Algorithmes adaptatifs pour la simulation moléculaire

Les simulations moléculaires sont devenues un outil essentiel en biologie, chimie et physique. Malheureusement, elles restent très couteuses. Dans cette thèse, nous proposons des algorithmes qui accélèrent les simulations moléculaires en regroupant des particules en plusieurs objets rigides. Nous étudions d'abord plusieurs algorithmes de recherche de voisins dans le cas des grands objets rigides, et démontrons que les algorithmes hiérarchiques permettent d'obtenir des accélérations importantes. En conséquence, nous proposons une technique pour construire une représentation hiérarchique d'un graphe moléculaire arbitraire. Nous démontrons l'usage de cette technique pour la mécanique adaptative en angles de torsion, une méthode de simulation qui décrit les molécules comme des objets rigides articulés. Enfin, nous introduisons ARPS - Adaptively Restrained Particle Simulations ("Simulations de particules restreintes de façon adaptative") - une méthode mathématiquement fondée capable d'activer et de désactiver les degrés de liberté en position. Nous proposons deux stratégies d'adaptation, et illustrons les avantages de ARPS sur plusieurs exemples. En particulier, nous démontrons comment ARPS permet de choisir finement le compromis entre précision et vitesse, ainsi que d'obtenir rapidement des statistiques non biaisées sur les systèmes moléculaires.Molecular simulations have become an essential tool in biology, chemistry and physics. Unfortunately, they still remain computationally challenging. In this dissertation, we propose algorithms that accelerate molecular simulations by clustering particles into rigid bodies. We first study several neighbor-search algorithms for large rigid bodies, and show that hierarchy-based algorithms may provide significant speedups. Accordingly, we propose a technique to build a hierarchical representation of an arbitrary molecular graph. We show how this technique can be used in adaptive torsion-angle mechanics, a simulation method that describes molecules as articulated rigid bodies. Finally, we introduce ARPS - Adaptively Restrained Particle Simulations - a mathematically-grounded method able to switch positional degrees of freedom on and off. We propose two switching strategies, and illustrate the advantages of ARPS on various examples. In particular, we show how ARPS allow us to smoothly trade between precision and speed, and efficiently collect unbiased statistics on molecular systems.SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF

IM-UFF: extending the Universal Force Field for interactive molecular modeling

International audienceThe universal force field (UFF) is a broadly applicable classical force field that contains parameters for almost every atom type of the periodic table. This force field is non-reactive, i.e. the topology of the system under study is considered as fixed and no creation or breaking of covalent bonds is possible. This paper introduces interactive modeling-UFF (IM-UFF), an extension of UFF that combines the possibility to significantly modify molecular structures (as with reactive force fields) with a broad diversity of supported systems thanks to the universality of UFF. Such an extension lets the user easily build and edit molecular systems interactively while being guided by physics based inter-atomic forces. This approach introduces weighted atom types and weighted bonds, used to update topologies and atom parameterizations at every time step of a simulation. IM-UFF has been evaluated on a large set of benchmarks and is proposed as a self-contained implementation integrated in a new module for the SAMSON software platform for computational nanoscience available at http://www.samson-connect.net

UNIVERSITY INTELLECTUAL CAPITAL FORMATION AND DEVELOPMENT

Purpose of the study: One of the most important terms to solve the problems of the education system is the educational institution’s intellectual capital, which significantly transforms the role and functions of the modern educator. The purpose of the article is to identify the essence of the University's intellectual capital and to justify the trajectory of its development, due to the needs and capabilities of education stakeholders. Methodology: Based on the methodology of education quality management the article justifies the leading role of quality education as an imperative of the University development. Intellectual capital is considered from the standpoint of organizational resources that determine the cost of the final product – the quality of education and the competitive position of the University; its development is carried out based on the project-target approach. Results: Modern requirements for the intellectual capital of the educational organization are revealed, the role and essence of pedagogical activity of teachers of higher education institutions in its formation are shown. The importance of continuous improvement of hard and soft competencies of University teachers as a way of incrementing intellectual capital is shown. The adaptive model’s design of University teachers’ career strategies based on design-target mechanisms is presented that determines the organizational development of the University. Applications of this study: The results determined the possibility to consider organizational and human knowledge and competence as a special type of investment to improve the functioning of the University. The recommendations for the construction of models of the University intellectual capital management are presented. The article is intended for employees of the education system, educators, researchers, and heads of the University departments. Novelty/Originality of this study: The contribution is made to the theory of the University’s social and cognitive management based on expanding the powers of quality management in the field of intellectual capital management

Мнение педиатра

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Assessing Adherence to Healthy Dietary Habits Through the Urinary Food Metabolome:Results From a European Two-Center Study

BACKGROUND: Diet is one of the most important modifiable lifestyle factors in human health and in chronic disease prevention. Thus, accurate dietary assessment is essential for reliably evaluating adherence to healthy habits. OBJECTIVES: The aim of this study was to identify urinary metabolites that could serve as robust biomarkers of diet quality, as assessed through the Alternative Healthy Eating Index (AHEI-2010). DESIGN: We set up two-center samples of 160 healthy volunteers, aged between 25 and 50, living as a couple or family, with repeated urine sampling and dietary assessment at baseline, and 6 and 12 months over a year. Urine samples were subjected to large-scale metabolomics analysis for comprehensive quantitative characterization of the food-related metabolome. Then, lasso regularized regression analysis and limma univariate analysis were applied to identify those metabolites associated with the AHEI-2010, and to investigate the reproducibility of these associations over time. RESULTS: Several polyphenol microbial metabolites were found to be positively associated with the AHEI-2010 score; urinary enterolactone glucuronide showed a reproducible association at the three study time points [false discovery rate (FDR): 0.016, 0.014, 0.016]. Furthermore, other associations were found between the AHEI-2010 and various metabolites related to the intake of coffee, red meat and fish, whereas other polyphenol phase II metabolites were associated with higher AHEI-2010 scores at one of the three time points investigated (FDR < 0.05 or β ≠ 0). CONCLUSION: We have demonstrated that urinary metabolites, and particularly microbiota-derived metabolites, could serve as reliable indicators of adherence to healthy dietary habits. CLINICAL TRAIL REGISTRATION: www.ClinicalTrials.gov, Identifier: NCT03169088

Dynamics of heart rate variability in rats with streptozotocin-induced diabetes

Background: Diabetes mellitus (DM) has a negative impact on all organs. This is due to insufficiency of blood supply and the disruption of the trophic function of the nervous system. One of the most serious complication of DM is diabetic foot caused be vascular and neurological reasons. Correction of vascular disorders is effectively treated by modern therapeutic approaches, but the damage of nervous system has been studied insufficiently. Aims: To investigate the dynamics of damage to the vegetative nervous system on the laboratory model of DM. Materials and methods: DM in rats was induced by injection of streptozotocin at a dose of 65 mg/kg in citrate buffer (DM group). The control group of rats received a citrate buffer equivalent (CB group). Rats with DM were given a maintenance therapy with insulin in a dose of 2 units/kg/day. On 42 days of experience, a round wound with a diameter of 2 cm on the back of the animals was observed. Before the DM simulation, then on the 42, 50, 58 and 66 days of its development, an electrocardiogram (ECG) was recorded in the rats at a frequency of 2 kHz digitising in a state of calm wakefulness and after cold exposure. For 5 minutes ECG fragments, heart rate and heart rate variability (HRV) in the temporal domain were calculated, characterising: 1) the total heart rate variability (tHRV) according to SDRR, SDHR, KVRR and KVHR; 2) the effect of the parasympathetic department of the autonomic nervous system (aANS) for RMSSD and pNN3; 3) the contribution of the sympathetic department of the ANS (sANS) by SDAvgRR, SDAvgHR. The spectral parameters were estimated in the frequency domain: the total power of the spectrum is TR (range: 0&ndash;2.5 Hz), the powers in the low and high frequency ranges are LF (range: 0.2&ndash;0.8 Hz) and HF (range: 0.8&ndash;2.5 Hz) LF/HF. Weekly, the tail withdrawal time was measured in a temperature pain test (55&deg;C). Results: During the development of diabetes, the level of glucose in the blood increased 4&ndash;7 times compared with the normal level. The reaction time of the pain test in rats with DM increased by 20%&ndash;30% at the end of the experiment. At 42 days, the development of bradycardia (267 beats/min) was observed in rats with DM. The indicators of tHRV decreased by a factor of 2 due to a decrease in the contribution of sANS. The reaction to CP in the SD group differs from the norm by the severity of the individual components of the HRV structure, which indicates functional denervation of the heart and the development of diabetic neuropathy. Conclusions: As the diabetes progressed, signs of neuropathy were observed. The overall HRV parameters decreased, the ratio of the contributions of sANS and pANS to the regulation of heart rate changed, and the temperature sensitivity decreased

Electrical activity in rat retina in a streptozotocin-induced diabetes model

Objectives: Diabetic retinopathy remains the major cause of blindness among the working-age population of developed countries. Considering this, experimental models of diabetes involving laboratory animals are important for assessing clinically significant methods to determine early pathologic alterations of the retina. The early detection of diabetic retinopathy in combination with a search for new pathogenetic targets will enable focusing on new strategies to limit the development of critical changes in the retina and to prolong retinal functioning during the development of diabetes mellitus. Aim: This study aimed to define parameters of electroretinography test that identifies changes due to retinal impairment in diabetes. Methods: Experimental diabetes was induced in Wistar rats by intraperitoneally injecting streptozocin (65 mg/kg; group DM). The control group (CB) received intraperitoneal injections of the vehicle, i.e. citric buffer. On each consecutive day of the experiment, all rats received insulin detemir (2 u/kg). Ophthalmoscopy and electroretinography were conducted before initiating the experiment and after 50, 58 and 66 days of injectin sptreptozocin. Results: Amid 2u\kg insulin injection the glucose level in venous blood in DM group amounted to 30-40 mM. The ophthalmoscopy showed that the optic nerve disk paled by the 50th day, with its line erasing. During electroretinography, wave amplitude in oscillatory potential test tended to decrease. -wave latency of photopic system increased with -wave latency of photopic system and - and -waves latency of scotopic system not altering. In addition, the amplitude of rhythmic stimulation of 8 and 12 Hz decreased. Conclusion: The most apparent parameters of electroretinography for modelling streptozocin-induced diabetes are wave amplitude during the oscillatory potential test, photopic B-wave latency and the amplitude of rhythmic stimulation. These results suggest that in diabetes, ischaemic injury is an important cause of early dysfunction of inner retinal layers

Adaptive algorithms for molecular simulation

Les simulations moléculaires sont devenues un outil essentiel en biologie, chimie et physique. Malheureusement, elles restent très coûteuses. Dans cette thèse, nous proposons des algorithmes qui accélèrent les simulations moléculaires en regroupant des particules en plusieurs objets rigides. Nous étudions d’abord plusieurs algorithmes de recherche de voisins dans le cas des grands objets rigides, et démontrons que les algorithmes hiérarchiques permettent d’obtenir des accélérations importantes. En conséquence, nous proposons une technique pour construire une représentation hiérarchique d’un graphe moléculaire arbitraire. Nous démontrons l’usage de cette technique pour la mécanique adaptative en angles de torsion, une méthode de simulation qui décrit les molécules comme des objets rigides articulés. Enfin, nous introduisons ARPS – Adaptively Restrained Particle Simulations (“Simulations de particules restreintes de façon adaptative”) – une méthode mathématiquement fondée capable d’activer et de désactiver les degrés de liberté en position. Nous proposons deux stratégies d’adaptation, et illustrons les avantages de ARPS sur plusieurs exemples. En particulier, nous démontrons comment ARPS permet de choisir finement le compromis entre précision et vitesse, ainsi que de calculer rapidement des proprietésstatiques d’équilibre sur les systèmes moléculaires.Molecular simulations have become an essential tool in biology, chemistry and physics. Unfortunately, they still remain computationally challenging. In this dissertation, we propose algorithms that accelerate molecular simulations by clustering particles into rigid bodies.We first study several neighbor-search algorithms for large rigid bodies, and show that hierarchy-based algorithms may provide significant speedups. Accordingly, we propose a technique to build a hierarchical representation of an arbitrary molecular graph. We show how this technique can be used in adaptive torsion-angle mechanics, a simulation method that describes molecules as articulated rigid bodies. Finally, we introduce ARPS – Adaptively Restrained Particle Simulations – a mathematically-grounded method able to switch positional degrees of freedom on and off. We propose two switching strategies, and illustrate the advantages of ARPS on various examples. In particular, we show how ARPS allow us to smoothly trade between precision and speed, and to efficiently compute correct static equilibrium properties on molecular systems

Algorithmes adaptatifs pour la simulation moléculaire

Molecular simulations have become an essential tool in biology, chemistry and physics. Unfortunately, they still remain computationally challenging. In this dissertation, we propose algorithms that accelerate molecular simulations by clustering particles into rigid bodies.We first study several neighbor-search algorithms for large rigid bodies, and show that hierarchy-based algorithms may provide significant speedups. Accordingly, we propose a technique to build a hierarchical representation of an arbitrary molecular graph. We show how this technique can be used in adaptive torsion-angle mechanics, a simulation method that describes molecules as articulated rigid bodies. Finally, we introduce ARPS – Adaptively Restrained Particle Simulations – a mathematically-grounded method able to switch positional degrees of freedom on and off. We propose two switching strategies, and illustrate the advantages of ARPS on various examples. In particular, we show how ARPS allow us to smoothly trade between precision and speed, and to efficiently compute correct static equilibrium properties on molecular systems.Les simulations moléculaires sont devenues un outil essentiel en biologie, chimie et physique. Malheureusement, elles restent très coûteuses. Dans cette thèse, nous proposons des algorithmes qui accélèrent les simulations moléculaires en regroupant des particules en plusieurs objets rigides. Nous étudions d’abord plusieurs algorithmes de recherche de voisins dans le cas des grands objets rigides, et démontrons que les algorithmes hiérarchiques permettent d’obtenir des accélérations importantes. En conséquence, nous proposons une technique pour construire une représentation hiérarchique d’un graphe moléculaire arbitraire. Nous démontrons l’usage de cette technique pour la mécanique adaptative en angles de torsion, une méthode de simulation qui décrit les molécules comme des objets rigides articulés. Enfin, nous introduisons ARPS – Adaptively Restrained Particle Simulations (“Simulations de particules restreintes de façon adaptative”) – une méthode mathématiquement fondée capable d’activer et de désactiver les degrés de liberté en position. Nous proposons deux stratégies d’adaptation, et illustrons les avantages de ARPS sur plusieurs exemples. En particulier, nous démontrons comment ARPS permet de choisir finement le compromis entre précision et vitesse, ainsi que de calculer rapidement des proprietésstatiques d’équilibre sur les systèmes moléculaires