499 research outputs found

    Multiplexed single-photon-state preparation using a fiber-loop architecture

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    © 2015 American Physical Society. Heralded spontaneous parametric down-conversion (SPDC) has become the mainstay for single-photon-state preparation in present-day photonics experiments. Because they are heralded, in principle one knows when a single photon has been prepared. However, the heralding efficiencies in experimentally realistic SPDC sources are typically very low. To overcome this, multiplexing techniques have been proposed which employ a bank of SPDC sources in parallel and route successfully heralded photons to the output, thereby effectively boosting the heralding efficiency. However, running a large bank of independent SPDC sources is costly and requires complex switching. We analyze a multiplexing technique based on time-bin encoding that allows the heralding efficiency of just a single SPDC source to be increased. The scheme is simple and experimentally viable using present-day technology. We analyze the operation of the scheme in terms of experimentally realistic considerations, such as losses, detector inefficiency, and pump power

    A database of microRNA expression patterns in Xenopus laevis

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    MicroRNAs (miRNAs) are short, non-coding RNAs around 22 nucleotides long. They inhibit gene expression either by translational repression or by causing the degradation of the mRNAs they bind to. Many are highly conserved amongst diverse organisms and have restricted spatio-temporal expression patterns during embryonic development where they are thought to be involved in generating accuracy of developmental timing and in supporting cell fate decisions and tissue identity. We determined the expression patterns of 180 miRNAs in Xenopus laevis embryos using LNA oligonucleotides. In addition we carried out small RNA-seq on different stages of early Xenopus development, identified 44 miRNAs belonging to 29 new families and characterized the expression of 5 of these. Our analyses identified miRNA expression in many organs of the developing embryo. In particular a large number were expressed in neural tissue and in the somites. Surprisingly none of the miRNAs we have looked at show expression in the heart. Our results have been made freely available as a resource in both XenMARK and Xenbase

    Renewing Criminalized and Hegemonic Cultural Landscapes

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    The Mafia's long historical pedigree in Mezzogiorno, Southern Italy, has empowered the Mafioso as a notorious, uncontested, and hegemonic figure. The counter-cultural resistance against the mafiosi culture began to be institutionalized in the early 1990s. Today, Libera Terra is the largest civil society organization in the country that uses the lands confiscated from the Mafia as a space of cultural repertoire to realize its ideals. Deploying labor force through volunteer participation, producing biological fruits and vegetables, and providing information to the students on the fields are the principal cultural practices of this struggle. The confiscated lands make the Italian experience of anti-Mafia resistance a unique example by connecting the land with the ideals of cultural change. The sociocultural resistance of Libera Terra conveys a political message through these practices and utters that the Mafia is not invincible. This study draws the complex panorama of the Mafia and anti-Mafia movement that uses the ‘confiscated lands’ as cultural and public spaces for resistance and socio-cultural change. In doing so, this article sheds new light on the relationship between rural criminology and crime prevention policies in Southern Italy by demonstrating how community development practice of Libera Terra changes the meaning of landscape through iconographic symbolism and ethnographic performance

    Prdm1- and Sox6-mediated transcriptional repression specifies muscle fibre type in the zebrafish embryo

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    The zebrafish u-boot (ubo) gene encodes the transcription factor Prdm1, which is essential for the specification of the primary slow-twitch muscle fibres that derive from adaxial cells. Here, we show that Prdm1 functions by acting as a transcriptional repressor and that slow-twitch-specific muscle gene expression is activated by Prdm1-mediated repression of the transcriptional repressor Sox6. Genes encoding fast-specific isoforms of sarcomeric proteins are ectopically expressed in the adaxial cells of ubotp39 mutant embryos. By using chromatin immunoprecipitation, we show that these are direct targets of Prdm1. Thus, Prdm1 promotes slow-twitch fibre differentiation by acting as a global repressor of fast-fibre-specific genes, as well as by abrogating the repression of slow-fibre-specific genes

    Distinct Mechanisms for Induction and Tolerance Regulate the Immediate Early Genes Encoding Interleukin 1β and Tumor Necrosis Factor α

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    Interleukin-1β and Tumor Necrosis Factor α play related, but distinct, roles in immunity and disease. Our study revealed major mechanistic distinctions in the Toll-like receptor (TLR) signaling-dependent induction for the rapidly expressed genes (IL1B and TNF) coding for these two cytokines. Prior to induction, TNF exhibited pre-bound TATA Binding Protein (TBP) and paused RNA Polymerase II (Pol II), hallmarks of poised immediate-early (IE) genes. In contrast, unstimulated IL1B displayed very low levels of both TBP and paused Pol II, requiring the lineage-specific Spi-1/PU.1 (Spi1) transcription factor as an anchor for induction-dependent interaction with two TLR-activated transcription factors, C/EBPβ and NF-κB. Activation and DNA binding of these two pre-expressed factors resulted in de novo recruitment of TBP and Pol II to IL1B in concert with a permissive state for elongation mediated by the recruitment of elongation factor P-TEFb. This Spi1-dependent mechanism for IL1B transcription, which is unique for a rapidly-induced/poised IE gene, was more dependent upon P-TEFb than was the case for the TNF gene. Furthermore, the dependence on phosphoinositide 3-kinase for P-TEFb recruitment to IL1B paralleled a greater sensitivity to the metabolic state of the cell and a lower sensitivity to the phenomenon of endotoxin tolerance than was evident for TNF. Such differences in induction mechanisms argue against the prevailing paradigm that all IE genes possess paused Pol II and may further delineate the specific roles played by each of these rapidly expressed immune modulators. © 2013 Adamik et al

    Specific mediator inhibition by the NO donors SNP and NCX 2057 in the peripheral lung: implications for allergen-induced bronchoconstriction

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    <p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine potential therapeutic effect of the two NO donors NCX 2057 (3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid) 4-(nitrooxy)butyl ester) and SNP (sodium nitroprusside) on the early allergic airway response in the peripheral lung.</p> <p>Methods</p> <p>The experiments were performed in guinea pig lung parenchyma (GPLP) derived from ovalbumin (OVA) sensitized guinea pigs. The effects of NCX 2057 and SNP were evaluated by contractile responses and mediator release during OVA challenge. The generation of nitrite and nitrate was assessed by chemiluminescence. Statistical analysis was evaluated by ANOVA.</p> <p>Results</p> <p>Cumulatively increasing concentrations of OVA (1–10,000 ng/ml) induced concentration-dependent contractions of the GPLP that were reduced by NCX 2057 (100 μM, p < 0.001) and SNP (100 μM, p < 0.05). Antigen-induced eicosanoid release was decreased by NCX 2057 (100 μM, p < 0.001) but not by SNP (100 μM), whereas the release of histamine was reduced by SNP (100 μM, p < 0.001) but not by NCX 2057 (100 μM). In addition, NCX 2057 (0.1–100 μM), but not SNP (0.1–100 μM), relaxed leukotriene D<sub>4 </sub>(10 nM) precontracted GPLP (p < 0.01). The guanylyl cyclase inhibitor ODQ had no effect on the NCX 2057 mediated relaxation. SNP released significantly less nitrite than NCX 2057.</p> <p>Conclusion</p> <p>Although both SNP and NCX 2057 reduced the release of pro-inflammatory mediators, their profiles were distinctly different. Furthermore, NCX 2057 also induced smooth muscle dilation in the GPLP. The findings point to specific anti-inflammatory effects of different NO donors in the peripheral lung tissue.</p

    RNA polymerase II stalling promotes nucleosome occlusion and pTEFb recruitment to drive immortalization by Epstein-Barr virus

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    Epstein-Barr virus (EBV) immortalizes resting B-cells and is a key etiologic agent in the development of numerous cancers. The essential EBV-encoded protein EBNA 2 activates the viral C promoter (Cp) producing a message of ~120 kb that is differentially spliced to encode all EBNAs required for immortalization. We have previously shown that EBNA 2-activated transcription is dependent on the activity of the RNA polymerase II (pol II) C-terminal domain (CTD) kinase pTEFb (CDK9/cyclin T1). We now demonstrate that Cp, in contrast to two shorter EBNA 2-activated viral genes (LMP 1 and 2A), displays high levels of promoter-proximally stalled pol II despite being constitutively active. Consistent with pol II stalling, we detect considerable pausing complex (NELF/DSIF) association with Cp. Significantly, we observe substantial Cp-specific pTEFb recruitment that stimulates high-level pol II CTD serine 2 phosphorylation at distal regions (up to +75 kb), promoting elongation. We reveal that Cp-specific pol II accumulation is directed by DNA sequences unfavourable for nucleosome assembly that increase TBP access and pol II recruitment. Stalled pol II then maintains Cp nucleosome depletion. Our data indicate that pTEFb is recruited to Cp by the bromodomain protein Brd4, with polymerase stalling facilitating stable association of pTEFb. The Brd4 inhibitor JQ1 and the pTEFb inhibitors DRB and Flavopiridol significantly reduce Cp, but not LMP1 transcript production indicating that Brd4 and pTEFb are required for Cp transcription. Taken together our data indicate that pol II stalling at Cp promotes transcription of essential immortalizing genes during EBV infection by (i) preventing promoter-proximal nucleosome assembly and ii) necessitating the recruitment of pTEFb thereby maintaining serine 2 CTD phosphorylation at distal regions

    Texture variations suppress suprathreshold brightness and colour variations

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    Discriminating material changes from illumination changes is a key function of early vision. Luminance cues are ambiguous in this regard, but can be disambiguated by co-incident changes in colour and texture. Thus, colour and texture are likely to be given greater prominence than luminance for object segmentation, and better segmentation should in turn produce stronger grouping. We sought to measure the relative strengths of combined luminance, colour and texture contrast using a suprathreshhold, psychophysical grouping task. Stimuli comprised diagonal grids of circular patches bordered by a thin black line and contained combinations of luminance decrements with either violet, red, or texture increments. There were two tasks. In the Separate task the different cues were presented separately in a two-interval design, and participants indicated which interval contained the stronger orientation structure. In the Combined task the cues were combined to produce competing orientation structure in a single image. Participants had to indicate which orientation, and therefore which cue was dominant. Thus we established the relative grouping strength of each cue pair presented separately, and compared this to their relative grouping strength when combined. In this way we observed suprathreshold interactions between cues and were able to assess cue dominance at ecologically relevant signal levels. Participants required significantly more luminance and colour compared to texture contrast in the Combined compared to Separate conditions (contrast ratios differed by about 0.1 log units), showing that suprathreshold texture dominates colour and luminance when the different cues are presented in combination

    Antimicrobial Stewardship from Policy to Practice: Experiences from UK Antimicrobial Pharmacists

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    Antimicrobial stewardship in the UK has evolved dramatically in the last 15 years. Factors driving this include initial central funding for specialist pharmacists and mandatory reductions in healthcare-associated infections (particularly Clostridium difficile infection). More recently, the introduction of national stewardship guidelines, and an increased focus on stewardship as part of the UK five-year antimicrobial resistance strategy, have accelerated and embedded developments. Antimicrobial pharmacists have been instrumental in effecting changes at an organizational and national level. This article describes the evolution of the antimicrobial pharmacist role, its impact, the progress toward the actions listed in the five-year resistance strategy, and novel emerging areas in stewardship in the UK
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