86 research outputs found
Inactivating mutations and X-ray crystal structure of the tumor suppressor OPCML reveal cancer-associated functions
OPCML, a tumor suppressor gene, is frequently silenced epigenetically in ovarian and other cancers. Here we report, by analysis of databases of tumor sequences, the observation of OPCML somatic missense mutations from various tumor types and the impact of these mutations on OPCML function, by solving the X-ray crystal structure of this glycoprotein to 2.65 A resolution. OPCML consists of an extended arrangement of three immunoglobulin-like domains and homodimerizes via a network of contacts between membrane-distal domains. We report the generation of a panel of OPCML variants with representative clinical mutations and demonstrate clear phenotypic effects in vitro and in vivo including changes to anchorage-independent growth, interaction with activated cognate receptor tyrosine kinases, cellular migration, invasion in vitro and tumor growth in vivo. Our results suggest that clinically occurring somatic missense mutations in OPCML have the potential to contribute to tumorigenesis in a variety of cancers
Oracle-based optimization applied to climate model calibration
In this paper, we show how oracle-based optimization can be effectively used for the calibration of an intermediate complexity climate model. In a fully developed example, we estimate the 12 principal parameters of the C-GOLDSTEIN climate model by using an oracle- based optimization tool, Proximal-ACCPM. The oracle is a procedure that finds, for each query point, a value for the goodness-of-fit function and an evaluation of its gradient. The difficulty in the model calibration problem stems from the need to undertake costly calculations for each simulation and also from the fact that the error function used to assess the goodness-of-fit is not convex. The method converges to a Fbest fit_ estimate over 10 times faster than a comparable test using the ensemble Kalman filter. The approach is simple to implement and potentially useful in calibrating computationally demanding models based on temporal integration (simulation), for which functional derivative information is not readily available
The June 2016 Optical and Gamma-Ray Outburst and Optical Micro-Variability of the Blazar 3C454.3
The quasar 3C454.3 underwent a uniquely-structured multi-frequency outburst
in June 2016. The blazar was observed in the optical band by several
ground-based telescopes in photometric and polarimetric modes, at -ray
frequencies by the \emph{Fermi}\ Large Area Telescope, and at 43 GHz with the
Very Long Baseline Array. The maximum flux density was observed on 2016 June 24
at both optical and -ray frequencies, reaching
mJy and ph cm s, respectively. The June 2016
outburst possessed a precipitous decay at both -ray and optical
frequencies, with the source decreasing in flux density by a factor of 4 over a
24-hour period in band. Intraday variability was observed throughout the
outburst, with flux density changes between 1 and 5 mJy over the course of a
night. The precipitous decay featured statistically significant quasi-periodic
micro-variability oscillations with an amplitude of - about the
mean trend and a characteristic period of 36 minutes. The optical degree of
polarization jumped from to nearly 20\% during the outburst, while
the position angle varied by \sim120\degr. A knot was ejected from the 43 GHz
core on 2016 Feb 25, moving at an apparent speed .
From the observed minimum timescale of variability
hr and derived Doppler factor
, we find a size of the emission region
cm. If the quasi-periodic micro-variability
oscillations are caused by periodic variations of the Doppler factor of
emission from a turbulent vortex, we derive a rotational speed of the vortex
.Comment: 19 pages, 13 figures, 3 tables, accepted to the Astrophysical Journal
2019 March
Diet and Cell Size Both Affect Queen-Worker Differentiation through DNA Methylation in Honey Bees (Apis mellifera, Apidae)
Young larvae of the honey bee (Apis mellifera) are totipotent; they can become either queens (reproductives) or workers (largely sterile helpers). DNA methylation has been shown to play an important role in this differentiation. In this study, we examine the contributions of diet and cell size to caste differentiation.We measured the activity and gene expression of one key enzyme involved in methylation, Dnmt3; the rates of methylation in the gene dynactin p62; as well as morphological characteristics of adult bees developed either from larvae fed with worker jelly or royal jelly; and larvae raised in either queen or worker cells. We show that both diet type and cell size contributed to the queen-worker differentiation, and that the two factors affected different methylation sites inside the same gene dynactin p62.We confirm previous findings that Dnmt3 plays a critical role in honey bee caste differentiation. Further, we show for the first time that cell size also plays a role in influencing larval development when diet is kept the same
Managing software engineers and their knowledge
This chapter begins by reviewing the history of software engineering as a profession, especially the so-called software crisis and responses to it, to help focus on what it is that software engineers do. This leads into a discussion of the areas in software engineering that are problematic as a basis for considering knowledge management issues. Some of the previous work on knowledge management in software engineering is then examined, much of it not actually going under a knowledge management title, but rather âlearningâ or âexpertiseâ. The chapter goes on to consider the potential for knowledge management in software engineering and the different types of knowledge management solutions and strategies that might be adopted, and it touches on the crucial importance of cultural issues. It concludes with a list of challenges that knowledge management in software engineering needs to address
Multi-Wavelength Variability of BL Lacertae Measured with High Time Resolution
In an effort to locate the sites of emission at different frequencies and
physical processes causing variability in blazar jets, we have obtained high
time-resolution observations of BL Lacertae over a wide wavelength range: with
the \emph{Transiting Exoplanet Survey Satellite} (TESS) at 6,000-10,000 \AA\
with 2-minute cadence; with the Neil Gehrels \emph{Swift} satellite at optical,
UV, and X-ray bands; with the Nuclear Spectroscopic Telescope Array at hard
X-ray bands; with the \emph{Fermi} Large Area Telescope at -ray
energies; and with the Whole Earth Blazar Telescope for measurement of the
optical flux density and polarization. All light curves are correlated, with
similar structure on timescales from hours to days. The shortest timescale of
variability at optical frequencies observed with TESS is hr. The
most common timescale is ~hr, comparable with the minimum timescale of
X-ray variability, 14.5 hr. The multi-wavelength variability properties cannot
be explained by a change solely in the Doppler factor of the emitting plasma.
The polarization behavior implies that there are both ordered and turbulent
components to the magnetic field in the jet. Correlation analysis indicates
that the X-ray variations lag behind the -ray and optical light curves
by up to days. The timescales of variability, cross-frequency lags,
and polarization properties can be explained by turbulent plasma that is
energized by a shock in the jet and subsequently loses energy to synchrotron
and inverse Compton radiation in a magnetic field of strength GComment: 33 pages, 25 figures, 14 tables. Accepted to Ap
Emission-line Variability during a Nonthermal Outburst in the Gamma-Ray Bright Quasar 1156+295
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.We present multi-epoch optical spectra of the Îł-ray bright blazar 1156+295 (4C +29.45, Ton 599) obtained with the 4.3 m Lowell Discovery Telescope. During a multiwavelength outburst in late 2017, when the Îł-ray flux increased to 2.5 Ă 10â6 phot cmâ2 sâ1 and the quasar was first detected at energies â„100 GeV, the flux of the Mg ii λ2798 emission line changed, as did that of the Fe emission complex at shorter wavelengths. These emission-line fluxes increased along with the highly polarized optical continuum flux, which is presumably synchrotron radiation from the relativistic jet, with a relative time delay of âČ2 weeks. This implies that the line-emitting clouds lie near the jet, which points almost directly toward the line of sight. The emission-line radiation from such clouds, which are located outside the canonical accretion-disk related broad-line region, may be a primary source of seed photons that are up-scattered to Îł-ray energies by relativistic electrons in the jet. © 2022. The Author(s). Published by the American Astronomical Society.This research was supported in part by NASA Fermi guest investigator program grants 80NSSC19K1504 and 80NSSC20K1565. We thank A. Tchekhovskoy for discussion of possible origins of the variable line-emitting clouds. These results made use of the Lowell Discovery Telescope (LDT) at Lowell Observatory. Lowell Observatory is a private, non-profit institution dedicated to astrophysical research and public appreciation of astronomy, and operates the LDT in partnership with Boston University, the University of Maryland, the University of Toledo, Northern Arizona University and Yale University. This study was based in part on observations conducted using the 1.8 m Perkins Telescope Observatory (PTO) in Arizona, which is owned and operated by Boston University. I.A. acknowledges financial support from the Spanish "Ministerio de Ciencia e InnovaciĂłn" (MCINN) through the "Center of Excellence Severo Ochoa" award for the Instituto de AstrofĂsica de AndalucĂa-CSIC (SEV-2017-0709). Acquisition and reduction of the MAPCAT data were supported in part by MICINN through grants AYA2016-80889-P and PID2019-107847RB-C44. The MAPCAT observations were carried out at the German-Spanish Calar Alto Observatory, which is jointly operated by Junta de AndalucĂa and Consejo Superior de Investigaciones CientĂficas. Data from the Steward Observatory spectropolarimetric monitoring project were used; this program was supported by Fermi Guest Investigator grants NNX08AW56G, NNX09AU10G, NNX12AO93G, and NNX15AU81G. C.C. acknowledges support from the European Research Council (ERC) under the European Union Horizon 2020 research and innovation program under the grant agreement No. 771282.Peer reviewe
Polarized blazar X-rays imply particle acceleration in shocks
Most of the light from blazars, active galactic nuclei with jets of magnetized plasma that point nearly along the line of sight, is produced by high-energy particles, up to around 1âTeV. Although the jets are known to be ultimately powered by a supermassive black hole, how the particles are accelerated to such high energies has been an unanswered question. The process must be related to the magnetic field, which can be probed by observations of the polarization of light from the jets. Measurements of the radio to optical polarizationâthe only range available until nowâprobe extended regions of the jet containing particles that left the acceleration site days to years earlier1,2,3, and hence do not directly explore the acceleration mechanism, as could X-ray measurements. Here we report the detection of X-ray polarization from the blazar Markarian 501 (Mrk 501). We measure an X-ray linear polarization degree Î X of around 10%, which is a factor of around 2 higher than the value at optical wavelengths, with a polarization angle parallel to the radio jet. This points to a shock front as the source of particle acceleration and also implies that the plasma becomes increasingly turbulent with distance from the shock
The 13th Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-IV Survey Mapping Nearby Galaxies at Apache Point Observatory
The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) began observations in July 2014. It pursues three core programs: APOGEE-2,MaNGA, and eBOSS. In addition, eBOSS contains two major subprograms: TDSS and SPIDERS. This paper describes the first data release from SDSS-IV, Data Release 13 (DR13), which contains new data, reanalysis of existing data sets and, like all SDSS data releases, is inclusive of previously released data. DR13 makes publicly available 1390 spatially resolved integral field unit observations of nearby galaxies from MaNGA,the first data released from this survey. It includes new observations from eBOSS, completing SEQUELS. In addition to targeting galaxies and quasars, SEQUELS also targeted variability-selected objects from TDSS and X-ray selected objects from SPIDERS. DR13 includes new reductions ofthe SDSS-III BOSS data, improving the spectrophotometric calibration and redshift classification. DR13 releases new reductions of the APOGEE-1data from SDSS-III, with abundances of elements not previously included and improved stellar parameters for dwarf stars and cooler stars. For the SDSS imaging data, DR13 provides new, more robust and precise photometric calibrations. Several value-added catalogs are being released in tandem with DR13, in particular target catalogs relevant for eBOSS, TDSS, and SPIDERS, and an updated red-clump catalog for APOGEE.This paper describes the location and format of the data now publicly available, as well as providing references to the important technical papers that describe the targeting, observing, and data reduction. The SDSS website, http://www.sdss.org, provides links to the data, tutorials and examples of data access, and extensive documentation of the reduction and analysis procedures. DR13 is the first of a scheduled set that will contain new data and analyses from the planned ~6-year operations of SDSS-IV.PostprintPeer reviewe
The 16th Data Release of the Sloan Digital Sky Surveys: First Release from the APOGEE-2 Southern Survey and Full Release of eBOSS Spectra
This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17)
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