Transcriptional and Epigenetic Regulation of Human CD4+ T Helper Lineage Specification

Activated T helper (Th) cells have ability to differentiate into functionally distinct Th1, Th2 and Th17 subsets through a series of overlapping networks that include signaling and transcriptional control and the epigenetic mechanisms to direct immune responses. However, inappropriate execution in the differentiation process and abnormal function of these Th cells can lead to the development of several immune mediated diseases. Therefore, the thesis aimed at identifying genes and gene regulatory mechanisms responsible for Th17 differentiation and to study epigenetic changes associated with early stage of Th1/Th2 cell differentiation. Genome wide transcriptional profiling during early stages of human Th17 cell differentiation demonstrated differential regulation of several novel and currently known genes associated with Th17 differentiation. Selected candidate genes were further validated at protein level and their specificity for Th17 as compared to other T helper subsets was analyzed. Moreover, combination of RNA interference-mediated downregulation of gene expression, genome-wide transcriptome profiling and chromatin immunoprecipitation followed by massive parallel sequencing (ChIP-seq), combined with computational data integration lead to the identification of direct and indirect target genes of STAT3, which is a pivotal upstream transcription factor for Th17 cell polarization. Results indicated that STAT3 directly regulates the expression of several genes that are known to play a role in activation, differentiation, proliferation, and survival of Th17 cells. These results provide a basis for constructing a network regulating gene expression during early human Th17 differentiation. Th1 and Th2 lineage specific enhancers were identified from genome-wide maps of histone modifications generated from the cells differentiating towards Th1 and Th2 lineages at 72h. Further analysis of lineage-specific enhancers revealed known and novel transcription factors that potentially control lineage-specific gene expression. Finally, we found an overlap of a subset of enhancers with SNPs associated with autoimmune diseases through GWASs suggesting a potential role for enhancer elements in the disease development. In conclusion, the results obtained have extended our knowledge of Th differentiation and provided new mechanistic insights into dysregulation of Th cell differentiation in human immune mediated diseases.

Innovation Process and Organizational Adoption of Disruptive Innovation: Empirical Evidence from Finnish Bio-Economy Companies.

The thesis aims to build a coherent view and understanding of the innovation process and organizational technology adoption in Finnish bio-economy companies with a focus on innovations of a disruptive nature. Disruptive innovations are exceptional hence in order to create generalizations and a unified view of the subject the perspective is also on less radical innovations. Other interests of the thesis are how ideas are discovered and generated and how the nature of the innovation and size of the company affect the technology adoption and innovation process. The data was collected by interviewing six small and six large Finnish bio-economy companies. The results suggest companies regardless of size consider innovation as a core asset in the competitive markets. Organizations want to be considered innovators and early adopters yet these qualities are limited by certain, mainly resource-based factors. In addition the industry, scalability and Finland’s geographical location when seeking funding provide certain challenges. The innovation process may be considered relatively similar whether the idea or technology stems from an internal or external source suggesting the technology adoption process can in fact be linked to the innovation process theories. Thus the thesis introduces a new theoretical model which based on the results of the study and the theories of technology adoption and innovation process aims on characterizing how ideas and technology from both external and internal sources generate into innovations. The innovation process is in large bio-economy companies most often similar to or a modified version of the stage-gate model, while small companies generally have less structured processes. Nevertheless the more disruptive the innovation, the less it fits in the structured processes. This implies disruptive innovation cannot be put in a certain mould but it is rather processed case-by-case.

Social media in the purchasing of knowledge-intensive business services

The purpose of this thesis was to understand how industrial buyers utilize social media in the purchasing of knowledge-intensive business services. By combining theories from past research a theoretical framework was formed to visualize the role of the social media at the different stages of the purchasing process. The subject was approached from the industrial buyers’ perspective instead of the knowledge-intensive business firm. The research was conducted using two qualitative research methods: interviews and netnography. The selected interviewees have been involved in the decision-making unit for purchasing knowledge-intensive business services. Additionally all of them are using various social media. Based on the interviews social media is used merely to support decision-making. Some of the interviewees had also shared their own experiences about the service and collaboration with the service provider with other social media users. Based on the interviews two social media were chosen for closer examination. The findings from netnography support the results from the interviews. The outcome of knowledgeintensive business services is dependable of the professionals. Therefore the information is used during decision-making process to confirm the formed image of the service, and the professionals of the service provider. Information obtained from social media complements information provided by the supplier. Even though the interviewees had not themselves used social media to find information about the service during search process, finding from netnography suggest it to exist. Industrial buyers ask other users’ opinions and experience about the services, and receive recommendations to them. Some recommendations are given publicly, but more discreet information is shared in private conversations. Observations in social media show that industrial buyers might be exposed to triggers to promote problem recognition as well. Companies share news and successful customer cases through their social media profiles, which might affect the industrial buyers, but to confirm this requires further research. The industrial buyers’ use of social media during different purchasing processes of knowledgeintensive business services can be conceptualize based on the findings. This helps companies to create right content to their social media pages, and encourage professionals to develop their networks in social media.

Open Access in Times of Knowledge Unlatched : Cooperative Action for Books and Journals

Presentation at the seminar "Publishers and Funders for OA in Finland", Helsinki, May 24, 2016