Combinatorics of BB-orbits and Bruhat--Chevalley order on involutions

Let $B$ be the group of invertible upper-triangular complex $n\times n$ matrices, $\mathfrak{u}$ the space of upper-triangular complex matrices with zeroes on the diagonal and $\mathfrak{u}^*$ its dual space. The group $B$ acts on $\mathfrak{u}^*$ by $(g.f)(x)=f(gxg^{-1})$, $g\in B$, $f\in\mathfrak{u}^*$, $x\in\mathfrak{u}$. To each involution $\sigma$ in $S_n$, the symmetric group on $n$ letters, one can assign the $B$-orbit $\Omega_{\sigma}\in\mathfrak{u}^*$. We present a combinatorial description of the partial order on the set of involutions induced by the orbit closures. The answer is given in terms of rook placements and is dual to A. Melnikov's results on $B$-orbits on $\mathfrak{u}$. Using results of F. Incitti, we also prove that this partial order coincides with the restriction of the Bruhat--Chevalley order to the set of involutions.Comment: 27 page

Reinitiation of protein synthesis in Escherichia coli can be induced by mRNA cis-elements unrelated to canonical translation initiation signals

AbstractIn Eubacteria, de novo translation of some internal cistrons may be inefficient or impossible unless the 5′ neighboring cistron is also translated (translational coupling). Translation reinitiation is an extreme case of translational coupling in which translation of a message depends entirely on the presence of a nearby terminating ribosome. In this work, the characteristics of mRNA cis-elements inducing the reinitiation process in Escherichia coli have been investigated using a combinatorial approach. A number of novel translational reinitiation sequences (TRSs) were thus identified, which show a wide range of reinitiation activities fully dependent on a translational coupling event and unrelated to the presence/absence of secondary structure or mRNA stability. Moreover, some of the isolated TRSs are similar to intercistronic sequences present in the E. coli genome

Проблемы разработки стратегии построения технологии контекстного обучения педагогов

AIMS/HYPOTHESIS: The evidence on the association between pioglitazone use and bladder cancer is contradictory, with many studies subject to allocation bias. The aim of our study was to examine the effect of exposure to pioglitazone on bladder cancer risk internationally across several cohorts. The potential for allocation bias was minimised by focusing on the cumulative effect of pioglitazone as the primary endpoint using a time-dependent approach. METHODS: Prescription, cancer and mortality data from people with type 2 diabetes were obtained from six populations across the world (British Columbia, Finland, Manchester, Rotterdam, Scotland and the UK Clinical Practice Research Datalink). A discrete time failure analysis using Poisson regression was applied separately to data from each centre to model the effect of cumulative drug exposure on bladder cancer incidence, with time-dependent adjustment for ever use of pioglitazone. These were then pooled using fixed and random effects meta-regression. RESULTS: Data were collated on 1.01 million persons over 5.9 million person-years. There were 3,248 cases of incident bladder cancer, with 117 exposed cases and a median follow-up duration of 4.0 to 7.4 years. Overall, there was no evidence for any association between cumulative exposure to pioglitazone and bladder cancer in men (rate ratio [RR] per 100 days of cumulative exposure, 1.01; 95% CI 0.97, 1.06) or women (RR 1.04; 95% CI 0.97, 1.11) after adjustment for age, calendar year, diabetes duration, smoking and any ever use of pioglitazone. No association was observed between rosiglitazone and bladder cancer in men (RR 1.01; 95% CI 0.98, 1.03) or women (RR 1.00; 95% CI 0.94, 1.07). CONCLUSIONS/INTERPRETATION: The cumulative use of pioglitazone or rosiglitazone was not associated with the incidence of bladder cancer in this large, pooled multipopulation analysis

Fire Activity and Severity in the Western US Vary along Proxy Gradients Representing Fuel Amount and Fuel Moisture

Numerous theoretical and empirical studies have shown that wildfire activity (e.g., area burned) at regional to global scales may be limited at the extremes of environmental gradients such as productivity or moisture. Fire activity, however, represents only one component of the fire regime, and no studies to date have characterized fire severity along such gradients. Given the importance of fire severity in dictating ecological response to fire, this is a considerable knowledge gap. For the western US, we quantify relationships between climate and the fire regime by empirically describing both fire activity and severity along two climatic water balance gradients, actual evapotranspiration (AET) and water deficit (WD), that can be considered proxies for fuel amount and fuel moisture, respectively. We also concurrently summarize fire activity and severity among ecoregions, providing an empirically based description of the geographic distribution of fire regimes. Our results show that fire activity in the western US increases with fuel amount (represented by AET) but has a unimodal (i.e., humped) relationship with fuel moisture (represented by WD); fire severity increases with fuel amount and fuel moisture. The explicit links between fire regime components and physical environmental gradients suggest that multivariable statistical models can be generated to produce an empirically based fire regime map for the western US. Such models will potentially enable researchers to anticipate climate-mediated changes in fire recurrence and its impacts based on gridded spatial data representing future climate scenarios

CD47 plays a critical role in T-cell recruitment by regulation of LFA-1 and VLA-4 integrin adhesive functions

CD47 plays an important but incompletely understood role in the innate and adaptive immune responses. CD47, also called integrin-associated protein, has been demonstrated to associate in cis with β1 and β3 integrins. Here we test the hypothesis that CD47 regulates adhesive functions of T-cell α4β1 (VLA-4) and αLβ2 (LFA-1) in in vivo and in vitro models of inflammation. Intravital microscopy studies reveal that CD47(−/−) Th1 cells exhibit reduced interactions with wild-type (WT) inflamed cremaster muscle microvessels. Similarly, murine CD47(−/−) Th1 cells, as compared with WT, showed defects in adhesion and transmigration across tumor necrosis factor-α (TNF-α)–activated murine endothelium and in adhesion to immobilized intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion protein 1 (VCAM-1) under flow conditions. Human Jurkat T-cells lacking CD47 also showed reduced adhesion to TNF-α–activated endothelium and ICAM-1 and VCAM-1. In cis interactions between Jurkat T-cell β2 integrins and CD47 were detected by fluorescence lifetime imaging microscopy. Unexpectedly, Jurkat CD47 null cells exhibited a striking defect in β1 and β2 integrin activation in response to Mn(2+) or Mg(2+)/ethylene glycol tetraacetic acid treatment. Our results demonstrate that CD47 associates with β2 integrins and is necessary to induce high-affinity conformations of LFA-1 and VLA-4 that recognize their endothelial cell ligands and support leukocyte adhesion and transendothelial migration

Impact of light on Hypocrea jecorina and the multiple cellular roles of ENVOY in this process

<p>Abstract</p> <p>Background</p> <p>In fungi, light is primarily known to influence general morphogenesis and both sexual and asexual sporulation. In order to expand the knowledge on the effect of light in fungi and to determine the role of the light regulatory protein ENVOY in the implementation of this effect, we performed a global screen for genes, which are specifically effected by light in the fungus <it>Hypocrea jecorina </it>(anamorph <it>Trichoderma reesei</it>) using Rapid Subtraction Hybridization (RaSH). Based on these data, we analyzed whether these genes are influenced by ENVOY and if overexpression of ENVOY in darkness would be sufficient to execute its function.</p> <p>Results</p> <p>The cellular functions of the detected light responsive genes comprised a variety of roles in transcription, translation, signal transduction, metabolism, and transport. Their response to light with respect to the involvement of ENVOY could be classified as follows: (i) ENVOY-mediated upregulation by light; (ii) ENVOY-independent upregulation by light; (iii) ENVOY-antagonized upregulation by light; ENVOY-dependent repression by light; (iv) ENVOY-independent repression by light; and (v) both positive and negative regulation by ENVOY of genes not responsive to light in the wild-type. ENVOY was found to be crucial for normal growth in light on various carbon sources and is not able to execute its regulatory function if overexpressed in the darkness.</p> <p>Conclusion</p> <p>The different responses indicate that light impacts fungi like <it>H. jecorina </it>at several cellular processes, and that it has both positive and negative effects. The data also emphasize that ENVOY has an apparently more widespread cellular role in this process than only in modulating the response to light.</p

Wildland fire deficit and surplus in the western United States, 1984-2012

Wildland fire is an important disturbance agent in the western US and globally. However, the natural role of fire has been disrupted in many regions due to the influence of human activities, which have the potential to either exclude or promote fire, resulting in a fire deficit or fire surplus, respectively. In this study, we developed a model of expected area burned for the western US as a function of climate from 1984 to 2012. We then quantified departures from expected area burned to identify geographic regions with fire deficit or surplus. We developed our model of area burned as a function of several climatic variables from reference areas with low human influence; the relationship between climate and fire is strong in these areas. We then quantified the degree of fire deficit or surplus for all areas of the western US as the difference between expected (as predicted with the model) and observed area burned from 1984 to 2012. Results indicate that many forested areas in the western US experienced a fire deficit from 1984 to 2012, likely due to fire exclusion by human activities. We also found that large expanses of non-forested regions experienced a fire surplus, presumably due to introduced annual grasses and the prevalence of anthropogenic ignitions. The heterogeneity in patterns of fire deficit and surplus among ecoregions emphasizes fundamentally different ecosystem sensitivities to human influences and suggests that large scale adaptation and mitigation strategies will be necessary in order to restore and maintain resilient, healthy, and naturally functioning ecosystems

Superior Prophylactic Effectiveness of a Recombinant FVIIIFc Over Standard Half-Life FVIII in Hemophilia A: A-SURE Study.

Objectives The 24-month, prospective, non-interventional, European multicenter A-SURE study evaluated the real-world effectiveness of prophylaxis using an extended half-life recombinant factor VIII (FVIII) Fc fusion protein, efmoroctocog alfa (hereinafter rFVIIIFc), compared with prophylaxis using standard half-life (SHL) FVIII products in patients with hemophilia A. Methods Primary endpoints were annualized bleeding rate (ABR), annualized injection frequency, and annualized factor consumption. A comparative study design unique for an observational hemophilia study was implemented to reduce potential confounding in effectiveness estimates, wherein each patient prescribed rFVIIIFc was matched with one receiving SHL FVIII. Propensity scores were used for adjustment in statistical analyses. Results Outcomes for all primary endpoints were significantly better in the rFVIIIFc group (n = 184) compared with the SHL FVIII group (n = 170): mean ABR 1.5 versus 2.3 (difference of -0.8; p = 0.0147); mean annualized injection frequency 114.4 versus 169.2 (difference of -54.8; p &lt; 0.0001); and mean annualized factor consumption 243 024.2 versus 288 718.6 International Units (difference of 45 694.5; p = 0.0003). rFVIIIFc was well tolerated, with no inhibitor development. Conclusions rFVIIIFc has superior prophylactic effectiveness versus SHL FVIII, providing higher bleed protection with fewer injections and lower factor consumption