519 research outputs found
Probabilistic Structural Analysis Program
NASA/NESSUS 6.2c is a general-purpose, probabilistic analysis program that computes probability of failure and probabilistic sensitivity measures of engineered systems. Because NASA/NESSUS uses highly computationally efficient and accurate analysis techniques, probabilistic solutions can be obtained even for extremely large and complex models. Once the probabilistic response is quantified, the results can be used to support risk-informed decisions regarding reliability for safety-critical and one-of-a-kind systems, as well as for maintaining a level of quality while reducing manufacturing costs for larger-quantity products. NASA/NESSUS has been successfully applied to a diverse range of problems in aerospace, gas turbine engines, biomechanics, pipelines, defense, weaponry, and infrastructure. This program combines state-of-the-art probabilistic algorithms with general-purpose structural analysis and lifting methods to compute the probabilistic response and reliability of engineered structures. Uncertainties in load, material properties, geometry, boundary conditions, and initial conditions can be simulated. The structural analysis methods include non-linear finite-element methods, heat-transfer analysis, polymer/ceramic matrix composite analysis, monolithic (conventional metallic) materials life-prediction methodologies, boundary element methods, and user-written subroutines. Several probabilistic algorithms are available such as the advanced mean value method and the adaptive importance sampling method. NASA/NESSUS 6.2c is structured in a modular format with 15 elements
Profiling Sterols in Cerebrotendinous Xanthomatosis: Utility of Girard Derivatization and High Resolution Exact Mass LC-ESI-MSn Analysis
In this study we profile free 3-oxo sterols present in plasma from patients affected with the neurodegenerative disorder of sterol and bile acid metabolism cerebrotendinous xanthomatosis (CTX), utilizing a combination of charge-tagging and LC-ESI-MSn performed with an LTQ-Orbitrap Discovery instrument. In addition, we profile sterols in plasma from 24-month-old cyp27A1 gene knockout mice lacking the enzyme defective in CTX. Charge-tagging was accomplished by reaction with cationic Girard\u27s P (GP) reagent 1-(carboxymethyl) pyridinium chloride hydrazide, an approach uniquely suited to studying the 3-oxo sterols that accumulate in CTX, as Girard\u27s reagent reacts with the sterol oxo moiety to form charged hydrazone derivatives. The ability to selectively generate GP-tagged 3-oxo-4-ene and 3-oxo-5(H) saturated plasma sterols enabled ESI-MSn analysis of these sterols in the presence of a large excess (3 orders of magnitude) of cholesterol. Often cholesterol detected in biological samples makes it challenging to quantify minor sterols, with cholesterol frequently removed prior to analysis. We derivatized plasma (10μl) without SPE removal of cholesterol to ensure detection of all sterols present in plasma. We were able to measure 4-cholesten-3-one in plasma from untreated CTX patients (1207±302ng/ml, mean±SD, n=4), as well as other intermediates in a proposed pathway to 5α-cholestanol. In addition, a number of bile acid precursors were identified in plasma using this technique. GP-tagged sterols were identified utilizing high resolution exact mass spectra (±5ppm), as well as MS2 ([M]+→) spectra that possessed characteristic neutral loss of 79Da (pyridine) fragment ions, and MS3 ([M]+→[M-79]+→) spectra that provided additional structurally informative fragment ions. © 2010 Elsevier B.V
Using Quantum Confinement to Uniquely Identify Devices
Modern technology unintentionally provides resources that enable the trust of
everyday interactions to be undermined. Some authentication schemes address
this issue using devices that give unique outputs in response to a challenge.
These signatures are generated by hard-to-predict physical responses derived
from structural characteristics, which lend themselves to two different
architectures, known as unique objects (UNOs) and physically unclonable
functions (PUFs). The classical design of UNOs and PUFs limits their size and,
in some cases, their security. Here we show that quantum confinement lends
itself to the provision of unique identities at the nanoscale, by using
fluctuations in tunnelling measurements through quantum wells in resonant
tunnelling diodes (RTDs). This provides an uncomplicated measurement of
identity without conventional resource limitations whilst providing robust
security. The confined energy levels are highly sensitive to the specific
nanostructure within each RTD, resulting in a distinct tunnelling spectrum for
every device, as they contain a unique and unpredictable structure that is
presently impossible to clone. This new class of authentication device operates
with few resources in simple electronic structures above room temperature.Comment: 13 pages, 3 figure
TL1A Selectively Enhances IL-12/IL-18-Induced NK Cell Cytotoxicity against NK-Resistant Tumor Targets
# The Author(s) 2010. This article is published with open access at Springerlink.com Introduction TL1A (TNFSF15) augments IFN-γ production by IL-12/IL-18 responsive human T cells. Its ligand, death domain receptor 3 (DR3), is induced by activation on T and NK cells. Although IL-12/IL-18 induces DR3 expression on most NK cells, addition of TL1A minimally increases IFN-
A disordered region controls cBAF activity via condensation and partner recruitment
Intrinsically disordered regions (IDRs) represent a large percentage of overall nuclear protein content. The prevailing dogma is that IDRs engage in non-specific interactions because they are poorly constrained by evolutionary selection. Here, we demonstrate that condensate formation and heterotypic interactions are distinct and separable features of an IDR within the ARID1A/B subunits of the mSWI/SNF chromatin remodeler, cBAF, and establish distinct sequence grammars underlying each contribution. Condensation is driven by uniformly distributed tyrosine residues, and partner interactions are mediated by non-random blocks rich in alanine, glycine, and glutamine residues. These features concentrate a specific cBAF protein-protein interaction network and are essential for chromatin localization and activity. Importantly, human disease-associated perturbations in ARID1B IDR sequence grammars disrupt cBAF function in cells. Together, these data identify IDR contributions to chromatin remodeling and explain how phase separation provides a mechanism through which both genomic localization and functional partner recruitment are achieved
GibbsST: a Gibbs sampling method for motif discovery with enhanced resistance to local optima
BACKGROUND: Computational discovery of transcription factor binding sites (TFBS) is a challenging but important problem of bioinformatics. In this study, improvement of a Gibbs sampling based technique for TFBS discovery is attempted through an approach that is widely known, but which has never been investigated before: reduction of the effect of local optima. RESULTS: To alleviate the vulnerability of Gibbs sampling to local optima trapping, we propose to combine a thermodynamic method, called simulated tempering, with Gibbs sampling. The resultant algorithm, GibbsST, is then validated using synthetic data and actual promoter sequences extracted from Saccharomyces cerevisiae. It is noteworthy that the marked improvement of the efficiency presented in this paper is attributable solely to the improvement of the search method. CONCLUSION: Simulated tempering is a powerful solution for local optima problems found in pattern discovery. Extended application of simulated tempering for various bioinformatic problems is promising as a robust solution against local optima problems
Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria
The similarity in the genetic regulation of
arthropod and vertebrate appendage formation has been
interpreted as the product of a plesiomorphic gene
network that was primitively involved in bilaterian
appendage development and co-opted to build appendages
(in modern phyla) that are not historically related
as structures. Data from lophotrochozoans are needed to
clarify the pervasiveness of plesiomorphic appendage forming
mechanisms. We assayed the expression of three
arthropod and vertebrate limb gene orthologs, Distal-less
(Dll), dachshund (dac), and optomotor blind (omb), in
direct-developing juveniles of the polychaete Neanthes
arenaceodentata. Parapodial Dll expression marks premorphogenetic
notopodia and neuropodia, becoming restricted
to the bases of notopodial cirri and to ventral
portions of neuropodia. In outgrowing cephalic appendages,
Dll activity is primarily restricted to proximal
domains. Dll expression is also prominent in the brain. dac
expression occurs in the brain, nerve cord ganglia, a pair
of pharyngeal ganglia, presumed interneurons linking a
pair of segmental nerves, and in newly differentiating
mesoderm. Domains of omb expression include the brain,
nerve cord ganglia, one pair of anterior cirri, presumed
precursors of dorsal musculature, and the same pharyngeal
ganglia and presumed interneurons that express dac.
Contrary to their roles in outgrowing arthropod and
vertebrate appendages, Dll, dac, and omb lack comparable
expression in Neanthes appendages, implying independent
evolution of annelid appendage development. We infer
that parapodia and arthropodia are not structurally or
mechanistically homologous (but their primordia might
be), that Dll’s ancestral bilaterian function was in sensory
and central nervous system differentiation, and that
locomotory appendages possibly evolved from sensory
outgrowths
Mouse SPNS2 Functions as a Sphingosine-1-Phosphate Transporter in Vascular Endothelial Cells
Sphingosine-1-phosphate (S1P), a sphingolipid metabolite that is produced inside
the cells, regulates a variety of physiological and pathological responses via
S1P receptors (S1P1–5). Signal transduction between cells consists of
three steps; the synthesis of signaling molecules, their export to the
extracellular space and their recognition by receptors. An S1P concentration
gradient is essential for the migration of various cell types that express S1P
receptors, such as lymphocytes, pre-osteoclasts, cancer cells and endothelial
cells. To maintain this concentration gradient, plasma S1P concentration must be
at a higher level. However, little is known about the molecular mechanism by
which S1P is supplied to extracellular environments such as blood plasma. Here,
we show that SPNS2 functions as an S1P transporter in vascular endothelial cells
but not in erythrocytes and platelets. Moreover, the plasma S1P concentration of
SPNS2-deficient mice was reduced to approximately 60% of wild-type, and
SPNS2-deficient mice were lymphopenic. Our results demonstrate that SPNS2 is the
first physiological S1P transporter in mammals and is a key determinant of
lymphocyte egress from the thymus
Does country of origin affect brand associations? The case of Italian brands in China
none3noFindings related to how country of origin affects consumers’ product evaluations are still not consistent. Previous studies are mainly based on experiments and the results related to consumer judgements come from the elaboration of scores given to semantic scale items. Considering that brand image consists of a network of associations, the aim of this research is to evaluate how country of origin affects this entire network. An experiment was conducted involving 301 Chinese subjects to test the hypothesis that country stereotypes can be transferred to brands.noneFrancesca Checchinato, Marta Disegna, Tiziano VescoviChecchinato, Francesca; Disegna, Marta; Vescovi, Tizian
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