Search results for "Design"
showing 10 items of 5885 documents
Evaluating the stability of pharmacophore features using molecular dynamics simulations.
2016
Abstract Molecular dynamics simulations of twelve protein—ligand systems were used to derive a single, structure based pharmacophore model for each system. These merged models combine the information from the initial experimental structure and from all snapshots saved during the simulation. We compared the merged pharmacophore models with the corresponding PDB pharmacophore models, i.e., the static models generated from an experimental structure in the usual manner. The frequency of individual features, of feature types and the occurrence of features not present in the static model derived from the experimental structure were analyzed. We observed both pharmacophore features not visible in …
Recent advances on CDK inhibitors: An insight by means of in silico methods
2017
The cyclin dependent kinases (CDKs) are a small family of serine/threonine protein kinases that can act as a potential therapeutic target in several proliferative diseases, including cancer. This short review is a survey on the more recent research progresses in the field achieved by using in silico methods. All the "armamentarium" available to the medicinal chemists (docking protocols and molecular dynamics, fragment-based, de novo design, virtual screening, and QSAR) has been employed to the discovery of new, potent, and selective inhibitors of cyclin dependent kinases. The results cited herein can be useful to understand the nature of the inhibitor-target interactions, and furnish an ins…
Expectation or Sensorial Reality? An Empirical Investigation of the Biodynamic Calendar for Wine Drinkers.
2017
International audience; The study's aim was to investigate a central tenet of biodynamic philosophy as applied to wine tasting, namely that wines taste different in systematic ways on days determined by the lunar cycle. Nineteen New Zealand wine professionals tasted blind 12 Pinot noir wines at times determined within the biodynamic calendar for wine drinkers as being favourable (Fruit day) and unfavourable (Root day) for wine tasting. Tasters rated each wine four times, twice on a Fruit day and twice on a Root day, using 20 experimenter-provided descriptors. Wine descriptors spanned a range of varietal-relevant aroma, taste, and mouthfeel characteristics, and were selected with the aim of …
The TeRiFiQ project: Combining technologies to achieve significant binary reductions in sodium, fat and sugar content in everyday foods whilst optimi…
2017
International audience; Most developed countries are confronted with rising rates of diseases related to unhealthy eating habits, particularly the excessive consumption of salt, saturated fat and free sugars. However, fat, sugars and salt in food influence not only its nutritional qualities but also its sensory properties, safety (e.g. shelf life) and affordability. The main challenge is to formulate healthier foods that are acceptable to consumers. In this context, the overall objective of TeRiFiQ was to achieve significant binary reductions in the salt-fat and sugar-fat contents of frequently consumed food products around Europe, while, at the same time, ensuring the products’ nutritional…
Large strain stimulation promotes extracellular matrix production and stiffness in an elastomeric scaffold model
2016
Mechanical conditioning of engineered tissue constructs is widely recognized as one of the most relevant methods to enhance tissue accretion and microstructure, leading to improved mechanical behaviors. The understanding of the underlying mechanisms remains rather limited, restricting the development of in silico models of these phenomena, and the translation of engineered tissues into clinical application. In the present study, we examined the role of large strip-biaxial strains (up to 50%) on ECM synthesis by vascular smooth muscle cells (VSMCs) micro-integrated into electrospun polyester urethane urea (PEUU) constructs over the course of 3 weeks. Experimental results indicated that VSMC …
Trial Design and Endpoints in Hepatocellular Carcinoma: AASLD Consensus Conference
2020
Proper trial design is critical for the success of clinical investigations. Hepatocellular carcinoma (HCC) is a complex disease that has several unique properties. In 2008, after the approval of sorafenib, a panel of experts proposed guidelines for trial design and endpoints in HCC that have been instrumental during the last decade and provided a framework to allow an homogeneous analysis of reported investigations. Since then, several phase III studies have been reported and novel challenges have emerged. A panel of experts conveyed by AASLD organized a Special Topic Conference on trial design and endpoints to address those emerging challenges. This review summarizes the analysis and concl…
Inoculation of airborne conidia of Penicillium chrysogenum on the surface of a solid medium
2016
International audience; To reproduce a fungal contamination of food products by airborne conidia, a method to inoculate a few number (in the range 1-9) of conidia on the surface of agar media was developed. This technique would allow to determine accurately the time to detection of fungal colonies, then the mould free shelf-life of food products by using dry conidia. The method was based on dry-harvesting the conidia in the lid by gently taping the bottom of the dishes where sporulating mycelium was grown, retaining the conidia on glass beads, and, aseptically transferring the beads to successive Petri dishes to "dilute" the samples. Among the eleven factors tested by means of an experiment…
Variance component analysis to assess protein quantification in biomarker discovery. Application to MALDI-TOF mass spectrometry.
2017
International audience; Controlling the technological variability on an analytical chain is critical for biomarker discovery. The sources of technological variability should be modeled, which calls for specific experimental design, signal processing, and statistical analysis. Furthermore, with unbalanced data, the various components of variability cannot be estimated with the sequential or adjusted sums of squares of usual software programs. We propose a novel approach to variance component analysis with application to the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) technology and use this approach for protein quantification by a classical signal processing algori…
Search of Chemical Scaffolds for Novel Antituberculosis Agents
2005
3 A method to identify chemical scaffolds potentially active against Mycobacterium tuberculosis is presented. The molecular features of a set of structurally heterogeneous antituberculosis drugs were coded by means of structural invariants. Three tech- niques were used to obtain equations able to model the antituberculosis activity: linear discriminant analysis, multilinear re- gression, and shrinkage estimation-ridge regression. The model obtained was statistically validated through leave-n-out test, and an external set and was applied to a database for the search of new active agents. The selected compounds were assayed in vitro, and among those identified as active stand reserpine, N,N,N…
Additives for vaccine storage to improve thermal stability of adenoviruses from hours to months
2016
Up to 80% of the cost of vaccination programmes is due to the cold chain problem (that is, keeping vaccines cold). Inexpensive, biocompatible additives to slow down the degradation of virus particles would address the problem. Here we propose and characterize additives that, already at very low concentrations, improve the storage time of adenovirus type 5. Anionic gold nanoparticles (10−8–10−6 M) or polyethylene glycol (PEG, molecular weight ∼8,000 Da, 10−7–10−4 M) increase the half-life of a green fluorescent protein expressing adenovirus from ∼48 h to 21 days at 37 °C (from 7 to >30 days at room temperature). They replicate the known stabilizing effect of sucrose, but at several orders of…