152 research outputs found

    Random Walks in Changing Environments

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    Mixing time of random walk on dynamical random cluster

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    We study the mixing time of a random walker who moves inside a dynamical random cluster model on the d-dimensional torus of side-length n. In this model, edges switch at rate \mu between open and closed, following a Glauber dynamics for the random cluster model with parameters p,q. At the same time, the walker jumps at rate 1 as a simple random walk on the torus, but is only allowed to traverse open edges. We show that for small enough p the mixing time of the random walker is of order n^2/\mu. In our proof we construct of a non-Markovian coupling through a multi-scale analysis of the environment, which we believe could be more widely applicable

    Mixing time of random walk on dynamical random cluster

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    We study the mixing time of a random walker who moves inside a dynamical random cluster model on the d-dimensional torus of side-length n. In this model, edges switch at rate \mu between open and closed, following a Glauber dynamics for the random cluster model with parameters p,q. At the same time, the walker jumps at rate 1 as a simple random walk on the torus, but is only allowed to traverse open edges. We show that for small enough p the mixing time of the random walker is of order n^2/\mu. In our proof we construct of a non-Markovian coupling through a multi-scale analysis of the environment, which we believe could be more widely applicable

    Mixing time of random walk on dynamical random cluster

    Get PDF
    We study the mixing time of a random walker who moves inside a dynamical random cluster model on the d-dimensional torus of side-length n. In this model, edges switch at rate \mu between open and closed, following a Glauber dynamics for the random cluster model with parameters p,q. At the same time, the walker jumps at rate 1 as a simple random walk on the torus, but is only allowed to traverse open edges. We show that for small enough p the mixing time of the random walker is of order n^2/\mu. In our proof we construct of a non-Markovian coupling through a multi-scale analysis of the environment, which we believe could be more widely applicable

    Evaluation of the Efficacy of Low-Particle-Size Toothpastes against Extrinsic Pigmentations: A Randomized Controlled Clinical Trial

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    Stain-removing domiciliary protocols are focused on the elimination of dental extrinsic pigmentations by the application of abrasive toothpastes, extensively available in commerce. The goal of the present study is to evaluate the efficacy of two different stain removal molecule-formulated toothpastes by the reduction of clinical parameters: the micro-cleaning crystals and activated charcoal. A total of 40 participants with extrinsic dental pigmentations were enrolled and divided into two groups: a Control group, assigned to a toothpaste with micro-cleaning crystals (Colgate Sensation White); and a Trial group, with microparticle-activated charcoal toothpaste (Coswell Blanx Black). At T0 (baseline), T1 (10 days), T2 (1 month), and T3 (3 months), clinical parameters, including Lobene stain index calculated for intensity and extension, plaque control record, and bleeding on probing, were measured. Statistically significant differences were found in both groups (p < 0.05): a reduction of extrinsic pigmentation, both in intensity and extension, was obtained in the Control group, but their total elimination could be achieved only in the Trial group with the activated charcoal molecule, though without significant difference between the groups (p > 0.05). No intergroup differences were found for each timeframe for PCR, BoP, LSI-I, and LSI-E. Both tested toothpastes can be recommended for domiciliary oral hygiene of patients with extrinsic pigmentations

    Biomimetic hydroxyapatite nanocrystals are an active carrier for Salmonella bacteriophages

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    open access articlePurpose: The use of bacteriophages represents a valid alternative to conventional antimicrobial treatments, overcoming the widespread bacterial antibiotic resistance phenomenon. In this work, we evaluated whether biomimetic hydroxyapatite (HA) nanocrystals are able to enhance some properties of bacteriophages. The final goal of this study was to demonstrate that biomimetic HA nanocrystals can be used for bacteriophage delivery in the context of bacterial infections, and contribute – at the same time – to enhance some of the biological properties of the same bacteriophages such as stability, preservation, antimicrobial activity, and so on. Materials and methods: Phage isolation and characterization were carried out by using Mitomycin C and following double-layer agar technique. The biomimetic HA water suspension was synthesized in order to obtain nanocrystals with plate-like morphology and nanometric dimensions. The interaction of phages with the HA was investigated by dynamic light scattering and Zeta potential analyses. The cytotoxicity and intracellular killing activities of the phage–HA complex were evaluated in human hepatocellular carcinoma HepG2 cells. The bacterial inhibition capacity of the complex was assessed on chicken minced meat samples infected with Salmonella Rissen. Results: Our data highlighted that the biomimetic HA nanocrystal–bacteriophage complex was more stable and more effective than phages alone in all tested experimental conditions. Conclusion: Our results evidenced the important contribution of biomimetic HA nanocrystals: they act as an excellent carrier for bacteriophage delivery and enhance its biological characteristics. This study confirmed the significant role of the mineral HA when it is complexed with biological entities like bacteriophages, as it has been shown for molecules such as lactoferrin

    Development and subunit composition of synaptic NMDA receptors in the amygdala: NR2B Synapses in the adult central amygdala

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    NMDA receptors are well known to play an important role in synaptic development and plasticity. Functional NMDA receptors are heteromultimers thought to contain two NR1 subunits and two or three NR2 subunits. In central neurons, NMDA receptors at immature glutamatergic synapses contain NR2B subunits and are largely replaced by NR2A subunits with development. At mature synapses, NMDA receptors are thought to be multimers that contain either NR1/NR2A or NR1/NR2A/NR2B subunits, whereas receptors that contain only NR1/NR2B subunits are extrasynaptic. Here, we have studied the properties of NMDA receptors at glutamatergic synapses in the lateral and central amygdala. We find that NMDA receptor-mediated synaptic currents in the central amygdala in both immature and mature synapses have slow kinetics and are substantially blocked by the NR2B-selective antagonists (1S, 2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propano and ifenprodil, indicating that there is no developmental change in subunit composition. In contrast, at synapses on pyramidal neurons in the lateral amygdala, whereas NMDA EPSCs at immature synapses are slow and blocked by NR2B-selective antagonists, at mature synapses their kinetics are faster and markedly less sensitive to NR2B-selective antagonists, consistent with a change from NR2B to NR2A subunits. Using real-time PCR and Western blotting, we show that in adults the ratio of levels of NR2B to NR2A subunits is greater in the central amygdala than in the lateral amygdala. These results show that the subunit composition synaptic NMDA receptors in the lateral and central amygdala undergo distinct developmental changes

    Platelet Function Testing in Patients with Acute Ischemic Stroke: An Observational Study

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    Background: The measurement of platelet reactivity in patients with stroke undergoing antiplatelet therapies is not commonly performed in clinical practice. We assessed the prevalence of therapy responsiveness in patients with stroke and further investigated differences between patients on prevention therapy at stroke onset and patients naive to antiplatelet medications. We also sought differences in responsiveness between etiological subtypes and correlations between Clopidogrel responsiveness and genetic polymorphisms. Methods: A total of 624 stroke patients on antiplatelet therapy were included. Two different groups were identified: "non-naive patients", and "naive patients". Platelet function was measured with multiple electrode aggregometry, and genotyping assays were used to determine CYP2C19 polymorphisms. Results: Aspirin (ASA) responsiveness was significantly more frequent in naive patients compared with non-naive patients (94.9% versus 82.6%, P < .0010). A better responsiveness to ASA compared with Clopidogrel or combination therapy was found in the entire population (P < .0010), in non-naive patients (P < .0253), and in naive patients (P < .0010). Multivariate analysis revealed a strong effect of Clopidogrel as a possible "risk factor" for unresponsiveness (odds ratio 3.652, P < .0001). No difference between etiological subgroups and no correlations between responsiveness and CYP2C19 polymorphisms were found. Conclusion: In our opinion, platelet function testing could be potentially useful in monitoring the biological effect of antiplatelet agents. A substantial proportion of patients with stroke on ASA were "resistant", and the treatment with Clopidogrel was accompanied by even higher rates of unresponsiveness. Longitudinal studies are needed to assess whether aggregometry might supply individualized prognostic information and whether it can be considered a valid tool for future prevention strategies

    Resource-effective serosurveillance for the detection of West Nile Virus in Switzerland using abattoir samples of free-range laying hens

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    West Nile virus (WNV) is an important zoonotic pathogen maintained in a natural transmission cycle between mosquitoes and birds as reservoir hosts. In dead-end hosts, such as humans, infection may result in fatal neurologic disease translating into disease and death-related suffering and increased health care costs. In humans, WNV may also be transmitted through blood transfusions and organ transplants. WNV is not present in Switzerland yet, but competent vector species (especially Culex pipiens and Aedes japonicus) are prevalent and an introduction of the virus, likely through wild birds, is expected at any time. Therefore, it is important for Switzerland to be prepared and establish a surveillance system for WNV to initiate increased prevention activities, such as the screening of blood and organ donations and public education activities in case virus circulation is detected. The long-term goal of these surveillance measures would be a reduced infection rate in humans resulting in less suffering and reduced health care costs. To provide the basis for a pragmatic and resource-effective WNV surveillance program, this study used aliquots of serum samples of free-range laying hens taken at the abattoir and collected in the frame of the ongoing Swiss Avian Influenza and Newcastle Disease monitoring program for a 2-year period. All 961 aliquots were analyzed using a commercial competitive WNV enzyme-linked immunosorbent assay (ELISA). The study allowed to set up sampling and laboratory routines as a basis for future WNV surveillance activities. At this stage there is no evidence for circulation of WNV in Switzerland

    CYP1A1 Variability In Human Populations

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    The human cytochrome P4501A1 (CYP1A1) enzyme plays an important role in the metabolism of xenobiotics and endogenous substrates. Because polymorphisms within the CYP1A1 gene have been shown to be associated with various cancer risks and with the predicting clinical efficacy of some chemotherapies in different populations, most studies focus on their clinical significance. We, however, were interested in evaluating whether the polymorphisms could be used to distinguish human populations. Four single nucleotide CYP1A1 polymorphisms (rs4646903/ g.75011641; rs1048943/g.75012985; g.75012235; and rs1799814/ g.75012987) were analysed via PCR-RFLP assay in 1,195 individuals of various human groups from all over the world. In order to gain a more complete view of the genetic variability of the CYP1A1 gene, different statistical analyses were performed upon the populations of the present study and upon the limited data gleaned from previously studied populations. The allele and haplotype frequencies vary among populations: the rs4646903 (C) and rs1048943 (G) have been found to be nearly always linked and were found at the highest frequencies in Native Americans, while the variant associated to the position g.75012235 was only detected in certain African populations. Our work clearly indicates that the CYP1A1 polymorphisms differ among populations and that the prediction of genotypes constitutes an important aspect of precision medicine since some variants were associated with certain cancers and rs1048943 show strong association with optimized chemotherapy. Moreover, the CYP1A1 gene plays an important role in the metabolism of xenobiotics and it is likely that its frequencies could be strongly influenced by environmental factors
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