Development of a multicellular co-culture model of normal and cystic fibrosis human airways in vitro

Cystic fibrosis (CF) is the most common lethal inherited disease among Caucasians and arises due to mutations in a chloride channel, called cystic fibrosis transmembrane conductance regulator. A hallmark of this disease is the chronic bacterial infection of the airways, which is usually, associated with pathogens such as Pseudomonas aeruginosa, S. aureus and recently becoming more prominent, B. cepacia. The excessive inflammatory response, which leads to irreversible lung damage, will in the long term lead to mortality of the patient at around the age of 40 years. Understanding the pathogenesis of CF currently relies on animal models, such as those employing genetically-modified mice, and on single cell culture models, which are grown either as polarised or non-polarised epithelium in vitro. Whilst these approaches partially enable the study of disease progression in CF, both types of models have inherent limitations. The overall aim of this thesis was to establish a multicellular co-culture model of normal and CF human airways in vitro, which helps to partially overcome these limitations and permits analysis of cell-to-cell communication in the airways. These models could then be used to examine the co-ordinated response of the airways to infection with relevant pathogens in order to validate this approach over animals/single cell models. Therefore epithelial cell lines of non-CF and CF background were employed in a co-culture model together with human pulmonary fibroblasts. Co-cultures were grown on collagen-coated permeable supports at air-liquid interface to promote epithelial cell differentiation. The models were characterised and essential features for investigating CF infections and inflammatory responses were investigated and analysed. A pseudostratified like epithelial cell layer was established at air liquid interface (ALI) of mono-and co-cultures and cell layer integrity was verified by tight junction (TJ) staining and transepithelial resistance measurements (TER). Mono- and co-cultures were also found to secrete the airway mucin MUC5AC. Influence of bacterial infections was found to be most challenging when intact S. aureus, B. cepacia and P. aeruginosa were used. CF mono- and co-cultures were found to mimic the hyperinflammatory state found in CF, which was confirmed by analysing IL-8 secretions of these models. These co-culture models will help to elucidate the role fibroblasts play in the inflammatory response to bacteria and will provide a useful testing platform to further investigate the dysregulated airway responses seen in CF.

Evaluation of modern intraocular lenses

Accommodating Intraocular Lenses (IOLs), multifocal IOLs (MIOLs) and toric IOLs are designed to provide a greater level of spectacle independency post cataract surgery. All of these IOLs are reliant on the accurate calculation of intraocular lens power determined through reliable ocular biometry. A standardised defocus area metric and reading performance index metric were devised for the evaluation of the range of focus and the reading ability of subjects implanted with presbyopic correcting IOLs. The range of clear vision after implantation of an MIOL is extended by a second focal point; however, this results in the prevalence of dysphotopsia. A bespoke halometer was designed and validated to assess this photopic phenomenon. There is a lack of standardisation in the methods used for determining IOL orientation and thus rotation. A repeatable, objective method was developed to allow the accurate assessment of IOL rotation, which was used to determine the rotational and positional stability of a closed loop haptic IOL. A new commercially available biometry device was validated for use with subjects prior to cataract surgery. The optical low coherence reflectometry instrument proved to be a valid method for assessing ocular biometry and covered a wider range of ocular parameters in comparison with previous instruments. The advantages of MIOLs were shown to include an extended range of clear vision translating into greater reading ability. However, an increased prevalence of dysphotopsia was shown with a bespoke halometer, which was dependent on the MIOL optic design. Implantation of a single optic accommodating IOL did not improve reading ability but achieved high subjective ratings of near vision. The closed-loop haptic IOL displayed excellent rotational stability in the late period but relatively poor rotational stability in the early period post implantation. The orientation error was compounded by the high frequency of positional misalignment leading to an extensive overall misalignment of the IOL. This thesis demonstrates the functionality of new IOL lens designs and the importance of standardised testing methods, thus providing a greater understanding of the consequences of implanting these IOLs. Consequently, the findings of the thesis will influence future designs of IOLs and testing methods.

Situation-specific cognitive behavioural self-therapy for erroneously suspected allergy or intolerance to a food:a short self-assessment tool

The recall of personal experiences relevant to a claim of food allergy or food intolerance is assessed by a psychologically validated tool for evidence that the suspected food could have caused the adverse symptom suffered. The tool looks at recall from memory of a particular episode or episodes when food was followed by symptoms resulting in self-diagnosis of food allergy or intolerance compared to merely theoretical knowledge that such symptoms could arise after eating the food. If there is detailed recall of events that point to the food as a potential cause of the symptom and the symptom is sufficiently serious, the tool user is recommended to seek testing at an allergy clinic or by the appropriate specialist for a non-allergic sensitivity. If what is recalled does not support the logical possibility of a causal connection between eating that food and occurrence of the symptom, then the user of the tool is pointed to other potential sources of the problem. The user is also recommended to investigate remedies other than avoidance of the food that had been blamed.

Are few-mode fibres a practical solution to the capacity crunch?

In this paper, we compare the nonlinear Shannon capacity of few-mode fibre systems operating with spatial-temporal digital signal processing to the nonlinear Shannon capacity of single-mode fibre systems operating with spectral-temporal digital signal processing. Combining these results with estimates of digital signal processing complexity for each option offers valuable insights to system designers.

HI!MVC: Hierarchical MVC Framework for WEB Applications

This paper presents Hi!MVC, a framework for developing high interactive web applications with a MVC Architecture. Nowadays, to manage, extend and correct web applications can be difficult due to the navigational paradigm they are based on. Hi!MVC framework helps to make these tasks easier. This framework allows building a web based interface, generating each page from the objects that represent its state. Every class to be showed in the interface is associated with two entities: its html representation (view) and its interactions in the view manager (controller). The whole html page is generated by composition of views according to the composition relationship of objects. Interactions between user and application are managed by the controller associated to the view which shows interaction elements (links or forms). Hi!MVC allows building web interface in a hierarchical and distributed way. There are other frameworks and APIs offering MVC architectures to web applications, but we think that they are not applying exactly the same concepts. While they keep on basing their architectures on the navigational paradigm we are offering a new point of view based on an innovator hierarchical model. First, we present the main ideas of our proposal. Next, we expose how to implement it using different Java technologies. Finally, we make a first approach to our hierarchical MVC model. We also compare shortly our proposal with the previously cited technologies.

Probabilistic multiple model neural network based leak detection system:experimental study

This paper presents an effective decision making system for leak detection based on multiple generalized linear models and clustering techniques. The training data for the proposed decision system is obtained by setting up an experimental pipeline fully operational distribution system. The system is also equipped with data logging for three variables; namely, inlet pressure, outlet pressure, and outlet flow. The experimental setup is designed such that multi-operational conditions of the distribution system, including multi pressure and multi flow can be obtained. We then statistically tested and showed that pressure and flow variables can be used as signature of leak under the designed multi-operational conditions. It is then shown that the detection of leakages based on the training and testing of the proposed multi model decision system with pre data clustering, under multi operational conditions produces better recognition rates in comparison to the training based on the single model approach. This decision system is then equipped with the estimation of confidence limits and a method is proposed for using these confidence limits for obtaining more robust leakage recognition results.

Extending Object-Oriented Network Protocols via alternative Transportation Bindings (Web Services over XMPP)

Distributed and/or composite web applications are driven by intercommunication via web services, which employ application-level protocols, such as SOAP. However, these protocols usually rely on the classic HTTP for transportation. HTTP is quite efficient for what it does — delivering web page content, but has never been intended to carry complex web service oriented communication. Today there exist modern protocols that are much better fit for the job. Such a candidate is XMPP. It is an XML-based, asynchronous, open protocol that has built-in security and authentication mechanisms and utilizes a network of federated servers. Sophisticated asynchronous multi-party communication patterns can be established, effectively aiding web service developers. This paper’s purpose is to prove by facts, comparisons, and practical examples that XMPP is not only better suited than HTTP to serve as middleware for web service protocols, but can also contribute to the overall development state of web services.

Connecting social media to e-commerce:cold-start product recommendation using microblogging information

In recent years, the boundaries between e-commerce and social networking have become increasingly blurred. Many e-commerce websites support the mechanism of social login where users can sign on the websites using their social network identities such as their Facebook or Twitter accounts. Users can also post their newly purchased products on microblogs with links to the e-commerce product web pages. In this paper, we propose a novel solution for cross-site cold-start product recommendation, which aims to recommend products from e-commerce websites to users at social networking sites in 'cold-start' situations, a problem which has rarely been explored before. A major challenge is how to leverage knowledge extracted from social networking sites for cross-site cold-start product recommendation. We propose to use the linked users across social networking sites and e-commerce websites (users who have social networking accounts and have made purchases on e-commerce websites) as a bridge to map users' social networking features to another feature representation for product recommendation. In specific, we propose learning both users' and products' feature representations (called user embeddings and product embeddings, respectively) from data collected from e-commerce websites using recurrent neural networks and then apply a modified gradient boosting trees method to transform users' social networking features into user embeddings. We then develop a feature-based matrix factorization approach which can leverage the learnt user embeddings for cold-start product recommendation. Experimental results on a large dataset constructed from the largest Chinese microblogging service Sina Weibo and the largest Chinese B2C e-commerce website JingDong have shown the effectiveness of our proposed framework.

Perceptions of self-testing for chlamydia:understanding and predicting self-test use

Background: Self-testing technology allows people to test themselves for chlamydia without professional support. This may result in reassurance and wider access to chlamydia testing, but anxiety could occur on receipt of positive results. This study aimed to identify factors important in understanding self-testing for chlamydia outside formal screening contexts, to explore the potential impacts of self-testing on individuals, and to identify theoretical constructs to form a Framework for future research and intervention development. Methods: Eighteen university students participated in semi-structured interviews; eleven had self-tested for chlamydia. Data were analysed thematically using a Framework approach. Results: Perceived benefits of self-testing included its being convenient, anonymous and not requiring physical examination. There was concern about test accuracy and some participants lacked confidence in using vulvo-vaginal swabs. While some participants expressed concern about the absence of professional support, all said they would seek help on receiving a positive result. Factors identified in Protection Motivation Theory and the Theory of Planned Behaviour, such as response efficacy and self-efficacy, were found to be highly salient to participants in thinking about self-testing. Conclusions: These exploratory findings suggest that self-testing independently of formal health care systems may no more negatively impact people than being tested by health care professionals. Participants’ perceptions about self-testing behaviour were consistent with psychological theories. Findings suggest that interventions which increase confidence in using self-tests and that provide reassurance of test accuracy may increase self-test intentions.

Uncovering the root cause of ethnic difference in ability testing:differential test functioning, test familiarity and trait optimism as explanations of ethnic group differences

The present research represents a coherent approach to understanding the root causes of ethnic group differences in ability test performance. Two studies were conducted, each of which was designed to address a key knowledge gap in the ethnic bias literature. In Study 1, both the LR Method of Differential Item Functioning (DIF) detection and Mixture Latent Variable Modelling were used to investigate the degree to which Differential Test Functioning (DTF) could explain ethnic group test performance differences in a large, previously unpublished dataset. Though mean test score differences were observed between a number of ethnic groups, neither technique was able to identify ethnic DTF. This calls into question the practical application of DTF to understanding these group differences. Study 2 investigated whether a number of non-cognitive factors might explain ethnic group test performance differences on a variety of ability tests. Two factors – test familiarity and trait optimism – were able to explain a large proportion of ethnic group test score differences. Furthermore, test familiarity was found to mediate the relationship between socio-economic factors – particularly participant educational level and familial social status – and test performance, suggesting that test familiarity develops over time through the mechanism of exposure to ability testing in other contexts. These findings represent a substantial contribution to the field’s understanding of two key issues surrounding ethnic test performance differences. The author calls for a new line of research into these performance facilitating and debilitating factors, before recommendations are offered for practitioners to ensure fairer deployment of ability testing in high-stakes selection processes.

An incremental multilinear system for human face learning and recognition

This dissertation establishes a novel system for human face learning and recognition based on incremental multilinear Principal Component Analysis (PCA). Most of the existing face recognition systems need training data during the learning process. The system as proposed in this dissertation utilizes an unsupervised or weakly supervised learning approach, in which the learning phase requires a minimal amount of training data. It also overcomes the inability of traditional systems to adapt to the testing phase as the decision process for the newly acquired images continues to rely on that same old training data set. Consequently when a new training set is to be used, the traditional approach will require that the entire eigensystem will have to be generated again. However, as a means to speed up this computational process, the proposed method uses the eigensystem generated from the old training set together with the new images to generate more effectively the new eigensystem in a so-called incremental learning process. In the empirical evaluation phase, there are two key factors that are essential in evaluating the performance of the proposed method: (1) recognition accuracy and (2) computational complexity. In order to establish the most suitable algorithm for this research, a comparative analysis of the best performing methods has been carried out first. The results of the comparative analysis advocated for the initial utilization of the multilinear PCA in our research. As for the consideration of the issue of computational complexity for the subspace update procedure, a novel incremental algorithm, which combines the traditional sequential Karhunen-Loeve (SKL) algorithm with the newly developed incremental modified fast PCA algorithm, was established. In order to utilize the multilinear PCA in the incremental process, a new unfolding method was developed to affix the newly added data at the end of the previous data. The results of the incremental process based on these two methods were obtained to bear out these new theoretical improvements. Some object tracking results using video images are also provided as another challenging task to prove the soundness of this incremental multilinear learning method.

ALBA: A Political Tool for Venezuela’s Foreign Policy

Despite its founding by Hugo Chávez on the heels of the failed Free Trade Area for the Americas (FTAA) negotiations which took place November 2003, the Bolivarian Alliance for the Americas (ALBA, as it is known for its Spanish acronym) has evolved into a political tool that uses “social power” to facilitate Venezuela‟s positioning as the leader of the anti-U.S. agenda in the region. Fostering political favors and goodwill through the financing of social development projects, ALBA has created a political environment whereby countries on the take and their respective leaders seem deterred from taking public opposing viewpoints to Chávez. To that end, it has provided billions in economic aid to several nations in Latin American and the Caribbean, winning their favor and support for its policies. To date, ALBA counts on eight member nations. Besides Venezuela, it includes Antigua and Barbuda, Bolivia, Cuba, Dominica, Ecuador, Nicaragua, and Saint Vincent and the Grenadines. It also has several observer nations, among them, Grenada, Haiti, Paraguay, Uruguay, and a non-Latin American country, Syria. Throughout its recent history Venezuela has used its oil wealth to pursue political capital. Under the Chávez government it is doing so as part of a strategic effort countering the U.S. Following Cuba‟s demise in the region as the anti-American socialist camp leader, Chávez is attempting to step into Cuba‟s shoes, picking up where Cuba left off over a decade ago and has used the ALBA as a mechanism to help promote his foreign policy. Relying on its own resources, not those of the Soviet Union as Cuba once did, Venezuela has already shown its influence in the international arena, challenging U.S. positions at the Organization of American States (OAS), the United Nations, and even in matters having little if nothing to do with the region, such as Iran‟s nuclear proliferation. Taking advantage of Venezuela‟s oil prices bonanza, Chávez has been spreading economic aid throughout the region, funding several development projects. From stepping in to buy Bolivia‟s soy beans when the U.S. ceased doing so, to helping finance and construct an airport in Dominica, Venezuela‟s ALBA has provided assistance to many states in the region. As in the past, Venezuela has invested significantly both in time and money in the Caribbean, providing development assistance and oil at a discount to Haiti, St. Kitts and Nevis, and the Dominican Republic, although the latter two are neither member nor observer states of ALBA. The aid Chávez has been spreading around may be coming at a cost. It seems it has begun to cause cracks within the CARICOM community, where ALBA already counts on six of its 15 members, leading experts and leaders in the region to question traditional alliances to each other and the U.S. Yet, ALBA‟s ability to influence through aid is dependent on the Venezuelan economy. Its success hinges on continued Venezuelan oil sales at stable prices and the ability of Chávez to remain in power.

The Use of the Military for Law Enforcement Activities in Central America

Faced with the violence, criminality and insecurity now threatening peace and democratic governance in Central America, the region’s governments have decided to use the Armed Forces to carry out actions in response to criminal actions, looking to improve their performance. Although public demand for including the Armed Forces in these functions takes place within a legally legitimate framework, it is motivated by tangible circumstances such as increased levels of violence, delinquency and crime. Despite being coupled with the perception of institutional weakness within the security and judicial system (particularly police) and the recognition of prestige, efficiency, discipline and severity in fulfilling the Armed Forces’ missions, these arguments are insufficient to legitimize the use of the military as a police force. Within this context, this paper reflects on the implications or consequences of the use of the Armed Forces in duties traditionally assigned to the police in the Central American region with the goal of contributing to the debate on this topic taking place in the Americas. To achieve this end, first we will focus on understanding the actual context in which a decision is made to involve the Armed Forces in security duties in the region. Second, we will examine the effects and implications of this decision on the Armed Forces’ relations within their respective societies. Third and finally, considering this is already a reality in the region, this paper will provide recommendations. The main findings of this research, resulting from the application of an analyticaldescriptive and historically based study, are organized in three dimensions: the political dimension, by implication referring to the relationship between the ultimate political authority and the Armed Forces; the social dimension, by implication the opinion of citizens; and other implications not only affecting the structural and cultural organization of armies and police but also the complementary operational framework within a context of comprehensive response by the State. As a main conclusion, it poses there is an environment conducive to the use of the Armed Forces in citizen’s security, in view of the impact of threats provoked by criminal structures of a military nature currently operating in Central America. However, this participation creates an inevitable social and political impact if implemented in isolation or given a political leading role and/or operational autonomy. This participation poses risks to the institutions of the Armed Forces and the police as well. Finally, this paper identifies an urgent need for the Armed Forces’ role to be more clearly defined with regard to security matters, limiting it to threats that impact States’ governability and existence. Nonetheless, Central American States should seek a COMPREHENSIVE response to current crime and violence, using all necessary institutions to confront these challenges, but with defined roles and responsibilities for each and dynamic coordination to complement their actions.

A Fuzzy Preprocessing Module for Optimizing the Access Network Selection in Wireless Networks

A heterogeneous wireless network is characterized by the presence of different wireless access technologies that coexist in an overlay fashion. These wireless access technologies usually differ in terms of their operating parameters. On the other hand, Mobile Stations (MSs) in a heterogeneous wireless network are equipped with multiple interfaces to access different types of services from these wireless access technologies. The ultimate goal of these heterogeneous wireless networks is to provide global connectivity with efficient ubiquitous computing to these MSs based on the Always Best Connected (ABC) principle. This is where the need for intelligent and efficient Vertical Handoffs (VHOs) between wireless technologies in a heterogeneous environment becomes apparent. This paper presents the design and implementation of a fuzzy multicriteria based Vertical Handoff Necessity Estimation (VHONE) scheme that determines the proper time for VHO, while considering the continuity and quality of the currently utilized service, and the end-users' satisfaction.

A Method for Testing Object Localization as a Function of Eod Amplitude in the Weakly Electric Fish Brachyhypopomus Pinnicaudatus

I would like to thank Dr. Philip Stoddard for his patience and guidance throughout the past four years. He has not only taught me about behavior and electricity, but he has also taught me how to think scientifically. Vielka Salazar for making herself available to answer my questions and to help me with my projects. Montserrat Alfaro for providing me with support under times of frustration. Fabian A. Pal, who has often made himself available when I needed help to finish my projects, for being supportive, and for believing in me and my abilities. Most importantly, I would like to thank my parents who have shown tremendous support and patience during the past years. I would also like to thank the Honors Committee, specially Dr. Richards for taking the time to review my thesis and helping me modify it. Finally, I would like to thank the MARC program for providing me with financial assistance and the opportunity to perform this project.