226 research outputs found
A Search for Exozodiacal Clouds with Kepler
Planets embedded within dust disks may drive the formation of large scale
clumpy dust structures by trapping dust into resonant orbits. Detection and
subsequent modeling of the dust structures would help constrain the mass and
orbit of the planet and the disk architecture, give clues to the history of the
planetary system, and provide a statistical estimate of disk asymmetry for
future exoEarth-imaging missions. Here we present the first search for these
resonant structures in the inner regions of planetary systems by analyzing the
light curves of hot Jupiter planetary candidates identified by the Kepler
mission. We detect only one candidate disk structure associated with KOI 838.01
at the 3-sigma confidence level, but subsequent radial velocity measurements
reveal that KOI 838.01 is a grazing eclipsing binary and the candidate disk
structure is a false positive. Using our null result, we place an upper limit
on the frequency of dense exozodi structures created by hot Jupiters. We find
that at the 90% confidence level, less than 21% of Kepler hot Jupiters create
resonant dust clumps that lead and trail the planet by ~90 degrees with optical
depths >~5*10^-6, which corresponds to the resonant structure expected for a
lone hot Jupiter perturbing a dynamically cold dust disk 50 times as dense as
the zodiacal cloud.Comment: 22 pages, 6 figures, Accepted for publication in Ap
Malic enzyme 1 absence in synovial sarcoma shifts antioxidant system dependence and increases sensitivity to ferroptosis induction with ACXT-3102
PURPOSE: To investigate the metabolism of synovial sarcoma (SS) and elucidate the effect of malic enzyme 1 absence on SS redox homeostasis.
EXPERIMENTAL DESIGN: ME1 expression was measured in SS clinical samples, SS cell lines, and tumors from an SS mouse model. The effect of ME1 absence on glucose metabolism was evaluated utilizing Seahorse assays, metabolomics, and C13 tracings. The impact of ME1 absence on SS redox homeostasis was evaluated by metabolomics, cell death assays with inhibitors of antioxidant systems, and measurements of intracellular reactive oxygen species (ROS). The susceptibility of ME1-null SS to ferroptosis induction was interrogated in vitro and in vivo.
RESULTS: ME1 absence in SS was confirmed in clinical samples, SS cell lines, and an SS tumor model. Investigation of SS glucose metabolism revealed that ME1-null cells exhibit higher rates of glycolysis and higher flux of glucose into the pentose phosphate pathway (PPP), which is necessary to produce NADPH. Evaluation of cellular redox homeostasis demonstrated that ME1 absence shifts dependence from the glutathione system to the thioredoxin system. Concomitantly, ME1 absence drives the accumulation of ROS and labile iron. ROS and iron accumulation enhances the susceptibility of ME1-null cells to ferroptosis induction with inhibitors of xCT (erastin and ACXT-3102). In vivo xenograft models of ME1-null SS demonstrate significantly increased tumor response to ACXT-3102 compared with ME1-expressing controls.
CONCLUSIONS: These findings demonstrate the translational potential of targeting redox homeostasis in ME1-null cancers and establish the preclinical rationale for a phase I trial of ACXT-3102 in SS patients. See related commentary by Subbiah and Gan, p. 3408
Metabolic compensation activates pro-survival mTORC1 signaling upon 3-phosphoglycerate dehydrogenase inhibition in osteosarcoma
Osteosarcoma is the most common pediatric and adult primary malignant bone cancer. Curative regimens target the folate pathway, downstream of serine metabolism, with high-dose methotrexate. Here, the rate-limiting enzyme in the biosynthesis of serine from glucose, 3-phosphoglycerate dehydrogenase (PHGDH), is examined, and an inverse correlation between PHGDH expression and relapse-free and overall survival in osteosarcoma patients is found. PHGDH inhibition in osteosarcoma cell lines attenuated cellular proliferation without causing cell death, prompting a robust metabolic analysis to characterize pro-survival compensation. Using metabolomic and lipidomic profiling, cellular response to PHGDH inhibition is identified as accumulation of unsaturated lipids, branched chain amino acids, and methionine cycle intermediates, leading to activation of pro-survival mammalian target of rapamycin complex 1 (mTORC1) signaling. Increased mTORC1 activation sensitizes cells to mTORC1 pathway inhibition, resulting in significant, synergistic cell death in vitro and in vivo. Identifying a therapeutic combination for PHGDH-high cancers offers preclinical justification for a dual metabolism-based combination therapy for osteosarcoma
BVRI Light Curves for 29 Type Ia Supernovae
BVRI light curves are presented for 27 Type Ia supernovae discovered during
the course of the Calan/Tololo Survey and for two other SNe Ia observed during
the same period. Estimates of the maximum light magnitudes in the B, V, and I
bands and the initial decline rate parameter m15(B) are also given.Comment: 17 pages, figures and tables are not included (contact first author
if needed), to appear in the Astronomical Journa
UBVRI Light Curves of 44 Type Ia Supernovae
We present UBVRI photometry of 44 type-Ia supernovae (SN Ia) observed from
1997 to 2001 as part of a continuing monitoring campaign at the Fred Lawrence
Whipple Observatory of the Harvard-Smithsonian Center for Astrophysics. The
data set comprises 2190 observations and is the largest homogeneously observed
and reduced sample of SN Ia to date, nearly doubling the number of
well-observed, nearby SN Ia with published multicolor CCD light curves. The
large sample of U-band photometry is a unique addition, with important
connections to SN Ia observed at high redshift. The decline rate of SN Ia
U-band light curves correlates well with the decline rate in other bands, as
does the U-B color at maximum light. However, the U-band peak magnitudes show
an increased dispersion relative to other bands even after accounting for
extinction and decline rate, amounting to an additional ~40% intrinsic scatter
compared to B-band.Comment: 84 authors, 71 pages, 51 tables, 10 figures. Accepted for publication
in the Astronomical Journal. Version with high-res figures and electronic
data at http://astron.berkeley.edu/~saurabh/cfa2snIa
Taking the Measure of the Universe: Precision Astrometry with SIM PlanetQuest
Precision astrometry at microarcsecond accuracy has application to a wide
range of astrophysical problems. This paper is a study of the science questions
that can be addressed using an instrument that delivers parallaxes at about 4
microarcsec on targets as faint as V = 20, differential accuracy of 0.6
microarcsec on bright targets, and with flexible scheduling. The science topics
are drawn primarily from the Team Key Projects, selected in 2000, for the Space
Interferometry Mission PlanetQuest (SIM PlanetQuest). We use the capabilities
of this mission to illustrate the importance of the next level of astrometric
precision in modern astrophysics. SIM PlanetQuest is currently in the detailed
design phase, having completed all of the enabling technologies needed for the
flight instrument in 2005. It will be the first space-based long baseline
Michelson interferometer designed for precision astrometry. SIM will contribute
strongly to many astronomical fields including stellar and galactic
astrophysics, planetary systems around nearby stars, and the study of quasar
and AGN nuclei. SIM will search for planets with masses as small as an Earth
orbiting in the `habitable zone' around the nearest stars using differential
astrometry, and could discover many dozen if Earth-like planets are common. It
will be the most capable instrument for detecting planets around young stars,
thereby providing insights into how planetary systems are born and how they
evolve with time. SIM will observe significant numbers of very high- and
low-mass stars, providing stellar masses to 1%, the accuracy needed to
challenge physical models. Using precision proper motion measurements, SIM will
probe the galactic mass distribution and the formation and evolution of the
Galactic halo. (abridged)Comment: 54 pages, 28 figures, uses emulateapj. Submitted to PAS
Cosmological parameters from SDSS and WMAP
We measure cosmological parameters using the three-dimensional power spectrum
P(k) from over 200,000 galaxies in the Sloan Digital Sky Survey (SDSS) in
combination with WMAP and other data. Our results are consistent with a
``vanilla'' flat adiabatic Lambda-CDM model without tilt (n=1), running tilt,
tensor modes or massive neutrinos. Adding SDSS information more than halves the
WMAP-only error bars on some parameters, tightening 1 sigma constraints on the
Hubble parameter from h~0.74+0.18-0.07 to h~0.70+0.04-0.03, on the matter
density from Omega_m~0.25+/-0.10 to Omega_m~0.30+/-0.04 (1 sigma) and on
neutrino masses from <11 eV to <0.6 eV (95%). SDSS helps even more when
dropping prior assumptions about curvature, neutrinos, tensor modes and the
equation of state. Our results are in substantial agreement with the joint
analysis of WMAP and the 2dF Galaxy Redshift Survey, which is an impressive
consistency check with independent redshift survey data and analysis
techniques. In this paper, we place particular emphasis on clarifying the
physical origin of the constraints, i.e., what we do and do not know when using
different data sets and prior assumptions. For instance, dropping the
assumption that space is perfectly flat, the WMAP-only constraint on the
measured age of the Universe tightens from t0~16.3+2.3-1.8 Gyr to
t0~14.1+1.0-0.9 Gyr by adding SDSS and SN Ia data. Including tensors, running
tilt, neutrino mass and equation of state in the list of free parameters, many
constraints are still quite weak, but future cosmological measurements from
SDSS and other sources should allow these to be substantially tightened.Comment: Minor revisions to match accepted PRD version. SDSS data and ppt
figures available at http://www.hep.upenn.edu/~max/sdsspars.htm
Kepler eclipsing binary stars. VII. the catalogue of eclipsing binaries found in the entire Kepler data set
The primary Kepler Mission provided nearly continuous monitoring of ~200,000 objects with unprecedented photometric precision. We present the final catalog of eclipsing binary systems within the 105 deg2 Kepler field of view. This release incorporates the full extent of the data from the primary mission (Q0-Q17 Data Release). As a result, new systems have been added, additional false positives have been removed, ephemerides and principal parameters have been recomputed, classifications have been revised to rely on analytical models, and eclipse timing variations have been computed for each system. We identify several classes of systems including those that exhibit tertiary eclipse events, systems that show clear evidence of additional bodies, heartbeat systems, systems with changing eclipse depths, and systems exhibiting only one eclipse event over the duration of the mission. We have updated the period and galactic latitude distribution diagrams and included a catalog completeness evaluation. The total number of identified eclipsing and ellipsoidal binary systems in the Kepler field of view has increased to 2878, 1.3% of all observed Kepler targets
Cardiovascular Risk with Non-Steroidal Anti-Inflammatory Drugs: Systematic Review of Population-Based Controlled Observational Studies
David Henry and colleagues reevaluate the evidence from observational studies on the cardiovascular risk associated with non-steroidal anti-inflammatory drugs
Nucleotide and phylogenetic analyses of the Chlamydia trachomatis ompA gene indicates it is a hotspot for mutation
<p>Abstract</p> <p>Background</p> <p>Serovars of the human pathogen <it>Chlamydia trachomatis </it>occupy one of three specific tissue niches. Genomic analyses indicate that the serovars have a phylogeny congruent with their pathobiology and have an average substitution rate of less than one nucleotide per kilobase. In contrast, the gene that determines serovar specificity, <it>ompA</it>, has a phylogenetic association that is not congruent with tissue tropism and has a degree of nucleotide variability much higher than other genomic loci. The <it>ompA </it>gene encodes the major surface-exposed antigenic determinant, and the observed nucleotide diversity at the <it>ompA </it>locus is thought to be due to recombination and host immune selection pressure. The possible contribution of a localized increase in mutation rate, however, has not been investigated.</p> <p>Results</p> <p>Nucleotide diversity and phylogenetic relationships of the five constant and four variable domains of the <it>ompA </it>gene, as well as several loci surrounding <it>ompA</it>, were examined for each serovar. The loci flanking the <it>ompA </it>gene demonstrated that nucleotide diversity increased monotonically as <it>ompA </it>is approached and that their gene trees are not congruent with either <it>ompA </it>or tissue tropism. The variable domains of the <it>ompA </it>gene had a very high level of non-synonymous change, which is expected as these regions encode the surface-exposed epitopes and are under positive selection. However, the synonymous changes are clustered in the variable regions compared to the constant domains; if hitchhiking were to account for the increase in synonymous changes, these substitutions should be more evenly distributed across the gene. Recombination also cannot entirely account for this increase as the phylogenetic relationships of the constant and variable domains are congruent with each other.</p> <p>Conclusions</p> <p>The high number of synonymous substitutions observed within the variable domains of <it>ompA </it>appears to be due to an increased mutation rate within this region of the genome, whereas the increase in nucleotide substitution rate and the lack of phylogenetic congruence in the regions flanking <it>ompA </it>are characteristic motifs of gene conversion. Together, the increased mutation rate in the <it>ompA </it>gene, in conjunction with gene conversion and positive selection, results in a high degree of variability that promotes host immune evasion.</p
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