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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.
Human factors in space station architecture 1: Space station program implications for human factors research
The space station program is based on a set of premises on mission requirements and the operational capabilities of the space shuttle. These premises will influence the human behavioral factors and conditions on board the space station. These include: launch in the STS Orbiter payload bay, orbital characteristics, power supply, microgravity environment, autonomy from the ground, crew make-up and organization, distributed command control, safety, and logistics resupply. The most immediate design impacts of these premises will be upon the architectural organization and internal environment of the space station.
Factors influencing the ultrasonic stress wave factor evaluation of composite material structures
To demonstrate that the finite-element model can be used to investigate some of the factors influencing the ultrasonic stress wave evaluation of materials, a hypothetical case was studied in which classical vibration theory was used. Vibration analysis and experiments for the undamaged case were conducted on an isotropic aluminum plate and a unidirectional graphite-epoxy plate, using a point source to excite the plates. The finite-element solution correlated within eight percent with the exact method. The frequencies predicted by the finite-element model were observed in the experiments in both plates, although in the composite plate, additional frequencies were observed which could not be accounted for. Damaged isotropic plates were also considered. The effects of increasing damage severity with constant damage area, and increasing damage area with constant severity on the resonant frequencies were analyzed.
Crew Factors in Flight Operations: A Survey of Fatigue Factors in Corporate/Executive A Viation Operations - 8
Corporate flight crews face unique challenges including unscheduled flights, quickly changing schedules, extended duty days, long waits, time zone changes, and peripheral tasks. Most corporate operations are regulated by Part 91 FARs which set no flight or duty time limits. The objective of this study was to identify operationally significant factors that may influence fatigue, alertness, and performance in corporate operations. In collaboration with the National Business Aircraft Association and the Flight Safety Foundation, NASA developed and distributed a retrospective survey comprising 107 questions addressing demographics, home sleep habits, flight experience, duty schedules, fatigue during operations, and work environment. Corporate crewmembers returned 1,488 surveys. Respondents averaged 45.2 years of age, had 14.9 years of corporate flying experience, and 9,750 total flight hours. The majority (89%) rated themselves as 'good' or 'very good' sleepers at home. Most (82%) indicated they are subject to call for duty and described an average duty day of 9.9 h. About two-thirds reported having a daily duty time limit and over half (57%) reported a daily flight time limit. Nearly three-quarters (71%) acknowledged having 'nodded off' during a flight. Only 21% reported that their flight departments offer training on fatigue issues. Almost three-quarters (74%) described fatigue as a 'moderate' or 'serious' concern, and a majority (61%) characterized it as a common occurrence. Most (85%) identified fatigue as a 'moderate' or 'serious' safety issue.
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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Project Factors: Developing a Digital Classification System for Project 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.
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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Structural basis of elongation factor 2 switching
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