YSM Issue 91.3

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PHOTOGRAPHY BY XINYUAN CHEN Researchers and doctors can now read PET images to directly measure cognitive decline using the tracer 11 C-UCB-J to measure protein SV2A and identify the synaptic density in the brain. occurs. With the development of SV2A- PET imaging, researchers are now able to measure synaptic connections in the brains of living humans using tracers that bind to this protein. Because the measurement of SV2A can indicate synaptic density and synaptic loss, it can be used to measure cognitive decline. Researchers used a radioactive tracer, called 11C-UCB-J, that binds to the SV2A protein, and set out to compare whether tracer binding of SV2A could be used as a quantitative measure of synaptic density. These measurements were taken using Positron Emission Tomography (PET) scans, an imaging test that uses radioactive tracers to detect targeted areas in the body. PET scans of patients injected with radioactive tracer 11C-UCB-J can detect SV2A and show how much is present. Researchers found that patients affected by Alzheimer’s had a reduced amount of the tracer binding to SV2A in the hippocampus, a region of the brain involved with memory. This may be confirmation that the cognitive decline of Alzheimer’s is directly related to a reduction of synaptic density. Furthermore, the measurement of protein SV2A will help to evaluate changes in synaptic density overtime. This may lead to early detection of disease and faster drug development. “There is so much variability in this disease–in the way it progresses and in the exact types of symptoms people have,” Mecca said. Prevention Current medications for Alzheimer’s do not stop the progression of disease and have only a modest effect. “We do not recommend early treatment right now with current medications since there is no evidence that they help during early disease stages,” said Mecca. In addition, the potential benefit must be balanced with the possible negative side effects associated with medication use. For some patients, current medications are more of a burden than an aid. “Once the patient has lost a lot of synaptic density, it may be too late,” Chen said. As a result, future treatments may need to begin as early as possible. The earlier that experimental treatments may begin, the better chance there is for it to work. Though amyloid PET is a great tool for detecting early signs of disease, and identifying a high-risk population, these scans are not helpful without effective preventive treatment. “People are very knowledgeable, [and] if they feel like they have something, they will find a specialist to check if it is really cognitive decline or just their anxiety,” Chen said. In this way, education for detecting Alzheimer’s symptoms is necessary, and self-awareness–differentiating between accidentally forgetting your keys on the way to work and getting lost on the way home after taking the same route every day for three years–is very important. In addition to drugs, Alzheimer’s patients may be treated for neuropsychological symptoms, such as depression, anxiety, or irritability. Educating family members, finding resources for support, and enrolling in behavioral therapy are all methods for reducing the progression of this disease. For some, the neurodegenerative decline of Alzheimer’s seems to occur much faster than others. Those with a strong family history for this disease are at a higher risk for developing Alzheimer’s, but inherited genetic ABOUT THE AUTHOR neuroscience PHOTOGRAPHY BY XINYUAN CHEN Dr. Mecca, a member of the Yale research team, is pictured in front of PET images of the brain, which exhibit the differences in synaptic density between a normal adult and an Alzheimer’s patient. Alzheimer’s from a single gene mutation is extremely rare. “[Alzheimer’s] is an unavoidable disease unless you can really find what the cause for this disease is,” Chen said. The research team hopes to increase the number of participants in this study and collaborate with other Alzheimer’s research teams to better study the measurement of synaptic density and cognitive decline–especially how synaptic density changes over time. In addition to studying synaptic density, these researchers are pursuing other projects to further explore the impact of other proteins and signals in the brain that contribute to Alzheimer’s. One project aims to use tracers to identify a relationship between neurofibrillary tangles and patterns of synaptic density. “There is a lot we can do to characterize this disease, and also some goals for developing tools that can help us to do good clinical trials to find disease cures,” Mecca said. The future of Alzheimer’s research is a positive one. With a better understanding for the mechanisms of this disease, there is a greater chance at detecting Alzheimer’s disease early and slowing its progression–and maybe even preventing it from ever occurring. LAUREN KIM LAUREN KIM is a sophomore prospective Neuroscience major in Timothy Dwight College. She has been writing for the Yale Scientific since her freshman year. She also volunteers at Yale New Haven Hospital in the Elder Horizons program and is a member of Yale’s varsity fencing team. THE AUTHOR WOULD LIKE TO THANK Ming-Kai Chen and Adam Mecca for their time and enthusiasm for sharing their research. FURTHER READING Chen, Ming-Kai, Adam P. Mecca, et al. “Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging.” JAMA Neurology 75, no. 10 (2018): 1215. doi:10.1001/jamaneurol.2018.1836. FOCUS www.yalescientific.org October 2018 Yale Scientific Magazine 20
FOCUS applied physics L U M On June 10, 2000, hundreds of thousands of eager pedestrians traversed the newly opened London Millennium Footbridge. However, as more and more pedestrians filtered across, the bridge started to sway. Panicked, they shifted their weight in the opposite direction to counteract the oscillations. Yet, the pedestrians’ synchronous efforts only compounded the swaying, and the amplitude of the bridge’s oscillations increased. The problem became so severe that the Millennium Bridge had to be closed later in the day, only to be reopened two years later, fitted with a $6-million damping system designed to counteract this effect. Extensive analysis led engineers to conclude that resonance, the phenomenon in which an external force with a particular frequency amplifies existing oscillations, was behind the dramatic movements of the Millennium Bridge. But resonance can be useful, especially when it comes to laser energetics. At Yale, a team of physicists from Professor Peter Rakich’s lab developed a new silicon-based laser that uses resonant sound waves to amplify light, representing a milestone in the field of silicon photonics. What is silicon photonics? The field of photonics emerged with the invention of the laser in 1960. In traditional lasers, light of a specific frequency is emitted by pumping atoms into an excited state, leading to “laser gain.” When the increase in energy reaches a certain threshold, lasing occurs. The next big development in information technology was optical fibers, which transmit light signals through a glass core. Light can encode more information in its wave properties than electrons, with little loss over thousands of miles. However, optical devices used to process optical signals are often bulky, spanning entire table tops. Today, silicon-based photonics offers the promise of miniaturizing these systems onto single chips. Rakich believes that silicon photonic systems can revolutionize optics similar to how transistors revolutionized the digital age by eliminating the need for rooms full of vacuum tubes. More importantly, silicon is a naturally abundant element with a massive preexisting processing infrastructure, serving the $400 billion semiconductor industry. “If you’re building things out of silicon, as a friend of mine used to say, ‘You’re riding the silicon freight train,’” Rakich said. However, it has proved difficult to produce a laser based purely on silicon—due to certain intrinsic material properties, silicon is not predisposed to provide laser gain. Silicon optical waveguides, which are structures which guide light waves in the medium, suffer from significant dissipation of energy that could otherwise have contributed to laser gain. Stimulated Brillouin scattering in silicon The new silicon system uses resonantly-driven sound waves to provide the requisite laser gain. It parallels the Millennium Bridge phenomenon, with silicon as the bridge and light waves as the pedestrians. Just as pedestrians walking at a particular frequency caused the bridge to oscillate, input light, also known as “pump light,” generates elastic waves, commonly known as sound, when oscillating at the natural frequency of silicon. Here, the researchers saw an opportunity to exploit a phenomenon called Brillouin scattering, in which the resulting sound waves in turn interact with the light, moving some light energy into a lower-frequency output channel. The process is self-amplifying—the stronger the sound waves, the more sound-light interaction, and the more energy pouring into the output channel—to the point where the sufficient gain for lasing is achieved. But Brillouin scattering had never been observed in silicon. It requires a “hybrid” waveguide that can confine both light and sound waves to the same region in silicon, enabling their Brillouin interaction. This is a difficult problem due to the structure of silicon chips, which have a semiconducting silicon layer atop a layer of silica—the oxidized form of silicon. Light waves naturally confine themselves to silicon, but sound waves spontaneously dissipate their energy down into the silica layer. To address this problem, the Rakich group devised a “suspended” waveguide that encompasses a ridge along the center of the silicon layer to conduct light waves, as well as slots on a micrometer scale punched uniformly along the sides of the ridge. These form “hard boundaries” off which sound waves can bounce, forcing them to stay within the top silicon layer. The researchers then wrapped the linear waveguide back on itself, A N E L E C T R I C U N I O N creating a “racetrack” for the waves to circulate and amplify, leading to enough laser gain to offset the energy loss and produce Brillouin lasing in silicon for the first time. Unique Brillouin behavior The first of its kind, the new system does not behave like a conventional Brillouin laser. Traditional Brillouin lasers absorb light noise from the input pump wave, so that the emitted light becomes spectrally purified. In this system, however, the emitted light was spectrally identical to the pump light. Instead, output sound became spectrally purified. For this new regime of Brillouin lasing, the researchers had to construct a new theoretical framework to understand it. “It was all very different, very new physics,” said Nils Otterstrom, lead author of the paper. This system embodies original design concepts that are important for Brillouin lasing in & H E 21 Yale Scientific Magazine October 2018 www.yalescientific.org
Page 1 and 2: Yale Scientific Established in 1894
Page 3 and 4: TABLE OF CONTENTS VOL. 91 ISSUE NO.
Page 5 and 6: SCIENCE SURROUNDS US While the Yale
Page 7 and 8: Imagine if we could turn all the wo
Page 9 and 10: psychology NEWS WIRING OF PSYCHOPAT
Page 11 and 12: ecology NEWS HIPPOPOTAMI AS ENGINEE
Page 13 and 14: FOCUS cell biology The fundamental
Page 15 and 16: medicine FOCUS If you have ever bee
Page 17 and 18: medicine FOCUS ivary gland, but it
Page 19: FOCUS neuroscience Alzheimer’s is
Page 23 and 24: FOCUS materials science On June 10,
Page 25 and 26: SCIENCE IN THE LIBERAL ARTS: a refl
Page 27 and 28: applied physics FEATURE SEAS OF ELE
Page 29 and 30: physical chemistry FEATURE van der
Page 31 and 32: materials science FEATURE tigue. Au
Page 33 and 34: SEIZURES biomedical engineering FEA
Page 35 and 36: epurposed By: Katie Schlick Rags to
Page 37 and 38: ALUMNI PROFILE ERIC FOSSUM (PhD ’
Page 39 and 40: As the string ensemble emerges, we

YSM Issue 91.3

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