Mapping and Introgression of QTL Involved in Fruit Shape Transgressive Segregation into 'Piel de Sapo' Melon (Cucumis melo L.)

A mapping F2 population from the cross ‘Piel de Sapo’ × PI124112 was selectively genotyped to study the genetic control of morphological fruit traits by QTL (Quantitative Trait Loci) analysis. Ten QTL were identified, five for FL (Fruit Length), two for FD (Fruit Diameter) and three for FS (Fruit Shape). At least one robust QTL per character was found, flqs8.1 (LOD = 16.85, R2 = 34%), fdqs12.1 (LOD = 3.47, R2 = 11%) and fsqs8.1 (LOD = 14.85, R2 = 41%). flqs2.1 and fsqs2.1 cosegregate with gene a (andromonoecious), responsible for flower sex determination and with pleiotropic effects on FS. They display a positive additive effect (a) value, so the PI124112 allele causes an increase in FL and FS, producing more elongated fruits. Conversely, the negative a value for flqs8.1 and fsqs8.1 indicates a decrease in FL and FS, what results in rounder fruits, even if PI124112 produces very elongated melons. This is explained by a significant epistatic interaction between fsqs2.1 and fsqs8.1, where the effects of the alleles at locus a are attenuated by the additive PI124112 allele at fsqs8.1. Roundest fruits are produced by homozygous for PI124112 at fsqs8.1 that do not carry any dominant A allele at locus a (PiPiaa). A significant interaction between fsqs8.1 and fsqs12.1 was also detected, with the alleles at fsqs12.1 producing more elongated fruits. fsqs8.1 seems to be allelic to QTL discovered in other populations where the exotic alleles produce elongated fruits. This model has been validated in assays with backcross lines along 3 years and ultimately obtaining a fsqs8.1-NIL (Near Isogenic Line) in ‘Piel de Sapo’ background which yields round melons.

A multidisciplinary reference framework to support innovative design, implementation and assessment of chronic care models

Hoy en día, por primera vez en la historia, la mayor parte de la población podrá vivir hasta los sesenta años y más (United Nations, 2015). Sin embargo, todavía existe poca evidencia que demuestre que las personas mayores, estén viviendo con mejor salud que sus padres, a la misma edad, ya que la mayoría de los problemas de salud en edades avanzadas están asociados a las enfermedades crónicas (WHO, 2015). Los sistemas sanitarios de los países desarrollados funcionan adecuadamente cuando se trata del cuidado de enfermedades agudas, pero no son lo suficientemente eficaces en la gestión de las enfermedades crónicas. Durante la última década, se han realizado esfuerzos para mejorar esta gestión, por medio de la utilización de estrategias de prevención y de reenfoque de la provisión de los servicios de atención para la salud (Kane et al. 2005). Según una revisión sistemática de modelos de cuidado de salud, comisionada por el sistema nacional de salud Británico, pocos modelos han conceptualizado cuáles son los componentes que hay que utilizar para proporcionar un cuidado crónico efectivo, y estos componentes no han sido suficientemente estructurados y articulados. Por lo tanto, no hay suficiente evidencia sobre el impacto real de cualquier modelo existente en la actualidad (Ham, 2006). Las innovaciones podrían ayudar a conseguir mejores diagnósticos, tratamientos y gestión de pacientes crónicos, así como a dar soporte a los profesionales y a los pacientes en el cuidado. Sin embargo, la forma en las que estas innovaciones se proporcionan no es lo suficientemente eficiente, efectiva y amigable para el usuario. Para mejorar esto, hace falta crear equipos de trabajo y estrategias multidisciplinares. En conclusión, hacen falta actividades que permitan conseguir que las innovaciones sean utilizadas en los sistemas de salud que quieren mejorar la gestión del cuidado crónico, para que sea posible: 1) traducir la “atención sanitaria basada en la evidencia” en “conocimiento factible”; 2) hacer frente a la complejidad de la atención sanitaria a través de una investigación multidisciplinaria; 3) identificar una aproximación sistemática para que se establezcan intervenciones innovadoras en el cuidado de salud. El marco de referencia desarrollado en este trabajo de investigación es un intento de aportar estas mejoras. Las siguientes hipótesis han sido propuestas: Hipótesis 1: es posible definir un proceso de traducción que convierta un modelo de cuidado crónico en una descripción estructurada de objetivos, requisitos e indicadores clave de rendimiento. Hipótesis 2: el proceso de traducción, si se ejecuta a través de elementos basados en la evidencia, multidisciplinares y de orientación económica, puede convertir un modelo de cuidado crónico en un marco descriptivo, que define el ciclo de vida de soluciones innovadoras para el cuidado de enfermedades crónicas. Hipótesis 3: es posible definir un método para evaluar procesos, resultados y capacidad de desarrollar habilidades, y asistir equipos multidisciplinares en la creación de soluciones innovadoras para el cuidado crónico. Hipótesis 4: es posible dar soporte al desarrollo de soluciones innovadoras para el cuidado crónico a través de un marco de referencia y conseguir efectos positivos, medidos en indicadores clave de rendimiento. Para verificar las hipótesis, se ha definido una aproximación metodológica compuesta de cuatro Fases, cada una asociada a una hipótesis. Antes de esto, se ha llevado a cabo una “Fase 0”, donde se han analizado los antecedentes sobre el problema (i.e. adopción sistemática de la innovación en el cuidado crónico) desde una perspectiva multi-dominio y multi-disciplinar. Durante la fase 1, se ha desarrollado un Proceso de Traducción del Conocimiento, elaborado a partir del JBI Joanna Briggs Institute (JBI) model of evidence-based healthcare (Pearson, 2005), y sobre el cual se han definido cuatro Bloques de Innovación. Estos bloques consisten en una descripción de elementos innovadores, definidos en la fase 0, que han sido añadidos a los cuatros elementos que componen el modelo JBI. El trabajo llevado a cabo en esta fase ha servido también para definir los materiales que el proceso de traducción tiene que ejecutar. La traducción que se ha llevado a cabo en la fase 2, y que traduce la mejor evidencia disponible de cuidado crónico en acción: resultado de este proceso de traducción es la parte descriptiva del marco de referencia, que consiste en una descripción de un modelo de cuidado crónico (se ha elegido el Chronic Care Model, Wagner, 1996) en términos de objetivos, especificaciones e indicadores clave de rendimiento y organizada en tres ciclos de innovación (diseño, implementación y evaluación). Este resultado ha permitido verificar la segunda hipótesis. Durante la fase 3, para demostrar la tercera hipótesis, se ha desarrollado un método-mixto de evaluación de equipos multidisciplinares que trabajan en innovaciones para el cuidado crónico. Este método se ha creado a partir del método mixto usado para la evaluación de equipo multidisciplinares translacionales (Wooden, 2013). El método creado añade una dimensión procedural al marco. El resultado de esta fase consiste, por lo tanto, en una primera versión del marco de referencia, lista para ser experimentada. En la fase 4, se ha validado el marco a través de un caso de estudio multinivel y con técnicas de observación-participante como método de recolección de datos. Como caso de estudio se han elegido las actividades de investigación que el grupo de investigación LifeStech ha desarrollado desde el 2008 para mejorar la gestión de la diabetes, actividades realizadas en un contexto internacional. Los resultados demuestran que el marco ha permitido mejorar las actividades de trabajo en distintos niveles: 1) la calidad y cantidad de las publicaciones; 2) se han conseguido dos contratos de investigación sobre diabetes: el primero es un proyecto de investigación aplicada, el segundo es un proyecto financiado para acelerar las innovaciones en el mercado; 3) a través de los indicadores claves de rendimiento propuestos en el marco, una prueba de concepto de un prototipo desarrollado en un proyecto de investigación ha sido transformada en una evaluación temprana de una intervención eHealth para el manejo de la diabetes, que ha sido recientemente incluida en Repositorio de prácticas innovadoras del Partenariado de Innovación Europeo en Envejecimiento saludable y activo. La verificación de las 4 hipótesis ha permitido demonstrar la hipótesis principal de este trabajo de investigación: es posible contribuir a crear un puente entre la atención sanitaria y la innovación y, por lo tanto, mejorar la manera en que el cuidado crónico sea procurado en los sistemas sanitarios. ABSTRACT Nowadays, for the first time in history, most people can expect to live into their sixties and beyond (United Nations, 2015). However, little evidence suggests that older people are experiencing better health than their parents, and most of the health problems of older age are linked to Chronic Diseases (WHO, 2015). The established health care systems in developed countries are well suited to the treatment of acute diseases but are mostly inadequate for dealing with CDs. Healthcare systems are challenging the burden of chronic diseases by putting more emphasis on the prevention of disease and by looking for new ways to reorient the provision of care (Kane et al., 2005). According to an evidence-based review commissioned by the British NHS Institute, few models have conceptualized effective components of care for CDs and these components have been not structured and articulated. “Consequently, there is limited evidence about the real impact of any of the existing models” (Ham, 2006). Innovations could support to achieve better diagnosis, treatment and management for patients across the continuum of care, by supporting health professionals and empowering patients to take responsibility. However, the way they are delivered is not sufficiently efficient, effective and consumer friendly. The improvement of innovation delivery, involves the creation of multidisciplinary research teams and taskforces, rather than just working teams. There are several actions to improve the adoption of innovations from healthcare systems that are tackling the epidemics of CDs: 1) Translate Evidence-Based Healthcare (EBH) into actionable knowledge; 2) Face the complexity of healthcare through multidisciplinary research; 3) Identify a systematic approach to support effective implementation of healthcare interventions through innovation. The framework proposed in this research work is an attempt to provide these improvements. The following hypotheses have been drafted: Hypothesis 1: it is possible to define a translation process to convert a model of chronic care into a structured description of goals, requirements and key performance indicators. Hypothesis 2: a translation process, if executed through evidence-based, multidisciplinary, holistic and business-oriented elements, can convert a model of chronic care in a descriptive framework, which defines the whole development cycle of innovative solutions for chronic disease management. Hypothesis 3: it is possible to design a method to evaluate processes, outcomes and skill acquisition capacities, and assist multidisciplinary research teams in the creation of innovative solutions for chronic disease management. Hypothesis 4: it is possible to assist the development of innovative solutions for chronic disease management through a reference framework and produce positive effects, measured through key performance indicators. In order to verify the hypotheses, a methodological approach, composed of four Phases that correspond to each one of the stated hypothesis, was defined. Prior to this, a “Phase 0”, consisting in a multi-domain and multi-disciplinary background analysis of the problem (i.e.: systematic adoption of innovation to chronic care), was carried out. During phase 1, in order to verify the first hypothesis, a Knowledge Translation Process (KTP) was developed, starting from the JBI Joanna Briggs Institute (JBI) model of evidence-based healthcare was used (Pearson, 2005) and adding Four Innovation Blocks. These blocks represent an enriched description, added to the JBI model, to accelerate the transformation of evidence-healthcare through innovation; the innovation blocks are built on top of the conclusions drawn after Phase 0. The background analysis gave also indication on the materials and methods to be used for the execution of the KTP, carried out during phase 2, that translates the actual best available evidence for chronic care into action: this resulted in a descriptive Framework, which is a description of a model of chronic care (the Chronic Care Model was chosen, Wagner, 1996) in terms of goals, specified requirements and Key Performance Indicators, and articulated in the three development cycles of innovation (i.e. design, implementation and evaluation). Thanks to this result the second hypothesis was verified. During phase 3, in order to verify the third hypothesis, a mixed-method to evaluate multidisciplinary teams working on innovations for chronic care, was created, based on a mixed-method used for the evaluation of Multidisciplinary Translational Teams (Wooden, 2013). This method adds a procedural dimension to the descriptive component of the Framework, The result of this phase consisted in a draft version of the framework, ready to be tested in a real scenario. During phase 4, a single and multilevel case study, with participant-observation data collection, was carried out, in order to have a complete but at the same time multi-sectorial evaluation of the framework. The activities that the LifeStech research group carried out since 2008 to improve the management of diabetes have been selected as case study. The results achieved showed that the framework allowed to improve the research activities in different directions: the quality and quantity of the research publications that LifeStech has issued, have increased substantially; 2 project grants to improve the management of diabetes, have been assigned: the first is a grant funding applied research while the second is about accelerating innovations into the market; by using the assessment KPIs of the framework, the proof of concept validation of a prototype developed in a research project was transformed into an early stage assessment of innovative eHealth intervention for Diabetes Management, which has been recently included in the repository of innovative practice of the European Innovation Partnership on Active and Health Ageing initiative. The verification of the 4 hypotheses lead to verify the main hypothesis of this research work: it is possible to contribute to bridge the gap between healthcare and innovation and, in turn, improve the way chronic care is delivered by healthcare systems.

Metodología para la determinación de los parámetros de planificación de los nodos e infraestructuras logísticas en un territorio, considerando en su planificación el impacto sobre los diferentes componentes territoriales

Esta tesis presenta el diseño y la aplicación de una metodología que permite la determinación de los parámetros para la planificación de nodos e infraestructuras logísticas en un territorio, considerando además el impacto de estas en los diferentes componentes territoriales, así como en el desarrollo poblacional, el desarrollo económico y el medio ambiente, presentando así un avance en la planificación integral del territorio. La Metodología propuesta está basada en Minería de Datos, que permite el descubrimiento de patrones detrás de grandes volúmenes de datos previamente procesados. Las características propias de los datos sobre el territorio y los componentes que lo conforman hacen de los estudios territoriales un campo ideal para la aplicación de algunas de las técnicas de Minería de Datos, tales como los ´arboles decisión y las redes bayesianas. Los árboles de decisión permiten representar y categorizar de forma esquemática una serie de variables de predicción que ayudan al análisis de una variable objetivo. Las redes bayesianas representan en un grafo acíclico dirigido, un modelo probabilístico de variables distribuidas en padres e hijos, y la inferencia estadística que permite determinar la probabilidad de certeza de una hipótesis planteada, es decir, permiten construir modelos de probabilidad conjunta que presentan de manera gráfica las dependencias relevantes en un conjunto de datos. Al igual que con los árboles de decisión, la división del territorio en diferentes unidades administrativas hace de las redes bayesianas una herramienta potencial para definir las características físicas de alguna tipología especifica de infraestructura logística tomando en consideración las características territoriales, poblacionales y económicas del área donde se plantea su desarrollo y las posibles sinergias que se puedan presentar sobre otros nodos e infraestructuras logísticas. El caso de estudio seleccionado para la aplicación de la metodología ha sido la República de Panamá, considerando que este país presenta algunas características singulares, entra las que destacan su alta concentración de población en la Ciudad de Panamá; que a su vez a concentrado la actividad económica del país; su alto porcentaje de zonas protegidas, lo que ha limitado la vertebración del territorio; y el Canal de Panamá y los puertos de contenedores adyacentes al mismo. La metodología se divide en tres fases principales: Fase 1: Determinación del escenario de trabajo 1. Revisión del estado del arte. 2. Determinación y obtención de las variables de estudio. Fase 2: Desarrollo del modelo de inteligencia artificial 3. Construcción de los ´arboles de decisión. 4. Construcción de las redes bayesianas. Fase 3: Conclusiones 5. Determinación de las conclusiones. Con relación al modelo de planificación aplicado al caso de estudio, una vez aplicada la metodología, se estableció un modelo compuesto por 47 variables que definen la planificación logística de Panamá, el resto de variables se definen a partir de estas, es decir, conocidas estas, el resto se definen a través de ellas. Este modelo de planificación establecido a través de la red bayesiana considera los aspectos de una planificación sostenible: económica, social y ambiental; que crean sinergia con la planificación de nodos e infraestructuras logísticas. The thesis presents the design and application of a methodology that allows the determination of parameters for the planning of nodes and logistics infrastructure in a territory, besides considering the impact of these different territorial components, as well as the population growth, economic and environmental development. The proposed methodology is based on Data Mining, which allows the discovery of patterns behind large volumes of previously processed data. The own characteristics of the territorial data makes of territorial studies an ideal field of knowledge for the implementation of some of the Data Mining techniques, such as Decision Trees and Bayesian Networks. Decision trees categorize schematically a series of predictor variables of an analyzed objective variable. Bayesian Networks represent a directed acyclic graph, a probabilistic model of variables divided in fathers and sons, and statistical inference that allow determine the probability of certainty in a hypothesis. The case of study for the application of the methodology is the Republic of Panama. This country has some unique features: a high population density in the Panama City, a concentration of economic activity, a high percentage of protected areas, and the Panama Canal. The methodology is divided into three main phases: Phase 1: definition of the work stage. 1. Review of the State of the art. 2. Determination of the variables. Phase 2: Development of artificial intelligence model 3. Construction of decision trees. 4. Construction of Bayesian Networks. Phase 3: conclusions 5. Determination of the conclusions. The application of the methodology to the case study established a model composed of 47 variables that define the logistics planning for Panama. This model of planning established through the Bayesian network considers aspects of sustainable planning and simulates the synergies between the nodes and logistical infrastructure planning.

Dynamics of Centromeres during Metaphase–Anaphase Transition in Fission Yeast: Dis1 Is Implicated in Force Balance in Metaphase Bipolar Spindle

In higher eukaryotic cells, the spindle forms along with chromosome condensation in mitotic prophase. In metaphase, chromosomes are aligned on the spindle with sister kinetochores facing toward the opposite poles. In anaphase A, sister chromatids separate from each other without spindle extension, whereas spindle elongation takes place during anaphase B. We have critically examined whether such mitotic stages also occur in a lower eukaryote, Schizosaccharomyces pombe. Using the green fluorescent protein tagging technique, early mitotic to late anaphase events were observed in living fission yeast cells. S. pombe has three phases in spindle dynamics, spindle formation (phase 1), constant spindle length (phase 2), and spindle extension (phase 3). Sister centromere separation (anaphase A) rapidly occurred at the end of phase 2. The centromere showed dynamic movements throughout phase 2 as it moved back and forth and was transiently split in two before its separation, suggesting that the centromere was positioned in a bioriented manner toward the poles at metaphase. Microtubule-associating Dis1 was required for the occurrence of constant spindle length and centromere movement in phase 2. Normal transition from phase 2 to 3 needed DNA topoisomerase II and Cut1 but not Cut14. The duration of each phase was highly dependent on temperature.

The application of genetically engineered herpes simplex viruses to the treatment of experimental brain tumors.

Due to lack of effective therapy, primary brain tumors are the focus of intense investigation of novel experimental approaches that use vectors and recombinant viruses. Therapeutic approaches have been both indirect, whereby vectors are used, or direct to allow for direct cell killing by the introduced virus. Genetically engineered herpes simplex viruses are currently being evaluated as an experimental approach to eradicate malignant human gliomas. Initial studies with gamma (1)34.5 mutants, R3616 (from which both copies of the gamma (1)34.5 gene have been deleted) and R4009 (a construct with two stop codons inserted into the gamma (1)34.5 gene), have been assessed. In a syngeneic scid mouse intracranial tumor model, recombinant herpes simplex virus can be experimentally used for the treatment of brain tumors. These viruses and additional engineered viruses were subsequently tested in human glioma cells both in vitro and in vivo. Using a xenogeneic scid mouse intracranial glioma model, R4009 therapy of established tumors significantly prolonged survival. Most importantly, long-term survival was achieved, with histologic evidence that R4009 eradicated intracranial tumors in this model. Furthermore, the opportunity to evaluate gamma (1)34.5 mutants that have enhanced oncolytic activity, e.g., R8309 where the carboxyl terminus of the gamma (1)34.5 gene has been replaced by the murine homologue, MyD116, are considered.

Equine severe combined immunodeficiency: a defect in V(D)J recombination and DNA-dependent protein kinase activity.

V(D)J rearrangement is the molecular mechanism by which an almost infinite array of specific immune receptors are generated. Defects in this process result in profound immunodeficiency as is the case in the C.B-17 SCID mouse or in RAG-1 (recombination-activating gene 1) or RAG-2 deficient mice. It has recently become clear that the V(D)J recombinase most likely consists of both lymphoid-specific factors and ubiquitously expressed components of the DNA double-strand break repair pathway. The deficit in SCID mice is in a factor that is required for both of these pathways. In this report, we show that the factor defective in the autosomal recessive severe combined immunodeficiency of Arabian foals is required for (i) V(D)J recombination, (ii) resistance to ionizing radiation, and (iii) DNA-dependent protein kinase activity.

Influência do uso de amostras de referência no julgamento perceptivo-auditivo da oclusiva glotal

Objetivos: estabelecer amostras de referência constituídas por gravações julgadas com consenso como representativas da presença ou ausência da oclusiva glotal (OG) e comparar julgamentos perceptivo-auditivos da presença e ausência da OG com e sem o uso de amostras de referência. Metodologia: o estudo foi dividido em duas etapas. Durante a ETAPA 1, 480 frases referentes aos sons oclusivos e fricativos produzidas por falantes com história de fissura labiopalatina foram julgadas por três fonoaudiólogas experientes quanto à identificação da OG. As frases foram julgadas individualmente e aquelas que não apresentaram consenso inicial foram julgadas novamente de maneira simultânea. As amostras julgadas com consenso com relação à presença ou ausência da OG durante produção das seis consoantes-alvo oclusivas e seis fricativas foram selecionadas para estabelecer um Banco de Amostras Representativas da OG. A ETAPA 2 consistiu na seleção de 48 amostras de referência referentes aos 12 sons de interesse e 120 amostras experimentais e, o julgamento dessas amostras experimentais por três grupos de juízes, cada grupo com três juízes com experiências distintas com relação ao julgamento de fala na fissura de palato. Os juízes julgaram as amostras experimentais duas vezes, primeiro sem acesso às referências e, após uma semana, com acesso às referências. Resultados: os julgamentos realizados na ETAPA 1 evidenciaram consenso com relação a OG em 352 amostras, sendo 120 frases com produção adequada para os sons de interesse e 232 representativas do uso da OG. Essas 352 amostras constituíram o Banco de amostras Representativas da OG. Os resultados da ETAPA 2 indicaram que ao comparar a média do valor de Kappa obtida para os 12 sons de interesse em cada um dos grupos nos julgamentos sem e com acesso às amostras de referência a concordância para o grupo 1 (G1) passou de regular (K=0,35) para moderada (K=0,55), para o grupo 2 (G2) passou de moderada (K=0,44) para substancial (K=0,76) e para o grupo 3 (G3) passou de substancial (K=0,72) para quase perfeita (K=0,83). Observou-se que as melhores concordâncias ocorreram para o grupo dos fonoaudiólogos experientes (G3), seguido dos fonoaudiólogos recém-formados (G2), com as piores observadas para o grupo de alunos de graduação (G1). Conclusão: um Banco de Amostras de Referência Representativas da OG foi estabelecido e os julgamentos perceptivo-auditivos de juízes com uso das amostras de referência foram obtidos com concordância inter-juízes e porcentagem de acertos melhor do que os julgamentos sem acesso às referências. Os resultados sugerem a importância do uso de amostras de referência para minimizar a subjetividade da avaliação perceptivo auditiva da fala.

Tracing the Origins of Athlete Development Models in Sport: a Citation Path Analysis

Reviews of the sport psychology literature have identified a number of models of athlete development in sport (Alfermann & Stambulova, 2007; Durand-Bush &Salmela, 2001). However, minimal research has investigated the origins of knowledge from which each model was developed. The purpose of this study was to systematically examine the influential texts responsible for providing the basis of athlete development models in sport. A citation path analysis of the sport psychology literature was used to generate a knowledge development path of seven athlete development models in sport. The analysis identified influential texts and authors in the conceptualization of athlete development. The popula-tion of 229 texts (articles, books, book chapters) was selected in two phases. Phase1 texts were articles citing seven articles depicting models of athlete development(n  75). Phase 2 included texts cited three or more times by Phase 1 articles (n  154). The analysis revealed how the scholarship of Benjamin Bloom (1985) has been integrated into the field of sport psychology, and how two articles appearing in 1993 and 2003 helped shape present conceptualizations of athlete development

EU Naval Force EUNAVFOR MED sets sail in troubled waters. CEPS Commentary, 26 June 2015

Apprehending pirates in the Indian Ocean is one thing. Defeating the networks through which smugglers traffic migrants through North Africa is quite another. The European Union’s new naval force deployment in the Mediterranean - EUNAVFOR MED - drew criticism from international partners and the general public alike when plans for a “boat-sinking” operation were unveiled, raising fears about unacceptable levels of violence and collateral damage; a European version of Mexico’s drug war. Yet the problems of EUNAVFOR MED lie less in clumsy public diplomacy than in the perilous mismatch between its stated objectives and the absence of a clear strategy and mandate, and this creates both operational and political risks for member states. Phase 1 of the operation: surveillance and assessment, has begun with no legal mandate to carry out the crucial phases 2 and 3: seek and destroy, whose military planning and outcomes are undetermined. Despite these limitations, the naval force could nevertheless mark a turning point in the EU’s security narrative, because it means that the Union is finally addressing the threats to security and the humanitarian tragedies in its southern neighbourhood.

Application of infra-red techniques to military training.

"Contract Nonr 61339-759."

Thebes flood hazard mitigation program.

"October, 1985."

Investigative procedures.

Loose-leaf for updating.

Design Expressions and Dynamic Evaluation of CFST Bridges Subjected to Seismic Hazards

Thesis (Ph.D.)--University of Washington, 2016-06

Induction of Therapeutic T-Cell Responses to Subdominant Tumor-associated Viral Oncogene after Immunization with Replication-incompetent Polyepitope Adenovirus Vaccine

The EBV-encoded latent membrane proteins (LMP1 and LMP2), which are expressed in various EBV-associated malignancies have been proposed as a potential target for CTL-based therapy. However, the precursor frequency for LMP-specific CTL is generally low, and immunotherapy based on these antigens is often compromised by the poor immunogenicity and potential threat from their oncogenic potential. Here we have developed a replication-incompetent adenoviral vaccine that encodes multiple HLA class I-restricted CTL epitopes from LMP1 and LMP2 as a polyepitope. Immunization with this polyepitope vaccine consistently generated strong LMP-specific CTL responses in HLA A2/K-b mice, which can be readily detected by both ex vivo and in vivo T-cell assays. Furthermore, a human CTL response to LMP antigens can be rapidly expanded after stimulation with this recombinant polyepitope vector. These expanded T cells displayed strong lysis of autologous target cells sensitized with LMP1 and/or LMP2 CTL epitopes. More importantly, this adenoviral vaccine was also successfully used to reverse the outgrowth of LMP1-expressing tumors in HLA A2/K-b mice. These studies demonstrate that a replication-incompetent adenovirus polyepitope vaccine is an excellent tool for the induction of a protective CTL response directed toward multiple LMP CTL epitopes restricted through common HLA class I alleles prevalent in different ethnic groups where EBV-associated malignancies are endemic.

Costs increase as ritualized fighting progresses within and between phases in the sierra dome spider, Neriene litigiosa

Magnitudes and patterns of energy expenditure in animal contests are seldom measured, but can be critical for predicting contest dynamics and understanding the evolution of ritualized fighting behaviour. In the sierra dome spider, males compete for sexual access to females and their webs. They show three distinct phases of fighting behaviour, escalating from ritualized noncontact display (phase 1) to cooperative wrestling (phase 2), and finally to unritualized, potentially fatal fighting (phase 3). Using CO2 respirometry, we estimated energetic costs of male-male combat in terms of mean and maximum metabolic rates and the rate of increase in energy expenditure. We also investigated the energetic consequences of age and body mass, and compared fighting metabolism to metabolism during courtship. All three phases involved mean energy expenditures well above resting metabolic rate (3.5 X, 7.4 X and 11.5 X). Both mean and maximum energy expenditure became substantially greater as fights escalated through successive phases. The rates of increase in energy use during phases 2 and 3 were much higher than in phase 1. In addition, age and body mass affected contest energetics. These results are consistent with a basic prediction of evolutionarily stable strategy contest models, that sequences of agonistic behaviours should be organized into phases of escalating energetic costs. Finally, higher energetic costs of escalated fighting compared to courtship provide a rationale for first-male sperm precedence in this spider species. (C) 2004 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.