This new code to model stellar collisions is more expeditious than the established code used for numerical simulations. The research came from a unique collaboration between experimental computer scientists and astrophysicists in the Louisiana State University Department of Physics & Astronomy, the LSU Center for Computation & Technology, Indiana University Kokomo and Macquarie University, Australia, culminating in over of a year of benchmark testing and scientific simulations, supported by multiple NSF grants, including one specifically designed to break the barrier between computer science and astrophysics.

“Thanks to a significant effort across this collaboration, we now have a reliable computational framework to simulate stellar mergers,” said Patrick Motl, professor of physics at Indiana University Kokomo. “By substantially reducing the computational time to complete a simulation, we can begin to ask new questions that could not be addressed when a single-merger simulation was precious and very time consuming. We can explore more parameter space, examine a simulation at very high spatial resolution or for longer times after a merger, and we can extend the simulations to include more complete physical models by incorporating radiative transfer, for example.”

Recently published in Monthly Notices of the Royal Astronomical Society, “Octo-Tiger: A New, 3D Hydrodynamic Code for Stellar Mergers That Uses HPX Parallelisation,” investigates the code performance and precision through benchmark testing. The authors, Dominic C. Marcello, postdoctoral researcher; Sagiv Shiber, postdoctoral researcher; Juhan Frank, professor; Geoffrey C. Clayton, professor; Patrick Diehl, research scientist; and Hartmut Kaiser, research scientist, all at Louisiana State University — together with collaborators Orsola De Marco, professor at Macquarie University and Patrick M. Motl, professor at Indiana University Kokomo — compared their results to analytic solutions, when known and other grid-based codes, such as the popular FLASH. In addition, they computed the interaction between two white dwarfs from the early mass transfer through to the merger and compared the results with past simulations of similar systems.

“A test on Australia’s fastest supercomputer, Gadi (#25 in the World’s Top 500 list), showed that Octo-Tiger, running on a core count over 80,000, displays excellent performance for large models of merging stars,” De Marco said. “With Octo-Tiger, we cannot only reduce the wait time dramatically, but our models can answer many more of the questions we care to ask.”

Octo-Tiger is currently optimized to simulate the merger of well-resolved stars that can be approximated by barotropic structures, such as white dwarfs or main sequence stars. The gravity solver conserves angular momentum to machine precision, thanks to a correction algorithm. This code uses HPX parallelization, allowing the overlap of work and communication and leading to excellent scaling properties to solve large problems in shorter time frames.

“This paper demonstrates how an asynchronous task-based runtime system can be used as a practical alternative to Message Passing Interface to support an important astrophysical problem,” Diehl said.

The research outlines the current and planned areas of development aimed at tackling a number of physical phenomena connected to observations of transients.

“While our particular research interest is in stellar mergers and their aftermath, there are a variety of problems in computational astrophysics that Octo-Tiger can address with its basic infrastructure for self-gravitating fluids,” Motl said.

The animation (https://www.youtube.com/watch?v=hg9MQNLLJw4) was prepared by Shiber, who says: “Octo-Tiger shows remarkable performance both in the accuracy of the solutions and in scaling to tens of thousands of cores. These results demonstrate Octo-Tiger as an ideal code for modeling mass transfer in binary systems and in simulating stellar mergers.”

Scientists have attempted for years to balance the potent pain-relieving properties of opioids with their numerous negative side effects — with mostly mixed results.

Work by John Traynor, Ph.D., and Andrew Alt, Ph.D., and their team at the University of Michigan Edward F. Domino Research Center, funded by the National Institute on Drug Abuse, seeks to side-step these problems by harnessing the body’s own ability to block pain.

All opioid drugs — from poppy-derived opium to heroin — work on receptors that are naturally present in the brain and elsewhere in the body. One such receptor, the mu-opioid receptor, binds to natural pain-killers in the body called endogenous endorphins and enkephalins. Drugs acting on the mu-opioid receptor can cause addiction as well as unwanted side effects like drowsiness, problems with breathing, constipation and nausea.

“Normally, when you are in pain, you are releasing endogenous opioids, but they’re just not strong enough or long lasting enough,” says Traynor. The team had long hypothesized that substances called positive allosteric modulators could be used to enhance the body’s own endorphins and enkephalins. In a new paper published in PNAS, they demonstrate that a positive allosteric modulator known as BMS-986122 can boost enkephalins’ ability to activate the mu-opioid receptor.

What’s more, unlike opioid drugs, positive allosteric modulators only work in the presence of endorphins or enkephalins, meaning they would only kick in when needed for pain relief. They do not bind to the receptor in the way that opioids do instead binding in a different location that enhances its ability to respond to the body’s pain-relieving compounds.

“When you need enkephalins, you release them in a pulsatile fashion in specific regions of the body, then they are metabolized quickly,” explains Traynor. “In contrast, a drug like morphine floods the body and brain and sticks around for several hours.”

The team demonstrated the modulator’s ability to stimulate the mu-opioid receptor by isolating the purified receptor and measuring how it responds to enkephalins. “If you add the positive allosteric modulator, you need a lot less enkephalin to get the response.”

Additional electrophysiology and mouse experiments confirmed that the opioid receptor was more strongly activated by the body’s pain-relieving molecules leading to pain relief. In contrast the modulator showed much reduced side effects of depression of breathing, constipation and addiction liability.

Their next goal is to measure their ability to enhance activation of endogenous opioids under conditions of stress or chronic pain, explains Traynor, to ensure that they are effective but don’t lead to more dangerous responses like depression of breathing.

“While these molecules won’t solve the opioid crisis,” says Traynor, “they could slow it and prevent it from happening again because patients in pain could take this type of a drug instead of a traditional opioid drug.”

Story Source:

Materials provided by Michigan Medicine – University of Michigan. Original written by Kelly Malcom. Note: Content may be edited for style and length.

A new study sequencing the genome of four species of sifakas, a genus of lemurs found only in Madagascar’s forests, reveals that these animals’ taste for leaves runs all the way to their genes, which are also more diverse than expected for an endangered species.

Sifakas are folivores, meaning that the bulk of their diet is composed of leaves. Leaves can be difficult to digest and full of toxic compounds meant to prevent them from being eaten. Unlike our carefully selected spinach, tree leaves also don’t taste great, and are not very nutritious.

Because of that, leaf-eaters typically have all sorts of adaptations, such as a longer digestive tract with special pouches where bacteria help break down the food.

In a new study appearing April 23 in Science Advances, researchers sequenced genomes from Coquerel’s (Propithecus coquereli), Verreaux’s (P. verreauxi), golden-crowned (P. tattersalli), and diademed (P. diadema) sifakas. The individuals sequenced had been wild-born but were housed at the Duke Lemur Center, with the exception of two Verreaux’s sifakas, one wild and one born in captivity.

These four species are found in different habitats in Madagascar, ranging from arid deciduous forests to rainforests, but share a similar diet.

The genomes showed molecular evidence for adaptations to neutralize and eliminate leaves’ toxic compounds, optimize the absorption of nutrients, and detect bitter tastes. Their genome shows patterns of molecular evolution similar to those found in other distantly related herbivores, such as the colobus monkeys from Central Africa, and domestic cattle.

Yet despite being such fine-tuned leaf-eating machines, sifakas can eat more than just leaves. They eat lots of fruits when those are in season and will also happily munch on flowers.

“Sifakas can take advantage of foods that are higher energy and are more nutrient dense, and can fall back and subsist on leaves in times of scarcity,” said Elaine Guevara, assistant research professor of Evolutionary Anthropology at Duke University and lead author of the study.

This dietary flexibility may have given them an advantage over their strictly leaves-only or fruit-only cousins in the face of threats such as forest fragmentation and disturbance.

Indeed, the analysis also showed that sifakas are genetically more diverse than would be expected for a critically endangered species on an island of shrinking habitats.

“These animals do seem to have very healthy levels of genetic diversity, which is very surprising,” said Guevara

Guevara and her team gauged genome heterozygosity, which is a measure of genetic diversity and an indicator of population size. Species at high risk for extinction tend to have only small populations left, and very low heterozygosity.

Sifakas do not follow this pattern and show far higher heterozygosity than other primates or other species of critically endangered mammals. Heterozygous populations tend to be more resilient to threats such as climate change, habitat loss, and new pathogens.

However, sifakas have very long generation times, averaging 17 years, so the loss of genetic diversity may take decades to become obvious. Guevara says that the genetic diversity found in this study may actually reflect how healthy populations were 50 years ago, prior to a drastic increase in deforestation rates in Madagascar.

“Sifakas are still critically endangered, their population numbers are decreasing, and habitat loss is accelerating drastically,” said Guevara.

There is still room for optimism. By not being picky eaters, sifakas may be less sensitive to deforestation and habitat fragmentation than primates with more restricted diets, allowing them to survive in areas with less-than-pristine forests.

“I’ve seen sifakas at the Lemur Center eat dead pine needles,” said Guevara. “Their diet is really flexible.”

Their greater genetic diversity may therefore mean that there is still hope for sifakas, if their habitats receive and maintain protection and strategic management.

“Sifakas still have a good chance if we act. Our results are all the more reason to do everything we can to help them,” said Guevara.

This work was funded by the Center for the Advanced Study of Human Paleobiology at The George Washington University, Duke University, and the Wenner-Gren Foundation. Genome sequencing and assembly were funded by National Human Genome Research Institute grant U54 HG003273 to Richard Gibbs (HGSC, Baylor College of Medicine).

About the size of a Rubik’s cube and encased in clear acrylic, the seismometer has a sleek, consumer-ready look. The device’s geophone detects incoming ground motion, while onboard hardware and software translate the geophone’s electrical signals into a digital waveform. The device has detected all earthquakes over magnitude 3.0 around Los Angeles since September 2020.

When earthquakes are stronger than the alert threshold set by the user, the device can sound the onboard alarm for on-site warning, send a text message to local subscribers of the regional warning service, and can be controlled from a smartphone.

He presented her research on the device at the Seismological Society of America (SSA)’s 2021 Annual Meeting.She also won a SSA Student Travel Grant, the only high school student among all recipients, to attend the conference free of charge. She is a student at Palos Verdes Peninsula High School in Rolling Hills Estates. He thanks her science research class teacher, Melissa Klose, for her guidance on scientific research methods and her support in pursuing research opportunities.

He researched, designed, built, and tested the entire device over a summer and fall spent at home under COVID-19 restrictions. Her home lab occupies a corner of a bedroom with “bedside drawers full of little wires and extra geophones and components.” she said.

There was also the bathroom she borrowed where the bright light was good for soldering. For acrylic laser cutting, her dad helped her drag a table out of the garage into the yard as a safety precaution.

“I did — don’t tell my mom — but I did one time have a little bit of a fire,” she admitted.

The seismometer device fills a gap in current earthquake early warning systems, He said, by providing a consumer-friendly, low-cost but built-for-purpose alternative to more expensive, scientific-grade systems like the West Coast’s ShakeAlert system. Her device offers a way for people in earthquake zones to gain a few to tens of seconds of warning to take action and automatically shut down utilities and machinery at work.

He has set up a nonprofit, Melior Earth, to help her get the device to those who need an inexpensive earthquake early warning system. “I do have hopes that I would be able to provide this to lower-income families and neighborhoods with less earthquake-proof infrastructure,” she said.

Quiet Under Quarantine

He got the idea for the seismometer after reading a paper about the unusual seismic “quiet” that descended over the earth when COVID-19 lockdowns brought a halt to much human activity. “I was wondering whether I would be able to measure that from my own home,” she recalled, “and then that quickly evolved into, I wonder if I can measure in my own home and apply it to earthquake early warning?”

She began reading about earthquake early warning and building a giant three-ring binder of highlighted papers, including many from SSA journals. One of her favorite researchers in the field was Richard M. Allen, director of the Berkeley Seismology Lab.

“I really enjoyed the way he explained earthquake early warning systems and the current systems’ limitations,” He said.

The research gave He the confidence that she could build a low-cost device for earthquake early warning, taking a consumer-based approach versus the conventional public station-based approach. After that, it was time to figure out the components, the programming and the design. She didn’t have much expertise going into the project, however, given much of the skills and knowledge needed were outside of school curriculum.

“I went to an MIT hackathon the other day, and what they said is that the secret for hackers is that they just google everything, right?” she said. “And that’s kind of like what I did for this project, like, oh, I don’t know how this works, just google it!'”

As He will discuss in her SSA presentation, the device evolved over time as her skills improved and she solved design problems along the way. Along with its alert and notification functions, the final design contains a data card that can hold up to four years’ worth of standard earthquake waveform files that can also be used for seismological studies.

“Hey, You Guys Hear That?”

He plugged in her first seismometer one night after midnight last September. “And then I went to sleep, and then the next day I woke up and there had been an earthquake in Los Angeles and I was like, oh, it’s fate!”

She compared the seismic signal captured by her device to one produced by a U.S. Geological Survey station near her house, “and the waveform looked the same,” she recalled.

One of the early successes of her testing period came when “my family was all in the living room and we were all talking and the device started beeping and I said, ‘Hey, you guys hear that?’ And they were like, ‘is it an earthquake?’ and then the pendant lights started shaking,” she said.

The seismometer has since successfully detected several recent earthquakes in Southern California, and He has competed in science fairs at her school district and Los Angeles County. There, she won the International Science and Engineering Fair (ISEF) Finalist award, which moves her on to compete at the international level next. In addition, she won the Association of Women Geoscientists Award, the Cheryl Saban Self-Worth Foundation for Women & Girls 1st Place Award and Scholarship, and the Professional Engineers in California Government’s Marylin Jorgenson-Reece Award of Excellence and Scholarship.

He, who turned 17 in February, is working on getting a utility patent for the device. She plans to use her nonprofit to drive consumer adoption for the device, especially making earthquake early warning accessible for the lower-income countries, regions and population.

“The whole point of it is that it would be a consumer product, but I’m not focused on the monetary gain of it,” she explained. “I’m more focused on the science of it and just the impact in general on people and on earthquake disaster prevention.”

The exoskeleton is externally powered by motors and controlled by an algorithm. When the researchers optimized it for speed, participants walked, on average, 42 percent faster than when they were wearing normal shoes and no exoskeleton. The results of this study were published April 20 in IEEE Transactions on Neural Systems and Rehabilitation Engineering.

“We were hoping that we could increase walking speed with exoskeleton assistance, but we were really surprised to find such a large improvement,” said Steve Collins, associate professor of mechanical engineering at Stanford and senior author of the paper. “Forty percent is huge.”

For this initial set of experiments, the participants were young, healthy adults. Given their impressive results, the researchers plan to run future tests with older adults and to look at other ways the exoskeleton design can be improved. They also hope to eventually create an exoskeleton that can work outside the lab, though that goal is still a ways off.

“My research mission is to understand the science of biomechanics and motor control behind human locomotion and apply that to enhance the physical performance of humans in daily life,” said Seungmoon Song, a postdoctoral fellow in mechanical engineering and lead author of the paper. “I think exoskeletons are very promising tools that could achieve that enhancement in physical quality of life.”

Walking in the loop

The ankle exoskeleton system tested in this research is an experimental emulator that serves as a testbed for trying out different designs. It has a frame that fastens around the upper shin and into an integrated running shoe that the participant wears. It is attached to large motors that sit beside the walking surface and pull a tether that runs up the length of the back of the exoskeleton. Controlled by an algorithm, the tether tugs the wearer’s heel upward, helping them point their toe down as they push off the ground.

For this study, the researchers had 10 participants walk with five different modes of operation. They walked in normal shoes without the exoskeleton, with the exoskeleton turned off and with the exoskeleton turned on with three different modes: optimized for speed, optimized for energy use, and a placebo mode adjusted to make them walk more slowly. In all of the tests, participants walked on a treadmill that adapts to their speed.

The mode that was optimized for speed — which resulted in the 42 percent increase in walking pace — was created through a human-in-the-loop process. An algorithm repeatedly adjusted the exoskeleton settings while the user walked, with the goal of improving the user’s speed with each adjustment. Finding the speed-optimized mode of operation took about 150 rounds of adjustment and two hours per person.

In addition to greatly increasing walking speed, the speed-optimized mode also reduced energy use, by about 2 percent per meter traveled. However, that result varied widely from person to person, which is somewhat expected, given that it was not an intentional feature of that exoskeleton mode.

“The study was designed to specifically answer the scientific question about increasing walking speed,” Song said. “We didn’t care too much about the other performance measures, like comfort or energy. However, seven out of 10 participants not only walked faster but consumed less energy, which really shows how much potential exoskeletons have for helping people in an efficient way.”

The settings that were optimized specifically for energy use were borrowed from a previous experiment. In the current study, this mode decreased energy use more than the speed-optimized settings but did not increase speed as much. As intended, the placebo mode both slowed down participants and boosted their energy use.

Better, faster, stronger

Now that the researchers have attained such significant speed assistance, they plan to focus future versions of the ankle exoskeleton emulator on reducing energy use consistently across users, while also being more comfortable.

In considering older adults specifically, Collins and his lab wonder whether future designs could reduce pain caused by weight on joints or improve balance. They plan to conduct similar walking tests with older adults and hope those provide encouraging results as well.

“A 40 percent increase in speed is more than the difference between younger adults and older adults,” said Collins. “So, it’s possible that devices like this could not only restore but enhance self-selected walking speed for older individuals and that’s something that we’re excited to test next.”

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Materials provided by Stanford University. Original written by Taylor Kubota. Note: Content may be edited for style and length.

One of the challenges in creating these so-called synthetic embryos is to generate all the cell types normally found in a young embryo before it implants into the wall of the uterus. Some of these cells eventually give rise to the placenta. Others become the amniotic sac in which the fetus grows. Both the placenta and the amniotic sac are crucial for the survival of the fetus, and defects in these embryo components are major causes of early pregnancy loss.

A group of scientists from Gladstone Institutes, the Center for iPS Cell Research and Application (CiRA) from Kyoto University, and the RIKEN Center for Biosystems Dynamics Research in Kobe, Japan, has now demonstrated the presence of precursors of the placenta and the amniotic sac in synthetic embryos they created from mouse stem cells.

“Our findings provide strong evidence that our system is a good model for studying the early, pre-implantation stages of embryo development,” says Kiichiro Tomoda, PhD, research investigator at the recently opened iPS Cell Research Center at Gladstone and first author of the study published in the journal Stem Cell Reports. “Using this model, we will be able to dissect the molecular events that take place during these early stages, and the signals that the different embryonic cells send to each other.”

Ultimately, this knowledge might help scientists develop strategies to decrease infertility due to early embryonic development gone awry.

The new findings could also shed light on a defining property of the earliest embryo cells that has been difficult to capture in the lab: their ability to produce all the cell types found in the embryo and, ultimately, the whole body. Scientists refer to this property as “totipotency.”

“Totipotency is a very unique and short-lived property of early embryonic cells,” says Cody Kime, PhD, an investigator at the RIKEN Center for Biosystems Dynamics Research and the study’s senior author.

“It has been much harder to harness in the lab than pluripotency,” he adds, referring to the ability of some cells to give rise to several — but not all — cell types. “A very exciting prospect of our work is the ability to understand how we can reprogram cells in the lab to achieve totipotency.”

Growing the Fundamental Components of Early Embryos in the Lab

To generate synthetic embryos, the scientists started from mouse pluripotent stem cells that normally give rise to the fetus only — not the placenta or amniotic sac. They can grow these cells, called epiblast stem cells, and multiply them indefinitely in the lab.

In previous work, the team had discovered a combination of nutrients and chemicals that could make epiblast stem cells assemble into small cell structures that closely resemble pre-implantation embryos. In fact, the structures could even reach the implantation stage when transferred into female mice, though they degenerated shortly thereafter.

“This meant that we might successfully reprogram the epiblast cells to revert to an earlier stage, when embryonic cells are totipotent, and provided a clue to how we might generate both the fetus and the tissues that support its implantation,” explains Tomoda, who is also a program-specific research center associate professor at CiRA.

To build on that work and better understand the reprogramming process, the scientists needed molecular resolution. In their new study, they turned to single-cell RNA sequencing, a technique that allows scientists to study individual cells based on the genes they turn on or off.

After analyzing thousands of individual cells reprogrammed from epiblast stem cells, and sifting the data through computer-powered analyses, they confirmed that, after 5 days of reprogramming, some cells closely resembled all three precursors of the fetus, the placenta, and the amniotic sac.

Moreover, as they were grown in the lab for a few more days, the three cell types displayed more distinct molecular profiles with striking similarity to real embryonic model cells. This is the same as would be expected during the growth of a normal embryo, when the three tissues acquire distinct physical properties and biological functions.

“Our single-cell RNA-sequencing analysis confirms the emergence in our synthetic embryo system of the cell types that lead to the three fundamental components of an early mammalian embryo,” says Kime. “In addition, it unveils in amazing detail the genes and biological pathways involved in the development of these precursors and their maturation into specific tissues.”

This knowledge provides a comprehensive backdrop against which to understand the mechanisms of early embryo development and the possible causes of its failure.

For now, the scientists plan to work on ways to increase the efficiency of their reprogramming process, so as to reliably produce large amounts of pre-implantation-like synthetic embryos for further studies. This would allow them to carry out experiments that were up to now unthinkable, such as large-scale screens for gene mutations that disrupt early embryos. And it may shed light on the causes of pregnancy loss due to early embryo failure.

They also want to better understand the molecular steps involved in reprogramming. In particular, they plan to look earlier than 5 days into the reprogramming process, with the hope of pinpointing truly totipotent cells at the origin of their synthetic embryos.

“The discovery that we could reprogram cells to adopt earlier, more pluripotent states revolutionized developmental biology 15 years ago,” says Tomoda, referring to the discovery of induced pluripotent stem cells by his and Kime’s mentor, Nobel Laureate Shinya Yamanaka.

“In the last few years, the field of synthetic embryology utilizing stem cells has seen a true explosion,” he says. “Our method of generating synthetic embryos is simpler than others, and quite efficient. We think it will be a great resource for many labs.”