Simulating Reionization: Character and Observability

In recent years there has been considerable progress in our understanding of the nature and properties of the reionization process. In particular, the numerical simulations of this epoch have made a qualitative leap forward, reaching sufficiently large scales to derive the characteristic scales of the reionization process and thus allowing for realistic observational predictions. Our group has recently performed the first such large-scale radiative transfer simulations of reionization, run on top of state-of-the-art simulations of early structure formation. This allowed us to make the first realistic observational predictions about the Epoch of Reionization based on detailed radiative transfer and structure formation simulations. We discuss the basic features of reionization derived from our simulations and some recent results on the observational implications for the high-redshift Ly-alpha sources.Comment: 3 pages, to appear in the Proceedings of First Stars III, Santa Fe, July 2007, AIP Conference Serie

Generality of shear thickening in suspensions

Suspensions are of wide interest and form the basis for many smart fluids. For most suspensions, the viscosity decreases with increasing shear rate, i.e. they shear thin. Few are reported to do the opposite, i.e. shear thicken, despite the longstanding expectation that shear thickening is a generic type of suspension behavior. Here we resolve this apparent contradiction. We demonstrate that shear thickening can be masked by a yield stress and can be recovered when the yield stress is decreased below a threshold. We show the generality of this argument and quantify the threshold in rheology experiments where we control yield stresses arising from a variety of sources, such as attractions from particle surface interactions, induced dipoles from applied electric and magnetic fields, as well as confinement of hard particles at high packing fractions. These findings open up possibilities for the design of smart suspensions that combine shear thickening with electro- or magnetorheological response.Comment: 11 pages, 9 figures, accepted for publication in Nature Material

Peroxisome Proliferator-Activated Receptor alpha (PPAR alpha) down-regulation in cystic fibrosis lymphocytes

Background: PPARs exhibit anti-inflammatory capacities and are potential modulators of the inflammatory response. We hypothesized that their expression and/or function may be altered in cystic fibrosis (CF), a disorder characterized by an excessive host inflammatory response. Methods: PPARα, β and γ mRNA levels were measured in peripheral blood cells of CF patients and healthy subjects via RT-PCR. PPARα protein expression and subcellular localization was determined via western blot and immunofluorescence, respectively. The activity of PPARα was analyzed by gel shift assay. Results: In lymphocytes, the expression of PPARα mRNA, but not of PPARβ, was reduced (-37%; p < 0.002) in CF patients compared with healthy persons and was therefore further analyzed. A similar reduction of PPARα was observed at protein level (-26%; p < 0.05). The transcription factor was mainly expressed in the cytosol of lymphocytes, with low expression in the nucleus. Moreover, DNA binding activity of the transcription factor was 36% less in lymphocytes of patients (p < 0.01). For PPARα and PPARβ mRNA expression in monocytes and neutrophils, no significant differences were observed between CF patients and healthy persons. In all cells, PPARγ mRNA levels were below the detection limit. Conclusion: Lymphocytes are important regulators of the inflammatory response by releasing cytokines and antibodies. The diminished lymphocytic expression and activity of PPARα may therefore contribute to the inflammatory processes that are observed in CF

Pre-Diagnostic Plasma 25-Hydroxyvitamin D Levels and Risk of Non-Melanoma Skin Cancer in Women

Recent reports have shown that vitamin D status was inversely associated with the risk of various cancers. However, few studies examined the association between vitamin D levels and risk of skin cancer.We prospectively evaluated the association between baseline plasma 25(OH)D levels and the risk of incident squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) among 4,641 women from the Nurses' Health Study (NHS) and the NHS II with 510 incident BCC cases and 75 incident SCC cases. We used multivariate logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs).Plasma 25(OH)D levels were positively associated with risk of BCC after adjusting for age at blood draw, season of blood draw, lab batch, hair color, burning tendency, the number of sunburns, and ultra-violet B flux of residence at blood collection. Women in the highest quartile of 25(OH)D had more than 2-fold increased risk of BCC compared with women in the lowest quartile (OR = 2.07, 95% CI = 1.52-2.80, P for trend <0.0001). We also found a significantly positive association between plasma 25(OH)D levels and SCC risk after adjusting for the same covariates (OR, highest vs. lowest quartile = 3.77, 95% CI = 1.70-8.36, P for trend= 0.0002).In this prospective study of women, plasma vitamin D levels were positively associated with non-melanoma skin cancer risk. Considering that most circulating vitamin D is due to sun exposure, the positive association between plasma vitamin D and non-melanoma skin cancer is confounded by sun exposure. Our data suggest that one-time measurement of plasma vitamin D levels may reasonably reflect long-term sun exposure and predict the risk of non-melanoma skin cancer

Associations of Serum 25-Hydroxyvitamin D, Parathyroid Hormone and Calcium with Cardiovascular Risk Factors: Analysis of 3 NHANES Cycles (2001–2006)

Increasing evidence suggests a role for mineral metabolism in cardiovascular disease risk. 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), and calcium may be directly associated with cardiovascular risk factors or mediated by each other.We combined data for adult participants in three cycles of the National Health and Nutrition Examination Survey (2001-2, 2003-4, 2005-6), a representative sample of the civilian, non-institutionalized US population (N = 3,958). Using this data we examined joint associations of 25(OH)D, PTH and calcium with a range of cardiovascular risk factors. 25(OH)D was inversely associated with fasting insulin (mean difference in insulin per 1 standard deviation 25(OH)D: -0.053 (95%CI: -0.091, -0.015)), glucose (-0.046 95%CI: -0.081, -0.012) and systolic blood pressure (SBP) (-0.032 95%CI: -0.062, -0.001), and positively associated with high density lipoprotein cholesterol HDL-c (0.088 95%CI: 0.044, 0.148), after adjustment for ethnicity, smoking, socio-economic status and waist circumference. PTH was positively associated with diastolic blood pressure (0.110, 95%CI: 0.055, 0.164) in confounder adjusted models, but was not associated with other cardiovascular risk factors. Albumin adjusted calcium was associated with triglycerides (0.102 95%CI: 0.063, 0.141), postload glucose (0.078, 95%CI: 0.025, 0.130), fasting insulin (0.074, 95%CI: 0.044, 0.104), HbA1c (0.070, 95%CI: 0.036, 0.105), SBP (0.064, 95%CI: 0.028, 0.100), fasting glucose (0.055, 95%CI: 0.018, 0.092) and low density lipoprotein cholesterol (0.052, 95%CI: 0.014, 0.091). With mutual adjustment for each other, these associations remained essentially unchanged.Lower levels of 25(OH)D and higher levels of calcium and PTH appear to be associated with different cardiovascular risk factors and may therefore affect cardiovascular disease risk through different mechanisms

A novel class of microRNA-recognition elements that function only within open reading frames.

MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3' side rather than the 5' seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences of miRNAs that target CDS versus the 3' UTR and suggest that CDS-targeted miRNAs may use a translational quality-control-related mechanism to regulate translation in mammalian cells

Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain

Background: Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated. Methodology: In a large sample of healthy individuals (N = 303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e.g., Stampa algorigthm), yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs. Principal findings/results: In a whole-brain analysis, the polymorphism rs1800795 (−174 C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = −10, z = −15; F(2,286) = 8.54, puncorrected = 0.0002; pAlphaSim-corrected = 0.002; cluster size k = 577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses. Conclusions/significance: These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted.Bernhard T Baune, Carsten Konrad, Dominik Grotegerd, Thomas Suslow, Eva Birosova, Patricia Ohrmann, Jochen Bauer, Volker Arolt, Walter Heindel, Katharina Domschke, Sonja Schöning, Astrid V Rauch, Christina Uhlmann, Harald Kugel and Udo Dannlowsk

Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES) but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS), infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird") compared to AGS cells stably transfected with Cav1 (AGS/Cav1). Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1) to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87) and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1) to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs) in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells

The new scalar politics of evaluation: An emerging governance role for evaluation

In this article we analyze how roles for evaluation are described and argued for in key texts produced and/or promoted by three influential international networks: the High Level Forum on Aid Effectiveness; the Organisation for Economic Cooperation and Development Assistance Committee’s Network on Development Evaluation; and the Network of Networks for Impact Evaluation. We contend that these complex multilateral networks are working supranationally through soft power to promote: common standards of evaluation practice; a dominant model of evaluation (impact evaluation); and new evaluation roles, relationships and practices for the field of development. Moreover, we argue that this emerging complex multilateral agenda for evaluation may position evaluation and evaluators within a global governance strategy allowing greater influence to international development organizations. We conclude with a discussion of the implications of the analysis for evaluators working in the field of international development