The research, published in Cell Reports by Assistant Professor Kshitiz in collaboration with Dr. Junaid Afzal in the cardiology department at the University of California San Francisco, presents a method that accelerates maturation of human cardiac cells towards a state suitable enough to be a surrogate for preclinical drug testing.

“There is a very strong need to create human cardiac constructs for all sorts of applications. Small animal models just do not recapitulate human heart biology, and human samples are scarce,” says Kshitiz. “This matters because all drugs need to be tested for their toxicity to heart. It is widely believed that a large number of them unnecessarily fail clinical trials because we do not have human samples to test them with.”

Kshitiz and Afzal first identified the need to create a matured human cardiac tissue during their time together at Johns Hopkins Medicine.

“When methods were developed to differentiate human pluripotent stem cells to cardiac cells, it created a big hope that finally we will have human heart constructs to work with,” said Afzal. “While it is straightforward to get human cardiac cells, they are similar to fetal cells. What we need is adult cells.”

Cardiovascular safety is the number one cause for failure of preclinical drug development, and there is a long standing need to create human cardiac tissue models to test drugs for cardiotoxicity. Currently, the small animal heart models display vastly different biochemical, physiological, and genetic features from humans — making it difficult to replicate the human heart in preclinical studies. In particular, it is very difficult to perform metabolic assessment of current cardiac constructs. Heart beats continuously and is a highly metabolically active organ.

“Metabolic and redox maturation is critical for heart cells, and we are able to achieve it and possibly create a gold standard — fundamentally shifting our expectations of creating a metabolically mature cardiac tissue,” the researchers said.

In the study, the researchers utilized the cardiac biology in an adult human heart to rapidly mature differentiated cardiac cells into a more adult-like state. Within 30 days, the researchers achieved cardiac cells that displayed structural, mechanical, metabolic, and electrophysiological characteristics close to adult heart muscle.

The researchers are optimistic that this application will not only be used for preclinical drug testing, but can also be used in future precision disease modeling to study disease mechanisms and test for regenerative therapies. The researchers hope that the many drugs that fail unnecessarily due to non-human methods will be salvaged for cures for cancer, immune and neurological diseases.

UConn Health researchers Yamin Liu, Wenquang Du, Yasir Suhail, Pengyu Zong, Jianlin Feng, Visar Ajeti, Maya Yankova, Alix Deymier, and Lixia Yue also contributed to this study.

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Materials provided by University of Connecticut. Original written by Courtney Chandler. Note: Content may be edited for style and length.

Astronomers using Hubble and other telescopes have deduced that the star blew off a huge piece of its visible surface in 2019.

This has never before been seen on a star. Our petulant Sun routinely goes through mass ejections of its outer atmosphere, the corona. But those events are orders of magnitude weaker than what was seen on Betelgeuse. The first clue came when the star mysteriously darkened in late 2019. An immense cloud of obscuring dust formed from the ejected surface as it cooled. Astronomers have now pieced together a scenario for the upheaval. And the star is still slowly recovering; the photosphere is rebuilding itself. And the interior is reverberating like a bell that has been hit with a sledgehammer, disrupting the star’s normal cycle. This doesn’t mean the monster star is going to explode any time soon, but the late-life convulsions may continue to amaze astronomers.

Analyzing data from NASA’s Hubble Space Telescope and several other observatories, astronomers have concluded that the bright red supergiant star Betelgeuse quite literally blew its top in 2019, losing a substantial part of its visible surface and producing a gigantic Surface Mass Ejection (SME). This is something never before seen in a normal star’s behavior.

Our Sun routinely blows off parts of its tenuous outer atmosphere, the corona, in an event known as a Coronal Mass Ejection (CME). But the Betelgeuse SME blasted off 400 billion times as much mass as a typical CME!

The monster star is still slowly recovering from this catastrophic upheaval. “Betelgeuse continues doing some very unusual things right now; the interior is sort of bouncing,” said Andrea Dupree of the Center for Astrophysics | Harvard & Smithsonian in Cambridge, Massachusetts.

These new observations yield clues as to how red stars lose mass late in their lives as their nuclear fusion furnaces burn out, before exploding as supernovae. The amount of mass loss significantly affects their fate. However, Betelgeuse’s surprisingly petulant behavior is not evidence the star is about to blow up anytime soon. So the mass loss event is not necessarily the signal of an imminent explosion.

Dupree is now pulling together all the puzzle pieces of the star’s petulant behavior before, after, and during the eruption into a coherent story of a never-before-seen titanic convulsion in an aging star.

This includes new spectroscopic and imaging data from the STELLA robotic observatory, the Fred L. Whipple Observatory’s Tillinghast Reflector Echelle Spectrograph (TRES), NASA’s Solar Terrestrial Relations Observatory spacecraft (STEREO-A), NASA’s Hubble Space Telescope, and the American Association of Variable Star Observers (AAVSO). Dupree emphasizes that the Hubble data was pivotal to helping sort out the mystery.

“We’ve never before seen a huge mass ejection of the surface of a star. We are left with something going on that we don’t completely understand. It’s a totally new phenomenon that we can observe directly and resolve surface details with Hubble. We’re watching stellar evolution in real time.”

The titanic outburst in 2019 was possibly caused by a convective plume, more than a million miles across, bubbling up from deep inside the star. It produced shocks and pulsations that blasted off the chunk of the photosphere leaving the star with a large cool surface area under the dust cloud that was produced by the cooling piece of photosphere. Betelgeuse is now struggling to recover from this injury.

Weighing roughly several times as much as our Moon, the fractured piece of photosphere sped off into space and cooled to form a dust cloud that blocked light from the star as seen by Earth observers. The dimming, which began in late 2019 and lasted for a few months, was easily noticeable even by backyard observers watching the star change brightness. One of the brightest stars in the sky, Betelgeuse is easily found in the right shoulder of the constellation Orion.

Even more fantastic, the supergiant’s 400-day pulsation rate is now gone, perhaps at least temporarily. For almost 200 years astronomers have measured this rhythm as evident in changes in Betelgeuse’s brightness variations and surface motions. Its disruption attests to the ferocity of the blowout.

The star’s interior convection cells, which drive the regular pulsation may be sloshing around like an imbalanced washing machine tub, Dupree suggests. TRES and Hubble spectra imply that the outer layers may be back to normal, but the surface is still bouncing like a plate of gelatin dessert as the photosphere rebuilds itself.

Though our Sun has coronal mass ejections that blow off small pieces of the outer atmosphere, astronomers have never witnessed such a large amount of a star’s visible surface get blasted into space. Therefore, surface mass ejections and coronal mass ejections may be different events.

Betelgeuse is now so huge now that if it replaced the Sun at the center of our solar system, its outer surface would extend past the orbit of Jupiter. Dupree used Hubble to resolve hot spots on the star’s surface in 1996. This was the first direct image of a star other than the Sun.

NASA’s Webb Space Telescope may be able to detect the ejected material in infrared light as it continues moving away from the star.

With trillions of individuals migrating every year, insects are some of the most common migrating animals on Earth. They include species of renown, such as the monarch butterfly, as well as species of enormous societal and environmental importance, such as locusts, mosquitos, and bees. But even though insect migrants far outnumber better-known migrants, such as birds or mammals, their migration is the least understood form of long-range animal movement.

The problem, for the most part, has been methodological. “Studying insects on the move is a formidable challenge,” says first author Myles Menz, who conducted the research at MPI-AB and is now a lecturer at James Cook University in Australia. “They’re usually too numerous to mark and find again, and too small to carry tracking devices.”

Much of what we know about insect migration has come from studies that sample insects at a single moment in time, such as through radar or direct observation, which has left vast blank spots in our knowledge. “Understanding what insects do during migration, and how they respond to weather, is a last frontier in migration science,” says Menz.

The current study, which followed radio-tagged individuals in a light aircraft, is the first to continuously study nocturnal migrating insects in the wild and represents the longest distance over which any insect has been continuously tracked in the field. The team, which includes researchers from the MPI-AB and University of Konstanz in Germany and the University of Exeter in the UK, focused on the death’s-head hawkmoth—a large, nocturnal migrant that travels up to 4000 kilometers between Europe and Africa every year. Like many insects, the species is a multi-generational migrant, which means that no individual knows the entire route.

At the MPI-AB in Konstanz, Germany, the team reared caterpillars until adulthood in the laboratory to ensure that individuals were naïve. When moths emerged as adults, they were fixed with radio tags weighing 0.2 grams—less than 15% of adults’ body weight. “The moths would probably eat more weight than that in a night, so these tags are extremely light for the insects,” says Menz.

The researchers released the tagged moths and waited for flight to begin, after which they chose a single individual to follow at a time. The team followed 14 moths each for up to 80 kilometers or 4 hours—a stretch long enough to be considered migratory flight—using antennas mounted on a Cessna airplane to detect precise locations every five to 15 minutes. Insects were followed in the south-south-west direction from Konstanz into the Alps, which follows the route taken by hawkmoths towards the Mediterranean and Northwest Africa.

Due to practical constraints of flying in an aircraft, the scientists tracked moths continuously until the insects stopped on route. “When you’re in an airplane, it becomes extremely difficult to wait for the insects to begin migrating again because you would have to be in the air when this happens, which could be anytime in the night,” says senior author Martin Wikelski, a movement ecologist from the MPI-AB and University of Konstanz, who piloted the plane during the study.

The results show that moths maintained perfectly straight trajectories for long distances during flight. This was not because they waited for favorable tailwinds. Rather, they employed a range of flight strategies to buffer against prevailing winds, allowing them to hold their course throughout the night. When winds were favorable, they flew high and slow, allowing the air to carry them. But during harsh headwinds or cross winds, they flew low to the ground and increased speed to keep control of their path.

Says Menz: “For years it was assumed that insect migration was mostly about getting blown around. But we show that insects are capable of being great navigators, on par with birds, and are far less vulnerable to wind conditions than we thought.”

“By showing that it is technically possible to continuously monitor individual insects over migration, and to observe their flight behavior in detail, we hope to inspire more studies to answer many more big questions in this area.”

For the study authors, the next step is to answer the question of how moths are able to maintain such straight lines. “Based on past lab work, it’s possible that the insects are using internal compasses, both visual and magnetic, to chart their way around the world,” says Menz.

Did primordial black holes help or hinder formation of the universe’s first stars, eventually born about 100 million years later?

Supercomputer simulations helped investigate this cosmic question, thanks to simulations on the Stampede2 supercomputer of the Texas Advanced Computing Center (TACC), part of The University of Texas at Austin.

“We found that the standard picture of first-star formation is not really changed by primordial black holes,” said Boyuan Liu, a post-doctoral researcher at the University of Cambridge. Liu is the lead author of computational astrophysics research published August 2022 in the Monthly Notices of the Royal Astronomical Society.

In the early universe, the standard model of astrophysics holds that black holes seeded the formation of halo-like structures by virtue of their gravitational pull, analogous to how clouds form by being seeded by dust particles. This is a plus for star formation, where these structures served as scaffolding that helped matter coalesce into the first stars and galaxies.

However, a black hole also causes heating by gas or debris falling into it. This forms a hot accretion disk around the black hole, which emits energetic photons that ionize and heat the surrounding gas.

And that’s a minus for star formation, as gas needs to cool down to be able to condense to high enough density that a nuclear reaction is triggered, setting the star ablaze.

“We found that these two effects — black hole heating and seeding — almost cancel each other out and the final impact is small for star formation,” Liu said.

Depending on which effect wins over the other, star formation can be accelerated, delayed or prevented by primordial black holes. “This is why primordial black holes can be important,” he added.

Liu emphasized that it is only with state-of-the-art cosmological simulations that one can understand the interplay between the two effects.

Regarding the importance of primordial black holes, the research also implied that they interact with the first stars and produce gravitational waves. “They may also be able to trigger the formation of supermassive black holes. These aspects will be investigated in follow-up studies,” Liu added.

For the study, Liu and colleagues used cosmological hydrodynamic zoom-in simulations as their tool for state-of-the-art numerical schemes of the gravity hydrodynamics, chemistry and cooling in structure formation and early star formation.

“A key effect of primordial black holes is that they are seeds of structures,” Liu said. His team built the model that implemented this process, as well as incorporating the heating from primordial black holes.

They then added a sub-grid model for black hole accretion and feedback. The model calculates at each timestep how a black hole accretes gas and also how it heats its surroundings.

“This is based on the environment around the black hole known in the simulations on the fly,” Liu said.

XSEDE awarded the science team allocations on the Stampede2 system of TACC.

“Supercomputing resources in computational astrophysics are absolutely vital,” said study co-author Volker Bromm, professor and chair, Department of Astronomy, UT Austin.

Bromm explained that in theoretical astrophysics, the ruling paradigm for understanding the formation and evolution of cosmic structure is to use ab initio simulations, which follow the ‘playbook’ of the universe itself — the governing equations of physics.

The simulations use data from the universe’s initial conditions to high precision based on observations of the cosmic microwave background. Simulation boxes are then set up that follow the cosmic evolution timestep by timestep.

But the challenges in computational simulation of structure formation lie in the way large scales of the universe — millions to billions of light years and billions of years — mesh with the atomic scales where stellar chemistry happens.

“The microcosm and the macrocosm interact,” Bromm said.

“TACC and XSEDE resources have been absolutely vital for us to push the frontier of computation astrophysics. Everyone who is at UT Austin — faculty members, postdocs, students — benefits from the fact that we have such a premier supercomputing center. I’m extremely grateful,” Bromm added.

“If we look into one typical structure that can form the first stars, we need around one million elements to fully resolve this halo or structure,” Liu said. “This is why we need to use supercomputers at TACC.”

Liu said that using Stampede2, a simulation running on 100 cores can complete in just a few hours versus years on a laptop, not to mention the bottlenecks with memory and reading or writing data.

“The overall game plan with our work is that we want to understand how the universe was transformed from the simple initial conditions of the Big Bang,” explained Bromm.

The structures that emerged from the Big Bang were driven by the dynamical importance of dark matter.

The nature of dark matter remains one of the biggest mysteries in science.

The clues of this hypothetical yet unobservable substance are undeniable, seen in the impossible rotational speeds of galaxies. The mass of all the stars and planets in galaxies like our Milky Way do not have enough gravity to keep them from flying apart. The ‘x-factor’ is called dark matter, yet laboratories have not yet directly detected it.

However, gravitational waves have been detected, first by LIGO in 2015.

“It is possible that primordial black holes can explain these gravitational wave events that we have been detecting over the past seven years,” Liu said. “This just motivates us.”

Said Bromm: “Supercomputers are enabling unprecedented new insights into how the universe works. The universe provides us with extreme environments that are extremely challenging to understand. This also gives motivation to build ever-more-powerful computation architectures and devise better algorithmic structures. There’s great beauty and power to the benefit of everyone.”

The study, “Effects of stellar-mass primordial black holes on first star formation,” was published August 2022 in the Monthly Notices of the Royal Astronomical Society. The study authors are Boyuan Liu, Saiyang Zhang, and Volker Bromm of the University of Texas at Austin. Liu is now at the University of Cambridge.

To accomplish this, the researchers began with 3D-printed lattice materials and incorporated networks of air-filled channels into the structure during the printing process. By measuring how the pressure changes within these channels when the structure is squeezed, bent, or stretched, engineers can receive feedback on how the material is moving.

These lattice materials are composed of single cells in a repeating pattern. Changing the size or shape of the cells alters the material’s mechanical properties, such as stiffness or hardness. For instance, a denser network of cells makes a stiffer structure.

This technique could someday be used to create flexible soft robots with embedded sensors that enable the robots understand their posture and movements. It might also be used to produce wearable smart devices, like customized running shoes that provide feedback on how an athlete’s foot is impacting the ground.

“The idea with this work is that we can take any material that can be 3D-printed and have a simple way to route channels throughout it so we can get sensorization with structure. And if you use really complex materials, then you can have motion, perception, and structure all in one,” says co-lead author Lillian Chin, a graduate student in the MIT Computer Science and Artificial Intelligence Laboratory (CSAIL).

Joining Chin on the paper are co-lead author Ryan Truby, a former CSAIL postdoc who is now as assistant professor at Northwestern University; Annan Zhang, a CSAIL graduate student; and senior author Daniela Rus, the Andrew and Erna Viterbi Professor of Electrical Engineering and Computer Science and director of CSAIL. The paper is published in Science Advances.

Architected materials

The researchers focused their efforts on lattices, a type of “architected material,” which exhibits customizable mechanical properties based solely on its geometry. For instance, changing the size or shape of cells in the lattice makes the material more or less flexible.

While architected materials can exhibit unique properties, integrating sensors is notoriously challenging. Engineers typically must place sensors on the outside, which is tough because the lattice is full of holes so there is little material to work with. Also, when sensors are placed on the outside, they are not fully integrated with the material and can be affected by noise that comes from a soft material’s movements.

Instead, Chin and her collaborators used 3D printing to incorporate air-filled channels directly into the struts that form the lattice. When the structure is moved or squeezed, those channels deform and the volume of air inside changes. The researchers can measure the corresponding change in pressure with an off-the-shelf pressure sensor, which gives feedback on how the material is deforming.

Because they are incorporated into the material, these “fluidic sensors” are more accurate than sensors placed on the outside of a structure.

“If you stretch out a rubber band, it takes a little time to come back into place. But since we are using air and the deformations are relatively stable, we don’t get these same time-varying properties. The information that comes out of our sensor is a lot cleaner,” Chin says.

“Sensorizing” structures

The researchers incorporate channels into the structure using digital light processing 3D printing. In this method, the structure is drawn out of a pool of resin and hardened into a precise shape using projected light. An image is projected onto the wet resin and areas struck by the light are cured.

But as the process continues, the sticky resin tends to drip and get stuck inside the channels. The researchers had to work quickly to remove excess resin before it was cured, using a mix of pressurized air, vacuum, and intricate cleaning.

“We will have to do more brainstorming from the design side to think about that cleaning process, since it is the main challenge,” she says.

They used this process to create several lattice structures and demonstrated how the air-filled channels generated clear feedback when the structures were squeezed and bent.

Building off these results, they also incorporated sensors into a new class of materials developed for motorized soft robots known as handed shearing auxetics, or HSAs. HSAs can be twisted and stretched simultaneously, which enables them to be used as effective soft robotic actuators. But they are difficult to “sensorize” because of their complex forms.

They 3D printed an HSA soft robot capable of several movements, including bending, twisting, and elongating. They ran the robot through a series of movements for more than 18 hours and used the sensor data to train a neural network that could accurately predict the robot’s motion.

Chin was impressed by the results — the fluidic sensors were so accurate she had difficulty distinguishing between the signals the researchers sent to the motors and the data that came back from the sensors.

“Materials scientists have been working hard to optimize architected materials for functionality. This seems like a simple, yet really powerful idea to connect what those researchers have been doing with this realm of perception. As soon as we add sensing, then roboticists like me can come in and use this as an active material, not just a passive one,” she says.

“Sensorizing soft robots with continuous skin-like sensors has been an open challenge in the field. This new method provides accurate proprioceptive capabilities for soft robots and opens the door for exploring the world through touch” says Rus.

In the future, Chin looks forward to finding new applications for this technique, such as creating football helmets tailored to a specific player’s head that have sensing capabilities within the internal structure. This could increase the accuracy of feedback from on-field collisions and improve player safety. She is also interested in utilizing machine learning to push the boundaries of tactile sensing for robotics.

This research was supported, in part, by the National Science Foundation, the Schmidt Science Fellows Program in partnership with the Rhodes Trust, an NSF Graduate Fellowship, and the Fannie and John Hertz Foundation.