Culture

DURHAM, N.C. -- In late 2018, the U.S. National Marine Fisheries Service proposed a rule change that would reverse current policy and allow the agency to use public funds to underwrite low-interest, fixed-term loans for the construction of new commercial fishing vessels.

The proposed change, which is still pending final approval, lacks scientific merit and should be rejected, according to a new analysis by a Duke University economist.

"We just spent millions buying out a bunch of fishing vessels to reduce overcapacity in our federal fisheries. Now we want to spend millions more to put them back in. That's a total waste of taxpayer dollars," said Martin D. Smith, George M. Woodwell Distinguished Professor of Environmental Economics at Duke's Nicholas School of the Environment.

"The notion that the government should subsidize commercial fishing beyond what the market deems profitable is a turn away from a market economy," he said. "For an administration that rails against socialism, it's bizarre that it would place more faith in big government to price vessel loans than in the private banking industry."

Smith published his peer-reviewed policy analysis April 5 in Science.

Aside from being fiscally unwise, the proposed rule change undercuts long-term sustainability objectives in U.S. fisheries, Smith argues. It also ignores the most current science on fisheries' interconnectivity and is unfair to taxpayers, other industries and future fishers, who will face a sharp disadvantage competing for available loans, he said.

If the proposed rule change is approved and finalized, it could also undermine global efforts to reduce illegal, unreported and unregulated fishing, and increase harmful impacts on habitats and non-targeted by-catch species, he argues, because boats and crews go where the fish are.

"The latest science teaches us that fisheries are interconnected and leakage from one to the others is a real thing. If there are too many boats in one fishery, there's little to stop fishers from seeking better opportunities by moving to another fishery," Smith explained.

As more and more fishers do this, the problems linked to excess capacity can spread to other fisheries -- including fisheries that currently are well-managed. These problems include overfishing, weak economic performance, increased by-catch and habitat impacts and unsafe working conditions on fishing vessels. The policy might also lead to an increased risk of the "race to fish" in which fishers ratchet up the number and power of their fishing vessels early each season to catch as much of the fisheries' limited supply of fish as possible before their competitors can.

The issues can also spread to unregulated fisheries or those in the high seas, beyond U.S. jurisdiction.

"It becomes like a giant game of Whack-a-Mole," Smith said. "You whack a problem back in one fishery, and it pops up again somewhere else."

The use of subsidies for new vessel loans has been prohibited under U.S. policy since the 2007 reauthorization of the Magnuson-Stevens Fishery Conservation and Management Act. In the ensuing years, fishery managers have made substantial progress in reducing overfishing and rebuilding fisheries by adopting scientifically sound management practices, such as catch shares, to address overcapacity. Smith said the amount of money the U.S. now spends on "bad subsidies" that encourage overfishing or excess capacity is very small by global standards.

"If the new rule allowing taxpayer money to be spent on vessel loans is finalized, it could undo this progress and undermine our country's global leadership on reducing subsidies and maintaining a consistent commitment to fight illegal, unreported and unregulated fishing," Smith said.

No date has been publicly announced for when the proposed rule change might be finalized, but many experts expect it will be this spring.

"Rejecting the rule change would signal a commitment to fairness and foresight," Smith said. "It would mark a step away from outdated management approaches that ignore the fact that fish stocks are connected ecologically, fishing vessels can range across the water, and the ownership of vessels and other fishing capital can cross political boundaries," he said.

"These are the realities, and our policy should reflect them."

With the growth of 3D printing, it's entirely possible to 3D print your own prosthetic from models found in open-source databases.

But those models lack personalized electronic user interfaces like those found in costly, state-of-the-art prosthetics.

Now, a Virginia Tech professor and his interdisciplinary team of undergraduate student researchers have made inroads in integrating electronic sensors with personalized 3D-printed prosthetics -- a development that could one day lead to more affordable electric-powered prosthetics.

This newly published research out of the lab of Blake Johnson, a Virginia Tech assistant professor in industrial and systems engineering, took a step forward in improving the functionalities of 3D-printed personalized wearable systems.

By integrating electronic sensors at the intersection between a prosthetic and the wearer's tissue, the researchers can gather information related to prosthetic function and comfort, such as the pressure across wearer's tissue, that can help improve further iterations of the these types of prosthetics.

The integration of materials within form-fitting regions of 3D-printed prosthetics via a conformal 3D printing technique, instead of manual integration after printing, could also pave the way for unique opportunities in matching the hardness of the wearer's tissue and and integrating sensors at different locations across the form-fitting interface. Unlike traditional 3D printing that involves depositing material in a layer-by-layer fashion on a flat surface, conformal 3D printing allows for deposition of materials on curved surfaces and objects.

According to Yuxin Tong, an industrial and systems engineering graduate student and first author of the published study, the ultimate goal is to create engineering practices and processes that can reach as many people as possible, starting with an effort to help develop a prosthetic for one local teen.

"Hopefully, every parent could follow the description from the paper we published and develop a low-cost personalized prosthetic hand for his or her child," Tong said.

To develop the prosthetics integrated with electronic sensors, the researchers started with 3D scanning data, which is similar to taking pictures at various angles to get the full form of an object -- in this case, a mold of the teenager's limb.

They then used 3D scanning data to guide the integration of sensors into the form-fitting cavity of the prosthetic using a conformal 3D printing technique.

The process developed by the research team will lend itself to further applications in personalized medicine and design of wearable systems.

"Personalizing and modifying the properties and functionalities of wearable system interfaces using 3D scanning and 3D printing opens the door to the design and manufacture of new technologies for human assistance and health care as well as examining fundamental questions associated with the function and comfort of wearable systems," Johnson said.

Johnson's research into prosthetic hands was inspired when he learned about his colleague's daughter, Josie Fraticelli, then 12-years old, who had been born with amniotic band syndrome. While in utero, the development of her hand stopped. String-like amniotic bands restricted blood flow and affected the development of right hand, causing a lack of formation beyond the knuckles.

Johnson used his related research expertise in additive biomanufacturing and a team of interdisciplinary undergraduate researchers to 3D print the bionic hand for Fraticelli that would become the basis of the now-published research.

As they worked with Fraticelli, they continued tweaking the prototype prosthetic by developing new additive manufacturing techniques that would allow for a better fit to Fraticelli's palm, creating a more comfortable, form-fitting prosthetic device.

They validated that the personalization of the prosthetic increased the contact between Fraticelli's tissue and the prosthesis by nearly fourfold as compared to non-personalized devices. This increased contact area helped them pinpoint where to deploy sensing electrode arrays to test the pressure distribution, which helped them to further improve the design.

Sensing experiments were conducted using two personalized prosthetics with and without sensing electrode arrays. By running these experiments with Fraticelli, they found that the pressure distribution was different when she relaxed her hand versus holding her hand in a flexed posture.

"The mismatch between the soft skin and the rigid interface is still a problem that will reduce the conformity," said Tong. "The sensing electrode arrays may open another new area to improve the prosthetics design from the perspective of distributing a better balance of pressure."

Overall, Fraticelli does feel that the new personalized prosthetic improves her comfort level. Since her hand is soft and changeable under different postures and the prosthetic material is rigid and fixed, the level of conformity may continue to change.

Personalized prosthetics still have space for improvements, and Johnson's team will continue to research and develop new techniques in additive manufacturing to make improvements on wearable bionic devices.

TROY, N.Y. --Hypertrophic cardiomyopathy is best known for revealing itself in one certain way: as an unexpected, fatal heart attack during strenuous exercise. But researchers suspect as many as 300 mutations can individually cause enlargement of the heart that renders it vulnerable to strain. Recent studies examining three of those mutations at the molecular level found separate mechanisms at work, said Rensselaer Polytechnic Institute muscle protein and contraction expert Doug Swank, whose most recent paper on the topic was published today in the Journal of Physiology.

"Our work suggests that a simple one-size-fits-all hypothesis about how these mutations lead to an enlarged heart and to the disease is not likely to be the case. It's likely to be multiple mechanisms, perhaps depending on where the mutation is found in the protein or what it does to the protein," said Swank, a professor of biological sciences and member of the Rensselaer Center for Biotechnology and Interdisciplinary Studies.

Swank's research on hypertrophic cardiomyopathy is being conducted in collaboration with researchers at San Diego State University and Johns Hopkins University, with support from the National Institutes of Health.

The current paper and a previous study published in eLife in 2018 examine two mutations in myosin, a lever-shaped muscle protein that generates force to contract heart muscle tissue. Like all proteins, muscle proteins are chains of amino acids twisted into a three-dimensional shape that determines their function. But mutations slightly alter the composition of the amino acid chain, which also changes the shape of the protein and its performance.

Swanks' lab expresses the mutation in the wing muscle of a fruit fly, making it possible to examine how the mutations impact mechanical properties like force production, work and power. The eLife study looked at a mutation in myosin known as K146N (the mutation name is derived from the name of the affected amino acid residue and how it is altered in myosin). Examinations of fruit fly muscles with this mutation supported the "increased contractility hypothesis," which proposes that the heart is spending more time in a contracted state than in a relaxed state.

Ordinarily, as filaments of the myosin protein absorb energy, they bind to filaments of the protein actin and bend back upon themselves, pulling on the actin filaments and contracting the muscle.

"Our results for K146N indicated that the myosin bound longer to actin than it normally does," said Swank. "Considering that hundreds of these myosin molecules are doing this all the time, if they stay bound longer, at any given time you're going to have more myosin heads bound and pulling together than you otherwise would. So that gives you more force."

But the newly released Journal of Physiology study looked at an R249Q mutation and found a nearly opposite result. Fruit fly muscle with a R249Q mutation, which typically produces a less severe form of the disease, generated less force, less work, and less power. Swank said this result suggests that, in the heart, such a mutation is unlikely to be causing increased contractility - and yet it yields a similar outcome.

A third study to be published in the near future describes a mechanism for a mutation in another heart protein.

"Our hope is that, as we continue to understand how these mutations affect muscle contraction, a few general mechanisms will emerge which will make it possible to devise a group of treatments to address the disease," said Swank.

New research has indicated that people with autism have an altered sense of self, which may explain some of the differences shown in social functioning.

The study, which was carried out by scientists at Anglia Ruskin University and published in the journal Autism, involved a group of 51 adults, half with and half without autism.

It is the first time that responses to the self-altering 'full body illusion', which simulates an out of body experience, have been measured in people with autism.

The research found that, unlike neurotypical participants, people with autism do not experience the 'full body illusion'. This is a test that causes people to experience their self as being located outside of their body and to identify with their own virtual 'avatar' viewed through virtual reality goggles.

The scientists also measured the size of the participants' peripersonal space. This is the area of space directly around our body which the brain treats in a special way as it enables us to interact with the external world. They found that this area of space, that defines the boundaries of self, is smaller in people with autism.

A smaller peripersonal space may explain certain behaviours sometimes seen in individuals with autism, such as approaching others more closely than social norms prescribe, or having difficulty considering communications coming from outside their personal space as being directed towards them.

First author, PhD student Cari-lene Mul, said: "For a long time autism has been considered a disorder of the self as some people with autism have difficulties accessing memories about themselves and using personal pronouns such as 'me' and 'I'.

"We wanted to find out whether arguably more fundamental aspects of the self - the feeling that your body belongs to you and that your self is located within it - might be altered in people with autism."

Senior author of the study Dr Jane Aspell, Senior Lecturer in Psychology at Anglia Ruskin University, added: "The findings of our study show that the 'bodily' self is less flexible in people with autism and their brains may combine sensory information about their bodies in a different way.

"These differences in self may relate to, and partly explain, differences in self processing and problems with social functioning, including the ability to empathise with others."

The Nuffield Council on Bioethics has published a briefing note outlining the factors that can contribute to disagreements between parents and healthcare staff about the care and treatment of critically ill babies and young children. It concludes that the Government and NHS leaders could do more to foster good, collaborative relationships between parents and healthcare staff across the UK.

The care and treatment of critically ill children often involves complexity and uncertainty. Disagreements can arise between parents and healthcare staff about the best course of action, and sometimes these become entrenched. Recent high-profile court cases in the UK have highlighted the damaging effects that these kinds of disagreements can have on everyone involved.

The reasons why disagreements develop are wide ranging, but include poor communication - such as conflicting messages being given to families by different members of staff, or the use of insensitive language - and delays in seeking resolution interventions, such as mediation.

The Nuffield Council has highlighted areas of action for healthcare policy-makers and NHS leaders that could help to prevent prolonged and damaging disagreements developing in future, or to resolve them more quickly. Overall, the aim should be:

good communication between families and staff and an understanding of differing perspectives

appropriate involvement of parents in discussions and decisions about the care and treatment of their child

timely use of resolution interventions, such as mediation, in cases of disagreement

attention to the profound psychological effects that disagreements can have for families and staff.

Professor Ann Gallagher, member of the Nuffield Council on Bioethics, and Professor of Ethics and Care at the University of Surrey says:

"Disagreements about the care and treatment of critically ill children can be extremely distressing for parents and for everybody involved, particularly if the case is referred to the courts. Every situation is different, but we have tried to understand some of the common causes of disagreements by talking to parents, healthcare staff and range of other people with expertise in this area.

"We heard that problems can start early, with poor communication leading to a breakdown of trust, or parents feeling they are excluded from medical conversations about their child. Healthcare staff can feel they are not adequately supported to deal with conflict.

"Although there is a lot of good practice already out there, we think more could be done at a national level to support good, collaborative relationships between families and healthcare staff leading to shared decision-making. We want to prompt policy makers and NHS leaders to think carefully about how the damaging and protracted disagreements that we have seen in recent years can be avoided in future."

Areas of action

The Council suggests that, amongst other measures, those responsible for national policy making in relation to healthcare practice should consider:

supporting hospital trusts across the UK to develop processes for recognising and managing disagreements between parents and healthcare staff, such as introducing conflict management frameworks and increasing timely access to resolution interventions

making ethics, communication and conflict management training for paediatric healthcare staff more widely available, or even compulsory

improving access to and awareness of children's palliative care services.

Amongst other measures, those involved in leading NHS trusts and hospitals should consider:

providing parents with a trusted and appropriately trained healthcare professional as a central point of communication

exploring ways in which those parents who want to can be more involved in discussions and decisions about their critically ill child, including having access to their child's medical records

ensuring healthcare staff involved in disagreements are better supported by, for example, developing conflict management frameworks, providing more psychological support, and protecting them from abuse and intimidation.

ORLANDO, Fla., April 3, 2019 -- Lead leaching from pipes into the water supply is a serious public health concern. And if water sources or treatment regimens are changed, the new chemistry can cause water distribution systems that were previously safe to begin releasing toxic lead, as the crisis in Flint, Michigan, demonstrated a few years ago. Today, scientists will describe a cost-effective and quick method that could overcome these problems and make lead pipes safe for carrying drinking water.

The researchers will present their results today at the American Chemical Society (ACS) Spring 2019 National Meeting & Exposition. ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features nearly 13,000 presentations on a wide range of science topics.

A brand-new video on the research is available at http://bit.ly/HLS_Lead_Pipes.

"More than 18 million people in the U.S. are currently at risk of developing health problems from lead leaching from pipes in their water distribution systems," says Gabriel Lobo, a doctoral student who is presenting the work at the meeting. Lead poisoning in young children can cause a broad range of symptoms, including brain damage, learning difficulties, and slowed growth and development. Adult exposure can cause high blood pressure, memory difficulties, miscarriages and other conditions.

Historically, many municipalities installed iron water mains that were connected to individual buildings by lead water pipes. In a typical lead pipe, chemicals in the water cause the inside wall of the pipe to corrode, releasing lead ions into the water, Lobo explains. To address this problem, municipalities add corrosion inhibitors to the water. Over time, these added phosphates react with the lead ions to create compounds that deposit on the inside of the pipe. This coating, or "scale," blocks other lead ions from leaching from the pipe into the water, making the pipe safe for water distribution. However, in Flint, the drinking water source was changed to a source that had different water quality, and concurrently, the city of Flint stopped using corrosion control measures. The protective scale dissolved, and toxic lead ions leached into the water.

Lobo became involved in this issue when his adviser, Ashok Gadgil, Ph.D., began to focus on finding a solution for the lead problems in Flint. Gadgil's team is at the University of California, Berkeley, and Gadgil is also affiliated with Lawrence Berkeley National Laboratory.

After a few months of intense effort, Gadgil and his team came up with an electrochemical approach to the problem. They applied a small external voltage to a sample of pipe to speed up corrosion. As usual, the freed lead ions then reacted with phosphates in the water to form scale. The process took just a few hours, compared with a couple of years for the usual scaling method. Lobo hopes this process could quickly restore the protective coating in the pipes in Flint, where scale has still not recoated the pipes.

The researchers have tested their process in the laboratory but caution that they haven't yet conducted any trials on lead pipes in the ground. For real-world applications, Gadgil envisions attaching external connectors to a homeowner's pipe at the water meter and at other junctions in the pipes, and then threading another wire through the pipes to complete the circuit. "The idea is that we wouldn't have to dig the whole pipe out, so we could keep the cost low," Gadgil explains. "Replacing all the plumbing in one house would cost several thousand dollars, whereas our process would cost less than one tenth of that."

Currently, the group is working with experts from a local water utility in California to determine the practical parameters for a test under real-world conditions. They are also planning to conduct a test later this year at an Oakland school where normal scale buildup isn't happening in the pipes.

A press conference on this topic will be held Wednesday, April 3, at 10:30 a.m. Eastern time in the Orange County Convention Center. Reporters may check-in at the press center, Room W231B, or watch live on YouTube http://bit.ly/ACSLive_Orlando2019 ("ACSLive_Orlando2019" is case-sensitive). To ask questions online, sign in with a Google account.

Plants can't run away to avoid being eaten, so instead they employ a variety of chemical defenses to keep herbivores at bay. Understanding plant chemical defenses is critical for keeping crops healthy, and for answering a variety of more academic questions about ecology and evolution. However, current techniques for assessing plant chemical defenses are time consuming and require impractically large amounts of plant tissue. In research presented in a recent issue of Applications in Plant Sciences, Dr. Chandra Jack and colleagues devised a new technique for assessing plant chemical defenses that is less laborious and more practical for a variety of experimental applications.

Traditional methods of measuring defense compounds use light to measure different chemicals in leaves using an apparatus called a spectrophotometer. These methods require large tissue samples, meaning that multiple leaves must be pooled together, collapsing meaningful variation. The technique reported here, using a microplate reader, detected activity in samples smaller than 10 mg, or 2% of the traditional tissue sample weight.

"One of the biggest constraints is the amount of tissue that is needed for traditional spectrophotometer-based assays," said Dr. Jack, the lead author of the study. "Now, because researchers don't have to combine leaves from a single plant, they can better explore localized versus systemic responses, or monitor individual plant response over time... It allows us to measure population-level variation and to parse out the influence of environment on genes."

"The other constraint is the time needed to carry out these experiments," said Dr. Jack. The huge amounts of labor and time required to carry out assays using spectrophotometric methods put serious constraints on the number of samples that can be assessed. This limits feasible experimental designs, and consequently the types of questions one can hope to answer. Additionally, both the time and tissue demands of traditional methods make it more difficult to re-run a sample or reproduce a result. In this study, researchers were able to conduct a set of assays that would normally take 41 hours in only six hours.

Plant chemical defense is complex, involving the production of multiple compounds at once. While traditional techniques require separate extractions to assay each class of defense compounds, the technique presented here uses consolidated preparation buffers and protocols to extract multiple compounds at once. This makes it practical to measure a wider range of chemical responses, providing a more nuanced and higher-resolution picture of plant defense. "Plants produce so many secondary metabolites and enzymes in response to herbivore attack, that the story of plant defenses is not complete unless you assay multiple compounds," said Dr. Jack.

The method presented here, in which sample preparation buffers are consolidated and samples are run simultaneously on a microplate, vastly reduces the time and expense of assaying defense compounds. "For us it was a case of necessity being the mother of invention," said Dr. Jack. "I was planning to set up an experiment...and couldn't find high-throughput assays to accomplish what was needed." But in developing this technique, the authors opened up avenues of inquiry into plant defenses for others. Researchers can now investigate multiple defense compounds at once, look at localized and systemic responses, compare a larger sample of individuals, and replicate their findings much more feasibly than before.

"Originally, this wasn't going to be a stand-alone project," said Dr. Jack. "However, as we combed through the literature and invested so much time into the protocol, we realized that this would be useful for the scientific community and could impact so many different fields."

Melanomas tend to be "hot" or "cold" - if they're hot, immunotherapy lights melanoma tumors like beacons for elimination by the immune system; but 40-50 percent of melanomas are cold, making them invisible to the immune system, and patients with cold tumors tend to show little benefit from immunotherapies. The problem is that it's been impossible to distinguish a hot melanoma from a cold one - the solution has been to administer immunotherapy and hope for the best, often leading to wasted time and resources. Now a University of Colorado Cancer Center study presented at the American Association for Cancer Research (AACR) Annual Meeting 2019 identifies a possible way to predict which melanomas are hot and cold: Tumors with mutations in genes leading to over-activation of the NF-kB signaling pathway were more than three times as likely to respond to anti-PD1 immunotherapy compared with tumors in which these changes were absent.

"I want to do a little more examination, but we're pretty close to pinpointing high NF-kB as a predictor of response," says Carol Amato, MS, investigator at CU Cancer Center and senior professional research assistant.

One factor hypothesized to create a "hot" tumor is the overall tumor mutation burden - the total number of mutations a tumor holds - with the idea being that more mutations would create more differences between tumor and healthy tissue, leading to a higher likelihood that the immune system will recognize tumor tissue as foreign and work to eliminate it.

However, Amato and colleagues including William Robinson, MD, PhD, and first author Keith Wells, MD, show that while overall tumor mutation burden may increase the chance of important genetic changes, the immune system's ability to see tumor tissue may depend more on specific, important changes than on overall mutation burden.

To discover what these changes are, the group leveraged patient samples gathered over the course of a decade by the Robinson lab in the Colorado Skin Cancer Biorepository.

"Basically, a few years back, we decided to do whole-exome sequencing on our biorepository, about 500 melanoma samples in all. In this project, we asked which of these 400 patients had been treated with immunotherapy, and whether genetic or genomic features of their tumors could predict response to treatment," Amato says.

Of 52 patients treated with anti-PD1 immunotherapies, 21 responded favorably to therapy, and 31 showed little or no benefit. Sixty-seven percent of those responding favorably had alterations in genes associated with the NF-kB signaling pathway, compared with only 19 percent in patients whose tumors did not respond to immunotherapy.

"NF-kB is a complex pathway - sometimes it's bad and sometimes it's good. The cell context may be different than the treatment context," Amato says.

What she means is that, on one hand, over-active NF-kB signaling has been implicated in the development of many cancers ("sometimes it's bad"). But on the other hand, over-active NF-kB signaling may also allow immunotherapies to better target existing cancers ("sometimes it's good").

"What we show is that cancers with alterations that over-activate the NF-kB may better benefit from immunotherapy," Amato says.

Exactly why this is the case is complex and requires looking inside the NF-kB signaling pathway to a specific mutation in NFKBIE, a negative regulator of NF-kB. This mutation, G34E, found only in tumors that responded to immunotherapy, has an effect like removing a limiter on NF-kB, allowing increased activation of this pathway. Then, when especially activated, the transcription factor NF-kB was able to pass into the cell nucleus, where it magnified the expression of the gene CD83.

"And it's CD83 that we think is enhancing responsiveness of the tumor to immunotherapy," Amato says, explaining this action by suggesting that CD83 may be presenting antigens on the surface of tumor cells that make these cells more visible to the immune system.

When the group artificially increased NFKBIE G34E mutations, they saw increased NF-kB signaling. And this activity was independent of many of the genetic alterations commonly seen in melanoma, for example, BRAF and NRAS mutations.

"Even beyond tumor mutation burden, these specific changes could help doctors predict which melanoma patients will respond and which patients will not respond to anti-PD1 immunotherapies," Amato says.

During the period in which the papaya (Carica papaya) is ripening, its cell walls separate, making the tissue softer and more digestible because the cell contents become accessible and the sucrose in the fruit is more easily extracted.

Sugarcane roots have recently been found to undergo a similar process. Their cell walls are modified during development to form gas-filled intercellular spaces in a type of tissue known as aerenchyma.

"Aerenchyma is very common in crops grown in flooded fields, such as rice, since it supports them or enables them to float in water while also allowing the submerged parts of the plant to breathe in oxygen and breathe out carbon gas," said Marcos Buckeridge, a professor in the University of São Paulo's Bioscience Institute (IB-USP) in Brazil.

In recent years, Buckeridge and collaborators have focused on studying the genes involved in sugarcane root cell separation with the aim of developing transgenic varieties of sugarcane in which the process occurs in other parts of the plant, such as the stem, where biomass and sucrose accumulate. The cell walls in these varieties would be as soft as in a papaya - hence the nickname "papaya sugarcane" - and could more easily be degraded to produce second-generation bioethanol (obtained from biomass) on a large scale.

Researchers affiliated with Brazil's National Institute of Science and Technology of Bioethanol (INCT Bioethanol, one of several such research centers supported by São Paulo Research Foundation - FAPESP in São Paulo State in partnership with the National Council for Scientific and Technological Development (CNPq), have now taken an important step in this direction.

Partnering with colleagues from other universities and research institutions in Brazil and abroad, they described the first gene sequences involved in sugarcane root cell separation and elucidated their functions in this process. The results of the study were published, in the Journal of Experimental Botany.

"If we succeed in promoting cell wall separation in the sugarcane stem, it will be possible not only to reduce the amount of enzyme cocktails used for enzymatic hydrolysis [degradation of the carbohydrates in sugarcane trash and bagasse and their conversion into fermentable sugar] to obtain second-generation ethanol but also to increase sucrose extraction," Buckeridge, principal investigator for INCT Bioethanol, told.

The researchers sequenced two genes considered essential to the initial stages of aerenchyma development in sugarcane roots. The first was scRAV1, which encodes the RAV transcription factor that controls plant leaf aging. The second was scEPG1, which encodes endopolygalacturonase (EPG), an enzyme that degrades the pectin that keeps cells together, thereby contributing to cell separation and the softening of fruit tissue via aerenchyma formation.

Owing to the complexity of the sugarcane genome, which has several copies of each chromosome and numerous variants of each gene, the two genes were sequenced from 17 artificial bacterial chromosome clones containing genomic regions homologous to those of the R570 sugarcane variety.

The gene sequences were compared with those of the corresponding regions of Sorghum bicolor (the sorghum genome closely resembles the sugarcane genome). A similar sequence from each of the two genes was expressed in tobacco leaves for transactivation assays to see which other genes they activated.

"Tobacco is easy to transform genetically and serves as a model to demonstrate how mechanisms like this actually work," Buckeridge said.

Analysis of the genomic regions and the transactivation assays showed that scRAV1 controls early pectin degradation during sugarcane root aerenchyma formation and that the protein produced by scRAV1 binds to the scEPG1 promoter, blocking transcription of this gene.

"Our findings pave the way for using biotechnology for the genetic manipulation of sugarcane to boost the production of second-generation ethanol," Buckeridge said.
First step

The researchers developed a sugarcane variety with enhanced expression of scRAV1. They also discovered a microRNA (a molecule that regulates gene expression) capable of specifically inhibiting scRAV1 and stimulating the expression of scEPG1throughout the plant.

"In this genetically transformed variety, we're starting to see what seems to be a softening of the sugarcane cell wall, similar to the effect we want. The stems of some of the plants, for example, are unable to stay erect. This could be the first step toward the development of papaya sugarcane," Buckeridge said.

CORVALLIS, Ore. - Efforts to curtail the flow of cocaine into the United States from South America have made drug trafficking operations more widespread and harder to eradicate, according to new research published this week in Proceedings of the National Academy of Sciences.

The National Science Foundation supported the study, which included an Oregon State University geographer and was led by Nicholas Magliocca from University of Alabama. The collaboration also included researchers from The Ohio State University, Northern Arizona University, Arizona State University, Texas State University-San Marcos, the University of Wyoming and the U.S. Fish and Wildlife Service.

"It really is surprising how the model matches our observations," said David Wrathall of OSU's College of Earth, Ocean and Atmospheric Sciences. "Our team consists of researchers who worked in different parts of Central America during the 2000s and witnessed a massive surge of drugs into the region that coincided with a reinvigoration of the war on drugs. We asked ourselves: did drug interdiction push drug traffickers into these places?"

The findings are important because after five decades, the United States' war on drugs has yet to prove itself effective or cost-efficient for dealing with cocaine trafficking, the researchers note. The study comes at a time of increased attention on Central American migrants fleeing drug-related violence in their home countries.

The scientists developed a computer model named NarcoLogic that shows how drug traffickers respond to interdiction strategies and tactics. It differs from previous approaches because it models local- and network-level trafficking dynamics at the same time.

Interdiction efforts are linked to the spread and fragmentation of trafficking routes - a phenomenon known as the "balloon and cockroach effect." When interdiction efforts are focused in one location, drug traffickers simply relocate.

"Between 1996 and 2017, the Western Hemisphere transit zone grew from 2 million to 7 million square miles, making it more difficult and costly for law enforcement to track and disrupt trafficking networks," Wrathall said. "But as trafficking spread, it triggered a host of smuggling-related collateral damages: violence, corruption, proliferation of weapons, and extensive and rapid environmental destruction, which has been the focus of my work."

Since the Nixon Administration launched the war on drugs in 1971 and declared drug abuse to be "public enemy No. 1," the United States has spent an estimated $1 trillion on drug prevention and enforcement efforts.

That includes roughly $5 billion annually on cocaine interdiction, without having much effect on the drug's supply or its price, the researchers say.

"Wholesale cocaine prices in the United States have actually dropped significantly since 1980, deaths from cocaine overdose are rising, and counterdrug forces intercept cocaine shipments at a low rate. More cocaine entered the United States in 2015 than in any other year," Wrathall said. "And one thing people who support interdiction and those who don't can agree on is that change is needed. This model can help determine what that change should look like."

The researchers' main hypothesis, borne out by comparing NarcoLogic's predictions of where, when and how cocaine shipments were trafficked from2000-14 against the actual patterns recorded in interdiction databases, was that trafficking operations didn't become more widespread and resilient because of ineffective interdiction - but did so simply as a result of interdiction.

"The study is a victory for observation and theory. This model successfully recreates the dynamic our team had observed," Wrathall said. "It tells us that increased interdiction will continue to push traffickers into new areas, spreading networks, and allowing them to continue to move drugs north."

DETROIT - Allowing for more quality measures in the federal government's Quality Star Rating program would create a fairer and more equitable model for assessing the level of quality at U.S. acute-care hospitals, according to a Henry Ford Health System study.

Researchers found that recognizing four fundamental quality factors in the safety of care category and assigning more equal weights to the eight measures in that category would modify the rating system's current scoring methodology and produce more accurate and informative results.

"Since the star ratings introduction in 2016, the ratings have been met with skepticism because of the methodology," says David Nerenz, Ph.D., director emeritus of Henry Ford's Center for Policy and Health Services Research and the study's lead author. "In our study, we believe we've identified a simple and straightforward solution in the safety of care domain that would make these ratings more meaningful and unbiased."

The study is published online in the American Journal of Medical Quality.

Created by the Centers for Medicare & Medicaid Services (CMS), the rating system assigns a score of one to five stars - five being the highest - based on a set of 57 individual quality measures across seven categories: mortality, readmission, safety of care, patient experience, effectiveness of care, timeliness of care and efficient use of medical imaging.

The first four categories each account for 22 percent of a hospital's total score, while the last three each count for four percent. A complex weighting scheme is used to assign an importance to each measure in each category, and the scheme for the safety of care category makes only one of the eight measures really count.

For their study, Dr. Nerenz and his team of researchers sought to evaluate the current methodology and how an alternative approach might affect the ratings scoring. Researchers performed principal components analyses on a subset of 674 hospitals in the December 2017 national data set that reported on eight safety measures used at the time. Then they assigned equal weight to each of the measures instead of the model employed by CMS and considered the number of cases at a hospital and how it impacted the accuracy of each measure.

The effect of applying this alternative methodology was illustrated in a single hospital, whose safety category score was markedly different (+1.65) compared to CMS' current methodology (-2.35). That was enough difference to move the score from below average to above average. Assigning equal weight to each measure had a "pronounced effect," researchers wrote.

"A stated aim of the Hospital Star Ratings program is to effectively summarize available hospital performance measures on Hospital Compare into a single, summary rating," says Brian Waterman, Ph.D., MPH, vice president of Analytic Business Solutions for the Missouri Hospital Association and a study co-author. "Our study results indicate that the current form of the methodology employed by CMS likely leaves important information about safety of care effectively out of the mix."

Researchers say the designers of the ratings system were well intentioned in creating a system that would be both "simple and patient-friendly" for consumers. However, the methodology is so highly complex that it has led to confusion and "very significant consequences for the ratings of individual hospitals." Further refining the methodology, they say, would better summarize the quality measures and "offer greater upside for consumers and providers."

Biodiversity hotspot Madagascar is one of the world's biggest islands, and home to some of its biggest insects. Now German scientists have discovered two new species of giant stick insect, living only in the dry forests of Madagascar's northernmost tip.

One giant female measures a whopping 24cm - but it is the smaller males that are most striking. At sexual maturity these daredevils abandon their stick-like camouflage for dazzling blue or many-colored shining armor.

Writing in Frontiers in Ecology and Evolution, the researchers describe their rare and exciting findings, and wonder at the reproductive success of the least stick-like stick insects on the planet.

When two become four

"Nearly all of the 3000+ known species of stick insects try to be inconspicuous and just look like twigs," says senior author Dr. Sven Bradler of the University of Göttingen, Germany. "There are a very few, very large exceptions - and we have just discovered a couple more of them."

The authors re-examined specimens they'd previously identified as odd-looking examples of two existing giant stick insect species, whose adult males remarkably are bright blue or multicolored.

"These were similar in size - 15 to 24cm - but generally less spiny and a bit differently colored than typical examples of their kind," explains Bradler. "Now genetic tests confirm that the quirky individuals are in fact two new species, distinct from the original two but part of the same group." explains Bradler.

Bradler's reclassification places members of this group of species as close evolutionary relatives to other Madagascan stick insects, rather than cousins from overseas as previously thought. This is a potentially major finding, as it challenges the prevailing view that sticks insects colonized Madagascar multiple times.

He who dares, wins

The discovery also prompted the researchers to wonder: what reproductive advantage do these males gain from their bright colors, that is worth exposing themselves to predators?

The first author Dr. Frank Glaw of the Bavarian State Collection of Zoology in Munich, and colleagues bred the new giant stick insect species in captivity to observe their behavior.

"Males of one species started mating attempts only when they achieved their bright blue color."

This might suggest that the males use their bright coloring to attract a mate. However, it is hard to believe the males could find a mate before being eaten - unless their bright coloring acts as a deterrent to predators.

"Males searching for a mate have to move about more, so pretending to be a stick becomes tricky. Better perhaps to plump for the opposite: a brightly colored warning."

Bright colors - suggestive of toxicity - keep safe vivid members of other typically camouflaged species, like lividly colored Madagascan frogs.

"In support of this, all stick insects have neck glands that repellant substances, and these are typically well-developed in brightly colored species. Alternatively, like the Madagascan frogs some giant stick insects may have developed the ability to accumulate toxins from their food."

But testing these hypotheses will be tough, admits Glaw.

Bradler adds "More than one factor may have played a role in the evolution of this remarkably conspicuous coloration. So even with more data on mate selection, habits, predators, natural food plants, toxins produced by defense glands and possible accumulation of toxins among giant stick insects, finding evidence for these ideas may prove difficult."

Colorful stick insects have a bright future

Whatever its function, the splendid coloring of the male giant stick insects could make them a strong flagship species to promote the unique biodiversity of Madagascar, and the need for its protection.

"Already the once-uncertain future of these two new species seems secured, with their forest habitat in northern Madagascar a hotspot for conservation priorities," says Glaw. "It is vital to maintain awareness and motivation to keep logging at bay. This precious area also harbors the highest density of critically endangered reptiles in Madagascar and is home of one of the most threatened primate species in the world, the lemur Lepilemur septentrionalis."

Computing--Broader impacts of bullying

Oak Ridge National Laboratory is using artificial intelligence to analyze data from published medical studies associated with bullying to reveal the potential of broader impacts, such as mental illness or disease. Search results from a computing method known as literature-based discovery could help identify long-term negative consequences of bullying behavior and could inform better-targeted intervention programs. For the study, ORNL's S. M. Shamimul Hasan applied the algorithm, through a biomedical document retrieval system, to the publicly available medical database Semantic MEDLINE to discover various direct and indirect effects of bullying. "The method uses a three-level approach to detect relationships, for example, from bullying to psychological distress--which is a direct impact--to epilepsy, an indirect consequence," Hasan said. While the advanced analytical tool makes intelligent inferences, Hasan said for now the process requires a "human in the loop" to validate the connections. He hopes to further enhance the tool's capabilities. [Contact: Sara Shoemaker, (865) 576-9219; shoemakerms@ornl.gov]

Image: https://www.ornl.gov/sites/default/files/2019-03/bullying_img_1.png

Caption: Using artificial intelligence, Oak Ridge National Laboratory analyzed data from published medical studies to reveal the potential of direct and indirect impacts of bullying. Their results could help identify long-term consequences and could inform better-targeted intervention programs. Credit: S. M. Shamimul Hasan/Oak Ridge National Laboratory, U.S. Dept. of Energy

Grid--Wrap-around sensors

Scientists at Oak Ridge National Laboratory have developed a low-cost, printed, flexible sensor that can wrap around power cables to precisely monitor electrical loads from household appliances to support grid operations. Using an inkjet printer, researchers deposited wires on a flexible plastic substrate, then wove in a magnetic strip to channel the flux produced by an electric current, making the sensor suitable to install in tight spaces. When tested on conductors in the lab and on a building HVAC unit, the sensor measured responses of up to 90 amps of electrical current, and is expected to exceed 500 amps in larger applications. "These inexpensive sensors provide crucial, real-time usage data needed to monitor and control devices such as smart HVAC and water heaters for better power grid efficiency and resilience," said ORNL's Pooran Joshi. The team is currently testing new materials, electronics and packaging to increase the sensor's range and applications while keeping costs low. [Contact: Stephanie Seay, seaysg@ornl.gov; (865) 576-9894]

Image: https://www.ornl.gov/sites/default/files/2019-03/2019-P01298.jpg

Caption: ORNL scientists have created a low-cost, compact, printed sensor that can collect and transmit data on electrical appliances for better load monitoring. Credit: Genevieve Martin/Oak Ridge National Laboratory, U.S. Dept. of Energy

Nuclear--Remote-controlled reactors

Oak Ridge National Laboratory scientists are evaluating paths for licensing remotely operated microreactors, which could provide clean energy sources to hard-to-reach communities, such as isolated areas in Alaska. "Current regulatory guidance was written when remote operations of nuclear reactors were not possible, so this is a new frontier," said ORNL's Randy Belles. The flexibility of microreactors--which could power thousands of homes for a decade without refueling and be easily transported due to their compact size--could allow operators to autonomously control them using advanced computing systems. This would help limit onsite staffing, and increase economic viability. "Our team's evaluations aim to address several licensing questions that come with remote operations, such as handling cybersecurity, staffing and manipulations of the controls," Belles said. The next step is advising Nuclear Regulatory Committee staff about the guidance needed to make deployment possible. [Contact: Jason Ellis, (865) 241-5819; ellisjk@ornl.gov]

Image: https://www.ornl.gov/sites/default/files/2019-04/Micro%20Reactor%202-03%5B1%5D.jpg

Caption: Oak Ridge National Laboratory scientists are evaluating current regulatory guidance to understand the potential challenges in licensing remotely operated microreactors. Microreactors could offer unique mobility and flexibility--opening the possibility for nuclear energy to reach isolated areas. Credit: Adam Malin/Oak Ridge National Laboratory, U.S. Dept. of Energy

Clean Water--Better separations

A team of scientists led by Oak Ridge National Laboratory used carbon nanotubes to improve a desalination process that attracts and removes ionic compounds such as salt from water using charged electrodes. Carbon nanotubes have superior ability to conduct electricity. When applied to the desalination process known as flow-electrode capacitive deionization, the nanotubes boosted electroconductivity by 13.2 times and increased the desalination rate by 34 percent, with only a slight increase in solution viscosity. The result was salt water removal efficiency of 93.6 percent, as detailed in ACS Sustainable Chemistry & Engineering. "The process is particularly good at treating industrial wastewater and could help meet the global challenge of fresh water availability," said ORNL's Costas Tsouris. He added that exploring the use of carbon fiber in the process could result in similar improvements at a lower cost. [Contact: Stephanie Seay, seaysg@ornl.gov, 865-576-9894]

Image: https://www.ornl.gov/sites/default/files/2019-04/DesalDiagram-.jpg

Caption: Scientists used carbon nanotubes that enhanced conductivity and sped up a salt water removal process known as flow-electrode capacitive deionization. Reprinted with permission from Kexin Tang, et al., "Enhanced Water Desalination by Increasing the Electroconductivity of Carbon Powders for High-Performance Flow-Electrode Capacitive Deionization." ACS Sustainable Chemistry & Engineering. Copyright 2019. American Chemical Society.

Using newly discovered archival materials, Igor Fedyukin of the Higher School of Economics, in collaboration with Robert Collis (Drake University) and Ernest A. Zitser (Duke University), sheds light on the significance and context surrounding a Spanish diplomat's initiative which sought to establish an informal men's club called the 'Order of the Anti-Sober' at Peter II's court. Their study was published in The International History Review.

In the late 17th - early 18th centuries, various fraternities, societies and associations were gaining popularity throughout Europe among the elite. Their motives were often not particularly serious: the informal gatherings often served as an occasion for drinking and socializing. However, these associations often provided venues for discussing and solving important political issues, forging political alliances, and laying the groundwork for future political parties.

In 1728, in St. Petersburg, Russia, the Duke of Liria, a Spanish Ambassador, sought to start such a club at Peter II's court. It was to be called the 'Order of the Anti-Sober'.

When James Francis Fitz-James Stuart (1696-1738), Duke of Liria and Spain's first permanent envoy to Russia, was preparing to depart on his diplomatic mission, he knew in advance how he would go about achieving his objectives in St. Petersburg. As he intimated in a letter to his uncle and heir to the British throne James (III) Stuart, the envoy planned to rely on 'the varieties of [his] wines', since 'in that part of the world all affairs are concluded on a bottle'.

Such assumptions should not be too surprising: during the reign of Peter the Great, the Russian court was known for its boisterous feasts and carnivals with heavy drinking. It appears only natural that Liria would have the same stereotype about the court of Peter the Great's teenage grandson, Emperor Peter II (1715-1730, r. 1728-1730), who reigned by the time the envoy arrived.

However, the behavior and alcohol consumption of Russian elites of those times were in fact not so different from their European counterparts. In the 18th-century European royal courts, informal meetings with a narrow circle of confidants were quite popular, where the aroma of wine was an integral element. There is evidence of the existence of such societies as 'The Order of the Wine Grape' (Ordre de la Grappe) in Arles, France, 'The Order of the Medusa' (Ordre de la Meduse) in Toulon, and 'The Order of the Drinks' (Ordre de la Boisson) in Avignon. A 'Collegium of Tobacco Smokers' (Tabakskollegium) existed at the court of King Friedrich Wilhelm I of Prussia. According to the diary by Friedrich Wilhelm von Bergholz, a gentleman of the bedchamber to Duke Karl Friedrich of Holstein-Gottorp, who resided in Russia throughout the early 1720s, the creation of mock orders was a common practice in the context of small northern European courts. These societies were a platform for entertainment and informal interaction for diplomats and the ruling elites. So the Duke of Liria's intention to create a closed club named future 'Order of the Anti-sober' (Ordre des Antisobres) was quite in line with that era's political culture trends.

Rules of the Club

The charter of the 'Order of the Anti-Sober', which was discovered in French archives, mentions the Epiphany of 1728 as the date of the order foundation. It is known that the Duke of Liria, who had come to Russia and had been introduced at the court not long before that, officially participated in a foreign diplomats' assembly for the first time around these dates.

The surviving text of the charter has, of course, a boisterous, mocking tone. For example, the first article mockingly refers to the Old Testament and requires order members to exhibit 'eternal antipathy' towards the 'sect' of teetotalers and all those who practiced the 'vice of sobriety'. Another rule had it that the 'cavaliers' of the order had to be pleasant in their interactions and be able to mock without turning to malice. Pointedly, the lack of these qualities could be forgiven if a candidate had a 'good cook' and 'excellent wines'.

The planned order was intended as a space for socializing, uninterrupted by any personal or political tensions. The members were instructed to leave all their ranks and titles at the door and limit the length of their speeches to two minutes to avoid the 'dread' of 'yawning' and the 'unpardonable crime' of boredom.

No more than three dishes were to be put on the table during the meals, since 'profusion is the irreconcilable enemy of delicacy.' In addition, nobody was to force other members to eat and drink beyond the dictates of their own appetite.

The members of the order were to observe secrecy, in a manner similar to other secretive societies. There would also be special marks, signs, and rituals, allowing a member to recognize his fellows wherever they met. The members were supposed to greet each other by exclaiming 'Long live the Epiphany at the 59th Degree!' - a countersign marking the latitude of St. Petersburg, the location of the order foundation.

Women were barred from entering the order. This was explained by the necessity to temper the 'ardor of certain desires' and contribute to the 'sweet harmony' and 'happiness' to which the prospective members of this 'august and incomparable order' aspired.

Article 11 of the charter mandated that the members maintain sincere, close, and cordial relations with one another and exclude all prejudices, such as those that are caused by religious or national differences. To this end, the charter even banned all 'ceremonial toasts' honouring monarchs and any other 'potentates'.

The violators of these rules were to be condemned to 'travel 20 years in Russia without a bed and without a cook, in winter without a fur jacket, in summer without ice.'

According to the researchers, the exclusion of women and the explicitly apolitical nature of the meetings were very much in the spirit of English Freemasonry, as articulated in 1723 by James Anderson.

Motives to Create the Club

The Duke of Liria was, in fact, a servant to two masters: Philip V, the sovereign who appointed him Spain's first official diplomatic representative in Russia, and James (III) Stuart, the Jacobite claimant to the British throne, with whom the duke maintained secret correspondence and to whom he professed boundless loyalty.

In 1725, Spain signed The Treaty of Vienna with Austria, which opposed the signatories of the Treaty of Hanover, most notably, France, Great Britain, and Prussia. Under such a balance of powers, Philip V commissioned Liria to persuade Russia to join the Treaty of Vienna and, probably, even dispatch a fleet that would land in England, overthrow George I, and restore the Stuart dynasty.

In St. Petersburg, Liria was going to count on Duke Karl Friedrich of Schleswig-Holstein-Gottorp, spouse of tsar's daughter Anna Petrovna, member of Russia's Supreme Privy Council and an important political player at the court of his mother-in-law, Empress Catherine I. Karl Friedrich's claims to both the Holstein territory annexed by the king of Denmark and to the Swedish throne were very much central to the hostility between Russia and Britain. Liria was therefore hoping to talk Karl Friedrich into acting against the Hanoverian Alliance.

But over the course of the Spanish envoy's six-month journey from Madrid to St. Petersburg, the diplomatic situation in Europe changed. In March 1727, the government of George I managed to persuade Sweden to join the Hanover alliance. In June, Catherine I passed away. These conditions led to the expulsion of the Duke of Holstein-Gottorp, whose support was to be instrumental to Liria, from Russia.

The charter of the 'Order of the Anti-Sober' establishes Liria as Grand Master, but it also names Baron Mardefeld, Prussian Ambassador in Russia, 'Protector' of the order. It appears such courtesy towards the Prussian diplomat was made in pursuit of some clear political goals. On the one hand, by the moment of Liria's arrival to Russia in November 1727, Mardefeld had spent a full decade in St. Petersburg and probably knew more about Russian domestic politics than most of the other foreign residents. On the other hand, Mardefeld had been charged with repairing the strategic relationship between Russia and the Hanoverian Alliance, a diplomatic rapprochement that Liria was specifically tasked with preventing. The Prussian diplomat also supported the candidacy of a Saxon prince to the Polish throne, whereas Liria was intriguing in favor of an alternative claimant for the crown. Apparently, some opportunities for close and informal meetings with the Prussian diplomat as part of a mock order would be very useful for Liria.

Meanwhile, researchers have no further evidence on whether the 'Order of the Anti-Sober' was created or not. Neither reports by Liria himself, nor known papers by Mardefeld, include any intentions on creating a closed drinking club in St. Petersburg. But this does not mean that informal interaction over a bottle of wine was not used by diplomats as a political tool. It is known that the Duke of Liria hosted regular dinner parties for diplomats, the young Russian monarch, and his confidants. At such parties, over 500 bottles of wine could be emptied, and, undoubtedly, political talk was an integral part of them. As a result, Liria managed to assume very good positions at Peter II's court. Unfortunately, however, the teenage monarch died soon, and the international political situation quickly changed. As a result, Liria's embassy did not achieve any outstanding diplomatic results. Mock orders as a space for informal socializing for the elites soon started to be replaced by Masonic Lodges: Jacobites, advocates of the overthrown Stuart dynasty in Europe, played a key role in their popularization.