237 research outputs found
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
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
Constraints on Muon Decay Parameters from Neutrino Mass
We use experimental limits on the neutrino mass to derive modelâindependent 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
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 âchaperoneâ activities and their recently discovered and diverse âimmunoactiveâ 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+Foxp3â) 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 âαSyn/Hsp70â experimental group as measured by IFN-Îł and IL-17 secretion, and higher IL-10 levels when stimulated with LPS. Finally, serum levels of Th1-cytokine IFN-Îł 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 âHSP-chaperoned amyloid/aggregating proteinsâ 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 âmisfoldingâ neurodegenerative disorders.España, Ministerio de EconomĂa y Competitividad SAF-2012/39720Junta de AndalucĂa P10-CTS-6928Junta de AndalucĂa P11-CTS-816
ĐĐœĐ°Đ»ĐžĐ· ĐŒĐ”ŃĐŸĐŽĐŸĐČ ĐČОбŃĐŸĐŽĐžĐ°ĐłĐœĐŸŃŃĐžĐșĐž ĐŒĐ”ŃĐ°Đ»Đ»ĐŸŃДжŃŃĐžŃ ŃŃĐ°ĐœĐșĐŸĐČ
ĐŠĐ”Đ»Ń ŃĐ°Đ±ĐŸŃŃ - ĐČŃŃĐ°Đ±ĐŸŃĐșĐ° ŃĐ”ĐșĐŸĐŒĐ”ĐœĐŽĐ°ŃĐžĐč ĐżĐŸ ĐżŃĐžĐŒĐ”ĐœĐ”ĐœĐžŃ ĐŒĐ”ŃĐŸĐŽĐŸĐČ ĐČОбŃĐŸĐŽĐžĐ°ĐłĐœĐŸŃŃĐžĐșĐž ĐŒĐ”ŃĐ°Đ»Đ»ĐŸŃДжŃŃĐžŃ
ŃŃĐ°ĐœĐșĐŸĐČ ĐČ ĐșĐŸĐœĐșŃĐ”ŃĐœĐŸĐč Đ·Đ°ĐŽĐ°ŃĐ”. ĐбŃĐ”ĐșŃ ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžŃ - ĐŒĐ”ŃĐŸĐŽŃ Đž ĐșĐŸĐŒĐżĐ»Đ”ĐșŃŃ ĐČОбŃĐŸĐŽĐžĐ°ĐłĐœĐŸŃŃĐžĐșĐž ĐŒĐ”ŃĐ°Đ»Đ»ĐŸŃДжŃŃĐžŃ
ŃŃĐ°ĐœĐșĐŸĐČ. ĐŃĐ”ĐŽĐŒĐ”Ń ĐžŃŃĐ»Đ”ĐŽĐŸĐČĐ°ĐœĐžŃ â ŃĐžŃŃĐ”ĐŒĐ°ŃОзаŃĐžŃ Đž ĐŸĐ±ĐŸĐ±ŃĐ”ĐœĐžĐ” ĐŒĐ”ŃĐŸĐŽĐŸĐČ ĐČОбŃĐŸĐŽĐžĐ°ĐłĐœĐŸŃŃĐžĐșĐž ĐŒĐ”ŃĐ°Đ»Đ»ĐŸŃДжŃŃĐžŃ
ŃŃĐ°ĐœĐșĐŸĐČ. ĐĐșŃŃĐ°Đ»ŃĐœĐŸŃŃŃ - ĐŸŃŃŃŃŃŃĐČОД ĐżŃĐŸŃŃĐŸĐč ĐŽĐ»Ń ŃДалОзаŃОО ĐŒĐ”ŃĐŸĐŽĐžĐșĐž ĐČОбŃĐŸĐžŃĐżŃŃĐ°ĐœĐžĐč. Đ ĐżŃĐŸŃĐ”ŃŃĐ” ŃĐ°Đ±ĐŸŃŃ Đ±ŃлО ŃĐ°ŃŃĐŒĐŸŃŃĐ”ĐœŃ ŃазлОŃĐœŃĐ” ĐŒĐ”ŃĐŸĐŽŃ ĐČОбŃĐŸĐŽĐžĐ°ĐłĐœĐŸŃŃĐžĐșĐž ĐŒĐ”ŃĐ°Đ»Đ»ĐŸŃДжŃŃĐžŃ
ŃŃĐ°ĐœĐșĐŸĐČ, ŃĐŽĐ”Đ»Đ°ĐœŃ ĐżŃĐ”ĐŽĐ»ĐŸĐ¶Đ”ĐœĐžŃ ĐżĐŸ ĐżŃĐžĐŒĐ”ĐœĐ”ĐœĐžŃ ĐŒĐ”ŃĐŸĐŽĐŸĐČ ĐČОбŃĐŸĐŽĐžĐ°ĐłĐœĐŸŃŃĐžĐșĐž ĐŒĐ”ŃĐ°Đ»Đ»ĐŸŃДжŃŃĐžŃ
ŃŃĐ°ĐœĐșĐŸĐČ ĐČ ĐșĐ°Đ¶ĐŽĐŸĐč ĐșĐŸĐœĐșŃĐ”ŃĐœĐŸĐč Đ·Đ°ĐŽĐ°ŃĐ”, ŃĐŸĐ·ĐŽĐ°ĐœĐ° ŃĐœĐžĐČĐ”ŃŃĐ°Đ»ŃĐœĐ°Ń ĐŒĐ”ŃĐŸĐŽĐžĐșĐ° ĐżŃĐŸĐČĐ”ĐŽĐ”ĐœĐžŃ ĐČОбŃĐŸĐŽĐžĐ°ĐłĐœĐŸŃŃĐžĐșĐž ĐŒĐ”ŃĐ°Đ»Đ»ĐŸŃДжŃŃĐžŃ
ŃŃĐ°ĐœĐșĐŸĐČ ĐŽĐžĐ°ĐłĐœĐŸŃŃĐžŃĐ”ŃĐșĐžĐŒ ĐșĐŸĐŒĐżĐ»Đ”ĐșŃĐŸĐŒ "ĐОбŃĐŸŃДгОŃŃŃĐ°ŃĐŸŃ-Đ2".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 Parkinsonâs 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 ââchaperoneââ activities and their recently discovered and diverse ââimmunoactiveââ 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 ââaSyn/Hsp70ââ 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 ââHSP-chaperoned amyloid/ aggregating proteinsââ 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 ââmisfoldingââ 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
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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 â„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
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
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