Endogenous human cytomegalovirus gB is efficiently presented by MHC class II molecules to CD4+ CTL

Human cytomegalovirus (HCMV) infects endothelial, epithelial, and glial cells in vivo. These cells can express MHC class II proteins, but are unlikely to play important roles in priming host immunity. Instead, it seems that class II presentation of endogenous HCMV antigens in these cells allows recognition of virus infection. We characterized class II presentation of HCMV glycoprotein B (gB), a membrane protein that accumulates extensively in endosomes during virus assembly. Human CD4+ T cells specific for gB were both highly abundant in blood and cytolytic in vivo. gB-specific CD4+ T cell clones recognized gB that was expressed in glial, endothelial, and epithelial cells, but not exogenous gB that was fed to these cells. Glial cells efficiently presented extremely low levels of endogenous gB--expressed by adenovirus vectors or after HCMV infection--and stimulated CD4+ T cells better than DCs that were incubated with exogenous gB. Presentation of endogenous gB required sorting of gB to endosomal compartments and processing by acidic proteases. Although presentation of cellular proteins that traffic into endosomes is well known, our observations demonstrate for the first time that a viral protein sorted to endosomes is presented exceptionally well, and can promote CD4+ T cell recognition and killing of biologically important host cells

Self-disseminating vaccines for emerging infectious diseases.

Modern human activity fueled by economic development is profoundly altering our relationship with microorganisms. This altered interaction with microbes is believed to be the major driving force behind the increased rate of emerging infectious diseases from animals. The spate of recent infectious disease outbreaks, including Ebola virus disease and Middle East respiratory syndrome, emphasize the need for development of new innovative tools to manage these emerging diseases. Disseminating vaccines are one such novel approach to potentially interrupt animal to human (zoonotic) transmission of these pathogens

Explicit computation of shear three-point correlation functions: the one-halo model case

We present a method for calculating explicit expressions of the shear three-point function for various cosmological models. The method is applied here to the one-halo model in case of power law density profiles for which results are detailed. The three-point functions are found to reproduce to a large extent patterns in the shear correlations obtained in numerical simulations and may serve as a guideline to implement optimized methods for detecting the shear three-point function. In principle, the general method presented here can also be applied for other models of matter correlation.Comment: 8 pages, 6 figures, submitted to A

The Wide Integral Field Infrared Spectrograph: Commissioning Results and On-sky Performance

We have recently commissioned a novel infrared ($0.9-1.7$ $\mu$m) integral field spectrograph (IFS) called the Wide Integral Field Infrared Spectrograph (WIFIS). WIFIS is a unique instrument that offers a very large field-of-view (50$^{\prime\prime}$ x 20$^{\prime\prime}$) on the 2.3-meter Bok telescope at Kitt Peak, USA for seeing-limited observations at moderate spectral resolving power. The measured spatial sampling scale is $\sim1\times1^{\prime\prime}$ and its spectral resolving power is $R\sim2,500$ and $3,000$ in the $zJ$ ($0.9-1.35$ $\mu$m) and $H_{short}$ ($1.5-1.7$ $\mu$m) modes, respectively. WIFIS's corresponding etendue is larger than existing near-infrared (NIR) IFSes, which are mostly designed to work with adaptive optics systems and therefore have very narrow fields. For this reason, this instrument is specifically suited for studying very extended objects in the near-infrared such as supernovae remnants, galactic star forming regions, and nearby galaxies, which are not easily accessible by other NIR IFSes. This enables scientific programs that were not originally possible, such as detailed surveys of a large number of nearby galaxies or a full accounting of nucleosynthetic yields of Milky Way supernova remnants. WIFIS is also designed to be easily adaptable to be used with larger telescopes. In this paper, we report on the overall performance characteristics of the instrument, which were measured during our commissioning runs in the second half of 2017. We present measurements of spectral resolving power, image quality, instrumental background, and overall efficiency and sensitivity of WIFIS and compare them with our design expectations. Finally, we present a few example observations that demonstrate WIFIS's full capability to carry out infrared imaging spectroscopy of extended objects, which is enabled by our custom data reduction pipeline.Comment: Published in the Proceedings of SPIE Astronomical Telescopes and Instrumentation 2018. 17 pages, 13 figure

Human cytomegalovirus-encoded pUL7 is a novel CEACAM1-like molecule responsible for promotion of angiogenesis.

UNLABELLED: Persistent human cytomegalovirus (HCMV) infection has been linked to several diseases, including atherosclerosis, transplant vascular sclerosis (TVS), restenosis, and glioblastoma. We have previously shown that factors secreted from HCMV-infected cells induce angiogenesis and that this process is due, at least in part, to increased secretion of interleukin-6 (IL-6). In order to identify the HCMV gene(s) responsible for angiogenesis promotion, we constructed a large panel of replication-competent HCMV recombinants. One HCMV recombinant deleted for UL1 to UL10 was unable to induce secretion of factors necessary for angiogenesis. Fine mapping using additional HCMV recombinants identified UL7 as a viral gene required for production of angiogenic factors from HCMV-infected cells. Transient expression of pUL7 induced phosphorylation of STAT3 and ERK1/2 MAP kinases and production of proangiogenic factors, including IL-6. Addition of recombinant pUL7 to cells was sufficient for angiogenesis and was again associated with increased IL-6 expression. Analysis of the UL7 structure revealed a conserved domain similar to the immunoglobulin superfamily domain and related to the N-terminal V-like domain of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Our report therefore identifies UL7 as a novel HCMV-encoded molecule that is both structurally and functionally related to cellular CEACAM1, a proangiogenic factor highly expressed during vasculogenesis. IMPORTANCE: A hallmark of cytomegalovirus (CMV) infection is its ability to modulate the host cellular machinery, resulting in the secretion of factors associated with long-term diseases such as vascular disorders and cancer. We previously demonstrated that HCMV infection alters the types and quantities of bioactive proteins released from cells (designated the HCMV secretome) that are involved in the promotion of angiogenesis and wound healing. A key proangiogenic and antiapoptotic factor identified from a proteomic-based approach was IL-6. In the present report, we show for the first time that HCMV UL7 encodes a soluble molecule that is a structural and functional homologue of the CEACAM1 proangiogenic cellular factor. This report thereby identifies a critical component of the HCMV secretome that may be responsible, at least in part, for the vascular dysregulation associated with persistent HCMV infection

The Coyote Universe I: Precision Determination of the Nonlinear Matter Power Spectrum

Near-future cosmological observations targeted at investigations of dark energy pose stringent requirements on the accuracy of theoretical predictions for the clustering of matter. Currently, N-body simulations comprise the only viable approach to this problem. In this paper we demonstrate that N-body simulations can indeed be sufficiently controlled to fulfill these requirements for the needs of ongoing and near-future weak lensing surveys. By performing a large suite of cosmological simulation comparison and convergence tests we show that results for the nonlinear matter power spectrum can be obtained at 1% accuracy out to k~1 h/Mpc. The key components of these high accuracy simulations are: precise initial conditions, very large simulation volumes, sufficient mass resolution, and accurate time stepping. This paper is the first in a series of three, with the final aim to provide a high-accuracy prediction scheme for the nonlinear matter power spectrum.Comment: 18 pages, 22 figures, minor changes to address referee repor

Analysis of Andean blackberry (Rubus glaucus) production models obtained by means of artificial neural networks exploiting information collected by small-scale growers in Colombia and publicly available meteorological data

The Andean blackberry (Rubus glaucus) is an important source of income in hillside regions of Colombia. However, growers have little reliable information on the factors that affect the development and yield of the crop, and therefore there is a dearth of information onhowto effectively manage the crop. Site specific information recorded by small-scale producers of the Andean blackberry on their production systems and soils coupled with publicly available meteorological data was used to develop models of such production systems. Multilayer perceptrons and Self-Organizing Maps were used as computational models in the identification and visualization of the most important variables for modeling the production of Andean blackberry. Artificial neural networks were trained with information from 20 sites in Colombia where the Andean blackberry is cultivated. Multilayer perceptrons predicted with a reasonable degree of accuracy the production response of the crop. The soil depth, the average temperature, external drainage, and the accumulated precipitation of the first month before harvest were critical determinants of productivity. A proxy variable of location was used to describe overall differences in management between farmers groups. The use of this proxy indicated that, even under essentially similar environmental conditions, large differences in production could be assigned to management effects. The information obtained can be used to determine sites that are suitable for Andean blackberry production, and to transfer ofmanagement practices from sites of high productivity to sites with similar environmental conditions which currently have lower levels of productivity

Cosmological constraints from the capture of non-Gaussianity in Weak Lensing data

Weak gravitational lensing has become a common tool to constrain the cosmological model. The majority of the methods to derive constraints on cosmological parameters use second-order statistics of the cosmic shear. Despite their success, second-order statistics are not optimal and degeneracies between some parameters remain. Tighter constraints can be obtained if second-order statistics are combined with a statistic that is efficient to capture non-Gaussianity. In this paper, we search for such a statistical tool and we show that there is additional information to be extracted from statistical analysis of the convergence maps beyond what can be obtained from statistical analysis of the shear field. For this purpose, we have carried out a large number of cosmological simulations along the {\sigma}8-{\Omega}m degeneracy, and we have considered three different statistics commonly used for non-Gaussian features characterization: skewness, kurtosis and peak count. To be able to investigate non-Gaussianity directly in the shear field we have used the aperture mass definition of these three statistics for different scales. Then, the results have been compared with the results obtained with the same statistics estimated in the convergence maps at the same scales. First, we show that shear statistics give similar constraints to those given by convergence statistics, if the same scale is considered. In addition, we find that the peak count statistic is the best to capture non-Gaussianities in the weak lensing field and to break the {\sigma}8-{\Omega}m degeneracy. We show that this statistical analysis should be conducted in the convergence maps: first, because there exist fast algorithms to compute the convergence map for different scales, and secondly because it offers the opportunity to denoise the reconstructed convergence map, which improves non-Gaussian features extraction.Comment: Accepted for publication in MNRAS (11 pages, 5 figures, 9 tables

Simulations of Wide-Field Weak Lensing Surveys I: Basic Statistics and Non-Gaussian Effects

We study the lensing convergence power spectrum and its covariance for a standard LCDM cosmology. We run 400 cosmological N-body simulations and use the outputs to perform a total of 1000 independent ray-tracing simulations. We compare the simulation results with analytic model predictions. The semi-analytic model based on Smith et al.(2003) fitting formula underestimates the convergence power by ~30% at arc-minute angular scales. For the convergence power spectrum covariance, the halo model reproduces the simulation results remarkably well over a wide range of angular scales and source redshifts. The dominant contribution at small angular scales comes from the sample variance due to the number fluctuations of halos in a finite survey volume. The signal-to-noise ratio for the convergence power spectrum is degraded by the non-Gaussian covariances by up to a factor 5 for a weak lensing survey to z_s ~1. The probability distribution of the convergence power spectrum estimators, among the realizations, is well approximated by a chi-square distribution with broadened variance given by the non-Gaussian covariance, but has a larger positive tail. The skewness and kurtosis have non-negligible values especially for a shallow survey. We argue that a prior knowledge on the full distribution may be needed to obtain an unbiased estimate on the ensemble averaged band power at each angular scale from a finite volume survey.Comment: 11 pages, 11 figures. Accepted for publication in the Astrophysical Journal. Corrected typo in the equation of survey window function below Equation (18). The results unchange