Constraints on Muon Decay Parameters from Neutrino Mass

We derive model-independent constraints on chirality-changing terms in the muon decay Lagrangian using limits on neutrino mass. We consider all dimension-six operators invariant under the gauge symmetry of the Standard Model which contribute to either a Dirac neutrino mass or muon decay. Taking an upper limit on neutrino mass of 1 eV, we derive limits on the contributions of chirality-changing operators to the Michel parameters four orders of magnitude tighter than the current experimental constraints. We also identify two operators which, due to their flavor structure, are not constrained by neutrino mass. If near-future experiments find contributions to muon decay from these operators, it could indicate interesting flavor structure in physics beyond the SM.Comment: 4 pages, contribution to the proceedings of CIPANP 2006 (May 30-June 3, 2006), Rio Grande, Puerto Ric

Constraints on Muon Decay Parameters from Neutrino Mass

We use experimental limits on the neutrino mass to derive model‐independent upper bounds on various muon decay parameters. We find that the bounds obtained in this way are improved by more than three orders of magnitude over current experimental limits

Neutrino Mass Implications for Muon Decay Parameters

We use the scale of neutrino mass to derive model-independent naturalness constraints on possible contributions to muon decay Michel parameters from new physics above the electroweak symmetry-breaking scale. Focusing on Dirac neutrinos, we obtain a complete basis of effective dimension four and dimension six operators that are invariant under the gauge symmetry of the Standard Model and that contribute to both muon decay and neutrino mass. We show that -- in the absence of fine tuning -- the most stringent bounds on chirality-changing operators relevant to muon decay arise from one-loop contributions to neutrino mass. The bounds we obtain on their contributions to the Michel parameters are four or more orders of magnitude stronger than bounds previously obtained in the literature. We also show that there exist chirality-changing operators that contribute to muon decay but whose flavor structure allows them to evade neutrino mass naturalness bounds. We discuss the implications of our analysis for the interpretation of muon decay experiments.Comment: 19 pages, 4 figure

Chaperoned amyloid proteins for immune manipulation: a-Synuclein/Hsp70 shifts immunity toward a modulatory phenotype

α-Synuclein (αSyn) is a 140-residue amyloid-forming protein whose aggregation is linked to Parkinson's disease (PD). It has also been found to play a critical role in the immune imbalance that accompanies disease progression, a characteristic that has prompted the search for an effective αSyn-based immunotherapy. In this study, we have simultaneously exploited two important features of certain heat-shock proteins (HSPs): their classical “chaperone” activities and their recently discovered and diverse “immunoactive” properties. In particular, we have explored the immune response elicited by immunization of C57BL/6 mice with an αSyn/Hsp70 protein combination in the absence of added adjuvant. Our results show differential effects for mice immunized with the αSyn/Hsp70 complex, including a restrained αSyn-specific (IgM and IgG) humoral response as well as minimized alterations in the Treg (CD4+CD25+Foxp3+) and Teff (CD4+Foxp3−) cell populations, as opposed to significant changes in mice immunized with αSyn and Hsp70 alone. Furthermore, in vitro-stimulated splenocytes from immunized mice showed the lowest relative response against αSyn challenge for the “αSyn/Hsp70” experimental group as measured by IFN-γ and IL-17 secretion, and higher IL-10 levels when stimulated with LPS. Finally, serum levels of Th1-cytokine IFN-γ and immunomodulatory IL-10 indicated a unique shift toward an immunomodulatory/immunoprotective phenotype in mice immunized with the αSyn/Hsp70 complex. Overall, we propose the use of functional “HSP-chaperoned amyloid/aggregating proteins” generated with appropriate HSP-substrate protein combinations, such as the αSyn/Hsp70 complex, as a novel strategy for immune-based intervention against synucleinopathies and other amyloid or “misfolding” neurodegenerative disorders.España, Ministerio de Economía y Competitividad SAF-2012/39720Junta de Andalucía P10-CTS-6928Junta de Andalucía P11-CTS-816

Анализ методов вибродиагностики металлорежущих станков

Цель работы - выработка рекомендаций по применению методов вибродиагностики металлорежущих станков в конкретной задаче. Объект исследования - методы и комплексы вибродиагностики металлорежущих станков. Предмет исследования – систематизация и обобщение методов вибродиагностики металлорежущих станков. Актуальность - отсутствие простой для реализации методики виброиспытаний. В процессе работы были рассмотрены различные методы вибродиагностики металлорежущих станков, сделаны предложения по применению методов вибродиагностики металлорежущих станков в каждой конкретной задаче, создана универсальная методика проведения вибродиагностики металлорежущих станков диагностическим комплексом "Виброрегистратор-М2".The aim of the work is to develop recommendations on the application of vibration diagnostics methods for metal-cutting machine tools in a specific task. The object of research is methods and complexes of vibration diagnostics of metal cutting machines. The subject of the study is the systematization and generalization of methods of vibration diagnostics of metal-cutting machines. Actuality is the absence of a simple vibration testing technique. In the course of the work various methods of vibration diagnostics of metal cutting machines were considered, suggestions were made on the application of vibration diagnostics methods for metal cutting machines in each specific task, a universal technique for performing vibration diagnostics of metal cutting machines with the Vibroregistrator-M2

Chaperoned amyloid proteins for immune manipulation: A-synuclein/hsp70 shifts immunity toward a modulatory phenotype

a-Synuclein (aSyn) is a 140-residue amyloid-forming protein whose aggregation is linked to Parkinson’s disease (PD). It has also been found to play a critical role in the immune imbalance that accompanies disease progression, a characteristic that has prompted the search for an effective aSyn-based immunotherapy. In this study, we have simultaneously exploited two important features of certain heat-shock proteins (HSPs): their classical ‘‘chaperone’’ activities and their recently discovered and diverse ‘‘immunoactive’’ properties. In particular, we have explored the immune response elicited by immunization of C57BL/6 mice with an aSyn/Hsp70 protein combination in the absence of added adjuvant. Our results show differential effects for mice immunized with the aSyn/Hsp70 complex, including a restrained aSyn-specific (IgM and IgG) humoral response as well as minimized alterations in the Treg (CD4 CD25 Foxp3 ) and Teff (CD4 Foxp3 ) cell populations, as opposed to significant changes in mice immunized with aSyn and Hsp70 alone. Furthermore, in vitro-stimulated splenocytes from immunized mice showed the lowest relative response against aSyn challenge for the ‘‘aSyn/Hsp70’’ experimental group as measured by IFN-g and IL-17 secretion, and higher IL-10 levels when stimulated with LPS. Finally, serum levels of Th1-cytokine IFN-g and immunomodulatory IL-10 indicated a unique shift toward an immunomodulato-ry/immunoprotective phenotype in mice immunized with the aSyn/Hsp70 complex. Overall, we propose the use of functional ‘‘HSP-chaperoned amyloid/ aggregating proteins’’ generated with appropriate HSP-substrate protein combinations, such as the aSyn/Hsp70 complex, as a novel strategy for immune-based intervention against synucleinopathies and other amyloid or ‘‘misfolding’’ neurodegenerative disorders.Financial support was provided by the Carlos III Institute of Health of Spain (Spanish Ministry of Economy and Competitiveness) according to the Strategic Action in Health (CP10/00527 to CR; PI14-01600 to DP) with co-funding by FEDER funds, the Spanish Ministry of Economy and Competitiveness (SAF-2012/39720 to CR), the Andalusian Ministry of Economy, Science and Innovation (P10-CTS-6928 and P11-CTS-8161 to DP) and the PAIDI Program from the Andalusian Government (CTS- 677 to DP). ALG holds a FPU Predoctoral Fellowship from the Spanish Ministry of Education (AP-2009/3816). The works of EJDG and CMD are supported by the Wellcome Trust, and the UK Medical, and Biotechnological and Biological Sciences Research Councils

Longitudinal assessment of cognitive and psychosocial functioning after Hurricanes Katrina and Rita: Exploring disaster impact on middle-aged, older, and oldest-old adults

The authors examined the effects of Hurricanes Katrina and Rita on cognitive and psychosocial functioning in a lifespan sample of adults 6-14 months after the storms. Participants were recruited from the Louisiana Healthy Aging Study. Most were assessed during the immediate impact period and retested for this study. Analyses of pre- and post-disaster cognitive data confirmed that storm-related decrements in working memory for middle-aged and older adults observed in the immediate impact period had returned to pre-hurricane levels in the post-disaster recovery period. Middle-aged adults reported more storm-related stressors and greater levels of stress than the two older groups at both waves of testing. These results are consistent with a burden perspective on post-disaster psychological reactions. © 2012 Wiley Periodicals, Inc

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) \u3c 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p \u3c 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment