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Wednesday, April 25th, 2018
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Implantable islet cells come with their own oxygen supply Since the 1960s, researchers have been interested in the possibility of treating type 1 diabetes by transplanting islet cells — the pancreatic cells that are responsible for producing insulin when blood glucose concentration increases.
Implementing this approach has proven challenging, however. One obstacle is that once the islets are transplanted, they will die if they don’t receive an adequate supply of oxygen. Now, researchers at MIT, working with a company called Beta-O2 Technologies, have developed and tested an implantable device that furnishes islet cells with their own supply of oxygen, via a chamber that can be replenished every 24 hours.
“Getting oxygen to these cells is a difficult problem,” says Clark Colton, an MIT professor of chemical engineering and the senior author of the study. “The benefits of this approach are: you keep the islets alive to perform their function, you don’t need as much tissue, and you reduce the ability of the implants to provoke an immune response.”
Tests of these implants in rats showed that nearly 90 percent of the islets remained viable for several months, and most of the rats maintained normal blood glucose levels throughout that time.
Yoav Evron of Beta-O2 Technologies is the lead author of the study, which appears in the April 25 issue of Scientific Reports.
Protecting islets
Type 1 diabetes occurs when a patient’s own immune system destroys pancreas’ islet cells, so the patient can no longer produce insulin, which is necessary for the body to absorb sugar from the bloodstream. Early attempts to treat patients by transplanting islets from cadavers were unsuccessful because the islets didn’t survive after transplantation.
One of the reasons the transplanted islets failed is that they were attacked by the patients’ immune systems. To protect the transplanted cells, researchers have begun developing implants in which the islets are encapsulated in a material such as a polymer. However, a remaining challenge is making sure that the islets receive enough oxygen, Colton says.
In a healthy pancreas, all islet cells come into contact with capillaries, allowing them to receive oxygen-rich blood, at an oxygen partial pressure of about 100 millimeters of mercury (mm Hg). (Partial pressure is a measure of the concentration of an individual gas within a mixture of gases). When doctors first tried to transplant islets into diabetic patients, many of the cells did not have any direct contact with capillaries, so their oxygen supply was too low.
Previous research in Colton’s laboratory discovered that the outer surface of islets needs to be exposed to at least 50 mm Hg of oxygen to remain viable and produce insulin normally. Through a series of experiments, the MIT team, working with researchers at Beta-O2 Technologies, determined the operating conditions of the device needed for islets to stay alive and function for long periods of time while assembled in a compact form small enough to be implanted in human patients.
In the device tested in the Scientific Reports paper, islets are encapsulated in a slab of alginate, a polysaccharide produced by algae, about 600 microns thick. A membrane on one side of slab keeps out immune cells and large proteins but allows insulin, nutrients, and oxygen through. Below the slab is the gas chamber, about 5 millimeters thick, which carries atmospheric gases such as nitrogen and carbon dioxide in addition to oxygen. Oxygen flows from the chamber, across the semipermeable membrane, and into the islets embedded in the alginate slab.
As oxygen diffuses through the slab, it is gradually consumed, so the oxygen partial pressure continually drops. To ensure that the partial pressure remains at least 50 mm Hg for 24 hours, the researchers found that they needed to begin with an oxygen partial pressure of 500 mm Hg in the gas chamber.
After 24 hours, the oxygen supply is replenished through a port — a device implanted under the skin and connected to a catheter that leads to the encapsulated islets, which are also implanted under the skin.
Long-term survival
In tests in diabetic mice without immunosuppression, the researchers showed that nearly 90 percent of the islets survived the entire transplant period, which ranged from 11 weeks to eight months. They also found that most of these animals’ blood sugar levels remained normal while the devices were implanted, then rebounded to diabetic levels after they were removed.
Another benefit of this approach is that, because most of the islet cells remain alive, they are less likely to provoke an immune response. When cells die, they break down, and the resulting fragments of protein and DNA are more likely to attract the attention of the immune system.
“By keeping the cells alive, you minimize the immune response,” Colton says.
James Shapiro, a professor of surgery, medicine, and surgical oncology at the University of Alberta, who has been running an islet transplantation program there for the past 20 years, says he believes this approach holds great promise and could help to eliminate the need to give islet transplantation patients drugs to suppress their immune system.
“This kind of device can protect the cells from immune attack and deliver oxygen in a way that allows more cells to survive,” says Shapiro, who was not involved in the study. “This would allow islet cells to be transplanted in patients without antirejection drugs, which would dramatically improve the safety of what we’re doing today with islet cell transplantation.”
Researchers at Beta-O2 Technologies are now working on new versions of the device in which an oxygen storage chamber is implanted below the skin, separate from the islets. This version would only need to be replenished once a week, which could be more appealing for patients.
The research was funded, in part, by the Israeli Ministry of Sciences. | | 12:30p |
Introducing a user-friendly, step-by-step guide to conducting comparative product evaluations According to the World Bank, over 1.1 billion people have lifted themselves from extreme poverty since 1990. But even as the global outlook on extreme poverty improves, billions of people continue to struggle to access basic human needs, like water, food, shelter, health care and energy. In response to these challenges, innovators around the world have developed a preponderance of cost-effective, locally implemented solutions, from solar lanterns and water filters to improved cookstoves and refugee shelters.
With such a dizzying array of products on the market, development professionals often struggle to cut through the hype associated with novel technologies, and many are hesitant to pursue innovative approaches to stubborn development challenges, given the high stakes of working with economically vulnerable populations.
MIT researchers are now seeking to help development professionals overcome these challenges by using design thinking, together with a methodology for comparative technology evaluation that is five years in the making.
A Practitioner's Guide to Technology Evaluation in Global Development offers a user-friendly, step-by-step framework to help organizations identify development solutions that are most likely to succeed in a given context. Co-authored by the MIT Comprehensive Initiative on Technology Evaluation (CITE), a program supported by the U.S. Agency for International Development (USAID), and the Technology Exchange Lab, a Cambridge-based non-governmental organization, the Practitioner’s Guide builds upon five years of research and over 12 comparative evaluations conducted by CITE across eight countries.
A methodology for all
CITE was founded in 2013 as a leading member of USAID’s Higher Education Solutions Network, a coalition of seven universities seeking to leverage the talent of students, researchers, and faculty towards solving major global development challenges. Since then, CITE has evaluated "hardware solutions" — like solar lanterns, solar-powered water pumps, and water test kits — while also evaluating systems-level solutions, such as how distribution models affect the uptake of malaria-diagnostics, and how food-aid packaging impacts the quality and quantity of international food assistance through complex supply chains.
Throughout this work, CITE researchers from across the Institute — from MIT D-Lab, the Department of Urban Studies and Planning (DUSP), Center for Transporation and Logistics (CTL), and Sociotechnical Systems Research Center (SSRC) — developed and iterated upon a multi-disciplinary evaluation methodology known as ‘3S’ framework, which evaluates technologies from three vantages including: suitability (how well products perform technically), scalability (how effective products are at reaching consumers at scale), and sustainability (how products are adopted and used over time).
While CITE effectively applied its methodology across multiple sectors, past evaluations included rigorous lab testing, and support from faculty, graduate students and additional partners. According to CITE Associate Director Joanne Mathias, “through the Practitioner’s Guide we aim to empower practitioners and smaller-scale NGOs with the tools required to find solutions that work, regardless of the resources or facilities they have at their disposal.”
From lab to field
Translating five years of academic research into a user-friendly toolkit is no small task. By teaming up with the Technology Exchange Lab (TEL) to co-author the guide, CITE sought out a partner capable of articulating their evaluation methodology to a non-academic audience, while also weaving concepts of human-centered design into the evaluation process. Founded by two MIT Sloan School of Management alumni, TEL works with community-based organizations around the world to implement innovative solutions to problems of poverty.
“Partnering with CITE to develop the Practitioner’s Guide was a natural fit,” says TEL Programs Director Brennan Lake. “So much emphasis is made on driving innovation and research through universities, which is fantastic, but there is a bottleneck when it comes to putting research into practice, and making innovative approaches and development solutions as accessible as possible to communities on the ground.”
Indeed, the Practitioner’s Guide includes real-world examples of everyday challenges faced by development practitioners — such as how to make data-driven trade-offs between a product’s quality, affordability, and time to implement — as well as case studies based off of past CITE evaluations. The Practitioner’s Guide was also designed to be modular, so that organizations at various stages of project development could make use of CITE’s methodology.
“Most aid agencies and international NGOs already have strict procurement protocols in place,” Lake notes. “The Practitioner’s Guide provides program officers with discrete tools for evidence-based decision making, while also offering a more comprehensive framework for NGOs and community-based organizations looking to build programs from the ground up.”
A Practitioner’s Guide for Technology Evaluation in Global Development is now available on the CITE and TEL websites. CITE’s research is funded by the USAID U.S. Global Development Lab. CITE is led by principal investigator Bishwapriya Sanyal of MIT’s Department of Urban Studies and Planning, and supported by MIT faculty and staff from D-Lab, the Priscilla King Gray Public Service Center, Sociotechnical Systems Research Center, the Center for Transportation and Logistics, School of Engineering, and Sloan School of Management.
In addition to Lake, co-authors of the guide include Jennifer Green, CITE evaluation lead, and Éadaoin Ilten of the Technology Exchange Lab. Additional support was provided by Joanne Mathias. | | 12:55p |
Keeping the balance: How flexible nuclear operation can help add more wind and solar to the grid In the Southwestern United States, the country’s sunniest region, sunlight can shine down for up to 14 hours a day. This makes the location ideal for implementing solar energy — and the perfect test-bed for MIT Energy Initiative (MITEI) researcher Jesse Jenkins and his colleagues at Argonne National Laboratory to model the benefits of pairing renewable resources with more flexible operation of nuclear power plants. They report their findings in a new paper published in Applied Energy.
During summer 2015, Jenkins worked as a research fellow with Argonne National Laboratory on two power systems projects: one on the role of energy storage in a low-carbon electricity grid, and the other on the role of nuclear plants. Linking the two projects, he says, is the goal of using new sources of operating flexibility to integrate more renewable resources into the grid.
In power grids, supply and demand hang in a delicate balance on a second-to-second timeframe. Flexible backup energy sources must stay online at all times to maintain this equilibrium by meeting small variations in demand throughout the day or stepping in quickly if a power plant should suddenly go offline. If supply ever gets too far out of step with demand, devices designed to protect transmission lines and sensitive electronics from damage will quickly trip into action, causing blackouts as they work to shed demand or generation and restore the balance. Currently, certain coal, oil, natural gas, and hydro plants take on the important role of providing these standby capacity services, known as frequency regulation and operating reserves.
Nuclear power plants generally operate at full capacity, but they are also technically capable of more flexible operation. This capability lets them respond dynamically to seasonal changes in demand or hourly changes in market prices. Reactors could also provide the standby backup regulation and reserve services needed to balance supply and demand. According to Jenkins, all reactor designs now being licensed or built in the U.S., Canada, and Europe are capable of flexible operation, as are many older reactors now in service.
“We primarily rely on gas and coal plants to meet all those flexibility needs today, while we operate our nuclear plants fixed, or ‘must-run,’ 24/7,” says Jenkins. “The question here is: What would the benefits be if we stopped operating them so inflexibly, if we started using more of their technical capabilities to ‘ramp’ output up and down on different time scales from seconds to hours to seasons?” The answer, he says, is less reliance on the gas and coal plants — and more renewable energy integration.
As markets increasingly incorporate variable renewables like wind and solar, maintaining the supply-demand balance becomes more complicated. Energy demand changes over the course of the day, usually staying low overnight, spiking briefly in the morning, and then peaking in the evening when people come home from work.
“Throughout these daily and seasonal changes in electricity use, there is a constant level of demand, known as the ‘base load,’ which is invariant,” says Jenkins. “Since nuclear plants have very low operating costs and cost a lot up-front to build, they are economically well-suited to operating all the time to meet this base load.” He adds, “That’s why when nuclear plants were originally licensed in the U.S., it wasn’t really necessary for them to play a role in following demand patterns throughout the day, and so nuclear plants in the U.S. weren’t licensed to operate that way.”
However, nuclear power plants were designed for flexibility “because the engineers who designed them envisioned a world in which nuclear took over the whole system,” Jenkins explains. This never really happened, except in France, which gets over 70 percent of its electricity from nuclear and has accordingly operated some of its nuclear plants to follow changing demand for years.
Now, as power grids around the world incorporate more and more variable renewable resources like wind and solar, the value of flexibility is increasing. Nuclear plants in places with increasing renewable energy penetration, like Germany, are therefore also moving toward flexible operation.
Because power systems today have very little energy storage capability, there are a growing number of places, from California and Iowa to Germany and China, where excess renewable energy might be produced on a sunny or windy day and must simply be wasted. Rather than disabling a solar panel or wind turbine, Jenkins points out, it makes more sense to operate the nuclear plant at a lower output and to absorb as much free wind or sun as possible. And operating nuclear plants flexibly has benefits beyond integrating renewable energy and reducing carbon dioxide emissions: By cutting the amount of wasted fuel, flexible operation can increase revenue for reactor owners, enhance system reliability, and reduce electricity costs for consumers.
Optimization models are helpful in simulating the potential economic and environmental benefits of incorporating renewables, but current models for electric power systems still represent nuclear units as inflexible, must-run resources. Jenkins and the research team at Argonne are closing this gap by developing a new approach to modeling flexible nuclear operation and employing this novel technique to study the potential benefits in power systems with relatively high shares of variable renewable energy sources. They simulated six cases in the American Southwest, ranging from inflexible nuclear plants, to plants with moderate flexibility, to those with high flexibility.
Modeling flexible nuclear plant operation poses its own challenges. A nuclear reactor has a range of operating constraints that arise from the physics of nuclear reactors and are distinct from the technical constraints on more conventional coal- or gas-fired power plants. For example, the minimum stable output of a nuclear reactor changes over the course of the fuel irradiation cycle, and production can’t be ramped up or down too quickly without causing a strain on the nuclear fuel rods and the reactor itself. “The task was to try to synthesize the main physical engineering constraints limiting the ability of reactors to change their output on different timescales, and then translate that into the mathematical constraints that we use in modeling and optimization for the power system,” says co-author Audun Botterud, a principal research scientist in Argonne’s Energy Systems Division and in MIT’s Laboratory for Information and Decision Systems.
The research team created a “mixed integer linear programming” (MILP) formulation that accounts for the specific operating constraints on ramp maneuvers of nuclear power plants. “It’s a mathematical program that minimizes the cost of operating the power grid over the whole year while respecting the engineering constraints that power system operators and individual power plants have to maintain,” Jenkins explains. The simulation works in two stages, optimizing for demand predicted one day in advance and then in real time — matching the way the electricity markets work in the U.S.
The MILP formulation has applications beyond the specific region studied. “The general findings would hold in other places with similar shares of these two resources [nuclear and renewables],” says Jenkins. And, importantly, the study demonstrates how one of the world’s biggest sources of low-carbon energy (nuclear) and the world’s fastest growing energy source (renewables) can work together rather than replace each other.
“What this study shows is that rather than shut down nuclear plants, you can operate them in a way that makes room for renewables,” says Jenkins. “It shows that flexible nuclear plants can play much better with variable renewables than many people think, which might lead to reevaluations of the role of these two resources together.”
“Bridging the different knowledge bases, between folks who do power system modeling at the grid level and nuclear engineers and physicists who understand the details of nuclear reactor dynamics, was the most challenging but also the most interesting and productive aspect of this project,” says Jenkins. “These are two communities that don’t always talk to each other, and they speak different languages and have different backgrounds and expertise. This kind of collaboration is an example of the unique interdisciplinary work that can happen at a place like a national laboratory or the MIT Energy Initiative.”
This research was supported by Argonne National Laboratory and the National Science Foundation. |
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