Asymptotic stability condition for stochastic Markovian systems of differential equations

summary:Asymptotic stability of the zero solution for stochastic jump parameter systems of differential equations given by ${\rm d} X(t) = A(\xi (t))X(t) {\rm d} t + H(\xi (t))X(t) {\rm d} w(t)$, where $\xi (t)$ is a finite-valued Markov process and w(t) is a standard Wiener process, is considered. It is proved that the existence of a unique positive solution of the system of coupled Lyapunov matrix equations derived in the paper is a necessary asymptotic stability condition

Structural Condition Assessment Of Prestressed Concrete Transit Guideways

Objective condition assessment is essential to make better decisions for safety and serviceability of existing civil infrastructure systems. This study explores the condition of an existing transit guideway system that has been in service for thirty-five years. The structural system is composed of six-span continuous prestressed concrete bridge segments. The overall transit system incorporates a number of continuous bridges which share common design details, geometries, and loading conditions. The original analysis is based on certain simplifying assumptions such as rigid behavior over supports and simplified tendon/concrete/steel plate interaction. The current objective is to conduct a representative study for a more accurate understanding of the structural system and its behavior. The scope of the study is to generate finite element models (FEMs) to be used in static and dynamic parameter sensitivity studies, as well load rating and reliability analysis of the structure. The FEMs are used for eigenvalue analysis and simulations. Parameter sensitivity studies consider the effect of changing critical parameters, including material properties, prestress loss, and boundary and continuity conditions, on the static and dynamic structural response. Load ratings are developed using an American Association for State Highway Transportation Officials Load and Resistance Factor Rating (AASHTO LRFR) approach. The reliability of the structural system is evaluated based on the data obtained from various finite element models. Recommendations for experimental validation of the FEM are presented. This study is expected to provide information to make better decisions for operations, maintenance and safety requirements; to be a benchmark for future studies, to establish a procedure and methodology for structural condition assessment, and to contribute to the general research body of knowledge in condition assessment and structural health monitoring

A Distinct Pool of Nav1.5 Channels at the Lateral Membrane of Murine Ventricular Cardiomyocytes.

Background: In cardiac ventricular muscle cells, the presence of voltage-gated sodium channels Na <sub>v</sub> 1.5 at the lateral membrane depends in part on the interaction between the dystrophin-syntrophin complex and the Na <sub>v</sub> 1.5 C-terminal PDZ-domain-binding sequence Ser-Ile-Val (SIV motif). α1-Syntrophin, a PDZ-domain adaptor protein, mediates the interaction between Na <sub>v</sub> 1.5 and dystrophin at the lateral membrane of cardiac cells. Using the cell-attached patch-clamp approach on cardiomyocytes expressing Na <sub>v</sub> 1.5 in which the SIV motif is deleted (ΔSIV), sodium current (I <sub>Na</sub> ) recordings from the lateral membrane revealed a SIV-motif-independent I <sub>Na</sub> . Since immunostaining has suggested that Na <sub>v</sub> 1.5 is expressed in transverse (T-) tubules, this remaining I <sub>Na</sub> might be carried by channels in the T-tubules. Of note, a recent study using heterologous expression systems showed that α1-syntrophin also interacts with the Na <sub>v</sub> 1.5 N-terminus, which may explain the SIV-motif independent I <sub>Na</sub> at the lateral membrane of cardiomyocytes. Aim: To address the role of α1-syntrophin in regulating the I <sub>Na</sub> at the lateral membrane of cardiac cells. Methods and Results: Patch-clamp experiments in cell-attached configuration were performed on the lateral membranes of wild-type, α1-syntrophin knockdown, and ΔSIV ventricular mouse cardiomyocytes. Compared to wild-type, a reduction of the lateral I <sub>Na</sub> was observed in myocytes from α1-syntrophin knockdown hearts. Similar to ΔSIV myocytes, a remaining I <sub>Na</sub> was still recorded. In addition, cell-attached I <sub>Na</sub> recordings from lateral membrane did not differ significantly between non-detubulated and detubulated ΔSIV cardiomyocytes. Lastly, we obtained evidence suggesting that cell-attached patch-clamp experiments on the lateral membrane cannot record currents carried by channels in T-tubules such as calcium channels. Conclusion: Altogether, these results suggest the presence of a sub-pool of sodium channels at the lateral membrane of cardiomyocytes that is independent of α1-syntrophin and the PDZ-binding motif of Na <sub>v</sub> 1.5, located in membrane domains outside of T-tubules. The question of a T-tubular pool of Na <sub>v</sub> 1.5 channels, however, remains open

Fishing for Prion Protein Function

The prion protein is infamous for its role in devastating neurological diseases, but its normal, physiological function has remained mysterious. A new study uses the experimentally tractable zebrafish model to obtain fresh clues to this puzzle

Recombinase mediated cassette exchange into genomic targets using an adenovirus vector

Recombinase mediated cassette exchange (RMCE) is a process in which site-specific recombinases exchange one gene cassette flanked by a pair of incompatible target sites for another cassette flanked by an identical pair of sites. Typically one cassette is present in the host genome, whereas the other gene cassette is introduced into the host cell by chemical or biological means. We show here that the frequency of cassette exchange is dependent on the relative and absolute quantities of the transgene cassette and the recombinase. We were able to successfully modify genomic targets not only by electroporation or chemically mediated gene transfer but also by using an adenovirus vector carrying both the transgene cassette to be inserted and the recombinase coding region. RMCE proceeds efficiently in cells in which the adenovirus vector is able to replicate. In contrast, insufficient quantities of the transgene cassette are produced in cells in which the virus cannot replicate. Additional transfection of the transgene cassette significantly enhances the RMCE frequency. This demonstrates that an RMCE system in the context of a viral vector allows the site directed insertion of a transgene into a defined genomic site

The Actin Gene Family: Function Follows Isoform

Although actin is often thought of as a single protein, in mammals it actually consists of six different isoforms encoded by separate genes. Each isoform is remarkably similar to every other isoform, with only slight variations in amino acid sequence. Nevertheless, recent work indicates that actin isoforms carry out unique cellular functions. Here, we review evidence drawn from localization studies, mouse models, and biochemical characterization to suggest a model for how in vivo mixing of actin isoforms may influence cytoskeletal function in cells. © 2010 Wiley-Liss, Inc

Polymorphisms at codons 108 and 189 in murine PrP play distinct roles in the control of scrapie incubation time

Rona Barron - ORCID: 0000-0003-4512-9177 https://orcid.org/0000-0003-4512-9177Item not available from this repository.Susceptibility to transmissible spongiform encephalopathies (TSEs) is associated strongly with PrP polymorphisms in humans, sheep and rodents. In mice, scrapie incubation time is controlled by polymorphisms at PrP codons 108 (leucine or phenylalanine) and 189 (threonine or valine), but the precise role of each polymorphism in the control of disease is unknown. The L108F and T189V polymorphisms are present in distinct structural regions of PrP and thus provide an excellent model with which to investigate the role of PrP structure and gene variation in TSEs. Two unique lines of transgenic mice, in which 108F and 189V have been targeted separately into the endogenous murine Prnp a gene, have been produced. TSE inoculation of inbred lines of mice expressing all allelic combinations at codons 108 and 189 has revealed a complex relationship between PrP allele and incubation time. It has been established that both codons 108 and 189 control TSE incubation time, and that each polymorphism plays a distinct role in the disease process. Comparison of ME7 incubation times in mouse lines that are heterozygous at both codons has also identified a previously unrecognized intramolecular interaction between PrP codons 108 and 189.https://doi.org/10.1099/vir.0.80525-086pubpub

Doppel and PrPC co-immunoprecipitate in detergent-resistant membrane domains of epithelial FRT cells

Dpl (doppel) is a paralogue of the PrPC (cellular prion protein), whose misfolded conformer (the scrapie prion protein, PrPSc) is responsible for the onset of TSEs (transmissible spongiform encephalopathies) or prion diseases. It has been shown that the ectopic expression of Dpl in the brains of some lines of PrP-knockout mice provokes cerebellar ataxia, which can be rescued by the reintroduction of the PrP gene, suggesting a functional interaction between the two proteins. It is, however, still unclear where, and under which conditions, this event may occur. In the present study we addressed this issue by analysing the intracellular localization and the interaction between Dpl and PrPC in FRT (Fischer rat thyroid) cells stably expressing the two proteins separately or together. We show that both proteins localize prevalently on the basolateral surface of FRT cells, in both singly and doubly transfected clones. Interestingly we found that they associate with DRMs (detergent-resistant membranes) or lipid rafts, from where they can be co-immunoprecipitated in a cholesterol-dependent fashion. Although the interaction between Dpl and PrPC has been suggested before, our results provide the first clear evidence that this interaction occurs in rafts and is dependent on the integrity of these membrane microdomains. Furthermore, both Dpl and PrPC could be immunoprecipitated with flotillin-2, a raft protein involved in endocytosis and cell signalling events, suggesting that they share the same lipid environment