Search results for "Application"
showing 10 items of 5559 documents
Can NF-κB Be Considered a Valid Drug Target in Neoplastic Diseases? Our Point of View
2020
Multidrug resistance (MDR), of the innate and acquired types, is one of major problems in treating tumor diseases with a good chance of success. In this review, we examine the key role of nuclear factor-kappa B (NF-κB) to induce MDR in three tumor models characterized precisely by innate or acquired MDR, in particular triple negative breast cancer (TNBC), hepatocellular carcinoma (HCC), and acute myeloid leukemia (AML). We also present different pharmacological approaches that our group have employed to reduce the expression/activation of this transcriptional factor and thus to restore chemo-sensitivity. Finally, we examine the latest scientific evidence found by other groups, the most sign…
Distribution of clozapine and desmethylclozapine between blood and brain in rats.
1999
Desmethylclozapine is the major metabolite of clozapine in serum. Although the metabolite is pharmacologically active in vitro, the occurrence of desmethylclozapine in brain under steady-state conditions and its role for clinical actions of clozapine are unclear. In this study 20 male Sprague-Dawley rats received five oral doses of clozapine 20 mg/kg at 1.5-h intervals. At 0.5, 1, 2 and 5 h after the last administration, at a time four animals were killed for analysis of clozapine and desmethylclozapine concentrations in serum and brain. The treatment yielded steady-state serum concentrations of clozapine that are considered as therapeutically effective in man. Desmethylclozapine concentrat…
A multilevel object-oriented modelling methodology for physiologically-based pharmacokinetics (PBPK): Evaluation with a semi-mechanistic pharmacokine…
2019
Abstract Background and objective The aims of this study are (i) to assess the predictive reliability of the physiologically based software PhysPK versus the well-known population approach software NONMEM for the cited semi-mechanistic PK model, (ii) to determine whether these modelling approaches are interchangeable and (iii) to compare acausal with causal modelling approaches in the framework of semi-mechanistic PK models. Methods A semi-mechanistic model was proposed, which assumed oral administration of a solid dosage form with a peripheral compartment and two active metabolites. The model incorporates intestinal transit, dissolution limited by solubility, variable efflux transporter ex…
Modeling Drug-Induced Anorexia by Molecular Topology
2012
Molecular topology (MT) has demonstrated to be a very good technique for describing molecular structures and to predict physical, chemical, and biological properties of compounds. In this paper, a topological-mathematical model based on MT has been developed for identifying drug compounds showing anorexia as a side effect. An external validation (test set) has been carried out, yielding over an 80% correct classification in the active and inactive compounds. These results reinforce the role of MT as a potential useful tool for predicting drug side effects.
The Effectiveness of Vitamin E Treatment in Alzheimer’s Disease
2019
Vitamin E was proposed as treatment for Alzheimer’s disease many years ago. However, the effectiveness of the drug is not clear. Vitamin E is an antioxidant and neuroprotector and it has anti-inflammatory and hypocholesterolemic properties, driving to its importance for brain health. Moreover, the levels of vitamin E in Alzheimer’s disease patients are lower than in non-demented controls. Thus, vitamin E could be a good candidate to have beneficial effects against Alzheimer’s. However, evidence is consistent with a limited effectiveness of vitamin E in slowing progression of dementia; the information is mixed and inconclusive. The question is why does vitamin E fail to tre…
Impulsively-controlled systems and reverse dwell time: A linear programming approach
2015
We present a receding horizon algorithm that converges to the exact solution in polynomial time for a class of optimal impulse control problems with uniformly distributed impulse instants and governed by so-called reverse dwell time conditions. The cost has two separate terms, one depending on time and the second monotonically decreasing on the state norm. The obtained results have both theoretical and practical relevance. From a theoretical perspective we prove certain geometrical properties of the discrete set of feasible solutions. From a practical standpoint, such properties reduce the computational burden and speed up the search for the optimum thus making the algorithm suitable for th…
Quantized Dissensus in Networks of Agents subject to Death and Duplication
2012
Dissensus is a modeling framework for networks of dynamic agents in competition for scarce resources. Originally inspired by biological cells behaviors, it fits also marketing, finance and many other application areas. Competition is often unstable in the sense that strong agents, those having access to large resources, gain more and more resources at the expense of weak agents. Thus, strong agents duplicate when reaching a critical amount of resources, whereas weak agents die when loosing all their resources. To capture all these phenomena we introduce systems with a discrete time gossip and unstable state dynamics interrupted by discrete events affecting the network topology. Invariancy o…
Mode-superposition correction method for deterministic and stochastic analysis of structural systems
2001
The role played by the modal analysis in the framework of structural dynamics is fundamental from both deterministic and stochastic point of view. However the accuracy obtained by means of the classical modal analysis is not always satisfactory. Therefore it is clear the importance of methods able to correct the modal response in such a way to obtain the required accuracy. Many methods have been proposed in the last years but they are meaningful only when the forcing function is expressed by an analytical function. Moreover in stochastic analysis they fail for white noise excitation. In the paper a method able to give a very accurate response for both deterministic and stochastic input is p…
GAIML: A New Language for Verbal and Graphical Interaction in Chatbots
2008
Natural and intuitive interaction between users and complex systems is a crucial research topic in human-computer interaction. A major direction is the definition and implementation of systems with natural language understanding capabilities. The interaction in natural language is often performed by means of systems called chatbots. A chatbot is a conversational agent with a proper knowledge base able to interact with users. Chatbots appearance can be very sophisticated with 3D avatars and speech processing modules. However the interaction between the system and the user is only performed through textual areas for inputs and replies. An interaction able to add to natural language also graph…
Inferring slowly-changing dynamic gene-regulatory networks
2015
Dynamic gene-regulatory networks are complex since the interaction patterns between their components mean that it is impossible to study parts of the network in separation. This holistic character of gene-regulatory networks poses a real challenge to any type of modelling. Graphical models are a class of models that connect the network with a conditional independence relationships between random variables. By interpreting these random variables as gene activities and the conditional independence relationships as functional non-relatedness, graphical models have been used to describe gene-regulatory networks. Whereas the literature has been focused on static networks, most time-course experi…