京都大学 / 0048 / 新制・論文博士 / 博士(人間健康科学) / 乙第13303号 / 論人健博第6号 / 新制||人健||5(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 青山 朋樹, 教授 黒木 裕士, 教授 松田 秀一 / 学位規則第4条第2項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

Content: Chrome tanning is the commonest tanning agent in leather manufacture, and the discard of chrome tanned leather goods inevitably leads to chrome discharge that might have potential environmental risks. In this study, the kinetic behaviors of the release of chrome and organics were investigated by ICP-OES and TOC analyzers respectively. Deionized water was used as medium, and leaching tests were proceed at solid liquid ratio 1:20 as well as rotational speed 60 r/min to simulate the release of chrome tanned leather under natural conditions. The effect of temperature on the behavior kinetics was further explored. The results showed that the release of chrome and organics could be well fitted by the second-order kinetic equation, and the rate constant for the release process indicated the release of organics was faster than chrome. Then Tenax model was used to illustrate the release kinetics experiments of chrome to obtain the three release compartments (fast, slow and very slow). The results could provide the theoretical parameters for the assessment of risks of chrome-tanned leather. Take-Away: The second-order kinetic equation could describe the release of chrome and organics from chrome tanned leather under natural environment. The activation energy of the release of chrome and organics from leather could be obtained. The fast, slow and very slow compartments of chrome release could be obtained.

Daily injections for basal insulin therapy are far from ideal resulting in hypo/hyperglycemic episodes associated with fatal complications in type-1 diabetes patients. The purpose of this study was to develop a thermosensitive copolymer-based in situ depot forming delivery system to provide controlled release of insulin for extended duration following a single subcutaneous injection, closely mimicking physiological basal insulin requirement. Size and nature of the incorporated therapeutic were observed to affect the release profile of insulin. Modification with zinc and chitosan preserved thermal, conformational, and chemical stability of insulin during the entire duration of storage (up to 9 months at 4 °C) and release (up to 3 months at 37 °C). In vivo, daily administration of long-acting insulin, glargine, resulted in fluctuating blood glucose levels between 91 – 443 mg/dL in type 1 diabetic rats. However, single administration of oleic acid-grafted-chitosan-zinc-insulin complexes incorporated in copolymer formulation demonstrated slow diffusion of insulin complexes maintaining peak-free basal insulin level of 21 mU/L for 91 days. Sustained release of basal insulin also correlated with efficient glycemic control (blood glucose <120 mg/dL), prevention of diabetic ketoacidosis and absence of cataract development, unlike other treatment groups. The suggested controlled basal insulin delivery system has the potential to significantly improve patient compliance by improving glycemic control and eliminating life-threatening diabetes complications. Furthermore, oleic acid-grafted-chitosan (CO) nanomicelles were investigated as a non-viral vector to deliver plasmid DNA encoding short hairpin RNA (shRNA) against pro-inflammatory cytokines to adipose tissue macrophages and adipocytes for the treatment of insulin resistance. Nanomicelles modified using mannose (COM) and adipose homing peptide (AHP) (COA) showed significantly higher uptake and transfection efficiency in inflamed macrophages- adipocytes co culture owing to glucose transporter-1 and prohibitin receptor mediated internalization, respectively. Ligand modified nanomicelles loaded with shRNA against tumor necrosis factor alpha (COM-TNFα) and monocyte chemoattractant protein-1 (COA-MCP1) demonstrated significant attenuation of pro-inflammatory cytokines and improved insulin sensitivity and glucose tolerance in obese-diabetic mice for six weeks post treatment with single dose of optimized formulation. Overall, chitosan nanomicelles mediated targeted gene therapy can help attenuate inflammation, the chief underlying cause of insulin resistance, thereby helping reverse the progression of diabetes. / National Institutes of Health (NIH) grant R15GM114701 / ND EPSCoR seed award FAR0030636

As autonomy increases in today’s vehicles, the demands increase on both safety and comfort functions. Vehicle Hold, which holds the vehicle stationary without requiring the driver to press the brake pedal, is an example of such as function. This thesis aims to develop a concept for a Drive Away Release from this hold state, following several requirements regarding such as rollback, comfort, manual and autonomous drive mode, driving direction, road inclinations, with or without a trailer, and following the safety standard ISO 26262. In order to develop the concept function, a study of the state-of-the-art was made, followed by modeling the dynamics and control. The control algorithm was validated and tested first by running co-simulations between Matlab/Simulink and CarMaker. It was then implemented in a test vehicle. The test vehicle did not have all systems which are usually provided, demanding estimations to be made, such as the road inclination and vehicle mass. For manual drive mode, the driver controls the propulsion torque, and the control algorithm is based on releasing the brakes depending on estimations of the gravitational and propulsion torques. For autonomous drive mode, the vehicle is supposed to follow an acceleration reference. The control algorithm for autonomous drive mode is then extended with two feedforward compensators, one from reference and one from the gravitational torque, which is regarded as a disturbance, and with a feedback PI controller. To ensure that rollback do not occur at drive away release, a rollback prevention safety feature was also developed. The results of both the simulations and the test drives show that the concept function provides comfortable drive-off for most inclinations, drive modes and directions, without causing an undesired rollback

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This diploma thesis is focused on development and characterization of hydrogel materials for agricultural use. In the experimental section, different methods of preparing these materials were designed and optimized according to previous literature review. In the characterization of resulting materials, the main attention was paid to the kinetics of swelling, to the solubility, the leaching of nitrate and of humic compounds. Thermogravimetric analysis represented another important characterization technique, which provided information about the content and form of water bound in the material. The development of the material aimed mainly at an agricultural application providing the delivery of nutrients to soil and regulation of water content in soil.

Notre laboratoire a récemment mis en évidence la réaction de cycloaddition entre les sydnones et les alcynes terminaux ou cycliques. Ces réactions sont bioorthogonales et possèdent la particularité de former deux produits : l’un provenant de la ligation (click) des deux partenaires réactionnels par cycloaddition (3+2), l’autre provenant d’un relargage (release) par réaction de rétro Diels-Alder. Le potentiel de ce type de réaction est très grand de par le nombre d’applications possibles que ce soit dans le domaine de la bioconjugaison, du marquage fluorescent ou de la libération de principes actifs.Les sydnones sont des composés hétérocycliques dipolaires qui appartiennent à la famille des mésoioniques. Cette thèse vise à découvrir de nouvelles réactions de ligation et de coupure mettant en jeu ces mésoioniques et des dipolarophiles. Vingt-cinq mésoioniques et trois familles de dipolarophiles ont été synthétisés et criblées.Lors du premier criblage, la réactivité des composés mésoioniques avec un alcyne terminal, sous une catalyse au cuivre, a été explorée. Neuf conditions de catalyse ont été testées. Ce criblage a mis en évidence la cycloaddition entre les aza-iminosydnones et les alcynes terminaux dont le produit formé dépend du système catalytique et de la nature de l’alcyne.La deuxième famille de dipolarophiles testée est celle des cycloalcynes. Nous avons découvert que, les dithiolium-olates réagissaient avec les cycloalcynes peu encombrés et que les sydnone-imines réagissent avec tous les cyloalcynes de manière bioorthogonale en libérant une molécule complexe.Enfin, les cycloalcènes ont été testés comme dipolarophiles. Dans cette partie, les résultats préliminaires du criblage nous ont amené à modifier la structure de la sydnone pour permettre la libération d’une molécule complexe. / Our laboratory has recently discovered the cycloaddition between sydnones and cyclic or terminal alkynes. These reactions are bioorthogonal and generate two products: one coming from the (3+2) cycloaddition (click) between both partners and the second from a cleavage step (release) through a retro Diels-Alder reaction. This type of new reactions would be of prime importance in the development of new reagents useful for bioconjugation and drug delivery applications.Sydnones are dipolar heterocycles belonging to the large family of compounds known as mesoionics. This work aims at discovering new chemoselective and bioorthogonal processes between mesoionic compounds and various dipolarophiles, that undergo in a same reaction both ligation and cleavage. Twenty-five mesoionics and three types of dipolarophiles were synthetized and screened.For the first screening, the reactivity between mesoionics and terminal alkyne, under a copper catalysis, was studied. Nine conditions of catalysis were tested. This screening revealed the cycloaddition between aza-iminosydnones and terminal alkynes. The structure of the formed products depends on the catalytic system and the nature of the alkyne used.The second type of dipolarophiles screened was cyclic alkynes. Dithiolium-olates were found to react with non-hindered cyclic alkynes. On the other side, imino-sydnones react with all cycloalkynes to afford a click product together with a released molecule.Finally, cycloalkenes were screened. Thanks to preliminary results from a screening, we engineered new sydnones to allow the release of a complex molecule after the cycloaddition step

The production of rape and other leaf vegetables for local and export markets by smallholder farmers in sub-Saharan Africa has been constrained by soil fertility depletion associated with continuous cropping with inadequate addition of major nutrients like Nitrogen (N), Phosphorus (P) and Potassium (K). Biomass transfer of multipurpose tree prunings (usually legumes) to croplands has been shown to significantly increase the availability of soil N. Nitrogen mineralization of the leguminous biomass provides a major pathway through which the fixed N becomes available for use by other plants. The extent to which a specific type of plant residue influences soil fertility, crop growth and N recovery is in part determined by its biochemical qualities, decomposition patterns and the concurrent timing of nutrient release and crop nutrient demand. Consequently, the main challenge with the use of biomass from leguminous trees is to ensure that the release of N from mineralization is synchronised with the crop‟s demand. The utilization of multipurpose tree prunings as a source of nitrogen for the production of rape (Brassica napus L.) and spinach (Spinacea olearacea L.) was studied in a series of experiments. Prunings of four leguminous tree prunings commonly found in agroforestry systems namely Leucaena leucocephala, Calliandra calothyrsus, Acacia angustissima and Acacia karoo were used. The objectives of the study were: i) To determine the effect of chemical composition of the various leguminous tree prunings and their decomposition and N release patterns and ii) To evaluate the short term nutrient supply of the various leguminous tree prunings with or without supplemental inorganic nitrogen on the growth and yield responses of rape and spinach, respectively. Results indicated that rates of decomposition and N release decreased in the order: L. leucocephala > A. angustissima > C. calothyrsus > A. karoo. The ratios of lignin-to-N (r = 0.85) and soluble condensed tannins-to-N (r = 0.89) were negatively correlated with N release. The rates of decomposition and nitrogen mineralization of the prunings used as soil ameliorants were best predicted by their (lignin+soluble condensed tannin)-to-N ratios (r = 0.91). Soil amelioration with the various leguminous prunings significantly increased yields (P < 0.05) relative to the yields of plots that did not receive any amelioration. Total biomass, leaf number, area and size as well as saleable leaf yields increased linearly for all treatments. The quality of the prunings used as soil ameliorants significantly affected (P < 0.05) the efficiency of N recovery. Prunings of L. leucocephala which were the most labile had higher nutrient recovery rates and increased yields compared to the other leguminous amendments. Soil amendment with prunings of A. karoo on the other hand, which were the most recalcitrant, resulted in relatively lower N recovery rates. Supplementation of pruning-N with inorganic fertilizer further increased yields over the 0N treatment, indicating improved N recovery by the leafy vegetables. Crop growth and rates of nitrogen recovery of the leafy vegetables were corroborated by the short term nutrient supply capabilities of the leguminous prunings. Leguminous tree prunings can be used as a source of N for vegetable production as evidenced by the higher yields realized from amending the soil with the various prunings relative to the unfertilized plants. However, the rate and amount of N mineralized from the prunings and hence the net benefit obtained by the crop determines their suitability for vegetable production. / Dissertation (MSc Agric)--University of Pretoria, 2013. / gm2014 / Plant Production and Soil Science / Unrestricted

Introduction: The most common symptom of ankyloglossia is breastfeeding problems. Lately, more attention has been given to problems beyond infancy, like with speech and mobility. There is limited research done in that area though, and there is no research made comparing indication groups with each other.Aim: To investigate if there is a difference in the self-experienced benefit of the tongue-tie release, in relation to the indication for cutting the tongue-tie.Methods: A retrospective survey of all patients who underwent a tongue-tie release in Örebro county under a period of two years. The patient, or their caregiver if the patient was under 18 years old, were contacted for a telephone survey. 73 patients completed the survey.Results: The results demonstrated no significant difference in self-experienced benefit between the indication-groups. 88% of all patients included in the study experienced benefit, 98% of these patients had a primary (n=57) or secondary (n=6) symptom that got better. The remaining 2% (n=1) experienced benefit despite any symptom relief because of the possible future benefit. The 12% that did not experience benefit did not experience any symptom relief from the surgery.Conclusions: The self-experienced benefit after the tongue-tie release was high in general, without differences between the indication-groups. It turned out to be important to ask for other symptoms than just the primary to see the whole picture. More research with a larger study population is encouraged.

Orientador: Renato Grillo / Resumo: Inúmeros sistemas nanoestruturados vêm sendo desenvolvidos para o transporte e liberação modificada de defensivos agrícolas nos últimos anos. Tais sistemas vêm se mostrando uma potencial ferramenta para reduzir a toxicidade destes ingredientes ativos no ambiente, bem como vêm melhorando a eficiência de pesticidas no campo. Entretanto pouco se conhece sobre o destino, toxicidade e mecanismos de ação destes nanocarreadores no ambiente. Neste sentido, o objetivo do presente trabalho foi desenvolver potenciais sistemas de liberação modificada, encapsulando o herbicida atrazina (ATZ) em carreadores lipídicos nanoestruturados (CLNs) sem e contendo nanopartículas inorgânicas (magnéticas (Fe3O4@AO) e plasmônicas (Au@CTAB)), a fim de construir um sistema de liberação marcado que possa ser rastreado, auxiliando assim em futuras análises destes nanocarreadores no ambiente. Para o desenvolvimento das nanoformulações a técnica de emulsificação/evaporação solvente foi aplicada e diversos métodos físico-químicos foram empregados para a sua caracterização. As nanoformulações permaneceram estáveis por mais de 60 dias à temperatura ambiente. Além disso, os CLNs demostraram ter índice de polidispersão (PDI) < 0,2, potencial zeta entre -5,38 ± 0,27 a -23,5 ± 1,25 mV e uma eficiência de encapsulação maior que 90 % para a ATZ. As análises de microscopia eletrônica de varredura (MEV) revelaram ausência de agregados e morfologia esférica ao sistema. Além disso, as técnicas de espectroscopia de Infra... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Numerous nanostructured systems have been developed for the transportation and modified release of crop protection products in recent years. Such systems have been shown to be a potential tool to reduce the toxicity of these active ingredients in the environment, as well as improving the efficiency of pesticides in the field. However, little is known about the fate, toxicity and mechanisms of action of these nanocarriers in the environment. In this sense, the objective of the present work was to develop potential modified release systems, encapsulating the herbicide atrazine (ATZ) in nanostructured lipid carriers (CLNs) without and containing inorganic (magnetic (Fe3O4 @ AO) and plasma (Au @ CTAB)) nanoparticles) , in order to build a marked release system that can be tracked, thus assisting in future analyzes of these nanocarriers in the environment. For the development of nanoformulations, the solvent emulsification / evaporation technique was applied and several physical-chemical methods were used for its characterization. The nanoformulations remained stable for more than 60 days at room temperature. In addition, CLNs have been shown to have a polydispersity index (PDI) <0.2, zeta potential between -5.38 ± 0.27 to -23.5 ± 1.25 mV and an encapsulation efficiency greater than 90% for the ATZ. Scanning electron microscopy (SEM) analyzes revealed the absence of aggregates and spherical morphology to the system. In addition, Infrared spectroscopy (FTIR) and X-ray (DRX) techniq... (Complete abstract click electronic access below) / Mestre