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Two human antibodies to a meningococcal serogroup B vaccine antigen enhance binding of complement Factor H by stabilizing the Factor H binding site
Microbial pathogens bind host complement regulatory proteins to evade the immune system. The bacterial pathogen Neisseria meningitidis, or meningococcus, binds several complement regulators, including human Factor H (FH). FH binding protein (FHbp) is a component of two licensed meningococcal vaccines and in mice FHbp elicits antibodies that inhibit binding of FH to FHbp, which defeat the bacterial evasion mechanism. However, humans vaccinated with FHbp develop antibodies that enhance binding of FH to the bacteria, which could limit the effectiveness of the vaccines. In the present study, we show that two vaccine-elicited antibody fragments (Fabs) isolated from different human subjects increase binding of complement FH to meningococcal FHbp by ELISA. The two Fabs have different effects on the kinetics of FH binding to immobilized FHbp as measured by surface plasmon resonance. The 1.7- and 2.0-Å resolution X-ray crystal structures of the Fabs in complexes with FHbp illustrate that the two Fabs bind to similar epitopes on the amino-terminal domain of FHbp, adjacent to the FH binding site. Superposition models of ternary complexes of each Fab with FHbp and FH show that there is likely minimal contact between the Fabs and FH. Collectively, the structures reveal that the Fabs enhance binding of FH to FHbp by altering the conformations and mobilities of two loops adjacent to the FH binding site of FHbp. In addition, the 1.5 Å-resolution structure of one of the isolated Fabs defines the structural rearrangements associated with binding to FHbp. The FH-enhancing human Fabs, which are mirrored in the human polyclonal antibody responses, have important implications for tuning the effectiveness of FHbp-based vaccines.
Form factors for dark matter capture by the Sun in effective theories
In the effective theory of isoscalar and isovector dark matter-nucleon interactions mediated by a heavy spin-1 or spin-0 particle, 8 isotope-dependent nuclear response functions can be generated in the dark matter scattering by nuclei. We compute the 8 nuclear response functions for the 16 most abundant elements in the Sun, i.e. H, {sup 3}He, {sup 4}He, {sup 12}C, {sup 14}N, {sup 16}O, {sup 20}Ne, {sup 23}Na, {sup 24}Mg, {sup 27}Al, {sup 28}Si, {sup 32}S, {sup 40}Ar, {sup 40}Ca, {sup 56}Fe, and {sup 59}Ni, through numerical shell model calculations. We use our response functions to compute the rate of dark matter capture by the Sun for all isoscalar and isovector dark matter-nucleon effective interactions, including several operators previously considered for dark matter direct detection only. We study in detail the dependence of the capture rate on specific dark matter-nucleon interaction operators, and on the different elements in the Sun. We find that a so far neglected momentum dependent dark matter coupling to the nuclear vector charge gives a larger contribution to the capture rate than the constant spin-dependent interaction commonly included in dark matter searches at neutrino telescopes. Our investigation lays the foundations for model independent analyses of dark matter induced neutrino signals from the Sun. The nuclear response functions obtained in this study are listed in analytic form in an appendix, ready to be used in other projects.
Generalised form factor dark matter in the Sun
We study the effects of energy transport in the Sun by asymmetric dark matter with momentum and velocity-dependent interactions, with an eye to solving the decade-old Solar Abundance Problem. We study effective theories where the dark matter-nucleon scattering cross-section goes as v{sub rel}{sup 2n} and q{sup 2n} with n=−1,0,1 or 2, where v{sub rel} is the dark matter-nucleon relative velocity and q is the momentum exchanged in the collision. Such cross-sections can arise generically as leading terms from the most basic nonstandard DM-quark operators. We employ a high-precision solar simulation code to study the impact on solar neutrino rates, the sound speed profile, convective zone depth, surface helium abundance and small frequency separations. We find that the majority of models that improve agreement with the observed sound speed profile and depth of the convection zone also reduce neutrino fluxes beyond the level that can be reasonably accommodated by measurement and theory errors. However, a few specific points in parameter space yield a significant overall improvement. A 3–5 GeV DM particle with σ{sub SI}∝q{sup 2} is particularly appealing, yielding more than a 6σ improvement with respect to standard solar models, while being allowed by direct detection and collider limits. We provide full analytical capture expressions for q- and v{sub rel}-dependent scattering, as well as complete likelihood tables for all models.
Nitrogen-to-protein conversion factors revisited for applications of microalgal biomass conversion to food, feed and fuel
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Λ c → Λ * ( 1520 ) form factors from lattice QCD and improved analysis of the Λ b → Λ * ( 1520 ) and Λ b → Λ c * ( 2595 , 2625 ) form factors
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Seven years of aerosol scattering hygroscopic growth measurements from SGP: Factors influencing water uptake: Aerosol Scattering Hygroscopic Growth
Long-term measurements of changes in the aerosol scattering coefficient hygroscopic growth at the U.S. Department of Energy Southern Great Plains site provide information on the seasonal as well as size and chemical dependence of aerosol hygroscopic growth. Annual average sub 10 um fRH values (the ratio of aerosol scattering at 85%/40% RH) were 1.75 and 1.87 for the gamma and kappa fit algorithms, respectively. The study found higher growth rates in the winter and spring seasons that correlated with high aerosol nitrate mass fraction. FRH, exhibited strong, but differing correlations with the scattering Ångström exponent and backscatter fraction, two optical size-dependent parameters. The aerosol organic fraction had a strong influence, with fRH decreasing with increases in the organic mass fraction and absorption Ångström exponent and increasing with the aerosol single scatter albedo. Uncertainty analysis if the fit algorithms revealed high uncertainty at low scattering coefficients and slight increases in uncertainty at high RH and fit parameters values.
The role of environmental driving factors in historical and projected carbon dynamics of wetland ecosystems in Alaska
Abstract Wetlands are critical terrestrial ecosystems in Alaska, covering ~177,000 km 2 , an area greater than all the wetlands in the remainder of the United States. To assess the relative influence of changing climate, atmospheric carbon dioxide (CO 2 ) concentration, and fire regime on carbon balance in wetland ecosystems of Alaska, a modeling framework that incorporates a fire disturbance model and two biogeochemical models was used. Spatially explicit simulations were conducted at 1‐km resolution for the historical period (1950–2009) and future projection period (2010–2099). Simulations estimated that wetland ecosystems of Alaska lost 175 Tg carbon (C) in the historical period. Ecosystem C storage in 2009 was 5,556 Tg, with 89% of the C stored in soils. The estimated loss of C as CO 2 and biogenic methane (CH 4 ) emissions resulted in wetlands of Alaska increasing the greenhouse gas forcing of climate warming. Simulations for the projection period were conducted for six climate change scenarios constructed from two climate models forced under three CO 2 emission scenarios. Ecosystem C storage averaged among climate scenarios increased 3.94 Tg C/yr by 2099, with variability among the simulations ranging from 2.02 to 4.42 Tg C/yr. These increases were driven primarily by increases in net primary production (NPP) that were greater than losses from increased decomposition and fire. The NPP increase was driven by CO 2 fertilization (~5% per 100 parts per million by volume increase) and by increases in air temperature (~1% per °C increase). Increases in air temperature were estimated to be the primary cause for a projected 47.7% mean increase in biogenic CH 4 emissions among the simulations (~15% per °C increase). Ecosystem CO 2 sequestration offset the increase in CH 4 emissions during the 21st century to decrease the greenhouse gas forcing of climate warming. However, beyond 2100, we expect that this forcing will ultimately increase as wetland ecosystems transition from being a sink to a source of atmospheric CO 2 because of (1) decreasing sensitivity of NPP to increasing atmospheric CO 2 , (2) increasing availability of soil C for decomposition as permafrost thaws, and (3) continued positive sensitivity of biogenic CH 4 emissions to increases in soil temperature.
Computational Evaluation of Factors Governing Catalytic 2-Keto Acid Decarboxylation
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Role of the X and n factors in ion-irradiation induced phase transformations of Mn+1AXn phases
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Review of polymers for heat exchanger applications: Factors concerning thermal conductivity
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