It starts with a question and a possible explanation. From there, the leader tests to see whether he or she was right. If the initial information suggests the original possibility was accurate, the leader runs several other tests to confirm the result.

Scientists and researchers follow that formula to crack nature’s code. They tend to get excited when, for example, they find a certain gene appears to be involved in a particular disease. Researchers can be as disappointed as little league ballplayers after losing a close game if they find no such connection.

Jesse Gillis, an assistant professor of computational genomics at Cold Spring Harbor Laboratory, however, thinks many of those so-called negative results can be as constructive as finding positive ones. “Negative results are so valuable,” he said. Negative results help scientists understand all the available information and not just the usual suspects, especially in genetic disorders.

Often, tests for the role of key genes in diseases come up with some candidates almost every time, like P53, he said. P53 is a tumor suppressor gene, which means that, when it functions correctly, it prevents cells from developing into potentially deadly tumors. When other genes have some connection to a disease, they are often related to a gene like P53.

The interpretation of results is dominated by genes for which scientists already have considerable amounts of information. The interpretation of what is going on with numerous genes tends to be dominated by several important genes.

Gillis works in a field of computational biology in which researchers are looking for combinations of genes, RNA, and proteins that all could play a role in a disease. He studies a scientific field called “guilt by association,” in which combinations of mutations, signals, or defects might increase the likelihood of developing a complicated disorder, in which people with similar symptoms have a range of genetic differences.

He uses guilt by association to understand the combination of mutations which might increase the likelihood of developing a disorder like schizophrenia or autism.

Gillis hopes to be able to look closely into what these genes have in common to “be able to say when we have false positives.” In his opinion, attempts to give comprehensive lists of the genes causing complex disorders could produce false positives that could be as high as 50 percent. He says there is something of a specificity problem, where the overlaps among genes that might have a connection to schizophrenia are not specific enough.

Before he came to CSHL, Gillis conducted post-doctoral research in the laboratory of Paul Pavlidis, an associate professor at the University of British Columbia. Gillis impressed his former lab director. Gillis is “super-smart, serious and [a] skeptical scientist who is not afraid to question deep assumptions in our field,” Pavlidis offered.

Gillis said the notion of guilt by association is an older idea. Scaling that up to apply it to expressing a disease goes back to around the turn of the millennium, when scientists started applying computational principals to these data ranges.

Where Gillis hopes to make a difference is finding something meaningful to say based on the data, instead of echoing other findings.

Gillis, who grew up in Toronto, said he “always liked messy data.” He was not as excited by the typical experiment where scientists tested one hypothesis and the results either worked or they didn’t. He enjoyed studying data-driven discovery, where he could look at a combination of data that was diverse and potentially challenging to understand and interpret.

Gillis’s scientific curiosity is, in part, a product of his childhood environment. His father is a math professor, while his mother started her doctorate in developmental psychology by watching him play as a child.

Most of his American experiences have been on Long Island. He has been so busy setting up his lab — he arrived a year and a half ago — that he hasn’t had many opportunities to pursue his penchant for sailing.

Gillis hopes to have more data to work with in the coming years. “If I say genes are likely to have a property x or this set of genes is likely to have a property x, it matters how prevalent that property is,” he said. “If a gene is always important” then finding it has a role in a disease doesn’t “validate the reason it’s important in this context.”

The negative result might tell scientists more because “the gene not showing up is the more unusual finding.”

Their world stretches from the treetops of Madagascar to the rain forests of Brazil to the salmon feeding grounds of bears in Alaska.

They study a wide range of animals, at the same time that they dedicate their work to the survival of species with uncertain futures.

Russell Mittermeier, Carl Safina, and Patricia Wright not only share a connection to Stony Brook University and to conservation, but they are also three of six finalists for the biennial Indianapolis Prize, considered the top award for the world’s conservationists. The award, which is administered by the Indianapolis Zoo, considers conservation candidates from all over the world. The winner, who will receive the Eli Lilly Medal and a $250,000 prize, will be announced on May 13.

“I am very proud of these outstanding members of our faculty,” SBU President Stanley said through an emailed statement to the Times Beacon Record Newspapers.

The three finalists recently attended an Earth Day tweet-up at the Student Activity Center at Stony Brook, where they shared their views on the prize, on conservation, and on the Long Island ecosystem. It was the first-ever Tweet-Up for the University. Members of the school, including Stanley and representatives from the Indianapolis Zoo, attended the discussion.

“Having three of the six finalists from Stony Brook speaks to the institution’s tradition of academic excellence and commitment to field work that positively impacts genuine conservation,” Rob Shumaker, the vice president of Conservation & Life Sciences at the Indianapolis Zoo, said after the meeting.

On the positive side, the tweeting trio talked of a comeback for a bird of national symbolic importance that hasn’t nested on Long Island since Dwight Eisenhower was president.

“Here on Long Island, for the first time in 60 years, we have a nesting pair of bald eagles,” said Safina. The head of the Blue Ocean Institute, Safina has written six books on threats facing the world’s habitats.

One of the strongest pieces of advice each of the Stony Brook finalists offered is to see animals in their natural habitat.

“Once you get out there, you’re connected for life,” Mittermeier, a leading field biologist who is also the president of Conservation International, told a combination of about 200 people in attendance at the SAC and those gathered in a virtual crowd through Twitter.

“Visiting places is not a trivial part of the fight for wildlife conservation,” Safina echoed.

Indeed, in 2012, Stony Brook inaugurated a new research, education and conservation building on the boundary of Ranomafana National Park in Madagascar called NamanaBe Hall. Stanley attended the inauguration, along with dignitaries from Madagascar.

The university president agreed that the experience of seeing these animals in the wild brings a new perspective.

“Observing [creatures] in their natural habitat brings a completely new level of awareness and appreciation for them and it is an extraordinary experience,” Stanley said.

Wright, who has studied lemurs for over a quarter of a century, was recently featured in an Imax movie narrated by Morgan Freeman called “Island of Lemurs: Madagascar.” The film, which Wright has seen 16 times and includes footage of lemurs on that island, shows the interactions of lemur social groups. Back in her office after the tweet up, Wright shared a chart that tracks how one female lemur leader lost her role in a “hostile takeover,” only to assume the same position with another group.

Wright, who helped establish Ranomafana National Park in 1991, calls the lemurs “her family,” along with her daughter and her well-traveled graduate students who have been to Madagascar and Peru.

Mittermeier, meanwhile, discussed how conservation groups are looking to turn the 2016 Olympic spotlight for host city Rio de Janeiro on some of Brazil’s conservation efforts.

Conservation International is joining other groups to suggest that the mascot could either be the muriqui or the golden lion tamarin. The muriqui, which weighs between 10 and 20 pounds, is an endangered monkey that is found only in the Atlantic coast forests of Brazil. Mittermeier also is urging the Olympics to use the tamarin, a monkey with reddish brown hair around its head and face that is considered a conservation success story, as an image on gold medals.

While he won’t likely be making an appearance in Brazil, Stony Brook’s own mascot Wolfie prowled around the ballroom during the Earth Day Tweet-Up.

Stony Brook officials said they were pleased with their first-ever tweet up and are interested in hosting this type of event again. The talented trio said it would be an honor to win the prize and that it underscores the appreciation for the value of their work.

As for why conservation is important, Safina explained, “it’s about trying to be human without ruining the world.”

Wright said she felt she “couldn’t be a person if she let all these animals go extinct.”

Ivan Iossifov is using computer programs to try to understand the genetic piece of the autism puzzle. An assistant professor at Cold Spring Harbor Laboratory, Iossifov is comparing the genome of people with autism with the sequences from their unaffected siblings.

Iossifov explores areas of the genome where mutations might increase the risk of autism. He is searching for a “list of genes that, when you take it, can lead to autism directly or can increase the risk of a child being autistic,” he said. “Some genes are frequently mutated in autism.”

He can approach this mission by looking at “every nucleotide in each parent and each sibling,” he said. “We can zoom in on very particular genes.”

Historically, he said, genetic technology first allowed scientists to look for large-scale copy-number events, where a sequence of DNA might be repeated more frequently for one group of people than for another. As genetic sequencing has matured, however, he has been able to focus on nucleotide-level genetic variants, such as single base-pair substitutions.

“The new-generation sequencing technology becomes cheaper and faster amazingly quickly,” he said. “That does allow us to perform research that was unfeasible even five years ago.”

Iossifov said the research he’s conducting may help doctors and scientists understand some of the genetic components of autism. So far, his research shows that early genetic-based diagnosis is difficult. He estimates that he needs about ten times more genetic data in families before genetic-based diagnoses can become useful. While he said he is not an expert in autism, he said he strongly believes “that the earlier a child can be reliably diagnosed, the better.”

More broadly, Iossifov is interested in a large scope of neurodevelopment disorders as well as cancer. In the last few years, however, he’s focused considerable effort and attention on autism.
Autism, he explained, seems to require the kind of approach he has to research, looking at the big picture and narrowing that down to individual genes or even base pairs. So far, he has looked at the 1 percent of the nucleotides in the human genome that encode genes.

“We have been carefully examining each variant for its potential effect on the gene it belongs to,” he said. “We analyze thousands of families, focusing in on de novo variants,” variants present in a child and not in her parents.

Iossifov is now planning to extend his analysis over the complete genome. He is hoping to hire new staff before long, to help with data collection and analysis.

Iossifov is grateful for the backing of the Simons Foundation, which provided funding and supported the collection of many of the genetic samples he is studying. He hopes the foundation will continue to endorse efforts to scrutinize additional areas of the genome, even those that other scientists hadn’t previously considered, to find other regions where he might discover “interesting variants.”

Iossifov splits his time between Philadelphia, where his wife Ani Nenkova works in the Department of Computer and Information Science at the University of Pennsylvania, and Long Island. The couple have a four-year old son Pascal, whom they call “Paco.”
When he’s on Long Island, he enjoys visiting beaches. Iossifov said he speaks “one and a half” languages, although, at this point, he’s not sure which is the half. He grew up speaking Bulgarian, but his friends at home suggest he’s developed an American accent in his native tongue. “I apparently sound funny” speaking Bulgarian, he said.

Iossifov said his parents didn’t push him to do anything in particular, although he is following somewhat in the footsteps of his father, who is a retired chemist.

In terms of teaching their son about the world, Iossifov and Nenkova encourage him to understand that “he can go deeper,” in whatever he learns.

Iossifov is excited to continue working with autism. “Autism is a complex disorder and is highly prevalent. Any progress on autism would be great on many aspects.”

When it spreads, it becomes more difficult to treat. Understanding metastatic cancer presents significant challenges to doctors and scientists in part because the disease is different in the liver than it is in the lungs.

Lloyd Trotman, an associate professor at Cold Spring Harbor Laboratory, has created a mouse model of prostate cancer that becomes metastatic. By exploring what happens to cells in different areas, Trotman hopes to get a better understanding of cancer as it spreads.

“New technology allows us to tag cells when they are at the metastatic site,” he said. He can look at “how they differ from where they started.”

When prostate cancer becomes metastatic, the cells “forget about their identity,” Trotman said. They become more like cells that are developing, which means they are not as dependent on male hormones for their survival. This change in their identity makes them difficult to treat with hormone therapy.

By developing these metastatic models of prostate cancer, Trotman has been able to do preclinical studies of drugs designed to treat the original disease and its metastatic form. He has worked with scientists from Cornell University, the Dana-Farber Cancer Institute, and the Memorial Sloan Kettering Cancer Center.

“We can ask if a drug specifically is beneficial against metastatic cancer and especially against the hormone-refractory kind,” he said.
Trotman’s research also explores how cancers that were in remission become active again. “Most [treatments] will not be curative,” he said. “Why? If it works, but then the disease comes back, what is driving the disease? What is it that the drug is doing wrong at the point that it was looking good? What limit does the drug need to push to be curative?”

With his model of the disease, he can track the changes in a living animal. He can see how the cancerous cells are glowing in areas including the liver, lymph nodes, lungs, and bone. “Our hope is that by making these things visible at a very primitive level, we can see it first, then harvest it, and read the sequencing,” he said.

Trotman’s approach has won him the admiration of other scientists. “For an early career scientist, his work stands out as particularly innovative,” said Scott Lowe, a cancer biologist and chairman of the Geoffrey Beene Cancer Research Center at Memorial Sloan Kettering.
Lowe was deputy director of the cancer center at Cold Spring Harbor Laboratory, where he was involved in recruiting Trotman to join CSHL. “His research on an important cancer gene caught our attention,” Lowe said. He described Trotman as an “enthusiastic scientist who strives to address the most important questions in his field.”

Trotman explained that his goal isn’t just to understand how the genome works to cause cancer, but to figure out how to cure metastatic prostate disease. He wants to see where potentially effective drugs fail and to figure out what they should be doing differently. If he develops the kind of data he hopes to explore with the mouse, he would then argue that the same kind of analysis is necessary in humans, to make sure the model and the reality in humans are aligned.

While he’s focused on prostate cancer, Trotman said he would like to find a methodology that allows him to combat and understand cancer on a broader scale.

Born in the United States, Trotman moved to Switzerland when he was 2 years old. He attended high school and received his doctorate in Switzerland. He returned to New York to do his postdoctoral work at Sloan Kettering. He became a faculty member at Cold Spring Harbor Laboratory in 2007. Trotman’s Swiss background enabled him to become fluent in English, German, French and Swedish.

A resident of Oyster Bay, Trotman lives with his wife Eva Frosch, who runs the gallery Frosch & Portmann in New York City, and their sons Liam, 8, and Finn, 5.

Trotman loves summers on Long Island, where he can surf on the south shore and head to the beaches on the North Shore.
Trotman said he hopes his mouse model of prostate cancer can help uncover how cancer progresses, becomes metastatic, and resists drug treatment.

“There are many theories about how diseases like cancer evolve,” he said. His model can “help bring [the research] down to a level where everybody can see it.”

Paul Bingham and Zuzana Zachar, a husband-and-wife team at Stony Brook University, have spent the better part of a decade exploring a way to disrupt cancer’s energy supply line.

They have developed a compound that takes advantage of the different way cancer cells produce energy. With the help of other scientists at Stony Brook, including James Marecek in the Chemistry Department, they created another form of lipoate, called CPI-613, that doesn’t foster cancer growth.

“It’s like a Trojan horse,” explained Zachar, who is an assistant professor in the Department of Biochemistry and Cell Biology. “It has no catalytic ability,” which means that it looks like a key molecule for a cancer pathway in mitochondria, but doesn’t act like it.

By shutting down tumor cell mitochondria, the researchers are able to trigger several cell-death pathways selectively, explained Bingham, who is an associate professor in the same department. The scientists anticipate lower vulnerability to evolved resistance because the CPI-613 attacks two enzyme targets at the same time.

The Stony Brook team are in Phase II trials of this drug at Wake Forest University with patients who have leukemia and lymphoma.

“We saw a 38 percent response rate [among patients who were not responding to other therapies] in the first Phase I trial we completed” said Timothy Pardee, an assistant professor who conducted those trials and is performing a similar function in Phase II. While he believes the treatment has extended people’s lives, he cautioned that “it’s important to remember that these are very early results.”

The scientists have to generate significant evidence to be confident in their approach, both for basic science and for use with patients, Bingham said.

Even though the treatment has shown promise, it’s possible that cancers may respond to this approach the way they have to so many other treatments, by finding another way to avoid selective eradication. While the treatment the couple has worked on is designed to minimize this risk, they will only know whether they have been successful after extensive testing.

“Until we get more clinical experience, we can’t know that natural selection operating on cancer cells doesn’t have a diabolical trick we haven’t thought about,” Bingham said.

Robert Haltiwanger, the chairman of the Department of Biochemistry and Cell Biology, said scientists had known since the 1930’s that the metabolism of cancer cells is different from that of normal cells. Bingham and Zachar have developed a compound that “seems to have an effect,” which means it has potential in a “wide variety of cancers.” In addition to contributing to cancer research, Bingham is also a “very popular lecturer,” said Haltiwanger.

Bingham and Zachar, who had done extensive work on the fruit fly Drosophila, began looking at cancer metabolism in the late 1990’s as a “side project.” That showed enough promise for them to transform it into a full-time pursuit.

Bingham grew up in the rural Midwest, attending high school in a small town in a farming area of central Illinois that produces corn and soybeans. He received his doctorate from Harvard University in the Department of Biochemistry and Molecular Biology.

Zachar was born in what is now the Czech Republic. She moved to Ghana, West Africa when she was 10 and emigrated to the United States in 1968, settling near Chicago, Ill. She was at the University of North Carolina, Chapel Hill and Bingham was at the National Institute of Environmental Health Sciences in North Carolina when they met.

“We didn’t grow up as clinical researchers,” Bingham said. “We came up as basic, fundamental” scientists who were “drawn later in our careers into clinical work. When I was told we were going to work with people, my first reaction was anxiety for fear of doing harm.”

The researchers, who are residents of South Setauket and have lived on Long Island for 32 years, love the hiking trails.

They expressed satisfaction at the prospect of contributing to an effort that might aid in cancer treatment. Bingham said the research has particular meaning for him.

His mother, Doris Rorhman Bingham, died of cancer when he was 16. “Had she lived another 10 or 20 years, my life would have been completely different,” he said. “I still think of her almost every day.”

Zachar said the couple feel fortunate to be able to do this kind of work., “Saving other families from what [Bingham’s] family went through would be supremely fulfilling,” she said.

The human body not only defends itself against bacteria and viruses, but it also has a system to suppress or prevent tumors. Cancers, however, weaken this defense.

Sumita Bhaduri-McIntosh, an assistant professor in the Department of Pediatrics and in the Department of Molecular Genetics and Microbiology at Stony Brook University, has recently discovered a step cells take to weaken the cell’s defenses and become cancerous.

Using the Epstein-Barr virus, which causes mononucleosis and which more than 90 percent of people carry, Bhaduri-McIntosh has been able to turn healthy cells into those that divide and grow uncontrollably.

“If we take B cells (a part of the immune system) from healthy individuals and isolate those cells, we can infect them with EBV in the lab, where the virus expresses its own cancer,” she said. “This allows us to systematically examine a variety of cellular events, from minute one until we have these proliferating cells.”

Human cells have a defense called DNA damage response. This system is a set of mechanisms operating in every dividing cell that finds damage or defects in the genetic code and slows down or pauses the process of copying DNA and promotes repair of the damaged code, Bhaduri-McIntosh explained.

The virus she inserted triggered the activation and increased production of the cellular protein STAT3. Scientists knew this protein could drive gene expression and was an important ingredient in many human cancers. What they didn’t know, however, was that it also muted DNA damage response.

The results of these experiments were recently published in the journal the Proceedings of the National Academy of Sciences of the United States of America.

This finding “reveals a novel mechanism for development of cancer,” said Ayman El-Guindy, an assistant professor in the Division of Pediatric Infectious Diseases at Yale School of Medicine, where Bhaduri-McIntosh was a postdoctoral fellow and an assistant professor. Disruption of these pathways can “lead to accumulation of mutations in our genome that can ultimately cause cancer.”

El-Guindy suggested the kind of work Bhaduri-McIntosh is doing, while filled with the potential to help people, faces financial obstacles.

“While it is unfortunate that basic research is increasingly underfunded and has suffered multiple budget cuts in recent years, Dr. Bhaduri-Mcintosh’s discovery highlights the importance of basic research to develop new remedies against cancer,” El-Guindy said.

While a majority of people have the EBV, Bhaduri-McIntosh reassured people that it is extremely rare for it to become cancerous, especially in North America.

“There are EBV-related cancers that occur and are quite prevalent in other parts of the world,” including endemic Burkitt lymphoma in equatorial Africa, nasopharyngeal cell carcinoma in Southeast Asia and AIDS lymphomas.

Cancers caused by EBV can occur in as many as one in five solid-organ transplant recipients, triggered by the immunity-suppressing drugs that keep the recipient from rejecting the new organ.

A native of India, Bhaduri-McIntosh has a medical degree and a Ph.D. She sees patients as an attending physician at Stony Brook Children’s Hospital, although she spends most of her time doing research.

“When I was going through medical school in India, infectious disease is an even bigger scourge than in the western world,” she said. “You see it all around you, with tuberculosis, leprosy and parasitic diseases.” Studying infectious disease was “a very natural connection.”

Becoming an infectious disease expert “fed the detective urge,” she said, as symptoms don’t necessarily point to a specific diagnosis.

In one case when she was at Yale, she worked with a 10-year-old boy with multiorgan failure, while his bone marrow was making blood cells that were being destroyed. In an investigation of family members, she helped discover that some of them had a mutation.

The boy had a bone marrow transplant and, from the last she heard, “is doing rather well.”

Bhaduri-McIntosh credits her success to her parents in India and to her Wading River-based family. She and her husband, Michael McIntosh, the science adviser to the Foreign Animal Disease Diagnostic Laboratory on Plum Island, have a 14-year-old son, Rohin, and a 12-year-old daughter, Uma. She called the three of them “absolutely, veritable rocks.” She is also grateful for the support of the Pediatrics and Molecular Genetics departments.

When she’s not in the lab or helping patients, Bhaduri-McIntosh likes to sing. She was trained in Indian classical music. Nowadays, she sings Indian contemporary, as well as Western, music.

As for her career, working with patients and in research makes her better in both arenas, she said.

They know it works, but they’re not exactly sure how. They mix ingredients with something that helps make everything happen and, like a magician, wave their wand and get the rabbit, or in this case, the clean hydrogen, they were trying to produce. Except that, in their world, nature is the one whose slight of hand remains a mystery.

That’s where Argentinian-born Dario Stacchiola and his Brookhaven National Laboratory team of two postdoctoral researchers and one graduate student come in. An associate chemist, Stacchiola is trying to figure out the small steps in between the beginning of a reaction and the creation of this form of hydrogen, which is suitable for fuel cells in cars and industrial chemical processing.

While Stacchiola recognizes the possibility of a commercial use of his analysis down the road, he emphasizes that he is on a basic scientific mission. “Our end goal is not to get a commercial catalyst,” he said. “We are a step removed from that transition. We are really trying to look at the atomic level.”

Stacchiola’s curiosity about catalysts has earned him the admiration of his colleagues and coworkers. He is “well-respected not only across the lab, but also in our field,” said Ashleigh Baber, a postdoctoral researcher who has worked in his lab for three years.

His “knowledge of catalysis, coupled with his strength in experimental physical chemistry give him a unique perspective on how to approach and tackle important issues and holes in the field.”
Indeed, one of those many holes is understanding the intermediate reactions in the water-gas shift reaction, which is used to purify hydrogen and remove carbon monoxide.

“There are at least four different mechanisms proposed” for that reaction, Stacchiola said, with each one involving between five and 10 steps. His experiments helped to “narrow it down to two probable mechanisms.”

One of the big problems for scientists looking for these intermediate steps is that these reactions are easiest to see under cold, high-vacuum conditions, where the scientists don’t have to worry about interactions between the reactions they’re testing and atoms in the air. In those conditions, some of the intermediate chemicals generated during the reaction don’t form.

Using the latest technology, including near-ambient X-ray photoelectron spectroscopy, near-ambient pressure infrared reflection absorption spectroscopy, density functional theory computational analysis and scanning tunneling microscope, they were able to look behind the curtain in some of these steps at more everyday temperatures and pressures.

“We are now starting to see processes happen that we couldn’t see at lower pressures,” he said. He sees the stabilization of weak intermediates at the interface of oxide and metal nanoparticles in catalysts.

Scientists had predicted that the reactions Stacchiola studies would involve a carboxyl group, which is present in most organic acids and is made up of carbon, two oxygen atoms and hydrogen. These groups hadn’t been found on metal or oxide surfaces in this process. His research detected a product derived from the carboxyl group that was attached to the metal oxide interface of nanoparticles.

Scientists had predicted the likelihood of this carboxyl group for about a decade. The discovery of this combination of atoms was the closest thing to a “Eureka” moment he has had, Stacchiola said.

At conferences, Stacchiola has met with people who are trying to improve the efficiency of these reactions and who are looking to optimize the perimeter of oxide-metal interfaces.

Baber explained that “even small increases in catalytic efficiency extrapolate to huge savings in large-scale industrial processes.”
A resident of South Setauket, Stacchiola lives with his wife, Zulema Cabail, who does research and teaches microbiology at Stony Brook, and their 11-year-old daughter, Sofia, whose name, he said, is easy to reproduce in any language, which is helpful for a couple from Argentina who have lived in South America, Europe and North America.

As for his work, Stacchiola said he is driven by some of the same curiosities he had as a child, where he needed to understand how things worked. “I never felt very comfortable with black boxes,” he said.

Warren Stern is helping win business for a department he just joined a year ago. A senior advisor in the Nonproliferation and National Security Department at Brookhaven National Laboratory, Stern is working on a domestic program through the National Nuclear Security Administration’s Global Threat Reduction Initiative that seeks to enhance security and response capabilities at facilities in the United States that use highly radioactive materials.

As a part of the Response Experts Group, he helps the program “ensure an effective response if there ever is an incident,” he said.

The work with the Office of Global Threat Reduction is “our first work in years” with that office, explained Carol Kessler, the chairwoman of the department where Stern works. Stern, who has helped the BNL group increase its business, “is an excellent proposal ideas person and writer, an important combination for success in this area.”

On a broader level, Stern’s work encompasses deterring potential diversion of nuclear energy into nuclear weapons, ensuring an effective response to any catastrophe, and finding the best use of technology to monitor nuclear sites. “We succeed when we deter others from taking steps,” he said. “The goal is to deter diversions by enhancing the chances of detection.”

Governments and the private sector acquire technology in a variety of ways, Stern said. He and experts at BNL and other national laboratories help these governments acquire the best technology. “When you’re thinking about something as broad as inspections and verifications” of nuclear material, it’s “not as straightforward as going to Consumer Reports,” he said.

Stern also works with a team at BNL to create a course that helps international inspectors prepare for certain types of monitoring. As the course director, he put the exercises together, which includes simulations where he plays the role of a state. The course, which is focused on hands-on work, is designed to train international inspectors related to nonproliferation.

When other countries come to the International Atomic Energy Association, the IAEA sometimes calls on experts like Stern and others at BNL to travel to other regions to compare these country’s laws, regulations and activities in the context of international standards.

Stern journeyed to Lithuania and Jordan to “examine and evaluate” their regulations. Each visit lasted about two weeks. He toured their facilities, had broad access to a range of government officials and emergency response teams.

“Often,” he said, “failures in response have nothing to do with technology and everything to do with basic lines of communication and responsibilities given to a variety of organizations. There is a false understanding of how things would work.”

Experts like Stern try to be aware of the politics of any international situation. If, for example, a nuclear facility is on the border of two countries that don’t have good international relations, he and the advisory team still encourage the need for a unified emergency response approach. “While that may not be feasible politically, it doesn’t keep us from recommending” that as a course of action, he said.

Stern is a “role model” for many people in the department “as a leader on how to think up new ideas for work that will help our customers achieve their goals,” Kessler said.

Stern spends much of his time in Washington, D.C., where many of the government agencies, such as the Department of Energy and the State Department, are headquartered.

Up until he joined BNL, Stern was a long-standing member of the government, where he worked at the State Department, directing the office responsible for developing and implementing U.S. nuclear safety and radiological security policies.

He also worked at the Central Intelligence Agency, where he acted as intelligence officer for the Office of Scientific and Weapons Research. He served as former Sen. Hillary Clinton’s nuclear fellow and adviser in 2002 and 2003, where he offered advice on nuclear energy, waste and safety and security. He was appointed by President Obama to lead the Domestic Nuclear Detection Office at the Department of Homeland Security.
Stern has two children, Benjamin, who is at Virginia Tech, and Matthew, who is in high school.
Stern prides himself on having relied on human energy to commute to his high-powered jobs in Washington, biking the five to seven miles to work each day. He has brought his two-wheeled ride to Long Island, where he enjoys pedaling along the North Shore.

As for what keeps him up at night, Stern said, “We have a long way to go to have an effective emergency response system for nuclear threats.”

Despite the back pain, foot problems, and other stresses and strains humans feel when walking, we’re pretty good at it. That’s especially true when you compare humans to chimpanzees or other primates.

“Chimpanzees, our closest primate relative, use a lot of energy to walk around,” explained Matthew O’Neill, an instructor in the Anatomical Sciences Department at Stony Brook. “Their cost of walking is 75 percent higher than human walking.”

O’Neill is broadly interested in understanding what role energy use played in human evolutionary history. He believes part of what makes humans unique is the low energy we expend when we walk.

“The energy cost of walking is largely determined by the mechanics of how our pelvis and hind limbs work,” he said. He explores what is different about the way humans walk. If energy were the equivalent of a financial budget, spending less on walking and getting around would allow humans to use those resources in other areas.

“The less we have to use in a given day for locomotion, the more we can allocate to things like maintaining tissue health or on other aspects of living our lives,” O’Neill said.

O’Neill is interested in understanding when and why the human body began to look and work the way it does. Fossils, he said, tell him when humans might have changed the way they walked from our ancestors, while studying humans and chimpanzees may help explain why.

He looks at the forces humans and chimps apply to the ground and the way their limbs move. He uses musculoskeletal models to calculate how bones, muscles and tendons work while walking. He can then try to understand how these different tissues work. One of the areas where he’s collecting data is in how much energy individual muscles consume.

O’Neill’s colleague at Stony Brook, anatomical sciences professor Susan Larson, who has worked with him for five years, called his work “ground-breaking.” For many years, she said, “researchers have been compiling observations characterizing how primates walk, but we didn’t really have much in the way of mechanical explanations for why they display many of these characteristics.”

Larson said O’Neill’s work moves beyond simple descriptive studies to explore “potential underlying mechanical reasons governing their manner of walking.”

O’Neill was recently a collaborator on a broader study on energy use in humans compared with other primates. The main result from that study showed that humans, chimps and other primates use about half as much energy in a 24 hour period as do other mammals, such as mice, antelopes and sea lions. That, O’Neill said, may be information for understanding why primates seem to live longer than other mammals.“There’s simply less wear and tear on our bodies” because of the lower energy lifestyle than other animals have.”

In that study, O’Neill contributed data from research he had done in North Carolina when he was at Duke University on ring-tailed lemurs. There, he had measured daily energy use for these primates, who normally live in Madagascar.

O’Neill is involved in other collaborations as well, including one with Larson, two other Stony Brook faculty members and a researcher from the University of Massachusetts, on a project to develop a computational model of an ape walking on two legs. Once completed, they can use the model to run simulation studies to explore different suggested characteristics of the earliest form of bipedal locomotion, Larson said.

O’Neill is “one of a handful of a new generation of biological anthropologists who are bringing new rigor in the analytical methods applied to studying our own evolution,” Larson added.

O’Neill said he would like to know more about how walking and human walking capabilities evolved. “What I want to do is take information that’s available now and combine it with what we know of living species and get reliable predictions about how a [taxon] might have walked,” he said.

A resident of St. James, O’Neill lives with his wife, Karen Baab, an assistant professor in the Department of Anthropology at Stony Brook, and their infant daughter. The snow has kept them from enjoying rides out on the North Fork, which they hope to resume this spring.

As for looking out at how walking might change in humans, O’Neill, who described his own walk as “slow and lumbering,” said humans don’t need to walk the way we used to, when our “survivorship depended on walking.” As a result, he doesn’t see “a lot changing” in the foreseeable future in the way humans walk.

What humans, or any other animals, think about the world can be seen in pathways that flash around in the brain, forming connections that inform a view of anything from the smell of steaming hot pizza to directions to a rink for a roller-skating party.

Combining behavioral electrophysiology with quantitative psychophysics and optogenetics, Adam Kepecs, an associate professor at Cold Spring Harbor Laboratory, is specifically looking at how rats report confidence in their decisions.

Looking at the frontal cortex in the brain, Kepecs studies the kinds of neurons that fire as the rat is weighing its options in the face of uncertainty. He likens the process to receiving directions to a restaurant and then following a route until there is no sign of the dining establishment.

“At some point, you will wonder, ‘Is the restaurant coming up or should I turn around?’” he said. “Presumably, the more confident you are, the longer you will keep driving. That’s exactly what we can do with rats. We can repeat [this experiment] hundreds of times a day by manipulating the instructions.”

To further the restaurant search analogy, that would be the equivalent of receiving instructions that were slightly garbled through a cell phone or where foliage obscured a sign a driver was expecting to see.
The directions the rat receives, Kepecs said, come from olfactory or auditory cues rather than visual ones. “We’re testing how you could turn this initial confidence into a choice,” he said. “We want to see how long do [they] wait.”

The analysis of the data he and his team of eight people collect comes from comparing a statistical evaluation of neurons that are within tens of microns of each other and the decisions that come from a rat that is faced with a choice about staying the course.

“This is a great statistical evaluation of how likely a decision was correct,” Kepecs said. Kepecs said these kinds of experiments enable him to study basic behaviors that get to the heart of how the rats process information and weigh that against what’s happening around them. “We’re trying to ask a big psychological question and we need to reduce it to an elemental behavior and turn it into something we can study as neuroscientists,” he said.

While Kepecs isn’t yet ready to extend his research to humans, he said the implications and applications of this research could include helping people who struggle with problems such as obsessive compulsive disorder. “If you lose confidence about your actions, you might repeat them,” he said. “This is the kind of thing [his research] is moving towards.”

Kepecs’ colleagues appreciate his approach to his research. “He is an outstanding scientist,” said Anthony Zador, the program chair of neuroscience at CSHL. He has a “well-earned reputation for being creative and innovative.”

In a separate line of experiments, Kepecs is also working with a region deep within the brain, called the nucleus basalis. Degeneration in this area has been linked to Alzheimer’s disease, Parkinson’s dementia and age-related cognitive declines.

Indeed, Kepecs recently received the 2014 Memory and Cognitive Disorders Award from the McKnight Endowment Fund for Neuroscience, which provides $100,000 a year for three years. The award supports research designed to solve problems of neurological and psychiatric diseases, with an emphasis on those that affect cognition and memory.

“This area has been a puzzle,” said Kepecs. “It’s made up of many cell types. Until now, there was no way of recording identified cells. What we’re trying to do is record from identified cholinergic neurons, to figure out what they’re telling the rest of the brain.”

Kepecs studied computer science in his native Budapest, Hungary. He was fascinated with the way the mind works. “I have a deep interest in the mind and computer science was my route,” he explained. A resident of Huntington, Kepecs is married with two children.

Kepecs said he is excited to take the next steps in linking activity in neural circuits to confidence. “How can you study anything that’s internal to your brain?” he asked. That is what his experiments on neurons and behavior are designed to examine.