Search results for "Simulation."

Ensemble-based ADME-Tox profiling and virtual screening for the discovery of new inhibitors of the Leishmania mexicana cysteine protease CPB2.8ΔCTE

2018

Abstract: In an effort to identify novel molecular warheads able to inhibit Leishmania mexicana cysteine protease CPB2.8CTE, fused benzo[b]thiophenes and ,'-triketones emerged as covalent inhibitors binding the active site cysteine residue. Enzymatic screening showed a moderate-to-excellent activity (12%-90% inhibition of the target enzyme at 20m). The most promising compounds were selected for further profiling including in vitro cell-based assays and docking studies. Computational data suggest that benzo[b]thiophenes act immediately as non-covalent inhibitors and then as irreversible covalent inhibitors, whereas a reversible covalent mechanism emerged for the 1,3,3'-triketones with a Y-to…

Synthesis and biological evaluation of a D-ring-contracted analogue of lamellarin D

2017

A D-ring contracted analogue of the strongly cytotoxic marine pyrrole alkaloid lamellarin D was synthesized and investigated for its antiproliferative action towards a wild type and a multidrug resistant (MDR) cancer cell line. The compound was found to inhibit tumor cell growth at submicromolar concentrations and showed a lower relative resistance in the MDR cell line than the antitumor drug camptothecin to which lamellarin D shows cross resistance and with which lamellarin D shares the same binding site.

Comparative analysis of virtual screening approaches in the search for novel EphA2 receptor antagonists

2015

The EphA2 receptor and its ephrin-A1 ligand form a key cell communication system, which has been found overexpressed in many cancer types and involved in tumor growth. Recent medicinal chemistry efforts have identified bile acid derivatives as low micromolar binders of the EphA2 receptor. However, these compounds suffer from poor physicochemical properties, hampering their use in vivo. The identification of compounds able to disrupt the EphA2-ephrin-A1 complex lacking the bile acid scaffold may lead to new pharmacological tools suitable for in vivo studies. To identify the most promising virtual screening (VS) protocol aimed at finding novel EphA2 antagonists, we investigated the ability of…

(H, ρ)-induced dynamics and the quantum game of life

2017

Abstract We propose an extended version of quantum dynamics for a certain system S , whose evolution is ruled by a Hamiltonian H, its initial conditions, and a suitable set ρ of rules, acting repeatedly on S . The resulting dynamics is not necessarily periodic or quasi-periodic, as one could imagine for conservative systems with a finite number of degrees of freedom. In fact, it may have quite different behaviors depending on the explicit forms of H, ρ as well as on the initial conditions. After a general discussion on this (H, ρ)-induced dynamics, we apply our general ideas to extend the classical game of life, and we analyze several aspects of this extension.

Social Simulation Based on Cellular Automata: Modeling Language Shifts

2011

Nowadays, language shifts (i.e., a community of speakers stops using their traditional language and speaks a new one in all communication settings) may produce a massive extinction of languages throughout the world. In this context, an important task for social sciences research should therefore be to achieve a deep comprehension of language shifts. However, modeling the social and behavioral variables that guide the social behavior of individuals and groups has traditionally been tricky in all the social sciences. In this situation, social simulation provides a tool for testing hypotheses and building models of social phenomena (see, for example, Gilbert, 1996; Gilbert & Toitzsch, 2005; an…

A Simulation Model of a Tandem Coordinated Supply Chain

2010

This paper presents a study of a coordinated production inventory-system. In the proposed model, any echelon considers its successors as part of its inventory system and generates the replenishment order on the basis of operational information of its partners. We show that the coordinated decision making allows elimination of information distortion along the chain. Furthermore, we show how the bottom-up transmission of inefficiencies, typical of traditional supply chains, is avoided.

Comparative computational analysis of different active site conformations and substrates in a chalcone isomerase catalyzed reaction.

2006

Chalcone isomerase catalyzes the transformation of chalcones to flavanones. We present a computational study of the rate-limiting chemical step, an intramolecular Michael addition of a 2'-oxyanion to the alpha,beta-double bound. By using quantum mechanical/molecular mechanical hybrid methods we traced the free-energy profiles associated with the reaction of two different substrates (chalcone and 6'-deoxychalcone) in two different conformations of the active site that are described in the different crystallographic structures available. We have obtained significant differences (about 4 kcal/mol) in the free-energy barriers calculated for the two active sites. According to our results, the ac…

Channel aggregation with guard-band in D-OFDM based CRNs: Modeling and performance evaluation

2016

Channel aggregation (CA) techniques can offer flexible channel allocation and improve overall system performance in multi-channel cognitive radio networks (CRNs). Although many CA techniques have been proposed and studied, the impact of guard-band on CA for channel access has not been addressed in-depth. In this paper, we study the guard-band allocation mechanisms in discontinuous-orthogonal frequency division multiplexing (D-OFDM) based CRNs, and investigate the impact of guard-band sharing on SU flows when CA is enabled. Continuous time Markov chain (CTMC) based models have been developed in order to investigate the stochastic behavior of PU and SU flows. Based on our mathematical analysi…

SHARING THE BENEFITS OF COOPERATION IN HIGH SEAS FISHERIES: A CHARACTERISTIC FUNCTION GAME APPROACH

1998

Thermomechanical effects in the flow of a fluid in porous media

2002

This paper deals with analysis, by methods of extended thermodynamics, of the thermomechanical effects which arise in the flow of a weakly viscous fluid in a porous medium. Under the hypothesis that the fluid fills all the interstices among the powder and that the size of the powder grains and of the interstices is much lower than a suitable characteristic length, linearized field equations are written, which include, in a natural way, terms which take into account the Dufour, Soret, and virtual mass effects. As a limiting case when the evolution time of the heat flux goes to infinite and no entropy flux is carried, the flow of liquid helium II in a porous medium is obtained.