Eine Dysregulation neuro-immunologischer Interaktionen und eine veränderte Stressantwort werden als Teil der Pathogenese der Rheumatoiden Arthrtitis (RA) diskutiert. Dabei könnte eine autonome Dysfunktion eine wichtige Rolle spielen. Um dem nachzugehen, wurde an Patienten mit unterschiedlicher Krankheitsaktivität die Aktivität des autonomen Nervensystems in Ruhe und in Reaktion auf minor Stress sowie erstmals deren Assoziation zu Gen-Polymorphismen β2- adrenerger Rezeptoren (β2ARs), welche sich u.a. auf Immunzellen befinden, untersucht. Zur Bestimmung autonomer Aktivität wurde an 112 RA- und 48 Osteoarthrose-Patienten die sympathische Hautantwort (SSR) sowie die Herzratenvariabilität (HRV) getestet. Standardisierte Stresstests kamen zur Anwendung. Eine Allel-spezifische Polymerase-Ketten-Reaktion diente zur Ermittlung der Varianten des β2ARs an Aminosäureposition 16, 27 und 164. Es konnte gezeigt werden, dass die autonome Aktivität bei RA in Ruhe durch eine signifikant erhöhte Herzfrequenz, ein Überwiegen des Sympathikus im Verhältnis zum Parasympathikus sowie eine signifikant erniedrigte Parasympathikusaktivität gekennzeichnet ist. Die Stressantwort bei RA war signifikant häufiger pathologisch als bei der Kontrollgruppe und durch signifikante Hypoaktivität und Hyporeaktivität des Parasympathikus sowie eine signifikant erniedrigte HRV charakterisiert. Das Zusammenspiel beider Schenkel des ANS erschien gestört. Die SSR-Werte befanden sich im Normbereich. Schlechtere Werte waren jedoch signifikant mit hohem CRP assoziiert. Desweiteren war Heterozygotie an allen Gen-Positionen der β2ARs signifikant mit RA assoziiert. Gln27Gln (signifikant häufiger für Gesunde) ging mit signifikant niedrigerer Krankheitsaktivität einher. Starkes Überwiegen des SNS in Ruhe sowie niedrige parasympathische Aktivität (HRV-Daten) waren signifikant mit hoher Krankheitsaktivität assoziiert. Zusammenfassend weist die vorliegende Arbeit auf eine autonome Dysregulation bei Patienten mit RA hin, was mit klinischen Parametern der RA assoziiert war. Weiterhin unterstreicht die Studie die Assoziation von β2AR Polymorphismen mit einer RA und liefert einen weiteren Beitrag zum Verständnis der Pathogenese dieser Erkrankung.

Motivation Hypertension is a pertinent health problem for urban black African men (hereafter referred to as African). Sympathetic hyperactivity and a dominant α-adrenergic response pattern have both been implicated as contributing factors to their poor cardiovascular health. In addition to the deleterious effect of neurogenic hypertension on target organs, sympathetic hyperactivity may promote the accelerated progression of left ventricular hypertrophy and structural vascular disease. Aim The overarching aim of this study is to scrutinize autonomic control of the cardiovascular system in a cohort of urban African and Caucasian men during a mental challenge. Associations were investigated between potential sympatho-vagal imbalance, blood pressure and target organ damage markers to determine cardiovascular risk in ethnic male groups. Methodology The SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) study involved the participation of 200 male teachers (99 African and 101 Caucasian) in the Kenneth Kaunda Education District of the North-West Province, South Africa. Of the participant group, HIV-infected (13 African) and clinically confirmed diabetics (1 Caucasian and 6 African men) were excluded from further analyses. Stratification was based on ethnicity and further as indicated through statistical interaction effects. Cardiovascular and autonomic responses were assessed during rest and on stressor exposure (cold pressor test and Stroop colour-word conflict test). Autonomic measures included baroreceptor sensitivity (BRS), 3-methoxy-4-hydroxy-phenylglycol (MHPG) and nitric oxide metabolite (NOx) levels. Cardiovascular variables consisted of blood pressure, cardiac output, stroke volume, total peripheral resistance, heart rate, arterial compliance and ST-segment from the 12-lead electrocardiogram. Markers of target organ damage included the Cornell product (indication of left ventricular hypertrophy) and carotid intima-media thickness as indication of structural vascular disease. Means and proportions were compared by means of standard t-test and Chi-square test, respectively. Significant differences of mean cardiovascular and autonomic measures between ethnic male groups were also determined through analysis of covariance. Uni- and multivariate regression analyses were employed to demonstrate associations between target organ damage, cardiovascular and autonomic markers. Results and conclusion of each manuscript To assess autonomic nervous system and cardiovascular function as well as target organ damage, we clearly focussed on responses where our participants were challenged. Markers of autonomic responses assessed were baroreceptor sensitivity, 3-methoxy-4-hydroxyphenylglycol and nitric oxide metabolites.  The first manuscript (Chapter 2) focused on left ventricular hypertrophy as marker of target organ damage, blood pressure and baroreceptor sensitivity as marker of autonomic function. The objective was to determine whether BRS was significantly lower in African men than in the Caucasian men. Furthermore, the possible association between attenuation of BRS and increased levels of ambulatory blood pressure as well as left ventricular hypertrophy was investigated in these population groups. Results revealed that the African men had significantly lower BRS stress responses. This attenuated BRS profile was coupled with dominant α-adrenergic response patterns, which was associated with an elevation of ambulatory blood pressure. BRS attenuation (rest and stress response) was not associated with left ventricular hypertrophy. It was concluded that lower BRS, especially during stress, may pose a significant health threat for urban African men regarding the development or promotion of α-adrenergic-driven hypertension and higher cardiovascular disease risk.  The aim of the second sub-study (Chapter 3) was to investigate possible associations between structural vascular disease (carotid intima-media thickness as marker), autonomic function (MHPG as marker) and nocturnal blood pressure in the African and Caucasian men. Results showed a higher prevalence of nocturnal hypertension in the African men, with night-time blood pressure significantly higher compared to the Caucasian men. In the African and Caucasian men, carotid intima-media thickness was linearly predicted by nocturnal systolic and diastolic blood pressure respectively. In conclusion, no associations were demonstrated between MHPG and carotid intimamedia thickness or between MHPG and nocturnal blood pressure. Elevated nocturnal blood pressure evidently seems to promote structural vascular disease in this cohort of urban African and Caucasian men.  The aim of the third manuscript presented in Chapter 4, was to investigate bioavailability of NO during mental challenge (autonomic function marker) and the possible association with structural vascular disease (carotid intima-media thickness as marker). In the African men, an attenuated NOx response was demonstrated to the Stroop colour-word conflict test. After stratification into high and low NOx response groups, in the African men with a low NOx response enhanced α-adrenergic with significant STsegment depression responses was demonstrated indicating reduced myocardial oxygen supply during mental stressor exposure. Only in the African men, a ST-segment depression was significantly associated with structural vascular disease. It was concluded that the African men demonstrated a vulnerable cardiovascular profile. In this cohort of African men, the significant association between structural vascular disease and myocardial ischemia may particularly indicate a possible higher risk for future cardiovascular events. General conclusion Through the assessment of autonomic and cardiovascular responses a possible higher cardiovascular risk was demonstrated in the African men. In this cohort sympathetic hyperactivity was evident, coupled with dominant vascular response patterns and reduced myocardial oxygen supply during mental stress exposure. Based on these findings, this population group’s risk for accelerated target organ damage, as well as for future cardiovascular events, appear significantly higher than those of the Caucasian male cohort. / Thesis (PhD (Physiology))--North-West University, Potchefstroom Campus, 2013.

Motivation Hypertension is a pertinent health problem for urban black African men (hereafter referred to as African). Sympathetic hyperactivity and a dominant α-adrenergic response pattern have both been implicated as contributing factors to their poor cardiovascular health. In addition to the deleterious effect of neurogenic hypertension on target organs, sympathetic hyperactivity may promote the accelerated progression of left ventricular hypertrophy and structural vascular disease. Aim The overarching aim of this study is to scrutinize autonomic control of the cardiovascular system in a cohort of urban African and Caucasian men during a mental challenge. Associations were investigated between potential sympatho-vagal imbalance, blood pressure and target organ damage markers to determine cardiovascular risk in ethnic male groups. Methodology The SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) study involved the participation of 200 male teachers (99 African and 101 Caucasian) in the Kenneth Kaunda Education District of the North-West Province, South Africa. Of the participant group, HIV-infected (13 African) and clinically confirmed diabetics (1 Caucasian and 6 African men) were excluded from further analyses. Stratification was based on ethnicity and further as indicated through statistical interaction effects. Cardiovascular and autonomic responses were assessed during rest and on stressor exposure (cold pressor test and Stroop colour-word conflict test). Autonomic measures included baroreceptor sensitivity (BRS), 3-methoxy-4-hydroxy-phenylglycol (MHPG) and nitric oxide metabolite (NOx) levels. Cardiovascular variables consisted of blood pressure, cardiac output, stroke volume, total peripheral resistance, heart rate, arterial compliance and ST-segment from the 12-lead electrocardiogram. Markers of target organ damage included the Cornell product (indication of left ventricular hypertrophy) and carotid intima-media thickness as indication of structural vascular disease. Means and proportions were compared by means of standard t-test and Chi-square test, respectively. Significant differences of mean cardiovascular and autonomic measures between ethnic male groups were also determined through analysis of covariance. Uni- and multivariate regression analyses were employed to demonstrate associations between target organ damage, cardiovascular and autonomic markers. Results and conclusion of each manuscript To assess autonomic nervous system and cardiovascular function as well as target organ damage, we clearly focussed on responses where our participants were challenged. Markers of autonomic responses assessed were baroreceptor sensitivity, 3-methoxy-4-hydroxyphenylglycol and nitric oxide metabolites.  The first manuscript (Chapter 2) focused on left ventricular hypertrophy as marker of target organ damage, blood pressure and baroreceptor sensitivity as marker of autonomic function. The objective was to determine whether BRS was significantly lower in African men than in the Caucasian men. Furthermore, the possible association between attenuation of BRS and increased levels of ambulatory blood pressure as well as left ventricular hypertrophy was investigated in these population groups. Results revealed that the African men had significantly lower BRS stress responses. This attenuated BRS profile was coupled with dominant α-adrenergic response patterns, which was associated with an elevation of ambulatory blood pressure. BRS attenuation (rest and stress response) was not associated with left ventricular hypertrophy. It was concluded that lower BRS, especially during stress, may pose a significant health threat for urban African men regarding the development or promotion of α-adrenergic-driven hypertension and higher cardiovascular disease risk.  The aim of the second sub-study (Chapter 3) was to investigate possible associations between structural vascular disease (carotid intima-media thickness as marker), autonomic function (MHPG as marker) and nocturnal blood pressure in the African and Caucasian men. Results showed a higher prevalence of nocturnal hypertension in the African men, with night-time blood pressure significantly higher compared to the Caucasian men. In the African and Caucasian men, carotid intima-media thickness was linearly predicted by nocturnal systolic and diastolic blood pressure respectively. In conclusion, no associations were demonstrated between MHPG and carotid intimamedia thickness or between MHPG and nocturnal blood pressure. Elevated nocturnal blood pressure evidently seems to promote structural vascular disease in this cohort of urban African and Caucasian men.  The aim of the third manuscript presented in Chapter 4, was to investigate bioavailability of NO during mental challenge (autonomic function marker) and the possible association with structural vascular disease (carotid intima-media thickness as marker). In the African men, an attenuated NOx response was demonstrated to the Stroop colour-word conflict test. After stratification into high and low NOx response groups, in the African men with a low NOx response enhanced α-adrenergic with significant STsegment depression responses was demonstrated indicating reduced myocardial oxygen supply during mental stressor exposure. Only in the African men, a ST-segment depression was significantly associated with structural vascular disease. It was concluded that the African men demonstrated a vulnerable cardiovascular profile. In this cohort of African men, the significant association between structural vascular disease and myocardial ischemia may particularly indicate a possible higher risk for future cardiovascular events. General conclusion Through the assessment of autonomic and cardiovascular responses a possible higher cardiovascular risk was demonstrated in the African men. In this cohort sympathetic hyperactivity was evident, coupled with dominant vascular response patterns and reduced myocardial oxygen supply during mental stress exposure. Based on these findings, this population group’s risk for accelerated target organ damage, as well as for future cardiovascular events, appear significantly higher than those of the Caucasian male cohort. / Thesis (PhD (Physiology))--North-West University, Potchefstroom Campus, 2013.

Communication network technologies have been evolving exponentially in the late decades. These innovations increase the network capabilities and open new horizons to creating novel and original services. The heterogeneity in equipment qualifications increases the level of complexity in the technological advancement. In such environment, service management has become an everyday challenge to service providers. Important efforts have been deployed to innovate in the exploitation of intelligent devices in the home and other private locations. In this Thesis, we propose a framework for self-configuration of devices within Hone Area Networks. We propose a device self-configuration architecture based on IBM Monitor-Analyze-Plan-Execute using Knowledge autonomic control loop. To prove the validity of our system architecture and support its applicability, we developed a prototype system that gives a general control loop implementation for device self-configuration using the CPE WAN Management Protocol. A video streaming scenario is implemented and used to evaluate validity our framework.

Computing systems' complexity appears to be approaching the limits of human capabilities. To cope with the rapidly growing complexity of operating, managing and integrating computing systems, one of the most promising options is Autonomic Systems, which are computing systems that can manage themselves given high-level objectives from administrators. Self-management means that the system self configures at run time to increase responsiveness and agility, self-heals to improve business resiliency, self-optimizes to improve operational efficiency and self-protects itself from malicious attacks. While traditional approaches to computer systems are often centralized and hierarchical, Autonomic Systems are highly distributed with complex connectivity and interactions, rendering centralized management schemes infeasible. In this thesis, we describe the design and implementation of a decentralized architecture based on mobile multi-agent systems-an approach to building Autonomic Systems. Based on the proposed architecture, we developed a prototype application-an electronic marketplace, which achieves a set of desired features of Autonomic Systems such as autonomy, hiding complexity and self-healing. We put forth Autonomic Systems, a self-managing distributed computing system, as a new and promising application domain for multi-agent system ideas and argue that an Agent-based approach is well suited to construct Autonomic Systems.

Autonomic computing has become more prevalent and, hence, its evaluation is becoming more important. In this thesis, we address the issue of evaluating the software architecture of self-healing applications with respect to the changes and adaptation over long periods of time. To facilitate this evaluation, we developed an analysis and reasoning framework for the architecture of self-healing systems. The reasoning framework is based on attribute-based architectural styles (ABASs) and is tailored to selected quality attributes. When an autonomic system evolves, the proposed reasoning framework can be used to re-analyze the system and verify certain quality attributes. The explicitly available relationship between architecture and quality attributes not only helps in documenting the current architecture design, but also allows developers to reuse the architectural analysis during long-term evolution when the original system designers are long gone. Hence, the proposed framework can facilitate both design and maintenance of self-healing systems. In order to develop the analysis and reasoning framework, we identified key quality attributes for self-healing systems. We have also defined new autonomic-specific quality attributes for the self-healing systems, which includes support for detecting anomalous system behaviour, support for failure diagnosis, support for simulation of expected behaviour, support for differencing between expected and actual behaviour, and support for testing of correct behaviour. Further, we customized the ISO 9126 quality model to the quality requirements of self-healing systems, considering both traditional attributes as well as newly defined autonomic-specific attributes.

Present-day IT environments are complex, heterogeneous tangles of hardware, middleware and software from multiple venders that are becoming increasingly difficult to integrate, install, configure, tune and maintain. In order to combat this increasing level of complexity, automating many of the functions associated with computing today seems to be a reasonable solution. IBM, inspired by the autonomic nervous system of the human body which regulates without any conscious intervention, chose to call this paradigm Autonomic Computing-computing using adaptive and self-managing systems with minimal human intervention. Autonomic computing poses several research challenges. In an endeavor to hide complexity, autonomic systems give up, to a certain extent, accountability to the user. Consequently, autonomic systems exhibit fewer cause and effect relationships and therefore engender trust and adoption issues. In other words, the system itself takes over control whereby it may or may not operate as per user expectations during its operation. Our goal is to develop a framework of trust that will be useful for developers of autonomic computing applications or self-managed systems dealing with trust issues. Our approach gathers key trust topics, issues, nomenclature, taxonomies, and user task models from the literature which are then distilled and pruned to form our own trust framework which is intended to aid developers in the design of self-managed systems. We then use IBM`s Tivoli provisioning system, which is one of the most successful autonomic systems, to consolidate our framework. Finally, we evaluate our framework by trying to identify the strengths and weaknesses with respect to trust of self-managed systems by performing a case study on a non-deployed autonomic e-Commerce prototype.

Advances in technologies have made an unprecedented range and variety of computing resources available. A number of fields have sought to take maximum advantage of these resources, with grid computing being one of the more successful. However, the increasing complexity of these heterogeneous, distributed systems has compromised users’ ability to manage them effectively. Autonomic computing, which seeks to hide the complexity of systems by making them self-managing, offers a potential solution. In order to produce autonomic managers for grid systems, realistic input is required for development and testing. This thesis proposes a model that can be used to provide simulated input, utilizing existing system logs. The simulator adheres to the standards and specifications recognized in both autonomic and grid services, and provides the detailed, accurate information that is required by developers.

Web applications have become increasingly popular in recent years. They are widely used in security-critical areas, such as financial, medical, and military systems. Meanwhile, the number and sophistication of attacks against web applications have increased rapidly. It is important for organizations and companies to add security functions to existing web application servers in order to maintain the confidentiality of critical information. One common approach to protect web systems is to build an Intrusion Detection and Prevention System (IDPS). In this thesis, we propose an IDPS framework to detect and prevent web attacks by employing Aspect-Oriented Programming (AOP) and Autonomic Computing (AC) technologies. This framework can also be used to discover whether a web application under protection has abilities to prevent certain web attacks itself. We developed a prototyping tool to implement the functionality of this framework partially. We evaluated this tool on two Java web applications to detect and prevent Cross Scripting Site (XSS) and Structured Query Language (SQL) Injection, which are two of the most common web attacks. The experimental results show that the prototyping tool based on AOP and AC technologies can be applied to detect and prevent the two common web attacks effectively.

Self-adaptive and self-managing systems optimize their own behaviour according to high-level objectives and constraints. One way for human administrators to effectively specify goals for such optimization problems is using policies. Over the past decade, researchers produced various approaches, models and techniques for policy specification in different areas including distributed systems, communication networks, web services, autonomic computing, and cloud computing. Research challenges range from characterizing policies for ease of specification in particular application domains to categorizing policies for achieving good solution qualities for particular algorithmic techniques. The contributions of this thesis are threefold. Firstly, we give a mathematical formulation for each of the three policy types, action, goal and utility function policies, introduced in the policy framework by Kephart and Walsh. In particular, we introduce a first precise characterization of goal policies for optimization problems. Secondly, this thesis introduces a mathematical framework that adds structure to the underlying optimization problem for different types of policies. Structure is added either to the objective function or the constraints of the optimization problem. These mathematical structures, imposed on the underlying problem, progressively increase the quality of the solutions obtained when using the greedy optimization technique. Thirdly, we show the applicability of our framework through case studies by analyzing several optimization problems encountered in self-adaptive and self-managing systems, such as resource allocation, quality of service management, and Service Level Agreement (SLA) profit optimization to provide quality guarantees for their solutions. Our approach combines the algorithmic results by Edmonds, Fisher et al., and Mestre, and the policy framework of Kephart and Walsh. Our characterization and approach will help designers of self-adaptive and self-managing systems formulate optimization problems, decide on algorithmic strategies based on policy requirements, and reason about solution qualities. / Graduate / 0984