| 11. |
- Taes, I, et al.
(författare)
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Tau levels do not influence human ALS or motor neuron degeneration in the SOD1G93A mouse
- 2010
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Ingår i: Neurology. - : American Academy of Neurology & Lippincott, Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 74:21, s. 1687-1693
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Tidskriftsartikel (refereegranskat)abstract
- Background: The microtubule-associated protein tau is thought to play a pivotal role in neurodegeneration. Mutations in the tau coding gene MAPT are a cause of frontotemporal dementia, and the H1/H1 genotype of MAPT, giving rise to higher tau expression levels, is associated with progressive supranuclear palsy, corticobasal degeneration, and Parkinson disease (PD). Furthermore, tau hyperphosphorylation and aggregation is a hallmark of Alzheimer disease (AD), and reducing endogenous tau has been reported to ameliorate cognitive impairment in a mouse model for AD. Tau hyperphosphorylation and aggregation have also been described in amyotrophic lateral sclerosis (ALS), both in human patients and in the mutant SOD1 mouse model for this disease. However, the precise role of tau in motor neuron degeneration remains uncertain. Methods: The possible association between ALS and the MAPT H1/H2 polymorphism was studied in 3,540 patients with ALS and 8,753 controls. Furthermore, the role of tau in the SOD1G93A mouse model for ALS was studied by deleting Mapt in this model. Results: The MAPT genotype of the H1/H2 polymorphism did not influence ALS susceptibility (odds ratio = 1.08 [95% confidence interval 0.99–1.18], p = 0.08) and did not affect the clinical phenotype. Lowering tau levels in the SOD1G93A mouse failed to delay disease onset (p = 0.302) or to increase survival (p = 0.557). Conclusion: These findings suggest that the H1/H2 polymorphism in MAPT is not associated with human amyotrophic lateral sclerosis, and that lowering tau levels in the mutant SOD1 mouse does not affect the motor neuron degeneration in these animals.
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| 15. |
- Bosch, Jan, 1967, et al.
(författare)
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Binding Time and Evolution
- 2013
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Ingår i: Systems and Software Variability Management. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 9783642365829 ; , s. 57-73
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- © Springer-Verlag Berlin Heidelberg 2013. Software variability, as a powerful mechanism that enables the construction of different artifacts from a common architecture, enables the realization of variation points and variants at different times or stages. The moment in which the variability is bound to concrete design choices provides a flexible way to delay our design decisions to later stages during the software development process.
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| 16. |
- Bosch, Jan, 1967, et al.
(författare)
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Dynamic Variability in Software-Intensive Embedded System Families
- 2012
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Ingår i: Computer. - 0018-9162 .- 1558-0814. ; 45:10, s. 28-35
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Dynamic software product lines address many of the challenges of building highly configurable software and use runtime variability mechanisms to support automatic decision making.
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| 17. |
- Bosch, Jackie, et al.
(författare)
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n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia.
- 2012
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 367:4, s. 309-18
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The use of n-3 fatty acids may prevent cardiovascular events in patients with recent myocardial infarction or heart failure. Their effects in patients with (or at risk for) type 2 diabetes mellitus are unknown.METHODS: In this double-blind study with a 2-by-2 factorial design, we randomly assigned 12,536 patients who were at high risk for cardiovascular events and had impaired fasting glucose, impaired glucose tolerance, or diabetes to receive a 1-g capsule containing at least 900 mg (90% or more) of ethyl esters of n-3 fatty acids or placebo daily and to receive either insulin glargine or standard care. The primary outcome was death from cardiovascular causes. The results of the comparison between n-3 fatty acids and placebo are reported here.RESULTS: During a median follow up of 6.2 years, the incidence of the primary outcome was not significantly decreased among patients receiving n-3 fatty acids, as compared with those receiving placebo (574 patients [9.1%] vs. 581 patients [9.3%]; hazard ratio, 0.98; 95% confidence interval [CI], 0.87 to 1.10; P=0.72). The use of n-3 fatty acids also had no significant effect on the rates of major vascular events (1034 patients [16.5%] vs. 1017 patients [16.3%]; hazard ratio, 1.01; 95% CI, 0.93 to 1.10; P=0.81), death from any cause (951 [15.1%] vs. 964 [15.4%]; hazard ratio, 0.98; 95% CI, 0.89 to 1.07; P=0.63), or death from arrhythmia (288 [4.6%] vs. 259 [4.1%]; hazard ratio, 1.10; 95% CI, 0.93 to 1.30; P=0.26). Triglyceride levels were reduced by 14.5 mg per deciliter (0.16 mmol per liter) more among patients receiving n-3 fatty acids than among those receiving placebo (P<0.001), without a significant effect on other lipids. Adverse effects were similar in the two groups.CONCLUSIONS: Daily supplementation with 1 g of n-3 fatty acids did not reduce the rate of cardiovascular events in patients at high risk for cardiovascular events. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.).
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| 18. |
- Capilla, R., et al.
(författare)
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An overview of Dynamic Software Product Line architectures and techniques: Observations from research and industry
- 2014
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Ingår i: Journal of Systems and Software. - : Elsevier BV. - 0164-1212. ; 91:1, s. 3-23
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Tidskriftsartikel (refereegranskat)abstract
- Over the last two decades, software product lines have been used successfully in industry for building families of systems of related products, maximizing reuse, and exploiting their variable and configurable options. In a changing world, modern software demands more and more adaptive features, many of them performed dynamically, and the requirements on the software architecture to support adaptation capabilities of systems are increasing in importance. Today, many embedded system families and application domains such as ecosystems, service-based applications, and self-adaptive systems demand runtime capabilities for flexible adaptation, reconfiguration, and post-deployment activities. However, as traditional software product line architectures fail to provide mechanisms for runtime adaptation and behavior of products, there is a shift toward designing more dynamic software architectures and building more adaptable software able to handle autonomous decision-making, according to varying conditions. Recent development approaches such as Dynamic Software Product Lines (DSPLs) attempt to face the challenges of the dynamic conditions of such systems but the state of these solution architectures is still immature. In order to provide a more comprehensive treatment of DSPL models and their solution architectures, in this research work we provide an overview of the state of the art and current techniques that, partially, attempt to face the many challenges of runtime variability mechanisms in the context of Dynamic Software Product Lines. We also provide an integrated view of the challenges and solutions that are necessary to support runtime variability mechanisms in DSPL models and software architectures. (C) 2014 Elsevier Inc. All rights reserved.
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| 19. |
- Capilla, R., et al.
(författare)
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The Promise and Challenge of Runtime Variability
- 2011
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Ingår i: Computer. - 0018-9162 .- 1558-0814. ; 44:12, s. 93-95
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Runtime variability offers a good choice for many systems that experience dynamic changes in their quality and context.
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| 20. |
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