3,659 research outputs found

    Double exponential stability of quasi-periodic motion in Hamiltonian systems

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    We prove that generically, both in a topological and measure-theoretical sense, an invariant Lagrangian Diophantine torus of a Hamiltonian system is doubly exponentially stable in the sense that nearby solutions remain close to the torus for an interval of time which is doubly exponentially large with respect to the inverse of the distance to the torus. We also prove that for an arbitrary small perturbation of a generic integrable Hamiltonian system, there is a set of almost full positive Lebesgue measure of KAM tori which are doubly exponentially stable. Our results hold true for real-analytic but more generally for Gevrey smooth systems

    Elevated hepatocyte growth factor levels in osteoarthritis osteoblasts contribute to their altered response to bone morphogenetic protein-2 and reduced mineralization capacity

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    PURPOSE: Clinical and in vitro studies suggest that subchondral bone sclerosis due to abnormal osteoblasts is involved in the progression of osteoarthritis (OA). Human osteoblasts isolated from sclerotic subchondral OA bone tissue show an altered phenotype, a decreased canonical Wnt/ß-catenin pathway, and a reduced mineralization in vitro as well as in vivo. These alterations were linked with an abnormal response to BMP-2. OA osteoblasts release factors such as the hepatocyte growth factor (HGF) that contribute to cartilage loss whereas chondrocytes do not express HGF. HGF can stimulate BMP-2 expression in human osteoblasts, however, the role of HGF and its effect in OA osteoblasts remains unknown. Here we investigated whether elevated endogenous HGF levels in OA osteoblasts are responsible for their altered response to BMP-2. METHODS: We prepared primary human subchondral osteoblasts using the sclerotic medial portion of the tibial plateaus of OA patients undergoing total knee arthroplasty, or from tibial plateaus of normal individuals obtained at autopsy. The expression of HGF was evaluated by qRT-PCR and the protein production by western blot analysis. HGF expression was reduced with siRNA technique whereas its activity was inhibited using the selective inhibitor PHA665752. Alkaline phosphatase activity (ALPase) and osteocalcin release were measured by substrate hydrolysis and EIA respectively. Canonical Wnt/β-catenin signaling (cWnt) was evaluated both by target gene expression using the TOPflash TCF/lef luciferase reporter assay and western blot analysis of β-catenin levels in response to Wnt3a stimulation. Mineralization in response to BMP-2 was evaluated by alizarin red staining. RESULTS: The expression of HGF was increased in OA osteoblasts compared to normal osteoblasts and was maintained during their in vitro differentiation. OA osteoblasts released more HGF than normal osteoblasts as assessed by western blot analysis. HGF stimulated the expression of TGF-β1. BMP-2 dose-dependently (1 to 100ng/ml) stimulated both ALPase and osteocalcin in normal osteoblasts whereas, it inhibited them in OA osteoblasts. HGF-siRNA treatments reversed this response in OA osteoblasts and restored the BMP-2 response. cWnt is reduced in OA osteoblasts compared to normal, and HGF-siRNA treatments increased cWnt in OA osteoblasts almost to normal. Smad1/5/8 phosphorylation in response to BMP-2, which is reduced in OA osteoblasts, was corrected when these cells were treated with PHA665752. The BMP-2-dependent mineralization of OA osteoblasts, which is also reduced compared to normal, was only partially restored by PHA665752 treatment whereas 28days treatment with HGF reduced the mineralization of normal osteoblasts. CONCLUSION: OA osteoblasts expressed more HGF than normal osteoblasts. Increased endogenous HGF production in OA osteoblasts stimulated the expression of TGF-β1 and reduced their response to BMP-2. Inhibiting HGF expression or HGF signaling restored the response to BMP-2 and Smad1/5/8 signaling. In addition, decreased HGF signaling partly corrects the abnormal mineralization of OA osteoblasts while increased HGF prevents the normal mineralization of normal osteoblasts. In summary, we hypothesize that sustained elevated HGF levels in OA osteoblasts drive their abnormal phenotype and is implicated in OA pathophysiology

    A method for the reconstruction of unknown non-monotonic growth functions in the chemostat

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    We propose an adaptive control law that allows one to identify unstable steady states of the open-loop system in the single-species chemostat model without the knowledge of the growth function. We then show how one can use this control law to trace out (reconstruct) the whole graph of the growth function. The process of tracing out the graph can be performed either continuously or step-wise. We present and compare both approaches. Even in the case of two species in competition, which is not directly accessible with our approach due to lack of controllability, feedback control improves identifiability of the non-dominant growth rate.Comment: expansion of ideas from proceedings paper (17 pages, 8 figures), proceedings paper is version v

    Designing cost-sharing methods for Bayesian games

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    We study the design of cost-sharing protocols for two fundamental resource allocation problems, the Set Cover and the Steiner Tree Problem, under environments of incomplete information (Bayesian model). Our objective is to design protocols where the worst-case Bayesian Nash equilibria, have low cost, i.e. the Bayesian Price of Anarchy (PoA) is minimized. Although budget balance is a very natural requirement, it puts considerable restrictions on the design space, resulting in high PoA. We propose an alternative, relaxed requirement called budget balance in the equilibrium (BBiE).We show an interesting connection between algorithms for Oblivious Stochastic optimization problems and cost-sharing design with low PoA. We exploit this connection for both problems and we enforce approximate solutions of the stochastic problem, as Bayesian Nash equilibria, with the same guarantees on the PoA. More interestingly, we show how to obtain the same bounds on the PoA, by using anonymous posted prices which are desirable because they are easy to implement and, as we show, induce dominant strategies for the players

    Seismic risk in the city of Al Hoceima (north of Morocco) using the vulnerability index method, applied in Risk-UE project

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    The final publication is available at Springer via http://dx.doi.org/10.1007/s11069-016-2566-8Al Hoceima is one of the most seismic active regions in north of Morocco. It is demonstrated by the large seismic episodes reported in seismic catalogs and research studies. However, seismic risk is relatively high due to vulnerable buildings that are either old or don’t respect seismic standards. Our aim is to present a study about seismic risk and seismic scenarios for the city of Al Hoceima. The seismic vulnerability of the existing residential buildings was evaluated using the vulnerability index method (Risk-UE). It was chosen to be adapted and applied to the Moroccan constructions for its practicality and simple methodology. A visual inspection of 1102 buildings was carried out to assess the vulnerability factors. As for seismic hazard, it was evaluated in terms of macroseismic intensity for two scenarios (a deterministic and probabilistic scenario). The maps of seismic risk are represented by direct damage on buildings, damage to population and economic cost. According to the results, the main vulnerability index of the city is equal to 0.49 and the seismic risk is estimated as Slight (main damage grade equal to 0.9 for the deterministic scenario and 0.7 for the probabilistic scenario). However, Moderate to heavy damage is expected in areas located in the newer extensions, in both the east and west of the city. Important economic losses and damage to the population are expected in these areas as well. The maps elaborated can be a potential guide to the decision making in the field of seismic risk prevention and mitigation strategies in Al Hoceima.Peer ReviewedPostprint (author's final draft

    Advanced Feature Extraction and Dimensionality Reduction for Unmanned Underwater Vehicle Fault Diagnosis

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    This paper presents a novel approach to the diagnosis of blade faults in an electric thruster motor of unmanned underwater vehicles (UUVs) under stationary operating conditions. The diagnostic approach is based on the use of discrete wavelet transforms (DWT) as a feature extraction tool and a dynamic neural network (DNN) for fault classification. The DNN classifies between healthy and faulty conditions of the trolling motor by analyzing the stator current and vibration signals. To overcome feature redundancy, which affects diagnosis reliability, the Orthogonal Fuzzy Neighbourhood Discriminant Analysis (OFNDA) approach is found to be the most effective. Four faulty conditions were analyzed under laboratory conditions, and the results obtained from experiment demonstrate the effectiveness and reliability of the proposed methodology in classifying the different faults faster and more accurately

    Women and Illegal Activities: Gender Differences and Women's Willingness to Comply Over Time

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    In recent years the topics of illegal activities such as corruption or tax evasion have attracted a great deal of attention. However, there is still a lack of substantial empirical evidence about the determinants of compliance. The aim of this paper is to investigate empirically whether women are more willing to be compliant than men and whether we observe (among women and in general) differences in attitudes among similar age groups in different time periods (cohort effect) or changing attitudes of the same cohorts over time (age effect) using data from eight Western European countries from the World Values Survey and the European Values Survey that span the period from 1981 to 1999. The results reveal higher willingness to comply among women and an age rather than a cohort effect. Working Paper 06-5

    Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.

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    Abstract Introduction Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI). Methods Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. Results We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. Conclusions In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship
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