Efficient Photometric Selection of Quasars from the Sloan Digital Sky Survey: 100,000 z<3 Quasars from Data Release One

We present a catalog of 100,563 unresolved, UV-excess (UVX) quasar candidates to g=21 from 2099 deg^2 of the Sloan Digital Sky Survey (SDSS) Data Release One (DR1) imaging data. Existing spectra of 22,737 sources reveals that 22,191 (97.6%) are quasars; accounting for the magnitude dependence of this efficiency, we estimate that 95,502 (95.0%) of the objects in the catalog are quasars. Such a high efficiency is unprecedented in broad-band surveys of quasars. This ``proof-of-concept'' sample is designed to be maximally efficient, but still has 94.7% completeness to unresolved, g<~19.5, UVX quasars from the DR1 quasar catalog. This efficient and complete selection is the result of our application of a probability density type analysis to training sets that describe the 4-D color distribution of stars and spectroscopically confirmed quasars in the SDSS. Specifically, we use a non-parametric Bayesian classification, based on kernel density estimation, to parameterize the color distribution of astronomical sources -- allowing for fast and robust classification. We further supplement the catalog by providing photometric redshifts and matches to FIRST/VLA, ROSAT, and USNO-B sources. Future work needed to extend the this selection algorithm to larger redshifts, fainter magnitudes, and resolved sources is discussed. Finally, we examine some science applications of the catalog, particularly a tentative quasar number counts distribution covering the largest range in magnitude (14.2<g<21.0) ever made within the framework of a single quasar survey.Comment: 35 pages, 11 figures (3 color), 2 tables, accepted by ApJS; higher resolution paper and ASCII version of catalog available at http://sdss.ncsa.uiuc.edu/qso/nbckde

AAPM Medical Physics Practice Guideline 2.a: Commissioning and quality assurance of X-ray–based image-guided radiotherapy systems

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8,000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. 1

RNA polymerase II senses obstruction in the DNA minor groove via a conserved sensor motif

RNA polymerase II (pol II) encounters numerous barriers during transcription elongation, including DNA strand breaks, DNA lesions, and nucleosomes. Pyrrole-imidazole (Py-Im) polyamides bind to the minor groove of DNA with programmable sequence specificity and high affinity. Previous studies suggest that Py-Im polyamides can prevent transcription factor binding, as well as interfere with pol II transcription elongation. However, the mechanism of pol II inhibition by Py-Im polyamides is unclear. Here we investigate the mechanism of how these minor-groove binders affect pol II transcription elongation. In the presence of site-specifically bound Py-Im polyamides, we find that the pol II elongation complex becomes arrested immediately upstream of the targeted DNA sequence, and is not rescued by transcription factor IIS, which is in contrast to pol II blockage by a nucleosome barrier. Further analysis reveals that two conserved pol II residues in the Switch 1 region contribute to pol II stalling. Our study suggests this motif in pol II can sense the structural changes of the DNA minor groove and can be considered a “minor groove sensor.” Prolonged interference of transcription elongation by sequence-specific minor groove binders may present opportunities to target transcription addiction for cancer therapy

A novel secreted protein, MYR1, is central to Toxoplasma’s manipulation of host cells

The intracellular protozoan Toxoplasma gondii dramatically reprograms the transcriptome of host cells it infects, including substantially up-regulating the host oncogene c-myc. By applying a flow cytometry-based selection to infected mouse cells expressing green fluorescent protein fused to c-Myc (c-Myc–GFP), we isolated mutant tachyzoites defective in this host c-Myc up-regulation. Whole-genome sequencing of three such mutants led to the identification of MYR1 (Myc regulation 1; TGGT1_254470) as essential for c-Myc induction. MYR1 is a secreted protein that requires TgASP5 to be cleaved into two stable portions, both of which are ultimately found within the parasitophorous vacuole and at the parasitophorous vacuole membrane. Deletion of MYR1 revealed that in addition to its requirement for c-Myc up-regulation, the MYR1 protein is needed for the ability of Toxoplasma tachyzoites to modulate several other important host pathways, including those mediated by the dense granule effectors GRA16 and GRA24. This result, combined with its location at the parasitophorous vacuole membrane, suggested that MYR1 might be a component of the machinery that translocates Toxoplasma effectors from the parasitophorous vacuole into the host cytosol. Support for this possibility was obtained by showing that transit of GRA24 to the host nucleus is indeed MYR1-dependent. As predicted by this pleiotropic phenotype, parasites deficient in MYR1 were found to be severely attenuated in a mouse model of infection. We conclude, therefore, that MYR1 is a novel protein that plays a critical role in how Toxoplasma delivers effector proteins to the infected host cell and that this is crucial to virulence

Insulin regulates carboxypeptidase E by modulating translation initiation scaffolding protein eIF4G1 in pancreatic β cells

Insulin resistance, hyperinsulinemia, and hyperproinsulinemia occur early in the pathogenesis of type 2 diabetes (T2D). Elevated levels of proinsulin and proinsulin intermediates are markers of β-cell dysfunction and are strongly associated with development of T2D in humans. However, the mechanism(s) underlying β-cell dysfunction leading to hyperproinsulinemia is poorly understood. Here, we show that disruption of insulin receptor (IR) expression in β cells has a direct impact on the expression of the convertase enzyme carboxypeptidase E (CPE) by inhibition of the eukaryotic translation initiation factor 4 gamma 1 translation initiation complex scaffolding protein that is mediated by the key transcription factors pancreatic and duodenal homeobox 1 and sterol regulatory element-binding protein 1, together leading to poor proinsulin processing. Reexpression of IR or restoring CPE expression each independently reverses the phenotype. Our results reveal the identity of key players that establish a previously unknown link between insulin signaling, translation initiation, and proinsulin processing, and provide previously unidentified mechanistic insight into the development of hyperproinsulinemia in insulin-resistant states

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management

Surveillance of emerging drugs of abuse in Hong Kong: Validation of an analytical tool

© 2015, Hong Kong Academy of Medicine Press. All rights reserved. Objective: To validate a locally developed chromatography-based method to monitor emerging drugs of abuse whilst performing regular drug testing in abusers. Design: Cross-sectional study. Setting: Eleven regional hospitals, seven social service units, and a tertiary level clinical toxicology laboratory in Hong Kong. Participants: A total of 972 drug abusers and high-risk individuals were recruited from acute, rehabilitation, and high-risk settings between 1 November 2011 and 31 July 2013. A subset of the participants was of South Asian ethnicity. In total, 2000 urine or hair specimens were collected. Main outcome measures: Proof of concept that surveillance of emerging drugs of abuse can be performed whilst conducting routine drug of abuse testing in patients. Results: The method was successfully applied to 2000 samples with three emerging drugs of abuse detected in five samples: PMMA (paramethoxymethamphetamine), TFMPP [1-(3-trifluoromethylphenyl)piperazine], and methcathinone. The method also detected conventional drugs of abuse, with codeine, methadone, heroin, methamphetamine, and ketamine being the most frequently detected drugs. Other findings included the observation that South Asians had significantly higher rates of using opiates such as heroin, methadone, and codeine; and that ketamine and cocaine had significantly higher detection rates in acute subjects compared with the rehabilitation population. Conclusions: This locally developed analytical method is a valid tool for simultaneous surveillance of emerging drugs of abuse and routine drug monitoring of patients at minimal additional cost and effort. Continued, proactive surveillance and early identification of emerging drugs will facilitate prompt clinical, social, and legislative management.Link_to_subscribed_fulltex

Surface Morphologies in a Mars-Analog Ca-Sulfate Salar, High Andes, Northern Chile

Salar de Pajonales, a Ca-sulfate salt flat in the Chilean High Andes, showcases the type of polyextreme environment recognized as one of the best terrestrial analogs for early Mars because of its aridity, high solar irradiance, salinity, and oxidation. The surface of the salar represents a natural climate-transition experiment where contemporary lagoons transition into infrequently inundated areas, salt crusts, and lastly dry exposed paleoterraces. These surface features represent different evolutionary stages in the transition from previously wetter climatic conditions to much drier conditions today. These same stages closely mirror the climate transition on Mars from a wetter early Noachian to the Noachian/Hesperian. Salar de Pajonales thus provides a unique window into what the last near-surface oases for microbial life on Mars could have been like in hypersaline environments as the climate changed and water disappeared from the surface. Here we open that climatological window by evaluating the narrative recorded in the salar surface morphology and microenvironments and extrapolating to similar paleosettings on Mars. Our observations suggest a strong inter-dependence between small and large scale features that we interpret to be controlled by extrabasinal changes in environmental conditions, such as precipitation-evaporation-balance changes and thermal cycles, and most importantly, by internal processes, such as hydration/dehydration, efflorescence/deliquescence, and recrystallization brought about by physical and chemical processes related to changes in groundwater recharge and volcanic processes. Surface structures and textures record a history of hydrological changes that impact the mineralogy and volume of Ca-sulfate layers comprising most of the salar surface. Similar surface features on Mars, interpreted as products of freeze-thaw cycles, could, instead, be products of water-driven, volume changes in salt deposits. On Mars, surface manifestations of such salt-related processes would point to potential water sources. Because hygroscopic salts have been invoked as sources of localized, transient water sufficient to support terrestrial life, such structures might be good targets for biosignature exploration on Mars