CD4+ T cell hyporesponsiveness after repeated exposure to Schistosoma mansoni larvae is dependent upon interleukin-10

The effect that multiple percutaneous exposures to Schistosoma larvae has on the development of early CD4+ lymphocyte reactivity is unclear, yet it is important in the context of humans living in areas where schistosomiasis is endemic. In a murine model of multiple infections, we show that exposure of mice to repeated doses (4×) of Schistosoma mansoni cercariae, compared to a single dose (1×), results in CD4+ T cell hyporesponsiveness within the skin-draining lymph nodes (sdLN), manifested as reduced CD4+ cell proliferation and cytokine production. FoxP3+ CD4+ regulatory T cells were present in similar numbers in the sdLN of 4× and 1× mice and thus are unlikely to have a role in effecting hyporesponsiveness. Moreover, anergy of the CD4+ cell population from 4× mice was slight, as proliferation was only partly circumvented through the in vitro addition of exogenous interleukin-2 (IL-2), and the in vivo blockade of the regulatory molecule PD1 had a minimal effect on restoring responsiveness. In contrast, IL-10 was observed to be critical in mediating hyporesponsiveness, as CD4+ cells from the sdLN of 4× mice deficient for IL-10 were readily able to proliferate, unlike those from 4× wild-type cohorts. CD4+ cells from the sdLN of 4× mice exhibited higher levels of apoptosis and cell death, but in the absence of IL-10, there was significantly less cell death. Combined, our data show that IL-10 is a key factor in the development of CD4+ T cell hyporesponsiveness after repeated parasite exposure involving CD4+ cell apoptosis

Book of the Occurrences of the Times to Jeshurun in the Land of Israel - Ḳorot ha-ʻitim li-Yeshurun be-ʾErets Yiśraʾel

This work was authored by Menahem Mendel me-Kaminitz (an ancestor of one of the current translators David Cook) following his first attempt to settle in the Land of Israel in 1834

Large Magellanic Cloud Microlensing Optical Depth with Imperfect Event Selection

I present a new analysis of the MACHO Project 5.7 year Large Magellanic Cloud (LMC) microlensing data set that incorporates the effects of contamination of the microlensing event sample by variable stars. Photometric monitoring of MACHO LMC microlensing event candidates by the EROS and OGLE groups has revealed that one of these events is likely to be a variable star, while additional data has confirmed that many of the other events are very likely to be microlensing. This additional data on the nature of the MACHO microlensing candidates is incorporated into a simple likelihood analysis to derive a probability distribution for the number of MACHO microlens candidates that are true microlensing events. This analysis shows that 10-12 of the 13 events that passed the MACHO selection criteria are likely to be microlensing events, with the other 1-3 being variable stars. This likelihood analysis is also used to show that the main conclusions of the MACHO LMC analysis are unchanged by the variable star contamination. The microlensing optical depth toward the LMC is = 1.0 +/- 0.3 * 10^{-7}. If this is due to microlensing by known stellar populations, plus an additional population of lens objects in the Galactic halo, then the new halo population would account for 16% of the mass of a standard Galactic halo. The MACHO detection exceeds the expected background of 2 events expected from ordinary stars in standard models of the Milky Way and LMC at the 99.98% confidence level. The background prediction is increased to 3 events if maximal disk models are assumed for both the MilkyWay and LMC, but this model fails to account for the full signal seen by MACHO at the 99.8% confidence level.Comment: 20 pages, 2 postscript figues, accepted by Ap

Harm A. Weber academic center, post-occupancy building performance and comfort perceptions

The Weber Center at Judson University, a mixed mode, naturally ventilated building in a continental climate, has been in operation for just over a year, with initial occupancy in August 2007. This paper compares the design objectives and building performance expectations against the first year of actual energy consumption in a first of a series of post-occupancy evaluations. The paper contrasts the building performance with general user satisfaction and perceptions of comfort through a post- occupancy evaluation of user surveys and interviews. The innovations involved in this building, particularly mechanical strategies atypical in contemporary practice within this climate and region, have introduced some interesting problems that have been documented in the post-occupancy evaluation process, while confirming many of the original intentions of the design

Harm A. Weber academic center, post-occupancy building performance and comfort perceptions

The Weber Center at Judson University, a mixed mode, naturally ventilated building in a continental climate, has been in operation for just over a year, with initial occupancy in August 2007. This paper compares the design objectives and building performance expectations against the first yearof actual energy consumption in a first of a series of post-occupancy evaluations. The paper contrasts the building performance with general user satisfaction and perceptions of comfort through a post occupancy evaluation of user surveys and interviews. The innovations involved in this building, particularly mechanical strategies atypical in contemporary practice within this climate and region, have introduced some interesting problems that have been documented in the post-occupancy evaluation process, while confirming many of the original intentions of the design

Photometric Confirmation of MACHO Large Magellanic Cloud Microlensing Events

We present previously unpublished photometry of three Large Magellanic Cloud (LMC) microlensing events and show that the new photometry confirms the microlensing interpretation of these events. These events were discovered by the MACHO Project alert system and were also recovered by the analysis of the 5.7 year MACHO data set. This new photometry provides a substantial increase in the signal-to-noise ratio over the previously published photometry and in all three cases, the gravitational microlensing interpretation of these events is strengthened. The new data consist of MACHO-Global Microlensing Alert Network (GMAN) follow-up images from the CTIO 0.9 telescope plus difference imaging photometry of the original MACHO data from the 1.3m "Great Melbourne" telescope at Mt. Stromlo. We also combine microlensing light curve fitting with photometry from high resolution HST images of the source stars to provide further confirmation of these events and to show that the microlensing interpretation of event MACHO-LMC-23 is questionable. Finally, we compare our results with the analysis of Belokurov, Evans & Le Du who have attempted to classify candidate microlensing events with a neural network method, and we find that their results are contradicted by the new data and more powerful light curve fitting analysis for each of the four events considered in this paper. The failure of the Belokurov, Evans & Le Du method is likely to be due to their use of a set of insensitive statistics to feed their neural networks.Comment: 29 pages with 8 included postscript figures, accepted by the Astrophysical Journa

Time Course of Changes in Peripheral Blood Gene Expression During Medication Treatment for Major Depressive Disorder.

Changes in gene expression (GE) during antidepressant treatment may increase understanding of the action of antidepressant medications and serve as biomarkers of efficacy. GE changes in peripheral blood are desirable because they can be assessed easily on multiple occasions during treatment. We report here on GE changes in 68 individuals who were treated for 8 weeks with either escitalopram alone, or escitalopram followed by bupropion. GE changes were assessed after 1, 2, and 8 weeks of treatment, with significant changes observed in 156, 121, and 585 peripheral blood gene transcripts, respectively. Thirty-one transcript changes were shared between the 1- and 8-week time points (seven upregulated, 24 downregulated). Differences were detected between the escitalopram- and bupropion-treated subjects, although there was no significant association between GE changes and clinical outcome. A subset of 18 genes overlapped with those previously identified as differentially expressed in subjects with MDD compared with healthy control subjects. There was statistically significant overlap between genes differentially expressed in the current and previous studies, with 10 genes overlapping in at least two previous studies. There was no enrichment for genes overexpressed in nervous system cell types, but there was a trend toward enrichment for genes in the WNT/β-catenin pathway in the anterior thalamus; three genes in this pathway showed differential expression in the present and in three previous studies. Our dataset and other similar studies will provide an important source of information about potential biomarkers of recovery and for potential dysregulation of GE in MDD

Modifying the Einstein Equations off the Constraint Hypersuface

A new technique is presented for modifying the Einstein evolution equations off the constraint hypersurface. With this approach the evolution equations for the constraints can be specified freely. The equations of motion for the gravitational field variables are modified by the addition of terms that are linear and nonlocal in the constraints. These terms are obtained from solutions of the linearized Einstein constraints.Comment: 4 pages, 1 figure, uses REVTe