Distribution System Reliability Evaluation Taking Circuit Capacity into Consideration

IntroductionAnalysis of customerfailure statistics formostpower utilities has shown that distribution systemevents make the greatest contribution to theunavailability of supply to customers. Thereliability of the distribution must be properlyevaluated to ensure acceptable levels ofreliabilityand quality of supply to the consumer.Historically distribution system reliability hasbeen evaluated using the connectivity method,which is based on the criterion of total loss ofcontinuity ( TLOC) and i…     

Historical phenology: grape ripening as a past climate indicator

French records of grape-harvest dates in Burgundy were used to reconstruct spring-summer temperatures from 1370 to 2003 using a process-based phenology model developed for the Pinot Noir grape. Our results reveal that temperatures as high as those reached in the 1990s have occurred several times in Burgundy since 1370. However, the summer of 2003 appears to have been extraordinary, with temperatures that were probably higher than in any other year since 1370.     

Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1

The evolutionary conservation of T lymphocyte subsets bearing T-cell receptors (TCRs) using invariant alpha-chains is indicative of unique functions. CD1d-restricted natural killer T (NK-T) cells that express an invariant Valpha14 TCRalpha chain have been implicated in microbial and tumour responses, as well as in auto-immunity. Here we show that T cells that express the canonical hValpha7.2-Jalpha33 or mValpha19-Jalpha33 TCR rearrangement are preferentially located in the gut lamina propria of humans and mice, respectively, and are therefore genuine mucosal-associated invariant T (MAIT) cells. Selection and/or expansion of this population requires B lymphocytes, as MAIT cells are absent in B-cell-deficient patients and mice. In addition, we show that MAIT cells are selected and/or restricted by MR1, a monomorphic major histocompatibility complex class I-related molecule that is markedly conserved in diverse mammalian species. MAIT cells are not present in germ-free mice, indicating that commensal flora is required for their expansion in the gut lamina propria. This indicates that MAIT cells are probably involved in the host response at the site of pathogen entry, and may regulate intestinal B-cell activity.     

RIPK4 activity in keratinocytes is controlled by the SCF<Superscript>β-TrCP</Superscript> ubiquitin ligase to maintain cortical actin organization

RIPK4 is a key player in epidermal differentiation and barrier formation. RIPK4 signaling pathways controlling keratinocyte proliferation and differentiation depend on its kinase activity leading to Dvl2, Pkp1 and IRF6 phosphorylation and NF-κB activation. However, the mechanism regulating RIPK4 activity levels remains elusive. We show that cultured keratinocytes display constitutive active phosphorylated RIPK4 while PKC signaling can trigger RIPK4 activation in various non-keratinocyte cell lines, in which RIPK4 is present in a non-phosphorylated state. Interestingly, we identified the SCF^β-TrCP ubiquitin E3 ligase complex responsible for regulating the active RIPK4 protein level. The SCF^β-TrCP complex binds to a conserved phosphodegron motif in the intermediate domain of RIPK4, subsequently leading to K48-linked ubiquitinylation and degradation. The recruitment of β-TrCP is dependent on RIPK4 activation and trans-autophosphorylation. β-TrCP knock-down resulted in RIPK4-dependent formation of actin stress fibers, cell scattering and increased cell motility, suggesting that tight control of RIPK4 activity levels is crucial to maintain cell shape and behavior in keratinocytes.     

Modeling European industrial production with multivariate singular spectrum analysis: A cross‐industry analysis

In this paper, an optimized multivariate singular spectrum analysis (MSSA) approach is proposed to find leading indicators of cross‐industry relations between 24 monthly, seasonally unadjusted industrial production (IP) series for German, French, and UK economies. Both recurrent and vector forecasting algorithms of horizontal MSSA (HMSSA) are considered. The results from the proposed multivariate approach are compared with those obtained via the optimized univariate singular spectrum analysis (SSA) forecasting algorithm to determine the statistical significance of each outcome. The data are rigorously tested for normality, seasonal unit root hypothesis, and structural breaks. The results are presented such that users can not only identify the most appropriate model based on the aim of the analysis, but also easily identify the leading indicators for each IP variable in each country. Our findings show that, for all three countries, forecasts from the proposed MSSA algorithm outperform the optimized SSA algorithm in over 70% of cases. Accordingly, this new approach succeeds in identifying leading indicators and is a viable option for selecting the SSA choices L and r, which minimizes a loss function.     

The Eyes Absent proteins in development and disease

The Eyes Absent (EYA) proteins, first described in the context of fly eye development, are now implicated in processes as disparate as organ development, innate immunity, DNA damage repair, photoperiodism, angiogenesis, and cancer metastasis. These functions are associated with an unusual combination of biochemical activities: tyrosine phosphatase and threonine phosphatase activities in separate domains, and transactivation potential when associated with a DNA-binding partner. EYA mutations are linked to multiorgan developmental disorders, as well as to adult diseases ranging from dilated cardiomyopathy to late-onset sensorineural hearing loss. With the growing understanding of EYA biochemical and cellular activity, biological function, and association with disease, comes the possibility that the EYA proteins are amenable to the design of targeted therapeutics. The availability of structural information, direct links to disease states, available animal models, and the fact that they utilize unconventional reaction mechanisms that could allow specificity, suggest that EYAs are well-positioned for drug discovery efforts. This review provides a summary of EYA structure, activity, and function, as they relate to development and disease, with particular emphasis on recent findings.     

Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24

Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 x 10(-8)) and 1.14 (trend; P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 x 10(-4)). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer.     

Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons

We report that Sir2 activation through increased sir-2.1 dosage or treatment with the sirtuin activator resveratrol specifically rescued early neuronal dysfunction phenotypes induced by mutant polyglutamines in transgenic Caenorhabditis elegans. These effects are dependent on daf-16 (Forkhead). Additionally, resveratrol rescued mutant polyglutamine-specific cell death in neuronal cells derived from HdhQ111 knock-in mice. We conclude that Sir2 activation may protect against mutant polyglutamines.     

Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster

Loss of cell polarity and cancer are tightly correlated, but proof for a causative relationship has remained elusive. In stem cells, loss of polarity and impairment of asymmetric cell division could alter cell fates and thereby render daughter cells unable to respond to the mechanisms that control proliferation. To test this hypothesis, we generated Drosophila melanogaster larval neuroblasts containing mutations in various genes that control asymmetric cell division and then assayed their proliferative potential after transplantation into adult hosts. We found that larval brain tissue carrying neuroblasts with mutations in raps (also called pins), mira, numb or pros grew to more than 100 times their initial size, invading other tissues and killing the hosts in 2 weeks. These tumors became immortal and could be retransplanted into new hosts for years. Six weeks after the first implantation, genome instability and centrosome alterations, two traits of malignant carcinomas, appeared in these tumors. Increasing evidence suggests that some tumors may be of stem cell origin. Our results show that loss of function of any of several genes that control the fate of a stem cell's daughters may result in hyperproliferation, triggering a chain of events that subverts cell homeostasis in a general sense and leads to cancer.