PBxplore: a tool to analyze local protein structure and deformability with Protein Blocks

This paper describes the development and application of a suite of tools, called PBxplore, to analyze the dynamics and deformability of protein structures using Protein Blocks (PBs). Proteins are highly dynamic macromolecules, and a classical way to analyze their inherent flexibility is to perform molecular dynamics simulations. The advantage of using small structural prototypes such as PBs is to give a good approximation of the local structure of the protein backbone. More importantly, by reducing the conformational complexity of protein structures, PBs allow analysis of local protein deformability which cannot be done with other methods and had been used efficiently in different applications. PBxplore is able to process large amounts of data such as those produced by molecular dynamics simulations. It produces frequencies, entropy and information logo outputs as text and graphics. PBxplore is available at https://github.com/pierrepo/PBxplore and is released under the open-source MIT license

Możliwość stosowania narzędzi modelowania ewakuacji dla taboru kolejowego

Evacuation modelling technology offers designers and regulators of train new opportunities to rigorously test designs and theories in order to improve the passengers’ safety. This paper deals with the opportunity to use these tools for the railway industry. The FDS+Evac and buildingEXODUS softwares are used to model and simulate the evacuation of rolling stock. Firstly, in order to demonstrate the reliability of these tools to calculate the complete evacuation time, a comparative study was achieved between a real test, simulations done with FDS+Evac and simulations done with buildingEXODUS. Multiple simulations are performed to capture the stochastic variations in egress times. The philosophy of this comparative study is to realize the real test in one hand, and to use evacuation modelling tools with the incoming data (population, train geometry, initial position of the people, and known characteristics of the population) of the real test in another hand. The goal is not to stall the simulations results with the real test but to analyze the results of calculations by themselves. The following study highlights the interest of using evacuation modelling for the railway industry and shows their reliability in order to satisfy the TSI RST HS 2008/232/CE and the future TSI LOC&PAS. A confrontation „modelling – full-scale test” is presented and analysed.Technika modelowania ewakuacji daje konstruktorom i ciałom nadzorującym pociągi nowe możliwości rygorystycznego sprawdzenie konstrukcji i teorii tak, aby poprawić bezpieczeństwo pasażerów. W artykule omówiono możliwość zastosowania tych narzędzi w kolejnictwie. Do modelowania i symulacji ewakuacji pasażerów z taboru kolejowego stosuje się programy komputerowe FDS+Evac oraz buildingEXODUS. Po pierwsze, dla zademonstrowania niezawodności tych narzędzi do obliczenia całkowitego czasu ewakuacji, dokonano analizy porównawczej dla próby rzeczywistej, symulacji przeprowadzonej za pomocą FDS+Evac i za pomocą buildingEXODUS. Wykonano symulacje wielokrotne w celu uchwycenia wariacji stochastycznych czasów wyjścia. Intencją tej analizy porównawczej jest z jednej strony reali-zacja próby rzeczywistej, a z drugiej strony użycie narzędzi modelowania ewakuacji z wykorzystaniem danych pochodzących z prób rzeczywistych (liczba osób, geometria pociągu, położenie początkowe osób, znana charakterystyka populacji osób). Celem nie jest tu konfrontacja wyników symulacji i wyników próby rzeczywistej, ale analiza wyników obliczeń jako takich. Wykonana następnie analiza podkreśla zainteresowanie modelowaniem ewakuacji w kolejnictwie i pokazuje jego wiarygodność przy spełnieniu normy TSI RST HS 2008/232/CE i przyszłej TSI LOC&PAS. Przedstawiono i przeanalizowano zestawienie „Modelowanie – próba w skali naturalnej

Analytical multi-step homogenization methodology for a stack of thin films in microelectronics

International audienc

Modelling and analysis of the stress distribution in a multi-thin film system Pt/USG/Si

International audienc

Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT) with Enhanced Activity

Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide to form N-methylnicotinamide. Overexpression of NNMT is associated with a variety of diseases, including a number of cancers and metabolic disorders, suggesting a role for NNMT as a potential therapeutic target. By structural modification of a lead NNMT inhibitor previously developed in our group, we prepared a diverse library of inhibitors to probe the different regions of the enzyme’s active site. This investigation revealed that incorporation of a naphthalene moiety, intended to bind the hydrophobic nicotinamide binding pocket via π–π stacking interactions, significantly increases the activity of bisubstrate-like NNMT inhibitors (half-maximal inhibitory concentration 1.41 μM). These findings are further supported by isothermal titration calorimetry binding assays as well as modeling studies. The most active NNMT inhibitor identified in the present study demonstrated a dose-dependent inhibitory effect on the cell proliferation of the HSC-2 human oral cancer cell line.Microbial Biotechnolog