08371 Abstracts Collection -- Fault-Tolerant Distributed Algorithms on VLSI Chips

From September the $7^{text{th}}$, 2008 to September the $10^{text{th}}$, 2008 the Dagstuhl Seminar 08371 ``Fault-Tolerant Distributed Algorithms on VLSI Chips \u27\u27 was held in Schloss Dagstuhl~--~Leibniz Center for Informatics. The seminar was devoted to exploring whether the wealth of existing fault-tolerant distributed algorithms research can be utilized for meeting the challenges of future-generation VLSI chips. During the seminar, several participants from both the VLSI and distributed algorithms\u27 discipline, presented their current research, and ongoing work and possibilities for collaboration were discussed. Abstracts of the presentations given during the seminar as well as abstracts of seminar results and ideas are put together in this paper. The first section describes the seminar topics and goals in general. Links to extended abstracts or full papers are provided, if available

Dagstuhl Seminar 08371 on Fault-Tolerant Distributed Algorithms on VLSI Chips

Abstract The Dagstuhl seminar 08371 on Fault-Tolerant Distributed Algorithms on VLSI Chips was devoted to exploring whether the wealth of existing fault-tolerant distributed algorithms research can be utilized for meeting the challenges of futuregeneration VLSI chips. Participants from both the distributed fault-tolerant algorithms community, interested in this emerging application domain, and from the VLSI systems-on-chip and digital design community, interested in well-founded system-level approaches to fault-tolerance, surveyed the current state-of-the-art and tried to identify possibilities to work together. The seminar clearly achieved its purpose: It became apparent that most existing research in Distributed Algorithms is too heavy-weight for being immediately applied in the "core" VLSI design context, where power, area etc. are scarce resources. At the same time, however, it was recognized that emerging trends like large multicore chips and increasingly critical applications create new and promising application domains for fault-tolerant distributed algorithms. We are convinced that the very fruitful cross-community interactions that took place during the Dagstuhl seminar will contribute to new research activities in those areas

Pharmacological targeting of the protein synthesis mTOR/4E-BP1 pathway in cancer-associated fibroblasts abrogates pancreatic tumourchemoresistance

International audiencePancreatic ductal adenocarcinoma (PDAC) is extremely stroma-rich. Cancer-associated fibroblasts (CAFs) secrete proteins that activate survival and promote chemoresistance of cancer cells. Our results demonstrate that CAF secretome-triggered chemoresistance is abolished upon inhibition of the protein synthesis mTOR/4E-BP1 regulatory pathway which we found highly activated in primary cultures of -SMA-positive CAFs, isolated from human PDAC resections. CAFs selectively express the sst1 somatostatin receptor. The SOM230 analogue (Pasireotide) activates the sst1 receptor and inhibits the mTOR/4E-BP1 pathway and the resultant synthesis of secreted proteins including IL-6. Consequently, tumour growth and chemoresistance in nude mice xenografted with pancreatic cancer cells and CAFs, or with pieces of resected human PDACs, are reduced when chemotherapy (gemcitabine) is combined with SOM230 treatment. While gemcitabine alone has marginal effects, SOM230 is permissive to gemcitabine-induced cancer cell apoptosis and acts as an antifibrotic agent. We propose that selective inhibition of CAF protein synthesis with sst1-directed pharmacological compounds represents an anti-stromal-targeted therapy with promising chemosensitization potential

Temporal Orientation and its Relationships with Organizationally Valued Outcomes: Results from a 14 Country Investigation

In this investigation we were concerned with the cultural covariates of temporal orientation in 14 different national contexts. Data were collected from United States of America (US), Australia, Germany, Poland, Chile, Venezuela, Turkey, United Arab Emirates (UAE), India, Indonesia, Malaysia Japan, South Korea and China. Analyses show that collectivistic cultural orientation tends to be relatively important in the prediction of three facets of temporal orientation (i.e. emphasis on planning and scheduling; sense of time and attitude towards time)

Anticholinergic and Sedative Medications Are Associated With Neurocognitive Performance of Well Treated People With Human Immunodeficiency Virus.

Background We previously showed that anticholinergic (ACH) medications contribute to self-reported neurocognitive impairment (NCI) in elderly people with human immunodeficiency virus (PWH). The current cross-sectional study further evaluated the effect of ACH and sedative drugs on neurocognitive function in PWH who underwent comprehensive neuropsychological evaluation. Methods A medication review was performed in PWH enrolled in the prospective Neurocognitive Assessment in Metabolic and Aging Cohort within the Swiss HIV Cohort Study. Neurocognitive functions were analyzed in 5 domains (motor skills, speed of information, attention/working memory, executive functions, and verbal learning memory). The effect of ACH and sedative medications on neurocognitive functioning was evaluated using linear regression models for the continuous (mean z-score) outcome and multivariable logistic regression models for the binary (presence/absence) outcome. Results A total of 963 PWH (80% male, 92% Caucasian, 96% virologically suppressed, median age 52) were included. Fourteen percent of participants were prescribed ≥1 ACH medication and 9% were prescribed ≥1 sedative medication. Overall, 40% of participants had NCI. Sedative medication use was associated with impaired attention/verbal learning and ACH medication use with motor skills deficits both in the continuous (mean z-score difference -0.26 to -0.14, P < .001 and P = .06) and binary (odds ratio [OR], ≥1.67; P < .05) models. Their combined use was associated with deficits in overall neurocognitive functions in both models (mean z-score difference -0.12, P = .002 and OR = 1.54, P = .03). These associations were unchanged in a subgroup analysis of participants without depression (n = 824). Conclusions Anticholinergic and sedative medications contribute to NCI. Clinicians need to consider these drugs when assessing NCI in PWH

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

EU-Verordnung Öko-Landbau

Die Revision der EU-Öko-Verordnung wurde im Aktionsplan 2004 festgelegt. Die neue Verordnung 834/2007 ersetzt die der-zeit gültige EU-Öko-Verordnung 2092/91. Erstmals werden in der vorgeschlagenen EU-Öko-Verordnung die Ziele und Grundsätze der ökologischen Erzeugung beschrieben. Anbau und die Tiererzeugung sollen bodengebunden erfolgen und die Aquakultur nachhaltig