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Daniel Dunaief

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By Daniel Dunaief

Daniel Dunaief

I have been working out at a gym, where my routine consists mostly of pushing my body as long as I can on a treadmill, bike or elliptical machine until my sweat has soaked through my T-shirt. I play mind games while I’m running, telling myself that I can take a break once I get to 3 miles, or maybe 4 or closer to 5.

Each time I hit a milestone, I think about how much better I’ll feel if I can go just a bit farther, even as I’m taking an inventory of all the barking body parts, which typically includes my knees and back.

What helps get me over the hump lately, though, is the music I listen to as I work out.

I started with a collection of ’80s songs, hoping, perhaps, that the combination of familiar tunes from my youth would make my body remember the energy that defined this younger period.

As I was running, the songs reminded me of the times I danced with friends at Ward Melville High School, played Uno in a friend’s living room or decorated a Christmas tree with another friend who patiently showed a group of us how to thread popcorn and cranberries through a line.

As I was running, a montage of these images played through my head, making me feel as if my legs were turning back the clock. Fortunately, no one at my gym looks closely at me or my facial expressions, so I could indulge in musical — and life — nostalgia without interruption or without questions from people wondering what I was thinking as I reacted to people who have long since gone their separate ways.

For a few days, I switched to my favorite singer, Billy Joel. Hearing the words from “Only The Good Die Young,” “Piano Man,” and “Movin’ Out,” brought me back to the study breaks I took in high school when I stared out the window between my house and the neighbor’s colorful Santa sleigh down the street, hoping that the snow forecast for that evening was sufficient to close school the next day.

I’m planning to see Billy Joel in concert before too long, so I switched to another genre, playing the soundtrack from the original 1975 version of the musical, “A Chorus Line.” While others rarely cite it as one of their favorite musicals, I know it was the song “Nothing,” in which Diana Morales receives nonstop criticism from her teacher Mr. Karp, that brought to life the magic of Broadway for me. 

I always measured every other performance, including of musicals like “West Side Story” that I supported by playing clarinet in the pit orchestra, against the desperate hopes of each of the cast members in a chorus line to “make it” into the show.

Eventually, I needed a pulsating beat, so I shifted to exercise music, which, of course, included songs from “Rocky the Musical,” as well as other inspirational films. Each time the beat got faster, I found another pocket of energy that helped me conquer the next mile, using the beat as a metronome for my legs.

Music, in all its forms, serves many functions, allowing us to connect with the artist, to travel on an acoustic journey, to remember friends, and to exercise feelings and emotions even as we exercise the rest of our bodies.

I coached many sports when my children were younger. If I could do it over again, I would have added contemporary music to mundane practices to spice up the experience in real time and to inspire me on the nostalgia treadmill.

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By Daniel Dunaief

It’s a big leap from an encouraging start to a human, especially when it comes to deadly diseases like amyotrophic lateral sclerosis, or Lou Gehrig’s disease. Cold Spring Harbor Laboratory Associate Professor Molly Hammell knows that all too well.

Hammell has been studying a linkage between a mutated form of a protein called TDP-43 and ALS for eight years. About a year and a half ago, she worked with 178 human samples from the New York Genome Center’s ALS Consortium and found a connection between a subset of people with the disease and the presence of abnormal aggregate forms of the protein.

“It’s really rewarding to see evidence in clinical samples from the processes that we predicted from cell culture and animal models,” she explained in an email.

Molly Hammell. Photo from CSHL

About 30 percent of the people with ALS Hammell examined had pathology of this protein in the upper motor neurons of the upper cortex. In this area, the mutated form of TDP allowed more so-called jumping genes to transcribe themselves. A normal TDP protein silences these jumping genes, keeping order amid potential gene chaos. The change in the protein, however, can reduce the ability of the protein to serve this important molecular biology maintenance function.

By using complementary studies of cell culture, the associate professor tried to determine whether knocking out or reducing the concentration of normal TDP caused an increase in these retrotransposons.

When she knocked out the TDP, she found a de-silencing of these jumping genes “was rapid,” she said. “We could see that in the samples we collected.”

Before she got the larger sample, Hammell worked with a smaller pilot data set of 20 patients. She found that three of the patients had this abnormal protein and an active set of these jumping genes.

“It’s hard to make an argument for something you’d only seen in three patients,” she said. “Getting that second, independent much larger cohort convinced us this is real and it’s repeatable, no matter whose patient cohort we’re looking at.”

Several diseases show similar TDP pathology, including Alzheimer’s and fronto-temporal dementia. She started with ALS because she believed “if we’re ever going to see” the link between the mutated protein and a disorder, she would “see it here” because a larger fraction of patients with ALS have TDP-43 pathology than any other disease.

The findings with ALS are a compelling start and offer a potential explanation for the role of the defective protein in these other conditions.

“We think it’s possible in a subset of patients with other neurodegenerative diseases that there might be overlapping” causes, Hammell said “We’re trying to get more data to branch out and better understand overlapping alterations.”

With these other diseases, she and her colleagues would like to explore whether TDP pathology is a necessary precondition in conjunction with some other molecular biological problems or whether these conditions can proceed without the disrupted protein.

The reaction among researchers working on ALS to Hammell’s finding has been encouraging.

Hemali Phatnani, the director of the Center for Genomics of Neurodegenerative Disease at the New York Genome Center, suggested Hammell’s work “opens up really interesting lines of investigation” into a potential disease mechanism for ALS. The research suggests a “testable hypothesis.”

Phatnani, who has been in her role for about five years, said she and Hammell speak frequently and that they serve as sounding boards for each other, adding that Hammell is “definitely a well-regarded member of the community.” 

Hammell has also been working through the Neurodegeneration Challenge Network in the Chan Zuckerberg Initiative, or CZI. This work brings together scientists who study Alzheimer’s, Parkinson’s, ALS and Huntington’s diseases. The group works to develop new approaches to the treatment and prevention of these diseases. These scientists, which includes researchers from Harvard University, Stanford University, Vanderbilt and Mount Sinai, among others, have webinars once a month and attend a conference each year.

Hammell was one of 17 researchers awarded the Ben Barres Early Career Acceleration Award from the CZI in 2018, which helped fund the research. She thinks the scientists from the CZI are excited about the general possibility that there’s overlapping disease mechanisms, which her work or research from other scientists in the effort might reveal. The CZI is “trying to get researchers working on different diseases to share their results to see if that’s the case,” she explained in an email.

She recognizes that numerous molecular and cellular changes also occur during the course of a disease.“There are always skeptics,” Hammell concedes. In her experiments, she sees what has happened in patient samples, but not what caused it to happen. She also has evidence that the retrotransposon silencing happens because of TDP-43 pathology.

“What we still need to confirm is whether or not the retrotransposons are themsleves contributing to killing the neurons,” she said.

If Hammell confirms a mechanistic link, other studies may lead to a treatment akin to the approach researchers have taken with viruses that alter the genetic code.

Future therapies for a subset of patients could include antiviral treatments that select specific genes.

Over time, she said her lab has cautiously added more resources to this work. As she has gotten increasingly encouraging results, she has hired more scientists who dedicate their work to this effort, which now includes two postdoctoral fellows, two graduate students and three staff scientists.

Some scientists in her lab still explore technology development and are devoted to fixing the experimental methods and data analysis strategies she uses to look for transposon activity.

Hammell is inspired by the recent results and recalled how she found what she expected in human samples about 18 months ago. She said she was “giddy” and she ran into someone else’s lab to “make sure I hadn’t done it incorrectly. It’s really exciting to see that your research might have an impact.”

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By Daniel Dunaief

Daniel Dunaief

You know the face dogs make when they’re taking care of their business? I’m not talking about number one. I’m talking about the big whopper: number two. For many dogs, I imagine that is the equivalent of the human concentration face, as we ponder everything from what we should have for dinner, to the best route home in a traffic jam, to the best use of our time on a Friday night when we’re exhausted but know we could contribute to our area through community service.

My dog must know that I’m watching him closely because every time he finds exactly the right spot to release the contents of his bowels, he turns his back to me. Before he enters his squatting position, he looks back over his shoulder to make sure no one or everyone is watching him. He’s easily distracted in the moment of separation from his solid waste.

I respect his wishes and give him his moment of privacy once he starts the process. Now, of course, much as we might watch them as they relieve themselves, I know that they watch us closely, wondering why we’re so meticulous, or not, as the case may be, about scooping up everything they’ve dropped.

My dog still seems to think that he’s doing sufficient cleanup duties by kicking a few blades of grass in the general direction of his creation. He starts tugging on the leash immediately after that, sending a nonverbal signal from his neck to my hand, as if to say, “I got this one, let’s move to that flower bed where Marshmallow left me a secret scented note.”

As I bent down recently to clean up his mess, he saw one of his favorite couples. That’s not exactly a fair characterization, as almost any combination of two people would immediately rank among his favorites if one or both of them came over to him and rubbed his stomach while he turned over on his back and dangled his paws in the air, as if he were at a canine nail salon. The challenge for me, as he was pulling, tugging and twisting on the leash, was to do the impossible: Chat with his human friends, keep him from knocking one or both of them over with his enthusiasm and politely scoop up his poop.

I waited for a moment to retrieve my retriever’s droppings, hoping that he’d calm down enough to allow me to bend my knees and lift the boulders from the ground. No such luck, as he seemed to be playing twist-the-leash-around-the-human-legs game.

One of the many sensory problems with my dog’s poop is that the longer it remains in place, the more it seems to spread out and sink into the ground. Knowing this, I was eager to bag it and to move on during our walk.

Just as the couple finally disengaged from my dog and his leash, another dog and his owner appeared, causing my dog’s tail to wag so violently that it looked like those whirling propellers on an old airplane. While my dog darted and retreated from his much bigger and more mellow friend, I got farther away from his droppings. In the back of my mind, I wondered whether I could, just this once, leave his biodegradable droppings where they landed.

When the other dog and his owner took off, my dog and I returned to the expanding pile. I’m convinced that my dog watched the entire pickup routine with rapt fascination, knowing he’d succeeded in extending the process into something considerably more challenging for the human scrunching his nose at the other end of the leash.

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Ken Dill. Photo from SBU

By Daniel Dunaief

Over the course of decades, aging skin tends to wrinkle, revealing laugh or frown lines built up through a lifetime of laughter, tears and everything in between. Similarly, when people age, the proteins in their bodies don’t fold up as neatly. Free radicals cause these misfolded proteins, which are then susceptible to further damage.

The cumulative effect of these misfolded proteins, which is a part of natural cell aging, can contribute to cell death and, ultimately, the death of an individual.

Researchers have typically focused on the way one or two proteins unfold as damage increases from oxygen that has an uneven number of electrons.

Ken Dill. Photo from SBU

Ken Dill, a distinguished professor and director of the Laufer Center for Physical and Quantitative Biology at Stony Brook University, and colleagues including Adam de Graff, a former postdoctoral researcher in Dill’s lab who is currently a senior scientist at Methuselah Health based in Cambridge, England, and Mantu Santra, a postdoctoral researcher in Dill’s lab, recently published research that explored the global effects of unfolding on the proteome. Their model represents average proteins, not individual proteins, detail by detail.

Researchers use the roundworm as a model of human aging because of the similarity of the main processes. The worm model presents opportunities to explore the cumulative effect on proteins because of its shorter life span. Worms in normal conditions typically live about 20 days. Worms, however, that are subjected to higher temperatures or that live in the presence of free radicals can survive for only a few hours.

The shorter life span correlates with the imbalance between the rate at which cells create new proteins and the collapse of misfolded proteins damaged by free radicals, the scientists explained in a paper published online recently in the journal Proceedings of the National Academy of Sciences.

While numerous processes occur during aging, including changes in DNA, lipids and energy processes, Dill explained that organisms, from worms, to flies, to mice to humans experience increasing oxidative damage over the course of their lives.

“The evidence made us think about proteome collapse as a dominant process,” Dill said.

De Graff explained that the paper uses the premise that “certain conformations of a protein are much more susceptible to oxidative damage than others. If you’re folded, you’re pretty safe.”

In the past, researchers have considered linking the way protein misfolding leads to cell death to a potential approach to cancer. If, for example, scientists could subject specific cancer cells to oxidative damage and to develop an accumulation of misfolded proteins, they could selectively kill those cells.

A few years ago, researchers explored the possibility of developing a therapeutic strategy that tapped into the mechanism of cell death. To survive with an accumulation of mutated proteins, cancer cells have increased the levels of chaperone concentrations because they need to handle numerous mutated, incorrectly folded proteins. 

A drug called 17-AAG aimed to reduce the chaperones. It worked for some cancers but not others and had side effects. New efforts are continuing in this area, Dill said.

Other researchers, including De Graff, are looking at ways to improve protein folding and, potentially, provide therapeutic benefits for people as they age.

At Methuselah Health De Graff and his colleagues are leveraging the fact that certain conformations are more susceptible to damage and thus the creation of altered “proteoforms.” Identifying these proteoforms could be key to the early detection of disease and the development of preventative treatments, De Graff explained.

Methuselah Health is not interested in treating the downstream symptoms of disease but, rather, its upstream causes.

Going forward, Dill hopes other experimental scientists continue to generate data that enables a closer look at the link between oxidative damage, protein misfolding and cell death.

Some people in the aging field look at individual proteins, he explained. In neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, which are associated and correlated with protein misfolding, scientists are taking numerous approaches. So far, however, researchers haven’t found a successful approach to tackle aging or diseases by altering misfolded proteins.

Dill hopes people will come to appreciate a role for modeling in understanding such varied cellwide processes such as aging. “How do we convey to people who are used to thinking about detailed biochemistry why modeling matters at all?” he asked. “We have our work cut out for us to communicate what we think matters and a way forward in terms of drug discovery.”

Theoretically, some proteins that are at a high enough concentration might be more important in the aging and cell death process than others, Dill said. “If you could reduce their concentration, you might pull the cell back from the tipping point for other proteins,” he said, but researchers know too little about if or how they should do this. He credits De Graff and Santra with doing considerable work to bring this study together.

A resident of Port Jefferson with his wife, Jolanda Schreurs, Dill is pleased that their house has solar panels. 

The couple’s son Tyler is married and has purchased a house in San Diego. Despite professing a lack of interest in biology at an early age, Tyler is working as a staff development engineer for Illumina, a company that makes DNA sequencing machines.

The couple’s younger son Ryan is earning his doctorate as a physical chemist at the University of Colorado in Boulder. He works with lasers, solar energy and quantum entanglements.

As for the most recent research, Dill suggested that it is “premised on the importance of oxidative damage, including by free radicals, which is now well established,” he explained in an email. “It then seeks to explain their effects on how proteins fold and misfold.”

De Graff added that the model in the PNAS paper attempts to “understand the consequences of slowed protein synthesis and turnover” that occurs during aging.

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By Daniel Dunaief

Daniel Dunaief

I wonder how the creators of the show “Seinfeld,” Larry David and Jerry Seinfeld, would portray today’s world? The answer resides in their approaches to other ideas and conflicts that became the focal point for shows that continue in reruns almost every day.

In one show, Elaine, played by Julia Louis-Dreyfus, is dating furniture mover Carl (David James Elliott). When Elaine finds out that Carl is a pro- lifer, they decide to end their relationship.

In Washington, D.C., and indeed throughout the country, that seems tame compared with the passions people feel when they share their views about the president and about the upcoming election of 2020.

I could imagine an entire modern “Seinfeld” episode dedicated to the efforts people take to avoid discussing politics. Changing the subject, walking out of the room and pretending they can’t hear each other seems like a way these characters might keep the political genie locked in the bottle, allowing them to enjoy the company of anyone and everyone, even if those people disagree with their views on national politics.

We play out that scenario regularly wherever we go, whether we’re looking to date someone or just chat with someone in a line at the deli, on vacation or at the Department of Motor Vehicles.

We are so concerned that we might offend the other person or that he or she might offend us.

When did we become so incapable of speaking with each other? Are we determined to live in echo chambers, where we only listen and speak with the people whose ideas, thoughts and words match our own?

Come on, that’s not how democracy is supposed to work. We can and should be capable of hearing from other Americans whose ideas differ from our own. In addition to the land, the flag, the monuments, the Constitution, the history and so many other facets of American life that we share, we owe it to ourselves and to future generations to be able to listen to each other and to remain open to ideas and opportunities.

Are we afraid that someone who seems rational and reasonable might convince us to change our mind? Are our ideas so fragile and our confidence so weak that we can’t have an informed discussion about our views and our ideas?

Surely, we are better than some homogenized party line. We are a land of rugged individualists, who can and should find a way to advance our local, state and national best interests to give everyone an equal opportunity.

It’s not up to the leaders to tell us what to think, who to be and how to live. We have the chance to make those decisions for ourselves. At their best, those leaders are working to give us a shot at pursuing the American Dream which, last time I checked, doesn’t belong exclusively to one political party or another.

By not talking with each other, we increase the tension that separates the parties and the people who support them. Rather than waiting for a bipartisan detente in Washington, we can and should gather ideas about each other.

If they were still making the show today, the characters from “Seinfeld” might have helped us laugh about how entrenched we have become in dealing with our differences. We, however, aren’t living in a TV show and we owe it to ourselves to gather real information, to listen to other people and to bridge the divide that’s causing the fabric to fray of a country we all call home. 

We can learn and grow from making decisions for ourselves, instead of following the same script with every conversation.

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William Farr. Photo by Anja von der Linden

By Daniel Dunaief

It’s not exactly a symphony, with varying sounds, tones, cadences and resonances all working together to take the listener on an auditory journey through colors, moods and meaning. In fact, the total length of the distortion is so short — about 0.1 seconds — that it’s a true scratch-your-ear-and-you’ll-miss-it moment.

And yet, astrophysicists like William Farr, an associate professor in the Department of Physics and Astronomy at Stony Brook University and a group leader in gravitational wave astronomy with the Simons Foundation Flatiron Institute, are thrilled that they have been able to measure distortions in space and time that occur at audio frequencies that they can convert into sounds. These distortions were made millions or even billions of years ago from merging black holes.

Farr, in collaboration with a team of scientists from various institutions, recently published a paper in Physical Review Letters on the topic. 

While the ability to detect sounds sent hurtling through space billions of years before Tyrannosaurus Rex stalked its prey on Earth with its mammoth jaw and short forelimbs offers some excitement in and of itself, Farr and other scientists are intrigued by the implications for basic physical principles.

General relativity, a theory proposed by Albert Einstein over 100 years ago, offers specific predictions about gravitational waves traveling through space.“The big excitement is that we checked those predictions and they matched what we saw. It’s a very direct test of general relativity and its predictions about a super extreme environment near a black hole,” said Farr. There are other tests of general relativity, but none that directly test its predictions so close to the event horizon of a black hole, he explained.

General relativity predicts a spectrum of tones from a black hole, much like quantum mechanics predicts a spectrum line from a hydrogen atom, Farr explained.

The result of this analysis “provides another striking confirmation of the theory of general relativity and also demonstrates that there are even more exciting things that can be done with gravitational wave astrophysics,” Marilena Loverde, an assistant professor of physics at the C. N. Yang Institute for Theoretical Physics at Stony Brook University, explained in an email. Loverde suggested that Farr is “particularly well-known for bringing powerful new statistical techniques to extract science from vast astrophysical data sets.”

Farr and his colleagues discovered two distortions that they converted into tones from one merger event. By measuring the frequency of the first one, they could predict the frequency for all the other tones generated in the event. They detected one more event, whose frequency and decay rate were consistent with general relativity given the accuracy of the measurement.

So, what does the merger of two black holes sound like, from billions of light years away? Farr suggested it was like a “thunk” sent over that tremendous distance. The pitch of that sound varies depending on the masses of the black holes. The difference in sound is akin to the noise a bear makes compared with a chipmunk: A larger black hole, or animal, in this comparison, makes a noise with a deeper pitch.

He used data from the Laser Interferometer Gravitational-Wave Observatory, or LIGO, which is a twin system located in Livingston, Louisiana, and Hanford, Washington. LIGO had collected data from black hole merger events over a noncontinuous six-month period from 2015 to 2017.

Farr chose the loudest one, which came from 1.5 billion years ago. Farr was using data from the instrument, which collects gravitational waves as they reach the two different locations, when it was less sensitive. Given the original data, he might not have discovered anything. He was, however, delighted to discover the first tone.

If something that far away emitted a gravitational wave sound that lasts such a short period of time, how, then, could the LIGO team and Farr’s analysis be sure the sound originated with the cosmic collision?

“We make ‘extreme’ efforts to be sure about this,” Farr explained in an email. “It is one reason we built two instruments (so that something weird happening in one does not fool us).” He said he makes sure the signal is consistently recorded in both concurrently. To rule out distortions that might come from other events, like comets slamming into exoplanets, he can measure the frequency of the event and its amplitude.

Black holes form when stars collapse. After the star that, in this case, was likely around 25 times the mass of the sun, exploded, what was left behind had an enormous mass. When another, nearby star becomes a black hole, the two black holes develop an orbit like their progenitor stars. When these stars become black holes, they will emit enough gravitational waves to shrink the orbit, leading to a merger over a few billion years. That’s what he “heard” from the last second or fraction of a second.

Farr expects to have the chance to analyze considerably more data over the next few months. First, he is working to analyze data that has already been released and then he will explore data from this year’s observations, which includes about 25 more mergers.

“The detectors are getting more sensitive,” he said. This year, scientists can see about 30 percent further than they could in the first and second observing runs, which translates into seeing over twice the total volume.

Farr has been at Stony Brook for almost a year. Prior to his arrival, he had lived in England for five years. He and his wife, Rachel, who have a 3½-year-old daughter, Katherine, live in Stony Brook.

As for his work, Farr is thrilled that he will have a chance to study more of these black hole merger sounds that, while not exactly Mozart, are, nonetheless, music to his ears. “Each different event tells us different things about how stars form and evolve,” he said.

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By Daniel Dunaief

Daniel Dunaief

We are back to shopping for college. There’s a familiar rhythm to this search that, the second time through, brings a more relaxed pace. Now that my wife and I have taken about a dozen college tours, we’ve noticed patterns. Please find below some observations:

• The library gets quieter the higher its location. Every school we’ve toured has suggested that people will throw visual daggers at you on the top floor if you drop your pencil. Move to a lower floor to cough. In the effort to differentiate one school from another, a clever college ought to invert the quiet pyramid. The logistics would be challenging, with people stepping onto a floor of silence, but it would make clear how serious students were in the library and would defy the usual expectations about noise on each floor.

• Showcase dorm rooms aren’t real. Yes, the rooms everyone sees are, of course, actual rooms, but they have considerably less stuff, no irrational roommates who scream in their sleep, and are better lit than the freshmen rooms most of our kids will occupy. Somehow, the temperature in these rooms is perfect for almost everyone. Many rooms, however, are way too hot or too cold for one, two or the three people jammed into a space that will feel like the garbage chute in the original “Star Wars” as the year progresses.

• Some tour guides will share their food choices, preferences and idiosyncrasies because it makes them charming. We may not have the same aversion to Vegan Tuesdays, but we will undoubtedly remember the school because some lacrosse player in desperate need of a haircut who sings hates vegan food.

• Tour guides are friendly. Yeah, I know, shocking, right? But, while they are talking to us, many wave to friends as they speak. Are they really waving at someone? Is one person walking back and forth? The whole “everyone loves me and I love everyone” shtick seems rehearsed. Then again, maybe tour guides really do have friends everywhere.

• Some information sessions and tours seem to have left something crucial out of the discussion: Who wouldn’t be a great fit for their extraordinary school? Schools might save themselves — and prospective students — trouble if they helped these eager high school seniors and juniors get a better idea of what might not work for them. None of the schools offer an amalgamated profile of the type of student who typically transfers anywhere else. They should, right? Wouldn’t it help to know that the snow which starts in September and ends in May drives some students away? Or that the competitive atmosphere on campus doesn’t work for some students? What have the schools learned from some of their admissions mistakes?

• People on tours generally look and sound tired. Most of the kids seem to be praying that their parents don’t embarrass them by asking too many questions. When asked what they plan to major in, they respond with something like “blobology” or “Idunnonotsure.” The introductory phase of the tour rarely creates cohesion among a group taking turns to hold doors open for each other.

• Tour guides attempt to share college humor by highlighting their personal deficiencies. In between waving to their extended group of friends, these guides point to a chemistry building or a music hall and suggest that they have absolutely no skills in those fields whatsoever and are in awe of their peers, who seem to be speaking a foreign language when they explain their passion for molecular biology.

• These guides pick majors and minors like they’re at an ice cream store: They have one scoop of biology, two small scoops of elementary education and sociology, and a sprinkling of criminal justice.

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Jessica Schleider. Photo from SBU

By Daniel Dunaief

Many teenagers who are struggling with depression need help. According to several estimates, less than half of teens with depression receive treatment that would help them manage through everything from negative feelings toward themselves and their lives to a lack of control over events during the day.

Jessica Schleider, an assistant professor of clinical psychology in the College of Arts and Sciences at Stony Brook University, wants to offer teenagers battling depression a new kind of assistance.

Jessica Schleider on a hike with her dog Penny. Photo by David Payne

Schleider is seeking participants for a new study, called Project Track to Treat, that offers teenagers from 11 to 16 years old symptom-tailored treatment. After participating teens respond to surveys she sends them on smartphones, she will provide single-session, computer-based interventions that address symptoms such as hopelessness or withdrawal from daily activities.

Schleider recently received a five-year, $2 million Early Independence Award from the National Institutes of Health to test the benefits of these half-hour computer sessions.

The funds will go toward study staff, the cost of recruiting youths and families for the study, equipment, statistical packages for the analyses she plans to run and compensation for the families who take part.

“A vast majority of teenagers who experience depression never access treatment,” Schleider said, potentially because teens are not typically in a position where they can seek out treatment on their own. “Between the lack of access to services and the limited potency of services, there needs to be a broader array of options and layers we can provide.”

In the world of clinical psychology, three to four months is generally considered brief treatment. A single computer-based session that a teenager can access at any time offers support during a much shorter time frame.

The idea behind the briefer, more targeted intervention is that it could offer help. The goal of the session is to create positive momentum, to teach teens useful skills for coping with depression-related difficulties, and to offer it in a setting where modern teenagers spend much of their time, online, Schleider suggested.

Jessica Shleider with husband David Payne and their dog Penny.
Photo from Jessica Schleider

“For young people who would never go to a therapist, the question may be whether there is something else that could help, and [Schleider’s] work may offer one such ‘something else,’” John Weisz, a professor in the Department of Psychology at Harvard University, wrote in an email. It’s also possible, explained Weisz, who has known Schleider since 2013 when she worked in his lab, that a single session might encourage teenagers to believe that other types of therapy can also help if they try.

Part of the motivation for this study is to determine if the nature of the symptoms — which she will explore through survey questions — can inform how teenagers will respond to a single, therapeutic session.

Schleider created these programs from available research in psychology and education. She adapted some of those programs to these specific circumstances and she taught herself rudimentary coding with html. She currently has three programs available on her website, which interested parents and teenagers can explore at www.schleiderlab.org/participate.

The teenagers participating in the study will receive questions a few times a day for three weeks about how they are feeling, checking to see any signs of depression. From those interactions, Schleider will be able to determine which symptom is the most central and which might lead to other symptoms over time. She hopes to take parameters from that to see if those symptoms predict how much a participant will respond to a session.

Schleider will also measure how teenagers respond to training through the study. If their emotional state deteriorates, the researchers can intervene and can monitor the level of risk and refer any cases appropriately. “Our top priority as researchers is to make sure the kids are taken care of,” she said.

She was skeptical before she started working on brief sessions. “I was on the side of, of course you can’t do anything in one session,” Schleider said. “I thought you need several sessions to make a sustained change.”

In looking at the available research, however, she discovered that through 50 randomized control trials in 2017, the magnitude of the effect of the trials was between small to medium range, which matched the effect of sessions ranging from an hour to 16 sessions for other teenagers. After her study, she realized that “there is something to this. We need to do more work to find out what to do and how to harness it for our youth.”

Through monitoring over two years, Schleider hopes to gain a better awareness of who will benefit from this session and under what time frame they might see an improvement.

She hopes teenagers can share their thoughts and ideas for how to improve these programs. She also offers some of these teenagers to help reconstruct the content and language and references.

Teenagers who don’t participate in the Track to Treat study can participate in an anonymous Project Yes effort, which is a program evaluation initiative. These participants can offer feedback on these sessions.

For a subset of teenagers, one session likely won’t be sufficient. 

Weisz suggested that Schleider, who joined Stony Brook last year, is a “terrific addition” to the university and the community. “I believe her work will reflect very well on both.” Weisz added that Schleider’s colleagues in the Department of Psychology at Stony Brook “are among the finest psychological scientists in the nation,” where Schleider can “take her work to a very high level.”

Schleider, who joined Stony Brook last year, lives in Coram with her husband, David Payne, who is a medical resident in radiology at Stony Brook Hospital. 

As for her work, Schleider said she recognizes that there is no panacea, but that this approach is “something when the alternative is nothing.”

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Photo from YouTube

By Daniel Dunaief

Daniel Dunaief

Looking back at the six-game American League Championship Series, it’s clear that the Houston Astros were the better team. Tough as it is to write that when my fan allegiance is with the Yankees, the Astros had more clutch hitting, better defense, and better starting and relief pitching. Yes, the two teams were fairly evenly matched when it came to runs scored. The Yankees covered up many of their sins — and deficiencies — with a few timely long balls and some standout pitching performances from Masahiro Tanaka and James Paxton.

While hindsight is always perfect, because we know who failed and who succeeded, I want to ask an obvious question. Why was our designated hitter doing little more than striking out? It’s clear that our enigmatic catcher Gary Sánchez, who has a talent for crushing balls deep into the night, seems to disappear at big moments.

And, while we’re playing the hindsight game, it seems obvious that closer Aroldis Chapman, who has lost a few miles per hour on his fastball and now relies on an effective slider, should have avoided pitching to José Altuve with two outs, a runner on first and a defensive replacement on deck for Houston.

So, one at a time. Edwin Encarnación was a compelling pickup from Seattle Mariners during the season, offering a few moments of ball-bashing power. Perhaps because of injury, or maybe because he was trying to hit a defining titanic home run, he couldn’t do much of anything in the postseason. The same seems true for the multimillion dollar Giancarlo Stanton.

Given that both can hit huge home runs and are capable of changing the complexion of a low-scoring game, I understand the urge to put them in, but, at some point, if they are not getting it done, why not go with other options? Sure, Cameron Maybin doesn’t hit as many home runs and isn’t as physically imposing. 

If manager Aaron Boone had inserted him into the lineup, would he have taken away the possibility of using Maybin as a late-inning defensive replacement? That’s possible. OK, then, how about using Austin Romine as the designated hitter? Yes, I understand that Boone might also have been saving him to give Sánchez a break in a game where defense takes precedence.

If either of them had become an unconventional designated hitter, would fans be screaming about the panic move if they had failed? Yes, of course, they would. But at least Boone would have been trying something — anything — when he seemed wedded to a script that wasn’t working in a short series.

The same thing holds true for Adam Ottavino. The guy was a great pitcher during the season, but he ran into the postseason twilight zone. It happens. Sit him down and don’t let him affect the outcome of games.

As for Sánchez, he may have hit batting practice pitches into the next county, but that’s irrelevant. He wasn’t getting it done at or behind the plate. Maybe even a single day off would have changed his approach and would have helped. In a short series, managers can’t wait to see if something that’s not working turns around. The team — and its desperate fans — don’t have the luxury of that kind of time.

The question for next year isn’t whether the Yankees will get a starting pitcher who can throw more innings than the present incumbents, or whether Stanton will make a meaningful postseason contribution. The question is: Will Boone buy into the idea of a team game and give other players a chance? After all, the last time the Yankees won the World Series was a decade ago, in 2009.

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Peter Koo. Photo by ©Gina Motisi, 2019/ CSHL

By Daniel Dunaief

We built a process that works, but we don’t know why. That’s what one of the newest additions to Cold Spring Harbor Laboratory hopes to find out.

Researchers have applied artificial intelligence in many areas in biology and health care. These systems are making useful predictions for the tasks they are trained to perform. Artificial intelligence, however, is mostly a hands-off process. After these systems receive training for a particular task, they learn patterns on their own that help them make predictions.

How these machines learn, however, has become as much of a black box as the human brains that created these learning programs in the first place. Deep learning is a way to build hierarchical representations of data, explained Peter Koo, an assistant professor at the Simons Center for Quantitative Biology at CSHL, who studies the way each layer transforms data and the next layer builds upon this in a hierarchical manner.

Koo, who earned his doctorate at Yale University and performed his postdoctoral research at Harvard University, would like to understand exactly what the machines we created are learning and how they are coming up with their conclusions.

“We don’t understand why [these artificial intelligence programs] are making their predictions,” Koo said. “My postdoctoral research and future research will continue this line of work.”

Koo is not only interested in applying deep learning to biological problems to do better, but he’s also hoping to extract out what knowledge these machines learn from the data sets to understand why they are performing better than some of the traditional methods.

“How do we guide black box models to learn biologically meaningful” information? he asked. “If you have a data set and you have a predictive model that predicts the data well, you assume it must have learned something biologically meaningful,” he suggested. “It turns out, that’s not always the case.”

Deep learning can pick up other trends or links in the data that might not be biologically meaningful. In a simplistic example, an artificial intelligence weather system that tracked rain patterns during the spring might conclude, after seven rainy Tuesdays, that it rains on Tuesdays, even if the day of the week and the rain don’t have a causative link.

“If the model is trained with limited data that is not representative, it can easily learn patterns that are correlative in the training data,” Koo said. He tries to combat this in practice by holding out some data, which is called validating data. Scientists use it to evaluate how well the model generalizes to new data.

Koo plans to collaborate with numerous biologists at Cold Spring Harbor Laboratory, as well as other quantitative biologists, like assistant professors Justin Kenney and David McCandlish.

In an email, Kenney explained that the Simons Center is “very interested in moving into this area, which is starting to have a major impact on biology just as it has in the technology industry.”

The quantitative team is interested in high-throughput data sets that link sequence to function, which includes assays for protein binding, gene expression, protein function and a host of others. Koo plans to take a “top down” approach to interpret what the models have learned. The benefit of this perspective is that it doesn’t set any biases in the models.

Deep learning, Koo suggested, is a rebranding of artificial neural networks. Researchers create a network of simple computational units and collectively they become a powerful tool to approximate functions.

A physicist by training, Koo taught himself his expertise in deep learning, Kenney wrote in an email. “He thinks far more deeply about problems than I suspect most researchers in this area do,” he  wrote. Kenney is moving in this area himself as well, because he sees a close connection between the problem of how artificial intelligence algorithms learn to do things and how biological systems mechanistically work.

While plenty of researchers are engaged in the field of artificial intelligence, interpretable deep learning, which is where Koo has decided to make his mark, is a considerably smaller field.

“People don’t trust it yet,” Koo said. “They are black box models and people don’t understand the inner workings of them.” These systems learn some way to relate input function to output predictions, but scientists don’t know what function they have learned.

Koo chose to come to Cold Spring Harbor Laboratory in part because he was impressed with the questions and discussions during the interview process.

Koo, daughter Evie (left) and daughter Yeonu (right) during Halloween last year. Photo by Soohyun Cho

He started his research career in experimental physics. As an undergraduate, he worked in a condensed matter lab of John Clarke at the University of California at Berkeley. He transitioned to genomics, in part because he saw a huge revolution in next-generation sequencing. He hopes to leverage what he has learned to make an impact toward precision medicine. 

Biological researchers were sequencing all kinds of cancers and were trying to make an impact toward precision medicine. “To me, that’s a big draw,” Koo said, “to make contributions here.”

A resident of Jericho, Koo lives with his wife, Soohyun Cho, and their 6-year-old daughter Evie and their 4-year old-daughter Yeonu.

Born and raised in the Los Angeles area, he joined the Army Reserves after high school, attended community college and then transferred to UC Berkeley to get his bachelor’s degree in physics.

As for his decision to join Cold Spring Harbor Laboratory, Koo said he is excited with the opportunity to combine his approach to his work with the depth of research in other areas. 

“Cold Spring Harbor Laboratory is one of those amazing places for biological research,” Koo said. “What brought me here is the quantitative biology program. It’s a pretty new program” that has “incredibly deep thinkers.”

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