Direct Mediation and Metastable Supersymmetry Breaking for SO(10)

We examine a metastable $\mathcal{N}=1$ Macroscopic SO(N) SQCD model of Intriligator, Seiberg and Shih (ISS). We introduce various baryon and meson deformations, including multitrace operators and explore embedding an SO(10) parent of the standard model into two weakly gauged flavour sectors. Direct fundamental messengers and the symmetric pseudo-modulus messenger mediate SUSY breaking to the MSSM. Gaugino and sfermion masses are computed and compared for each deformation type. We also explore reducing the rank of the magnetic quark matrix of the ISS model and find an additional fundamental messenger.Comment: 43 pages, Latex. Version to appear in JHEP

Holographic Vitrification

We establish the existence of stable and metastable stationary black hole bound states at finite temperature and chemical potentials in global and planar four-dimensional asymptotically anti-de Sitter space. We determine a number of features of their holographic duals and argue they represent structural glasses. We map out their thermodynamic landscape in the probe approximation, and show their relaxation dynamics exhibits logarithmic aging, with aging rates determined by the distribution of barriers.Comment: 100 pages, 25 figure

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

It’s all about the money? A qualitative study of healthcare worker motivation in urban China

Background China’s healthcare reform programme continues to receive much attention. Central to these discussions has been how the various financial incentives underpinning reform efforts are negatively impacting on the healthcare workforce. Research continues to document these trends, however, qualitative analysis of how these incentives impact on the motivation of healthcare workers remains underdeveloped. Furthermore, the application of motivational theories to make sense of healthcare worker experiences has yet to be undertaken. Methods The purpose of our paper is to present a comparative case study account of healthcare worker motivation across urban China. It draws on semi structured interviews (n = 89) with a range of staff and organisations across three provinces. In doing so, the paper analyses how healthcare worker motivation is influenced by a variety of financial incentives; how motivation is influenced by the opportunities for career development; and how motivation is influenced by the day to day pressures of meeting patient expectations. Results The experience of healthcare workers in China highlights how a reliance on financial incentives has challenged their ability to maintain the values and ethos of public service. Our findings suggest greater attention needs to be paid to the motivating factors of improved income and career development. Further work is also needed to nurture and develop the motivation of healthcare workers through the building of trust between fellow workers, patients, and the public. Conclusions Through the analysis of healthcare worker motivation, our paper presents a number of ways China can improve its current healthcare reform efforts. It draws on the experience of other countries in calling for policy makers to support alternative approaches to healthcare reform that build on multiple channels of motivation to support healthcare workers

Regulation of membrane ruffling by polarized STIM1 and ORAI1in cortactin-rich domains

La movilidad celular y la migración requieren la reorganización del citoesqueleto cortical en el borde principal de las células y la entrada de Ca2 + extracelular es esencial para esta reorganización. Sin embargo, la naturaleza molecular de los reguladores de esta vía es desconocida. Este trabajo contribuye a comprender el papel de STIM1 y ORAI1 en la promoción de la ondulación de la membrana al mostrar que la fosfo-STIM1 se localiza en el borde principal de las células, y que tanto phospho-STIM1 como ORAI1 se localizan conjuntamente con la cortactina (CTTN), un regulador del citoesqueleto en las zonas de rizo de la membrana. Las líneas celulares STIM1-KO y ORAI1-KO se generaron mediante la edición del genoma CRISPR / Cas9 en células U2OS. En ambos casos, las células KO presentaron una reducción notable de la entrada de Ca2 + operada por el almacén (SOCE) que se rescató mediante la expresión de STIM1-mCherry y ORAI1-mCherry. Estos resultados demostraron que SOCE regula la deformación de la membrana en el borde anterior de las células. Por otra parte, ORAI1 endógeno y ORAI1-GFP sobreexpresado coinmuno precipitado con CTTN endógeno. Este último resultado, además del fenotipo de las células KO, la preservación de la co-localización de ORAI1-CTTN durante el fruncido, y la inhibición de la rizo de la membrana por parte del inhibidor del canal de Ca2 + SKF96365, apoya aún más un vínculo funcional entre el SOCE y el fruncido de la membrana.Cell motility and migration requires the reorganization of the cortical cytoskeleton at the leading edge of cells and extracellular Ca2+ entry is essential for this reorganization. However the molecular nature of the regulators of this pathway is unknown. This work contributes to understanding the role of STIM1 and ORAI1 in the promotion of membrane ruffling by showing that phospho-STIM1 localizes at the leading edge of cells, and that both phospho-STIM1 and ORAI1 co-localize with cortactin (CTTN), a regulator of the cytoskeleton at membrane ruffling areas. STIM1-KO and ORAI1-KO cell lines were generated by CRISPR/Cas9 genome editing in U2OS cells. In both cases, KO cells presented a notable reduction of store-operated Ca2+ entry (SOCE) that was rescued by expression of STIM1-mCherry and ORAI1-mCherry. These results demonstrated that SOCE regulates membrane ruffling at the leading edge of cells. Moreover, endogenous ORAI1 and overexpressed ORAI1-GFP co-immuno precipitated with endogenous CTTN. This latter result, in addition to the KO cells’ phenotype, the preservation of ORAI1-CTTN co-localization during ruffling, and the inhibition of membrane ruffling g by the Ca2+- channel inhibitor SKF96365, further supports a functional link between SOCE and membrane ruffling.• Ministerio de Economía y Competitividad y Fondo Social Europeo. Becas BFU2011-22798 y BFU2014-52401-P, para Francisco Javier Martín Romero • Consejo de Investigación Médica. Beca MC_UU_12016 / 2, para Darío R. Alessi • Ministerio de Economía y Competitividad. Beca BES-2012-052061, para Aida María López Guerrero • Gobierno de Extremadura. Ayuda PD10081, para Patricia Tomás Martín • Ministerio de Educación, Cultura y Deporte. Beca FPU13 / 03430, para Carlos Pascual Caro • Consejo de Investigación Médica. Ayuda MR / K015869 / 1, para Graeme Ball • EMBO. Beca ASTF-311-2014, para Eulalia Pozo Guisado • Ministerio de Educación, Cultura Española y Deporte. Beca PRX14 / 00176, para Francisco Javier Martín RomeropeerReviewe

Polymorphism analysis of the CTLA-4 gene in paracoccidioidomycosis patients

The CTLA-4 protein is expressed in activated T cells and plays an essential role in the immune response through its regulatory effect on T cell activation. Polymorphisms of the CTLA-4 gene have been correlated with autoimmune, neoplastic and infectious illnesses. This work aimed to verify possible associations between single nucleotide polymorphisms (SNPs) in CTLA-4, -318C/T in the promoter and +49A/G in exon 1 and paracoccidioidomycosis (PCM) caused by Paracoccidioides brasiliensis. For this purpose, 66 chronic form PCM patients and 76 healthy controls had their allele, genotype and haplotype frequencies determined. The genetic admixture structure of the patients and controls was evaluated to eliminate ancestral bias. The comparison of frequencies indicated no significant differences between patients and controls that could link the SNPs to PCM. Groups were admixture matched with no difference observed in population ancestry inference, indicating that the absence of association between CTLA-4 polymorphisms and PCM could not be attributed to ancestral bias. This study showed that there was no association between the CTLA-4 SNPs -318 and +49 and the resistance or susceptibility to PCM

The deuteron: structure and form factors

A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets