26 research outputs found
Computer aided synthesis: a game theoretic approach
In this invited contribution, we propose a comprehensive introduction to game
theory applied in computer aided synthesis. In this context, we give some
classical results on two-player zero-sum games and then on multi-player non
zero-sum games. The simple case of one-player games is strongly related to
automata theory on infinite words. All along the article, we focus on general
approaches to solve the studied problems, and we provide several illustrative
examples as well as intuitions on the proofs.Comment: Invitation contribution for conference "Developments in Language
Theory" (DLT 2017
Extending Finite Memory Determinacy to Multiplayer Games
We show that under some general conditions the finite memory determinacy of a
class of two-player win/lose games played on finite graphs implies the
existence of a Nash equilibrium built from finite memory strategies for the
corresponding class of multi-player multi-outcome games. This generalizes a
previous result by Brihaye, De Pril and Schewe. For most of our conditions we
provide counterexamples showing that they cannot be dispensed with.
Our proofs are generally constructive, that is, provide upper bounds for the
memory required, as well as algorithms to compute the relevant winning
strategies.Comment: In Proceedings SR 2016, arXiv:1607.0269
Proteasome Activator Enhances Survival of Huntington's Disease Neuronal Model Cells
In patients with Huntington's disease (HD), the proteolytic activity of the ubiquitin proteasome system (UPS) is reduced in the brain and other tissues. The pathological hallmark of HD is the intraneuronal nuclear protein aggregates of mutant huntingtin. We determined how to enhance UPS function and influence catalytic protein degradation and cell survival in HD. Proteasome activators involved in either the ubiquitinated or the non-ubiquitinated proteolysis were overexpressed in HD patients' skin fibroblasts or mutant huntingtin-expressing striatal neurons. Following compromise of the UPS, overexpression of the proteasome activator subunit PA28γ, but not subunit S5a, recovered proteasome function in the HD cells. PA28γ also improved cell viability in mutant huntingtin-expressing striatal neurons exposed to pathological stressors, such as the excitotoxin quinolinic acid and the reversible proteasome inhibitor MG132. These results demonstrate the specific functional enhancements of the UPS that can provide neuroprotection in HD cells
Ubiquitination is involved in secondary growth, not initial formation of polyglutamine protein aggregates in C. elegans
Disease-Associated Mutant Ubiquitin Causes Proteasomal Impairment and Enhances the Toxicity of Protein Aggregates
Protein homeostasis is critical for cellular survival and its dysregulation has been implicated in Alzheimer's disease (AD) and other neurodegenerative disorders. Despite the growing appreciation of the pathogenic mechanisms involved in familial forms of AD, much less is known about the sporadic cases. Aggregates found in both familial and sporadic AD often include proteins other than those typically associated with the disease. One such protein is a mutant form of ubiquitin, UBB+1, a frameshift product generated by molecular misreading of a wild-type ubiquitin gene. UBB+1 has been associated with multiple disorders. UBB+1 cannot function as a ubiquitin molecule, and it is itself a substrate for degradation by the ubiquitin/proteasome system (UPS). Accumulation of UBB+1 impairs the proteasome system and enhances toxic protein aggregation, ultimately resulting in cell death. Here, we describe a novel model system to investigate how UBB+1 impairs UPS function and whether it plays a causal role in protein aggregation. We expressed a protein analogous to UBB+1 in yeast (Ubext) and demonstrated that it caused UPS impairment. Blocking ubiquitination of Ubext or weakening its interactions with other ubiquitin-processing proteins reduced the UPS impairment. Expression of Ubext altered the conjugation of wild-type ubiquitin to a UPS substrate. The expression of Ubext markedly enhanced cellular susceptibility to toxic protein aggregates but, surprisingly, did not induce or alter nontoxic protein aggregates in yeast. Taken together, these results suggest that Ubext interacts with more than one protein to elicit impairment of the UPS and affect protein aggregate toxicity. Furthermore, we suggest a model whereby chronic UPS impairment could inflict deleterious consequences on proper protein aggregate sequestration
The additional value of patient-reported health status in predicting 1-year mortality after invasive coronary procedures: A report from the Euro Heart Survey on Coronary Revascularisation
Objective: Self-perceived health status may be helpful in identifying patients at high risk for adverse outcomes. The Euro Heart Survey on Coronary Revascularization (EHS-CR) provided an opportunity to explore whether impaired health status was a predictor of 1-year mortality in patients with coronary artery disease (CAD) undergoing angiographic procedures. Methods: Data from the EHS-CR that included 5619 patients from 31 member countries of the European Society of Cardiology were used. Inclusion criteria for the current study were completion of a self-report measure of health status, the EuroQol Questionnaire (EQ-5D) at discharge and information on 1-year follow-up, resulting in a study population of 3786 patients. Results: The 1-year mortality was 3.2% (n = 120). Survivors reported fewer problems on the five dimensions of the EQ-5D as compared with non-survivors. A broad range of potential confounders were adjusted for, which reached a p<0.10 in the unadjusted analyses. In the adjusted analyses, problems with self-care (OR 3.45; 95% CI 2.14 to 5.59) and a low rating (≤ 60) on health status (OR 2.41; 95% CI 1.47 to 3.94) were the most powerful independent predictors of mortality, among the 22 clinical variables included in the analysis. Furthermore, patients who reported no problems on all five dimensions had significantly lower 1-year mortality rates (OR 0.47; 95% CI 0.28 to 0.81). Conclusions: This analysis shows that impaired health status is associated with a 2-3-fold increased risk of all-cause mortality in patients with CAD, independent of other conventional risk factors. These results highlight the importance of including patients' subjective experience of their own health status in the evaluation strategy to optimise risk stratification and management in clinical practice
Crosstalk Between Macroautophagy and Chaperone-Mediated Autophagy: Implications for the Treatment of Neurological Diseases
Inequalities for the De Pril Approximation to the Distribution of the Number of Policies with Claims
Investigation of an electromagnetic calorimeter based on liquid krypton
Effects determining the energy and spatial resolution of a calorimeter based on liquid krypton have been studied. With cathode strips of 10 mm a spatial resolution of 0.4 mm has been obtained in a cosmic rays test. The energy resolution of the calorimeter (0.4 ton of krypton) has been measured with positrons, achieving a rms of 5.7% at E = 130 MeV and 1.7% at E = 1200 MeV. The measurements are compared to Monte Carlo simulations
Space and energy resolutions in a liquid krypton e.m. calorimeter
Results of the experimental measurement of space and energy resolutions of a liquid krypton (LKr) e.m. calorimeter are presented. A prototype has been exposed to a positron test-beam in the energy range 130-1300 MeV at the VEPP-3 storage ring