Looking through binoculars from the bleachers at a baseball game, at an eagle as it alights on a distant tree or at a constellation in a cloudless night are all much easier with a clear lens. A smudge, crack or even a hair on the lens can make that long-distance gazing considerably more challenging, as the images become blurry and our eyes struggle to interpret the difference between what’s out there and the defect in our binoculars.

The same holds true for radiation detectors. Constructed with bars of crystals, the detectors have applications in everything from medical imaging to see tumors to peering deep into the universe for signature radiation signals to detecting the movement of nuclear materials to help prevent an attack or accident.

A significant challenge with these detectors has been the defects that appear as the crystal grows. Scientists work on two fronts to deal with these imperfections: They improve the quality of the crystals, and they develop ways to compensate for the imperfections.

At Brookhaven National Laboratory, physicist Aleksey Bolotnikov has made significant contributions to improving detector performance despite the flaws in the crystal.

“We veto the interactions in the ‘bad’ regions of the crystals,” Bolotnikov explained.

Working with a team of scientists at BNL, including Giuseppe Camarda, Utpal Roy, Anwar Hossain and Ge Yang, Bolotnikov has been able to measure the coordinates of these defects with high accuracy. This allows the researchers to improve the detecting capability and reduce the cost by increasing the acceptance rates of the crystals.

Recently, Bolotnikov authored a paper in Applied Physics Letters in which he increased the size and thickness of the crystals. The thicker crystals are important in detecting weak sources.

Bolotnikov has “been able to establish new records for the thickness of semiconductor gamma-ray detectors operating at room temperature,” offered Ralph James, who heads Bolotnikov’s department and has collaborated with him ever since he arrived 20 years ago. “This is a critical step in the move to replace many traditional radiation-sensing instruments used today.”

The biggest market for these detectors with thicker crystals is in nuclear medical instruments for oncology and cardiology, James said.

Bolotnikov explained that the team at BNL combines researchers with expertise in a range of areas. Roy grows the crystals, while a group from the instrumentation division led by Gianluigi De Geronimo facilitates the work as a “top expert in readout electronics.” By tapping into his expertise in nuclear physics and nuclear engineering, Bolotnikov is  also able to design and develop new detectors.

James credits his colleague with significant advances in detector technology. “His new position-sensitive device design has rendered outstanding results that have approached the theoretical limits for energy resolution,” James said.

The work of Bolotnikov and the team has earned them national recognition. Bolotnikov was a part of three R&D Magazine’s R&D 100 Awards, in 2006, 2009 and 2014.

Last fall, he received the Room Temperature Semiconductor Detector Scientist Award from the Institute of Electrical and Electronics Engineers. The award recognized a scientist who had done the most to impact room temperature semiconductor detectors and could be given either for a lifetime of work or for a single accomplishment.

The award is “well earned,” James said. Bolotnikov’s votes among the awards committee “surpassed others by far.”

Like other members of his team, James said Bolotnikov works most waking hours. “I can count on a quick response from him via emails during the evenings,” James said.

Born in a small city near Moscow, Bolotnikov first came to Long Island around 1991. He now lives in Setauket with his wife Mila, who is a teacher for North Shore Montessori. His daughter Dasha works at BlackRock, while his son Vassili works for a small management company affiliated with Stony Brook Hospital.

Bolotnikov, who said he enjoys his work, suggested that the effort to improve technology generates new ideas, which “creates the new background or basis for writing proposals for the next cycle of work.”

Bolotnikov continues to work on increasing the size of the crystals in the detectors. At some point, the larger sizes can become prohibitively expensive. An alternative, he suggested, is to use gamma-ray focusing optics, concentrating gamma rays coming from large areas toward a reasonably sized detector. “This, he said, “is a new horizon.”

Imagine a pizza restaurant. Every day, the chef cooks a certain number of pies. At a specific point, the kitchen reaches a maximum. What if that restaurant could double its production?

That’s what Zachary Lippman, an associate professor at Cold Spring Harbor Laboratory, and colleagues in Israel did, except that instead of doubling his pizzas, he doubled the amount of fruit his tomato plants produced.

Lippman used the same kind of mutations that agriculturalists have employed for centuries to increase crop yields.

“The approach we took was to find new mutations and design specific screens” that would favor flowering instead of bushiness, Lippman said.

Lippman and collaborators from Israel created a tool kit of genes that balance between the hormones florigen and anti-florigen. The first one, florigen, promotes flowering and flower and fruit production. The second one, anti-florigen, promotes shoot and leaf production.

Florigen and anti-florigen are “like this yin and yang,” Lippman said. “We found mutations in genes that affect the florigen/anti-florigen paradigm.”

By cross breeding these mutations, Lippman and his associates were able to pinpoint what he described as “an optimal architecture,” which originates from an optimal balance of flowering signals, he said.

This genetic tool kit could have applications to other agricultural crops, such as soybeans, which, Lippman explained, share many growth similarities to tomatoes.

With the world population expected to reach 9 billion by the middle of this century, these kinds of discoveries could prove important in increasing food production, Lippman said. He is thinking of testing this tool kit in cowpea, a major crop related to soybean that is grown in Africa.

“The major advance in the present work is the illustration that fine tuning of signals from these hormones can help improve tomato field performance and thus, similar, directed changes can be applied in other plants,” explained Yuval Eshed a professor in the Department of Plant and Environmental Sciences at the Weizmann Institute of Science in Israel who collaborated with Lippman on this study. Eshed has worked with Lippman for almost a decade and called his partner “an outstanding scientist” who is “original, thorough and trustable.”

The approach Lippman and his team took does not involve inserting DNA into the plant but rather comes from the development of mutations, Lippman said.

“It’s the standard idea of classic genetic modification,” Lippman said. “We were able to design a way to find and select for mutations much faster than what Mother Nature has given us by using what people have been doing for decades.”

The genetic tool kit, with several specific mutations, gives scientists and, potentially, tomato producers a chance to boost the production without compromising the plant or the taste of the tomato.

At the same time there is no difference in the fruit quality or the plant, he said. “Sugar is unaffected,” he offered.

To be sure, like some animals bred in a zoo or plants farmers have used for hundreds or even thousands of years, these new tomato plants, with their collection of mutations designed to increase yield, would not fair as well outside of the confines of a farm. “What’s optimal in nature is not what’s optimal in agriculture,” Lippman explained. “We’re selecting for growing in greenhouses or fields.”

Lippman used this tool kit in cherry, plum and beefsteak tomatoes. He is hoping to test all major varieties of tomato, including slicing tomatoes for burgers, grape tomatoes and cocktails. This approach should work across the types of tomatoes, but he hasn’t conducted those tests yet. He has had some contact from companies that grow tomatoes and will likely enter a collaboration soon.

Lippman said introducing these new mutations into the elite breeding lines of tomato farmers may create some complications. “We don’t know how those mutations will respond” in the designer tomatoes agricultural companies use, he said. “One combination might work in one variety, whereas another combination might work in another variety.” The tool kit, however, provides a genetic resource.

“This summer, we repeated the experiment for a fourth time,” he said. He organized these plants in a row according to their mutations. “If you walk down the row, you could see the progressive quantitative increase,” with the plants going from bushy to less bushy to almost a tree. To see the yield [change] was even more impressive.”

Lippman, who has been working for for six years at CSHL, said these results are “by far the most important work to come out of my lab. This is the most fun” he’s had conducting research.

Defeating a deadly enemy requires preventing that killer from traveling to key areas and wreaking irreversible damage. Stony Brook’s Jian Cao, an associate professor in the Department of Medicine, is seeking ways to prevent the enemy, in this case cancer, from making its deadly journey through the body.

Recognized for ground-breaking work he did in Japan, Cao has focused on understanding how to stop a tissue-degrading enzyme called matrix mettalloproteinases, or MMP.

“Understanding the scientific basis for metastasis has been the most challenging aspect of cancer research,” said Stanley Zucker, a professor emeritus in the Department of Medicine at Stony Brook who has collaborated with Cao for close to two decades. “No one has yet figured out a treatment that specifically interferes with the metastatic process.”

Cao, who was born in China and trained with a renowned Japanese biologist, Motoharu Seiki, explained that scientists have focused their attention on disrupting the catalytic site, the place where the MMP breaks apart cell-cell adhesion molecules.

Clinical trials of an inhibitor or blocker for that site failed because of a lack of selectivity. He now focuses on a different area, called a hemopexin domain, that is required for enhanced cell migration. He has developed inhibitors targeting different MMPs.

“We have identified the region that is required for MMP-mediated cell migration, then, we developed inhibitors to target this region,” he said. “We found or developed regions that specifically interfere” with their signaling pathway that leads to enhanced cell migration.

He uses a small protein and synthetic compounds that don’t destroy the enzyme, but rather render it ineffective in spreading cancer.

There are 25 forms of MMP. For breast cancer, for example, MMP-14 activates MMP-2, which activates MMP-9. Based on other research, all these MMP’s play an important role in breast cancer metastasis, Cao said. “We identified regions that are required for enhanced cell migration that are specific and selective for each MMP,” he said.

Cao said his work has generated attention from pharmaceutical companies that are hoping to develop treatments for metastatic forms of cancer. A company reached out to him recently because they “want to collaborate to license our inhibitors,” he said.

Cao’s scientific peers lauded his results and his approach. “Many top investigators in the field consider Dr. Cao to be the best scientist to have entered the rapidly expanding field of MMPs in the past 20 years,” said Zucker. “Dr. Cao gained worldwide recognition for his research contributions to Dr. Seiki’s laboratory in Japan.”

In addition to working with these MMP inhibitors, Cao also has a three-dimensional drug screening test. Cao looks to see whether drugs that might be approved for other uses might have anti-cancer properties. The National Institute of Health’s National Center for Advanced Translational Sciences created a program aimed at repurposing old drugs for new uses. He has seen some benefit from a psychiatric drug that can interfere with cell migration and can inhibit cancer invasion.

At the recent 2014 Gloria and Mark Snyder Symposium for Cancer Medicine, Cao presented his research on a gene he cloned, called CeMIP, that is normally expressed in the central nervous system.

After analyzing thousands of patients, he found that people who have a high level of this gene have a shorter survival period with breast cancer. Those with less of this gene survive longer.
Knocking out this gene in highly aggressive breast cancer in animal models causes cancers to become less invasive.

He is studying a promoter region of this gene that selectively hits the on switch. He hopes to develop a compound that interferes with the CeMIP protein.

A resident of South Setauket, Cao lives with his wife, Qiang Zhao, who is also a scientist working on cancer at Stony Brook, and their 16-year-old son Kevin.

His work often includes going to the lab seven days a week. Cao is “the hardest working scientist I’ve ever encountered,” said Zucker.

“His productivity is outstanding in terms of publication and new research grants.”

Cao believes he is on the right track to develop possible treatments to battle cancer as it spreads. “If you can stop the invasion,” he said, “you can prevent metastasis.”

Bo Li looks closely at red and green colors. He is not preparing Christmas decorations, but rather is looking at the way different neurons in a region of the brain light up in response to an increase or decrease in fear.

An associate professor in the Neuroscience Department at Cold Spring Harbor Laboratory, Li is studying a small area in the mouse brain called the amygdala. His results may help guide pharmaceutical companies and other researchers as they look for ways to help people suffering with post-traumatic stress disorder.

In the central amygdala, he found two cell populations that likely play some role with fear. One of those cell populations promotes fear. He believes the other suppresses fear. Ongoing studies, he said, will provide answers about the other cells soon. Once he understands both, he will look for ways to affect their activity.

Understanding fear responses is just one of the areas where Li studies neurons in the brain. He also does research on animal models of depression and schizophrenia, hoping to find differences researchers can exploit to provide early detection, treatment and prevention.

Fritz Henn, a visiting professor at Cold Spring Harbor Laboratory who collaborated with Li when Li was a post-doctoral fellow, said he is a “rising star in neuroscience research.”

In post-traumatic stress disorder, people who witness or experience stressful and potentially life-threatening experiences develop a sustained level of fear, even after removed from stresses like the life-and-death struggles of war. This trauma can diminish the quality of life as people struggle with emotional scars that don’t seem to heal.

By looking at the neurons of mice, Li is able to use genetic technology to explore an area that contains about 10,000 neurons. He uses scientific advances that enable him to separate neurons in different categories. These different types of neurons are labeled by a marker, which glows in green, yellow or red. He can also use viruses that specifically recognize these neurons and enable him to see a higher or reduced activity level for these neurons in a fear response.

Using an optical fiber that is about 150 microns, which is about the thickness of a human hair, Li can shine a light on the amygdala to see signals that are then collected through a computer. His analysis allows him to record changes in the signals sent by these different types of cells. Henn called Li’s research “state of the art.”

By collaborating with other scientists at Cold Spring Harbor Laboratory to do gene sequencing, Li can look at what other proteins are expressed by these different cells.

“It’s just a matter of time to gather the data and come to conclusions,” he said. He believes this research will make substantial scientific progress in the next five years. The clinical applications will likely take longer, he predicted.

The amygdala is an area that scientists have known for a long time controls emotion and emotional memory. As a result, researchers on Long Island and elsewhere in the world are putting considerable energy and time into understanding the specific cellular functions in this region.

His work on schizophrenia presents other challenges because it’s difficult to mimic the kind of symptoms humans exhibit, including hallucinations and reasoning problems.
Li is looking at the genes linked to schizophrenia and finding similar genes in mice.

“Going from genes to behavior is a big gap,” he said. “We need to fill that in.” He is working on genes in his lab that he knows cause problems in some brain circuits to understand depression as well.

“We know a particular circuit in the brain [called the lateral habenula circuit] is important for reward, learning and punishment,” he said. “When this circuit is impaired, it can cause depression.”

Li lives on campus at Cold Spring Harbor with his wife, Shirley Guo, who is also a scientist and works for Kadmon, a biotechnology company in New York City that is developing medicines for a range of diseases and provides treatment of hepatitis C. The couple have an 11-year-old daughter, Serena, who is an avid tennis player.

Li called Cold Spring Harbor a “fantastic environment” and said it is “one of the best in the world for doing science.”

They both compete in triathlons. They live three blocks from each other in Poquott and work at Stony Brook University. And thanks to a chance meeting in a park near their home, they have worked together to gather information about a medical problem that is likely to become more common as the baby boomer generation ages: Alzheimer’s disease.

A professor in the departments of neurosurgery and medicine at Stony Brook Medical School, William Van Nostrand created a mouse model of Alzheimer’s disease. Realizing, however, that he needed someone with an expertise in behavior, he turned to his longtime collaborator John Robinson, a professor in integrative neuroscience in the psychology department at Stony Brook.

Recently, the physically fit tandem showed how the collection of a protein called amyloid beta around small capillaries in their model of Alzheimer’s results in signs of the disease, even before the typical collection of amyloid plaques in the brain resulted in the cognitive decline associated with the disease.

The study shows, Van Nostrand said, that a small amount of amyloid buildup in the blood vessels is “very potent at driving impairment.” That could be a result of inflammation or inflammatory pathways or changes in the blood flow, he speculated.

While scientists and doctors had known about the build up of amyloid proteins in the vessels and in plaques, they hadn’t compared the changes in the affected region in a side-by-side way while monitoring a deterioration in behavior.

Van Nostrand was cautious about extending the results of this study to humans. He suggested that this result might be “an earlier indicator” or even a “potential contributor” to the disease and impairment later on.
“A lot more work needs to be done in looking at how this translates into humans,” Van Nostrand said.

Additionally, the amyloid accumulation is not the whole story, as defects in tau proteins, which are responsible for stabilizing polymers that contribute to maintaining cell structure, also play a role in Alzheimer’s symptoms. Most recent work, Van Nostrand explained, suggests that amyloid is likely an important initiator of other problems.

A complex disease, Alzheimer’s can vary from patient to patient. Indeed, there are people who show no signs of any deterioration in their intellectual abilities who have “lots of pathology, but they haven’t hit that tipping point yet,” where the disease progresses from the physical stage to mental impairment, Van Nostrand said.

As for what’s next for the productive collaboration, Robinson suggested they are interested in how lifestyle factors, such as diet, exercise and lifelong learning, help or hurt the chances of developing symptoms of Alzheimer’s.

The two scientist/athletes recognize, Robinson said, that their own athletic pursuits may help their health over the longer term, although the connection with Alzheimer’s or any other disease is difficult to make.

“If you ask Bill and me, ‘Do you think we’ll live longer because of this?’ We’d both say, yes. That’s a bias we recognize,” Robinson said. Robinson said he has collaborated with many researchers since he started working at Stony Brook in 1994 and called the connection with Van Nostrand one of his longest standing scientific partnerships.

As for their athletic training, the duo have traveled together to triathlons in Montauk and in New Jersey. Van Nostrand often competes in longer races (like Ironman competitions).

The two sometimes compete in the same triathlon, where Robinson sees his colleague’s feet amid the churned bubbles at the beginning of a race, while Van Nostrand listens over his shoulder for Robinson during the run.

While Van Nostrand has had a successful collaboration with Robinson, he has another collaboration even closer to home. His wife, Judianne Davis, who has been working with him for over 20 years, is his lab manager.

A swimmer, Davis has an interest in her family that is unique: she enters sheepherding competitions with her border collie. Van Nostrand has two sons from a previous marriage (26-year-old Joffrey and 21-year-old Kellen). The couple has an eight-year-old daughter, Waela, who is also a swimmer.

Robinson met his wife, Alice Cialella, a group leader of the Scientific Information Systems Group at Brookhaven National Laboratory, on a college track team and the couple still trains together. The Poquott pair have a 16-year-old daughter Zoe, who, naturally, runs cross country and track at Ward Melville High School.

One of Davis’ dogs helped facilitate a meeting between the two researchers. Davis was walking her dog in a park near their homes when she met Robinson.

It’s a “strong collaboration,” Van Nostrand said, and has “worked out really well.”

They ask far-reaching questions, from looking at exactly how fleeting flame is to exploring supernova to studying chemistry and materials for clean energy production to examining the interaction of clouds with aerosols. The eight researchers who conduct a broad range of experiments using computers and a large numbers of data points are part of a growing one-year old group called the Institute for Advanced Computational Science.

A combined effort of Stony Brook University and Brookhaven National Laboratory, the IACS was created to use computers and their applications to solve problems in the physical sciences, life sciences, medicine, sociology, industry and finance.

The analysis of wide-ranging data is “incredibly broad and has a high payoff,” said Robert Harrison, director of the IACS, who moved to Long Island from Tennessee last year.

Funded with a $10 million donation from an anonymous contributor combined with a matching donation from the Simons Foundation, the IACS plans to hire an additional eight researchers over the next few years. Stony Brook is in the process of building a facility in what used to be the north half of the Life Sciences Library.

Harrison described computational sciences as a “very competitive” area for recruiting, which requires state-of-the-art facilities to build the best faculty and student team. The group has already purchased a $550,000 system from IBM.

Harrison, who is also the head of BNL’s Computational Sciences Center, said IACS faculty can contribute to the National Synchrotron Light Source II.

The new facility, which will open in 2015, will produce X-rays that are 10,000 times stronger than the current light source and will allow scientists to look at the molecular structure of anything from batteries as they wear down to the development of marine shells to superconductors.

Once experiments begin at the NSLS-II, the ability to process information will become especially important. The new light source “will create a lot of data at high rates,” said Reinhold Mann, the associate laboratory director for Environmental, Biological and Computational Sciences Directorate. “We need to manage the data and archive and analyze it. That needs to happen on the fly, as the data comes in. It’s a unique challenge [that requires] applied math, networking and connectivity.”

Mann, who is Harrison’s supervisor, has known him for over 10 years. Harrison leads by example and has an engaging vision, Mann said. He has a “good combination of skills on the technical and communication and people side.”

Harrison expects the computational science group to become a part of a team that enables researchers with different expertise to collaborate. “If you want to design a new fuel cell for clean energy production, by turning methanol into energy,” Harrison offered as a possible example, then “you [will work in] chemistry, material sciences and engineering. In order to understand the device, you might need to look inside it by using X-rays from the new light source.”

When he first visited Long Island in February of 2011, Harrison was surprised at how cold, raw and beautiful the area was. He said he marvels at the world around him. People are “surrounded by this miracle” he said. “Pick up a leaf and look under it at the insects or the pores in the leaf. There is all this wondrous stuff.”

Harrison and his three sisters (including a twin sister) are the first generation in their family to attend college. Harrison said he recalls sitting with his father, a World War II veteran who served in the British Army in India and who left school at the age of 14, when he was 17.

“My father didn’t understand what stars in the night sky were,” he said. Harrison suggested that understanding the “world around us” might give people “more confidence that things are okay.”

A resident of Port Jefferson, Harrison said he writes snippets of programs every day. He marvels at the rate of advancement in computers. His $700 cell phone is 10 times faster than the $20 million supercomputer he used for his Ph.D. thesis. He believes he is like many other scientists when it comes to facing an unfamiliar situation. He sees a problem as an opportunity to build knowledge.

“You work your way out of the maze,” he said, “and at each step, you learn. Even the dead ends” can provide information.

Some objects are like closed boxes. They have some observable properties but scientists don’t know exactly what is happening inside or why.

That’s where experimental physicists like Mark Dean and his colleagues at Brookhaven National Laboratory enter the picture. Dean fires X-rays with a specific energy level at copper oxide-containing materials (compounds that have copper and oxygen). To determine what’s going on inside, he sees how the X-rays change in energy and direction.

“We try to understand materials at a fairly fundamental level,” Dean said. “We think of that as a recipe that can be used for future technology.”

Copper oxide materials have magnetic properties and act as superconductors. Typical conductors have resistance, which reduces the amount of electricity received.

Superconductors, however, don’t have any resistance, which makes them potentially more efficient materials to send electricity. The catch, however, is that most superconductors require temperatures at near absolute zero — the universe’s coldest possible temperature — which makes them less practical. The energy required to cool the superconductors can be higher than the cost savings from avoiding the resistance of typical conductors.

Dean is focused on understanding the relationship between magnetism and superconductivity in these copper oxide substances.

The X-rays he fires into a material kick an electron out of the core of an atom, sending it up into a higher energy state where that electron can interact magnetically. That makes the X-rays sensitive to the magnetic properties of the material, he explained.

When a new electron replaces the one that was kicked out, it emits an X-ray photon. Dean measures the direction and energy loss of the photon in a process called resonant inelastic X-ray scattering.

Dean studies flat planes of compounds with copper and oxygen that are stacked on top of each other. These objects have superconducting properties at a relatively high temperature — about 90 Celsius degrees above absolute zero. That is still incredibly cold by human standards: about 300 degrees below zero on the Fahrenheit scale.

In the world of superconductors, that is considered “very warm,” or about a factor of 10 higher temperature than most normal superconductors, he said.

In terms of the energy trade-off between benefiting from the properties of a superconducting material and keeping that object cold enough to function, it is “becoming closer and closer to break-even,” Dean said. In five to 10 years, “we might hope to see some more areas where it’s economic” to use superconductors instead of conventional wiring.

Researchers discovered objects with copper and oxygen that had superconducting properties about 25 years ago and have been studying them extensively. To this point, they have “yet to find a satisfactory explanation of this phenomenon,” Dean said.

Dean is eager to refine the experiments when the National Synchrotron Light Source II comes online in 2015. At the NSLS-II, researchers will produce X-rays that are 10,000 times brighter than the current NSLS, enabling researchers to analyze the structure of new materials.

Chris Howard, a lecturer in the Department of Physics and Astronomy at University College in London, U.K., has confidence that Dean, with whom he has collaborated since 2007, will build on his success.

Dean is “currently proving his ability with a string of important and far-reaching publications in superconductivity and materials physics,” Howard offered. He called Dean a “real doer” and observed that he “is rapidly gaining the respect of the community he works in.” Howard appreciates the combination of Dean’s technical expertise, scientific discipline, writing skills, analytical skills and experimentation abilities.

Growing up in Broadstairs, Kent, a coastal town in southeast England, Dean developed an interest in science when he was young, where nature, through insects and wildlife documentaries and trips to zoos, appealed to him.

“As I grew older, the elegance of physics is what caught me,” he said. “The idea to conceptualize something and write down a formula: it’s such a beautifully efficient way of explaining something. You can convey a spectacular amount of information if you know how to write down the formula to describe it.”

A resident of Rocky Point, Dean came to the United States immediately after earning his doctorate. He enjoys mountain biking.

As for his work, Dean said the first semiconductor transistor was made at Bell Labs without any thought for its possible connection to the computer. It was made by scientists who were working to understand the properties of semiconductors. They didn’t realize this would lead to a semiconductor-based computer.

In a similar way, he said, by studying materials with novel properties, scientists will create “opportunities to make interesting new devices.”