4,311 research outputs found

    Evolution of interface binding strengths in simplified model of protein quaternary structure.

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    The self-assembly of proteins into protein quaternary structures is of fundamental importance to many biological processes, and protein misassembly is responsible for a wide range of proteopathic diseases. In recent years, abstract lattice models of protein self-assembly have been used to simulate the evolution and assembly of protein quaternary structure, and to provide a tractable way to study the genotype-phenotype map of such systems. Here we generalize these models by representing the interfaces as mutable binary strings. This simple change enables us to model the evolution of interface strengths, interface symmetry, and deterministic assembly pathways. Using the generalized model we are able to reproduce two important results established for real protein complexes: The first is that protein assembly pathways are under evolutionary selection to minimize misassembly. The second is that the assembly pathway of a complex mirrors its evolutionary history, and that both can be derived from the relative strengths of interfaces. These results demonstrate that the generalized lattice model offers a powerful new idealized framework to facilitate the study of protein self-assembly processes and their evolution

    Characteristics of surface-water flows in the ridge and slough landscape of Everglades National Park: implications for particulate transport

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    Over the last one hundred years, compartmentalization and water management activities have reduced water flow to the ridge and slough landscape of the Everglades. As a result, the once corrugated landscape has become topographically and vegetationally uniform. The focus of this study was to quantify variation in surface flow in the ridge and slough landscape and to relate flow conditions to particulate transport and deposition. Over the 2002–2003 and 2003–2004 wet seasons, surface velocities and particulate accumulation were measured in upper Shark River Slough in Everglades National Park. Landscape characteristics such as elevation, plant density and biomass also were examined to determine their impact on flow characteristics and material transport. The results of this study demonstrate that the release of water during the wet season not only increases water levels, but also increased flow speeds and particulate transport and availability. Further, flow speeds were positively and significantly correlated with water level thereby enhancing particulate transport in sloughs relative to ridges especially during peak flow periods. Our results also indicate that the distribution of biomass in the water column, including floating plants and periphyton, affects velocity magnitude and shape of vertical profiles, especially in the sloughs where Utricularia spp. and periphyton mats are more abundant. Plot clearing experiments suggest that the presence of surface periphyton and Utricularia exert greater control over flow characteristics than the identity (i.e., sawgrass or spike rush) or density of emergent macrophytes, two parameters frequently incorporated into models describing flow through vegetated canopies. Based on these results, we suggest that future modeling efforts must take the presence of floating biomass, such as Utricularia, and presence of periphyton into consideration when describing particulate transport

    Energy Spectrum Evolution of a Diffuse Field in Elastic Body Caused by Weak Nonlinearity

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    We study the evolution of diffuse elastodynamic spectral energy density under the influence of weak nonlinearity. It is shown that the rate of change of this quantity is given by a convolution of the linear energy at two frequencies. Quantitative estimates are given for sample aluminum and fused silica blocks of experimental interest.Comment: 9 pages, 3 figures; revised for better presentatio

    Biocompatibility and biofilm inhibition of N,N-hexyl,methyl-polyethylenimine bonded to Boston Keratoprosthesis materials

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    The biocompatibility and antibacterial properties of N,N-hexyl,methyl-polyethylenimine (HMPEI) covalently attached to the Boston Keratoprosthesis (B-KPro) materials was evaluated. By means of confocal and electron microscopies, we observed that HMPEI-derivatized materials exert an inhibitory effect on biofilm formation by Staphylococcus aureus clinical isolates, as compared to the parent poly(methyl methacrylate) (PMMA) and titanium. There was no additional corneal epithelial cell cytotoxicity of HMPEI-coated PMMA compared to that of control PMMA in tissue cultures in vitro. Likewise, no toxicity or adverse reactivity was detected with HMPEI-derivatized PMMA or titanium compared to those of the control materials after intrastromal or anterior chamber implantation in rabbits in vivo.Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (Contract DAAD-19-D-0002

    Development of a screening tool to identify female survivors of gender-based violence in a humanitarian setting:qualitative evidence from research among refugees in Ethiopia.

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    PMC3695841BACKGROUND: High levels of gender-based violence (GBV) persist among conflict-affected populations and within humanitarian settings and are paralleled by under-reporting and low service utilization. Novel and evidence-based approaches are necessary to change the current state of GBV amongst these populations. We present the findings of qualitative research, which were used to inform the development of a screening tool as one potential strategy to identify and respond to GBV for females in humanitarian settings. METHODS: Qualitative research methods were conducted from January-February 2011 to explore the range of experiences of GBV and barriers to reporting GBV among female refugees. Individual interview participants (n=37) included female refugees (≥15 years), who were survivors of GBV, living in urban or one of three camps settings in Ethiopia, and originating from six conflict countries. Focus group discussion participants (11 groups; 77 participants) included health, protection and community service staff working in the urban or camp settings. Interviews and discussions were conducted in the language of preference, with assistance by interpreters when needed, and transcribed for analysis by grounded-theory technique. RESULTS: Single and multiple counts of GBV were reported and ranged from psychological and social violence; rape, gang rape, sexual coercion, and other sexual violence; abduction; and physical violence. Domestic violence was predominantly reported to occur when participants were living in the host country. Opportunistic violence, often manifested by rape, occurred during transit when women depended on others to reach their destination. Abduction within the host country, and often across borders, highlighted the constant state of vulnerability of refugees. Barriers to reporting included perceived and experienced stigma in health settings and in the wider community, lack of awareness of services, and inability to protect children while mothers sought services. CONCLUSIONS: Findings demonstrate that GBV persists across the span of the refugee experience, though there is a transition in the range of perpetrators and types of GBV that are experienced. Further, survivors experience significant individual and system barriers to disclosure and service utilization. The findings suggest that routine GBV screening by skilled service providers offers a strategy to confidentially identify and refer survivors to needed services within refugee settings, potentially enabling survivors to overcome existing barriers.JH Libraries Open Access Fun

    Structural variant-based pangenome construction has low sensitivity to variability of haplotype-resolved bovine assemblies

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    Advantages of pangenomes over linear reference assemblies for genome research have recently been established. However, potential effects of sequence platform and assembly approach, or of combining assemblies created by different approaches, on pangenome construction have not been investigated. Here we generate haplotype-resolved assemblies from the offspring of three bovine trios representing increasing levels of heterozygosity that each demonstrate a substantial improvement in contiguity, completeness, and accuracy over the current Bos taurus reference genome. Diploid coverage as low as 20x for HiFi or 60x for ONT is sufficient to produce two haplotype-resolved assemblies meeting standards set by the Vertebrate Genomes Project. Structural variant-based pangenomes created from the haplotype-resolved assemblies demonstrate significant consensus regardless of sequence platform, assembler algorithm, or coverage. Inspecting pangenome topologies identifies 90 thousand structural variants including 931 overlapping with coding sequences; this approach reveals variants affecting QRICH2, PRDM9, HSPA1A, TAS2R46, and GC that have potential to affect phenotype

    Structural variant-based pangenome construction has low sensitivity to variability of haplotype-resolved bovine assemblies

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    Advantages of pangenomes over linear reference assemblies for genome research have recently been established. However, potential effects of sequence platform and assembly approach, or of combining assemblies created by different approaches, on pangenome construction have not been investigated. Here we generate haplotype-resolved assemblies from the offspring of three bovine trios representing increasing levels of heterozygosity that each demonstrate a substantial improvement in contiguity, completeness, and accuracy over the current Bos taurus reference genome. Diploid coverage as low as 20x for HiFi or 60x for ONT is sufficient to produce two haplotype-resolved assemblies meeting standards set by the Vertebrate Genomes Project. Structural variant-based pangenomes created from the haplotype-resolved assemblies demonstrate significant consensus regardless of sequence platform, assembler algorithm, or coverage. Inspecting pangenome topologies identifies 90 thousand structural variants including 931 overlapping with coding sequences; this approach reveals variants affecting QRICH2, PRDM9, HSPA1A, TAS2R46, and GC that have potential to affect phenotype

    Pair Instability Supernovae: Light Curves, Spectra, and Shock Breakout

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    For the initial mass range (140 < M < 260 Msun) stars die in a thermonuclear runaway triggered by the pair-production instability. The supernovae they make can be remarkably energetic (up to ~10^53 ergs) and synthesize considerable amounts of radioactive isotopes. Here we model the evolution, explosion, and observational signatures of representative pair-instability supernovae (PI SNe) spanning a range of initial masses and envelope structures. The predicted light curves last for hundreds of days and range in luminosity, from very dim to extremely bright, L ~ 10^44 ergs/s. The most massive events are bright enough to be seen at high redshift, but the extended light curve duration (~1 year) -- prolonged by cosmological time-dilation -- may make it difficult to detect them as transients. An alternative approach may be to search for the brief and luminous outbreak occurring when the explosion shock wave reaches the stellar surface. Using a multi-wavelength radiation-hydrodynamics code we calculate that, in the rest-frame, the shock breakout transients of PI SNe reach luminosities of 10^45-10^46 ergs/s, peak at wavelengths ~30-170 Angstroms, and last for several hours. We explore the detectability of PI SNe emission at high redshift, and discuss how observations of the light curves, spectra, and breakout emission can be used to constrain the mass, radius, and metallicity of the progenitor.Comment: submitted to Ap
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