1,168 research outputs found
Master of Science
thesisThe University of Utah Seismograph Stations recorded 293 earthquakes (3.0 < M < 5.9) between April 17, 2007 and June 30, 2012. During this time, four-element infrasound data were collected from three permanent (NOQ, BGU, and EPU; installed 2006 - 2007) and six temporary (BRP, WMU, HWU, FSU, LCM, and PSU; installed summer of 2010) seismo-acoustic arrays. Unique epicentral infrasound observations from nine earthquakes with M 3.6 - 5.9 are identified and characterized. The detections were recorded from normal, oblique normal, and strike-slip faulting earthquakes at distances of 156 - 695 km and depths of 5 - 12 km. We use ray-tracing through ground-to- space atmospheric models from the epicenters to each array to determine the atmospheric turning altitude and associated wind velocities. Distance and wind corrected amplitudes match previously determined scaling relations. However, the duration observations from smaller magnitude earthquakes suggest the possibility of an additional scaling relation for events M < 4.6. This possible change in duration scaling relation is inconsistent with the hypothesis that infrasound duration scales with the areal extent of the epicentral region subjected to a threshold peak ground acceleration. The predicted ground motions show that the area subject to the threshold increases more rapidly with increased magnitudes. Overall, the small percentage of infrasound detections from the total possible suggests that infrasound is not a robust method of detecting and characterizing small earthquake sources
Inhibition of the HEG1-KRIT1 interaction increases KLF4 and KLF2 expression in endothelial cells
The Kruppel-like Factors 2 and 4 (KLF2/4) are transcription factors and master regulators of endothelial cells (ECs) phenotype and homeostasis. KLF2/4 are important blood-flow-responsive genes within ECs that differentially regulate the expression of factors that confer anti-inflammatory, antithrombotic, and antiproliferative effects in ECs. We found that genetic inactivation of endothelial Krit1 (Krev interaction trapped protein 1) or Heg1 (Heart of glass) led to upregulation of KLF2/4 expression levels. We also observed that vasoprotective proteins, endothelial nitric oxide synthase (eNOS) and thrombomodulin (TM), are upregulated by the increase of KLF2/4 as a result of loss of endothelial KRIT1. Here, we developed a high-throughput screening assay to identify inhibitors of the HEG1-KRIT1 interaction and identified sirtinol (HKi001) as a promising hit inhibitor. The crystal structure of sirtinol bound to the KRIT1 FERM domain confirmed the primary screening results and ultimately led to the identification of a fragment-like inhibitor (HKi002), which occupies the HEG1 pocket producing comparable activity. These findings suggest that these inhibitors block the interaction by competing with the HEG1 for binding to KRIT1 FERM domain. Moreover, our results demonstrate that HKi002 upregulates KLF2/4 gene expression in two types of human ECs. These results reveal an unexpected role of inhibiting the HEG1-KRIT1 interaction and provide a proof-of-concept that pharmacological manipulation of this complex may offer new opportunities to induce expression of KLF2/4 as vasoprotective factors
Rapidly Decaying Supernova 2010X: A Candidate ".Ia" Explosion
We present the discovery, photometric and spectroscopic follow-up
observations of SN 2010X (PTF 10bhp). This supernova decays exponentially with
tau_d=5 days, and rivals the current recordholder in speed, SN 2002bj. SN 2010X
peaks at M_r=-17mag and has mean velocities of 10,000 km/s. Our light curve
modeling suggests a radioactivity powered event and an ejecta mass of 0.16
Msun. If powered by Nickel, we show that the Nickel mass must be very small
(0.02 Msun) and that the supernova quickly becomes optically thin to
gamma-rays. Our spectral modeling suggests that SN 2010X and SN 2002bj have
similar chemical compositions and that one of Aluminum or Helium is present. If
Aluminum is present, we speculate that this may be an accretion induced
collapse of an O-Ne-Mg white dwarf. If Helium is present, all observables of SN
2010X are consistent with being a thermonuclear Helium shell detonation on a
white dwarf, a ".Ia" explosion. With the 1-day dynamic-cadence experiment on
the Palomar Transient Factory, we expect to annually discover a few such
events.Comment: 6 pages, 5 figures; Minor Changes; Note correction in Fig 4 caption;
published by ApJ
Circulating Markers Reflect Both Anti- and Pro-Atherogenic Drug Effects in ApoE-Deficient Mice
Background: Current drug therapy of atherosclerosis is focused on treatment of major risk factors, e.g. hypercholesterolemia while in the future direct disease modification might provide additional benefits. However, development of medicines targeting vascular wall disease is complicated by the lack of reliable biomarkers. In this study, we took a novel approach to identify circulating biomarkers indicative of drug efficacy by reducing the complexity of the in vivo system to the level where neither disease progression nor drug treatment was associated with the changes in plasma cholesterol.Results: ApoE-/- mice were treated with an ACE inhibitor ramipril and HMG-CoA reductase inhibitor simvastatin. Ramipril significantly reduced the size of atherosclerotic plaques in brachiocephalic arteries, however simvastatin paradoxically stimulated atherogenesis. Both effects occurred without changes in plasma cholesterol. Blood and vascular samples were obtained from the same animals. In the whole blood RNA samples, expression of MMP9, CD14 and IL-1RN reflected pro and anti-atherogenic drug effects. In the plasma, several proteins, e.g. IL-1β, IL-18 and MMP9 followed similar trends while protein readout was less sensitive than RNA analysis.Conclusion: In this study, we have identified inflammation-related whole blood RNA and plasma protein markers reflecting anti-atherogenic effects of ramipril and pro-atherogenic effects of simwastatin in a mouse model of atherosclerosis. This opens an opportunity for early, non-invasive detection of direct drug effects on atherosclerotic plaques in complex in vivo systems
Structural basis for CRISPR RNA-guided DNA recognition by Cascade
The CRISPR (clustered regularly interspaced short palindromic repeats) immune system in prokaryotes uses small guide RNAs to neutralize invading viruses and plasmids. In Escherichia coli, immunity depends on a ribonucleoprotein complex called Cascade. Here we present the composition and low-resolution structure of Cascade and show how it recognizes double-stranded DNA (dsDNA) targets in a sequence-specific manner. Cascade is a 405-kDa complex comprising five functionally essential CRISPR-associated (Cas) proteins (CasA1B2C6D1E1) and a 61-nucleotide CRISPR RNA (crRNA) with 5′-hydroxyl and 2′,3′-cyclic phosphate termini. The crRNA guides Cascade to dsDNA target sequences by forming base pairs with the complementary DNA strand while displacing the noncomplementary strand to form an R-loop. Cascade recognizes target DNA without consuming ATP, which suggests that continuous invader DNA surveillance takes place without energy investment. The structure of Cascade shows an unusual seahorse shape that undergoes conformational changes when it binds target DNA.
Discovery of an intermediate-luminosity red transient in M51 and its likely dust-obscured, infrared-variable progenitor
We present the discovery of an optical transient (OT) in Messier 51,
designated M51 OT2019-1 (also ZTF19aadyppr, AT 2019abn, ATLAS19bzl), by the
Zwicky Transient Facility (ZTF). The OT rose over 15 days to an observed
luminosity of (), in the
luminosity gap between novae and typical supernovae (SNe). Spectra during the
outburst show a red continuum, Balmer emission with a velocity width of
km s, Ca II and [Ca II] emission, and absorption features
characteristic of an F-type supergiant. The spectra and multiband light curves
are similar to the so-called "SN impostors" and intermediate-luminosity red
transients (ILRTs). We directly identify the likely progenitor in archival
Spitzer Space Telescope imaging with a m luminosity of
and a color redder than 0.74 mag, similar
to those of the prototype ILRTs SN 2008S and NGC 300 OT2008-1. Intensive
monitoring of M51 with Spitzer further reveals evidence for variability of the
progenitor candidate at [4.5] in the years before the OT. The progenitor is not
detected in pre-outburst Hubble Space Telescope optical and near-IR images. The
optical colors during outburst combined with spectroscopic temperature
constraints imply a higher reddening of mag and higher
intrinsic luminosity of
() near peak than seen in previous ILRT
candidates. Moreover, the extinction estimate is higher on the rise than on the
plateau, suggestive of an extended phase of circumstellar dust destruction.
These results, enabled by the early discovery of M51 OT2019-1 and extensive
pre-outburst archival coverage, offer new clues about the debated origins of
ILRTs and may challenge the hypothesis that they arise from the
electron-capture induced collapse of extreme asymptotic giant branch stars.Comment: 21 pages, 5 figures, published in ApJ
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