Wound repair is a complex series of events that begins immediately after wounding, and can continue for a number of months to years. Various physiological and mechanical factors may impair the healing response, resulting in a chronic wound, characterised by a sustained inflammatory response. One of the main cells involved in both the inflammatory phase and proliferation phase of wound healing is the macrophage. There are thought to be different activation states which allow the macrophage to be involved in the two different phases of wound healing, namely the classically activated macrophage and the alternatively activated macrophage. Changes in the number of classically activated/alternatively activated macrophages in the wound is likely to have an effect on wound healing. Therefore a more thorough understanding of macrophage activation states during wound healing would broaden the understanding of the role of this cell in this process. The overall aim of this project was to investigate whether diabetic bone marrow progenitor cells or macrophages respond to activation stimuli differently in comparison to wild type cells. The hypothesis of this thesis is that diabetic macrophages will not respond to appropriate stimuli and thus alternative and classical macrophages will not behave 'appropriately', resulting in impaired healing. The results of this thesis indicate that impaired wound healing in the diabetic environment may be due to both the diabetic wound environment itself and intrinsic differences in diabetic macrophages. This work indicates that signals from the wound environment activates and influences macrophages, as these cells do not express activation markers until they enter the wound environment. However, the culture system devised in this study indicates that even before activation with signals they would receive in the wound environment, diabetic cells are more pro-inflammatory and have impaired migration. In addition, these macrophages respond differently to activation supporting the hypothesis that the macrophages are intrinsically different and that diabetic cells do not behave 'appropriately' which could contribute to impaired wound healing.

Yes / Earthquake response spectrum is the most popular tool in the seismic analysis and design of structures. In the case of combined primary-secondary (P-S) systems, the response of the supporting P substructure is generally evaluated without considering the S substructure, which in turn is only required to bear displacements and/or forces imposed by the P substructure (¿cascade¿ approach). In doing so, however, dynamic interaction between the P and S components is neglected, and the seismic-induced response of the S substructure may be heavily underestimated or overestimated. In this paper, a novel CQC (Complete Quadratic Combination) rule is proposed for the seismic response of linear light S substructures attached to linear P substructures. The proposed technique overcomes the drawbacks of the cascade approach by including the effects of dynamic interaction and different damping in the substructures directly in the cross-correlation coefficients. The computational effort is reduced by using the eigenproperties of the decoupled substructures and only one earthquake response spectrum for a reference value of the damping ratio.

This work topic is development and history of intelligent wiring systems in Czech Republic as well as abroad. The firs paragraphs describe following: intelligent wiring systems, the differences between classic and intelligent wiring systems and consequently is described the intelligent wiring system itself (types, principles, advantages, disadvantages etc.). Detailed description of system Inels follows in the next chapters. This system is supposed to be the fundamental matter of this work and is used in consequent suggestions for intelligent wiring system that is defined at the end of the theoretical part of this work. At the conclusion the economic evaluation of various wiring options and assessment by the multicriteria analysis (MCA) will be provided.

Indiana University-Purdue University Indianapolis (IUPUI) / Differences in voluntary consumption of ethanol have been negatively correlated with differences in initial sensitivity and tolerance to ethanol’s pharmacological effects. From this perspective, both adolescent and adult alcohol-nonpreferring (NP) rats would be expected to be initially more sensitive to the sedative and hypothermic effects of ethanol and fail to acquire tolerance to those effects than preferring (P) rats. The first objective of this experiment was to assess alcohol-induced hypothermia and locomotor sedation in adolescent and adult P and NP rats over five consecutive daily administrations (saline, 1.5 g/kg, or 3.0 g/kg ethanol 17%v/v), testing the hypothesis that the P rats would acquire tolerance to the hypothermic response whereas the NP rats would not show changes across days. In addition, it was hypothesized that there would be age-related differences in initial sensitivity to ethanol, evident by adolescent rats displaying less ethanol-induced hypothermia and locomotor sedation than adult rats on Day 1. The second objective was to determine if conditioning was occurring between the administration environment and the hypothermic response and locomotor sedation elicited by ethanol exposure, via a sixth injection of saline. Female rats were surgically implanted with intraperitoneal Mini Mitter telemetry probes on postnatal day 25 or 85 and experimental manipulations began five days later. Data were collected every minute; temperature data were then converted to change from baseline scores and locomotor data were totaled for each session. On Day 1, maximum temperature reduction elicited by the 3.0 g/kg dose was greater in the NP rats than the P rats, regardless of age. That dose also produced greater levels of locomotor sedation in the adult rats compared to the adolescent rats, regardless of line. The 1.5 g/kg dose of ethanol produced a greater hypothermic response in adult rats compared to adolescent rats, locomotor activity was reduced equally across the groups. With repeated administrations, NP adult rats displayed sensitization to the hypothermic response elicited from the 3.0 g/kg dose; in contrast, tolerance to the hypothermic response was found within the 1.5 g/kg dose for the adolescent P, adult P, and the adult NP rats. Repeated saline administrations also resulted in tolerance to the hypothermic response associated with administration in the adult NP and adolescent P rats. On the Day 6 saline administrations, adult rats which had previously been exposed to the 3.0 g/kg dose, maintained their baseline body temperatures better than both of the other exposure groups. Adolescent rats failed to show any signs of conditioning when administered saline on Day 6. Contrary to prediction the P rats failed to acquire tolerance to the 3.0 g/kg dose for either measure; and the line difference in ethanol-induce hypothermia was due to sensitization of the hypothermic response in adult NP rats. These results also provide further support that adolescent rats are less sensitive to the initial aversive effects of ethanol at the 1.5 g/kg dose for ethanol-induced hypothermia and the 3.0 g/kg dose for locomotor activity. The current experiment provides evidence that initial sensitivity as well as the acquisition of tolerance to ethanol-induced hypothermia may be behavioral phenotypes correlated with selection for high and low alcohol drinking preference.

Idiopathic Pulmonary Fibrosis (IPF) is a debilitating respiratory disorder that is characterized by a progressive decline in lung function. Originating through unknown etiology, it is essentially an unchecked wound healing response that causes the build-up of excessive scar tissue in the lung interstitial tissue with a heavy toll on the patient’s respiratory capacity. Pro-fibrotic alternatively activated macrophages (M2) have been linked as an important contributor to the fibrotic remodeling of the lung. Previous Ask research indicates that targeting M2 macrophages is possible through the use of the Dectin-1 receptor, a transmembrane cell surface receptor found in high abundance on M2 macrophages. Activating the Dectin-1 receptor through the use of beta-glucan, a ligand the receptor has a high affinity for, initiates a pro-inflammatory response within the naturally immunosuppressive macrophage and can alter its activity to be less fibrogenic. Our data suggest that M2 polarization of naïve macrophages can be inhibited in vitro by beta-glucan microparticles. Additionally, we have found that polarized M2 macrophages adopt M1-like characteristics when treated with beta-glucan microparticles, in a process that is largely Dectin-1 dependent. M2 cell surface marker CD206, increased levels of which are associated with rapidly progressing IPF, shows significantly decreased frequency of expression in M2 macrophages treated with beta-glucan microparticles. Our assessment for cell-specific uptake of beta-glucan microparticles suggests an important role of the Dectin-1 receptor for significantly increased uptake in murine wild-type M2 macrophages relative to their Dectin-1 knockout counterpart. The use of beta-glucan microparticles as a potential anti-fibrotic therapeutic was assessed in the bleomycin model of fibrotic lung disease. Mice given bleomycin and treated with beta-glucan displayed decreased soluble collagen content and TGFB expression within lung homogenate relative to fibrotic bleomycin control mice. Overall, these results provide insight into the use of beta-glucan as a potential activity modulator of macrophage function in IPF and the possibility of its use as a therapeutic. / Thesis / Master of Science (MSc)

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with worsening respiratory symptoms and physiological impairment. Pulmonary fibrosis is a chronic lung disease characterized by forming scar tissue (fibrosis) in the lungs. Alternatively activated macrophages (M2) known as pro-fibrotic are known to contribute to the fibrotic remodeling of the lung. In addition to the polarization of slices from naïve to pro-fibrotic, the addition of anti-fibrotic therapeutics reprogram slices back to a naïve condition. To polarize the slices, naïve slices are incubated with a previously investigated method in the lab known as the polarization cocktail. The polarization cocktail can be achieved by adding of IL-4, IL-6 and IL-13 to naïve(M0) slices in the Precision Cut lung slice (PCLS) model. For the therapeutic model, slices are incubated with the polarization cocktail and subsequently with the therapeutic. Our results have shown that the precision cut lung slice model can mimic previously investigated in-vivo experiments with the polarization cocktail. Secondly, the addition of therapeutics result in the slices exhibiting lower amounts of M2 markers and arginase activity concluding the model is suitable for the polarization and reprogramming of macrophages. / Thesis / Master of Science in Medical Sciences (MSMS)