Kehittämistutkimus: Tieto- ja viestintätekniikkaa kemian opetukseen

The main aim of the present study was to develop information and communication technology (ICT) based chemistry education. The goals for the study were to support meaningful chemistry learning, research-based teaching and diffusion of ICT innovations. These goals were used as guidelines that form the theoretical framework for this study. This Doctoral Dissertation is based on eight-stage research project that included three design researches. These three design researches were scrutinized as separate case studies in which the different cases were formed according to different design teams: i) one researcher was in charge of the design and teachers were involved in the research process, ii) a research group was in charge of the design and students were involved in the research process, and iii) the design was done by student teams, the research was done collaboratively, and the design process was coordinated by a researcher. The research projects were conducted using mixed method approach, which enabled a comprehensive view on education design. In addition, the three central areas of design research: problem analysis, design solution and design process were included in the research, which was guided by the main research questions formed according to these central areas: 1) design solution: what kind of elements are included in ICT-based learning environments that support meaningful chemistry learning and diffusion of innovation, 2) problem analysis: what kind of new possibilities the designed learning environments offer for the support of meaningful chemistry learning, and 3) design process: what kind of opportunities and challenges does collaboration bring to the design of ICT-based learning environments? The main research questions were answered according to the analysis of the survey and observation data, six designed learning environments and ten design narratives from the three case studies. Altogether 139 chemistry teachers and teacher students were involved in the design processes. The data was mainly analysed by methods of qualitative content analysis. The first main result from the study give new information on the meaningful chemistry learning and the elements of ICT-based learning environment that support the diffusion of innovation, which can help in the development of future ICT-education design. When the designed learning environment was examined in the context of chemistry education, it was evident that an ICT-based chemistry learning environment supporting the meaningful learning of chemistry motivates the students and makes the teacher s work easier. In addition, it should enable the simultaneous fulfilment of several pedagogical goals and activate higher-level cognitive processes. The learning environment supporting the diffusion of ICT innovation is suitable for Finnish school environment, based on open source code, and easy to use with quality chemistry content. According to the second main result, new information was acquired about the possibilities of ICT-based learning environments in supporting meaningful chemistry learning. This will help in setting the goals for future ICT education. After the analysis of design solutions and their evaluations, it can be said that ICT enables the recognition of all elements that define learning environments (i.e. didactic, physical, technological and social elements). The research particularly demonstrates the significance of ICT in supporting students motivation and higher-level cognitive processes as well as versatile visualization resources for chemistry that ICT makes possible. In addition, research-based teaching method supports well the diffusion of studied innovation on individual level. The third main result brought out new information on the significance of collaboration in design research, which guides the design of ICT education development. According to the analysis of design narratives, it can be said that collaboration is important in the execution of scientifically reliable design research. It enables comprehensive requirement analysis and multifaceted development, which improves the reliability and validity of the research. At the same time, it sets reliability challenges by complicating documenting and coordination, for example. In addition, a new method for design research was developed. Its aim is to support the execution of complicated collaborative design projects. To increase the reliability and validity of the research, a model theory was used. It enables time-pound documenting and visualization of design decisions that clarify the process. This improves the reliability of the research. The validity of the research is improved by requirement definition through models. This way learning environments that meet the design goals can be constructed. The designed method can be used in education development from comprehensive to higher level. It can be used to recognize the needs of different interest groups and individuals with regard to processes, technology and substance knowledge as well as interfaces and relations between them. The developed method has also commercial potential. It is used to design learning environments for national and international market.

DNA damage recognition in the normal epithelium of human prostate and seminal vesicles

Prostate cancer is one of the most prevalent cancer types in men. The development of prostate tumors is known to require androgen exposure, and several pathways governing cell growth are deregulated in prostate tumorigenesis. Recent genetic studies have revealed that complex gene fusions and copy - number alterations are frequent in prostate cancer, a unique feature among solid tumors. These chromosomal aberrations are though to arise as a consequence of faulty repair of DNA double strand breaks (DSB). Most repair mechanisms have been studied in detail in cancer cell lines, but how DNA damage is detected and repaired in normal differentiated human cells has not been widely addressed. The events leading to the gene fusions in prostate cancer are under rigorous studies, as they not only shed light on the basic pathobiologic mechanisms but may also produce molecular targets for prostate cancer treatment and prevention. Prostate and seminal vesicles are part of the male reproductive system. They share similar structure and function but differ dramatically in their cancer incidence. Approximately fifty primary seminal vesicle carcinomas have been reported worldwide. Surprisingly, only little is known on why seminal vesicles are resistant to neoplastic changes. As both tissues are androgen dependent, it is a mystery that androgen signaling would only lead to tumors in prostate tissue. In this work, we set up novel ex vivo human tissue culture models of prostate and seminal vesicles, and used them to study how DNA damage is recognized in normal epithelium. One of the major DNA - damage inducible pathways, mediated by the ATM kinase, was robustly activated in all main cell types of both tissues. Interestingly, we discovered that secretory epithelial cells had less histone variant H2A.X and after DNA damage lower levels of H2AX were phosphorylated on serine 139 (γH2AX) than in basal or stromal cells. γH2AX has been considered essential for efficient DSB repair, but as there were no significant differences in the γH2AX levels between the two tissues, it seems more likely that the role of γH2AX is less important in postmitotic cells. We also gained insight into the regulation of p53, an important transcription factor that protects genomic integrity via multiple mechanisms, in human tissues. DSBs did not lead to a pronounced activation of p53, but treatments causing transcriptional stress, on the other hand, were able to launch a notable p53 response in both tissue types. In general, ex vivo culturing of human tissues provided unique means to study differentiated cells in their relevant tissue context, and is suited for testing novel therapeutic drugs before clinical trials. In order to study how prostate and seminal vesicle epithelial cells are able to activate DNA damage induced cell cycle checkpoints, we used primary cultures of prostate and seminal vesicle epithelial cells. To our knowledge, we are the first to report isolation of human primary seminal vesicle cells. Surprisingly, human prostate epithelial cells did not activate cell cycle checkpoints after DSBs in part due to low levels of Wee1A, a kinase regulating CDK activity, while primary seminal vesicle epithelial cells possessed proficient cell cycle checkpoints and expressed high levels of Wee1A. Similarly, seminal vesicle cells showed a distinct activation of the p53 - pathway after DSBs that did not occur in prostate epithelial cells. This indicates that p53 protein function is under different control mechanisms in the two cell types, which together with proficient cell cycle checkpoints may be crucial in protecting seminal vesicles from endogenous and exogenous DNA damaging factors and, as a consequence, from carcinogenesis. These data indicate that two very similar organs of male reproductive system do not respond to DNA damage similarly. The differentiated, non - replicating cells of both tissues were able to recognize DSBs, but under proliferation human prostate epithelial cells had deficient activation of the DNA damage response. This suggests that prostate epithelium is most vulnerable to accumulating genomic aberrations under conditions where it needs to proliferate, for example after inflammatory cellular damage.

Bounded turning circles are weak-quasicircles

We show that a metric Jordan curve $\Gamma$ is \emph{bounded turning} if and only if there exists a \emph{weak-quasisymmetric} homeomorphism $\phi\colon \mathsf{S}^1 \to \Gamma$.