A topological substructural molecular design approach (TOPS-MODE) has been used to formulate structural rules for binding of substrates of P-glycoprotein (P-gp). We first review some of the models developed in the recent literature for predicting binding to P-gp. Then, we develop a model using TOPS-MODE, which is able to identify 88.4% of substrates and 84.2% of non-substrates. When the model is presented to an external prediction set of 100 substrates and 77 nonsubstrates it identifies correctly 81.8% of all cases. Using TOPS-MODE strategy we found structural contributions for binding to P-gp, which identifies 24 structural fragments responsible for such binding. We then carried out a chemico-biological analysis of some of the structural fragments found as contributing to P-gp binding of substrates. We show that in general the model developed so far can be used as a virtual screening method for identifying substrates of P-gp from large libraries of compounds.
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http://dx.doi.org/10.2174/138161210792389243 | DOI Listing |
Evaluation practices in the French-speaking countries of the West African Economic and Monetary Union (WAEMU) are poorly understood and infrequently documented. Our study is a descriptive analysis that elucidates how stakeholders are conceptualized and involved in evaluation processes in WAEMU. In these countries, evaluators are concerned about the weak stakeholder involvement in evaluation activity and call for greater stakeholder engagement, juxtaposed to the challenges of doing so.
View Article and Find Full Text PDFShock
January 2025
Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 599 Taylor Road, Room 209, Piscataway, NJ, USA 08854.
Introduction: Coagulopathy following traumatic injury impairs stable blood clot formation and exacerbates mortality from hemorrhage. Understanding how these alterations impact blood clot stability is critical to improving resuscitation. Furthermore, the incorporation of machine learning algorithms to assess clinical markers, coagulation assays and biochemical assays allows us to define the contributions of these factors to mortality.
View Article and Find Full Text PDFLangmuir
January 2025
Chemistry and Structure of novel Materials, University of Siegen, Paul-Bonatz Strasse 9-11, 57068 Siegen, Germany.
The surface charge of metal oxides is an important property that significantly contributes to a wide range of phenomena, including adsorption, catalysis, and material science. The surface charge can be predicted by determining the isoelectric point (IEP) of a material and the pH of a solution. Although there have been several studies of the IEP of metal oxide (nano)particles, only a few have reported the IEP of metal oxide films.
View Article and Find Full Text PDFPLoS Biol
January 2025
Carney Institute for Brain Science, Department of Cognitive & Psychological Sciences, Brown University, Providence, Rhode Island, United States of America.
The basal ganglia (BG) play a key role in decision-making, preventing impulsive actions in some contexts while facilitating fast adaptations in others. The specific contributions of different BG structures to this nuanced behavior remain unclear, particularly under varying situations of noisy and conflicting information that necessitate ongoing adjustments in the balance between speed and accuracy. Theoretical accounts suggest that dynamic regulation of the amount of evidence required to commit to a decision (a dynamic "decision boundary") may be necessary to meet these competing demands.
View Article and Find Full Text PDFAnn Med
December 2025
Department of Joint and Sports Medicine, Zhongnan Hospital, Wuhan University, Wuhan, China.
As life expectancy among patients infected with the human immunodeficiency virus (HIV) increases, a growing number of complications have been observed. This population displays an elevated risk of ischemic necrosis of the femoral head in comparison to the general population, which may be attributed to HIV infection, antiretroviral medication use, and hormone application. Patients infected with the human immunodeficiency virus (HIV) who also have necrosis of the femoral head tend to present at an earlier age, with a rapid disease progression and a high incidence of bilateral onset.
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