659 research outputs found
Standard Operating Procedure and Workplan for the Terrestrial Environmental Observation Network (TEON) – Arctic Landscape Conservation Cooperative: Kuparuk River Basin and Adjacent Catchments
TABLE OF CONTENTS ................................................................................................................. i
DISCLAIMER ................................................................................................................................ ii
CONVERSION FACTORS, UNITS, WATER QUALITY UNITS, VERTICAL AND
HORIZONTAL DATUM, ABBREVIATIONS AND SYMBOLS .............................................. iii
1 INTRODUCTION .................................................................................................................. 1
2 STATION HISTORY ............................................................................................................. 5
3 DATA COLLECTION METHODS ....................................................................................... 8
3.1 Air Temperature and Relative Humidity ........................................................................ 12
3.2 Wind Speed and Direction ............................................................................................. 14
3.3 Radiation ........................................................................................................................ 15
3.3.1 Net Radiation .......................................................................................................... 15
3.3.2 Shortwave Radiation ............................................................................................... 16
3.3.3 Longwave Radiation ............................................................................................... 17
3.4 Summer Precipitation ..................................................................................................... 18
3.5 Snow Depth .................................................................................................................... 18
3.6 Field Snow Survey ......................................................................................................... 20
3.7 Water Levels .................................................................................................................. 21
3.8 Discharge Measurements ............................................................................................... 23
3.8.1 Acoustic Doppler Current Profiler .......................................................................... 25
4 STATION TELEMETRY ..................................................................................................... 28
5 DATALOGGER PROGRAM .............................................................................................. 30
6 METADATA ........................................................................................................................ 31
7 QUALITY CONTROL AND DATA PROCESSING .......................................................... 32
8 DATA REPORTING AND ARCHIVING ........................................................................... 33
9 REFERENCES ..................................................................................................................... 36
10 APPENDIX LIST ................................................................................................................. 3
Advanced Manned Launch System (AMLS) study
To assure national leadership in space operations and exploration in the future, NASA must be able to provide cost effective and operationally efficient space transportation. Several NASA studies and the joint NASA/DoD Space Transportation Architecture Studies (STAS) have shown the need for a multi-vehicle space transportation system with designs driven by enhanced operations and low costs. NASA is currently studying an advanced manned launch system (AMLS) approach to transport crew and cargo to the Space Station Freedom. Several single and multiple stage systems from air-breathing to all-rocket concepts are being examined in a series of studies potential replacements for the Space Shuttle launch system in the 2000-2010 time frame. Rockwell International Corporation, under contract to the NASA Langley Research Center, has analyzed a two-stage all-rocket concept to determine whether this class of vehicles is appropriate for the AMLS function. The results of the pre-phase A study are discussed
RETRACTED . Christopher Lipina, Clare Stretton, Simon Hastings, Jonathan S. Hundal, Ken Mackie, Andrew J. Irving, and Harinder S. Hundal. Regulation of MAP Kinase–Directed Mitogenic and Protein Kinase B–Mediated Signaling by Cannabinoid Receptor Type 1 in Skeletal Muscle Cells. Diabetes 2010;59:375–385. DOI: 10.2337/db09-0979. PMID: 19933999. PMCID: PMC2809953
Ariel - Volume 6 Number 4
Editors
Mark Dembert
J.D. Kanofsky
Frank Chervenak
John Lammie
Curt Cummings
Entertainment
Robert Breckenridge
Joe Conti
Gary Kaskey
Photographer
Larry Glazerman
Overseas Editor
Mike Sinason
Humorist
Jim McCann
Staff
Ken Jaffe
Bob Sklaroff
Halley Faust
Jim Burk
Ariel - Volume 6 Number 4 (Alternate Version)
Editors
Mark Dembert
J.D. Kanofsky
Frank Chervenak
John Lammie
Curt Cummings
Entertainment
Robert Breckenridge
Joe Conti
Gary Kaskey
Photographer
Larry Glazerman
Overseas Editor
Mike Sinason
Humorist
Jim McCann
Staff
Kenn Jaffe
Bob Sklaroff
Halley Faust
Jim Burke
Jay Amsterdam
Morton A. Klein
Nancy Redfer
Development of a small molecule that corrects misfolding and increases secretion of Z α1 -antitrypsin.
Severe α1 -antitrypsin deficiency results from the Z allele (Glu342Lys) that causes the accumulation of homopolymers of mutant α1 -antitrypsin within the endoplasmic reticulum of hepatocytes in association with liver disease. We have used a DNA-encoded chemical library to undertake a high-throughput screen to identify small molecules that bind to, and stabilise Z α1 -antitrypsin. The lead compound blocks Z α1 -antitrypsin polymerisation in vitro, reduces intracellular polymerisation and increases the secretion of Z α1 -antitrypsin threefold in an iPSC model of disease. Crystallographic and biophysical analyses demonstrate that GSK716 and related molecules bind to a cryptic binding pocket, negate the local effects of the Z mutation and stabilise the bound state against progression along the polymerisation pathway. Oral dosing of transgenic mice at 100 mg/kg three times a day for 20 days increased the secretion of Z α1 -antitrypsin into the plasma by sevenfold. There was no observable clearance of hepatic inclusions with respect to controls over the same time period. This study provides proof of principle that "mutation ameliorating" small molecules can block the aberrant polymerisation that underlies Z α1 -antitrypsin deficiency
Aggravation of allergic airway inflammation by cigarette smoke in mice is CD44-dependent
Background : Although epidemiological studies reveal that cigarette smoke (CS) facilitates the development and exacerbation of allergic asthma, these studies offer limited information on the mechanisms involved. The transmembrane glycoprotein CD44 is involved in cell adhesion and acts as a receptor for hyaluronic acid and osteopontin. We aimed to investigate the role of CD44 in a murine model of CS-facilitated allergic airway inflammation.
Methods : Wild type (WT) and CD44 knock-out (KO) mice were exposed simultaneously to house dust mite (HDM) extract and CS. Inflammatory cells, hyaluronic acid (HA) and osteopontin (OPN) levels were measured in bronchoalveolar lavage fluid (BALF). Proinflammatory mediators, goblet cell metaplasia and peribronchial eosinophilia were assessed in lung tissue. T-helper (Th) 1, Th2 and Th17 cytokine production was evaluated in mediastinal lymph node cultures.
Results : In WT mice, combined HDM/CS exposure increased the number of inflammatory cells and the levels of HA and OPN in BALF and Th2 cytokine production in mediastinal lymph nodes compared to control groups exposed to phosphate buffered saline (PBS)/CS, HDM/Air or PBS/Air. Furthermore, HDM/CS exposure significantly increased goblet cell metaplasia, peribronchial eosinophilia and inflammatory mediators in the lung. CD44 KO mice exposed to HDM/CS had significantly fewer inflammatory cells in BALF, an attenuated Th2 cytokine production, as well as decreased goblet cells and peribronchial eosinophils compared to WT mice. In contrast, the levels of inflammatory mediators were similar or higher than in WT mice.
Conclusion : We demonstrate for the first time that the aggravation of pulmonary inflammation upon combined exposure to allergen and an environmental pollutant is CD44-dependent. Data from this murine model of concomitant exposure to CS and HDM might be of importance for smoking allergic asthmatics
The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies
Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology
Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans
Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have
fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in
25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16
regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of
correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP,
while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in
Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium
(LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region.
Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant
enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the
refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa,
an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of
PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent
signals within the same regio
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