You Can't Get Through Szekeres Wormholes - or - Regularity, Topology and Causality in Quasi-Spherical Szekeres Models

The spherically symmetric dust model of Lemaitre-Tolman can describe wormholes, but the causal communication between the two asymptotic regions through the neck is even less than in the vacuum (Schwarzschild-Kruskal-Szekeres) case. We investigate the anisotropic generalisation of the wormhole topology in the Szekeres model. The function E(r, p, q) describes the deviation from spherical symmetry if \partial_r E \neq 0, but this requires the mass to be increasing with radius, \partial_r M > 0, i.e. non-zero density. We investigate the geometrical relations between the mass dipole and the locii of apparent horizon and of shell-crossings. We present the various conditions that ensure physically reasonable quasi-spherical models, including a regular origin, regular maxima and minima in the spatial sections, and the absence of shell-crossings. We show that physically reasonable values of \partial_r E \neq 0 cannot compensate for the effects of \partial_r M > 0 in any direction, so that communication through the neck is still worse than the vacuum. We also show that a handle topology cannot be created by identifying hypersufaces in the two asymptotic regions on either side of a wormhole, unless a surface layer is allowed at the junction. This impossibility includes the Schwarzschild-Kruskal-Szekeres case.Comment: zip file with LaTeX text + 6 figures (.eps & .ps). 47 pages. Second replacement corrects some minor errors and typos. (First replacement prints better on US letter size paper.

Structure formation in the Lemaitre-Tolman model

Structure formation within the Lemaitre-Tolman model is investigated in a general manner. We seek models such that the initial density perturbation within a homogeneous background has a smaller mass than the structure into which it will develop, and the perturbation then accretes more mass during evolution. This is a generalisation of the approach taken by Bonnor in 1956. It is proved that any two spherically symmetric density profiles specified on any two constant time slices can be joined by a Lemaitre-Tolman evolution, and exact implicit formulae for the arbitrary functions that determine the resulting L-T model are obtained. Examples of the process are investigated numerically.Comment: LaTeX 2e plus 14 .eps & .ps figure files. 33 pages including figures. Minor revisions of text and data make it more precise and consistent. Currently scheduled for Phys Rev D vol 64, December 15 issu

Development of Methods for Cross-Sectional HIV Incidence Estimation in a Large, Community Randomized Trial

Background Accurate methods of HIV incidence determination are critically needed to monitor the epidemic and determine the population level impact of prevention trials. One such trial, Project Accept, a Phase III, community-randomized trial, evaluated the impact of enhanced, community-based voluntary counseling and testing on population-level HIV incidence. The primary endpoint of the trial was based on a single, cross-sectional, post-intervention HIV incidence assessment. Methods and Findings Test performance of HIV incidence determination was evaluated for 403 multi-assay algorithms [MAAs] that included the BED capture immunoassay [BED-CEIA] alone, an avidity assay alone, and combinations of these assays at different cutoff values with and without CD4 and viral load testing on samples from seven African cohorts (5,325 samples from 3,436 individuals with known duration of HIV infection [1 month to >10 years]). The mean window period (average time individuals appear positive for a given algorithm) and performance in estimating an incidence estimate (in terms of bias and variance) of these MAAs were evaluated in three simulated epidemic scenarios (stable, emerging and waning). The power of different test methods to detect a 35% reduction in incidence in the matched communities of Project Accept was also assessed. A MAA was identified that included BED-CEIA, the avidity assay, CD4 cell count, and viral load that had a window period of 259 days, accurately estimated HIV incidence in all three epidemic settings and provided sufficient power to detect an intervention effect in Project Accept. Conclusions In a Southern African setting, HIV incidence estimates and intervention effects can be accurately estimated from cross-sectional surveys using a MAA. The improved accuracy in cross-sectional incidence testing that a MAA provides is a powerful tool for HIV surveillance and program evaluation

Unshielded asymmetric transmit-only and endorectal receive-only radiofrequency coil for \u3csup\u3e23\u3c/sup\u3eNa MRI of the prostate at 3 tesla

Background To develop and optimize radiofrequency (RF) hardware for the detection of endogenous sodium ( Na) by 3.0 Tesla (T) MRI in the human prostate. Methods A transmit-only receive-only (TORO) RF system of resonators consisting of an unshielded, asymmetric, quadrature birdcage (transmit), and an endorectal (ER), linear, surface (receive) coil were developed and tested on a 3T MRI scanner. Two different ER receivers were constructed; a single-tuned ( Na) and a dual-tuned ( H/ Na). Both receivers were evaluated by the measurements of signal-to-noise ratio (SNR) and B homogeneity. For tissue sodium concentration (TSC) quantification, vials containing known sodium concentrations were incorporated into the ER. The system was used to measure the prostate TSC of three men (age 55-±-5 years) with biopsy-proven prostate cancer. Results B field inhomogeneity of the asymmetric transmitter was estimated to be less than 5%. The mean SNR measured in a region of interest within the prostate using the single-tuned ER coil was 54.0-±-4.6. The mean TSC in the central gland was 60.2-±-5.7 mmol/L and in the peripheral gland was 70.5-±-9.0 mmol/L. Conclusion A TORO system was developed and optimized for Na MRI of the human prostate which showed good sensitivity throughout the prostate for quantitative measurement of TSC. 23 23 1 23 23 1

α3β1 integrin in epidermis promotes wound angiogenesis and keratinocyte-to-endothelial-cell crosstalk through the induction of MRP3

During cutaneous wound healing, epidermal keratinocytes play essential roles in the secretion of factors that promote angiogenesis. However, specific cues in the wound microenvironment that trigger the production of pro-angiogenic factors by keratinocytes, and the cellular receptors that mediate this response, remain unclear. In this study, we exploited a model of conditional integrin knockout to demonstrate impaired wound angiogenesis in mice that lack α3β1 integrin in epidermis. In addition, we used genetic and shRNA approaches to determine that α3β1-integrin deficiency in keratinocytes leads to reduced mRNA and protein expression of the pro-angiogenic factor mitogen-regulated protein 3 (MRP3; also known as PRL2C4), and to demonstrate that this regulation provides a mechanism of keratinocyte-to-endothelial-cell crosstalk that promotes endothelial-cell migration. Finally, we showed that the impaired wound angiogenesis in epidermis-specific α3-integrin-knockout mice is correlated with reduced expression of MRP3 in wounded epidermis. These findings identify a novel role for α3β1 integrin in promoting wound angiogenesis through a mechanism of crosstalk from epidermal to endothelial cells, and they implicate MRP3 in this integrin-dependent crosstalk. Such a mechanism represents a novel paradigm for integrin-mediated regulation of wound angiogenesis that extends beyond traditional roles for integrins in cell adhesion and migration.This is an article from Journal of Cell Science 122 (2009): 1778, doi:10.1242/jcs.040956. Posted with permission.</p

α3β1 integrin in epidermis promotes wound angiogenesis and keratinocyte-to-endothelial-cell crosstalk through the induction of MRP3

During cutaneous wound healing, epidermal keratinocytes play essential roles in the secretion of factors that promote angiogenesis. However, specific cues in the wound microenvironment that trigger the production of pro-angiogenic factors by keratinocytes, and the cellular receptors that mediate this response, remain unclear. In this study, we exploited a model of conditional integrin knockout to demonstrate impaired wound angiogenesis in mice that lack α3β1 integrin in epidermis. In addition, we used genetic and shRNA approaches to determine that α3β1-integrin deficiency in keratinocytes leads to reduced mRNA and protein expression of the pro-angiogenic factor mitogen-regulated protein 3 (MRP3; also known as PRL2C4), and to demonstrate that this regulation provides a mechanism of keratinocyte-to-endothelial-cell crosstalk that promotes endothelial-cell migration. Finally, we showed that the impaired wound angiogenesis in epidermis-specific α3-integrin-knockout mice is correlated with reduced expression of MRP3 in wounded epidermis. These findings identify a novel role for α3β1 integrin in promoting wound angiogenesis through a mechanism of crosstalk from epidermal to endothelial cells, and they implicate MRP3 in this integrin-dependent crosstalk. Such a mechanism represents a novel paradigm for integrin-mediated regulation of wound angiogenesis that extends beyond traditional roles for integrins in cell adhesion and migration

Coordinate integrin and c-Met signaling regulate Wnt gene expression during epithelial morphogenesis

Integrin receptors for the extracellular matrix and receptor tyrosine kinase growth factor receptors represent two of the major families of receptors that transduce into cells information about the surrounding environment. Wnt proteins are a major family of signaling molecules that regulate morphogenetic events. There is presently little understanding of how the expression of Wnt genes themselves is regulated. In this study, we demonstrate that α3β1 integrin, a major laminin receptor involved in the development of the kidney, and c-Met, the receptor for hepatocyte growth factor, signal coordinately to regulate the expression of Wnt7b in the mouse. Wnt signals in turn appear to regulate epithelial cell survival in the papilla of the developing kidney, allowing for the elongation of epithelial tubules to form a mature papilla. Together, these results demonstrate how signals from integrins and growth factor receptors can be integrated to regulate the expression of an important family of signaling molecules so as to regulate morphogenetic events

Epithelial cell α3β1 integrin links β-catenin and Smad signaling to promote myofibroblast formation and pulmonary fibrosis

Pulmonary fibrosis, in particular idiopathic pulmonary fibrosis (IPF), results from aberrant wound healing and scarification. One population of fibroblasts involved in the fibrotic process is thought to originate from lung epithelial cells via epithelial-mesenchymal transition (EMT). Indeed, alveolar epithelial cells (AECs) undergo EMT in vivo during experimental fibrosis and ex vivo in response to TGF-β1. As the ECM critically regulates AEC responses to TGF-β1, we explored the role of the prominent epithelial integrin α3β1 in experimental fibrosis by generating mice with lung epithelial cell–specific loss of α3 integrin expression. These mice had a normal acute response to bleomycin injury, but they exhibited markedly decreased accumulation of lung myofibroblasts and type I collagen and did not progress to fibrosis. Signaling through β-catenin has been implicated in EMT; we found that in primary AECs, α3 integrin was required for β-catenin phosphorylation at tyrosine residue 654 (Y654), formation of the pY654–β-catenin/pSmad2 complex, and initiation of EMT, both in vitro and in vivo during the fibrotic phase following bleomycin injury. Finally, analysis of lung tissue from IPF patients revealed the presence of pY654–β-catenin/pSmad2 complexes and showed accumulation of pY654–β-catenin in myofibroblasts. These findings demonstrate epithelial integrin–dependent profibrotic crosstalk between β-catenin and Smad signaling and support the hypothesis that EMT is an important contributor to pathologic fibrosis