Business process management heuristics in IT service management: a case study for incident management

This research aims to understand how Business process management (BPM) can be applied for the improvement of Information Technology service management (ITSM) processes. A case study is conducted for the improvement of the time performance of the incident management process, since it is pointed as a quick win for ITSM. The results obtained identified three best practices—activity automation, activity elimination and integral technology—as the best suited for the improvement of the time performance of the incident management process. Using a simulation tool for business processes, it was revealed that the employment of these best practices in the analysed incident management process eliminates the effort required in the 1st support level and reduces in 10.7% the average processing time in the 2nd support level

Workshop on meibomian gland dysfunction

Federal University of São Paulo Department of OphthalmologyUniversidade de São Paulo epartment of Ophthalmology, Otorhinolaryngology, and Head and Neck SurgerySchepens Eye Research InstituteHarvard Medical School Department of OphthalmologyTear Film & Ocular Surface SocietyUNIFESP, Department of OphthalmologySciEL

Potentiation of morphine-induced antinociception and locomotion by citalopram is accompanied by anxiolytic-like effects

Morphine and related opioids are the mainstay of analgesic treatment, especially in patients suffering chronic pain. Besides their antinociceptive effects they may also exhibit anxiolytic-like properties that could contribute to pain relief. The pharmacological manipulation of the serotonergic system may not only modulate pain transmission and processing but also other behavioral effects of opioids. The present study aimed to analyze the effect of the concurrent treatment with citalopram, a selective serotonin reuptake inhibitor, on the antinociceptive, locomotor and anxiety-related effects induced by acute and subchronic administration of morphine in mice. Citalopram (15 mg/kg) enhanced the acute antinociceptive effects of morphine when concurrently administered as evidenced by a two-fold increase in the ED50 for the antinociceptive effect of morphine in the hot-plate test. Chronic studies also revealed that concurrent citalopram treatment (15 mg/kg) delayed the development of tolerance to the thermal antinociceptive effects of morphine. Additionally, morphine-induced hyperlocomotion was potentiated by citalopram as assessed in the open-field test and in the spontaneous activity recording in the home cage, a behavioral outcome to which tolerance or desensitization was not developed. Interestingly, chronic administration of both drugs promoted an anxiolytic effect as evidenced by the increased central activity in the open field test. Future investigations on this pharmacological interaction, such as the possible translational research in clinics, might have consequences in future strategies for the therapeutic management of pain.This research was supported by the grant SAF2010-15663 from the Spanish Government (MINECO). We thank David Ramos and Raquel Lanza for their technical assistance in handling living animals. We kindly appreciate Belen Palacio support for video footage and editing and Dr. Albert Adell for the critical reading of the manuscript

Differential toxicity of antifungal protein AFP against mutants of Fusarium oxysporum

Antifungal protein (AFP) from Aspergillus giganteus was assayed for toxicity against the Fusarium oxysporum wild-type strain and mutants in genes involved in cell signaling (ΔpacC, pacCc Δfmk1) or cell-wall biogenesis (ΔchsV, Δchs7, Δgas1). The mutants were classified into two groups according to their sensitivity to AFP: ΔpacC, Δgas1 and Δchs7, which were significantly more resistant to AFP than the wild-type, and pacCC, Δfmk1 and ΔchsV, which were more sensitive. Western blot analysis revealed increased binding of AFP to the three resistant mutants, ΔpacC, Δgas1 and Δchs7, but also to ΔchsV, indicating that differential binding may not be a key determinant for sensitivity. Addition of Ca2+ or K+ dramatically reduced antifungal activity and binding of AFP, suggesting that these cations compete for the same targets as AFP at the surface of the fungal cell. [Int Microbiol 2009; 12(2):115-121

The CORDEX Flagship Pilot Study in southeastern South America: a comparative study of statistical and dynamical downscaling models in simulating daily extreme precipitation events

The aim of this work is to present preliminary results of the statistical and dynamical simulations carried out within the framework of the Flagship Pilot Study in southeastern South America (FPS-SESA) endorsed by the Coordinated Regional Climate Downscaling Experiments (CORDEX) program. The FPS-SESA initiative seeks to promote inter-institutional collaboration and further networking with focus on extreme rainfall events. The main scientific aim is to study multi-scale processes and interactions most conducive to extreme precipitation events through both statistical and dynamical downscaling techniques, including convection-permitting simulations. To this end, a targeted experiment was designed considering the season October 2009 to March 2010, a period with a record number of extreme precipitation events within SESA. Also, three individual extreme events within that season were chosen as case studies for analyzing specific regional processes and sensitivity to resolutions. Four dynamical and four statistical downscaling models (RCM and ESD respectively) from different institutions contributed to the experiment. In this work, an analysis of the capability of the set of the FPS-SESA downscaling methods in simulating daily precipitation during the selected warm season is presented together with an integrated assessment of multiple sources of observations and available CORDEX Regional Climate Model simulations. Comparisons among all simulations reveal that there is no single model that performs best in all aspects evaluated. The ability in reproducing the different features of daily precipitation depends on the model. However, the evaluation of the sequence of precipitation events, their intensity and timing suggests that FPS-SESA simulations based on both RCM and ESD yield promising results. Most models capture the extreme events selected, although with a considerable spread in accumulated values and the location of heavy precipitation.Thanks to CORDEX for endorsing the FPS-SESA. This work was supported by the University of Buenos Aires 2018- 20020170100117BA grant; JMG, MLB, SAS, RPR funding from the Spanish Research Council (CSIC) I-COOP+ Program “reference COOPB20374”. JMG, JF and AL-G acknowledge support from the Spanish R&D Program through projects MULTI-SDM (CGL2015-66583-R) and INSIGNIA (CGL2016-79210-R), co-funded by the European Regional Development Fund (ERDF/FEDER). AL-G acknowledges support from the Spanish R&D Program through the predoctoral contract BES-2016-078158. Universidad de Cantabria simulations have been carried out on the Altamira Supercomputer at the Instituto de Física de Cantabria (IFCA-CSIC), member of the Spanish Supercomputing Network. MB acknowledges support from the Simons Associateship of the Abdus Salam International Centre for Theoretical Physics. RH acknowledges support from the project LTT17007 funded by the Ministry of Education, Youth, and Sports of the Czech Republic

Loss of Hierarchical Imprinting Regulation at the Prader-Willi/Angelman Syndrome Locus in Human iPSCs

The human chr15q11-q13 imprinted cluster is linked to several disorders, including Prader-Willi (PWS) and Angelman (AS) syndromes. Recently, disease modeling approaches based on induced pluripotent stem cells (iPSCs) have been used to study these syndromes. A concern regarding the use of these cells for imprinted disease modeling is the numerous imprinting defects found in many iPSCs. Here, by reprogramming skin fibroblasts from a control and AS individuals, we generated several iPSC lines and addressed the stability of imprinting status across the PWS/AS domain. We focused on three important regulatory DNA elements which are all differentially methylated regions (DMRs), methylated on the maternal allele: the PWS imprinting center (PWS-IC), which is a germline DMR and the somatic NDN and MKRN3 DMRs, hierarchically controlled by PWS-IC. Normal PWS-IC methylation pattern was maintained in most iPSC lines; however, loss of maternal methylation in one out of five control iPSC lines resulted in a monoallelic to biallelic switch for many imprinted genes in this domain. Surprisingly, MKRN3 DMR was found aberrantly hypermethylated in all control and AS iPSCs, regardless of the methylation status of the PWS-IC master regulator. This suggests a loss of hierarchical control of imprinting at PWS/AS region. We confirmed these results in established iPSC lines derived using different reprogramming procedures. Overall, we show that hierarchy of imprinting control in donor cells might not apply to iPSCs, accounting for their spectrum of imprinting alterations. Such differences in imprinting regulation should be taken into consideration for the use of iPSCs in disease modeling.info:eu-repo/semantics/publishedVersio

Aryl-hydrocarbon receptor-interacting protein regulates tumorigenic and metastatic properties of colorectal cancer cells driving liver metastasis

12 p.-5 fig.-1 tab.Background: Liver metastasis is the primary cause of colorectal cancer (CRC)-associated death. Aryl-hydrocarbon receptor-interacting protein (AIP), a putative positive intermediary in aryl-hydrocarbon receptor-mediated signalling, is overexpressed in highly metastatic human KM12SM CRC cells and other highly metastatic CRC cells.Methods: Meta-analysis and immunohistochemistry were used to assess the relevance of AIP. Cellular functions and signalling mechanisms mediated by AIP were assessed by gain-of-function experiments and in vitro and in vivo experiments.Results: A significant association of high AIP expression with poor CRC patients’ survival was observed. Gain-of-function and quantitative proteomics experiments demonstrated that AIP increased tumorigenic and metastatic properties of isogenic KM12C (poorly metastatic) and KM12SM (highly metastatic to the liver) CRC cells. AIP overexpression dysregulated epithelial-to-mesenchymal (EMT) markers and induced several transcription factors and Cadherin-17 activation. The former induced the signalling activation of AKT, SRC and JNK kinases to increase adhesion, migration and invasion of CRC cells. In vivo, AIP expressing KM12 cells induced tumour growth and liver metastasis. Furthermore, KM12C (poorly metastatic) cells ectopically expressing AIP became metastatic to the liver.Conclusions: Our data reveal new roles for AIP in regulating proteins associated with cancer and metastasis to induce tumorigenic and metastatic properties in colon cancer cells driving liver metastasis.This work was supported by the financial support of the PI17CIII/00045 and PI20CIII/00019 grants from the AES-ISCIII program to RB. J Hendrix acknowledges funding by UH-BOF (BOF20TT06). J Hofkens acknowledges financial support from the Research Foundation-Flanders (FWO, Grant No. ZW15_09-G0H6316N), the Flemish government through long-term structural funding Methusalem (CASAS2, Meth/15/04) and the MPI as MPI fellow. S.R. acknowledges the financial support of the KU Leuven through the internal C1 funding (KU Leuven (C14/16/053)). GSF is the recipient of a predoctoral contract (grant number 1193818 N) supported by The Flanders Research Foundation (FWO). The FPU predoctoral contract to AMC is supported by the Spanish Ministerio de Educación, Cultura y Deporte.Peer reviewe