What Automated Planning Can Do for Business Process Management

Business Process Management (BPM) is a central element of today organizations. Despite over the years its main focus has been the support of processes in highly controlled domains, nowadays many domains of interest to the BPM community are characterized by ever-changing requirements, unpredictable environments and increasing amounts of data that influence the execution of process instances. Under such dynamic conditions, BPM systems must increase their level of automation to provide the reactivity and flexibility necessary for process management. On the other hand, the Artificial Intelligence (AI) community has concentrated its efforts on investigating dynamic domains that involve active control of computational entities and physical devices (e.g., robots, software agents, etc.). In this context, Automated Planning, which is one of the oldest areas in AI, is conceived as a model-based approach to synthesize autonomous behaviours in automated way from a model. In this paper, we discuss how automated planning techniques can be leveraged to enable new levels of automation and support for business processing, and we show some concrete examples of their successful application to the different stages of the BPM life cycle

Automatic business process model extension to repair constraint violations

Consider an artifact-centric business process model, containing both a data model and a process model. When executing the process, it may happen that some of the data constraints from the data model are violated. Bearing this in mind, we propose an approach to automatically generate an extension to the original business process model that, when executed after a constraint violation, repairs the contents of the data leaving it in a new consistent state.Peer ReviewedPostprint (author's final draft

TLR9 polymorphisms in African populations: no association with severe malaria, but evidence of cis-variants acting on gene expression

BACKGROUND: During malaria infection the Toll-like receptor 9 (TLR9) is activated through induction with plasmodium DNA or another malaria motif not yet identified. Although TLR9 activation by malaria parasites is well reported, the implication to the susceptibility to severe malaria is not clear. The aim of this study was to assess the contribution of genetic variation at TLR9 to severe malaria. METHODS: This study explores the contribution of TLR9 genetic variants to severe malaria using two approaches. First, an association study of four common single nucleotide polymorphisms was performed on both family- and population-based studies from Malawian and Gambian populations (n>6000 individual). Subsequently, it was assessed whether TLR9 expression is affected by cis-acting variants and if these variants could be mapped. For this work, an allele specific expression (ASE) assay on a panel of HapMap cell lines was carried out. RESULTS: No convincing association was found with polymorphisms in TLR9 for malaria severity, in either Gambian or Malawian populations, using both case-control and family based study designs. Using an allele specific expression assay it was observed that TLR9 expression is affected by cis-acting variants, these results were replicated in a second experiment using biological replicates. CONCLUSION: By using the largest cohorts analysed to date, as well as a standardized phenotype definition and study design, no association of TLR9 genetic variants with severe malaria was found. This analysis considered all common variants in the region, but it is remains possible that there are rare variants with association signals. This report also shows that TLR9 expression is potentially modulated through cis-regulatory variants, which may lead to differential inflammatory responses to infection between individuals

Impact of pharmaceutical promotion on prescribing decisions of general practitioners in Eastern Turkey

<p>Abstract</p> <p>Background</p> <p>Commercial sources of information are known to have greater influence than scientific sources on general practitioners' (GPs) prescribing behavior in under developed and developing countries. The study aimed to determine the self-reported impact of pharmaceutical promotion on the decision-making process of prescription of GPs in Eastern Turkey.</p> <p>Methods</p> <p>A cross-sectional, exploratory survey was performed among 152 GPs working in the primary health centers and hospitals in Erzurum province of Eastern Turkey in 2006. A self-administered structured questionnaire was used. The questionnaire included questions regarding sociodemographics, number of patients per day, time per patient, frequency of sales representative visits to GPs, participation of GPs in training courses on prescribing (in-service training, drug companies), factors affecting prescribing decision, reference sources concerning prescribing and self-reported and self-rated effect of the activities of sales representatives on GPs prescribing decisions.</p> <p>Results</p> <p>Of 152 subjects, 53.3% were male and 65.8% were working at primary health care centers, respectively. Mean patient per day was 58.3 ± 28.8 patients per GP. For majority of the GPs (73.7%), the most frequent resource used in case of any problems in prescribing process was drug guides of pharmaceutical companies. According to self-report of the GPs, their prescribing decisions were affected by participation in any training activity of drug companies, frequent visits by sales representatives, high number of patient examinations per day and low year of practice (p < 0.05 for all).</p> <p>Conclusion</p> <p>The results of this study suggest that for the majority of the GPs, primary reference sources concerning prescribing was commercial information provided by sales representatives of pharmaceutical companies, which were reported to be highly influential on their decision-making process of prescribing by GPs. Since this study was based on self-report, the influence reported by the GPs may have been underestimated.</p

FcRn-mediated antibody transport across epithelial cells revealed by electron tomography

The neonatal Fc receptor (FcRn) transports maternal IgG across epithelial barriers, thereby providing the fetus or newborn with humoral immunity before its immune system is fully functional. In newborn rats, FcRn transfers IgG from milk to blood by apical-to-basolateral transcytosis across intestinal epithelial cells. The pH difference between the apical (pH 6.0–6.5) and basolateral (pH 7.4) sides of intestinal epithelial cells facilitates the efficient unidirectional transport of IgG, because FcRn binds IgG at pH 6.0–6.5 but not at pH 7 or more. As milk passes through the neonatal intestine, maternal IgG is removed by FcRn-expressing cells in the proximal small intestine (duodenum and jejunum); remaining proteins are absorbed and degraded by FcRn-negative cells in the distal small intestine (ileum). Here we use electron tomography to make jejunal transcytosis visible directly in space and time, developing new labelling and detection methods to map individual nanogold-labelled Fc within transport vesicles and simultaneously to characterize these vesicles by immunolabelling. Combining electron tomography with a nonperturbing endocytic label allowed us to conclusively identify receptor-bound ligands, resolve interconnecting vesicles, determine whether a vesicle was microtubule-associated, and accurately trace FcRn-mediated transport of IgG. Our results present a complex picture in which Fc moves through networks of entangled tubular and irregular vesicles, only some of which are microtubule-associated, as it migrates to the basolateral surface. New features of transcytosis are elucidated, including transport involving multivesicular body inner vesicles/tubules and exocytosis through clathrin-coated pits. Markers for early, late and recycling endosomes each labelled vesicles in different and overlapping morphological classes, revealing spatial complexity in endo-lysosomal trafficking

Loss of Sugar Detection by GLUT2 Affects Glucose Homeostasis in Mice

International audienceBACKGROUND: Mammals must sense the amount of sugar available to them and respond appropriately. For many years attention has focused on intracellular glucose sensing derived from glucose metabolism. Here, we studied the detection of extracellular glucose concentrations in vivo by invalidating the transduction pathway downstream from the transporter-detector GLUT2 and measured the physiological impact of this pathway. METHODOLOGY/PRINCIPAL FINDINGS: We produced mice that ubiquitously express the largest cytoplasmic loop of GLUT2, blocking glucose-mediated gene expression in vitro without affecting glucose metabolism. Impairment of GLUT2-mediated sugar detection transiently protected transgenic mice against starvation and streptozotocin-induced diabetes, suggesting that both low- and high-glucose concentrations were not detected. Transgenic mice favored lipid oxidation, and oral glucose was slowly cleared from blood due to low insulin production, despite massive urinary glucose excretion. Kidney adaptation was characterized by a lower rate of glucose reabsorption, whereas pancreatic adaptation was associated with a larger number of small islets. CONCLUSIONS/SIGNIFICANCE: Molecular invalidation of sugar sensing in GLUT2-loop transgenic mice changed multiple aspects of glucose homeostasis, highlighting by a top-down approach, the role of membrane glucose receptors as potential therapeutic targets