1,267 research outputs found
The International Crop Information System manages geneological; phenotypic and genotypic data in a wheat breeding program
Lysyl hydroxylase 2b (LH2b) is known to increase pyridinoline cross-links, making collagen less susceptible to enzymatic degradation. Previously, we observed a relationship between LH2b and osteoarthritis-related fibrosis in murine knee joint. For this study, we investigate if transforming growth factor-beta (TGF-) and connective tissue growth factor (CTGF) regulate procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) (gene encoding LH2b) and LH2b expression differently in osteoarthritic human synovial fibroblasts (hSF). Furthermore, we investigate via which TGF- route (Smad2/3P or Smad1/5/8P) LH2b is regulated, to explore options to inhibit LH2b during fibrosis. To answer these questions, fibroblasts were isolated from knee joints of osteoarthritis patients. The hSF were stimulated with TGF- with or without a kinase inhibitor of ALK4/5/7 (SB-505124) or ALK1/2/3/6 (dorsomorphin). TGF-, CTGF, constitutively active (ca)ALK1 and caALK5 were adenovirally overexpressed in hSF. The gene expression levels of PLOD1/2/3, CTGF and COL1A1 were analyzed with Q-PCR. LH2 protein levels were determined with western blot. As expected, TGF- induced PLOD2/LH2 expression in hSF, whereas CTGF did not. PLOD1 and PLOD3 were not affected by either TGF- or CTGF. SB-505124 prevented the induction of TGF--induced PLOD2, CTGF and COL1A1. Surprisingly, dorsomorphin completely blocked the induction of CTGF and COL1A1, whereas TGF--induced PLOD2 was only slightly reduced. Overexpression of caALK5 in osteoarthritic hSF significantly induced PLOD2/LH2 expression, whereas caALK1 had no effect. We showed, in osteoarthritic hSF, that TGF- induced PLOD2/LH2 via ALK5 Smad2/3P. This elevation of LH2b in osteoarthritic hSF makes LH2b an interesting target to interfere with osteoarthritis-related persistent fibrosis
The International Crop Information System manages geneological; phenotypic and genotypic data in a wheat breeding program
Strategically Equivalent Contests
Using a two-player Tullock-type contest, we show that intuitively and structurally different contests can be strategically equivalent. Strategically equivalent contests generate the same best response functions and, as a result, the same equilibrium efforts. However, strategically equivalent contests may yield different equilibrium payoffs. We propose a simple two-step procedure to identify strategically equivalent contests. Using this procedure, we identify contests that are strategically equivalent to the original Tullock contest, and provide new examples of strategically equivalent contests. Finally, we discuss possible contest design applications and avenues for future theoretical and empirical research
Self-similarity in the chemical evolution of galaxies and the delay-time distribution of SNe Ia
Recent improvements in the age dating of stellar populations and single stars allow us to study the ages and abundance of stars and galaxies with unprecedented accuracy. We here compare the relation between age and α-element abundances for stars in the solar neighborhood to that of local, early-type galaxies. We find these two relations to be very similar. Both fall into two regimes with a shallow slope for ages younger than ~9 Gyr and a steeper slope for ages older than that value. This quantitative similarity seems surprising because of the different types of galaxies and scales involved. For the sample of early-type galaxies we also show that the data are inconsistent with literature delay-time distributions of either single- or double-Gaussian shape. The data are consistent with a power-law delay-time distribution. We thus confirm that the delay-time distribution inferred for the Milky Way from chemical evolution arguments must also apply to massive early-type galaxies. We also offer a tentative explanation for the seeming universality of the age-[α/Fe] relation: it is the manifestation of averaging different stellar populations with varying chemical evolution histories
Gas inflow and outflow in an interacting high-redshift galaxy The remarkable host environment of GRB 080810 at z=3.35
We reveal multiple components of an interacting galaxy system at z ≈ 3.35 through a detailed analysis of the exquisite high-resolution Keck/HIRES spectrum of the afterglow of a gamma-ray burst (GRB). Through Voigt-profile fitting of absorption lines from the Lyman series, we constrain the neutral hydrogen column density to NH i ≤ 1018.35 cm-2 for the densest of four distinct systems at the host redshift of GRB 080810, which is among the lowest NH i ever observed in a GRB host, even though the line of sight passes within a projected 5 kpc of the galaxy centres. By detailed analysis of the corresponding metal absorption lines, we derive chemical, ionic, and kinematic properties of the individual absorbing systems, and thus build a picture of the host as a whole. Striking differences between the systems imply that the line of sight passes through several phases of gas: the star-forming regions of the GRB host; enriched material in the form of a galactic outflow; the hot and ionised halo of a second interacting galaxy falling towards the host at a line-of-sight velocity of 700 km s-1; and a cool metal-poor cloud that may represent one of the best candidates yet for the inflow of metal-poor gas from the intergalactic medium
The parametrization of gas flows in discs in the Auriga simulations
We study the radial motions of cold, star-forming gas in the secular evolution phase of a set of 14 magnetohydrodynamical cosmological zoom-in simulations of Milky Way-mass galaxies. We study the radial transport of material within the disc plane in a series of concentric rings. For the gas in each ring at a given time we compute two quantities as a function of time and radius: (1) the radial bulk flow of the gas and (2) the radial spread of the gas relative to the bulk flow. Averaging the data from all the haloes, we find that the radial spread increases with radius in the form of a power law with strong secondary dependencies on the fraction of accreted material and the local radial velocity dispersion of the gas. We find that the bulk motion of gas is well described in the inner disc regions by a radially independent mean inwards flow speed of . The spread around this value relates to the change in angular momentum of the gas and also the amount of accreted material. These scalings from fully cosmological, MHD simulations of galaxy formation can then be used in semi-Analytic models to better parametrize the radial flow of gas in discs
Stellar migration in the Auriga simulations
We study the presence and importance of stellar migration in the evolution of 17 Milky-Way like disc galaxies with stellar mass 10 < log(M∗/M·) < 11 from the Auriga suite of zoom-in cosmological hydrodynamical simulations. We compare the birth radii of the stars to their radii at z = 0 for each system and present mean values of the strength of stellar migration as a function of radius and stellar age which vary between 1-4 kpc. We also investigate the effect of migration on age and metallicity radial profiles in the discs. We find several cases of age gradient flattening due to migration, but significant changes to metallicity profiles only for older stellar populations and discs that develop a strong bar. Furthermore, we study stellar migration from the perspective of the change of the galactocentric radius (ΔR) and orbital guiding centre radius (ΔRg) of stellar particles between given time intervals. We find that stars migrate approximately as a diffusion process only in the outer parts of the discs and for particular galaxies that have a weak bar. Strongly barred galaxies in our sample show larger stellar migration but its timestep evolution is slower-than-diffusion. Finally, we give parametrizations that encapsulate the dependence of the strength of the radial migration as a function of time and radius, for incorporation into (semi-)analytic models of galaxy evolution
An IP-10 (CXCL10)-derived peptide inhibits angiogenesis
Angiogenesis plays a critical role in processes such as organ development, wound healing, and tumor growth. It requires well-orchestrated integration of soluble and matrix factors and timely recognition of such signals to regulate this process. Previous work has shown that newly forming vessels express the chemokine receptor CXC receptor 3 (CXCR3) and, activation by its ligand IP-10 (CXCL10), both inhibits development of new vasculature and causes regression of newly formed vessels. To identify and develop new therapeutic agents to limit or reverse pathological angiogenesis, we identified a 21 amino acid fragment of IP-10, spanning the α-helical domain residues 77-98, that mimic the actions of the whole IP-10 molecule on endothelial cells. Treatment of the endothelial cells with the 22 amino acid fragment referred to as IP-10p significantly inhibited VEGF-induced endothelial motility and tube formation in vitro, properties critical for angiogenesis. Using a Matrigel plug assay in vivo, we demonstrate that IP-10p both prevented vessel formation and induced involution of nascent vessels. CXCR3 neutralizing antibody was able to block the inhibitory effects of the IP-10p, demonstrating specificity of the peptide. Inhibition of endothelial function by IP-10p was similar to that described for IP-10, secondary to CXCR3-mediated increase in cAMP production, activation of PKA inhibiting cell migration, and inhibition of VEGF-mediated m-calpain activation. IP-10p provides a novel therapeutic agent that inhibits endothelial cell function thus, allowing for the modulation of angiogenesis. © 2012 Yates-Binder et al
Algorithms in the Ultra-Wide Word Model
The effective use of parallel computing resources to speed up algorithms in
current multi-core parallel architectures remains a difficult challenge, with
ease of programming playing a key role in the eventual success of various
parallel architectures. In this paper we consider an alternative view of
parallelism in the form of an ultra-wide word processor. We introduce the
Ultra-Wide Word architecture and model, an extension of the word-RAM model that
allows for constant time operations on thousands of bits in parallel. Word
parallelism as exploited by the word-RAM model does not suffer from the more
difficult aspects of parallel programming, namely synchronization and
concurrency. For the standard word-RAM algorithms, the speedups obtained are
moderate, as they are limited by the word size. We argue that a large class of
word-RAM algorithms can be implemented in the Ultra-Wide Word model, obtaining
speedups comparable to multi-threaded computations while keeping the simplicity
of programming of the sequential RAM model. We show that this is the case by
describing implementations of Ultra-Wide Word algorithms for dynamic
programming and string searching. In addition, we show that the Ultra-Wide Word
model can be used to implement a nonstandard memory architecture, which enables
the sidestepping of lower bounds of important data structure problems such as
priority queues and dynamic prefix sums. While similar ideas about operating on
large words have been mentioned before in the context of multimedia processors
[Thorup 2003], it is only recently that an architecture like the one we propose
has become feasible and that details can be worked out.Comment: 28 pages, 5 figures; minor change
Accelerated in vivo proliferation of memory phenotype CD4+ T-cells in human HIV-1 infection irrespective of viral chemokine co-receptor tropism.
CD4(+) T-cell loss is the hallmark of HIV-1 infection. CD4 counts fall more rapidly in advanced disease when CCR5-tropic viral strains tend to be replaced by X4-tropic viruses. We hypothesized: (i) that the early dominance of CCR5-tropic viruses results from faster turnover rates of CCR5(+) cells, and (ii) that X4-tropic strains exert greater pathogenicity by preferentially increasing turnover rates within the CXCR4(+) compartment. To test these hypotheses we measured in vivo turnover rates of CD4(+) T-cell subpopulations sorted by chemokine receptor expression, using in vivo deuterium-glucose labeling. Deuterium enrichment was modeled to derive in vivo proliferation (p) and disappearance (d*) rates which were related to viral tropism data. 13 healthy controls and 13 treatment-naive HIV-1-infected subjects (CD4 143-569 cells/ul) participated. CCR5-expression defined a CD4(+) subpopulation of predominantly CD45R0(+) memory cells with accelerated in vivo proliferation (p = 2.50 vs 1.60%/d, CCR5(+) vs CCR5(-); healthy controls; P<0.01). Conversely, CXCR4 expression defined CD4(+) T-cells (predominantly CD45RA(+) naive cells) with low turnover rates. The dominant effect of HIV infection was accelerated turnover of CCR5(+)CD45R0(+)CD4(+) memory T-cells (p = 5.16 vs 2.50%/d, HIV vs controls; P<0.05), naïve cells being relatively unaffected. Similar patterns were observed whether the dominant circulating HIV-1 strain was R5-tropic (n = 9) or X4-tropic (n = 4). Although numbers were small, X4-tropic viruses did not appear to specifically drive turnover of CXCR4-expressing cells (p = 0.54 vs 0.72 vs 0.44%/d in control, R5-tropic, and X4-tropic groups respectively). Our data are most consistent with models in which CD4(+) T-cell loss is primarily driven by non-specific immune activation
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