419 research outputs found

    Crib dock permit and construction standards in the upper great lakes

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    This study explored the permitting, design, and construction of crib docks in the Les Cheneaux and Drummond Island region of Michigan. It employed an exploratory two-phase mixed-methods research design: first to qualitatively explore and define the problem, and then to quantitatively evaluate a convenience sample of crib docks to determine appropriate permit and construction norms that meet functional requirements while addressing ecological and waterway concerns. The variables considered included siting, design, superstructure, and ground anchorage. The qualitative findings demonstrated that the USACE and MDEQ are the approving agencies for crib docks and oppose new crib dock construction permits, because they consume Great Lakes bottomland and create waterway obstacles. While the agencies do approve crib dock construction permits, the norms are vague and ill-defined. Conversely, the USFS and MDNR promote the use of submerged crib-based structures to enhance fish habitat. The findings also showed that local governments consider crib docks to be temporary structures even though they last 30 years. Because they are temporary structures, the local governments do not require them to meet state residential construction code requirements. These contradictory position and lack of code standards leaves dock applicants in a confusing, frustrating position. The quantitative findings reflected the lack of code enforcement and showed that crib docks could be made significantly safer and more environmentally friendly by imposing key design and structural norms. The conclusions and recommendations outline government policy actions to better define the crib dock approval process and propose standards for the approval and v construction of crib docks. The recommendations also outline additional research to further clarify the remaining inconsistencies in this multi-jurisdictional construction code issue

    Rotavirus A Genome Segments Show Distinct Segregation and Codon Usage Patterns

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    Reassortment of the Rotavirus A (RVA) 11-segment dsRNA genome may generate new genome constellations that allow RVA to expand its host range or evade immune responses. Reassortment may also produce phylogenetic incongruities and weakly linked evolutionary histories across the 11 segments, obscuring reassortment-specific epistasis and changes in substitution rates. To determine the co-segregation patterns of RVA segments, we generated time-scaled phylogenetic trees for each of the 11 segments of 789 complete RVA genomes isolated from mammalian hosts and compared the segments’ geodesic distances. We found that segments 4 (VP4) and 9 (VP7) occupied significantly different tree spaces from each other and from the rest of the genome. By contrast, segments 10 and 11 (NSP4 and NSP5/6) occupied nearly indistinguishable tree spaces, suggesting strong co-segregation. Host-species barriers appeared to vary by segment, with segment 9 (VP7) presenting the weakest association with host species. Bayesian Skyride plots were generated for each segment to compare relative genetic diversity among segments over time. All segments showed a dramatic decrease in diversity around 2007 coinciding with the introduction of RVA vaccines. To assess selection pressures, codon adaptation indices and relative codon deoptimization indices were calculated with respect to different host genomes. Codon usage varied by segment with segment 11 (NSP5) exhibiting significantly higher adaptation to host genomes. Furthermore, RVA codon usage patterns appeared optimized for expression in humans and birds relative to the other hosts examined, suggesting that translational efficiency is not a barrier in RVA zoonosis

    Potent and Broad Inhibition of HIV-1 by a Peptide from the gp41 Heptad Repeat-2 Domain Conjugated to the CXCR4 Amino Terminus.

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    HIV-1 entry can be inhibited by soluble peptides from the gp41 heptad repeat-2 (HR2) domain that interfere with formation of the 6-helix bundle during fusion. Inhibition has also been seen when these peptides are conjugated to anchoring molecules and over-expressed on the cell surface. We hypothesized that potent anti-HIV activity could be achieved if a 34 amino acid peptide from HR2 (C34) were brought to the site of virus-cell interactions by conjugation to the amino termini of HIV-1 coreceptors CCR5 or CXCR4. C34-conjugated coreceptors were expressed on the surface of T cell lines and primary CD4 T cells, retained the ability to mediate chemotaxis in response to cognate chemokines, and were highly resistant to HIV-1 utilization for entry. Notably, C34-conjugated CCR5 and CXCR4 each exhibited potent and broad inhibition of HIV-1 isolates from diverse clades irrespective of tropism (i.e., each could inhibit R5, X4 and dual-tropic isolates). This inhibition was highly specific and dependent on positioning of the peptide, as HIV-1 infection was poorly inhibited when C34 was conjugated to the amino terminus of CD4. C34-conjugated coreceptors could also inhibit HIV-1 isolates that were resistant to the soluble HR2 peptide inhibitor, enfuvirtide. When introduced into primary cells, CD4 T cells expressing C34-conjugated coreceptors exhibited physiologic responses to T cell activation while inhibiting diverse HIV-1 isolates, and cells containing C34-conjugated CXCR4 expanded during HIV-1 infection in vitro and in a humanized mouse model. Notably, the C34-conjugated peptide exerted greater HIV-1 inhibition when conjugated to CXCR4 than to CCR5. Thus, antiviral effects of HR2 peptides can be specifically directed to the site of viral entry where they provide potent and broad inhibition of HIV-1. This approach to engineer HIV-1 resistance in functional CD4 T cells may provide a novel cell-based therapeutic for controlling HIV infection in humans

    Future climate analysis -- 10,000 years to 1,000,000 years after present

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    The purpose of this report is to provide quantified estimates of temperature and precipitation and estimate the timing of climate states in the Yucca Mountain, Nevada, area for the period from 10,000 to 1,000,000 years beyond the present. Primary tasks are limited to: 1) selecting modern analog climate stations for three different magnitude glacial stages; and, 2) determining the timing of future climate states using orbital parameter data and Devils Hole and Owens Lake records. These estimates are intended to be used as input to models of the infiltration process to assess the performance of the natural and engineered systems of a potential underground geologic repository for the storage of radioactive nuclear waste. This report uses the methodology established and the assumptions set forth in USGS 2000a, Sections 5 and 6, which provide predictions of future climate for the next 10,000 years. USGS 2000a (Table 2, p. 66) identified present-day meteorological stations to represent three potential future climate states: modern (interglacial), monsoon, and glacial transition (intermediate) in the Yucca Mountain area. Table 2 of USGS 2000a also includes estimated durations of these climate states. This analysis uses the same approach as USGS 2000a and estimates the duration, magnitude, and timing of climate for the next 1,000,000 years based on the celestial mechanics theory (calculated earth-orbital parameters) and their relation to the Devil\u27s Hole, Nevada, paleoclimatological record and the Owens Lake, California, record (Figure 1-1). This report identifies four potential future climate states (interglacial, monsoon, intermediate, and full glacial) for the next 1,000,000 years and proposes minor changes in climate predictions for the next 10,000 years from those described in USGS 2000a. This report also identifies present-day meteorological stations that represent the four future climate states, describes a process to estimate the timing of future climate states, and provides timing and duration of climate states for the next 1,000,000 years. The timing and duration of climate states (interglacial, monsoon, intermediate, and full glacial) may be used as part of the process to address the peak dose within the period of geologic stability. The level of confidence obtained by this methodology is suitable for its intended use (40 CFR 197.35). Although the Environmental Protection Agency (EPA) in 40 CFR Part 197, Public Health and Environmental Radiation Protection Standards for Yucca Mountain, Nevada, sets a period of 10,000 years for which the U.S. Department of Energy (DOE) must demonstrate compliance with the proposed radiological standard, both the National Academy of Sciences and the EPA have suggested that estimating climate for the next 1,000,000 years would help in design and licensing decisions. Based on the geologic record, climate is likely to be much wetter and/or cooler beyond 10,000 years after present, when a peak dose would be most likely to occur. It should be noted that the EPA states in 40 CFR Part 197 that the Nuclear Regulatory Commission (NRC) is not to use the additional analysis in determining compliance with 40 CFR Part 197

    Parent-Researcher Perspectives on Role Intersectionality Related to Autism Research

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    Although parents of children with autism who are also experts in a related profession have been instrumental in shaping current practices, there is little known about parent-researchers and the benefits and obstacles to including individuals with these intersectional identities on autism focused research teams. The following study used collaborative autoethnographies from three parent-researchers hired for a large scale, federally funded project. The parent-researchers, and co-authors, collaborated on all phases of the reported study. Common themes generated from the shared perspectives included: prioritizing children and professional sacrifices; professional training as an asset for parents; potential bias toward parents in professional contexts; assets as parent-professionals; and obstacles for maintaining intersectional roles of parent-professionals. Recommendations for autism researchers and considerations for employing and supporting parent-researchers are discussed

    Interactions of Mast Cell Tryptase with Thrombin Receptors and PAR-2

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    Tryptase is a serine protease secreted by mast cells that is able to activate other cells. In the present studies we have tested whether these responses could be mediated by thrombin receptors or PAR-2, two G-protein-coupled receptors that are activated by proteolysis. When added to a peptide corresponding to the N terminus of PAR-2, tryptase cleaved the peptide at the activating site, but at higher concentrations it also cleaved downstream, as did trypsin, a known activator of PAR-2. Thrombin, factor Xa, plasmin, urokinase, plasma kallikrein, and tissue kallikrein had no effect. Tryptase also cleaved the analogous thrombin receptor peptide at the activating site but less efficiently. When added to COS-1 cells expressing either receptor, tryptase stimulated phosphoinositide hydrolysis. With PAR-2, this response was half-maximal at 1 nM tryptase and could be inhibited by the tryptase inhibitor, APC366, or by antibodies to tryptase and PAR-2. When added to human endothelial cells, which normally express PAR-2 and thrombin receptors, or keratinocytes, which express only PAR-2, tryptase caused an increase in cytosolic Ca2+. However, when added to platelets or CHRF-288 cells, which express thrombin receptors but not PAR-2, tryptase caused neither aggregation nor increased Ca2+. These results show that 1) tryptase has the potential to activate both PAR-2 and thrombin receptors; 2) for PAR-2, this potential is realized, although cleavage at secondary sites may limit activation, particularly at higher tryptase concentrations; and 3) in contrast, although tryptase clearly activates thrombin receptors in COS-1 cells, it does not appear to cleave endogenous thrombin receptors in platelets or CHRF-288 cells. These distinctions correlate with the observed differences in the rate of cleavage of the PAR-2 and thrombin receptor peptides by tryptase. Tryptase is the first protease other than trypsin that has been shown to activate human PAR-2. Its presence within mast cell granules places it in tissues where PAR-2 is expressed but trypsin is unlikely to reach

    The Lower Main Sequence and the Orbital Period Distribution of Cataclysmic Variable Stars

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    The color-magnitude diagram of the lower main sequence, as measured from a volume-limited sample of nearby stars, shows an abrupt downward jump between Mv = 12 and 13. This jump indicates that the observed mass-radius relationship steepens between 0.3 and 0.2 solar masses, but theoretical models show no such effect. It is difficult to isolate the source of this disagreement: the observational mass-radius relationship relies upon transformations that may not be sufficiently accurate, while the theoretical relationship relies upon stellar models that may not be sufficiently complete, particularly in their treatment of the complex physics governing the interior equation-of-state. If the features in the observationally derived mass-radius relationship are real, their existence provides a natural explanation for the well-known gap in the orbital period distribution of cataclysmic variables. This explanation relies only upon the observed mass-radius relationship of low-mass stars, and does not require ad hoc changes in magnetic braking or in the structure of cataclysmic variable secondaries. If correct, it will allow broader application of cataclysmic variable observations to problems of basic stellar physics.Comment: 27 pages, 10 postscript figures, AASTeX (aaspp4), accepted by Ap

    The Transit Light Curve Project. XIII. Sixteen Transits of the Super-Earth GJ 1214b

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    We present optical photometry of 16 transits of the super-Earth GJ 1214b, allowing us to refine the system parameters and search for additional planets via transit timing. Starspot-crossing events are detected in two light curves, and the star is found to be variable by a few percent. Hence, in our analysis, special attention is given to systematic errors that result from star spots. The planet-to-star radius ratio is 0.11610+/-0.00048, subject to a possible upward bias by a few percent due to the unknown spot coverage. Even assuming this bias to be negligible, the mean density of planet can be either 3.03+/-0.50 g cm^{-3} or 1.89+/-0.33 g cm^{-3}, depending on whether the stellar radius is estimated from evolutionary models or from an empirical mass-luminosity relation combined with the light curve parameters. One possible resolution is that the orbit is eccentric (e approximately equal to 0.14), which would favor the higher density, and hence a much thinner atmosphere for the planet. The transit times were found to be periodic within about 15s, ruling out the existence of any other super-Earths with periods within a factor-of-two of the known planet.Comment: Accepted in Ap

    Quantification of Entry Phenotypes of Macrophage-Tropic HIV-1 across a Wide Range of CD4 Densities

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    Defining a macrophage-tropic phenotype for HIV-1 to assess a role in pathogenesis is complicated by the fact that HIV-1 isolates vary continuously in their ability to enter monocyte-derived macrophages (MDMs) in vitro, and MDMs vary in their ability to support HIV-1 entry. To overcome these limitations, we identified consistent differences in entry phenotypes between five paired blood-derived, T cell-tropic HIV-1 env genes, four of which are CCR5-using (R5) and one of which is CXCR4-using (X4), and cerebrospinal fluid (CSF)-derived, R5 macrophage-tropic env genes. We performed entry assays using the CD4- and CCR5-inducible Affinofile cell line, expressing a range of CD4 levels that approximates the range from MDMs to CD4+ T cells. The macrophage-tropic viruses were significantly better at infecting cells expressing low levels of CD4 than the T cell-tropic viruses from the same subjects, with the titration of CD4 providing a distinctive and quantitative phenotype. This difference in CD4 utilization was not due to macrophage-tropic viruses being CD4 independent. Furthermore, macrophage-tropic viruses did not differ from paired T cell-tropic viruses in their ability to use low levels of CCR5 (tpaired = −1.39; P = 0.24) or their use of an alternative conformation of CCR5. We also infected MDMs with a panel of viruses and observed that infectivity of each virus differed across four donors and between three preparations from a single donor. We concluded that the evolutionary transition from replication in T cells to that in macrophages involves a phenotypic transition to acquire the ability to infect cells expressing low levels of CD4 and that this phenotype is more reliably measured in Affinofile cells than in macrophages
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