scholarly journals Optimal selection policies for a sequence of candidate drugs

2008 ◽  
Vol 40 (02) ◽  
pp. 359-376 ◽  
Author(s):  
C. Charalambous ◽  
J. C. Gittins

Pharmaceutical companies have to face huge risks and enormous costs of production before they can produce a drug. Efficient allocation of resources is essential to help in maximizing profits. Yu and Gittins (2007) described a model and associated software for determining efficient allocations for a preclinical research project. This is the starting point for this paper. We provide explicit optimal policies for the selection of successive candidate drugs for two restricted versions of the Yu and Gittins (2007) model. To some extent these policies are likely to be applicable to the unrestricted model.

2008 ◽  
Vol 40 (2) ◽  
pp. 359-376 ◽  
Author(s):  
C. Charalambous ◽  
J. C. Gittins

Pharmaceutical companies have to face huge risks and enormous costs of production before they can produce a drug. Efficient allocation of resources is essential to help in maximizing profits. Yu and Gittins (2007) described a model and associated software for determining efficient allocations for a preclinical research project. This is the starting point for this paper. We provide explicit optimal policies for the selection of successive candidate drugs for two restricted versions of the Yu and Gittins (2007) model. To some extent these policies are likely to be applicable to the unrestricted model.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Natascha Ingrid Drude ◽  
Lorena Martinez Gamboa ◽  
Meggie Danziger ◽  
Ulrich Dirnagl ◽  
Ulf Toelch

The purpose of preclinical research is to inform the development of novel diagnostics or therapeutics, and the results of experiments on animal models of disease often inform the decision to conduct studies in humans. However, a substantial number of clinical trials fail, even when preclinical studies have apparently demonstrated the efficacy of a given intervention. A number of large-scale replication studies are currently trying to identify the factors that influence the robustness of preclinical research. Here, we discuss replications in the context of preclinical research trajectories, and argue that increasing validity should be a priority when selecting experiments to replicate and when performing the replication. We conclude that systematically improving three domains of validity – internal, external and translational – will result in a more efficient allocation of resources, will be more ethical, and will ultimately increase the chances of successful translation.


2020 ◽  
Vol 81 (6) ◽  
pp. 23-31
Author(s):  
M. I. Vasileva

The aim of the study was to investigate approaches to the formation of general educational skills. A survey examining the design and research process was carried out by 6th-grade Russian students over the course of an extracurricular project entitled «Names of Modern Professions». In the paper, the selection of the «Lexicology» section for such activities carried out by school pupils is substantiated and stages of work on the project are described. The applied methodology involves theoretical analysis of scientific literature, formative experimentation, analysis of products of educational activities, observation and description. It is concluded that the design of extracurricular research activities in the Russian language contributes to the formation of general educational competencies in conducting surveys and searching for information on the basis of subject skills.


2020 ◽  
pp. 123-150
Author(s):  
Julia Saviello

Smell and taste – of the five senses these are the two most strongly stimulated by smoking tobacco. The article presents an in-depth analysis of the reflection of both these forms of sensory perception in textual and visual sources concerning the early consumption of the herb. In a first step, tobacco’s changing reception, first as medicine and then as stimulant, is traced through the years of its increasing distribution in Europe, starting in the middle of the 16th century. As this overview reveals, at that time the still little known substance gave rise to new forms of sense perception. Following recent studies on smell and gustation, which have stressed the need to take into account the interactions between these senses, the article probes the manifold stimulation of the senses by tobacco with reference to allegorical representations and genre scenes addressing the five senses. The smoking of tobacco was thematized in both of these art forms as a means of visualizing either smell or taste. Yet, these depictions show no indication of any deliberate engagement with the exchange of sense data between mouth and nose. The question posed at the end of this paper is whether this holds true also for early smoker’s still lifes. In the so-called toebakjes or rookertjes, a subgenre of stilllife painting that, like tobacco, was still a novelty at the beginning of the 17th century, various smoking paraphernalia – such as rolled or cut tobacco, pipes and tins – are arrayed with various kinds of foods and drinks. Finally, the article addresses a selection of such smoker’s still lifes, using the toebakje by Pieter Claesz., probably the first of its kind, as a starting point and the work by Georg Flegel as a comparative example. Through their selection of objects, both offer a complex image of how tobacco engages different senses.


2020 ◽  
Vol 16 (6) ◽  
pp. 784-795
Author(s):  
Krisnna M.A. Alves ◽  
Fábio José Bonfim Cardoso ◽  
Kathia M. Honorio ◽  
Fábio A. de Molfetta

Background:: Leishmaniosis is a neglected tropical disease and glyceraldehyde 3- phosphate dehydrogenase (GAPDH) is a key enzyme in the design of new drugs to fight this disease. Objective:: The present study aimed to evaluate potential inhibitors of GAPDH enzyme found in Leishmania mexicana (L. mexicana). Methods: A search for novel antileishmanial molecules was carried out based on similarities from the pharmacophoric point of view related to the binding site of the crystallographic enzyme using the ZINCPharmer server. The molecules selected in this screening were subjected to molecular docking and molecular dynamics simulations. Results:: Consensual analysis of the docking energy values was performed, resulting in the selection of ten compounds. These ligand-receptor complexes were visually inspected in order to analyze the main interactions and subjected to toxicophoric evaluation, culminating in the selection of three compounds, which were subsequently submitted to molecular dynamics simulations. The docking results showed that the selected compounds interacted with GAPDH from L. mexicana, especially by hydrogen bonds with Cys166, Arg249, His194, Thr167, and Thr226. From the results obtained from molecular dynamics, it was observed that one of the loop regions, corresponding to the residues 195-222, can be related to the fitting of the substrate at the binding site, assisting in the positioning and the molecular recognition via residues responsible for the catalytic activity. Conclusion:: he use of molecular modeling techniques enabled the identification of promising compounds as inhibitors of the GAPDH enzyme from L. mexicana, and the results obtained here can serve as a starting point to design new and more effective compounds than those currently available.


2012 ◽  
Vol 45 (4) ◽  
pp. 41 ◽  
Author(s):  
M. K. Saha ◽  
Santanu Das ◽  
A. Bandyopadhyay ◽  
S. Bandyopadhyay

2012 ◽  
Vol 45 (4) ◽  
pp. 41
Author(s):  
M. K. Saha ◽  
Santanu Das ◽  
A. Bandyopadhyay ◽  
S. Bandyopadhyay

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