During the development of multicellular organisms, organs grow to well-defined shapes and sizes. The proper size and patterning of tissues are ensured by signaling molecules as e.g. morphogens. Secreted from a restricted source, morphogens spread into the adjacent target tissue where they form a graded concentration profile. Upon binding of the morphogens to receptors on the cell surfaces, the morphogenetic signal is transduced inside the cell via the phosphorylation of transcription factors, which subsequently regulate the expression of different target genes. Thus, cell fates are determined by the local concentration of such morphogens. In this work, we investigate three key aspects of morphogenetic signaling processes in growing tissues. First, we study the mechanics of tissue growth via cell division and cell death. We examine the rearrangements of cells on large scales and times by developing a continuum theory which describes the growing tissue as an active complex fluid. In our description we include anisotropic stresses generated by oriented cell division, and we show that average cellular trajectories exhibit anisotropic scaling behaviors. Our description is used to study experimentally measured shape changes of the developing wing disk of the fruit fly Drosophila melanogaster. Second, we focus on the spreading of morphogens in growing tissues. We show that the flow field of cell movements due to oriented cell division and cell death causes a drift term in the morphogen transport equation, which captures the stretching and dilution of the concentration profile. Comparing our theoretical results to recent experiments in the Drosophila wing disk, we find that the transport of the morphogen Dpp is mainly intracellular. We moreover show that the decay length of the Dpp gradient increases during development as a result of changing degradation rate and diffusion coefficient, whereas the drift of molecules due to growth is negligible. Thus growth does not affect the decay length of the gradient, but the decay length of the gradient might affect the tissue growth rate as discussed in this work. Finally, we develop a microscopic theoretical description of the intracellular transduction machinery of morphogenetic signals within an individual cell. Our description captures the kinetics of the trafficking of proteins between different cellular compartments in response to receptor-bound signaling molecules. Analyzing experimental data at the Drosophila neuromuscular junction, we show that the morphogenetic signaling is modulated by synaptic signaling via neuronal action potentials.

Till följd av att Europeiska unionen försöker uppnå de globala klimatmål som ställts i och med Agenda 2030, uppkommer även förslaget Ecodesign for Sustainable Products Regulations (ESPR) av den Europeiska kommissionen. Förordningen har i mål att skapa en större hållbarhet på den europeiska produktmarknaden genom att kravställa redovisning som kan främja cirkularitet inom framtida produktlivscykler. Med ESPR framkommer även begreppet kring digitala produktpass (DPP), en digital representation av en fysisk produkt som redovisar produktrelaterad data i syfte av att främja cirkularitet, transparens och mer hållbara konsumentmönster. Det digitala produktpasset är en central del av ESPR och gäller för samtliga produkter som säljs på den europeiska marknaden. Denna studie har undersökt hur ett praktiskt fall av implementation av digitala produktpass har tagit form hos en svensk, medelstor möbeltillverkare. Studien har undersökt hur dynamiken, som uppstått på grund av ESPR i en tillverkningsbaserad sektor, tagit form och vilka förberedelser, problem samt möjligheter som uppstått i och med förordningen. Genom kvalitativa intervjuer med centrala aktörer inom IT- och möbelproduktion har studien identifierat kritiska områden kring behovet av standardisering, utmaningar som medföljer teknologin samt osäkerheter kring validitet av data. Trots de tekniska och organisatoriska hinder som uppkommit, visar resultatet även på fördelar och möjligheter med DPP såsom ökad hållbarhet, större tillförlitlighet till kunder samt möjligheter till utökade och effektivisering av befintliga affärsprocesser och affärsmodeller. / In response to the European Union’s efforts to meet the global climate goals set forth by Agenda 2030, the European Commission has introduced the Ecodesign for Sustainable Products Regulations (ESPR). The regulation aims to enhance sustainability in the European product market by requiring disclosures that can promote circularity in future product life cycles. With the introduction of ESPR, the concept of Digital Product Passports (DPP) emerged. A digital representation of a physical product that documents product-related data with the goal of promoting circularity, transparency, and more sustainable consumer patterns. The digital product passport is a central part of the ESPR and will apply to all products sold on the European market. This study has examined a practical case of how implementing digital product passports has taken shape at a medium-sized Swedish furniture manufacturer. The study explores the dynamics that have arisen due to ESPR in a manufacturing-based sector, examining the preparations done, problems that have arisen and opportunities that have emerged due to the regulation. Through semi-structured, qualitative interviews with key actors within IT and furniture production, the study has identified critical areas concerning the need for standardization, challenges associated with the technology and uncertainties regarding validity of data. Despite technical and organizational obstacles that have arisen, the results of this study also highlight the advantages and opportunities of DPPs, such as increased sustainability, greater reliability for customers, and opportunities to expand and streamline existing business processes and models.

This diploma thesis deals with optical properties of organic semiconductors and measuring method of absorption edge. Project is focused on absorption of light in organic semiconductors. This work also describes device for measuring of absorption edge.

Introduction: Type 1 diabetes mellitus is a chronic metabolic disease caused by autoimmune destruction of pancreatic beta cells. The theory of the disease onset is derived from study of a disease course in non-obese diabetic (NOD) mice, in which the diabetes occurs due to a dysregulation of the immune system. Experimental and clinical studies showed that the autoimmunity may be abrogated by immune intervention, which if initiated early enough may at least slow down the ongoing beta cells lost and preserve residual insulin secretion. But immune intervention alone is not sufficient to restore normoglycemia in the majority of cases. Several interventional studies showed that stimulation of proliferation and/or regeneration of beta cells are necessary to restore normoglycemia in animal models. Aim of the study: To find out, if the combination of a potent immunosuppression (murine anti-thymocyte globulin (mATG), gusperimus) together with stimulation of islet regeneration (sitagliptin) will be able to slow down or reverse the course of the disease. Another aim is to identify the mechanism by which the substances act. Material and methods: All experiments were performed in female NODShiLtJ (H2g7 ) mice. The following parameters were examined at day 0, 7, 14 and 28: blood glucose, subpopulations of...

Introduction: Type 1 diabetes mellitus is a chronic metabolic disease caused by autoimmune destruction of pancreatic beta cells. The theory of the disease onset is derived from study of a disease course in non-obese diabetic (NOD) mice, in which the diabetes occurs due to a dysregulation of the immune system. Experimental and clinical studies showed that the autoimmunity may be abrogated by immune intervention, which if initiated early enough may at least slow down the ongoing beta cells lost and preserve residual insulin secretion. But immune intervention alone is not sufficient to restore normoglycemia in the majority of cases. Several interventional studies showed that stimulation of proliferation and/or regeneration of beta cells are necessary to restore normoglycemia in animal models. Aim of the study: To find out, if the combination of a potent immunosuppression (murine anti-thymocyte globulin (mATG), gusperimus) together with stimulation of islet regeneration (sitagliptin) will be able to slow down or reverse the course of the disease. Another aim is to identify the mechanism by which the substances act. Material and methods: All experiments were performed in female NODShiLtJ (H2g7 ) mice. The following parameters were examined at day 0, 7, 14 and 28: blood glucose, subpopulations of...

O diabetes mellitus do tipo 1 (DM1) é uma doença autoimune caracterizada pela destruição seletiva de células pancreáticas produtoras de insulina. Existem diversas formas de tratamento do DM1, tais como administração de insulina, imunossupressores, transplantes de pâncreas ou de ilhotas pancreáticas, porém todos se mostram ineficientes em algum aspecto. Recentemente, uma nova classe de medicamentos, os inibidores da enzima dipeptidil peptidase 4 (iDPP-4), demonstrou eficiência terapêutica e segurança no tratamento de pacientes com diabetes mellitus do tipo 2 devido ao aumento do hormônio peptídeo-1 semelhante ao glucagon (GLP-1, do inglês glucagon-like peptide-1). Além disso, o uso de inibidores de DPP-4 em modelos experimentais de DM1 demonstrou proteção das células pancreáticas contra apoptose, estimulação de neogênese de ilhotas pancreáticas e melhora do controle homeostático da glicose. Esse presente projeto teve como objetivo avaliar o perfil imunológico e endocrinológico da administração do inibidor de DPP-4 (MK0431) em DM1 experimental quimicamente induzido por estreptozotocina em camundongos C57Bl/6. Os animais diabéticos foram tratados com ração controle ou ração contendo inibidor de DPP-4 (4g MK0431/Kg de ração) ad libitum durante 30 e 90 dias. Durante o tratamento os animais tiveram glicemia, peso e teste de tolerância oral à glicose avaliados. Ao final do tratamento, os animais foram eutanasiados e o sangue, baço, timo, linfonodos pancreáticos e pâncreas foram coletados. Após 30 dias de tratamento com inibidor, foi observado um aumento do hormônio GLP-1 no soro, além de um padrão imunológico favorável. Dentre os mecanismos imunológicos, foi possível observar um aumento de células T reguladoras (CD4+CD25+Foxp3+) no baço e uma diminuição da citocina IFN- no homogenato pancreático. Após 90 dias de tratamento com inibidor, também foi detectado um aumento de insulina e GLP-1 séricos e uma diminuição nos níveis glicêmicos dos animais tratados. Observou-se uma redução no padrão inflamatório no microambiente pancreático, caracterizado pela diminuição das citocinas TNF- e IFN- no homogenato pancreático e por uma redução da freqüência de macrófagos CD11b+ nos linfonodos pancreáticos. Os resultados obtidos neste projeto contribuíram para validar a eficácia terapêutica da administração de inibidor de DPP-4 no tratamento do DM1 experimental, bem como os mecanismos imunológicos e endocrinológicos envolvidos. Sem a ocorrência de efeitos tóxicos relevantes, o uso de inibidores de DPP-4 pode se tornar uma alternativa terapêutica para o tratamento do DM1 em humanos, que constitui uma doença crônica associada à baixa qualidade de vida em longo prazo e necessidade de tratamento de alto custo. / Davanso, M.R. Immunoendocrinological analyses after administration of dipeptidyl-peptidase-4 inhibitor on experimental type 1 diabetes. 2012. 105p. Thesis (Masters Degree) School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, 2012. Type 1 Diabetes Mellitus (DM1) is an autoimmune disease characterized by the selective destruction of the insulin-producing pancreatic cells. Several forms of treatment for DM1 are current known such as insulin administration, immunosuppressors, pancreas or pancreatic islets transplantation, however, they all are inefficient in some aspect. Recently, a new class of drugs, the dipeptidyl-peptidase-4 inhibitors (iDPP-4) showed therapeutic efficacy and safety in the treatment with type 2 diabetes mellitus patients due to an increase in the glucagon-like peptide-1 (GLP-1). In addition, the use of DPP-4 inhibitors in experimental models of DM1 has demonstrated a protection of pancreatic cells against apoptosis, stimulation of pancreatic islets neogenesis and improvement in the glucose homeostatic control. This project evaluated the immunological and endocrinological profile of the DPP-4 (MK0431) inhibitor administration in experimental chemically induced DM1 by streptozotocin in C57BI/6 mice. The diabetic animals were treated with either a normal chow diet or diet containing DPP-4 inhibitor (4g MK0431/Kg of diet) ad libitum during 30 and 90 days. During the treatment the animals were evaluated regarding glycemia, weight, and oral glucose tolerance test. At the end of the treatment, the animals were killed and the blood, spleen, thymus, pancreatic lymph nodes and pancreas were collected. After 30 days of treatment with inhibitor, it was observed an increase in the hormone GLP-1 in the serum, besides a favorable immunological pattern. Among the immunologic mechanisms, it was possible to observe an increase in the regulator T cells (CD4+CD25+Foxp3+) of the spleen and a decrease in the cytokine IFN- in the pancreatic homogenate. After 90 days of treatment with inhibitor, it was also noticed an increase in the insulin and serum GLP-1 levels as well as a decrease in the glycemic levels in the treated animals. It was observed a reduction in the inflammatory pattern in the pancreatic microenvironment characterized by a decrease in the cytokines TNF- and IFN- in the pancreatic homogenate and by a reduction in the frequency of CD11b+ macrophages in the pancreatic lymph nodes. The results obtained in this project contributed to validate the therapeutic efficacy of the DPP-4 inhibitor administration in the treatment of experimental DM1, as well as the immunological and endocrinological mechanisms involved. Without the occurrence of relevant toxic effects, the use of DPP-4 inhibitors may become a therapeutic alternative for the treatment of DM1 in humans, which constitutes a chronic disease associated to low life quality and need for high cost treatment.

No description available.

Morphogens are secreted signalling molecules that are expressed in restricted groups of cells within the developing tissue. From there, they are secreted and travel throughout the target field and form concentration gradients. These concentration profiles endow receiving cells with positional information. A number of experiments in Drosophila demonstrated that the morphogen Decapentaplegic (Dpp) forms activity gradients by inducing the expression of several target genes above distinct concentration thresholds at different distances from the source. This way, Dpp contributes to developmental fates in the target field such as the Drosophila wing disc. Although the tissue distribution as well as the actual shape and size of the Dpp morphogen concentration gradient has been visualized, the cell biological mechanisms through which the morphogen forms and maintains a gradient are still a subject of debate. Two hypotheses as to the dominant mechanism of movement have been proposed that can account for Dpp spreading throughout the Drosophila wing imaginal target tissue: extracellular diffusion and planar transcytosis, i. e. endocytosis and resecretion of the ligand that is thereby transported through the cells. Here, I present data indicating that implications of a theoreticalanalysis of Dpp spreading, where Dpp transport through the target tissue is solely based on extracellular diffusion taking into account receptor binding and subsequent internalization, are inconsistent with experimental results. By performing Fluorescence Recovery After Photobleaching (FRAP) experiments, I demonstrate a key role of Dynamin-mediated endocytosis for Dpp gradient formation. In addition, I show that most of GFP-Dpp traffics through endocytic compartments at the receiving epithelial cells, probably recycled through apical recycling endosomes (ARE). Finally, a Dpp recycling assay based on subcellular photouncage of ligand is presented to address specifically the Dpp recycling event at the receiving cells.

2012年總統大選，民進黨的「三隻小豬」運動，堪稱是台灣選舉史上前所未見的造勢動員模式，此一「大事件」甚至破天荒，在2016年總統大選繼續沿用，因此本研究聚焦： 　　一、「三隻小豬」之事件發展，起源於台南三胞胎孩童把存在小豬撲滿裡的零錢，捐獻給要參選2012年總統的蔡英文，竟然在民進黨總統大選過程中，成為競選過程的「大事件」。二、「三隻小豬」之策略形成，民進黨如何運用這個「綠營最有效的募款工具」，在競選過程中，募得高達2.012億台幣的政治獻金。三、「三隻小豬」之媒體評論，以東森新聞報導為研究文本，2012選戰中，報導三隻小豬的則數，是平安福的將近四倍之多。三隻小豬，讓民進黨獲得的免費廣告效益，估計在10至20億台幣之間。 本研究者因為職務之故，能貼身採訪蔡英文陣營，因此採用「參與觀察、深度訪談」兩種研究方法，獲得第一手的訊息資料，再就東森新聞選舉過程中所報導「蔡英文」和「三隻小豬」的97篇相關文稿進行「內容分析」。 根據卡方檢定和ANOVA檢定的分析結果，本研究發現在蔡英文競選過程中，有三項值得觀察的顯著差異。並歸納出「三隻小豬」運動，此一大事件，具備不同於以往選舉的六大特色，包括：創新性、象徵性、互動性、在地性、參與性、持續性等。 / In the 2012 presidential election, The DPP’s Three Little Pigs campaign was so called the history of Taiwan's unprecedented mobilization election campaign. Four years later, in the 2016 presidential election, this “Mega Event” is to be continued, so this study highlights: First, the "Three Little Pigs" event that originated in Tainan, triplets’ children save money in a piggy bank, they donated the changes to the 2012 presidential candidate Tsai Ing-wen, set off political waves in the DPP election process unexpected. Second, how the "Three Little Pigs" policy formed, DPP proper use of this "come out of the gift," during the campaign, they raised up to NT$ 201.2 million in political contributions. Three Little Pigs can be described as the most effective fund-raising tool for the Green Camp. Third, the media covering regarding "Three Little Pigs" campaign, take the ETTV new scripts as study texts, during the 2012 election campaign, the number of covering stories in the Three Little Pigs is four times more than Ma Ying-jeou’s lucky charm. The DPP obtained about NT$ 1 to 2 billion free advertising effectiveness via Three Little Pigs movement. It is because of the researchers’ position; the researcher was able to interview Tsai camp closely. This research adopted "participant observation, in-depth interviews," these two methods, to obtain first-hand information and message. The researcher did "content analysis", to analyze 97 ETTV news stories regarding to "Tsai Ing-wen" and "The Three Little Pigs," in the presidential election. According to the analysis results of the chi-square test and ANOVA test, this study found that when Tsai Ing-wen was running for presidential campaign, there are three significant differences worth observing. Meanwhile, to conclude "The Three Little Pigs" mega event campaign, there are six characteristics different from previous elections, including: innovation, symbolic, interaction, localization, participation, sustainability and so on.

Social and environmental justice for a growing and developing global population requires significant increases in energy use. A possible means of contributing to this energy increase is to incinerate plutonium from spent fuel of pressurised light water reactors (Pu(PWR)) in high-temperature reactors such as the Pebble Bed Modular Reactor Demonstration Power Plant 400 MWth (PBMR-DPP-400). Previous studies showed that at low temperatures a 3 g Pu(PWR) loading per fuel sphere or less had a positive uniform temperature reactivity coefficient (UTC) in a PBMR DPP-400. The licensing of this fuel design is consequently unlikely. In the present study it was shown by diffusion simulations of the neutronics, using VSOP-99/05, that there is a fuel design containing thorium and plutonium that achieves a negative maximum UTC. Further, a fuel design containing 12 g Pu(PWR) loading per fuel sphere achieved a negative maximum UTC as well as the other PBMR (Ltd.) safety limits of maximum power per fuel sphere, fast fluence and maximum temperatures. It is proposed that the low average thermal neutron flux, caused by reduced moderation and increased absorption of thermal neutrons due to the higher plutonium loading, is responsible for these effects. However, to fully understand the mechanisms involved a detailed quantitative analysis of the roll of each factor is required. A 12 g Pu(PWR) loading per fuel sphere analysis shows a burn-up of 180.7 GWd/tHM which is approximately double the proposed PBMR (Ltd.) low enriched uranium fuel burn-up. The spent fuel has only a decrease of 24.5 % in the Pu content which is sub-optimal with respect to proliferation and waste disposal objectives. Incinerating Pu(PWR) in the PBMR-DPP 400 MWth is potentially licensable and economically feasible and should be considered for application by industry. / MIng (Nuclear Engineering), North-West University, Potchefstroom Campus, 2012