could incentivize advisors to alter their voting habits.

The findings are published in a research letter in the Journal of the American Academy of Dermatology.

"It's known from previous studies that financial payments to FDA advisors can take place after a drug is approved but this is the first time we've researched and seen that this trend spans to the dermatology field," said Robert Dellavalle, MD, PhD, professor of dermatology and public health at the University of Colorado School of Medicine.

Dellavalle adds, "It's hard to control post-advisory financial relationships since it's not on the record going into the committee and top doctors can be paid as ongoing academic advisors for a variety of reasons. Regardless, financial conflicts of interest in medical research are important to discuss and monitor."

Physician advisors serve as external experts in determining whether a new medical therapy is fit for the U.S. market. Of the advisors analyzed, 54 percent received at least one payment from pharmaceutical companies. Twenty-seven percent accepted more than $1,000, 15 percent accepted more than $50,000 and nine percent took more than a $100,000. The advisors received a mean of more than $47,000. For the majority of the drugs examined, payments from competitors outnumbered payments from manufacturers.

The study analyzed Open Payment data, a national transparency program that collects and publishes information about financial relationships between the health care industry (i.e., drug and device companies) and providers (i.e., physicians and teaching hospitals). The study focused on payments made by U.S. physicians who advised FDA committees during the approval of ten dermatologic therapies.

Since the output of renewable energy such as photovoltaic generation tends to fluctuate, the power system can be viewed as a large-scale complex system with uncertainty. To stabilize the balance of supply and demand of electricity, we need an energy management system to control this. In recent years, energy management systems have been actively researched against the background of the liberalization of power and the spread of smart meters that visualize the power consumption. Koichi Kobayashi, associate professor at Hokkaido University, Shun-ichi Azuma, professor at Nagoya University, and Nobuyuki Yamaguchi, associate professor at Tokyo University of Science etc. developed demand response analysis and control technologies focusing on time-varying power generation costs.

Demand response is one of the methods in energy management systems. Demand response is defined as "when the supply-demand balance is tight, consumers conserve the power consumption and change the power consumption pattern according to the setting of the electricity price or the payment of incentives (rewards)." The cost-effectiveness has not been clarified.

The introduction of the "aggregator" that controls the power consumption of consumers has attracted much attention. In this framework, aggregators trade between electric power companies and consumers, instead of direct trade between consumers and electric companies. Aggregators manage hundreds of consumers and control their power consumption in response to requests from electric companies. By the introduction of aggregators, control of the whole power system becomes easier.

During a day, the cost-effectiveness of demand response fluctuates depending on the demand and supply of electricity. It is expected that this fluctuation becomes larger by the spread of renewable energy. Demand response is aimed at maintaining the balance between supply and demand, and its cost-effectiveness has not been focused. However, in the future, it will be important to evaluate the economic value of demand response, focusing on the power generation cost and the adjustment cost (the cost required to adjust power consumption) at each time. Furthermore, it is necessary to develop control strategies that maximize the economic value of demand response.

In order for demand response to produce the economic value, the unit price of power generation costs needs to fluctuate greatly during the day. If the difference between the highest and lowest generation costs is large compared to the adjustment costs, then demand response produces the economic value. In this research, more specifically, we derived the condition that "demand response produces the economic value if the difference between the highest price and the lowest price is more than twice the adjustment cost". Because it is a simple condition, it can also be used as a guide to calculate the rewards to consumers.

Next, in order to maximize the economic value, a control method for demand response is developed based on model predictive control in which the optimal control strategy is found by the prediction via a mathematical model. In the simulation, the effectiveness of the proposed method is presented by using the data from the Japan Electric Power Exchange as a forecast value of the power generation cost and the power consumption.

A meta-analysis of dietary information recorded in the bones of ancient animals and humans recovered from sites scattered across the Eurasian steppe, from the Caucasus region to Mongolia, demonstrates that pastoralists spread domesticated crops across the steppe through their trade and social networks. Researchers from Kiel University sifted through previously published stable isotopic data and applied new quantitative analyses that calibrate human dietary intake against environmental inputs. The results have allowed them to better isolate the timing of the incorporation of agricultural products into the diets of pastoral nomads and, crucially, link burgeoning socio-political networks to this dietary transformation.

Through a big data project that explored over a thousand stable isotope data points, researchers were able to find evidence for an early transition to agriculture - based on dietary intake across Eurasia. "Our understanding of the pace of crop transmission across the Eurasian steppe has been surprisingly unclear due in part to a focus on the excavation of cemeteries, rather than settlements where people threw out their food," says Alicia Ventresca Miller, lead author, formerly of Kiel University and currently at the Max Planck Institute for the Science of Human History. "Even when settlement sites are excavated, the preservation of carbonized seed remains is often poor. This is what makes stable isotope analyses of human remains from this region so valuable - it provides direct insights into the dietary dynamics of ancient pastoralists who inhabited diverse environments."

Millet spreads across the Eurasian steppe

Millet, originally domesticated in China, appears to have been occasionally consumed at low levels by pastoralists inhabiting the far-flung regions of Siberia and southeastern Kazakhstan, possibly as early as the late third millennium. This initial uptake of millet coincided with the expansion of trans-regional networks across the steppe, when objects and ideas were first regularly exchanged over long-distances.

However, it was not until a thousand years later that millet became a regular feature of pastoralist diets. This timing coincides with the intensification of complex political structures at the transition to the Iron Age. Burgeoning socio-political confederations drove a marked increase in the exchange of costly prestige goods, which strengthened political networks - and facilitated the transfer of cultigens.

Wheat and Barley in the Trans-Urals

Despite taking part in these political networks, groups in the Trans-Urals invested in wheat and barley farming rather than millet. A dietary focus on wheat and barley may have been due to different farming techniques, greater water availability, or a higher value on these cultigens. "Our research suggests that cultigens were converted from a rare luxury during the Bronze Age to a medium demarcating elite participation in political networks during the Iron Age," states Cheryl Makarewicz of Kiel University.

Regional variation in millet consumption

While herding of livestock was widespread, not all regions adopted millet. In southwest Siberia, dietary intake was focused on pastoral animal products and locally available wild plants and fish. In contrast, the delayed adoption of millet by populations in Mongolia during the Late Iron Age coincides with the rise of the Xiongnu nomadic empire. "This is particularly interesting because it suggests that communities in Mongolia and Siberia opted out of the transition to millet agriculture, while continuing to engage with neighboring groups," explains Ventresca Miller.

This study shows the great potential of using the available isotope record to provide evidence for human dietary intake in areas where paleobotany is understudied. Further research should clarify the exact type of grains, for example broomcorn or foxtail millet, were fundamental to the shift in dietary intake and how networks of exchange linked different regions.

"Green revolution" in the early 1950s, the extensive cultivation of Dwarf Rice solves the food problem in developing countries. At present, chronic infection with hepatitis B virus (HBV) has been a major public health problem. According to the announcement from World Health Organization (WHO), an estimated 257 million people are chronically infected with hepatitis B. Recent studies have shown that the expression level of hepatitis B virus surface antigen gene (HBsAg) is correlated with the occurrence of HCC or fibrosis severity in transgenic mice and HBV infection patients, therefore, HBsAg becomes a rising target for drug design for the treatment of hepatitis B.

In a study recently published in Biomaterials, Dr. Zhi Hong and Dr. Chen-Yu Zhang from Nanjing University and the collaborators report that the small silencing RNA sequences against HBsAg generated in edible lettuce (Lactuca sativa L.) can specifically bind and inhibit gene expression in p21-HBsAg knock-in transgenic mice at a relatively low amount when compared to synthetic siRNAs. More importantly, continuous administration of amiRNA-containing decoction relieves the liver injury in transgenic mice without extra negative effects even after 15-month treatment.

This work utilizes the plant endogenous microRNA biogenesis machinery to produce methylated short interfering sequences for increasing the stability of target siRNAs while reducing the cost of production. Therefore, this work not only provide an affordable treatment strategy for chronic hepatitis B patients in developing countries, but also reduces the required dose of RNAi drugs to minimize the potential side effects of RNAi therapy and allow the administration for a relatively long period or in conjunction with other antiviral drugs.

To those patients in immune-tolerant phase or resistant to conventional antivirus treatment, this RNAi-based therapy may effectively reduce their risk of liver injury by daily consumption of vegetable decoction containing HBsAg silencing RNAs.

If we take a long view, this method may also be applicable to the treatment of hepatitis C or other infectious diseases due to the effective, less toxic and financially viable strategy to produce short interfering sequences using engineered plants. It can be predicted that plant derived siRNAs will bring a "green revolution" in RNAi tools and therapeutics.

When we look back, the Green Revolution has brought us a richer food supply. At the same time, we should also know that the daily food is also changing ourselves, in which the small RNAs we take from food may play an important role.

Replenishing venom takes time and energy - so it pays to be stingy with stings.

According to researchers at the Australian National Institute of Tropical Health and Medicine, scorpions adapt their bodies, their behavior and even the composition of their venom, for efficient control of prey and predators.

Writing in Frontiers in Ecology and Evolution, they say it's not just the size of the stinger, but also how it's used that matters.

Stingy stingers

"Scorpions can store only a limited volume of venom, that takes time and energy to replenish after use," says lead author Edward Evans. "Meanwhile the scorpion has a reduced capacity to capture prey or defend against predators, so the costs of venom use are twofold."

As a result, over 400 million years of evolution scorpions have developed a variety of strategies to minimize venom use.

The most obvious of these is to avoid using venom at all.

"Research has shown the lighter, faster male specimens of one species are more likely to flee from danger compared to the heavier-bodied females, rather than expend energy using toxins," notes Evans. "Others - particularly burrowing species - depend instead on their large claws or 'pedipalps', and have a small, seldom-used stinging apparatus."

When immobility, threat or lively prey forces venom use, scorpions can adjust the volume they inject - both within each sting and through the application of multiple stings.

"Scorpions can hold prey in their pedipalps and judiciously apply stings, just until it stops struggling."

At the other extreme, when the survival stakes are high some species abandon precision and spray their venom through the air.

"Spraying venom defensively is potentially wasteful but can avoid dangerous close contact with predators such as grasshopper mice, which disarm scorpions by biting off their tails."

Venom versatility

Scorpions can also tailor the composition of their venom to a target - both on-the-fly, and more precisely over weeks of exposure.

For starters, any given sting has three levels: dry, prevenom or venom.

As a light deterrent, a scorpion may sting with no venom at all. A 'wet' sting begins with clear, salty prevenom - essentially a "stun" setting - and might go no further.

"Research on prevenom suggests it contains an extremely high potassium salt concentration, which may cause quick paralysis in insects and pain in vertebrates," says Evans. "It seems to regenerate quickly and presumably at a low metabolic cost."

If things get heavy, the scorpion can go on to inject or spray a thick, milky, protein-rich venom.

"Venom injection is reserved for more active, persistent or sizeable targets. It is more toxic, but once spent can take weeks to replenish - leaving the scorpion vulnerable and with limited prey options."

Recent work by the James Cook University group suggests that scorpions can make more personalized changes to venom composition, in response to extended periods of predator exposure.

"Repeated encounters with a surrogate vertebrate predator - a taxidermied mouse - over a six week period led the scorpion Hormurus waigiensis to produce a higher relative abundance of a particular group of toxins, including some with vertebrate predator-specific activity," explains senior author Dr. David Wilson.

How exactly the change occurs remains unknown, however.

"Future work is needed to investigate how far observed changes in venom composition and use are due to adaptive responses - and to identify the precise stimuli for change," Wilson and Evans conclude.

Researchers from the University of Hong Kong, University of Tennessee, University of British Columbia, and Arizona State University published a new paper in the Journal of Marketing that seeks the optimal strategy for communicating the value of cocreated innovations in order to drive consumer purchase and acceptance in the marketplace.

The study forthcoming in the July issue of the Journal of Marketing, titled "Successfully Communicating a Cocreated Innovation," is authored by Helen Si Wang, Charles Noble, Darren Dahl, and Sungho Park.

Online platforms make it easy and inexpensive for companies to run contests, gather customers' ideas, and commercialize the most promising ideas into finished products. This is a key reason cocreation has been adopted as a key innovation strategy by nearly 78% of large companies. Thus far, however, the strategy has yielded disappointing results. One of the most heralded cocreation firms, Quirky, withdrew 70% of its 500-plus cocreated innovations between 2009 and 2014 because of stagnant sales and filed for bankruptcy thereafter. And at Apple's App Store, 80% of the apps do not generate enough revenue to survive for more than a few months.

Is the cocreation model a legitimate strategy to drive innovation and adoption of resulting products--or is it flawed by design? Marketing communications is often regarded as one of the major influences on innovation adoption and creators typically take two approaches to marketing new products. They either share a consumer creation or genesis story (also called user-generated content or UGC) or use more traditional, firm-generated content (FGC) that often stresses a feature's products and benefits. This research shows that it is wise to combine these strategies but with an interesting twist on conventional advertising wisdom.

When sharing a genesis story, creators tend to take one of two tacks: 1) an approach-oriented message about how they achieved new or desired outcomes; or 2) an avoidance-oriented message that promises to help users avoid unpleasant or undesirable outcomes they themselves experienced. Advertising best practice stresses that a firm should use consistent messaging to communicate with customers.

This practice does not hold up to scrutiny in the area of co-created products, however. Instead, the researchers found that a mixed or "mismatch" communication strategy works best to speed individual and mass consumer adoption. A mismatch communication strategy means that if the product creator's claim is approach-oriented, the firm should use an avoidance-oriented and vice versa.

As an example, for the cocreated Starbucks® Doubleshot Energy Mexican Mocha Coffee Drink, the creators' authentic message was approach-oriented and focused on "Embracing winter... fueling me with all of the winter warmth and energy I want." When the researchers combined this with an avoidance firm message, "What the world can't miss this winter... say bye-bye to the winter chill and blues" to make a mismatch strategy, adoption levels increased compared to when the approach firm message was used--"What the world desires this winter... makes you embrace all the winter warmth and joy."

Key findings from five studies include:

Products using a mismatch strategy were adopted 56.1% of the time compared to 26.3% of those using matching communication strategies.

This approach works best with low-expertise consumers who reference their own life stories when buying and using goods. High-expertise consumers are less motivated by this approach.

Firms using a mismatch communication strategy are 10% more likely to experience early takeoff, which is critical to the mass adoption of the innovation.

"This research offers important implications for managers and companies seeking to leverage the creative power of the crowd in developing innovations," says Wang. Noble adds, "Our findings challenge the conventional wisdom in many marketing campaigns. If you want takeoff, mismatch your message with the innovator creator's message."

(June 7, 2019) –- For more than a year, GozNym, a gang of five Russian cyber criminals, stole login credentials and emptied bank accounts from unaware Americans. To detect and quickly respond to escalating cyber-attacks like these, researchers at The University of Texas at San Antonio (UTSA) have developed the first framework to score the agility of cyber attackers and defenders. The cyber agility project was funded by the Army Research Office.

“Cyber agility isn’t just about patching a security hole, it’s about understanding what happens over time. Sometimes when you protect one vulnerability, you expose yourself to 10 others,” said computer science alumnus Jose Mireles ’17, who now works for the U.S. Department of Defense and co-developed this first known framework as part of his UTSA master’s thesis. “In car crashes, we understand how to test for safety using the rules of physics. It is much harder to quantify cybersecurity because scientists have yet to figure out what are the rules of cybersecurity. Having formal metrics and measurement to understand the attacks that occur will benefit a wide range of cyber professionals.”

To develop a quantifiable framework, Mireles collaborated with fellow UTSA student Eric Ficke, researchers at Virginia Tech, U.S. Air Force Research Laboratory, and the U.S. Army Combat Capabilities Development Command Army Research Laboratory (CCDC ARL). The project was conducted under the supervision of UTSA Professor Shouhuai Xu, who serves as the director of the UTSA Laboratory for Cybersecurity Dynamics.

Together, they used a honeypot—a computer system that lures real cyber-attacks—to attract and analyze malicious traffic according to time and effectiveness. As both the attackers and the defenders created new techniques, the researchers were able to better understand how a series of engagements transformed into an adaptive, responsive and agile pattern or what they called an evolution generation.

The framework proposed by the researchers will help government and industry organizations visualize how well they out-maneuver attacks. This groundbreaking work will be published in an upcoming issue of IEEE Transactions on Information Forensics and Security, a top cybersecurity journal.

“The cyber agility framework is the first of its kind and allows cyber defenders to test out numerous and varied responses to an attack,” said Xu. “This is an outstanding piece of work as it will shape the investigation and practice of cyber agility for the many years to come.”

"The DoD and US Army recognize that the Cyber domain is as important a battlefront as Ground, Air and Sea," said Purush Iyer, Ph.D. division chief, network sciences at Army Research Office, an element of CCDC ARL. "Being able to predict what the adversaries will likely do provides opportunities to protect and to launch countermeasures."

Mireles added, “A picture or graph in this case is really worth more than 1,000 words. Using our framework, security professionals will recognize if they’re getting beaten or doing a good job against an attacker.”

UTSA is home to the nation’s top cybersecurity program, an interdisciplinary approach that spans three colleges: the College of Business, College of Engineering and College of Sciences. Research centers and outreach programs provide UTSA students and faculty with additional opportunities to explore the various facets of this high demand and ever-changing field.

The Department of Computer Science, housed in the UTSA College of Sciences, offers bachelor’s, master’s and doctoral degree programs that support more than 1,360 undergraduate students and 68 graduate students. Its major research units include the UTSA Institute for Cyber Security, which operates the FlexCloud and FlexFarm laboratories dedicated to both basic and applied cybersecurity research, and the UTSA Center for Infrastructure Assurance and Security (CIAS), which focuses on the cybersecurity maturity of cities and communities while conducting national cyber defense competitions for high school and college students.

San Antonio is home to one of the largest concentrations of cybersecurity experts and industry leaders outside Washington, D.C., which uniquely positions the city and UTSA to lead the nation in cybersecurity research and workforce development.

Social media-based movements like #BlackLivesMatter and #SayHerName have taken off over the past decade as a response to highly scrutinized police shootings of African American people. Recordings from body cameras or bystanders are frequently posted online and shared by activists and others as a way to press for police accountability.

But those videos may also have deleterious effects on the mental health of young members of the same racial communities as the victims in those shootings, suggests a new study published today in the Journal of Adolescent Health.

Previous research has linked exposure to violent media with trauma, and other research has connected actual police killings in a given region to poor mental health in same-race communities. Study authors say this study is the first to explore the relationship between repeated youth exposure to traumatic events online with mental health.

"Increased exposure to traumatic events online, whether they involve members of one's own racial-ethnic group or those of other racial-ethnic groups, are related to poor mental health outcomes," said lead author Brendesha Tynes, an associate professor of education and psychology at the USC Rossier School of Education.

Data were collected from a nationally representative sample of 302 Black and Hispanic adolescents ages 11-19. African American and Hispanic participants were asked about police shootings, immigrants being detained by federal border agents, and beatings.

Study participants reported the frequency of their exposure to traumatic events online, depressive symptoms, PTSD symptoms, and other demographic information.

Though not establishing causality, the researchers' findings showed that Hispanic participants reported significantly more depressive symptoms than African American participants. Female participants reported significantly more depressive and PTSD symptoms than male participants. This was true for teens that viewed violence involving both African Americans and Hispanic individuals.

"The study shows that the increase in depressive and PTSD symptoms crosses racial and ethnic lines - in other words, the mental health of both African American and Latinx teens may be linked to viewing any racial violence, not just that which depicts their own racial or ethnic group," Tynes said.

Pew Internet Research's most recent (2018) survey of adolescent technology usage shows that 45 percent of youth report they are online "almost constantly."

Given such high internet use, the researchers suggested that mental health professionals and educators have conversations with young people of color about their exposure to racial violence online, and that those professionals should also take steps to improve their own cultural competency.

"The videos of these injustices should be public and people should continue to record and post them," Tynes said. "The findings show that mental health problems are exacerbated with exposure, so viewers should be mindful of their viewing practices, auto-play settings and how they think about the event after they've seen it. They should exhaust all technological, personal and community resources to protect themselves and thrive in the face of these seemingly ubiquitous events."