815 research outputs found

    Shuttle/spacelab contamination environment and effects handbook

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    This handbook is intended to assist users of the Spacelab/Space Transportation System by providing contamination environments and effects information that may be of value in planning, designing, manufacturing, and operating a space flight experiment. A summary of available molecular and particulate contamination data on the Space Transportation System and its facilities is presented. Contamination models, contamination effects, and protection methods information are also presented. In addition to contamination, the effects of the space environments at STS altitudes on spacecraft materials are included. Extensive references, bibliographies, and contacts are provided

    Novel cell adhesion/migration pathways are predictive markers of HDAC inhibitor resistance in cutaneous T cell lymphoma

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    BACKGROUND: Treatment for Cutaneous T Cell Lymphoma (CTCL) is generally not curative. Therefore, selecting therapy that is effective and tolerable is critical to clinical decision-making. Histone deacetylase inhibitors (HDACi), epigenetic modifier drugs, are commonly used but effective in only ~30% of patients. There are no predictive markers of HDACi response and the CTCL histone acetylation landscape remains unmapped. We sought to identify pre-treatment molecular markers of resistance in CTCL that progressed on HDACi therapy. METHODS: Purified T cells from 39 pre/post-treatment peripheral blood samples and skin biopsies from 20 patients were subjected to RNA-seq and ChIP-seq for histone acetylation marks (H3K14/9ā€Æac, H3K27ac). We correlated significant differences in histone acetylation with gene expression in HDACi-resistant/sensitive CTCL. We extended these findings in additional CTCL patient cohorts (RNA-seq, microarray) and using ELISA in matched CTCL patient plasma. FINDINGS: Resistant CTCL exhibited high levels of histone acetylation, which correlated with increased expression of 338 genes (FDRā€Æ\u3cā€Æ0Ā·05), including some novel to CTCL: BIRC5 (anti-apoptotic); RRM2 (cell cycle); TXNDC5, GSTM1 (redox); and CXCR4, LAIR2 (cell adhesion/migration). Several of these, including LAIR2, were elevated pre-treatment in HDACi-resistant CTCL. In CTCL patient plasma (nā€Æ=ā€Æ6), LAIR2 protein was also elevated (pā€Æ\u3cā€Æ0Ā·01) compared to controls. INTERPRETATION: This study is the first to connect genome-wide differences in chromatin acetylation and gene expression to HDACi-resistance in primary CTCL. Our results identify novel markers with high pre-treatment expression, such as LAIR2, as potential prognostic and/or predictors of HDACi-resistance in CTCL. FUNDING: NIH:CA156690, CA188286; NCATS: WU-ICTS UL1 TR000448; Siteman Cancer Center: CA091842

    cis-regulatory circuits regulating NEK6 kinase overexpression in transformed B cells Are super-enhancer independent

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    Alterations in distal regulatory elements that controlĀ gene expression underlie many diseases, including cancer. Epigenomic analyses of normal and diseased cells have produced correlative predictions for connections between dysregulated enhancers and target genes involved in pathogenesis. However, with few exceptions, these predicted cis-regulatory circuits remain untested. Here, we dissect cis-regulatory circuits that lead to overexpression of NEK6, a mitosis-associated kinase, in human B cell lymphoma. We find that only a minor subset of predicted enhancers is required for NEK6 expression. Indeed, an annotated super-enhancer is dispensable for NEK6 overexpression and for maintaining the architecture of a B cell-specific regulatory hub. A CTCF cluster serves as a chromatin and architectural boundary to block communication of the NEK6 regulatory hub with neighboring genes. Our findings emphasize that validation of predicted cis-regulatory circuits and super-enhancers is needed to prioritizeĀ transcriptional control elements as therapeutic targets

    Failure of the ERBE scanner instrument aboard NOAA 10 spacecraft and results of failure analysis

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    The Earth Radiation Budget Experiment (ERBE) scanner instrument on the NOAA 10 spacecraft malfunctioned on May 22, 1989, after more than 4 years of in-flight operation. After the failure, all instrument operational mode commands were tested and the resulting data analyzed. Details of the tests and analysis of output data are discussed therein. The radiometric and housekeeping data appear to be valid. However, the instrument will not correctly execute operational scan mode commands or the preprogrammed calibration sequences. The data indicate the problem is the result of a failure in the internal address decoding circuity in one of the ROM (read only memory) chips of the instrument computer

    The Iowa Homemaker vol.6, no.2

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    Table of Contents Dedication, page 1 Invitation to The House by Maybelle A. Payton, page 2 Dedication of the Home Economics Hall, page 3 Home Economics of Tomorrow by Anna E. Richardson, page 5 And Now Comes the Fulfillment by Joanna M. Hansen, page 6 Pioneering in Home Economics by Josephine McMullen, page 8 With the Iowa State Home Economics Association, page 6 The Past Decade in Home Economics at I. S. C., page 9 The Dean MacKay Auditorium by Thirza Hull, page 10 Division of Home Economics by Marcia E. Turner, page 11 ā€˜Twas Team Work That Did It, page 12 Omicron Nu by Cora B. Miller, page 13 Girlsā€™ 4-H Clubs, page 14 With the Iowa State Home Economics Association, page 1

    Sea anemones may thrive in a high CO2 world

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    Increased seawater pCO 2, and in turn 'ocean acidification' (OA), is predicted to profoundly impact marine ecosystem diversity and function this century. Much research has already focussed on calcifying reef-forming corals (Class: Anthozoa) that appear particularly susceptible to OA via reduced net calcification. However, here we show that OA-like conditions can simultaneously enhance the ecological success of non-calcifying anthozoans, which not only play key ecological and biogeochemical roles in present day benthic ecosystems but also represent a model organism should calcifying anthozoans exist as less calcified (soft-bodied) forms in future oceans. Increased growth (abundance and size) of the sea anemone (Anemonia viridis) population was observed along a natural CO 2 gradient at Vulcano, Italy. Both gross photosynthesis (P G) and respiration (R) increased with pCO 2 indicating that the increased growth was, at least in part, fuelled by bottom up (CO 2 stimulation) of metabolism. The increase of P G outweighed that of R and the genetic identity of the symbiotic microalgae (Symbiodinium spp.) remained unchanged (type A19) suggesting proximity to the vent site relieved CO 2 limitation of the anemones' symbiotic microalgal population. Our observations of enhanced productivity with pCO 2, which are consistent with previous reports for some calcifying corals, convey an increase in fitness that may enable non-calcifying anthozoans to thrive in future environments, i.e. higher seawater pCO 2. Understanding how CO 2-enhanced productivity of non- (and less-) calcifying anthozoans applies more widely to tropical ecosystems is a priority where such organisms can dominate benthic ecosystems, in particular following localized anthropogenic stress. Ā© 2012 Blackwell Publishing Ltd

    Determining subpopulation methylation profiles from bisulfite sequencing data of heterogeneous samples using DXM

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    Epigenetic changes, such as aberrant DNA methylation, contribute to cancer clonal expansion and disease progression. However, identifying subpopulation-level changes in a heterogeneous sample remains challenging. Thus, we have developed a computational approach, DXM, to deconvolve the methylation profiles of major allelic subpopulations from the bisulfite sequencing data of a heterogeneous sample. DXM does not require prior knowledge of the number of subpopulations or types of cells to expect. We benchmark DXM\u27s performance and demonstrate improvement over existing methods. We further experimentally validate DXM predicted allelic subpopulation-methylation profiles in four Diffuse Large B-Cell Lymphomas (DLBCLs). Lastly, as proof-of-concept, we apply DXM to a cohort of 31 DLBCLs and relate allelic subpopulation methylation profiles to relapse. We thus demonstrate that DXM can robustly find allelic subpopulation methylation profiles that may contribute to disease progression using bisulfite sequencing data of any heterogeneous sample
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