Pancreatic islet transplantation to treat diabetes - defining molecular tools to select suitable islets [abstract]

Comparative Medicine - OneHealth and Comparative Medicine Poster SessionA complete understanding of pancreatic islet biology is essential to the development of preventive or curative interventions for diabetes. It has been known that subpopulations of islets of different sizes exist; however, whether they are biologically and functionally unique has not been investigated. As an example, our work comparing the biology of large versus small islets isolated from rats showed that small islets were superior to large islets in in vitro function and in transplantation outcomes. These results provided the stimulus for an improved approach to islet transplantation in humans. The work also led to new questions regarding the basic physiology of healthy islets. Through collaboration between our University of Kansas Medical Center and Children's Mercy Hospital teams, we determined that small islets secrete higher amount of insulin in vitro when compared to the large islets. We sought to identify whether the islet subpopulations showed differences at the molecular level and thus we investigated their protein expression profiles using two-dimensional polyacrylamide gel electrophoresis (2D PAGE). We found that the protein repertoire in the small and large islets differed significantly. Specifically, some proteins were found only in one type of islets, small or large, while they were missing or their expression levels were different in the other subpopulation. We identified some of the proteins by liquid chromatography - mass spectrometry. Immunofluorescence performed on small and large islets in pancreatic sections, with antibodies against identified proteins, confirmed that the proteins were present in one subpopulation of islets. Of these proteins, at least one was unique to large islets and can potentially be used as a marker to distinguish in vivo between islets that are high-insulin producers and those that fail to secrete significant amounts in insulin. Our long-term goal is to monitor the fate of the different islet populations during diabetes development. In addition, markers like this can be used to determine the best islet subpopulation for transplantation. The data support our hypothesis that integral differences exist between small and large islets that might determine the islets' unique properties under normal conditions and during the development of diabetes. These differences may also influence islet subpopulation behavior in transplantation affecting the outcome

Фізико-хімічна геотехнологія

Розглянуто принципові засади геотехнологічного видобування різнома- нітних корисних копалин. Викладено питання розкриття та підготовки родовищ за допомогою свердловинної розробки, проаналізовано способи буріння і кріп- лення геотехнологічних свердловин, а такж застосоване обладнання. Розкрито сутність технологічних процесів, які виконуються при диспергуванні гірських порід, розчиненні солей, вилуговуванні металів, підземній виплавці сірки і га- зифікації вугілля, видобуванні в’язкої нафти та сланцьового газу. Навчальний посібник призначений для студентів, які навчаються за спе- ціальністю «Розробка родовищ та видобування корисних копалин», а також для студентів інших спеціальностей гірничих вузів і факультетів та інженерно- технічних працівників підприємств і проектних організацій гірничовидобувних галузей промисловості України

A capacity management tool for a portfolio of industrialization projects

The management of a project portfolio is a complex decision process because it encompasses the achievement of multiple objectives. A critical point that increases the complexity in the decision-making process of a portfolio manager is the allocation of human resources to manage the projects of the portfolio, project managers, which is crucial to the organization’s performance. In this case, the project manager can manage more than one project simultaneously and it is necessary to assign project managers to the projects, considering that project activities have an amount of work to be accomplished. The main objective of this work was to provide support for this capacity management problem, which aims to provide an easier decision-making process for the capacity management of an industrialization project portfolio. Therefore, it was developed: a hybrid model that creates a schedule respecting the resource constraints and the established due dates; a recommendation system that considers project managers’ allocation and projects requirements; and, an automatic status report that allows identifying the project portfolio capacity usage.This work is supported by: European Structural and Investment Funds in the FEDER component, through the Operational Competitiveness and Internationalization Programme (COMPETE 2020) [Project nº 39479; Funding Reference: POCI-01-0247-FEDER-39479]

Mitochondrial translocation of oxidized cofilin induces caspase-independent necrotic-like programmed cell death of T cells

Oxidative stress leads to T-cell hyporesponsiveness or death. The actin-binding protein cofilin is oxidized during oxidative stress, which provokes a stiff actin cytoskeleton and T-cell hyporesponsiveness. Here, we show that long-term oxidative stress leads to translocation of cofilin into the mitochondria and necrotic-like programmed cell death (PCD) in human T cells. Notably, cofilin mutants that functionally mimic oxidation by a single mutation at oxidation-sensitive cysteins (Cys-39 or Cys-80) predominately localize within the mitochondria. The expression of these mutants alone ultimately leads to necrotic-like PCD in T cells. Accordingly, cofilin knockdown partially protects T cells from the fatal effects of long-term oxidative stress. Thus, we introduce the oxidation and mitochondrial localization of cofilin as the checkpoint for necrotic-like PCD upon oxidative stress as it occurs, for example, in tumor environments

The design of the wide field monitor for LOFT

LOFT (Large Observatory For x-ray Timing) is one of the ESA M3 missions selected within the Cosmic Vision program in 2011 to carry out an assessment phase study and compete for a launch opportunity in 2022-2024. The phase-A studies of all M3 missions were completed at the end of 2013. LOFT is designed to carry on-board two instruments with sensitivity in the 2-50 keV range: a 10 m 2 class Large Area Detector (LAD) with a <1{\deg} collimated FoV and a wide field monitor (WFM) making use of coded masks and providing an instantaneous coverage of more than 1/3 of the sky. The prime goal of the WFM will be to detect transient sources to be observed by the LAD. However, thanks to its unique combination of a wide field of view (FoV) and energy resolution (better than 500 eV), the WFM will be also an excellent monitoring instrument to study the long term variability of many classes of X-ray sources. The WFM consists of 10 independent and identical coded mask cameras arranged in 5 pairs to provide the desired sky coverage. We provide here an overview of the instrument design, configuration, and capabilities of the LOFT WFM. The compact and modular design of the WFM could easily make the instrument concept adaptable for other missions.Comment: Proc. SPIE 9144, Space Telescopes and Instrumentation 2014: Ultraviolet to Gamma Ray, 91442

VvNPR1.1 est l’orthologue d’AtNPR1 et sa surexpression provoque l’activation constitutive des gènes PR et la résistance à Erysiphe necator chez Vitis vinifera

La compréhension des bases moléculaires des mécanismes de résistance de la Vigne aux agresseurs biotiques constitue un prérequis à la recherche de moyens de lutte alternatifs aux pesticides. Chez Arabidopsis, NPR1 (Non expressor of PR genes 1) joue un rôle clé dans la voie de signalisation régulée par l’acide salicylique et responsable de la mise en place de la résistance aux agents pathogènes biotrophes et de la résistance systémique acquise (SAR). Nous avons identifié deux gènes homologues d’AtNPR1 chez la Vigne : VvNPR1.1 et VvNPR1.2. La caractérisation fonctionnelle de ces deux gènes montre que la surexpression de VvNPR1.1 dans le mutant npr1-2 d’Arabidopsis permet, contrairement `a VvNPR1.2, de restaurer l’expression de PR1 après traitement par du SA ou inoculation bactérienne, ainsi que la résistance à Pseudomonas syringae pv. maculicola, un agent pathogène virulent. VvNPR1.1 apparaît donc comme l’orthologue fonctionnel d’AtNPR1, alors que VvNPR1.2 assure vraisemblablement une fonction différente. La surexpression stable de VvNPR1.1 en fusion avec la GFP a également pu être réalisée chez V. vinifera cv. Chardonnay, grâce à une technique de transformation par A. tumefaciens de cals embryogènes de Vigne. Les résultats obtenus sur les plantules transformées montrent une localisation constitutive de VvNPR1-GFP dans le noyau, ainsi qu’une expression élevée des protéines PR en l’absence d’infection. De plus, les vignes surexprimant VvNPR1-GFP montrent clairement une augmentation de la r´esistance vis-à-vis de l’infection par Erysiphe necator, l’agent de l’oïdium. La forte conservation de séquence des gènes VvNPR1 chez les Vitaceae ainsi que l’ensemble de ces résultats souligne l’importance de la voie régulée par le SA et NPR1 pour la résistance aux agents pathogènes biotrophes chez la Vigne

Knowledge and attitudes of primary healthcare patients regarding population-based screening for colorectal cancer

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess the extent of knowledge of primary health care (PHC) patients about colorectal cancer (CRC), their attitudes toward population-based screening for this disease and gender differences in these respects.</p> <p>Methods</p> <p>A questionnaire-based survey of PHC patients in the Balearic Islands and some districts of the metropolitan area of Barcelona was conducted. Individuals between 50 and 69 years of age with no history of CRC were interviewed at their PHC centers.</p> <p>Results</p> <p>We analyzed the results of 625 questionnaires, 58% of which were completed by women. Most patients believed that cancer diagnosis before symptom onset improved the chance of survival. More women than men knew the main symptoms of CRC. A total of 88.8% of patients reported that they would perform the fecal occult blood test (FOBT) for CRC screening if so requested by PHC doctors or nurses. If the FOBT was positive and a colonoscopy was offered, 84.9% of participants indicated that they would undergo the procedure, and no significant difference by gender was apparent. Fear of having cancer was the main reason for performance of an FOBT, and also for not performing the FOBT, especially in women. Fear of pain was the main reason for not wishing to undergo colonoscopy. Factors associated with reluctance to perform the FOBT were: <b><it>(i) </it></b>the idea that that many forms of cancer can be prevented by exercise and, <b><it>(ii) </it></b>a reluctance to undergo colonoscopy if an FOBT was positive. Factors associated with reluctance to undergo colonoscopy were: <b><it>(i) </it></b>residence in Barcelona, <b><it>(ii) </it></b>ignorance of the fact that early diagnosis of CRC is associated with better prognosis, <b><it>(iii) </it></b>no previous history of colonoscopy, and <b><it>(iv) </it></b>no intention to perform the FOBT for CRC screening.</p> <p>Conclusion</p> <p>We identified gaps in knowledge about CRC and prevention thereof in PHC patients from the Balearic Islands and the Barcelona region of Spain. If fears about CRC screening, and CRC per se, are addressed, and if it is emphasized that CRC is preventable, participation in CRC screening programs may improve.</p

Flow shop rescheduling under different types of disruption

This is an Accepted Manuscript of an article published by Taylor & Francis in International Journal of Production Research on 2013, available online:http://www.tandfonline.com/10.1080/00207543.2012.666856Almost all manufacturing facilities need to use production planning and scheduling systems to increase productivity and to reduce production costs. Real-life production operations are subject to a large number of unexpected disruptions that may invalidate the original schedules. In these cases, rescheduling is essential to minimise the impact on the performance of the system. In this work we consider flow shop layouts that have seldom been studied in the rescheduling literature. We generate and employ three types of disruption that interrupt the original schedules simultaneously. We develop rescheduling algorithms to finally accomplish the twofold objective of establishing a standard framework on the one hand, and proposing rescheduling methods that seek a good trade-off between schedule quality and stability on the other.The authors would like to thank the anonymous referees for their careful and detailed comments that helped to improve the paper considerably. This work is partially financed by the Small and Medium Industry of the Generalitat Valenciana (IMPIVA) and by the European Union through the European Regional Development Fund (FEDER) inside the R + D program "Ayudas dirigidas a Institutos tecnologicos de la Red IMPIVA" during the year 2011, with project number IMDEEA/2011/142.Katragjini Prifti, K.; Vallada Regalado, E.; Ruiz García, R. (2013). Flow shop rescheduling under different types of disruption. International Journal of Production Research. 51(3):780-797. https://doi.org/10.1080/00207543.2012.666856S780797513Abumaizar, R. J., & Svestka, J. A. (1997). Rescheduling job shops under random disruptions. International Journal of Production Research, 35(7), 2065-2082. doi:10.1080/002075497195074Adiri, I., Frostig, E., & Kan, A. H. G. R. (1991). Scheduling on a single machine with a single breakdown to minimize stochastically the number of tardy jobs. Naval Research Logistics, 38(2), 261-271. doi:10.1002/1520-6750(199104)38:23.0.co;2-iAkturk, M. S., & Gorgulu, E. (1999). Match-up scheduling under a machine breakdown. European Journal of Operational Research, 112(1), 81-97. doi:10.1016/s0377-2217(97)00396-2Allahverdi, A. (1996). Two-machine proportionate flowshop scheduling with breakdowns to minimize maximum lateness. Computers & Operations Research, 23(10), 909-916. doi:10.1016/0305-0548(96)00012-3Arnaout, J. P., & Rabadi, G. (2008). Rescheduling of unrelated parallel machines under machine breakdowns. International Journal of Applied Management Science, 1(1), 75. doi:10.1504/ijams.2008.020040Artigues, C., Billaut, J.-C., & Esswein, C. (2005). Maximization of solution flexibility for robust shop scheduling. European Journal of Operational Research, 165(2), 314-328. doi:10.1016/j.ejor.2004.04.004Azizoglu, M., & Alagöz, O. (2005). Parallel-machine rescheduling with machine disruptions. IIE Transactions, 37(12), 1113-1118. doi:10.1080/07408170500288133Bean, J. C., Birge, J. R., Mittenthal, J., & Noon, C. E. (1991). Matchup Scheduling with Multiple Resources, Release Dates and Disruptions. Operations Research, 39(3), 470-483. doi:10.1287/opre.39.3.470Caricato, P., & Grieco, A. (2008). An online approach to dynamic rescheduling for production planning applications. International Journal of Production Research, 46(16), 4597-4617. doi:10.1080/00207540601136225CHURCH, L. K., & UZSOY, R. (1992). Analysis of periodic and event-driven rescheduling policies in dynamic shops. International Journal of Computer Integrated Manufacturing, 5(3), 153-163. doi:10.1080/09511929208944524Cowling, P., & Johansson, M. (2002). Using real time information for effective dynamic scheduling. European Journal of Operational Research, 139(2), 230-244. doi:10.1016/s0377-2217(01)00355-1Curry, J., & Peters *, B. (2005). Rescheduling parallel machines with stepwise increasing tardiness and machine assignment stability objectives. International Journal of Production Research, 43(15), 3231-3246. doi:10.1080/00207540500103953DUTTA, A. (1990). Reacting to Scheduling Exceptions in FMS Environments. IIE Transactions, 22(4), 300-314. doi:10.1080/07408179008964185Ghezail, F., Pierreval, H., & Hajri-Gabouj, S. (2010). Analysis of robustness in proactive scheduling: A graphical approach. Computers & Industrial Engineering, 58(2), 193-198. doi:10.1016/j.cie.2009.03.004Goren, S., & Sabuncuoglu, I. (2008). Robustness and stability measures for scheduling: single-machine environment. IIE Transactions, 40(1), 66-83. doi:10.1080/07408170701283198Hall, N. G., & Potts, C. N. (2004). Rescheduling for New Orders. Operations Research, 52(3), 440-453. doi:10.1287/opre.1030.0101Herrmann, J. W., Lee, C.-Y., & Snowdon, J. L. (1993). A Classification of Static Scheduling Problems. Complexity in Numerical Optimization, 203-253. doi:10.1142/9789814354363_0011Herroelen, W., & Leus, R. (2005). Project scheduling under uncertainty: Survey and research potentials. European Journal of Operational Research, 165(2), 289-306. doi:10.1016/j.ejor.2004.04.002Hozak, K., & Hill, J. A. (2009). Issues and opportunities regarding replanning and rescheduling frequencies. International Journal of Production Research, 47(18), 4955-4970. doi:10.1080/00207540802047106Huaccho Huatuco, L., Efstathiou, J., Calinescu, A., Sivadasan, S., & Kariuki, S. (2009). Comparing the impact of different rescheduling strategies on the entropic-related complexity of manufacturing systems. International Journal of Production Research, 47(15), 4305-4325. doi:10.1080/00207540701871036Jensen, M. T. (2003). Generating robust and flexible job shop schedules using genetic algorithms. IEEE Transactions on Evolutionary Computation, 7(3), 275-288. doi:10.1109/tevc.2003.810067King, J. R. (1976). The theory-practice gap in job-shop scheduling. Production Engineer, 55(3), 137. doi:10.1049/tpe.1976.0044Kopanos, G. M., Capón-García, E., Espuña,, A., & Puigjaner, L. (2008). Costs for Rescheduling Actions: A Critical Issue for Reducing the Gap between Scheduling Theory and Practice. Industrial & Engineering Chemistry Research, 47(22), 8785-8795. doi:10.1021/ie8005676Lee, C.-Y., Leung, J. Y.-T., & Yu, G. (2006). Two Machine Scheduling under Disruptions with Transportation Considerations. Journal of Scheduling, 9(1), 35-48. doi:10.1007/s10951-006-5592-7Li, Z., & Ierapetritou, M. (2008). Process scheduling under uncertainty: Review and challenges. Computers & Chemical Engineering, 32(4-5), 715-727. doi:10.1016/j.compchemeng.2007.03.001Liao, C. J., & Chen, W. J. (2004). Scheduling under machine breakdown in a continuous process industry. Computers & Operations Research, 31(3), 415-428. doi:10.1016/s0305-0548(02)00224-1Mehta, S. V. (1999). Predictable scheduling of a single machine subject to breakdowns. International Journal of Computer Integrated Manufacturing, 12(1), 15-38. doi:10.1080/095119299130443MUHLEMANN, A. P., LOCKETT, A. G., & FARN, C.-K. (1982). Job shop scheduling heuristics and frequency of scheduling. International Journal of Production Research, 20(2), 227-241. doi:10.1080/00207548208947763Nawaz, M., Enscore, E. E., & Ham, I. (1983). A heuristic algorithm for the m-machine, n-job flow-shop sequencing problem. Omega, 11(1), 91-95. doi:10.1016/0305-0483(83)90088-9O’Donovan, R., Uzsoy, R., & McKay, K. N. (1999). Predictable scheduling of a single machine with breakdowns and sensitive jobs. International Journal of Production Research, 37(18), 4217-4233. doi:10.1080/002075499189745Özlen, M., & Azizoğlu, M. (2009). Generating all efficient solutions of a rescheduling problem on unrelated parallel machines. International Journal of Production Research, 47(19), 5245-5270. doi:10.1080/00207540802043998Pfeiffer, A., Kádár, B., & Monostori, L. (2007). Stability-oriented evaluation of rescheduling strategies, by using simulation. Computers in Industry, 58(7), 630-643. doi:10.1016/j.compind.2007.05.009Pierreval, H., & Durieux-Paris, S. (2007). Robust simulation with a base environmental scenario. European Journal of Operational Research, 182(2), 783-793. doi:10.1016/j.ejor.2006.07.045Damodaran, P., Hirani, N. S., & Gallego, M. C. V. (2009). Scheduling identical parallel batch processing machines to minimise makespan using genetic algorithms. European J. of Industrial Engineering, 3(2), 187. doi:10.1504/ejie.2009.023605Qi, X., Bard, J. F., & Yu, G. (2006). Disruption management for machine scheduling: The case of SPT schedules. International Journal of Production Economics, 103(1), 166-184. doi:10.1016/j.ijpe.2005.05.021Rangsaritratsamee, R., Ferrell, W. G., & Kurz, M. B. (2004). Dynamic rescheduling that simultaneously considers efficiency and stability. Computers & Industrial Engineering, 46(1), 1-15. doi:10.1016/j.cie.2003.09.007Ruiz, R., & Stützle, T. (2007). A simple and effective iterated greedy algorithm for the permutation flowshop scheduling problem. European Journal of Operational Research, 177(3), 2033-2049. doi:10.1016/j.ejor.2005.12.009Sabuncuoglu, I., & Goren, S. (2009). Hedging production schedules against uncertainty in manufacturing environment with a review of robustness and stability research. International Journal of Computer Integrated Manufacturing, 22(2), 138-157. doi:10.1080/09511920802209033Sabuncuoglu, I., & Kizilisik, O. B. (2003). Reactive scheduling in a dynamic and stochastic FMS environment. International Journal of Production Research, 41(17), 4211-4231. doi:10.1080/0020754031000149202Salveson, M. E. (1952). On a Quantitative Method in Production Planning and Scheduling. Econometrica, 20(4), 554. doi:10.2307/1907643Samarghandi, H., & ElMekkawy, T. Y. (2011). An efficient hybrid algorithm for the two-machine no-wait flow shop problem with separable setup times and single server. European J. of Industrial Engineering, 5(2), 111. doi:10.1504/ejie.2011.039869Subramaniam *, V., Raheja, A. S., & Rama Bhupal Reddy, K. (2005). Reactive repair tool for job shop schedules. International Journal of Production Research, 43(1), 1-23. doi:10.1080/0020754042000270412Taillard, E. (1990). Some efficient heuristic methods for the flow shop sequencing problem. European Journal of Operational Research, 47(1), 65-74. doi:10.1016/0377-2217(90)90090-xTaillard, E. (1993). Benchmarks for basic scheduling problems. European Journal of Operational Research, 64(2), 278-285. doi:10.1016/0377-2217(93)90182-mValente, J. M. S., & Schaller, J. E. (2010). Improved heuristics for the single machine scheduling problem with linear early and quadratic tardy penalties. European J. of Industrial Engineering, 4(1), 99. doi:10.1504/ejie.2010.029572Vallada, E., & Ruiz, R. (2010). Genetic algorithms with path relinking for the minimum tardiness permutation flowshop problem☆. Omega, 38(1-2), 57-67. doi:10.1016/j.omega.2009.04.002Vieira, G. E., Herrmann, J. W., & Lin, E. (2000). Predicting the performance of rescheduling strategies for parallel machine systems. Journal of Manufacturing Systems, 19(4), 256-266. doi:10.1016/s0278-6125(01)80005-4Vieira, G. E., Herrmann, J. W., & Lin, E. (2003). Journal of Scheduling, 6(1), 39-62. doi:10.1023/a:1022235519958Yang, J., & Yu, G. (2002). Journal of Combinatorial Optimization, 6(1), 17-33. doi:10.1023/a:1013333232691Zandieh, M., & Gholami, M. (2009). An immune algorithm for scheduling a hybrid flow shop with sequence-dependent setup times and machines with random breakdowns. International Journal of Production Research, 47(24), 6999-7027. doi:10.1080/0020754080240063

The Large Observatory for x-ray timing

The Large Observatory For x-ray Timing (LOFT) was studied within ESA M3 Cosmic Vision framework and participated in the final down-selection for a launch slot in 2022-2024. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument, LOFT will study the behaviour of matter under extreme conditions, such as the strong gravitational field in the innermost regions of accretion flows close to black holes and neutron stars, and the supra-nuclear densities in the interior of neutron stars. The science payload is based on a Large Area Detector (LAD, 10 m2 effective area, 2-30 keV, 240 eV spectral resolution, 1° collimated field of view) and a WideField Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g. GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the status of the mission at the end of its Phase A study