Measuring on Lattices

Previous derivations of the sum and product rules of probability theory relied on the algebraic properties of Boolean logic. Here they are derived within a more general framework based on lattice theory. The result is a new foundation of probability theory that encompasses and generalizes both the Cox and Kolmogorov formulations. In this picture probability is a bi-valuation defined on a lattice of statements that quantifies the degree to which one statement implies another. The sum rule is a constraint equation that ensures that valuations are assigned so as to not violate associativity of the lattice join and meet. The product rule is much more interesting in that there are actually two product rules: one is a constraint equation arises from associativity of the direct products of lattices, and the other a constraint equation derived from associativity of changes of context. The generality of this formalism enables one to derive the traditionally assumed condition of additivity in measure theory, as well introduce a general notion of product. To illustrate the generic utility of this novel lattice-theoretic foundation of measure, the sum and product rules are applied to number theory. Further application of these concepts to understand the foundation of quantum mechanics is described in a joint paper in this proceedings.Comment: 13 pages, 7 figures, Presented at the 29th International Workshop on Bayesian and Maximum Entropy Methods in Science and Engineering: MaxEnt 200

Cultural Norms Shaping Research Group Interviews with Chinese American Immigrants

Practical knowledge on how to tailor research methods for Asian Americans is relatively scarce despite the rapid population growth of this ethnic group and the ongoing calls for greater cultural competence among researchers. Based on a 4-year qualitative study of family and cultural issues in diabetes management among Chinese American immigrants, this article presents data-based analyses of culturally nuanced group interview processes, and recommendations for conducting culturally appropriate group interviews. Group interview processes were prominently shaped by 4 cultural norms: sensitivity to social hierarchy, monitoring public display of strong emotions, face concerns, and emphasis on group harmony. Strategies for facilitating open and dynamic group interviews in the presence of these norms were identified. Skillful facilitation of group processes, either by accommodating or diffusing norms, was required to promote participant rapport and encourage disclosure of everyday experience

Acculturation and Bicultural Efficacy Effects on Chinese American Immigrants’ Diabetes and Health Management

The primary goal of this study was to examine effects of bicultural efficacy, or perceived confidence in dealing with bicultural acculturation stressors, on type 2 diabetes management and health for first-generation, Cantonese-speaking, Chinese American immigrants (N=162) recruited for a larger community-based diabetes intervention study (Chesla et al., 2013). The current study also tested whether a new Bicultural Efficacy in Health Management (BEFF-HM) scale is a more robust predictor of diabetes and health outcomes than proxy (years in the U.S.) and general acculturation measures. Hierarchical regression analyses of cross-sectional data revealed that high BEFF-HM was significantly related to positive outcomes on five of six diabetes and health measures as hypothesized after accounting for participant characteristics, proxy and general acculturation measures, and social support. Proxy and general acculturation measures failed to predict any study outcome supporting our secondary hypothesis that BEFF-HM is a better predictor of Chinese American immigrants’ diabetes and health management. An immigrant-focused research approach advances understanding of acculturation and bicultural efficacy effects on health by identifying key acculturation domains for study

Cell-Cycle Modulation of Transcription Termination Factor Sen1

Many non-coding transcripts (ncRNA) generated by RNA polymerase II in S. cerevisiae are terminated by the Nrd1-Nab3-Sen1 complex. However, Sen1 helicase levels are surprisingly low compared with Nrd1 and Nab3, raising questions regarding how ncRNA can be terminated in an efficient and timely manner. We show that Sen1 levels increase during the S and G2 phases of the cell cycle, leading to increased termination activity of NNS. Overexpression of Sen1 or failure to modulate its abundance by ubiquitin-proteasome-mediated degradation greatly decreases cell fitness. Sen1 toxicity is suppressed by mutations in other termination factors, and NET-seq analysis shows that its overexpression leads to a decrease in ncRNA production and altered mRNA termination. We conclude that Sen1 levels are carefully regulated to prevent aberrant termination. We suggest that ncRNA levels and coding gene transcription termination are modulated by Sen1 to fulfill critical cell cycle-specific functions

Bivariate causal mixture model quantifies polygenic overlap between complex traits beyond genetic correlation.

Accumulating evidence from genome wide association studies (GWAS) suggests an abundance of shared genetic influences among complex human traits and disorders, such as mental disorders. Here we introduce a statistical tool, MiXeR, which quantifies polygenic overlap irrespective of genetic correlation, using GWAS summary statistics. MiXeR results are presented as a Venn diagram of unique and shared polygenic components across traits. At 90% of SNP-heritability explained for each phenotype, MiXeR estimates that 8.3 K variants causally influence schizophrenia and 6.4 K influence bipolar disorder. Among these variants, 6.2 K are shared between the disorders, which have a high genetic correlation. Further, MiXeR uncovers polygenic overlap between schizophrenia and educational attainment. Despite a genetic correlation close to zero, the phenotypes share 8.3 K causal variants, while 2.5 K additional variants influence only educational attainment. By considering the polygenicity, discoverability and heritability of complex phenotypes, MiXeR analysis may improve our understanding of cross-trait genetic architectures

SENP3 Promotes an Mff-Primed Bcl-x L -Drp1 Interaction Involved in Cell Death Following Ischemia

Dysregulation of the mitochondrial fission machinery has been linked to cell death following ischemia. Fission is largely dependent on recruitment of Dynamin-related protein 1 (Drp1) to the receptor Mitochondrial fission factor (Mff) located on the mitochondrial outer membrane (MOM). Drp1 is a target for SUMOylation and its deSUMOylation, mediated by the SUMO protease SENP3, enhances the Drp1-Mff interaction to promote cell death in an oxygen/glucose deprivation (OGD) model of ischemia. Another interacting partner for Drp1 is the Bcl-2 family member Bcl-x(L), an important protein in cell death and survival pathways. Here we demonstrate that preventing Drp1 SUMOylation by mutating its SUMO target lysines enhances the Drp1-Bcl-x(L) interaction in vivo and in vitro. Moreover, SENP3-mediated deSUMOylation of Drp1 promotes the Drp1-Bcl-x(L) interaction. Our data suggest that Mff primes Drp1 binding to Bcl-x(L) at the mitochondria and that Mff and Bcl-x(L) can interact directly, independent of Drp1, through their transmembrane domains. Importantly, SENP3 loss in cells subjected to OGD correlates with reduced Drp1-Bcl-x(L) interaction, whilst recovery of SENP3 levels in cells subjected to reoxygenation following OGD correlates with increased Drp1-Bcl-x(L) interaction. Expressing a Bcl-x(L) mutant with defective Drp1 binding reduces OGD plus reoxygenation-evoked cell death. Taken together, our results indicate that SENP3-mediated deSUMOlyation promotes an Mff-primed Drp1-Bcl-x(L) interaction that contributes to cell death following ischemia

Women using a web‐based digital health coaching programme for stress management: stress sources, symptoms and soping strategies

Researchers have proposed and tested many theories to understand gender differences in stress experiences. However, little research has identified differences between subgroups of women in terms of stress sources, symptoms, coping strategies and help‐seeking behaviour. The purpose of this study was to examine these characteristics of women seeking help for stress management through a digital health coaching programme. We examined cross‐sectional data from 63,690 women between the ages of 18 and 59 years who participated in the stress management programme from 2001 to 2008. We divided the sample into age groups to identify developmental patterns in their stress characteristics. Work , time demands and psychological reactions to stress were consistent concerns, whereas between‐group comparisons indicated diverse stress characteristics by age group. Importantly, women at all ages reported being uncomfortable asking for help. The findings suggest that technology‐based solutions like digital health coaching may reach women who may not otherwise seek or receive help for stress management. The results also emphasize the importance of considering the unique characteristics of women when providing them stress management interventions. Copyright © 2011 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87059/1/smi1389.pd

SENP3-mediated deSUMOylation of dynamin-related protein 1 promotes cell death following ischaemia

Global increases in small ubiquitin‐like modifier (SUMO)‐2/3 conjugation are a neuroprotective response to severe stress but the mechanisms and specific target proteins that determine cell survival have not been identified. Here, we demonstrate that the SUMO‐2/3‐specific protease SENP3 is degraded during oxygen/glucose deprivation (OGD), an in vitro model of ischaemia, via a pathway involving the unfolded protein response (UPR) kinase PERK and the lysosomal enzyme cathepsin B. A key target for SENP3‐mediated deSUMOylation is the GTPase Drp1, which plays a major role in regulating mitochondrial fission. We show that depletion of SENP3 prolongs Drp1 SUMOylation, which suppresses Drp1‐mediated cytochrome c release and caspase‐mediated cell death. SENP3 levels recover following reoxygenation after OGD allowing deSUMOylation of Drp1, which facilitates Drp1 localization at mitochondria and promotes fragmentation and cytochrome c release. RNAi knockdown of SENP3 protects cells from reoxygenation‐induced cell death via a mechanism that requires Drp1 SUMOylation. Thus, we identify a novel adaptive pathway to extreme cell stress in which dynamic changes in SENP3 stability and regulation of Drp1 SUMOylation are crucial determinants of cell fate