Wednesday, May 1st, 2019

Time	Event
12:30p	Quantum measurement could improve gravitational wave detection sensitivity Minutes before dawn on Sept. 14, 2015, the Laser Interferometer Gravitational-wave Observatory (LIGO) became the first-ever instrument on Earth to directly detect a gravitational wave. This work, led by the LIGO Scientific Collaboration with prominent roles from MIT and Caltech, was the first confirmation of this consequence of Albert Einstein’s theory of general relativity — 100 years after he first predicted it. The groundbreaking detection represented an enormous step forward in the field of astrophysics. In the years since, scientists have striven to achieve even greater sensitivity in the LIGO detectors. New research has taken investigators one step closer to this goal. Nergis Mavalvala, the Curtis and Kathleen Marble Professor of Astrophysics at MIT, postdoc Robert Lanza, graduate student Nancy Aggarwal, and their collaborators at Louisiana State University (LSU) recently conducted experiments that could help overcome a future limitation in Advanced LIGO. In their laboratory study, the team successfully measured a type of noise that will soon hold the LIGO instruments back from detecting gravitational waves with greater sensitivity. Their study, reported recently in Nature, was the first to measure an important source of quantum noise at room temperature and at frequencies relevant to gravitational wave detectors. Funded by the National Science Foundation, this work could enable researchers to understand this limiting noise source and test ideas for circumventing it to further increase LIGO’s sensitivity to gravitational waves. In addition to future applications for improving LIGO’s detection abilities, Mavalvala says these observations of quantum effects at room temperature could help scientists learn more about how quantum mechanics can disturb the precision of measurements generally — and how best to get around these quantum noise limits. “This result was important for the gravitational wave community,” says Mavalvala. “But more broadly, this is essentially a room-temperature quantum resource, and that's something that many communities should care about.” Sensitivity upgrade LIGO has undergone upgrades since its first gravitational wave searches in 2002; the currently operating version of the instrumentation is called Advanced LIGO following major upgrades in 2015. But to get LIGO to its maximum design sensitivity, Mavalvala says her team needs to be able to conduct experiments and test improvement strategies in the laboratory rather than on the LIGO instruments themselves. LIGO’s astrophysical detection work is too important to interfere with, so she and her collaborators have developed instruments in the lab that can mimic the sensitivity of the real thing. In this case, the team aimed to reproduce processes that occur in LIGO to measure a type of noise called quantum radiation pressure noise (QRPN). In LIGO, gravitational waves are detected by using lasers to probe the motion of mirrors. The mirrors are suspended as pendulums, allowing them to have periodic motion similar to a mass on a spring. When laser beams hit the movable mirrors, the momentum carried by the light applies pressure on the mirror and causes them to move slightly. “I like to think of it like a pool table,” says Aggarwal. “When your white cue ball strikes the ball in front of it, the cue ball comes back but it still moves the other ball. When a photon that was traveling forward then travels backwards, the momentum went somewhere; [in this case] that momentum went into the mirror.” The quantum nature of light, which is made up of photons, dictates that there are quantum fluctuations in the number of photons hitting the mirrors, creating an uncertain amount of force on the mirrors at any given moment. This uncertainty results in random perturbations of the mirror. When the laser power is high enough, this QRPN can interfere with gravitational wave detection. At Advanced LIGO’s full design sensitivity, with many hundreds of kilowatts of laser power hitting 40-kilogram mirrors, QRPN will become a dominant limitation. Minuscule mirrors To address this imminent issue, Mavalvala, Aggarwal, and their collaborators designed an experiment to recreate the effects of QRPN in a laboratory setting. One challenge was that the team could not use lasers as powerful as those in Advanced LIGO in their lab experiments. The greater the laser power and the lighter the mass of the mirror oscillator, the stronger the radiation pressure-driven motion. To be able to detect this motion with less laser power, they needed to create an extremely low-mass mirror oscillator. They scaled down the 40-kilogram mirrors of Advanced LIGO with a 100-nanogram mirror oscillator (less than the mass of a grain of salt). The team also faced the significant challenge of designing a mirror oscillator that could exhibit quantum behavior at room temperature. Previously, observing quantum effects like QRPN required cryogenic cooling so that the motion due to heat energy of the oscillator would not mask the QRPN. In addition to being challenging and impractical, vibrations associated with cryogenic cooling interferes with LIGO’s operation, so conducting experiments at room temperature would be more readily applicable to LIGO itself. After many iterations of design and testing, Mavalvala and her MIT colleagues designed a mirror oscillator that allowed the team to reach a low enough level of thermally driven fluctuations that the mirror motion was dominated by QRPN at room temperature — the first-ever study to do so. “It’s really pretty mind-boggling that we can observe this room-temperature, macroscopic object — you can see it with the naked eye if you squint enough — being pushed around by quantum fluctuations,” Mavalvala says. “Its thermal jitter is small enough that it’s being tickled ever-so-slightly by quantum fluctuations, and we can measure that.” This was also the first study to detect QRPN at frequencies relevant to gravitational wave detectors. Their success means that they can now design additional experiments that reflect the radiation pressure conditions in Advanced LIGO itself. “This experiment mimics an important noise source in Advanced LIGO,” says Mavalvala. “It's now a test bed where we can try out new ideas for improving Advanced LIGO without impinging on the instrument’s own operating time.” Advanced LIGO does not yet run its lasers at strong enough power for QRPN to be a limiting factor in gravitational wave detections. But, as the instruments become more sensitive, this type of noise will soon become a problem and limit Advanced LIGO’s capabilities. When Mavalvala and her collaborators recognized QRPN as an imminent issue, they strove to recreate its effects in the laboratory so that they can start exploring ways to overcome this challenge. “We've known for a long time that this QRPN would be a limitation for Advanced LIGO,” says Mavalvala. “Now that we are able to reproduce that effect in a laboratory setting, we can start to test ideas for how to improve that limit.” Mavalvala’s primary collaborator at LSU was Thomas Corbitt, an associate professor of physics and astronomy. Corbitt was formerly a graduate student and post-doctoral scholar in Mavalvala’s lab at MIT. They have since collaborated for many years. “This is the first time this effect has been observed in a system similar to gravitational wave interferometers and in LIGO’s frequency band,” says Corbitt. “While this work was motivated by the imperative to make ever-more-sensitive gravitational wave detectors, it is of wide interest.” New directions Since the original detection of a binary black hole merger in 2015, LIGO has also captured signals from collisions of neutron stars, as well as additional black hole collisions. These waves ripple outward from interactions that can take place more than a billion light years away. While LIGO’s capabilities are impressive, Mavalvala and her team plan to continue finding ways to make LIGO even more powerful. Before they collide, black holes, for example, orbit each other slowly and at lower frequencies. As the two black holes get closer, their orbits speed up and they swirl around each other at high speeds and high frequencies. If Advanced LIGO becomes sensitive enough to pick up lower frequencies, Mavalvala says we may someday detect these systems earlier in the process, before the pair collides, allowing us to draw an ever-clearer picture of these distant spacetime phenomena. She and her team aim to make sure that factors such as QRPN don’t limit Advanced LIGO’s growing power. “At this moment in time, Advanced LIGO is the best it can be at its job: to look out at the sky and detect gravitational wave events,” says Mavalvala. “In parallel, we have all of these ideas for making it better, and we have to be able to try those out in laboratories. This measurement allows that to happen with QRPN for the first time.” (Comment on this)
12:59p	A comprehensive map of how Alzheimer’s affects the brain MIT researchers have performed the first comprehensive analysis of the genes that are expressed in individual brain cells of patients with Alzheimer’s disease. The results allowed the team to identify distinctive cellular pathways that are affected in neurons and other types of brain cells. This analysis could offer many potential new drug targets for Alzheimer’s, which afflicts more than 5 million people in the United States. “This study provides, in my view, the very first map for going after all of the molecular processes that are altered in Alzheimer’s disease in every single cell type that we can now reliably characterize,” says Manolis Kellis, a professor of computer science and a member of MIT’s Computer Science and Artificial Intelligence Laboratory and of the Broad Institute of MIT and Harvard. “It opens up a completely new era for understanding Alzheimer’s.” The study revealed that a process called axon myelination is significantly disrupted in patients with Alzheimer’s. The researchers also found that the brain cells of men and women vary significantly in how their genes respond to the disease. Kellis and Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory, are the senior authors of the study, which appears in the May 1 online edition of Nature. MIT postdocs Hansruedi Mathys and Jose Davila-Velderrain are the lead authors of the paper. Single-cell analysis The researchers analyzed postmortem brain samples from 24 people who exhibited high levels of Alzheimer’s disease pathology and 24 people of similar age who did not have these signs of disease. All of the subjects were part of the Religious Orders Study, a longitudinal study of aging and Alzheimer’s disease. The researchers also had data on the subjects’ performance on cognitive tests. The MIT team performed single-cell RNA sequencing on about 80,000 cells from these subjects. Previous studies of gene expression in Alzheimer’s patients have measured overall RNA levels from a section of brain tissue, but these studies don’t distinguish between cell types, which can mask changes that occur in less abundant cell types, Tsai says. “We wanted to know if we could distinguish whether each cell type has differential gene expression patterns between healthy and diseased brain tissue,” she says. “This is the power of single-cell-level analysis: You have the resolution to really see the differences among all the different cell types in the brain.” Using the single-cell sequencing approach, the researchers were able to analyze not only the most abundant cell types, which include excitatory and inhibitory neurons, but also rarer, non-neuronal brain cells such as oligodendrocytes, astrocytes, and microglia. The researchers found that each of these cell types showed distinct gene expression differences in Alzheimer’s patients. Some of the most significant changes occurred in genes related to axon regeneration and myelination. Myelin is a fatty sheath that insulates axons, helping them to transmit electrical signals. The researchers found that in the individuals with Alzheimer’s, genes related to myelination were affected in both neurons and oligodendrocytes, the cells that produce myelin. Most of these cell-type-specific changes in gene expression occurred early in the development of the disease. In later stages, the researchers found that most cell types had very similar patterns of gene expression change. Specifically, most brain cells turned up genes related to stress response, programmed cell death, and the cellular machinery required to maintain protein integrity. Bruce Yankner, a professor of genetics and neurology at Harvard Medical School, described the study as “a tour de force of molecular pathology.” “This is the first comprehensive application of single-cell RNA sequencing technology to Alzheimer’s disease,” says Yankner, who was not involved in the research. “I anticipate this will be a very valuable resource for the field and will advance our understanding of the molecular basis of the disease.” Sex differences The researchers also discovered correlations between gene expression patterns and other measures of Alzheimer’s severity such as the level of amyloid plaques and neurofibrillary tangles, as well as cognitive impairments. This allowed them to identify “modules” of genes that appear to be linked to different aspects of the disease. “To identify these modules, we devised a novel strategy that involves the use of an artificial neural network and which allowed us to learn the sets of genes that are linked to the different aspects of Alzheimer’s disease in a completely unbiased, data-driven fashion,” Mathys says. “We anticipate that this strategy will be valuable to also identify gene modules associated with other brain disorders.” The most surprising finding, the researchers say, was the discovery of a dramatic difference between brain cells from male and female Alzheimer’s patients. They found that excitatory neurons and other brain cells from male patients showed less pronounced gene expression changes in Alzheimer’s than cells from female individuals, even though those patients did show similar symptoms, including amyloid plaques and cognitive impairments. By contrast, brain cells from female patients showed dramatically more severe gene-expression changes in Alzheimer’s disease, and an expanded set of altered pathways. “That’s when we realized there’s something very interesting going on. We were just shocked,” Tsai says. So far, it is unclear why this discrepancy exists. The sex difference was particularly stark in oligodendrocytes, which produce myelin, so the researchers performed an analysis of patients’ white matter, which is mainly made up of myelinated axons. Using a set of MRI scans from 500 additional subjects from the Religious Orders Study group, the researchers found that female subjects with severe memory deficits had much more white matter damage than matched male subjects.  More study is needed to determine why men and women respond so differently to Alzheimer’s disease, the researchers say, and the findings could have implications for developing and choosing treatments. “There is mounting clinical and preclinical evidence of a sexual dimorphism in Alzheimer’s predisposition, but no underlying mechanisms are known. Our work points to differential cellular processes involving non-neuronal myelinating cells as potentially having a role. It will be key to figure out whether these discrepancies protect or damage the brain cells only in one of the sexes — and how to balance the response in the desired direction on the other,” Davila-Velderrain says. The researchers are now using mouse and human induced pluripotent stem cell models to further study some of the key cellular pathways that they identified as associated with Alzheimer’s in this study, including those involved in myelination. They also plan to perform similar gene expression analyses for other forms of dementia that are related to Alzheimer’s, as well as other brain disorders such as schizophrenia, bipolar disorder, psychosis, and diverse dementias. The research was funded by the National Institutes of Health, the JBP Foundation, and the Swiss National Science Foundation. (Comment on this)
2:30p	Study: For low-income countries, climate action pays off by 2050 The following announcement was released jointly by MIT and the International Food Policy Research Institute. Successful global efforts to substantially limit greenhouse gas emissions would likely boost GDP growth of poorer countries over the next 30 years, according to new research published in Climatic Change. Researchers examined the impact global climate change mitigation would have on the economies of poorer countries — specifically Malawi, Mozambique, and Zambia. Devastation in Mozambique and Malawi recently caused by cyclones Idai and Kenneth vividly demonstrate the crippling impact that extreme weather events can have on these economies. Climate change is widely expected to increase the intensity and frequency of extreme weather events such as extreme heat, droughts, and floods as well as to magnify the destructive power of cyclones like Idai and Kenneth due to sea-level rise. The study shows that beyond the benefits of reduced extreme weather in the long term, global mitigation efforts would also lower oil prices in coming decades, resulting in a significant economic boon for most poorer countries.  “It is abundantly clear that many low-income countries will bear the brunt of climate change impacts over the long term, and that successful efforts to rein in emissions will lessen this blow,” says lead author Channing Arndt, director of the Environment and Production Technology Division at the International Food Policy Research Institute (IFPRI). “Our research now provides another rationale for robust climate action: the economic benefits of mitigation arrive much sooner than previously thought.” Lowering greenhouse gas emissions creates two sources of economic gain for poorer countries. First, effective global mitigation policies would reduce changes in local weather patterns and lower the odds of damaging extreme events, allowing for more economic growth than if climate change is unimpeded and more extreme weather damages economic activity.  Second, successful mitigation policies would cause oil prices to drop due to a reduction in oil demand. If richer nations take the lead in restraining their oil use, lower-income countries will be able to transition somewhat later while benefiting from much lower oil prices during the transition period. Since nearly all low-income countries are net oil importers, such price drops would represent a significant economic windfall. The research suggests that by 2050 these two sources of economic benefit together could increase the average GDP of Malawi, Mozambique, and Zambia by between 2 and 6 percentage points — gains that cannot occur if greenhouse gas emissions continue unabated. “Previous research into the economic impacts of global climate mitigation has tended to group oil exporters, such as Nigeria and Angola, and oil importers, such as Malawi and Zambia, together in a single aggregate region that both exports and imports oil,” says Sergey Paltsev, deputy director of the MIT Joint Program on the Science and Policy of Global Change. “When you look at the impacts on a country level though, most low-income countries benefit not only from having a more stable climate but also from lower fuel prices, because they are net fuel importers and the import volumes are large relative to the size of their economies.” How emissions policies should be structured globally remains an open question. The models producing these results assume that low-income countries are afforded space to transition more slowly because their contributions to global emissions are relatively low and such exemption allows low-income countries to proceed with the benefit of experience accumulated elsewhere. But the researchers caution that for climate mitigation to be effective, some developing countries cannot be exempted for long — many middle-income countries will soon need to adhere to required emissions reductions. “The impact of climate change is not likely to be distributed equally across the planet, and neither are any costs associated with reducing emissions,” says Arndt. “We want to limit the deleterious effects of climate change on the environment and on people, particularly poor people, while avoiding harming development prospects in the process. The gains from effective mitigation shown by this research could help us achieve this goal.” (Comment on this)

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