PREDICTION OF DNA METHYLATION BASED ON GENOMIC ARCHITECTURE AND APPLICATIONS OF POSITIONAL WEIGHT MATRICES

Gene silencing due to epigenetic mechanisms shows evidence of significant contributions to cancer development. We hypothesis that the genetic architecture based on retrotransposon elements surrounding the transcription start site, plays an important role in the suppression and promotion of DNA methylation. In our investigation we found a high rate of SINE and LINEs retrotransposon elements near the transcription start site of unmethylated genes when compared to methylated genes. The presence of these elements were positively associated with promoter methylation, contrary to logical expectations, due to the malicious effects of retrotransposon elements which insert themselves randomly into the genome causing possible loss of gene function. In our genome wide analysis of human genes, results suggested that 22% of the genes in cancer were predicted to be methylation-prone; in cancer these genes are generally down-regulated and function in the development process. In summary, our investigation validated our hypothesis and showed that these widespread genomic elements in cancer are highly associated with promoter DNA methylation and may further participate in influencing epigenetic regulation.

APPLICATIONS OF EPHB4 RECEPTOR SPECIFIC PEPTIDES IN TARGETED CANCER IMAGING AND THERAPY

EphB4 receptors, a member of the largest family of receptor tyrosine kinases, are found over-expressed in a variety of tumors cells including glioma cells as well as angiogenic blood vessels. Noninvasive imaging of EphB4 could potentially increase early detection rates, monitor response to therapy directed against EphB4, and improve patient outcomes. Targeted delivery of EphB4 receptor specific peptide conjugated hollow gold nanoshells (HAuNS) into tumors has great potential in cancer imaging and photothermal therapy. In this study, we developed an EphB4 specific peptide named TNYL-RAW and labeled with radioisotope 64Cu and Cy5.5 dye. We also conjugate this specific peptide with hollow gold nanoshells (HAuNS) to evaluate targeted photothermal therapy of cancers. In vitro, 64Cu-DOTA-TNYL- RAW specifically bind to CT26 and PC-3M cells but not to A549 cells. In vivo, Small-animal PET/CT clearly showed the significant uptake of 64Cu-DOTA-TNYL-RAW in CT26 and PC-3M tumors but not in A549 tumors. Furthermore, µPET/CT and near-infrared optical imaging clearly showed the uptake of the dual labeled TNYL-RAW peptide in both U251 and U87 tumors in the brains of nude mice. In U251 tumors, Cy5.5-labeled peptide can bind to EphB4-expressing tumor blood vessels and tumors cells. But in U87 models, dual labeled peptide only could bind to tumor associated blood vessels. Also, Irradiation of PC-3M and CT-26 cell treated with TNYL-PEG-HAuNS nanopatilces with near-infrared (NIR) laser resulted in selective destruction of these cells in vitro. EphB4 targeted TNYL-PEG-HAuNS showed more photothermal killing effect on CT26 tumor model than PEG-HAuNS did. In summary, tumors with overexpression of EphB4 receptors can be noninvasively visualized by micro PET/CT with 64Cu labeled or dual labeled TNYL-RAW peptide. Targeted delivery of TNYL-RAW conjugated HAuNS into tumors can greatly improve the treatment effect of photothermal therapy. The information acquired with this study should be advantageous in improving diagnostics and future applications in photothermal ablation therapy in clinical.

Calving Giant Icebergs: Old Principles, New Applications

Earth-orbiting satellites can now monitor calving of large icebergs from ice shelves bordering the marine West Antarctic Ice Sheet, and recent calving events have stimulated interest in calving mechanisms. To advance this interest pioneering work in brittle and ductile fracture mechanics is reviewed, leading to a new application to calving of giant icebergs from Antarctic ice shelves. The aim is to view iceberg calving as more than terminal events for Antarctic ice when glaciologists lose interest. Instead calving launches Antarctic ice into the larger dynamic system of Earth's climate machine. This encourages a holistic approach to glaciology.

Cloud-based Orchestration of Multimedia Services and Applications

The Mobile Cloud Networking project develops among others, several virtualized services and applications, in particular: (1) IP Multimedia Subsystem as a Service that gives the possibility to deploy a virtualized and on-demand instance of the IP Multimedia Subsystem platform, (2) Digital Signage Service as a Service that is based on a re-designed Digital Signage Service architecture, adopting the cloud computing principles, and (3) Information Centric Networking/Content Delivery Network as a Service that is used for distributing, caching and migrating content from other services. Possible designs for these virtualized services and applications have been identified and are being implemented. In particular, the architectures of the mentioned services were specified, adopting cloud computing principles, such as infrastructure sharing, elasticity, on-demand and pay-as-you-go. The benefits of Reactive Programming paradigm are presented in the context of Interactive Cloudified Digital Signage services in a Mobile Cloud Platform, as well as the benefit of interworking between different Mobile Cloud Networking Services as Digital Signage Service and Content Delivery Network Service for better performance of Video on Demand content deliver. Finally, the management of Service Level Agreements and the support of rating, charging and billing has also been considered and defined.

Immigrant students’ psychological adjustment in the school context: A meta-synthesis of qualitative research on acculturation

This contribution focuses on the characteristics of the school context and their impact on immigrant students’ acculturation and adjustment at school. Research suggests that the ways immigrants acculturate is related to their well being (e.g. Phinney, et al., 2001; Ward & Rana-Deuba, 1999), although findings have been contradictory across methods and studies (e.g. Rogler, 1991; Escobar & Vega, 2001). Debates in acculturation research currently center on issues of acculturation measurement (e.g. Berry, 2009; Rudmin, 2009), as most research is conducted in the quantitative tradition. In addition, some have suggested (Birman, 2011) that research on acculturation in the tradition of cross-cultural psychology adopts an overly individualistic perspective, and lacks attention to the specific contexts of acculturation. Alternatively, the contextual approach proposes that the relationship between acculturation and adjustment is shaped by the surrounding context (Birman & Simon, 2013). For immigrant children, schools are the setting where the process of acculturation unfolds, and an important context in which to study their adjustment and well being (Birman, et al., 2007; Makarova & Herzog, 2011). Though rarely used in this tradition of acculturation research (Chirkov, 2009), qualitative methods are uniquely suited to gain insight to facilitate theory development, as well as appreciate the contextual nature of the acculturation process. Yet we are not aware of efforts to synthesize the empirical qualitative literature on this topic. Applying the methodology of meta-synthesis for qualitatieve research (Walsh & Downe, 2005) our contribution attempts to integrate results from qualitative studies on impact of acculturation on immigrant students’ psychological adjustment in the school context. For this purpose 84 articles which matched the inclusion criteria were selected. Overall, the results of our study show that within the school context a number of structural as well as process characteristics can be identified as crucial for immigrant youth psychological adjustment. Moreover, our findings indicate that immigrant youths’ psychological adjustment is related to other individual outcomes of acculturation in the school context such as behavioral adjustment, peer-relationships, academic achievement and identity development of immigrant youth.

Does the (structural) context matter? Analysing individual and structural factors of members’ commitment to sports clubs

Introduction: Over the last decades, Swiss sports clubs have lost their "monopoly" in the market for sports-related services and increasingly are in competition with other sports providers. For many sport clubs long-term membership cannot be seen as a matter of course. Current research on sports clubs in Switzerland – as well as for other European countries – confirms the increasing difficulties in achieving long-term member commitment. Looking at recent findings of the Swiss sport clubs report (Lamprecht, Fischer & Stamm, 2012), it can be noted, that a decrease in memberships does not equally affect all clubs. There are sports clubs – because of their specific situational and structural conditions – that have few problems with member fluctuation, while other clubs show considerable declines in membership. Therefore, a clear understanding of individual and structural factors that trigger and sustain member commitment would help sports clubs to tackle this problem more effectively. This situation poses the question: What are the individual and structural determinants that influence the tendency to continue or to quit the membership? Methods: Existing research has extensively investigated the drivers of members’ commitment at an individual level. As commitment of members usually occurs within an organizational context, the characteristics of the organisation should be also considered. However, this context has been largely neglected in current research. This presentation addresses both the individual characteristics of members and the corresponding structural conditions of sports clubs resulting in a multi-level framework for the investigation of the factors of members’ commitment in sports clubs. The multilevel analysis grant a adequate handling of hierarchically structured data (e.g., Hox, 2002). The influences of both the individual and context level on the stability of memberships are estimated in multi-level models based on a sample of n = 1,434 sport club members from 36 sports clubs. Results: Results of these multi-level analyses indicate that commitment of members is not just an outcome of individual characteristics, such as strong identification with the club, positively perceived communication and cooperation, satisfaction with sports clubs’ offers, or voluntary engagement. It is also influenced by club-specific structural conditions: stable memberships are more probable in rural sports clubs, and in clubs that explicitly support sociability, whereas sporting-success oriented goals in clubs have a destabilizing effect. Discussion/Conclusion: The proposed multi-level framework and the multi-level analysis can open new perspectives for research concerning commitment of members to sports clubs and other topics and problems of sport organisation research, especially in assisting to understand individual behavior within organizational contexts. References: Hox, J. J. (2002). Multilevel analysis: Techniques and applications. Mahwah: Lawrence Erlbaum. Lamprecht, M., Fischer, A., & Stamm, H.-P. (2012). Die Schweizer Sportvereine – Strukturen, Leistungen, Herausforderungen. Zurich: Seismo.

"Does the context matter?” Individuelle und strukturelle Faktoren der Mitgliederbindung in Sportvereinen

Einleitung Folgt man den aktuellen Sportentwicklungsberichten, dann sehen sich zunehmend mehr Sportvereine mit Mitgliederfluktuationen sowie stagnierenden bzw. zurückgehenden Mitglie- derzahlen konfrontiert (Lamprecht et al. 2012). Jedoch werden nicht alle Vereine in gleichem Maße mit instabilen Mitgliedschaftsverhältnissen konfrontiert. So gibt es mit Blick auf die Mitgliederstruktur Vereine, die – aufgrund ihrer spezifischen situativen und strukturellen Bedingungen – kaum Probleme mit Mitgliederfluktuation und Vereinsaustritten haben, wohin- gegen andere Vereine mitunter erhebliche Mitgliederrückgänge verzeichnen. Demnach ist zu vermuten, dass sich das soziale Handeln der Vereinsmitglieder je nach Organisationsprofil der Vereine unterscheidet. Zwar werden Verknüpfungen von Individual- und korrespondierenden Strukturdaten innerhalb der Sportvereinsforschung bereits seit geraumer Zeit gefordert (z.B. Nagel, 2007), aber bis heute nicht konsequent umgesetzt. Es stellt sich deshalb die Frage, welche organisations- und individuumsbezogenen Faktoren für die Mitgliederbindung in Sportvereinen eine Rolle spielen? Theoretisch-methodisches Vorgehen Im Zusammenhang mit der Frage der Mitgliederbindung wird davon ausgegangen, dass kontextuelle Bedingungen individuelle Entscheidungen strukturieren und somit persönliche Handlungsketten beeinflussen können (Coleman, 1990). Auf dieser Grundlage wird ein Mehr- ebenenmodell entwickelt, das neben individuellen Merkmalen auch die Strukturbedingungen von Sportvereinen berücksichtigt, die im Zusammenhang mit der individuellen Wahlhandlung zwischen stabiler Mitgliedschaft oder Austritt stehen. Der organisationale Kontext Sportverein wird dabei als Interessenorganisation konzeptualisiert, der mit seinen Kontexteigenschaften als Gelegenheits- und Opportunitätsstruktur, als kultureller sowie sozialer Bezugsrahmen gewisse Anreize schafft („Logik der Situation“), die gemäss individueller Präferenzen („Logik der Selektion“) zu Parametern des Mitgliederhandelns werden können. Die aus dem Modell abgeleiteten Annahmen werden auf der Grundlage einer Mitglieder- befragung (n = 1.434) in 36 Schweizer Sportvereinen empirisch geprüft. Die adäquate Methode, welche die hierarchische Datenstruktur (jede Messung auf der Individualebene kann eindeutig einer Messung auf der Vereinsebene zugeordnet werden) adäquat berücksichtigt und folglich das entwickelte theoretische Modell statistisch umsetzt, ist die Mehrebenenanalyse (z.B. Hox, 2002). Entsprechend wird der Einfluss der Individual- und Kontextebene auf die Mitglieder- bindung in Sportvereinen anhand unterschiedlicher Mehrebenenmodelle (Random Intercept, Random Slope sowie Cross-Level Interaktionen) geschätzt. Ergebnisse Die Analysen machen deutlich, dass sich die dauerhafte Mitgliedschaft in Sportvereinen nicht allein auf individuelle Merkmale der Mitgliedschaft, wie eine ausgeprägte Verbundenheit, ein positiv wahrgenommenes soziales Miteinander, die Zufriedenheit mit der Vereinsarbeit sowie die ehrenamtliche Mitarbeit zurückführen lässt. Darüber hinaus nehmen auch vereinsspezi-fische Strukturbedingungen Einfluss auf die Mitgliederbindung, wobei in ländlich geprägten Sportvereinen und in Vereinen, die Geselligkeit explizit fordern und in denen das Vereinsziel sportlicher Erfolg eher eine untergeordnete Rolle spielt, die Austrittswahrscheinlichkeit geringer ist. Diskussion Die Befunde machen deutlich, dass für eine dauerhafte Mitgliedschaft sowohl zweckorientierte Nutzenüberlegungen als auch solidargemeinschaftliche Handlungsorientierungen eine zentrale Rolle spielen, so dass eine ausschließliche Dienstleistungs- bzw. Kundenorientierung als Strategie der Mitgliederbindung in Sportvereinen, wie sie vielfach (auch von Verbänden) nahegelegt wird, zu kurz greifen dürfte. Weiterhin zeigt sich, dass der Sportverein als Ort der Geselligkeit nicht nur Werte des sozialen Miteinanders und solidarischen Verhaltens vermittelt, sondern auch als Katalysator der Stabilität der Mitgliedschaft wirkt, sofern entsprechende Gelegenheiten zur Verfügung stehen. Im Zusammenhang mit der Mitgliederbindung scheint damit gerade jene vereinskulturelle Orientierung von Vereinen bedeutsam, die im Zuge der Modernisierung von Vereinsangeboten gern als überholt erachtet wird. Literatur Coleman, J. S. (1990). Foundations of social theory. Cambridge, MA: Belknap. Hox, J. (2002). Multilevel analysis. Techniques and applications. Mahwah: Erlbaum. Lamprecht, M., Fischer, A. & Stamm, H.-P. (2012). Die Schweizer Sportvereine – Strukturen, Leistungen, Herausforderungen. Zürich: Seismo. Nagel, S. (2007). Akteurtheoretische Analyse der Sportvereinsentwicklung – ein theoretisch- methodischer Bezugsrahmen. Sportwissenschaft, 37, 186–201.

Service level agreements-driven management of distributed applications in cloud computing environments

Advancements in cloud computing have enabled the proliferation of distributed applications, which require management and control of multiple services. However, without an efficient mechanism for scaling services in response to changing workload conditions, such as number of connected users, application performance might suffer, leading to violations of Service Level Agreements (SLA) and possible inefficient use of hardware resources. Combining dynamic application requirements with the increased use of virtualised computing resources creates a challenging resource Management context for application and cloud-infrastructure owners. In such complex environments, business entities use SLAs as a means for specifying quantitative and qualitative requirements of services. There are several challenges in running distributed enterprise applications in cloud environments, ranging from the instantiation of service VMs in the correct order using an adequate quantity of computing resources, to adapting the number of running services in response to varying external loads, such as number of users. The application owner is interested in finding the optimum amount of computing and network resources to use for ensuring that the performance requirements of all her/his applications are met. She/he is also interested in appropriately scaling the distributed services so that application performance guarantees are maintained even under dynamic workload conditions. Similarly, the infrastructure Providers are interested in optimally provisioning the virtual resources onto the available physical infrastructure so that her/his operational costs are minimized, while maximizing the performance of tenants’ applications. Motivated by the complexities associated with the management and scaling of distributed applications, while satisfying multiple objectives (related to both consumers and providers of cloud resources), this thesis proposes a cloud resource management platform able to dynamically provision and coordinate the various lifecycle actions on both virtual and physical cloud resources using semantically enriched SLAs. The system focuses on dynamic sizing (scaling) of virtual infrastructures composed of virtual machines (VM) bounded application services. We describe several algorithms for adapting the number of VMs allocated to the distributed application in response to changing workload conditions, based on SLA-defined performance guarantees. We also present a framework for dynamic composition of scaling rules for distributed service, which used benchmark-generated application Monitoring traces. We show how these scaling rules can be combined and included into semantic SLAs for controlling allocation of services. We also provide a detailed description of the multi-objective infrastructure resource allocation problem and various approaches to satisfying this problem. We present a resource management system based on a genetic algorithm, which performs allocation of virtual resources, while considering the optimization of multiple criteria. We prove that our approach significantly outperforms reactive VM-scaling algorithms as well as heuristic-based VM-allocation approaches.

Energy Efficient Multimedia Communications in IEEE 802.11 Networks

During the last decade wireless mobile communications have progressively become part of the people’s daily lives, leading users to expect to be “alwaysbest-connected” to the Internet, regardless of their location or time of day. This is indeed motivated by the fact that wireless access networks are increasingly ubiquitous, through different types of service providers, together with an outburst of thoroughly portable devices, namely laptops, tablets, mobile phones, among others. The “anytime and anywhere” connectivity criterion raises new challenges regarding the devices’ battery lifetime management, as energy becomes the most noteworthy restriction of the end-users’ satisfaction. This wireless access context has also stimulated the development of novel multimedia applications with high network demands, although lacking in energy-aware design. Therefore, the relationship between energy consumption and the quality of the multimedia applications perceived by end-users should be carefully investigated. This dissertation addresses energy-efficient multimedia communications in the IEEE 802.11 standard, which is the most widely used wireless access technology. It advances the literature by proposing a unique empirical assessment methodology and new power-saving algorithms, always bearing in mind the end-users’ feedback and evaluating quality perception. The new EViTEQ framework proposed in this thesis, for measuring video transmission quality and energy consumption simultaneously, in an integrated way, reveals the importance of having an empirical and high-accuracy methodology to assess the trade-off between quality and energy consumption, raised by the new end-users’ requirements. Extensive evaluations conducted with the EViTEQ framework revealed its flexibility and capability to accurately report both video transmission quality and energy consumption, as well as to be employed in rigorous investigations of network interface energy consumption patterns, regardless of the wireless access technology. Following the need to enhance the trade-off between energy consumption and application quality, this thesis proposes the Optimized Power save Algorithm for continuous Media Applications (OPAMA). By using the end-users’ feedback to establish a proper trade-off between energy consumption and application performance, OPAMA aims at enhancing the energy efficiency of end-users’ devices accessing the network through IEEE 802.11. OPAMA performance has been thoroughly analyzed within different scenarios and application types, including a simulation study and a real deployment in an Android testbed. When compared with the most popular standard power-saving mechanisms defined in the IEEE 802.11 standard, the obtained results revealed OPAMA’s capability to enhance energy efficiency, while keeping end-users’ Quality of Experience within the defined bounds. Furthermore, OPAMA was optimized to enable superior energy savings in multiple station environments, resulting in a new proposal called Enhanced Power Saving Mechanism for Multiple station Environments (OPAMA-EPS4ME). The results of this thesis highlight the relevance of having a highly accurate methodology to assess energy consumption and application quality when aiming to optimize the trade-off between energy and quality. Additionally, the obtained results based both on simulation and testbed evaluations, show clear benefits from employing userdriven power-saving techniques, such as OPAMA, instead of IEEE 802.11 standard power-saving approaches.

An Exploratory Study of Data Quality Management Practices in the ERP Software Systems Context

Quality data are not only relevant for successful Data Warehousing or Business Intelligence applications; they are also a precondition for efficient and effective use of Enterprise Resource Planning (ERP) systems. ERP professionals in all kinds of businesses are concerned with data quality issues, as a survey, conducted by the Institute of Information Systems at the University of Bern, has shown. This paper demonstrates, by using results of this survey, why data quality problems in modern ERP systems can occur and suggests how ERP researchers and practitioners can handle issues around the quality of data in an ERP software Environment.

Study of Basic Wood Decay Mechanisms and Their Biotechnological Applications

The overall objective of this thesis was to gain further understanding of the non-enzymatic mechanisms involved in brown-rot wood decay, especially the role of pH, oxalic acid, and low molecular catecholate compounds on the dissolution and reduction of iron, and the formation of reactive oxygen species. Another focus of this study will be the potential application of a biomimetic free radical generating system inspired from fungi wood decay process, especially the non-enzymatic mechanism. The possible pathways of iron uptake and iron redox cycling in non-enzymatic brown-rot decay were investigated in this study. UV-Vis spectroscopy and HPLC were employed to study the kinetics and pathways of the interaction between iron and model catecholate compounds under different pH and chelator/iron molar ratio conditions. Iron chelation and reduction during early non-enzymatic wood decay processes have been studied in this thesis. The results indicate that the effects of the chelator/iron ratio, the pH, and other reaction parameters on the hydroxyl radical generation in a Fenton type system can be determined using ESR spin-trapping techniques. Data also support the hypothesis that superoxide radicals are involved in chelator-mediated Fenton processes. The mechanisms involved in free radical activation of Thermal Mechanical Pulp fibers were investigated. The activation of TMP fibers was evaluated by ESR measurement of free phenoxy radical generation on solid fibers. The results indicate that low molecular weight chelators can improve Fenton reactions, thus in turn stimulating the free radical activation of TMP fibers. A mediated Fenton system was evaluated for decolorization of several types of dyes. The result shows that the Fenton system mediated by a catecholate-type chelator effectively reduced the color of a diluted solution of synthetic dyes after 90 minutes of treatment at room temperature. The results show that compared to a neat Fenton process, the mediated Fenton decolorization process increased the production, and therefore the effective longevity, of hydroxyl radical species to increase the decolorization efficiency.