486 research outputs found
Introduction to the Special Volume on Globalization and E-Commerce
The ten papers in this special volume of CAIS focus on environmental and policy influences on the diffusion of e-commerce in selected countries in the Americas, Asia-Pacific, and Europe. They are part of a multi-year, multi-country study entitled, Impacts of Electronic Commerce in the Global Networked Economy: A Multi-Country Stud
Negotiating Agency and Control: Theorizing Human-Machine Communication from a Structurational Perspective
Intelligent technologies have the potential to transform organizations and organizing processes. In particular, they are unique from prior organizational technologies in that they reposition technology as agent rather than a tool or object of use. Scholars studying human-machine communication (HMC) have begun to theorize the dual role played by human and machine agency, but they have focused primarily on the individual level. Drawing on Structuration Theory (Giddens, 1984), we propose a theoretical framework to explain agency in HMC as a process involving the negotiation of control between human and machine agents. This article contributes to HMC scholarship by offering a framework and research agenda to guide future theory-building and research on the use of intelligent technologies in organizational contexts
Human liver glycogen phosphorylase inhibitors bind at a new allosteric site
AbstractBackground: Glycogen phosphorylases catalyze the breakdown of glycogen to glucose-1-phosphate for glycolysis. Maintaining control of blood glucose levels is critical in minimizing the debilitating effects of diabetes, making liver glycogen phosphorylase a potential therapeutic target.Results: The binding site in human liver glycogen phosphorylase (HLGP) for a class of promising antidiabetic agents was identified crystallographically. The site is novel and functions allosterically by stabilizing the inactive conformation of HLGP. The initial view of the complex revealed key structural information and inspired the design of a new class of inhibitors which bind with nanomolar affinity and whose crystal structure is also described.Conclusions: We have identified the binding site of a new class of allosteric HLGP inhibitors. The crystal structure revealed the details of inhibitor binding, led to the design of a new class of compounds, and should accelerate efforts to develop therapeutically relevant molecules for the treatment of diabetes
A Standardized Novel Method to Measure Radiographic Root Changes after Endodontic Therapy in Immature Teeth
Outcome studies of endodontic treatment of necrotic immature permanent teeth rely on radiographic measures as surrogates of whether the treatment achieved regeneration/revascularization/revitalization. An increase in radiographic root length and/or width is thought to result in a better long-term prognosis for the tooth. In this study a method to measure radiographic outcomes of endodontic therapies on immature teeth was developed and validated
Associations of NINJ2 sequence variants with incident ischemic stroke in the Cohorts for Heart and Aging in Genomic Epidemiology (CHARGE) consortium
Background<p></p>
Stroke, the leading neurologic cause of death and disability, has a substantial genetic component. We previously conducted a genome-wide association study (GWAS) in four prospective studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and demonstrated that sequence variants near the NINJ2 gene are associated with incident ischemic stroke. Here, we sought to fine-map functional variants in the region and evaluate the contribution of rare variants to ischemic stroke risk.<p></p>
Methods and Results<p></p>
We sequenced 196 kb around NINJ2 on chromosome 12p13 among 3,986 European ancestry participants, including 475 ischemic stroke cases, from the Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, and Framingham Heart Study. Meta-analyses of single-variant tests for 425 common variants (minor allele frequency [MAF] ≥ 1%) confirmed the original GWAS results and identified an independent intronic variant, rs34166160 (MAF = 0.012), most significantly associated with incident ischemic stroke (HR = 1.80, p = 0.0003). Aggregating 278 putatively-functional variants with MAF≤ 1% using count statistics, we observed a nominally statistically significant association, with the burden of rare NINJ2 variants contributing to decreased ischemic stroke incidence (HR = 0.81; p = 0.026).<p></p>
Conclusion<p></p>
Common and rare variants in the NINJ2 region were nominally associated with incident ischemic stroke among a subset of CHARGE participants. Allelic heterogeneity at this locus, caused by multiple rare, low frequency, and common variants with disparate effects on risk, may explain the difficulties in replicating the original GWAS results. Additional studies that take into account the complex allelic architecture at this locus are needed to confirm these findings
The Chandra Source Catalog
The Chandra Source Catalog (CSC) is a general purpose virtual X-ray
astrophysics facility that provides access to a carefully selected set of
generally useful quantities for individual X-ray sources, and is designed to
satisfy the needs of a broad-based group of scientists, including those who may
be less familiar with astronomical data analysis in the X-ray regime. The first
release of the CSC includes information about 94,676 distinct X-ray sources
detected in a subset of public ACIS imaging observations from roughly the first
eight years of the Chandra mission. This release of the catalog includes point
and compact sources with observed spatial extents <~ 30''. The catalog (1)
provides access to the best estimates of the X-ray source properties for
detected sources, with good scientific fidelity, and directly supports
scientific analysis using the individual source data; (2) facilitates analysis
of a wide range of statistical properties for classes of X-ray sources; and (3)
provides efficient access to calibrated observational data and ancillary data
products for individual X-ray sources, so that users can perform detailed
further analysis using existing tools. The catalog includes real X-ray sources
detected with flux estimates that are at least 3 times their estimated 1 sigma
uncertainties in at least one energy band, while maintaining the number of
spurious sources at a level of <~ 1 false source per field for a 100 ks
observation. For each detected source, the CSC provides commonly tabulated
quantities, including source position, extent, multi-band fluxes, hardness
ratios, and variability statistics, derived from the observations in which the
source is detected. In addition to these traditional catalog elements, for each
X-ray source the CSC includes an extensive set of file-based data products that
can be manipulated interactively.Comment: To appear in The Astrophysical Journal Supplement Series, 53 pages,
27 figure
Statistical Characterization of the Chandra Source Catalog
The first release of the Chandra Source Catalog (CSC) contains ~95,000 X-ray
sources in a total area of ~0.75% of the entire sky, using data from ~3,900
separate ACIS observations of a multitude of different types of X-ray sources.
In order to maximize the scientific benefit of such a large, heterogeneous
data-set, careful characterization of the statistical properties of the
catalog, i.e., completeness, sensitivity, false source rate, and accuracy of
source properties, is required. Characterization efforts of other, large
Chandra catalogs, such as the ChaMP Point Source Catalog (Kim et al. 2007) or
the 2 Mega-second Deep Field Surveys (Alexander et al. 2003), while
informative, cannot serve this purpose, since the CSC analysis procedures are
significantly different and the range of allowable data is much less
restrictive. We describe here the characterization process for the CSC. This
process includes both a comparison of real CSC results with those of other,
deeper Chandra catalogs of the same targets and extensive simulations of
blank-sky and point source populations.Comment: To be published in the Astrophysical Journal Supplement Series (Fig.
52 replaced with a version which astro-ph can convert to PDF without issues.
Ampullary cancers harbor ELF3 tumor suppressor gene mutations and exhibit frequent WNT dysregulation
The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small-molecule inhibitors of β-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis
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