Identificación of ERBB4 and SOX1 role in central nervous system tumors. Implication in medulloblastoma and glioblastoma.

223 p.Los tumores cerebrales, como el glioblastoma (GBM) en adultos y el meduloblastoma (MB) en niños, representan uno de los retos más importantes de la medicina actual, ya que resisten a las terapias disponibles, recurren y se diseminan. Dichos tumores presentan una alta heterogeneidad, ya que albergan una subpoblación de células madre tumorales (CSCs), responsables de la metástasis, resistencia a tratamientos y recurrencia tumoral. Además, la desregulación de aquellos genes relacionados con el desarrollo embrionario y el mantenimiento de las células madre, como ERBB4 y SOX1, parece ser crítica para el desarrollo y la progresión del fenotipo canceroso. La presente tesis doctoral tiene como objetivo principal determinar la función de ambos genes en el GBM y el MB, así como establecer su relación con las CSCs específicas de cada tumor (GSCs y MBSCs, respectivamente). En primer lugar, observamos que ERBB4 tiene una función esencial en el desarrollo del cerebelo, controlando la población de las células progenitoras y su proceso de migración. Además, determinamos que ERBB4 se encuentra altamente expresado en los MBs del Grupo 4 y SOX1 en los del Grupo SHH, asociándose en ambos casos a una peor supervivencia. Al inhibir la expresión de ERBB4 y SOX1, observamos una reducción de la viabilidad celular, capacidad de autorrenovación, y de iniciación y progresión tumoral. Asimismo, identificamos un enriquecimiento de la expresión de SOX1 y ERBB4 en las MBSCs. También establecimos una relación entre la elevada expresión de SOX1 y una peor supervivencia en GBM, además del enriquecimiento de su expresión en las GSCs. Por último, al inhibir la expresión de SOX1 en GBM, observamos una disminución de la capacidad de proliferación, iniciación y progresión tumoral. En conjunto, nuestros resultados sugieren un papel oncogénico hasta ahora no descrito de ERBB4 y SOX1 en MB y GBM. Además, este trabajo propone la inhibición de ERBB4 y SOX1 como una estrategia terapéutica prometedora para atacar las CSCs y así combatir la resistencia a las terapias

An Ontology for Formalizing and Automating the Strategic Planning Process

From late 1980s and early twenty-first century, the environment where the organizations develop and act, has become increasingly uncertain and complex. Under these conditions, organizations have detected the need to move towards a more participatory model to address and reduce the complexity, based on information and knowledge as core assets to reduce environmental uncertainty and thereby ensure better decision-making. This new form of governance involves changes in the Strategic Planning process that are aligned with the characteristics of the new organizational model. Ontologies, as theories of content that allow the formalization of processes and knowledge, are a key element in this context. The aim of this paper is to formally define an ontology that could be defined in the future using the Web Ontology Language (OWL) that meets the standards approved by the World Wide Web Consortium (W3C) and that is used to formalize the process of SP, as well as the knowledge that is created and flows among the several participants in the process

A Grammatical Approach to the Modeling of an Autonomous Robot

Virtual Worlds Generator is a grammatical model that is proposed to define virtual worlds. It integrates the diversity of sensors and interaction devices, multimodality and a virtual simulation system. Its grammar allows the definition and abstraction in symbols strings of the scenes of the virtual world, independently of the hardware that is used to represent the world or to interact with it. A case study is presented to explain how to use the proposed model to formalize a robot navigation system with multimodal perception and a hybrid control scheme of the robot. The result is an instance of the model grammar that implements the robotic system and is independent of the sensing devices used for perception and interaction. As a conclusion the Virtual Worlds Generator adds value in the simulation of virtual worlds since the definition can be done formally and independently of the peculiarities of the supporting devices

Debugging of Web Applications with Web-TLR

Web-TLR is a Web verification engine that is based on the well-established Rewriting Logic--Maude/LTLR tandem for Web system specification and model-checking. In Web-TLR, Web applications are expressed as rewrite theories that can be formally verified by using the Maude built-in LTLR model-checker. Whenever a property is refuted, a counterexample trace is delivered that reveals an undesired, erroneous navigation sequence. Unfortunately, the analysis (or even the simple inspection) of such counterexamples may be unfeasible because of the size and complexity of the traces under examination. In this paper, we endow Web-TLR with a new Web debugging facility that supports the efficient manipulation of counterexample traces. This facility is based on a backward trace-slicing technique for rewriting logic theories that allows the pieces of information that we are interested to be traced back through inverse rewrite sequences. The slicing process drastically simplifies the computation trace by dropping useless data that do not influence the final result. By using this facility, the Web engineer can focus on the relevant fragments of the failing application, which greatly reduces the manual debugging effort and also decreases the number of iterative verifications.Comment: In Proceedings WWV 2011, arXiv:1108.208

Hydraulic transient in residential buildings with a direct pump connection

This paper consists of an experimental and numerical study into transient behaviour in a residential building. The analysed effects occur by centrifugal pumps when they start with a direct supply (fixed-speed pumps are connected to the service pipe without an atmospheric tank). Direct supply increases the transient effect and places higher demands on the water main. The properties of such an installation were analysed using a hydraulic model in order to detect the most unfavourable scenario. The results were compared to experimental data. Basic hydraulics demonstrates that a pressure drop occurs during the startup. The magnitude mainly depends on the pump capacity. But, numerical and field results show that other variables related to service pipe design could also negatively affect the pressure surge. The study provides water utilities with information about the influence of the different variables on pressure surge magnitude and basic design criteria to minimize these effects.This work was supported by the Ministerio de Educacion y Ciencia of the Spanish Government under Grant No CGL2005-03666.Soriano Olivares, J.; Arregui De La Cruz, F.; Espert Alemany, VB.; García-Serra García, J. (2014). Hydraulic transient in residential buildings with a direct pump connection. Urban Water Journal. 2014:1-13. https://doi.org/10.1080/1573062X.2014.989860S1132014Basupi, I., Kapelan, Z., & Butler, D. (2013). Reducing life-cycle carbon footprint in the (re)design of water distribution systems using water demand management interventions. Urban Water Journal, 11(2), 91-107. doi:10.1080/1573062x.2012.750374Bergant, A., Tijsseling, A. S., Vítkovský, J. P., Covas, D. I. C., Simpson, A. R., & Lambert, M. F. (2008). Parameters affecting water-hammer wave attenuation, shape and timing—Part 1: Mathematical tools. Journal of Hydraulic Research, 46(3), 373-381. doi:10.3826/jhr.2008.2848Cantor, K. P., Lynch, C. F., Hildesheim, M., Dosemeci, M., Lubin, J., Alavanja, M., & Craun, G. (1998). Drinking Water Source and Chlorination Byproducts I. Risk of Bladder Cancer. Epidemiology, 9(1), 21-28. doi:10.1097/00001648-199801000-00007Clark, R. M., Sivaganesan, M., Selvakumar, A., & Sethi, V. (2002). Cost Models for Water Supply Distribution Systems. Journal of Water Resources Planning and Management, 128(5), 312-321. doi:10.1061/(asce)0733-9496(2002)128:5(312)Colombo, A. F., Lee, P., & Karney, B. W. (2009). A selective literature review of transient-based leak detection methods. Journal of Hydro-environment Research, 2(4), 212-227. doi:10.1016/j.jher.2009.02.003Courtis, B. J., West, J. R., & Bridgeman, J. (2009). Chlorine demand-based predictive modeling of THM formation in water distribution networks. Urban Water Journal, 6(6), 407-415. doi:10.1080/15730620903038461Covas, D., Stoianov, I., Ramos, H., Graham, N., Maksimović, Č., & Butler, D. (2004). Water hammer in pressurized polyethylene pipes: conceptual model and experimental analysis. Urban Water Journal, 1(2), 177-197. doi:10.1080/15730620412331289977Criminisi, A., Fontanazza, C. M., Freni, G., & Loggia, G. L. (2009). Evaluation of the apparent losses caused by water meter under-registration in intermittent water supply. Water Science and Technology, 60(9), 2373-2382. doi:10.2166/wst.2009.423Davis, A. (2004). Hydraulic transients in transmission and distribution systems. Urban Water Journal, 1(2), 157-166. doi:10.1080/15730620412331289968De Marchis, M., Fontanazza, C. M., Freni, G., La Loggia, G., Napoli, E., & Notaro, V. (2010). A model of the filling process of an intermittent distribution network. Urban Water Journal, 7(6), 321-333. doi:10.1080/1573062x.2010.519776Fontanazza, C. M., Notaro, V., Puleo, V., & Freni, G. (2014). The apparent losses due to metering errors: a proactive approach to predict losses and schedule maintenance. Urban Water Journal, 12(3), 229-239. doi:10.1080/1573062x.2014.882363Golfinopoulos, S. K. (2000). The occurrence of trihalomethanes in the drinking water in Greece. Chemosphere, 41(11), 1761-1767. doi:10.1016/s0045-6535(00)00062-xHua, F., West, J. ., Barker, R. ., & Forster, C. . (1999). Modelling of chlorine decay in municipal water supplies. Water Research, 33(12), 2735-2746. doi:10.1016/s0043-1354(98)00519-3Jung, B. S., & Karney, B. (2004). Fluid transients and pipeline optimization using GA and PSO: the diameter connection. Urban Water Journal, 1(2), 167-176. doi:10.1080/15730620412331289995Kanakoudis, V., & Muhammetoglu, H. (2013). Urban Water Pipe Networks Management Towards Non-Revenue Water Reduction: Two Case Studies from Greece and Turkey. CLEAN - Soil, Air, Water, 42(7), 880-892. doi:10.1002/clen.201300138Kanakoudis, V., & Papadopoulou, A. (2014). Allocating the cost of the carbon footprint produced along a supply chain, among the stakeholders involved. Journal of Water and Climate Change, 5(4), 556-568. doi:10.2166/wcc.2014.101Kanakoudis, V., & Tsitsifli, S. (2010). Results of an urban water distribution network performance evaluation attempt in Greece. Urban Water Journal, 7(5), 267-285. doi:10.1080/1573062x.2010.509436Kirmeyer, G.J., Richards, W., and Dery-Smith, C., 1994. An assessment of water distribution systems and associated needs.Report of the American Water Work. Denver, CO: Association Research Foundation.Kitis, M., Yigita, N. O., Harmana, B. I., Muhammetoglu, H., Muhammetoglu, A., Karadirek, I. E., … Palancic, I. (2010). Occurrence of Trihalomethanes in Chlorinated Groundwaters with Very Low Natural Organic Matter and Bromide Concentrations. Environmental Forensics, 11(3), 264-274. doi:10.1080/15275922.2010.495935Levesque, S., Rodriguez, M. J., Serodes, J., Beaulieu, C., & Proulx, F. (2006). Effects of indoor drinking water handling on trihalomethanes and haloacetic acids. Water Research, 40(15), 2921-2930. doi:10.1016/j.watres.2006.06.004Mohamed, H. I., & Gad, A. A. M. (2011). Effect of Cold-Water Storage Cisterns on Drinking-Water Quality. Journal of Water Resources Planning and Management, 137(5), 448-455. doi:10.1061/(asce)wr.1943-5452.0000132Nieuwenhuijsen, M. J. (2000). Chlorination disinfection byproducts in water and their association with adverse reproductive outcomes: a review. Occupational and Environmental Medicine, 57(2), 73-85. doi:10.1136/oem.57.2.73Pezzinga, G. (2000). Evaluation of Unsteady Flow Resistances by Quasi-2D or 1D Models. Journal of Hydraulic Engineering, 126(10), 778-785. doi:10.1061/(asce)0733-9429(2000)126:10(778)Rodriguez, M. J., Sérodes, J.-B., & Levallois, P. (2004). Behavior of trihalomethanes and haloacetic acids in a drinking water distribution system. Water Research, 38(20), 4367-4382. doi:10.1016/j.watres.2004.08.018Rossman, L. A., Clark, R. M., & Grayman, W. M. (1994). Modeling Chlorine Residuals in Drinking‐Water Distribution Systems. Journal of Environmental Engineering, 120(4), 803-820. doi:10.1061/(asce)0733-9372(1994)120:4(803)Schafer, C. A., & Mihelcic, J. R. (2012). Effect of storage tank material and maintenance on household water quality. Journal - American Water Works Association, 104(9), E521-E529. doi:10.5942/jawwa.2012.104.0125Soyupak, S., Kilic, H., Karadirek, I. E., & Muhammetoglu, H. (2011). On the usage of artificial neural networks in chlorine control applications for water distribution networks with high quality water. Journal of Water Supply: Research and Technology-Aqua, 60(1), 51-60. doi:10.2166/aqua.2011.086Tamari, S., & Ploquet, J. (2012). Determination of leakage inside buildings with a roof tank. Urban Water Journal, 9(5), 287-303. doi:10.1080/1573062x.2012.660959Thorley, A.R.D., 2004. Fluid Transients in Pipeline Systems. London: Professional Engineering Publishing.Tsukamoto, H., & Ohashi, H. (1982). Transient Characteristics of a Centrifugal Pump During Starting Period. Journal of Fluids Engineering, 104(1), 6-13. doi:10.1115/1.3240859Villanueva, C. ., Kogevinas, M., & Grimalt, J. . (2003). Haloacetic acids and trihalomethanes in finished drinking waters from heterogeneous sources. Water Research, 37(4), 953-958. doi:10.1016/s0043-1354(02)00411-6Wilo, A. (2007). Intelligent pumps for building automation systems. World Pumps, 2007(490), 26-32. doi:10.1016/s0262-1762(07)70252-3Woolschlager, J., Rittmann, B., & Piriou, P. (2005). Water quality decay in distribution systems – problems, causes, and new modeling tools. Urban Water Journal, 2(2), 69-79. doi:10.1080/15730620500144027Wylie, E.B. and Streeter, V.L., 1993. Fluid Transients in Systems. Englewood Cliffs, NJ: Prentice Hall

Content-Based Organisation of Virtual Repositories of DICOM Objects

The integration of multi-centre medical image data to create knowledge repositories for research and training activities has been an aim targeted since long ago. This paper presents an environment to share, to process and to organise medical imaging data according to a structured framework in which the image reports play a key role. This environment has been validated on a clinical environment, facing problems such as firewalls and security restrictions, in the frame of the CVIMO (Valencian Cyberinfrastructure of Medical Imaging in Oncology) project. The environment uses a middleware called TRENCADIS (Towards a Grid Environment for Processing and Sharing DICOM Objects) that provides users with the management of multiple administrative domains, data encryption and decryption on the fly and semantic indexation of images. Data is structured into four levels: Global data available, virtual federated storages of studies shared across a vertical domain, subsets for projects or experiments on the virtual storage and individual searches on these subsets. This structure of levels gives the needed flexibility for organising authorisation, and hides data that are not relevant for a given experiment. The main components and interactions are shown in the document, outlining the workflows and explaining the different approaches considered, including the protocols used and the difficulties met. © 2009 Elsevier B.V. All rights reserved.The authors wish to thanks the financial support received from Valencia Region Ministry of Enterprises, University (Conselleria de Empresa, Universidad y Ciencia) to develop the project "Ciberinfraestructura Valenciana de Imagen medica Oncologica", with reference GVEMP06/04.Blanquer Espert, I.; Hernández García, V.; Meseguer Anastasio, JE.; Segrelles Quilis, JD. (2009). Content-Based Organisation of Virtual Repositories of DICOM Objects. Future Generation Computer Systems. 25(6):627-637. https://doi.org/10.1016/j.future.2008.12.004S62763725

Development of an antibody-based capture enzyme-linked immunosorbent assay for detecting echinostoma caproni (trematoda) in experimentally infected rats: kinetics of coproantigen excretion

The present study reports on the development of a coproantigen capture enzyme-linked immunosorbent assay (ELISA) for detecting Echinostoma caproni in experimentally infected rats. The capture ELISA was based on polyclonal rabbit antibodies that recognize excretory–secretory (ES) antigens. The detection limit of pure ES was 3 ng/ml in sample buffer and 60 ng/ml in fecal samples. The test was evaluated using a follow-up of 10 rats experimentally infected with 100 metacercariae of E. caproni, and the results were compared with those of other diagnostic methods such as parasitological examination and antibody titers determined by indirect ELISA. Coproantigens were detected in all the infected rats from the first day postinfection (DPI). The period of maximal coproantigen excretion was between 7 and 21 DPI. The values remained positive until 49–56 DPI, coinciding with the disappearance of the eggs in the stool samples of the infected rats. The kinetics of coproantigen detection were correlated with those of egg output. The present assay provides an alternative tool for the diagnosis of the echinostome infections. The proposed capture ELISA makes possible an earlier diagnosis than that provided by parasitological examination and indirect ELISA and also allows for the differentiation of past and current infections. Our results show that this assay can also be used to monitor the course of echinostome infections.Toledo Navarro, Rafael, [email protected] ; Espert Fernandez, Ana M., [email protected] ; Marcilla Diaz, Antonio, [email protected] ; Esteban Sanchis, Jose Guillermo, [email protected]

Improving knowledge management through the support of image examination and data annotation using DICOM structured reporting

[EN] An important effort has been invested on improving the image diagnosis process in different medical areas using information technologies. The field of medical imaging involves two main data types: medical imaging and reports. Developments based on the DICOM standard have demonstrated to be a convenient and widespread solution among the medical community. The main objective of this work is to design a Web application prototype that will be able to improve diagnosis and follow-on of breast cancer patients. It is based on TRENCADIS middleware, which provides a knowledge-oriented storage model composed by federated repositories of DICOM image studies and DICOM-SR medical reports. The full structure and contents of the diagnosis reports are used as metadata for indexing images. The TRENCADIS infrastructure takes full advantage of Grid technologies by deploying multi-resource grid services that enable multiple views (reports schemes) of the knowledge database. The paper presents a real deployment of such Web application prototype in the Dr. Peset Hospital providing radiologists with a tool to create, store and search diagnostic reports based on breast cancer explorations (mammography, magnetic resonance, ultrasound, pre-surgery biopsy and post-surgery biopsy), improving support for diagnostics decisions. A technical details for use cases (outlining enhanced multi-resource grid services communication and processing steps) and interactions between actors and the deployed prototype are described. As a result, information is more structured, the logic is clearer, network messages have been reduced and, in general, the system is more resistant to failures.The authors wish to thank the financial support received from The Spanish Ministry of Education and Science to develop the project "CodeCloud", with reference TIN2010-17804.Salavert Torres, J.; Segrelles Quilis, JD.; Blanquer Espert, I.; Hernández García, V. (2012). Improving knowledge management through the support of image examination and data annotation using DICOM structured reporting. Journal of Biomedical Informatics. 45(6):1066-1074. https://doi.org/10.1016/j.jbi.2012.07.004S1066107445

GridIMAGE: A Novel Use of Grid Computing to Support Interactive Human and Computer-Assisted Detection Decision Support

This paper describes a Grid-aware image reviewing system (GridIMAGE) that allows practitioners to (a) select images from multiple geographically distributed digital imaging and communication in medicine (DICOM) servers, (b) send those images to a specified group of human readers and computer-assisted detection (CAD) algorithms, and (c) obtain and compare interpretations from human readers and CAD algorithms. The currently implemented system was developed using the National Cancer Institute caGrid infrastructure and is designed to support the identification of lung nodules on thoracic computed tomography. However, the infrastructure is general and can support any type of distributed review. caGrid data and analytical services are used to link DICOM image databases and CAD systems and to interact with human readers. Moreover, the service-oriented and distributed structure of the GridIMAGE framework enables a flexible system, which can be deployed in an institution (linking multiple DICOM servers and CAD algorithms) and in a Grid environment (linking the resources of collaborating research groups). GridIMAGE provides a framework that allows practitioners to obtain interpretations from one or more human readers or CAD algorithms. It also provides a mechanism to allow cooperative imaging groups to systematically perform image interpretation tasks associated with research protocols

Kinetics of echinostoma caproni (trematoda: echinostomatidae) antigens in feces and serum of experimentally infected hamsters and rats

This study reports on the kinetics of antibody production to Echinostoma caproni and the dynamics of antigens in feces and sera in 2 experimental hosts (hamsters and rats) that display different degrees of susceptibility with this echinostome. Echinostoma caproni produced chronic infections in hamsters, whereas rats lost the infection at 49–56 days postinfection (DPI). Hamsters developed higher antibody responses than rats, probably in relation to different intestinal absorptions of worm antigens in each host species. The levels of coproantigens were indicative of the course of infection in each host. Positive coproantigen levels were detected at 1–2 DPI in both hosts, and the values remained positive until the end of the experiment in hamsters; in rats, the coproantigen levels reverted to negative values, coinciding with the loss of infection. High levels of circulating antigens were detected in hamsters from 21 DPI to the end of the study. In contrast, low levels of E. caproni seroantigens were detected in rats only. These observations may reflect the differences in local inflammatory responses induced by E. caproni in each host species.Toledo Navarro, Rafael, [email protected] ; Espert Fernandez, Ana M., [email protected] ; Marcilla Diaz, Antonio, [email protected] ; Esteban Sanchis, Jose Guillermo, [email protected]