7,345 research outputs found
Design of a single axis simulator for satellite control system testing and for low torque measurement
Single axis simulator design for satellite control system testing and low torque measuremen
Gene expression in large pedigrees: analytic approaches.
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
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 of measures
one can recognize by purely combinatorial means if \algB supports a strictly
positive measure with property . 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
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
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Midwinter suppression of baroclinic storm activity on Mars: observations and models
Baroclinic instability and intense traveling wave activity on Mars is well known to occur in “storm zones” (Hollingsworth et al. 1996) close to the edge of the advancing or retreating polar ice cap. Such activity usually sets in during Martian fall and continues until the onset of the summer season when large-scale instability mostly ceases as the atmosphere is no longer baroclinically unstable. The stormy season is typically characterized by large-scale, zonally-propagating waves with zonal wavenumbers m = 1-3, the lower wavenumber modes typically penetrating to considerable altitude though may also be surface-intensified.
As we show below, however, some observations suggest that this eddy activity does not persist uniformly throughout the autumn, winter and spring seasons, but appears to die down quite consistently within 10 sols or so either side of the winter solstice. This midwinter ‘solsticial pause’ appears to be a sufficiently consistent feature of each winter season in both hemispheres to be regarded as a significant feature of Martian climatology, and could affect a variety of aspects of Martian meteorology including global heat and momentum transport, occurrence of dust storms etc.
A somewhat similar phenomenon has also been documented for the Earth (e.g. Nakamura 1992; Penny et al. 2010), especially in relation to seasonal variations in the north Pacific storm tracks. The cause of this phenomenon is still not well established, though suggested mechanisms include the effects of enhanced barotropic shear (the so-called ‘barotropic governor’ (James & Gray 1986) and interactions with topography over central Asia.
In this presentation we examine evidence for this phenomenon in the assimilated record of Martian climate from the Thermal Emission Spectrometer on board the Mars Global Surveyor mission (MGSTES), in conjunction with the UK version of the LMD-Oxford-OU-IAA Mars GCM (Forget et al. 1999; Montabone et al. 2006; Lewis et al. 2007). This is further corroborated in other evidence from seasonal variations in the incidence of local and regional dust storms that owe their origin to circumpolar baroclinic storms. We also discuss the extent to which this ‘solsticial pause’ phenomenon is reproduced in stand-alone atmospheric models and present results of some simulations to test a number of hypotheses for its dynamical origin on Mars
Analysis of Accordion DNA Stretching Revealed by The Gold Cluster Ruler
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
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.
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.
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
Semiflexible macromolecules in dilute solution under very good solvent
conditions are modeled by self-avoiding walks on the simple cubic lattice
( dimensions) and square lattice ( dimensions), varying chain
stiffness by an energy penalty for chain bending. In the absence
of excluded volume interactions, the persistence length of the
polymers would then simply be with , the bond length being the lattice spacing,
and is the thermal energy. Using Monte Carlo simulations applying the
pruned-enriched Rosenbluth method (PERM), both and the chain length
are varied over a wide range ), and
also a stretching force is applied to one chain end (fixing the other end
at the origin). In the absence of this force, in a single crossover from
rod-like behavior (for contour lengths less than ) to swollen coils
occurs, invalidating the Kratky-Porod model, while in 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 , while
theories based on the Kratky-Porod model are found to work in for stiff
chains in an intermediate regime of chain extensions. While for 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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