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Power of 3

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Partha Mitra at the Shanghai Natural History Museum in China where he was giving a talk to children on how birds learn to sing.

By Daniel Dunaief

Throw a giant, twisted multi-colored ball of yarn on the floor, each strand of which contains several different colored parts. Now, imagine that the yarn, instead of being easy to grasp, has small, thin, short intertwined strings. It would be somewhere between difficult and impossible to tease apart each string.

Instead of holding the strings and looking at each one, you might want to construct a computer program that sorted through the pile.

That’s what Partha Mitra, a professor at Cold Spring Harbor Laboratory, is doing, although he has constructed an artificial intelligence program to look for different parts of neurons, such as axons, dendrites and soma, in high resolution images.

Partha Mitra at the Owl Cafe in Tokyo

Working with two dimensional images which form a three dimensional stock, he and a team of scientists have performed a process called semantic segmentation, in which they delineated all the different neuronal compartments in an image.

Scientists who design machine learning programs generally take two approaches: they either train the machine to learn from data or they tailor them based on prior knowledge. “There is a larger debate going on in the machine learning community,” Mitra said.

His effort attempts to take this puzzle to the next step, which hybridizes the earlier efforts, attempting to learn from the data with some prior knowledge structure built in. “We are moving away from the purely data driven” approach, he explained.

Mitra and his colleagues recently published a paper about their artificial intelligence-driven neuroanatomy work in the journal Nature Machine Intelligence.

For postmortem human brains, one challenge is that few whole-brain light microscopic data sets exist. For those that do exist, the amount of data is large enough to tax available resources.

Indeed, the total amount of storage to study one brain at light microscope resolution is one petabyte of data, which amounts to a million megapixel images.

“We need an automated method,” Mitra said. “We are on the threshold of where we are getting data a cellular resolution of the human brain. You need these techniques” for that discovery. Researchers are on the verge of getting more whole-brain data sets more routinely.

Mitra is interested in the meso-scale architecture, or the way groups of neurons are laid out in the brain. This is the scale at which species-typical structures are visible. Individual cells would show strong variation from one individual to another. At the mesoscale, however, researchers expect the same architecture in brains of different neurotypical individuals of the same species.

Trained as a physicist, Mitra likes the concreteness of the data and the fact that neuroanatomical structure is not as contingent on subtle experimental protocol differences.

He said behavioral and neural activity measurements can depend on how researchers set up their study and appreciates the way anatomy provides physical and architectural maps of brain cells.

The amount of data neuroanatomists have collected exceeds the ability of these specialists to interpret it, in part because of the reduction in cost of storing the information. In 1989, a human brain worth of light microscope data would have cost approximately the entire budget for the National Institutes of Health based on the expense of hard disk storage at the time. Today, Mitra can buy that much data storage every year with a small fraction of his NIH grant.

“There has been a very big change in our ability to store and digitize data,” he said. “What we don’t have is a million neuroanatomists looking at this. The data has exploded in a systematic way. We can’t [interpret and understand] it unaided by the computer.”

Mitra described the work as a “small technical piece of a larger enterprise,” as the group tries to address whether it’s possible to automate what a neuroanatomist does. Through this work, he hopes computers might discover common principals of the anatomy and construction of neurons in the brain.

While the algorithms and artificial intelligence will aid in the process, Mitra doesn’t expect the research to lead to a fully automated process. Rather, this work has the potential to accelerate the process of studying neuroanatomy.

Down the road, this kind of understanding could enable researchers and ultimately health care professionals to compare the architecture and circuitry of brains from people with various diseases or conditions with those of people who aren’t battling any neurological or cognitive issues.

“There’s real potential to looking at” the brains of people who have various challenges, Mitra said.

The paper in Nature Machine Intelligence reflected a couple of years of work that Mitra and others did in parallel with other research pursuits.

A resident of Midtown, Mitra, his wife Tatiana and their seven-year-old daughter have done considerable walking around the city during the pandemic.

The couple created a virtual exhibit for the New York Hall of Science in the Children’s Science Museum in which they described amazing brains. A figurative sculptor, Tatiana provided the artwork for the exhibition.

Mitra, who has been at Cold Spring Harbor Laboratory since 2003, said neuroanatomy has become increasingly popular over the last several years. He would like to enhance the ability of the artificial intelligence program in this field.

“I would like to eliminate the human proofreading,” he said. “We are still actively working on the methodology.”

Using topological methods, Mitra has also traced single neurons. He has published that work through a preprint in bioRxiv.

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Christina Joselevitch

By Daniel Dunaief

Children knock on the door of 1313 Gluto Lane, a favorite house for Halloween. The resident, known for providing coveted confections at a rapid rate, immediately comes to the door, asks no questions about the Halloween costumes that might slow the process down and, with almost super-human speed, dumps candy into open bags and closes the door.

Word spreads about the house on Gluto Lane. Soon, the doorbell rings at a furious pace, with children eager to get the best candy of this difficult year and move on to the next house.

At first, with Trick or Treaters coming at a regular pace, the process works, but then, something goes awry, creepy music begins and the door doesn’t open.

That’s what’s happening in bipolar retinal cells in the goldfish Christina Joselevitch, a Postdoctoral Associate in the Neurobiology and Behavior Department at Stony Brook University’s Renaissance School of Medicine, is studying.

Known for their incredible speed at releasing neurotransmitters stored in circular vesicles, these bipolar retinal cells go through a depression in which they can’t release the neurotransmitter glutamate despite repeated signals for the release of the neurotransmitter.

“When you stimulate those cells very strongly, with two stimuli close apart, they suffer depression,” Joselevitch said. “Nobody knew why, if they’re able to signal constantly, they should suffer from depression.

To be sure, Joselevitch was working with extreme stimulation to probe the limits of the system and understand its underpinnings. This is not necessarily how these cells work. She said the researchers don’t know if retinal neurons experience synaptic depression under normal conditions and what function depression would have in bipolar cell physiology, in vision or in signaling processing in general.

In a recent publication in the Journal of Neuroscience, Joselevitch described at least two processes that contribute to this slowdown, which she describes as the rate limiting steps. The vesicles need to get to the membrane and they need to get ready to mature before they are release. Once vesicles move towards the cell membrane, they don’t immediately fuse and send their neurotransmitter into the synapse between cells. In some cells, such as the retinal photoreceptors and bipolar cells and in hair cells of the ear and lateral line in fish and in cells of the pineal gland, they gather in a ribbon close to calcium entry points.

Scientists have two theories of the ribbon function. The first is that it could act as a conveyor belt and speed up vesicle priming and delivery to the membrane and the second is that it could set a constant pace for vesicle delivery.

Joselevitch’s results suggest that the vesicles attach to the ribbon, where they go through a maturation process. These paired-pulse depressions don’t just occur in fish: they also affect the ability of mammalian cells to respond to a second stimulus.

These cellular phenomena show the limits of the system. Indeed, Joselevitch likened the process to a car that has reached its maximum speed. Pushing down harder or more on the accelerator won’t enable further acceleration.

The impact of this work is “broad,” she said. Studying this process could enable a stronger awareness of the steps in fast-acting processes in the nervous system. Such research could also provide an understanding about processes that go awry in various neurological diseases.

In an email, Professor Lonnie Wollmuth, who is the principal investigator for the Stony Brook lab in which Joselevitch works, described Joselevitch as “invaluable to our on-going efforts to study presynaptic mechanisms in the retina.” He wrote that she was an “outstanding and very careful scientist” who is “passionate” about her research and has served as a mentor for others in the lab.  Joselevitch has been working in Wollmuth’s lab for about 16 months.

Synaptic transmission is fundamental to all brain function, Wollmuth explained. “Changes in the strength of synaptic transmission underlie basic higher order brain functions like learning and memory,” the Stony Brook Professor wrote. Joselevitch’s experiments “reveal mechanisms of presynaptic vesicle release at all synapses and provide novel insights into the processing of vesicles at ribbon synapses.”

Based on Joselevitch’s work, Wollmuth’s lab has submitted a large National Institutes of Health grant to the National Eye Institute to study the molecular components of presynaptic release in the retina. She has also started to integrate her work with Alzheimer’s Disease, as proteins found in that disease disrupt the molecular machinery involved in presynaptic release.

A native of Brazil, Joselevitch has been at Stony Brook University since last July. She is on sabbatical with the University of São Paulo. She is hoping to participate in these studies in New York for a few more years.

She said she was “always a nerd,” and liked to study languages. With varying levels of proficiency, she speaks five languages: Portuguese, English, German, Dutch, and Spanish. At one point, she wanted to be an astronaut, but her mother Carmen dissuaded her from pursuing that interest.

Joselevitch had planned to return to Brazil to see her family in April, but had to cancel that plan because of a travel ban from the COVID-19 pandemic. She said her parents have been “good sports” and her father has bought a smartphone so he can talk through Skype or WhatsApp with his scientist daughter.

Joselevitch enjoys biking, hiking, singing and playing guitar and has been productive during the pandemic, writing papers and proposals. Stony Brook is nominating her work for consideration for the Warren Alpert Distinguished Scholar Award.

Wollmuth wrote that Joselevitch’s research forms “the foundation for future experiments to address the molecular components of vesicle dynamics.” Once they are identified, researchers can modulate and protect them in brain diseases.

Citing author James Joyce, Joselevitch explained her focus on neurons in the fish eye, which, she hopes, may lead to a broader understanding of neurology and disease. When asked why he wrote about Dublin when he could describe other places he’s visited, Joyce responded, “In the particular is contained the universal.”

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Jeremy Borniger. Photo from CSHL

By Daniel Dunaief

Much as New Yorkers might want to minimize sleep, even during the pandemic when the need to be active and succeed is hampered by limited options, the body needs rest not only for concentration and focus, but also for the immune system.

Recently, Assistant Professor Jeremy Borniger, who joined Cold Spring Harbor Laboratory in January, collaborated with his former colleagues at Stanford University to publish research in the journal Science Advances that sheds light on the mechanism involved in this linkage.

Doctors and researchers had known for a long time that the release of glucocorticoids like cortisol, a stress hormone, can suppress the ability to fight off an infection. “That happens in people that are chronically stressed, even after surgery,” said Borniger in a recent interview.

A comprehensive understanding of the link between neuronal cells that are active during stress and a compromised immune system could help develop new ways to combat infections. The Stanford-led study provides evidence in a mouse model of the neuronal link between stress-induced insomnia and a weakened immune system.

Ideally, scientists would like to understand the neural pathways involved, which could help them design more targeted approaches for controlling the immune system using natural circuitry, according to Borniger.

Scientists could take similar approaches to the therapies involved with Parkinson’s, depression and obesity to increase or decrease the activity of the immune system in various disease states, instead of relying on a broader drug that hits other targets throughout the body.

In theory, by controlling these neurons, their gene products or their downstream partners, researchers could offer a way to fight off infections caused by stress.

While their studies didn’t look at how to gauge the effect of various types of sleep, such as napping or even higher or lower quality rest, their efforts suggest that sleep can help protect against stress-triggered infections.

The total amount and the structure of sleep play roles in this feedback loop. The variability among people makes any broad categorization about sleep needs difficult, as some people function well with six hours of sleep, while others need closer to eight or nine hours per day.

“Scientists are still working out how the brain keeps track of how much sleep it needs to rest and recover,” Borniger explained. “If we can figure this out, then, in principle, we could mess with the amount of sleep one needs without jeopardizing health.”

Researchers don’t know much about the circuitry controlling sleep amount. Borniger recognizes that the conclusions from this study are consistent with what doctors and parents have known for years, which is that sleep is important to overall health. The research also identifies a brain circuit that may be responsible for the way sleep buffers stress and immune responses.

People who have trouble sleeping because of elevated stress from an upcoming deadline often have a flare up of diseases they might have had under control previously, such as herpes viruses or psoriasis. These diseases opportunistically reemerge when the immune system is weakened.

The major finding in this study is not that the connection exists, but that the researchers, including principal investigator Luis de Lecea and first author Shi-Bin Li at Stanford, found the neural components.

While the studies of these linkages in the hypothalamus of mice were consistent across individuals, the same can’t be said for anecdotal and epidemiological evidence in humans, in part because the mice in the study were genetically identical.

For humans, age, sex, prior experiences, diet, family history and other factors make the linkage harder to track.

Even though researchers can’t control for as many variables with humans as they can with mice, however, several other studies have shown that stress promotes insomnia and poor immune function.

Borniger emphasized that he is the second author on the paper, behind Li and was involved in tracking the immune system component of the work.

Borniger and de Lecea are continuing to collaborate to see if drugs that target the insomnia neurons block the effect of stress on the immune system.

Now that he has moved into the refurbished Demerec Laboratory at CSHL, Borniger plans to work on projects to investigate how to use the nervous system to control anti-tumor immunity in models of breast and colorectal cancer, among others.

By understanding this process, Borniger can contribute to ways to manipulate these cells and the immune system to combat cancer and other inflammatory diseases.

Ideally, he’d like to be a part of collaborations that explore the combination of manipulating nervous and immune systems to combat cancer.

Borniger came to Cold Spring Harbor Laboratory because he was eager to collaborate with fellow scientists on site, including those who look at the immune system and metabolism. He appreciates how researchers at the famed research center look at how bodies and the brain respond to a growing tumor and would like to explore how tumors “influence nerves and then, reciprocally, how nerves influence tumor progression.”

The first few steps towards working at CSHL started in 2018, when Tobias Janowitz, Assistant Professor at CSHL, saw a paper Borniger published on breast cancer and asked him to give a 15-minute talk as a part of a young scholars symposium.

Borniger grew up in Washington, DC, attended college at Indiana University, went to graduate school at Ohio State and conducted his post-doctoral work at Stanford. Coming to CSHL brings him back to the East Coast.

Borniger and his fiancée Natalie Navarez, Associate Director of Faculty Diversity at Columbia University, met when they were in the same lab at Stanford. The couple had planned to get married this year. During the pandemic, they have put those plans on hold and may get married at City Hall.

Borniger and Navarez, who live on campus at Hooper House at CSHL, look forward to exploring opportunities to run, hike and swim on Long Island.

The new CSHL researcher appreciates the new opportunities on Long Island.

“This sort of collaborative atmosphere is what I would have in my Utopian dream,” Borniger said.

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Taken around 1890, the photo above includes Lucas Cheadle’s great, great grandparents Martin Van Buren Cheadle and his wife Mary Vera with their children, from left, Overton, Ellis, Lurena and Thomas (who is Cheadle’s great grandfather).

By Daniel Dunaief

In joining Cold Spring Harbor Laboratory, Lucas Cheadle has continued his professional and personal journey far from his birthplace in Ada, Oklahoma.

Then again, his travels, which included graduate work in New Haven at Yale University and, most recently, post doctoral research in Boston at Harvard Medical School, wasn’t nearly as arduous or life threatening as the forced trip his ancestors had to take.

In 1837, Cheadle’s great, great, great grandparents had to travel from Pontotoc, Mississippi to southern Indian Territory, which is now near Tishomingo, Oklahoma as a part of the Trail of Tears. Native American tribes, including members of Cheadle’s family who are Chickasaw, cleared out of their lands to make way for Caucasian settlers.

Lucas Cheadle

Proud of his biracial heritage, which includes Chickasaw, Choctaw, and Cherokee lineages, Cheadle hopes to make his mark professionally in his studies of the development of the brain (see article on page B). At the same time, he hopes to explore ways to encourage other members of the Chickasaw tribe to enter the fields of science, technology, engineering and mathematics.

One of three sons of a mixed Chickasaw father named Robert Cheadle and a Caucasian mother named Cheryl, Cheadle would eventually like to provide the kind of internship opportunities through his own lab that he had during his high school years.

Indeed, during the summer of his junior year, Cheadle did a health care internship, in which he shadowed different types of physicians. He watched active surgeries and observed a psychiatrist during patient visits. After that summer, Cheadle thought he might become a psychiatrist as well because he knew he was interested in the study of the brain.

Down the road, Cheadle envisions having one or two people learn as interns in the lab during the summer. Longer term, Cheadle hopes other investigators might also pitch in to provide additional scientific opportunities for more Native American high school students.

Growing up in Oklahoma, Cheadle never felt he stood out as a member of the Chickasaw tribe or as a biracial student.

His father, Robert, was active with the tribe, serving as a tribal judge and then as a legislative attorney for the Chickasaw. His grandfather, Overton Martin Cheadle, was a legislator.

Through their commitment to the Chickasaw, Cheadle felt a similar responsibility to give back to the tribe. “It was an incredibly important part of their professional lives and it was a passion” to help others, he said. “I’m driven by that spirit.”

His father took people in who had nowhere to go. In a few cases, people he put up robbed the family. Even after they robbed him, Cheadle’s father took them back. When Robert Cheadle died earlier this year, one of the people whom Cheadle supported helped out with his funeral arrangements.

Driven to accomplish his mission as a scientist, Lucas Cheadle feels he can reach out to help high school students and others interested in science during his research journey.

“The better I can do, the more I can help,” Cheadle said. He hopes to “open doors for other people.”

With some of these efforts to encourage STEM participation among Native Americans, Cheadle hopes to collaborate with John Herrington, a Chickasaw astronaut who took a Native American flute into space during one of his missions. “It would be wonderful to discuss this” with Herrington, “if he has time for me,” said Cheadle.

In modern times, the Chickasaw tribe has made “good strides” in being successful. One challenge to that success, however, is that it has included assimilation.“The main goal is to hold onto the heritage as much as we can,” said Cheadle.

As for now, he plans to honor his heritage in his lab by “working hard to create a safe, respectful environment where people’s unique backgrounds and characteristics are supported and embraced. I try to create a space where diversity can thrive.”

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Lucas Cheadle. Photo from CSHL

By Daniel Dunaief

One of the newest additions to Cold Spring Harbor Laboratory’s neuroscience program, Lucas Cheadle, who is an assistant professor, is exploring the early environmental factors at a molecular level that shape the neurological development of the mouse visual system.

While nature and nurture combine to produce the individuals each life form becomes, Cheadle is focused on the ways nurture, specifically, shapes the pathways in the brain that affect the development of sight.

Microglia are an unlikely player in this environmentally-triggered development, as doctors and researchers previously saw these cells primarily as participants in neurinflammation.

That is not the case anymore, with Cheadle and other scientists demonstrating over the past decade or so that microglia play important parts in the healthy brain. Cheadle, specifically, has demonstrated that these cells play a role in experience-dependent circuit development.

Indeed, the process of circuit refinement in the developing brain, which Cheadle describe as being among the “most complex structures in the known universe,” is akin to a room full of half-full boxes, which represent synaptic connections between neurons.

The brain begins with numerous little boxes that make the room difficult to navigate. As the brain consolidates the important items into a smaller number of larger boxes and removes the smaller boxes, the room becomes more manageable.

This is consistent with what Cheadle has seen during refinement. A smaller number of synapses become stronger and are maintained, while others are removed. This promotes the efficiency and precision of neural processing, he explained.

When the contents of some of those boxes disappear, however, the result can lead to neurodegenerative diseases like Alzheimer’s, in which a person struggles to find memories that may have been unwittingly cleared out.

Cheadle, who most recently was a post doctoral researcher at Harvard Medical School, is exploring the way microglia shape the connections between the eyes and the brain between when a mouse is born and when it reaches one month of age.

His work has shown that microglial cells are required for the sensory-dependent phase of visual circuit development. Disrupting signals between microglia and neurons affects synapse elimination, akin to removing the smaller boxes, which is important for circuit function.

Indeed, prior to work Cheadle and others have done in recent years with these cells in the brain, researchers thought microglia in the brain were quiescent, or inactive, after birth, except for their role in brain injury, disease pathology and neuroinflammation.

Until the first week of life, microglia engulf and then digest synaptic connections between some neurons, in a process called phagocytosis. During the sensory-dependent phase of refinement in the third week after birth, which Cheadle demonstrated in a paper published this month in the journal Neuron, microglia stop phagocytosis and rely on cytokines to break down synapses.

The cytokine pathway Cheadle discovered, called TWEAK, which is a ligand expressed by microglia, and Fn14, a receptor expressed by neurons, becomes active between eye opening, which is around two weeks, and peaks at about four weeks old.

When mice don’t have exposure to important visual stimuli during this critical period, the circuit has too many synaptic connections, which reduces the effectiveness of the developing visual system.

While Cheadle is working on visual development, specifically, he is interested in the broader implications of this work in the context of the environmental signals that affect the development of the brain.

In that broader context, the processes involved in autism and schizophrenia could reflect a period in which individuals have an overabundance of synapses that weren’t sufficiently pruned and refined.

Despite the fact that researchers hypothesized that synaptic pruning may lead to these disorders decades ago, they still have a limited awareness of whether and how this might happen. Studying the way microglia contribute to healthy circuit development could provide important clues about these processes.

Some epidemiological evidence points to the linkage between immune activity and neurodevelopmental disorders. In 1918 and 1919, during the Spanish Flu pandemic, children born during that period had a higher incidence of an autism or schizophrenia later in life.

Other evidence shows an interaction between immune activation and neurodevelopmental dysfunction, including the genetic loci associated with such disorders and increased inflammatory markers in the blood and brains of people with such disorders. “There’s really no question that there is a link,” Cheadle explained. “The nature of the link is still poorly understood.”

While earlier epidemiological data raises questions about the current pandemic, it doesn’t provide a definitive answer because “we still don’t quite understand what the nuanced molecular factors are that link the immune activation to the increase in disease prevalence,” Cheadle suggested.

“There’s a real chance that having COVID during pregnancy may impact the development of the offsprings’ nervous systems as has been seen in other infections,” Cheadle wrote. “While it is not the current priority of COVID research, it certainly warrants studying.”

Cheadle hopes to understand the “underlying principals of disorders” he said.

A resident of Huntington, Cheadle lives five minutes from the lab. He plans to rent for now because he didn’t want to start a new lab and move into a new house at the same time.

Cheadle has hired a technician and is in the process of hiring another. A post doctoral scientist will join his lab in November.

Early on in his life, Cheadle said he was fascinated with the interface between the world and biology. He wanted to understand how human brains interpret the information that comes from our senses. Everything culminated, professionally, in his interest in neurobiological mechanisms.

Currently, Cheadle is also interested in the looming behavior of mice. In the field, when mice see a bird that is flying slowly overhead, they are more likely to make a mad dash for safety, running into weeds or for cover from a tree. When the bird, however, is flying too rapidly, the mice freeze.

“I’m intrigued to find out whether the dichotomy of fight or flight could be shifted by the function of microglia,” he said. “I like to understand something at a functional level and dissect it to a molecular level.”

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James Misewich Photo from BNL

By Daniel Dunaief

Even as the pandemic continues to cast a pall over the prospects for the economy, the federal government is finding ways to support science. Recently, as a part of a $625 billion award to a host of institutions, the Department of Energy earmarked $115 million over five years for a part of a project led by Brookhaven National Laboratory.

The science, called quantum information systems, could have applications in a wide range of industries, from health care to defense to communications, enabling higher levels of artificial intelligence than the current binary system computers have used for decades. By benefiting from the range of options between the 0s and 1s that typically dictate computer codes, researchers can speed up and enhance the development of programs that use artificial intelligence.

The investment “underscores the confidence the federal government has with respect to how important this technology is,” said James Misewich, the Associate Laboratory Director for Energy and Photon Sciences at BNL. “Despite the challenges of the time, this was a priority.”

Local leaders hailed the effort for its scientific potential and for the future benefit to the Long Island economy.

“I have seen strong support inside of Congress and the administration for funding requests coming out of the Department of Energy for ideas on how to move the DOE’s mission forward,” said U.S. Rep. Lee Zeldin (R-NY-1). “I have also seen a very high level of appreciation and respect for BNL, its leadership, its staff, its mission and its potential.”

Zeldin said the average American spends more time than ever engaging with technologies and other discoveries that were made possible by the first quantum revolution. “Here we are on the verge of a second quantum revolution and BNL is at the forefront of it,” Zeldin said.

Zeldin sees limitless possibilities for quantum information science, as researchers believe these efforts will lead to advancements in health care, financial services, national security and other aspects of everyday life. “This next round of quantum advancements seeks to overcome some of the vulnerabilities that were identified and the imperfections in the first wave,” he said.

State Senator James Gaughran (D-Northport) expects quantum science to provide a significant benefit to the region. “We believe this is going to be a major part of our economic future,” he said. “It is a huge victory for Long Island.”

The return on investment for the state and the federal government will also materialize in jobs growth. This is “going to employ a lot of people,” Gaughran said. “It will help to rebuild the type of economy we need on Long Island. The fact that we are on the front lines of that will lead to all sorts of private sector development.”

While the technology has enormous potential, it is still in early enough stages that research groups need to work out challenges before they can fully exploit quantum technology. BNL, specifically, will make quantum error correction a major part of their effort.

As quantum computers start working, they run into a limitation called a noisy intermediate scale quantum problem, or NISQ. These problems come from errors that lower the confidence of getting the right answer. The noise is a current limitation for the best quantum computers. “They can only go so far before you end up with an error that is fatal” to the computing process, Misewich said.

By using the co-design center for quantum advantage, Misewich and his partners hope to use the materials that “beat the NISQ error by having the combination of folks with a great team that are all talking to one another.”

The efforts will use a combination of classical computing and theory to determine the next steps in the process of building a reliable quantum information system-driven computer.

Misewich’s group is also focusing on communication. The BNL scientists hope to provide a network that enables distributed computing. In classical computing, this occurs regularly, as computer scientists distribute a problem over multiple computers.

Similarly, with quantum computing, scientists plan to distribute the problem across computers that need to talk to each other.

Misewich is pleased with the combination of centers that will collaborate through this effort. “The federal government picked these centers because they are somewhat complementary,” he said. The BNL-led team has 24 partners, which include IBM, Stony Brook University, SUNY Polytechnic Institute, Yale University, Princeton University, the Massachusetts Institute of Technology, Harvard University, Columbia University and Howard University, among others.

“We had to identify the best team and bring in the right people to fill the gaps,” Misewich explained.

Using a combination of federal funds and money from New York State, BNL plans to build a new beamline at the National Synchrotron Lightsource II, which will operate at very low temperatures, allowing scientists to study the way these materials work under real word conditions.

BNL would like the work they are doing to have an application in calculations in three areas: the theory of the nucleus, quantum chemistry, which explores ways to design better materials, and catalysis.

A quantum computer could help make inroads in some challenging calculations related to electron-electron interactions in superconducting materials, Misewich said, adding that the entire team feels a “tremendous sense of excitement” about the work they are doing.”

Indeed, the group has been working together for close to two years, which includes putting the team in place, identifying the problems they want to tackle and developing a compelling strategy for the research to make a difference.

The group is expecting to produce a considerable amount of research and will likely develop various patents that will “hopefully transfer the technology so companies can start to build next generation devices,” Misewich said.

Along with local leaders, Misewich hopes these research efforts will enable the transfer of this technology to a future economy for New York State.

This effort will also train a numerous graduate and post doctoral students, who will be the “future leaders that are going to drive that economy,” Misewich said.

The research will explore multiple levels of improvement in the design of quantum computers which they hope will all work at the same time to provide an exponential improvement in the ability of the computer to help solve problems and analyze data.

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Anže Slosar. Photo from BNL

By Daniel Dunaief

Ever since Ancient Romans and Greeks looked to the stars at night, humans have turned those pinpricks of light that interrupt the darkness into mythological stories.

Two years from now, using a state-of-the-art telescope located in Cerro Pachón ridge in Northern Chile, scientists may take light from 12 billion light years away and turn it into a factual understanding of the forces operating on distant galaxies, causing the universe to expand and the patterns of movement for those pinpricks of light.

While they are awaiting the commissioning of the Vera C. Rubin Observatory, researchers including Brookhaven National Laboratory Physicist Anže Slosar are preparing for a deluge of daily data — enough to fill 15 laptops each night.

An analysis coordinator of the Large Synoptic Survey Telescope’s dark energy science collaboration, Slosar and other researchers from around the world will have a unique map with catalogs spanning billions of galaxies.

Anže Slosar

“For the past five years, we have been getting ready for the data without having any data,” said Slosar. Once the telescope starts producing information, the information will come out at a tremendous rate.

“Analyzing it will be a major undertaking,” Slosar explained in an email. “We are getting ready and hope that we’ll be ready in time, but the proof is in the pudding.”

The Vera C. Rubin Observatory is named for the late astronomer who blazed a trail for women in the field from the time she earned her Bachelor’s Degree from Vassar until she made an indelible mark studying the rotation of stars.

Slosar called Rubin a “true giant of astronomy” whose work was “instrumental in the discovery of dark matter.”

Originally called the Large Synoptic Survey Telescope (LSST), the Rubin Observatory has several missions, including understanding dark matter and dark energy, monitoring hazardous asteroids and the remote solar system, observing the transient optical sky and understanding the formation and structure of the Milky Way.

The study of the movement of distant galaxies, as well as the way objects interfere with the light they send into space, helps cosmologists such as Slosar understand the forces that affect the universe as well as current and ancient history since the Big Bang.

According to Slosar, the observatory will address some of its goals by collecting data in five realms including examining large structures, which are clustered in the sky. By studying the statistical properties of the galaxies as a function of their distance, scientists can learn about the forces operating on them.

Another area of study involves weak lensing. A largely statistical measure, weak lensing allows researchers to explore how images become distorted when their light source passes near a gravitational force. The lensing causes the image to appear as if it were printed on a cloth and stretched out so that it becomes visually distorted.

In strong lensing, a single image can appear as two sources of light when it passes through a dense object. Albert Einstein worked out the mathematical framework that allows researchers to make these predictions. The first of thousands of strong lensing effects was discovered in 1979. Slosar likens this process to the way light behind a wine glass bends and appears to be coming from two directions as it passes around and through the glass.

The fourth effect, called a supernova, occurs when an exploding star reaches critical mass and collapses under its own weight, releasing enough light to make a distant star brighter than an entire galaxy. A supernova in the immediate vicinity of Earth would be so bright, “it would obliterate all life on Earth.”

With the observatory scanning the entire sky, scientists might see these supernova every day. Using the brightness of the supernova, scientists can determine the distance to the object.

Scientists hope they will be lucky enough to see a supernova in a strongly lensed galaxy. Strong lensing amplifies the light and would allow scientists to see the supernova that are otherwise too distant for the telescope to observe.

Finally, the observatory can explore galaxy clusters, which are a rare collection of galaxies. The distribution of these galaxies in these clusters and how they are distributed relative to each other can indicate the forces operating within and between them.

The BNL scientist, who is originally from Slovenia, is a group leader for the BNL team, which has seven researchers, including post docs. As the analysis coordinator of the dark energy science collaboration, he also coordinates 300 people. Their efforts, he said, involve a blend of independent work following their particular interests and a collective effort to prepare for the influx of data.

Slosar said his responsibility is to have a big-picture overview of all the pieces the project needs. He is thrilled that this project, which was so long in the planning and development stage, is now moving closer to becoming a reality. He said he has spent five years on the project, while some people at BNL have spent closer to 20 years, as LSST was conceived as a dark matter telescope in 1996.

Scientists hope the observatory will produce new information that informs current understanding and forms the basis of future theories.

As a national laboratory, BNL was involved in numerous phases of development for the observatory, which had several different leaders. The SLAC National Accelerator in Stanford led the development of the camera that will be integrated into the telescope. BNL will also continue to play a role in the data analysis and interpretation.

“Fundamentally, I just want to understand how the universe operates and why it is like this and not different,” said Slosar.

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COVID-era Human Language Analysis Lab Meeting in July, top row from left, MZ Zamani, Matthew Matero, Nikita Soni ; bottom row from left, Adithya Ganesan, Oscjar Kjell, Linh Pham and H. Andrew Schwartz in the middle. Photos taken July, 2020

By Daniel Dunaief

Computers might not be able to tell you how they are doing, unless they run a diagnostic test, but they might be able to tell you how you are doing.

Using artificial intelligence, a team of scientists at Stony Brook University recently received a $2.5 million grant from the National Institutes of Health to study how social media posts and mobile phone data may be able to predict excess drinking among restaurant workers.

By using data from texting, social media and mobile phone apps, these researchers, led by Andrew Schwartz, an Assistant Professor in the Department of Computer Science, are hoping to use artificial intelligence to predict excessive drinking.

According to the National Institute of Alcohol Abuse and Alcoholism, unhealthy drinking involves seven drinks a week for women and 14 for men.

Schwartz said the study hopes to be able to address whether the researchers, including Richard Rosenthal, the Director of Addiction Psychiatry at Stony Brook Medicine and Christine DeLorenzo, Associate Professor in the Departments of Biomedical Engineering and Psychiatry, could “say what the mood predicts how much participants will be drinking in the future.”

By analyzing the content of texts and social media posts, Schwartz and a team that also involves scientists from the University of Pennsylvania will explore whether an increase in stress is more likely to happen before an increase in drinking.

The researchers will study the effect of empathy, which can be health promoting and health threatening. “We believe AI-behavior-based measures will work better than questionnaires for detecting an unhealthy style of empathy,” Schwartz explained in an email. The AI will search for non-obvious patterns of social media posts and texts to determine which type of empathy a person might demonstrate and whether that empathy could lead to a drinking spiral.

Empathy theoretically may add to stress for bartenders and restaurant workers as they often listen to customers who share their tale of woe with food service professionals and are also in a social job.

Indeed, amid the pandemic, where levels of stress are higher during periods of uncertainty about public health and in which restaurant workers might be more likely concerned about their employment, this study could provide a way to understand how increases in alcohol consumption develop potentially to inform new ways to interrupt a negative spiral. “The extra stress of job security is heightened right now” for restaurant workers, among others, Schwartz said.

By validating AI against accepted tools, the researchers hope to gauge the AI-decoded link between emotion and unhealthy drinking behavior by aligning what an individual is expressing in social media with indicators of their emotional state and drinking.

Participants in the study are filling out brief surveys several times a day.

In the long run, the scientists hope this kind of understanding will allow future public health professionals to offer support services to people without the cost of having to administer numerous questionnaires.

The researchers had received word that their proposal had received the kind of score from the NIH that suggested they would likely get funded last July. They could have received positive funding news any time from November through May, which was when they learned that they had secured the financial support to pursue their research.

The topic of study is “extremely relevant,” he added, amid the current uncertainty and the potential for a second wave in the fall or winter.

“We’re interested in studying how unhealthy drinking develops and how it plays out in people’s daily lives,” Schwartz said.

Social media provides a window into the emotional state of the participants in the research.

To be sure, the researchers aren’t looking at how people post about drinking, per se, online. Instead, the scientists are looking at how people in the study answer questions about their drinking in the regular questionnaires.

The researchers came together for this effort through the World Well Being Project, which is a research consortium in collaboration with scientists at the University of Pennsylvania, Stony Brook University and Stanford.

The project involves groups of computer scientists, psychologists and statisticians to develop new ways to measure psychological and medical well-being based on language in social media, according to the group’s web site, which describes “Authentic Happiness.”

In a recent study, 75,000 people voluntarily completed a personality questionnaire through Facebook and made their status updates available. Using these posts, the researchers were able to predict a user’s gender 92 percent of the time just by studying the language of their status updates.

Researchers in substance use approached the World Well Being Project, which Schwartz is a part of, about the topic of unhealthy alcohol use.

The Artificial Intelligence methods Schwartz is developing and that the scientists are testing through this grant are aimed at understanding how a person is changing their language over time through their digital footprint.

In the future, Schwartz believes this approach could contribute to personalized medicine.

“When someone is most at risk, apps that are validated [may be able to] detect these sorts of patterns,” he said. While this study doesn’t provide a personalized patient app, it should provide the tools for it, he explained.

Optimizing this work for false positive and false negatives is a part of this study. The researchers need to create the tools that can make predictions with minimal false positives and false negatives first and then hope it will be used to interact with patients.

In this type of artificial-intelligence driven work, researchers typically need about 500 words to come up with a conclusion about a person’s emotional state. A goal of this work is to get that number even lower.

Fotis Sotiropoulos, the Dean of the College of Engineering and Applied Sciences, offered his enthusiastic support for this effort.

Schwartz is blazing a trail in advancing AI tools for tackling major health challenges,” Sotiropoulos said in a statement. “His work is an ingenious approach using data-science tools, smart-phones and social media postings to identify early signs of alcohol abuse and alcoholism and guide interventions.”

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Ivar Strand Photo courtesy of BNL

By Daniel Dunaief

Ivar Strand had to put on a suit at home to interview virtually for a new job.

In the midst of the pandemic, Brookhaven National Laboratory was looking for a Manager of Research Partnerships in the Strategic Partnership Program and, despite the fact that the lab was limiting the people who were on site, was moving forward to fill a job opening.

“It was a strange situation,” Strand said, but the job piqued his interest, particularly because he’d be working with Martin Schoonen, the leader of BNL’s Strategic Partnership Programs office and an associate laboratory director for environment, biology, nonproliferation and national security. Schoonen and Strand, who worked together at Stony Brook in the late 1990’s, have known each other for over 25 years.

While Strand worked at Stony Brook as an Assistant Vice President of Sponsored Programs, he had a visiting appointment at BNL for five years, from 2005 to 2010. Several of the staff at BNL “remembered who I was, which made the transition a little bit easier,” he said.

Strand most recently worked at Long Island University, where he was the Executive Director in the Office of Sponsored Projects.

Schoonen was pleased to welcome Strand to the BNL fold. “[He is] taking on a pivotal role to develop contractual arrangements with potential partners and assist with growing and diversifying the labs funding sources,” Schoonen said in a statement.

In effect, Strand is facilitating collaborations among institutions. He will facilitate not only the connections and collaborations, but also encourage broadening and deepening professional connections to create either project specific or ongoing strategic partnerships

Strand will work to increase the awareness of the capabilities BNL can provide to researchers, entrepreneurs, and investors. The main drawback in a job he started on May 26 has been that he hasn’t been able to “build face-to-face relationships,” he said. Speaking with people for the first time through web-based platforms is not the same as running into someone who is walking across the site.

Building the relationship with the Department of Energy also represents a new challenge for Strand, who has previously worked with educational institutions as well as with Northwell Health.

“I spent my whole career building partnerships at various research institutions,” he said. After facilitating those collaborations, Strand has entered into agreements and then moved one. At BNL, he has the added dynamic of “making sure it satisfies the requirements of the DOE.” The scope of his work comprises all the research funding coming into the lab outside of the direct money that comes from the DOE, which represents about 90 percent of the funds for research at the lab.

Some of these other initiatives are collaborative, which involve DOE funds that also have a requirement to find a company to contribute financially, such as the Technology Commercialization Fund.

Working with finance and departmental business managers, Strand oversees the non-direct DOE money that comes in. When educational institutions and companies participate, particularly to supply funding, Strand and the strategic partnership team become a part of the conversation.

BNL often competes against the other national labs for major projects. Once the government selects a winner, as it did for the construction of the Electron Ion Collider, the DOE often asks the lead on the project to tap into the expertise and talents of the other institutions. When BNL recently won the EIC contract over Jefferson Laboratory in Virginia, the DOE asked BNL to partner with Jefferson to build the facility. New York State originally agreed to contribute $100 million to the construction of the EIC. Strand said the lab is hopeful that the commitment would come through.

In addition to the scientific discoveries that the EIC will bring, it is also a construction project that will provide the state with jobs. “I’m involved in some of the discussions in order to provide information about the project,” Strand said.

The transition to a government lab will require Strand to maneuver through structured agreements from the DOE, which is a bit of a challenge. The DOE uses structured agreements, while educational institutions also do but often are willing to use the agreements the sponsors propose.

Strand is pleased that BNL recently received approval to participate in the Atom Consortium, which was started by Glaxo and the University of California at San Francisco. The negotiation had been going on for several years. “It allows us to enhance our big data computing capabilities and expertise,” he explained.

Strand is excited about rejoining BNL. “I’ve always wanted to work in the lab and understand how best to build collaborations under the government umbrella,” he said.

Strand hoped his unconventional approach to some of the partnership challenges will work in the context of the structured environment of a national laboratory.

Indeed, in 2007, when he was working at Stony Brook, the university received the funds to buy a supercomputer. The two institutions, however, had decided to house the supercomputer at BNL, which made it a “challenging transaction” for all parties. He and others had to help Stony Brook become an enlisted partner, which allowed BNL to house the supercomputer on site.

In the bigger picture, Strand said he and Schoonen are reviewing where the lab will be from a strategic perspective in five years. In addition to industry, they are looking to collaborate with other federal sponsors with whom they haven’t traditionally partnered. They have to make sure that these efforts conform with DOE’s growth agenda.

A first-generation American whose parents were born in Norway, Strand said his parents met in the United States. A resident of South Setauket, Strand lives with his wife Maritza, who is an implementation specialist for ADT payroll. A tennis player and golfer, Strand alternates visiting and hosting his brother, who lives in Norway and is a veterinarian.

Strand is looking forward to his ongoing collaborations with Schoonen. “Having worked with him in the past, I have a lot of respect” for Schoonen, Strand said. “I jumped at the chance to be reunited with him. He’s an unbelievably great guy to work for.”

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Joel Hurowitz before the PIXL launch at the end of July. Photo by Tanya Hurowitz

By Daniel Dunaief

For six years, Joel Hurowitz worked as Deputy Principal Investigator on a team to build an instrument they would send to another planet.

Joel Hurowitz

An Assistant Professor of Geosciences at Stony Brook University, Hurowitz and the team led by Abigail Allwood at the NASA Jet Propulsion Laboratory created an instrument that would search for evidence of life that is likely long ago extinct on Mars.

The team designed a 10-pound machine (which will weigh less than four pounds in Mars’s lower gravity environment) that is about the size of a square lunchbox and houses x-ray equipment that can search along the surface of rocks for life that may have existed as long as three to four billion years ago.

Mars’s surface environment became less hospitable to life starting around three billion years ago, when the planet lost most of its atmosphere, causing the surface to dry out and become extremely cold. Surface life at this point likely became extinct.

Called the Planetary Instrument for X-ray Lithochemistry, or PIXL, the instrument was one of seven that lifted off at the end of July as part of a Mars 2020 mission. The Perseverance rover will land at the Jezero Crater on the Red Planet on February 18th, 2021.

After all that work, Hurowitz had planned to watch the launch with his family in Florida, but the pandemic derailed that plan.

“I got to watch the launch with my family,” Hurowitz said. He was on two zoom conferences, one with the Mars 2020 team and the other with members of the Department of Geosciences at Stony Brook. “It was a really special experience” and was the “best teleconference of the last six months,” he said.

As the rocket makes its 35.8 million mile journey to Mars, the JPL team will turn on the PIXL to monitor it, run health checks and do routine heating of the components to make sure it is operating. After the rocket lands, the rover will go through a commissioning period. Numerous subsystems need to be checked out, explained Hurowitz.

The first test for the PIXL will be to analyze a calibration target the researchers sent to Mars, to make sure the measurements coincide with the same data they collected numerous times on Earth. This ensures that the instrument is “working the way we want it to. That’ll happen in the first 40 sols.”

A sol is a day on Mars, which is slightly longer by about 40 minutes than a day on Earth.

Once it passes its calibration test, the PIXL can start collecting data. Hurowitz described the instrument as “incredibly autonomous.” It sits at the end of the rover’s arm. When the scientists find a rock they want to explore, the PIXL moves an inch away from the surface of the rock and opens its dust cover. The scientists take pictures with a camera and a set of laser beams. These beams help determine whether the PIXL is an optimal distance from the rock. If it isn’t, the instrument manipulates itself, using struts that allow it to extend or retract away from the rock.

Once PIXL gets in the right position, it fires an X-ray beam into the rock. The beam is about the diameter of a human hair. The x-ray that hits the rock is like wind going through chimes. Rather than make a familiar sound, the elements in the rock emit a specific x-ray signal as the atoms return to their ground state. Putting together the signals from the rock enables Hurowitz and the PIXL crew to determine its chemistry.

Even though the rocks are likely a combination of numerous elements, they “separate themselves cleanly in our spectra,” Hurowitz said. The SBU Geosciences expert expects the elements in the rocks to have different proportions than on Earth. Mars, for example, has more iron than sodium. A granite rock on Earth would likely have considerable sodium and some potassium, with a little iron.

Hurowitz and the PIXL team will be looking for rocks that may have evidence of prokaryotic organisms that are Mars’s versions of similar species found in undisturbed areas of Western Australia, where researchers discovered ancient fossilized life.

The rocks in Australia contain the oldest accepted fossilized forms of life, which are about 3.5 billion years old and are considered the best analogues for what the PIXL team might find on Mars.

In Australia, which is where Allwood grew up, scientists discovered microbial mats, which are single-celled organisms that build up, one layer after another, into a colony. These mats worked together to build up towards the sunlight, which fuels their metabolism. They use raw chemicals in the environment like dissolved sulfur, iron and manganese.

The Martian mats, if they find them, likely had to adapt to considerably different conditions than on Earth. The Martian environment may not have had large oceans or river systems and craters filled with lakes.

The scientists won’t be able to look for an individual microbe, but rather for indirect signals, such as laminated structures that formed in ways that are unique to microbial communities.

Hurowitz, Allwood and the PIXL team are looking for clues from an unusual lamination in the rock that they would likely associate with a microbial mat. By looking closely at the lamination, they may be able to develop hypotheses about whether a mat was taking chemicals out and depositing it to make a mineralized home for itself.

If they find rocks of interest, the rover’s drill will collect a sample and hermetically seal it in a tube.

A future mission to Mars, planned for 2026, could retrieve some of these samples, which, when they return, could confirm the presence of life on Mars. PIXL will continue to operate as long as the filament in the x-ray tube lasts, which should be between 1,300 and 1,400 uses.

Allwood, who shared an office with Hurowitz when they worked together at the Jet Propulsion Laboratory, said she approached him when she started assembling a team.

Finding life on Mars would answer a question that has intrigued those on Earth for thousands of years, Allwood said. Such Martian life would indicate that “we’re not alone. There was life and it was next door,” she said.

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