DEVELOPMENT AND IMPLEMENTATION OF A REMOTE AUDIT TOOL FOR HIGH DOSE RATE (HDR) 192IR BRACHYTHERAPY USING OPTICALLY STIMULATED LUMINESCENCE DOSIMETRY

This work aimed to create a mailable and OSLD-based phantom with accuracy suitable for RPC audits of HDR brachytherapy sources at institutions participating in NCI-funded cooperative clinical trials. An 8 × 8 × 10 cm3 prototype with two slots capable of holding nanoDot Al2O3:C OSL dosimeters (Landauer, Glenwood, IL) was designed and built. The phantom has a single channel capable of accepting all 192Ir HDR brachytherapy sources in current clinical use in the United States. Irradiations were performed with an 192Ir HDR source to determine correction factors for linearity with dose, dose rate, and the combined effect of irradiation energy and phantom construction. The uncertainties introduced by source positioning in the phantom and timer resolution limitations were also investigated. It was found that the linearity correction factor was where dose is in cGy, which differed from that determined by the RPC for the same batch of dosimeters under 60Co irradiation. There was no significant dose rate effect. Separate energy+block correction factors were determined for both models of 192Ir sources currently in clinical use and these vendor-specific correction factors differed by almost 2.6%. For Nucletron sources, this correction factor was 1.026±0.004 (99% Confidence Interval) and for Varian sources it was 1.000±0.007 (99% CI). Reasonable deviations in source positioning within the phantom and the limited resolution of the source timer had insignificant effects on the ability to measure dose. Overall measurement uncertainty of the system was estimated to be ±2.5% for both Nucletron and Varian source audits (95% CI). This uncertainty was sufficient to establish a ±5% acceptance criterion for source strength audits under a formal RPC audit program. Trial audits of eight participating institutions resulted in an average RPC-to-institution dose ratio of 1.000 with a standard deviation of 0.011.

Development of HIF-1α/HIF-1β heterodimerization inhibitors using a novel bioluminescence reporter assay system for in vitro high throughput screening and in vivo imaging

Tumor growth often outpaces its vascularization, leading to development of a hypoxic tumor microenvironment. In response, an intracellular hypoxia survival pathway is initiated by heterodimerization of hypoxia-inducible factor (HIF)-1α and HIF-1β, which subsequently upregulates the expression of several hypoxia-inducible genes, promotes cell survival and stimulates angiogenesis in the oxygen-deprived environment. Hypoxic tumor regions are often associated with resistance to various classes of radio- or chemotherapeutic agents. Therefore, development of HIF-1α/β heterodimerization inhibitors may provide a novel approach to anti-cancer therapy. To this end, a novel approach for imaging HIF-1α/β heterodimerization in vitro and in vivo was developed in this study. Using this screening platform, we identified a promising lead candidate and further chemically derivatized the lead candidate to assess the structure-activity relationship (SAR). The most effective first generation drug inhibitors were selected and their pharmacodynamics and anti-tumor efficacy in vivo were verified by bioluminescence imaging (BLI) of HIF-1α/β heterodimerization in the xenograft tumor model. Furthermore, the first generation drug inhibitors, M-TMCP and D-TMCP, demonstrated efficacy as monotherapies, resulting in tumor growth inhibition via disruption of HIF-1 signaling-mediated tumor stromal neoangiogenesis.

Functional analysis of the Galpha protein, GNA -3, in the development of Neurospora crassa using biochemical and genetic studies

Extracellular signals regulate fungal development and, to sense and respond to these cues, fungi evolved signal transduction pathways similar to those in mammalian systems. In fungi, heterotrimeric G proteins, composed of α, β, and γ subunits, transduce many signals, such as pheromones and nutrients, intracellularly to alter adenylyl cyclase and MAPK cascades activity. ^ Previously, the Gα proteins GNA-1 and GNA-2 were characterized in regulating development in the fungus Neurospora crassa. R. A. Baasiri isolated a third Gα, gna-3, and P. S. Rowley generated Δgna-3 mutants. GNA-3 belongs to a fungal Gα family that regulates cAMP metabolism and virulence. The Δ gna-3 sexual cycle is defective in homozygous crosses, producing inviable spores. Δgna-3 mutants have reduced aerial hyphae formation and derepressed asexual sporulation (conidiation), causing accumulation of asexual spores (conidia). These defects are similar to an adenylyl cyclase mutant, cr-1; cAMP supplementation suppressed Δ gna-3 and cr-1. Inappropriate conidiation and expression of a conidiation gene, con-10, were higher in Δ gna-3 than cr-1 submerged cultures; peptone suppressed conidiation. Adenylyl cyclase activity and expression demonstrated that GNA-3 regulates enzyme levels. ^ A Δgna-1 cr-1 was analyzed with F. D. Ivey to differentiate GNA-1 roles in cAMP-dependent and -independent pathways. Δ gna-1 cr-1 defects were worse than cr-1 and refractory to cAMP, suggesting that GNA-1 is necessary for sensing extracellular CAMP. Submerged culture conidiation was highest in Δgna-1 cr-1, and only high cell density Δgna-1 cultures conidiated, which correlated with con-10 levels. Transcription of a putative heat shock cognate protein was highest in Δgna-1 cr-1. ^ Functional relationships between the three Gαs was analyzed by constructing Δgna-1 Δgna-2 Δ gna-3, Δgna-1 Δgna-3, and Δgna-2 Δgna-3 strains. Δ gna-2 Δgna-3 strains exhibited intensified Δ gna-3 phenotypes; Δgna-1 Δgna-2 Δgna-3 and Δgna-1 Δ gna-3 strains were identical to Δgna-1 cr-1 on plates and were non-responsive to cAMP. The highest levels of conidiation and con-10 were detected in submerged cultures of Δ gna-1 Δgna-2 Δgna-3 and Δgna-1 Δgna-3 mutants, which was partially suppressed by peptone supplementation. Stimulation of adenylyl cyclase is completely deficient in Δgna-1 Δ gna-2 Δgna-3 and Δgna-1 Δ gna-3 strains. Δgna-3 and Δ gna-1 Δgna-3 aerial hyphae and conidiation defects were suppressed by mutation of a PKA regulatory subunit. ^

Seawater carbonate chemistry and early development of the sea urchin Lytechinus variegatus in a laboratory experiment using artificial seawater

Land-based aquaculture facilities often utilize additional bicarbonate sources such as commercial sea salts that are designed to boost alkalinity in order to buffer seawater against reductions in pH. Despite these preventative measures, many facilities are likely to face occasional reductions in pH and corresponding reductions in carbonate saturation states due to the accumulation of metabolic waste products. We investigated the impact of reduced carbonate saturation states (Omega Ca, Omega Ar) on embryonic developmental rates, larval developmental rates, and echinoplutei skeletal morphometrics in the common edible sea urchin Lytechinus variegatus under high alkalinity conditions. Commercial artificial seawater was bubbled with a mixture of air and CO2 gas to reduce the carbonate saturation state. Rates of embryonic and larval development were significantly delayed in both the low and extreme low carbonate saturation state groups relative to the control at a given time. Although symmetry of overall skeletal body lengths was not affected, allometric relationships were significantly different between treatment groups. Larvae reared under ambient conditions had significantly greater postoral arm and overall body lengths relative to body lengths than larvae grown under extreme low carbonate saturation state conditions, indicating that extreme changes in the carbonate system affected not only developmental rates but also larval skeletal shape. Reduced rates of embryonic development and delayed and altered larval skeletal growth are likely to negatively impact larval culturing of L. variegatus in land-based, intensive culture situations where calcite and aragonite saturation states are lowered by the accumulation of metabolic waste products.

The Technology Gap and the Growth of the Firm: A Case Study of China's Mobile-phone Handset Industry

We have examined the way in which local Chinese firms confronted with a technology gap have achieved growth, using the Chinese handset industry as a case study. Chinese local firms have lacked technology, and have therefore turned to outside firms for development, design, and manufacturing, while they themselves have focused on sales and marketing, using their advantage of familiarity with the Chinese market. Consequently, by establishing a growth condition in which their selection of boundaries counterbalances the technology gap they have been able to expand their market share in comparison with foreign firms.

Using the Spectrum Analyzer as an Educational Tool for Mobile Communications

Application of the spectrum analyzer for illustrating several concepts associated with mobile communications is discussed. Specifically, two groups of observable features are described. First, time variation and frequency selectivity of multipath propagation can be revealed by carrying out simple measurements on commercial-network GSM and UMTS signals. Second, the main time-domain and frequency-domain features of GSM and UMTS radio signals can be observed. This constitutes a valuable tool for teaching mobile communication courses.

Vision-based vehicle detection and tracking with a mobile camera using a statistical framework

En esta tesis se aborda la detección y el seguimiento automático de vehículos mediante técnicas de visión artificial con una cámara monocular embarcada. Este problema ha suscitado un gran interés por parte de la industria automovilística y de la comunidad científica ya que supone el primer paso en aras de la ayuda a la conducción, la prevención de accidentes y, en última instancia, la conducción automática. A pesar de que se le ha dedicado mucho esfuerzo en los últimos años, de momento no se ha encontrado ninguna solución completamente satisfactoria y por lo tanto continúa siendo un tema de investigación abierto. Los principales problemas que plantean la detección y seguimiento mediante visión artificial son la gran variabilidad entre vehículos, un fondo que cambia dinámicamente debido al movimiento de la cámara, y la necesidad de operar en tiempo real. En este contexto, esta tesis propone un marco unificado para la detección y seguimiento de vehículos que afronta los problemas descritos mediante un enfoque estadístico. El marco se compone de tres grandes bloques, i.e., generación de hipótesis, verificación de hipótesis, y seguimiento de vehículos, que se llevan a cabo de manera secuencial. No obstante, se potencia el intercambio de información entre los diferentes bloques con objeto de obtener el máximo grado posible de adaptación a cambios en el entorno y de reducir el coste computacional. Para abordar la primera tarea de generación de hipótesis, se proponen dos métodos complementarios basados respectivamente en el análisis de la apariencia y la geometría de la escena. Para ello resulta especialmente interesante el uso de un dominio transformado en el que se elimina la perspectiva de la imagen original, puesto que este dominio permite una búsqueda rápida dentro de la imagen y por tanto una generación eficiente de hipótesis de localización de los vehículos. Los candidatos finales se obtienen por medio de un marco colaborativo entre el dominio original y el dominio transformado. Para la verificación de hipótesis se adopta un método de aprendizaje supervisado. Así, se evalúan algunos de los métodos de extracción de características más populares y se proponen nuevos descriptores con arreglo al conocimiento de la apariencia de los vehículos. Para evaluar la efectividad en la tarea de clasificación de estos descriptores, y dado que no existen bases de datos públicas que se adapten al problema descrito, se ha generado una nueva base de datos sobre la que se han realizado pruebas masivas. Finalmente, se presenta una metodología para la fusión de los diferentes clasificadores y se plantea una discusión sobre las combinaciones que ofrecen los mejores resultados. El núcleo del marco propuesto está constituido por un método Bayesiano de seguimiento basado en filtros de partículas. Se plantean contribuciones en los tres elementos fundamentales de estos filtros: el algoritmo de inferencia, el modelo dinámico y el modelo de observación. En concreto, se propone el uso de un método de muestreo basado en MCMC que evita el elevado coste computacional de los filtros de partículas tradicionales y por consiguiente permite que el modelado conjunto de múltiples vehículos sea computacionalmente viable. Por otra parte, el dominio transformado mencionado anteriormente permite la definición de un modelo dinámico de velocidad constante ya que se preserva el movimiento suave de los vehículos en autopistas. Por último, se propone un modelo de observación que integra diferentes características. En particular, además de la apariencia de los vehículos, el modelo tiene en cuenta también toda la información recibida de los bloques de procesamiento previos. El método propuesto se ejecuta en tiempo real en un ordenador de propósito general y da unos resultados sobresalientes en comparación con los métodos tradicionales. ABSTRACT This thesis addresses on-road vehicle detection and tracking with a monocular vision system. This problem has attracted the attention of the automotive industry and the research community as it is the first step for driver assistance and collision avoidance systems and for eventual autonomous driving. Although many effort has been devoted to address it in recent years, no satisfactory solution has yet been devised and thus it is an active research issue. The main challenges for vision-based vehicle detection and tracking are the high variability among vehicles, the dynamically changing background due to camera motion and the real-time processing requirement. In this thesis, a unified approach using statistical methods is presented for vehicle detection and tracking that tackles these issues. The approach is divided into three primary tasks, i.e., vehicle hypothesis generation, hypothesis verification, and vehicle tracking, which are performed sequentially. Nevertheless, the exchange of information between processing blocks is fostered so that the maximum degree of adaptation to changes in the environment can be achieved and the computational cost is alleviated. Two complementary strategies are proposed to address the first task, i.e., hypothesis generation, based respectively on appearance and geometry analysis. To this end, the use of a rectified domain in which the perspective is removed from the original image is especially interesting, as it allows for fast image scanning and coarse hypothesis generation. The final vehicle candidates are produced using a collaborative framework between the original and the rectified domains. A supervised classification strategy is adopted for the verification of the hypothesized vehicle locations. In particular, state-of-the-art methods for feature extraction are evaluated and new descriptors are proposed by exploiting the knowledge on vehicle appearance. Due to the lack of appropriate public databases, a new database is generated and the classification performance of the descriptors is extensively tested on it. Finally, a methodology for the fusion of the different classifiers is presented and the best combinations are discussed. The core of the proposed approach is a Bayesian tracking framework using particle filters. Contributions are made on its three key elements: the inference algorithm, the dynamic model and the observation model. In particular, the use of a Markov chain Monte Carlo method is proposed for sampling, which circumvents the exponential complexity increase of traditional particle filters thus making joint multiple vehicle tracking affordable. On the other hand, the aforementioned rectified domain allows for the definition of a constant-velocity dynamic model since it preserves the smooth motion of vehicles in highways. Finally, a multiple-cue observation model is proposed that not only accounts for vehicle appearance but also integrates the available information from the analysis in the previous blocks. The proposed approach is proven to run near real-time in a general purpose PC and to deliver outstanding results compared to traditional methods.

Development of Interactive Materials by Engineering Students Using the Descartes Applets.

In a degree course such as Forestry Engineering, the general teaching objectives consist of explaining and helping students to understand the principles of Mechanics. For some time now we have encountered significant difficulties in teaching this subject due to the students' lack of motivation and to their insufficient prior preparation for the topic. If we add to this the discipline's inherent complexity and the students' preconceptions about the subject, these teaching difficulties become considerable. For this reason a series of didactic activities have been introduced sequentially in the teaching of this subject. This work describes the methodology, procedure and results for the action of developing a work project in groups using Descartes software. The results of this experiment can be considered very positive. Some of the critical preconceptions for learning the subject can be corrected, and the tutoring process in the classroom contributes to an improvement in teacherstudent communication. Since this scheme was established, the number of students taking part each academic year has increased, and this is the group with the greatest percentage of passing scores.

A robustness verification system for mobile phone authentication based on gestures using Linear Discriminant Analysis

This article evaluates an authentication technique for mobiles based on gestures. Users create a remindful identifying gesture to be considered as their in-air signature. This work analyzes a database of 120 gestures of different vulnerability, obtaining an Equal Error Rate (EER) of 9.19% when robustness of gestures is not verified. Most of the errors in this EER come from very simple and easily forgeable gestures that should be discarded at enrollment phase. Therefore, an in-air signature robustness verification system using Linear Discriminant Analysis is proposed to infer automatically whether the gesture is secure or not. Different configurations have been tested obtaining a lowest EER of 4.01% when 45.02% of gestures were discarded, and an optimal compromise of EER of 4.82% when 19.19% of gestures were automatically rejected.

Program development using abstract interpretation (and the ciao system preprocessor)

The technique of Abstract Interpretation has allowed the development of very sophisticated global program analyses which are at the same time provably correct and practical. We present in a tutorial fashion a novel program development framework which uses abstract interpretation as a fundamental tool. The framework uses modular, incremental abstract interpretation to obtain information about the program. This information is used to validate programs, to detect bugs with respect to partial specifications written using assertions (in the program itself and/or in system librarles), to genérate and simplify run-time tests, and to perform high-level program transformations such as múltiple abstract specialization, parallelization, and resource usage control, all in a provably correct way. In the case of validation and debugging, the assertions can refer to a variety of program points such as procedure entry, procedure exit, points within procedures, or global computations. The system can reason with much richer information than, for example, traditional types. This includes data structure shape (including pointer sharing), bounds on data structure sizes, and other operational variable instantiation properties, as well as procedure-level properties such as determinacy, termination, non-failure, and bounds on resource consumption (time or space cost). CiaoPP, the preprocessor of the Ciao multi-paradigm programming system, which implements the described functionality, will be used to illustrate the fundamental ideas.

A tutorial on program development and optimization using the Ciao preprocessor

We present in a tutorial fashion CiaoPP, the preprocessor of the Ciao multi-paradigm programming system, which implements a novel program development framework which uses abstract interpretation as a fundamental tool. The framework uses modular, incremental abstract interpretation to obtain information about the program. This information is used to validate programs, to detect bugs with respect to partial specifications written using assertions (in the program itself and/or in system libraries), to generate and simplify run-time tests, and to perform high-level program transformations such as multiple abstract specialization, parallelization, and resource usage control, all in a provably correct way. In the case of validation and debugging, the assertions can refer to a variety of program points such as procedure entry, procedure exit, points within procedures, or global computations. The system can reason with much richer information than, for example, traditional types. This includes data structure shape (including pointer sharing), bounds on data structure sizes, and other operational variable instantiation properties, as well as procedure-level properties such as determinacy, termination, non-failure, and bounds on resource consumption (time or space cost).

Generating context-aware recommendations using banking data in a mobile recommender system

The increasing adoption of smartphones by the society has created a new area of research in recommender systems. This new domain is based on using location and context-awareness to provide personalization. This paper describes a model to generate context-aware recommendations for mobile recommender systems using banking data in order to recommend places where the bank customers have previously spent their money. In this work we have used real data provided by a well know Spanish bank. The mobile prototype deployed in the bank Labs environment was evaluated in a survey among 100 users with good results regarding usefulness and effectiveness. The results also showed that test users had a high confidence in a recommender system based on real banking data.

Improving availability of mobile networks using a cluster routing protocol with redundant cluster head

We show a cluster based routing protocol in order to improve the convergence of the clusters and of the network it is proposed to use a backup cluster head. The use of a event discrete simulator is used for the implementation and the simulation of a hierarchical routing protocol called the Backup Cluster Head Protocol (BCHP). Finally it is shown that the BCHP protocol improves the convergence and availability of the network through a comparative analysis with the Ad Hoc On Demand Distance Vector (AODV)[1] routing protocol and Cluster Based Routing Protocol (CBRP)[2]

Sustainable development using fuzzy logic

Se utiliza la lógica borrosa para elaborar un modelo útil para analizar el desarrollo sostenible de proyectos. The sustainable development is defined as “the development that satisfies needs of the present time without endangering the capacity of future generations to satisfy theirs”. The term “sustainable development” represents that balance between the satisfaction of present needs and the future ones, offering options of technological and social growth for reducing the risks meaning trends of topical increase. The idea of sustainability can be analysed from three perspectives: environmental, social and economic