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      How diet affects tumors

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      In recent years, there has been some evidence that dietary interventions can help to slow the growth of tumors. A new study from MIT, which analyzed two different diets in mice, reveals how those diets affect cancer cells, and offers an explanation for why restricting calories may slow tumor growth.

      The study examined the effects of a calorically restricted diet and a ketogenic diet in mice with pancreatic tumors. While both of these diets reduce the amount of sugar available to tumors, the researchers found that only the calorically restricted diet reduced the availability of fatty acids, and this was linked to a slowdown in tumor growth.

      The findings do not suggest that cancer patients should try to follow either of these diets, the researchers say. Instead, they believe the findings warrant further study to determine how dietary interventions might be combined with existing or emerging drugs to help patients with cancer.

      “There’s a lot of evidence that diet can affect how fast your cancer progresses, but this is not a cure,” says Matthew Vander Heiden, director of MIT’s Koch Institute for Integrative Cancer Research and the senior author of the study. “While the findings are provocative, further study is needed, and individual patients should talk to their doctor about the right dietary interventions for their cancer.”

      MIT postdoc Evan Lien is the lead author of the paper, which appears today in Nature.

      Metabolic mechanism

      Vander Heiden, who is also a medical oncologist at Dana-Farber Cancer Institute, says his patients often ask him about the potential benefits of various diets, but there is not enough scientific evidence available to offer any definitive advice. Many of the dietary questions that patients have focus on either a calorie-restricted diet, which reduces calorie consumption by 25 to 50 percent, or a ketogenic diet, which is low in carbohydrates and high in fat and protein.

      Previous studies have suggested that a calorically restricted diet might slow tumor growth in some contexts, and such a diet has been shown to extend lifespan in mice and many other animal species. A smaller number of studies exploring the effects of a ketogenic diet on cancer have produced inconclusive results.

      “A lot of the advice or cultural fads that are out there aren’t necessarily always based on very good science,” Lien says. “It seemed like there was an opportunity, especially with our understanding of cancer metabolism having evolved so much over the past 10 years or so, that we could take some of the biochemical principles that we’ve learned and apply those concepts to understanding this complex question.”

      Cancer cells consume a great deal of glucose, so some scientists had hypothesized that either the ketogenic diet or calorie restriction might slow tumor growth by reducing the amount of glucose available. However, the MIT team’s initial experiments in mice with pancreatic tumors showed that calorie restriction has a much greater effect on tumor growth than the ketogenic diet, so the researchers suspected that glucose levels were not playing a major role in the slowdown.

      To dig deeper into the mechanism, the researchers analyzed tumor growth and nutrient concentration in mice with pancreatic tumors, which were fed either a normal, ketogenic, or calorie-restricted diet. In both the ketogenic and calorie-restricted mice, glucose levels went down. In the calorie-restricted mice, lipid levels also went down, but in mice on the ketogenic diet, they went up.

      Lipid shortages impair tumor growth because cancer cells need lipids to construct their cell membranes. Normally, when lipids aren’t available in a tissue, cells can make their own. As part of this process, they need to maintain the right balance of saturated and unsaturated fatty acids, which requires an enzyme called stearoyl-CoA desaturase (SCD). This enzyme is responsible for converting saturated fatty acids into unsaturated fatty acids.

      Both calorie-restricted and ketogenic diets reduce SCD activity, but mice on the ketogenic diet had lipids available to them from their diet, so they didn’t need to use SCD. Mice on the calorie-restricted diet, however, couldn’t get fatty acids from their diet or produce their own. In these mice, tumor growth slowed significantly, compared to mice on the ketogenic diet.

      “Not only does caloric restriction starve tumors of lipids, it also impairs the process that allows them to adapt to it. That combination is really contributing to the inhibition of tumor growth,” Lien says.

      Dietary effects

      In addition to their mouse research, the researchers also looked at some human data. Working with Brian Wolpin, an oncologist at Dana-Farber Cancer Institute and an author of the paper, the team obtained data from a large cohort study that allowed them to analyze the relationship between dietary patterns and survival times in pancreatic cancer patients. From that study, the researchers found that the type of fat consumed appears to influence how patients on a low-sugar diet fare after a pancreatic cancer diagnosis, although the data are not complete enough to draw any conclusions about the effect of diet, the researchers say.

      Although this study showed that calorie restriction has beneficial effects in mice, the researchers say they do not recommend that cancer patients follow a calorie-restricted diet, which is difficult to maintain and can have harmful side effects. However, they believe that cancer cells’ dependence on the availability of unsaturated fatty acids could be exploited to develop drugs that might help slow tumor growth.

      One possible therapeutic strategy could be inhibition of the SCD enzyme, which would cut off tumor cells’ ability to produce unsaturated fatty acids.

      “The purpose of these studies isn’t necessarily to recommend a diet, but it’s to really understand the underlying biology,” Lien says. “They provide some sense of the mechanisms of how these diets work, and that can lead to rational ideas on how we might mimic those situations for cancer therapy.”

      The researchers now plan to study how diets with a variety of fat sources — including plant or animal-based fats with defined differences in saturated, monounsaturated, and polyunsaturated fatty acid content — alter tumor fatty acid metabolism and the ratio of unsaturated to saturated fatty acids.

      The research was funded by the Damon Runyon Cancer Research Foundation, the National Institutes of Health, the Lustgarten Foundation, the Dana-Farber Cancer Institute Hale Family Center for Pancreatic Cancer Research, Stand Up to Cancer, the Pancreatic Cancer Action Network, the Noble Effort Fund, the Wexler Family Fund, Promises for Purple, the Bob Parsons Fund, the Emerald Foundation, the Howard Hughes Medical Institute, the MIT Center for Precision Cancer Medicine, and the Ludwig Center at MIT. More

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      Rover images confirm Jezero crater is an ancient Martian lake

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      The first scientific analysis of images taken by NASA’s Perseverance rover has now confirmed that Mars’ Jezero crater — which today is a dry, wind-eroded depression — was once a quiet lake, fed steadily by a small river some 3.7 billion years ago.

      The images also reveal evidence that the crater endured flash floods. This flooding was energetic enough to sweep up large boulders from tens of miles upstream and deposit them into the lakebed, where the massive rocks lie today.

      The new analysis, published today in the journal Science, is based on images of the outcropping rocks inside the crater on its western side. Satellites had previously shown that this outcrop, seen from above, resembled river deltas on Earth, where layers of sediment are deposited in the shape of a fan as the river feeds into a lake.

      Perseverance’s new images, taken from inside the crater, confirm that this outcrop was indeed a river delta. Based on the sedimentary layers in the outcrop, it appears that the river delta fed into a lake that was calm for much of its existence, until a dramatic shift in climate triggered episodic flooding at or toward the end of the lake’s history.

      “If you look at these images, you’re basically staring at this epic desert landscape. It’s the most forlorn place you could ever visit,” says Benjamin Weiss, professor of planetary sciences in MIT’s Department of Earth, Atmospheric and Planetary Sciences and a member of the analysis team. “There’s not a drop of water anywhere, and yet, here we have evidence of a very different past. Something very profound happened in the planet’s history.”

      As the rover explores the crater, scientists hope to uncover more clues to its climatic evolution. Now that they have confirmed the crater was once a lake environment, they believe its sediments could hold traces of ancient aqueous life. In its mission going forward, Perseverance will look for locations to collect and preserve sediments. These samples will eventually be returned to Earth, where scientists can probe them for Martian biosignatures.

      “We now have the opportunity to look for fossils,” says team member Tanja Bosak, associate professor of geobiology at MIT. “It will take some time to get to the rocks that we really hope to sample for signs of life. So, it’s a marathon, with a lot of potential.”

      Tilted beds

      On Feb. 18, 2021, the Perseverance rover landed on the floor of Jezero crater, a little more than a mile away from its western fan-shaped outcrop. In the first three months, the vehicle remained stationary as NASA engineers performed remote checks of the rover’s many instruments.

      During this time, two of Perseverance’s cameras, Mastcam-Z and the SuperCam Remote Micro-Imager (RMI), captured images of their surroundings, including long-distance photos of the outcrop’s edge and a formation known as Kodiak butte, a smaller outcop that planetary geologists surmise may have once been connected to the main fan-shaped outcrop but has since partially eroded.

      Once the rover downlinked images to Earth, NASA’s Perseverance science team processed and combined the images, and were able to observe distinct beds of sediment along Kodiak butte in surprisingly high resolution. The researchers measured each layer’s thickness, slope, and lateral extent, finding that the sediment must have been deposited by flowing water into a lake, rather than by wind, sheet-like floods, or other geologic processes.

      The rover also captured similar tilted sediment beds along the main outcrop. These images, together with those of Kodiak, confirm that the fan-shaped formation was indeed an ancient delta and that this delta fed into an ancient Martian lake.

      “Without driving anywhere, the rover was able to solve one of the big unknowns, which was that this crater was once a lake,” Weiss says. “Until we actually landed there and confirmed it was a lake, it was always a question.”

      Boulder flow

      When the researchers took a closer look at images of the main outcrop, they noticed large boulders and cobbles embedded in the youngest, topmost layers of the delta. Some boulders measured as wide as 1 meter across, and were estimated to weigh up to several tons. These massive rocks, the team concluded, must have come from outside the crater, and was likely part of bedrock located on the crater rim or else 40 or more miles upstream.

      Judging from their current location and dimensions, the team says the boulders were carried downstream and into the lakebed by a flash-flood that flowed up to 9 meters per second and moved up to 3,000 cubic meters of water per second.

      “You need energetic flood conditions to carry rocks that big and heavy,” Weiss says. “It’s a special thing that may be indicative of a fundamental change in the local hydrology or perhaps the regional climate on Mars.”

      Because the huge rocks lie in the upper layers of the delta, they represent the most recently deposited material. The boulders sit atop layers of older, much finer sediment. This stratification, the researchers say, indicates that for much of its existence, the ancient lake was filled by a gently flowing river. Fine sediments — and possibly organic material — drifted down the river, and settled into a gradual, sloping delta.

      However, the crater later experienced sudden flash floods that deposited large boulders onto the delta. Once the lake dried up, and over billions of years wind eroded the landscape, leaving the crater we see today.

      The cause of this climate turnaround is unknown, although Weiss says the delta’s boulders may hold some answers.

      “The most surprising thing that’s come out of these images is the potential opportunity to catch the time when this crater transitioned from an Earth-like habitable environment, to this desolate landscape wasteland we see now,” he says. “These boulder beds may be records of this transition, and we haven’t seen this in other places on Mars.”

      This research was supported, in part, by NASA. More

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      A robot that finds lost items

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      A busy commuter is ready to walk out the door, only to realize they’ve misplaced their keys and must search through piles of stuff to find them. Rapidly sifting through clutter, they wish they could figure out which pile was hiding the keys.

      Researchers at MIT have created a robotic system that can do just that. The system, RFusion, is a robotic arm with a camera and radio frequency (RF) antenna attached to its gripper. It fuses signals from the antenna with visual input from the camera to locate and retrieve an item, even if the item is buried under a pile and completely out of view.

      The RFusion prototype the researchers developed relies on RFID tags, which are cheap, battery-less tags that can be stuck to an item and reflect signals sent by an antenna. Because RF signals can travel through most surfaces (like the mound of dirty laundry that may be obscuring the keys), RFusion is able to locate a tagged item within a pile.

      Using machine learning, the robotic arm automatically zeroes-in on the object’s exact location, moves the items on top of it, grasps the object, and verifies that it picked up the right thing. The camera, antenna, robotic arm, and AI are fully integrated, so RFusion can work in any environment without requiring a special set up.

      While finding lost keys is helpful, RFusion could have many broader applications in the future, like sorting through piles to fulfill orders in a warehouse, identifying and installing components in an auto manufacturing plant, or helping an elderly individual perform daily tasks in the home, though the current prototype isn’t quite fast enough yet for these uses.

      “This idea of being able to find items in a chaotic world is an open problem that we’ve been working on for a few years. Having robots that are able to search for things under a pile is a growing need in industry today. Right now, you can think of this as a Roomba on steroids, but in the near term, this could have a lot of applications in manufacturing and warehouse environments,” said senior author Fadel Adib, associate professor in the Department of Electrical Engineering and Computer Science and director of the Signal Kinetics group in the MIT Media Lab.

      Co-authors include research assistant Tara Boroushaki, the lead author; electrical engineering and computer science graduate student Isaac Perper; research associate Mergen Nachin; and Alberto Rodriguez, the Class of 1957 Associate Professor in the Department of Mechanical Engineering. The research will be presented at the Association for Computing Machinery Conference on Embedded Networked Senor Systems next month.

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      Sending signals

      RFusion begins searching for an object using its antenna, which bounces signals off the RFID tag (like sunlight being reflected off a mirror) to identify a spherical area in which the tag is located. It combines that sphere with the camera input, which narrows down the object’s location. For instance, the item can’t be located on an area of a table that is empty.

      But once the robot has a general idea of where the item is, it would need to swing its arm widely around the room taking additional measurements to come up with the exact location, which is slow and inefficient.

      The researchers used reinforcement learning to train a neural network that can optimize the robot’s trajectory to the object. In reinforcement learning, the algorithm is trained through trial and error with a reward system.

      “This is also how our brain learns. We get rewarded from our teachers, from our parents, from a computer game, etc. The same thing happens in reinforcement learning. We let the agent make mistakes or do something right and then we punish or reward the network. This is how the network learns something that is really hard for it to model,” Boroushaki explains.

      In the case of RFusion, the optimization algorithm was rewarded when it limited the number of moves it had to make to localize the item and the distance it had to travel to pick it up.

      Once the system identifies the exact right spot, the neural network uses combined RF and visual information to predict how the robotic arm should grasp the object, including the angle of the hand and the width of the gripper, and whether it must remove other items first. It also scans the item’s tag one last time to make sure it picked up the right object.

      Cutting through clutter

      The researchers tested RFusion in several different environments. They buried a keychain in a box full of clutter and hid a remote control under a pile of items on a couch.

      But if they fed all the camera data and RF measurements to the reinforcement learning algorithm, it would have overwhelmed the system. So, drawing on the method a GPS uses to consolidate data from satellites, they summarized the RF measurements and limited the visual data to the area right in front of the robot.

      Their approach worked well — RFusion had a 96 percent success rate when retrieving objects that were fully hidden under a pile.

      “Sometimes, if you only rely on RF measurements, there is going to be an outlier, and if you rely only on vision, there is sometimes going to be a mistake from the camera. But if you combine them, they are going to correct each other. That is what made the system so robust,” Boroushaki says.

      In the future, the researchers hope to increase the speed of the system so it can move smoothly, rather than stopping periodically to take measurements. This would enable RFusion to be deployed in a fast-paced manufacturing or warehouse setting.

      Beyond its potential industrial uses, a system like this could even be incorporated into future smart homes to assist people with any number of household tasks, Boroushaki says.

      “Every year, billions of RFID tags are used to identify objects in today’s complex supply chains, including clothing and lots of other consumer goods. The RFusion approach points the way to autonomous robots that can dig through a pile of mixed items and sort them out using the data stored in the RFID tags, much more efficiently than having to inspect each item individually, especially when the items look similar to a computer vision system,” says Matthew S. Reynolds, CoMotion Presidential Innovation Fellow and associate professor of electrical and computer engineering at the University of Washington, who was not involved in the research. “The RFusion approach is a great step forward for robotics operating in complex supply chains where identifying and ‘picking’ the right item quickly and accurately is the key to getting orders fulfilled on time and keeping demanding customers happy.”

      The research is sponsored by the National Science Foundation, a Sloan Research Fellowship, NTT DATA, Toppan, Toppan Forms, and the Abdul Latif Jameel Water and Food Systems Lab. More

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      Researchers design sensors to rapidly detect plant hormones

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      Researchers from the Disruptive and Sustainable Technologies for Agricultural Precision (DiSTAP) interdisciplinary research group of the Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, and their local collaborators from Temasek Life Sciences Laboratory (TLL) and Nanyang Technological University (NTU), have developed the first-ever nanosensor to enable rapid testing of synthetic auxin plant hormones. The novel nanosensors are safer and less tedious than existing techniques for testing plants’ response to compounds such as herbicide, and can be transformative in improving agricultural production and our understanding of plant growth.

      The scientists designed sensors for two plant hormones — 1-naphthalene acetic acid (NAA) and 2,4-dichlorophenoxyacetic acid (2,4-D) — which are used extensively in the farming industry for regulating plant growth and as herbicides, respectively. Current methods to detect NAA and 2,4-D cause damage to plants, and are unable to provide real-time in vivo monitoring and information.

      Based on the concept of corona phase molecular recognition (​​CoPhMoRe) pioneered by the Strano Lab at SMART DiSTAP and MIT, the new sensors are able to detect the presence of NAA and 2,4-D in living plants at a swift pace, providing plant information in real-time, without causing any harm. The team has successfully tested both sensors on a number of everyday crops including pak choi, spinach, and rice across various planting mediums such as soil, hydroponic, and plant tissue culture.

      Explained in a paper titled “Nanosensor Detection of Synthetic Auxins In Planta using Corona Phase Molecular Recognition” published in the journal ACS Sensors, the research can facilitate more efficient use of synthetic auxins in agriculture and hold tremendous potential to advance plant biology study.

      “Our CoPhMoRe technique has previously been used to detect compounds such as hydrogen peroxide and heavy-metal pollutants like arsenic — but this is the first successful case of CoPhMoRe sensors developed for detecting plant phytohormones that regulate plant growth and physiology, such as sprays to prevent premature flowering and dropping of fruits,” says DiSTAP co-lead principal investigator Michael Strano, the Carbon P. Dubbs Professor of Chemical Engineering at MIT. “This technology can replace current state-of-the-art sensing methods which are laborious, destructive, and unsafe.”

      Of the two sensors developed by the research team, the 2,4-D nanosensor also showed the ability to detect herbicide susceptibility, enabling farmers and agricultural scientists to quickly find out how vulnerable or resistant different plants are to herbicides without the need to monitor crop or weed growth over days. “This could be incredibly beneficial in revealing the mechanism behind how 2,4-D works within plants and why crops develop herbicide resistance,” says DiSTAP and TLL Principal Investigator Rajani Sarojam.

      “Our research can help the industry gain a better understanding of plant growth dynamics and has the potential to completely change how the industry screens for herbicide resistance, eliminating the need to monitor crop or weed growth over days,” says Mervin Chun-Yi Ang, a research scientist at DiSTAP. “It can be applied across a variety of plant species and planting mediums, and could easily be used in commercial setups for rapid herbicide susceptibility testing, such as urban farms.”

      NTU Professor Mary Chan-Park Bee Eng says, “Using nanosensors for in planta detection eliminates the need for extensive extraction and purification processes, which saves time and money. They also use very low-cost electronics, which makes them easily adaptable for commercial setups.”

      The team says their research can lead to future development of real-time nanosensors for other dynamic plant hormones and metabolites in living plants as well.

      The development of the nanosensor, optical detection system, and image processing algorithms for this study was done by SMART, NTU, and MIT, while TLL validated the nanosensors and provided knowledge of plant biology and plant signaling mechanisms. The research is carried out by SMART and supported by NRF under its Campus for Research Excellence And Technological Enterprise (CREATE) program.

      DiSTAP is one of the five interdisciplinary research roups in SMART. The DiSTAP program addresses deep problems in food production in Singapore and the world by developing a suite of impactful and novel analytical, genetic, and biosynthetic technologies. The goal is to fundamentally change how plant biosynthetic pathways are discovered, monitored, engineered, and ultimately translated to meet the global demand for food and nutrients.

      Scientists from MIT, TTL, NTU, and National University of Singapore (NUS) are collaboratively developing new tools for the continuous measurement of important plant metabolites and hormones for novel discovery, deeper understanding and control of plant biosynthetic pathways in ways not yet possible, especially in the context of green leafy vegetables; leveraging these new techniques to engineer plants with highly desirable properties for global food security, including high yield density production, drought, and pathogen resistance and biosynthesis of high-value commercial products; developing tools for producing hydrophobic food components in industry-relevant microbes; developing novel microbial and enzymatic technologies to produce volatile organic compounds that can protect and/or promote growth of leafy vegetables; and applying these technologies to improve urban farming.

      DiSTAP is led by Michael Strano and Singapore co-lead principal investigator Professor Chua Nam Hai.

      SMART was established by MIT, in partnership with the NRF, in 2007. SMART, the first entity in CREATE, serves as an intellectual and innovation hub for research interactions between MIT and Singapore, undertaking cutting-edge research projects in areas of interest to both. SMART currently comprises an Innovation Center and five interdisciplinary research groups: Antimicrobial Resistance (AMR), Critical Analytics for Manufacturing Personalized-Medicine (CAMP), DiSTAP, Future Urban Mobility (FM), and Low Energy Electronic Systems (LEES). SMART is funded by the NRF. More

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      A new way to detect the SARS-CoV-2 Alpha variant in wastewater

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      Researchers from the Antimicrobial Resistance (AMR) interdisciplinary research group at the Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, alongside collaborators from Biobot Analytics, Nanyang Technological University (NTU), and MIT, have successfully developed an innovative, open-source molecular detection method that is able to detect and quantify the B.1.1.7 (Alpha) variant of SARS-CoV-2. The breakthrough paves the way for rapid, inexpensive surveillance of other SARS-CoV-2 variants in wastewater.

      As the world continues to battle and contain Covid-19, the recent identification of SARS-CoV-2 variants with higher transmissibility and increased severity has made developing convenient variant tracking methods essential. Currently, identified variants include the B.1.17 (Alpha) variant first identified in the United Kingdom and the B.1.617.2 (Delta) variant first detected in India.

      Wastewater surveillance has emerged as a critical public health tool to safely and efficiently track the SARS-CoV-2 pandemic in a non-intrusive manner, providing complementary information that enables health authorities to acquire actionable community-level information. Most recently, viral fragments of SARS-CoV-2 were detected in housing estates in Singapore through a proactive wastewater surveillance program. This information, alongside surveillance testing, allowed Singapore’s Ministry of Health to swiftly respond, isolate, and conduct swab tests as part of precautionary measures.

      However, detecting variants through wastewater surveillance is less commonplace due to challenges in existing technology. Next-generation sequencing for wastewater surveillance is time-consuming and expensive. Tests also lack the sensitivity required to detect low variant abundances in dilute and mixed wastewater samples due to inconsistent and/or low sequencing coverage.

      The method developed by the researchers is uniquely tailored to address these challenges and expands the utility of wastewater surveillance beyond testing for SARS-CoV-2, toward tracking the spread of SARS-CoV-2 variants of concern.

      Wei Lin Lee, research scientist at SMART AMR and first author on the paper adds, “This is especially important in countries battling SARS-CoV-2 variants. Wastewater surveillance will help find out the true proportion and spread of the variants in the local communities. Our method is sensitive enough to detect variants in highly diluted SARS-CoV-2 concentrations typically seen in wastewater samples, and produces reliable results even for samples which contain multiple SARS-CoV-2 lineages.”

      Led by Janelle Thompson, NTU associate professor, and Eric Alm, MIT professor and SMART AMR principal investigator, the team’s study, “Quantitative SARS-CoV-2 Alpha variant B.1.1.7 Tracking in Wastewater by Allele-Specific RT-qPCR” has been published in Environmental Science & Technology Letters. The research explains the innovative, open-source molecular detection method based on allele-specific RT-qPCR that detects and quantifies the B.1.1.7 (Alpha) variant. The developed assay, tested and validated in wastewater samples across 19 communities in the United States, is able to reliably detect and quantify low levels of the B.1.1.7 (Alpha) variant with low cross-reactivity, and at variant proportions down to 1 percent in a background of mixed SARS-CoV-2 viruses.

      Targeting spike protein mutations that are highly predictive of the B.1.1.7 (Alpha) variant, the method can be implemented using commercially available RT-qPCR protocols. Unlike commercially available products that use proprietary primers and probes for wastewater surveillance, the paper details the open-source method and its development that can be freely used by other organizations and research institutes for their work on wastewater surveillance of SARS-CoV-2 and its variants.

      The breakthrough by the research team in Singapore is currently used by Biobot Analytics, an MIT startup and global leader in wastewater epidemiology headquartered in Cambridge, Massachusetts, serving states and localities throughout the United States. Using the method, Biobot Analytics is able to accept and analyze wastewater samples for the B.1.1.7 (Alpha) variant and plans to add additional variants to its analysis as methods are developed. For example, the SMART AMR team is currently developing specific assays that will be able to detect and quantify the B.1.617.2 (Delta) variant, which has recently been identified as a variant of concern by the World Health Organization.

      “Using the team’s innovative method, we have been able to monitor the B.1.1.7 (Alpha) variant in local populations in the U.S. — empowering leaders with information about Covid-19 trends in their communities and allowing them to make considered recommendations and changes to control measures,” says Mariana Matus PhD ’18, Biobot Analytics CEO and co-founder.

      “This method can be rapidly adapted to detect new variants of concern beyond B.1.1.7,” adds MIT’s Alm. “Our partnership with Biobot Analytics has translated our research into real-world impact beyond the shores of Singapore and aid in the detection of Covid-19 and its variants, serving as an early warning system and guidance for policymakers as they trace infection clusters and consider suitable public health measures.”

      The research is carried out by SMART and supported by the National Research Foundation (NRF) Singapore under its Campus for Research Excellence And Technological Enterprise (CREATE) program.

      SMART was established by MIT in partnership with the National Research Foundation of Singapore (NRF) in 2007. SMART is the first entity in CREATE developed by NRF. SMART serves as an intellectual and innovation hub for research interactions between MIT and Singapore, undertaking cutting-edge research projects in areas of interest to both Singapore and MIT. SMART currently comprises an Innovation Center and five IRGs: AMR, Critical Analytics for Manufacturing Personalized-Medicine, Disruptive and Sustainable Technologies for Agricultural Precision, Future Urban Mobility, and Low Energy Electronic Systems.

      The AMR interdisciplinary research group is a translational research and entrepreneurship program that tackles the growing threat of antimicrobial resistance. By leveraging talent and convergent technologies across Singapore and MIT, AMR aims to develop multiple innovative and disruptive approaches to identify, respond to, and treat drug-resistant microbial infections. Through strong scientific and clinical collaborations, its goal is to provide transformative, holistic solutions for Singapore and the world. More

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      Engineering seeds to resist drought

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      As the world continues to warm, many arid regions that already have marginal conditions for agriculture will be increasingly under stress, potentially leading to severe food shortages. Now, researchers at MIT have come up with a promising process for protecting seeds from the stress of water shortage during their crucial germination phase, and even providing the plants with extra nutrition at the same time.

      The process, undergoing continued tests in collaboration with researchers in Morocco, is simple and inexpensive, and could be widely deployed in arid regions, the researchers say. The findings are reported this week in the journal Nature Food, in a paper by MIT professor of civil and environmental engineering Benedetto Marelli, MIT doctoral student Augustine Zvinavashe ’16, and eight others at MIT and at the King Mohammed VI Polytechnic University in Morocco.

      The two-layer coating the team developed is a direct outgrowth of years of research by Marelli and his collaborators in developing seed coatings to confer various benefits. A previous version enabled seeds to resist high salinity in the soil, but the new version is aimed at tackling water shortages.

      “We wanted to make a coating that is specific to tackling drought,” Marelli explains. “Because there is clear evidence that climate change is going to impact the basin of the Mediterranean area,” he says, “we need to develop new technologies that can help to mitigate these changes in the climate patterns that are going to make less water available to agriculture.”

      The new coating, taking inspiration from natural coatings that occur on some seeds such as chia and basil, is engineered to protect the seeds from drying out. It provides a gel-like coating that tenaciously holds onto any moisture that comes along, and envelops the seed with it.

      A second, inner layer of the coating contains preserved microorganisms called rhizobacteria, and some nutrients to help them grow. When exposed to soil and water, the microbes will fix nitrogen into the soil, providing the growing seedling with nutritious fertilizer to help it along.

      “Our idea was to provide multiple functions to the seed coating,” Marelli says, “not only targeting this water jacket, but also targeting the rhizobacteria. This is the real added value to our seed coating, because these are self-replicating microorganisms that can fix nitrogen for the plants, so they can decrease the amount of nitrogen-based fertilizers that are provided, and enrich the soil.”

      Early tests using soil from Moroccan test farms have shown encouraging results, the researchers say, and now field tests of the seeds are underway.

      Ultimately, if the coatings prove their value through further tests, the coatings are simple enough that they could be applied at a local level, even in remote locations in the developing world. “It can be done locally,” Zvinavashe says. “That’s one of the things we were thinking about while we were designing this. The first layer you could dip coat, and then the second layer, you can spray it on. These are very simple processes that farmers could do on their own.” In general, though, Zvinavashe says it would be more economical to do the coatings centrally, in facilities that can more easily preserve and stabilize the nitrogen-fixing bacteria.

      The materials needed for the coatings are readily available and often used in the food industry already, Marelli says. The materials are also fully biodegradable, and some of the compounds themselves can actually be derived from food waste, enabling the eventual possibility of closed-loop systems that continuously recycle their own waste.

      Although the process would add a small amount to the cost of the seeds themselves, Marelli says, it may also produce savings by reducing the need for water and fertilizer. The net balance of costs and benefits remains to be determined through further research.

      Although initial tests using common beans have shown promising results by a variety of measures, including root mass, stem height, chlorophyll content, and other metrics, the team has not yet cultivated a full crop from seeds with the new coating all the way through to harvest, which will be the ultimate test of its value. Assuming that it does improve harvest yields under arid conditions, the next step will be to extend the research to a variety of other important crop seeds, the researchers say.

      “The system is so simple that it can be applied to any seed,” Marelli says. “And we can design the seed coating to respond to different climate patterns.” It might even be possible to tailor coatings to the predicted rainfall of a particular growing season, he says.

      “This is very important work,” says Jason C. White, director of the Connecticut Agricultural Experiment Station and a professor of epidemiology at Yale University, who was not associated with this study. “Maintaining global food security in the coming decades will be among the most significant challenges we face as a species. … This approach fits the description of an important tool in that effort; sustainable, responsive and effective.”

      White says, “Seed coating technologies are not new, but nearly all existing approaches lack versatility or responsiveness.” The new work, he says, is “both novel and innovative,” and “really opens a new avenue of work for responsive seed coatings to mediate tolerance to a range of biotic and abiotic stressors.”

      The team included Julie Laurent, Salma Mouhib, Hui Sun, Henri Manu Effa Fouda, Doyoon Kim, Manal Mhada, and Lamfeddal Kouisni at MIT and at King Mohammad VI Polytechnic University in Ben-Guerir, Morocco. The work was partly supported by the U.S. Office of Naval Research, the National Science Foundation, and the MIT Paul M. Cook Career Development Professorship. More

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      Unleashing capacity at Heineken México with systems thinking from MIT

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      It’s no secret that a manufacturer’s ability to maintain and ideally increase production capability is the basis for long-run competitive success. But discovering a way to significantly increase production without buying a single piece of new equipment — that may strike you as a bit more surprising. 

      Global beer manufacturer Heineken is the second-largest brewer in the world. Founded in 1864, the company owns over 160 breweries in more than 70 countries and sells more than 8.5 million barrels of its beer brands in the United States alone. In addition to its sustained earnings, the company has demonstrated significant social and environmental responsibility, making it a globally admired brand. Now, thanks to a pair of MIT Sloan Executive Education alumni, the the firm has applied data-driven developments and AI augmentation to its operations, helping it solve a considerable production bottleneck that unleashed hidden capacity in the form of millions of cases of beer at its plant in México.

      Little’s Law, big payoffs

      Federico Crespo, CEO of fast-growing industrial tech company Valiot.io, and Miguel Aguilera, supply chain digital transformation and innovation manager at Heineken México, first met at the MIT Sloan Executive Education program Implementing Industry 4.0: Leading Change in Manufacturing and Operations. During this short course led by John Carrier, senior lecturer in the System Dynamics Group at MIT Sloan, Crespo and Aguilera acquired the tools they needed to spark a significant improvement process at Mexico’s largest brewery.

      Ultimately, they would use Valiot’s AI-powered technology to optimize the scheduling process in the presence of unpredictable events, drastically increasing the brewery throughput and improving worker experience. But it all started with a proper diagnosis of the problem using Little’s Law.

      Often referred to as the First Law of Operations, Little’s Law is named for John D.C. Little, a professor post tenure at MIT Sloan and an MIT Institute Professor Emeritus. Little proved that the three most important properties of any system — throughput, lead time, and work-in-process — must obey the following simple relationship:

      Little’s law formula says work-in-progress is equal to throughput multiplied by lead time.

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      Little’s Law is particularly useful for detecting and quantifying the presence of bottlenecks and lost throughput in any system. And it is one of the key frameworks taught in Carrier’s Implementing Industry 4.0 course.

      Crespo and Aguilera applied Little’s Law and worked backward through the entire production process, examining cycle times to assess wait times and identify the biggest bottlenecks in the brewery.

      Specifically, they discovered a significant bottleneck at the filtration stage. As beer moved from maturation and filtration to bright beer tanks (BBT), it was often held up waiting to be routed to the bottling and canning lines, due to various upsets and interruptions throughout the facility as well as real-time demand-based production updates.

      This would typically initiate a manual, time-intensive rescheduling process. Operators had to track down handwritten production logs to figure out the current state of the bottling lines and inventory the supply by manually entering the information into a set of spreadsheets stored on a local computer. Each time a line was down, a couple hours were lost.

      With the deficiency identified, the facility quickly took action to solve it.

      Bottlenecks introduce habits, which evolve into culture

      Once bottlenecks have been identified, the next logical step is to remove them. However, this can be particularly challenging, as persistent bottlenecks change the way the people work within the system, becoming part of worker identity and the reward system.

      “Culture can act to reject any technological advance, no matter how beneficial this technology may be to the overall system,” says Carrier. “But culture can also provide a powerful mechanism for change and serve as a problem-solving device.”

      The best approach to introducing a new technology, advises Carrier, is to find early projects that reduce human struggle, which inevitably leads to overall improvements in productivity, reliability, and safety.

      Heineken México’s digital transformation

      Working with Federico and his team at Valiot.io, and with full support of Sergio Rodriguez, vice president of manufacturing at Heineken México, Aguilera and the Monterrey brewery team began connecting the enterprise resource plan and in-floor sensors to digitize the brewing process. Valiot’s data monitors assured a complete data quality interaction with the application. Fed by real-time data, machine learning was applied for filtering and the BBT process to optimize the daily-optimized production schedule. As a result, BBT and filtration time were reduced in each cycle. Brewing capacity also increased significantly per month. The return on the investment was clear within the first month of implementation.

      The migration to digital has enabled Heineken México to have a real-time visualization of the bottling lines and filtering conditions in each batch. With AI constantly monitoring and learning from ongoing production, the technology automatically optimizes efficiency every step of the way. And, using the real-time visualization tools, human operators in the factory can now make adjustments on the fly without slowing down or stopping production. On top of that, the operators can do their jobs from home effectively, which has had significant benefits given the Covid-19 pandemic.

      The key practical aspects

      The Valoit team was required to be present on the floor with the operators to decode what they were doing, and the algorithm had to be constantly tested against performance. According to Sergio Rodriguez Garza, vice president supply chain for Heineken México, success was ultimately based on the fact that Valiot’s approach was impacting the profit and loss, not simply counting the number of use cases implemented.

      “The people who make the algorithms do not always know where the value in the facility is,” says Garza. “For this reason, it is important to create a bridge between the areas in charge of digitization and the areas in charge of the process. This process is not yet systematic; each plant has a different bottleneck, and each needs its own diagnosis. However, the process of diagnosis is systematic, and each plant manager is responsible for his/her own plant’s diagnosis of the bottleneck.”

      “A unique diagnosis is the key,” adds Carrier, “and a quality diagnosis is based on a fundamental understanding of systems thinking.” More

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      Using mechanics for cleaner membranes

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      Filtration membranes are critical to a wide variety of industries around the world. Made of materials as varied as cellulose, graphene, and nylon, they serve as the barriers that turn seawater into drinking water, separate and process milk and dairy products, and pull contaminants from wastewater. They serve as an essential technology to these and other industries but are plagued with an Achilles heel: fouling.

      Membrane fouling occurs when particles get deposited on the filter over time, clogging the system and limiting its effectiveness and efficiency. Efforts to clean, or de-foul, these membranes have typically relied on chemical processes, in which synthetic solvents are pumped through the membrane to flush the system. However, this results in losses in productivity and profit, all while raising environmental and workplace safety concerns associated with waste disposal.

      A solution to this challenge may soon be in sight. A team of researchers from the MIT Department of Mechanical Engineering, supported by a seed grant from MIT’s Abdul Latif Jameel Water and Food Systems Lab (J-WAFS), has found an alternative. Their solution was developed via a unique collaboration between researchers with expertise in fluid as well as structure dynamics.

      The team has developed a novel system that can mechanically clean membranes using controlled deformation. Their new approach, one of the first ever to combine membranes and mechanics, has the potential to be cheaper, faster, and more environmentally friendly than traditional membrane cleaning techniques, and is poised to revolutionize the way we think about filtration.

      “Fouling is the biggest problem that’s facing membranes. Being able to solve it would be a game-changer for everyone,” says Omar Labban PhD ’20 of the Department of Mechanical Engineering, a joint lead author of a new paper published in the Journal of Membrane Science.

      Controlling the pressure on either side of this membrane allows the layer of contaminants to peel off and wash away.

      Image courtesy of the researchers

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      The work got its start when two mechanical engineering professors saw the potential of uniting their areas of expertise. John Lienhard, the Abdul Latif Jameel Professor of Water and Mechanical Engineering and the director of J-WAFS, joined forces with Xuanhe Zhao, Professor of Mechanical Engineering and George N. Hatsopoulos Faculty Fellow. Lienhard is an international expert on water purification and desalination, while Zhao specializes in the field of soft materials.

      “Real-world problems, such as membrane fouling, inherently cut across disciplinary lines,” says Lienhard. “In this case, we faced both a problem of soft matter mechanics and of membrane desalination. Our team combined this disparate knowledge through a solid experimental program to achieve a more environmentally benign cleaning process.”

      The paper that details the team’s new approach was selected as an Editor’s Choice Article by the journal for February 2021. Paper co-authors Lienhard, Zhao, and Labban were also joined by co-lead author and member of the core research team driving this work, Grace Goon PhD ’20 of the Department of Aeronautics and Astronautics, and Zi Hao Foo, a former visiting student and current graduate student in mechanical engineering.

      The “Achilles heel” of filtration

      Fouling is the process through which particles are deposited on a membrane’s surface. While it occurs in any membrane filtration system, fouling is especially troublesome for desalination. As a process input, seawater has much more than salt that needs to be removed. Foulants, ranging from bacteria to organic material and minerals, can collect on reverse osmosis membranes very quickly. Once membranes become clogged, they are less effective, limiting the amount of clean water that can be produced as well as the purity of the end product.

      Unfortunately, the current cleaning solution is not ideal. Membranes used for desalination are cleaned with chemicals, which takes time, money, and resources away from filtration plant operation. Water desalination plant operators often have to stop production to flush their systems for several hours per cleaning cycle. For the dairy industry, operators need to clean the membranes multiples times a day. The chemical cocktails used to flush the systems are often proprietary, making desalination prohibitively expensive for some countries and municipalities. The environmental impact is also hefty because the plants then must figure out how to dispose of the large quantities of chemical waste without causing ecological and toxicological problems.

      Working together for a cleaner solution

      Motivated by efficiency, affordability, and environmental sustainability, the research team sought to develop a chemical-free solution enabled by the principles of mechanics. Goon, a member of the core research team, recounts the early days, when the team explored various vibration methods, including a stereo system, to shake the foulant layer off the membrane. From there, they moved on to experimenting with varying the pressure on either side of the membrane to weaken the bonded debris. Eventually, they were able to cause the layer to peel off.

      Their solution relies on a phenomenon known as membrane-foulant interfacial fatigue. Through subtle pressure changes, the team was able to gradually weaken and deform the bonded layer of foulants little by little until it could be washed away. Previous research strayed away from this method because of the fragility of the membranes, “but we’ve shown that if you’re able to actually control it properly, you can avoid damaging your membrane,” says Goon. Best of all, the method can be used on the industry-standard spiral wound membrane module, where the tightly spaced layers of membranes posed a challenge for other mechanical cleaning methods.

      While traditional chemical cleaning processes might be necessary to supplement this mechanical solution, this new method can reduce users’ reliance on chemical flushing, which benefits plant operators in multiple ways. The team’s calculations indicate that the shutdown time for cleaning would go down by a factor of six. With plants down less often, the total amount of clean water produced by the system can increase. “You’ll be saving on cost, you’ll be running the plant more, you’ll be getting more output. When cleaning no longer becomes a burden for the operator, the system is going to operate in a much better state in the long run,” explains Labban.

      These improvements provide tangible benefits to producers and consumers alike. During field research the team explored the market potential for this technology and spoke with plant operators across a number of industries who all expressed frustration with the cumbersome nature of the cleaning process. For the dairy industry alone, one that has already faced shrinking profits from the pandemic, the team estimates that a switch to mechanical cleaning could cut cleaning costs by half.

      The unique intersection of membrane technology and mechanical processes that this technology models provides a solution that many in the desalination field did not think was possible. “Suddenly you’re able to achieve a lot a lot more than before — your impact and change that you can accomplish becomes bigger,” says Labban of the chance to work on a multidisciplinary collaboration.

      The project not only brought together two specialties in the Department of Mechanical Engineering and the Department of Aeronautics and Astronautics. The team was also joined by Gabrielle Enns, Annetoinette Figueroa, Lara Ketonen, Hannah Mahaffey, Bryan T. Padilla, and Maisha Prome through MIT’s Undergraduate Research Opportunity Program. The unique perspective that each team member brought helped foster creativity and camaraderie around the lab.

      Because of the out-of-the-box approach that the interdisciplinary research team was taking, traditional funding mechanisms were not as readily available for this work. This is why the J-WAFS seed grant was so impactful. “Without J-WAFS, this work would not have happened,” says Labban. The grant allowed the research team to focus on the challenge as a primary research catalyst, as opposed to being limited to a particular technical process or structured outcome. This provided the team the freedom to take advantage of the cross-departmental collaboration that enabled the convergence of mechanics and membrane research in the name of better filtration strategies.

      The current paper primarily looks at organic foulants and the technique has only been evaluated for a limited number of industries. Looking forward, however, the team is excited to expand upon its research by applying the method across a variety of areas, including the energy and agriculture sectors. As long as membranes are being used, there is going to be a need to clean them. “We are excited to be solving the major bottleneck with membranes and desalination,” says Labban. “Nothing else compares to this challenge.” More