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  • richardmitnick 3:16 pm on December 4, 2020 Permalink | Reply
    Tags: , , , Harvard Gazette,   

    From Harvard Gazette and Broad Institute of Harvard and MIT: “New technology to investigate autism spectrum disorder” 

    Harvard University

    From Harvard Gazette

    and

    Broad Institute

    From Broad Institute of Harvard and MIT

    December 2, 2020
    Jessica Lau

    1
    Researchers applied the Perturb-Seq method to the developing mouse brain by introducing multiple genetic changes to cells (in red) and measuring how gene expression changed in individual cells. Credit: Paola Arlotta laboratory/Harvard University.

    Technology to identify potential biological mechanisms underlying autism spectrum disorder has been developed by scientists at Harvard University, the Broad Institute of MIT and Harvard, and MIT.

    The “Perturb-Seq” method investigates the function of many different genes in many different cell types at once, in a living organism. Scientists applied the large-scale method to study dozens of genes that are associated with autism spectrum disorder, identifying how specific cell types in the developing mouse brain are impacted by mutations.

    Published in the journal Science, the method is also broadly applicable to other organs, enabling scientists to better understand a wide range of disease and normal processes.

    “For many years, genetic studies have identified a multitude of risk genes that are associated with the development of autism spectrum disorder,” said said co-senior author Paola Arlotta, the Golub Family Professor of Stem Cell and Regenerative Biology at Harvard. “The challenge in the field has been to make the connection between knowing what the genes are, to understanding how the genes actually affect cells and ultimately behavior.

    “We applied the Perturb-Seq technology to an intact developing organism for the first time, showing the potential of measuring gene function at scale to better understand a complex disorder,” Arlotta explained.

    The study was also led by co-senior authors Aviv Regev, who was a core member of the Broad Institute during the study and is currently executive vice president of Genentech Research and Early Development, and Feng Zhang, a core member of the Broad Institute and an investigator at MIT’s McGovern Institute.

    To investigate gene function at a large scale, the researchers combined two powerful genomic technologies. They used CRISPR-Cas9 genome editing to make precise changes, or perturbations, in 35 different genes linked to autism spectrum disorder risk. Then, they analyzed changes in the developing mouse brain using single-cell RNA sequencing, which allowed them to see how gene expression changed in over 40,000 individual cells.

    By looking at the level of individual cells, the researchers could compare how the risk genes affected different cell types in the cortex — the part of the brain responsible for complex functions including cognition and sensation. They analyzed networks of risk genes together to find common effects.

    “We found that both neurons and glia — the non-neuronal cells in the brain — are directly affected by different sets of these risk genes,” said Xin Jin, lead author of the study and a Junior Fellow of the Harvard Society of Fellows. “Genes and molecules don’t generate cognition per se — they need to impact specific cell types in the brain to do so. We are interested in understanding how these different cell types can contribute to the disorder.”

    To get a sense of the model’s potential relevance to the disorder in humans, the researchers compared their results to data from post-mortem human brains. In general, they found that in the post-mortem human brains with autism spectrum disorder, some of the key genes with altered expression were also affected in the Perturb-seq data.

    “We now have a really rich dataset that allows us to draw insights, and we’re still learning a lot about it every day,” Jin said. “As we move forward with studying disease mechanisms in more depth, we can focus on the cell types that may be really important.”

    “The field has been limited by the sheer time and effort that it takes to make one model at a time to test the function of single genes. Now, we have shown the potential of studying gene function in a developing organism in a scalable way, which is an exciting first step to understanding the mechanisms that lead to autism spectrum disorder and other complex psychiatric conditions, and to eventually develop treatments for these devastating conditions,” said Arlotta, who is also an institute member of the Broad Institute and part of the Broad’s Stanley Center for Psychiatric Research. “Our work also paves the way for Perturb-Seq to be applied to organs beyond the brain, to enable scientists to better understand the development or function of different tissue types, as well as pathological conditions.”

    “Through genome sequencing efforts, a very large number of genes have been identified that, when mutated, are associated with human diseases. Traditionally, understanding the role of these genes would involve in-depth studies of each gene individually. By developing Perturb-seq for in vivo applications, we can start to screen all of these genes in animal models in a much more efficient manner, enabling us to understand mechanistically how mutations in these genes can lead to disease,” said Zhang, who is also the James and Patricia Poitras Professor of Neuroscience at MIT and a professor of brain and cognitive sciences and biological engineering at MIT.

    See the full article here .

    five-ways-keep-your-child-safe-school-shootings

    Please help promote STEM in your local schools.

    Stem Education Coalition

    Broad Institute Campus

    The Eli and Edythe L. Broad Institute of Harvard and MIT is founded on two core beliefs:
    This generation has a historic opportunity and responsibility to transform medicine by using systematic approaches in the biological sciences to dramatically accelerate the understanding and treatment of disease.
    To fulfill this mission, we need new kinds of research institutions, with a deeply collaborative spirit across disciplines and organizations, and having the capacity to tackle ambitious challenges.

    The Broad Institute is essentially an “experiment” in a new way of doing science, empowering this generation of researchers to:

    Act nimbly. Encouraging creativity often means moving quickly, and taking risks on new approaches and structures that often defy conventional wisdom.
    Work boldly. Meeting the biomedical challenges of this generation requires the capacity to mount projects at any scale — from a single individual to teams of hundreds of scientists.
    Share openly. Seizing scientific opportunities requires creating methods, tools and massive data sets — and making them available to the entire scientific community to rapidly accelerate biomedical advancement.
    Reach globally. Biomedicine should address the medical challenges of the entire world, not just advanced economies, and include scientists in developing countries as equal partners whose knowledge and experience are critical to driving progress.

    Harvard University

    3

    Harvard University campus
    Harvard University is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

     
  • richardmitnick 10:04 am on December 2, 2020 Permalink | Reply
    Tags: "Zooming to the ocean floor", Harvard Gazette   

    From Harvard Gazette: “Zooming to the ocean floor” 

    Harvard University

    From Harvard Gazette

    December 1, 2020
    Juan Siliezar

    Students follow researchers 3,000 meters under the sea.


    Credit: Peter R. Girguis

    Life is better under the sea. Take it from a group of Harvard undergraduates who in late October were among the first to glimpse life on the ocean floor about 10 miles off the coast of Santa Lucia, Calif.

    As part of their deep-sea biology course, OEB 119, more than 40 students were patched in via livestream and a satellite call to a team of researchers leading an exploration mission by the marine research vessel Nautilus. The students were able to see first-hand how deep-sea exploration happens, and even ask questions of the team controlling the vessel’s remote operated vehicle (ROV), Hercules, as it dove 3,000 meters into sea. They saw the sea urchins, red shrimp, deep-sea eel, and watched as the pilot of the ROV took a sample of a sea star.

    “Our class had the site up in one window and a Zoom with the class open in another,” said Max Christopher ’23. “The ROV pilots were able to tell us about how they navigate the seafloor with only a small line of sight in the darkness and the researchers helped explain what they were looking for on the bottom.”

    Kemi Ashing-Giwa ’22, added: “We learned not only about the many different species that inhabit the area, but also about how deep-sea exploration works on a logistical level. The whole experience was fantastic.”

    The virtual deep-sea adventure was set up by Professor of Organismic and Evolutionary Biology Peter R. Girguis, who is the course’s instructor and also an adjunct oceanographer in applied ocean physics and engineering at Woods Hole Oceanographic Institution. Girguis has led multiple cruises as a chief scientist with on the research vessel Nautilus, as well as onboard the Schmidt Ocean’s research vessel Falkor. He reached out to the National Oceanic and Atmospheric Administration and colleagues at the NOAA funded Ocean Exploration Trust, which operates the Nautilus, to connect with about having his students sit in on a mission.

    “A lot of it is really introducing students to the largest habitat on Earth,” Girguis said. “It was a way of having a shared experience on Zoom that felt more connected to one another than just a typical class.”

    See the full article here .

    five-ways-keep-your-child-safe-school-shootings

    Please help promote STEM in your local schools.

    Stem Education Coalition

    Harvard University campus
    Harvard University is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

     
  • richardmitnick 9:00 am on November 30, 2020 Permalink | Reply
    Tags: "Evidence of the interconnectedness of global climate", Analysis finds melting ice sheet affects a second thousands of miles away., , , Harvard Gazette, The study establishes an underappreciated connection between the stability of the Antarctic ice sheet and significant periods of melting in the Northern Hemisphere., The study models how this seesaw effect works., The study shows changes in the Antarctic ice sheet were caused by the melting of ice sheets in the Northern Hemisphere.   

    From Harvard Gazette: “Evidence of the interconnectedness of global climate” 

    Harvard University

    From Harvard Gazette

    November 25, 2020
    Juan Siliezar

    Analysis finds melting ice sheet affects a second thousands of miles away.

    1
    Credit: Kenichiro Tani

    To see how deeply interconnected the planet truly is, look no further than the massive ice sheets on the Northern Hemisphere and South Pole.

    Thousands of miles apart, they are hardly next-door neighbors, but according to new research from a team of international scientists — led by Natalya Gomez, Ph.D. ’14, and including Harvard Professor Jerry X. Mitrovica — what happens in one region has a surprisingly direct and outsized effect on the other, in terms of ice expanding or melting.

    The analysis, published in Nature, shows for the first time that changes in the Antarctic ice sheet were caused by the melting of ice sheets in the Northern Hemisphere. The influence was driven by sea-level changes caused by the melting ice in the north during the past 40,000 years. Understanding how this works can help climate scientists grasp future changes as global warming increases the melting of major ice sheets and ice caps, researchers said.

    The study models how this seesaw effect works. Scientists found that when ice on the Northern Hemisphere stayed frozen during the last peak of the Ice Age, about 20,000 to 26,000 years ago, it led to reduced sea levels in Antarctica and growth of the ice sheet there. When the climate warmed after that peak, the ice sheets in the north started melting, causing sea levels in the southern hemisphere to rise. This rising ocean triggered the ice in Antarctica to retreat to about the size it is today over thousands of years, a relatively quick response in geologic time.

    The question of what caused the Antarctic ice sheet to melt so rapidly during this warming period had been a longstanding enigma.

    “That’s the really exciting part of this,” said Mitrovica, the Frank B. Baird Jr. Professor of Science in the Department of Earth and Planetary Sciences. “What was driving these dramatic events in which the Antarctic released huge amounts of ice mass? This research shows that the events weren’t ultimately driven by anything local. They were driven by sea level rising locally but in response to the melting of ice sheets very far away. The study establishes an underappreciated connection between the stability of the Antarctic ice sheet and significant periods of melting in the Northern Hemisphere.”

    The retreat was consistent with the pattern of sea level change predicted by Gomez, now an assistant professor of earth and planetary sciences at McGill University, and colleagues in earlier work on the Antarctic continent. The next step is expanding the study to see where else ice retreat in one location drives retreat in another. That can provide insight on ice sheet stability at other times in the history, and perhaps in the future.

    “Looking to the past can really help us to understand how ice sheets and sea levels work,” Gomez said. “It gives us a better appreciation of how the whole Earth system works.”

    Along with Gomez and Mitrovica, the team of scientists on the project included researchers from Oregon State University and the University of Bonn in Germany. The rocks they focused on, called ice-rafted debris, were once embedded inside the Antarctic ice sheet. Fallen icebergs carried them into the Southern Ocean. Researchers determined when and where they were released from the ice sheet. They combined ice-sheet and sea-level modeling with sediment core samples from the ocean bottom near Antarctica to verify their findings. And researchers also looked at markers of past shorelines to see how the ice sheet’s edge has retreated.

    2
    This was taken in the Scotia Sea during the coring campaign in 2007. Credit: Michael Weber.

    Gomez has been researching ice sheets since she was a Graduate School of Arts and Sciences student in the Mitrovica Group. She led a study in 2010 that showed that gravitational effects of ice sheets are so strong that when ice sheets melt, the expected sea level rise from all that meltwater entering the oceans would be counterbalanced in nearby areas. Gomez showed that if all of the ice in the west Antarctic ice sheet melted, it could actually lower sea level near the ice by as much as 300 feet, but the sea level would rise significantly more than expected in the Northern Hemisphere.

    This paper furthered that study by asking how melting ice sheets in one part of the climate system affected another. In this case, the researchers looked at the ice sheets in the Northern Hemisphere that once covered North America and Northern Europe.

    By putting together modeling data on sea-level rise and ice-sheet melting with the debris left over from icebergs that broke off Antarctica during the Ice Age, the researchers simulated how sea levels and ice dynamics changed in both hemispheres over the past 40,000 years.

    The researchers were able to explain several periods of instability during the past 20,000 years when the Antarctic ice sheet went through phases of rapid melting known as “meltwater pulses.” In fact, according to their model, if not for these periods of rapid retreat, the Antarctic ice sheet, which covers almost 14 million square kilometers and weighs about 26 million gigatons, would be even more of a behemoth than it is now.

    With the geological records, which were collected primarily by Michael Webster from the University of Bonn, the researchers confirmed the timeline predicted by their model and saw that this sea-level change in Antarctica and the mass shedding corresponded with episodes of melting of ice sheets in the Northern Hemisphere.

    The data caught Gomez by surprise. More than anything, though, it deepened her curiosity about these frozen systems.

    “These ice sheets are really dynamic, exciting, and intriguing parts of the Earth’s climate system. It’s staggering to think of ice that is several kilometers thick, that covers an entire continent, and that is evolving on all of these different timescales with global consequences,” Gomez said. “It’s just motivation for trying to better understand these really massive systems that are so far away from us.”

    This work was partially supported by the Natural Sciences and Engineering Research Council, the Canada Research Chair, the Canadian Foundation for Innovation, the Deutsche Forschungsgemeinschaft, and NASA.

    See the full article here .

    five-ways-keep-your-child-safe-school-shootings

    Please help promote STEM in your local schools.

    Stem Education Coalition

    Harvard University campus
    Harvard University is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

     
  • richardmitnick 10:58 am on November 9, 2020 Permalink | Reply
    Tags: , , , , , , Harvard Gazette, ,   

    From Harvard Gazette: “Digging into the history of the cosmos” Cora Dvorkin 

    Harvard University

    From Harvard Gazette

    1
    A sense of discovery and adventure has come to define much of Cora Dvorkin’s work as an associate professor in the Department of Physics. Credit: Stephanie Mitchell/Harvard Staff Photographer.

    But lab members say award-winning cosmologist is equally invested in futures.

    Cora Dvorkin’s fascination with math and the cosmos started with her father, a family friend, and famed theoretical physicist Stephen Hawking.

    Drawn to math at an early age, Dvorkin remembers long discussions with her father and his friend about abstract mathematical concepts like the origin of infinity or zero and was 10 years old when first handed Hawking’s A Brief History of Time. It didn’t take long for a young Dvorkin, growing up in Buenos Aires, to become enthralled with the kinds of connections Hawkings was making.

    “I realized that I could access the kind of questions that I was interested in with the tool of mathematics,” Dvorkin said. “I had fun when my mind went out [in search of big answers] and then it came back, and I realized I was physically at this place, but I was flying somewhere else.”

    That sense of discovery and adventure has come to define much of her work as an associate professor in the FAS’ Department of Physics. There, the theoretical cosmologist uses advanced algorithms and machine learning to analyze data from satellites and telescopes all over the world to study the origins and composition of the early universe. Her lab’s main goal is trying to understand the nature of one of the universe’s most important and puzzling features: Dark Matter.

    “We use our computers to simulate the universe and to do our calculations,” said Dvorkin, who came to Harvard in 2014 as a fellow for the Institute for Theory and Computation at the Center for Astrophysics | Harvard & Smithsonian. “The data that we use are either from the cosmic microwave background [CMB], which is the afterglow from the Big Bang, or data from what is known as the large-scale structure of the universe, such as galaxy surveys or gravitational lensing, which is the light coming towards us [from distant galaxies] that’s deflected [and distorted] because of massive structures along the way.”

    Gravitational Lensing

    Gravitational Lensing NASA/ESA.

    CMB per ESA/Planck

    Laniakea supercluster. From Nature The Laniakea supercluster of galaxies R. Brent Tully, Hélène Courtois, Yehuda Hoffman & Daniel Pomarède at http://www.nature.com/nature/journal/v513/n7516/full/nature13674.html. Milky Way is the red dot.

    A lot of these structures are what’s known as Dark Matter. Scientists believe dark matter is the glue holding galaxies together and the organizing force giving the universe its overall structure. It comprises around 80 percent of all mass.

    Dark Matter Background
    Fritz Zwicky discovered Dark Matter in the 1930s when observing the movement of the Coma Cluster., Vera Rubin a Woman in STEM denied the Nobel, did most of the work on Dark Matter.

    Fritz Zwicky from http:// palomarskies.blogspot.com.

    Coma cluster via NASA/ESA Hubble.

    In modern times, it was astronomer Fritz Zwicky, in the 1930s, who made the first observations of what we now call dark matter. His 1933 observations of the Coma Cluster of galaxies seemed to indicated it has a mass 500 times more than that previously calculated by Edwin Hubble. Furthermore, this extra mass seemed to be completely invisible. Although Zwicky’s observations were initially met with much skepticism, they were later confirmed by other groups of astronomers.

    Thirty years later, astronomer Vera Rubin provided a huge piece of evidence for the existence of dark matter. She discovered that the centers of galaxies rotate at the same speed as their extremities, whereas, of course, they should rotate faster. Think of a vinyl LP on a record deck: its center rotates faster than its edge. That’s what logic dictates we should see in galaxies too. But we do not. The only way to explain this is if the whole galaxy is only the center of some much larger structure, as if it is only the label on the LP so to speak, causing the galaxy to have a consistent rotation speed from center to edge.

    Vera Rubin, following Zwicky, postulated that the missing structure in galaxies is dark matter. Her ideas were met with much resistance from the astronomical community, but her observations have been confirmed and are seen today as pivotal proof of the existence of dark matter.

    Astronomer Vera Rubin at the Lowell Observatory in 1965, worked on Dark Matter (The Carnegie Institution for Science).


    Vera Rubin measuring spectra, worked on Dark Matter (Emilio Segre Visual Archives AIP SPL).


    Vera Rubin, with Department of Terrestrial Magnetism (DTM) image tube spectrograph attached to the Kitt Peak 84-inch telescope, 1970. https://home.dtm.ciw.edu.

    The Vera C. Rubin Observatory currently under construction on the El Peñón peak at Cerro Pachón Chile, a 2,682-meter-high mountain in Coquimbo Region, in northern Chile, alongside the existing Gemini South and Southern Astrophysical Research Telescopes.

    LSST Data Journey, Illustration by Sandbox Studio, Chicago with Ana Kova.

    Catching a glimpse of it is exceedingly difficult, however. Dark matter doesn’t emit, reflect, or absorb light, making it essentially invisible to current instruments. Researchers instead infer things about dark matter through what its powerful gravity allows it to do: bend and focus the light around it, a phenomenon called gravitational lensing.

    In recent years, Dvorkin’s lab has been a leader in finding new approaches to learn about dark matter. One study published last year [Physical Review D], for instance involved, using a novel machine learning method to detect what’s known as subhalos, or small clumps of dark matter that live within larger halos of the dark matter holding a galaxy together. The halos basically create pockets where certain stars are confined. While they can’t be seen, these subhalos can be traced by analyzing the light distortion from the lensing effect. The problem is that the analysis is often expensive and can take weeks.

    “Most of the time you get no detections, so what I have been working on with a graduate student and now with a postdoc is if we can automate a procedure like direct detection, for example, using convolutional neural networks, making this process of detecting subhalos much faster,” Dvorkin said.

    The lab showed their strategy using machine learning can reduce the analysis to a few seconds rather than a few weeks using traditional methods.

    Other dark matter research involves looking at the early universe, which has included using cosmic microwave background observations to study the structure of dark matter and pioneering a method for investigating the shape of an aspect inflation known as “Generalized Slow Roll.” Along with colleagues at Harvard, MIT, and other universities, Dvorkin helped launch a new National Science Foundation institute for artificial intelligence, where she’ll apply some of her methods for detecting dark matter.

    Her current and past work has turned heads. Dvorkin received the Department of Energy Early Career award in 2019. She snagged the Scientist of the Year award given by the students interns and faculty at The Harvard Foundation for Intercultural and Race Relations in 2018 for her contributions to physics, cosmology and STEM Education. Dvorkin was named a Radcliffe Institute Fellowship from 2018 to 2019. And in 2012, she was given the Martin and Beate Block Award, an international prize given out annually to a promising young physicist by the Aspen Center for Physics.

    Professor of astronomy and physics Douglas Finkbeiner considers himself among Dvorkin’s fans — not only because her stellar work has led to a good-looking trophy case but also because of how she champions her collaborators, especially future scientists.

    “Cora is not just a builder of theories, but a builder of people,” he said. “It has been a joy to watch her students [and research associates] grow and mature into top-notch scientists.”

    The Dvorkin Group is comprised of 11 members, including seven graduate students and one undergrad.

    “We’ve got a really big group in comparison to any other research groups that I have been a part of,” said Bryan Ostdiek, one of the lab’s three postdoctoral fellows. “This makes everything very lively” and collaborative on projects, he said. It was especially evident before the pandemic, but still happens now through Zoom and Slack messaging.

    And that’s just the way Dvorkin likes it.

    “I still remember the time when I was a graduate student,” Dvorkin said. “I benefited a lot from discussions with my adviser, but I also benefited from discussions with other group members. I have tried to give postdocs the opportunity to work with students because at some point they will be applying for faculty jobs.”

    When it comes to projects lab members say Dvorkin is as hands-on as they need her to be, but that she also gives them the freedom they need to evaluate data or come up with their own ideas for research.

    Ana Diaz Rivero, A.M. ’18, a physics Ph.D. candidate at the Graduate School of Arts and Sciences, says she’s been able to get early experience authoring scientific papers through her work at the lab, including in leading journals like The Astrophysical Journal and Physical Review D. She’s also been invited to give a number of talks, including an upcoming one at the Max Planck Institute for Astrophysics.

    Rivero says she’s been working with Dvorkin since the start of her graduate experience at Harvard in 2016.

    “I got accepted into Harvard, and on the day of my acceptance she sent me an email saying congrats on getting into Harvard, and we set up a time to talk,” Rivero said. The pair had met at Columbia University at a talk Dvorkin was giving. “When I came to visit at Open House, I spoke to her, and I really liked her, and I told her what ideas I had, and she was super supportive of me working on them in her group. So, on Day One of Harvard, I started out on a research project with her, and we’ve written a lot of papers together since.”

    Outreach like that is important to Dvorkin, especially to increase inclusion and diversity in the field. It’s why in the past she’s given talks at the Harvard Foundation’s annual Albert Einstein Science Conference: Advancing Minorities and Women in Science, Technology, Engineering and Mathematics and why, more recently, she’s been in contact with the Black National Society of Physicists.

    “I’m very concerned about these topics, and I’m trying my best to do whatever I can to fight this problem,” Dvorkin said.

    Reasons like this is why the group’s youngest lab member says Dvorkin not only serves as an excellent mentor but as a role model for female scientists like herself.

    “In general, there aren’t a lot of women in physics and, in particular, there aren’t a lot of women in theoretical physics, so I really, really appreciate having her as a mentor,” said Maya Burhanpurkar ’22, a Harvard undergrad studying physics and computer science. “It shows me what’s possible as a woman in the field.”

    See the full article here .

    five-ways-keep-your-child-safe-school-shootings

    Please help promote STEM in your local schools.

    Stem Education Coalition

    Harvard University campus
    Harvard University is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

     
  • richardmitnick 9:37 am on October 21, 2020 Permalink | Reply
    Tags: "Enzymatic DNA synthesis sees the light", , , , Harvard Gazette   

    From Harvard Gazette: “Enzymatic DNA synthesis sees the light” 

    Harvard University


    From Harvard Gazette

    October 19, 2020
    Benjamin Boettner
    Wyss Institute Communications

    1
    Credit: iStock.

    Methods from the computer chip industry aid writing and storage of digital data in DNA.

    According to current estimates, the amount of data produced by humans and machines is rising at an exponential rate, with the digital universe doubling in size every two years. Very likely, the magnetic and optical data-storage systems at our disposal won’t be able to archive this fast-growing volume of digital 1s and 0s anymore at some point. Plus, they cannot safely store data for more than a century without degrading.

    One solution to this pending global data-storage problem could be the development of DNA — life’s very own information-storage system — into a digital data storage medium.

    Researchers already are encoding complex information consisting of digital code into DNA’s four-letter code comprised of its A, T, G, and C nucleotide bases. DNA is an ideal storage medium because it is stable over hundreds or thousands of years, has an extraordinary information density, and its information can be efficiently read (decoded) again with advanced sequencing techniques that are continuously getting less expensive.

    What lags behind is the ability to write (encode) information into DNA. The programmed synthesis of synthetic DNA sequences still is mostly performed with a decades-old chemical procedure, known as the “phosphoramidite method,” that takes many steps that, although being able to be multiplexed, can only generate DNA sequences with up to around 200 nucleotides in length and makes occasional errors. It also produces environmentally toxic by-products that are not compatible with a “clean data storage technology.”

    Previously, George Church’s team at Harvard’s Wyss Institute for Biologically Inspired Engineering and Harvard Medical School (HMS) has developed the first DNA storage approach that uses a DNA-synthesizing biological enzyme known as Terminal deoxynucleotidyl Transferase (TdT), which, in principle, can synthesize much longer DNA sequences with fewer errors. Now, the researchers have applied photolithographic techniques from the computer chip industry to enzymatic DNA synthesis, and thus developed a new method to multiplex TdT’s superior DNA writing ability. In their study published in Nature Communications, they demonstrated the parallel synthesis of 12 DNA strands with varying sequences on a 1.2 square millimeter array surface.

    “We have championed and intensively pursued the use of DNA as a data-archiving medium accessed infrequently, yet with very high capacity and stability. Breakthroughs by us and others have enabled an exponential rise in the amount of digital data encrypted in DNA,” said corresponding author Church. “This study and other advances in enzymatic DNA synthesis will push the envelope of DNA writing much further and faster than chemical approaches.”

    Church is a core faculty member at the Wyss Institute and lead of its Synthetic Biology Focus Area with DNA data storage as one of its technology development areas. He also is professor of genetics at HMS and Professor of Health Sciences and Technology at Harvard and MIT.

    While the group’s first strategy using the TdT enzyme as an effective tool for DNA synthesis and digital data storage controlled TdT’s enzyme activity with a second enzyme, they show in their new study that TdT can be controlled by the high-energy photons that UV-light is composed of. A high level of control is essential as the TdT enzyme needs to be instructed to add only one single or a short block made of one of the four A, T, G, C nucleotide bases to the growing DNA strand with high precision at each cycle of the DNA synthesis process.

    2
    This illustration shows how the Wyss’ team encoded the first measures of the 1985 Nintendo Entertainment System video game Super Mario BrothersTM “Overworld Theme” (input) in DNA and then decoded it again into a sound-bite (output). Credit: Wyss Institute at Harvard University.

    Using a special codec, a computational method that encodes digital information into DNA code and decodes it again, which Church’s team developed in their previous study, the researchers encoded the first two measures of the “Overworld Theme” sheet music from the 1985 Nintendo Entertainment System (NES) video game Super Mario Brothers within 12 synthetic DNA strands. They generated those strands on an array matrix with a surface measuring merely 1.2 square millimeters by extending short DNA “primer” sequences, which were extended in a 3×4 pattern, using their photolithographic approach.

    “We applied the same photolithographic approach used by the computer chip industry to manufacture chips with electrical circuits patterned with nanometer precision to write DNA,” said first author Howon Lee, a postdoctoral fellow in Church’s group at the time of the study. “This provides enzymatic DNA synthesis with the potential of unprecedented multiplexing in the production of data-encoding DNA strands.”

    Photolithography, like photography, uses light to transfer images onto a substrate to induce a chemical change. The computer chip industry miniaturized this process and uses silicon instead of film as a substrate. Church’s team now adapted the chip industry’s capabilities in their new DNA writing approach by substituting silicon with their array matrix consisting of microfluidic cells containing the short DNA primer sequences.

    In order to control DNA synthesis at primers positioned in the 3×4 pattern, the team directed a beam of UV-light onto a dynamic mask (as is done in computer chip manufacturing) — which essentially is a stencil of the 3×4 pattern in which DNA synthesis is activated — and shrunk the patterned beam on the other side of the mask with optical lenses down to the size of the array matrix.

    “The UV-light reflected from the mask pattern precisely hits the target area of primer elongation and frees up cobalt ions, which the TdT enzyme needs in order to function, by degrading a light-sensitive “caging” molecule that shields the ions from TdT,” said co-author Daniel Wiegand, research scientist at the Wyss Institute. “By the time the UV-light is turned off and the TdT enzyme deactivated again with excess caging molecules, it has added a single nucleotide base or a homopolymer block of one of the four nucleotide bases to the growing primer sequences.”

    This cycle can be repeated multiple times whereby in each round only one of the four nucleotide bases or a homopolymer of a specific nucleotide base is added to the array matrix. In addition, by selectively covering specific openings of the mask during each cycle, the TdT enzyme only adds that specific nucleotide base to DNA primers where it is activated by UV-light, allowing the researchers to fully program the sequence of nucleotides in each of the strands.

    “Photon-directed multiplexed enzymatic DNA synthesis on this newly instrumented platform can be further developed to enable much higher automated multiplexing with improved TdT enzymes, and, eventually make DNA-based data storage significantly more effective, faster, and cheaper,” said co-corresponding author Richie Kohman, a lead senior research scientist at the Wyss’ Synthetic Biology focus area, who helped coordinate the research in Church’s team at the Wyss Institute.

    “This new approach to enzyme-directed synthetic DNA synthesis by the Church team is a clever piece of bioinspired engineering that combines the power of DNA replication with one of the most controllable and robust manufacturing methods developed by humanity — photolithography — to provide a solution that brings us closer to the goal of establishing DNA as a usable data storage medium,” said the Wyss Institute’s Founding Director Don Ingber, who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS).

    Other authors on the study are additional members of Church’s team, including Kettner Griswold, and Sukunya Punthambaker, as well as Honggu Chun, Professor of Biomedical Engineering at Korea University. This work was funded by the Wyss Institute for Biologically Inspired Engineering.

    See the full article here.

    five-ways-keep-your-child-safe-school-shootings

    Please help promote STEM in your local schools.

    Stem Education Coalition

    Harvard University campus
    Harvard University is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

     
  • richardmitnick 10:55 am on October 7, 2020 Permalink | Reply
    Tags: "Deep learning takes on synthetic biology", Computational algorithms enable identification and optimization of RNA-based tools for myriad applications., Harvard Gazette,   

    From Harvard Gazette: “Deep learning takes on synthetic biology” 

    Harvard University

    October 7, 2020
    Lindsay Brownell
    Wyss Institute Communications

    Computational algorithms enable identification and optimization of RNA-based tools for myriad applications.

    DNA and RNA have been compared to “instruction manuals” containing the information needed for living “machines” to operate. But while electronic machines like computers and robots are designed from the ground up to serve a specific purpose, biological organisms are governed by a much messier, more complex set of functions that lack the predictability of binary code. Inventing new solutions to biological problems requires teasing apart seemingly intractable variables — a task that is daunting to even the most intrepid human brains.

    Two teams of scientists from the Wyss Institute at Harvard University and the Massachusetts Institute of Technology have devised pathways around this roadblock by going beyond human brains; they developed a set of machine learning algorithms that can analyze reams of RNA-based “toehold” sequences and predict which ones will be most effective at sensing and responding to a desired target sequence. As reported in two papers published concurrently today in Nature Communications, the algorithms could be generalizable to other problems in synthetic biology as well, and could accelerate the development of biotechnology tools to improve science and medicine and help save lives.

    The two papers in Nature Communications:

    Sequence-to-function deep learning frameworks for engineered riboregulators

    A deep learning approach to programmable RNA switches

    “These achievements are exciting because they mark the starting point of our ability to ask better questions about the fundamental principles of RNA folding, which we need to know in order to achieve meaningful discoveries and build useful biological technologies,” said Luis Soenksen, a postdoctoral fellow at the Wyss Institute and Venture Builder at MIT’s Jameel Clinic who is a co-first author of the first of the two papers.

    Getting a hold of toehold switches

    The collaboration between data scientists from the Wyss Institute’s Predictive BioAnalytics Initiative and synthetic biologists in Wyss core faculty member Jim Collins’ lab at MIT was created to apply the computational power of machine learning, neural networks, and other algorithmic architectures to complex problems in biology that have so far defied resolution.

    As a proving ground for their approach, the two teams focused on a specific class of engineered RNA molecules: toehold switches, which are folded into a hairpin-like shape in their “off” state. When a complementary RNA strand binds to a “trigger” sequence trailing from one end of the hairpin, the toehold switch unfolds into its “on” state and exposes sequences that were previously hidden within the hairpin, allowing ribosomes to bind to and translate a downstream gene into protein molecules. This precise control over the expression of genes in response to the presence of a given molecule makes toehold switches very powerful components for sensing substances in the environment, detecting disease, and other purposes.

    However, many toehold switches do not work very well when tested experimentally, even though they have been engineered to produce a desired output in response to a given input based on known RNA folding rules. Recognizing this problem, the teams decided to use machine learning to analyze a large volume of toehold switch sequences and use insights from that analysis to more accurately predict which toeholds reliably perform their intended tasks, which would allow researchers to quickly identify high-quality toeholds for various experiments.

    The first hurdle they faced was that there was no dataset of toehold switch sequences large enough for deep learning techniques to analyze effectively. The authors took it upon themselves to generate a dataset that would be useful to train such models.

    “We designed and synthesized a massive library of toehold switches, nearly 100,000 in total, by systematically sampling short trigger regions along the entire genomes of 23 viruses and 906 human transcription factors,” said Alex Garruss, a Harvard graduate student working at the Wyss Institute who is a co-first author of the first paper. “The unprecedented scale of this dataset enables the use of advanced machine learning techniques for identifying and understanding useful switches for immediate downstream applications and future design.”

    Armed with enough data, the teams first employed tools traditionally used for analyzing synthetic RNA molecules to see if they could accurately predict the behavior of toehold switches now that there were manifold more examples available. However, none of the methods they tried — including mechanistic modeling based on thermodynamics and physical features — were able to predict with sufficient accuracy which toeholds functioned better.

    A picture is worth a thousand base pairs

    The researchers then explored various machine learning techniques to see if they could create models with better predictive abilities. The authors of the first paper decided to analyze toehold switches not as sequences of bases, but rather as two-dimensional “images” of base-pair possibilities.

    “We know the baseline rules for how an RNA molecule’s base pairs bond with each other, but molecules are wiggly — they never have a single perfect shape, but rather a probability of different shapes they could be in,” said Nicolaas Angenent-Mari, a MIT graduate student working at the Wyss Institute and co-first author of the first paper. “Computer vision algorithms have become very good at analyzing images, so we created a picture-like representation of all the possible folding states of each toehold switch, and trained a machine learning algorithm on those pictures so it could recognize the subtle patterns indicating whether a given picture would be a good or a bad toehold.”

    2
    By using both models sequentially, the researchers were able to predict which toehold sequences would produce high-quality sensors. Credit: Wyss Institute at Harvard University.

    Another benefit of their visually-based approach is that the team was able to “see” which parts of a toehold switch sequence the algorithm “paid attention” to the most when determining whether a given sequence was “good” or “bad.” They named this interpretation approach Visualizing Secondary Structure Saliency Maps, or VIS4Map, and applied it to their entire toehold switch dataset. VIS4Map successfully identified physical elements of the toehold switches that influenced their performance, and allowed the researchers to conclude that toeholds with more potentially competing internal structures were “leakier” and thus of lower quality than those with fewer such structures, providing insight into RNA folding mechanisms that had not been discovered using traditional analysis techniques.

    “Being able to understand and explain why certain tools work or don’t work has been a secondary goal within the artificial intelligence community for some time, but interpretability needs to be at the forefront of our concerns when studying biology because the underlying reasons for those systems’ behaviors often cannot be intuited,” said Jim Collins, the senior author of the first paper. “Meaningful discoveries and disruptions are the result of deep understanding of how nature works, and this project demonstrates that machine learning, when properly designed and applied, can greatly enhance our ability to gain important insights about biological systems.” Collins is also the Termeer Professor of Medical Engineering and Science at MIT.

    Now you’re speaking my language

    While the first team analyzed toehold switch sequences as 2D images to predict their quality, the second team created two different deep learning architectures that approached the challenge using orthogonal techniques. They then went beyond predicting toehold quality and used their models to optimize and redesign poorly performing toehold switches for different purposes, which they report in the second paper.

    The first model, based on a convolutional neural network (CNN) and multi-layer perceptron (MLP), treats toehold sequences as 1D images, or lines of nucleotide bases, and identifies patterns of bases and potential interactions between those bases to predict good and bad toeholds. The team used this model to create an optimization method called STORM (Sequence-based Toehold Optimization and Redesign Model), which allows for complete redesign of a toehold sequence from the ground up. This “blank slate” tool is optimal for generating novel toehold switches to perform a specific function as part of a synthetic genetic circuit, enabling the creation of complex biological tools.

    “The really cool part about STORM and the model underlying it is that after seeding it with input data from the first paper, we were able to fine-tune the model with only 168 samples and use the improved model to optimize toehold switches. That calls into question the prevailing assumption that you need to generate massive datasets every time you want to apply a machine learning algorithm to a new problem, and suggests that deep learning is potentially more applicable for synthetic biologists than we thought,” said co-first author Jackie Valeri, a graduate student at MIT and the Wyss Institute.

    3
    Work by Wyss core faculty member Peng Yin in collaboration with Collins and others has demonstrated that different toehold switches can be combined to compute the presence of multiple “triggers,” similar to a computer’s logic board. Credit: Wyss Institute at Harvard University.

    The second model is based on natural language processing (NLP), and treats each toehold sequence as a “phrase” consisting of patterns of “words,” eventually learning how certain words are put together to make a coherent phrase. “I like to think of each toehold switch as a haiku poem: like a haiku, it’s a very specific arrangement of phrases within its parent language – in this case, RNA. We are essentially training this model to learn how to write a good haiku by feeding it lots and lots of examples,” said co-first author Pradeep Ramesh, a visiting postdoctoral fellow at the Wyss Institute and Machine Learning Scientist at Sherlock Biosciences.

    Ramesh and his co-authors integrated this NLP-based model with the CNN-based model to create NuSpeak (Nucleic Acid Speech), an optimization approach that allowed them to redesign the last 9 nucleotides of a given toehold switch while keeping the remaining 21 nucleotides intact. This technique allows for the creation of toeholds that are designed to detect the presence of specific pathogenic RNA sequences, and could be used to develop new diagnostic tests.

    The team experimentally validated both of these platforms by optimizing toehold switches designed to sense fragments from the SARS-CoV-2 viral genome. NuSpeak improved the sensors’ performances by an average of 160 percent, while STORM created better versions of four “bad” SARS-CoV-2 viral RNA sensors whose performances improved by up to 28 times.

    “A real benefit of the STORM and NuSpeak platforms is that they enable you to rapidly design and optimize synthetic biology components, as we showed with the development of toehold sensors for a COVID-19 diagnostic,” said co-first author Katie Collins, an undergraduate MIT student at the Wyss Institute who worked with MIT Associate Professor Timothy Lu, a corresponding author of the second paper.

    “The data-driven approaches enabled by machine learning open the door to really valuable synergies between computer science and synthetic biology, and we’re just beginning to scratch the surface,” said Diogo Camacho, a corresponding author of the second paper who is a Senior Bioinformatics Scientist and co-lead of the Predictive BioAnalytics Initiative at the Wyss Institute. “Perhaps the most important aspect of the tools we developed in these papers is that they are generalizable to other types of RNA-based sequences such as inducible promoters and naturally occurring riboswitches, and therefore can be applied to a wide range of problems and opportunities in biotechnology and medicine.

    Additional authors of the papers include Wyss core faculty member and Professor of Genetics at HMS George Church; and Wyss and MIT graduate students Miguel Alcantar and Bianca Lepe.

    “Artificial intelligence is wave that is just beginning to impact science and industry, and has incredible potential for helping to solve intractable problems. The breakthroughs described in these studies demonstrate the power of melding computation with synthetic biology at the bench to develop new and more powerful bioinspired technologies, in addition to leading to new insights into fundamental mechanisms of biological control,” said Don Ingber, the Wyss Institute’s founding director. Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children’s Hospital, as well as professor of bioengineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences.

    This work was supported by the DARPA Synergistic Discovery and Design program, the Defense Threat Reduction Agency, the Paul G. Allen Frontiers Group, the Wyss Institute for Biologically Inspired Engineering, Harvard University, the Institute for Medical Engineering and Science, the Massachusetts Institute of Technology, the National Science Foundation, the National Human Genome Research Institute, the Department of Energy, the National Institutes of Health, and a CONACyT grant.

    See the full article here .

    five-ways-keep-your-child-safe-school-shootings

    Please help promote STEM in your local schools.

    Stem Education Coalition

    Harvard University campus
    Harvard University is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

     
  • richardmitnick 9:05 am on September 14, 2020 Permalink | Reply
    Tags: "A cool first for Harvard", , Harvard Gazette, ,   

    From Harvard Gazette: “A cool first for Harvard” 

    Harvard University

    From Harvard Gazette

    September 11, 2020
    Juan Siliezar

    1
    Working with lasers in the Doyle Lab. Credit: Kris Snibbe/Harvard file photo.

    By slowing polyatomic molecule, scientists open new paths of quantum study.

    After firing the lasers and bombarding the ultracold molecule with light, the scientists gathered around the camera to check the results. By seeing how far the molecule expanded they would know almost instantly whether they were on the right track to chart new paths in quantum science by being the first to cool — aka, slow down — a particularly complex, six-atom molecule using nothing but light.

    “When we started out on the project we were optimistic but were not sure that we would see something that would show a very dramatic effect,” said Debayan Mitra, a postdoctoral researcher in Harvard’s Doyle Research Group. “We thought that we would need more evidence to prove that we were actually cooling the molecule, but then when we saw the signal, it was like, ‘Yeah, nobody will doubt that.’ It was big and it was right there.”

    The study led by Mitra and graduate student Nathaniel B. Vilas is the focus of a new paper published in Science. In it, the group describes using a novel method combining cryogenic technology and direct laser light to cool the nonlinear polyatomic molecule calcium monomethoxide (CaOCH3) to just above absolute zero.

    The scientists believe their experiment marks the first time such a large complex molecule has been cooled using laser light, and say it opens new avenues of study in quantum simulation and computation, particle physics, and quantum chemistry.

    “These kinds of molecules have structure that is ubiquitous in chemical and biological systems,” said John M. Doyle, the Henry B. Silsbee Professor of Physics and senior author on the paper. “Controlling perfectly their quantum states is basic research that could shed light on fundamental quantum processes in these building blocks of nature.”

    2
    Inside the lab of John Doyle (pictured), Harvard researchers were the first to cool a polyatomic molecule using light. Credit: Kris Snibbe/Harvard file photo.

    The use of lasers to control and atoms and molecules — the eventual building blocks of quantum computers — has been practiced since the 1960s and has since revolutionized atomic, molecular, and optical physics.

    The technique essentially works by firing a laser at the atoms and molecules, causing them to absorb the photons from the light and recoil in the opposite direction. This eventually slows them down and even stops them in their tracks. When this happens, quantum mechanics becomes the dominant way to describe and study their motions.

    “The idea is that on one end of the spectrum there are atoms that have very few quantum states,” Doyle said. Because of this, these atoms are easy to control with light, since they often remain in the same quantum state after absorbing and emitting light, he said. “With molecules, they have motion that does not occur in atoms — vibrations and rotations. When the molecule absorbs and emits light this process can sometimes make the molecule spin around or vibrate internally. When this happens, it is now in a different quantum state and absorbing and emitting light no longer works [to cool it]. We have to ‘calm the molecule down,’ get rid of its extra vibration before it can interact with the light the way we want.”

    Scientists — including those from the Doyle Group which is part of the Harvard Department of Physics and a member of the Harvard-MIT Center for Ultracold Atoms — have been able to cool a number of molecules using light, including diatomic and triatomic molecules, which each have two or three atoms.

    Polyatomic molecules, on the other hand, are much more complex and have proven much harder to manipulate because of all the vibrations and rotations.

    Scientists — including those from the Doyle Group which is part of the Harvard Department of Physics and a member of the Harvard-MIT Center for Ultracold Atoms — have been able to cool a number of molecules using light, including diatomic and triatomic molecules, which each have two or three atoms.

    Polyatomic molecules, on the other hand, are much more complex and have proven much harder to manipulate because of all the vibrations and rotations.

    To get around this, the group used a method they pioneered to cool diatomic and triatomic molecules. Researchers set up a sealed cryogenic chamber where they cooled helium to below four Kelvin (nearly 450 degrees below zero Fahrenheit). This chamber essentially acts as a refrigerator, in which the scientists created the molecule CaOCH3. Right off the bat, it began moving at a much slower velocity than it would normally, making it ideal for further cooling.

    Next came the lasers. They turned on two beams of light on the molecule, coming from opposing directions. The counterpropagating lasers prompted a reaction known as Sisyphus cooling. The reaction takes its name from the myth of Sisyphus, a Greek king who angered Zeus and was doomed to roll a giant boulder up a hill for eternity, only for it to roll back down when he nears the top.

    Essentially the same thing happens here with the molecule, Mitra said. When two identical laser beams are firing in opposite directions, they form a standing wave of light, stronger in some places and less intense in others. This wave forms a metaphorical hill for the molecule.

    The molecule “starts at the bottom of a hill formed by the counter-propagating laser beams, and it starts climbing that hill just because it has some kinetic energy in it and as it climbs that hill, slowly, the kinetic energy that was its velocity gets converted into potential energy and it slows down and slows down and slows down until it gets to the top of the hill where it’s the slowest,” Mitra said.

    At that point, the molecule moves closer to a region where the light intensity is high and the molecule is more likely absorb a photon that causes it to roll back down to the opposite side. “All [it] can do is keep doing this again and again and again,” Mitra said.

    By looking at images from cameras placed outside the sealed chamber, the scientists inspect how much a cloud of these molecules expands as it travels through the system. The narrower the cloud, the less kinetic energy it has — and therefore the colder it is.

    Analyzing the data further, the researchers saw just how cold. They took it from 22 millikelvin to about 1 millikelvin — just a few thousandths of a decimal point above absolute zero.

    The paper lays out ways to get the molecule even colder, and discusses some of the pathways that opens in a range of physical and chemical research frontiers. The scientists said the study is proof of concept that their method could be used to cool other carefully chosen complex molecules to advance quantum science.

    “What we did here is sort of extending the state of the art,” Mitra said. “It’s always been debated whether we would ever have technology that will be good enough to control complex molecules at the quantum level. This particular experiment is just a stepping stone.”

    This research was supported with funding from the National Science Foundation.

    See the full article here.

    five-ways-keep-your-child-safe-school-shootings

    Please help promote STEM in your local schools.

    Stem Education Coalition

    Harvard University campus
    Harvard University is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

     
  • richardmitnick 10:11 am on September 8, 2020 Permalink | Reply
    Tags: "Gesundheit" … to a star? Did Betelgeuse sneeze?, , , , , , Harvard Gazette, Posibility of a companion star to the Sun., The ‘Oumuamua debate continues.   

    From Harvard Gazette: “Far-out findings from the cosmos” 

    Harvard University

    From Harvard Gazette

    September 4, 2020
    Juan Siliezar

    1
    Artist’s conception of a potential solar companion, which theorists believe was developed in the sun’s birth cluster and later lost.
    Illustration by M. Weiss.

    Harvard astronomers research twin suns, a sneezing star, and ‘Oumuamua.

    It was a busy summer for scientists at the Center for Astrophysics | Harvard & Smithsonian.

    Researchers put forth a theory that indirectly nods to a famous Star Wars scene, resolved one mystery about the solar system’s first known interstellar visitor, and showed that a star can sort of “sneeze.” We caught up with them and asked about these far-out findings.

    A long time ago but not so far, far away

    It was an unforgettable scene in the first Star Wars movie: Young Luke, eager for adventure, storms out his house after fighting with his uncle about having to spend another year stuck at home. Outside he gazes up at the fiery twin suns of the planet Tatooine as they slide toward the horizon, John Williams’ The Force Theme rising in the background.

    While a new study from a pair of Harvard astronomers may not have the same visual power, it does reveal that a similar view of binary suns may have existed in our very own solar system roughly 4 billion years ago.

    In The Astrophysical Journal Letters, Avi Loeb, Frank B. Baird Jr. Professor of Science at Harvard, and Amir Siraj ’21, an astrophysics concentrator, theorize that the solar system originally had two suns instead of one, and if true that could have far-reaching implications for the origins of a dense cloud that surrounds the system and a possible ninth planet.

    First, a little info on the sun’s long-lost twin: Loeb and Siraj think it had the same mass as its companion and was formed alongside it when the solar system began, but was situated 1,000 times farther from the Earth than our own sun. As to its fate, the two researchers believe it drifted away well before the Earth formed.

    “The binary companion was [most likely] freed by the gravitational influence of a passing star in the sun’s dense birth environment,” Siraj said. “It could now be anywhere in the Milky Way galaxy.”

    Siraj and Loeb aren’t the first to theorize a two-star start to the solar system. In fact, most stars are born with companions. But Siraj and Loeb’s theory could help explain the formation of the Oort cloud — the sprawling sphere of debris that sits at the edge of the system and surrounds it.

    Many astronomers believe the Oort cloud formed with leftover chunks of rock and ice from our solar system and neighboring ones.

    Oort Cloud, The layout of the solar system, including the Oort Cloud, on a logarithmic scale. Credit: NASA, Universe Today.

    Siraj and Loeb say their two-sun theory could account for why the cloud is as dense as it is, since binary systems are far better at pulling in and capturing these types of objects than single-star systems.

    Such a system could also help explain the existence of a potential ninth planet that astronomers believe is out there — an undisputed one this time (no offense, Pluto). Their model supports the theory that this ninth planet was captured into the system, meaning it didn’t form here.

    2
    An artist’s rendering of ‘Oumuamua, a visitor from outside the solar system. Credit: The international Gemini Observatory/NOIRLab/NSF/AURA artwork by J. Pollard.

    The ‘Oumuamua debate continues

    The mystery surrounding our solar system’s first known interstellar visitor deepened after astronomers ruled out a major explanation in a new paper in The Astrophysical Journal Letters.

    The study rebuts a theory published earlier this year that suggests the object, dubbed ‘Oumuamua from the Hawaiian for scout, was a cosmic iceberg made of frozen hydrogen. Co-authored by Loeb, the paper concluded this is likely not the case because, if it was, the object wouldn’t have been able to make the journey intact. The scientists argue it would quickly melt or break apart when it passed close to a star. ‘Oumuamua didn’t even flinch when it passed the sun.

    The astronomers also looked at what it would take to form a hydrogen iceberg the size of ‘Oumuamua, and where it could have originated. They focused on one of the closest giant molecular clouds to Earth (only 17,000 light-years away). They found the environment there too inhospitable for iceberg formation — and so far away that it would be highly unlikely that it could have survived the journey, even if it somehow managed to form.

    The debate around ‘Oumuamua started in 2017, when it was first discovered by observers at the Haleakalā Observatory on the island of Maui in Hawaii. Among other theories, it has been hypothesized to be an interstellar asteroid, a comet, and even an alien artifact — Loeb himself suggested this in 2018 and has put out a body of work on the topic. He has a book on ‘Oumuamua, Extraterrestrial, due out early next year.

    All of this is to say that the truth on ‘Oumuamua is still out there, but perhaps it won’t be a mystery for long.

    “If ‘Oumuamua is a member of a population of similar objects on random trajectories, then the [new] Vera Rubin Observatory, which is scheduled to [be operational] next year, should detect roughly one ‘Oumuamua-like object per month,” Loeb said.

    Vera C. Rubin Observatory Telescope currently under construction on the El Peñón peak at Cerro Pachón Chile, a 2,682-meter-high mountain in Coquimbo Region, in northern Chile, alongside the existing Gemini South and Southern Astrophysical Research Telescopes, altitude 2,715 m (8,907 ft).

    “We will all wait with anticipation to see what it will find.”

    Gesundheit … to a star?

    3
    In the first two panels a bright, hot blob of plasma is ejected from the emergence of a huge convection cell on Betelgeuse’s surface. In panel three, gas rapidly expands outward, cooling to form an enormous cloud of obscuring dust grains. The final panel reveals the huge dust cloud blocking the light (as seen from Earth) from a quarter of the star’s surface. Credit: NASA, ESA, and E. Wheatley (STScI).

    This is the explanation a team of international astronomers led by Andrea Dupree, the CfA’s associate director, published in a paper in The Astrophysical Journal.

    Looking at recent observation data, researchers believe the dimming periods were most likely caused by the ejection and cooling of dense, hot gases. Between October and November 2019, data and images gathered by the Hubble Space Telescope showed intense, heated material moving out of the star’s extended atmosphere at 200,000 miles per hour. They believe this mass formed a soot-like dust cloud when it cooled that blocked the southern part of the star, accounting for its dimming in January and February.

    While researchers think they can account partially for the anomaly, they have other questions. They can’t, for example, determine how the outburst started or why, nor do they know why the star is losing mass at an exceedingly high rate.

    What they do know is that Betelgeuse dims every 420 days. But new observations between late June and early August of this year show it’s off schedule. The star is dimming roughly 300 days earlier than expected. Yet another new mystery.

    Researchers also believe Betelgeuse is nearing the end of its life and eventually will go supernova. In fact, it might have happened already, and we just haven’t seen it yet.

    “Betelgeuse is so far away, it takes about 750 years for the light to reach us on Earth,” Dupree said. “So, the light from Betelgeuse [we saw] left the star at about 1270 A.D. here on Earth.”

    See the full article here .

    five-ways-keep-your-child-safe-school-shootings

    Please help promote STEM in your local schools.

    Stem Education Coalition

    Harvard University campus
    Harvard University is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

     
  • richardmitnick 9:54 am on June 8, 2020 Permalink | Reply
    Tags: "A promise to a friend", , Harvard Gazette, In a first, researchers use base editing to correct recessive genetic deafness and restore partial hearing.   

    From Harvard Gazette: “A promise to a friend” 

    Harvard University

    From Harvard Gazette

    June 5, 2020
    Caitlin McDermott-Murphy

    1
    In a first, researchers use base editing to correct recessive genetic deafness and restore partial hearing.

    When Wei Hsi “Ariel” Yeh was an undergraduate, one of her close friends went from normal hearing to complete deafness in one month. He was 29 years old. Doctors didn’t know why then and still don’t. Frustrated and fearful for her friend, Yeh, who graduated last month with a Ph.D. from the Graduate School of Arts and Sciences, dedicated her research in chemistry to solving some of the vast genetic mysteries behind hearing loss.

    One in eight people aged 12 years or older in the U.S. has hearing loss in both ears. Technologies like hearing aids and cochlear implants can amplify sound but can’t correct the problem. Perhaps gene editing could, scientists decided, since genetic anomalies contribute to half of all cases.

    2
    David Liu is conducting research with Wei Hsi “Ariel” Yeh on gene editing. Credit: Stephanie Mitchell/Havard file photo

    Two years ago, Yeh and David R. Liu, Thomas Dudley Cabot Professor of the Natural Sciences and a member of the Broad Institute and the Howard Hughes Medical Institute (HHMI), repaired a dominant mutation and prevented hearing loss in a mouse model for the first time. But, Liu said, “Most genetic diseases are not caused by dominant mutations. They’re caused by recessive ones, including most genetic hearing losses.”

    Now, Liu, Yeh, and researchers at Harvard, the Broad, and HHMI have achieved another first: They restored partial hearing to mice with a recessive mutation in the gene TMC1 that causes complete deafness, the first successful example of genome editing to fix a recessive disease-causing mutation.

    Dominant disease mutations, meaning those that affect just one of the body’s two copies of a gene, in some ways are easier to attack. Knock out the bad copy, and the good one can come to the rescue. “But for recessive diseases,” Liu said, “you can’t do that. By definition, the recessive allele means that you have two bad copies. So, you can’t just destroy the bad copy.” You have to fix one or both.

    To hear, animals rely on hair cells in the inner ear, which ripple under the pressure of sound waves and send electrical impulses to the brain. The recessive mutation to TMC1 that Liu and Yeh hoped to correct causes rapid deterioration of those hair cells, leading to profound deafness in mice at just 4 weeks of age.

    Jeffrey Holt, professor of otolaryngology and neurology at the Harvard Medical School and an author of the paper [Nature Communications], successfully treated TMC1-related deafness with gene therapy by situating cells with healthy versions of the gene among the unhealthy to counteract the disease-causing mutation. But Volha “Olga” Shubina-Aleinik, a postdoctoral fellow in the Holt lab, said gene therapy may have a limited duration. “That is why we need more advanced techniques, such as gene editing, which may last a lifetime.”

    Yeh spent years designing a base editor that could find and erase the disease-causing mutation and replace it with the correct DNA code. But even after she demonstrated good results in vitro, there was a problem: Base editors are too large to fit in the traditional delivery vehicle, adeno-associated virus, or AAV. To solve this problem, the team split the base editor in half, sending each piece in with its own viral vehicle. Once inside, both viruses needed to infect the same cells so the two base editor halves could rejoin and head off to find their target. Despite the labyrinthine entry, the editor proved to be efficient, causing only a minimum of undesired deletions or insertions.

    “We saw very little evidence of off-target editing,” Liu said. “And we noticed that the edited animals had much-preserved hair-cell morphology and signal transduction, meaning the hair cells, the critical cells that convert sound waves to neuronal signals, appeared more normal and behaved more normally.”

    After the treatment, Yeh performed an informal test: She clapped her hands. Mice that had previously lost all hearing ability jumped and turned to look. Formal tests revealed the base editor worked, at least in part: Treated mice had partially restored hearing and could respond to loud and even some medium sounds, Yeh said.

    Of course, more work needs to be done before the treatment can be used in humans. Unedited cells continued to die, causing deafness to return even after the base editor restored function to others.

    But the study also proved that the clandestine AAV delivery method works. Already, Liu is using AAV to tackle other genetic diseases, including progeria (premature aging), sickle cell anemia, and degenerative motor diseases. “We’re actually going after quite a few genetic diseases now, including some prominent ones that have caused a lot of suffering and energized pretty passionate communities of patients and patient families to do anything to find a treatment,” Liu said. “For progeria, there’s no cure. The best treatments extend a child’s average lifespan from about 14 to 14.5 years.”

    For Yeh, whose friend is still living with hearing loss, genetic deafness remains her primary target. “There’s still a lot to explore,” she said. “There’s so much unknown.”

    See the full article here .

    five-ways-keep-your-child-safe-school-shootings

    Please help promote STEM in your local schools.

    Stem Education Coalition

    Harvard University campus
    Harvard University is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

     
  • richardmitnick 9:10 am on June 3, 2020 Permalink | Reply
    Tags: "Filling gaps in our understanding of how cities began to rise", A lone corpse found buried in a well was genetically linked to people who then lived in Central Asia not in part of present-day Turkey., Around 4000 years ago the Northern Levant experienced a relatively sudden introduction of new people., , Harvard Gazette, Insights DNA analysis can provide when traditional clues don’t tell the full story., , The corpse had many injuries and the way she was buried indicated a violent death., The earliest genetic glimpses of the movement and mingling of peoples in West Asia 8500 years ago., The genetic shifts point to a mass migration. The timing corresponds with a severe drought in Northern Mesopotamia which likely resulted in an exodus to the Northern Levant.   

    From Harvard Gazette: “Filling gaps in our understanding of how cities began to rise” 

    Harvard University

    From Harvard Gazette

    May 29, 2020
    Juan Siliezar

    1
    A wall painting from the Arslantepe archaeological site in Eastern Anatolia (present-day Turkey) around 3,400 BC. Image courtesy of Max Planck-Harvard Research Center for the Archaeoscience of the Ancient Mediterranean and Missione Archeologica Italiana nell’Anatolia Orientale, Sapienza University of Rome. Photo by Roberto Ceccaci

    International team provides some of the earliest genetic glimpses of the movement and mingling of peoples in West Asia 8,500 years ago.

    New genetic research from around one of the ancient world’s most important trading hubs offers fresh insights into the movement and interactions of inhabitants of different areas of Western Asia between two major events in human history: the origins of agriculture and the rise of some of the world’s first cities.

    The evidence [Cell] reveals that a high level of mobility led to the spread of ideas and material culture as well as intermingling of peoples in the period before the rise of cities, not the other way around, as previously thought. The findings add to our understanding of exactly how the shift to urbanism took place.

    The researchers, made up of an international team of scientists including Harvard Professor Christina Warinner, looked at DNA data from 110 skeletal remains in West Asia from the Neolithic to the Bronze Age, 3,000 to 7,500 years ago. The remains came from archaeological sites in the Anatolia (present-day Turkey); the Northern Levant, which includes countries on the Mediterranean coast such as Israel and Jordan; and countries in the Southern Caucasus, which include present-day Armenia and Azerbaijan.

    Based on their analysis, the scientists describe two events, one around 8,500 years ago and the other 4,000 years ago, that point to long-term genetic mixing and gradual population movements in the region.

    “Within this geographic scope, you have a number of distinct populations, distinct ideological groups that are interacting quite a lot, and it hasn’t really been clear to what degree people are actually moving or if this is simply just a high-contact area from trade,” said Warinner, assistant professor of anthropology in the Faculty of Arts and Sciences and the Sally Starling Seaver Assistant Professor at the Radcliffe Institute for Advanced Study. “Rather than this period being characterized by dramatic migrations or conquest, what we see is the slow mixing of different populations, the slow mixing of ideas, and it’s percolating out of this melting pot that we see the rise of urbanism — the rise of cities.”

    The study was led by the Max Planck-Harvard Research Center for the Archaeoscience of the Ancient Mediterranean and published in the journal Cell [above]. Warinner was a senior author on the paper.

    Historically, Western Asia, which includes today’s Middle East, is one of civilization’s most important geographical locations. Not only did it create some of humanity’s earliest cities, but its early trade routes laid the foundation for what would become the Silk Road, a route that commercially linked Asia, Africa, and Europe.

    Even before they connected with other regions, however, populations across Western Asia had already developed their own distinct traditions and systems of social organization. The areas studied in this paper played major roles in the evolution from farming to pastoral communities to early state-level societies.

    With the study, the researchers wanted to fill in some of the anthropological gaps between the origins of agriculture and of cities to get a better grip on how these different communities came together, a dynamic that is still not understood well.

    “What we see in archaeology is that the interconnectivity within Western Asia increased and areas such as Anatolia, the Northern Levant, and the Caucasus became a hub for [the] exchange of ideas and material culture,” said Eirini Skourtanioti, a Ph.D. student at the Max Planck Institute and the lead author of the study, in a video accompanying the release of the paper. “The goal of our study was to understand the role of human mobility throughout this process.”

    The authors came from many disciplines and countries, including Australia, Azerbaijan, France, Italy, Germany, South Korea, Turkey, and the U.S. They gathered 110 ancient remains from museums and labs around the world, and took samples from teeth and part of the temporal bone called the petrous, which houses the inner ear. The genetic analysis was conducted by scientists at the Max Planck Institute, including Warinner.

    The paper outlines how populations across Anatolia and the Southern Caucasus began mixing approximately 8,500 years ago. That resulted in a gradual change in genetic profile that over a millennium slowly spread across both areas and entered into what is now Northern Iraq. Known as a cline in genetics, this mixture indicated to the researchers ongoing human mobility in the area and the development of a regional genetic melting pot in and surrounding Anatolia.

    The other shift researchers detected wasn’t as gradual. They looked at samples from the ancient cities of Alalakh and Ebla in what is today Southern Turkey and Northern Syria, and saw that around 4,000 years ago the Northern Levant experienced a relatively sudden introduction of new people.

    The genetic shifts point to a mass migration. The timing corresponds with a severe drought in Northern Mesopotamia, which likely resulted in an exodus to the Northern Levant. The scientists can’t be sure, because they have no well-preserved genomes for people who lived in Mesopotamia.

    Along with findings on interconnectivity in the region, the paper presents new information about long-distance migration during the late Bronze Age, roughly 4,000 years ago. A lone corpse, found buried in a well, was genetically linked to people who then lived in Central Asia, not in part of present-day Turkey.

    “We can’t exactly know her story, but we can piece together a lot of information that suggests that either she or her ancestors were fairly recent migrants from Central Asia,” said Warinner, who is also a group leader in the Department of Archaeogenetics at the Max Planck Institute. “We don’t know the context in which they arrived in the Eastern Mediterranean, but this is a period of increasing connectivity in this part of the world.”

    The corpse had many injuries and the way she was buried indicated a violent death. Warinner hopes more genomic analysis can help unravel the ancient woman’s story.

    For Warinner, who earned her master’s in 2008 and her Ph.D. in 2010 from the Graduate School of Arts and Sciences, such studies are proof of the insights DNA analysis can provide when traditional clues don’t tell the full story.

    “What’s really interesting is that we see these populations are mixing genetically long before we see clear material culture evidence of this — so long before we see direct evidence in pottery or tools or any of these more conventional archaeological evidence artifacts,” Warinner said. “That’s important because sometimes we’re limited in how we see the past. We see the past through artifacts, through the evidence people leave behind. But sometimes events are happening that don’t leave traces in conventional ways, so by using genetics, we were able to access this much earlier mixing of populations that wasn’t apparent before.”

    This study was funded by the Max Planck Society and the Max Planck-Harvard Research Center for the Archaeoscience of the Ancient Mediterranean.

    See the full article here .

    five-ways-keep-your-child-safe-school-shootings

    Please help promote STEM in your local schools.

    Stem Education Coalition

    Harvard University campus
    Harvard University is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

     
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