A Practical Algorithm to Solve the Near-Congruence Problem for Rigid Molecules and Clusters.

We present an improved algorithm to solve the near-congruence problem for rigid molecules and clusters based on the iterative application of assignment and alignment steps with biased Euclidean costs. The algorithm is formulated as a quasi-local optimization procedure with each optimization step involving a linear assignment (LAP) and a singular value decomposition (SVD). The efficiency of the algorithm is increased by up to 5 orders of magnitude with respect to the original unbiased noniterative method and can be applied to systems with hundreds or thousands of atoms, outperforming all state-of-the-art methods published so far in the literature. The Fortran implementation of the algorithm is available as an open source library (https://github.com/qcuaeh/molalignlib) and is suitable to be used in global optimization methods for the identification of local minima or basins.

Advances in Our Understanding of the Interaction of Drugs with T-cells: Implications for the Discovery of Biomarkers in Severe Cutaneous Drug Reactions.

Drugs can activate different cells of the immune system and initiate an immune response that can lead to life-threatening diseases collectively known as severe cutaneous adverse reactions (SCARs). Antibiotics, anticonvulsants, and antiretrovirals are involved in the development of SCARs by the activation of αß naïve T-cells. However, other subsets of lymphocytes known as nonconventional T-cells with a limited T-cell receptor repertoire and innate and adaptative functions also recognize drugs and drug-like molecules, but their role in the pathogenesis of SCARs has only just begun to be explored. Despite 30 years of advances in our understanding of the mechanisms in which drugs interact with T-cells and the pathways for tissue injury seen during T-cell activation, at present, the development of useful clinical biomarkers for SCARs or predictive preclinical in vitro assays that could identify immunogenic moieties during drug discovery is an unmet goal. Therefore, the present review focuses on (i) advances in the understanding of the pathogenesis of SCARs reactions, (ii) a description of the interaction of drugs with conventional and nonconventional T-cells, and (iii) the current state of soluble blood circulating biomarker candidates for SCARs.