The antiapoptotic effect of overexpression c -erBb2 in breast cancer

Overexpression of the receptor tyrosine kinase p185ErbB2 confers taxol resistance in breast cancers and activation of p34Cdc2 is required for taxol-induced apoptosis and cytotoxicity. Here, we investigated the underlying mechanisms and found that overexpression of p185 ErbB2 inhibits taxol-induced apoptosis through two branches to inhibit activation of p34Cdc2. ^ Overexpression of p185ErbB2 in MDA-MB-435 cells by transfection transcriptionally upregulated p21Cip1, which associates with p34Cdc2, inhibits taxol-mediated p34Cdc2 activation, delays cell entrance to G2/M phase, and thereby inhibits taxol-induced apoptosis. In p21Cip1 antisense-transfected MDA-MB-435 cells or in p21−/− MEF cells, p185ErbB2 was unable to inhibit taxol-induced apoptosis. Therefore, p21Cip1 participates in the regulation of a G2/M checkpoint that contributes to resistance to taxol-induced apoptosis in p185ErbB2-overexpressing breast cancer cells. ^ Direct phosphorylation on Tyrosine-15 of p34Cdc2 by p185 ErbB2 receptor tyrosine kinase inhibits p34Cdc2 activation. The wild-type p185ErbB2 but not the kinase-defective mutant, when overexpressed in breast cancer cells, can phosphorylate p34Cdc2 on tyrosine (Tyr)15, an inhibitory phosphorylation site of p34 Cdc2. The kinase domain of the ErbB2 receptor was sufficient for binding to p34Cdc2 and directly phosphorylating the recombinant Cdc2. Phosphospecific Cdc2-Tyr15 immunoblot analyses, immunocomplex kinase assays, and phospho-amino acid analyses revealed that p185ErbB2 specifically phosphorylates Cdc2 on Tyr15. Phosphorylation of Cdc2-Tyr15 by ErbB2 is modulated during cell cycle and corresponded with delayed cell entry into G2/M phase. The kinase-defective p185ErbB2, which incapable of phosphorylating Cdc2-Tyr15, failed to inhibit taxol-induced activation and apoptosis, whereas the wild-type and the constitutive-active p185ErbB2 did. Increased Cdc2-Tyr15 phosphorylation was found in Erb132-overexpressing tumors from breast cancer patients. Thus, direct phosphorylation of Cdc2-Tyr15 by p185 ErbB2 RTK in breast cancer cells inhibits taxol-induced p34 Cdc2 activation and apoptosis, thereby conferring taxol resistance. ^

Semantic technologies in idea management systems: a model for interoperability, linking and filtering

Abstract Idea Management Systems are web applications that implement the notion of open innovation though crowdsourcing. Typically, organizations use those kind of systems to connect to large communities in order to gather ideas for improvement of products or services. Originating from simple suggestion boxes, Idea Management Systems advanced beyond collecting ideas and aspire to be a knowledge management solution capable to select best ideas via collaborative as well as expert assessment methods. In practice, however, the contemporary systems still face a number of problems usually related to information overflow and recognizing questionable quality of submissions with reasonable time and effort allocation. This thesis focuses on idea assessment problem area and contributes a number of solutions that allow to filter, compare and evaluate ideas submitted into an Idea Management System. With respect to Idea Management System interoperability the thesis proposes theoretical model of Idea Life Cycle and formalizes it as the Gi2MO ontology which enables to go beyond the boundaries of a single system to compare and assess innovation in an organization wide or market wide context. Furthermore, based on the ontology, the thesis builds a number of solutions for improving idea assessment via: community opinion analysis (MARL), annotation of idea characteristics (Gi2MO Types) and study of idea relationships (Gi2MO Links). The main achievements of the thesis are: application of theoretical innovation models for practice of Idea Management to successfully recognize the differentiation between communities, opinion metrics and their recognition as a new tool for idea assessment, discovery of new relationship types between ideas and their impact on idea clustering. Finally, the thesis outcome is establishment of Gi2MO Project that serves as an incubator for Idea Management solutions and mature open-source software alternatives for the widely available commercial suites. From the academic point of view the project delivers resources to undertake experiments in the Idea Management Systems area and managed to become a forum that gathered a number of academic and industrial partners. Resumen Los Sistemas de Gestión de Ideas son aplicaciones Web que implementan el concepto de innovación abierta con técnicas de crowdsourcing. Típicamente, las organizaciones utilizan ese tipo de sistemas para conectar con comunidades grandes y así recoger ideas sobre cómo mejorar productos o servicios. Los Sistemas de Gestión de Ideas lian avanzado más allá de recoger simplemente ideas de buzones de sugerencias y ahora aspiran ser una solución de gestión de conocimiento capaz de seleccionar las mejores ideas por medio de técnicas colaborativas, así como métodos de evaluación llevados a cabo por expertos. Sin embargo, en la práctica, los sistemas contemporáneos todavía se enfrentan a una serie de problemas, que, por lo general, están relacionados con la sobrecarga de información y el reconocimiento de las ideas de dudosa calidad con la asignación de un tiempo y un esfuerzo razonables. Esta tesis se centra en el área de la evaluación de ideas y aporta una serie de soluciones que permiten filtrar, comparar y evaluar las ideas publicadas en un Sistema de Gestión de Ideas. Con respecto a la interoperabilidad de los Sistemas de Gestión de Ideas, la tesis propone un modelo teórico del Ciclo de Vida de la Idea y lo formaliza como la ontología Gi2MO que permite ir más allá de los límites de un sistema único para comparar y evaluar la innovación en un contexto amplio dentro de cualquier organización o mercado. Por otra parte, basado en la ontología, la tesis desarrolla una serie de soluciones para mejorar la evaluación de las ideas a través de: análisis de las opiniones de la comunidad (MARL), la anotación de las características de las ideas (Gi2MO Types) y el estudio de las relaciones de las ideas (Gi2MO Links). Los logros principales de la tesis son: la aplicación de los modelos teóricos de innovación para la práctica de Sistemas de Gestión de Ideas para reconocer las diferenciasentre comu¬nidades, métricas de opiniones de comunidad y su reconocimiento como una nueva herramienta para la evaluación de ideas, el descubrimiento de nuevos tipos de relaciones entre ideas y su impacto en la agrupación de estas. Por último, el resultado de tesis es el establecimiento de proyecto Gi2MO que sirve como incubadora de soluciones para Gestión de Ideas y herramientas de código abierto ya maduras como alternativas a otros sistemas comerciales. Desde el punto de vista académico, el proyecto ha provisto de recursos a ciertos experimentos en el área de Sistemas de Gestión de Ideas y logró convertirse en un foro que reunión para un número de socios tanto académicos como industriales.

Energy requirements in pressure irrigation systems

Modernization of irrigation schemes, generally understood as transformation of surface irrigation systems into pressure –sprinkler and trickle- irrigation systems, aims at, among others, improving irrigation efficiency and reduction of operation and maintenance efforts made by the irrigators. However, pressure irrigation systems, in contrast, carry a serious energy cost. Energy requirements depend on decisions taken on management strategies during the operation phase, which are conditioned by previous decisions taken on the design project of the different elements which compose the irrigation system. Most of the countries where irrigation activity is significant bear in mind that modernization irrigation must play a key role in the agricultural infrastructure policies. The objective of this study is to characterize and estimate the mean and variation of the energy consumed by common types of irrigation systems and their management possibilities. The work includes all processes involved from the diversion of water into irrigation specific infrastructure to water discharge by the emitters installed on the crop fields. Simulation taking into account all elements comprising the irrigation system has been used to estimate the energy requirements of typical irrigation systems of several crop production systems. It has been applied to extensive and intensive crop systems, such us extensive winter crops, summer crops and olive trees, fruit trees and vineyards and intensive horticulture in greenhouses. The simulation of various types of irrigation systems and management strategies, in the framework imposed by particular cropping systems, would help to develop criteria for improving the energy balance in relation to the irrigation water supply productivity.

Analysis, monitoring, and management of quality of experience in video delivery services over IP

Esta tesis estudia la monitorización y gestión de la Calidad de Experiencia (QoE) en los servicios de distribución de vídeo sobre IP. Aborda el problema de cómo prevenir, detectar, medir y reaccionar a las degradaciones de la QoE desde la perspectiva de un proveedor de servicios: la solución debe ser escalable para una red IP extensa que entregue flujos individuales a miles de usuarios simultáneamente. La solución de monitorización propuesta se ha denominado QuEM(Qualitative Experience Monitoring, o Monitorización Cualitativa de la Experiencia). Se basa en la detección de las degradaciones de la calidad de servicio de red (pérdidas de paquetes, disminuciones abruptas del ancho de banda...) e inferir de cada una una descripción cualitativa de su efecto en la Calidad de Experiencia percibida (silencios, defectos en el vídeo...). Este análisis se apoya en la información de transporte y de la capa de abstracción de red de los flujos codificados, y permite caracterizar los defectos más relevantes que se observan en este tipo de servicios: congelaciones, efecto de “cuadros”, silencios, pérdida de calidad del vídeo, retardos e interrupciones en el servicio. Los resultados se han validado mediante pruebas de calidad subjetiva. La metodología usada en esas pruebas se ha desarrollado a su vez para imitar lo más posible las condiciones de visualización de un usuario de este tipo de servicios: los defectos que se evalúan se introducen de forma aleatoria en medio de una secuencia de vídeo continua. Se han propuesto también algunas aplicaciones basadas en la solución de monitorización: un sistema de protección desigual frente a errores que ofrece más protección a las partes del vídeo más sensibles a pérdidas, una solución para minimizar el impacto de la interrupción de la descarga de segmentos de Streaming Adaptativo sobre HTTP, y un sistema de cifrado selectivo que encripta únicamente las partes del vídeo más sensibles. También se ha presentado una solución de cambio rápido de canal, así como el análisis de la aplicabilidad de los resultados anteriores a un escenario de vídeo en 3D. ABSTRACT This thesis proposes a comprehensive approach to the monitoring and management of Quality of Experience (QoE) in multimedia delivery services over IP. It addresses the problem of preventing, detecting, measuring, and reacting to QoE degradations, under the constraints of a service provider: the solution must scale for a wide IP network delivering individual media streams to thousands of users. The solution proposed for the monitoring is called QuEM (Qualitative Experience Monitoring). It is based on the detection of degradations in the network Quality of Service (packet losses, bandwidth drops...) and the mapping of each degradation event to a qualitative description of its effect in the perceived Quality of Experience (audio mutes, video artifacts...). This mapping is based on the analysis of the transport and Network Abstraction Layer information of the coded stream, and allows a good characterization of the most relevant defects that exist in this kind of services: screen freezing, macroblocking, audio mutes, video quality drops, delay issues, and service outages. The results have been validated by subjective quality assessment tests. The methodology used for those test has also been designed to mimic as much as possible the conditions of a real user of those services: the impairments to evaluate are introduced randomly in the middle of a continuous video stream. Based on the monitoring solution, several applications have been proposed as well: an unequal error protection system which provides higher protection to the parts of the stream which are more critical for the QoE, a solution which applies the same principles to minimize the impact of incomplete segment downloads in HTTP Adaptive Streaming, and a selective scrambling algorithm which ciphers only the most sensitive parts of the media stream. A fast channel change application is also presented, as well as a discussion about how to apply the previous results and concepts in a 3D video scenario.

Assessment of innovative measures implemented in European bus systems using key performance indicators

This paper reports the results of the assessment of a range of measures implemented in bus systems in five European cities to improve the use of public transport by increasing its attractiveness and enhancing its image in urban areas. This research was conducted as part of the EBSF project (European Bus System of the Future) from 2008 to 2012. New buses (prototypes), new vehicle and infrastructure technologies, and operational best practices were introduced, all of which were combined in a system approach. The measures were assessed using multicriteria analysis to simultaneously evaluate a certain number of criteria that need to be aggregated. Each criterion is measured by one or more key performance indicators (KPI) calculated in two scenarios (reference scenario, with no measure implemented; and project scenario, with the implementation of some measures), in order to evaluate the difference in the KPI performance between the reference and project scenario. The results indicate that the measures produce a greater benefit in issues related to bus system productivity and customer satisfaction, with the greatest impact on aspects of perceptions of comfort, cleanliness and quality of service, information to passengers and environmental issues. The study also reveals that the implementation of several measures has greater social utility than very specific and isolated measures.

Modeling GHG emissions, N and C dynamics in Spanish agricultural soils.

To date, only few initiatives have been carried out in Spain in order to use mathematical models (e.g. DNDC, DayCent, FASSET y SIMSNIC) to estimate nitrogen (N) and carbon (C) dynamics as well as greenhouse gases (GHG) in Spanish agrosystems. Modeling at this level may allow to gain insight on both the complex relationships between biological and physicochemical processes, controlling the processes leading to GHG production and consumption in soils (e.g. nitrification, denitrification, decomposing, etc.), and the interactions between C and N cycles within the different components of the continuum plant-soil-environment. Additionally, these models can simulate the processes behind production, consumition and transport of GHG (e.g. nitrous oxide, N2O, and carbon dioxide, CO2) in the short and medium term and at different scales. Other sources of potential pollution from soils can be identified and quantified using these process-based models (e.g. NO3 y NH3).

Implementing fully homomorphic encryption schemes in FPGA-based systems

LLas nuevas tecnologías orientadas a la nube, el internet de las cosas o las tendencias "as a service" se basan en el almacenamiento y procesamiento de datos en servidores remotos. Para garantizar la seguridad en la comunicación de dichos datos al servidor remoto, y en el manejo de los mismos en dicho servidor, se hace uso de diferentes esquemas criptográficos. Tradicionalmente, dichos sistemas criptográficos se centran en encriptar los datos mientras no sea necesario procesarlos (es decir, durante la comunicación y almacenamiento de los mismos). Sin embargo, una vez es necesario procesar dichos datos encriptados (en el servidor remoto), es necesario desencriptarlos, momento en el cual un intruso en dicho servidor podría a acceder a datos sensibles de usuarios del mismo. Es más, este enfoque tradicional necesita que el servidor sea capaz de desencriptar dichos datos, teniendo que confiar en la integridad de dicho servidor de no comprometer los datos. Como posible solución a estos problemas, surgen los esquemas de encriptación homomórficos completos. Un esquema homomórfico completo no requiere desencriptar los datos para operar con ellos, sino que es capaz de realizar las operaciones sobre los datos encriptados, manteniendo un homomorfismo entre el mensaje cifrado y el mensaje plano. De esta manera, cualquier intruso en el sistema no podría robar más que textos cifrados, siendo imposible un robo de los datos sensibles sin un robo de las claves de cifrado. Sin embargo, los esquemas de encriptación homomórfica son, actualmente, drás-ticamente lentos comparados con otros esquemas de encriptación clásicos. Una op¬eración en el anillo del texto plano puede conllevar numerosas operaciones en el anillo del texto encriptado. Por esta razón, están surgiendo distintos planteamientos sobre como acelerar estos esquemas para un uso práctico. Una de las propuestas para acelerar los esquemas homomórficos consiste en el uso de High-Performance Computing (HPC) usando FPGAs (Field Programmable Gate Arrays). Una FPGA es un dispositivo semiconductor que contiene bloques de lógica cuya interconexión y funcionalidad puede ser reprogramada. Al compilar para FPGAs, se genera un circuito hardware específico para el algorithmo proporcionado, en lugar de hacer uso de instrucciones en una máquina universal, lo que supone una gran ventaja con respecto a CPUs. Las FPGAs tienen, por tanto, claras difrencias con respecto a CPUs: -Arquitectura en pipeline: permite la obtención de outputs sucesivos en tiempo constante -Posibilidad de tener multiples pipes para computación concurrente/paralela. Así, en este proyecto: -Se realizan diferentes implementaciones de esquemas homomórficos en sistemas basados en FPGAs. -Se analizan y estudian las ventajas y desventajas de los esquemas criptográficos en sistemas basados en FPGAs, comparando con proyectos relacionados. -Se comparan las implementaciones con trabajos relacionados New cloud-based technologies, the internet of things or "as a service" trends are based in data storage and processing in a remote server. In order to guarantee a secure communication and handling of data, cryptographic schemes are used. Tradi¬tionally, these cryptographic schemes focus on guaranteeing the security of data while storing and transferring it, not while operating with it. Therefore, once the server has to operate with that encrypted data, it first decrypts it, exposing unencrypted data to intruders in the server. Moreover, the whole traditional scheme is based on the assumption the server is reliable, giving it enough credentials to decipher data to process it. As a possible solution for this issues, fully homomorphic encryption(FHE) schemes is introduced. A fully homomorphic scheme does not require data decryption to operate, but rather operates over the cyphertext ring, keeping an homomorphism between the cyphertext ring and the plaintext ring. As a result, an outsider could only obtain encrypted data, making it impossible to retrieve the actual sensitive data without its associated cypher keys. However, using homomorphic encryption(HE) schemes impacts performance dras-tically, slowing it down. One operation in the plaintext space can lead to several operations in the cyphertext space. Because of this, different approaches address the problem of speeding up these schemes in order to become practical. One of these approaches consists in the use of High-Performance Computing (HPC) using FPGAs (Field Programmable Gate Array). An FPGA is an integrated circuit designed to be configured by a customer or a designer after manufacturing - hence "field-programmable". Compiling into FPGA means generating a circuit (hardware) specific for that algorithm, instead of having an universal machine and generating a set of machine instructions. FPGAs have, thus, clear differences compared to CPUs: - Pipeline architecture, which allows obtaining successive outputs in constant time. -Possibility of having multiple pipes for concurrent/parallel computation. Thereby, In this project: -We present different implementations of FHE schemes in FPGA-based systems. -We analyse and study advantages and drawbacks of the implemented FHE schemes, compared to related work.

Libraries Transforming Communities: The Value in an Academic Library Community at Lincoln University

Inman E. Page Library is coined as an, “Information Mall.” It houses special collections, archives, general reference services, computers, artistic programming, technological resources and space for different types of events. It is a modern academic library in the 21st century that was built on a legacy of scholarly opportunities for Lincoln University students, faculty, and our community in Jefferson City, MO and surrounding cities. The value that needs to be placed on this library is that it is an institution within an institution and should be given top priority as it pertains to continued funding, faculty support, and a place of higher learning that has a library etiquette. As well as, students need to understand the importance of how a library will affect their academic careers.

Loss of protein kinase C inhibition in the β-T594M variant of the amiloride-sensitive Na+ channel

We previously reported the presence of a novel variant (β-T594M) of the amiloride-sensitive Na+ channel (ASSC) in which the threonine residue at position 594 in the β-subunit has been replaced by a methionine residue. Electrophysiological studies of the ASSC on Epstein–Barr virus (EBV)-transformed lymphocytes carrying this variant showed that the 8-(4-chlorophenylthio) adenosine 3′:5′-cyclic monophosphate (8cpt-cAMP)-induced responses were enhanced when compared to wild-type EBV-transformed lymphocytes. Furthermore, in wild-type EBV-transformed cells, the 8cpt-cAMP-induced response was totally blocked by the phorbol ester, phorbol 12-myristate 13-acetate (PMA). This inhibitory effect of PMA was blocked by a protein kinase C inhibitor, chelerythrine. We now have identified individuals who are homozygous for this variant, and showed that PMA had no effect on the 8cpt-cAMP-induced responses in the EBV-transformed lymphocytes from such individuals. Cells heterozygous for this variant showed mixed responses to PMA, with the majority of cells partially inhibited by PMA. Our results demonstrate that an alteration in a single amino acid residue in the β-subunit of the ASSC can lead to a total loss of inhibition to PMA, and establish the β-subunit as having an important role in conferring a regulatory effect on the ASSC of lymphocytes.

Acquisition order and resource value in Cuscuta attenuata

Field observations showed that in its native Texas grasslands, dodder (Cuscuta attenuata) grows more vigorously in patches of mixed host species than in monospecific host patches. Field experiments with naturally occurring host individuals demonstrated that the parasite achieved greater volume when simultaneously infesting two hosts of differing species rather than two hosts of the same species, and that this effect depends on the order in which the parasite encounters those hosts. Sodium, acting as an osmoticum, is implicated as the factor responsible for experimentally produced as well as observed field patterns.