1,596 research outputs found

    Role of growth factors in the pathogenesis of tissue fibrosis in systemic sclerosis.

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    The most severe clinical and pathologic manifestations of systemic sclerosis (SSc) are the result of a fibrotic process characterized by the excessive and often progressive deposition of collagen and other connective tissue macromolecules in skin and numerous internal organs. The mechanisms involved in the initiation and progression of the remarkable fibrotic process in SSc remain largely unknown. Extensive recent studies have indicated that a variety of polypeptide growth factors play a crucial role in this process. The most commonly implicated growth factors include transforming growth factor beta (TGF-β), connective tissue growth factor (CTGF), platelet derived growth factor (PDGF), and vascular endothelial growth factor (VEGF). Here, the experimental evidence supporting the participation of various growth factors in the pathogenesis of the fibrotic process in SSc and the molecular mechanisms involved will be reviewed

    Constraining the History of the Sagittarius Dwarf Galaxy Using Observations of its Tidal Debris

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    We present a comparison of semi-analytic models of the phase-space structure of tidal debris with observations of stars associated with the Sagittarius dwarf galaxy (Sgr). We find that many features in the data can be explained by these models. The properties of stars 10-15 degrees away from the center of Sgr --- in particular, the orientation of material perpendicular to Sgr's orbit (c.f. Alard 1996) and the kink in the velocity gradient (Ibata et al 1997) --- are consistent with those expected for unbound material stripped during the most recent pericentric passage ~50 Myrs ago. The break in the slope of the surface density seen by Mateo, Olszewski & Morrison (1998) at ~ b=-35 can be understood as marking the end of this material. However, the detections beyond this point are unlikely to represent debris in a trailing streamer, torn from Sgr during the immediately preceding passage ~0.7 Gyrs ago, but are more plausibly explained by a leading streamer of material that was lost more that 1 Gyr ago and has wrapped all the way around the Galaxy. The observations reported in Majewski et al (1999) also support this hypothesis. We determine debris models with these properties on orbits that are consistent with the currently known positions and velocities of Sgr in Galactic potentials with halo components that have circular velocities v_circ=140-200 km/s. The best match to the data is obtained in models where Sgr currently has a mass of ~10^9 M_sun and has orbited the Galaxy for at least the last 1 Gyr, during which time it has reduced its mass by a factor of 2-3, or luminosity by an amount equivalent to ~10% of the total luminosity of the Galactic halo. These numbers suggest that Sgr is rapidly disrupting and unlikely to survive beyond a few more pericentric passages.Comment: 19 pages, 5 figures, accepted to Astronomical Journa

    Loss of Protein Stability and Function Caused by P228L Variation in NADPH-Cytochrome P450 Reductase Linked to Lower Testosterone Levels.

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    Cytochrome P450 oxidoreductase (POR) is the redox partner of steroid and drug-metabolising cytochromes P450 located in the endoplasmic reticulum. Mutations in POR cause a broad range of metabolic disorders. The POR variant rs17853284 (P228L), identified by genome sequencing, has been linked to lower testosterone levels and reduced P450 activities. We expressed the POR wild type and the P228L variant in bacteria, purified the proteins, and performed protein stability and catalytic functional studies. Variant P228L affected the stability of the protein as evidenced by lower unfolding temperatures and higher sensitivity to urea denaturation. A significant decline in the rate of electron transfer to cytochrome c and thiazolyl blue tetrazolium (MTT) was observed with POR P228L, while activities of CYP3A4 were reduced by 25% and activities of CYP3A5 and CYP2C9 were reduced by more than 40% compared with WT POR. The 17,20 lyase activity of CYP17A1, responsible for the production of the main androgen precursor dehydroepiandrosterone, was reduced to 27% of WT in the presence of the P228L variant of POR. Based on in silico and in vitro studies, we predict that the change of proline to leucine may change the rigidity of the protein, causing conformational changes in POR, leading to altered electron transfer to redox partners. A single amino acid change can affect protein stability and cause a severe reduction in POR activity. Molecular characterisation of individual POR mutations is crucial for a better understanding of the impact on different redox partners of POR

    Thermodynamic fluctuation relation for temperature and energy

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    The present work extends the well-known thermodynamic relation C=β2<δE2>C=\beta ^{2}< \delta {E^{2}}> for the canonical ensemble. We start from the general situation of the thermodynamic equilibrium between a large but finite system of interest and a generalized thermostat, which we define in the course of the paper. The resulting identity =1+<δE2>∂2S(E)/∂E2 =1+< \delta {E^{2}}% > \partial ^{2}S(E) /\partial {E^{2}} can account for thermodynamic states with a negative heat capacity C<0C<0; at the same time, it represents a thermodynamic fluctuation relation that imposes some restrictions on the determination of the microcanonical caloric curve β(E)=∂S(E)/∂E\beta (E) =\partial S(E) /\partial E. Finally, we comment briefly on the implications of the present result for the development of new Monte Carlo methods and an apparent analogy with quantum mechanics.Comment: Version accepted for publication in J. Phys. A: Math and The

    Angular momentum I ground state probabilities of boson systems interacting by random interactions

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    In this paper we report our systematic calculations of angular momentum II ground state probabilities (P(I)P(I)) of boson systems with spin ll in the presence of random two-body interactions. It is found that the P(0) dominance is usually not true for a system with an odd number of bosons, while it is valid for an even number of bosons, which indicates that the P(0) dominance is partly connected to the even number of identical particles. It is also noticed that the P(Imax)P(I_{max})'s of bosons with spin ll do not follow the 1/N (N=l+1N=l+1, referring to the number of independent two-body matrix elements) relation. The properties of the P(I)P(I)'s obtained in boson systems with spin ll are discussed.Comment: 8 pages and 3 figure

    Tracing Galaxy Formation with Stellar Halos I: Methods

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    If the favored hierarchical cosmological model is correct, then the Milky Way system should have accreted ~100-200 luminous satellite galaxies in the past \~12 Gyr. We model this process using a hybrid semi-analytic plus N-body approach which distinguishes explicitly between the evolution of light and dark matter in accreted satellites. This distinction is essential to our ability to produce a realistic stellar halo, with mass and density profile much like that of our own Galaxy, and a surviving satellite population that matches the observed number counts and structural parameter distributions of the satellite galaxies of the Milky Way. Our model stellar halos have density profiles which typically drop off with radius faster than those of the dark matter. They are assembled from the inside out, with the majority of mass (~80%) coming from the \~15 most massive accretion events. The satellites that contribute to the stellar halo have median accretion times of ~9 Gyr in the past, while surviving satellite systems have median accretion times of ~5 Gyr in the past. This implies that stars associated with the inner halo should be quite different chemically from stars in surviving satellites and also from stars in the outer halo or those liberated in recent disruption events. We briefly discuss the expected spatial structure and phase space structure for halos formed in this manner. Searches for this type of structure offer a direct test of whether cosmology is indeed hierarchical on small scales.Comment: 22 pages, 16 figures, submitted to Ap

    Formation and Evolution of Singularities in Anisotropic Geometric Continua

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    Evolutionary PDEs for geometric order parameters that admit propagating singular solutions are introduced and discussed. These singular solutions arise as a result of the competition between nonlinear and nonlocal processes in various familiar vector spaces. Several examples are given. The motivating example is the directed self assembly of a large number of particles for technological purposes such as nano-science processes, in which the particle interactions are anisotropic. This application leads to the derivation and analysis of gradient flow equations on Lie algebras. The Riemann structure of these gradient flow equations is also discussed.Comment: 38 pages, 4 figures. Physica D, submitte

    Garvey-Kelson relations and the new nuclear mass tables

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    Accepted for publication in Physical Review CWe discuss the Garvey-Kelson mass relations in an extended formalism and show how they can be used to test and improve the consistency of the most commonly used mass formulae, in order to achieve more accurate predictions

    N-transfer through aspen litter and feather moss layers after fertilization with ammonium nitrate and urea

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    When fertilizer is broadcast in boreal forest stands, the applied nutrients must pass through a thick layer of either feather moss or leaf litter which covers the forest floor. In a growth chamber experiment we tested the transfer of N through living feather moss or aspen litter when fertilized with urea ((NH2)2CO) or NH4NO3 at a rate of 100 kg ha−1 and under different watering regimes. When these organic substrates were frequently watered to excess they allowed the highest transfer of nutrients through, although 72% of the applied fertilizer was captured in the substrates. In a field experiment we also fertilized moss and aspen litter with urea ((NH2)2CO) or NH4NO3 at a more operationally relevant rate of 330 kg ha−1. We captured the NO3− or NH4+ by ion exchange resin at the substrate–mineral soil interface. In contrast to the growth chamber experiment, this fertilizer rate killed the moss and there was no detectable increase in nutrient levels in the aspen litter or feather moss layers. Instead, the urea was more likely transferred into the mineral soil; mineral soil of the urea treatment had 1.6 times as much extractable N compared to the NH4NO3 treatment. This difference between the growth chamber and field studies was attributed to observed fertilizer- damage to the living moss and possibly damage to the litter microflora due to the higher rate of fertilization in the field. In addition, the early and substantial rainfall after fertilization in the field experiment produced conditions for rapid leaching of N through the organic layers into the mineral soil. In the field, only 8% of the urea-N that was applied was captured by the ion exchange resin, while 34% was captured in for the NH4NO3 fertilization. Thus, the conditions for rapid leaching in the field moved much of the N in the form of urea through the organic layers and into the mineral soil before it was hydrolyzed
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