4HPR-X radiation mechanisms of interactions in non-small cell lung cancer (NSCLC) cells in vitro

Lung cancer is the leading cause of cancer death. However, poor survival using conventional therapies fuel the search for more rational interventions. The objective of this study was to design and implement a 4HPR-radiation interaction model in NSCLC, employing a traditional clinical modality (radiation), a relatively new, therapeutically unexplored agent (4HPR) and rationally combining them based on molecular mechanistic findings pertaining to their interactions. To test the hypothesis that 4HPR sensitizes cells to radiation-induced cell death via G2+M accumulation, we designed a working model consisting of H522 adenocarcinoma cells (p53, K-ras mutated) derived from an NSCLC patient; 4HPR at concentrations up to 10 μM; and X radiation up to 6 Gy generated by a patient-dedicated Phillips RT-250 X ray unit at 250 KV, 15 mA, 1.85 Gy/min. We found that 4HPR produced time- and dose-dependent morphological changes, growth inhibition, and DNA damage-inducing enhancement of reactive oxygen species. A transient G2+M accumulation of cells maximal at 24 h of continuous 4HPR exposure was used for irradiation time scheduling. Our data demonstrated enhanced cell death (both apoptotic and necrotic) in irradiated cells pre-treated with 4HPR versus those with either stressor alone. 4HPR's effect of increased NSCLC cells' radioresponse was confirmed by clonogenic assay. To explore these practical findings from a molecular mechanistic perspective, we further investigated and showed that levels of cyclin B1 and p34cdc2 kinase—both components of the mitosis promoting factor (MPF) regulating the G2/M transition—did not change following 4HPR treatment. Likewise, cdc25C phosphatase was not altered. However, enhanced p34cdc2 phosphorylation on its Thr14Tyr15 residues—indicative of its inactivation and increased expression of MPF negative regulators chk1 and wee1 kinases—were supportive of explaining 4HPR-treated cells' accumulation. Hence, p34cdc2 phosphorylation, chk1, and wee1 warrant further evaluation as potential molecular targets for 4HPR-X radiation combination. In summary, we (1) demonstrated that 4HPR not only induces cell death by itself, but also increases NSCLC cells' subsequent radioresponse, indicative of potential clinical applicability, and (2) for the first time, shed light on deciphering 4HPR-X radiation molecular mechanisms of interaction, including the finding of 4HPR's role as a p34cdc2 inactivator via Thr14Tyr15 phosphorylation. ^

Efectos dinámicos debidos al tráfico de ferrocarril sobre la infraestructura de vía y las estructuras

La vía tradicional sobre balasto sigue siendo una selección para las líneas de alta velocidad a pesar de los problemas técnicos y la prestación del funcionamiento. El problema de la vía sobre balasto es el proceso continuo del deterioro de éste debido a las cargas asociadas al tráfico ferroviario. En consecuencia es imprescindible un mantenimiento continuado para mantener un alineamiento adecuado de la vía. Por eso se surge la necesidad de comprender mejor el mecanismo involucrado en el deterioro de la vía y los factores claves que rigen su progresión a lo largo de ciclos de carga con el fin de reducir los costos del mantenimiento de la vía y mejorar el diseño de las nuevas vías. La presente tesis intenta por un lado desarrollar los modelos más adecuados y eficientes del vehículo y de la vía para los cálculos de los efectos dinámicos debido al tráfico de ferrocarril sobre la infraestructura de la vía sobre balasto, y por otro evaluar estos efectos dinámicos sobre el deterioro de la vía sobre balasto a largo plazo, empleando un adecuado modelo de predicción del deterioro de la misma. Se incluye en el trabajo una recopilación del estado del arte en lo referente a la dinámica de la vía, a la modelización del vehículo, de la vía y de la interacción entre ambos. También se hace un repaso al deterioro de la vía y los factores que influyen en su proceso. Para la primera línea de investigación de esta tesis, se han desarrollado los diferentes modelos del vehículo y de la vía y la modelización de la interacción entre ambos para los cálculos dinámicos en dos y tres dimensiones. En la interacción vehículo-vía, se ha empleado la formulación de contacto nodo-superficie para establecer la identificación de las superficies en contacto y el método de los multiplicadores de Lagrange para imponer las restricciones de contacto. El modelo de interacción se ha contrastado con los casos reportados en la literatura. Teniendo en cuenta el contacto no lineal entre rueda-carril y los perfiles de irregularidades distribuidas de la vía, se han evaluado y comparado los efectos dinámicos sobre el sistema vehículo-vía en la interacción de ambos, para distintas velocidades de circulación del vehículo, en los aspectos como la vibración del vehículo, fuerza de contacto, fuerza transmitida en los railpads, la vibración del carril. También se hace un estudio de la influencia de las propiedades de los componentes de la vía en la respuesta dinámica del sistema vehículo-vía. Se ha desarrollado el modelo del asiento de la vía que consiste en la implementación del modelo de acumulación de Bochum y del modelo de hipoplasticidad en la subrutina del usuario \UMAT" del programa ABAQUS. La implementación numérica ha sido comprobado al comparar los resultados de las simulaciones numéricas con los reportados en la literatura. Se ha evaluado la calidad geométrica de la vía sobre balasto de los tramos de estudio con datos reales de la auscultación proporcionados por ADIF (2012). Se ha propuesto una metodología de simulación, empleando el modelo de asiento, para reproducir el deterioro de la geometría de la vía. Se usan los perfiles de la nivelación longitudinal de la auscultación como perfiles de irregularidades iniciales de la vía en las simulaciones numéricas. También se evalúa la influencia de la velocidad de circulación sobre el deterioro de la vía. The traditional ballast track structures are still being used in high speed railways lines with success, however technical problems or performance features have led to ballast track solution in some cases. The considerable maintenance work is needed for ballasted tracks due to the track deterioration. Therefore it is very important to understand the mechanism of track deterioration and to predict the track settlement or track irregularity growth rate in order to reduce track maintenance costs and enable new track structures to be designed. This thesis attempts to develop the most adequate and efficient models for calculation of dynamic track load effects on railways track infrastructure, and to evaluate these dynamic effects on the track settlement, using a track settlement prediction model, which consists of the vehicle/track dynamic model previously selected and a track settlement law. A revision of the state of the knowledge regarding the track dynamics, the modelling of the vehicle, the track and the interaction between them is included. An overview related to the track deterioration and the factors influencing the track settlement is also done. For the first research of this thesis, the different models of vehicle, track and the modelling of the interaction between both have been developed. In the vehicle-track interaction, the node-surface contact formulation to establish the identification of the surfaces in contact and the Lagrange multipliers method to enforce contact constraint are used. The interaction model has been verified by contrast with some benchmarks reported in the literature. Considering the nonlinear contact between wheel-rail and the track irregularities, the dynamic effects on the vehicle-track system have been evaluated and compared, for different speeds of the vehicle, in aspects as vehicle vibration, contact force, force transmitted in railpads, rail vibration. A study of the influence of the properties of the track components on the the dynamic response of the vehicle-track system has been done. The track settlement model is developed that consist of the Bochum accumulation model and the hipoplasticity model in the user subroutine \UMAT" of the program ABAQUS. The numerical implementation has been verified by comparing the numerical results with those reported in the literature. The geometric quality of the ballast track has been evaluated with real data of auscultation provided by ADIF (2012). The simulation methodology has been proposed, using the settlement model for the ballast material, to reproduce the deterioration of the track geometry. The profiles of the longitudinal level of the auscultation is used as initial profiles of the track irregularities in the numerical simulation. The influence of the running speed on the track deterioration is also investigated.

Assessing urban mobility through participatory scenario building and combined utility-regret assessment

La planificación de la movilidad sostenible urbana es una tarea compleja que implica un alto grado de incertidumbre debido al horizonte de planificación a largo plazo, la amplia gama de paquetes de políticas posibles, la necesidad de una aplicación efectiva y eficiente, la gran escala geográfica, la necesidad de considerar objetivos económicos, sociales y ambientales, y la respuesta del viajero a los diferentes cursos de acción y su aceptabilidad política (Shiftan et al., 2003). Además, con las tendencias inevitables en motorización y urbanización, la demanda de terrenos y recursos de movilidad en las ciudades está aumentando dramáticamente. Como consecuencia de ello, los problemas de congestión de tráfico, deterioro ambiental, contaminación del aire, consumo de energía, desigualdades en la comunidad, etc. se hacen más y más críticos para la sociedad. Esta situación no es estable a largo plazo. Para enfrentarse a estos desafíos y conseguir un desarrollo sostenible, es necesario considerar una estrategia de planificación urbana a largo plazo, que aborde las necesarias implicaciones potencialmente importantes. Esta tesis contribuye a las herramientas de evaluación a largo plazo de la movilidad urbana estableciendo una metodología innovadora para el análisis y optimización de dos tipos de medidas de gestión de la demanda del transporte (TDM). La metodología nueva realizado se basa en la flexibilización de la toma de decisiones basadas en utilidad, integrando diversos mecanismos de decisión contrariedad‐anticipada y combinados utilidad‐contrariedad en un marco integral de planificación del transporte. La metodología propuesta incluye dos aspectos principales: 1) La construcción de escenarios con una o varias medidas TDM usando el método de encuesta que incorpora la teoría “regret”. La construcción de escenarios para este trabajo se hace para considerar específicamente la implementación de cada medida TDM en el marco temporal y marco espacial. Al final, se construyen 13 escenarios TDM en términos del más deseable, el más posible y el de menor grado de “regret” como resultado de una encuesta en dos rondas a expertos en el tema. 2) A continuación se procede al desarrollo de un marco de evaluación estratégica, basado en un Análisis Multicriterio de Toma de Decisiones (Multicriteria Decision Analysis, MCDA) y en un modelo “regret”. Este marco de evaluación se utiliza para comparar la contribución de los distintos escenarios TDM a la movilidad sostenible y para determinar el mejor escenario utilizando no sólo el valor objetivo de utilidad objetivo obtenido en el análisis orientado a utilidad MCDA, sino también el valor de “regret” que se calcula por medio del modelo “regret” MCDA. La función objetivo del MCDA se integra en un modelo de interacción de uso del suelo y transporte que se usa para optimizar y evaluar los impactos a largo plazo de los escenarios TDM previamente construidos. Un modelo de “regret”, llamado “referencedependent regret model (RDRM)” (modelo de contrariedad dependiente de referencias), se ha adaptado para analizar la contribución de cada escenario TDM desde un punto de vista subjetivo. La validación de la metodología se realiza mediante su aplicación a un caso de estudio en la provincia de Madrid. La metodología propuesta define pues un procedimiento técnico detallado para la evaluación de los impactos estratégicos de la aplicación de medidas de gestión de la demanda en el transporte, que se considera que constituye una herramienta de planificación útil, transparente y flexible, tanto para los planificadores como para los responsables de la gestión del transporte. Planning sustainable urban mobility is a complex task involving a high degree of uncertainty due to the long‐term planning horizon, the wide spectrum of potential policy packages, the need for effective and efficient implementation, the large geographical scale, the necessity to consider economic, social, and environmental goals, and the traveller’s response to the various action courses and their political acceptability (Shiftan et al., 2003). Moreover, with the inevitable trends on motorisation and urbanisation, the demand for land and mobility in cities is growing dramatically. Consequently, the problems of traffic congestion, environmental deterioration, air pollution, energy consumption, and community inequity etc., are becoming more and more critical for the society (EU, 2011). Certainly, this course is not sustainable in the long term. To address this challenge and achieve sustainable development, a long‐term perspective strategic urban plan, with its potentially important implications, should be established. This thesis contributes on assessing long‐term urban mobility by establishing an innovative methodology for optimizing and evaluating two types of transport demand management measures (TDM). The new methodology aims at relaxing the utility‐based decision‐making assumption by embedding anticipated‐regret and combined utilityregret decision mechanisms in an integrated transport planning framework. The proposed methodology includes two major aspects: 1) Construction of policy scenarios within a single measure or combined TDM policy‐packages using the survey method incorporating the regret theory. The purpose of building the TDM scenarios in this work is to address the specific implementation in terms of time frame and geographic scale for each TDM measure. Finally, 13 TDM scenarios are built in terms of the most desirable, the most expected and the least regret choice by means of the two‐round Delphi based survey. 2) Development of the combined utility‐regret analysis framework based on multicriteria decision analysis (MCDA). This assessment framework is used to compare the contribution of the TDM scenario towards sustainable mobility and to determine the best scenario considering not only the objective utility value obtained from the utilitybased MCDA, but also a regret value that is calculated via a regret‐based MCDA. The objective function of the utility‐based MCDA is integrated in a land use and transport interaction model and is used for optimizing and assessing the long term impacts of the constructed TDM scenarios. A regret based model, called referente dependent regret model (RDRM) is adapted to analyse the contribution of each TDM scenario in terms of a subjective point of view. The suggested methodology is implemented and validated in the case of Madrid. It defines a comprehensive technical procedure for assessing strategic effects of transport demand management measures, which can be useful, transparent and flexible planning tool both for planners and decision‐makers.

Integration of congestion pricing and intertemporal preferences rate integration in social welfare function

Many researchers have used theoretical or empirical measures to assess social benefits in transport policy implementation. However, few have measured social benefits by using discount rates, including the intertemporal preference rate of users, the private investment discount rate, and the intertemporal preference rate of the government. In general, the social discount rate used is the same for all social actors. This paper aims to assess a new method by integrating different types of discount rates belonging to different social actors to measure the real benefits of each actor in the short term, medium term, and long term. A dynamic simulation is provided by a strategic land use and transport interaction model. The method was tested by optimizing a cordon toll scheme in Madrid, Spain. Socioeconomic efficiency and environmental criteria were considered. On the basis of the modified social welfare function, the effects on the measure of social benefits were estimated and compared with the classical welfare function measures. The results show that the use of more suitable discount rates for each social actor had an effect on the selection and definition of optimal strategy of congestion pricing. The usefulness of the measure of congestion toll declines more quickly over time. This result could be the key to understanding the relationship between transport system policies and the distribution of social actors? benefits in a metropolitan context.

On-road visual vehicle tracking using Markov chain Monte Carlo with metropolis sampling

In this study, a method for vehicle tracking through video analysis based on Markov chain Monte Carlo (MCMC) particle filtering with metropolis sampling is proposed. The method handles multiple targets with low computational requirements and is, therefore, ideally suited for advanced-driver assistance systems that involve real-time operation. The method exploits the removed perspective domain given by inverse perspective mapping (IPM) to define a fast and efficient likelihood model. Additionally, the method encompasses an interaction model using Markov Random Fields (MRF) that allows treatment of dependencies between the motions of targets. The proposed method is tested in highway sequences and compared to state-of-the-art methods for vehicle tracking, i.e., independent target tracking with Kalman filtering (KF) and joint tracking with particle filtering. The results showed fewer tracking failures using the proposed method.

Estudio de la respuesta dinámica transversal de viaductos altos de líneas de ferrocarril de alta velocidad bajo la acción de cargas de uso

Es conocido que las dimensiones de los puentes de ferrocarril han ido cambiando debido a las estrictas condiciones de trazado impuestas en las líneas de alta velocidad. Además, la creciente preocupación de la sociedad por cuidar y proteger el medio ambiente, reflejado en la correspondiente normativa, ha generado nuevos condicionantes en el diseño de estas infraestructuras. En concreto, se ha limitado el movimiento de grandes volúmenes de terreno particularmente en los espacios protegidos. Por estas razones, hoy en día se proyectan y construyen puentes de ferrocarril más altos y más largos en todo el mundo. En España se han construido varios viaductos de pilas altas para líneas de alta velocidad. Ejemplos de estas infraestructuras son el Viaducto O’Eixo y el Viaducto de Barbantiño, situados en la línea de alta velocidad Madrid-Galicia, Estos viaductos altos se caracterizan por tener una mayor flexibilidad lateral y una frecuencia fundamental de oscilación baja, de hasta 0.2 Hz. La respuesta dinámica de este tipo de estructura puede aumentar como consecuencia de la aproximación entre la frecuencias propias de la misma y las de excitación debidas al paso del tren y a la acción del viento. Por lo tanto, estas estructuras pueden presentar problemas a la hora de cumplir con las limitaciones impuestas en las normas de diseño de puentes de ferrocarril, y otras, para garantizar la seguridad del tráfico y el confort de los viajeros. La respuesta dinámica lateral de viaductos de pilas altas no ha sido suficientemente estudiada en la literatura científica. Se pueden intuir varios de los motivos para explicar esta carencia. El primero es la relativamente reciente aparición de este tipo de viaductos asociados al desarrollo de la alta velocidad. Por otro lado, se hace necesario, para estudiar este tema, construir nuevos modelos numéricos adecuados para el estudio de la interacción dinámica lateral del puente y del tren. La interacción entre el puente y un tren viajando sobre él es un problema dinámico no lineal, dependiente del tiempo y de acoplamiento entre los dos subsistemas que intervienen (vehículo y puente). Los dos subsistemas, que pueden ser modelados como estructuras elásticas, interaccionan el uno con el otro a través de las fuerzas de contacto, que tiene una marcada naturaleza no lineal por el rozamiento entre rueda y carril, y por la geometría de los perfiles de estos dos elementos en contacto. En esta tesis, se desarrolla la formulación completa de un modelo no lineal de interacción tren-vía-puente-viento que reproduce adecuadamente las fuerzas laterales de contacto rueda-carril, fuerzas que van a tener una gran influencia en los índices de seguridad del tráfico. Este modelo se ha validado a partir de casos resueltos en la literatura científica, y de medidas experimentales tomadas en eventos dinámicos ocurridos en los viaductos de Arroyo de Valle y Arroyo de las Piedras. Puentes altos que han estado monitorizados en servicio durante dos años. En los estudios realizados en este trabajo, se cuantifican, empleando el modelo construido, los niveles de seguridad del tráfico y de confort de los pasajeros de trenes ligeros de alta velocidad, como el tren articulado AVE S-100, que viajan sobre viaductos altos sometidos, o no, a fuertes vientos laterales racheados. Finalmente, se ha obtenido el grado de mejora de la seguridad del tráfico y del confort de los viajeros, cuando se emplean pantallas anti-viento en el tablero y amortiguadores de masa sintonizados en la cabeza de las pilas de un viaducto alto. Resultando, el uso simultaneo de estos dos dispositivos (pantallas y amortiguadores de masa), en puentes altos de líneas de alta velocidad, una opción a considerar en la construcción de estas estructuras para elevar significativamente el nivel de servicio de las mismas. It is known that dimensions of railway bridges have been changing due to the strict high-speed lines layout parameters. Moreover, the growing concern of society to take care of and protect the environment, reflected in the corresponding regulations, has created new environment requirements for the design of these infrastructures. Particularly, the mentioned regulations do not allow designers to move far from terrain to build these railway lines. Due to all these reasons, longer and higher railway bridges are being designed and built around the world. In Spain, several high pier railway viaducts have been built for high speed lines. Barbantiño Viaduct and Eixo Viaduct, belonging to the Madrid-Galicia high speed line, are examples of this kind of structures. These high viaducts have great lateral flexibility and a low fundamental vibration frequency of down to 0.2 Hz. The dynamic response of high speed railway bridges may increase because of the approximation between the natural viaduct frequencies and the excitation ones due to the train travel and the wind action. Therefore, this bridge response could not satisfy the serviceability limits states, for traffic safety and for passenger comfort, considered by the design standards of high speed bridges. It is difficult to find papers in the scientific literature about the lateral response of high-speed trains travel over long viaducts with high piers. Several reasons could explain this issue. On one hand, the construction of this kind of viaduct is relatively recent and it is associated to the development of the high speed railway. On the other hand, in order to study the dynamic lateral interaction between the train and the high bridge, it is necessary to build new numerical and complex models. The interaction between the bridge-track subsystem and the vehicle subsystem travelling over the bridge is a coupling, nonlinear and time dependent problem. Both subsystems, train and bridge, which can be modelled as elastic structures, interact each other through the contact forces. These forces have a strong nonlinear nature due to the friction and the geometry of rail and wheel profiles. In this thesis, the full formulation of a train-track-bridge-wind nonlinear interaction model is developed. This model can reproduce properly the lateral contact wheel-rail forces, which have a great influence on traffic safety indices. The validation of the model built has been reached through interaction solved cases found in the scientific literature and experimental measures taken in dynamic events which happened at Arroyo de las Piedras and Arroyo del Valle Viaducts. These high bridges have been controlled during two years of service by means of structural health monitoring. In the studies carried out for this thesis, the levels of traffic safety and passenger comfort are quantified using the interaction model built, in the cases of high speed and light trains, as AVE S-100, travelling over high pier bridges and with or without lateral turbulent winds acting. Finally, the improvement rate of the traffic safety and passenger comfort has been obtained, when wind barriers are used at the bridge deck and tuned mass dampers are installed at the pier heads of a high viaduct. The installation of both devices, wind barriers and tuned mass damper, at the same time, turned out to be a good option to be considered in the design of high pier railway viaducts, to improve significantly the serviceability level of this kind of structures.

Negative activation enthalpies in the kinetics of protein folding.

Although the rates of chemical reactions become faster with increasing temperature, the converse may be observed with protein-folding reactions. The rate constant for folding initially increases with temperature, goes through a maximum, and then decreases. The activation enthalpy is thus highly temperature dependent because of a large change in specific heat (delta Cp). Such a delta Cp term is usually presumed to be a consequence of a large decrease in exposure of hydrophobic surfaces to water as the reaction proceeds from the denatured state to the transition state for folding: the hydrophobic side chains are surrounded by "icebergs" of water that melt with increasing temperature, thus making a large contribution to the Cp of the denatured state and a smaller one to the more compact transition state. The rate could also be affected by temperature-induced changes in the conformational population of the ground state: the heat required for the progressive melting of residual structure in the denatured state will contribute to delta Cp. By examining two proteins with different refolding mechanisms, we are able to find both of these two processes; barley chymotrypsin inhibitor 2, which refolds from a highly unfolded state, fits well to a hydrophobic interaction model with a constant delta Cp of activation, whereas barnase, which refolds from a more structured denatured state, deviates from this ideal behavior.

Role of potassium orbitals in the metallic behavior of K3picene

Detailed electronic structure calculations of picene clusters doped by potassium modeling the crystalline K3picene structure show that while two electrons are completely transferred from potassium atoms to the lowest-energy unoccupied molecular orbital of pristine picene, the third one remains closely attached to both material components. Multiconfigurational analysis is necessary to show that many structures of almost degenerate total energies compete to define the cluster ground state. Our results prove that the 4s orbital of potassium should be included in any interaction model describing the material. We propose a quarter-filled two-orbital model as the most simple model capable of describing the electronic structure of K-intercalated picene. Precise solutions obtained by a development of the Lanczos method show low-energy electronic excitations involving orbitals located at different positions. Consequently, metallic transport is possible in spite of the clear dominance of interaction over hopping.

The role of migration in urban transition : studies of the relationship between migration and modernisation for Brisbane and Stockholm

Wilbur Zelinsky formulated a Hypothesis of Mobility Transition in 1971,in which he tried to relate all aspects of mobility to the Demographic Transition and modernisation. This dissertation applies the theoretical framework, proposed by Zelinsky and extended to encompass a family of transitions, to understand migration patterns of city regions. The two city regions, Brisbane and Stockholm, are selected as case studies, representing important city regions of similar size, but drawn from contrasting historical settings. A comparison of the case studies with the theoretical framework aims to determine how the relative contributions of net migration, the source areas of migrants, and the migration intensity change with modernisation. In addition, the research also aims to identify aspects of modernisation affecting migration. These aspects of migration are analysed with a "historical approach" and a "multivariate approach". An extensive investigation into the city regions' historical background provides the source, from which evidence for a relationship between migration and modernisation is extracted. With this historical approach, similarities and differences in migration patterns are identified. The other research approach analyse multivariate data, from the last two decades, on migration flows and modernisation. Correlations between migration and key aspects of modernisation are tested with multivariate regression, based on an alternative version of a spatial interaction model. The project demonstrates that the changing functions of cities and the structural modernisation are influential on migration. Similar patterns are found, regarding the relative contributions of net migration and natural increase to population growth. The research finds links between these changes in the relative contribution of net migration and demographic modernisation. The findings on variations in urban and rural source areas of migrants to city regions do not contradict the expected pattern, but data limitations prevent definite conclusion to be drawn. The assessment of variations in migration intensity resulted in the expected pattern not being supported. Based on Swedish data, the hypothesised increase in migration intensity is rejected. Interactional migration data also show patterns different from those derived from the theoretical framework. The findings, from both research approaches, suggested that structural modernisation affected migration flows more than demographic modernisation. The findings lead to a formulation of hypothesised patterns for migration to city regions. The study provides an important research contribution by applying the two research approaches to city regions. It also combines the study of internal and international migration to address the research objectives within a framework of transitional change.

Managing careers and managing fairness : an organisational justice theory perspective on employee evaluations of, and reactions to, organisational career management practices

This thesis presents the results of a multi-method investigation of employee perceptions of fairness in relation to their career management experiences. Organisational justice theory (OJT) was developed as a theoretical framework and data were gathered via 325 quantitative questionnaires, 20 semi-structured interviews and the analysis of a variety of company documents and materials. The results of the questionnaire survey provided strong support for the salience of employee perceptions of justice in regard to their evaluations of organisational career management (OCM) practices, with statistical support emerging for both an agent-systems and interaction model of organisational justice. The qualitative semi-structured interviews provided more detailed analysis of how fairness was experienced in practice, and confirmed the importance of the OJT constructs of fairness within this career management context. Fairness themes to emerge from this analysis included, equity, needs, voice, bias suppression, consistency, ethicality, respect and feedback drawing on many of the central tenants of distributive, procedural, interpersonal and information justice. For the career management literature there is empirical confirmation of a new theoretical framework for understanding employee evaluations of, and reactions to, OCM practices. For the justice literatures a new contextual domain is explored and confirmed, thus extending further the influence and applicability of the theory. For practitioners a new framework for developing, delivering and evaluating their own OCM policies and systems is presented.

Effects of some 5-hydroxytryptamine and related ligands in anxiety models

Drugs acting at 5-HT receptors were evaluated on three animal models of anxiety. On the elevated X-maze test the majority of 5-HT1 agonists were found to be anxiogenic. However, ipsapirone was anxiolytic and buspirone and gepirone were inactive. The 5-HT2 agonist DOI and the 5-HT2 antagonist ritanserin were anxiolytic while ICI 169,369, a 5-HT2 antagonist was inactive. All 5-HT3 antagonists tested were inactive in this test, while the indirect serotomimetics zimeldine and fenfluramine were anxiogenic. Neither beta-adrenoceptor agonists nor antagonists had reproducible effects on anxiety in this model. Combined beta-1/beta-2 adrenoceptor antagonists reversed the anxiogenic effects of 8-OH-DPAT while selective beta-1 or beta-2 antagonists did not. On the social interaction model the 5-HT1 agonists 8-OH-DPAT, RU 24969 and 5-MeODMT were anxiogenic and ipsapirone was anxiolytic. The 5-HT2 agonist DOI and the beta-adrenoceptor- and 5-HT- antagonist pindolol were anxiolytic, while the 5-HT2 and 5-HT3 antagonists were inactive. In the marble burying test, the 5-HT upake inhibitors zimeldine, fluvoxamine, indalpine and citalopram, the 5-HT1B/5-HT1C agonists mCPP and TFMPP and the 5-HT2/5-HT1C agonist DOI reduced marble burying without affecting locomotor activity. 5-HT1A agonists and the 5-HT2 and 5-HT3 antagonists were without effect. Lesions of the dorsal raphe nucleus reversed the anxiogenic effects of 8-OH-DPAT in the X-maze model. The implication of these results for the understanding of the pharmacology of 5-HT in anxiety is discussed.

Enabling effective user interactions in content-based image retrieval

This paper presents an interactive content-based image retrieval framework—uInteract, for delivering a novel four-factor user interaction model visually. The four-factor user interaction model is an interactive relevance feedback mechanism that we proposed, aiming to improve the interaction between users and the CBIR system and in turn users overall search experience. In this paper, we present how the framework is developed to deliver the four-factor user interaction model, and how the visual interface is designed to support user interaction activities. From our preliminary user evaluation result on the ease of use and usefulness of the proposed framework, we have learnt what the users like about the framework and the aspects we could improve in future studies. Whilst the framework is developed for our research purposes, we believe the functionalities could be adapted to any content-based image search framework.

Numerical simulation for dynamic positioning in pack ice

This thesis investigates the numerical modelling of Dynamic Position (DP) in pack ice. A two-dimensional numerical model for ship-ice interaction was developed using the Discrete Element Method (DEM). A viscous-elastic ice rheology was adopted to model the dynamic behaviour of the ice floes. Both the ship-ice and the ice-ice contacts were considered in the interaction force. The environment forces and the hydrodynamic forces were calculated by empirical formulas. After the current position and external forces were calculated, a Proportional-Integral-Derivative (PID) control and thrust allocation algorithms were applied on the vessel to control its motion and heading. The numerical model was coded in Fortran 90 and validated by comparing computation results to published data. Validation work was first carried out for the ship-ice interaction calculation, and former researchers’ simulation and model test results were used for the comparison. With confidence in the interaction model, case studies were conducted to predict the DP capability of a sample Arctic DP vessel.

Seismic Response Analysis of a Full-Scale Base-Isolated Structure via Measurements and Modeling

The full-scale base-isolated structure studied in this dissertation is the only base-isolated building in South Island of New Zealand. It sustained hundreds of earthquake ground motions from September 2010 and well into 2012. Several large earthquake responses were recorded in December 2011 by NEES@UCLA and by GeoNet recording station nearby Christchurch Women's Hospital. The primary focus of this dissertation is to advance the state-of-the art of the methods to evaluate performance of seismic-isolated structures and the effects of soil-structure interaction by developing new data processing methodologies to overcome current limitations and by implementing advanced numerical modeling in OpenSees for direct analysis of soil-structure interaction.

This dissertation presents a novel method for recovering force-displacement relations within the isolators of building structures with unknown nonlinearities from sparse seismic-response measurements of floor accelerations. The method requires only direct matrix calculations (factorizations and multiplications); no iterative trial-and-error methods are required. The method requires a mass matrix, or at least an estimate of the floor masses. A stiffness matrix may be used, but is not necessary. Essentially, the method operates on a matrix of incomplete measurements of floor accelerations. In the special case of complete floor measurements of systems with linear dynamics, real modes, and equal floor masses, the principal components of this matrix are the modal responses. In the more general case of partial measurements and nonlinear dynamics, the method extracts a number of linearly-dependent components from Hankel matrices of measured horizontal response accelerations, assembles these components row-wise and extracts principal components from the singular value decomposition of this large matrix of linearly-dependent components. These principal components are then interpolated between floors in a way that minimizes the curvature energy of the interpolation. This interpolation step can make use of a reduced-order stiffness matrix, a backward difference matrix or a central difference matrix. The measured and interpolated floor acceleration components at all floors are then assembled and multiplied by a mass matrix. The recovered in-service force-displacement relations are then incorporated into the OpenSees soil structure interaction model.

Numerical simulations of soil-structure interaction involving non-uniform soil behavior are conducted following the development of the complete soil-structure interaction model of Christchurch Women's Hospital in OpenSees. In these 2D OpenSees models, the superstructure is modeled as two-dimensional frames in short span and long span respectively. The lead rubber bearings are modeled as elastomeric bearing (Bouc Wen) elements. The soil underlying the concrete raft foundation is modeled with linear elastic plane strain quadrilateral element. The non-uniformity of the soil profile is incorporated by extraction and interpolation of shear wave velocity profile from the Canterbury Geotechnical Database. The validity of the complete two-dimensional soil-structure interaction OpenSees model for the hospital is checked by comparing the results of peak floor responses and force-displacement relations within the isolation system achieved from OpenSees simulations to the recorded measurements. General explanations and implications, supported by displacement drifts, floor acceleration and displacement responses, force-displacement relations are described to address the effects of soil-structure interaction.

Multilevel Governance and Accountability: Does Decentralization Promote Good Governance?

Today, the trend towards decentralization is far-reaching. Proponents of decentralization have argued that decentralization promotes responsive and accountable local government by shortening the distance between local representatives and their constituency. However, in this paper, I focus on the countervailing effect of decentralization on the accountability mechanism, arguing that decentralization, which increases the number of actors eligible for policy making and implementation in governance as a whole, may blur lines of responsibility, thus weakening citizens’ ability to sanction government in election. By using the ordinary least squares (OLS) interaction model based on historical panel data for 78 countries in the 2002 – 2010 period, I test the hypothesis that as the number of government tiers increases, there will be a negative interaction between the number of government tiers and decentralization policies. The regression results show empirical evidence that decentralization policies, having a positive impact on governance under a relatively simple form of multilevel governance, have no more statistically significant effects as the complexity of government structure exceeds a certain degree. In particular, this paper found that the presence of intergovernmental meeting with legally binding authority have a negative impact on governance when the complexity of government structure reaches to the highest level.