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  • richardmitnick 5:09 pm on February 5, 2021 Permalink | Reply
    Tags: "Breakthrough in Quantum Photonics Promises a New Era in Optical Circuits", A quantum optical circuit uses light sources that generate individual light particles or photons on-demand one-at-a-time acting as information carrying bits., , , , For the first time researchers can create scalable quantum photonic chips using well-established semiconductor processing techniques., In recently published work researchers at USC have shown that single photons can indeed be emitted in a uniform way from quantum dots arranged in a precise pattern., , , , , The method of aligning quantum dots was first developed at USC by the lead PI Professor Anupam Madhukar and his team nearly thirty years ago., The optical circuit requires these single photon sources to be arranged on a semiconductor chip in a regular pattern., These light sources are nano-sized semiconductor “quantum dots”., This work also sets a new world-record of ordered and scalable quantum dots in terms of the simultaneous purity of single-photon emission greater than 99.5%., University of Southern California, Until now there has been a significant barrier to the development of such circuits.,   

    From USC Viterbi School of Engineering at University of Southern California: “Breakthrough in Quantum Photonics Promises a New Era in Optical Circuits” 

    From USC Viterbi School of Engineering

    at

    USC bloc

    University of Southern California

    February 3, 2021
    Greta Harrison

    A world-first method to enable quantum optical circuits that use photons—light particles—heralds a new future for secure communication and quantum computing.

    1
    Photon Waves. Credit: Wikimedia Commons.

    The modern world is powered by electrical circuitry on a “chip”—the semiconductor chip underpinning computers, cell phones, the internet, and other applications. In the year 2025, humans are expected to be creating 175 zettabytes (175trillion gigabytes) of new data. How can we ensure the security of sensitive data at such a high volume? And how can we address grand-challenge-like problems, from privacy and security to climate change, leveraging this data, especially given the limited capability of current computers?

    A promising alternative is emerging quantum communication and computation technologies . For this to happen, however, it will require the widespread development of powerful new quantum optical circuits­; circuits that are capable of securely processing the massive amounts of information we generate every day. Researchers in USC’s Mork Family Department of Chemical Engineering and Materials Science have made a breakthrough to help enable this technology.

    While a traditional electrical circuit is a pathway along which electrons from an electric charge flow, a quantum optical circuit uses light sources that generate individual light particles, or photons, on-demand, one-at-a-time, acting as information carrying bits (quantum bits or qubits). These light sources are nano-sized semiconductor “quantum dots”–tiny manufactured collections of tens of thousands to a million atoms packed within a volume of linear size less than a thousandth of the thickness of typical human hair buried in a matrix of another suitable semiconductor.

    They have so far been proven to be the most versatile on-demand single photon generators. The optical circuit requires these single photon sources to be arranged on a semiconductor chip in a regular pattern. Photons with nearly identical wavelength from the sources must then be released in a guided direction. This allows them to be manipulated to form interactions with other photons and particles to transmit and process information.

    Until now, there has been a significant barrier to the development of such circuits. For example, in current manufacturing techniques quantum dots have different sizes and shapes and assemble on the chip in random locations. The fact that the dots have different sizes and shapes mean that the photons they release do not have uniform wavelengths. This and the lack of positional order make them unsuitable for use in the development of optical circuits.

    In recently published work, researchers at USC have shown that single photons can indeed be emitted in a uniform way from quantum dots arranged in a precise pattern. It should be noted that the method of aligning quantum dots was first developed at USC by the lead PI, Professor Anupam Madhukar, and his team nearly thirty years ago, well before the current explosive research activity in quantum information and interest in on-chip single-photon sources. In this latest work, the USC team has used such methods to create single-quantum dots, with their remarkable single-photon emission characteristics. It is expected that the ability to precisely align uniformly-emitting quantum dots will enable the production of optical circuits, potentially leading to novel advancements in quantum computing and communications technologies.

    The work, published in APL Photonics, was led by Jiefei Zhang, currently a research assistant professor in the Mork Family Department of Chemical Engineering and Materials Science, with corresponding author Anupam Madhukar, Kenneth T. Norris Professor in Engineering and Professor of Chemical Engineering, Electrical Engineering, Materials Science, and Physics.

    “The breakthrough paves the way to the next steps required to move from lab demonstration of single photon physics to chip-scale fabrication of quantum photonic circuits,” Zhang said. “This has potential applications in quantum (secure) communication, imaging, sensing and quantum simulations and computation.”

    Madhukar said that it is essential that quantum dots be ordered in a precise way so that photons released from any two or more dots can be manipulated to connect with each other on the chip. This will form the basis of building unit for quantum optical circuits.

    “If the source where the photons come from is randomly located, this can’t be made to happen.” Madhukar said.

    “The current technology that is allowing us to communicate online, for instance using a technological platform such as Zoom, is based on the silicon integrated electronic chip. If the transistors on that chip are not placed in exact designed locations, there would be no integrated electrical circuit,” Madhukar said. “It is the same requirement for photon sources such as quantum dots to create quantum optical circuits.”

    The research is supported by the Air Force Office of Scientific Research (AFOSR) and the U.S. Army Research Office (ARO).

    “This advance is an important example of how solving fundamental materials science challenges, like how to create quantum dots with precise position and composition, can have big downstream implications for technologies like quantum computing,” said Evan Runnerstrom, program manager, Army Research Office, an element of the U.S. Army Combat Capabilities Development Command’s Army Research Laboratory. “This shows how ARO’s targeted investments in basic research support the Army’s enduring modernization efforts in areas like networking.”

    To create the precise layout of quantum dots [Stress-Engineered Quantum Dots: Nature’s Way] for the circuits, the team used a method called SESRE (substrate-encoded size-reducing epitaxy) developed in the Madhukar group in the early 1990s. In the current work, the team fabricated regular arrays of nanometer-sized mesas (Fig. 1(a)) with a defined edge orientation, shape (sidewalls) and depth on a flat semiconductor substrate, composed of gallium arsenide (GaAs). Quantum dots are then created on top of the mesas by adding appropriate atoms using the following technique.

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    Figure. (a) Scanning electron microscope (SEM) image of starting nanometer-sized mesa array created on a flat semiconductor substrate; (b) Schematic of mesa profile evolution during material deposition with the black arrows indicating atom migration direction leading first to GaAs size-reduction (the SESRE approach) and then switching to the deposition of quantum dot material InAs (red) on the size-reduced mesa top and back to GaAs to bury the red InAs; A SEM image of the mesa bearing the single quantum dot is shown below; (c) Indicates the realized quantum dot array buried under a planarized GaAs surface shown symbolically as a translucent overlayer to enable visualization (GaAs is opaque).

    First, incoming gallium (Ga) atoms gather on the top of the nanoscale mesas (black arrows in Fig 1.(b)) attracted by surface energy forces, where they deposit GaAs (black outline on mesa top, Fig. 1(b)). Then, the incoming flux is switched to indium (In) atoms, to in turn deposit indium arsenide (InAs) (red region in Fig. 1(b)), followed back by Ga atoms to form GaAs and hence create the desired individual quantum dots (upper image in Fig. 1(b)) that end up releasing single photons. To be useful for creating optical circuits, the space between the pyramid-shaped nano-mesas needs to be filled by material that flattens the surface. The final chip is shown schematically in Fig. 1(c), where opaque GaAs is depicted as a translucent overlayer under which the quantum dots are located.

    “This work also sets a new world-record of ordered and scalable quantum dots in terms of the simultaneous purity of single-photon emission greater than 99.5%, and in terms of the uniformity of the wavelength of the emitted photons, which can be as narrow as 1.8nm, which is a factor of 20 to 40 better than typical quantum dots,” Zhang said.

    Zhang said that with this uniformity, it becomes feasible to apply established methods such as local heating or electric fields to fine-tune the photon wavelengths of the quantum dots to exactly match each other, which is necessary for creating the required interconnections between different quantum dots for circuits.

    This means that for the first time researchers can create scalable quantum photonic chips using well-established semiconductor processing techniques. In addition, the team’s efforts are now focused on establishing how identical the emitted photons are from the same and/or from different quantum dots. The degree of indistinguishability is central to quantum effects of interference and entanglement, that underpin quantum information processing –communication, sensing, imaging, or computing.

    Zhang concluded: “We now have an approach and a material platform to provide scalable and ordered sources generating potentially indistinguishable single-photons for quantum information applications. The approach is general and can be used for other suitable material combinations to create quantum dots emitting over a wide range of wavelengths preferred for different applications, for example fiber-based optical communication or the mid-infrared regime, suited for environmental monitoring and medical diagnostics,” Zhang said.

    Gernot S. Pomrenke, AFOSR Program Officer, Optoelectronics and Photonics said that reliable arrays of on-demand single photon sources on-chip were a major step forward.

    “This impressive growth and material science work stretches over three decades of dedicated effort before research activities in quantum information were in the mainstream,” Pomrenke said. “Initial AFOSR funding and resources from other DoD agencies have been critical in realizing the challenging work and vision by Madhukar, his students, and collaborators. There is a great likelihood that the work will revolutionize the capabilities of data centers, medical diagnostics, defense and related technologies.”

    The paper’s co-authors include Qi Huang and Lucas Jordao from USC’s Mork Family Department of Chemical Engineering and Materials Science, Swarnabha Chattaraj from the Ming Hsieh Department of Electrical and Computer Engineering and Siyuan Lu from the IBM Thomas J. Watson Research Center.

    See the full article here .

    five-ways-keep-your-child-safe-school-shootings

    Please help promote STEM in your local schools.

    Stem Education Coalition

    The USC Viterbi School of Engineering (formerly the USC School of Engineering) is located at the University of Southern California in the United States. It was renamed following a $52 million donation by Andrew Viterbi, co-founder of Qualcomm Inc. The USC Viterbi School of Engineering celebrated its 100th birthday in conjunction with the university’s 125th birthday.

    With over $135 million in external funding support, the school is among the nation’s highest in volume of research activity.

    Research centers have played a major role in development of multiple technologies, including early development of the Internet when USC researcher Jonathan Postel was an editor of communications-protocol for the fledgling internet, also known as ARPANET.

    Major research centers

    Alfred Mann Institute – business incubator for medical device development in preparation for commercialization

    Center for Biomimetic Microelectronic Systems – National Science Foundation Engineering Research Center

    Center for Risk and Economic Analysis of Terrorism Events (CREATE) – interdisciplinary national research center funded by the U.S. Department of Homeland Security

    Center for Systems and Software Engineering (CSSE) – research the relationship between systems, software, and users.

    Collaborative High Altitude Flow Facility (CHAFF) – Space and Vacuum Science research group, a funded Air Force Research Laboratory

    Information Sciences Institute (housed at a separate facilities in Marina del Rey, California and Arlington, Virginia) – played a major role in the development of the Internet, and continues to be a major research center in computer science

    Institute for Creative Technologies – conducts research in virtual reality and immersive digital environment

    Integrated Media Systems Center – National Science Foundation’s Exclusive Engineering Research Center for multimedia and Internet research

    Pacific Earthquake Engineering Research Center (PEER) Partner Institution – Current Research

    USC campus

    The University of Southern California is one of the world’s leading private research universities. An anchor institution in Los Angeles, a global center for arts, technology and international business, USC’s diverse curricular offerings provide extensive opportunities for interdisciplinary study, and collaboration with leading researchers in highly advanced learning environments. With a strong tradition of integrating liberal and professional education, USC fosters a vibrant culture of public service and encourages students to cross academic as well as geographic boundaries in their pursuit of knowledge.

     
  • richardmitnick 4:48 pm on September 4, 2020 Permalink | Reply
    Tags: After a big quake ends the tectonic plates that meet at the fault boundary settle into a go-along- get-along phase., , Deep underground forces explain quakes on San Andreas Fault", , , Earthquake physics, , Gradually motion across chunks of granite and quartz- the Earth's bedrock- generates heat due to friction., Most of California seismicity originates from the first 10 miles of the crust but some tremors on the San Andreas Fault take place much deeper., , , Quakes of magnitude 6 have shaken the Parkfield section of the fault at fairly regular intervals in 1857; 1881; 1901; 1922; 1934; 1966; and 2004 according to the USGS., , University of Southern California, When friction pushes temperatures above 650 degrees Fahrenheit the rock blocks grow less solid and more fluid-like.   

    From University of Southern California via phys.org: “Deep underground forces explain quakes on San Andreas Fault” 

    USC bloc

    From University of Southern California

    via


    phys.org

    1
    Credit: Unsplash/CC0 Public Domain.

    Rock-melting forces occurring much deeper in the Earth than previously understood appear to drive tremors along a notorious segment of California’s San Andreas Fault, according to new USC research that helps explain how quakes happen.

    The study from the emergent field of earthquake physics looks at temblor mechanics from the bottom up, rather than from the top down, with a focus on underground rocks, friction and fluids. On the segment of the San Andreas Fault near Parkfield, Calif., underground excitations—beyond the depths where quakes are typically monitored—lead to instability that ruptures in a quake.

    “Most of California seismicity originates from the first 10 miles of the crust, but some tremors on the San Andreas Fault take place much deeper,” said Sylvain Barbot, assistant professor of Earth sciences at the USC Dornsife College of Letters, Arts and Sciences. “Why and how this happens is largely unknown. We show that a deep section of the San Andreas Fault breaks frequently and melts the host rocks, generating these anomalous seismic waves.”The newly published study appears in Science Advances. Barbot, the corresponding author, collaborated with Lifeng Wang of the China Earthquake Administration in China.

    The findings are significant because they help advance the long-term goal of understanding how and where earthquakes are likely to occur, along with the forces that trigger temblors. Better scientific understanding helps inform building codes, public policy and emergency preparedness in quake-ridden areas like California. The findings may also be important in engineering applications where the temperature of rocks is changed rapidly, such as by hydraulic fracturing.

    Parkfield was chosen because it is one of the most intensively monitored epicenters in the world. The San Andreas Fault slices past the town, and it’s regularly ruptured with significant quakes. Quakes of magnitude 6 have shaken the Parkfield section of the fault at fairly regular intervals in 1857, 1881, 1901, 1922, 1934, 1966 and 2004, according to the U.S. Geological Survey. At greater depths, smaller temblors occur every few months.So what’s happening deep in the Earth to explain the rapid quake recurrence?

    Using mathematical models and laboratory experiments with rocks, the scientists conducted simulations based on evidence gathered from the section of the San Andreas Fault extending up to 36 miles north of—and 16 miles beneath—Parkfield. They simulated the dynamics of fault activity in the deep Earth spanning 300 years to study a wide range of rupture sizes and behaviors.

    The researchers observed that, after a big quake ends, the tectonic plates that meet at the fault boundary settle into a go-along, get-along phase. For a spell, they glide past each other, a slow slip that causes little disturbance to the surface.

    But this harmony belies trouble brewing. Gradually, motion across chunks of granite and quartz, the Earth’s bedrock, generates heat due to friction. As the heat intensifies, the blocks of rock begin to change. When friction pushes temperatures above 650 degrees Fahrenheit, the rock blocks grow less solid and more fluid-like. They start to slide more, generating more friction, more heat and more fluids until they slip past each other rapidly—triggering an earthquake.

    “Just like rubbing our hands together in cold weather to heat them up, faults heat up when they slide. The fault movements can be caused by large changes in temperature,” Barbot said. “This can create a positive feedback that makes them slide even faster, eventually generating an earthquake.”

    It’s a different way of looking at the San Andreas Fault. Scientists typically focus on movement in the top of Earth’s crust, anticipating that its motion in turn rejiggers the rocks deep below. For this study, the scientists looked at the problem from the bottom up.

    “It’s difficult to make predictions,” Barbot added, “so instead of predicting just earthquakes, we’re trying to explain all of the different types of motion seen in the ground.”

    See the full article here.

    Earthquake Alert

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    Earthquake Alert

    Earthquake Network projectEarthquake Network is a research project which aims at developing and maintaining a crowdsourced smartphone-based earthquake warning system at a global level. Smartphones made available by the population are used to detect the earthquake waves using the on-board accelerometers. When an earthquake is detected, an earthquake warning is issued in order to alert the population not yet reached by the damaging waves of the earthquake.

    The project started on January 1, 2013 with the release of the homonymous Android application Earthquake Network. The author of the research project and developer of the smartphone application is Francesco Finazzi of the University of Bergamo, Italy.

    Get the app in the Google Play store.

    3
    Smartphone network spatial distribution (green and red dots) on December 4, 2015

    Meet The Quake-Catcher Network

    QCN bloc

    Quake-Catcher Network

    The Quake-Catcher Network is a collaborative initiative for developing the world’s largest, low-cost strong-motion seismic network by utilizing sensors in and attached to internet-connected computers. With your help, the Quake-Catcher Network can provide better understanding of earthquakes, give early warning to schools, emergency response systems, and others. The Quake-Catcher Network also provides educational software designed to help teach about earthquakes and earthquake hazards.

    After almost eight years at Stanford, and a year at CalTech, the QCN project is moving to the University of Southern California Dept. of Earth Sciences. QCN will be sponsored by the Incorporated Research Institutions for Seismology (IRIS) and the Southern California Earthquake Center (SCEC).

    The Quake-Catcher Network is a distributed computing network that links volunteer hosted computers into a real-time motion sensing network. QCN is one of many scientific computing projects that runs on the world-renowned distributed computing platform Berkeley Open Infrastructure for Network Computing (BOINC).

    The volunteer computers monitor vibrational sensors called MEMS accelerometers, and digitally transmit “triggers” to QCN’s servers whenever strong new motions are observed. QCN’s servers sift through these signals, and determine which ones represent earthquakes, and which ones represent cultural noise (like doors slamming, or trucks driving by).

    There are two categories of sensors used by QCN: 1) internal mobile device sensors, and 2) external USB sensors.

    Mobile Devices: MEMS sensors are often included in laptops, games, cell phones, and other electronic devices for hardware protection, navigation, and game control. When these devices are still and connected to QCN, QCN software monitors the internal accelerometer for strong new shaking. Unfortunately, these devices are rarely secured to the floor, so they may bounce around when a large earthquake occurs. While this is less than ideal for characterizing the regional ground shaking, many such sensors can still provide useful information about earthquake locations and magnitudes.

    USB Sensors: MEMS sensors can be mounted to the floor and connected to a desktop computer via a USB cable. These sensors have several advantages over mobile device sensors. 1) By mounting them to the floor, they measure more reliable shaking than mobile devices. 2) These sensors typically have lower noise and better resolution of 3D motion. 3) Desktops are often left on and do not move. 4) The USB sensor is physically removed from the game, phone, or laptop, so human interaction with the device doesn’t reduce the sensors’ performance. 5) USB sensors can be aligned to North, so we know what direction the horizontal “X” and “Y” axes correspond to.

    If you are a science teacher at a K-12 school, please apply for a free USB sensor and accompanying QCN software. QCN has been able to purchase sensors to donate to schools in need. If you are interested in donating to the program or requesting a sensor, click here.

    BOINC is a leader in the field(s) of Distributed Computing, Grid Computing and Citizen Cyberscience.BOINC is more properly the Berkeley Open Infrastructure for Network Computing, developed at UC Berkeley.

    Earthquake safety is a responsibility shared by billions worldwide. The Quake-Catcher Network (QCN) provides software so that individuals can join together to improve earthquake monitoring, earthquake awareness, and the science of earthquakes. The Quake-Catcher Network (QCN) links existing networked laptops and desktops in hopes to form the worlds largest strong-motion seismic network.

    Below, the QCN Quake Catcher Network map
    QCN Quake Catcher Network map

    ShakeAlert: An Earthquake Early Warning System for the West Coast of the United States

    The U. S. Geological Survey (USGS) along with a coalition of State and university partners is developing and testing an earthquake early warning (EEW) system called ShakeAlert for the west coast of the United States. Long term funding must be secured before the system can begin sending general public notifications, however, some limited pilot projects are active and more are being developed. The USGS has set the goal of beginning limited public notifications in 2018.

    Watch a video describing how ShakeAlert works in English or Spanish.

    The primary project partners include:

    United States Geological Survey
    California Governor’s Office of Emergency Services (CalOES)
    California Geological Survey
    California Institute of Technology
    University of California Berkeley
    University of Washington
    University of Oregon
    Gordon and Betty Moore Foundation

    The Earthquake Threat

    Earthquakes pose a national challenge because more than 143 million Americans live in areas of significant seismic risk across 39 states. Most of our Nation’s earthquake risk is concentrated on the West Coast of the United States. The Federal Emergency Management Agency (FEMA) has estimated the average annualized loss from earthquakes, nationwide, to be $5.3 billion, with 77 percent of that figure ($4.1 billion) coming from California, Washington, and Oregon, and 66 percent ($3.5 billion) from California alone. In the next 30 years, California has a 99.7 percent chance of a magnitude 6.7 or larger earthquake and the Pacific Northwest has a 10 percent chance of a magnitude 8 to 9 megathrust earthquake on the Cascadia subduction zone.

    Part of the Solution

    Today, the technology exists to detect earthquakes, so quickly, that an alert can reach some areas before strong shaking arrives. The purpose of the ShakeAlert system is to identify and characterize an earthquake a few seconds after it begins, calculate the likely intensity of ground shaking that will result, and deliver warnings to people and infrastructure in harm’s way. This can be done by detecting the first energy to radiate from an earthquake, the P-wave energy, which rarely causes damage. Using P-wave information, we first estimate the location and the magnitude of the earthquake. Then, the anticipated ground shaking across the region to be affected is estimated and a warning is provided to local populations. The method can provide warning before the S-wave arrives, bringing the strong shaking that usually causes most of the damage.

    Studies of earthquake early warning methods in California have shown that the warning time would range from a few seconds to a few tens of seconds. ShakeAlert can give enough time to slow trains and taxiing planes, to prevent cars from entering bridges and tunnels, to move away from dangerous machines or chemicals in work environments and to take cover under a desk, or to automatically shut down and isolate industrial systems. Taking such actions before shaking starts can reduce damage and casualties during an earthquake. It can also prevent cascading failures in the aftermath of an event. For example, isolating utilities before shaking starts can reduce the number of fire initiations.

    System Goal

    The USGS will issue public warnings of potentially damaging earthquakes and provide warning parameter data to government agencies and private users on a region-by-region basis, as soon as the ShakeAlert system, its products, and its parametric data meet minimum quality and reliability standards in those geographic regions. The USGS has set the goal of beginning limited public notifications in 2018. Product availability will expand geographically via ANSS regional seismic networks, such that ShakeAlert products and warnings become available for all regions with dense seismic instrumentation.

    Current Status

    The West Coast ShakeAlert system is being developed by expanding and upgrading the infrastructure of regional seismic networks that are part of the Advanced National Seismic System (ANSS); the California Integrated Seismic Network (CISN) is made up of the Southern California Seismic Network, SCSN) and the Northern California Seismic System, NCSS and the Pacific Northwest Seismic Network (PNSN). This enables the USGS and ANSS to leverage their substantial investment in sensor networks, data telemetry systems, data processing centers, and software for earthquake monitoring activities residing in these network centers. The ShakeAlert system has been sending live alerts to “beta” users in California since January of 2012 and in the Pacific Northwest since February of 2015.

    In February of 2016 the USGS, along with its partners, rolled-out the next-generation ShakeAlert early warning test system in California joined by Oregon and Washington in April 2017. This West Coast-wide “production prototype” has been designed for redundant, reliable operations. The system includes geographically distributed servers, and allows for automatic fail-over if connection is lost.

    This next-generation system will not yet support public warnings but does allow selected early adopters to develop and deploy pilot implementations that take protective actions triggered by the ShakeAlert notifications in areas with sufficient sensor coverage.

    Authorities

    The USGS will develop and operate the ShakeAlert system, and issue public notifications under collaborative authorities with FEMA, as part of the National Earthquake Hazard Reduction Program, as enacted by the Earthquake Hazards Reduction Act of 1977, 42 U.S.C. §§ 7704 SEC. 2.

    For More Information

    Robert de Groot, ShakeAlert National Coordinator for Communication, Education, and Outreach
    rdegroot@usgs.gov
    626-583-7225

    Learn more about EEW Research

    ShakeAlert Fact Sheet

    ShakeAlert Implementation Plan

    five-ways-keep-your-child-safe-school-shootings

    Please help promote STEM in your local schools.

    Stem Education Coalition

    USC campus

    The University of Southern California is one of the world’s leading private research universities. An anchor institution in Los Angeles, a global center for arts, technology and international business, USC’s diverse curricular offerings provide extensive opportunities for interdisciplinary study, and collaboration with leading researchers in highly advanced learning environments. With a strong tradition of integrating liberal and professional education, USC fosters a vibrant culture of public service and encourages students to cross academic as well as geographic boundaries in their pursuit of knowledge.

     
  • richardmitnick 9:11 am on April 25, 2019 Permalink | Reply
    Tags: "Researchers create the first maps of two melatonin receptors essential for sleep", , , Melatonin receptors belong to a group of membrane receptors called G protein-coupled receptors (GPCRs) which regulate almost all the physiological and sensory processes in the human body., MT1 and MT2 receptors, , These receptors oversee our clock genes- the timekeepers of the body’s internal clock or circadian rhythm., University of Southern California, When our circadian rhythms are disrupted it can lead to a number of downstream symptoms increasing the risk of cancer Type 2 diabetes and mood disorders., When there’s light the production of melatonin is inhibited; but when darkness comes that's the signal for our brains to go to sleep.,   

    From SLAC National Accelerator Lab: “Researchers create the first maps of two melatonin receptors essential for sleep” 

    From SLAC National Accelerator Lab

    April 24, 2019

    Andrew Gordon
    agordon@slac.stanford.edu
    (650) 926-2282

    Written by Ali Sundermier

    1
    The behavior of humans and all animals is governed by a variety of natural cycles. The shift of seasons, tides, and day and night influences animal breeding and mating, predator-prey relationships, migration and foraging. Melatonin, depicted as a constellation in the night sky, is the key molecule that allows one of the most stable of these external cycles, a 24-hour day-night rhythm, to be correlated to an internal cycle, with responses at the level of individual cells and the whole animal. High melatonin levels during night time induce sleep-promoting properties by acting through melatonin receptors, depicted in the central reference point of the image composition. (Yekaterina Kadyshevskaya/Bridge Institute of the University of Southern California)

    A better understanding of how these receptors work could enable scientists to design better therapeutics for sleep disorders, cancer and Type 2 diabetes.

    An international team of researchers used an X-ray laser at the Department of Energy’s SLAC National Accelerator Laboratory to create the first detailed maps of two melatonin receptors that tell our bodies when to go to sleep or wake up, and guide other biological processes. A better understanding of how they work could enable researchers to design better drugs to combat sleep disorders, cancer and Type 2 diabetes. Their findings were published in two papers today in Nature: Structural basis of ligand recognition at the human MT1 melatonin receptor; XFEL structures of the human MT2 melatonin receptor reveal the basis of subtype selectivity.

    The team, led by the University of Southern California, used X-rays from SLAC’s Linac Coherent Light Source (LCLS) to map the receptors, MT1 and MT2, bound to four different compounds that activate them: an insomnia drug, a drug that mixes melatonin with the antidepressant serotonin, and two melatonin analogs.

    SLAC/LCLS

    They discovered that both melatonin receptors contain narrow channels embedded in the fatty membranes of the cells in our bodies. These channels only allow melatonin – which can exist in both water and fat – to pass through and bind to the receptors, blocking serotonin, which has a similar structure but is only happy in watery environments. They also uncovered how some much larger compounds may only target MT1 and not MT2, despite the structural similarities between the two receptors. This should inform the design of drugs that selectively target MT1, which so far has been challenging.

    “These receptors perform immensely important functions in the human body and are major drug targets of high interest to the pharmaceutical industry,” said Linda Johansson, a postdoctoral scholar at USC who led the structural work on MT2. “Through this work we were able to obtain a highly detailed understanding of how melatonin is able to bind to these receptors.”

    Time for bed

    People do it, birds do it, fish do it. Almost all living beings in the animal kingdom sleep, and for good reason.

    “It’s critical for the brain to take rest and process and store memories that we have accumulated during the day,” said co-author Alex Batyuk, a scientist at SLAC. “Melatonin is the hormone that regulates our sleep-wake cycles. When there’s light, the production of melatonin is inhibited, but when darkness comes that’s the signal for our brains to go to sleep.”

    Melatonin receptors belong to a group of membrane receptors called G protein-coupled receptors (GPCRs) which regulate almost all the physiological and sensory processes in the human body. MT1 and MT2 are found in many places throughout the body, including the brain, retina, cardiovascular system, liver, kidney, spleen and intestine.

    These receptors oversee our clock genes, the timekeepers of the body’s internal clock, or circadian rhythm. In a perfect world, our internal clocks would sync up with the rising and setting of the sun. But when people travel across time zones, work overnight shifts or spend too much time in front of screens or other artificial sources of blue light, these timekeepers are thrown out of whack.

    Controlling the rhythm

    When our circadian rhythms are disrupted, it can lead to a number of downstream symptoms, increasing the risk of cancer, Type 2 diabetes and mood disorders. MT1 in particular plays an important role in controlling these rhythms but designing drugs that can selectively target this receptor has proven difficult. Many people take over-the-counter melatonin supplements to combat sleep issues or shift their circadian rhythms, but these drugs often wear off within hours and can produce unwanted side effects.

    By cracking the blueprints of these receptors and mapping how ligands bind to and activate them, the researchers lit the way for others to design drugs that are safer, more effective and capable of selectively targeting each receptor.

    “Since the discovery of melatonin 60 years ago, there have been many landmark discoveries that led to this moment,” said Margarita L. Dubocovich, a State University of New York Distinguished Professor of pharmacology and toxicology at the University at Buffalo who pioneered the identification of functional melatonin receptors in the early 80s and provided an outside perspective on this research. “Despite remarkable progress, discovery of selective MT1 drugs has remained elusive for my team and researchers around the world. The elucidation of the crystal structures for the MT1 and MT2 receptors opens up an exciting new chapter for the development of drugs to treat sleep or circadian rhythm disorders known to cause psychiatric, metabolic, oncological and many other conditions.”

    Harvesting crystals

    To map biomolecules like proteins, researchers often use a method called X-ray crystallography, scattering X-rays off of crystallized versions of these proteins and using the patterns this creates to obtain a three-dimensional structure. Until now, the challenge with mapping MT1, MT2 and similar receptors was how difficult it was to grow large enough crystals to obtain high-resolution structures.

    “With these melatonin receptors, we really had to go the extra mile,” said Benjamin Stauch, a scientist at USC who led the structural work on MT1. “Many people had tried to crystallize them without success, so we had to be a little bit inventive.”

    A key piece of this research was the unique method the researchers used to grow their crystals and to collect X-ray diffraction data from them. For this research, the team expressed these receptors in insect cells and extracted them by using detergent. They mutated these receptors to stabilize them, enabling crystallization. After purifying the receptors, they placed them in a membrane-like gel, which supports crystal growth directly from the membrane environment. After obtaining microcrystals suspended in this gel, they used a special injector to create a narrow stream of crystals that they zapped with X-rays from LCLS.

    “Because of the tiny crystal size, this work could only be done at LCLS,” said Vadim Cherezov, a USC professor who supervised both studies. “Such small crystals do not diffract well at synchrotron sources as they quickly suffer from radiation damage. X-ray lasers can overcome the radiation damage problem through the ‘diffraction-before-destruction’ principle.”

    The researchers collected hundreds of thousands of images of the scattered X-rays to figure out the three-dimensional structure of these receptors. They also tested the effects of dozens of mutations to deepen their understanding of how the receptors work.

    3
    The researchers showed that both melatonin receptors contain narrow channels embedded in the cell’s fatty membranes. These channels only allow melatonin, which can exist happily in both water and fat, to pass through, preventing serotonin, which has a similar structure but is only happy in watery environments, from binding to the receptor. They also uncovered how some much larger compounds only target MT1 despite the structural similarities between the two receptors. (Greg Stewart/SLAC National Accelerator Laboratory)

    In addition to discovering tiny, gatekeeping melatonin channels in the receptors, the researchers were able to map Type 2 diabetes-associated mutations onto the MT2 receptor, for the first time seeing the exact location of these mutations in the receptor.

    Laying the groundwork

    In these experiments, the researchers only looked at compounds that activate the receptors, known as agonists. To follow up, they hope to map the receptors bound to antagonists, which block the receptors. They also hope to use their techniques to investigate other GPCR receptors in the body.

    “As a structural biologist, it was exciting to see the structure of these receptors for the first time and analyze them to understand how these receptors selectively recognize their signaling molecules,” Cherezov said. “We’ve known about them for decades but until now no one could say how they actually look. Now we can analyze them to understand how they recognize specific molecules, which we hope lays the groundwork for better, more effective drugs.”

    The team also included researchers from the University of North Carolina at Chapel Hill; Stanford University; Arizona State University; the University of Lille in France; and the University at Buffalo. LCLS is a DOE Office of Science user facility. This research was largely supported by the National Institutes of Health and the National Science Foundation BioXFEL Science and Technology Center.

    See the full article here .


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    SLAC/LCLS


    SLAC/LCLS II projected view


    SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the DOE’s Office of Science.

     
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