HLA-Associated viral mutations are common in human immunodeficiency virus type 1 elite controllers

Elite controllers (EC) of human immunodeficiency virus type 1 (HTV-1) maintain viremia below the limit of detection without antiretroviral treatment. Virus-specific cytotoxic CD8+ T lymphocytes are believed to play a crucial role in viral containment, but the degree of immune imprinting and compensatory mutations in EC is unclear. We obtained plasma gag, pol, and nef sequences from HLA-diverse subjects and found that 30 to 40% of the predefined HLA-associated polymorphic sites show evidence of immune selection pressure in EC., compared to approximately 50% of the sites in chronic progressors. These data indicate ongoing viral replication and escape from cytotoxic T lymphocytes are present even in strictly controlled HTV-1 infection

A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells

Viral mutational escape can reduce or abrogate recognition by the T cell receptor (TCR) of virus-specific CD8+ T cells. However, very little is known about the impact of cytotoxic T lymphocyte (CTL) epitope mutations on interactions between peptide–major histocompatibility complex (MHC) class I complexes and MHC class I receptors expressed on other cell types. Here, we analyzed a variant of the immunodominant human leukocyte antigen (HLA)-B2705–restricted HIV-1 Gag KK10 epitope (KRWIILGLNK) with an L to M amino acid substitution at position 6 (L6M), which arises as a CTL escape variant after primary infection but is sufficiently immunogenic to elicit a secondary, de novo HIV-1–specific CD8+ T cell response with an alternative TCR repertoire in chronic infection. In addition to altering recognition by HIV-1–specific CD8+ T cells, the HLA-B2705–KK10 L6M complex also exhibits substantially increased binding to the immunoglobulin-like transcript (ILT) receptor 4, an inhibitory MHC class I–specific receptor expressed on myelomonocytic cells. Binding of the B2705–KK10 L6M complex to ILT4 leads to a tolerogenic phenotype of myelomonocytic cells with lower surface expression of dendritic cell (DC) maturation markers and co-stimulatory molecules. These data suggest a link between CTL-driven mutational escape, altered recognition by innate MHC class I receptors on myelomonocytic cells, and functional impairment of DCs, and thus provide important new insight into biological consequences of viral sequence diversificatio

Characteristic QSO Accretion Disk Temperatures from Spectroscopic Continuum Variability

Using Sloan Digital Sky Survey (SDSS) quasar spectra taken at multiple epochs, we find that the composite flux density differences in the rest frame wavelength range 1300-6000 AA can be fit by a standard thermal accretion disk model where the accretion rate has changed from one epoch to the next (without considering additional continuum emission components). The fit to the composite residual has two free parameters: a normalizing constant and the average characteristic temperature $\bar{T}^*$. In turn the characteristic temperature is dependent on the ratio of the mass accretion rate to the square of the black hole mass. We therefore conclude that most of the UV/optical variability may be due to processes involving the disk, and thus that a significant fraction of the UV/optical spectrum may come directly from the disk.Comment: 31 pages, 8 figure

Multivisceral intestinal transplantation: Surgical pathology

We report the diagnostic surgical pathology of two children who underwent multivisceral abdominal transplantation and survived for 1 month and 6 months. There is little relevant literature, and diagnostic criteria for the various clinical possibilities are not established; this is made more complicated by the simultaneous occurrence of more than one process. We based our interpretations on conventional histology, augmented with immunohistology, including HLA staining that distinguished graft from host cells in situ. In some instances functional analysis of T cells propagated from the same biopsies was available and was used to corroborate morphological interpretations. A wide spectrum of changes was encountered. Graft-versus-host disease, a prime concern before surgery, was not seen. Rejection was severe in 1 patient, not present in the other, and both had evidence of lymphoproliferative disease, which was related to Epstein-Barr virus. Bacterial translocation through the gut wall was also a feature in both children. This paper documents and illustrates the various diagnostic possibilities.. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Orbital and stochastic far-UV variability in the nova-like system V3885 Sgr

Highly time-resolved time-tagged FUSE satellite spectroscopic data are analysed to establish the far-ultraviolet (FUV) absorption line characteristics of the nova-like cataclysmic variable binary, V3885 Sgr. We determine the temporal behaviour of low (Ly_beta, CIII, NIII) and high (SIV, PV, OVI) ion species, and highlight corresponding orbital phase modulated changes in these lines. On average the absorption troughs are blueshifted due to a low velocity disc wind outflow. Very rapid (~ 5 min) fluctuations in the absorption lines are isolated, which are indicative of stochastic density changes. Doppler tomograms of the FUV lines are calculated which provide evidence for structures where a gas stream interacts with the accretion disc. We conclude that the line depth and velocity changes as a function of orbital phase are consistent with an asymmetry that has its origin in a line-emitting, localised disc-stream interaction region.Comment: Accepted for publication in MNRA

Wave Scattering through Classically Chaotic Cavities in the Presence of Absorption: An Information-Theoretic Model

We propose an information-theoretic model for the transport of waves through a chaotic cavity in the presence of absorption. The entropy of the S-matrix statistical distribution is maximized, with the constraint $=\alpha n$: n is the dimensionality of S, and $0\leq \alpha \leq 1, \alpha =0(1)$ meaning complete (no) absorption. For strong absorption our result agrees with a number of analytical calculations already given in the literature. In that limit, the distribution of the individual (angular) transmission and reflection coefficients becomes exponential -Rayleigh statistics- even for n=1. For $n\gg 1$ Rayleigh statistics is attained even with no absorption; here we extend the study to $\alpha <1$. The model is compared with random-matrix-theory numerical simulations: it describes the problem very well for strong absorption, but fails for moderate and weak absorptions. Thus, in the latter regime, some important physical constraint is missing in the construction of the model.Comment: 4 pages, latex, 3 ps figure

A commentary on key methodological developments related to nutritional life cycle assessment (nLCA) generated throughout a 6-year strategic scientific programme

Rothamsted Research (RRes) is the world's oldest agricultural research centre, notable for the development of the first synthetic fertilizer (superphosphate) and long-term farming experiments (LTEs) spanning over 170 years. In 2015, RRes recruited several life cycle assessment (LCA) experts and began adopting the method to utilize high resolution agronomical data covering livestock (primarily ruminants), grassland/forage productivity and quality, and arable systems established on its North Wyke Farm Platform (NWFP) and the LTEs. The NWFP is a UK ‘National Bioscience Research Infrastructure’ (NBRI) developed for informing and testing systems science utilising high-resolution data to determine whether it is possible to produce nutritious food sustainably. Thanks largely to the multidisciplinary knowledge at RRes, and its collaborators, its LCA Team has been at the forefront of methodological advances during a 6-year Institute Strategic Programme (ISP) ‘Soil-to-Nutrition’ (S2N). While S2N investigated the co-benefits and trade-offs of new mechanistic understanding of efficient nutrient use across scales from pot to landscape, this commentary specifically synthesizes progress in incorporating human nutrition in the context of environmental footprinting, known as ‘nutritional LCA’ (nLCA). We conclude our commentary with a brief discussion on future pathways of exploration and methodological developments covering various activities along entire agri-food supply-chains

Measurement of Superluminal optical tunneling times in double-barrier photonic bandgaps

Tunneling of optical pulses at 1.5 micron wavelength through double-barrier periodic fiber Bragg gratings is experimentally investigated. Tunneling time measurements as a function of barrier distance show that, far from the resonances of the structure, the transit time is paradoxically short, implying Superluminal propagation, and almost independent of the distance between the barriers. These results are in agreement with theoretical predictions based on phase time analysis and also provide an experimental evidence, in the optical context, of the analogous phenomenon expected in Quantum Mechanics for non-resonant superluminal tunneling of particles across two successive potential barriers. [Attention is called, in particular, to our last Figure]. PACS nos.: 42.50.Wm, 03.65.Xp, 42.70.Qs, 03.50.De, 03.65.-w, 73.40.GkComment: LaTeX file (8 pages), plus 5 figure

Excited-State Effective Masses in Lattice QCD

We apply black-box methods, i.e. where the performance of the method does not depend upon initial guesses, to extract excited-state energies from Euclidean-time hadron correlation functions. In particular, we extend the widely used effective-mass method to incorporate multiple correlation functions and produce effective mass estimates for multiple excited states. In general, these excited-state effective masses will be determined by finding the roots of some polynomial. We demonstrate the method using sample lattice data to determine excited-state energies of the nucleon and compare the results to other energy-level finding techniques.Comment: 18 pages, 6 figure