László Muka

55014317300

Publications - 13

Investigating ABCB1-mediated drug-drug interactions: Considerations for in vitro and in vivo assay design

Zsuzsanna Rajnai Péter Szerémy László Muka Zsolt Fekete Péter Krajcsi Tasha K. Ritchie Zsolt Sáfár Gábor Imre Balázs Vaskó Joseph K. Zolnerciks Krisztina Herédi-Szabó Isabelle Ragueneau-Majlessi Károly Mogyorósi Franciska Erdo

Publication Name: Current Drug Metabolism

Publication Date: 2016-06-01

Volume: 17

Issue: 5

Page Range: 430-455

Description:

Background: ABCB1 is a key ABC efflux transporter modulating the pharmacokinetics of a large percentage of drugs. ABCB1 is also a site of transporter mediated drug-drug interactions (tDDI). It is the transporter most frequently tested for tDDIs both in vitro and in the clinic. Objective: Understanding the limitations of various in vitro and in vivo models, therefore, is crucial. In this review we cover regulatory aspects of ABCB1 mediated drug transport as well as inhibition and the available models and methods. We also discuss protein structure and mechanistic aspects of transport as ABCB1 displays complex kinetics that involves multiple binding sites, potentiation of transport and probe-dependent IC50 values. Results: Permeability of drugs both passive and mediated by transporters is also a covariate that modulates apparent kinetic values. Levels of expression as well as lipid composition of the expression system used in in vitro studies have also been acknowledged as determinates of transporter activity. ABCB1-mediated clinical tDDIs are often complex as multiple transporters as well as metabolic enzymes may play a role. This complexity often masks the role of ABCB1 in tDDIs. Conclusion: It is expected that utilization of in vitro data will further increase with the refinement of simulations. It is also anticipated that transporter humanized preclinical models have a significant impact and utility.

Open Access: Yes

DOI: 10.2174/1389200217666160105111304

Evaluation and improvement of parallel discrete event simulation performance predictions: A rough-set-based approach

László Muka István Derka

Publication Name: Acta Polytechnica Hungarica

Publication Date: 2016-01-01

Volume: 13

Issue: 6

Page Range: 125-145

Description:

Simulation performance prediction methods make possible the realization of performance improvement potentials of Parallel Discrete Event Simulation (PDES) methods, important in the analysis of complex systems and large-scale networks. Currently, high performance execution environments (emerging clusters and computing clouds) advance the development of quality/cost analysis capabilities of performance prediction methods. In this paper, for the evaluation and management of prediction correctness/cost, the efficacy, efficiency and effectiveness coefficients and improvement operations are defined for predictions. The performance coefficients and improvement operations are embedded in the rough-set-modeling and learning process and presented as an enhancement approach of the conventional Coupling Factor Method (CFM). A case study based on the CFM analysis of PDES of a closed queuing network model is presented. In the example, after rough-modeling and train-and-test analysis, the correctness/cost evaluation and effectiveness improvement operations are shown for series of predictions and the feedback connection to modeling refinement phase is demonstrated too.

Open Access: Yes

DOI: DOI not available

Towards the efficient simulation of telecommunication systems in heterogeneous distributed execution environments

László Muka István Derka Gábor Lencse

Publication Name: 2013 36th International Conference on Telecommunications and Signal Processing Tsp 2013

Publication Date: 2013-10-21

Volume: Unknown

Issue: Unknown

Page Range: 304-310

Description:

An introduction is given to the topics of the parallel and distributed simulation and of the modeling of telecommunications systems. Our practical modeling concept for simulation in heterogeneous execution environment is presented. Its logical topology is a star shaped network of homogeneous clusters. The load balancing and the coupling factor criteria are set up for building models of telecommunications systems so that the simulation may produce good speed-up in a heterogeneous distributed execution environment. A case study is given with the open source OMNeT++ discrete-event simulation system and its parallel CQN (closed queueing network) sample model executed by 64 CPU cores of four different types. Our criteria are heavily supported by the results of our experiments. © 2013 IEEE.

Open Access: Yes

DOI: 10.1109/TSP.2013.6613941

Improving performance prediction of parallel and distributed discrete event simulation: A rough sets-based approach

László Muka István Derka

Publication Name: 11th International Industrial Simulation Conference 2013 Isc 2013

Publication Date: 2013-01-01

Volume: Unknown

Issue: Unknown

Page Range: 95-100

Description:

The rapid growth of complexity of communication networks - including grids, cloud systems and services - increases the need for the use and performance prediction of parallel and distributed discrete event simulation. The paper aims at the decreasing the overall cost of simulation by improving the performance prediction of simulation particularly for the phases with uncertain and vague information. Involving rough sets-based methods, the paper introduces how the efficiency of the well known coupling factor method of the performance prediction of parallel and distributed simulation can be improved. According to the presented results, the prediction can merely be based on the maintainable lookahead feature of the designed simulation model. Using the rough set analysis, the paper also describes how the number of simulation experiments necessary for prediction can be limited without the decrease of accuracy of prediction.

Open Access: Yes

DOI: DOI not available

Creating and using Key Network-Performance Indicators to support the design of change of enterprise infocommunication infrastructure

László Muka Gergely Muka

Publication Name: Simulation Series

Publication Date: 2012-12-10

Volume: 44

Issue: BOOK 12

Page Range: 176-181

Description:

Nowadays, an increasing number of organisations have to make decisions about the change and optimization of their enterprise infocommunication infrastructure. The usual approach of performance (using QoS, SLA) is not user (enterprise) centred and complex enough to help ICT (Information and Communication Technology) experts to support management decisions. The paper proposes a strategic management inspired, user centred and complex method of creating KNPIs (Key Network-Performance Indicators) for the measurement. In the paper, a case study is introduced to illustrate the creation and the use of KNPIs: alternatives are generated for the change, and using KNPIs, the feasibility, capacity, quality and financial aspects - integrating also the business impact and the influence of user experience - of the change of the enterprise infocommunication infrastructure are examined and compared. In the case study, to the analysis and prediction of the necessary enterprise network capacities, network traffic simulation is used. Financial modelling is also applied in comparing the alternatives.

Open Access: Yes

DOI: DOI not available

Creating and using key network-performance indicators to support the design of change of enterprise infocommunication infrastructure

László Muka Gergely Muka

Publication Name: Proceedings of the 2012 International Symposium on Performance Evaluation of Computer and Telecommunication Systems Spects 12 Part of Summersim 2012 Multiconference

Publication Date: 2012-10-08

Volume: Unknown

Issue: Unknown

Page Range: Unknown

Description:

Nowadays, an increasing number of organisations have to make decisions about the change and optimization of their enterprise infocommunication infrastructure. The usual approach of performance (using QoS, SLA) is not user (enterprise) centred and complex enough to help ICT (Information and Communication Technology) experts to support management decisions. © 2012 Society for Modeling & Sim.

Open Access: Yes

DOI: DOI not available

Meta-level performance management of simulation of organizational information systems: The problem context state approach

László Muka Gábor Lencse

Publication Name: Infocommunications Journal

Publication Date: 2011-06-01

Volume: 3

Issue: 2

Page Range: 20-27

Description:

Simulation has become a frequently used tool for the analysis of ICT and BP systems and for fitting the features of these systems with each other and with the goals of the enterprise. For example, the change management of ERP (Enterprise Resource Planning) systems is a significant generator of the need for the common analysis of ICT/BP systems and the use of simulation may play crucial role in their analysis. The paper formulates the problem context state approach to the meta-level performance management of simulation in the form of efficiency management principles. The formulation is based on the investigation of the features of the dynamic behavior of problem contexts - using the 4-state and 2-state models of problem context types - for the common modeling and simulation of organizational ICT/BP systems. The process of the occurrence and elimination of the methodological gap is explained too.

Open Access: Yes

DOI: DOI not available

Cooperating modelling methods for performance evaluation of interconnected infocommunication and business process systems

László Muka Gábor Lencse

Publication Name: Esm 2008 2008 European Simulation and Modelling Conference Modelling and Simulation 2008

Publication Date: 2008-01-01

Volume: Unknown

Issue: Unknown

Page Range: 404-411

Description:

This paper describes how the rapid and detailed modelling and simulation methods can be used to increase the efficiency of mixed simulation projects initiated to support the design of interconnected ICT (Information and Communication Technology) and BP (Business Process) systems. A system of cooperating rapid and detailed methods for critical and non- critical parts of systems is introduced in the phase of preliminary and detailed modelling. The method of translation of information of conceptual models that had been built prior to simulation is described, too. New methods using rapid models to model the ICT and BP systems functioning as environment for the detailed models are presented. A novel method for preliminary modelling based only on cooperating system of rapid models is described. © 2008 EUROSIS-ETI.

Open Access: Yes

DOI: DOI not available

Managing the resolution of simulation models

László Muka Gábor Lencse

Publication Name: Esm 2008 2008 European Simulation and Modelling Conference Modelling and Simulation 2008

Publication Date: 2008-01-01

Volume: Unknown

Issue: Unknown

Page Range: 38-42

Description:

A novel approach based on inflation and deflation is proposed for managing the resolution of simulation models. Different methods are proposed for manual or automatic deflation. An example is given how a topology description language can be extended to support the inflation/deflation concept. Dynamic management of the model resolution is introduced using the method called inflate-the-next and also two of its possible improvements. © 2008 EUROSIS-ETI.

Open Access: Yes

DOI: DOI not available

Combination and interworking of four modelling methods for infocommunications and business process systems

László Muka Gábor Lencse

Publication Name: 5th International Industrial Simulation Conference 2007 Isc 2007

Publication Date: 2007-01-01

Volume: Unknown

Issue: Unknown

Page Range: 350-354

Description:

This paper describes how we can use four modelling methods together. We model Information and Communication Technology (ICT) systems and Business Process (BP) systems. The aim of the modelling is to experiment with the models, that is, simulation. Two of the methods are the detailed modelling of the ICT and of the BP systems, as we usually do that for discrete event simulation. The other two methods are those that enable us to make rapid performance analysis of these systems, namely Traffic-Flow Analysis (TEA) for ICT systems and Entity Flow-phase Analysis (EFA) for BP systems. The solutions for the combination and interworking of these methods are described.

Open Access: Yes

DOI: DOI not available

Investigation of the spatial distribution algorithm of the traffic flow analysis and of the entity flow-phase analysis

László Muka Gábor Lencse

Publication Name: Esm 2007 2007 European Simulation and Modelling Conference Modelling and Simulation 2007

Publication Date: 2007-01-01

Volume: Unknown

Issue: Unknown

Page Range: 291-295

Description:

This paper investigates an important algorithm that is used in both the Traffic-Flow Analysis and the Entity Flow-phase Analysis. These methods are similar to each other and can be used for the fast and approximate (performance) analysis of Information and Communication Technology (ICT) systems and Business Process (BP) systems. Both methods contain an algorithm for the spatial distribution of the traffic (or entities) in the system. It is shown how the error of the spatial distribution can be measured, and the effect of the so called size of routing unit parameter of two algorithms is investigated.

Open Access: Yes

DOI: DOI not available

Convergence of the key algorithm of traffic-flow analysis

László Muka Gábor Lencse

Publication Name: Journal of Computing and Information Technology

Publication Date: 2006-01-01

Volume: 14

Issue: 2

Page Range: 133-139

Description:

The traffic-flow analysis (TFA) [1] is a novel method for the performance estimation of communication systems. TFA is a combination of simulation and numerical methods. In the first step, TFA distributes the traffic in units of properly chosen size using the actual routing algorithm of the network. In the second step, TFA adjusts the time distribution of the traffic according to the finite capacities of the network. The convergence of the algorithm used in the second step of TFA is proven in this paper. The speed of convergence is also examined.

Open Access: Yes

DOI: 10.2498/cit.2006.02.04

Expanded scope of traffic-flow analysis: Entity flow-phase analysis for rapid performance evaluation of enterprise process systems

László Muka Gábor Lencse

Publication Name: Esm 2006 2006 European Simulation and Modelling Conference Modelling and Simulation 2006

Publication Date: 2006-01-01

Volume: Unknown

Issue: Unknown

Page Range: 94-98

Description:

This paper describes entity-flow phase analysis (EFA) which is a method for fast performance analysis of organisational process systems. EFA, similarly to traffic-flow analysis for communication systems (TFA), uses the combined approach of simulation and numerical methods. In simulation projects initiated to support the design of Information and Communication Technology (ICT) system and Business Process (BP) system in an organisation the parallel analysis of different systems may be efficient. EFA is a promising evaluation method to be applied for systems with determined BP and ICT subsystems in an organisational environment.

Open Access: Yes

DOI: DOI not available