51 research outputs found

    Dynamics on the path space of generalized Bratteli diagrams

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    Bratteli-Vershik models have been very successfully applied to the study of dynamics on compact metric spaces and, in particular, in Cantor dynamics. In this paper, we study dynamics on the path spaces of generalized Bratteli diagrams that form models for non-compact Borel dynamical systems. Generalized Bratteli diagrams have countably infinite many vertices at each level, thus the corresponding incidence matrices are also countably infinite. We emphasize differences (and similarities) between generalized and classical Bratteli diagrams. Our main results: (i) We utilize Perron-Frobenius theory for countably infinite matrices to establish criteria for the existence and uniqueness of tail invariant path-space measures (both probability and Ļƒ\sigma-finite). (ii) We provide criteria for the topological transitivity of the tail equivalence relation. (iii) We describe classes of stationary generalized Bratteli diagrams (hence Borel dynamical systems) that: (a) do not support a probability tail invariant measure, (b) do not admit a continuous Vershik map, (c) are not uniquely ergodic with respect to the tail equivalence relation. (iv) We provide an application of the theory of stochastic matrices to analyze diagrams with positive recurrent incidence matrices

    Cytoprotective Activated Protein C Averts Nlrp3 Inflammasomeā€“Induced Ischemia-Reperfusion Injury Via Mtorc1 Inhibition

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    Cytoprotection by activated protein C (aPC) after ischemia-reperfusion injury (IRI) is associated with apoptosis inhibition. However, IRI is hallmarked by inflammation, and hence, cell-death forms disjunct from immunologically silent apoptosis are, in theory, more likely to be relevant. Because pyroptosis (ie, cell death resulting from inflammasome activation) is typically observed in IRI, we speculated that aPC ameliorates IRI by inhibiting inflammasome activation. Here we analyzed the impact of aPC on inflammasome activity in myocardial and renal IRIs. aPC treatment before or after myocardial IRI reduced infarct size and Nlrp3 inflammasome activation in mice. Kinetic in vivo analyses revealed that Nlrp3 inflammasome activation preceded myocardial injury and apoptosis, corroborating a pathogenic role of the Nlrp3 inflammasome. The constitutively active Nlrp3A350V mutation abolished the protective effect of aPC, demonstrating that Nlrp3 suppression is required for aPC-mediated protection from IRI. In vitro aPC inhibited inflammasome activation in macrophages, cardiomyocytes, and cardiac fibroblasts via proteinase-activated receptor 1 (PAR-1) and mammalian target of rapamycin complex 1 (mTORC1) signaling. Accordingly, inhibiting PAR-1 signaling, but not the anticoagulant properties of aPC, abolished the ability of aPC to restrict Nlrp3 inflammasome activity and tissue damage in myocardial IRI. Targeting biased PAR-1 signaling via parmodulin-2 restricted mTORC1 and Nlrp3 inflammasome activation and limited myocardial IRI as efficiently as aPC. The relevance of aPC-mediated Nlrp3 inflammasome suppression after IRI was corroborated in renal IRI, where the tissue protective effect of aPC was likewise dependent on Nlrp3 inflammasome suppression. These studies reveal that aPC protects from IRI by restricting mTORC1-dependent inflammasome activation and that mimicking biased aPC PAR-1 signaling using parmodulins may be a feasible therapeutic approach to combat IRI

    Precision Targeting of Bacterial Pathogen Via Bi-Functional Nanozyme Activated by Biofilm Microenvironment

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    Human dental caries is an intractable biofilm-associated disease caused by microbial interactions and dietary sugars on the host\u27s teeth. Commensal bacteria help control opportunistic pathogens via bioactive products such as hydrogen peroxide (H2O2). However, high-sugar consumption disrupts homeostasis and promotes pathogen accumulation in acidic biofilms that cause tooth-decay. Here, we exploit the pathological (sugar-rich/acidic) conditions using a nanohybrid system to increase intrinsic H2O2 production and trigger pH-dependent reactive oxygen species (ROS) generation for efficient biofilm virulence targeting. The nanohybrid contains glucose-oxidase that catalyzes glucose present in biofilms to increase intrinsic H2O2, which is converted by iron oxide nanoparticles with peroxidase-like activity into ROS in acidic pH. Notably, it selectively kills Streptococcus mutans (pathogen) without affecting Streptococcus oralis (commensal) via preferential pathogen-binding and in situ ROS generation. Furthermore, nanohybrid treatments potently reduced dental caries in a rodent model. Compared to chlorhexidine (positive-control), which disrupted oral microbiota diversity, the nanohybrid had significant higher efficacy without affecting soft-tissues and the oral-gastrointestinal microbiomes, while modulating dental health-associated microbial activity in vivo. The data reveal therapeutic precision of a bi-functional hybrid nanozyme against a biofilm-related disease in a controlled-manner activated by pathological conditions. Ā© 2020 The Author

    Parametric Study on Dimensional Control of ZnO Nanowalls and Nanowires by Electrochemical Deposition

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    A simple electrochemical deposition technique is used to synthesize both two-dimensional (nanowall) and one-dimensional (nanowire) ZnO nanostructures on indium-tin-oxide-coated glass substrates at 70Ā°C. By fine-tuning the deposition conditions, particularly the initial Zn(NO3)2Ā·6H2O electrolyte concentration, the mean ledge thickness of the nanowalls (50ā€“100 nm) and the average diameter of the nanowires (50ā€“120 nm) can be easily varied. The KCl supporting electrolyte used in the electrodeposition also has a pronounced effect on the formation of the nanowalls, due to the adsorption of Clāˆ’ ions on the preferred (0001) growth plane of ZnO and thereby redirecting growth on the (100) and (20) planes. Furthermore, evolution from the formation of ZnO nanowalls to formation of nanowires is observed as the KCl concentration is reduced in the electrolyte. The crystalline properties and growth directions of the as-synthesized ZnO nanostructures are studied in details by glancing-incidence X-ray diffraction and transmission electron microscopy

    Highlights From the Annual Meeting of the American Epilepsy Society 2022

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    With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia

    Long-Range Temporal Correlations Reflect Treatment Response in the Electroencephalogram of Patients with Infantile Spasms

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    Infantile spasms syndrome is an epileptic encephalopathy in which prompt diagnosis and treatment initiation are critical to therapeutic response. Diagnosis of the disease heavily depends on the identification of characteristic electroencephalographic (EEG) patterns, including hypsarrhythmia. However, visual assessment of the presence and characteristics of hypsarrhythmia is challenging because multiple variants of the pattern exist, leading to poor inter-rater reliability. We investigated whether a quantitative measurement of the control of neural synchrony in the EEGs of infantile spasms patients could be used to reliably distinguish the presence of hypsarrhythmia and indicate successful treatment outcomes. We used autocorrelation and Detrended Fluctuation Analysis (DFA) to measure the strength of long-range temporal correlations in 21 infantile spasms patients before and after treatment and 21 control subjects. The strength of long-range temporal correlations was significantly lower in patients with hypsarrhythmia than control patients, indicating decreased control of neural synchrony. There was no difference between patients without hypsarrhythmia and control patients. Further, the presence of hypsarrhythmia could be classified based on the DFA exponent and intercept with 92% accuracy using a support vector machine. Successful treatment was marked by a larger increase in the DFA exponent compared to those in which spasms persisted. These results suggest that the strength of long-range temporal correlations is a marker of pathological cortical activity that correlates with treatment response. Combined with current clinical measures, this quantitative tool has the potential to aid objective identification of hypsarrhythmia and assessment of treatment efficacy to inform clinical decision-making
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