A scala library for spatial sensitivity analysis

The sensitivity analysis and validation of simulation models require specific approaches in the case of spatial models. We describe the spatialdata scala library providing such tools, including synthetic generators for urban configurations at different scales, spatial networks, and spatial point processes. These can be used to parametrize geosimulation models on synthetic configurations, and evaluate the sensitivity of model outcomes to spatial configuration. The library also includes methods to perturb real data, and spatial statistics indicators, urban form indicators, and network indicators. It is embedded into the OpenMOLE platform for model exploration, fostering the application of such methods without technical constraints

Organic livestock farming systems in the Massif Central: evolution (2008-2011) and analysis of the technical and economic performances and drivers

The “Organic Farming Massif Central” hub and fifteen partners lead a program on sustainability and on the technical and economic operation of OF livestock systems in the Massif Central. This systemic and multi-year study (2008-2011) is based on data from a constant sample over four years, from 56 farms comprising four types of products: cattle and sheep, dairy and meat. Over 4 years, the technical and economic results are quite stable, and at a good level, but with great variability inter-farms. With lower labor productivity, but with a more diversified crop rotation, a good food self-sufficiency and good technical skills, the farms with the highest income get an income more than four times higher than the farms with the lowest income

Identification and characterization of an irreversible inhibitor of CDK2

Irreversible inhibitors that modify cysteine or lysine residues within a protein kinase ATP binding site offer, through their distinctive mode of action, an alternative to ATP-competitive agents. 4-((6-(Cyclohexylmethoxy)- 9H-purin-2-yl)amino)benzenesulfonamide (NU6102) is a potent and selective ATP-competitive inhibitor of CDK2 in which the sulfonamide moiety is positioned close to a pair of lysine residues. Guided by the CDK2/NU6102 structure, we designed 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300), which binds covalently to CDK2 as shown by a co-complex crystal structure. Acute incubation with NU6300 produced a durable inhibition of Rb phosphorylation in SKUT-1B cells, consistent with it acting as an irreversible CDK2 inhibitor. NU6300 is the first covalent CDK2 inhibitor to be described, and illustrates the potential of vinyl sulfones for the design of more potent and selective compounds

Assessing the impact of forest structure disturbances on the arboreal movement and energetics of orangutans—An agent-based modeling approach

This is the final version. Available from Frontiers Media via the DOI in this record. Data availability statement: The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary material.Agent-based models have been developed and widely employed to assess the impact of disturbances or conservation management on animal habitat use, population development, and viability. However, the direct impacts of canopy disturbance on the arboreal movement of individual primates have been less studied. Such impacts could shed light on the cascading effects of disturbances on animal health and fitness. Orangutans are an arboreal primate that commonly encounters habitat quality deterioration due to land-use changes and related disturbances such as forest fires. Forest disturbance may, therefore, create a complex stress scenario threatening orangutan populations. Due to forest disturbances, orangutans may adapt to employ more terrestrial, as opposed to arboreal, movements potentially prolonging the search for fruiting and nesting trees. In turn, this may lead to changes in daily activity patterns (i.e., time spent traveling, feeding, and resting) and available energy budget, potentially decreasing the orangutan's fitness. We developed the agent-based simulation model BORNEO (arBOReal aNimal movEment mOdel), which explicitly describes both orangutans' arboreal and terrestrial movement in a forest habitat, depending on distances between trees and canopy structures. Orangutans in the model perform activities with a motivation to balance energy intake and expenditure through locomotion. We tested the model using forest inventory data obtained in Sebangau National Park, Central Kalimantan, Indonesia. This allowed us to construct virtual forests with real characteristics including tree connectivity, thus creating the potential to expand the environmental settings for simulation experiments. In order to parameterize the energy related processes of the orangutans described in the model, we applied a computationally intensive evolutionary algorithm and evaluated the simulation results against observed behavioral patterns of orangutans. Both the simulated variability and proportion of activity budgets including feeding, resting, and traveling time for female and male orangutans confirmed the suitability of the model for its purpose. We used the calibrated model to compare the activity patterns and energy budgets of orangutans in both natural and disturbed forests. The results confirm field observations that orangutans in the disturbed forest are more likely to experience deficit energy balance due to traveling to the detriment of feeding time. Such imbalance is more pronounced in males than in females. The finding of a threshold of forest disturbances that affects a significant change in activity and energy budgets suggests potential threats to the orangutan population. Our study introduces the first agent-based model describing the arboreal movement of primates that can serve as a tool to investigate the direct impact of forest changes and disturbances on the behavior of species such as orangutans. Moreover, it demonstrates the suitability of high-performance computing to optimize the calibration of complex agent-based models describing animal behavior at a fine spatio-temporal scale (1-m and 1-s granularity).UKR

Parallel Optimisation of Potency and Pharmacokinetics Leading to the Discovery of a Pyrrole Carboxamide ERK5 Chemical Tool

[Image: see text] The nonclassical extracellular signal-related kinase 5 (ERK5) mitogen-activated protein kinase pathway has been implicated in increased cellular proliferation, migration, survival, and angiogenesis; hence, ERK5 inhibition may be an attractive approach for cancer treatment. However, the development of selective ERK5 inhibitors has been challenging. Previously, we described the development of a pyrrole carboxamide high-throughput screening hit into a selective, submicromolar inhibitor of ERK5 kinase activity. Improvement in the ERK5 potency was necessary for the identification of a tool ERK5 inhibitor for target validation studies. Herein, we describe the optimization of this series to identify nanomolar pyrrole carboxamide inhibitors of ERK5 incorporating a basic center, which suffered from poor oral bioavailability. Parallel optimization of potency and in vitro pharmacokinetic parameters led to the identification of a nonbasic pyrazole analogue with an optimal balance of ERK5 inhibition and oral exposure

Testing unrolling optimization technique for quasi random numbers

International audienc

A Generic Toolkit for Stochastic Simulation Distribution

International audienc

Evaluer la résilience des socio-écosystèmes : coupler la théorie de la viabilité avec l'apprentissage actif à partir de kd-trees. Application à la coexistence des langues.

International audienceThis paper proposes a new algorithm to compute the resilience of a social system or an ecosystem when it is defined in the framework of the mathematical viability theory. It is applied to the problem of language coexistence: Although bilingual societies do exist, many languages have disappeared and some seem endangered presently. Mathematical models of language competition generally conclude that one language will disappear, except when the relative prestige of the languages can be modified. The viability theory provides concepts and tools that are suitable to study the resilience, but with severe computational limits since it uses extensive search on regular grids. The method we propose considers the computation of the viability output sets as an active learning problem with the objective of restraining the number of calls to the model and information storage. We adapt a kd-tree algorithm to approximate the level sets of the resilience value. We prove that this algorithm converges to the output sets defined by the viability theory (viability kernel and capture basin). The resilience value we compute can then be used to propose a policy of action in risky situations such as migration flows.Cet article propose un algorithme couplé pour calculer la résilience d'un socio-écosystème dans le cadre de la théorie mathématique de la viabilité, illustré sur le problème des sociétés bilingues. Les modèles mathématiques de telles sociétés montrent que l'extinction d'un langage est en général inéluctable, sauf s'il est possible de modifier le prestige des langues. La méthode de calcul de la résilience que nous proposons repose sur un algorithme adapté des kd-trees. La convergence de l'algorithme de viabilité dans ce cadre est démontrée. Le calcul de la résilience est utilisé pour proposer des politiques d'action en cas de flux migratoires

Simulations stochastiques en environnements distribués (Application aux grilles de calcul)

CLERMONT FD-MSH (631132214) / SudocSudocFranceF