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Sam Aronson. Photo courtesy of BNL

By Daniel Dunaief

Sam Aronson, the retired head of Brookhaven National Laboratory, has set his sights on a new project far from Long Island.

Teaming up with Acacia Leakey, the project management and engineering consultant of a company called SOSAED and a member of the famed family that has made seminal discoveries about human evolution in Kenya, Aronson would like to stimulate the growth of businesses through the use of solar power that provides products and services.

“This [part of Africa] is an area where there’s really little infrastructure,” Aronson said. “We’re looking to help people get up on the economic pyramid.”

The people Aronson and Leakey would like to help are representative of the one billion people without access to electric power. Two-thirds of them live in sub-Saharan Africa.

Through SOSAED — which stands for Sustainable Off-grid Solutions for African Economic Development — Aronson and Leakey are working with the Turkana Basin Institute of northern Kenya, Stony Brook University, Strathmore University in Nairobi and other Kenyan educational institutions and businesses to integrate business creation in off-grid areas into the larger Kenyan economic ecosystem.

The group would like to create a business model, using local workers and managers, for a range of companies, Leakey explained.

SOSAED plans to start with a small-scale solar-powered clothing production business, which would create affordable clothing for the heat, including skirts, shirts and shorts. SOSAED expects to build this plant adjacent to the TBI research facility.

Ideally, the manufacturer will make the clothing from local material. The clothing business is a pilot project to see whether the model can work for other types of projects in other areas. The Turkana Basin Institute will provide some of the infrastructure, while SOSAED will acquire the equipment and the raw materials and training to do the work.

SOSAED hopes the project will become “self-sustaining when it’s up and running,” Aronson said. “To be sustainable, it has to be the work of local people.” He hopes what will differentiate this effort from other groups’ attempts to build economic development is the commitment to maintenance by people living and working in the area.

“To an extent, the suitability of technology is rarely rigorously considered when humanitarian or generic development projects are implemented,” Leakey explained in an email. “Not only are the skills required for maintenance an important consideration, the availability of spare parts and the motivation and ability to pay for these are also important.”

Developing a system that includes upkeep by people living and working in the area could “make a project move ahead on its own steam,” Aronson said. The area has limited infrastructure, although some of that is changing as new roads and government-funded water projects begin.

Leakey suggested that a long-term project would need extensive participation of the users in every step of the development and implementation. “The project will likely look very different once complete to how we envisage it now, and part of our success (if it comes) will lie in working in a way which allows a great degree of flexibility as it is unlikely we’ll design the ‘right’ system the first time around,” she explained in an email.

In areas with mature systems, Leakey suggested that some organizations had difficulty changing direction, retrofitting existing systems or adapting new technology. New York, she explained, is struggling to adopt sustainable technologies to the extent that it could. “Legislative and physical infrastructure imposes unfortunate roadblocks in the way of clean technologies,” she wrote in an email. “We’re fortunate that with electricity provision we have a fairly blank slate” in Kenya and that the “Kenya government also recognizes the value of off-grid initiatives.”

Leakey appreciates the support TBI played in helping to create SOSAED and is grateful for the ongoing assistance. Through Stony Brook University, SOSAED is beginning to engage business students on economic questions. In the future, the group may also work with engineering students on technological challenges.

“Research may include developing new productive uses of solar power, optimizing the existing system and using the site to rigorously test technologies developed at Stony Brook,” she explained.

Aronson’s initial interest in this project came from his technological connection to Brookhaven National Laboratory, where he retired as the director in 2015. He has been eager to bring new technology to a population he is confident they can help in a “way that makes sense to them and addresses their needs.”

With the support of the Turkana Basin Institute and Stony Brook, Aronson hopes to have a functioning solar hub and factory near TBI that serves a few surrounding villages within the next 18 months. “That’s a very ambitious goal,” he acknowledged. “We’re working in an environment that, because of the history and development, people you’re trying to serve are somewhat skeptical that you’re serious and that you have the staying power to make something that looks like what you’re talking about work.” 

While Aronson and Leakey are continuing to make connections in Kenya with government officials and residents interested in starting businesses, they are searching for ways to make this effort financially viable.

SOSAED is raising money through philanthropic grants and foundations to get the project going. Eventually, they hope to approach venture capital firms who are patient and prepared to invest for the longer term in a number of projects.

After they have an initial example, they will approach other financial backers with more than just a good idea, but with a model they hope will work in other locations.

Aronson lauded the effort and knowledge of Leakey. “We wouldn’t be making much progress right now for a variety of reasons in Kenya if [Leakey] hadn’t come on board,” Aronson said. “I value in the extreme her ability to get the work done.”

SOSAID would like to submit proposals to funding sources that can drive this concept forward.

If this effort takes root, Aronson believes there is a “tremendous market out there.” That would mean this would “become a much bigger organization.”

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Gábor Balázsi. Photo by Dmitry Nevozhay

By Daniel Dunaief

An especially hot July day can send hordes of people to Long Island beaches. A cooler July temperature, however, might encourage people to shop at a mall, catch a movie or stay at home and clean out clutter.

Similarly, genes in yeast respond to changes in temperature.

Gábor Balázsi, the Henry Laufer associate professor of physical and quantitative biology at Stony Brook University, recently published research in the Proceedings of the National Academy of Sciences on the effect of temperature changes on yeast genes.

“We are looking at single cells and at genetic systems and we can dissect and understand gene by gene with a high level of detail,” said Balázsi, who used synthetic genetic systems to allow him to dissect and understand how temperature affects these genes.

Understanding the basic science of how genes in individual cells respond to temperature differences could have broad applications. In agriculture, farmers might need to know how genes or gene circuits that provide resistance to a pathogen or drought tolerance react when the temperature rises or falls.

Similarly, researchers using genetically designed biological solutions to environmental problems, like cleanups at toxic spills, would need to understand how a change in temperature can affect their systems.

Lingchong You, an associate professor of biomedical engineering at Duke University, believes the research is promising.

“Understanding how temperature will influence the dynamics of gene circuits is intrinsically interesting and could serve as a foundation for the future,” You said. Researchers “could potentially design gene circuits to program the cell such that the cell will somehow remember its experience with the fluctuating temperatures,” which could provide clues about the experience of the cell.

Balázsi suggested the goal of his work is to understand the robustness of human control over cells in nonstandard conditions.

While other researchers have explored the effects of gene expression for hundreds of genes at different temperatures, Balázsi looked more precisely at single genes and human-made synthetic gene circuits in individual cells. He discovered various effects by inserting a two-gene circuit into yeast.

At the whole-cell level when temperatures rise from 30°C to 38°C, some cells continued growing, albeit at a slower rate, while others stopped growing and started to consume their proteins.

For the second type of cells, changing temperatures can lead to cell death. If the temperature comes down to normal levels soon enough, however, researchers can rescue those cells.

“How this decision happens is a question that should be addressed in the future,” Balázsi said.

While the dilution of all proteins slows down, the chemical reactions in which they participate speed up at a higher temperature, much like children who become more active after receiving sugar at a birthday party.

At another level, certain individual molecules change their movement between conformations at a higher temperature. Proteins wiggle more between different folding conformations even if they don’t change composition. This affects their ability to bind DNA.

Balázsi said he is fortunate that he works through the Laufer Center for Physical and Quantitative Biology, which partly supported the work, where he was able to find a collaborator to do molecular dynamic simulations. Based on the pioneering experiments of postdoctoral fellow Daniel Charlebois, with help from undergraduate researcher Sylvia Marshall, the team collected data for abnormal behaviors of well-characterized synthetic gene circuits. They worked with Kevin Hauser, a former Stony Brook graduate research assistant, who explained how the altered conformational movements affected how the protein and cells behaved.

The way proteins fold and move between conformations determines what they do.

Gábor Balázsi with his daughter Julianna at West Meadow Beach
Photo from Gábor Balázsi

Taking his observations and experiments further, Balázsi found that proteins that were unbound to a small molecule didn’t experience a change in their conformation. When they were linked up, however, they demonstrated a new behavior when heated. This suggests that understanding the effects of temperature on these genetic systems requires an awareness of the proteins involved, as well as the state of their interaction with other molecules.

While Balázsi explored several ways temperature changes affect the yeast proteins, he acknowledged that other levels or forces might emerge that dictate the way these proteins change.

Additionally, temperature changes represent just one of many environmental factors that could control the way the genetic machinery of a cell changes. The pH, or acidity, of a system might also change a gene or group of genes.

A main overarching question remains as to how much basic chemical and physical changes combine with biological effects to give predictable, observable changes in the behaviors of genes and living cells.

Balázsi may test other cell types. So far, he’s only looked at yeast cells. He would also like to know the order in which the various levels of reactions — from the whole cell to the molecular level — occur.

He is interested in cancer research and possibly defense applications and would like to take a closer look at the way temperature or other environmental factors impact human disease processes and progression or think about their relevance for homeland security or biological solutions to renewable energy.

Balázsi recognizes that he and others in this field have numerous hurdles to overcome to find acceptable appreciation for the application of synthetic gene circuits.

“It’s not so simple to engineer these cells reliably,” he said. “Some roadblocks need to be eliminated to convince people it’s feasible and useful.”

Balázsi suggested that the field of virology might benefit from pursuing some of these research questions. Viruses move from the environment or even from other hosts into humans. Avian influenza, for example, can begin inside a bird and wind up affecting people. These viruses “might have different expression patterns in birds versus humans,” he said.

Ultimately, he added, this kind of scientific pursuit is “multipronged and the applications are numerous.”

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Francis Alexander. Photo from BNL

By Daniel Dunaief

Now what? It’s a question that affects everyone from the quarterback who wins the Super Bowl — who often says something about visiting a Disney facility — to the student who earns a college degree, to the researcher who has published a paper sharing results with the scientific community.

For some, the path forward is akin to following footsteps in the snow, moving ever closer to a destination for which a path is clear. For others, particularly those developing new technology, looking to unlock mysteries, the path is more like trudging through unfamiliar terrain.

The technology at facilities like Brookhaven National Laboratory, which includes the powerful National Synchrotron Light Source II and the Center for Functional Nanomaterials, among others, enables scientists to see processes at incredibly fine scales.

While these sites offer the promise of providing a greater ability to address questions such as what causes some batteries to die sooner than others, they also cost considerable money to use, putting pressure on researchers to ask the most fruitful question or pursue research that has the greatest chance for success.

Francis Alexander. Photo from BNL

That’s where people like Francis Alexander, the deputy director of Brookhaven National Laboratory’s Computational Science Initiative, and his team at BNL can add considerable value. Alexander takes what researchers have discovered, couples it with other knowledge, and helps guide his fellow laboratory scientists to the next steps in their work — even if he, himself, isn’t conducting these experiments.

“Given our theoretical understanding of what’s going on, as imperfect as that may be, we take that understanding — the theory plus the experimental data — and determine what experiments we should do next,” Alexander said. “That will get us to our goal more quickly with limited resources.”

This approach offers a mutually reinforcing feedback loop between discoveries and interpretations of those discoveries, helping researchers appreciate what their results might show, while directing them toward the next best experiment.

The experiments, in turn, can either reinforce the theory or can challenge previous ideas or results, forcing theoreticians like Alexander to use that data to reconstruct models that take a wide range of information into account.

Alexander is hoping to begin a project in which he works on developing products with specific properties. He plans to apply his knowledge of theoretical physics to polymers that will separate or grow into different structures. “We want to grow a structure with a [particular] function” that has specific properties, he said.

This work is in the early stages in which the first goal is to find the linkage between what is known about some materials and what scientists can extrapolate based on the available experiments and data.

Alexander said the aerospace industry has “models of everything they do.” They run “complex computer simulations [because] they want to know how they’d design something and which design to carry out.”

Alexander is currently the head of a co-design center, ExaLearn, that focuses on exascale, machine-learning technologies. The center is the sixth through the Exascale Computing Project. Growth in the amount of data and computational power is rapidly changing the world of machine learning and artificial intelligence. The applications for this type of technology range from computational and experimental science to engineering and the complex systems that support them.

Ultimately, the exascale project hopes to create a scalable and sustainable software framework for machine learning that links applied math and computer science communities to create designs for learning.

Alexander “brings to machine learning a strong background in science that is often lacking in the field,” Edward Dougherty, a distinguished professor in the Department of Electrical and Computer Engineering at Texas A&M, wrote in an email. He is an “excellent choice to lead the exascale machine learning effort at Brookhaven.”

Alexander is eager to lead an attempt he suggested would advance scientific and national security work at the Department of Energy. “There are eight national laboratories involved and all the labs are on an equal level,” he said. 

One of the goals of the exascale computing project is to build machines capable of 10 to the 18th operations per second. “There’s this enormous investment of DOE” in this project, Alexander said.

Once the project is completely operational, Alexander expects that this work will take about 30 percent of his time. About 20 percent of the time, he’ll spend on other projects, which leaves him with about half of his workweek dedicated to management.

The deputy director recognizes that he will be coordinating an effort that involves numerous scientists accustomed to setting their own agenda.

Dougherty suggested that Alexander’s connections would help ensure his success, adding that he has “established a strong network of contacts in important application areas such as health care and materials.

The national laboratories are akin to players in a professional sporting league. They compete against each other regularly, bidding for projects and working to be the first to make a new discovery. Extending the sports metaphor, members of these labs often collaborate on broad projects, like players on an all-star team competing against similar teams from other nations or continents.

Alexander grew up in Ohio and wound up working at Los Alamos National Laboratory in New Mexico  for over 20 years. He came to BNL in 2017 because he felt he “had the opportunity to build something almost from the ground up.” The program he had been leading at Los Alamos was large and well developed, even as it was still growing. 

The experimental scientists at BNL have been receptive to working with Alexander, which has helped him achieve some of his early goals.

Ultimately, Alexander hopes his work increases the efficiency of numerous basic and applied science efforts. He hopes to help experimental scientists understand “what technologies we should develop that will be feasible” and “what technologies would be most useful to carry experiments out.”

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Stony Brook University Hospital. File photo

Most people only think about Lyme disease when taking a hike in a park, but for many doctors, the condition weighs heavily on their minds every day.

Dr. Benjamin Luft, director and principal investigator of Stony Brook WTC Wellness Program, is one of those doctors. He is currently working on two clinical studies examining the disease. One involves those who continue to present symptoms after being treated, and the other study involves Latinos on Long Island who work in the landscaping and agricultural fields.

In a recent phone interview, Luft said the clinical study involving Latinos is a straightforward one, where the aim is to help a population that has been underserved and understudied due to their work schedules. The other study is more involved.

After being bitten by a tick infected with a bacterium called Borrelia burgdorferi, many people with a bull’s eye rash or flulike symptoms may receive treatment and feel better; but there are those who will continue to suffer for a prolonged period, even years, with a variety of complaints like aches, pains and brain fogginess. Luft said at times there may be no clear signs of the disease in the body, but doctors may find evidence of it after thorough neuropsychological exams that can detect subtle abnormalities.

Dr. Benjamin Luft is one of the doctors at Stony Brook Medicine looking for answers when it comes to those who continue to suffer from Lyme disease after treatment. Photo from Stony Brook Medicine

“This study is really geared toward diagnosing and to find ways to be able to monitor the disease,” Luft said, adding in the future his hope is to conduct studies testing new ways to treat Lyme disease.

The doctor said it’s essential to receive a diagnosis because if Lyme disease is left untreated, it can lead to joint swelling, arthritis, neuropathies, meningitis or cardiac problems.

When Stony Brook University recently began making a more significant investment in its imagining facilities, Luft said he saw a chance to find an answer for those with chronic symptoms.

“I thought this is the opportunity to see what is going on in the brain of these patients with using X-ray techniques and radiological techniques which may give us some insight,” he said.

He said with cutting-edge neuroimaging studies researchers can look for evidence of inflammation in the brain which may be a reaction to the infection.

“That would be an important thing to do because it may give us another target for therapy,” Luft said. “A lot of the therapy that we now use is really just geared toward the organism itself, but it’s not really geared toward the body’s reaction to the organism which may also have to be treated in order to alleviate some of these symptoms.”

The doctor has studied Lyme disease for more than 30 years. When he arrived at SBU from Stanford University Hospital, he was involved in work with AIDs and age-related diseases, but he said at the university’s clinic in the 1980s many people complained of Lyme disease problems and there were no effective therapies at the time. Many of the first therapies and treatments used today were developed at SBU, he said, but there have always been people who haven’t responded well to those treatments.

“So that’s been something that’s been bothering me for many years as to why that is,” Luft said.

He said he will present initial data, which is promising, from the clinical imagining study at a conference in Barcelona, Spain, later this month and hopes to get more patients for the clinical study. Those who are interested can call 631-601-5615. Subjects must meet stringent criteria including not having any other disease, having serological evidence of Lyme disease and a clear history that they had the rash.

In addition to Luft’s studies, Dr. Christy Beneri, assistant professor of pediatrics at SBU, and her team are working on a pilot study to look at newer diagnostic tools to establish a better way to diagnose early Lyme disease.

“We also will be doing work on understanding tick epidemiology in our area and working with the local health department to understand potential new tick-borne pathogens,” Beneri said.

Stony Brook Lyme Disease Laboratory has been performing Lyme disease testing on clinical specimens since 1984. Both inpatients and outpatients can have a Lyme ELISA screening test and Western blots confirmatory test at Stony Brook Medicine. Almost 10,000 screenings were done in 2017 at the hospital, which has been actively working with state senators for funding for Lyme disease outreach and research, according to Beneri.

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Giovanni Alfonso Borelli

By Elof Axel Carlson

Elof Axel Carlson

Scientists have a tradition of citing those whose work helped shape their own ideas and experiments. Almost every scientific paper has a list of such journal articles or books cited by the authors of a published article in a peer-reviewed journal. Usually these references are to recent work that the author or authors have read. 

But one could chase back the references of each cited article and keep doing this to work that was published in the 1600s. Before that things get more complicated because science as we know it dates to the Renaissance. Most of those cited names are forgotten to us and we are taught the names of only a few of these many scientists. 

Thus, we single out the major contributors like Galileo and his work supporting the Copernican theory that Earth and other planets move around the sun. We cite Vesalius’s work on human anatomy, the first accurate depiction of the organs of the human body. We also cite Harvey’s work on the circulation of the blood. What these all have in common is the belief that living organisms are like machines and the laws of physics apply to interpreting their structure and function. 

One of the forgotten contributors to this view of life was Giovanni Alfonso Borelli (1608–1679). Born in Naples, he was the son of a Spanish father, Miguel Alonso, and an Italian mother, Laura Porrello. His father had been exiled from Spain for association with a heretic. This led young Giovanni at the age of 20 to change his baptismal name from Giovanni Francesco Antonio Alonso to the fully Italian sounding Giovanni Alfonso Borelli, which was a version of his mother’s surname Porrello. 

At that time Naples was a Spanish colony and Borelli grew up with his sympathies for Italian culture and political rule. He became a mathematician and astronomer first. He worked out the orbits of Galileo’s discovery of the four large moons of Jupiter and showed they were ellipses. He showed that a comet of 1664 had a parabolic path and was farther than the moon, contradicting church belief then that the comets were not as far as the moon. Isaac Newton cited his work.  

Borelli shifted to medicine and showed that the motions of animals was caused by muscle contractions and the mathematics of levers, pulleys and other machines applied to the components of the body that he studied. He rejected the prevailing view that motion was caused by a vital fluid in the muscles coming from nerves by cutting muscles and showing no such fluids were released. Instead he worked out the center of gravity for different activities of animals and founded the field of biomechanics.  

He kept moving whenever his Spanish ancestry was revealed or when he contradicted fellow scientists who clung to Aristotelian theories that Borelli rejected as nonscientific. In his later life while writing his works, he was supported by Queen Christina of Sweden who went into exile in Rome after converting to Catholicism. He taught mathematics in the convent school that she established and she paid for the publication of his book on animal motion that he dedicated to her.  

Elof Axel Carlson is a distinguished teaching professor emeritus in the Department of Biochemistry and Cell Biology at Stony Brook University.

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Above, Brian Colle, who enjoys surf fishing, with a false albacore that he caught at the Shinnecock Inlet. Photo by B. Colle

By Daniel Dunaief

In August of 2014, Islip experienced record rainfall, with over 13 inches coming down in a 24-hour stretch — more than the typical rainfall for an entire summer and a single day record for New York state. The rain required emergency rescues for motorists whose cars suddenly died after more than 5 inches of rain fell in a single hour.

What if, however, that rain had fallen just 50 miles west, in Manhattan, where the population density is much higher and where people travel to and from work on subways that can become flooded from storms that carry less precipitation?

An image of an ice crystal Colle examined during a Nor’easter. Image from B. Colle

Brian Colle, professor of atmospheric sciences and director of the Institute for Terrestrial and Planetary Atmospheres at the School of Marine and Atmospheric Sciences at Stony Brook University, is part of a group that is studying flood risks in the New York metro area during extreme storms that could bring heavy rains, storm surge or both. The team is exploring mitigation strategies that may help reduce flooding.

“The risk for an Islip event for somewhere in the NYC-Long Island area may be about one in 100 years (but this is being further quantified in this project), and this event illustrates that it is not a matter of whether it will occur in NYC, but a matter of when,” Colle explained in a recent interview.

The group, which is led by Brooklyn College, received $1.8 million in funding from New York City’s Department of Environmental Protection and the Mayor’s Office of Recovery & Resiliency. It also includes experts from The New School, the Stevens Institute of Technology and Colorado State University.

The co-principal investigators are Assistant Professor Brianne Smith and Professor Jennifer Cherrier, who are in the Department of Earth and Environmental Sciences at Brooklyn College–CUNY.

Smith, who had worked with Colle in the past, had recruited him to join this effort. They had “been wanting to do studies of flooding for New York City for a long time,” Smith said. “When the city came out with this” funding for research, Colle was “the first person I thought of.”

Malcolm Bowman, a distinguished service professor at Stony Brook University, holds his colleague, whom he has known for a dozen years, in high regard. Colle is “a leading meteorologist on regional weather patterns,” he wrote in an email. 

Colle is interested in the atmospheric processes that produce rainfall of 2 or 3 inches per hour. “It takes a unique part of the atmosphere to do that,” he said. The three main ingredients are lots of moisture, lift along a wind boundary, and an unstable atmosphere that allows air parcels, or a volume of air, to rise, condense and produce precipitation.

Representatives from the local airports, the subway systems and response units have been eager to get these predictions, so they can prepare mitigation efforts.

Brooklyn College – CUNY project co-leads Brianne Smith (left) and Jennifer Cherrier at Grand Army Plaza in Brooklyn in early September. Photo by John Mara

This group has taken an ambitious approach to understanding and predicting the course of future storms. Typically, scientists analyze storms using 100- to 200-kilometer grid spacing. In extreme rainfall events during coastal storms, scientists and city planners, however, need regional spacing of 20 kilometers. Looking at storms in finer detail may offer a more realistic assessment of local precipitation.

Researchers are anticipating more heavy rainfall events, akin to the one that recently caused flooding in Port Jefferson.

A warmer climate will create conditions for more heavy rains. Water vapor increases about 6 to 7 percent for every degree increase in Celsius. If the climate rises two to four degrees as expected by the end of the century, this would increase water vapor by 13 to 25 percent, Colle said.

The group includes experts from several disciplines. “Each of the scientists is highly aware of how integrative the research is,” Cherrier said. The researchers are asking, “How can we provide the best scientific foundation for the decisions” officials need to make. If, as predicted, the storms become more severe, there will be some “hard decisions to make.”

Smith suggested that a visible project led by women can encourage the next generation of students. Women undergraduates can appreciate the opportunity their female professors have to lead “cool projects,” she said. 

Raised from the time he was 4 in Ohio, Colle said he was a “typical weather geek” during his childhood. The blizzard of 1978 fascinated him. After moving to Long Island in 1999, Colle used to sit in a weather shed and collect ice crystals during nor’easters. He would study how the shape of these crystals changed during storms. An avid surf fisherman, Colle said there is “not a better place to observe weather” than standing near the water and fishing for striped bass, fluke, bluefish and false albacore. A resident of Mount Sinai, Colle lives with his wife Jennifer, their 16-year-old son Justin and their 13-year-old son Andrew.

As for his work on flood risks around the New York metro area, Colle said the group is producing monthly reports. The effort will end in December. “The urgency is definitely there,” he acknowledged. Heavy rainfall has increased the need to understand rain, particularly when combined with surge flooding.

A transportation study written over a decade ago describes storm surge and rainfall risk. That study, however, included a prediction of 1 to 2 inches of rainfall an hour, which is far less than the 5 inches an hour that hit Long Island in 2014.

“Once you start seeing that, there’s a lot of people who are nervous about that risk and want to get a best estimate of what could happen,” Colle said.

Cherrier described New York City as being “quite progressive” in gathering information and formulating data. “The city wants to be prepared as soon as possible.”

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Leila Esmailzada, kneeling, with another BeLocal team member Caroline Rojosoa (in the black argyle sweater) distribute trial briquettes. Photo courtesy of BeLocal

By Daniel Dunaief

Leila Esmailzada set out to change the world but first had to perform a task that turns many people’s stomachs: clean someone else’s vomit off the floor.

The Stony Brook University graduate student, who is in the master’s Program in Public Health, traveled to Madagascar for a second consecutive summer with the nonprofit BeLocal Group to help several teams of student engineers put into place projects designed to improve the lives of the Malagasy people.

Before they could help anyone else, however, these students, many of them recent graduates from the College of Engineering, fought off a series of viruses, including a particularly painful stomach bug.

Esmailzada said she saw cleaning the vomit off the floor as part of the big picture.

“Compassion really plays into being abroad for your work and for your team, because you realize that everybody came here for a shared mission,” Esmailzada said. “What happens along the way is sometimes just a result of the path that brought them here.”

Briquettes lay out to dry in Madagascar. Photo courtesy of BeLocal

Indeed, beyond Esmailzada’s compassion, her ability to continue to accomplish tasks in the face of unexpected and potentially insurmountable obstacles encouraged BeLocal, a group started by Laurel Hollow residents Mickie and Jeff Nagel and Eric Bergerson, to ask her to become the group’s first executive director.

“I can’t say enough about [Esmailzada] being so resourceful over there,” said Mickie Nagel, who visited the island nation of Madagascar the last two years with Esmailzada. “She thinks about things in a different way. You can have the best product, but if you can’t connect it to the Malagasy and understand more deeply what they need, what their concerns or wants are” the project won’t be effective.

This past summer BeLocal tried to create two engineering design innovations that had originated from senior projects at SBU. In one of them, the engineers had designed a Da Vinci bridge, borrowing a model from the famous inventor, to help villagers cross a stream on their way to the market or to school. When the makeshift bridge constructed from a log or tree got washed away or cracked, the residents found it difficult to get perishable products to the market.

The first challenge the group faced was the lack of available bamboo, which they thought they had secured months before their visit.

“When the bamboo wasn’t delivered, I figured we were now going to do research on bamboo,” Nagel explained in an email, reflecting the group’s need to react, or, as she suggests, pivot, to another approach.

When they finally got bamboo, they learned that it was cut from the periphery of a patch of bamboo that borders on a national park. Government officials confiscated the bamboo before it reached BeLocal.

“We were happy to see that law enforcement recognized and acted on the ‘gray area rules’ of conserving the national park, which shows that the hard work Madagascar is putting into conservation is actually paying off,” Esmailzada said. She eventually found another provider who could deliver the necessary bamboo a few days later. This time, an important material was cut down from a local farm.

While they had the bamboo, they didn’t know how to cure it to prepare it for construction. Uncured, the bamboo could have become a soggy and structural mess. “We did try to cure [it] a few different ways, but we really didn’t have the time needed to properly treat all of it,” Nagel said. “We didn’t anticipate the bamboo not arriving cured since it was what we had been working on for months.”

Nagel credits the bridge team with adjusting to the new circumstances, constructing two girder bridges over creeks for more market research.

The BeLocal team also worked on a project to create briquettes that are healthier than the firewood the Malagasy now use for cooking. The wood produces considerable smoke, which has led to respiratory diseases and infections for people who breathe it in when they cook.

The group produced briquettes toward the end of their summer trip and presented their technique to an audience of about 120 locals, which reflected the interest the Malagasy had shown in the process during its development.

This fall, BeLocal is working on ways to move forward with sharing the briquette technique, which they hope to refine before the new year. BeLocal wants to develop clubs at Stony Brook and at the University of Fianarantsoa in Madagascar that can work together.

While BeLocal will continue to share senior design ideas on its website (www.belocalgrp.com) with interested engineers, the group is focusing its energy on perfecting the briquettes and getting them to people’s homes in Madagascar.

Nagel admired Esmailzada’s approach to the work and to the people in Madagascar.

Esmailzada said she studied how people in Madagascar interact and tried to learn from that, before approaching them with a product or process. She believes it’s important to consider the cultural boundaries when navigating the BeLocal projects, realizing that “you are not the first priority in a lot of these villagers’ lives in general. You have to understand they won’t meet and speak with you. It’s a reasonable expectation to ask maybe three times for something before you think you can get it done.”

Esmailzada also developed a routine that allowed her to shift from one potential project to another, depending on what was manageable at any given time.

The Stony Brook graduate student is delighted to be an ongoing part of the BeLocal effort.

“I love working with an organization that has the passion and vision as large as BeLocal,” she explained. “This work is fulfilling because you are working toward the chance of improving the well-being of another person or community.”

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Above, Mikala Egeblad works with graduate student Emilis Bružas in the Watson School of Biological Sciences. Photo from Pershing Square Soon Cancer Research Alliance

By Daniel Dunaief

For some people, cancer goes into remission and remains inactive. For others, the cancer that’s in remission returns. While doctors can look for risk factors or genetic mutations, they don’t know why a cancer may come back at the individual level.

In a mouse model of breast and prostate cancers, Mikala Egeblad, an associate professor at Cold Spring Harbor Laboratory, has found an important driver of cancer activation and metastasis: inflammation. When mice with cancer also have inflammation, their cancer is likely to become more active. Those who don’t have inflammation, or whose inflammation is treated quickly, can keep the dreaded disease in check. Cancer cells “may be dormant or hibernating and not doing any harm at all,” she said. “We speculated what might be driving them from harmless to overt metastasis.”

Egeblad cautioned that this research, which was recently published in the journal Science, is on mice and that humans may have different processes and mechanisms.

CSHL’s Mikala Egeblad. Photo from Pershing Square Soon Cancer Research Alliance

“It is critical to verify whether the process happens in humans,” Egeblad suggested in an email, which she will address in her ongoing research. Still, the results offer a window into the way cancer can become active and then spread from the lungs. She believes this is because the lungs are exposed to so many external stimuli. She is also looking into the relevance for bone, liver and brain metastases. The results of this research have made waves in the scientific community.

“This study is fantastic,” declared Zena Werb, a professor of anatomy and associate director for basic science at the Helen Diller Family Comprehensive Cancer Center at the University of California in San Francisco. “When [Egeblad] first presented it at a meeting six months ago, the audience was agog. It was clearly the best presentation of the meeting!”

Werb, who oversaw Egeblad’s research when Egeblad was a postdoctoral scientist, suggested in an email that this is the first significant mechanism that could explain how cancer cells awaken and will “change the way the field thinks.”

Egeblad credits a team of researchers in her lab for contributing to this effort, including first author Jean Albrengues, who is a postdoctoral fellow. This group showed that there’s a tipping point for mice — mice with inflammation that lasts six days develop metastasis.

Egeblad has been studying a part of the immune system called neutrophil extracellular traps, which trap and kill bacteria and yeast. Egeblad and other researchers have shown that some cancers trick these NETs to aid the cancer in metastasizing.

In the new study, inflammation causes cancer cells that are not aggressive to develop NETs, which leads to metastasis. The traps and enzymes on it “change the scaffold that signals that cancer should divide and proliferate instead of sitting there dormant,” Egeblad said.

To test out her theory about the role of enzymes and the NETs, Egeblad blocked the cascade in six different ways, including obstructing the altered tissue scaffold with antibodies. When mice have the antibody, their ability to activate cancer cells after inflammation is prevented or greatly reduced, she explained.

The numbers from her lab are striking: in 100 mice with inflammation, 94 developed metastatic cancer. When she treated these mice with any of the approaches to block the inflammation pathway, 60 percent of them survived, while the remaining 40 percent had a reduced metastatic cancer burden in the lungs.

If inflammation is a key part of determining the cancer prognosis, it would help cancer patients to know, and potentially treat, inflammation even when they don’t show any clinical signs of such a reaction.

In mice, these NETs spill into the blood. Egeblad is testing whether these altered NETs are also detectable in humans. She could envision this becoming a critical marker for inflammation to track in cancer survivors.

The epidemiological data for humans is not as clear cut as the mouse results in Egeblad’s lab. Some of these epidemiological studies, however, may not have identified the correct factor.

Egeblad thinks she needs to look specifically at NETs and not inflammation in general to find out if these altered structures play a role for humans. “We would like to measure levels of NETs and other inflammatory markers in the blood over time and determine if there is a correlation between high levels and risk of recurrence,” she explained, adding that she is starting a study with the University of Kansas.

Werb suggested that inflammation can be pro-tumor or anti-tumor, possibly in the same individual, which could make the net effect difficult to determine.

“By pulling the different mechanisms apart, highly significant effects may be there,” Werb wrote in an email. Other factors including mutation and chromosomal instability and other aspects of the microenvironment interact with inflammation in a “vicious cycle.”

In humans, inflammation may be a part of the cancer dynamic, which may involve other molecular signals or pathways, Egeblad said.

She has been discussing a collaboration with Cold Spring Harbor Laboratory’s Doug Fearon, whose lab is close to hers.

Fearon has been exploring how T-cells could keep metastasis under control. Combining their approaches, she said, cancer might need a go signal, which could come from inflammation, while it also might need the ability to alter the ability of T-cells from stopping metastasis.

In her ongoing efforts to understand the process of metastasis, Egeblad is also looking at creating an antibody that works in humans and plans to continue to build on these results. “We now have a model for how inflammation might cause cancer recurrence,” she said. 

“We are working very actively on multiple different avenues to understand the human implications, and how best to target NETs to prevent cancer metastasis.”

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placozoa

By Elof Axel Carlson

Elof Axel Carlson

Biologists classify living things using a system that Carl Linnaeus (1707–1778) introduced in the 18th century and that has grown in detail over the decades as new forms of life are found and studied. Humans are familiar with being vertebrates (a class of the phylum Chordata). Chordates are animals with a spinal cord, spine or an embryonic structure called a notochord. There are 55,000 chordate species. So far there are 109 phyla covering plants, animals, protozoa, fungi, bacteria and archaea, which are less precisely organized into kingdoms and domains.  

One phylum, first discovered in 1883, consisted of just one species until recently. These are the Placozoa (placo = flat and zoa = animal). They are small (about an eighth of an inch or 1 mm) and are roughly disc shaped with three layers. The top layer has cells with a hairlike thread called a cilium. The bottom layer is also ciliated but has additional cells that take in food from the ocean muck on which the placozoa live. The middle layer has amebalike cells and fiber-bearing cells that contract, making the placozoa lumpy in appearance.  

They reproduce by forming a bud that enlarges and eventually pinches off to produce identical twins. In laboratories, some of the placozoa produce sex cells (sperm and eggs), but these rarely survive the embryonic stage with about 150 cells at the time they die. No such embryos are found in samples of ocean sediments where placozoa dwell. Their DNA has been analyzed and it shows they have a past history of doubling their gene number and rearranging the sequences of their genes as they have moved about the oceans for more than 500 million years.  

Today three species are recognized from samplings around the world. They have about 12,000 genes and portions of these they share with sponges (the phylum Porifera) and comb jellies (the phylum Ctenophora).

Note that the placozoa do not have organized tissues (we have epithelial, muscular, connective and nervous tissues), a basic symmetry (we have a bilateral or left and right sides that are roughly mirror images) or body organs (we have kidneys, lungs, internal bones and eyes, ears, a nose and mouth). They have no nerve cells, muscle cells, bony structure, intestines or sense organs.  

What makes the placozoa interesting to biologists in this molecular era is the opportunity to compare the genomes of related phyla and see what genes they have to work out a molecular tree similar to the trees of life that have been worked out by comparative anatomists since Darwin’s theory of evolution provided a model of how to organize life. They represent the launching state of life before the familiar phyla of sponges, worms and more complex phyla appear in the fossil records.  

Most of the familiar phyla appear in the Cambrian era about 500 million years ago, and the placozoa are first seen in rocks designated as Ediacaran, which existed 100 million years earlier. Rocks can be dated by isotopes present in atoms that have decayed over the millennia. 

Of future interest will be identifying genes in later phyla and genes in placozoa and how they function in these different organizations of life. Also, it will be interesting to follow the genes in placozoa and in their ancestors back to protozoa in the animal kingdom. As interesting as placozoa are, they are too small to be adopted as pets in saltwater aquariums and hard to differentiate without a lens from the muck that accumulates in a fish tank.     

Elof Axel Carlson is a distinguished teaching professor emeritus in the Department of Biochemistry and Cell Biology at Stony Brook University.

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Aaron Sasson. Photo courtesy of Stony Brook Medicine

By Daniel Dunaief

Thanks to the efforts of Stony Brook University School of Medicine’s Chief of Surgical Oncology Aaron Sasson and numerous doctors and researchers at Stony Brook, Long Island has its first National Pancreas Foundation Center.

A nonprofit organization, the National Pancreas Foundation goes through an extensive screening process to designate such centers around the country, recognizing those that focus on multidisciplinary treatment of pancreatic cancer. The NPF offers this distinction to those institutions that treat the whole patient and that offer some of the best outcomes and improved quality of life for people suffering with a disease who have an 8 percent survival rate five years after diagnosis.

Sasson appreciates the team effort at the medical school. “As opposed to one person leading this, there are many people here who are required to have an interest in pancreatic cancer,” he said. “We are not only looking to build a great infrastructure for the treatment of pancreatic cancer, but we’re also looking to build a team for research on pancreatic cancer.”

Sasson highlighted the research efforts led by Yusuf Hannun, the director of the Cancer Center at SBU, who has helped attract a “tremendous number of scientists” to engage in research into this disease.

The recognition by the NPF helps the university recruit physicians who are clinically interested in developing ways to improve the outcome for patients.

Pancreatic cancer presents particular challenges complicated by its biological aggressiveness, its difficulty to detect and by the many subtypes of this disease. “It’s similar to lung and breast cancer,” Sasson said. “There are many facets of those cancers. You can’t lump them all together.”

Researchers and clinicians are still trying to understand pancreatic cancer in greater detail. Once they have done that, they can advance to treating the possible subtypes.

Numerous researchers at SBU have developed collaborations with scientists at Cold Spring Harbor Laboratory. David Tuveson, the director of the National Cancer Institute-designated Cancer Center, has engaged in collaborations with SBU scientists in his work on organoids, which are model human organs grown in a lab. Scientists use organoids to test drugs and molecular pathways involved in pancreatic cancer.

Members of the Long Island community can take comfort in the continuing dedication of the numerous staff members committed to finding a cure. “Residents of Suffolk County and Long Island should be proud of what Stony Brook has been able to accomplish,” Sasson said.

Stony Brook University has been involved in several clinical efforts. The university developed a drug called CPI-613, for which Rafael Pharmaceuticals is in the early stage of clinical trials in combination with other drugs.

In early stages, the treatment increases the vulnerability of cancer cells to numerous other drugs. Newark, New Jersey-based Rafael Pharmaceuticals is testing this treatment in pancreatic cancer and in acute myeloid leukemia.

At SBU facilities, Sasson explained that researchers and clinicians are taking a multidisciplinary approach in their work. One study, he said, is exploring the effects of a kind of radiation therapy for a subpopulation of pancreatic cancer that combines expertise in radiology, gastroenterology, pathology and medical and surgical oncology.

Sasson himself is interested in screening and biomarkers. At least half of his work is related to pancreatic cancer. When he thinks about people who have battled pancreatic cancer, several patients come to mind. He had a patient who was about 80 at the time of his diagnosis. His primary doctor told him to get his affairs in order.

“We operated on him and he lived another six or seven years,” Sasson recalls. “He was grateful to see his grandchildren graduate and to see his great-grandbabies being born.”

While every patient is unlikely to have the same outcome, Sasson said surrendering to the disease and preparing for the inevitable may not be the only option, as there may be other courses of action.

Another patient had advanced pancreatic cancer for 18 months before Sasson met her. She had received no treatment and yet the cancer didn’t progress, which is “almost unheard of and unbelievable.” In fact, the case defied medical expectations so dramatically that the doctors conducted two more biopsies to confirm that she had pancreatic cancer. “She did well for many years despite having advanced pancreatic cancer.”

In another case, a patient was receiving surveillance for lung cancer every three months. In between those visits, he had developed metastatic pancreatic cancer. This patient example and the previous one show the range of cancer progression.

The value of having an integrated clinical and research program is that scientists can look for subtle clues and signals amid the reality of cancer with a wide range of outcomes. Indeed, scientists attend the weekly tumor board meeting, so they can learn about the clinical aspects of the disease. Doctors also attend research collaborations so they can hear about developments in the lab.

Rather than dictating how researchers and clinicians should collaborate, Sasson hopes to facilitate an environment that sparks these partnerships.

Sasson joined Stony Brook Medical School almost three years ago. He said he is “impressed with the caliber of physicians.” It took time to get the critical mass and organization for pancreatic cancer to match the number of basic science investigators.

“I’m hopeful for the progress we’ll be able to make to treat this terrible disease,” he said.

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