Assembly and architecture of the EBV B cell entry triggering complex.

Epstein-Barr Virus (EBV) is an enveloped double-stranded DNA virus of the gammaherpesvirinae sub-family that predominantly infects humans through epithelial cells and B cells. Three EBV glycoproteins, gH, gL and gp42, form a complex that targets EBV infection of B cells. Human leukocyte antigen (HLA) class II molecules expressed on B cells serve as the receptor for gp42, triggering membrane fusion and virus entry. The mechanistic role of gHgL in herpesvirus entry has been largely unresolved, but it is thought to regulate the activation of the virally-encoded gB protein, which acts as the primary fusogen. Here we study the assembly and function of the reconstituted B cell entry complex comprised of gHgL, gp42 and HLA class II. The structure from negative-stain electron microscopy provides a detailed snapshot of an intermediate state in EBV entry and highlights the potential for the triggering complex to bring the two membrane bilayers into proximity. Furthermore, gHgL interacts with a previously identified, functionally important hydrophobic pocket on gp42, defining the overall architecture of the complex and playing a critical role in membrane fusion activation. We propose a macroscopic model of the initiating events in EBV B cell fusion centered on the formation of the triggering complex in the context of both viral and host membranes. This model suggests how the triggering complex may bridge the two membrane bilayers, orienting critical regions of the N- and C- terminal ends of gHgL to promote the activation of gB and efficient membrane fusion

Liquid-Solid Transition of Hard Spheres Under Gravity

We investigate the liquid-solid transition of two dimensional hard spheres in the presence of gravity. We determine the transition temperature and the fraction of particles in the solid regime as a function of temperature via Even-Driven molecular dynamics simulations and compare them with the theoretical predictions. We then examine the configurational statistics of a vibrating bed from the view point of the liquid-solid transition by explicitly determining the transition temperature and the effective temperature, T, of the bed, and present a relation between T and the vibration strength.Comment: 14 total pages, 4 figure

Systems-Based Design of Bi-Ligand Inhibitors of Oxidoreductases: Filling the Chemical Proteomic Toolbox

Genomics-driven growth in the number of enzymes of unknown function has created a need for better strategies to characterize them. Since enzyme inhibitors have traditionally served this purpose, we present here an efficient systems-based inhibitor design strategy, enabled by bioinformatic and NMR structural developments. First, we parse the oxidoreductase gene family into structural subfamilies termed pharmacofamilies, which share pharmacophore features in their cofactor binding sites. Then we identify a ligand for this site and use NMR-based binding site mapping (NMR SOLVE) to determine where to extend a combinatorial library, such that diversity elements are directed into the adjacent substrate site. The cofactor mimic is reused in the library in a manner that parallels the reuse of cofactor domains in the oxidoreductase gene family. A library designed in this manner yielded specific inhibitors for multiple oxidoreductases

Comparison of Direct vs. Indirect Ventilation Rate Determination for Manure Belt Laying Hen Houses

Direct measurement of ventilation rate in livestock housing can be a formidable task due to uncontrollable variations in fan and system performance as caused by factors such as operation static pressure, fan belt condition, and dust accumulation on shutters and blades. Indirect, CO2-balance method offers a potentially viable, more flexible alternative to estimating ventilation rate. The reliability of CO2 balance method depends on the validity of relationship between CO2 production and metabolic rate of the animals and the knowledge of CO2 generation by the housing environment. Metabolic rates of modern laying hens have recently been quantified in intensive large-scale laboratory measurements. However, performance of the indirect method remains to be evaluated under field production conditions. This paper compares ventilation rates of a commercial laying hen house with manure belt (manure removed daily) obtained from direct measurement based on in-situ fan performance and runtime vs. indirect determination based on CO2 balance. The results indicate that indirect determination based on CO2 balance was well in agreement with that of direct measurement. Application of the CO2-balance method to evaluate building ventilation rate can improve the affordability and versatility of poultry emission studies

Comparison of Direct vs. Indirect Ventilation Rate Determinations in Layer Barns using Manure Belts

Direct measurement of building ventilation rate in livestock housing is a formidable task due to uncontrollable variations in fan and system performance that are caused by factors such as building static pressure, fan belt slippage, and dust accumulation on shutters and blades. Estimating building ventilation rate by an indirect method based on a CO2 balance offers a potentially viable alternative to direct measurement. The validity of the CO2 balance method depends on the validity of relationship between CO2 production inside the building and metabolic rate of the animals and the knowledge of CO2 generation by the housing environment. Metabolic rates of modern laying hens have recently been quantified in intensive large-scale laboratory measurements. However, performance of the indirect method remains to be evaluated under field conditions. This article compares building ventilation rates obtained by direct measurement and by a CO2 balance. The test was conducted at a commercial laying hen house that used manure belts with daily manure removal. The results indicate that ventilation rates estimated by the indirect method were not significantly different (P \u3e 0.2) from those as determined by the direct measurement when the averaging or integration time interval was 2 h or longer. Careful application of the indirect method could greatly improve the affordability and versatility of endeavors toward quantifying air emissions from confined animal housing

Pion Form Factors in Holographic QCD

Using a holographic dual model of QCD, we compute the pion electromagnetic form factor F_pi(Q^2) in the spacelike momentum transfer region, as well as pion couplings to vector mesons g_rho^(n) pi pi. Spontaneous and explicit chiral symmetry breaking are intrinsic features of this particular holographic model. We consider variants with both ``hard-wall'' and ``soft-wall'' infrared cutoffs, and find that the F_pi(Q^2) data tend to lie closer to the hard-wall model predictions, although both are too shallow for large Q^2. By allowing the parameters of the soft-wall model (originally fixed by observables such as m_rho) to vary, one finds fits that tend to agree better with F_pi(Q^2). We also compute the pion charge radius for a variety of parameter choices, and use the values of f^(n)_rho, g_{rho^(n) pi pi} and m^(n)_rho to observe the saturation of F_pi(0) by rho poles.Comment: 17 pages, 2 figures, revised fits using consistent normalization of f_pi. References update

An Ellam Scheme for Advection-Diffusion Equations in Two Dimensions

We develop an Eulerian{Lagrangian localized adjoint method (ELLAM) to solve two-dimensional advection-diusion equations with all combinations of inflow and outflow Dirichlet, Neumann, and flux boundary conditions. The ELLAM formalism provides a systematic framework for implementation of general boundary conditions, leading to mass-conservative numerical schemes. The computational advantages of the ELLAM approximation have been demonstrated for a number of one-dimensional transport systems; practical implementations of ELLAM schemes in multiple spatial dimensions that require careful algorithm development are discussed in detail in this paper. Extensive numerical results are presented to compare the ELLAM scheme with many widely used numerical methods and to demonstrate the strength of the ELLAM scheme