Molecular mechanisms of silver nanoparticles activity on cellular level

Nanocząstki obecne w środowisku, zarówno pochodzenia naturalnego i antropogeniczne, mają wpływ na ludzkie zdrowie. Mimo intensywnych badań prowadzonych w celu wyjaśnienia aktywności biologicznej nanocząstek srebra w dalszym ciągu mechanizmy ich działania, zwłaszcza te związane ze stresem oksydacyjnym i nitrozacyjnym pozostają niejasne. Badania zostały przeprowadzone z użyciem linii komórkowych HepG2 oraz LIUHMES jako modeli badawczych. Pomiary wewnątrzkomórkowej produkcji anionorodnika ponadtlenkowego w mitochondriach i cytoplazmie, nadtlenku wodoru oraz tlenku azotu wykonano przy użyciu technik cytometrii przepływowej w oparciu o fluorescencję specyficznych sond. Pomiary Nadtlenku wodoru w mitochondriach wykonano z użyciem białka reporterowego HyPer-mito. Poziom nitrotyrozyny oceniony z użyciem technik immunochemicznych. Aktywność enzymatycznych składników obrony antyoksydacyjnej określono z użyciem klasycznych metod absorpcjometrycznych. Ocena transkryptomu dla białek z rodziny ABC i białek związanych ze stresem oksydacyjnym została przeprowadzona z użyciem komercyjnie dostępnych zestawów starterów. W toku badań wykazano, że dostępność glukozy moduluje toksyczność nanocząstek srebra i jest to związane z uaktywnieniem mechanizmów obrony antyoksydacyjnej przez wzmożoną aktywność łańcucha mitochondrialnego, oraz że typy komórek silnie zależne od glikolizy są bardziej podatne na toksyczny efekt nanomateriałów indukujących stres oksydacyjny. Nanocząsteczki srebra nie wykazały właściwości modulujących stres nitrozacyjny w sposób bezpośredni, ale wpływają na ekspresję białek związanych z obroną przed stresem nitrozacyjnym. Ponadto, prekursorowe komórki neuronalne są bardziej podatne na zmiany w ekspresji genów ABC, niż dojrzałe neurony, a profil zmian wywołany przez nanocząstki srebra jest podobny do profilu zmian podczas różnicowania. Zaproponowano mechanizm skutkujący zaburzeniem w homeostazie cholesterolu mediowany przez zmiany w ekspresji genu ABCA1, indukowany przez aktywację czynnika transkrypcyjnego LXR przez nanocząstki srebra.1. Projekt POIG "rola transporterów oporności wielolekowej w farmakokinetyce i toksykologii - testy in vitro i in vivo w praktyce farmaceutycznej i klinicznej", nr 01.01.02-10-005/08. 2. Projekt Narodowego Centrum Nauki uzyskany w toku procedury konkursowej PRELUDIUM. Tytuł: "Rola nanocząstek srebra w regulacji poziomu oraz modulacji aktywności białek zaangażowanych w sekrecję beta-amyloidu", nr re,: 2014/13/N/NZ1/00976. 3. Dotacje celowe na działalność związaną z prowadzeniem badań naukowych lub prac rozwojowych oraz zadań z nimi związanych, służących rozwojowi młodych naukowców oraz uczestników studiów doktoranckich w roku 2017

Performance Analysis of Shared-Memory Bus-Based Multiprocessors Using Timed Petri Nets

In shared-memory bus-based multiprocessors, the number of processors is often limited by the (shared) bus; when the utilization of the bus approaches 100%, processors spend an increasing amount of time waiting to get access to the bus (and shared memory) and this degrades their performance. The limitations imposed by the bus depend upon many parameters, and different parameters affect the performance in different ways. This chapter uses timed Petri nets to model shared-memory bus-based multiprocessors at the instruction execution level and shows how the performance of processors and the system are affected by different modeling parameters. Discrete-event simulation of the developed net models is used to get performance results

On Some Multi-Site Multi-Season Streamflow Generation Models

The relative performance of some multi-site multi-season models is compared with respect to their adequacy for simulating monthly streamflow sequences. The three models brought under examination are the extended version of the multi-variate model proposed by Matalas (1967), the model formulated by Young and Pisano (1968), and the disaggregation model of Valencia and Schaake (1972). Computer implementation of these models has been accomplished in the form of the Multi-site Multi-season Streamflow Generation Package (MMSGP). Evaluation and comparison of the models has been carried out in terms of statistical flow parameters only. Some of these parameters are not explicitly built into the model structure. At the end, some general comments concerning applicability of each model are presented. [Since this phase of investigations was completed, Mejia and Roussele (1976) have proposed modification of the disaggregation model which will be taken into account in the further work on the MMSGP.

Interval identification of FMR parameters for spin reorientation transition in (Ga,Mn)As

In this work we report results of ferromagnetic resonance studies of a 6% 15 nm (Ga,Mn)As layer, deposited on (001)-oriented GaAs. The measurements were performed with in-plane oriented magnetic field, in the temperature range between 5K and 120K. We observe a temperature induced reorientation of the effective in-plane easy axis from [-110] to [110] direction close to the Curie temperature. The behavior of magnetization is described by anisotropy fields, H_{eff} (= 4\piM -H_{2\perp}), H_{2\parallel}, and H_{4\parallel}. In order to precisely investigate this reorientation, numerical values of anisotropy fields have been determined using powerful - but still largely unknown - interval calculations. In simulation mode this approach makes possible to find all the resonance fields for arbitrarily oriented sample, which is generally intractable analytically. In 'fitting' mode we effectively utilize full experimental information, not only those measurements performed in special, distinguished directions, to reliably estimate the values of important physical parameters as well as their uncertainties and correlations.Comment: 3 pages, 3 figures. Presented at The European Conference "Physics of Magnetism 2011" (PM'11), June 27 - July 1, 2011, Poznan, Polan

Modeling Quality of Service Techniques for Packet-Switched Networks

Quality of service is the ability to provide different priorities to different applications, users or dataflows, or to guarantee a certain level of performance to a dataflow. The chapter uses timed Petri nets to model techniques that provide the quality of service in packet-switched networks and illustrates the behavior of developed models by performance characteristics of simple examples. These performance characteristics are obtained by discrete-event simulation of analyzed models

Table-driven analyses in the SPICE-PAC circuit simulation package

Recent applications of SPICE-PAC to transistor parameter extraction and hierarchical simulation require rather flexible circuit analyses, performed for irregularly distributed values of independent variables. An implementation of table-driven analyses (DC, AC, and time-domain) is described in which tables of arbitrarily distributed independent variables (voltages, frequencies, or timepoints) are used rather than the fixed-step strategy implemented in SPICE-like simulators. Simple examples are used to illustrate applications of table-driven analyses. The simple example of MOS inverter modeling shows that data-driven elements can provide the accuracy needed in practical applications, while reducing significantly the computational effort required for evaluation of complex models of semiconductor device

Symbolic Analysis of Timed Petri Nets

In timed Petri nets temporal properties are associated with transitions as transition firing times (or occurrence times). Specific properties of timed nets, such as boundedness or absence of deadlocks, can depend upon temporal properties and sometimes even a small change of these properties has a significant effect on the net’s behavior (e.g., a bounded net becomes unbounded or vice versa). The objective of symbolic analysis of timed nets is to provide information about the net’s behavior which is independent of specific temporal properties, i.e., which describes preperties of the whole class of timed nets with the same structure

Siphon-Based Verification of Component Compatibility

In component-based systems, two interacting components are compatible if any sequence of services requested by one component can be provided by the other. This concept of compatibility can easily be extended to a set of interacting components. Checking the compatibility of interacting components is essential for any dependable software system. Recently, an approach to verification of component compatibility has been proposed in which the behavior of individual components (at component interfaces) was modeled by labeled Petri nets. Moreover, the composition of interacting components was designed in such a way that all component incompatibilities were manifested by deadlocks in the composed model. Consequently, the verification of component compatibility is performed by deadlock analysis of the composed model. One of techniques for deadlock analysis is based on net structures called siphons. Siphon-based verification of component compatibility is the subject of this paper

STRUCTURAL METHODS IN PERFORMANCE ANALYSIS OF DISCRETE-EVENT SYSTEMS

Timed Petri nets, a formalism developed specifically for representation of concurrent activities, are popular models of discrete-event system. For net models which can be decomposed into simple cyclic subnets, the performance can be determined on the basis of components, without the exhaustive analysis of the behavior of the whole system; such an approach is known as structural analysis. The paper overviews the formal basic concepts of structural methods and uses manufacturing cells as an illustration of structural analysis