2,197 research outputs found

    Beyond non-backtracking:Non-cycling network centrality measures

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    Walks around a graph are studied in a wide range of fields, from graph theory and stochastic analysis to theoretical computer science and physics. In many cases it is of interest to focus on non-backtracking walks; those that do not immediately revisit their previous location. In the network science context,imposing a non-backtracking constraint on traditional walk-based node centrality measures is known to offer tangible benefits. Here, we use the Hashimoto matrix construction to characterize, generalize and study such non-backtracking centrality measures. We then devise a recursive extension that systematically removes triangles, squares and, generally, all cycles up to a given length. By characterizing the spectral radius of appropriate matrix power series, we explore how the universality results on the limiting behaviour of classical walk-based centrality measures extend to these non-cycling cases. We also demonstrate that the new recursive construction gives rise to practical centrality measures that can be applied to large scale networks

    K-ATP channel gene expression is induced by urocortin and mediates its cardioprotective effect

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    Background-Urocortin is a novel cardioprotective agent that can protect cardiac myocytes from the damaging effects of ischemia/reperfusion both in culture and in the intact heart and is effective when given at reperfusion.Methods and Results-We have analyzed global changes in gone expression in cardiac myocytes after urocortin treatment using gene chip technology. We report that urocortin specifically induces enhanced expression of the Kir 6.1 cardiac potassium channel subunit. On the basis of this finding, we showed that the cardioprotective effect of urocortin both in isolated cardiac cells and in the intact heart is specifically blocked by both generalized and mitochondrial-specific K-ATP channel blockers, whereas the cardioprotective effect of cardiotrophin-1 is unaffected. Conversely, inhibiting the Kir 6.1 channel subunit greatly enhances cardiac cell death after ischemia.Conclusions-This is, to our knowledge, the first report of the altered expression of a K-ATP. channel subunit induced by a cardioprotective agent and demonstrates that K-ATP, channel opening is essential for the effect of this novel cardioprotective agent

    Automated Suturing For Pacemaker Lead Placement Via Video Guided Minimally Invasive Surgical Access

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    The placement of permanent and temporary cardiac epicardial pacemaker leads through minimally invasive cardiac surgery (MICS) access remains a challenge. A reliable ergonomic approach for remote lead placement requires improved technology. We present a novel means to enable the remote placement of epicardial leads using automated suturing devices and videoscopy

    Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders.

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    Common Variable Immunodeficiency Disorders (CVIDs) are the most prevalent cause of primary antibody failure. CVIDs are highly variable and a genetic causes have been identified in <5% of patients. Here, we performed whole genome sequencing (WGS) of 34 CVID patients (94% sporadic) and combined them with transcriptomic profiling (RNA-sequencing of B cells) from three patients and three healthy controls. We identified variants in CVID disease genes TNFRSF13B, TNFRSF13C, LRBA and NLRP12 and enrichment of variants in known and novel disease pathways. The pathways identified include B-cell receptor signalling, non-homologous end-joining, regulation of apoptosis, T cell regulation and ICOS signalling. Our data confirm the polygenic nature of CVID and suggest individual-specific aetiologies in many cases. Together our data show that WGS in combination with RNA-sequencing allows for a better understanding of CVIDs and the identification of novel disease associated pathways

    Central Iliac Arteriovenous Anastomosis for Hypertension: Targeting Mechanical Aspects of the Circulation

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    Dr. Lobo reports personal fees from ROX Medical, St Jude Medical, and Cardiosonic, and grants from Medtronic. Dr. Stanton reports that ROX Medical funded the ROX CONTROL HTN study. Dr. Sobotka reports personal fees and equity from ROX Medical; equity in Cibiem, Ablative Solutions, and Rainbow Medical; and personal fees from Abbott Ventures and Boston Scientific

    Second-order Democratic Aggregation

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    Aggregated second-order features extracted from deep convolutional networks have been shown to be effective for texture generation, fine-grained recognition, material classification, and scene understanding. In this paper, we study a class of orderless aggregation functions designed to minimize interference or equalize contributions in the context of second-order features and we show that they can be computed just as efficiently as their first-order counterparts and they have favorable properties over aggregation by summation. Another line of work has shown that matrix power normalization after aggregation can significantly improve the generalization of second-order representations. We show that matrix power normalization implicitly equalizes contributions during aggregation thus establishing a connection between matrix normalization techniques and prior work on minimizing interference. Based on the analysis we present {\gamma}-democratic aggregators that interpolate between sum ({\gamma}=1) and democratic pooling ({\gamma}=0) outperforming both on several classification tasks. Moreover, unlike power normalization, the {\gamma}-democratic aggregations can be computed in a low dimensional space by sketching that allows the use of very high-dimensional second-order features. This results in a state-of-the-art performance on several datasets

    Communities of practice for contemporary leadership development and knowledge exchange through work-based learning

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    This study explores the experiences of leaders who have led organisations and teams through an extended period of crisis management whilst completing a UK work-based master’s programme. This paper examines contemporary approaches to work-based learning and explores the effect of organisational and workforce demands in a volatile era of global economic uncertainty. Theoretical and conceptual foundations relating to experiential learning, digital education and communities of learning are analysed and discussed. Taking an inductive qualitative approach, the study analyses semi-structured questionnaire data from senior leaders. The widespread adoption of technology exposes challenges to facilitation and the academic-employer interface, impacting upon learning communities and knowledge exchange opportunities. The findings also suggest enhanced leaders’ adaptive traits, including confidence and self-reliance. This study illuminates critical issues associated with contemporary workbased learning, specifically relating to prolonged macro uncertainty and the effect upon workplaces as sites of knowledge and learning, and risks to dynamic relationships between the psychosocial work environment, genuine opportunities to learn and learner well-being. This work seeks to inform the design of future programs, specifically in terms developing inter and intra-organisational communities of learning and knowledge exchange to enhance best practice and inculcate crucial leadership skills

    The Imprint of Galaxy Formation on X-ray Clusters

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    It is widely believed that structure in the Universe evolves hierarchically, as primordial density fluctuations, amplified by gravity, collapse and merge to form progressively larger systems. The structure and evolution of X-ray clusters, however, seems at odds with this hierarchical scenario for structure formation. Poor clusters and groups, as well as most distant clusters detected to date, are substantially fainter than expected from the tight relations between luminosity, temperature and redshift predicted by these models. Here we show that these discrepancies arise because, near the centre, the entropy of the hot, diffuse intracluster medium (ICM) is higher thaachievablethroughgravitationalcollapse,indicatingsubstantialnongravitationalheatingoftheICM.Weestimatethisexcessentropyforthefirsttime,andarguethatitrepresentsarelicoftheenergeticwindsthroughwhichforminggalaxiespollutedtheICMwithmetals.Energetically,thisisonl achievable through gravitational collapse, indicating substantial non-gravitational heating of the ICM. We estimate this excess entropy for the first time, and argue that it represents a relic of the energetic winds through which forming galaxies polluted the ICM with metals. Energetically, this is onl possible if the ICM is heated at modest redshift (z \ltsim 2) but prior to cluster collapse, indicating that the formation of galaxies precedes that of clusters and that most clusters have been assembled very recently.Comment: 5 pages, plus 2 postscript figures (one in colour), accepted for publication in Natur

    The intestinal expulsion of the roundworm Ascaris suum is associated with eosinophils, intra-epithelial T cells and decreased intestinal transit time

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    Ascaris lumbricoides remains the most common endoparasite in humans, yet there is still very little information available about the immunological principles of protection, especially those directed against larval stages. Due to the natural host-parasite relationship, pigs infected with A. suum make an excellent model to study the mechanisms of protection against this nematode. In pigs, a self-cure reaction eliminates most larvae from the small intestine between 14 and 21 days post infection. In this study, we investigated the mucosal immune response leading to the expulsion of A. suum and the contribution of the hepato-tracheal migration. Self-cure was independent of previous passage through the liver or lungs, as infection with lung stage larvae did not impair self-cure. When animals were infected with 14-day-old intestinal larvae, the larvae were being driven distally in the small intestine around 7 days post infection but by 18 days post infection they re-inhabited the proximal part of the small intestine, indicating that more developed larvae can counter the expulsion mechanism. Self-cure was consistently associated with eosinophilia and intra-epithelial T cells in the jejunum. Furthermore, we identified increased gut movement as a possible mechanism of self-cure as the small intestinal transit time was markedly decreased at the time of expulsion of the worms. Taken together, these results shed new light on the mechanisms of self-cure that occur during A. suum infections

    Alcohol consumption and lifetime change in cognitive ability:a gene × environment interaction study

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    Studies of the effect of alcohol consumption on cognitive ability are often confounded. One approach to avoid confounding is the Mendelian randomization design. Here, we used such a design to test the hypothesis that a genetic score for alcohol processing capacity moderates the association between alcohol consumption and lifetime change in cognitive ability. Members of the Lothian Birth Cohort 1936 completed the same test of intelligence at age 11 and 70 years. They were assessed for recent alcohol consumption in later life and genotyped for a set of four single-nucleotide polymorphisms in three alcohol dehydrogenase genes. These variants were unrelated to late-life cognition or to socioeconomic status. We found a significant gene × alcohol consumption interaction on lifetime cognitive change (p = 0.007). Individuals with higher genetic ability to process alcohol showed relative improvements in cognitive ability with more consumption, whereas those with low processing capacity showed a negative relationship between cognitive change and alcohol consumption with more consumption. The effect of alcohol consumption on cognitive change may thus depend on genetic differences in the ability to metabolize alcohol
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