5,231 research outputs found

    Role of the Netrin-like Domain of Procollagen C-Proteinase Enhancer-1 in the Control of Metalloproteinase Activity

    Get PDF
    The netrin-like (NTR) domain is a feature of several extracellular proteins, most notably the N-terminal domain of tissue inhibitors of metalloproteinases (TIMPs), where it functions as a strong inhibitor of matrix metalloproteinases and some other members of the metzincin superfamily. The presence of a C-terminal NTR domain in procollagen C-proteinase enhancers (PCPEs), proteins that stimulate the activity of astacin-like tolloid proteinases, raises the possibility that this might also have inhibitory activity. Here we show that both long and short forms of the PCPE-1 NTR domain, the latter beginning at the N-terminal cysteine known to be critical for TIMP activity, show no inhibition, at micromolar concentrations, of several members of the metzincin superfamily, including matrix metalloproteinase-2, bone morphogenetic protein-1 (a tolloid proteinase), and different ADAMTS (a disintegrin and a metalloproteinase with thrombospondin motifs) proteinases from the adamalysin family. In contrast, we report that the NTR domain within PCPE-1 leads to superstimulation of bone morphogenetic protein-1 activity in the presence of heparin and heparan sulfate. These observations point to a new mechanism whereby binding to cell surface-associated or extracellular heparin-like sulfated glycosaminoglycans might provide a means to accelerate procollagen processing in specific cellular and extracellular microenvironments

    Modern and possible paleotsunami deposits in Samenoura, Sanriku Coast, and their relation to tsunami source mechanisms

    Get PDF
    Samenoura is situated in the bay head of a small inlet on the Pacific coast of Oshika Peninsula, one of the nearest places to the epicenter of the 2011 Tohoku-oki Earthquake. According to the Joint Survey Group, wave heights were measured at more than 20 m near the coastline. This area was severely damaged as a result of both co-seismic subsidence and tsunami inundation. We carried out field surveys of the Tohoku-oki and paleotsunami deposits at Samenoura in March, May and October 2013. Sandy deposits laid down by the Tohoku-oki tsunami were up to 20 cm thick at locations with an elevation greater than 10 m, and were several cm thick within the forest higher up. The tsunami deposit also contained numerous shell fragments and foraminifera. Although some possible sources of the tsunami deposits can be attributed to narrow sandy beaches near the study area, the deposition of such a thick sandy deposit is more or less enigmatic, considering the steep Ria-type coastal topography.Using a gouge auger and geoslicer, we found at least two sand layers intercalated within muddy sediments. A volcanic ash layer, which corresponds to the AD 915 Towada-a tephra, was also identified from a horizon between these sand layers. The underlying sand layer was most probably laid down by the 869 Jogan earthquake tsunami, one of the large-scale events known to have affected the region. Previous studies of the Jogan tsunami have proposed several possible source models that involve an interplate thrust earthquake. Given that the local bathymetry and topography of Samenoura Bay may be sensitive to the waveform of a large-scale tsunami, paleotsunami deposits found from this area may be the key to determining the source mechanisms of events on the Sanriku Coast.In this presentation, the possible correlation of the sandy deposits with known paleotsunami events based on detailed radiocarbon dating is discussed. The hydrodynamic character and processes of tsunami sediment erosion and deposition in Samenoura Bay are analyzed using numerical modeling of both interplate and outer-rise earthquake scenarios.Copyright on Japan Geoscience Union Meeting, 2014

    Tsunamis in the geological record: Making waves with a cautionary tale from the Mediterranean

    Get PDF
    This is the final version of the article. Available from AAAS via the DOI in this record.From 2000 to 2015, tsunamis and storms killed more than 430,000 people worldwide and affected a further >530 million, with total damages exceeding US$970 billion. These alarming trends, underscored by the tragic events of the 2004 Indian Ocean catastrophe, have fueled increased worldwide demands for assessments of past, present, and future coastal risks. Nonetheless, despite its importance for hazard mitigation, discriminating between storm and tsunami deposits in the geological record is one of the most challenging and hotly contended topics in coastal geoscience. To probe this knowledge gap, we present a 4500-year reconstruction of "tsunami" variability from the Mediterranean based on stratigraphic but not historical archives and assess it in relation to climate records and reconstructions of storminess. We elucidate evidence for previously unrecognized "tsunami megacycles" with three peaks centered on the Little Ice Age, 1600, and 3100 cal. yr B.P. (calibrated years before present). These ~1500-year cycles, strongly correlated with climate deterioration in the Mediterranean/North Atlantic, challenge up to 90% of the original tsunami attributions and suggest, by contrast, that most events are better ascribed to periods of heightened storminess. This timely and provocative finding is crucial in providing appropriately tailored assessments of coastal hazard risk in the Mediterranean and beyond.Financial support for this work was provided by Labex OT-Med (ANR-11-LABX-0061). Additional assistance was provided by the Institut Universitaire de France (CLIMSORIENT project), ANR Geomar (ANR-12-SENV- 0008-01), A*MIDEX (ANR-11-IDEX-0001-02), and Partenariat Hubert Curien PROCOPE (33361WG). J.G. benefited from a research fellowship at Chrono-environnement funded by the Région Bourgogne-Franche-Comté

    The phase diagram of the lattice Calogero-Sutherland model

    Full text link
    We introduce a {\it lattice} version of the Calogero Sutherland model adapted to describe 1/d21/d^2 pairwise interacting steps with discrete positions on a vicinal surface. The configurational free energy is obtained within a transfer matrix method. The full phase diagram for attractive and for repulsive interaction is deduced. For attraction, critical temperatures of faceting transitions are found to depend on step density.Comment: latex PRBCalogSuth.tex, 6 files, 4 pages [SPEC-S00/900

    Diffusive counter dispersion of mass in bubbly media

    Full text link
    We consider a liquid bearing gas bubbles in a porous medium. When gas bubbles are immovably trapped in a porous matrix by surface-tension forces, the dominant mechanism of transfer of gas mass becomes the diffusion of gas molecules through the liquid. Essentially, the gas solution is in local thermodynamic equilibrium with vapor phase all over the system, i.e., the solute concentration equals the solubility. When temperature and/or pressure gradients are applied, diffusion fluxes appear and these fluxes are faithfully determined by the temperature and pressure fields, not by the local solute concentration, which is enslaved by the former. We derive the equations governing such systems, accounting for thermodiffusion and gravitational segregation effects which are shown not to be neglected for geological systems---marine sediments, terrestrial aquifers, etc. The results are applied for the treatment of non-high-pressure systems and real geological systems bearing methane or carbon dioxide, where we find a potential possibility of the formation of gaseous horizons deep below a porous medium surface. The reported effects are of particular importance for natural methane hydrate deposits and the problem of burial of industrial production of carbon dioxide in deep aquifers.Comment: 10 pages, 5 figures, 1 table, Physical Review

    Classical simulation of measurement-based quantum computation on higher-genus surface-code states

    Full text link
    We consider the efficiency of classically simulating measurement-based quantum computation on surface-code states. We devise a method for calculating the elements of the probability distribution for the classical output of the quantum computation. The operational cost of this method is polynomial in the size of the surface-code state, but in the worst case scales as 22g2^{2g} in the genus gg of the surface embedding the code. However, there are states in the code space for which the simulation becomes efficient. In general, the simulation cost is exponential in the entanglement contained in a certain effective state, capturing the encoded state, the encoding and the local post-measurement states. The same efficiencies hold, with additional assumptions on the temporal order of measurements and on the tessellations of the code surfaces, for the harder task of sampling from the distribution of the computational output.Comment: 21 pages, 13 figure

    Extreme Mountain Ultra-Marathon Leads to Acute but Transient Increase in Cerebral Water Diffusivity and Plasma Biomarkers Levels Changes.

    Get PDF
    Background: Pioneer studies demonstrate the impact of extreme sport load on the human brain, leading to threatening conditions for athlete's health such as cerebral edema. The investigation of brain water diffusivity, allowing the measurement of the intercellular water and the assessment of cerebral edema, can give a great contribution to the investigation of the effects of extreme sports on the brain. We therefore assessed the effect of supra-physiological effort (extreme distance and elevation changes) in mountain ultra-marathons (MUMs) athletes combining for the first time brain magnetic resonance imaging (MRI) and blood parameters. Methods:This longitudinal study included 19 volunteers (44.2 ± 9.5 years) finishing a MUM (330 km, elevation + 24000 m). Quantitative measurements of brain diffusion-weighted images (DWI) were performed at 3 time-points: Before the race, upon arrival and after 48 h. Multiple blood biomarkers were simultaneously investigated. Data analyses included brain apparent diffusion coefficient (ADC) and physiological data comparisons between three time-points. Results:The whole brain ADC significantly increased from baseline to arrival (p = 0.005) and then significantly decreased at recovery (p = 0.005) to lower values than at baseline (p = 0.005). While sodium, potassium, calcium, and chloride as well as hematocrit (HCT) changed over time, the serum osmolality remained constant. Significant correlations were found between whole brain ADC changes and osmolality (p = 0.01), cholesterol (p = 0.009), c-reactive protein (p = 0.04), sodium (p = 0.01), and chloride (p = 0.002) plasma level variations. Conclusions:These results suggest the relative increase of the inter-cellular volume upon arrival, and subsequently its reduction to lower values than at baseline, indicating that even after 48 h the brain has not fully recovered to its equilibrium state. Even though serum electrolytes may only indirectly indicate modifications at the brain level due to the blood brain barrier, the results concerning osmolality suggest that body water might directly influence the change in cerebral ADC. These findings establish therefore a direct link between general brain inter-cellular water content and physiological biomarkers modifications produced by extreme sport

    Pan-European early switch/early discharge opportunities exist for hospitalised patients with methicillin-resistant <em>Staphylococcus</em> <em>aureus</em> complicated skin and soft-tissue infections

    Get PDF
    AbstractThe objective of this study was to document pan-European real-world treatment patterns and healthcare resource use and estimate opportunities for early switch (ES) from intravenous (IV) to oral antibiotics and early discharge (ED) in hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft tissue infections (cSSTIs). This retrospective observational medical chart review study enrolled 342 physicians across 12 European countries who collected data from 1542 patients with documented MRSA cSSTI who were hospitalized (July 2010 to June 2011) and discharged alive (by July 2011). Data included clinical characteristics and outcomes, hospital length of stay (LOS), MRSA-targeted IV and oral antibiotic use, and ES and ED eligibility according to literature-based and expert-validated criteria. The most frequent initial MRSA-active antibiotics were vancomycin (50.2%), linezolid (15.1%), clindamycin (10.8%), and teicoplanin (10.4%). Patients discharged with MRSA-active antibiotics (n = 480) were most frequently prescribed linezolid (42.1%) and clindamycin (19.8%). IV treatment duration (9.3 ± 6.5 vs. 14.6 ± 9.9 days; p <0.001) and hospital LOS (19.1 ± 12.9 vs. 21.0 ± 18.2 days; p 0.162) tended to be shorter for patients switched from IV to oral treatment than for patients who received IV treatment only. Of the patients, 33.6% met ES criteria and could have discontinued IV treatment 6.0 ± 5.5 days earlier, and 37.9% met ED criteria and could have been discharged 6.2 ± 8.2 days earlier. More than one-third of European patients hospitalized for MRSA cSSTI could be eligible for ES and ED, resulting in substantial reductions in IV days and bed-days, with potential savings of €2000 per ED-eligible patient
    corecore