The development of the advanced web shop based on purchase history

The goal of thesis is to develop a typical web shop application with some additional functionality. This functionality enables web shop customers to browse products in a more efficient way and thus makes shop more profitable. For this purpose, we developed a specific mechanism that handles product presentation in customer adapted way. First we describe technologies used for development. Programing language C# is presented shortly as well as some other frameworks (ASP.net, Entity framework,), libraries (LINQ) and other web technologies (HTML, CSS, AJAX). For storing and manipulating data a database with tables in MS SQL database is created. Furthermore we take a look at requirements, idea and logic of solution. We present solution design and present how specific functionality behaves in case of different user types. We present a solution analysis where a comparison with other similar solutions and user tests are shown. Finally we discuss problems during the development and possibilities about the future improvements

Successive statistical and structure-based modeling to identify chemically novel kinase inhibitors

Kinases are frequently studied in the context of anticancer drugs. Their involvement in cell responses, such as proliferation, differentiation, and apoptosis, makes them interesting subjects in multitarget drug design. In this study, a workflow is presented that models the bioactivity spectra for two panels of kinases: (1) inhibition of RET, BRAF, SRC, and S6K, while avoiding inhibition of MKNK1, TTK, ERK8, PDK1, and PAK3, and (2) inhibition of AURKA, PAK1, FGFR1, and LKB1, while avoiding inhibition of PAK3, TAK1, and PIK3CA. Both statistical and structure-based models were included, which were thoroughly benchmarked and optimized. A virtual screening was performed to test the workflow for one of the main targets, RET kinase. This resulted in 5 novel and chemically dissimilar RET inhibitors with remaining RET activity of 50 value of 5.1 for the most active compound. The experimental validation of inhibitors for RET strongly indicates that the multitarget workflow is able to detect novel inhibitors for kinases, and hence, this workflow can potentially be applied in polypharmacology modeling. We conclude that this approach can identify new chemical matter for existing targets. Moreover, this workflow can easily be applied to other targets as well.Toxicolog

A Cross-Site Analysis of Neotropical Bird Hunting Profiles

© The Author(s) 2017. Subsistence hunting of neotropical birds is common and widespread in the tropical forests of Latin America. Although its sustainability under different scenarios is subject to debate, hunting has already contributed to the decline and local extirpation of several taxa and is considered to be a significant threat to a range of large-bodied species. Gaining a better understanding of the variability of hunting patterns, as well as the factors that can potentially be used to predict them, is important if we are to develop conservation strategies that target the species most likely to be experiencing declines. In this article, we examine the avian hunting profiles of 65 communities in the neotropics. We describe their variability and look at the relationship between a hunting profile and (a) its geographical location, (b) the community’s age, (c) the community’s population size, and (d) the year in which the survey was carried out. We find that there is a significant but weak relationship between a community’s geographic location and the composition of its bird hunting profile, and that prey profiles can be considerably different even among close neighbors. We found no relationship between a community’s age or size and the mean biomass of bird prey hunted. Our results challenge the assumption that older and larger settlements have a predictable impact upon avian prey communities and suggest that cultural preferences or the starting availability of prey species can change rapidly over short distances

Predicting binding affinities for GPCR ligands using free-energy perturbation

Medicinal ChemistryDrug Delivery Technolog

Interacting with GPCRs: Using Interaction Fingerprints for Virtual Screening

Medicinal Chemistr

Immobilization of active substances

The invention relates to a method for immobilizing an active substance, wherein a mixture is prepared of the active substance and a carrier material in a liquid phase, whereafter the liquid phase is converted to a solid phase, the carrier material being an esterified polysaccharide. The invention further relates to the use of an esterified polysaccharide for fixing or immobilizing active substances, in particular odorous substances

Immobilization of active substances

The invention relates to a method for immobilizing an active substance, wherein a mixture is prepared of the active substance and a carrier material in a liquid phase, whereafter the liquid phase is converted to a solid phase, the carrier material being an esterified polysaccharide. The invention further relates to the use of an esterified polysaccharide for fixing or immobilizing active substances, in particular odorous substances

Selecting an Optimal Number of Binding Site Waters To Improve Virtual Screening Enrichments Against the Adenosine A_2A Receptor

A major challenge in structure-based virtual screening (VS) involves the treatment of explicit water molecules during docking in order to improve the enrichment of active compounds over decoys. Here we have investigated this in the context of the adenosine A_2A receptor, where water molecules have previously been shown to be important for achieving high enrichment rates with docking, and where the positions of some binding site waters are known from a high-resolution crystal structure. The effect of these waters (both their presence and orientations) on VS enrichment was assessed using a carefully curated set of 299 high affinity A_2A antagonists and 17,337 decoys. We show that including certain crystal waters greatly improves VS enrichment and that optimization of water hydrogen positions is needed in order to achieve the best results. We also show that waters derived from a molecular dynamics simulation  without any knowledge of crystallographic waters  can improve enrichments to a similar degree as the crystallographic waters, which makes this strategy applicable to structures without experimental knowledge of water positions. Finally, we used decision trees to select an ensemble of structures with different water molecule positions and orientations that outperforms any single structure with water molecules. The approach presented here is validated against independent test sets of A_2A receptor antagonists and decoys from the literature. In general, this water optimization strategy could be applied to any target with waters-mediated protein–ligand interactions