7,345 research outputs found

    Design of a single axis simulator for satellite control system testing and for low torque measurement

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    Single axis simulator design for satellite control system testing and low torque measuremen

    Gene expression in large pedigrees: analytic approaches.

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    BackgroundWe currently have the ability to quantify transcript abundance of messenger RNA (mRNA), genome-wide, using microarray technologies. Analyzing genotype, phenotype and expression data from 20 pedigrees, the members of our Genetic Analysis Workshop (GAW) 19 gene expression group published 9 papers, tackling some timely and important problems and questions. To study the complexity and interrelationships of genetics and gene expression, we used established statistical tools, developed newer statistical tools, and developed and applied extensions to these tools.MethodsTo study gene expression correlations in the pedigree members (without incorporating genotype or trait data into the analysis), 2 papers used principal components analysis, weighted gene coexpression network analysis, meta-analyses, gene enrichment analyses, and linear mixed models. To explore the relationship between genetics and gene expression, 2 papers studied expression quantitative trait locus allelic heterogeneity through conditional association analyses, and epistasis through interaction analyses. A third paper assessed the feasibility of applying allele-specific binding to filter potential regulatory single-nucleotide polymorphisms (SNPs). Analytic approaches included linear mixed models based on measured genotypes in pedigrees, permutation tests, and covariance kernels. To incorporate both genotype and phenotype data with gene expression, 4 groups employed linear mixed models, nonparametric weighted U statistics, structural equation modeling, Bayesian unified frameworks, and multiple regression.Results and discussionRegarding the analysis of pedigree data, we found that gene expression is familial, indicating that at least 1 factor for pedigree membership or multiple factors for the degree of relationship should be included in analyses, and we developed a method to adjust for familiality prior to conducting weighted co-expression gene network analysis. For SNP association and conditional analyses, we found FaST-LMM (Factored Spectrally Transformed Linear Mixed Model) and SOLAR-MGA (Sequential Oligogenic Linkage Analysis Routines -Major Gene Analysis) have similar type 1 and type 2 errors and can be used almost interchangeably. To improve the power and precision of association tests, prior knowledge of DNase-I hypersensitivity sites or other relevant biological annotations can be incorporated into the analyses. On a biological level, eQTL (expression quantitative trait loci) are genetically complex, exhibiting both allelic heterogeneity and epistasis. Including both genotype and phenotype data together with measurements of gene expression was found to be generally advantageous in terms of generating improved levels of significance and in providing more interpretable biological models.ConclusionsPedigrees can be used to conduct analyses of and enhance gene expression studies

    Measure Recognition Problem

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    This is an article in mathematics, specifically in set theory. On the example of the Measure Recognition Problem (MRP) the article highlights the phenomenon of the utility of a multidisciplinary mathematical approach to a single mathematical problem, in particular the value of a set-theoretic analysis. MRP asks if for a given Boolean algebra \algB and a property Φ\Phi of measures one can recognize by purely combinatorial means if \algB supports a strictly positive measure with property Φ\Phi. The most famous instance of this problem is MRP(countable additivity), and in the first part of the article we survey the known results on this and some other problems. We show how these results naturally lead to asking about two other specific instances of the problem MRP, namely MRP(nonatomic) and MRP(separable). Then we show how our recent work D\v zamonja and Plebanek (2006) gives an easy solution to the former of these problems, and gives some partial information about the latter. The long term goal of this line of research is to obtain a structure theory of Boolean algebras that support a finitely additive strictly positive measure, along the lines of Maharam theorem which gives such a structure theorem for measure algebras

    High power coupled CO2 waveguide laser array

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    A hollow-bore ridge waveguide technique for phase locking arrays of coupled CO2 rf excited waveguide lasers was demonstrated. Stable phase-locked operation of two- and three-channel arrays has been demonstrated at the 50 W output level. Preliminary experiments with a five-element array generated an output power of 95 W but phase-locked operation was not conclusively demonstrated

    Analysis of Accordion DNA Stretching Revealed by The Gold Cluster Ruler

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    A promising new method for measuring intramolecular distances in solution uses small-angle X-ray scattering interference between gold nanocrystal labels (Mathew-Fenn et al, Science, 322, 446 (2008)). When applied to double stranded DNA, it revealed that the DNA length fluctuations are strikingly strong and correlated over at least 80 base pair steps. In other words, the DNA behaves as accordion bellows, with distant fragments stretching and shrinking concertedly. This hypothesis, however, disagrees with earlier experimental and computational observations. This Letter shows that the discrepancy can be rationalized by taking into account the cluster exclusion volume and assuming a moderate long-range repulsion between them. The long-range interaction can originate from an ion exclusion effect and cluster polarization in close proximity to the DNA surface.Comment: 9 pages, 4 figures, to appear in Phys. Rev.

    A new geometric invariant on initial data for Einstein equations

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    For a given asymptotically flat initial data set for Einstein equations a new geometric invariant is constructed. This invariant measure the departure of the data set from the stationary regime, it vanishes if and only if the data is stationary. In vacuum, it can be interpreted as a measure of the total amount of radiation contained in the data.Comment: 5 pages. Important corrections regarding the generalization to the non-time symmetric cas

    Enhanced Integrin α4β1-Mediated Adhesion Contributes to a Mobilization Defect of Endothelial Progenitor Cells in Diabetes.

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    Diabetes is associated with a deficit of circulating endothelial progenitor cells (EPCs), which has been attributed to their defective mobilization from the bone marrow. The basis for this mobilization defect is not completely understood, and we sought to determine if hyperglycemic conditions enhanced EPC adhesion. We found that culturing EPCs in high glucose media increased adhesion to bone marrow stromal cells. This enhanced adhesion was associated with decreased expression of protein kinase A regulatory subunit 1β (PRKAR1β), activation of protein kinase A (PKA), and phosphorylation of α4-integrin on serine 988. This potentiated adhesion was reversed by treatment with a PKA inhibitor, overexpression of PRKAR1β, or expression of a phosphorylation-defective α4-integrin variant (α4[S988A]). Using a model of type 1 diabetes, we showed that α4(S988A)-expressing mice have more circulating EPCs than their wild-type counterparts. Moreover, diabetic α4(S988A) mice demonstrate enhanced revascularization after hind limb ischemia. Thus, we have identified a novel signaling mechanism activating PKA in diabetes (downregulation of an inhibitory regulatory subunit) that leads to deficits of circulating EPCs and impaired vascular repair, which could be reversed by α4-integrin mutation

    Cloned mouse cells with natural killer function and cloned suppressor T cells express ultrastructural and biochemical features not shared by cloned inducer T cells.

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    We have examined the morphology, cytochemistry, and biochemistry of mouse leukocyte subsets by analyzing cloned leukocyte populations specialized to perform different immunologic functions. Cloned cells expressing high-affinity plasma membrane receptors for IgE and mediating natural killer (NK) lysis and cloned antigen-specific suppressor T cells contained prominent osmiophilic cytoplasmic granules similar by ultrastructure to those of mouse basophils. Both clones also incorporated 35SO4 into granule-associated sulfated glycosaminoglycans, expressed a characteristic ultrastructural pattern of nonspecific esterase activity, incorporated exogenous [3H]5-hydroxytryptamine, and contained cytoplasmic deposits of particulate glycogen. By contrast, cloned inducer T cells lacked cytoplasmic granules and glycogen, incorporated neither 35SO4 nor [3H]5-hydroxytryptamine, and differed from the other clones in pattern of nonspecific esterase activity. These findings establish that certain cloned cells with NK activity and cloned suppressor T cells express morphologic and biochemical characteristics heretofore associated with basophilic granulocytes. However, these clones differ in surface glycoprotein expression and immunologic function, and the full extent of the similarities and differences among these populations and basophils remains to be determined

    Stretching Semiflexible Polymer Chains: Evidence for the Importance of Excluded Volume Effects from Monte Carlo Simulation

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    Semiflexible macromolecules in dilute solution under very good solvent conditions are modeled by self-avoiding walks on the simple cubic lattice (d=3d=3 dimensions) and square lattice (d=2d=2 dimensions), varying chain stiffness by an energy penalty ϵb\epsilon_b for chain bending. In the absence of excluded volume interactions, the persistence length p\ell_p of the polymers would then simply be p=b(2d2)1qb1\ell_p=\ell_b(2d-2)^{-1}q_b^{-1} with qb=exp(ϵb/kBT)q_b= \exp(-\epsilon_b/k_BT), the bond length b\ell_b being the lattice spacing, and kBTk_BT is the thermal energy. Using Monte Carlo simulations applying the pruned-enriched Rosenbluth method (PERM), both qbq_b and the chain length NN are varied over a wide range (0.005qb1,  N50000(0.005 \leq q_b \leq 1, \; N \leq 50000), and also a stretching force ff is applied to one chain end (fixing the other end at the origin). In the absence of this force, in d=2d=2 a single crossover from rod-like behavior (for contour lengths less than p\ell_p) to swollen coils occurs, invalidating the Kratky-Porod model, while in d=3d=3 a double crossover occurs, from rods to Gaussian coils (as implied by the Kratky-Porod model) and then to coils that are swollen due to the excluded volume interaction. If the stretching force is applied, excluded volume interactions matter for the force versus extension relation irrespective of chain stiffness in d=2d=2, while theories based on the Kratky-Porod model are found to work in d=3d=3 for stiff chains in an intermediate regime of chain extensions. While for qb1q_b \ll 1 in this model a persistence length can be estimated from the initial decay of bond-orientational correlations, it is argued that this is not possible for more complex wormlike chains (e.g. bottle-brush polymers). Consequences for the proper interpretation of experiments are briefly discussed.Comment: 23 pages, 17 figures, 2 tables, to be published in J. Chem. Phys. (2011
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