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      Estimating the informativeness of data

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      Not all data are created equal. But how much information is any piece of data likely to contain? This question is central to medical testing, designing scientific experiments, and even to everyday human learning and thinking. MIT researchers have developed a new way to solve this problem, opening up new applications in medicine, scientific discovery, cognitive science, and artificial intelligence.

      In theory, the 1948 paper, “A Mathematical Theory of Communication,” by the late MIT Professor Emeritus Claude Shannon answered this question definitively. One of Shannon’s breakthrough results is the idea of entropy, which lets us quantify the amount of information inherent in any random object, including random variables that model observed data. Shannon’s results created the foundations of information theory and modern telecommunications. The concept of entropy has also proven central to computer science and machine learning.

      The challenge of estimating entropy

      Unfortunately, the use of Shannon’s formula can quickly become computationally intractable. It requires precisely calculating the probability of the data, which in turn requires calculating every possible way the data could have arisen under a probabilistic model. If the data-generating process is very simple — for example, a single toss of a coin or roll of a loaded die — then calculating entropies is straightforward. But consider the problem of medical testing, where a positive test result is the result of hundreds of interacting variables, all unknown. With just 10 unknowns, there are already 1,000 possible explanations for the data. With a few hundred, there are more possible explanations than atoms in the known universe, which makes calculating the entropy exactly an unmanageable problem.

      MIT researchers have developed a new method to estimate good approximations to many information quantities such as Shannon entropy by using probabilistic inference. The work appears in a paper presented at AISTATS 2022 by authors Feras Saad ’16, MEng ’16, a PhD candidate in electrical engineering and computer science; Marco-Cusumano Towner PhD ’21; and Vikash Mansinghka ’05, MEng ’09, PhD ’09, a principal research scientist in the Department of Brain and Cognitive Sciences. The key insight is, rather than enumerate all explanations, to instead use probabilistic inference algorithms to first infer which explanations are probable and then use these probable explanations to construct high-quality entropy estimates. The paper shows that this inference-based approach can be much faster and more accurate than previous approaches.

      Estimating entropy and information in a probabilistic model is fundamentally hard because it often requires solving a high-dimensional integration problem. Many previous works have developed estimators of these quantities for certain special cases, but the new estimators of entropy via inference (EEVI) offer the first approach that can deliver sharp upper and lower bounds on a broad set of information-theoretic quantities. An upper and lower bound means that although we don’t know the true entropy, we can get a number that is smaller than it and a number that is higher than it.

      “The upper and lower bounds on entropy delivered by our method are particularly useful for three reasons,” says Saad. “First, the difference between the upper and lower bounds gives a quantitative sense of how confident we should be about the estimates. Second, by using more computational effort we can drive the difference between the two bounds to zero, which ‘squeezes’ the true value with a high degree of accuracy. Third, we can compose these bounds to form estimates of many other quantities that tell us how informative different variables in a model are of one another.”

      Solving fundamental problems with data-driven expert systems

      Saad says he is most excited about the possibility that this method gives for querying probabilistic models in areas like machine-assisted medical diagnoses. He says one goal of the EEVI method is to be able to solve new queries using rich generative models for things like liver disease and diabetes that have already been developed by experts in the medical domain. For example, suppose we have a patient with a set of observed attributes (height, weight, age, etc.) and observed symptoms (nausea, blood pressure, etc.). Given these attributes and symptoms, EEVI can be used to help determine which medical tests for symptoms the physician should conduct to maximize information about the absence or presence of a given liver disease (like cirrhosis or primary biliary cholangitis).

      For insulin diagnosis, the authors showed how to use the method for computing optimal times to take blood glucose measurements that maximize information about a patient’s insulin sensitivity, given an expert-built probabilistic model of insulin metabolism and the patient’s personalized meal and medication schedule. As routine medical tracking like glucose monitoring moves away from doctor’s offices and toward wearable devices, there are even more opportunities to improve data acquisition, if the value of the data can be estimated accurately in advance.

      Vikash Mansinghka, senior author on the paper, adds, “We’ve shown that probabilistic inference algorithms can be used to estimate rigorous bounds on information measures that AI engineers often think of as intractable to calculate. This opens up many new applications. It also shows that inference may be more computationally fundamental than we thought. It also helps to explain how human minds might be able to estimate the value of information so pervasively, as a central building block of everyday cognition, and help us engineer AI expert systems that have these capabilities.”

      The paper, “Estimators of Entropy and Information via Inference in Probabilistic Models,” was presented at AISTATS 2022. More

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      Looking forward to forecast the risks of a changing climate

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      On April 11, MIT announced five multiyear flagship projects in the first-ever Climate Grand Challenges, a new initiative to tackle complex climate problems and deliver breakthrough solutions to the world as quickly as possible. This article is the third in a five-part series highlighting the most promising concepts to emerge from the competition, and the interdisciplinary research teams behind them.

      Extreme weather events that were once considered rare have become noticeably less so, from intensifying hurricane activity in the North Atlantic to wildfires generating massive clouds of ozone-damaging smoke. But current climate models are unprepared when it comes to estimating the risk that these increasingly extreme events pose — and without adequate modeling, governments are left unable to take necessary precautions to protect their communities.

      MIT Department of Earth, Atmospheric and Planetary Science (EAPS) Professor Paul O’Gorman researches this trend by studying how climate affects the atmosphere and incorporating what he learns into climate models to improve their accuracy. One particular focus for O’Gorman has been changes in extreme precipitation and midlatitude storms that hit areas like New England.

      “These extreme events are having a lot of impact, but they’re also difficult to model or study,” he says. Seeing the pressing need for better climate models that can be used to develop preparedness plans and climate change mitigation strategies, O’Gorman and collaborators Kerry Emanuel, the Cecil and Ida Green Professor of Atmospheric Science in EAPS, and Miho Mazereeuw, associate professor in MIT’s Department of Architecture, are leading an interdisciplinary group of scientists, engineers, and designers to tackle this problem with their MIT Climate Grand Challenges flagship project, “Preparing for a new world of weather and climate extremes.”

      “We know already from observations and from climate model predictions that weather and climate extremes are changing and will change more,” O’Gorman says. “The grand challenge is preparing for those changing extremes.”

      Their proposal is one of five flagship projects recently announced by the MIT Climate Grand Challenges initiative — an Institute-wide effort catalyzing novel research and engineering innovations to address the climate crisis. Selected from a field of almost 100 submissions, the team will receive additional funding and exposure to help accelerate and scale their project goals. Other MIT collaborators on the proposal include researchers from the School of Engineering, the School of Architecture and Planning, the Office of Sustainability, the Center for Global Change Science, and the Institute for Data, Systems and Society.

      Weather risk modeling

      Fifteen years ago, Kerry Emanuel developed a simple hurricane model. It was based on physics equations, rather than statistics, and could run in real time, making it useful for modeling risk assessment. Emanuel wondered if similar models could be used for long-term risk assessment of other things, such as changes in extreme weather because of climate change.

      “I discovered, somewhat to my surprise and dismay, that almost all extant estimates of long-term weather risks in the United States are based not on physical models, but on historical statistics of the hazards,” says Emanuel. “The problem with relying on historical records is that they’re too short; while they can help estimate common events, they don’t contain enough information to make predictions for more rare events.”

      Another limitation of weather risk models which rely heavily on statistics: They have a built-in assumption that the climate is static.

      “Historical records rely on the climate at the time they were recorded; they can’t say anything about how hurricanes grow in a warmer climate,” says Emanuel. The models rely on fixed relationships between events; they assume that hurricane activity will stay the same, even while science is showing that warmer temperatures will most likely push typical hurricane activity beyond the tropics and into a much wider band of latitudes.

      As a flagship project, the goal is to eliminate this reliance on the historical record by emphasizing physical principles (e.g., the laws of thermodynamics and fluid mechanics) in next-generation models. The downside to this is that there are many variables that have to be included. Not only are there planetary-scale systems to consider, such as the global circulation of the atmosphere, but there are also small-scale, extremely localized events, like thunderstorms, that influence predictive outcomes.

      Trying to compute all of these at once is costly and time-consuming — and the results often can’t tell you the risk in a specific location. But there is a way to correct for this: “What’s done is to use a global model, and then use a method called downscaling, which tries to infer what would happen on very small scales that aren’t properly resolved by the global model,” explains O’Gorman. The team hopes to improve downscaling techniques so that they can be used to calculate the risk of very rare but impactful weather events.

      Global climate models, or general circulation models (GCMs), Emanuel explains, are constructed a bit like a jungle gym. Like the playground bars, the Earth is sectioned in an interconnected three-dimensional framework — only it’s divided 100 to 200 square kilometers at a time. Each node comprises a set of computations for characteristics like wind, rainfall, atmospheric pressure, and temperature within its bounds; the outputs of each node are connected to its neighbor. This framework is useful for creating a big picture idea of Earth’s climate system, but if you tried to zoom in on a specific location — like, say, to see what’s happening in Miami or Mumbai — the connecting nodes are too far apart to make predictions on anything specific to those areas.

      Scientists work around this problem by using downscaling. They use the same blueprint of the jungle gym, but within the nodes they weave a mesh of smaller features, incorporating equations for things like topography and vegetation or regional meteorological models to fill in the blanks. By creating a finer mesh over smaller areas they can predict local effects without needing to run the entire global model.

      Of course, even this finer-resolution solution has its trade-offs. While we might be able to gain a clearer picture of what’s happening in a specific region by nesting models within models, it can still make for a computing challenge to crunch all that data at once, with the trade-off being expense and time, or predictions that are limited to shorter windows of duration — where GCMs can be run considering decades or centuries, a particularly complex local model may be restricted to predictions on timescales of just a few years at a time.

      “I’m afraid that most of the downscaling at present is brute force, but I think there’s room to do it in better ways,” says Emanuel, who sees the problem of finding new and novel methods of achieving this goal as an intellectual challenge. “I hope that through the Grand Challenges project we might be able to get students, postdocs, and others interested in doing this in a very creative way.”

      Adapting to weather extremes for cities and renewable energy

      Improving climate modeling is more than a scientific exercise in creativity, however. There’s a very real application for models that can accurately forecast risk in localized regions.

      Another problem is that progress in climate modeling has not kept up with the need for climate mitigation plans, especially in some of the most vulnerable communities around the globe.

      “It is critical for stakeholders to have access to this data for their own decision-making process. Every community is composed of a diverse population with diverse needs, and each locality is affected by extreme weather events in unique ways,” says Mazereeuw, the director of the MIT Urban Risk Lab. 

      A key piece of the team’s project is building on partnerships the Urban Risk Lab has developed with several cities to test their models once they have a usable product up and running. The cities were selected based on their vulnerability to increasing extreme weather events, such as tropical cyclones in Broward County, Florida, and Toa Baja, Puerto Rico, and extratropical storms in Boston, Massachusetts, and Cape Town, South Africa.

      In their proposal, the team outlines a variety of deliverables that the cities can ultimately use in their climate change preparations, with ideas such as online interactive platforms and workshops with stakeholders — such as local governments, developers, nonprofits, and residents — to learn directly what specific tools they need for their local communities. By doing so, they can craft plans addressing different scenarios in their region, involving events such as sea-level rise or heat waves, while also providing information and means of developing adaptation strategies for infrastructure under these conditions that will be the most effective and efficient for them.

      “We are acutely aware of the inequity of resources both in mitigating impacts and recovering from disasters. Working with diverse communities through workshops allows us to engage a lot of people, listen, discuss, and collaboratively design solutions,” says Mazereeuw.

      By the end of five years, the team is hoping that they’ll have better risk assessment and preparedness tool kits, not just for the cities that they’re partnering with, but for others as well.

      “MIT is well-positioned to make progress in this area,” says O’Gorman, “and I think it’s an important problem where we can make a difference.” More

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      Computing our climate future

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      On Monday, MIT announced five multiyear flagship projects in the first-ever Climate Grand Challenges, a new initiative to tackle complex climate problems and deliver breakthrough solutions to the world as quickly as possible. This article is the first in a five-part series highlighting the most promising concepts to emerge from the competition, and the interdisciplinary research teams behind them.

      With improvements to computer processing power and an increased understanding of the physical equations governing the Earth’s climate, scientists are continually working to refine climate models and improve their predictive power. But the tools they’re refining were originally conceived decades ago with only scientists in mind. When it comes to developing tangible climate action plans, these models remain inscrutable to the policymakers, public safety officials, civil engineers, and community organizers who need their predictive insight most.

      “What you end up having is a gap between what’s typically used in practice, and the real cutting-edge science,” says Noelle Selin, a professor in the Institute for Data, Systems and Society and the Department of Earth, Atmospheric and Planetary Sciences (EAPS), and co-lead with Professor Raffaele Ferrari on the MIT Climate Grand Challenges flagship project “Bringing Computation to the Climate Crisis.” “How can we use new computational techniques, new understandings, new ways of thinking about modeling, to really bridge that gap between state-of-the-art scientific advances and modeling, and people who are actually needing to use these models?”

      Using this as a driving question, the team won’t just be trying to refine current climate models, they’re building a new one from the ground up.

      This kind of game-changing advancement is exactly what the MIT Climate Grand Challenges is looking for, which is why the proposal has been named one of the five flagship projects in the ambitious Institute-wide program aimed at tackling the climate crisis. The proposal, which was selected from 100 submissions and was among 27 finalists, will receive additional funding and support to further their goal of reimagining the climate modeling system. It also brings together contributors from across the Institute, including the MIT Schwarzman College of Computing, the School of Engineering, and the Sloan School of Management.

      When it comes to pursuing high-impact climate solutions that communities around the world can use, “it’s great to do it at MIT,” says Ferrari, EAPS Cecil and Ida Green Professor of Oceanography. “You’re not going to find many places in the world where you have the cutting-edge climate science, the cutting-edge computer science, and the cutting-edge policy science experts that we need to work together.”

      The climate model of the future

      The proposal builds on work that Ferrari began three years ago as part of a joint project with Caltech, the Naval Postgraduate School, and NASA’s Jet Propulsion Lab. Called the Climate Modeling Alliance (CliMA), the consortium of scientists, engineers, and applied mathematicians is constructing a climate model capable of more accurately projecting future changes in critical variables, such as clouds in the atmosphere and turbulence in the ocean, with uncertainties at least half the size of those in existing models.

      To do this, however, requires a new approach. For one thing, current models are too coarse in resolution — at the 100-to-200-kilometer scale — to resolve small-scale processes like cloud cover, rainfall, and sea ice extent. But also, explains Ferrari, part of this limitation in resolution is due to the fundamental architecture of the models themselves. The languages most global climate models are coded in were first created back in the 1960s and ’70s, largely by scientists for scientists. Since then, advances in computing driven by the corporate world and computer gaming have given rise to dynamic new computer languages, powerful graphics processing units, and machine learning.

      For climate models to take full advantage of these advancements, there’s only one option: starting over with a modern, more flexible language. Written in Julia, a part of Julialab’s Scientific Machine Learning technology, and spearheaded by Alan Edelman, a professor of applied mathematics in MIT’s Department of Mathematics, CliMA will be able to harness far more data than the current models can handle.

      “It’s been real fun finally working with people in computer science here at MIT,” Ferrari says. “Before it was impossible, because traditional climate models are in a language their students can’t even read.”

      The result is what’s being called the “Earth digital twin,” a climate model that can simulate global conditions on a large scale. This on its own is an impressive feat, but the team wants to take this a step further with their proposal.

      “We want to take this large-scale model and create what we call an ‘emulator’ that is only predicting a set of variables of interest, but it’s been trained on the large-scale model,” Ferrari explains. Emulators are not new technology, but what is new is that these emulators, being referred to as the “Earth digital cousins,” will take advantage of machine learning.

      “Now we know how to train a model if we have enough data to train them on,” says Ferrari. Machine learning for projects like this has only become possible in recent years as more observational data become available, along with improved computer processing power. The goal is to create smaller, more localized models by training them using the Earth digital twin. Doing so will save time and money, which is key if the digital cousins are going to be usable for stakeholders, like local governments and private-sector developers.

      Adaptable predictions for average stakeholders

      When it comes to setting climate-informed policy, stakeholders need to understand the probability of an outcome within their own regions — in the same way that you would prepare for a hike differently if there’s a 10 percent chance of rain versus a 90 percent chance. The smaller Earth digital cousin models will be able to do things the larger model can’t do, like simulate local regions in real time and provide a wider range of probabilistic scenarios.

      “Right now, if you wanted to use output from a global climate model, you usually would have to use output that’s designed for general use,” says Selin, who is also the director of the MIT Technology and Policy Program. With the project, the team can take end-user needs into account from the very beginning while also incorporating their feedback and suggestions into the models, helping to “democratize the idea of running these climate models,” as she puts it. Doing so means building an interactive interface that eventually will give users the ability to change input values and run the new simulations in real time. The team hopes that, eventually, the Earth digital cousins could run on something as ubiquitous as a smartphone, although developments like that are currently beyond the scope of the project.

      The next thing the team will work on is building connections with stakeholders. Through participation of other MIT groups, such as the Joint Program on the Science and Policy of Global Change and the Climate and Sustainability Consortium, they hope to work closely with policymakers, public safety officials, and urban planners to give them predictive tools tailored to their needs that can provide actionable outputs important for planning. Faced with rising sea levels, for example, coastal cities could better visualize the threat and make informed decisions about infrastructure development and disaster preparedness; communities in drought-prone regions could develop long-term civil planning with an emphasis on water conservation and wildfire resistance.

      “We want to make the modeling and analysis process faster so people can get more direct and useful feedback for near-term decisions,” she says.

      The final piece of the challenge is to incentivize students now so that they can join the project and make a difference. Ferrari has already had luck garnering student interest after co-teaching a class with Edelman and seeing the enthusiasm students have about computer science and climate solutions.

      “We’re intending in this project to build a climate model of the future,” says Selin. “So it seems really appropriate that we would also train the builders of that climate model.” More

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      MIT announces five flagship projects in first-ever Climate Grand Challenges competition

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      MIT today announced the five flagship projects selected in its first-ever Climate Grand Challenges competition. These multiyear projects will define a dynamic research agenda focused on unraveling some of the toughest unsolved climate problems and bringing high-impact, science-based solutions to the world on an accelerated basis.

      Representing the most promising concepts to emerge from the two-year competition, the five flagship projects will receive additional funding and resources from MIT and others to develop their ideas and swiftly transform them into practical solutions at scale.

      “Climate Grand Challenges represents a whole-of-MIT drive to develop game-changing advances to confront the escalating climate crisis, in time to make a difference,” says MIT President L. Rafael Reif. “We are inspired by the creativity and boldness of the flagship ideas and by their potential to make a significant contribution to the global climate response. But given the planet-wide scale of the challenge, success depends on partnership. We are eager to work with visionary leaders in every sector to accelerate this impact-oriented research, implement serious solutions at scale, and inspire others to join us in confronting this urgent challenge for humankind.”

      Brief descriptions of the five Climate Grand Challenges flagship projects are provided below.

      Bringing Computation to the Climate Challenge

      This project leverages advances in artificial intelligence, machine learning, and data sciences to improve the accuracy of climate models and make them more useful to a variety of stakeholders — from communities to industry. The team is developing a digital twin of the Earth that harnesses more data than ever before to reduce and quantify uncertainties in climate projections.

      Research leads: Raffaele Ferrari, the Cecil and Ida Green Professor of Oceanography in the Department of Earth, Atmospheric and Planetary Sciences, and director of the Program in Atmospheres, Oceans, and Climate; and Noelle Eckley Selin, director of the Technology and Policy Program and professor with a joint appointment in the Institute for Data, Systems, and Society and the Department of Earth, Atmospheric and Planetary Sciences

      Center for Electrification and Decarbonization of Industry

      This project seeks to reinvent and electrify the processes and materials behind hard-to-decarbonize industries like steel, cement, ammonia, and ethylene production. A new innovation hub will perform targeted fundamental research and engineering with urgency, pushing the technological envelope on electricity-driven chemical transformations.

      Research leads: Yet-Ming Chiang, the Kyocera Professor of Materials Science and Engineering, and Bilge Yıldız, the Breene M. Kerr Professor in the Department of Nuclear Science and Engineering and professor in the Department of Materials Science and Engineering

      Preparing for a new world of weather and climate extremes

      This project addresses key gaps in knowledge about intensifying extreme events such as floods, hurricanes, and heat waves, and quantifies their long-term risk in a changing climate. The team is developing a scalable climate-change adaptation toolkit to help vulnerable communities and low-carbon energy providers prepare for these extreme weather events.

      Research leads: Kerry Emanuel, the Cecil and Ida Green Professor of Atmospheric Science in the Department of Earth, Atmospheric and Planetary Sciences and co-director of the MIT Lorenz Center; Miho Mazereeuw, associate professor of architecture and urbanism in the Department of Architecture and director of the Urban Risk Lab; and Paul O’Gorman, professor in the Program in Atmospheres, Oceans, and Climate in the Department of Earth, Atmospheric and Planetary Sciences

      The Climate Resilience Early Warning System

      The CREWSnet project seeks to reinvent climate change adaptation with a novel forecasting system that empowers underserved communities to interpret local climate risk, proactively plan for their futures incorporating resilience strategies, and minimize losses. CREWSnet will initially be demonstrated in southwestern Bangladesh, serving as a model for similarly threatened regions around the world.

      Research leads: John Aldridge, assistant leader of the Humanitarian Assistance and Disaster Relief Systems Group at MIT Lincoln Laboratory, and Elfatih Eltahir, the H.M. King Bhumibol Professor of Hydrology and Climate in the Department of Civil and Environmental Engineering

      Revolutionizing agriculture with low-emissions, resilient crops

      This project works to revolutionize the agricultural sector with climate-resilient crops and fertilizers that have the ability to dramatically reduce greenhouse gas emissions from food production.

      Research lead: Christopher Voigt, the Daniel I.C. Wang Professor in the Department of Biological Engineering

      “As one of the world’s leading institutions of research and innovation, it is incumbent upon MIT to draw on our depth of knowledge, ingenuity, and ambition to tackle the hard climate problems now confronting the world,” says Richard Lester, MIT associate provost for international activities. “Together with collaborators across industry, finance, community, and government, the Climate Grand Challenges teams are looking to develop and implement high-impact, path-breaking climate solutions rapidly and at a grand scale.”

      The initial call for ideas in 2020 yielded nearly 100 letters of interest from almost 400 faculty members and senior researchers, representing 90 percent of MIT departments. After an extensive evaluation, 27 finalist teams received a total of $2.7 million to develop comprehensive research and innovation plans. The projects address four broad research themes:

      To select the winning projects, research plans were reviewed by panels of international experts representing relevant scientific and technical domains as well as experts in processes and policies for innovation and scalability.

      “In response to climate change, the world really needs to do two things quickly: deploy the solutions we already have much more widely, and develop new solutions that are urgently needed to tackle this intensifying threat,” says Maria Zuber, MIT vice president for research. “These five flagship projects exemplify MIT’s strong determination to bring its knowledge and expertise to bear in generating new ideas and solutions that will help solve the climate problem.”

      “The Climate Grand Challenges flagship projects set a new standard for inclusive climate solutions that can be adapted and implemented across the globe,” says MIT Chancellor Melissa Nobles. “This competition propels the entire MIT research community — faculty, students, postdocs, and staff — to act with urgency around a worsening climate crisis, and I look forward to seeing the difference these projects can make.”

      “MIT’s efforts on climate research amid the climate crisis was a primary reason that I chose to attend MIT, and remains a reason that I view the Institute favorably. MIT has a clear opportunity to be a thought leader in the climate space in our own MIT way, which is why CGC fits in so well,” says senior Megan Xu, who served on the Climate Grand Challenges student committee and is studying ways to make the food system more sustainable.

      The Climate Grand Challenges competition is a key initiative of “Fast Forward: MIT’s Climate Action Plan for the Decade,” which the Institute published in May 2021. Fast Forward outlines MIT’s comprehensive plan for helping the world address the climate crisis. It consists of five broad areas of action: sparking innovation, educating future generations, informing and leveraging government action, reducing MIT’s own climate impact, and uniting and coordinating all of MIT’s climate efforts. More

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      Emery Brown earns American Institute for Medical and Biological Engineering Pierre Galletti Award

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      The American Institute for Medical and Biological Engineering has awarded its highest honor this year to Emery N. Brown, the Edward Hood Taplin Professor of Computational Neuroscience and Health Sciences and Technology in The Picower Institute for Learning and Memory and the Institute for Medical Engineering and Science at MIT.

      Brown, who is also an anesthesiologist at Massachusetts General Hospital and the Warren M. Zapol Professor at Harvard Medical School, received the 2022 Pierre M. Galletti Award during the national organization’s Annual Event held on March 25.

      For decades, Brown’s lab has uniquely unified three fields: neuroscience, statistics, and anesthesiology. He is renowned for the development of statistical methods and signal-processing algorithms to enable and improve analysis of neural activity measurements. The work has had numerous applications including studies of learning and memory, brain-computer interfaces, and systems neuroscience. He has also pioneered investigations of how general anesthetic drugs work in the brain to induce and maintain simultaneous but reversible states of unconsciousness, amnesia, immobility, and analgesia. Building on these improvements in fundamental understanding, his lab engineers systems to improve monitoring of patient state and anesthetic dosing during surgery. Optimizing doses of general anesthetic drugs can improve patient care in many ways, including by minimizing side effects such as post-operative delirium and by improving post-operative pain management.

      AIMBE said Brown earned the award in recognition of his “significant contributions to neuroscience data analysis and for characterizing the neurophysiology of anesthesia-induced unconsciousness and demonstrating how it can be reliably monitored in real time using electroencephalogram recordings.”

      Brown, who is also a faculty member in MIT’s Department of Brain and Cognitive Sciences, is now working to develop a research center at MIT dedicated to taking neuroscience-based approaches to advance anesthesiology.

      “I am extremely honored and grateful to the AIMBE for choosing me to receive the 2022 Galletti Award in recognition of my research deciphering the neuroscience of how anesthetics work,” he says. “I would like to express my gratitude to my collaborators, post-doctoral fellows, students, research assistants, and clinical coordinators who have made this possible.” More

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      Ocean vital signs

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      Without the ocean, the climate crisis would be even worse than it is. Each year, the ocean absorbs billions of tons of carbon from the atmosphere, preventing warming that greenhouse gas would otherwise cause. Scientists estimate about 25 to 30 percent of all carbon released into the atmosphere by both human and natural sources is absorbed by the ocean.

      “But there’s a lot of uncertainty in that number,” says Ryan Woosley, a marine chemist and a principal research scientist in the Department of Earth, Atmospheric and Planetary Sciences (EAPS) at MIT. Different parts of the ocean take in different amounts of carbon depending on many factors, such as the season and the amount of mixing from storms. Current models of the carbon cycle don’t adequately capture this variation.

      To close the gap, Woosley and a team of other MIT scientists developed a research proposal for the MIT Climate Grand Challenges competition — an Institute-wide campaign to catalyze and fund innovative research addressing the climate crisis. The team’s proposal, “Ocean Vital Signs,” involves sending a fleet of sailing drones to cruise the oceans taking detailed measurements of how much carbon the ocean is really absorbing. Those data would be used to improve the precision of global carbon cycle models and improve researchers’ ability to verify emissions reductions claimed by countries.

      “If we start to enact mitigation strategies—either through removing CO2 from the atmosphere or reducing emissions — we need to know where CO2 is going in order to know how effective they are,” says Woosley. Without more precise models there’s no way to confirm whether observed carbon reductions were thanks to policy and people, or thanks to the ocean.

      “So that’s the trillion-dollar question,” says Woosley. “If countries are spending all this money to reduce emissions, is it enough to matter?”

      In February, the team’s Climate Grand Challenges proposal was named one of 27 finalists out of the almost 100 entries submitted. From among this list of finalists, MIT will announce in April the selection of five flagship projects to receive further funding and support.

      Woosley is leading the team along with Christopher Hill, a principal research engineer in EAPS. The team includes physical and chemical oceanographers, marine microbiologists, biogeochemists, and experts in computational modeling from across the department, in addition to collaborators from the Media Lab and the departments of Mathematics, Aeronautics and Astronautics, and Electrical Engineering and Computer Science.

      Today, data on the flux of carbon dioxide between the air and the oceans are collected in a piecemeal way. Research ships intermittently cruise out to gather data. Some commercial ships are also fitted with sensors. But these present a limited view of the entire ocean, and include biases. For instance, commercial ships usually avoid storms, which can increase the turnover of water exposed to the atmosphere and cause a substantial increase in the amount of carbon absorbed by the ocean.

      “It’s very difficult for us to get to it and measure that,” says Woosley. “But these drones can.”

      If funded, the team’s project would begin by deploying a few drones in a small area to test the technology. The wind-powered drones — made by a California-based company called Saildrone — would autonomously navigate through an area, collecting data on air-sea carbon dioxide flux continuously with solar-powered sensors. This would then scale up to more than 5,000 drone-days’ worth of observations, spread over five years, and in all five ocean basins.

      Those data would be used to feed neural networks to create more precise maps of how much carbon is absorbed by the oceans, shrinking the uncertainties involved in the models. These models would continue to be verified and improved by new data. “The better the models are, the more we can rely on them,” says Woosley. “But we will always need measurements to verify the models.”

      Improved carbon cycle models are relevant beyond climate warming as well. “CO2 is involved in so much of how the world works,” says Woosley. “We’re made of carbon, and all the other organisms and ecosystems are as well. What does the perturbation to the carbon cycle do to these ecosystems?”

      One of the best understood impacts is ocean acidification. Carbon absorbed by the ocean reacts to form an acid. A more acidic ocean can have dire impacts on marine organisms like coral and oysters, whose calcium carbonate shells and skeletons can dissolve in the lower pH. Since the Industrial Revolution, the ocean has become about 30 percent more acidic on average.

      “So while it’s great for us that the oceans have been taking up the CO2, it’s not great for the oceans,” says Woosley. “Knowing how this uptake affects the health of the ocean is important as well.” More

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      Improving predictions of sea level rise for the next century

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      When we think of climate change, one of the most dramatic images that comes to mind is the loss of glacial ice. As the Earth warms, these enormous rivers of ice become a casualty of the rising temperatures. But, as ice sheets retreat, they also become an important contributor to one the more dangerous outcomes of climate change: sea-level rise. At MIT, an interdisciplinary team of scientists is determined to improve sea level rise predictions for the next century, in part by taking a closer look at the physics of ice sheets.

      Last month, two research proposals on the topic, led by Brent Minchew, the Cecil and Ida Green Career Development Professor in the Department of Earth, Atmospheric and Planetary Sciences (EAPS), were announced as finalists in the MIT Climate Grand Challenges initiative. Launched in July 2020, Climate Grand Challenges fielded almost 100 project proposals from collaborators across the Institute who heeded the bold charge: to develop research and innovations that will deliver game-changing advances in the world’s efforts to address the climate challenge.

      As finalists, Minchew and his collaborators from the departments of Urban Studies and Planning, Economics, Civil and Environmental Engineering, the Haystack Observatory, and external partners, received $100,000 to develop their research plans. A subset of the 27 proposals tapped as finalists will be announced next month, making up a portfolio of multiyear “flagship” projects receiving additional funding and support.

      One goal of both Minchew proposals is to more fully understand the most fundamental processes that govern rapid changes in glacial ice, and to use that understanding to build next-generation models that are more predictive of ice sheet behavior as they respond to, and influence, climate change.

      “We need to develop more accurate and computationally efficient models that provide testable projections of sea-level rise over the coming decades. To do so quickly, we want to make better and more frequent observations and learn the physics of ice sheets from these data,” says Minchew. “For example, how much stress do you have to apply to ice before it breaks?”

      Currently, Minchew’s Glacier Dynamics and Remote Sensing group uses satellites to observe the ice sheets on Greenland and Antarctica primarily with interferometric synthetic aperture radar (InSAR). But the data are often collected over long intervals of time, which only gives them “before and after” snapshots of big events. By taking more frequent measurements on shorter time scales, such as hours or days, they can get a more detailed picture of what is happening in the ice.

      “Many of the key unknowns in our projections of what ice sheets are going to look like in the future, and how they’re going to evolve, involve the dynamics of glaciers, or our understanding of how the flow speed and the resistances to flow are related,” says Minchew.

      At the heart of the two proposals is the creation of SACOS, the Stratospheric Airborne Climate Observatory System. The group envisions developing solar-powered drones that can fly in the stratosphere for months at a time, taking more frequent measurements using a new lightweight, low-power radar and other high-resolution instrumentation. They also propose air-dropping sensors directly onto the ice, equipped with seismometers and GPS trackers to measure high-frequency vibrations in the ice and pinpoint the motions of its flow.

      How glaciers contribute to sea level rise

      Current climate models predict an increase in sea levels over the next century, but by just how much is still unclear. Estimates are anywhere from 20 centimeters to two meters, which is a large difference when it comes to enacting policy or mitigation. Minchew points out that response measures will be different, depending on which end of the scale it falls toward. If it’s closer to 20 centimeters, coastal barriers can be built to protect low-level areas. But with higher surges, such measures become too expensive and inefficient to be viable, as entire portions of cities and millions of people would have to be relocated.

      “If we’re looking at a future where we could get more than a meter of sea level rise by the end of the century, then we need to know about that sooner rather than later so that we can start to plan and to do our best to prepare for that scenario,” he says.

      There are two ways glaciers and ice sheets contribute to rising sea levels: direct melting of the ice and accelerated transport of ice to the oceans. In Antarctica, warming waters melt the margins of the ice sheets, which tends to reduce the resistive stresses and allow ice to flow more quickly to the ocean. This thinning can also cause the ice shelves to be more prone to fracture, facilitating the calving of icebergs — events which sometimes cause even further acceleration of ice flow.

      Using data collected by SACOS, Minchew and his group can better understand what material properties in the ice allow for fracturing and calving of icebergs, and build a more complete picture of how ice sheets respond to climate forces. 

      “What I want is to reduce and quantify the uncertainties in projections of sea level rise out to the year 2100,” he says.

      From that more complete picture, the team — which also includes economists, engineers, and urban planning specialists — can work on developing predictive models and methods to help communities and governments estimate the costs associated with sea level rise, develop sound infrastructure strategies, and spur engineering innovation.

      Understanding glacier dynamics

      More frequent radar measurements and the collection of higher-resolution seismic and GPS data will allow Minchew and the team to develop a better understanding of the broad category of glacier dynamics — including calving, an important process in setting the rate of sea level rise which is currently not well understood.  

      “Some of what we’re doing is quite similar to what seismologists do,” he says. “They measure seismic waves following an earthquake, or a volcanic eruption, or things of this nature and use those observations to better understand the mechanisms that govern these phenomena.”

      Air-droppable sensors will help them collect information about ice sheet movement, but this method comes with drawbacks — like installation and maintenance, which is difficult to do out on a massive ice sheet that is moving and melting. Also, the instruments can each only take measurements at a single location. Minchew equates it to a bobber in water: All it can tell you is how the bobber moves as the waves disturb it.

      But by also taking continuous radar measurements from the air, Minchew’s team can collect observations both in space and in time. Instead of just watching the bobber in the water, they can effectively make a movie of the waves propagating out, as well as visualize processes like iceberg calving happening in multiple dimensions.

      Once the bobbers are in place and the movies recorded, the next step is developing machine learning algorithms to help analyze all the new data being collected. While this data-driven kind of discovery has been a hot topic in other fields, this is the first time it has been applied to glacier research.

      “We’ve developed this new methodology to ingest this huge amount of data,” he says, “and from that create an entirely new way of analyzing the system to answer these fundamental and critically important questions.”  More

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      in Data Management & Statistics

      An “oracle” for predicting the evolution of gene regulation

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      Despite the sheer number of genes that each human cell contains, these so-called “coding” DNA sequences comprise just 1 percent of our entire genome. The remaining 99 percent is made up of “non-coding” DNA — which, unlike coding DNA, does not carry the instructions to build proteins.

      One vital function of this non-coding DNA, also called “regulatory” DNA, is to help turn genes on and off, controlling how much (if any) of a protein is made. Over time, as cells replicate their DNA to grow and divide, mutations often crop up in these non-coding regions — sometimes tweaking their function and changing the way they control gene expression. Many of these mutations are trivial, and some are even beneficial. Occasionally, though, they can be associated with increased risk of common diseases, such as Type 2 diabetes, or more life-threatening ones, including cancer.

      To better understand the repercussions of such mutations, researchers have been hard at work on mathematical maps that allow them to look at an organism’s genome, predict which genes will be expressed, and determine how that expression will affect the organism’s observable traits. These maps, called fitness landscapes, were conceptualized roughly a century ago to understand how genetic makeup influences one common measure of organismal fitness in particular: reproductive success. Early fitness landscapes were very simple, often focusing on a limited number of mutations. Much richer datasets are now available, but researchers still require additional tools to characterize and visualize such complex data. This ability would not only facilitate a better understanding of how individual genes have evolved over time, but would also help to predict what sequence and expression changes might occur in the future.

      In a new study published on March 9 in Nature, a team of scientists has developed a framework for studying the fitness landscapes of regulatory DNA. They created a neural network model that, when trained on hundreds of millions of experimental measurements, was capable of predicting how changes to these non-coding sequences in yeast affected gene expression. They also devised a unique way of representing the landscapes in two dimensions, making it easy to understand the past and forecast the future evolution of non-coding sequences in organisms beyond yeast — and even design custom gene expression patterns for gene therapies and industrial applications.

      “We now have an ‘oracle’ that can be queried to ask: What if we tried all possible mutations of this sequence? Or, what new sequence should we design to give us a desired expression?” says Aviv Regev, a professor of biology at MIT (on leave), core member of the Broad Institute of Harvard and MIT (on leave), head of Genentech Research and Early Development, and the study’s senior author. “Scientists can now use the model for their own evolutionary question or scenario, and for other problems like making sequences that control gene expression in desired ways. I am also excited about the possibilities for machine learning researchers interested in interpretability; they can ask their questions in reverse, to better understand the underlying biology.”

      Prior to this study, many researchers had simply trained their models on known mutations (or slight variations thereof) that exist in nature. However, Regev’s team wanted to go a step further by creating their own unbiased models capable of predicting an organism’s fitness and gene expression based on any possible DNA sequence — even sequences they’d never seen before. This would also enable researchers to use such models to engineer cells for pharmaceutical purposes, including new treatments for cancer and autoimmune disorders.

      To accomplish this goal, Eeshit Dhaval Vaishnav, a graduate student at MIT and co-first author; Carl de Boer, now an assistant professor at the University of British Columbia; and their colleagues created a neural network model to predict gene expression. They trained it on a dataset generated by inserting millions of totally random non-coding DNA sequences into yeast, and observing how each random sequence affected gene expression. They focused on a particular subset of non-coding DNA sequences called promoters, which serve as binding sites for proteins that can switch nearby genes on or off.

      “This work highlights what possibilities open up when we design new kinds of experiments to generate the right data to train models,” Regev says. “In the broader sense, I believe these kinds of approaches will be important for many problems — like understanding genetic variants in regulatory regions that confer disease risk in the human genome, but also for predicting the impact of combinations of mutations, or designing new molecules.”

      Regev, Vaishnav, de Boer, and their coauthors went on to test their model’s predictive abilities in a variety of ways, in order to show how it could help demystify the evolutionary past — and possible future — of certain promoters. “Creating an accurate model was certainly an accomplishment, but, to me, it was really just a starting point,” Vaishnav explains.

      First, to determine whether their model could help with synthetic biology applications like producing antibiotics, enzymes, and food, the researchers practiced using it to design promoters that could generate desired expression levels for any gene of interest. They then scoured other scientific papers to identify fundamental evolutionary questions, in order to see if their model could help answer them. The team even went so far as to feed their model a real-world population dataset from one existing study, which contained genetic information from yeast strains around the world. In doing so, they were able to delineate thousands of years of past selection pressures that sculpted the genomes of today’s yeast.

      But, in order to create a powerful tool that could probe any genome, the researchers knew they’d need to find a way to forecast the evolution of non-coding sequences even without such a comprehensive population dataset. To address this goal, Vaishnav and his colleagues devised a computational technique that allowed them to plot the predictions from their framework onto a two-dimensional graph. This helped them show, in a remarkably simple manner, how any non-coding DNA sequence would affect gene expression and fitness, without needing to conduct any time-consuming experiments at the lab bench.

      “One of the unsolved problems in fitness landscapes was that we didn’t have an approach for visualizing them in a way that meaningfully captured the evolutionary properties of sequences,” Vaishnav explains. “I really wanted to find a way to fill that gap, and contribute to the long-standing vision of creating a complete fitness landscape.”

      Martin Taylor, a professor of genetics at the University of Edinburgh’s Medical Research Council Human Genetics Unit who was not involved in the research, says the study shows that artificial intelligence can not only predict the effect of regulatory DNA changes, but also reveal the underlying principles that govern millions of years of evolution.

      Despite the fact that the model was trained on just a fraction of yeast regulatory DNA in a few growth conditions, he’s impressed that it’s capable of making such useful predictions about the evolution of gene regulation in mammals.

      “There are obvious near-term applications, such as the custom design of regulatory DNA for yeast in brewing, baking, and biotechnology,” he explains. “But extensions of this work could also help identify disease mutations in human regulatory DNA that are currently difficult to find and largely overlooked in the clinic. This work suggests there is a bright future for AI models of gene regulation trained on richer, more complex, and more diverse datasets.”

      Even before the study was formally published, Vaishnav began receiving queries from other researchers hoping to use the model to devise non-coding DNA sequences for use in gene therapies.

      “People have been studying regulatory evolution and fitness landscapes for decades now,” Vaishnav says. “I think our framework will go a long way in answering fundamental, open questions about the evolution and evolvability of gene regulatory DNA — and even help us design biological sequences for exciting new applications.” More