Even images obtained by the world’s best ground-based telescopes are blurry due to the atmosphere’s shifting pockets of air. While seemingly harmless, this blur obscures the shapes of objects in astronomical images, sometimes leading to error-filled physical measurements that are essential for understanding the nature of our universe.

Now researchers at Northwestern University and Tsinghua University in Beijing have unveiled a new strategy to fix this issue. The team adapted a well-known computer-vision algorithm used for sharpening photos and, for the first time, applied it to astronomical images from ground-based telescopes. The researchers also trained the artificial intelligence (AI) algorithm on data simulated to match the Vera C. Rubin Observatory’s imaging parameters, so, when the observatory opens next year, the tool will be instantly compatible.

While astrophysicists already use technologies to remove blur, the adapted AI-driven algorithm works faster and produces more realistic images than current technologies. The resulting images are blur-free and truer to life. They also are beautiful — although that’s not the technology’s purpose.

“Photography’s goal is often to get a pretty, nice-looking image,” said Northwestern’s Emma Alexander, the study’s senior author. “But astronomical images are used for science. By cleaning up images in the right way, we can get more accurate data. The algorithm removes the atmosphere computationally, enabling physicists to obtain better scientific measurements. At the end of the day, the images do look better as well.”

The research will be published March 30 in the Monthly Notices of the Royal Astronomical Society.

Alexander is an assistant professor of computer science at Northwestern’s McCormick School of Engineering, where she runs the Bio Inspired Vision Lab. She co-led the new study with Tianao Li, an undergraduate in electrical engineering at Tsinghua University and a research intern in Alexander’s lab.

When light emanates from distant stars, planets and galaxies, it travels through Earth’s atmosphere before it hits our eyes. Not only does our atmosphere block out certain wavelengths of light, it also distorts the light that reaches Earth. Even clear night skies still contain moving air that affects light passing through it. That’s why stars twinkle and why the best ground-based telescopes are located at high altitudes where the atmosphere is thinnest.

“It’s a bit like looking up from the bottom of a swimming pool,” Alexander said. “The water pushes light around and distorts it. The atmosphere is, of course, much less dense, but it’s a similar concept.”

The blur becomes an issue when astrophysicists analyze images to extract cosmological data. By studying the apparent shapes of galaxies, scientists can detect the gravitational effects of large-scale cosmological structures, which bend light on its way to our planet. This can cause an elliptical galaxy to appear rounder or more stretched than it really is. But atmospheric blur smears the image in a way that warps the galaxy shape. Removing the blur enables scientists to collect accurate shape data.

“Slight differences in shape can tell us about gravity in the universe,” Alexander said. “These differences are already difficult to detect. If you look at an image from a ground-based telescope, a shape might be warped. It’s hard to know if that’s because of a gravitational effect or the atmosphere.”

To tackle this challenge, Alexander and Li combined an optimization algorithm with a deep-learning network trained on astronomical images. Among the training images, the team included simulated data that matches the Rubin Observatory’s expected imaging parameters. The resulting tool produced images with 38.6% less error compared to classic methods for removing blur and 7.4% less error compared to modern methods.

When the Rubin Observatory officially opens next year, its telescopes will begin a decade-long deep survey across an enormous portion of the night sky. Because the researchers trained the new tool on data specifically designed to simulate Rubin’s upcoming images, it will be able to help analyze the survey’s highly anticipated data.

For astronomers interested in using the tool, the open-source, user-friendly code and accompanying tutorials are available online.

“Now we pass off this tool, putting it into the hands of astronomy experts,” Alexander said. “We think this could be a valuable resource for sky surveys to obtain the most realistic data possible.”

The study, “Galaxy image deconvolution for weak gravitational lensing with unrolled plug-and-play ADMM,” used computational resources from the Computational Photography Lab at Northwestern University.

Shigella infections cause fever, stomach pain, and prolonged, sometimes bloody diarrhea for as long as a week. The bacteria sicken 450,000 people each year in the US alone. Although most people recover on their own, children and those with weakened immune systems are at risk of Shigella infections spreading to their bloodstream and causing kidney damage. Shigella infections are a significant cause of sickness and disability, but it’s difficult to study the bacteria because it only sickens primates like humans and apes — not animals easy to study in a lab. The bacteria cannot infect more typical lab animals such as mice.

Previous research had looked at how Shigella interacts with gasdermin-B, a critical part of our immune system that helps protect us against infection. Gasdermin-B is member of a protein family called gasdermin, which includes gasdermin-A, -B, -C, -D, -E and -F. It was thought that when gasdermin-B detects an invader, such as bacteria, it begins to poke holes in the cell’s wall, causing it to burst open and release chemicals that induce inflammation and call reinforcements from the immune system. But the past research studies on gasdermin-B were contradictory; some confirmed its role in cell death during infection, but others contradicted the idea.

UConn School of Medicine immunologist Jianbin Ruan and a team of colleagues from UConn Health wanted to clarify whether gasdermin-B actually does cause cell death in the case of microbial invasion; they also wanted to figure out why it doesn’t do this when Shigella is the invader.

The team needed to take a close look at gasdermin-B. They expressed the protein, purified it, and then cooled the protein down to very low temperatures so it would hold still while they took pictures of it with an electron microscope.

“We collected hundreds of thousands of images to build the 3D models of protein molecules at the atomic level. Through these models we will understand what these proteins look like and how they do their job,” said Chengliang Wang, research fellow in the Ruan lab and first author of the study.

Their research confirms previous research and provides evidence that Shigella bacteria grab onto a specific segment of gasdermin-B in humans. However, the mouse version of the protein has a different shape that prevents Shigella from latching onto it, resulting in the rapid clearance of the bacteria and preventing infection. This finding helps explain why Shigella is unable to infect mice.

Since human gasdermin-B can be configured in six slightly differing proteins, or isoforms, the team expressed all six then looked at how these isoforms behaved inside cells, and they found something surprising: some of the isoforms of gasdermin-B did indeed poke holes to cause cell death — but other isoforms did not.

“Previously, people didn’t understand why studies contradicted each other. We show that only two of the isoforms of gasdermin-B cause pyroptosis, or cell death,” says Ruan. Those two isoforms contain a specific protein segment that is absent in the other gasdermin-B isoforms, as shown by their cryogenic electron microscopy structure.

The finding may explain many mysteries of cell death, and life. Cancer cells, for example, are notoriously long lived and unlikely to die via pyroptosis. It may be that these cancer cells express only gasdermin-B isoforms that don’t poke holes in cell walls.

However, we don’t yet know what these other isoforms are doing. It may be that the different isoforms of gasdermin-B play significant and distinctive roles depending on where they are in the body, and different cell types preferentially express different isoforms.

“The protein structures that our team discovered have significant implications for drug development. Specifically, they can inform the design of small molecule drugs that modulate gasdermin-B activity,” explains Ruan. “These drugs could potentially be used to treat a range of conditions, including cancer, inflammatory and autoimmune diseases, and infectious diseases by either suppressing or enhancing the immune response. Our findings thus hold promise for the development of novel therapies to address these pressing medical needs.”

The researchers, including several scientists from the University of Colorado Boulder, published their findings today in the journal Science.

To tell the stories of horses in the West, the team closely examined about two dozen sets of animal remains found at sites ranging from New Mexico to Kansas and Idaho. The researchers come from 15 countries and multiple Native American groups, including the Lakota, Comanche and Pawnee nations.

“What unites everyone is the shared vision of telling a different kind of story about horses,” said William Taylor, a corresponding author of the study and curator of archaeology at the CU Museum of Natural History. “Focusing only on the historical record has underestimated the antiquity and the complexity of Indigenous relationships with horses across a huge swath of the American West.”

For many of the scientists involved, the research holds deep personal significance, added Taylor, who grew up in Montana where his grandfather was a rancher.

“We’re looking at parts of the country that are extraordinarily important to the people on this project,” he said.

The researchers drew on archaeozoology, radiocarbon dating, DNA sequencing and other tools to unearth how and when horses first arrived in various regions of today’s United States. Based on the team’s calculations, Indigenous communities were likely riding and raising horses as far north as Idaho and Wyoming by at least the first half of the 17th Century — as much as a century before records from Europeans had suggested.

Groups like the Comanche, in other words, may have begun to form deep bonds with horses mere decades after the animals arrived in the Americas on Spanish boats.

The results line up with a wide range of Indigenous oral histories.

“All this information has come together to tell a bigger, broader, deeper story, a story that natives have always been aware of but has never been acknowledged,” said Jimmy Arterberry, co-author of the new study and tribal historian of the Comanche Nation in Oklahoma.

Study co-author Carlton Shield Chief Gover agreed, noting that the love of horses may be one thing that extends across societies and borders.

“People are fascinated by horses. They’ve grown up with horses,” said Shield Chief Gover, a citizen of the Pawnee Nation of Oklahoma and curator for public anthropology at the Indiana University Museum of Archaeology and Anthropology. “We can talk to one another through our shared love of an animal.”

Mud Pony

For many Native American communities that shared love goes a long way back.

The Pawnee, for example, tell the story of “Mud Pony,” a boy who began seeing visions of strange creatures in his sleep.

“He makes these little mud figurines of these animals he sees in his dreams, and, overnight, they become alive,” Shield Chief Gover said. “That’s how you get horses.”

European historical records from the colonial period, however, have tended to favor a more recent origin story for horses in the West. Many scholars have suggested that Native American communities didn’t begin caring for horses until after the Pueblo Revolt of 1680. During this event, Pueblo people in what is today New Mexico temporarily overthrew Spanish rule, releasing European livestock in the process.

Taylor, also an assistant professor of anthropology at CU Boulder, and his colleagues didn’t think it fit as an origin story for the relationships between humans and horses in the West: “We thought: There’s something fishy about this story.”

Clues in bone

With funding from the U.S. National Science Foundation (NSF), they formed an equine dream team that includes archaeologists from the University of Oklahoma and University of New Mexico. Geneticist Ludovic Orlando and Lakota scholar Yvette Running Horse Collin took part from the University of Toulouse.

“This research demonstrates how multiple different types of data can be integrated to address the fascinating historical question of how and when horses spread across the West,” said NSF Archaeology program director John Yellen.

The researchers began collecting as much data as they could on horses remains from the West. DNA evidence, for example, suggests that most Indigenous horses had descended from Spanish and Iberian horses, with British horses becoming more common in the 18^th and 19^th Centuries.

“Our analyses show it was born and raised locally,” Taylor said. “It was cared for, and when that animal passed, there was extraordinary significance to that event.”

The remains of this horse, along with several others from the study, also seemed to date back to around the turn of the 17th Century, decades before the start of the Pueblo Revolt.

How animals like it arrived in Wyoming isn’t clear, but it’s likely that Europeans weren’t involved in their initial transport.

Shield Chief Gover explained that few Indigenous people will be surprised by the results of the study. But the team’s findings may help to illustrate for academic scientists just how important these animals were to the history of Indigenous peoples. The Pawnee, who lived in Nebraska, for example, rode horses on twice-a-year buffalo hunts, traveling farther and faster into the “sea of grass” of the Great Plains. Comanche also galloped on horseback to hunt buffalo, while owning a lot of horses was a sign of wealth.

“I don’t want to diminish the reverence and the respect we have for horses,” Arterberry said. “We see them as gifts the Creator gave us, and, because of that, we survived and thrived and became who we are today.”

Respecting horses

Study co-author Chance Ward, a master’s student in Museum and Field Studies at CU Boulder, would like to see the archaeology community begin to treat those relationships with more respect. He was born and raised on the Cheyenne River Reservation in South Dakota, which is home to four bands of the Lakota Nation. Ward grew up listening to his mother’s childhood stories about riding ponies in the Bear Creek community. His father’s parents started a ranch on the reservation where members of the family practice rodeo today.

He explained that many researchers don’t handle animal remains with the same care they reserve for cultural objects and human remains.

“They tend to be thrown into a box or bag where they hit against each other and break,” Ward said. “This project is a chance for us as Native people to put our voices out there and take better care of important and sacred animals in museum collections.”

In the study, published March 30 in Cell, the researchers investigated how a T cell-based immunotherapy was able to destroy melanoma tumors even though many of the tumor cells lacked the markers or “antigens” targeted by the T cells. They found that the T cells, in attacking the tumors, activated a swarm of neutrophils — which in turn killed the tumor cells that the T cells couldn’t eliminate. The findings could lead to new immunotherapies that harness this unexpected but potent antitumor immune response.

“We have tended to think of innate cells as immune cells that, at best, can help stimulate an initial T cell response to a tumor. In addition, many studies have shown that neutrophils support tumor progression, but here we reveal that they can have a critical role in eliminating and finishing off a tumor that would otherwise escape a T cell therapy,” said study co-senior author Dr. Taha Merghoub, deputy director of the Sandra and Edward Meyer Cancer Center, the Margaret and Herman Sokol Professor of Oncology Research and a professor of pharmacology at Weill Cornell Medicine, and co-director of the Ludwig Collaborative Laboratory.

“This work clearly shows us that the monolithic term ‘neutrophil’ needs to be more specific, based on the use of single-cell technology,” said co-senior author Dr. Jedd Wolchok, the Meyer Director of the Meyer Cancer Center and a professor of medicine at Weill Cornell Medicine, co-director of the Ludwig Collaborative Laboratory and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center. “In the past, this general term referred to a population of cells that were not thought to be helpful in controlling tumors. We now know that a subset of these cells is critical in optimizing engineered T cell therapies to overcome heterogeneity.”

Cancer immunotherapies, which harness or boost immune cells’ ability to attack malignant cells, have begun to revolutionize cancer treatment over the past decade. In some cases, these therapies have essentially cured advanced cancer patients who would have had no hope of survival otherwise. Yet for most cancers, immunotherapies are effective in only a minority of patients. In general, researchers still have much to learn about how anticancer immunotherapies work and how their effectiveness can be improved.

In the study, the researchers investigated an experimental immunotherapy that includes a drug to boost T cell activity and proliferation, plus T cells that have been engineered to recognize a melanoma-associated antigen. Tumors sometimes can evade an immunotherapy targeting a specific tumor antigen simply by ceasing to express that antigen — the tumor cells that don’t express the antigen are called “escape variants.” However, the researchers found that their boosted T cell therapy could eliminate melanomas, in standard mouse models, even when a large portion of the melanoma cells lacked the targeted antigen, Trp1.

Ultimately, they determined that the initial anti-tumor activity of the T cells against Trp1-expressing melanoma cells triggered a secondary tumor-killing response — from neutrophils. These white blood cells are best known as first-responders to infections and wounds. As members of the evolutionary older “innate” immune system, they do not target specific antigens in the way that T cells do. Yet the researchers concluded that the neutrophils summoned by their T-cell immunotherapy were indeed responsible for killing off the remaining, non-Trp1-expressing melanoma cells — at least in part by secreting the highly reactive molecule nitric oxide.

As part of the study, the researchers identified a characteristic gene expression pattern in the antitumor neutrophils, and found that in a widely used database on melanoma patients, the greater presence of this gene-expression “signature” in biopsied tumor samples was associated with better outcomes for patients.

The results were especially surprising because prior studies have shown that neutrophils around a tumor often act as allies of the tumor — the tumor co-opts them to help it survive and spread, which they do in part by suppressing other elements of antitumor immunity.

In any case, the new findings suggest that in the context of a strong immunotherapy that includes engineered T-cells targeting tumor antigens, and a general boosting of T-cell functions, neutrophils can play a significant antitumor role — in fact, an essential role in mopping up escape variant tumor cells that would otherwise keep the tumor alive.

“Conventional T cell-based therapies have been successful in treating cancers, but they are not as effective against heterogenous tumors, which have antigen escape variants that can be invisible to the immune system,” said Dr. Daniel Hirschhorn, an assistant professor of research in pharmacology at Weill Cornell Medicine. “It was incredibly surprising to discover that T cell-educated neutrophils can eliminate these ‘invisible’ tumor cells. This discovery highlights the importance of mobilizing multiple arms of the immune system in the fight against cancer.”

The researchers now are continuing to study these anti-tumor neutrophils, to determine how they can best be induced and directed — as cancer-fighters on their own, or as enhancers of other immunotherapies.

“I also hope that we can find a way to use measures of these antitumor neutrophils in tumor biopsies as biomarkers that help us choose the best therapies for patients,” Dr. Merghoub said.