Search results for "simulations"
showing 10 items of 288 documents
Two differential binding mechanisms of FG-nucleoporins and nuclear transport receptors
2018
Summary Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC). Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an “archetypal-fuzzy” complex through the rapid formation and breakage of interactions with many individual FG motifs. Here, we use single-molecule studies combined with atomistic simulations to show that, in sharp contrast, FG-Nup214 undergoes a coupled reconfiguration-binding mechanism when interacting with the export receptor CRM1. Association and dissociation rate constants are more than an order of magnitude lowe…
Intermittent targeted therapies and stochastic evolution in patients affected by chronic myeloid leukemia
2016
Front line therapy for the treatment of patients affected by chronic myeloid leukemia (CML) is based on the administration of tyrosine kinase inhibitors, namely imatinib or, more recently, axitinib. Although imatinib is highly effective and represents an example of a successful molecular targeted therapy, the appearance of resistance is observed in a proportion of patients, especially those in advanced stages. In this work, we investigate the appearance of resistance in patients affected by CML, by modeling the evolutionary dynamics of cancerous cell populations in a simulated patient treated by an intermittent targeted therapy. We simulate, with the Monte Carlo method, the stochastic evolu…
Parsimonious Scenario for the Emergence of Viroid-Like Replicons De Novo
2019
This article belongs to the Special Issue Viroid-2018: International Conference on Viroids and Viroid-Like RNAs. Viroids are small, non-coding, circular RNA molecules that infect plants. Different hypotheses for their evolutionary origin have been put forward, such as an early emergence in a precellular RNA World or several de novo independent evolutionary origins in plants. Here, we discuss the plausibility of de novo emergence of viroid-like replicons by giving theoretical support to the likelihood of different steps along a parsimonious evolutionary pathway. While Avsunviroidae-like structures are relatively easy to obtain through evolution of a population of random RNA sequences of fixe…
Searching for Chymase Inhibitors among Chamomile Compounds Using a Computational-Based Approach
2018
Inhibitors of chymase have good potential to provide a novel therapeutic approach for the treatment of cardiovascular diseases. We used a computational approach based on pharmacophore modeling, docking, and molecular dynamics simulations to evaluate the potential ability of 13 natural compounds from chamomile extracts to bind chymase enzyme. The results indicated that some chamomile compounds can bind to the active site of human chymase. In particular, chlorogenic acid had a predicted binding energy comparable or even better than that of some known chymase inhibitors, interacted stably with key amino acids in the chymase active site, and appeared to be more selective for chymase than other …
Insights into the inhibited form of the redox-sensitive SufE-like sulfur acceptor CsdE
2017
17 p.-8 fig.
Collective Cell Migration in a Fibrous Environment: A Hybrid Multiscale Modelling Approach
2021
International audience; The specific structure of the extracellular matrix (ECM), and in particular the density and orientation of collagen fibres, plays an important role in the evolution of solid cancers. While many experimental studies discussed the role of ECM in individual and collective cell migration, there are still unanswered questions about the impact of nonlocal cell sensing of other cells on the overall shape of tumour aggregation and its migration type. There are also unanswered questions about the migration and spread of tumour that arises at the boundary between different tissues with different collagen fibre orientations. To address these questions, in this study we develop …
EXTERNAL RECIRCULATION IN PRS TYPE TURBINE: EXPERIMENTAL AND NUMERICAL RESULTS.
2022
Cavitation is a relevant phenomenon for structural safety and noise level in hydraulic turbines, occurring when water pressure falls below the vapor value at a given temperature. In this case bubbles of vapor grow inside the liquid and move along with it. When the pressure returns above the vapor value the bubble collapses, and the pressure can locally achieve very high values, up to 7000 bars (Kumar & Saini, 2010). Moreover, if the bubble was confined also by the solid wall of a blade, the solid particles suspended in the fluid can be transported by the fluid ones and hit the solid wall at very high velocity, generating erosion. Cavitation is also the source of high frequency noise, ve…
Permeability of three-dimensional random fiber webs
1998
We report the results of essentially ab initio simulations of creeping flow through large threedimensional random fiber webs that closely resemble fibrous sheets such as paper and nonwoven fabrics. The computational scheme used in this Letter is that of the lattice-Boltzmann method and contains no free parameters concerning the properties of the porous medium or the dynamics of the flow. The computed permeability of the web is found to be in good agreement with experimental data, and confirms that permeability depends exponentially on porosity over a large range of porosity. [S0031-9007(97)05087-4]
Response of AGATA segmented HPGe detectors to gamma rays up to 15.1MeV
2013
WOS: 000314826000009
Genetic structure and differentiation from early bronze age in the mediterranean island of sicily: Insights from ancient mitochondrial genomes
2022
Sicily is one of the main islands of the Mediterranean Sea, and it is characterized by a variety of archaeological records, material culture and traditions, reflecting the history of migrations and populations’ interaction since its first colonization, during the Paleolithic. These deep and complex demographic and cultural dynamics should have affected the genomic landscape of Sicily at different levels; however, the relative impact of these migrations on the genomic structure and differentiation within the island remains largely unknown. The available Sicilian modern genetic data gave a picture of the current genetic structure, but the paucity of ancient data did not allow so far to make p…