700 research outputs found

    Flexible Session Management in a Distributed Environment

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    Many secure communication libraries used by distributed systems, such as SSL, TLS, and Kerberos, fail to make a clear distinction between the authentication, session, and communication layers. In this paper we introduce CEDAR, the secure communication library used by the Condor High Throughput Computing software, and present the advantages to a distributed computing system resulting from CEDAR's separation of these layers. Regardless of the authentication method used, CEDAR establishes a secure session key, which has the flexibility to be used for multiple capabilities. We demonstrate how a layered approach to security sessions can avoid round-trips and latency inherent in network authentication. The creation of a distinct session management layer allows for optimizations to improve scalability by way of delegating sessions to other components in the system. This session delegation creates a chain of trust that reduces the overhead of establishing secure connections and enables centralized enforcement of system-wide security policies. Additionally, secure channels based upon UDP datagrams are often overlooked by existing libraries; we show how CEDAR's structure accommodates this as well. As an example of the utility of this work, we show how the use of delegated security sessions and other techniques inherent in CEDAR's architecture enables US CMS to meet their scalability requirements in deploying Condor over large-scale, wide-area grid systems

    Intraperitoneal bevacizumab for control of malignant ascites due to advanced-stage gastrointestinal cancers: A multicentre double-blind, placebo-controlled phase II study - AIO SUP-0108

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    PURPOSE: Malignant ascites is debilitating for patients with advanced cancer. As shown previously, tumour cell production of vascular endothelial growth factor might be a major cause of the formation of malignant ascites. Intraperitoneal bevacizumab could therefore be an option for symptom control in refractory ascites. PATIENTS AND METHODS: Patients with advanced gastrointestinal cancer and malignant ascites who had undergone paracentesis at least twice within the past 4 weeks were randomly assigned in a 2:1 ratio to intraperitoneal bevacizumab (400 mg absolute) or placebo after paracentesis. During the 8-week treatment period, a minimum interval of 14 d was kept between the applications of the study drug. Primary end-point was paracentesis-free survival (ParFS). RESULTS: Fifty-three patients (median age 63 years) were randomised. Forty-nine patients received at least one study drug application and qualified for the main analysis. The proportion of patients with at least one common toxicity criteria grade III-V event was similar with 20/33 (61%) on bevacizumab and 11/16 (69%) on placebo. Median ParFS was 14 d (95% confidence interval [CI]: 11-17) in the bevacizumab arm and 10.5 d (95% CI: 7-21) on placebo (hazard ratio 0.74, 95% CI: 0.40-1.37; P = 0.16). The longest paracentesis-free period was 19 d on bevacizumab (range 6-66 d) and 17.5 d in the placebo arm (range 4-42) (P = 0.85). Median overall survival was 64 d (95% CI: 45-103) on bevacizumab compared to 31.5 d (95% CI: 20-117) on placebo (P = 0.31). CONCLUSION: Intraperitoneal bevacizumab was well tolerated. Overall, treatment did not result in a significantly better symptom control of malignant ascites. However, patients defined by specific immune characteristics may benefit

    Witterungsextreme und ihre Bedeutung für die jährlichen Ertragsabweichungen von Winterweize

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    KlimafolgenFür die Landwirtschaft stellen Witterungsereignisse mit signifikanten Abweichungen von langjährigen Mittel eine große Herausforderung dar. Witterungsextreme wie Starkregen, Hitzeperioden während kritischer phänologischer Phasen wie beispielsweise der Blüte oder längere niederschlagsfreie Zeiten haben oftmals direkte Auswirkungen auf den Ertrag und die Qualität der Ernteprodukte. Durch den Klimawandel werden zudem die Wiederkehr von Extremereignissen und die Intensität von Witterungsereignissen beeinflusst. Die Bedeutung der Witterungsextreme für die jährlichen Ertragsschwankungen von Winterweizen wurde durch die Auswertung der Langzeitversuche des JKI in Dahnsdorf, Brandenburg untersucht. Die Klimadaten entstammen der Wetterstation auf dem Versuchsfeld und fehlende Daten sind durch Interpolation von umliegenden Klimastationen auf diesen Standort für die Zeit von 1993-2013 erzeugt worden. Während des Untersuchungszeitraums betrug die jährliche Durchschnittstemperatur 9.6°C und der Jahresniederschlag lag bei 587 mm. Die Anzahl aufeinanderfolgender Tage ohne Niederschlag (NCDWP) von April-September und die Temperatur >25°C (NHD) zur Blüte von Winterweizen im Zeitraum vom 1.-21.Juni in Kombination mit unterschiedlichen Pflanzenschutzstrategien wurde hinsichtlich der Bedeutung für die jährlichen Ertragsschwankungen analysiert. Sowohl bei den NCDWP als auch bei den NHD konnte für den Betrachtungszeitraum für die Werte oberhalb des 80%-igen Perzentils eine leichte Zunahme beider Extrema für diesen Standort gefunden werden (Zunahme von 5 auf 6 bei NHD und 14 auf 15 bei NCDWP). Eine Regressionsanalyse für den Zeitraum von 1996-2007 ergab für beide Extrema ertragsrelevante Auswirkungen auf die jährlichen Ertragsschwankungen. Hierbei zeigten die NHD eine deutlich stärkere ertragsrelevante Auswirkung als die NCDWP bei Winterweizen, abhängig von den jeweiligen Pflanzenschutzstrategien

    BIOHYBRID – Biohybrid templates for peripheral nerve regeneration

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    [Excerpt] Peripheral nerve injuries represent a major cause for morbidity and disability in affected patients and cause substantial costs for society in a global perspective. It has been estimated that peripheral nerve injuries affect 2.8% of trauma patients,many of whom acquire life-long disability (Noble et al., 1998). With respect to an incidence of nerve injuries of 13.9/100,000 inhabitants per year (Asplund et al., 2009) and the number of inhabitants in the EU (495,000,000 inhabitants in 2007), the number of peripheral nerve injuries requiring repair and reconstruction, excluding nerve injuries by amputations, may be 70,000 annually only in EU countries. Related to peripheral nerve injuries, the costs for society are substantial and consist of direct (costs for surgery, outpatient visits and rehabilitation) and indirect (lost production) costs. Individual median and ulnar nerve injuries in the forearm have total costs of EUR 51,000 and 31,000, respectively, where around 85% of the costs consist of loss of production (Rosberg et al., 2005), still excluding costs for adjusted quality of life ( Eriksson et al., 2011) . Thus, one may estimate that the annual costs only in the EU may be as high as EUR 2.2 billion, indicating that improved treatment strategies for peripheral nerve injuries may not only improve the situation for patients, but may also significantly reduce costs for society. [...](undefined

    Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene / allele-specific silencing of mutant huntingtin

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    Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion in the huntingtin gene (HTT) that results in a toxic gain of function in the mutant huntingtin protein (mHTT). Reducing the expression of mHTT is therefore an attractive therapy for HD. However, wild-type HTT protein is essential for development and has critical roles in maintaining neuronal health. Therapies for HD that reduce wild-type HTT may therefore generate unintended negative consequences. We have identified single-nucleotide polymorphism (SNP) targets in the human HD population for the disease-specific targeting of the HTT gene. Using primary cells from patients with HD and the transgenic YAC18 and BACHD mouse lines, we developed antisense oligonucleotide (ASO) molecules that potently and selectively silence mHTT at both exonic and intronic SNP sites. Modification of these ASOs with S-constrained-ethyl (cET) motifs significantly improves potency while maintaining allele selectively in vitro. The developed ASO is potent and selective for mHTT in vivo after delivery to the mouse brain. We demonstrate that potent and selective allele-specific knockdown of the mHTT protein can be achieved at therapeutically relevant SNP sites using ASOs in vitro and in vivo

    Developing Healthy Kids in Healthy Communities: Eight Evidence-based Strategies for Preventing High-risk Behaviour.

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    Australian youth engage in behaviour that threatens their health and wellbeing. National surveys report that about a third of young Australians have tried an illicit drug. High rates of substance use and risky sexual behaviour among young Australians suggest that effective prevention efforts based on empirical evidence need to be expanded. Church-associated organisations are an untapped resource that could be used to improve the health and welfare of young people. We describe eight evidence-based elements to consider in designing strategies to prevent high-risk behaviour in young people
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