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Daniel Dunaief

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Photo from YouTube

By Daniel Dunaief

Daniel Dunaief

We take so much of our life for granted. In some ways, it’s natural and necessary. After all, if we got up and stared out our window and marveled at the combination of sun and shade on the branches rocking in the wind, bent down to admire the dew clinging to the grass and breathed deeply of the newly blossoming trees every morning, we might never get our kids to school and ourselves to work.

And yet, all the news about the spread of this new virus and the ensuing reaction to protect the population — from closing schools to avoiding subways to staying away from large crowds — gives us an opportunity to appreciate the things, people and sensory experiences we take for granted.

No one will miss the scent of urine wafting up through the subways during a hot summer day when switching problems make everyone stand four, five and six deep on the platform, waiting for the next overcrowded and overheated subway car to arrive.

Still, we may miss so many other sensory, social and everyday experiences if and when we have to lock ourselves in our homes, waiting for the “all clear” sign.

So, what are some of those experiences? It depends on whom you ask and what time of year the question arises.

I appreciate the joy of people watching. After living in Manhattan for decades, I’ve learned to swing my eyes across the street inconspicuously, while I seemed lost in thought or even pretended to be on an invisible phone. Times Square, with its superabundant tourists speaking uncountable languages, wearing unrecognizable colognes and walking in all manner of shoes, is a great place to start.

But then, the line for the Statue of Liberty and Ellis Island offers a similar variety of people from all over the world. Instead of billboards of half-naked and incredibly tone and muscular bodies advertising Broadway shows and underwear, the backdrop for the people watching at the ferry lines includes the unpredictable waves of the Hudson River, which has its own personality, ranging from near stillness to foaming white caps.

Closer to home and nearer to summer, West Meadow Beach blends the natural with the call of the seagulls across the enormous intertidal zone and the salty, wind-carried scent; and the anthropogenic with the plaintive cry of babies overheated by the hot sun, the sound of music vibrating from sound systems and the sight of happy teenagers taking their first lick of their soft-serve ice cream cones.

I enjoy watching the end of a hard-fought tennis match, when two or four people come to the net and exchange pleasant handshakes and share thoughts about a good match or a good game.

The crowds at sporting events, many of whom we might not choose from a potential lineup of friends, become a part of memorable games and evenings, as we exchange high fives with inebriated strangers, share insights about what we would do if we were the manager of the team, or congratulate the parent of one of the players on our daughter’s team for the improvement in her game.

Despite the fact that I tend to avoid a crowded elevator car, an overstuffed subway or even an escalator with too many tired bodies waiting for a machine to bring them to the top, I will miss the chance to share some of these experiences with the random strangers who might become friends, the fellow sports fans who might offer a game-within-a-game entertainment, or the chance encounter with a long-lost friend whose winsome smile is the same as it was decades ago in an eighth-grade math class.

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Maureen O’Leary. Photo courtesy of SBU

By Daniel Dunaief

Like the great white shark that needs to keep swimming to stay alive, scientific databases that provide resources to researchers from all over the world can’t stay still or they risk losing their usefulness and reliability.

The directors of these resources need to find funds that will ensure that the data remains accessible and that users, who range from high school students conducting work for a class to the chairman of research departments at colleges, can benefit from the availability of information.

Maureen O’Leary. Photo from SBU

Maureen O’Leary, a Professor and Graduate Program Director at the Department of Anatomical Sciences at the Renaissance School of Medicine at Stony Brook University, is looking to ensure that Morphobank, a web application and database that allows scientists around the world to share raw data on the structure of various organisms to help determine their evolutionary links, receives funds that sustain its mission.

O’Leary helped start MorphoBank in 2000 to encourage researchers to share data and propel science forward and is currently the director. By making observations of the structures of organisms available in one place online, she hoped to help advance the field of phylogenetics — the relationships among organisms in a family tree — while cutting down on the need to reproduce data from the same fossils at museums or other sites.

Up to this point, O’Leary has found financial support for the effort through grants from the National Science Foundation, the American Museum of Natural History and the National Oceanographic and Atmospheric Administration.

Looking to the future, however, O’Leary wanted to create a financial plan that would ensure ongoing funding for a database that has not only helped researchers explore data, but has also enabled collaborators to share information privately in a non-public area of MorphoBank.

O’Leary has been working with Phoenix Bioinformatics, a nonprofit group based in Fremont, California that has developed funding models for databases. Phoenix started its operations in 2013 after the staff of TAIR, a curated database for plant genome information, lost its grant funding.

The business is in the early stages of helping O’Leary with Morphobank, said Eva Huala, the Executive Director of Phoenix and a founding member of TAIR.

Phoenix has helped construct a financial model that is similar to the way university libraries and scientists pay for subscriptions to journals. The prices vary depending on the database the library subscribes to and the amount of usage of that database from the university. 

Huala said Phoenix is providing software that helps recruit members. The company is also enabling users to see whether their institution is supporting MorphoBank. So far, the Executive Director is “encouraged by the response. We know that this often takes several months or longer for libraries to decide” to lend financial support, she said.

The cost of running MorphoBank is connected to the time people spend curating as well as fixing bugs or managing computer-related challenges. Without software patches and fixes, the databases can run into problems.

Universities often require their researchers to make sure the data they collect is available to the scientific community, Huala explained, adding that MorphoBank can give scientists a way to “demonstrate the impact of their research” by offering download and viewing statistics for their data.

Mike D’Emic, an Assistant Professor in Biology at Adelphi University and a member of the Executive Committee of MorphoBank, has used the database for over seven years.

D’Emic suggested that MorphoBank “saves people from reinventing the wheel in doing science” by providing free, raw data. Scientists don’t have to travel to museums or other sites to gather the same information.

An early career researcher or student might have a small grant to visit three or four museums. These scientists can “supplement that data set with information from MorphoBank that’s multiple times the value of a grant they would have gotten,” D’Emic noted.

Scientists can freely use data from MorphoBank that would have taken tens of thousands of dollars to acquire. This includes photographs of a dinosaur skull from distant countries or CT scans that can be expensive to produce.

D’Emic, who helped convince the Adelphi library to provide financial support for the database, said MorphoBank addresses bug reports quickly, fixing problems with a few days.

Prior to O’Leary’s effort to start MorphoBank, a researcher might need to search through the appendices or the published reports from other scientists in their field to access raw data for tree building, sometimes retyping by hand large spreadsheets of numerical scores.

MorphoBank has been “invaluable and transformative in terms of the way people access and replicate science,” D’Emic said.

Some journals have started urging authors to publish their data online. The Journal of Vertebrate Paleontology strongly recommends uploading dataset, character descriptions and images to an online repository.

“For not too much money, MorphoBank has a huge impact on science,” D’Emic said, who said it was a cost effective boost to evolutionary biology and related fields

Scientists have changed significantly in their approach to sharing information. Around 30 years ago, some researchers wouldn’t always share their raw data. Other scientists would then have to spend thousands of dollars to travel to places like Thailand, Australian and Madagascar.

“People have come around” and are more comfortable exchanging data, sometimes as they produce it, D’Emic said. “MorphoBank has been an integral venue for convincing people you should share.”

O’Leary believes researchers have evolved in the way they think about the information they collect as a part of their studies.“We have reached a social transition where scientists get used to not only writing a paper and walking away, but making sure the data content is in a digitally reusable format,” she said.

O’Leary feels fortunate to have received funding for over two decades for MorphoBank. She plans to remain the director when MorphoBank moves to Phoenix. It’s an “important and dynamic tool” and she feels a “responsibility to allow its continuity.”

 

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Stock photo

By Daniel Dunaief

Daniel Dunaief

I just celebrated an incredible birthday, thanks to the thoughtfulness of friends and family who took the time to talk with me and shop for greatly appreciated gifts.

Each year, these birthdays have the potential to be challenging, especially given that mine often comes some time around school midterms. Even though I’m no longer watching the calendar to see how many days I have left before I have to take a big test, I still ride that roller coaster vicariously with my children. This year, however, enormous and difficult tests didn’t hang over us, like the academic sword of Damocles.

For starters, before my birthday celebration kicked in, my sister-in-law and brother-in-law sent me AirPods. I knew I was supposed to open the gift on my birthday, but I’m not exactly the most patient person when it comes to opening presents. Gee, I wonder where my kids get that trait?

Anyway, the reaction from my son was almost as enjoyable as the present itself. When he saw me wearing them, he said, “How did you get those?” as if the question were an accusation. “My friends all have them.”

My daughter did a test run with me, chatting with me on FaceTime while she stared at my ears instead of at my uneven sideburns or the hairy bridge connecting my eyebrows. It’s increasingly rare these days for anything I do, say or wear to be considered “up to date,” so this wonderful gift hit the mark.

I’m enjoying using the AirPods at the gym, where I don’t have to worry about the wire bouncing around when I’m running or after I’ve exercised, when I’m panting as I lean over the water fountain.

The best part, though, is that they allow me to talk with someone while I’m walking my dog and picking up his droppings. I don’t have to worry about the wire coming lose when he suddenly pulls hard on the leash to chase a rabbit or to run away from the sudden noise a desiccated leaf makes when it blows in the wind behind us. Yes, despite his 90-pound body, he finds the unexpected noise from leaves threatening.

While I insisted to my wife that she didn’t need to buy anything for me, she purchased several items of clothing, like shorts and shirts that fit, look good and are incredibly comfortable. She also got this terrific jacket that repels the white dog hair that has rendered the rest of my outerwear ridiculous when interacting with members of the general public.

This birthday we ventured to the Big Easy, where the ubiquitous music still resonates. We took a paddleboat ride and heard about the Mississippi River and the site of the Battle of New Orleans. The oak trees lining the bank are about 250 to 300 years old, which means that the same trees stood in the same spot during the battle. 

My teenage son, who isn’t always the picture of patience with his demanding dad, played with me and allowed me to hug him in public during the weekend. That was better than any gift he could have purchased. My daughter, meanwhile, celebrated vicariously from college. A few of her friends wandered into the screen and wished me the best.

Finally, I connected by phone with college roommates, nephews, brothers and my mom, who was a critical part of that day so many years ago. Birthdays have, at times, made me feel older and displaced. This one, with the meaningful conversations, the laughter with my wife and children and the chats with friends and relatives, as well as the “cool” gifts, made me feel so young.

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Members of the team at Brookhaven Lab’s Accelerator Test Facility from left, Mark Palmer, Dejan Trbojevic, Stephen Brooks, George Mahler, Steven Trabocchi, Thomas Roser, and Mikhail Fedurin. Photo from BNL

By Daniel Dunaief

Scientists at Brookhaven National Laboratory and Cornell University have tested and developed a new “green” accelerator. Capturing and reusing the energy from electrons that are decelerating, the newly designed model, called CBETA, will have uses in everything from computer chip manufacture to medicine to missile defense to basic science.

Employing permanent magnets, which require no energy to operate, and superconducting material, these researchers brought to fruition an idea first formulated in 1965 by Maury Tigner, professor emeritus at Cornell University.

“It was talked about for many years,” said Thomas Roser, who just completed his 10th year as chairman of the Collider-Accelerator Department at Brookhaven National Laboratory. “To put everything together in an energy efficient way could have a significant impact for the future.”

Indeed, the new design could lower the energy needs of a future facility like the Electron Ion Collider, which BNL plans to complete in 2030.

“We all have a responsibility to contribute to the well-being” of the planet, including in efforts to reduce the energy consumption of devices used to unlock the mysteries of the universe and produce future technology, said Roser.

Schematic of the Cornell-BNL
ERL Test Accelerator.
Image courtesy of Cornell University

One of the many advantages of the new accelerator design, which was tested in the early morning hours of Dec. 24 at Cornell, is that it captures and reuses the energy in a multi-turn particle accelerator. The idea of the accelerator was to enable beams of different energy to travel through the same magnets on slightly different paths in an oblong structure. 

The design is akin to a relay race on a running track. Each lane has runners that move at their own speeds. When it is time for one of the runners to slow down and leave the track, she shares the energy from her sprint with an intermediary, which drives the next runner forward at a rapid pace, while she decelerates in a nearby loop.

In the case of the accelerator, the intermediary is a superconducting radio frequency cavity.

A key design feature is that multiple beams recirculate in these cavities four times. This cuts down on future construction costs and reduces the size of an accelerator from about a football field to a single experimental hall, according to information from Cornell.

A fresh electron beam allows researchers to get a better quality beam than in the traditional way of operating an accelerator, in a ring that would circulate continuously. 

“The beam is always refreshed, and what gets recirculated is the energy,” Roser said.

The high quality, bright beam creates bright lasers that companies may be able to use to manufacture new chips for computer or phone technology. These accelerators could also make infrared lasers that could melt objects. This type of application could help with defense department efforts to thwart an incoming missile. While BNL is taking steps to work on applications in other areas, the Department of Energy laboratory is not involved in such missile defense applications.

In the medical arena, this kind of accelerator could enable the construction of smaller, simpler and lighter devices for proton therapy to treat cancer. The multi-energy beam transport of CBETA would allow the building of more compact and less expensive gantries that deliver beams to the patient.

Using different energies at the same time, doctors could “treat cancers at different depths inside the body,” Roser said. “That’s an application for this unique transport.” Proton therapy could become cheaper and available in more hospitals with this approach, he asserted.

For Dejan Trbojevic, the principal investigator on the CBETA project and a senior physicist from BNL, the successful test of the concept was a validation of over 20 years of work.

“You can do a lot of simulations assuming realistic errors,” but the actual experiment demonstrating the concept “makes a big difference,” he explained in an email.

The BNL scientist was at Cornell in late December, where he and his colleagues celebrated the results with champagne.

Trbojevic, who had developed the concept of using a single beamline instead of multiple beamlines, hopes to use the new design to create a less expensive design to proton therapy treatment for cancer

“I’m trying to make this cheaper so more hospitals can have it,” Trbojevic said. He has already made contact with companies and a professor in Europe who hopes to use the design concept. He has also requested funding from the Department of Energy.

Beyond the excitement of the recent collaboration with Cornell on the new accelerator design, Roser reflected on his first decade as chairman of the Collider-Accelerator Department.

The BNL department is leading the world in many accelerator technologies and is collaborating closely with CERN, which was founded in Europe seven years after BNL.

Indeed, this year marks numerous celebrations for the department. The Relativistic Heavy Ion Collider, or RHIC, has been operating for 20 years and will become a part of the new Electron Ion Collider. At the same time, the Alternating Gradient Synchrotron, where research for three Nobel Prizes was conducted, marks its 60th year of generating scientific results.

And, to top off the historical trifecta, Ernest Courant, a former BNL Scientist who teamed up with Stanley Livingston and Hartland Snyder to create the strong focusing principle, turns 100 in March. Courant, who worked with Trbojevic on a paper describing the single beamline concept in 1999, helped provide a critical step for modern particle accelerators.

As it did 10 years ago, the department is rolling these three celebrations into one in June.

Courant can’t attend the event because he lives in a retirement home in Ann Arbor, Michigan near his son. BNL will likely show photos and video from Ernest’s birthday at the celebration.

As for the recently completed collaboration with Cornell, Roser believes the work is an important step.

“It’s a new concept and a new type” of accelerator, Roser said. “That doesn’t come around very often. There are cyclotrons and there are linear accelerators. This is a combination of a circular and linear accelerator put together in a new way.”

 

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The White House

By Daniel Dunaief

Daniel Dunaief

I want the weakest possible president in 2020.

As a representative democracy, the United States uses a system of governance that relies on checks and balances. Everything about the history of the country makes it clear that a collection of leaders, each with limited power, should reflect the diverse nature of the country, with states that have small populations getting equal representation in the Senate.

Whenever one of the three branches of government oversteps its bounds, the other two have the opportunity to keep that one in check. If, for example, the executive branch, through the president of the United States, takes actions that the legislative or executive branches find objectionable or questionable, Congress or the Supreme Court can hold that president accountable.

So, how do we ensure those checks and balances? Where do we find exactly the right kind of weak president who can do just his or her job without trying to tell the courts what to do or legislate new laws favorable to the officeholder?

Most presidents, including every candidate who seems to be running now, appear to be convinced that he or she will be a strong leader with a vision for the country that takes us to greater heights or that makes us a better nation.

That’s lovely, but no president can do it alone. The government should be a team effort, pulling together people with a drive to contribute to the world through public service and to represent not only personal opinions, but the values, goals and concerns of the entire nation.

That seems almost impossible, given the divided nature of the country as we enter the 2020 election, right? Someone is always winning and someone is always losing.

That doesn’t have to be the case if a president sees and understands the limits of their power.

While this may seem like a direct rebuke of President Donald Trump (R), it is not. If Vermont Sen. Bernie Sanders (I), who seems to be gaining momentum with each passing primary, wins the Democratic nomination and then becomes president, I don’t want him to be powerful, either.

Some of his ideas, like free college and Medicaid for all, seem compelling on the surface, but many Democrats, Republicans and Independents wonder how exactly he’ll pay for all of those ideas. I enjoy reading dystopian fiction, like “1984,” “The Giver,” and “Fahrenheit 451,” to name a few. The conclusions of all of them are that utopia doesn’t work and big government creates even bigger problems, particularly for the individual.

The idea of Medicaid for All may seem appealing because of the frustration so many people feel with their medical insurance, until they imagine the bureaucratic machine known as the federal government making decisions about their medical coverage. Many of us want to make informed choices.

That brings me back to the choice for president. In the next eight months or so, as we prepare for the onslaught of advertisements telling us how and why the other candidate may ruin our lives, We the People can do something about it. If we truly believe a Democrat will win the White House, we can vote for Republicans in Congress. If we believe Trump will continue to share his inspirational Twitter messages wishing everyone well — just a bit of sarcasm here — we should vote Democratic in all the other races.

I don’t want Sanders expanding government and running up a tab that even higher taxes seem incapable of paying, while I also don’t want Trump getting a free pass to follow his impulses where they take him and the rest of the country. For me, the best 2020 choice is a weak and controlled president.

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Lingbo Zhang Photo from CSHL

By Daniel Dunaief

In the span of a few months, Lingbo Zhang, a Cold Spring Harbor Laboratory fellow, has made discoveries involving two deadly blood cancers.

In September, Zhang, collaborating with researchers from Memorial Sloan Kettering Cancer Center and the National Institute of Diabetes and Digestive and Kidney Diseases, found a drug target that might eventually lead to a new treatment for myelodysplastic syndrome, which is a common form of blood cancer. The scientists published their work in the journal Science Translational Medicine.

In January, Zhang published work that analyzed the genes that are active in acute myeloid leukemia, which has a five-year survival rate of only 33 percent. 

By studying 230 genes, Zhang found that this form of blood cancer is addicted to higher concentrations of vitamin B6, creating a potential target for future therapy. The CSHL scientist published this work in the journal Cancer Cell.

“We feel humbled that we found a target” for a future AML therapy, Zhang said of his latest discovery. “My lab partners and I think one day we can potentially translate our knowledge into a real therapy. The translational part gives us the energy and encouragement to work hard.”

Indeed, Zhang explained that his work broadly focuses on blood cancer, in which he looks for questions of medical importance. With MDS, he started with the view that many patients with this disease do not respond to the typical treatment using a hormone called erythropoietin, or EPO.

Lingbo Zhang

People with MDS typically have too few red blood cells, which are made in bone marrow. The hormone EPO converts progenitor immature versions of red blood cells into the ones that function in the body. A small percentage of MDS patients, however, respond to EPO. This occurs because people with this disease have a smaller pool of progenitor cells.

Zhang and his colleagues went upstream of those progenitor cells, searching for defective processes earlier in the pathway. They found that a protein receptor, CHRM4, decreases the production of cells that might become red blood cells. 

By inhibiting that receptor, they hoped to restore the red blood cell making process. In mice that have the same blood features as human MDS, this approach worked, restoring the machinery that leads to the production of red blood cells.

With both the MDS and the leukemia studies, these discoveries might lead to a future treatment, but are not necessarily the final step between understanding molecular signals and developing treatments. These findings are transitioning from basic discoveries into the preclinical development of novel therapies, Zhang said.

For MDS, the treatment may be effective with the inhibitor itself, while for AML, it will potentially be effective as part of a therapy in combination with other treatments.

In his work on leukemia, Zhang said the research went through several phases, each of which took several months. For starters, he screened all the potential target genes. Once he performed the initial work, he conducted a validation study, exploring each gene, one by one. Finally, he worked to validate the study.

After all that work, he discovered the role that the gene that makes PDXK, the enzyme that helps cells use vitamin B6, plays in contributing to cancer. Normal, healthy cells use vitamin B6 during metabolism to produce energy and grow. As with most cancers, leukemia involves more cell division than in a healthy cell, which means that the PDXK enzyme is more active.

Scott Lowe, a collaborator on the research and former CSHL fellow who is now the chair of Cancer Biology and Genetics at Memorial Sloan Kettering, expressed surprised at the finding. “While the action of certain vitamins has previously been linked to cancer, the specific links between vitamin B6 identified here were unexpected,” he said in a press release.

A postdoctoral researcher in Zhang’s lab who has been working on the project for two years, Bo Li plans to continue this research and hopes to find a more mechanistic understanding of the discovery.

While this vitamin contributes to cancer, people with leukemia shouldn’t reduce their consumption of B6, which is necessary in healthy cells. If normal and cancer cells both need this vitamin, how could this be a target for drugs?

The difference, Zhang explained, is in the concentration of the enzyme and, as a result, the B6.

PDXK is higher in leukemia. Reducing its activity by inhibiting this activity could affect the disease.

Working with a collaborator at Memorial Sloan Kettering, Zhang is hoping to develop a better chemical compound with the right property to target the activity of this gene and enzyme.

To conduct research into different diseases and pathways, Zhang works with a group of “very talented and hard working people,” in his lab, which includes a few postdoctoral researchers, a doctoral student, a few undergraduates and a technician, bringing his lab’s staff to eight people. “We also have very good collaborators at other institutes and we are able to manage several projects in parallel,” he said.

Zhang said he likes basic and translational science. The basic science brings “beautiful new theories that identify a detail nature created.” He also feels driven to “translate some of these basic discoveries into a potential treatment,” he said. He is working with a foundation and the hospital and receives patient information from them, which encourages him to work hard to seek ways to “benefit them.”

Down the road, he hopes to understand the hierarchical process that leads from stem cells to mature blood cells. By identifying a majority of the players or the regulators, he may be able to understand the different processes involved in the course of numerous diseases.

As for his current work, Zhang is pleased with the potential translational benefit of both discoveries. “I feel very happy that we can identify a target for leukemia and MDS,” he said.

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Photo from METRO

By Daniel Dunaief

Daniel Dunaief

She could feel the tension mounting. She had been down this road, or, more specifically, on this runway, numerous times before.

Flying didn’t bother her. She had taken many flights before she met her husband. Since they’d been married, they had also taken trips each year.

That’s when the trouble started. He didn’t blame her, but as someone who shared his feelings and wanted to help him when she could, she often felt at a loss as this moment approached.

She looked at the stranger next to her, eager to encourage a new person to enter the dialogue and distract him from his frustration.

At first, the stranger didn’t engage in conversation, preferring to read his book and to look through the movie offerings on his phone.

The ride around the airport took a while, as the plane stopped a few times to let other flights land.

Unable to break the ice with the man on the other side of her, she turned to her husband and hoped the game they’d developed might help.

“Hey,” she said, “how long do you think it’ll take this time?”

He grumbled something between his gritted teeth.

“Well,” she said, not bothering to ask him to repeat himself when she felt that the words were less relevant than the angry emotion that built up inside of him. “I’m going with eight.”

“Eight?” he spit back at her incredulously. “No way! It’s going to be at least 12.”

When the plane stopped and the Jetway came out to meet it, the man started his stopwatch, holding it up so she could see.

After three minutes, the passenger on her other side, who had heard the abbreviated conversation and could feel the tension rising between them as the man glared, unblinking, at the front of the plane and all the passengers between him and the next step on his trip, decided to break the frustrated silence in their row.

“Are you guys guessing how long it’ll be before you get off the plane?” he asked.

“Yes,” she sighed, grateful for the relief from watching and taking care of her husband.

A flight attendant made an announcement.

“Excuse me, ladies and gentlemen, we’re waiting for a gate attendant to fix the lock on the other side. It should only be a few minutes,” she said.

The man near the window shook his head. The woman shrugged at what she hoped was her new ally.

“Well, we’ll just start now,” she offered, as she set her own stopwatch on her phone and encouraged him to follow the new timing.

“You see,” she said, “he gets angry when people aren’t ready to go after the
plane lands.”

He turned away from the front of the plane long enough to explain himself to the stranger near the aisle.

“They turn off the seatbelt sign and people don’t get their luggage,” he snarled, gesturing with his palm at all the offending passengers between the door to the rest of his travels and the seat that barely contained his irritation. 

“Look at them, sitting there. It’s going to take each of them a while to get off. They have to find their bags, pull them out and get off the plane.”

The stranger offered the weary wife a supportive look. She appreciated the gesture, even as she made sure all her items were ready to go.

“These things are beyond your control,” the stranger offered.

“That’s true, but it still bothers him,” she sighed as she held her bags tightly in her hand.

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From left, Martin Kaczocha, Robert Rizzo, Iwao Ojima and Lloyd Trotman. Photo from SBU

By Daniel Dunaief

Pulling together experts from a variety of fields, scientists at Stony Brook University and Cold Spring Harbor Laboratory have demonstrated promise in their efforts to tackle prostate cancer in a new way.

Led by Iwao Ojima, a distinguished professor of chemistry and director of the Institute of Chemical Biology and Drug Discovery at SBU, and Martin Kaczocha, an assistant professor in the Department of Anesthesiology at SBU, the multidisciplinary team recently received a five-year, $4.2 million grant from the National Cancer Institute.

The team is following up on its preliminary success with inhibitors of fatty acid binding protein 5, or FABP5. By tamping down on this protein in prostate cancer cells grown in the lab and in mouse models of the disease, these researchers treated metastatic cancer cells.

The scientists, who received a Translational Research Opportunities Seed Grant from the Renaissance School of Medicine at Stony Brook, were pleased with the next steps in their research.

“We’re happy that the National Cancer Institute validated our target,” said Kaczocha. It will help us “move forward and expand the scope of our work.”

From left, Robert Rizzo, Iwao Ojima, Martin Kaczocha and Lloyd Trotman. Photo from SBU

To be sure, scientists are generally cautiously optimistic about the translation between basic discoveries about mechanisms involved in cancer and the ability of doctors to use these findings in future therapies. Indeed, numerous promising early efforts haven’t always led to treatments. “Many tumors develop resistance to existing therapies through a variety of mechanisms,” said Kaczocha.

Still, the researchers involved in the current study hope the findings will eventually provide another tool in the treatment of prostate cancer.

The inhibitors scientists including Lloyd Trotman, a professor at Cold Spring Harbor Laboratory, are testing “appear to work in a context where [other treatments] lose efficacy. We hope this will translate” to a setting in which the researchers test their treatment in a mouse model of prostate cancer, explained Kaczocha. One of the goals of the NCI grant is to find further validation of this benefit.

Eventually, any possible treatment that utilizes these findings would involve a combination of inhibitors and existing therapeutics, Kaczocha said.

To create a product that might target this molecule, Ojima screened more than one million commercially available compounds on a computer. Out of over 1,000 compounds designed and analyzed, he selected about 120 for chemical synthesis and biological assay.

Artificial intelligence helps dig out known matters from a huge data, but not for newly created substances. Ojima found more than 30 compounds from the ones he synthesized and tested that were more advanced than the original project.

“It’s an ongoing process,” Ojima explained, adding that he believes he will find a more efficacious inhibitor. Ojima and Kaczocha are working with Robert Rizzo, a professor in the Department of Applied Mathematics & Statistics at SBU to develop these inhibitors.

Indeed, that process involves determining the stability, bioavailability and many other factors to minimize any adverse side effects

The side effects from this treatment connect to the original focus of the scientific team. As it turns out, inhibiting FABP5 causes pain relief because it reduces the breakdown of anandamide, or AEA, which is part of the body’s natural pain relief system. The inhibitors also have anti-inflammatory properties.

“This compound’s side effect is pretty beneficial for patients,” said Ojima.

The Long Island team is continuing to pursue the use of these compounds to manage pain as well.

Indeed, Kaczocha’s mother Zofia, who has pain associated with arthritis, asks him at least once a month when his drug will be available. The NCI grant will enable him and his colleagues to continue to build on their earlier work as they hope to translate their scientific discoveries into a clinical option.

“We are continuing our original research on the use of FABP5 inhibitors for pain control,” Ojima explained in an email.

As for their work with cancer, the inhibitors are “less cytotoxic,” Ojima said, and, in animal models, have been able to kill metastatic cancer cells that have become resistant to drug treatment. He suggested that the hope of this treatment is that it can sensitize the cancer cells or tumor to other therapies, which is a “promising approach.”

So far, Ojima, Kaczocha, Trotman and colleagues have tested this treatment only on tumors that haven’t yet metastasized, and not on tumors that have spread to other organs. “Our hope is that it may have some preventive effect in the early stages” of metastasis, Ojima said.

Ojima and Kaczocha were grateful for the seed grant from the medical school, which helped push the research forward. “A seed grant is very important for basic research,” Ojima added.

Other cancers, such as breast cancer, also have over expression of the same fatty acid binding protein. While the scientists are starting with prostate cancer, they hope to expand their work to other cancers as well, once they start gathering results.

La Jolla, California-based Artelo Biosciences partnered with these researchers starting in the spring of 2018. Artelo is licensing the patents for the target as well as the patents for lead compounds. Moving any compound through the beginning of the Food & Drug Administration testing is something Artelo will eventually take over, Kaczocha said. “They will have the financing to pursue this further,” he added.

As a researcher and a pharmacologist who is involved in basic and translational studies, Kaczocha said his hope is always to develop something in his career that will help patients.

Other research groups are also developing small molecule inhibitors to reduce the prevalence or activity of fatty acid binding proteins, but these other scientists have generally not focused on the role of these proteins in cancer. Fatty acid binding protein 4, for example, has a role in metabolic disorders.

“We have a relatively unique position where we are targeting prostate cancer” by reducing the activity and effect of this protein, Kaczocha said.

Trotman, whose lab has a unique animal model of prostate cancer that is a close mimic to the progression of prostate cancer in humans, offers an advantage in their research work, added Kaczocha.

 

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George Mackay as Lance Cpl. Schofield in a scene from the film Photo courtesy of Universal Pictures

By Daniel Dunaief

The film “1917” is a good news, bad news movie experience.

In a race against time, World War I soldiers Lance Cpl. Blake (played by Dean-Charles Chapman) and Lance Cpl. Schofield (George MacKay) maneuver through dangerous, German-controlled territory to stop an attack by the British that is destined to fail.

The good news for the Universal Pictures movie, which was written by Krysty Wilson-Cairns and Sam Mendes, is that it is a tour de force in direction and cinematography. Audiences track the movements of Schofield and Blake, who has a vested interest in completing a mission that will also likely save his brother, so closely that they feel as if they are on the battlefield. The soldiers trudge through mud, hunch low to avoid incoming bullets, and wade through icy cold water during their difficult mission.

The relatively unknown actors do an incredible job as everymen, portraying the soldiers asked to do the impossible with resources often limited to their survival instincts and their reliance on each other.

Photo courtesy of Universal Pictures

Directed by Mendes, the movie includes a few heart-stopping moments, as audience members in a packed theater hold their breaths along with the actors to avoid giving away their position to the unseen but omnipresent enemy.

Even the scenes that don’t involve bullets and combat have a gritty feel. The camera moves through cramped trenches, where the spaces narrow in some areas to places where barely two people can fit shoulder to shoulder.

The film succeeds in portraying so many elements of the horrors of the battlefield. The enormous responsibility of saving 1,600 men weighs heavily on the two soldiers. The film immerses the audience completely in the time period, the action and the goal.

The bad news is that the script is noticeably thin. We don’t know much about either character and, apart from the set up lines uttered by Colin Firth as Gen. Erinmore and Benedict Cumberbatch as Col. Mackenzie, the script isn’t nearly as memorable as the visuals.

Indeed, apart from compelling music, which includes an original score from Thomas Newman that was nominated for an Oscar, the movie could easily have been a silent film with a few subtitles sprinkled between the visuals.

As a movie watching experience, “1917” is immersive and compelling, but its visuals show a better story than its thin script.

Moving from one horrifying and dangerous scene to another, we feel as if we’re running alongside strangers we would like to succeed, if only to reach their important destination and save other troops for whom we have almost as much information as the two lance corporals.

Photo courtesy of Universal Pictures

At times, the R-rated movie has overtones with other war films, like “Gallipoli,” a Mel Gibson film with a far superior script, and even with “Saving Private Ryan,” the Steven Spielberg directed epic with Tom Hanks.

In many scenes in “1917,” the effort, amid raining bullets and bombs that fall everywhere, make it seem impossible to survive. Some of the bullet and bomb dodging strains credibility.

The film also includes a quietly touching scene between Schofield and a random French woman, who is caring for an infant. The dialog, however, doesn’t make much sense, though, as she speaks only French and he speaks English, and yet they seem to understand each other.

Looking past the shortcomings of “1917,” the film offers an engaging visual experience, even if we don’t become invested in the characters whose singular mission forms the action and scenery-driven plot.

Winner of 3 Academy Awards (Best Cinematography, Best Sound Mixing and Best Visiual Effects), “1917” is now playing in local theaters.

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Stock photo

By Daniel Dunaief

Daniel Dunaief

Twenty years ago this week, my wife and I got married.

Over the course of the next two decades, we have gone through numerous changes and challenges together, providing a united front for our children, hosting relatives during birthday parties and celebrating landmark occasions.

As I think about the many roles we’ve played in each other’s lives I am grateful for my wife, the teacher. In addition to taking time to help educate our children, she has also been an extraordinary educator for me.

Starting with something easy, she taught me to relax. Before I met her, I felt the need to move, almost all the time. Sitting on a beach, a bed or a rock at the top of the mountain seemed like a waste of time. Over the years, taking a moment to soak in the sun, to observe the trees and birds around us, or to talk and laugh about the events of the day have become increasingly enjoyable ways to spend time and connect.

While my wife has taught me the fine art of relaxing, she has also demonstrated an incredible work ethic, balancing between the needs of our family and the demands of her job. She finds time to respond to work emails, to read work material and to answer important calls, all while supporting our children at everything from sports scrimmages to concerts to graduations.

Neither of us is particularly fond of shopping. She has, however, demonstrated how to speed-shop in a store. She has a gift not only for finding what she or any member of our family needs — a black shirt for a coming concert, a white dress for a party or specific socks that are cool enough for school — but also doing it in the most efficient manner, enabling the four of us to race back to the car and on to other activities.

She has also taught me how to laugh. Of course I laughed before I met her, but the laughter wasn’t as frequent and it didn’t continue to help cement my relationship to someone as well as it does with my wife. The absurd surrounds us, if you know what to look for and how to find it.

Of course, I don’t necessarily cherish every lesson the same way. You see, my wife is a cat person, a trait she shares with her mother and siblings. When my wife was pregnant and during the months when she breastfed, I learned the fine art of scooping cat litter and, once a week, changing the pan. I learned how to do this unpleasant but necessary maintenance task as quickly as possible, leaving me with only a slight scent of cat litter on my clothes. Our young children enjoyed watching me expectorate for a full minute after the process ended.

She also taught me the sheer joy of walking the Earth with someone. Before I met her, I was an avid walker, trekking up and down West Meadow Beach, walking around neighborhoods in Manhattan and crossing the Brooklyn Bridge. Ever since then, we have covered thousands of miles in all types of terrain as we share our observations of everything from nature to the events of the day or week. Walking together in stride, I have felt a part of something larger and more meaningful than my own existence.

Ultimately, however, my wife taught me how to turn my dreams into a reality. When I was 13, I read about the Galapagos Islands. When I heard about how all the marine and island life ignores people, I knew I had to visit. Spurred on by my wife, we planned this journey, which in 2013 far exceeded my lofty expectations, just as each year does with the woman I married two decades ago.

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