Die Leber nimmt als Hauptzielorgan des metastasierenden Kolorektalkarzinoms (CRC) eine exponierte Rolle ein; bei mehr als 50 % der betroffenen Patienten werden im Laufe ihrer Tumorerkrankung Lebermetastasen diagnostiziert, die trotz multimodaler Therapiekonzepte immer noch den fatalen Kranksheitsverlauf bestimmen. Zwecks Entwicklung neuer Therapiestrategien ist ein fundiertes Verständnis der Entstehungsmechanismen und des Genexpressionsprofils der Metastasen erforderlich. Makrophagen wird in diesem Kontext ein großer Einfluss auf die Tumorentstehung und -progression zugeschrieben, weshalb von einer klinischen Relevanz der Makrophagenpolarisation auszugehen ist. Im Rahmen der vorliegenden Arbeit wurde mit der CRC Zelllinie CMT-93 ein syngenes, orthotopes Lebermetastasenmodell in C57BL/6N Mäusen etabliert. Basierend auf RNA Sequenzierungsdaten und bioinformatischen Analysemethoden wurde eine Entwicklung und fein abgestimmte Adaptation der CMT-93 Zellen im Zuge ihrer Propagation im hepatischen Milieu nachgewiesen. Diese resultierte in divergierenden Genexpressionsprofilen zwischen Zelllinie und Metastasen. Von insgesamt 3329 differentiell exprimierten Genen wurden mittels einer Selektionsliste 32 signifikant exprimierte Gene identifiziert. Insbesondere Matrix-Metalloproteasen (MMP-2, -7, -9), Chemokinrezeptoren (CXCR2, CXCR4), Zelladhäsionsgene (ITGA6, ITGB3) sowie Wif1 als Feinregulator des kanonischen Wnt Signalweges nehmen eine bedeutende Rolle ein und tragen zum Invasions- und Metastasierungsprofil von CMT-93 Zellen unter dem Einfluss des Lebermilieus bei. Invasive und aggressive Eigenschaften der CMT-93 induzierten Lebermetastasen wurden insbesondere im frühen und späten Metastasierungsstadium nachgewiesen. Hier wurde u.a. die Expression der EMT Marker Vimentin, MMP-7 und CD44, Ki-67, NFkb1 und Stat3 untersucht. Eine Gene Ontology Analyse und RNA Sequenzierungsdaten verschiedener Leberareale zeigten, dass die vielschichtige Interaktion zwischen CMT-93 Zellen und der hepatischen Mikroumgebung u.a. durch immunregulatorische Prozesse gesteuert wird, die in veränderten Genexpressionsprofilen zwischen Zelllinie, Metastase und tumorumgebendem Gewebe resultiert. In Lebermetastasen konnte eine Mischpopulation aus M1 und M2 Makrophagen nachgewiesen werden, die einen tendenziell M2 geprägten Charakter aufweisen. Dieser ist höchstwahrscheinlich an einer Stimulation der invasiven Eigenschaften der Tumorzellen beteiligt. Durch qRT-PCR und immunhistochemische Analysen konnten Hinweise gesammelt werden, dass nicht explizit die Quantität oder spezifische Lokalisation von Makrophagenphänotypen, sondern mutmaßlich eher das Zytokinprofil des Tumors und der Mikroumgebung und damit einhergehend der Polarisationsstatus der Makrophagen zum Metastasierungserfolg beiträgt. Eine Inkubation von CMT-93 Zellen mit konditionierten Medien der verschiedenen Makrophagenphänotypen bestätigte die Rolle sezernierter Faktoren. Eine indirekte Interaktion zwischen Tumorzelle und M2 Makrophagen reicht offensichtlich aus, um tumorstimulierende Eigenschaften, Aggressivität und Proliferationsfähigkeit der Zelllinie zu beeinflussen. Somit wurden Gene und Signalwege identifiziert, die relevant sind für eine erfolgreiche Induktion und Progression von Lebermetastasen infolge der Implantation von CRC-Zellen. Eine Adaptation des Genexpressionsprofils der CMT-93 Zelllinie im Zuge der Leberkolonisation konnte nachgewiesen werden. Das molekulare Profil bzw. die Gensignatur der Metastasen korrelierte dabei in hohem Maße mit der Migrations- und Invasionsfähigkeit der Tumorzellen. Insbesondere die Anwendung bioinformatischer Methoden erwies sich dabei als nützliches Werkzeug zur Analyse von großen Datensätzen, die mittels RNA Sequenzierung generiert wurden. Diese werden nun zur Formulierung prädiktiver Modelle der Metastasierungsvorgänge genutzt, um deregulierte Gene und damit einhergehend die Aggressivität von Tumorzellen gezielt identifizieren und konsekutiv beeinflussen zu können. Eine Analyse der Makrophagenphänotypen und ihrer Interaktion mit Tumorzellen verdeutlichte den durchaus tumorstimulierend geprägten Charakter der CMT-93 induzierten Lebermetastasen und den Einfluss des Zytokinprofils auf die Tumorprogression. Eine weiterführende Untersuchung der Makrophagenpolarisation bedarf jedoch eine rigorose Charakterisierung der Phänotypen anhand weiterer spezifischer Marker. Die subtile Analyse wird Rückschlüsse der organspezifischen Einflüsse des Zytokinprofils auf die kolorektale Karzinogenese erlauben.

African American (AA) men in the state of Alabama are affected by colorectal cancer (CRC) more than all other races. The purpose of this phenomenological study was to gain understanding of colorectal cancer screening health benefits in AA men in Mobile, Alabama. The health beliefs model (HBM) developed by Hochum, Rosemstock, and Kegels was used to to explore the barriers and facilitators to CRC screening in AA men with health insurance in Mobile, Alabama. The research questions explored knowledge, perceptions, and facilitators to CRC screening among AA men age 40 to 75. Participants were selected using purposive sampling and data were collected through face-to-face individual interviews with 13 participants living in Mobile, Al. Data were inductively coded and subjected to a thematic analysis procedure. The study findings revealed that participants had a general knowledge of cancer but a low awareness of CRC screening. Findings also revealed a perceived gap in CRC screening education from participants' doctors. Few reported understanding or remembering a conversation about the need for CRC screening during their last doctor's visit. There was no indication that age or level of education played a meaningful role in participants' knowledge or perception of CRC screening requirements. Positive social change implications stemming from this study include recommendations to Alabama public health officials and policy makers to invest in the development of intervention and education efforts to increase CRC screening among AA men, which in turn, may reduce CRC related morbidity and mortality.

Tourism has come to be recognised as a major contributor to national economies. In a knowledge-based economy (that emphasises the benefits of industry/government and academic research), a strong research base must underpin management of a tourist destination if it is to realise its full potential. The establishment of collaborative networks between industry, academia, and government in the strategic planning and management of cities and towns is becoming increasingly popular. However, the way in which the processes underlying these settings facilitate or inhibit eventual outcomes is poorly understood. If knowledge is to drive innovation and economic growth optimally, it is important not just to develop an understanding of the processes underlying the creation, diffusion and utilisation of knowledge in cooperative research settings, but also the relationships among them. Accordingly, the aim of this investigation is to examine the relationships among knowledge creation, diffusion and utilisation occurring in the Cooperative Research Centres (CRC) Program, specifically, the Gold Coast Visioning Project, with a view to identifying the most efficient means for formulating and disseminating research designed for industry and/or government application. Knowledge is defined as information that is imbued with meaning or relevance. However, this definition says little of the ways that individuals, groups and organisations acquire knowledge. While cognitive psychologists have produced several theories suggesting the structure and mechanisms of individual cognitive processes underlying the acquisition and use of knowledge, social scientists have sought to describe and explain the process by investigating the influence of social factors. Recent contributions to group learning have examined group composition, group size, familiarity among group members, and communication processes in an attempt to understand the ways in which groups acquire knowledge. Research shows that knowledge utilisation in organisations results from the interdependent influences of organisational processes and the control opportunities and control problems that arise through organisational structure. These frameworks provide accounts of how knowledge is utilised within an organisation, but not of how organisations learn. Recent research suggests that organisations learn through knowledge networks where organisational focus moves from the consideration and protection of boundaries to the management of (and care for) relationships. Therefore, organisations contain static (rules, norms and procedures) and dynamic (social relationships) elements that mutually influence the degree to which organisations learn. A synthesis of the available literature resulted in the development of a series of models that served not only to inform, but also be informed by the analysis of this investigation. A single case study, namely the Gold Coast Visioning Project, was used to examine the ways in which knowledge was created, disseminated and utilised in a CRC setting. This ethnographic investigation considered the process of knowledge creation through to utilisation at individual, group, organisational, and inter-organisational levels, while simultaneously examining the interrelated influences of social, cognitive, affective and communication factors. Throughout the project, data were collected through stakeholder interviews, various documents and participant observation of stakeholder meetings and workshops. Data were analysed using a grounded theory approach and methods of thick description. The results show that researchers and industry stakeholders bring different frames of reference, different expectations, and different knowledge bases to the exercise. This inhibited communication, and gave the appearance of dissension when, in fact, what was being sought was a common frame for understanding and communication. Additionally, the gap between industry and researcher worldviews generated the sense that industry was resisting or failing to understand what the research was seeking to achieve. Consequently, in order to manage the relationship, research plans and findings were communicated to industry in a teacher-to-student fashion, which fostered single-loop learning, and reduced industry stakeholders' sense of ownership in the process and findings. During the project, industry stakeholders frequently sought to have research come pre-packaged with "meaning", but researchers lacked the contextual knowledge necessary to specify the relevance of their research. The results also show that research findings need to be integrated and diffused to industry over time, and specific applications need to be formulated (and reformulated) in response to particular and changing needs of industry. As a result of this investigation, a model of 'best practice' has been developed with detailed recommendations for the design, implementation, and reporting of CRC-sponsored research to optimise its utility for end-users of such research. From a theoretical perspective, the findings of this study challenge the ways that current theories account for the ways in which knowledge is acquired and utilised since the results show that knowledge is constructed both socially and emotionally. Any investigation that seeks to understand how knowledge is acquired and utilised must consider social and affective influences. To ignore the role of emotion and values in the process of knowledge acquisition is to ignore a key component of an individual's reasoning capacity.

Cette thèse est dédiée à l'étude des systèmes de communications pour application aux services vidéo fournis par les réseaux radio mobiles. Ce travail met l'accent sur les systèmes point à multipoints et propose plusieurs améliorations : Dans un premier temps, on définit un système qui combine le décodage robuste aux retransmissions ARQ, et ce de telle façon à réduire le nombre de retransmissions tout en gardant le même niveau de qualité. Contrairement aux systèmes actuels (avec ou sans retransmissions), ce systèmes offre également la possibilité de choisir le compromis débit/qualité via un paramètre du système. Par la suite, on considère les sytèmes de transmission d'une vidéo scalable vers plusieurs terminaux. Des extensions des systèmes Go-Back-N (GBN) Automatic Repeat reQuest (ARQ) et Selective Repeat (SR) ARQ sont étudiées et comparées à un nouveau système. On montre que ce dernier limite les besoins de bufferisation au niveau du terminal récepteur tout en ayant des performances optimales (en termes de quantité de données transmises avec succès sur une période donnée). Finalement, on montre que même sous une contrainte débit on peut utiliser les retransmissions dans les communications point à multipoints à condition de ne pas dépasser une certaine limite sur le nombre d'utilisateurs. Si l'utilisation des retransmissions ARQ est introduite dans les sytèmes de Multicast/Broadcast 3GPP et/ou WiMAX, le système pourra garantir une qualité nominale à un certain nombre d'utilisateurs, ce qui n'est pas le cas des systèmes de Multicast/Broadcast actuels.

<p>Background: Many systems that Enea Epact AB develops for theirs customers communicates with computers. In order to meet the customers demands on cost effective solutions, Enea Epact wants to know if it is possible to implement a gigabit Ethernet controller in an FPGA. The controller shall be designed with the intent to meet the requirements of IEEE 802.3. </p><p>Aim: Find out if it is feasible to implement a gigabit Ethernet controller using an FPGA. In the meaning of feasible, certain constraints for size, speed and device must be met. </p><p>Method: Get an insight of the standard IEEE 802.3 and make a rough design of a gigabit Ethernet controller in order to identify parts in the standard that might cause problem when implemented in an FPGA. Implement the selected parts and evaluate the results. </p><p>Conclusion: It is possible to implement a gigabit Ethernet controller using an FPGA and the FPGA does not have to be a state-of-the-art device.</p>

Refugee children often experience social exclusion upon arrival in their new host countries. The United Nations Convention on the Rights of the Child (CRC) obligates States to ensure the social inclusion of all children, including refuges. While all but two countries have ratified the CRC, few have fully implemented it. In this thesis, I tested the hypothesis that the social inclusion of refugee children will be greater in a country that has more fully implemented the CRC (Sweden) than in a country where implementation is weaker (Canada). The results of a policy analysis supported the hypothesis. The findings of this study will contribute to the development of methods to measure the implementation of the CRC, as well as to our understanding of the relationships among human rights, domestic policy and children’s well-being.

Refugee children often experience social exclusion upon arrival in their new host countries. The United Nations Convention on the Rights of the Child (CRC) obligates States to ensure the social inclusion of all children, including refuges. While all but two countries have ratified the CRC, few have fully implemented it. In this thesis, I tested the hypothesis that the social inclusion of refugee children will be greater in a country that has more fully implemented the CRC (Sweden) than in a country where implementation is weaker (Canada). The results of a policy analysis supported the hypothesis. The findings of this study will contribute to the development of methods to measure the implementation of the CRC, as well as to our understanding of the relationships among human rights, domestic policy and children’s well-being.

Colorectal cancer (CRC) is a common malignancy which develops due to old age and lifestyle factors, low percent of patients afflicted by a genetic disorders. Half of all colorectal cancer patients are diagnosed after metastasis. The high rate of the late detection, emphasizes on the requirement of convenient and inexpensive diagnostic methods for comprehensive screening programs. The aim of this study was to discover proto-oncogenes mutation and assessment of tumor suppressor genes expression. Formalin fixed paraffin embedded (FFPE) histologically verified colorectal cancer samples were used. APC, KRAS and BRAF mutations were investigated using polymerase chain reaction (PCR) fragments and direct sequencing. Gene expression assessment of MLH1, MGMT and CDKN2A were achieved via quantitative polymerase chain reaction (qPCR). In the present study we could detect a novel transversion heterozygous mutation in APC gene codon 1365 in three patients. BRAF codon 600 mutation were detected in one patient. KRAS codon 12 mutation was discovered in one sample and also a novel transition mutation in codon 15 was detected in 6 patients. In 80% of cases, MLH1 and MGMT expression were undetectable, in remaining 20%, MLH1 expression were reduced, but MGMT showed both reduced and increased expression compared to control. In 100% of patients CDKN2A expression was undetectable. The rate of mutations in predetermined hotspot codons and amount of uncommon mutations into APC, BRAF and KRAS in Nepalese patients indicates the requirement of further investigation in CRC patients from that part of the world. Also, the expression rate of MLH1, MGMT, CDKN2A and deficiency of an information source emphasizes the necessity of whole genome CRC expression profiling data to comparison and conclusion. / <p>-</p> / -

Background: Many systems that Enea Epact AB develops for theirs customers communicates with computers. In order to meet the customers demands on cost effective solutions, Enea Epact wants to know if it is possible to implement a gigabit Ethernet controller in an FPGA. The controller shall be designed with the intent to meet the requirements of IEEE 802.3. Aim: Find out if it is feasible to implement a gigabit Ethernet controller using an FPGA. In the meaning of feasible, certain constraints for size, speed and device must be met. Method: Get an insight of the standard IEEE 802.3 and make a rough design of a gigabit Ethernet controller in order to identify parts in the standard that might cause problem when implemented in an FPGA. Implement the selected parts and evaluate the results. Conclusion: It is possible to implement a gigabit Ethernet controller using an FPGA and the FPGA does not have to be a state-of-the-art device.

On November 1989 the Convention on the Rights of the Child was adopted by the United Nations General Assembly. Today more than 20 years later the convention is ratified by all countries in the world except the USA. A question asked is however if the convention after 20 years of development work has in fact accomplished some positive effects for children around the world?   The aim of this thesis is to evaluate the implementation of the Convention on the Rights of the Child in selected states and to reach this aim some questions need to be answered:   What do the selected states do to realize the best interest of the child? What do the selected states do to guarantee all children’s right to survival and development? Do all children in the selected states have the same right to health and health services? Do all children in the selected states have the same right to education?   The material studied in this thesis is those reports that are to be sent periodically to the Committee on the Rights of the Child by all states. The result of this study shows that the Convention on the Rights of the Child has made some positive progresses when it comes to the situation of the child in the world. In the selected states of this study the awareness of the Rights of the Children is noticeable and according to the periodic reports the states continue to work and develop the implementation of the convention.