Culture

New way of designing systems against correlated disruptions uses negative probability

image: Yanfeng Ouyang, Professor of Civil and Environmental Engineering at the University of Illinois.

Image: 
University of Illinois at Urbana-Champaign Department of Civil and Environmental Engineering.

In March of 2011, a powerful earthquake off the coast of Japan triggered the automatic shutdown of reactors at the Fukushima Daiichi Nuclear Power Plant and simultaneously disrupted electricity lines that supported their cooling. Had the earthquake been the only disaster that hit that day, emergency backup generators would have prevented a meltdown. Instead, a tsunami immediately followed the earthquake, flooding the generators and leading to the most serious nuclear accident in recent history. For systems expert Yanfeng Ouyang, a professor of civil and environmental engineering (CEE) at the University of Illinois, it was a perfect example of the problem of designing systems against correlated disruptions.

Until now, systems engineers have struggled with the problem of planning for disaster impacts that are linked by correlation - like those of earthquakes and tsunamis - because of the cumbersome calculations necessary to precisely quantify the probabilities of all possible combinations of disruption occurrences. When correlation exists, the probability of a joint disruption is not simply the product of those of individual disruptions. This leaves gaps in our understanding of how to design infrastructure systems with the greatest disaster resistance and resilience.

Now Ouyang and fellow CEE researchers have developed a new method for designing and optimizing systems subject to correlated disruptions. This method eliminates the need for directly addressing the many combinations of disruptions that have made such problems difficult to model in the past. They described it in a paper published this month in Transportation Research Part B, Methodological, the latest in a series of related papers from recent years. One of the keys of their method was incorporating negative probability, a concept seemingly never before utilized for system design purposes.

"With this concept, we developed a new methodology to help design systems with which we had difficulty before, such that they can be more resistant to disasters and more resilient than before," said Ouyang, the George Krambles Endowed Professor in Rail and Public Transit, who led the series of work with former doctoral students including Siyang Xie (Ph.D. 18), now a research scientist at Facebook, and former postdoctoral researcher Kun
An, now a faculty member at Monash University in Australia.

The team's new computational method is widely applicable because it can be used to model and optimize any networked system - for example supply chains, transportation systems, communication networks, electrical grids and more. The method incorporates a virtual system of "supporting stations" to represent the correlated vulnerabilities of infrastructure components in the real world. This allows systems engineers to translate complex impacts of disasters on the components into simple and independent impacts on the supporting stations. For example, in the case of two warehouses whose operations may both be disrupted by a snowstorm, one imagines that their functionalities rely on some virtual power supply sources, each of which serves as a supporting station to the warehouses. By setting proper dependency between the two warehouses and these power sources, one can translate the correlated functionality states of the two warehouses into independent disruptions of the shared power supplies.

"We showed that any number of infrastructure components with any type of disruption correlation among them can be described by a properly set-up system of such virtual stations, where each of them fails only independently of each other," Ouyang said.
This construct makes the calculations considerably more manageable because it significantly reduces the complexity of representing failure correlations in the design model.

"We now have a new way of describing the system," Ouyang said. "We go from a system where there is correlation into an equivalent system where there is no correlation - every failure is now independent of the others, so the probabilities are much easier to compute."

In order to accurately represent the behavior of systems in the real world, the team had to introduce the concept of negative probability for station disruptions, which allows their models to address negatively correlated disruption risks of system components. While positive correlation indicates that infrastructure components have dependencies driving their behaviors under disasters to move in the same direction, negative correlation, on the contrary, expresses the idea that the effects of disasters on one component implies the opposite effects on another. For example, when two warehouses compete for limited resources, one would gain benefit when its competitor is under loss or experiencing difficulty. Similarly, if an area near a river is flooded, other areas downstream might be better off because the water pressure was released.

Although negative correlation is a well-known concept, negative probability sounds somewhat unorthodox. At first the researchers were unaware that a similar concept was already in use in the discipline of quantum mechanics; they just knew from mathematics that they needed to represent the possibility of a disaster affecting competing entities in opposite ways. Because they had to translate correlation from the real-world system to the virtual structure of supporting stations, the likelihood of a supporting station to be affected by a disaster had to incorporate the risk of multiple components, some of which would be negatively affected and some of which might be positively affected. The "failure propensity," as they originally called such a negative probability in a 2015 paper, of a supporting station could therefore be larger than 1 - or equivalently, the complement being negative.

To the best knowledge of the researchers, using this concept for engineering applications is brand new, enabling them to solve problems that were previously prohibitively difficult. The team hopes engineering designers of all kinds of networked infrastructure systems will embrace it, leading to smarter engineering designs for greater disaster resistance across a broad spectrum of system types.

Credit: 
University of Illinois Grainger College of Engineering

How to make self-driving cars safer on roads

image: In this example, a perception algorithm misclassifies the cyclist as a pedestrian

Image: 
Anand Balakrishnan

It's a big question for many people in traffic-dense cities like Los Angeles: When will self-driving cars arrive? But following a series of high-profile accidents in the United States, safety issues could bring the autonomous dream to a screeching halt.

At USC, researchers have published a new study that tackles a long-standing problem for autonomous vehicle developers: testing the system's perception algorithms, which allow the car to "understand" what it "sees."

Working with researchers from Arizona State University, the team's new mathematical method is able to identify anomalies or bugs in the system before the car hits the road.

Perception algorithms are based on convolutional neural networks, powered by machine learning, a type of deep learning. These algorithms are notoriously difficult to test, as we don't fully understand how they make their predictions. This can lead to devastating consequences in safety-critical systems like autonomous vehicles.

"Making perception algorithms robust is one of the foremost challenges for autonomous systems," said the study's lead author Anand Balakrishnan, a USC computer science PhD student.

"Using this method, developers can narrow in on errors in the perception algorithms much faster and use this information to further train the system. The same way cars have to go through crash tests to ensure safety, this method offers a pre-emptive test to catch errors in autonomous systems."

The paper, titled Specifying and Evaluating Quality Metrics for Vision-based Perception Systems, was presented at the Design, Automation and Test in Europe conference in Italy, Mar. 28.

Learning about the world

Typically autonomous vehicles "learn" about the world via machine learning systems, which are fed huge datasets of road images before they can identify objects on their own.

But the system can go wrong. In the case of a fatal accident between a self-driving car and a pedestrian in Arizona last March, the software classified the pedestrian as a "false positive" and decided it didn't need to stop.

"We thought, clearly there is some issue with the way this perception algorithm has been trained," said study co-author Jyo Deshmukh, a USC computer science professor and former research and development engineer for Toyota, specializing in autonomous vehicle safety.

"When a human being perceives a video, there are certain assumptions about persistence that we implicitly use: if we see a car within a video frame, we expect to see a car at a nearby location in the next video frame. This is one of several 'sanity conditions' that we want the perception algorithm to satisfy before deployment."

For example, an object cannot appear and disappear from one frame to the next. If it does, it violates a "sanity condition," or basic law of physics, which suggests there is a bug in the perception system.

Deshmukh and his PhD student Balakrishnan, along with USC PhD student Xin Qin and master's student Aniruddh Puranic, teamed up with three Arizona State University researchers to investigate the problem.

No room for error

The team formulated a new mathematical logic, called Timed Quality Temporal Logic, and used it to test two popular machine-learning tools--Squeeze Det and YOLO--using raw video datasets of driving scenes.

The logic successfully honed in on instances of the machine learning tools violating "sanity conditions" across multiple frames in the video. Most commonly, the machine learning systems failed to detect an object or misclassified an object.

For instance, in one example, the system failed to recognize a cyclist from the back, when the bike's tire looked like a thin vertical line. Instead, it misclassified the cyclist as a pedestrian. In this case, the system might fail to correctly anticipate the cyclist's next move, which could lead to an accident.

Phantom objects--where the system perceives an object when there is none--were also common. This could cause the car to mistakenly slam on the breaks--another potentially dangerous move.

The team's method could be used to identify anomalies or bugs in the perception algorithm before deployment on the road and allows developer to pinpoint specific problems.

The idea is to catch issues with perception algorithm in virtual testing, making the algorithms safer and more reliable. Crucially, because the method relies on a library of "sanity conditions," there is no need for humans to label objects in the test dataset--a time-consuming and often-flawed process.

In the future, the team hopes to incorporate the logic to retrain the perception algorithms when it finds an error. It could also be extended to real-time use, while the car is driving, as a real-time safety monitor.

Credit: 
University of Southern California

FAAH-OUT: Woman with novel gene mutation lives almost pain-free

A woman in Scotland can feel virtually no pain due to a mutation in a previously-unidentified gene, according to a research paper co-led by UCL.

She also experiences very little anxiety and fear, and may have enhanced wound healing due to the mutation, which the researchers say could help guide new treatments for a range of conditions, they report in the British Journal of Anaesthesia.

"We found this woman has a particular genotype that reduces activity of a gene already considered to be a possible target for pain and anxiety treatments," said one of the study's lead researchers, Dr James Cox (UCL Medicine).

"Now that we are uncovering how this newly-identified gene works, we hope to make further progress on new treatment targets."

At age 65, the woman sought treatment for an issue with her hip, which turned out to involve severe joint degeneration despite her experiencing no pain. At age 66, she underwent surgery on her hand, which is normally very painful, and yet she reported no pain after the surgery. Her pain insensitivity was diagnosed by Dr Devjit Srivastava, Consultant in Anaesthesia and Pain Medicine at an NHS hospital in the north of Scotland and co-lead author of the paper.

The woman tells researchers she has never needed painkillers after surgery such as dental procedures.

She was referred to pain geneticists at UCL and the University of Oxford, who conducted genetic analyses and found two notable mutations. One was a microdeletion in a pseudogene, previously only briefly annotated in medical literature, which the researchers have described for the first time and dubbed FAAH-OUT. She also had a mutation in the neighbouring gene that controls the FAAH enzyme.

Further tests by collaborators at the University of Calgary, Canada, revealed elevated blood levels of neurotransmitters that are normally degraded by FAAH, further evidence for a loss of FAAH function.

The FAAH gene is well-known to pain researchers, as it is involved in endocannabinoid signalling central to pain sensation, mood and memory. The gene now called FAAH-OUT was previously assumed to be a 'junk' gene that was not functional. The researchers found there was more to it than previously believed, as it likely mediates FAAH expression.

Mice that do not have the FAAH gene have reduced pain sensation, accelerated wound healing, enhanced fear-extinction memory and reduced anxiety.

The woman in Scotland experiences similar traits. She notes that in her lifelong history of cuts and burns (sometimes unnoticed until she can smell burning flesh), the injuries tend to heal very quickly. She is an optimist who was given the lowest score on a common anxiety scale, and reports never panicking even in dangerous situations such as a recent traffic incident. She also reports memory lapses throughout life such as forgetting words or keys, which has previously been associated with enhanced endocannabinoid signalling.

The researchers say that it's possible there are more people with the same mutation, given that this woman was unaware of her condition until her 60s.

"People with rare insensitivity to pain can be valuable to medical research as we learn how their genetic mutations impact how they experience pain, so we would encourage anyone who does not experience pain to come forward," said Dr Cox.

The research team is continuing to work with the woman in Scotland, and are conducting further tests in cell samples, in order to better understand the novel pseudogene.

"We hope that with time, our findings might contribute to clinical research for post-operative pain and anxiety, and potentially chronic pain, PTSD and wound healing, perhaps involving gene therapy techniques," said Dr Cox.

"The implications for these findings are immense," said Dr Srivastava.

"One out of two patients after surgery today still experiences moderate to severe pain, despite all advances in pain killer medications and techniques since the use of ether in 1846 to first 'annul' the pain of surgery. There have already been unsuccessful clinical trials targeting the FAAH protein - while we hope the FAAH-OUT gene could change things particularly for post-surgical pain, it remains to be seen if any new treatments could be developed based on our findings."

"The findings point towards a novel pain killer discovery that could potentially offer post-surgical pain relief and also accelerate wound healing. We hope this could help the 330 million patients who undergo surgery globally every year," Dr Srivastava said.

"I would be elated if any research into my own genetics could help other people who are suffering," the woman in Scotland commented.

"I had no idea until a few years ago that there was anything that unusual about how little pain I feel - I just thought it was normal. Learning about it now fascinates me as much as it does anyone else."

Credit: 
University College London

Cities under pressure

Cities to swelter as planners face unenviable trade-off between tackling climate change and quality of life, new research has shown.

The study, led by experts at Newcastle University, UK, has shown the challenge we face to reduce greenhouse gas emissions, increase cities' resilience to extreme weather and also give people quality space to live in.

Publishing the research in the journal Cities, the team have for the first time analysed the trade-offs between different sustainability objectives. These include minimising climate risks such as heat waves and flooding, reducing emissions from transport, constraining urban sprawl, making best use of our brownfield sites, ensuring adequate living space, and protecting green space which is important for our health and wellbeing.

Focussing on London - an example of a large rapidly growing city that is also at the forefront of tackling climate change - the team show the 'best case' scenario would be to increase development in a small number of central locations, such as East Barnet, Wood Green and Ealing.

Avoiding development along the Thames, this optimum plan would reduce flood risk, minimise transport emissions and reduce urban sprawl.

But, says author Dr Dan Caparros-Midwood, the trade-off will be more people exposed to extreme temperatures.

"Many of the lowest heat hazard areas coincide with the flood zone on the banks of the River Thames due to the cooling effect of blue infrastructure," explains Dr Caparros-Midwood, who carried out the work as part of his PhD at Newcastle University and is now a Senior GIS Specialist at Wood.

"But moving development away from the river while also protecting our green spaces and reducing sprawl really only leaves two options; either shrinking our homes or developing in higher heat risk areas.

"And while our study looked at London, this could apply to most cities in the world."

Building resilience in our cities

By 2050 it is estimated that two-thirds of the world's population will live in cities, highlighting the urgent need for urban development to be sustainable.

"Urban areas must radically transform if they are to reduce their greenhouse gas emissions and consumption of resources whilst also increasing their resilience to climate change and extreme weather," explains Professor Stuart Barr, co-author and part of the Geospatial Engineering group at Newcastle University.

Project lead Professor Richard Dawson, of the School of Engineering at Newcastle University, said the findings reinforced the scale of the challenge.

"We are already starting to see the impact of hotter summers and flooding on our cities," he says.

"Balancing trade-offs between these objectives is complex as it spans sectors such as energy, buildings, transport, and water.

"What our study shows in stark detail is this cannot be done using our current approach to planning and engineering our cities - difficult choices will have to be made."

Even in Europe, says Professor Dawson, only a quarter of cities have a comprehensive climate strategy. And yet, with the right impetus, we have the potential to accelerate and upscale action in our cities to tackle climate change.

"We have to be more creative about how we design and build our buildings and infrastructure," he says.

"This will include weaving green infrastructure into urban spaces; facilitating lifestyle choices such as walking and cycling that reduce energy demand, pollution and greenhouse gas emissions; and integrating new technologies that can shift carbon-intensive energy patterns by optimizing transport efficiency, vehicle sharing and reducing congestion.

"For the moment though, there are difficult, and often irreconcilable, trade-offs to be made in urban areas and we need to be making them now."

Credit: 
Newcastle University

Many NHS partnerships with drug companies are out of public sight

NHS organisations are entering into working partnerships with drug companies, but they are not making the details, and even existence, of many of these deals available to the public, reveals an investigation by The BMJ today.

These partnerships are used to support a variety of initiatives, including several projects to review the medication of people with ADHD, and more than 20 projects that focus on patients with age-related macular degeneration.

The BMJ, working with a team of university researchers, sent freedom of information requests to all 194 acute care NHS trusts in England to find out how many were involved in joint working arrangements in 2016 and 2017 and what joint working policies trusts had in place.

Joint working arrangement is the term used to refer to initiatives that involve shared investment by the NHS and drug companies. They are designed to bring benefits to patients, the NHS, and the companies.

Companies spent £3m in 2016 and £4.7m in 2017 on joint working arrangements, and under the NHS Long Term Plan, collaboration between health services and industry is set to treble over the next decade.

Yet the researchers found that a fifth of trusts would not release details of the deals, despite official guidance that joint working agreements must be conducted in an "open and transparent" manner.

Trusts are also expected to record and monitor all funding agreements related to the joint working projects, yet 13 (7%) said that they did not keep a central record of any such arrangements and so could not provide the information.

Even when trusts did provide details, the information they provided was often inaccurate or contradicted by other sources. Others claimed not to know about joint working arrangements at all.

Cathy Augustine of the Keep Our NHS Public campaigning group, argues that allowing industry to provide NHS services in this way helps to mask the degree of government under-resourcing.

While Robert Morley, executive secretary of Birmingham Local Medical Committee, says the lack of transparency by trusts over these arrangements is "truly shocking" and "blatant neglect of their obligations."

The industry says that joint working projects can accelerate the spread of new treatments for the benefit of patients. The BMJ found that many of the 93 projects running in 2016 and 2017 specifically referred to increasing the use of products marketed by the company funding the project.

Robert Morley says that the NHS should be taking the lead on determining the focus of projects to which it is committing investment, and he is concerned that these joint working arrangements "are being designed first and foremost around the interests of pharmaceutical companies."

John Puntis, a consultant paediatrician and secretary of Keep Our NHS Public, argues that the lack of expertise in NHS organisations in negotiating contractual arrangements has meant that the health service is often left at a disadvantage when collaborating with the industry.

"My concern would always be, 'What's in it for the private sector?' They never do these things purely for the benefit of the NHS and the benefit of patients," he says.

"They're often buying goodwill as well. Doctors say, 'Well, we're not influenced by the drug companies,' but clearly they are, because otherwise the industry wouldn't be pouring all the money into it," he adds.

Credit: 
BMJ Group

Heating up tumors could make CAR T therapy more effective, study finds

FINDINGS

A preclinical study led by scientists at the UCLA Jonsson Comprehensive Cancer suggests that heating solid tumors during CAR T-cell therapy can enhance the treatment's success.

The researchers found that when a heating technique called photothermal ablation was combined with the infusion of CAR T cells, it suppressed melanoma tumor growth for up to 20 days in mice. Among the mice that were treated with the combination, 33 percent were still tumor free after the 20-day mark.

BACKGROUND

T cells that have been genetically engineered with chimeric antigen receptor, or CAR, have successfully been used to treat many patients with lymphoma and leukemia. But CAR T cell therapy has been less successful for treating solid tumors because the tumors have a protective microenvironment, which makes it harder for the CAR T cells to break into the tumor and keep the T cells activated.

The UCLA scientists decided to test whether combining CAR T therapy with photothermal therapy could overcome that obstacle. Photothermal therapy is a minimally invasive technique that uses heat from laser energy to kill cancer cells; it is already being used to treat a variety of cancers and other medical conditions. The researchers tested a mild hyperthermia about 40 degrees Celsius (about 104 degrees Fahrenheit) to see if it could help enhance the CAR T cells to better attack the tumor.

METHOD

The UCLA-led team tested the technique in mice that were injected with human melanoma tumors. A photothermal agent was injected into the tumors and then irradiated with the laser to heat them. Then, CAR T cells were injected intravenously. Raising the temperature of the laser to about 40 degrees Celsius helped expand blood vessels associated with the tumor, enhancing T cell growth.

IMPACT

By enhancing the power of CAR T cell therapy, the technique could eventually improve the prognosis for people with hard-to-treat solid tumors. The researchers will continue testing the strategy in animals to optimize the heating duration and temperature before determining whether it can be tested on humans.

AUTHORS

Zhen Gu, a professor of bioengineering at the UCLA Samueli School of Engineering, member of the Jonsson Cancer Center and member of the California NanoSystems Institute at UCLA, is the study's co-senior author. The paper's other senior author is Dr. Gianpietro Dotti of the University of North Carolina, Chapel Hill. The first author is Qian Chen, a postdoctoral researcher in Gu's laboratory.

Credit: 
University of California - Los Angeles Health Sciences

Lipid vesicles transmit luminous or electrical signals

Liposomes are small spherical vesicles with walls comprising two layers of lipids and containing an aqueous core. These artificial structures have been developed for drug delivery or as carriers of active substances in cosmetic products. Another possible application involves the encapsulation of magnetic nanoparticles in liposomes to use them to transmit signals.

This possibility is discussed in an article published by a group of Brazilian researchers supported by São Paulo Research Foundation - FAPESP in Royal Society Open Science.

"Our research belongs to the sphere of basic science but has potential applications in such fields as computational signal transmission, for example. We built a model with two sets of liposomes. One type was nanometric, with a size of about 100 nanometers, and the other was a group of 'giants' measuring 10-20 micrometers," said Iseli Lourenço Nantes Cardoso.

Cardoso is a Full Professor at the Federal University of the ABC (UFABC) in Santo André, Brazil and was co-principal investigator for the study. The other principal investigator was Frank Nelson Crespilho, a professor at the University of São Paulo's São Carlos Chemistry Institute (IQSC-USP).

The nanometric and giant liposomes used in the model were designed to mimic drug carriers and cells, respectively, and to fuse with each other. Instead of delivering drugs, however, the nanometric liposomes transported magnetite nanoparticles with fluorophores (fluorescent molecules) or electrically charged lipids. The fluorophores and charged lipids were used to transmit signals, while the magnetic particles were used to control transmission by means of magnets.

"In the initial situation, the giant vesicles had no fluorophores, charges or magnetite nanoparticles. Upon fusing with the nanometric liposomes, which contained luminous or electrical information, the giant vesicles incorporated this information. They also incorporated the magnetic particles and hence could be drawn by a magnet to the signal-receiving station. This created the possibility of an on/off mechanism. When the magnet moves the vesicle toward the receiving station, we have the 'on' state. When it's in the opposite direction, we have the 'off' mode, and the signal is blocked," Cardoso explained.

"In the case of the light signal, the giant vesicles were conducted by a capillary tube to a fiber-optic connection and from there to a spectrofluorimeter, which recorded the fluorescence spectrum. For the electrical signal, we used a magneto-electrochemical signal transmission system. When the electrically charged molecules are conducted to an electrode by a magnet, a high signal occurs. If the magnet is removed, the signal is very low," he said.

According to the researchers, these devices can be used to perform Boolean logic operations in which the variables and functions have values only of 0 and 1. These would be combined in pairs to create four dyads: 0-0, 0-1, 1-0 and 1-1. The first dyad (0-0) would be the giant vesicle without fluorophores, charges or magnetite particles. With fluorophores but no magnetite, the device produces but does not transmit a light signal (0-1). With magnetite but no fluorophores, the giant vesicle can be transported but does not transmit a light signal (1-0). With both fluorophores and magnetite, it transmits a light signal (1-1).

The study was conducted as part of the Thematic Project "Interfaces in materials: electronic, magnetic, structural and transport properties", for which Professor Adalberto Fazzio is the principal investigator, and demonstrated for the first time that magnetic nanoparticles can be used at the liposome interface to transmit luminous or electrical signals.

Credit: 
Fundação de Amparo à Pesquisa do Estado de São Paulo

High-speed videos capture how kangaroo rat escapes rattlesnake attack

image: Timothy Higham is an associate professor at UC Riverside.

Image: 
I. Pittalwala, UC Riverside.

RIVERSIDE, Calif. - Kangaroo rats are abundant and seemingly defenseless seed-eating rodents that have to contend with a host of nasty predators, including rattlesnakes -- venomous pit vipers well known for their deadly, lightning-quick strikes. 

Research by a student-led team from UC Riverside, San Diego State University, and UC Davis now shows that desert kangaroo rats frequently foil snakes through a combination of fast reaction times, powerful evasive leaps, and mid-air, ninja-style kicks. 

Video of kangaroo rat defensively kicking a rattlesnake while jumping. More videos below.

Timothy Higham, an associate professor in the Department of Evolution, Ecology and Organismal Biology at UCR, is a coauthor on two papers published today in Functional Ecology and the Biological Journal of the Linnean Society that present detailed analyses of the behaviors and biomechanics of both kangaroo rats and rattlesnakes.

"Both rattlesnakes and kangaroo rats are extreme athletes, with their maximum performance occurring during these interactions," Higham said. "This makes the system excellent for teasing apart the factors that might tip the scale in this arms race." 

The research team documented the interactions between kangaroo rats and rattlesnakes in the wild by using radio telemetry to patiently track the hunting behavior of free-ranging rattlesnakes, and then placing high-speed cameras to record snakes hunting in locations frequented by kangaroo rats. The resultant videos provide the first ever detailed look at the maneuvers that kangaroo rats use to defend themselves against a deadly predator. 

"These lightning-fast and powerful maneuvers, especially when executed in nature, tell us about the effective strategies for escaping high-performing predators," Higham said. "Those that are successful at evading the strike will suggest ways in which the kangaroo rat might be evolving in response to the intricacies of the predatory movements."

A blink of the human eye can last just 150 milliseconds. In contrast, the research team found that the rattlesnakes frequently launched from absolute stillness to reach the kangaroo rats in less than 100 milliseconds. The researchers were surprised to find that the kangaroo rats turned out to be even faster, with typical reaction times around 70 milliseconds.  Their data indicate that some kangaroo rats initiated jumps within just 38 milliseconds of a snake starting its strike. 

"Kangaroo rats that responded quickly were frequently able to jump clear of the snake completely, leaving the serpent biting nothing but dust as the kangaroo rat rocketed 7-8 body lengths into the air," said Rulon Clark, an associate professor of biology at San Diego State University and a coauthor on both research papers. "But in perhaps the most surprising finding of our research, kangaroo rats that did not react quickly enough to avoid the strike had another trick up their sleeves: they often were able to avoid being envenomated by reorienting themselves in mid-air and using their massive haunches and feet to kick the snakes away, ninja-style."  

One video shot by the students on the research team shows a kangaroo rat successfully kicking a snake.  The snake is sent flying through the air and crashing to the ground several feet away while the kangaroo rat bounds off.  Such defensive kicks solved a mystery that had puzzled the team for years: the group's previous research showed that kangaroo rats often emerged from seemingly successful snake bites unscathed, but it was not clear how. The researchers even tested the blood of kangaroo rats to be sure that they weren't physiologically resistant to snake venom, the way some squirrel and opossum species are. 

"Our previous work used lower-speed cameras, and although it seemed as though snakes had successfully struck their prey, the movements of the animals at the moment of impact was too blurry to see details," said Malachi Whitford, a doctoral student at San Diego State University and the lead author on one of the papers.  "In this new work, we used cameras with much higher recording speed and resolution, which helped show in exquisite detail that kangaroo rats not only have record-breaking reaction time, but can also use their long tails to reorient their bodies while jumping, thereby optimally positioning themselves for both defensive kicking and landing on their feet."

Catching prey and avoiding predators are central to the reproductive success of animals.  Kangaroo rats' highly sensitive hearing allows them to hear low-frequency sounds and detect sudden surprise attacks, necessary for avoiding predators. They also have enlarged hindlimb muscles and thick tendons, allowing for the rapid vertical leaps and high accelerations. 

Rattlesnakes are classic ambush predators. They hunt by hiding and remaining nearly motionless for prolonged periods. They strike at prey that gets too close. The prey avoids being struck by initiating a successful evasive maneuver. In the wild, both predator and prey can alter the outcome at multiple stages of an interaction in ways not readily apparent in the lab. 

"Our work, which, to our knowledge, is the first to describe the kinematics of evasive leaps by bipedal rodents avoiding actual attacks from predators, supports the idea that bipedalism may have been favored in kangaroo rats because it allows for the rapid and powerful leaps needed to avoid ambush predators such as vipers and owls," said Grace Freymiller of San Diego State University, the student lead author of the second paper.

Credit: 
University of California - Riverside

Parental support linked to how well millennials transition to college life

image: Girl in front of computer looking stressed.

Image: 
pixabay

Researchers show that how well parents or guardians support millennials' psychological needs prior to their transition to college is an important predictor of their psychological well-being as they adapt to college life.

A new study published in The Journal of Social Psychology has assessed the role of parental relationships in mitigating millennials' worry prior to college transition by meeting their basic psychological needs of autonomy, competence and relatedness. The research discovered that millennials who perceive their parental relationships as supportive of their psychological needs are less likely to worry and adjust better to the transition to college, whereas parenting that feels over involved and controlling predicts less need satisfaction, higher levels of worry and poor psychological well-being.

"Millennial college students are experiencing poorer psychological health than any other previous generation," explained Mr Nathaniel Greene from the University of Missouri, who led the study.

"An early indication of student's well-being is their initial worry about college," he continued, "but understanding what factors might mitigate worry prior to millennials' transition into college is limited in current research."

Specifically, the researchers focused on whether worry, including guilt over academically succeeding family members, could be moderated through the student's parental relationship.

"Millennials have a uniquely close and communicative relationship with their parents," explained Dr Carrie Veronica Smith, who contributed to the study, "so we used the well-established 'Self-Determination Theory' to test if worry would be lower for students who perceive their parental relationships meet their three basic psychological needs: the need to be in control of one's actions (autonomy), the need to feel capable and effective (competence) and the need to feel close and connected to others (relatedness)," she continued.

355 students were surveyed during their two-day orientation visits to a public university in the southeast United States in the summer before their freshman year. Measurements of the participants' demographics, family achievement guilt, basic need satisfaction in the parental relationship, parental bonding and student worry were collected, and the data was subjected to statistical analyses to determine if higher levels of need satisfaction in the parental relationship were related to lower levels of worry and achievement guilt and if these outcomes would differ for first- and continuing-generation students.

Millennials who felt that their parents support their psychological needs reported less worry about their transition to college and lower family achievement guilt. But of the three basic psychological needs, autonomy was the most significant predictor of worry, suggesting that millennials' need to feel in control of their actions may be the most important need in combatting concerns about college. Meanwhile, millennials who felt their parents were over involved and controlling reported less need satisfaction and higher levels of worry and achievement guilt.

"We were surprised to see these results were true for both first- and continuing-generation students because past research has shown first-generation students likely suffer more from family achievement guilt and feelings of disconnection," explained Mr Greene. "But our results nicely highlight the universal importance of these basic needs," he continued.

Overall, the study identifies the importance of psychological need satisfaction in the parental relationship in offsetting millennials' worries about college and relating to their psychological well-being.

"Parents, peers and educators should support millennial students' basic needs for autonomy, competence and relatedness both before and after the transition to college, as they are essential to their overall psychological health" advised Mr Greene.

Credit: 
Taylor & Francis Group

Genetic tagging may help conserve the world's wildlife

image: Hair samples like this one can be collected to track animals using their DNA signatures, an approach providing benefits over traditional invasive methods such as ear tags and collars, according to a new study by UAlberta biologists.

Image: 
Clayton Lamb

Tracking animals using DNA signatures are ideally suited to answer the pressing questions required to conserve the world's wildlife, providing benefits over invasive methods such as ear tags and collars, according to a new study by University of Alberta biologists.

Genetic tagging, or the identification and tracking of individual animals using DNA, is a non-invasive method of conducting research that uses samples from shed hair, feathers, feces, or saliva.

"This method provides a toolkit that can answer many of the pressing questions in ecology and conservation and provides a 'one-stop-shop' for getting these answers," explained Clayton Lamb, PhD candidate and Vanier scholar in the Department of Biological Sciences and lead author on the study. "Other methods would generally need to be combined to acquire similar insight. Genetic tagging approaches are complementary to traditional approaches and add a powerful tool to the ecologists' toolkit."

In addition to being non-invasive--in fact, there's no need to handle individual animals at all--there are many benefits to using genetic tagging over other methods. Genetic tagging can cover more ground and is scalable, allowing scientists to examine overall population density or the composition of a single community. It also provides the ability to recognize individual animals with great precision, allowing scientists to research animals that are otherwise difficult to study.

Access to DNA sequencing technology has grown increasingly affordable since the 2000s, thereby increasing access and usability for ecologists and biologists around the globe. And it's a good thing too, as our world continues to change.

"As human pressures on the globe increase, scientists are tasked with identifying drivers of decline and mobilizing this evidence to promote mitigation," said Lamb. "Genetic tagging offers a powerful approach to parameterize such relationships across massive spatial extents, for difficult to sample species, and in a cost-effective and socially-acceptable manner."

Credit: 
University of Alberta

Sometimes it's not good to be green

image: July 10, 2014. Water flowing into a eutrophic lake from agricultural fields. Algae is already abundant in the stream where it has grown due to high nutrients and temperatures. Credit: John A. Downing/Minnesota Sea Grant.

Image: 
John A. Downing/Minnesota Sea Grant

The good news is global and local. Keeping inland lakes from turning green means less greenhouse gases entering the atmosphere and contributing to climate change. Healthy drinking water, fishing and recreation opportunities are also increased when waters are not green.

What's wrong with being green? Toxins released by algal blooms can ruin drinking water. When dense algae blooms die, the bacteria that decompose the algae also deplete oxygen in the water. Without oxygen, fish and other animals suffocate. Globally, such green waters are also an important contributor to atmospheric methane -- a greenhouse gas that is up to 34 times more potent than carbon dioxide.

"We estimate that the greening of the world's lakes will increase the emission of methane into the atmosphere by 30 to 90 percent during the next 100 years," said Jake Beaulieu of the United States Environmental Protection Agency and lead author of a paper on lake greening and greenhouse gas emissions published March 26, 2019 in the journal Nature Communications.

According to the authors, three distinct mechanisms are expected to induce increases in lake greening or eutrophication during the next 100 years. First, human populations are expected to increase by 50 percent by 2100. More people means more sewage and more fertilizers that runoff land. At current rates of population growth and climate change, eutrophication in lakes will increase by 25 to 200 percent by 2050 and double or quadruple by 2100.

Second, increased storms and stormwater runoff will increase the nutrient losses from land to inland waters. Third, as the climate warms, lakes will warm. Warmer waters produce more algae. Additionally, the area of the planet covered in water is expected to increase, which will result in more methane-emitting surface waters.

"It is really surprising how much eutrophication could increase in the next 50 to 100 years," said co-author John A. Downing of the University of Minnesota Sea Grant program. "People do four important things that affect eutrophication: they eat, they excrete, they make more people who eat and excrete, and they alter landscapes and climate," said Downing.

Using projected population growth and climate change, the authors simulated the eutrophication of lakes under four different and conservative scenarios of future phosphorus loading from low to high: 80, 130, 170, 200, and 220 percent of current levels.

"We used phosphorus because the relationship between phosphorus and plant or algae growth is well established," said co-author Tonya DelSontro of the University of Geneva. "Currently, the single largest source of atmospheric methane is wetlands. If the phosphorus in lakes triples, then methane emissions from lakes could be twice that of wetlands."

The authors used a statistical model they created in 2018 that correlates methane emissions with lake size and chlorophyll, which is a measure of high algal biomass stimulated by phosphorus. By using global distribution of lake size and total lake area, climatic heating of lakes, future phosphorus concentrations and storm-driven nutrient runoff they were able to estimate future lake methane emissions, which the authors say has not been done before.

The optimistic outcome is that improved nutrient management practices could reverse the greening or eutrophication of lakes and thereby reduce methane emissions. Additionally, local action to improve water quality could have important global consequences.

"In keeping and improving the quality of our fresh water we win twice," said Downing. "Once in the atmosphere and once back down here on Earth."

Credit: 
University of Minnesota

Future of elephants living in captivity hangs in the balance

Scientists at the University of Sheffield and University of Turku are looking at ways to boost captive populations of Asian elephants without relying on taking them from the wild.

Almost a third of Asian elephants are in captivity in countries like India, Myanmar and Thailand, mainly being used in the timber industry to drag logs or for tourism.

Sustaining wild populations is the conservation priority but, with so many individuals in captivity, maintaining sustainable captive populations with high welfare standards is also important for the future of the species.

The sustainability of these elephant populations has always relied on the capture of their wild counterparts, but now they are a protected species their future is uncertain.

In a joint research study, the University of Sheffield and the University of Turku, in Finland, working alongside The Myanma Timber Enterprise (MTE), investigated how trends in elephant capture from the wild influenced birth, death and population growth in 3,500 working elephants over 54 years.

Using birth and death rates from years where wild-capture was reduced the scientists assessed the outlook for captive elephants and found that the population is vulnerable to decline.

The research, published in Proceedings of the Royal Society B, suggests that immediate population declines may be reduced if survival in juvenile elephants is improved.

This could involve improving welfare standards during the training period, as the elephants are separated from their mothers and trained for work around the age of four, which can be stressful for them, and identifying pregnant females earlier and improving their welfare so they can provide for and bond with their calf.

John Jackson, PhD researcher from the University of Sheffield's Department of Animal and Plant Sciences and lead author of the paper, said: "Our model suggests we may see declines in captive elephants for up to 50 years so we must now work to ensure that the captive population is sustainable. With so many Asian elephants in captivity, we must safeguard both captive and wild elephant populations and the people living and working alongside them for the future of the species.

"One hopeful result is that we may see improvements in population growth if we are able to improve the survival of young elephants by just 10 per cent. This shows we can really make a difference by improving welfare for these vulnerable individuals in captivity."

He added: "Many of us have the opportunity to visit captive elephants used in tourism, particularly in Southeast Asia. We all have our part to play to ensure that the welfare of captive elephants is improved and this may have a positive effect on Asian elephants globally."

Professor Virpi Lummaa, from the University of Turku, who led the research, said: "The dependence of captive elephant populations on capture from the wild in the past is truly alarming. The problem with elephants is that they take so long to grow and reproduce and have very complex social lives, making them vulnerable to population declines when disturbed."

The University of Sheffield's Department of Animal and Plant Sciences is a leading department for whole organism biology, with the UK's highest concentration of animal and plant researchers.

It is among the top five animal and plant research centres in the country for research excellence, according to the last Research Excellence Framework in 2014.

Animal and plant scientists at Sheffield study in locations from the Polar Regions to the tropics, at scales from within cells up to entire ecosystems. Their research aims both to understand the fundamental processes that drive biological systems and to solve pressing environmental problems.

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University of Sheffield

Study shows that patients with or without cancer use different forms of marijuana

People with and without cancer are more likely, over time, to use a more potent form of medical marijuana with increasingly higher amounts of tetrahydrocannabinol (THC), a new study shows.

In a report publishing in the Journal of Palliative Medicine on March 26, researchers say that cancer patients were more likely to favor forms of medical marijuana with higher amounts of THC, which relieves cancer symptoms and the side effects of cancer treatment, including chronic pain, weight loss, and nausea.

By contrast, marijuana formulations higher in cannabidiol (CBD), which has been shown to reduce seizures and inflammation in other studies, were more popular among non-cancer patients, including those with epilepsy and multiple sclerosis, say the study authors.

Cancer patients were also more likely to prefer taking oil droplets containing medical marijuana under the tongue than "vaping".

"Although there is growing patient interest in medical cannabis, there is a scarcity of solid evidence about the benefits, risks, and patterns of use of marijuana products in various disease settings," says study lead investigator Arum Kim, MD, an assistant professor of medicine and rehabilitation medicine at NYU School of Medicine and director of the supportive oncology program at its Perlmutter Cancer Center. "Such information is important for delivering the best care."

Since 1996, 31 states, including New York in 2014, have legalized medical marijuana.

For the study, researchers analyzed data from 11,590 men and women in New York, of whom 1,990 (17.2 percent of the total patient cohort) were cancer patients who purchased and used cannabis products from Columbia Care LLC., a dispensary licensed in New York State, between January 2016 and December 2017.

The researchers caution that their data did not include the type of cancer the purchasers had, how much of what they bought was used, or whether marijuana was used for symptoms unrelated to the cancer. Nevertheless, the patterns of use among cancer patients were distinctly different from those of non-cancer patients.

Specifically, the study found that cancer and non-cancer patients used different dosages of cannabis formulations with dramatically different THC:CBD ratios. The two most common formulations contained THC and CBD, but one had twenty times more THC than CBD, whereas the other had the opposite ratio.

Over the two years of the study, the research team found that all types of patients increased their THC dose by approximately 0.20 milligrams per week.

"Our study provides valuable new information about how cancer patients are using marijuana," says study senior investigator Benjamin Han, MD, MPH, an assistant professor of medicine and population health at NYU School of Medicine. "In the absence of strong clinical research data for medical marijuana, identifying patterns of use offers some sense of how to guide patients who come in with questions for using medical marijuana, and what may or may not help them."

Researchers say they next plan to get more detailed information about how medical marijuana affects patient response to therapy and functional status at different stages of their disease, as well as the risks and side effects of treatment. Furthermore, the profiles of other cannabinoids besides THC and CBD in medical marijuana products warrant further research, according to the study authors.

Credit: 
NYU Langone Health / NYU Grossman School of Medicine

Microgels let medical implants fight off bacteria

Joint replacements are among the most common elective surgeries -- but around one in 100 patients suffer post-surgical infections, turning a routine procedure into an expensive and dangerous ordeal. Now, researchers at Stevens Institute of Technology have developed a "self-defensive surface" for these implants that release targeted micro-doses of antibiotics when bacteria approach, potentially sharply reducing infection rates.

The work, led by Matthew Libera, professor of materials science at Stevens, describes a method for coating implant surfaces with a lattice of microgels: flecks, each 100 times smaller than the diameter of a human hair, capable of absorbing certain antibiotics. The microgels' behavior is regulated by electrical charges, and the electrical activity of an approaching microbe causes them to leak antibiotics, preventing infections from taking root.

Microgels could be applied to a wide range of medical devices, including heart valves, tissue scaffolds, and even surgical sutures -- and with the market for hip implants alone forecasted to reach $9.1 billion by 2024, the technology has significant commercial potential. The United States Army, which helped fund the research, is also interested in deploying the technology in field hospitals, where infections currently occur in a quarter of combat injuries.

"The potential impact for patients, and for the healthcare system, is tremendous," said Libera, who chairs the Stevens Conference on Bacteria-Material Interactions. Stevens doctorate candidate Jing Liang and biomedical engineering professor Hongjun Wang collaborated on the study, which appears in the journal Biomaterials.

Post-surgical infections are tough to beat because as microbes colonize surfaces, they form antibiotic-resistant layers called biofilms. Libera and his team disrupt this cycle by killing microbes before they can gain a foothold. "It only takes one bacterium to cause an infection," Libera said. "But if we can prevent infection until healing is complete, then the body can take over."

Unlike conventional treatments that flood the whole body with antibiotics, the Stevens team's approach is highly targeted, releasing tiny amounts of antibiotics to kill individual bacteria. That dramatically reduces the selective pressures that give rise to antibiotic-resistant "superbugs" -- a big improvement over both systemic treatments and local approaches such as blending antibiotics into bone cement, releasing orders of magnitude less antibiotic into the patient's system.

Other self-defensive surfaces currently in development rely on microbes' metabolic byproducts to trigger the release of antibiotics -- a less surefire approach than the Libera's method, which can kill even dormant bacteria. The team's microgels are also remarkably resilient, surviving ethanol sterilization and remaining stable for weeks at a time. Microgels also respond appropriately to human tissue, retaining their antibiotic load until it's needed and promoting healthy bone growth around treated surfaces.

To apply microgels to a medical device such as a knee joint, surgeons could dunk the device in a specially prepared bath for a few seconds; a brief dip in a second bath would then charge the microgels with antibiotics. In theory, surgeons could prepare devices on demand, immediately before implanting them, using antibiotics tailored to a patient's specific risk factors.

So far the approach has been tested in vitro, and the team is still working to fine-tune the microgels and enable them to deliver a wider range of antibiotics. Securing approval from the U.S. Food and Drug Administration will be tricky, given the innovative nature of the technology, but Libera's team is working with industry partners to plan further demonstrations.

Credit: 
Stevens Institute of Technology

New 3-D printing approach makes cell-scale lattice structures

A new way of making scaffolding for biological cultures could make it possible to grow cells that are highly uniform in shape and size, and potentially with certain functions. The new approach uses an extremely fine-scale form of 3-D printing, using an electric field to draw fibers one-tenth the width of a human hair.

The system was developed by Filippos Tourlomousis, a postdoc at MIT's Center for Bits and Atoms, and six others at MIT and the Stevens Institute of Technology in New Jersey. The work is being reported in the journal Microsystems and Nanoengineering.

Many functions of a cell can be influenced by its microenvironment, so a scaffold that allows precise control over that environment may open new possibilities for culturing cells with particular characteristics, for research or eventually even medical use.

While ordinary 3-D printing produces filaments as fine as 150 microns (millionths of a meter), Tourlomousis says, it's possible to get fibers down to widths of 10 microns by adding a strong electric field between the nozzle extruding the fiber and the stage on which the structure is being printed. The technique is called melt electrowriting.

"If you take cells and put them on a conventional 3-D-printed surface, it's like a 2-D surface to them," he explains, because the cells themselves are so much smaller. But in a mesh-like structure printed using the electrowriting method, the structure is at the same size scale as the cells themselves, and so their sizes and shapes and the way they form adhesions to the material can be controlled by adjusting the porous microarchitecture of the printed lattice structure.

"By being able to print down to that scale, you produce a real 3-D environment for the cells," Tourlomousis says.

He and the team then used confocal microscopy to observe the cells grown in various configurations of fine fibers, some random, some precisely arranged in meshes of different dimensions. The large number of resulting images were then analyzed and classified using artificial intelligence methods, to correlate the cell types and their variability with the kinds of microenvironment, with different spacings and arrangements of fibers, in which they were grown.

Cells form proteins known as focal adhesions at the places where they attach themselves to the structure. "Focal adhesions are the way the cell communicates with the external environment," Tourlomousis says. "These proteins have measurable features across the cell body allowing us to do metrology. We quantify these features and use them to model and classify quite precisely individual cell shapes."

For a given mesh-like structure, he says, "we show that cells acquire shapes that are directly coupled with the substrate's architecture and with the melt electrowritten substrates," promoting a high degree of uniformity compared to nonwoven, randomly structured substrates. Such uniform cell populations could potentially be useful in biomedical research, he says: "It is widely known that cell shape governs cell function and this work suggests a shape-driven pathway for engineering and quantifying cell responses with great precision," and with great reproducibility.

He says that in recent work, he and his team have shown that certain type of stem cells grown in such 3-D-printed meshes survived without losing their properties for much longer than those grown on a conventional two-dimensional substrate. Thus, there may be medical applications for such structures, perhaps as a way to grow large quantities of human cells with uniform properties that might be used for transplantation or to provide the material for building artificial organs, he says. The material being used for the printing is a polymer melt that has already been approved by the FDA.

The need for tighter control over cell function is a major roadblock for getting tissue engineering products to the clinic. Any steps to tighten specifications on the scaffold, and thereby also tighten the variance in cell phenotype, are much needed by this industry, Tourlomousis says.

The printing system might have other applications as well, Tourlomousis says. For example, it might be possible to print "metamaterials" -- synthetic materials with layered or patterned structures that can produce exotic optical or electronic properties.

Credit: 
Massachusetts Institute of Technology