Reversed Expression of the JAK/STAT Pathway Related Proteins Prolactin Receptor and STAT5a in Normal and Abnormal Breast Epithelial Cells

The JAK/STAT pathway is important for cellular metabolism. One component, STAT5a, is activated in the breast upon prolactin to prolactin receptor (PRLR) binding facilitating the transcription of genes involved in lobule development. STAT5a was previously found to be expressed in most normal breast epithelial cells but not in many in situ or invasive carcinomas except secretory carcinomas which retain STAT5a expression. This report examines the JAK/STAT pathway in the breast through the detection of PRLR and STAT5a. Fifty breast tissues, including benign secretory change, microglandular adenosis, usual and atypical hyperplasia and in situ and invasive ductal carcinoma both usual and secretory, were obtained from the files of the Armed Forces Institute of Pathology. Sections were immunostained with antibodies to PRLR and STAT5a. PRLR was minimally detected on the surface of a few normal breast epithelial cells whereas STAT5a was greatly expressed in over 80% of normal cell nuclei. PRLR was also minimally detected in secretory carcinomas expressing STAT5a. However, the opposite pattern was seen in breast carcinomas lacking STAT5a expression. PRLR was abundantly expressed in these cells. This reversed expression may indicate a JAK/STAT pathway disturbance that could play a role in the initiation or maintenance of an abnormal breast phenotype

SpaceDock: A Performance Task Platform for Spaceflight Operations

Preliminary evidence during both short- and long-duration spaceflight indicates that perceptual-motor coordination changes occur and persist in-flight. However, there is presently no in-flight method for evaluating astronaut performance on mission-critical tasks such as docking. We present a portable platform we have developed for attempting and evaluating docking, and describe the results of a pilot study wherein flight novices learned the docking task. Methods: A dual-joystick, six degrees of freedom platform-called SpaceDock-was developed to enable portable, adaptable performance testing in a spaceflight operations setting. Upon this platform, a simplified docking task was created, involving a constant rate of approach towards a docking target and requiring the user to correct translation in two dimensions and attitude orientation along one dimension (either pitch or roll). Ten flight naive subjects performed the task over a 45 min period and all joystick inputs and timings were collected, from which we could successfully reconstruct travel paths, input profiles and relative target displacements. Results: Subjects exhibited significant improvements in docking over the course of the experiment. Learning to compensate for roll-alterations was robust, whereas compensation for pitch-alterations was not in evidence in this population and relatively short training period. Conclusion: The SpaceDock platform can provide a novel method for training and testing subjects, on a spaceflight-relevant task, and can be used to examine behavioral learning, strategy use, and has been adapted for use in brain imaging experiments

The Role of Helicity in Magnetic Reconnection: 3D Numerical Simulations

We demonstrate that conservation of global helicity plays only a minor role in determining the nature and consequences of magnetic reconnection in the solar atmosphere. First, we show that observations of the solar coronal magnetic field are in direct conflict with Taylor's theory. Next, we present results from three-dimensional MHD simulations of the shearing of bipolar and multi-polar coronal magnetic fields by photospheric footpoint motions, and discuss the implications of these results for Taylor's theory and for models of solar activity. The key conclusion of this work is that significant magnetic reconnection occurs only at very specific locations and, hence, the Sun's magnetic field cannot relax completely down to the minimum energy state predicted by conservation of global helicity.Comment: AGU LaTeX manuscript, 17 pages, 2 b-w figures, 4 color plate

An open algorithm to pre-process free text self-reported medications data in UK biobank

Introduction:UK Biobank is a large-scale biomedical research database with in-depth genetic and phenotypic information. However, baseline medication data are recorded as free text with semantic ambiguity and errors, potentially limiting their use for research. Aim: To develop a flexible, automated, and transparent algorithm to extract drug information from self-reported medication free text in the UK Biobank. Methods: We have proposed a 3-step approach: 1) filtering strings, 2) building a dictionary of candidate drugs, and 3) mapping drug names. In step 1, special characters and meaningless stop words were filtered using regular expressions and a common words repository. The common word repository can be manually tuned by adding or removing domain-specific words. In step 2, a dictionary of candidate drugs was built by referencing to UK Biobank official documents and the public ChEMBL Database which curates UK British national formulary, international non-proprietary name, and anatomical therapeutic chemical (ATC) codes. Finally, in step 3, the filtered strings were mapped to candidate drug dictionaries identified in step 2. The accuracy of the algorithm was evaluated by comparing its output with manual identification based on a random sample of 100 distinct medication strings. Results: A total of 7,944 distinct medication strings were reported by ~502,125 participants in the UK Biobank. Of these, 6,804 (85.6%) strings included at least one identifiable active ingredients. The accuracy of our algorithm against manual extraction was 9 6 %. Conclusion: Our algorithm is accurate and facilitates the automatic identification of drug names from self-reported medication strings in the UK Biobank. Its performance can be further improved by refining the “stopwords” dictionary. This tool could act as a standard pre-processor for phenotyping baseline drug use information and enable reproducible research into drug use and pharmacoepidemiology/pharmacogenomics in the UK Biobank

The linked survival prospects of siblings : evidence for the Indian states

This paper reports an analysis of micro-data for India that shows a high correlation in infant mortality among siblings. In 13 of 15 states, we identify a causal effect of infant death on the risk of infant death of the subsequent sibling (a scarring effect), after controlling for mother-level heterogeneity. The scarring effects are large, the only other covariate with a similarly large effect being mother’s (secondary or higher) education. The two states in which evidence of scarring is weak are Punjab, the richest, and Kerala, the socially most progressive. The size of the scarring effect depends upon the sex of the previous child in three states, in a direction consistent with son-preference. Evidence of scarring implies that policies targeted at reducing infant mortality will have social multiplier effects by helping avoid the death of subsequent siblings. Comparison of other covariate effects across the states offers some interesting new insights

Type II Quasars from the Sloan Digital Sky Survey: V. Imaging host galaxies with the Hubble Space Telescope

Type II quasars are luminous Active Galactic Nuclei whose centers are obscured by large amounts of gas and dust. In this paper we present 3-band HST images of nine type II quasars with redshifts 0.2 < z < 0.4 selected from the Sloan Digital Sky Survey based on their emission line properties. The intrinsic luminosities of these AGN are estimated to be -24 > M_B > -26, but optical obscuration allows their host galaxies to be studied unencumbered by bright nuclei. Each object has been imaged in three continuum filters (`UV', `blue' and `yellow') placed between the strong emission lines. The spectacular, high quality images reveal a wealth of details about the structure of the host galaxies and their environments. Six of the nine galaxies in the sample are ellipticals with de Vaucouleurs light profiles, one object has a well-defined disk component and the remaining two have marginal disks. Stellar populations of type II quasar hosts are more luminous (by a median of 0.3-0.7 mag, depending on the wavelength) and bluer (by about 0.4 mag) than are M* galaxies at the same redshift. When smooth fits to stellar light are subtracted from the images, we find both positive and negative residuals that become more prominent toward shorter wavelengths. We argue that the negative residuals are due to kpc-scale dust obscuration, while most positive residuals are due to the light from the nucleus scattered off interstellar material in the host galaxy. Scattered light makes a significant contribution to the broad band continuum emission and can be the dominant component of the extended emission in the UV in extreme cases.Comment: 51 pages, including 12 grey scale figures, 4 color figures, 5 tables. In press in AJ. Version with higher-resolution images available at http://www.astro.princeton.edu/~nadia/qso2.html. (Minor changes in response to the referee report

Survival and risk of adverse events in older patients receiving postoperative adjuvant chemotherapy for resected stages II-IIIA lung cancer: observational cohort study

Objective To compare the survival and risk of serious adverse events in older patients with stages II-IIIA non-small cell lung cancer treated with or without postoperative platinum based chemotherapy