408 research outputs found

    From Rotating Atomic Rings to Quantum Hall States

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    Considerable efforts are currently devoted to the preparation of ultracold neutral atoms in the emblematic strongly correlated quantum Hall regime. The routes followed so far essentially rely on thermodynamics, i.e. imposing the proper Hamiltonian and cooling the system towards its ground state. In rapidly rotating 2D harmonic traps the role of the transverse magnetic field is played by the angular velocity. For particle numbers significantly larger than unity, the required angular momentum is very large and it can be obtained only for spinning frequencies extremely near to the deconfinement limit; consequently, the required control on experimental parameters turns out to be far too stringent. Here we propose to follow instead a dynamic path starting from the gas confined in a rotating ring. The large moment of inertia of the fluid facilitates the access to states with a large angular momentum, corresponding to a giant vortex. The initial ring-shaped trapping potential is then adiabatically transformed into a harmonic confinement, which brings the interacting atomic gas in the desired quantum Hall regime. We provide clear numerical evidence that for a relatively broad range of initial angular frequencies, the giant vortex state is adiabatically connected to the bosonic ν=1/2\nu=1/2 Laughlin state, and we discuss the scaling to many particles.Comment: 9 pages, 5 figure

    Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence

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    Bis-(3 ',5 ') cyclic di-guanylate (cyclic di-GMP) is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc). This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K-d similar to 2 mu M). Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence

    Allele-specific miRNA-binding analysis identifies candidate target genes for breast cancer risk

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    Most breast cancer (BC) risk-associated single-nucleotide polymorphisms (raSNPs) identified in genome-wide association studies (GWAS) are believed to cis-regulate the expression of genes. We hypothesise that cis-regulatory variants contributing to disease risk may be affecting microRNA (miRNA) genes and/or miRNA binding. To test this, we adapted two miRNA-binding prediction algorithms-TargetScan and miRanda-to perform allele-specific queries, and integrated differential allelic expression (DAE) and expression quantitative trait loci (eQTL) data, to query 150 genome-wide significant ( P≤5×10-8 ) raSNPs, plus proxies. We found that no raSNP mapped to a miRNA gene, suggesting that altered miRNA targeting is an unlikely mechanism involved in BC risk. Also, 11.5% (6 out of 52) raSNPs located in 3'-untranslated regions of putative miRNA target genes were predicted to alter miRNA::mRNA (messenger RNA) pair binding stability in five candidate target genes. Of these, we propose RNF115, at locus 1q21.1, as a strong novel target gene associated with BC risk, and reinforce the role of miRNA-mediated cis-regulation at locus 19p13.11. We believe that integrating allele-specific querying in miRNA-binding prediction, and data supporting cis-regulation of expression, improves the identification of candidate target genes in BC risk, as well as in other common cancers and complex diseases.Funding Agency Portuguese Foundation for Science and Technology CRESC ALGARVE 2020 European Union (EU) 303745 Maratona da Saude Award DL 57/2016/CP1361/CT0042 SFRH/BPD/99502/2014 CBMR-UID/BIM/04773/2013 POCI-01-0145-FEDER-022184info:eu-repo/semantics/publishedVersio

    Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

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    Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion

    Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

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    Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

    Exploring CRM effectiveness: an institutional theory perspective

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    This study identifies the potential contribution that institutional theory can make to understanding the success of marketing practices. Based on institutional theory, we argue that the effectiveness of marketing practices decreases when firms are motivated to adopt such practices under the influence of institutional pressures originating in firms' environments. However, alignment between a practice and a firm's marketing strategy may buffer against these negative effects. We apply these insights to the case of customer relationship management (CRM). CRM is considered an important way to enhance customer loyalty and firm performance, but it has also been criticized for being expensive and for not living up to expectations. Empirical data from 107 organizations confirm that, in general, adopting CRM for mimetic motives is likely to result in fewer customer insights as a result of using this practice. Our study suggests that institutional theory has much to offer to the investigation of the effectiveness of marketing practices

    Recurrent airway obstructions in a patient with benign tracheal stenosis and a silicone airway stent: a case report

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    Airway stents (silicone and metal stents) are used to treat patients with benign tracheal stenosis, who are symptomatic and in whom tracheal surgical reconstruction has failed or is not appropriate. However airway stents are often associated with complications such as migration, granuloma formation and mucous hypersecretion, which cause significant morbidity, especially in patients with benign tracheal stenosis and relatively normal life expectancy. We report a patient who had frequent critical airway obstructions over 8 years due to granuloma and mucus hypersecretion in a silicone airway stent. The problem was resolved when the silicone stent was removed and replaced with a covered self expanding metal stent

    Anodization of nanoporous alumina on impurity-induced hemisphere curved surface of aluminum at room temperature

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    Nanoporous alumina which was produced by a conventional direct current anodization [DCA] process at low temperatures has received much attention in various applications such as nanomaterial synthesis, sensors, and photonics. In this article, we employed a newly developed hybrid pulse anodization [HPA] method to fabricate the nanoporous alumina on a flat and curved surface of an aluminum [Al] foil at room temperature [RT]. We fabricate the nanopores to grow on a hemisphere curved surface and characterize their behavior along the normal vectors of the hemisphere curve. In a conventional DCA approach, the structures of branched nanopores were grown on a photolithography-and-etched low-curvature curved surface with large interpore distances. However, a high-curvature hemisphere curved surface can be obtained by the HPA technique. Such a curved surface by HPA is intrinsically induced by the high-resistivity impurities in the aluminum foil and leads to branching and bending of nanopore growth via the electric field mechanism rather than the interpore distance in conventional approaches. It is noted that by the HPA technique, the Joule heat during the RT process has been significantly suppressed globally on the material, and nanopores have been grown along the normal vectors of a hemisphere curve. The curvature is much larger than that in other literatures due to different fabrication methods. In theory, the number of nanopores on the hemisphere surface is two times of the conventional flat plane, which is potentially useful for photocatalyst or other applications

    Factors associated with infant mortality in Nepal: a comparative analysis of Nepal demographic and health surveys (NDHS) 2006 and 2011

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    Background: Infant mortality is one of the priority public health issues in developing countries like Nepal. The infant mortality rate (IMR) was 48 and 46 per 1000 live births for the year 2006 and 2011, respectively, a slight reduction during the 5 years’ period. A comprehensive analysis that has identified and compared key factors associated with infant mortality is limited in Nepal, and, therefore, this study aims to fill the gap. Methods: Datasets from Nepal Demographic and Health Surveys (NDHS) 2006 and 2011 were used to identify and compare the major factors associated with infant mortality. Both surveys used multistage stratified cluster sampling techniques. A total of 8707 and 10,826 households were interviewed in 2006 and 2011, with more than 99% response rate in both studies. The survival information of singleton live-born infants born 5 years preceding the two surveys were extracted from the ‘childbirth’ dataset. Multiple logistic regression analysis using a hierarchical modelling approach with the backward elimination method was conducted. Complex Samples Analysis was used to adjust for unequal selection probability due to the multistage stratified cluster-sampling procedure used in both NDHS.Results: Based on NDHS 2006, ecological region, succeeding birth interval, breastfeeding status and type of delivery assistance were found to be significant predictors of infant mortality. Infants born in hilly region (AOR = 0.43, p = 0.013) and with professional assistance (AOR = 0.27, p = 0.039) had a lower risk of mortality. On the other hand, infants with succeeding birth interval less than 24 months (AOR = 6.66, p = 0.001) and those who were never breastfed (AOR = 1.62, p = 0.044) had a higher risk of mortality. Based on NDHS 2011, birth interval (preceding and succeeding) and baby’s size at birth were identified to be significantly associated with infant mortality. Infants born with preceding birth interval (AOR = 1.94, p = 0.022) or succeeding birth interval (AOR = 3.22, p = 0.002) shorter than 24 months had higher odds of mortality while those born with a very large or larger than average size had significantly lowered odds (AOR = 0.17, p = 0.008) of mortality. Conclusion: IMR and associated risk factors differ between NDHS 2006 and 2011 except ‘succeeding birth interval’ which attained significant status in the both study periods. This study identified the ecological region, birth interval, delivery assistant type, baby’s birth size and breastfeeding status as significant predictors of infant mortality
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