268 research outputs found
Report of the National Law Student Conference on Legal Education: Availability of Legal Education and Placement of Law Graduates
I Saab Aerostructures tillverkning av flygplansdelar, anvÀnds icke strukturbundet material, det vill sÀga material som inte har en angiven kvantifierad förbrukning per tillverkad enhet eller material vars angivna kvantifierade förbrukning per tillverkad enhet inte stÀmmer överens med verklig förbrukning. Personal pÄ inköpsavdelningen vet i vissa fall inte var ett specifikt icke strukturbundet material förbrukas, alltsÄ vilka tillverkningsavdelningar eller flygplansdelar som förbrukar materialet. LikasÄ saknas övergripande och gemensamma rutiner för hur material som klassas som icke strukturbundet material planeras och lagerstyrs. För att identifiera problemomrÄden i materialförsörjningen genomfördes en flödeskartlÀggning för att identifiera vilka olika typer av icke strukturbundet material som anvÀnds i Saab Aerostructures produktion samt hur dessa lagerstyrs mellan lager och buffertlager i produktion. Under flödeskartlÀggningen definierades sex olika materialgrupper tillhörande icke strukturbundet material. För att lagerstyra de identifierade materialgrupperna av icke strukturbundet material anvÀnds idag Ätta stycken lagerstyrningsmetoder. Saab Aerostructures har anlitat tredjepartslogistiker för att sköta merparten av dagens lagerstyrning. Lagerstyrningsmetoderna skiljer sig Ät beroende pÄ tredjepartslogistiker och materialgrupp av icke strukturbundet material. Resultatet frÄn genomförd kartlÀggning och analys pÄvisar att det finns förbÀttringspotential i flera utav dessa lagerstyrningsmetoder, samt att det Àr möjligt att reducera antalet lagerstyrningsmetoder genom att anvÀnda samma lagerstyrningsmetod för snarlika materialgrupper av icke strukturbundet material. Genomförd analys pÄvisar Àven behovet av ett förbÀttrat informationsflöde mellan beredning, inköp och produktion, nÀr det gÀller hanteringen av icke strukturbundet material. Konkreta ÄtgÀrder i form av rekommendationer, för att förbÀttra lagerstyrningen av icke strukturbundet material, presenteras i slutet av denna rapport.
Analyzing a Pattern-Based Model of a Real-Time Turntable System
AbstractDesigners of industrial real-time systems are commonly faced with the problem of complex system modeling and analysis, even if a component-based design paradigm is employed. In this paper, we present a case-study in formal modeling and analysis of a turntable system, for which the components are described in the SaveCCM language. The search for general principles underlying the internal structure of our real-time system has motivated us to propose three modeling patterns of common behaviors of real-time components, which can be instantiated in appropriate design contexts. The benefits of such reusable patterns are shown in the case-study, by allowing us to produce easy-to-read and manageable models for the real-time components of the turntable system. Moreover, we believe that the patterns may pave the way toward a generic pattern-based modeling framework targeting real-time systems in particular
Managing in conflict: How actors distribute conflict in an industrial network
IMP researchers have examined conflict as a threat to established business relationships and commercial exchanges, drawing on theories and concepts developed in organization studies. We examine cases of conflict in relationships from the oil and gas industry's service sector, focusing on conflicts of interest and resources, and conflict as experienced by actors. Through a comparative case study design, we propose an explanation of how actors manage conflict and manage in conflict given that they tend to value and maintain relationships beyond episodes of exchange. We consider conflicts in relationships from a network perspective, showing that actors experienced these while adapting to changes in their business setting, modifying their roles in that network. By identifying conflict with the organizing forms of relationship and network, we show how actors formulate conflict through pursuing and combining a number of strategies, distributing the conflict across an enlarged network
Semaphorin 6A knockout mice display abnormalities across ethologically-based topographies of exploration and in motor learning
Semaphorins are secreted or membrane-bound proteins implicated in neurodevelopmental processes of axon guidance and cell migration. Exploratory behaviour and motor learning was examined ethologically in Semaphorin 6A (Sema6A) mutant mice. The ethogram of initial exploration in Sema6A knockout mice was characterised by increased rearing to wall with decreased sifting; over subsequent habituation, locomotion, sniffing and rearing to wall were increased, with reduced habituation of rearing seated. Rotarod analysis indicated delayed motor learning in Sema6A heterozygous mutants. Disruption to the axonal guidance and cell migration processes regulated by Sema6A is associated with topographically specific disruption to fundamental aspects of behaviour, namely the ethogram of initial exploration and subsequent habituation to the environment, and motor learning
The ERCC1/XPF endonuclease is required for completion of homologous recombination at DNA replication forks stalled by inter-strand cross-links
Both the ERCC1-XPF complex and the proteins involved in homoIogous recombination (HR) have critical roles in inter-strand cross-link (ICL) repair. Here, we report that mitomycin C-induced lesions inhibit replication fork elongation. Furthermore, mitomycin C-induced DNA double-strand breaks (DSBs) are the result of the collapse of ICL-stalled replication forks. These are not formed through replication run off, as we show that mitomycin C or cisplatin-induced DNA lesions are not incised by global genome nucleotide excision repair (GGR). We also suggest that ICL-lesion repair is initiated either by replication or transcription, as the GGR does not incise ICL-lesions. Furthermore, we report that RAD51 foci are induced by cisplatin or mitomycin C independently of ERCC1, but that mitomycin C-induced HR measured in a reporter construct is impaired in ERCC1-defective cells. These data suggest that ERCC1âXPF plays a role in completion of HR in ICL repair. We also find no additional sensitivity to cisplatin by siRNA co-depletion of XRCC3 and ERCC1, showing that the two proteins act on the same pathway to promote survival
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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.
Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis
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Association between Class III Obesity (BMI of 40â59 kg/m2) and Mortality: A Pooled Analysis of 20 Prospective Studies
Background: The prevalence of class III obesity (body mass index [BMI]â„40 kg/m2) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity. Methods and Findings: In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex- and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year) and multivariable-adjusted hazard ratios for adults, aged 19â83 y at baseline, classified as obese class III (BMI 40.0â59.9 kg/m2) compared with those classified as normal weight (BMI 18.5â24.9 kg/m2). Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema) on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (1976â2009). Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences = 238.9 and 132.8 in men and women, respectively), followed by deaths from cancer (rate differences = 36.7 and 62.3 in men and women, respectively) and diabetes (rate differences = 51.2 and 29.2 in men and women, respectively). Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 40â44.9, 45â49.9, 50â54.9, and 55â59.9 kg/m2 was associated with an estimated 6.5 (95% CI: 5.7â7.3), 8.9 (95% CI: 7.4â10.4), 9.8 (95% CI: 7.4â12.2), and 13.7 (95% CI: 10.5â16.9) y of life lost. A limitation was that BMI was mainly ascertained by self-report. Conclusions: Class III obesity is associated with substantially elevated rates of total mortality, with most of the excess deaths due to heart disease, cancer, and diabetes, and major reductions in life expectancy compared with normal weight. Please see later in the article for the Editors' Summar
Distinct External Signals Trigger Sequential Release of Apical Organelles during Erythrocyte Invasion by Malaria Parasites
The invasion of erythrocytes by Plasmodium merozoites requires specific interactions between host receptors and parasite ligands. Parasite proteins that bind erythrocyte receptors during invasion are localized in apical organelles called micronemes and rhoptries. The regulated secretion of microneme and rhoptry proteins to the merozoite surface to enable receptor binding is a critical step in the invasion process. The sequence of these secretion events and the external signals that trigger release are not known. We have used time-lapse video microscopy to study changes in intracellular calcium levels in Plasmodium falciparum merozoites during erythrocyte invasion. In addition, we have developed flow cytometry based methods to measure relative levels of cytosolic calcium and study surface expression of apical organelle proteins in P. falciparum merozoites in response to different external signals. We demonstrate that exposure of P. falciparum merozoites to low potassium ion concentrations as found in blood plasma leads to a rise in cytosolic calcium levels through a phospholipase C mediated pathway. Rise in cytosolic calcium triggers secretion of microneme proteins such as the 175 kD erythrocyte binding antigen (EBA175) and apical membrane antigen-1 (AMA-1) to the merozoite surface. Subsequently, interaction of EBA175 with glycophorin A (glyA), its receptor on erythrocytes, restores basal cytosolic calcium levels and triggers release of rhoptry proteins. Our results identify for the first time the external signals responsible for the sequential release of microneme and rhoptry proteins during erythrocyte invasion and provide a starting point for the dissection of signal transduction pathways involved in regulated exocytosis of these key apical organelles. Signaling pathway components involved in apical organelle discharge may serve as novel targets for drug development since inhibition of microneme and rhoptry secretion can block invasion and limit blood-stage parasite growth
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