Heterotrimeric coiled-coils as viral fusion protein mimics

2010 Spring.Includes bibliographic references.Covers not scanned.Print version deaccessioned 2022.The a-helical coiled-coil, formed by the association and supercoiling of two or more a-helices, is a ubiquitous protein structure that mediates a wide range of biological activity. It is characterized by a heptad repeat of amino acids that serve to form both the hydrophobic core and electrostatic interfaces of the coiled-coil. Previous work in our lab showed the viability of designing a self-assembling heterotrimeric coiled-coil by sole manipulation of the hydrophobic core. This technique utilized a steric matching approach whereby one large side chain packed against two small ones. An added benefit to this type of control is that it allowed the freedom to explore additional interactions specific to the electrostatic interface. Many enveloped viruses, including HIV-1, incorporate trimeric coiled-coils in their fusion proteins, and, consequently, are involved in the pathway to infection. Through interactions at the electrostatic interfaces of the coiled-coils, these fusion proteins form a six-helix bundle called a trimer-of-hairpins. The formation of this structure is a precursor to membrane fusion of the viral and host cells, and, as a result, it has become a therapeutic target. The steric matching technique developed in our lab allows us to graft key contacts from the native 111 sequences onto a stable, heterotrimeric system and construct a mimic of the trimer-of-hairpins, as was done with HIV-I previously in our lab. The work that follows shows that a viable mimic of the Human Respiratory Syncytial Virus is also possible. A stable, self-assembling mimic was designed, synthesized and validated through various spectroscopic methods. Additionally, a mutant study was conducted to further refine our knowledge of the importance of the residues thought to be key to the formation of the trimer-of-hairpins. Other work was performed extending the process to the Human T-cell Leukemia Virus, bringing the possibility of a complete and stable mimic ever closer

Radio continuum observations of local star-forming galaxies using the Caltech Continuum Backend on the Green Bank Telescope

We observed radio continuum emission in 27 local (D < 70 Mpc) star-forming galaxies with the Robert C. Byrd Green Bank Telescope between 26 GHz and 40 GHz using the Caltech Continuum Backend. We obtained detections for 22 of these galaxies at all four sub-bands and four more marginal detections by taking the average flux across the entire bandwidth. This is the first detection (full or marginal) at these frequencies for 22 of these galaxies. We fit spectral energy distributions (SEDs) for all of the four-sub-band detections. For 14 of the galaxies, SEDs were best fit by a combination of thermal free-free and nonthermal synchrotron components. Eight galaxies with four-sub-band detections had steep spectra that were only fit by a single nonthermal component. Using these fits, we calculated supernova rates, total number of equivalent O stars, and star formation rates within each ~23 arcsecond beam. For unresolved galaxies, these physical properties characterize the galaxies' recent star formation on a global scale. We confirm that the radio-far-infrared correlation holds for the unresolved galaxies' total 33 GHz flux regardless of their thermal fractions, though the scatter on this correlation is larger than that at 1.4 GHz. In addition, we found that for the unresolved galaxies, there is an inverse relationship between the ratio of 33 GHz flux to total far-infrared flux and the steepness of the galaxy's spectral index between 1.4 GHz and 33 GHz. This relationship could be an indicator of the timescale of the observed episode of star formation.Comment: 36 pages, 9 figures; accepted for publication in ApJ. First and second author affiliation updated to reflect departmental name chang

Evolution of the fish sorting and debris handling system at the Swift Hydroelectric Project Floating Surface Collector for juvenile salmonids

The Swift Floating Surface Collector (FSC) began operation in 2012 and was the third of eight large scale surface collectors installed in the Pacific Northwest region of the United States since 2008. Downstream fish collection and sorting at Swift Dam was a key component of the Lewis River reintroduction program that reestablished passage of anadromous salmonids past PacifiCorp’s three large hydropower dams (510 MW Lewis River Hydroelectric Project) that blocked fish passage beginning in 1931. The Swift FSC floats to accommodate reservoir fluctuation of 90 feet and attracts fish with pumped surface flows of 600 cfs. After passing through a large V-screen, fish and debris enter a fish separator system designed to separate fish by girth into fry (≤3” long), smolts (≤10” long), and adult fish (\u3e10”). The separator system was designed as an evolution of similar systems studied on the Snake, Columbia, Yakima, and Cowlitz Rivers, and was optimized on lessons learned and to accommodate space constraints on the floating structure. Swift dam is the most upstream project on the Lewis river, so all flow entering the collector is unregulated and carries a heavy debris load. Operations staff are finding this system collects more debris than any of the other new FSC’s in the region. Several modifications to provide better debris exclusion, handling, and processing have been made and others are currently under design. These modifications also improve fish attraction, sorting, collection, and safety conditions for the operational staff. This presentation will review the original design goals and details, improvements made through 2017, highlight a new system currently under design planned to be operational in late 2018, and describe other ideas under consideration for adaptive management implementation. Lessons learned can be utilized at other downstream fish collectors with high debris loading

Using GES DISC Data to Study Kilauea Volcano of 2018

Kilauea volcano in Hawaii which erupted in early May 2018 injected massive amount of SO2 and ash into the atmosphere. The lava flow during the eruption destroyed many home and neighborhoods. The SO2 plume during the eruption of Kilauea volcano is analyzed from May to August 2018 using multiple satellite products such as Level 2 TROPspheric Monitoring Instrument (TROPOMI) and Level 3 Ozone Monitoring Instrument (OMI) from the NASA Goddard Earth Sciences Data and Information Services Center (GES DISC). GES DISC hosts multi-disciplinary Earth science data sets that can be used to analyze natural disasters, such as the Kilauea volcano. Additionally, GES DISC's Giovanni tool can be used to visualize these data. We acquired OMI through the subsetting function, which is processed by the GES DISC in-house developed backend software Level3/4 Regrider and Subsetter (L34RS) and TROPOMI using OPeNDAP.Data from the OMI OMSO2e product showed elevated levels of SO2 amounts during the eruption between May to August 2018. Similarly, ground-based stations at Hawaii Volcanoes National Park recorded higher SO2 concentrations during the same time period. This study uses wind direction from Modern-Era Retrospective analysis for Research and Applications, version 2 (MERRA-2) to analyze the transport and dispersion of SO2 plume and map lava flows from the volcano using thermal images from Visible Infrared Imaging Radiometer Suite (VIIRS). Furthermore, satellite observations combined with socioeconomic and public health data are used to analyze its impact in public health

Recruitment and baseline characteristics of the Community of Voices choir study to promote the health and well-being of diverse older adults.

Objective:To describe the recruitment and baseline results of the Community of Voices study that aims to examine the effect of a community choir intervention on the health and well-being of older adults from diverse racial/ethnic and socioeconomic backgrounds. Method:Using community-based participatory research methods, we recruited adults age 60 and over from 12 Administration on Aging-supported senior centers in San Francisco into a 2-arm cluster-randomized controlled trial of the community choir intervention. Multiple outreach methods were used. We tracked outreach, screening, and recruitment metrics and collected demographics and baseline outcomes via community-based, interviewer-administered surveys and performance measures of cognition, physical function, and psychosocial variables. Results:The study contacted 819 individuals, screened 636, and enrolled 390 diverse older adults over a 42-month, phased recruitment period. The mean age was 71.2 (SD = 7.3), and the majority were women. Two-thirds of the sample are non-white, and 20% of participants reported having financial hardship. Discussion:Outreach and recruitment methods used in the Community of Voices trial facilitated enrollment of a large proportion of minority and lower-SES older adults in the final sample. Similar recruitment approaches could serve as a model for recruiting diverse racial/ethnic and socioeconomic older adults into research

Sentinel-5P/TROPOMI and S-NPP/OMPS Data Support at GES DISC

The TROPspheric Monitoring Instrument (TROPOMI) on the Sentinel-5 Precursor (Sentinel-5P) is the first of the Atmospheric Composition Sentinels by the European Space Agency (ESA) that provides measurements of ozone, NO2, SO2, CH4, CO, formaldehyde, aerosols and cloud at high spatial, temporal and spectral resolutions. The early afternoon orbit of Sentinel-5P mission provides a strong synergy with the U.S. Suomi National Polar-orbiting Partnership (S-NPP) satellite, especially in that the S-NPP Ozone Monitoring and Profiling Suite (OMPS) facilitates high vertically resolved stratospheric and lower mesospheric ozone profiles. The NASA Goddard Earth Sciences Data and Information Services Center (GES DISC) supports over a thousand data collections in the Focus Areas of Atmospheric Composition, Water & Energy Cycles, and Climate Variability and it is the Distributed Active Archive Center (DAAC) that is curating both offline Sentinel-5P TROPOMI and S-NPP OMPS Level-1B (L1B) and Level-2 (L2) products. Through its convenient and enhanced tools/services such as OPeNDAP and L2 Subsetting, GES DISC offers air quality remote sensing user communities facile solutions for complex Earth science data and applications. This presentation will demonstrate TROPOMI and OMPS products including earthview radiance, solar irradiance, and currently available L2 datasets, as well as easy ways to access, visualize and subset data. The implementation of the End User License Agreement (EULA) between NASA GES DISC and all data users accessing data at GES DISC will be emphasized as well

Unveiling Extragalactic Star Formation Using Radio Recombination Lines: An Expanded Very Large Array Pilot Study With Ngc 253

Radio recombination lines (RRLs) are powerful, extinction-free diagnostics of the ionized gas in young, star-forming regions. Unfortunately, these lines are difficult to detect in external galaxies. We present the results of Expanded Very Large Array (EVLA) observations of the RRL and radio continuum emission at 33 GHz from NGC 253, a nearby nuclear starburst galaxy. We detect the previously unobserved H58{alpha} and H59{alpha} RRLs and make simultaneous sensitive measurements of the continuum. We measure integrated line fluxes of 44.3 {+-} 0.7 W m{sup -2} and 39.9 {+-} 0.8 W m{sup -2} for the H58{alpha} and H59{alpha} lines, respectively. The thermal gas in NGC 253 is kinematically complex with multiple velocity components. We constrain the density of the thermal gas to (1.4-4) x 10{sup 4} cm{sup -3} and estimate an ionizing photon flux of 1 x 10{sup 53} s{sup -1}. We use the RRL kinematics and the derived ionizing photon flux to show that the nuclear region of NGC 253 is not gravitationally bound, which is consistent with the outflow of gas inferred from the X-ray and H{alpha} measurements. The line profiles, fluxes, and kinematics of the H58{alpha} and H59{alpha} lines agree with those of RRLs at different frequencies confirming themore » accuracy of the previous, more difficult, high-frequency observations. We find that the EVLA is an order of magnitude more efficient for extragalactic RRL observations than the Very Large Array. These observations demonstrate both the power of the EVLA and the future potential of extragalactic RRL studies with the EVLA.« les

Unveiling Extragalactic Star Formation Using Radio Recombination Lines: An EVLA Pilot Study with NGC 253

Radio recombination lines (RRLs) are powerful, extinction-free diagnostics of the ionized gas in young, star-forming regions. Unfortunately, these lines are difficult to detect in external galaxies. We present the results of EVLA observations of the RRL and radio continuum emission at 33 GHz from NGC 253, a nearby nuclear starburst galaxy. We detect the previously unobserved H58a and H59a RRLs and make simultaneous sensitive measurements of the continuum. We measure integrated line fluxes of $44.3 \pm 0.7$ W m$^{-2}$ and $39.9 \pm 0.8$ W m$^{-2}$ for the H58a and H59a lines, respectively. The thermal gas in NGC 253 is kinematically complex with multiple velocity components. We constrain the density of the thermal gas to $1.4 - 4 \times 10^4$ cm$^{-3}$ and estimate an ionizing photon flux of $1 \times 10^{53}$ s$^{-1}$. We use the RRL kinematics and the derived ionizing photon flux to show that the nuclear region of NGC 253 is not gravitationally bound, which is consistent with the outflow of gas inferred from the X-ray and Halpha measurements. The line profiles, fluxes, and kinematics of the H58a and H59a lines agree with those of RRLs at different frequencies confirming the accuracy of the previous, more difficult, high frequency observations. We find that the EVLA is an order of magnitude more efficient for extragalactic RRL observations than the VLA. These observations demonstrate both the power of the EVLA and the future potential of extragalactic RRL studies with the EVLA.Comment: Accepted for publication in the ApJL EVLA Special Issue. Version with high resolution figures at http://www.astro.virginia.edu/~aak8t/data/rrl/ms.p

The construction and evaluation of a word association test for intermediate grades

Thesis (Ed.M.)--Boston Universit