<p>Upon activation mast cells release numerous proinflammatory mediators. With this feature, mast cells play an important role in host defense against pathogens, and are involved in tissue remodeling and wound healing. However, in cases of excessive inflammation the effects of mast cells are detrimental. This is observed in allergy, asthma, rheumatoid arthritis, atherosclerosis, certain types of heart failure, and in several other chronic destructive inflammations. Mast cell numbers are typically increased at inflammatory sites. There they act both directly, as effector cells, and in a regulatory manner, secreting agents that recruit and activate other immune cells.</p><p>The studies presented here investigated mechanisms regulating mast cell numbers at sites of inflammation, focusing on cell migration and regulation of survival/apoptosis. We report that SCF-induced mast cell migration requires p38 MAP kinase activity. Moreover, we found that SCF-mediated mast cell survival is regulated through downregulation of the proapoptotic Bcl-2 family member Bim, as well as through phoshorylation of Bim. SCF seems to control Bim protein levels via FOXO transcription factors, and to induce phosphorylation of Bim via the Mek/Erk and the PI3-kinase/Akt signaling pathways. Furthermore, mast cell death triggered by deprivation of SCF and/or IL-3 involves the Bim protein, as demonstrated using <i>bim</i>-/- mast cells. Additional studies revealed that IgE-receptor activation, which occurs in allergy, promotes both prosurvival and proapoptotic signaling events. This includes upregulation of Bim and the prosurvival Bcl-X_L and A1, as well as phosphorylation of Akt, FOXO factors, GSK-3β, IκB-α, Bad, and Bim. The simultaneous stimulation of prosurvival and proapoptotic signaling events could be a way to fine-tune the fate of mast cells after IgE-receptor activation and degranulation.</p><p>The new insights about mechanisms involved in mast cell migration and regulation of survival/apoptosis might prove useful for future efforts to design new drugs to be used for mast cell-associated diseases.</p>

Graduation date: 2006 / The design of a 10-bit pipelined charge redistribution DAC employing MOSCAPs biased in their accumulation mode is presented in this thesis. A switched capacitor filter and output buffer have also been designed for the system. The effect of MOSCAP nonlinearity on the performance of the pipelined charge redistribution DAC has been analyzed. MOS capacitors and their models available for simulation have been discussed. In addition, the effect of more general capacitor nonlinearities on the performance of the DAC has been presented.

Mast cells are essential effector cells in the immune system as they release several inflammatory mediators. An accumulation of mast cells has been described in inflammatory conditions such as asthma and allergic rhinitis. Increased mast cell number, in the skin and other organs, is also a characteristic in mastocytosis, a disease without an effective treatment. One explanation for the increase in mast cell number is migration of mast cells in the tissue. In our studies we utilised mast cell lines, including HMC-1; cell lines transfected with the c-kit gene; and in vitro developed mast cells. Our aim was to characterise, two variants of the HMC-1 cell line; the signalling pathways essential for mast cell migration towards TGF-β and SCF; and the mechanism regulating mast cell accumulation in mastocytosis. Our results help to explain inconsistent findings regarding mast cell biology when HMC-1 cells have been used as a model system. The two variants, which we name HMC-1560 and HMC-1560, 816, are used in different laboratories around the world. HMC-1560 and HMC-1560, 816 exhibited different characteristics regarding their karyotype, phenotype as well as their set of activating point mutations in the Kit receptor. Furthermore, divergent signalling pathways are of importance for mast cell migration towards TGF-β and SCF. The classical MAP kinase-signalling cascade was found to be of major relevance for TGF-β-induced migration. In contrast, this pathway had a modest impact on SCF-induced migration, which instead was highly dependent on p38 MAP kinase signalling. Finally, one mechanism for mast cell accumulation in mastocytosis appeared to be an activating point mutation in the gene for the Kit receptor. This mutation appeared to prone transfected cells and mast cell progenitors to a higher rate of migration towards SCF if compared with cells expressing wt Kit receptor. In conclusion, our results show the importance of two different MAP kinase signalling pathways and mutations in the Kit receptor for mast cell migration induced by various types of stimuli. This knowledge helps us to understand the mechanism

Mast cells are long-lived effector cells of importance for both acute and chronic inflammations. Mast cells can be activated in many different ways, leading to the release of inflammatory mediators. In contrast to most other inflammatory cells, activated mast cells have the capacity to recover, regranulate and thereby be activated again. In this thesis I have investigated the mechanisms involved in regulating activation-induced mast cell survival. We have found that cross-linking of FcεRI-bound IgE with an antigen (IgER-CL) induces a survival program in mast cells. Upon IgER-CL, mouse and human mast cells upregulate the pro-survival Bcl-2 family gene A1/Bfl-1. A1-/- mast cells degranulate upon FcεRI activation but they cannot recover most likely due to the lack of A1. Sensitized and provoked A1-/- mice exhibit lower amounts of mast cells compared to littermate controls. In contrast to mast cells, no Bfl-1 expression or survival promotion can be detected in basophils after IgER-CL. Another mast cell secretagogue, an adenosine receptor agonist, neither promoted upregulation of A1 nor survival. Although it is well established that mast cell survival is dependent on stem cell factor (SCF), it has not been described how this process is regulated. We have found that SCF promotes survival through Akt-mediated inhibition of the forkhead transcription factor FOXO3a and its transcriptional target Bim, a BH3-only pro-apoptotic protein. SCF-treatment prevents upregulation of Bim protein expression and leads to an upregulation of Bim phosphorylation through PI3-kinase and MEK-dependent pathways. Overexpression of FOXO3a causes an upregulation of Bim and induces mast cell apoptosis, even in the presence of SCF. Taken together, the work in this thesis demonstrates that A1/Bfl-1 and Bim play key roles in mast cell survival. These findings might be of importance in understanding the mechanisms of mast cell longevity and hence for possible new therapeutics used for mast cell-associated inflammations.

Upon activation mast cells release numerous proinflammatory mediators. With this feature, mast cells play an important role in host defense against pathogens, and are involved in tissue remodeling and wound healing. However, in cases of excessive inflammation the effects of mast cells are detrimental. This is observed in allergy, asthma, rheumatoid arthritis, atherosclerosis, certain types of heart failure, and in several other chronic destructive inflammations. Mast cell numbers are typically increased at inflammatory sites. There they act both directly, as effector cells, and in a regulatory manner, secreting agents that recruit and activate other immune cells. The studies presented here investigated mechanisms regulating mast cell numbers at sites of inflammation, focusing on cell migration and regulation of survival/apoptosis. We report that SCF-induced mast cell migration requires p38 MAP kinase activity. Moreover, we found that SCF-mediated mast cell survival is regulated through downregulation of the proapoptotic Bcl-2 family member Bim, as well as through phoshorylation of Bim. SCF seems to control Bim protein levels via FOXO transcription factors, and to induce phosphorylation of Bim via the Mek/Erk and the PI3-kinase/Akt signaling pathways. Furthermore, mast cell death triggered by deprivation of SCF and/or IL-3 involves the Bim protein, as demonstrated using bim-/- mast cells. Additional studies revealed that IgE-receptor activation, which occurs in allergy, promotes both prosurvival and proapoptotic signaling events. This includes upregulation of Bim and the prosurvival Bcl-XL and A1, as well as phosphorylation of Akt, FOXO factors, GSK-3β, IκB-α, Bad, and Bim. The simultaneous stimulation of prosurvival and proapoptotic signaling events could be a way to fine-tune the fate of mast cells after IgE-receptor activation and degranulation. The new insights about mechanisms involved in mast cell migration and regulation of survival/apoptosis might prove useful for future efforts to design new drugs to be used for mast cell-associated diseases.

No description available.

The presence of notches or cracks causes stresses to amplify in nearby regions. This phenomenon is studied by estimating the Stress Concentration Factor (SCF) for notches, and the Stress Intensity Factor (SIF) for cracks. In the present work, a semi-analytical method under the framework of linear elasticity is developed to give an estimate of these factors, particularly for cracks and notches in finite domains. The solution technique consists of analytically deriving a characteristic equation based on the general solution and homogeneous boundary conditions, and then using the series form of the reduced solution involving the (possibly complex-valued) roots of this characteristic equation to satisfy the remaining non-homogeneous boundary conditions. This last step has to be carried out numerically using, say, a weighted residual method. In contrast to infinite domain problems where a fully analytical solution is often possible, the presence of more boundaries, and a variety in configurations, makes the solution of finite do-main problems much more challenging compared to infinite domain ones, and these challenges are addressed in this work. The method is demonstrated on several classical and new problems including the problems of a semi-circular edge notch in a semi-infinite and finite plate, an elliptical hole in a plate, an edge-crack in a finite plate etc.

Neste trabalho está apresentada uma alternativa para o cálculo do fator de concentração de tensões (FCT) em juntas tubulares soldadas do tipo Y. Redes Neurais Artificiais (RNA) foram utilizadas para representar a distribuição de tensões ao longo da junta tubular para os casos de carregamento força axial no plano e momento fletor no plano. As RNA podem aprender a partir de um conjunto de dados sem a necessidade de uma expressão matemática entre as variáveis dependentes e independentes; representa uma vantagem sobre o procedimento normalmente utilizado, ou seja, as equações paramétricas. O modelo proposto representa um avanço no projeto de juntas tubulares, uma vez que evita a necessidade de se conhecer uma expressão matemática para representar a distribuição de tensões na junta e fornece um método mais preciso para avaliar a distribuição de tensões ao longo da junta soldada. O conjunto de dados utilizado foi formado a partir de simulações numéricas das juntas soldadas através do MEF, nas quais foi considerada a geometria do cordão de solda. / An alternative approach to calculate stress concentration factors (SCF) in Y-type welded tubular joints is presented. Artificial Neural Networks (ANN) were used to represent the stress distribution along the tubular joints in both in-plane axial force and in-plane bending moment load cases. ANN can learn from a database without establishing a mathematical expression between dependent and independent variables, which is an advantage over the usual parametric equations approach. The proposed model represents an improvement in the tubular joints design, since it avoids the previous knowing of a mathematical expression to represent the stress distribution in the joint and provides an accurate method to evaluate the stress distribution along the welded fillet joint. The database herein used was completed with FE simulations of tubular joints which consider the geometry of the weld fillet.

This thesis report presents a method to analyze the communication architecture for the Intelligent Transportation Systems (ITS). The report also includes a case study on ASN.1 notation and analysis of its encoding rules. Included in the report is also: (i) accompanying instruction on how to use ASN.1 compilers to produce the C/C++ message encoder/decoder, and (ii) analysis of Non-IP communications of Communication Access for Land Mobiles (CALM-FAST) protocol stack in ITS. The thesis is a part of the research project entitled “SCOOP”, a joint project between SCANIA CV AB and KTH. The purpose of this thesis is to contribute to the ultimate goal, which is to equip a vehicle with necessary hardware and software technology to provide a platooning behavior in the GCDC 2011 competition. This goal is achieved by the means of wireless communication system for both vehicle to vehicle and vehicle to road side units communications in the platoon. Overall, this thesis introduces the important usage of ASN.1 in implementation of cut-edge telecommunication systems especially in V2V and V2I communication; and clarifies the CALM-FAST protocol stack in mobile nodes. / Kartlägga CALM-FAST protokollet och hur det användes tillsammans med den i tävlingen GCDC 2011 fastslanga kommunikationsprotokollet. GCDC var ett tävling i kooperativ körning arrangerad och initierad av Hollänska TNO och gick ut på att få fordon att agera tillsammans beserat på information sänt via WLAN 802.11p. ASN.1 användes och ingick i analysen.

Polystyrene (PS) nanocomposite foams were prepared using supercritical fluid (SCF) CO2 as a solvent and blowing agent. PS was first in-situ polymerized with a range of concentrations of montmorillonite layered silicate (MLS). The polymerized samples were then compression molded into 1 to 2mm thick laminates. The laminates were foamed in a batch supercritical CO2 process at various temperatures and pressures from 60°-85°C and 7.6-12MPa. The resulting foams were analyzed by scanning electron microscopy to determine effect of MLS on cellular morphology. Differential scanning calorimetry was used to determine the impact of nanocomposite microstructure on glass transition of the foamed polymer. X-ray diffraction spectra suggested that the PS/MLS composite had an intercalated structure at both the 1% and 3% mixtures, and that the intercalation may be enhanced by the foaming process.