Proactive management of uncertainty to improve scheduling robustness in proces industries

Dinamisme, capacitat de resposta i flexibilitat són característiques essencials en el desenvolupament de la societat actual. Les noves tendències de globalització i els avenços en tecnologies de la informació i comunicació fan que s'evolucioni en un entorn altament dinàmic i incert. La incertesa present en tot procés esdevé un factor crític a l'hora de prendre decisions, així com un repte altament reconegut en l'àrea d'Enginyeria de Sistemes de Procés (PSE). En el context de programació de les operacions, els models de suport a la decisió proposats fins ara, així com també software comercial de planificació i programació d'operacions avançada, es basen generalment en dades estimades, assumint implícitament que el programa d'operacions s'executarà sense desviacions. La reacció davant els efectes de la incertesa en temps d'execució és una pràctica habitual, però no sempre resulta efectiva o factible. L'alternativa és considerar la incertesa de forma proactiva, és a dir, en el moment de prendre decisions, explotant el coneixement disponible en el propi sistema de modelització.Davant aquesta situació es plantegen les següents preguntes: què s'entén per incertesa? Com es pot considerar la incertesa en el problema de programació d'operacions? Què s'entén per robustesa i flexibilitat d'un programa d'operacions? Com es pot millorar aquesta robustesa? Quins beneficis comporta? Aquesta tesi respon a aquestes preguntes en el marc d'anàlisis operacionals en l'àrea de PSE. La incertesa es considera no de la forma reactiva tradicional, sinó amb el desenvolupament de sistemes proactius de suport a la decisió amb l'objectiu d'identificar programes d'operació robustos que serveixin com a referència pel nivell inferior de control de planta, així com també per altres centres en un entorn de cadenes de subministrament. Aquest treball de recerca estableix les bases per formalitzar el concepte de robustesa d'un programa d'operacions de forma sistemàtica. Segons aquest formalisme, els temps d'operació i les ruptures d'equip són considerats inicialment com a principals fonts d'incertesa presents a nivell de programació de la producció. El problema es modelitza mitjançant programació estocàstica, desenvolupant-se finalment un entorn d'optimització basat en simulació que captura les múltiples fonts d'incertesa, així com també estratègies de programació d'operacions reactiva, de forma proactiva. La metodologia desenvolupada en el context de programació de la producció s'estén posteriorment per incloure les operacions de transport en sistemes de múltiples entitats i incertesa en els temps de distribució. Amb aquesta perspectiva més àmplia del nivell d'operació s'estudia la coordinació de les activitats de producció i transport, fins ara centrada en nivells estratègic o tàctic. L'estudi final considera l'efecte de la incertesa en la demanda en les decisions de programació de la producció a curt termini. El problema s'analitza des del punt de vista de gestió del risc, i s'avaluen diferents mesures per controlar l'eficiència del sistema en un entorn incert.En general, la tesi posa de manifest els avantatges en reconèixer i modelitzar la incertesa, amb la identificació de programes d'operació robustos capaços d'adaptar-se a un ampli rang de situacions possibles, enlloc de programes d'operació òptims per un escenari hipotètic. La metodologia proposada a nivell d'operació es pot considerar com un pas inicial per estendre's a nivells de decisió estratègics i tàctics. Alhora, la visió proactiva del problema permet reduir el buit existent entre la teoria i la pràctica industrial, i resulta en un major coneixement del procés, visibilitat per planificar activitats futures, així com també millora l'efectivitat de les tècniques reactives i de tot el sistema en general, característiques altament desitjables per mantenir-se actiu davant la globalitat, competitivitat i dinàmica que envolten un procés.Dynamism, responsiveness, and flexibility are essential features in the development of the current society. Globalization trends and fast advances in communication and information technologies make all evolve in a highly dynamic and uncertain environment. The uncertainty involved in a process system becomes a critical problem in decision making, as well as a recognized challenge in the area of Process Systems Engineering (PSE). In the context of scheduling, decision-support models developed up to this point, as well as commercial advanced planning and scheduling systems, rely generally on estimated input information, implicitly assuming that a schedule will be executed without deviations. The reaction to the effects of the uncertainty at execution time becomes a common practice, but it is not always effective or even possible. The alternative is to address the uncertainty proactively, i.e., at the time of reasoning, exploiting the available knowledge in the modeling procedure itself. In view of this situation, the following questions arise: what do we understand for uncertainty? How can uncertainty be considered within scheduling modeling systems? What is understood for schedule robustness and flexibility? How can schedule robustness be improved? What are the benefits? This thesis answers these questions in the context of operational analysis in PSE. Uncertainty is managed not from the traditional reactive viewpoint, but with the development of proactive decision-support systems aimed at identifying robust schedules that serve as a useful guidance for the lower control level, as well as for dependent entities in a supply chain environment. A basis to formalize the concept of schedule robustness is established. Based on this formalism, variable operation times and equipment breakdowns are first considered as the main uncertainties in short-term production scheduling. The problem is initially modeled using stochastic programming, and a simulation-based stochastic optimization framework is finally developed, which captures the multiple sources of uncertainty, as well as rescheduling strategies, proactively. The procedure-oriented system developed in the context of production scheduling is next extended to involve transport scheduling in multi-site systems with uncertain travel times. With this broader operational perspective, the coordination of production and transport activities, considered so far mainly in strategic and tactical analysis, is assessed. The final research point focuses on the effect of demands uncertainty in short-term scheduling decisions. The problem is analyzed from a risk management viewpoint, and alternative measures are assessed and compared to control the performance of the system in the uncertain environment.Overall, this research work reveals the advantages of recognizing and modeling uncertainty, with the identification of more robust schedules able to adapt to a wide range of possible situations, rather than optimal schedules for a hypothetical scenario. The management of uncertainty proposed from an operational perspective can be considered as a first step towards its extension to tactical and strategic levels of decision. The proactive perspective of the problem results in a more realistic view of the process system, and it is a promising way to reduce the gap between theory and industrial practices. Besides, it provides valuable insight on the process, visibility for future activities, as well as it improves the efficiency of reactive techniques and of the overall system, all highly desirable features to remain alive in the global, competitive, and dynamic process environment

Differential expression of E-type prostanoid receptors 2 and 4 in microglia stimulated with lipopolysaccharide

[Background] Cyclooxygenase-2 (COX-2) is induced under inflammatory conditions, and prostaglandin E2 (PGE2) is one of the products of COX activity. PGE2 has pleiotropic actions depending on the activation of specific E-type prostanoid EP1-4 receptors. We investigated the involvement of PGE2 and EP receptors in glial activation in response to an inflammatory challenge induced by LPS.[Methods] Cultures of mouse microglia or astroglia cells were treated with LPS in the presence or absence of COX-2 inhibitors, and the production of PGE2 was measured by ELISA. Cells were treated with PGE2, and the effect on LPS-induced expression of TNF-α messenger RNA (mRNA) and protein was studied in the presence or absence of drug antagonists of the four EP receptors. EP receptor expression and the effects of EP2 and EP4 agonists and antagonists were studied at different time points after LPS.[Results] PGE2 production after LPS was COX-2-dependent. PGE2 reduced the glial production of TNF-α after LPS. Microglia expressed higher levels of EP4 and EP2 mRNA than astroglia. Activation of EP4 or EP2 receptors with selective drug agonists attenuated LPS-induced TNF-α in microglia. However, only antagonizing EP4 prevented the PGE2 effect demonstrating that EP4 was the main target of PGE2 in naïve microglia. Moreover, the relative expression of EP receptors changed during the course of classical microglial activation since EP4 expression was strongly depressed while EP2 increased 24 h after LPS and was detected in nuclear/peri-nuclear locations. EP2 regulated the expression of iNOS, NADPH oxidase-2, and vascular endothelial growth factor. NADPH oxidase-2 and iNOS activities require the oxidation of NADPH, and the pentose phosphate pathway is a main source of NADPH. LPS increased the mRNA expression of the rate-limiting enzyme of the pentose pathway glucose-6-phosphate dehydrogenase, and EP2 activity was involved in this effect.[Conclusions] These results show that while selective activation of EP4 or EP2 exerts anti-inflammatory actions, EP4 is the main target of PGE2 in naïve microglia. The level of EP receptor expression changes from naïve to primed microglia where the COX-2/PGE2/EP2 axis modulates important adaptive metabolic changes.This work was supported by the Spanish Ministerio de Economia y Competitividad (MINECO) (SAF2014-56279R) and the European Community FP7 (InMiND project no. 278850). EBT had an FPU PhD fellowship of MINECO.Peer reviewe

IL-10 deficiency exacerbates the brain inflammatory response to permanent ischemia without preventing resolution of the lesion

El pdf del artículo es la versión post-print.Stroke induces inflammation that can aggravate brain damage. This work examines whether interleukin-10 (IL-10) deficiency exacerbates inflammation and worsens the outcome of permanent middle cerebral artery occlusion (pMCAO). Expression of IL-10 and IL-10 receptor (IL-10R) increased after ischemia. From day 4, reactive astrocytes showed strong IL-10R immunoreactivity. Interleukin-10 knockout (IL-10 KO) mice kept in conventional housing showed more mortality after pMCAO than the wild type (WT). This effect was associated with the presence of signs of colitis in the IL-10 KO mice, suggesting that ongoing systemic inflammation was a confounding factor. In a pathogen-free environment, IL-10 deficiency slightly increased infarct volume and neurologic deficits. Induction of proinflammatory molecules in the IL-10 KO brain was similar to that in the WT 6 hours after ischemia, but was higher at day 4, while differences decreased at day 7. Deficiency of IL-10 promoted the presence of more mature phagocytic cells in the ischemic tissue, and enhanced the expression of M2 markers and the T-cell inhibitory molecule CTLA-4. These findings agree with a role of IL-10 in attenuating local inflammatory reactions, but do not support an essential function of IL-10 in lesion resolution. Upregulation of alternative immunosuppressive molecules after brain ischemia can compensate, at least in part, the absence of IL-10. © 2013 ISCBFM.Work supported by the Spanish Ministry of Economy (SAF2011-30492), and the European Community (FP7, grant agreements: n°201024 ARISE and n°278850 InMiND), and the ERANET-NEURON project (PRI-PIMNEU-2011-1342). IPP and EBT had PhD fellowships from the Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) of the Generalitat de Catalunya and the FPU program of the Spanish Ministry of Economy, respectively.Peer Reviewe

Induction of COX-2 enzyme and down-regulation of COX-1 expression by lipopolysaccharide (LPS) control prostaglandin E2 production in astrocytes

Pathological conditions and pro-inflammatory stimuli in the brain induce cyclooxygenase-2 (COX-2), a key enzyme in arachidonic acid metabolism mediating the production of prostanoids that, among other actions, have strong vasoactive properties. Although low basal cerebral COX-2 expression has been reported, COX-2 is strongly induced by pro-inflammatory challenges, whereas COX-1 is constitutively expressed. However, the contribution of these enzymes in prostanoid formation varies depending on the stimuli and cell type. Astrocyte feet surround cerebral microvessels and release molecules that can trigger vascular responses. Here, we investigate the regulation of COX-2 induction and its role in prostanoid generation after a pro-inflammatory challenge with the bacterial lipopolysaccharide (LPS) in astroglia. Intracerebral administration of LPS in rodents induced strong COX-2 expression mainly in astroglia and microglia, whereas COX-1 expression was predominant in microglia and did not increase. In cultured astrocytes, LPS strongly induced COX-2 and microsomal prostaglandin-E2 (PGE2) synthase-1, mediated by the MyD88-dependent NFκB pathway and influenced by mitogen-activated protein kinase pathways. Studies in COX-deficient cells and using COX inhibitors demonstrated that COX-2 mediated the high production of PGE2 and, to a lesser extent, other prostanoids after LPS. In contrast, LPS down-regulated COX-1 in an MyD88-dependent fashion, and COX-1 deficiency increased PGE2 production after LPS. The results show that astrocytes respond to LPS by a COX-2-dependent production of prostanoids, mainly vasoactive PGE2, and suggest that the coordinated down-regulation of COX-1 facilitates PGE2 production after TLR-4 activation. These effects might induce cerebral blood flow responses to brain inflammation

Pairs of refinable bivariate splines

SIGLEGBUnited Kingdo

Decision support framework for coordinated production and transport scheduling in SCM

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Proactive approach to address the uncertainty in short-term scheduling

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IL-4 is induced in the brain after ischemia and it down-regulates the inflammatory profile of microglia

Trabajo presentado en la VI Reunión de la Red Glial Española, celebrada en Oviedo, en septiembre de 2013Peer Reviewe

IL-4 Expression after Stroke and Alternative Microglia/Macrophage Activation

Comunicación presentada en el IX Simposi de Neurobiologia Experimental, celebrado los días 22 y 23 de octubre de 2014 en Barcelona y organizado por la Societat Catalana de Biologia del Institut d'Estudis CatalansStroke triggers inflammation that exacerbates brain tissue damage. The inflammatory reaction is naturally set up to clear the necrotic tissue and comprises a complex dynamic process evolving through various steps from initiation to resolution which are not fully elucidated. IL-4 is a cytokine mainly produced by lymphocytes that promotes an alternative anti-inflammatory M2 phenotype in macrophages. Mice deficient in IL-4 show worse stroke outcome suggesting that IL-4 may play a role in brain ischemia. The aim of this study was to identify the IL-4 expression in the brain after ischemia and investigate the effects of IL-4 on the inflammatory response of glial cells. Permanent middle cerebral artery occlusion (pMCAO) in mice produces low levels of IL-4 mRNA expression from 6 hours to 4 days post-ischemia, but it strongly increased at day 7. At this time, the expression of several inflammatory markers was attenuated while that of molecules involved in alternative M2 phenotype and tissue repair increased. Treatment of cultures of murine glia with recombinant IL-4 increasingly upregulated the expression of the M2 markers such as arginase-1 up to 48h while M1 markers are inhibited. This profile in glia was dependent on Jak1/Jak3/Stat6 pathway and requires a new protein synthesis. Microglia treated with IL-4 showed a reduced proinflammatory response when challenged with LPS. We suggest that initial proinflammatory milieu set after brain ischemia is followed by the upregulation of IL-4 and of markers of alternative M2 phenotype and that JAK/STAT pathways are involved. M1 glia can be reprogrammed by IL-4 switching to a M2 phenotypePeer Reviewe

Metaheuristic multiobjective optimisation approach for the scheduling of multiproduct batch chemical plants

This article introduces a novel framework to deal with the scheduling problem concerning batch chemical plants. The main contribution of this work in comparison with previous approaches relies on the fact that it includes the environmental impact as an objective to be optimised, integrated with other more commonly used as makespan and/or financial performance. To address this problem, an advanced planning and scheduling tool (APS), which includes an environmental evaluation module based on the Life Cycle Assessment (LCA) criteria, a temporisation algorithm and a financial module, coupled with a set of multiobjective genetic algorithms allows the computation of a set of non-dominated solutions in terms of the predefined criteria. This set of solutions can be used by the decision-maker in order to select the one that represents the right compromise among the different objectives.Peer Reviewe