627 research outputs found
An in vitro model of chronic wounding and its implication for age-related macular degeneration
Degeneration of the retinal pigment epithelium (RPE) plays a central role in age-related macular degeneration (AMD). Throughout life, RPE cells are challenged by a variety of cytotoxic stressors, some of which are cumulative with age and may ultimately contribute to drusen and lipofuscin accumulation. Stressors such as these continually damage RPE cells resulting in a state of chronic wounding. Current cell-based platforms that model a state of chronic RPE cell wounding are limited, and the RPE cellular response is not entirely understood. Here, we used the electric cell-substrate impedance sensing (ECIS) system to induce a state of acute or chronic wounding on differentiated human fetal RPE cells to analyze changes in the wound repair response. RPE cells surrounding the lesioned area employ both cell migration and proliferation to repair wounds but fail to reestablish their original cell morphology or density after repetitive wounding. Chronically wounded RPE cells develop phenotypic AMD characteristics such as loss of cuboidal morphology, enlarged size, and multinucleation. Transcriptomic analysis suggests a systemic misregulation of RPE cell functions in bystander cells, which are not directly adjacent to the wound. Genes associated with the major RPE cell functions (LRAT, MITF, RDH11) significantly downregulate after wounding, in addition to differential expression of genes associated with the cell cycle (CDK1, CDC6, CDC20), inflammation (IL-18, CCL2), and apoptosis (FAS). Interestingly, repetitive wounding resulted in prolonged misregulation of genes, including FAS, LRAT, and PEDF. The use of ECIS to induce wounding resulted in an over-representation of AMD-associated genes among those dysregulated genes, particularly genes associated with advanced AMD. This simple system provides a new model for further investigation of RPE cell wound response in AMD pathogenesis
BPS black holes, the Hesse potential, and the topological string
The Hesse potential is constructed for a class of four-dimensional N=2
supersymmetric effective actions with S- and T-duality by performing the
relevant Legendre transform by iteration. It is a function of fields that
transform under duality according to an arithmetic subgroup of the classical
dualities reflecting the monodromies of the underlying string compactification.
These transformations are not subject to corrections, unlike the
transformations of the fields that appear in the effective action which are
affected by the presence of higher-derivative couplings. The class of actions
that are considered includes those of the FHSV and the STU model. We also
consider heterotic N=4 supersymmetric compactifications. The Hesse potential,
which is equal to the free energy function for BPS black holes, is manifestly
duality invariant. Generically it can be expanded in terms of powers of the
modulus that represents the inverse topological string coupling constant,
, and its complex conjugate. The terms depending holomorphically on
are expected to correspond to the topological string partition function and
this expectation is explicitly verified in two cases. Terms proportional to
mixed powers of and are in principle present.Comment: 28 pages, LaTeX, added comment
Reversible Random Sequential Adsorption of Dimers on a Triangular Lattice
We report on simulations of reversible random sequential adsorption of dimers
on three different lattices: a one-dimensional lattice, a two-dimensional
triangular lattice, and a two-dimensional triangular lattice with the nearest
neighbors excluded. In addition to the adsorption of particles at a rate K+, we
allow particles to leave the surface at a rate K-. The results from the
one-dimensional lattice model agree with previous results for the continuous
parking lot model. In particular, the long-time behavior is dominated by
collective events involving two particles. We were able to directly confirm the
importance of two-particle events in the simple two-dimensional triangular
lattice. For the two-dimensional triangular lattice with the nearest neighbors
excluded, the observed dynamics are consistent with this picture. The
two-dimensional simulations were motivated by measurements of Ca++ binding to
Langmuir monolayers. The two cases were chosen to model the effects of changing
pH in the experimental system.Comment: 9 pages, 10 figure
Tissue mimicking materials for imaging and therapy phantoms: a review
Tissue mimicking materials (TMMs), typically contained within phantoms, have been used for many decades in both imaging and therapeutic applications. This review investigates the specifications that are typically being used in development of the latest TMMs. The imaging modalities that have been investigated focus around CT, mammography, SPECT, PET, MRI and ultrasound. Therapeutic applications discussed within the review include radiotherapy, thermal therapy and surgical applications. A number of modalities were not reviewed including optical spectroscopy, optical imaging and planar x-rays. The emergence of image guided interventions and multimodality imaging have placed an increasing demand on the number of specifications on the latest TMMs. Material specification standards are available in some imaging areas such as ultrasound. It is recommended that this should be replicated for other imaging and therapeutic modalities. Materials used within phantoms have been reviewed for a series of imaging and therapeutic applications with the potential to become a testbed for cross-fertilization of materials across modalities. Deformation, texture, multimodality imaging and perfusion are common themes that are currently under development
Black Hole Hair Removal: Non-linear Analysis
BMPV black holes in flat transverse space and in Taub-NUT space have
identical near horizon geometries but different microscopic degeneracies. It
has been proposed that this difference can be accounted for by different
contribution to the degeneracies of these black holes from hair modes, --
degrees of freedom living outside the horizon. In this paper we explicitly
construct the hair modes of these two black holes as finite bosonic and
fermionic deformations of the black hole solution satisfying the full
non-linear equations of motion of supergravity and preserving the supersymmetry
of the original solutions. Special care is taken to ensure that these solutions
do not have any curvature singularity at the future horizon when viewed as the
full ten dimensional geometry. We show that after removing the contribution due
to the hair degrees of freedom from the microscopic partition function, the
partition functions of the two black holes agree.Comment: 40 pages, LaTe
Discrete Information from CHL Black Holes
AdS_2/CFT_1 correspondence predicts that the logarithm of a Z_N twisted index
over states carrying a fixed set of charges grows as 1/N times the entropy of
the black hole carrying the same set of charges. In this paper we verify this
explicitly by calculating the microscopic Z_N twisted index for a class of
states in the CHL models. This demonstrates that black holes carry more
information about the microstates than just the total degeneracy.Comment: LaTeX file, 24 pages; v2: references adde
A Twist in the Dyon Partition Function
In four dimensional string theories with N=4 and N=8 supersymmetries one can
often define twisted index in a subspace of the moduli space which captures
additional information on the partition function than the ones contained in the
usual helicity trace index. We compute several such indices in type IIB string
theory on K3 x T^2 and T^6, and find that they share many properties with the
usual helicity trace index that captures the spectrum of quarter BPS states in
N=4 supersymmetric string theories. In particular the partition function is a
modular form of a subgroup of Sp(2,Z) and the jumps across the walls of
marginal stability are controlled by the residues at the poles of the partition
function. However for large charges the logarithm of this index grows as 1/n
times the entropy of a black hole carrying the same charges where n is the
order of the symmetry generator that is used to define the twisted index. We
provide a macroscopic explanation of this phenomenon using quantum entropy
function formalism. The leading saddle point corresponding to the attractor
geometry fails to contribute to the twisted index, but a Z_n orbifold of the
attractor geometry produces the desired contribution.Comment: LaTeX file, 35 pages; v2: references adde
The Epidemiology of Lead Toxicity in Adults: Measuring Dose and Consideration of Other Methodologic Issues
We review several issues of broad relevance to the interpretation of epidemiologic evidence concerning the toxicity of lead in adults, particularly regarding cognitive function and the cardiovascular system, which are the subjects of two systematic reviews that are also part of this mini-monograph. Chief among the recent developments in methodologic advances has been the refinement of concepts and methods for measuring individual lead dose in terms of appreciating distinctions between recent versus cumulative doses and the use of biological markers to measure these parameters in epidemiologic studies of chronic disease. Attention is focused particularly on bone lead levels measured by K-shell X-ray fluorescence as a relatively new biological marker of cumulative dose that has been used in many recent epidemiologic studies to generate insights into lead’s impact on cognition and risk of hypertension, as well as the alternative method of estimating cumulative dose using available repeated measures of blood lead to calculate an individual’s cumulative blood lead index. We review the relevance and interpretation of these lead biomarkers in the context of the toxico-kinetics of lead. In addition, we also discuss methodologic challenges that arise in studies of occupationally and environmentally exposed subjects and those concerning race/ethnicity and socioeconomic status and other important covariates
Preparation, structural characterisation and antibacterial properties of Ga-doped sol-gel phosphate-based glass
A sol-gel preparation of Ga-doped phosphate-based glass with potential application in antimicrobial devices has been developed. Samples of composition (CaO)(0.30)(Na2O)(0.20-x) (Ga2O3) (x) (P2O5)(0.50) where x = 0 and 0.03 were prepared, and the structure and properties of the gallium-doped sample compared with those of the sample containing no gallium. Analysis of the P-31 MAS NMR data demonstrated that addition of gallium to the sol-gel reaction increases the connectivity of the phosphate network at the expense of hydroxyl groups. This premise is supported by the results of the elemental analysis, which showed that the gallium-free sample contains significantly more hydrogen and by FTIR spectroscopy, which revealed a higher concentration of -OH groups in that sample. Ga K-edge extended X-ray absorption fine structure and X-ray absorption near-edge structure data revealed that the gallium ions are coordinated by six oxygen atoms. In agreement with the X-ray absorption data, the high-energy XRD results also suggest that the Ga3+ ions are octahedrally coordinated with respect to oxygen. Antimicrobial studies demonstrated that the sample containing Ga3+ ions had significant activity against Staphylococcus aureus compared to the control
General Gauge Mediation at the Weak Scale
We completely characterize General Gauge Mediation (GGM) at the weak scale by
solving all IR constraints over the full parameter space. This is made possible
through a combination of numerical and analytical methods, based on a set of
algebraic relations among the IR soft masses derived from the GGM boundary
conditions in the UV. We show how tensions between just a few constraints
determine the boundaries of the parameter space: electroweak symmetry breaking
(EWSB), the Higgs mass, slepton tachyons, and left-handed stop/sbottom
tachyons. While these constraints allow the left-handed squarks to be
arbitrarily light, they place strong lower bounds on all of the right-handed
squarks. Meanwhile, light EW superpartners are generic throughout much of the
parameter space. This is especially the case at lower messenger scales, where a
positive threshold correction to coming from light Higgsinos and winos is
essential in order to satisfy the Higgs mass constraint.Comment: 43 pages, 20 figures, mathematica package included in the sourc
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