Dephasing by a nonstationary classical intermittent noise

We consider a new phenomenological model for a $1/f^{\mu}$ classical intermittent noise and study its effects on the dephasing of a two-level system. Within this model, the evolution of the relative phase between the $|\pm>$ states is described as a continuous time random walk (CTRW). Using renewal theory, we find exact expressions for the dephasing factor and identify the physically relevant various regimes in terms of the coupling to the noise. In particular, we point out the consequences of the non-stationarity and pronounced non-Gaussian features of this noise, including some new anomalous and aging dephasing scenarii.Comment: Submitted to Phys. Rev.

L006 Role of serum response factor (SRF) on microrna expression in the cardiovascular system

Serum response factor (SRF) is a transcription factor of the MADS box family that regulates essential structural and metabolic genes in many tissues. Using a mouse Cre-Lox model, we have shown previously that SRF inactivation can result in severe cardiac and intestinal failure as well as angiogenic defects.We have performed transcriptomic analyses of gene expression alteration in the cardiac and vascular system following SRF inactivation (see other abstracts) and we found a large number of down-regulated genes but an even larger number that are up-regulated after SRF inactivation. This latter result was partly unexpected since SRF is mainly known as a positive regulator of transcription. While various hypotheses can account for this up-regulation, we chose to focus on the potential role of SRF in the control of miRNAs, which are endogenous small RNAs that can inhibit the expression of other mRNAs. Indeed, recent bioinformatic analyses revealed that more than 40 microRNAs contain SRF target sequences in their promoter region, suggesting a possible broad regulatory role of SRF for these microRNAs. It has already been shown by others that SRF regulates miR-1 and miR-133 expression during heart development, those miRs being essential for correct cardiogenesis and the control of cardiac hypertrophy. The aims of this project are: 1) To analyse the role of SRF in the regulation of microRNAs in the adult heart and vessels of mice by a transcriptomic approach and ChIP on Chip approach ; 2) To study the biological role of microRNAs regulated by SRF and their implications in development of cardiovascular disease.To analyse the role of SRF in microRNA regulation, we have started to extract total RNA from hearts of SRF conditional knockout mice at different stages and in basal and hypertrophic settings. Preliminary analysis of global microRNA expression profile of these samples using Illumina V2 microRNA beadarrays and characterization of the expression of putative SRF MiR targets by quantitative RT PCR will be presented

Mutations in the E2 glycoprotein and the 3\u27 untranslated region enhance chikungunya virus virulence in mice

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes debilitating musculoskeletal pain and inflammation and can persist for months to years after acute infection. Although studies of humans and experimentally infected animals suggest that CHIKV infection persists in musculoskeletal tissues, the mechanisms for this remain poorly understood. To evaluate this further, we isolated CHIKV from the serum of persistently infected Rag1 -/- mice at day 28. When inoculated into naive wild-type (WT) mice, this persistently circulating CHIKV strain displayed a capacity for earlier dissemination and greater pathogenicity than the parental virus. Sequence analysis revealed a nonsynonymous mutation in the E2 glycoprotein (E2 K200R) and a deletion within the 3' untranslated region (3'-UTR). The introduction of these changes into the parental virus conferred enhanced virulence in mice, although primary tropism for musculoskeletal tissues was maintained. The E2 K200R mutation was largely responsible for enhanced viral dissemination and pathogenicity, although these effects were augmented by the 3'- UTR deletion. Finally, studies with Irf3/Irf7 -/- and Ifnar1 -/- mice suggest that the E2 K200R mutation enhances viral dissemination from the site of inoculation independently of interferon regulatory factor 3 (IRF3)-, IRF7-, and IFNAR1-mediated responses. As our findings reveal viral determinants of CHIKV dissemination and pathogenicity, their further study should help to elucidate host-virus interactions that determine acute and chronic CHIKV infection

Vaccinia virus protein complex F12/E2 interacts with kinesin light chain isoform 2 to engage the kinesin-1 motor complex.

During vaccinia virus morphogenesis, intracellular mature virus (IMV) particles are wrapped by a double lipid bilayer to form triple enveloped virions called intracellular enveloped virus (IEV). IEV are then transported to the cell surface where the outer IEV membrane fuses with the cell membrane to expose a double enveloped virion outside the cell. The F12, E2 and A36 proteins are involved in transport of IEVs to the cell surface. Deletion of the F12L or E2L genes causes a severe inhibition of IEV transport and a tiny plaque size. Deletion of the A36R gene leads to a smaller reduction in plaque size and less severe inhibition of IEV egress. The A36 protein is present in the outer membrane of IEVs, and over-expressed fragments of this protein interact with kinesin light chain (KLC). However, no interaction of F12 or E2 with the kinesin complex has been reported hitherto. Here the F12/E2 complex is shown to associate with kinesin-1 through an interaction of E2 with the C-terminal tail of KLC isoform 2, which varies considerably between different KLC isoforms. siRNA-mediated knockdown of KLC isoform 1 increased IEV transport to the cell surface and virus plaque size, suggesting interaction with KLC isoform 1 is somehow inhibitory of IEV transport. In contrast, knockdown of KLC isoform 2 did not affect IEV egress or plaque formation, indicating redundancy in virion egress pathways. Lastly, the enhancement of plaque size resulting from loss of KLC isoform 1 was abrogated by removal of KLC isoforms 1 and 2 simultaneously. These observations suggest redundancy in the mechanisms used for IEV egress, with involvement of KLC isoforms 1 and 2, and provide evidence of interaction of F12/E2 complex with the kinesin-1 complex.This work was supported by grant G1000207 from the Medical Research Council, UK and grant 090315 from The Wellcome Trust. GLS is a Wellcome Trust Principal research Fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final published version. It first appeared at http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004723

Accountability and Transparency of Entrepreneurial Journalism: Unresolved ethical issues in crowdfunded journalism projects

Crowdfunding is a new business model in which journalists rely—and depend—on (micro-) payments by a large number of supporters to finance their reporting. In this form of entrepreneurial journalism the roles of publisher, fundraiser and journalist often overlap. This raises questions about conflicts of interest, accountability and transparency. The article presents the results of selected case studies in four different European countries—Germany (Krautreporter), Italy (Occhidellaguerra), the United Kingdom (Contributoria) and the Netherlands (De Correspondent)—as well as one US example (Kickstarter). The study used a two-step methodological approach: first a content analysis of the websites and the Twitter accounts with regard to practices of media accountability, transparency and user participation was undertaken. The aim was to investigate how far ethical challenges in crowdfunded entrepreneurial journalism are accounted for. Second, we present findings from semi-structured interviews with journalists from each crowdfunding. The study provides evidence about the ethical issues in this area, particularly in relation to production transparency and responsiveness. The study also shows that in some cases of crowdfunding (platforms), accountability is outsourced and implemented only through the audience participation

Absence of Two-Dimensional Bragg Glasses

The stability to dislocations of the elastic phase, or ``Bragg glass'', of a randomly pinned elastic medium in two dimensions is studied using the minimum-cost-flow algorithm for a disordered fully-packed loop model. The elastic phase is found to be unstable to dislocations due to the quenched disorder. The energetics of dislocations are discussed within the framework of renormalization group predictions as well as in terms of a domain wall picture.Comment: 5 pages, REVTEX, 3 figures included. Further information can be obtained from [email protected]

Validity of Remote Testing to In - Person Testing of 2 - Minute Walk Test and Stepping in Place Test

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