Search NASA⌕ Search

SEARCH · Search NASA

Results for “MEDICAL ELECTRONICS”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23

The Concept and Applications of a Dual Energy Storage Ring

A dual energy electron storage ring configuration is initially proposed as an electron cooler to cool the ion beam in a collider. It consists of two energy loops, the electron beam in the high energy loop undergoes the synchrotron radiation damping to obtain the desired beam property and the beam in the low energy loop is for cooling of the ion beam. The two different energy loops are connected by an energy recovery linac. A lattice design of such a dual energy storage ring has been completed and beam stability conditions are established. We performed numerical simulations to demonstrate the beam qualities and evaluated the cooling performance. In this paper, we present the study results and discuss possible applications of such a concept in many physics research and medical fields.

Dhital, B.↗

Programmable Cadence Timer

Electronic metronome paces users through wide range of exercise routines. Conceptual programmable cadence timer provides rhythmic aural and visual cues. Timer automatically changes cadence according to program entered by the user. It also functions as clock, stopwatch, or alarm. Modular pacer operated as single unit or as two units. With audiovisual module moved away from base module, user concentrates on exercise cues without distraction from information appearing on the liquid-crystal display. Variety of uses in rehabilitative medicine, experimental medicine, sports, and gymnastics. Used in intermittent positive-pressure breathing treatment, in which patient must rhythmically inhale and retain medication delivered under positive pressure; and in incentive spirometer treatment, in which patient must inhale maximally at regular intervals.

Hall, William A.↗

Development of Advanced, Radiation Resistant, Optical-based Detector Technology for Future Experiments.

The primary objective of this project has been to advance the design of high-performance electromagnetic (EM) calorimeters for future particle physics experiments, to identify and measure the timing, position and energy of electrons, positrons and gamma rays, particularly in high-luminosity environments with intense radiation and pileup conditions. To meet such challenges, the proposed research has focused on the development of ultra-compact, radiation-hard calorimeter modules, to provide excellent timing, spatial, and energy resolution. The work aligns with the DOE’s Basic Research Needs (BRN) for High Energy Physics (HEP) Instrumentation and the research team contributes actively to the Coordinating Panel on Advanced Detectors (CPAD) RDC9 calorimetry collaboration in the USA and the European Committee on Future Accelerators (ECFA) DRD-CALO calorimetry collaboration at CERN, the European Laboratory for Particle Physics located in Geneva, Switzerland. The research builds on the RADiCAL (radiation-hard, ultra-compact) modular sampling calorimeter approach, developed by the research team, which employs dense and very bright optical materials such as LYSO:Ce scintillator plates that are interleaved with very dense tungsten plates to minimize detector size while optimizing performance. The modules are comparable in size to a human index finger, dimensionally 14 mm x 14 mm in cross section and 135 mm in length. And despite the small size, the structure is capable of providing excellent timing and energy resolution. This is facilitated through the use of specialized quartz capillaries filled with wavelength-shifting filaments, positioned at various depths along the length of a module, to collect and guide light signals to silicon photomultipliers (SiPMs) which detect and convert the optical signals to electronic signals for analysis. The primary goals of this project have been: (1) Achieve a timing resolution to σ t ≤ 30 ps for high-energy electrons and photons, important for their association with specific events produced in colliding-beam experiments and for the detection of decays-in-flight of long-lived particles. The project has achieved this goal in beam tests of a single RADiCAL module at CERN, during which a timing resolution of σ t = 27 ps was measured for electrons of energy E = 150 GeV. Based upon a mathematical fit to the data measured over a broad energy range from low energy to high energy, a resolution of σ t ≤ 18 ps has been estimated for electrons of very high (TeV) energy. From these measurements and with further expected technical improvements, the timing resolution should reach σ t ≤ 10 ps, important for searches for discovery physics in upcoming and future experiments. (2) Achieve an energy resolution of σ E / E ≤ 10% / $\sqrt{E}$. The project has yet to achieve this goal, but is close to it, having measured a value of σ E / E ≤ 15.9% / $\sqrt{E}$ using a modular array. Ultimately, the resolution goal is expected to be reached by adjustments to material thicknesses within the modules, which will improve the sampling fraction to measure more precisely the shower energy for lower energy particles. The versatility of the modular RADiCAL approach enables the testing of advanced materials, photosensors and electronics, developed in collaboration with CPAD RDC and ECFA DRD-CALO groups. The structure can distinguish electrons, positrons and gamma rays from hadrons and muons and beam-induced backgrounds, making it a valuable tool in a variety of detector environments, including future circular colliders (FCC-ee, FCC-hh) proposed for the European Laboratory for Particle Physics (CERN), the muon-collider proposed for Fermi National Accelerator Laboratory (Fermilab), and searches for new physics in beam-dump, fixed target and forward-physics experiments. And, while designed with particle physics applications in mind, the technologies developed in this project have the potential for application more broadly in particle and nuclear physics, materials science, and medical physics, underscoring the far-reaching potential of this line of instrumentation research and development.

47 OTHER INSTRUMENTATION↗

Clinical knowledge extraction via sparse embedding regression (KESER) with multi-center large scale electronic health record data

The increasing availability of electronic health record (EHR) systems has created enormous potential for translational research. However, it is difficult to know all the relevant codes related to a phenotype due to the large number of codes available. Traditional data mining approaches often require the use of patient-level data, which hinders the ability to share data across institutions. In this project, we demonstrate that multi-center large-scale code embeddings can be used to efficiently identify relevant features related to a disease of interest. We constructed large-scale code embeddings for a wide range of codified concepts from EHRs from two large medical centers. We developed knowledge extraction via sparse embedding regression (KESER) for feature selection and integrative network analysis. We evaluated the quality of the code embeddings and assessed the performance of KESER in feature selection for eight diseases. Besides, we developed an integrated clinical knowledge map combining embedding data from both institutions. The features selected by KESER were comprehensive compared to lists of codified data generated by domain experts. Features identified via KESER resulted in comparable performance to those built upon features selected manually or with patient-level data. The knowledge map created using an integrative analysis identified disease-disease and disease-drug pairs more accurately compared to those identified using single institution data. Analysis of code embeddings via KESER can effectively reveal clinical knowledge and infer relatedness among codified concepts. KESER bypasses the need for patient-level data in individual analyses providing a significant advance in enabling multi-center studies using EHR data.

96 KNOWLEDGE MANAGEMENT AND PRESERVATION↗

Development of $\mathrm{AMOEBA}$ Polarizable Force Field for Rare-Earth La 3+ Interaction with Bioinspired Ligands

Rare-earth metals (REMs) are crucial for many important industries, such as power generation and storage, in addition to cancer treatment and medical imaging. One promising new REM refinement approach involves mimicking the highly selective and efficient binding of REMs observed in relatively recently discovered proteins. However, realizing any such bioinspired approach requires an understanding of the biological recognition mechanisms. In this report we developed a new classical polarizable force field based on the AMOEBA framework for modeling a lanthanum ion (La 3+ ) interacting with water, acetate, and acetamide, which have been found to coordinate the ion in proteins. The parameters were derived by comparing to high-level ab initio quantum mechanical (QM) calculations that include relativistic effects. The AMOEBA model, with advanced atomic multipoles and electronic polarization, is successful in capturing both the QM distance-dependent La 3+ –ligand interaction energies and experimental hydration free energy. A new scheme for pairwise polarization damping (POLPAIR) was developed to describe the polarization energy in La 3+ interactions with both charged and neutral ligands. Simulations of La3+ in water showed water coordination numbers and ion–water distances consistent with previous experimental and theoretical findings. Water residence time analysis revealed both fast and slow kinetics in water exchange around the ion. This new model will allow investigation of fully solvated lanthanum ion–protein systems using GPU-accelerated dynamics simulations to gain insights on binding selectivity, which may be applied to the design of synthetic analogues.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

The role of Tyr34 in proton coupled electron transfer and product inhibition of manganese superoxide dismutase

Human manganese superoxide dismutase (MnSOD) plays a crucial role in controlling levels of reactive oxygen species (ROS) by converting superoxide (O$^{•–}_{2}$) to molecular oxygen (O 2 ) and hydrogen peroxide (H 2 O 2 ) with proton-coupled electron transfers (PCETs). A key catalytic residue, Tyr34, determines the activity of human MnSOD and also becomes post-translationally inactivated by nitration in various diseases associated with mitochondrial dysfunction. Tyr34 has an unusual pK a due to its proximity to the Mn metal and undergoes cyclic deprotonation and protonation events to promote the electron transfers of MnSOD. Neutron diffraction, X-ray spectroscopy, and quantum chemistry calculations in oxidized, reduced and product inhibited enzymatic states shed light on the role of Tyr34 in MnSOD catalysis. The data identify the contributions of Tyr34 in MnSOD activity that support mitochondrial function and give a thorough characterization of how a single tyrosine modulates PCET catalysis. Product inhibition occurs by an associative displacement mechanism.

60 APPLIED LIFE SCIENCES↗

Matter in Extreme Conditions Upgrade (Conceptual Design Report)

The Linac Coherent Light Source (LCLS) X-ray Free Electron Laser (XFEL) is an open-access user facility that delivers ultrashort X-ray pulses that are nine orders of magnitude brighter than any prior source, able to probe the characteristics of matter with unprecedented spatial and temporal precision. The Matter in Extreme Conditions (MEC) instrument at LCLS combines the XFEL with high-power, short-pulse lasers to produce and study high energy density (HED) plasmas to develop the fundamental understanding of plasmas and matter in extreme environments. This has driven a remarkably rich array of high-profile scientific results with applications in fusion energy, isotope production, advanced materials, and medical and nuclear technology. The Matter in Extreme Conditions Upgrade (MEC-U) Project proposes a major upgrade to MEC that would significantly increase the power and repetition rate of the high intensity laser system to the petawatt level (PW, 10 15 Watts) at 10 Hz, increase the energy of the shock-driver laser to the kilojoule level (kJ), and expand the capabilities of the MEC instrument to support groundbreaking experiments enabled by the combination of high-power lasers with the world’s brightest X-ray source.

36 MATERIALS SCIENCE↗

Macromolecular crystallography and biology at the Linac Coherent Light Source

The Linac Coherent Light Source (LCLS) has significantly impacted the field of biology by providing advanced capabilities for probing the structure and dynamics of biological molecules with high precision. The ultrashort coherent X-ray pulses from the LCLS have enabled ultrafast, time-resolved, serial femtosecond crystallography that is inaccessible at conventional synchrotron light sources. Since the facility's founding, scientists have captured detailed insights into biological processes at atomic resolution and fundamental timescales. The ability to observe these processes in real time and under conditions closely resembling their natural state is transforming our approach to studying biochemical mechanisms and developing new medical and energy applications. This work recounts some of the history of the LCLS, advances in biological research enabled by the LCLS, key biological areas that have been impacted and how the LCLS has helped to unravel complex biological phenomena in these fields.

59 BASIC BIOLOGICAL SCIENCES↗

Structural and Mechanistic Advances in the Chemistry of Methyl-Coenzyme M Reductase (MCR)

Methane represents 34% of U.S. energy consumption and is a major greenhouse gas related to the global carbon cycle and energy production. However, current industrial practices significantly increase atmospheric methane levels, necessitating a deeper understanding of its biosynthesis and oxidation. Methyl-coenzyme M reductase (MCR) is central to biological methane metabolism, catalyzing the final step of methanogenesis and the first step in anaerobic methane oxidation. It is also a key target for strategies to capture and transform methane into value-added chemicals.The active site of MCR is a buried Ni-based cofactor only accessible by the substrates via a 50 Å long tunnel. Although the Ni(I) state is required to initiate catalysis, capturing this state remains a challenge for the current structural techniques. Recent advances in structural biology using X-ray Free-Electron Laser serial crystallography have provided insights into MCR's inactive Ni(II) state at room temperature and show promise for capturing its active Ni(I) form.Our team has established several critical aspects of the MCR mechanism using a combination of experimental and computational studies. MCR uses CH 3 -SCoM and CoBSH as substrates, producing methane and a disulfide product CoMSSCoB. Kinetic analysis showed that productive substrate binding requires CH 3 -SCoM to bind first, inducing conformational changes that optimize the active site for subsequent CoBSH binding. Following substrate binding, four proposed methane production/oxidation mechanisms were examined, establishing whether the reaction proceeds through an organometallic methyl-nickel(III), methyl anion ion, or methyl radical intermediate. Experimental measurements using CoBSH analogs successfully slowed the reaction, allowing for mechanistic insight that demonstrated the methyl radical pathway, where the initial interactions involve homolytic cleavage of the methyl-sulfur bond, generating a methyl radical that quickly abstracts the thiol hydrogen atom of CoBSH to form methane. Computational studies further confirmed that, compared to other mechanisms, the methyl radical mechanism is thermodynamically more favorable and accessible under physiological conditions.Spectroscopic and computational studies challenged the conventional understanding of substrate binding in MCR by proposing an alternative positioning of CH 3 -SCoM and CoMSSCoB in the active site pocket. The research suggested that CH 3 -SCoM (substrate) and CoMSSCoB (product) bind via their sulfonate groups to the Ni(I) center of cofactor F 430 . This binding allows for the reaction without substrate reorganization in the pocket but would require a long-range electron transfer. Altogether, the work summarized in this review reflects our current understanding of the enzyme's catalytic mechanism and structural dynamics. This is essential for developing efficient methane conversion technologies that could mitigate its environmental impact while harnessing energy-storage properties.

03 NATURAL GAS↗

High-resolution X-ray structure of Gln143Asn manganese superoxide dismutase captures multiple hydrogen peroxide-binding sites

Human mitochondrial manganese superoxide dismutase (MnSOD) converts superoxide into hydrogen peroxide and molecular oxygen, serving as a key defence against oxidative damage. Despite extensive studies, the full structural characterization of H 2 O 2 -binding sites in MnSOD remains largely unexplored. Previous H 2 O 2 -soaked MnSOD structures have identified two distinct H 2 O 2 -binding sites: one directly ligated to the catalytic manganese (LIG position) and another at the active-site gateway (PEO position) between the second-shell residues Tyr34 and His30. In this study, a kinetically impaired Gln143Asn MnSOD variant is used to trap and explore additional H 2 O 2 -binding sites beyond the second-shell solvent gate. In the wild-type enzyme, Gln143 mediates proton transfers with the manganese-bound solvent (WAT1) to drive redox cycling of the metal, which is necessary for effective superoxide dismutation. Substitution with Asn stalls catalysis because the increased distance from WAT1 disrupts critical proton-coupled electron-transfer (PCET) events, and the redox cycling of the active-site metal is impaired. This, in turn, stalls the electrostatic cycling of positive charge on the enzyme surface and enhances the likelihood of trapping transient H 2 O 2 -bound states in this variant. The results reveal several H 2 O 2 molecules leading up to the active site, in addition to the canonical LIG and PEO positions.

Dasgupta, Medhanjali [University of Nebraska Medic↗

Hexagonal boron nitride: Epitaxial growth and device applications

As a newest family member of the III-nitrides, BN is considered amongst the remaining frontiers in wide energy bandgap semiconductors with potentials for technologically significant applications in deep UV (DUV) optoelectronics, solid-state neutron detectors, electron emitters, single photon emitters, switching/memory devices, and super-capacitors. It was shown that it is possible to produce h-BN epilayers with high hexagonal phase purity, UV transparency, and film stoichiometry by employing nitrogen-rich growth conditions. The quasi-2D nature of h-BN supports unusually strong optical transitions near the band edge and a large exciton binding energy on the order of 0.7 eV. Since the isotope of B-10 has a large capture cross-section for thermal neutrons, h-BN is an ideal material for the fabrication of solid-state neutron detectors for special nuclear materials detection, well and geothermal logging, and medical imaging applications. Freestanding B-10 enriched h-BN (h- 10 BN) epilayers with varying thicknesses up to 200 μm have been successfully synthesized by metal organic chemical vapor deposition (MOCVD) as of this writing. By utilizing the conductivity anisotropy nature of h-BN, 1 cm 2 lateral detectors fabricated from 100 μm thick h-10BN epilayers have demonstrated a detection efficiency of 59% for thermal neutrons, which is the highest on record among all solid-state neutron detectors as of today. It was noted that high growth temperatures, long growth times and the use of sapphire substrate tend to incorporate oxygen related impurities into h- 10 BN epilayers, which strongly impacted the carrier mobility-lifetime (μτ) products and charge collection efficiencies of h- 10 BN neutron detectors. As the h-BN material technology further develops, improved carrier mobilities and μτ products will allow the fabrication of h-BN devices with enhanced performance.

42 ENGINEERING↗

Quaternary Semiconductor Cd1−xZnxTe1−ySey for High-Resolution, Room-Temperature Gamma-Ray Detection

The application of Cd0.9Zn0.1Te (CZT) single crystals, the primary choice for high-resolution, room-temperature compact gamma-ray detectors in the field of medical imaging and homeland security for the past three decades, is limited by the high cost of production and maintenance due to low detector grade crystal growth yield. The recent advent of its quaternary successor, Cd0.9Zn0.1Te1−ySey (CZTS), has exhibited remarkable crystal growth yield above 90% compared to that of ~33% for CZT. The inclusion of Se in appropriate stoichiometry in the CZT matrix is responsible for reducing the concentration of sub-grain boundary (SGB) networks which greatly enhances the compositional homogeneity and growth yield. SGB networks also host defect centers responsible for charge trapping, hence their reduced concentration ensures minimized charge trapping. Indeed, CZTS single crystals have shown remarkable improvement in electron charge transport properties and energy resolution over CZT detectors. However, our studies have found that the overall charge transport in CZTS is still limited by the hole trapping. In this article, we systematically review the advances in the CZTS growth techniques, its performance as room-temperature radiation detector, and the role of defects and their passivation studies needed to improve the performance of CZTS detectors further.

36 MATERIALS SCIENCE↗

Core Characterization of Bakken Shale from the Bedwell 33-52-1-1H Well, Sheridan County, Montana

The computed tomography (CT) facilities and the Multi-Sensor Core Logger (MSCL) at the National Energy Technology Laboratory (NETL) in Morgantown, West Virginia were used to characterize core of the Bedwell 33-52-1-1H well (API 25-091-21920), a wildcat field in Sheridan County, Montana. The primary impetus of this work is to provide a unique dataset to researchers at universities, national laboratories, geological surveys, and other locations for additional analyses. The resultant datasets are presented in this report and can be accessed from NETL's Energy Data eXchange (EDX) online system using the following link: https://edx.netl.doe.gov/dataset/bedwell-33-52-1-1h-well. The equipment and techniques used to characterize the full core were non-destructive, enabling future examinations and analyses to be performed on these cores. However, none of the equipment used was suitable for direct visualization of the pore space in fine-grained structures such as those found in shales; fractures, discontinuities, and millimeter scale features were readily detectable with the methods tested. Imaging with the NETL medical CT scanner was performed on the entire core. Qualitative analysis of the medical CT images, coupled with X-ray fluorescence (XRF), P-wave, and magnetic susceptibility measurements from the MSCL were useful in identifying zones of interest for more detailed analysis. A selection of samples (Table 1) were cored, sliced, and powdered for additional characterization analyses. These analyses did involve destructive subsampling of the full core at discrete sections, and the results are presented here in the context of the larger core description. Selected sections of the core were removed from the full core for detailed analyses using the following destructive techniques: bulk inductively coupled plasma-optical emission spectroscopy (ICP-OES), isolation of carbon and sulfur, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and higher resolution CT scan with NETL’s micro-CT scanning systems. The ability to quickly identify key areas for more detailed study with higher resolution will save time and resources in future studies. The combination of methods used provides a multi-scale analysis of the core; the resulting macro and micro descriptions are relevant to many subsurface energy related examinations traditionally performed at NETL.

04 OIL SHALES AND TAR SANDS↗

Using Electronic Noses to Detect Tumors During Neurosurgery

It has been proposed to develop special-purpose electronic noses and algorithms for processing the digitized outputs of the electronic noses for determining whether tissue exposed during neurosurgery is cancerous. At present, visual inspection by a surgeon is the only available intraoperative technique for detecting cancerous tissue. Implementation of the proposal would help to satisfy a desire, expressed by some neurosurgeons, for an intraoperative technique for determining whether all of a brain tumor has been removed. The electronic-nose technique could complement multimodal imaging techniques, which have also been proposed as means of detecting cancerous tissue. There are also other potential applications of the electronic-nose technique in general diagnosis of abnormal tissue. In preliminary experiments performed to assess the viability of the proposal, the problem of distinguishing between different types of cultured cells was substituted for the problem of distinguishing between normal and abnormal specimens of the same type of tissue. The figure presents data from one experiment, illustrating differences between patterns that could be used to distinguish between two types of cultured cancer cells. Further development can be expected to include studies directed toward answering questions concerning not only the possibility of distinguishing among various types of normal and abnormal tissue but also distinguishing between tissues of interest and other odorous substances that may be present in medical settings.

Homer, Margie L.↗

Spinoff 2012

Topics covered include: Water Treatment Technologies Inspire Healthy Beverages; Dietary Formulas Fortify Antioxidant Supplements; Rovers Pave the Way for Hospital Robots; Dry Electrodes Facilitate Remote Health Monitoring; Telescope Innovations Improve Speed, Accuracy of Eye Surgery; Superconductors Enable Lower Cost MRI Systems; Anti-Icing Formulas Prevent Train Delays; Shuttle Repair Tools Automate Vehicle Maintenance; Pressure-Sensitive Paints Advance Rotorcraft Design Testing; Speech Recognition Interfaces Improve Flight Safety; Polymers Advance Heat Management Materials for Vehicles; Wireless Sensors Pinpoint Rotorcraft Troubles; Ultrasonic Detectors Safely Identify Dangerous, Costly Leaks; Detectors Ensure Function, Safety of Aircraft Wiring; Emergency Systems Save Tens of Thousands of Lives; Oxygen Assessments Ensure Safer Medical Devices; Collaborative Platforms Aid Emergency Decision Making; Space-Inspired Trailers Encourage Exploration on Earth; Ultra-Thin Coatings Beautify Art; Spacesuit Materials Add Comfort to Undergarments; Gigapixel Images Connect Sports Teams with Fans; Satellite Maps Deliver More Realistic Gaming; Elemental Scanning Devices Authenticate Works of Art; Microradiometers Reveal Ocean Health, Climate Change; Sensors Enable Plants to Text Message Farmers; Efficient Cells Cut the Cost of Solar Power; Shuttle Topography Data Inform Solar Power Analysis; Photocatalytic Solutions Create Self-Cleaning Surfaces; Concentrators Enhance Solar Power Systems; Innovative Coatings Potentially Lower Facility Maintenance Costs; Simulation Packages Expand Aircraft Design Options; Web Solutions Inspire Cloud Computing Software; Behavior Prediction Tools Strengthen Nanoelectronics; Power Converters Secure Electronics in Harsh Environments; Diagnostics Tools Identify Faults Prior to Failure; Archiving Innovations Preserve Essential Historical Records; Meter Designs Reduce Operation Costs for Industry; Commercial Platforms Allow Affordable Space Research; Fiber Optics Deliver Real-Time Structural Monitoring; Camera Systems Rapidly Scan Large Structures; Terahertz Lasers Reveal Information for 3D Images; Thin Films Protect Electronics from Heat and Radiation; Interferometers Sharpen Measurements for Better Telescopes; and Vision Systems Illuminate Industrial Processes.

Source record↗

FrESCO: Framework for Exploring Scalable Computational Oncology

The National Cancer Institute (NCI) monitors population level cancer trends as part of its Surveillance, Epidemiology, and End Results (SEER) program. This program consists of state or regional level cancer registries which collect, analyze, and annotate cancer pathology reports. From these annotated pathology reports, each individual registry aggregates cancer phenotype information from electronic health records. This data is then used to create summary statistics about cancer incidence and mortality to facilitate population health monitoring. Extracting phenotypic information from these reports is a labor intensive task, requiring specialized knowledge about the reports and cancer. Automating the information extraction process from cancer pathology reports has the potential to improve data quality by extracting information in a consistent manner across registries. It can also improve patient outcomes by reducing the time from diagnosis, enabling rapid case ascertainment for clinical trials. Here we present FrESCO, a modular deep-learning natural language processing (NLP) library initially designed for extracting pathology information from clinical text documents. This repository is not solely limited to clinical medical text, but may also be used by researchers just getting started with NLP methods and those looking for a robust solution for their classification problems.

60 APPLIED LIFE SCIENCES↗

Cryo-EM structures reveal native GABA A receptor assemblies and pharmacology

Type A γ-aminobutyric acid receptors (GABA A Rs) are the principal inhibitory receptors in the brain and the target of a wide range of clinical agents, including anaesthetics, sedatives, hypnotics and antidepressants. However, our understanding of GABA A R pharmacology has been hindered by the vast number of pentameric assemblies that can be derived from 19 different subunits and the lack of structural knowledge of clinically relevant receptors. Here, we isolate native murine GABA A R assemblies containing the widely expressed α1 subunit and elucidate their structures in complex with drugs used to treat insomnia (zolpidem (ZOL) and flurazepam) and postpartum depression (the neurosteroid allopregnanolone (APG)). Using cryo-electron microscopy (cryo-EM) analysis and single-molecule photobleaching experiments, we uncover three major structural populations in the brain: the canonical α1β2γ2 receptor containing two α1 subunits, and two assemblies containing one α1 and either an α2 or α3 subunit, in which the single α1-containing receptors feature a more compact arrangement between the transmembrane and extracellular domains. Interestingly, APG is bound at the transmembrane α/β subunit interface, even when not added to the sample, revealing an important role for endogenous neurosteroids in modulating native GABA A Rs. Together with structurally engaged lipids, neurosteroids produce global conformational changes throughout the receptor that modify the ion channel pore and the binding sites for GABA and insomnia medications. Our data reveal the major α1-containing GABA A R assemblies, bound with endogenous neurosteroid, thus defining a structural landscape from which subtype-specific drugs can be developed.

59 BASIC BIOLOGICAL SCIENCES↗

Utility of MODIS Aerosol Optical Depth for Estimating PM2.5 Exposure in Environmental Public Health Surveillance

As part of the National Environmental Public Health Tracking Network (EPHTN) the National Center for Environmental Health (NCEH) at the Centers for Disease Control and Prevention (CDC) is leading a project called Health and Environment Linked for Information Exchange (HELIX-Atlanta). The goal of developing the National Environmental Public Health Tracking Network is to improve the health of communities. Currently, few systems exist at the state or national level to concurrently track many of the exposures and health effects that might be associated with environmental hazards. An additional challenge is estimating exposure to environmental hazards such as particulate matter whose aerodynamic diameter is less than or equal to 2.5 micrometers (PM(2.5)) HELIX-Atlanta's goal is to examine the feasibility of building an integrated electronic health and environmental data network in five counties of Metropolitan Atlanta, GA (Clayton, Cobb, DeKalb, Fulton, and Gwinnett counties). Under HELIX-Atlanta, pilot projects are being conducted to develop methods to characterize exposure; link health and environmental data; analyze the relationship between health and environmental factors; and communicate findings. NASA Marshall Space Flight Center (NASA/MSFC) is collaborating with CDC to combine NASA earth science satellite observations related to air quality and environmental monitoring data to model surface estimates of PM(2.5) concentrations that can be linked with clinic visits for asthma. From 1999-2000 there were over 9,400 hospitalizations per year in Georgia with asthma as the primary diagnosis. The majority of these hospitalizations occurred in medical facilities in the five most populous Metro-Atlanta counties. Hospital charges resulting from asthma in Georgia are approximately $59 million dollars annually. There is evidence in the research literature that asthmatic persons are at increased risk of developing asthma exacerbations with exposure to environmental factors, including PM(2.5). Thus, HELIX-Atlanta is focusing on methods for characterizing population exposure to PM(2.5) for the Atlanta metropolitan area that could be used in on-going surveillance. While use of the Air Quality System, (AQS) PM(2.5) data alone could meet HELIX Atlanta, specifications, there are only five AQS sites in the Atlanta area, thus the spatial coverage is not ideal. Also, the AQS ground observations are made at time intervals ranging from one hour to six days leaving some temporal gaps. NASA Moderate Resolution Imaging Spectroradiometer (MODIS) satellite Aerosol Optical Depth (AOD) data have the potential for estimating daily ground level PM(2.5) at 10 km resolution over the metropolitan Atlanta area supplementing the AQS ground observations and filling their spatial and temporal gaps.

Al-Hamdan, Mohammad↗