3,669 research outputs found
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 ( 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 x 20) 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 and
its spectral resolving power is and in the
( m) and ( 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
Lassa Virus Treatment Options
Lassa fever causes an approximate 5000 to 10,000 deaths annually in West Africa and cases have been imported into Europe and the Americas, challenging public health. Although Lassa virus was first described over 5 decades ago in 1969, no treatments or vaccines have been approved to treat or prevent infection. In this review, we discuss current therapeutics in the development pipeline for the treatment of Lassa fever, focusing on those that have been evaluated in humans or animal models. Several treatments, including the antiviral favipiravir and a human monoclonal antibody cocktail, have shown efficacy in preclinical rodent and non-human primate animal models and have potential for use in clinical settings. Movement of the promising preclinical treatment options for Lassa fever into clinical trials is critical to continue addressing this neglected tropical disease.</jats:p
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
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