165 research outputs found

    An integrated environmental and human systems modeling framework for Puget Sound restoration planning

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    Local, state, federal, tribal and private stakeholders have committed significant resources to restoring Puget Sound’s terrestrial-marine ecosystem. Though jurisdictional issues have promoted a fragmented approach to restoration planning, there is growing recognition that a more coordinated systems-based restoration approach is needed to achieve recovery goals. This presentation describes our collaborative effort to develop and apply an integrated environmental and human systems modeling framework for the Puget Sound Basin, inclusive of all marine and land areas (1,020 and 12,680 sq. mi.). Our goal is to establish a whole-basin systems modeling framework that dynamically simulates biophysical interactions and transfers (water, nutrients, contaminants, biota) across terrestrial-marine boundaries. The core environmental models include a terrestrial ecohydrological model (VELMA), an ocean circulation and biogeochemistry model (Salish Sea Model), and an ocean food web model (Atlantis). This environmental subsystem will be linked with an agent-based modeling subsystem (e.g., Envision) that allows human decision-makers to be represented in whole-basin simulations. The integrated environmental and human systems framework aims to facilitate discourse among different stakeholders and decision makers (agents) and enable them play out the ecological, social and economic consequences of alternative ecosystem restoration choices. All of these models are currently being applied in Puget Sound, but they have not yet been integrated. The linked models will better capture the propagation of human impacts throughout the terrestrial-marine ecosystem, and thereby provide a more effective decision support tool for addressing restoration of high priority environmental endpoints, such as the Vital Signs identified by the Puget Sound Partnership (http://www.psp.wa.gov/vitalsigns/). Our overview will include examples of existing stand-alone model applications, and conceptual plans for linking models across terrestrial-marine boundaries. The Puget Sound multi-model framework described here can potentially be expanded to address the entire Salish Sea transboundary ecosystem (https://www.eopugetsound.org/maps/salish-sea-basin-and-water-boundaries)

    Participant characteristics associated with withdrawal from a large randomized trial of spermicide effectiveness

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    BACKGROUND: In most recent large efficacy trials of barrier contraceptive methods, a high proportion of participants withdrew before the intended end of follow-up. The objective of this analysis was to explore characteristics of participants who failed to complete seven months of planned participation in a trial of spermicide efficacy. METHODS: Trial participants were expected to use the assigned spermicide for contraception for 7 months or until pregnancy occurred. In bivariable and multivariable analyses, we assessed the associations between failure to complete the trial and 17 pre-specified baseline characteristics. In addition, among women who participated for at least 6 weeks, we evaluated the relationships between failure to complete, various features of their first 6 weeks of experience with the spermicide, and characteristics of the study centers and population. RESULTS: Of the 1514 participants in this analysis, 635 (42%) failed to complete the study for reasons other than pregnancy. Women were significantly less likely to complete if they were younger or unmarried, had intercourse at least 8 times per month, or were enrolled at a university center or at a center that enrolled fewer than 4 participants per month. Noncompliance with study procedures in the first 6 weeks was also associated with subsequent early withdrawal, but dissatisfaction with the spermicide was not. However, many participants without these risk factors withdrew early. CONCLUSIONS: Failure to complete is a major problem in barrier method trials that seriously compromises the interpretation of results. Targeting retention efforts at women at high risk for early withdrawal is not likely to address the problem sufficiently

    Seasonal melting and the formation of sedimentary rocks on Mars, with predictions for the Gale Crater mound

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    A model for the formation and distribution of sedimentary rocks on Mars is proposed. The rate-limiting step is supply of liquid water from seasonal melting of snow or ice. The model is run for a O(10^2) mbar pure CO2 atmosphere, dusty snow, and solar luminosity reduced by 23%. For these conditions snow only melts near the equator, and only when obliquity >40 degrees, eccentricity >0.12, and perihelion occurs near equinox. These requirements for melting are satisfied by 0.01-20% of the probability distribution of Mars' past spin-orbit parameters. Total melt production is sufficient to account for aqueous alteration of the sedimentary rocks. The pattern of seasonal snowmelt is integrated over all spin-orbit parameters and compared to the observed distribution of sedimentary rocks. The global distribution of snowmelt has maxima in Valles Marineris, Meridiani Planum and Gale Crater. These correspond to maxima in the sedimentary-rock distribution. Higher pressures and especially higher temperatures lead to melting over a broader range of spin-orbit parameters. The pattern of sedimentary rocks on Mars is most consistent with a Mars paleoclimate that only rarely produced enough meltwater to precipitate aqueous cements and indurate sediment. The results suggest intermittency of snowmelt and long globally-dry intervals, unfavorable for past life on Mars. This model makes testable predictions for the Mars Science Laboratory rover at Gale Crater. Gale Crater is predicted to be a hemispheric maximum for snowmelt on Mars.Comment: Submitted to Icarus. Minor changes from submitted versio

    Distinct Type of Transmission Barrier Revealed by Study of Multiple Prion Determinants of Rnq1

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    Prions are self-propagating protein conformations. Transmission of the prion state between non-identical proteins, e.g. between homologous proteins from different species, is frequently inefficient. Transmission barriers are attributed to sequence differences in prion proteins, but their underlying mechanisms are not clear. Here we use a yeast Rnq1/[PIN+]-based experimental system to explore the nature of transmission barriers. [PIN+], the prion form of Rnq1, is common in wild and laboratory yeast strains, where it facilitates the appearance of other prions. Rnq1's prion domain carries four discrete QN-rich regions. We start by showing that Rnq1 encompasses multiple prion determinants that can independently drive amyloid formation in vitro and transmit the [PIN+] prion state in vivo. Subsequent analysis of [PIN+] transmission between Rnq1 fragments with different sets of prion determinants established that (i) one common QN-rich region is required and usually sufficient for the transmission; (ii) despite identical sequences of the common QNs, such transmissions are impeded by barriers of different strength. Existence of transmission barriers in the absence of amino acid mismatches in transmitting regions indicates that in complex prion domains multiple prion determinants act cooperatively to attain the final prion conformation, and reveals transmission barriers determined by this cooperative fold

    Architectures and biogenesis of non-flagellar protein appendages in Gram-negative bacteria

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    Bacteria commonly expose non-flagellar proteinaceous appendages on their outer surfaces. These extracellular structures, called pili or fimbriae, are employed in attachment and invasion, biofilm formation, cell motility or protein and DNA transport across membranes. Over the past 15 years, the power of molecular and structural techniques has revolutionalized our understanding of the biogenesis, structure, function and mode of action of these bacterial organelles. Here, we review the five known classes of Gram-negative non-flagellar appendages from a biosynthetic and structural point of view

    Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells

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    BACKGROUND: Prostate cancer cells communicate reciprocally with the stromal cells surrounding them, inside the prostate, and after metastasis, within the bone. Each tissue secretes factors for interpretation by the other. One stromally-derived factor, Hepatocyte Growth Factor (HGF), was found twenty years ago to regulate invasion and growth of carcinoma cells. Working with the LNCaP prostate cancer progression model, we found that these cells could respond to HGF stimulation, even in the absence of Met, the only known HGF receptor. The new HGF binding partner we find on the cell surface may help to clarify conflicts in the past literature about Met expression and HGF response in cancer cells. METHODS: We searched for Met or any HGF binding partner on the cells of the PC3 and LNCaP prostate cancer cell models, using HGF immobilized on agarose beads. By using mass spectrometry analyses and sequencing we have identified nucleolin protein as a novel HGF binding partner. Antibodies against nucleolin (or HGF) were able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. Western blots, RT-PCR, and immunohistochemistry were used to assess nucleolin levels during prostate cancer progression in both LNCaP and PC3 models. RESULTS: We have identified HGF as a major signaling component of prostate stromal-conditioned media (SCM) and have implicated the protein nucleolin in HGF signal reception by the LNCaP model prostate cancer cells. Antibodies that silence either HGF (in SCM) or nucleolin (on the cell surfaces) eliminate the adhesion-stimulatory effects of the SCM. Likewise, addition of purified HGF to control media mimics the action of SCM. C4-2, an LNCaP lineage-derived, androgen-independent human prostate cancer cell line, responds to HGF in a concentration-dependent manner by increasing its adhesion and reducing its migration on laminin substratum. These HGF effects are not due to shifts in the expression levels of laminin-binding integrins, nor can they be linked to expression of the known HGF receptor Met, as neither LNCaP nor clonally-derived C4-2 sub-line contain any detectable Met protein. Even in the absence of Met, small GTPases are activated, linking HGF stimulation to membrane protrusion and integrin activation. Membrane-localized nucelolin levels increase during cancer progression, as modeled by both the PC3 and LNCaP prostate cancer progression cell lines. CONCLUSION: We propose that cell surface localized nucleolin protein may function in these cells as a novel HGF receptor. Membrane localized nucleolin binds heparin-bound growth factors (including HGF) and appears upregulated during prostate cancer progression. Antibodies against nucleolin are able to ameliorate the stimulatory effects of HGF on met-negative prostate cancer cells. HGF-nucleolin interactions could be partially responsible for the complexity of HGF responses and met expression reported in the literature
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