Basigin and Embigin are members of the immunoglobulin superfamily that function as cell adhesion molecules. Studies of Basigin null mice revealed reproductive sterility, increased pain sensitivity, and blindness. It is thought that the mechanism causing blindness involves misexpression of monocarboxylate transporter 1 (MCT1) in the absence of Basigin. It is known that the transmembrane domain of Basigin interacts with MCT1. In the absence of Basigin, MCT1 does not localize to the plasma membrane of expressing cells and photoreceptor function is disrupted. Studies of the Basigin null mouse brain suggest that MCT1 is properly expressed, which suggests a separate mechanism causes the increased pain sensitivity in these animals, and also that a different protein directs MCT1 to the plasma membrane of expressing cells in mouse brain. Embigin is known to interact with MCT2 in neurons and with MCT1 in erythrocytes. It is not known, however, if Embigin normally interacts with MCT1 in the mouse brain or if Embigin acts to compensate for the lack of Basigin in the Basigin null animals. Therefore, the purpose of this study was to determine if Embigin normally interacts with MCT1, 2, or 4 in the mouse brain and if so, whether the interaction is similar to that between Basigin and MCT1. Expression of Basigin, Embigin, MCT1, MCT2, and MCT4 in mouse brain was assessed via immunoblotting and immunohistochemical analyses. In addition, recombinant protein probes corresponding to the Embigin transmembrane domain were generated for ELISA binding assays using endogenous mouse brain MCTs. It was determined that the proteins in question are rather ubiquitously expressed throughout the mouse brain, and that the cell adhesion molecules Basigin and Embigin may be co-expressed in the same cells as the MCT2 and MCT4 transporter proteins. In addition, it was determined that the Embigin transmembrane domain does not interact with the MCTs. The data therefore suggest that MCTs do not require Basigin or Embigin for plasma membrane expression in mouse brain.

Since the mid-1970s, top managers, politicians, and officials in both public and private institutions have promoted contracting-out services (privatization) as a means of increasing efficiency, flexibility, and quality. The privatization trend has occurred in many public sector organizations particularly in city services and prisons. Public health services are not immune to this trend. Today many county health departments have contracted the provision of public health services like womens health, primary care, and laboratory services. However, very few studies have analyzed the impact of these privatizations on cost, access, and health outcomes. Proponents favoring the private provision of these services argue that private providers are more efficient and can deliver these services at a lower cost. Also, because of better innovation, private providers can even improve quality. However, among opponents there is concern that a for-profit private provider might cut costs that adversely affects the quality of these services. The purpose of this dissertation is to analyze the effects of the privatization of primary care services on cost, access, and health outcomes in nine large counties in the state of Florida. In a survey of county health departments conducted in 1999, 61 out of 67 counties had outsourced at least one service. Primary care was the second most frequently privatized program. Womens health was the program most often privatized by counties. Using mixed models and logistic regression, a comparison was made between large counties that outsourced primary care services and counties that did not. Multiple years of data were obtained from federal and state sources for analysis.

Cattle ranching in Vermilion Parish is a social-techno-ecological system (STES) that is currently vulnerable due to changing social, technological and ecological conditions. In addressing ways to increase the adaptive capacity of cattle ranching in Vermilion Parish, I used a multiple, mixed method approach grounded in a critical constructivist framework. Constructivism is the idea that our relationship to facts is constructed by our social context. It is these perceptions that shape people’s actions. By looking at these perceptions through an emancipatory frame I was able to understand multiple interpretations of meaning, consciously address them, consider how they may have shaped our actions, and then alter those meanings and power relationships. In an effort to increase the adaptive capacity of cattle ranching in Vermilion Parish, my research focused on actions, why people perform those actions, and how to change them. This research connected the physical landscape of the marshes, the individual landscape of perception, and the conceptual landscape of resilience. If resilience is the ability of a system (cattle ranching in vermilion parish) to recover after a disturbance, adaptive capacity is when the actors within the system can influence that system’s resilience. I explored the history of cattle ranching in Vermilion Parish from three different, but overlapping perspectives – environmental, social, and technological. These perspectives compliment the information from interviews and 3CM sessions. These 15 interviews revealed the perception of 11 types of threats facing cattle ranching in Vermilion Parish. The body of literature surrounding resilience theory identifies traits of highly adaptive systems. The recommendations and suggestions outlined in Chapter 6 exist at the intersection of the actors’ perception of specific threats and the decidedly generalized traits of highly adaptive systems. These suggestions were geared towards increasing the adaptive capacity of cattle ranching in Vermilion Parish. Given these layered landscapes and their complexity, my recommendations were subject to feedback loops and long periods of integration. These recommendations contribute to the theoretical foundation detailed in Chapter 3 by identifying specific ways that the actors of this particular system may be able increase their own adaptive capacity. / text

This project is a study of the way that people use language actively to achieve certain ends in communication, the way that they organise their spoken discourse to construct, convincingly, the state of their lives, both ‘internal’ and ‘external’. It does this primarily through an analysis of the systematic properties of the descriptive, communicative and interpretative skills which members use in the accomplishment of the meanings central to everyday existence. More specifically, this project is a study of verbal accounts of, and doctor-patient interaction relating to, clinical depression. The project begins from the premise that most social studies of depression and its diagnosis have been subject to the same problematic treatment of language as a ‘transparent medium’ as the psychiatric frames upon which the modern clinical understanding of depression in the UK is itself based. I aim, in view of this, to demonstrate how hitherto neglected elements in the social analysis of the condition can be revealed with the application of an alternative methodology, a methodology which treats talk-in-interaction as a dynamic and constructive phenomenon rather than a neutral conduit for the passage of information. The empirical data takes the form of a set of General Practitioners from a single practice in the North West talking freely about depression and their experiences of diagnosing it, and actual consultations between these GPs and their patients. Drawing upon Wittgenstein, Ethnomethodology, Discursive Psychology and, particularly, Conversation Analysis this project examines the ways in which doctors and patients construct, negotiate and manage ‘depressive’ meanings in the course of medical interaction, always holding tightly to Wittgenstein’s maxim that practice gives words their significance.

Cancer is the second leading cause of mortality in the United States and the World, therefore, early effective prevention, diagnosis, and therapy is needed. Estrogens play a major role in the initiation and progression of breast cancer. Elevated lifetime exposure to estrogens is associated with an increased risk of developing breast cancer. Estrogens through influencing mitochondria contribute to estrogen induced breast carcinogenesis; however, the exact mitochondrial mechanisms underlying the estrogen carcinogenic effect in breast tissue are not clearly understood. For this dissertation, the mitotoxic and cytotoxic effects of triphenylphosphonium cation (TPP) and Origanum majorana organic extract (OME) as well as PEGylated bioconjugate of OME with TPP (P-OME-TPP) against human breast epithelial and cancer cell lines was investigated. Initially, TPP, a lipophilic cation, was used to check whether an imbalance in mitochondrial bioenergetics, in part, may be responsible for estrogen induced growth of breast cancer. The results showed that exposure of estrogen-dependent MCF-7 cells to 17 β-estradiol (E2) induced the metabolic activity, proliferation, mitochondrial bioenergetics, DNA damage, and formation of cellular and mitochondrial reactive oxidant species (ROS). These E2-induced endpoints were inhibited by co-treatment with TPP, indicating mitochondrial mechanisms, in part, may contribute to the development of breast cancer. Furthermore, O. majorana, widely used in the Middle East as a culinary aromatic medicinal herb, has been shown to possess an extensive range of biological activity including antioxidant, anti-inflammatory, and anti-tumor growth effects. Interestingly, the anticancer potential of O. majorana against breast cancer remains largely unexplored; therefore, the anticancer effect of O. majorana on breast cell lines was investigated. The results showed that E2-induced metabolic activity and growth were inhibited by OME in MCF-7 cells. The results also demonstrated that synthesized P-OME-TPP conjugate, compared to OME, was far more effective in exerting its cytotoxic effect through the inhibition of growth and mitochondrial metabolic activity in both highly metastatic, triple negative MDA-MB-231 and estrogen-dependent MCF-7 breast cancer cells. Altogether, these findings offer a new perspective on the utility of mitochondria-targeted lipophilic TPP cation and the potential of O. majorana extract to be developed as a new therapy against breast tumors.

Human essential hypertension affects over 75 million people in the United States, and can lead to death due to its several serious health complications such as hypertension-related cardiovascular disease. The purpose of this research was to understand how hypertension could cause physiological changes to the microcirculation, specifically the PO2 dependence of oxygen consumption (VO2) in skeletal muscle of normotensive and hypertensive rats. The Spontaneously Hypertensive Rat (SHR) strain was used as the diseased model, and Wistar-Kyoto (WKY) rats were used as controls to conduct this study. The SHR strain develops hypertension between 5-6 weeks after birth with an average systolic blood pressure of 150 mmHg. By arresting blood flow using an objective-mounted inflatable airbag, PO2 measurements were obtained along with an oxygen disappearance curve (ODC), which was used to calculate VO2 over various ranges of physiological PO2 values. PO2 and VO2 curves were analyzed based on Hill’s equation to fit the data and describe the PO2 dependence of VO2. When compared to the healthy Wistar-Kyoto rats, the SHRs exhibited a higher Vmax, or maximum rate of oxygen consumption. The average maximal rate of consumption by the hypertensive animal models could be a consequence of a “mitochondrial uncoupling” or some disconnect in the mitochondrial oxygen consumption and the normal corresponding ATP production. In conclusion, this project demonstrated that in situ muscle tissue from hypertensive and normotensive rats had a PO2 dependence of oxygen consumption over a wide range of physiological PO2 values and the hypertensive rats consumed oxygen at a higher maximal rate.

Since its beginnings in 1974, the Automated Clearing House (ACH) network has grown into one of the largest, safest, and most efficient payment systems in the world. An ACH transaction is an electronic funds transfer between bank accounts using a batch processing system. Currently, the ACH Network moves almost $43 trillion and 25 billion electronic financial transactions each year. With the increasing movement toward an electronic, interconnected and mobile infrastructure, it is critical that electronic payments work safely and efficiently for all users. ACH transactions carry sensitive data, such as a consumer's name, account number, tax identification number, account holder name, address, or social security number. ACH fraud consists of the theft of funds through the Automated Clearing House financial transaction network (Accounts Receivable & Order-to-Cash Network, 2012). If the transactions are intercepted by fraudulent activities, either during transit or during rest, the sensitive customer data can be used to steal the transferred funds, which can cause financial and reputational damage to ACH network participants and consumers. Even though the National Automated Clearing House Association (NACHA) requires ACH participants to use commercially reasonable encryption and authentication procedures, the risks associated with employee error or negligence, physical theft, and insider theft of data remain substantial. The ACH network that handles 40 billion transactions annually has consumer and corporate financial information. As the ACH network emerges as a prominent payment channel, proactive steps must be taken to guarantee consumer safety. The primary research question “How can opportunities to commit ACH fraud by insiders be inhibited by masking sensitive data in the ACH transactions life cycle?” is addressed employing design science research methodology with special focus on this specific question: Will use of Multi-step tokens in life cycle of ACH transactions lower the risk of sensitive data exposure? To demonstrate the extent to which the Multi-step tokens in the life cycle of ACH transactions lower the risk of sensitive data exposure, the following two sub-questions will be answered: • How to model and simulate sensitive data exposure risk in current ACH transaction life cycle? • How to model and simulate sensitive data exposure risk in the multi-step tokenized ACH transaction life cycle? The research findings through proof of concept simulations confirm that sensitive consumer personal identifiable information shared in ACH network can be made more secure from insider threat opportunities by multi-step tokenization of ACH data. In the to-be system, the real account number will not be used to post the actual financial transaction. Only tokenized account number will be used by RDFI (Receiving Depository Financial Institution) to post the financial transaction. Even if the ODFI (Originating Depository Financial Institution) initiate the financial transaction using real account number, RDFI will reject the transaction back to the originator to resend the transaction using the token value. For the same account number, RDFI will have different token values based on SEC (Standard Entry Class) code, origin, ODFI, transaction type etc. The account token value will be generated only if ODFI sends a token request separately to RDFI in a multi-step manner. The research findings suggest that multi-step tokenization can be used to generate and validate unique transaction path as a function of the transaction origin number, originating depository financial institution, Standard Entry class, Receiving depository financial institution and account number. Even if the account or token value gets misplaced, the data will be of no use to the person having the information. The cipher can be further strengthened by including additional unique ACH data elements. The findings stem from proof of concept development and testing of conceptual, empirical and simulated models of current ACH network, insider breach scenarios, and multi-step tokenized systems. The study findings were augmented by running different model scenarios and comparing the outputs for breaches, network traffic and costs. The study findings conclude with an implementation proposal of the findings in the ACH network and opportunities for further research on the topic.

The successful design, implementation, deployment, and use of mobile software applications is rare. While many mobile apps are developed, few succeed. This design science research project builds and evaluates CrashApp™, a mobile application that connects lawyers and clients before, during, and after car accidents. The effective, widespread use of this app depends on satisfying the needs of three groups of stakeholders – the end-users (clients), the owners (lawyers), and the software developers. The research objective is to investigate the key differences among the three stakeholder groups on evaluation criteria for mobile app success. Evaluation strategies and methods are selected to collect data that measures each group’s satisfaction with the constructed application artefact. Research contributions are the identification of multiple stakeholder groups and the ability to design rich evaluation strategies that provide measures of application success. Practice contributions are the design and development of a useful mobile app that provides needed services to the client and effective client connections for the law firm to interact with the clients. The project produced an instantiation of the design artefact CrashApp™ mobile application, which was evaluated with a naturalistic evaluation approach, including the following methods and techniques: focus groups, focused surveys, usability surveys, and real life tests and assessments.

Abstract In recent years the number of attacks on critical infrastructure has not only increased substantially but such attacks have also shown higher sophistication. With the increasing interconnection of information systems it is common that critical systems communicate and share information outside an organization’s networks for many different scenarios. In the academic world as well as in existing security implementations, focus is placed on individual aspects of the security process - for example, network security, legal and regulatory compliance and privacy - without considering the process on the whole. This work focuses on solving this security gap of critical infrastructure by providing solutions for emerging attack vectors. Using design science research methods, a model was developed that seeks to combine these individual security aspects to form a complete security management process (SMP). This SMP introduces, among others theories of security topics, recommended best practices and a security organization structure. An instantiation of the SMP model was implemented for a large-scale critical infrastructure. This work introduces the system developed, its architecture, personnel hierarchy and security relevant workflows. Due to employed surveillance networks, specialized requirements for bandwidth utilization while preserving data security were present. Thus algorithms for solving these requirements are introduced as sub-constructs. Other focus points are the managerial aspects of sensors deployed in surveillance networks and the automatic processing of the sensor data to perform data fusion. Algorithms for both tasks were developed for the specific system but could be generalized for other instantiations. Verification was performed by empirical studies of the instantiation in two separate steps. First the instantiation of the SMP was analyzed as a whole. One of the main quality factors of the instantiation is incident response time, especially in complex scenarios. Consequently measurements of response times when handling incidents compared to the traditional system were performed in different scenarios. System usability was then verified by user acceptance tests of operators and administrators. Both studies indicate significant improvements compared to traditional security systems. Secondly, the sub-constructs communication optimizations and the data fusion algorithm were verified showing substantial improvements in their corresponding areas. / Tiivistelmä Viime vuosina kriittisiin infrastruktuureihin on kohdistunut merkittävästi aiempaa enemmän erilaisia hyökkäyksiä. Tietojärjestelmien välisten yhteyksien lisääntymisen myötä myös kriittiset järjestelmät kommunikoivat nykyään keskenään ja jakavat tietoa organisaation sisäisten verkkojen ulkopuolellekin. Akateemisessa tutkimuksessa ja turvajärjestelmien toteutuksissa on huomio kohdistettu turvallisuutta koskevien prosessien yksittäisiin piirteisiin, kuten esimerkiksi verkkojen turvallisuuteen, lakien ja sääntöjen noudattamiseen ja yksityisyyteen, miettimättä prosesseja kokonaisuutena. Väitöstutkimuksen tavoitteena on ollut ratkaista tämä kriittisten infrastruktuurien turvallisuusongelma tarjoamalla ratkaisuja, jotka paljastavat mahdollisia hyökkäysreittejä. Väitöstutkimuksessa kehitettiin suunnittelutieteellisen tutkimuksen avulla lähestymistapa, joka yhdistää yksittäiset turvallisuusnäkökohdat ja muodostaa näin turvallisuuden kokonaishallinnan prosessin mallin. Malli hyödyntää erilaisia turvallisuusteorioita, suositeltuja hyviä käytäntöjä ja turvallisen organisaation rakennemalleja. Mallista kehitettiin esimerkkitoteutus laajamittaista kriittistä infrastruktuuria varten. Tämä väitöskirja esittelee kehitetyn järjestelmän, sen arkkitehtuurin, henkilökuntahierarkian ja turvallisuuden kannalta relevantit työnkulkukaaviot. Työssä huomioitiin laajan valvontaverkoston edellyttämät erityisvaatimukset tilanteessa, jossa tietoturvallisuuden säilyttäminen oli tärkeää. Myös näiden erityisvaatimuksiin liittyvien mallin osien ratkaisualgoritmit esitetään. Muita työn tuotoksia ovat hallinnolliset näkökulmat, jotka on huomioitava, kun valvonnalle tärkeitä sensoreita hallinnoidaan ja sensorien tuottamaa dataa yhdistellään. Algoritmit luotiin esimerkkiympäristöön, mutta niitä on mahdollista soveltaa muihinkin toteutuksiin. Toteutuksen oikeellisuuden todentamisessa käytettiin empiirisiä ympäristöjä kahdessa eri vaiheessa. Ensiksi turvallisuusprosessin kokonaishallinnan malli analysoitiin kokonaisuutena. Merkittävä laatutekijä oli havaintotapahtuman vasteaika erityisesti monimutkaisissa skenaarioissa. Siksi työssä esitellään eri skenaarioiden avulla tapahtumanhallinnan vasteaikojen mittauksia suhteessa perinteisiin järjestelmiin. Tämän jälkeen järjestelmän käytettävyys todennettiin operaattorien ja hallintohenkilöstön kanssa tehtyjen hyväksymistestien avulla. Testit osoittivat huomattavaa parannusta verrattuna perinteisiin turvajärjestelmiin. Toiseksi verifiointiin mallin osien kommunikaation optimointi ja algoritmien toimivuus erikseen ja niissäkin ilmeni huomattavia parannuksia perinteisiin järjestelmiin verrattuna.

M.A. (Political Science) / Recent studies in a diversity of social science disciplines indicate the growing importance of cross-cultural attitude surveys; and the central theme of this dissertation is the methodological implications thereof. This study aims (1) to make a contribution to the relatively small number of studies ,in South-Africa on the subject of Political Science research methodology, and' (2) to analyze systematically the methodological problems of cross-cultural research into political attitudes. The research problem was formulated as follows: How should cross-cultural survey research of a political nature be planned, structured and conducted to ensure reliability, validity and objectivity? The focus throughout the dissertation, was on two dimensions of the research process namely (1) research design and (2) data-collection, the latter being further divided in two main categories: instrument construction and instrument implementation. A theoretical framework (Chapter 2) was developed incorporating the different methodological factors to be taken into: account when designing and implementing a research project. This framework was applied to (1) survey research in general (Chapter 3), and (2) cross-cultural political attitude surveys (Chapter 4), Special attention was given to research conducted in South Africa. The last chapter contains (1) a summary of the most important considerations relevant to cross-cultural attitude research, and (2) an overview of the main problems of cross-cultural political attitude research in South Africa. The main finding of the study is that in cross-cultural attitude research in South Africa, too little attention is given to methodological issues - both in designing and implementing research projects. In particular, the explication of methodological issues and procedures in research articles and reports is recommended.