1,601 research outputs found
Identifying Varicella-Zoster Virus Latent Genomes in an Alternative Neuronal Latency Model
Varicella zoster virus (VZV) is the etiologic agent of chickenpox (varicella) upon primary infection and shingles (herpes zoster, HZ) upon reactivation from neuronal latency. Shingles is a debilitating disease of the elderly and immune impaired that is frequently complicated. Reactivation of VZV causing HZ is painful and can result in a chronic pain state known as postherpetic neuralgia (PHN) that is difficult to alleviate. HZ has also been linked to encephalitis, meningitis, vasculopathies and increased risk of stroke, all of which emphasize the continued public health demand for better treatments and/or vaccines. VZV latency and reactivation has not been well characterized because it presents monumental difficulties studying it in a laboratory setting. Its human-specific restriction requires human neuronal platforms for modeling neurotropism, latency and reactivation. Importantly, VZV genomes are found not only in neurons of sensory ganglia, but in those of autonomic, enteric and cranial ganglia, and possibly even the CNS. These latent genomes are difficult to characterize and are usually found only by performing end-stage methods of analyses, when tissues/cells need to be fixed or extracted. One aspect of this research was to explore methods that would better enable the identification of VZV genomes in latently infected cells and whether they could be applied in a live-cell in vitro setting. We have previously established that sensory-like neurons derived from human embryonic stem cells (hESC) can host both a productive VZV infection and a model state of VZV latency that can be experimentally reactivated. However, the maintenance of hESCs and their differentiation into sensory neurons for larger scale applications is exceedingly demanding. The second goal of this research was to evaluate an alternative neuron-like system that is more easily expandable for large-scale applications. We evaluated the proliferative human neuronal precursor cell line Lund human mesencephalic (LUHMES) cells. Differentiated LUHMES can easily be scaled to large numbers and show biochemical, morphological, and functional features of mature neurons. While both undifferentiated and differentiated LUHMES cells are fully permissive to VZV infection, current studies are addressing the potential of this system to host a VZV latent state, and whether this is experimentally reactivatable
RCS043938-2904.9: A New Rich Cluster of Galaxies at z=0.951
We present deep I, J_s, K_s imaging and optical spectroscopy of the newly
discovered Red-Sequence Cluster Survey cluster RCS043938-2904.9. This cluster,
drawn from an extensive preliminary list, was selected for detailed study on
the basis of its apparent optical richness. Spectroscopy of 11 members places
the cluster at z=0.951 +- 0.006, and confirms the photometric redshift estimate
from the (R-z) color-magnitude diagram. Analysis of the infrared imaging data
demonstrates that the cluster is extremely rich, with excess counts in the
Ks-band exceeding the expected background counts by 9 sigma. The properties of
the galaxies in RCS043938-2904.9 are consistent with those seen in other
clusters at similar redshifts. Specifically, the red-sequence color, slope and
scatter, and the size-magnitude relation of these galaxies are all consistent
with that seen in the few other high redshift clusters known, and indeed are
consistent with appropriately evolved properties of local cluster galaxies. The
apparent consistency of these systems implies that the rich, high-redshift RCS
clusters are directly comparable to the few other systems known at z ~ 1, most
of which have been selected on the basis of X-ray emission.Comment: 12 pages, 1 color figure. Accepted for publication on The ApJ Letter
Structure-based stabilization of insulin as a therapeutic protein assembly via enhanced aromatic-aromatic interactions
Key contributions to protein structure and stability are provided by weakly polar interactions, which arise from asymmetric electronic distributions within amino acids and peptide bonds. Of particular interest are aromatic side chains whose directional π-systems commonly stabilize protein interiors and interfaces. Here, we consider aromatic-aromatic interactions within a model protein assembly: the dimer interface of insulin. Semi-classical simulations of aromatic-aromatic interactions at this interface suggested that substitution of residue TyrB26 by Trp would preserve native structure while enhancing dimerization (and hence hexamer stability). The crystal structure of a [TrpB26]insulin analog (determined as a T3Rf3 zinc hexamer at a resolution of 2.25 Å) was observed to be essentially identical to that of WT insulin. Remarkably and yet in general accordance with theoretical expectations, spectroscopic studies demonstrated a 150-fold increase in the in vitro lifetime of the variant hexamer, a critical pharmacokinetic parameter influencing design of long-acting formulations. Functional studies in diabetic rats indeed revealed prolonged action following subcutaneous injection. The potency of the TrpB26-modified analog was equal to or greater than an unmodified control. Thus, exploiting a general quantum-chemical feature of protein structure and stability, our results exemplify a mechanism-based approach to the optimization of a therapeutic protein assembly
Theory of Abelian Projection
Analytic methods for Abelian projection are developed. A number of results
are obtained related to string tension measurements. It is proven that even
without gauge fixing, abelian projection yields string tensions of the
underlying non-Abelian theory. Strong arguments are given for similar results
in the case where gauge fixing is employed. The methods used emphasize that the
projected theory is derived from the underlying non-Abelian theory rather than
vice versa. In general, the choice of subgroup used for projection is not very
important, and need not be Abelian. While gauge fixing is shown to be in
principle unnecessary for the success of Abelian projection, it is
computationally advantageous for the same reasons that improved operators,
e.g., the use of fat links, are advantageous in Wilson loop measurements. Two
other issues, Casimir scaling and the conflict between projection and critical
universality, are also discussed.Comment: Minor corrections, new section added, 14 pages, 3 figures, RevTe
NASA ExoPAG Study Analysis Group 11: Preparing for the WFIRST Microlensing Survey
NASA's proposed WFIRST-AFTA mission will discover thousands of exoplanets
with separations from the habitable zone out to unbound planets, using the
technique of gravitational microlensing. The Study Analysis Group 11 of the
NASA Exoplanet Program Analysis Group was convened to explore scientific
programs that can be undertaken now, and in the years leading up to WFIRST's
launch, in order to maximize the mission's scientific return and to reduce
technical and scientific risk. This report presents those findings, which
include suggested precursor Hubble Space Telescope observations, a
ground-based, NIR microlensing survey, and other programs to develop and deepen
community scientific expertise prior to the mission.Comment: 35 pages, 5 Figures. A brief overview of the findings is presented in
the Executive Summary (2 pages
NICMOS and VLA Observations of the Gravitatonally Lensed Ultraluminous BAL Quasar APM~08279+5255: Detection of a Third Image
We present a suite of observations of the recently identified ultraluminous
BAL quasar APM 08279+5255, taken both in the infra-red with the NICMOS high
resolution camera on board the Hubble Space Telescope, and at 3.5cm with the
Very Large Array. With an inferred luminosity of ~5x10^15 Solar luminosities,
APM 08279+5255 is apparently the most luminous system known. Extant
ground-based images show that APM 08279+5255 is not point-like, but is instead
separated into two components, indicative of gravitational lensing. The much
higher resolution images presented here also reveal two point sources, A and B,
of almost equal brightness (f_B/f_A=0.782 +/- 0.010), separated by 0."378 +/-
0."001, as well as a third, previously unknown, fainter image, C, seen between
the brighter images. While the nature of C is not fully determined, several
lines of evidence point to it being a third gravitationally lensed image of the
quasar, rather than being the lensing galaxy. Simple models which recover the
relative image configuration and brightnesses are presented. While proving to
be substantially amplified, APM 08279+5255 possesses an intrinsic bolometric
luminosity of ~10^14 to 10^15 Solar luminosities and remains amongst the most
luminous objects known.Comment: 21 pages, 5 figures (2 as GIF files); accepted for publication in the
Astronomical Journa
The Multiplicity of M-Dwarfs in Young Moving Groups
We image 104 newly identified low-mass (mostly M-dwarf) pre-main sequence
members of nearby young moving groups with Magellan Adaptive Optics (MagAO) and
identify 27 binaries with instantaneous projected separation as small as 40
mas. 15 were previously unknown. The total number of multiple systems in this
sample including spectroscopic and visual binaries from the literature is 36,
giving a raw multiplicity rate of at least for this
population. In the separation range of roughly 1 - 300 AU in which infrared AO
imaging is most sensitive, the raw multiplicity rate is at least
for binaries resolved by the MagAO infrared camera (Clio). The
M-star sub-sample of 87 stars yields a raw multiplicity of at least
over all separations, for secondary
companions resolved by Clio from 1 to 300 AU ( for all known
binaries in this separation range). A combined analysis with binaries
discovered by the Search for Associations Containing Young stars shows that
multiplicity fraction as a function of mass and age over the range of 0.2 to
1.2 and 10 - 200 Myr appears to be linearly flat in both parameters
and across YMGs. This suggests that multiplicity rates are largely set by 100
Myr without appreciable evolution thereafter. After bias corrections are
applied, the multiplicity fraction of low-mass YMG members () is
in excess of the field.Comment: 25 page
The Incidence of Strong-Lensing Clusters in the Red-Sequence Cluster Survey
The incidence of giant arcs due to strong-lensing clusters of galaxies is
known to be discrepant with current theoretical expectations. This result
derives from a comparison of several cluster samples to predictions in the
framework of the currently favored CDM cosmology, and one possible
explanation for the discrepancy is that this cosmological model is not correct.
In this paper we discuss the incidence of giant arcs in the Red-Sequence
Cluster Survey (RCS), which again shows significant disagreement with
theoretical predictions. We briefly describe a total of eight strong lens
systems, seven of which are discussed here for the first time. Based on the
details of these systems, in particular on the ratio of single to multiple arc
systems, we argue that it may be possible to explain this discrepancy in the
currently favored cosmology, by modifying the details of the lenses themselves.
Specifically, the high incidence of multiple arc systems and their overall high
redshift suggests that a sub-population of the global cluster population is
responsible for much of the observed lensing. The lack of lensing clusters at
in the RCS indicates that a property associated with clusters at early
times results in the boosted lensing cross sections; likely a combination of
ellipticity and elongation along the line of sight, substructure, and changes
in the cluster mass profiles is responsible. Cluster mass, which should evolve
to globally higher values toward lower redshifts, is clearly not the most
significant consideration for the formation of giant arcs.Comment: ApJ, accepted version. Additions regarding surface brightness limits
and seeing effects, and further modeling discussio
A bright, spatially extended lensed galaxy at z = 1.7 behind the cluster RCS2 032727-132623
We present the discovery of an extremely bright and extended lensed source
from the second Red Sequence Cluster Survey (RCS2). RCSGA 032727-132609 is
spectroscopically confirmed as a giant arc and counter-image of a background
galaxy at , strongly-lensed by the foreground galaxy cluster RCS2
032727-132623 at . The giant arc extends over \,\arcsec and
has an integrated -band magnitude of 19.15, making it times larger
and times brighter than the prototypical lensed galaxy MS1512-cB58.
This is the brightest distant lensed galaxy in the Universe known to date. Its
location in the `redshift desert' provides unique opportunities to connect
between the large samples of galaxies known at and . We have
collected photometry in 9 bands, ranging from to , which densely
sample the rest-frame UV and optical light, including the age-sensitive
4000\AA\ break. A lens model is constructed for the system, and results in a
robust total magnification of for the counter-image; we
estimate an average magnification of for the giant arc based on
the relative physical scales of the arc and counter-image. Fits of
single-component spectral energy distribution (SED) models to the photometry
result in a moderately young age, \,Myr, small amounts of dust,
, and an exponentially declining star formation history with
\textit{e}-folding time \,Myr. After correcting for the lensing
magnification, we find a stellar mass of
. Allowing for episodic star
formation, an underlying old burst could contain up to twice the mass inferred
from single-component modeling. This stellar mass estimate is consistent with
the average stellar mass of a sample of `BM' galaxies () studied
by Reddy et al. (2006).Comment: 13 pages, 8 figures, abstract abridge
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