Viable Control of an Epidemiological Model

In mathematical epidemiology, epidemic control often aims at driving the number of infected individuals to zero, asymptotically. However , during the transitory phase, the number of infected can peak at high values. In this paper, we consider mosquito vector control in the Ross-Macdonald epidemiological model, with the goal of capping the proportion of infected by dengue at the peak. We formulate this problem as one of control of a dynamical system under state constraint. We allow for time-dependent fumigation rates to reduce the population of mosquito vector, in order to maintain the proportion of infected individuals by dengue below a threshold for all times. The so-called viability kernel is the set of initial states (mosquitoes and infected individuals) for which such a fumigation control trajectory exists. Depending on whether the cap on the proportion of infected is low, high or medium, we provide different expressions of the viability kernel. We also characterize so-called viable policies that produce, at each time, a fumigation rate as a function of current proportions of infected humans and mosquitoes, such that the proportion of infected humans remains below a threshold for all times. We provide a numerical application in the case of control of a dengue outbreak in 2013 in Cali, Colombia

Pattern Formation with a Compartmental Lateral Inhibition System

We propose a compartmental lateral inhibition system that generates contrasting patterns of gene expression between neighboring compartments. The system consists of a set of compartments interconnected by channels. Each compartment contains a colony of cells that produce diffusible molecules to be detected by the neighboring colony, and each cell is equipped with an inhibitory circuit that reduces its production when the detected signal is stronger. We develop a technique to analyze the steady-state patterns emerging from this lateral inhibition system and apply it to a specific implementation. The analysis shows that the proposed system indeed exhibits contrasting patterns within realistic parameter ranges.Comment: 9 pages, 6 figure

Des actions "hors les murs" pour promouvoir les bibliothèques et la lecture dans la cité: réflexion menée à partir d'un projet élaboré pour la Bibliothèque de la Ville de la Chaux-de-Fonds

Dans le cadre de mon Travail de Bachelor en information et documentation, la Bibliothèque de la Ville (BV) de La Chaux-de-Fonds m’a mandatée afin de mettre en place un projet de service de livres à la piscine en été. La BV souhaite offrir cette prestation dès 2009. Pour cela, elle voulait pouvoir se baser sur une étude détaillée des possibilités et des moyens nécessaires à sa réalisation. Il s’agissait de proposer des solutions concrètes et de fournir des données chiffrées, afin de monter un concept réalisable à la BV. Mon mandat consistait donc, d’une part, à déterminer les besoins relatifs à la réalisation du projet, et, d’autre part, à évaluer ses coûts afin de les inclure dans la demande de budget 2009. La Bibliothèque de Jeunes de La Chaux-de-Fonds a déjà mis en place un tel service destiné aux enfants, toutefois, aucune étude similaire n’a été réalisée au préalable. Ce projet s’inscrit dans le mouvement des actions «hors les murs» des bibliothèques et découle avant tout d’une volonté d’ouverture de l’institution. Il s’agit d’un outil de promotion de la bibliothèque, mais également de la lecture. Son rôle consiste à rendre la bibliothèque plus visible au sein de la cité et à déplacer le livre auprès des publics potentiels afin de les attirer au sein de la bibliothèque. Outre la Bibliothèque des Jeunes, la Bibliothèque de la Ville est la seule bibliothèque de lecture publique présente à la Chaux-de-Fonds. Elle est assez bien centrée, toutefois, la ville s’est considérablement développée sur ses abords depuis quelques années, créant ainsi une distance géographique de plus en plus importante entre la bibliothèque et les habitants de la périphérie. Ne parvenant pas à attirer ces derniers publics en ses murs, la BV a décidé d’aller à leur rencontre afin de leur présenter l’institution et ses ressources. Tout mon travail repose donc sur une réflexion sur la promotion de la lecture et de la bibliothèque au sein de la cité, et les besoins de l’animation ont été définis en fonction de celle-ci. Afin d’élaborer un projet concret et réalisable par la BV en 2009, j’ai effectué de nombreuses recherches et analyses. Il s’agissait tout d’abord de vérifier la cohérence du projet avec la politique générale de l’institution. Ensuite, j’ai recherché les services similaires proposés par d’autres bibliothèques, afin de prendre contact avec elles. Enfin, à partir des informations collectées, j’ai rédigé divers documents à l’intention de mon mandant, présentant les avantages et inconvénients des solutions existantes, ainsi que leurs coûts. J’ai essayé de présenter, dans ce travail, la méthodologie que j’ai adoptée pour la réalisation de mon mandat, d’une part, et, d’autre part, une marche à suivre plus générale sur laquelle peut se baser toute institution souhaitant s’investir dans une telle démarche. En parallèle, j’ai pris connaissance de documents traitant des actions «hors les murs» et de leurs enjeux. Par ailleurs, mon travail s’articule essentiellement autour des réflexions menées par Claudie Tabet dans son ouvrage La bibliothèque « hors les murs » (2004). La problématique plus générale que j’ai souhaité traiter est celle du rôle des bibliothèques publiques face aux inégalités d’accès à la culture, car les actions «hors les murs» peuvent constituer un moyen de réduire ces dernières. Par ailleurs, les textes fédérateurs attribuent un rôle social aux bibliothèques et à leurs acteurs dans la question de la démocratisation culturelle. Par ce travail, j’ai tenté de dégager les opportunités pour les bibliothèques de remplir cette fonction au sein de la communauté. À cette fin, j’ai essayé de répondre à plusieurs questions : • Quels sont les publics potentiels susceptibles d’être involontairement éloignés de l’offre de lecture publique? • Quels sont les autres acteurs locaux en contact avec ces publics ? • Quelles offres peuvent être mises en place pour répondre aux besoins de ces publics ? Les bibliothèques publiques cherchent aujourd’hui, par différentes démarches marketing, d’attirer de nouveaux usagers. Certains publics potentiels demeurent toutefois à l’écart de leur offre, éloignés par leur situation sociale ou par leur appréhension des bibliothèques. Par conséquent, il est également essentiel de chercher à réduire cet écart. Les actions «hors les murs» constituent un outil promotionnel et de rapprochement efficace, mais ne peuvent pas être étendues à tous les publics sans la participation d’acteurs extérieurs. En effet, les acteurs locaux qui sont en contacts avec des publics éloignés peuvent représenter des partenaires potentiels pour les bibliothèques. Il s’agit de chercher à connaître les associations ou institutions qui souhaitent développer une offre de lecture en direction de leur public ou qui en proposent déjà une et de créer des liens étroits avec ces derniers

BQ-NCO: Bisimulation Quotienting for Efficient Neural Combinatorial Optimization

Despite the success of neural-based combinatorial optimization methods for end-to-end heuristic learning, out-of-distribution generalization remains a challenge. In this paper, we present a novel formulation of Combinatorial Optimization Problems (COPs) as Markov Decision Processes (MDPs) that effectively leverages common symmetries of COPs to improve out-of-distribution robustness. Starting from a direct MDP formulation of a constructive method, we introduce a generic way to reduce the state space, based on Bisimulation Quotienting (BQ) in MDPs. Then, for COPs with a recursive nature, we specialize the bisimulation and show how the reduced state exploits the symmetries of these problems and facilitates MDP solving. Our approach is principled and we prove that an optimal policy for the proposed BQ-MDP actually solves the associated COPs. We illustrate our approach on five classical problems: the Euclidean and Asymmetric Traveling Salesman, Capacitated Vehicle Routing, Orienteering and Knapsack Problems. Furthermore, for each problem, we introduce a simple attention-based policy network for the BQ-MDPs, which we train by imitation of (near) optimal solutions of small instances from a single distribution. We obtain new state-of-the-art results for the five COPs on both synthetic and realistic benchmarks. Notably, in contrast to most existing neural approaches, our learned policies show excellent generalization performance to much larger instances than seen during training, without any additional search procedure

The Prostaglandin F Synthase Activity of the Human Aldose Reductase AKR1B1 Brings New Lenses to Look at Pathologic Conditions

Prostaglandins are important regulators of female reproductive functions to which aldose reductases exhibiting hydroxysteroid dehydrogenase activity also contribute. Our work on the regulation of reproductive function by prostaglandins (PGs), lead us to the discovery that AKR1B5 and later AKR1B1were highly efficient and physiologically relevant PGF synthases. PGE2 and PGF2α are the main prostanoids produced in the human endometrium and proper balance in their relative production is important for normal menstruation and optimal fertility. Recent evidence suggests that PGE2/EP2 and PGF2α/FP may constitute a functional dyad with physiological relevance comparable to the prostacyclin-thromboxane dyad in the vascular system. We have recently reported that AKR1B1 was expressed and modulated in association with PGF2α production in response to IL-1β in the human endometrium. In the present study, we show that the human AKR1B1 (gene ID: 231) also known as ALDR1 or ALR2 is a functional PGF2α synthase in different models of living cells and tissues. Using human endometrial cells, prostate, and vascular smooth muscle cells, cardiomyocytes and endothelial cells we demonstrate that IL-1β is able to up regulate COX-2 and AKR1B1 proteins as well as PGF2α production under normal glucose concentrations. We show that the promoter activity of AKR1B1 gene is increased by IL-1β particularly around the multiple stress response region containing two putative antioxidant response elements adjacent to TonE and AP1. We also show that AKR1B1 is able to regulate PGE2 production through PGF2α acting on its FP receptor and that aldose reductase inhibitors like alrestatin, Statil (ponalrestat), and EBPC exhibit distinct and characteristic inhibition of PGF2α production in different cell models. The PGF synthase activity of AKR1B1 represents a new and important target to regulate ischemic and inflammatory responses associated with several human pathologies

Defoliation of soybean expressing Cry1Ac by lepidopteran pests

Lepidoptera, stink bugs, and weevils are important pests in soybean. For lepidopteran control, insecticides and seed treatments are used. As an alternative, Bt soybean was developed to control primary pests of Lepidoptera such as Rachiplusia nu (Guenée) (Noctuidae), Chrysodeixis includens (Walker) (Noctuidae), Anticarsia gemmatalis Hübner (Erebidae), Helicoverpa gelotopoeon (Dyar) (Noctuidae), and Crocidosema aporema (Walsingham) (Tortricidae). However, the use of transgenic plants, and the resulting reduction of insecticide against target pests, may allow other pest species to become more prevalent in agricultural environments. Soybean expressing Cry1Ac against different lepidopteran nontarget and target insect pests was evaluated, and its performance was compared with non-Bt soybean with seed treatment. The treatments were Bt soybean, non-Bt soybean with seed treatment (Fortenza® diamide insecticide, Syngenta, Buenos Aires, Argentina), and non-Bt soybean without seed treatment. Larvae of H. gelotopoeon, Spodoptera albula (Walker) (Noctuidae), Spodoptera cosmiodes (Walker) (Noctuidae), Spodoptera eridania (Stoll) (Noctuidae), and Spodoptera frugiperda (J. E. Smith) (Lep.: Noctuidae) were used. The plants of each treatment were infested with larvae of each species, and the percentage of leaf damage produced by each species was recorded. The results showed that Bt soybean provided control of H. gelotopoeon and had a suppressive effect on S. frugiperda and S. albula. However, S. eridania and S. cosmiodes were not susceptible to the Cry1Ac protein in MON 87701 × MON 89788 soybean when evaluated by greenhouse infestation. Considering the performance of each species using non-Bt soybean without seed treatment, S. eridania would represent a potential risk in soybean crops.Fil: Murúa, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto de Tecnología Agroindustrial del Noroeste Argentino; Argentina. Gobierno de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Vera, Martín. Gobierno de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Herrero, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto de Tecnología Agroindustrial del Noroeste Argentino; Argentina. Gobierno de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Fogliata, Sofia Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Instituto de Tecnología Agroindustrial del Noroeste Argentino; Argentina. Gobierno de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Michel, Andrew. Ohio Agricultural Research And Development Center

Uncontrolled inexact information within bundle methods

International audienceWe consider convex nonsmooth optimization problems where additional information with uncontrolled accuracy is readily available. It is often the case when the objective function is itself the output of an optimization solver, as for large-scale energy optimization problems tackled by decomposition. In this paper, we study how to incorporate the uncontrolled linearizations into (proximal and level) bundle algorithms in view of generating better iterates and possibly accelerating the methods. We provide the convergence analysis of the algorithms using uncontrolled linearizations, and we present numerical illustrations showing they indeed speed up resolution of two stochastic optimization problems coming from energy optimization (two-stage linear problems and chance-constrained problems in reservoir management)

Single Mutations in Cytochrome P450 Oxidoreductase Can Alter the Specificity of Human Cytochrome P450 1A2-Mediated Caffeine Metabolism

Funding Information: F.E. and M.K.: UID/BIM/0009/2020 of the Portuguese Fundação para a Ciência e a Tecnologia (FCT) and HLTH-2022-STAYHLTH-02/grant agreement 101095679 of the European Horizon´s research and innovation program. Publisher Copyright: © 2023 by the authors.A unique cytochrome P450 (CYP) oxidoreductase (CPR) sustains activities of human microsomal CYPs. Its function requires toggling between a closed conformation enabling electron transfers from NADPH to FAD and then FMN cofactors and open conformations forming complexes and transferring electrons to CYPs. We previously demonstrated that distinct features of the hinge region linking the FAD and FMN domain (FD) modulate conformer poses and their interactions with CYPs. Specific FD residues contribute in a CYP isoform-dependent manner to the recognition and electron transfer mechanisms that are additionally modulated by the structure of CYP-bound substrate. To obtain insights into the underlying mechanisms, we analyzed how hinge region and FD mutations influence CYP1A2-mediated caffeine metabolism. Activities, metabolite profiles, regiospecificity and coupling efficiencies were evaluated in regard to the structural features and molecular dynamics of complexes bearing alternate substrate poses at the CYP active site. Studies reveal that FD variants not only modulate CYP activities but surprisingly the regiospecificity of reactions. Computational approaches evidenced that the considered mutations are generally in close contact with residues at the FD–CYP interface, exhibiting induced fits during complexation and modified dynamics depending on caffeine presence and orientation. It was concluded that dynamic coupling between FD mutations, the complex interface and CYP active site exist consistently with the observed regiospecific alterations.publishersversionpublishe