Streets, Railroads, and the Great Strike of 1877

International audienc

Subtle changes in chromatin loop contact propensity are associated with differential gene regulation and expression.

While genetic variation at chromatin loops is relevant for human disease, the relationships between contact propensity (the probability that loci at loops physically interact), genetics, and gene regulation are unclear. We quantitatively interrogate these relationships by comparing Hi-C and molecular phenotype data across cell types and haplotypes. While chromatin loops consistently form across different cell types, they have subtle quantitative differences in contact frequency that are associated with larger changes in gene expression and H3K27ac. For the vast majority of loci with quantitative differences in contact frequency across haplotypes, the changes in magnitude are smaller than those across cell types; however, the proportional relationships between contact propensity, gene expression, and H3K27ac are consistent. These findings suggest that subtle changes in contact propensity have a biologically meaningful role in gene regulation and could be a mechanism by which regulatory genetic variants in loop anchors mediate effects on expression

Increased expression of programmed death ligand 1 (PD-L1) in human pituitary tumors

PURPOSE: Subsets of pituitary tumors exhibit an aggressive clinical courses and recur despite surgery, radiation, and chemotherapy. Because modulation of the immune response through inhibition of T-cell checkpoints has led to durable clinical responses in multiple malignancies, we explored whether pituitary adenomas express immune-related biomarkers that could suggest suitability for immunotherapy. Specifically, programmed death ligand 1 (PD-L1) has emerged as a potential biomarker whose expression may portend more favorable responses to immune checkpoint blockade therapies. We thus investigated the expression of PD-L1 in pituitary adenomas. METHODS: PD-L1 RNA and protein expression were evaluated in 48 pituitary tumors, including functioning and non-functioning adenomas as well as atypical and recurrent tumors. Tumor infiltrating lymphocyte populations were also assessed by immunohistochemistry. RESULTS: Pituitary tumors express variable levels of PD-L1 transcript and protein. PD-L1 RNA and protein expression were significantly increased in functioning (growth hormone and prolactin-expressing) pituitary adenomas compared to non-functioning (null cell and silent gonadotroph) adenomas. Moreover, primary pituitary adenomas harbored higher levels of PD-L1 mRNA compared to recurrent tumors. Tumor infiltrating lymphocytes were observed in all pituitary tumors and were positively correlated with increased PD-L1 expression, particularly in the functional subtypes. CONCLUSIONS: Human pituitary adenomas harbor PD-L1 across subtypes, with significantly higher expression in functioning adenomas compared to non-functioning adenomas. This expression is accompanied by the presence of tumor infiltrating lymphocytes. These findings suggest the existence of an immune response to pituitary tumors and raise the possibility of considering checkpoint blockade immunotherapy in cases refractory to conventional management

Multiradar observations of the polar tongue of ionization

[1] We present a global view of large‐scale ionospheric disturbances during the main phase of a major geomagnetic storm. We find that the low‐latitude, auroral, and polar latitude regions are coupled by processes that redistribute thermal plasma throughout the system. For the large geomagnetic storm on 20 November 2003, we examine data from the high‐latitude incoherent scatter radars at Millstone Hill, Sondrestrom, and EISCAT Tromso, with SuperDARN HF radar observations of the high‐latitude convection pattern and DMSP observations of in situ plasma parameters in the topside ionosphere. We combine these with north polar maps of stormtime plumes of enhanced total electron content (TEC) derived from a network of GPS receivers. The polar tongue of ionization (TOI) is seen to be a continuous stream of dense cold plasma entrained in the global convection pattern. The dayside source of the TOI is the plume of storm enhanced density (SED) transported from low latitudes in the postnoon sector by the subauroral disturbance electric field. Convection carries this material through the dayside cusp and across the polar cap to the nightside where the auroral F region is significantly enhanced by the SED material. The three incoherent scatter radars provided full altitude profiles of plasma density, temperatures, and vertical velocity as the TOI plume crossed their different positions, under the cusp, in the center of the polar cap, and at the midnight oval/polar cap boundary. Greatly elevated F peak density (>1.5E12 m[superscript −3]) and low electron and ion temperatures (∼2500 K at the F peak altitude) characterize the SED/TOI plasma observed at all points along its high‐latitude trajectory. For this event, SED/TOI F region TEC (150–1000 km) was ∼50 TECu both in the cusp and in the center of the polar cap. Large, upward directed fluxes of O+ (>1.E14 m[superscript −2] s[superscript −1]) were observed in the topside ionosphere from the SED/TOI plume within the cusp

The effect of men's body attitudes and motivation for gym attendance

The current study integrates men's body attitudes with implicitly and explicitly measured motivation to investigate the role of these factors in predicting gym attendance. Male participants (N = 99) who regularly attended a gym were recruited to participate in an online questionnaire. Participants completed implicit and explicit measures of motivation, explicitly-measured men's body attitudes, and reported the average number of gym visits per week. Attitudes related to body fat and explicitly-measured autonomous motivation significantly predicted typical gym attendance. Implicitly-measured motivation significantly and negatively predicted gym attendance. Results indicate some support for a dual-systems account of gym attendance. Men's body attitudes and autonomous motivation influences gym attendance; however, implicitly-measured motivation showed antagonistic effects. While individuals may explicitly state their autonomous motivation for gym attendance, attendance may be influenced at the explicit level. Health and fitness professionals may improve gym attendance by focusing on people's reasons for attending a gym, facilitating autonomous motivation in clients, and minimising the influence of controlled reasons for exercise

Production of a long-term global water vapor and liquid water data set using ultra-fast methods to assimilate multi-satellite and radiosonde observations

There is a well-documented requirement for a comprehensive and accurate global moisture data set to assist many important studies in atmospheric science. Currently, atmospheric water vapor measurements are made from a variety of sources including radiosondes, aircraft and surface observations, and in recent years, by various satellite instruments. Creating a global data set from a single measuring system produces results that are useful and accurate only in specific situations and/or areas. Therefore, an accurate global moisture data set has been derived from a combination of these measurement systems. Under a NASA peer-reviewed contract, STC-METSAT produced two 5-yr (1988-1992) global data sets. One is the total column (integrated) water vapor data set and the other, a global layered water vapor data set using a combination of radiosonde observations, Television and Infrared Observation Satellite (TIROS) Operational Satellite (TOVS), and Special Sensor Microwave/Imager (SSM/I) data sets. STC-METSAT also produced a companion, global, integrated liquid water data set. The complete data set (all three products) has been named NVAP, an anachronym for NASA Water Vapor Project. STC-METSAT developed methods to process the data at a daily time scale and 1 x 1 deg spatial resolution

Production of long-term global water vapor and liquid water data set using ultra-fast methods to assimilate multi-satellite and radiosonde observations

In recent years climate research scientists have recognized the need for increased time and space resolution precipitable and liquid water data sets. This project is designed to meet those needs. Specifically, NASA is funding STC-METSAT to develop a total integrated column and layered precipitable water data set. This is complemented by a total column liquid water data set. These data are global in extent, 1 deg x 1 deg in resolution, with daily grids produced. Precipitable water is measured by a combination of in situ radiosonde observations and satellite derived infrared and microwave retrievals from four satellites. This project combines these data into a coherent merged product for use in global climate research. This report is the Year 2 Annual Report from this NASA-sponsored project and includes progress-to-date on the assigned tasks

Production of long-term global water vapor and liquid water data set using ultra-fast methods to assimilate multi-satellite and radiosonde observations

During the next decade, many programs and experiments under the Global Energy and Water Cycle Experiment (GEWEX) will utilize present day and future data sets to improve our understanding of the role of moisture in climate, and its interaction with other variables such as clouds and radiation. An important element of GEWEX will be the GEWEX Water Vapor Project (GVaP), which will eventually initiate a routine, real-time assimilation of the highest quality, global water vapor data sets including information gained from future data collection systems, both ground and space based. The comprehensive global water vapor data set being produced by METSAT Inc. uses a combination of ground-based radiosonde data, and infrared and microwave satellite retrievals. This data is needed to provide the desired foundation from which future GEWEX-related research, such as GVaP, can build. The first year of this project was designed to use a combination of the best available atmospheric moisture data including: radiosonde (balloon/acft/rocket), HIRS/MSU (TOVS) retrievals, and SSM/I retrievals, to produce a one-year, global, high resolution data set of integrated column water vapor (precipitable water) with a horizontal resolution of 1 degree, and a temporal resolution of one day. The time period of this pilot product was to be det3ermined by the availability of all the input data sets. January 1988 through December 1988 were selected. In addition, a sample of vertically integrated liquid water content (LWC) was to be produced with the same temporal and spatial parameters. This sample was to be produced over ocean areas only. Three main steps are followed to produce a merged water vapor and liquid water product. Input data from Radiosondes, TOVS, and SSMI/I is quality checked in steps one and two. Processing is done in step two to generate individual total column water vapor and liquid water data sets. The third step, and final processing task, involves merging the individual output products to produce the integrated water vapor product. A final quality control is applied to the merged data sets

Anxiety and avoidance in psychogenic nonepileptic seizures: the role of implicit and explicit anxiety

This study examined implicit and explicit anxiety in individuals with epilepsy and psychogenic nonepileptic seizures (PNESs) and explored whether these constructs were related to experiential avoidance and seizure frequency. Based on recent psychological models of PNESs, it was hypothesized that nonepileptic seizures would be associated with implicit and explicit anxiety and experiential avoidance. Explicit anxiety was measured by the State-Trait Anxiety Inventory; implicit anxiety was measured by an Implicit Relational Assessment Procedure; and experiential avoidance was measured with the Multidimensional Experiential Avoidance Questionnaire. Although both groups with epilepsy and PNESs scored similarly on implicit measures of anxiety, significant implicit–explicit anxiety discrepancies were only identified in patients with PNESs (p < .001). In the group with PNESs (but not in the group with epilepsy), explicit anxiety correlated with experiential avoidance (r = .63, p < .01) and frequency of seizures (r = .67, p < .01); implicit anxiety correlated with frequency of seizures only (r = .56, p < .01). Our findings demonstrate the role of implicit anxiety in PNESs and provide additional support for the contribution of explicit anxiety and experiential avoidance to this disorder

iPSCORE: A Resource of 222 iPSC Lines Enabling Functional Characterization of Genetic Variation across a Variety of Cell Types.

Large-scale collections of induced pluripotent stem cells (iPSCs) could serve as powerful model systems for examining how genetic variation affects biology and disease. Here we describe the iPSCORE resource: a collection of systematically derived and characterized iPSC lines from 222 ethnically diverse individuals that allows for both familial and association-based genetic studies. iPSCORE lines are pluripotent with high genomic integrity (no or low numbers of somatic copy-number variants) as determined using high-throughput RNA-sequencing and genotyping arrays, respectively. Using iPSCs from a family of individuals, we show that iPSC-derived cardiomyocytes demonstrate gene expression patterns that cluster by genetic background, and can be used to examine variants associated with physiological and disease phenotypes. The iPSCORE collection contains representative individuals for risk and non-risk alleles for&nbsp;95% of SNPs associated with human phenotypes through genome-wide association studies. Our study demonstrates the utility of iPSCORE for examining how genetic variants influence molecular and physiological traits in iPSCs and derived cell lines