京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22150号 / 医博第4541号 / 新制||医||1039(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 竹内 理, 教授 稲垣 暢也, 教授 杉田 昌彦 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

This master‘s thesis deals with ecotoxicity assessment of plasma-activated solutions. Various plasma-activated solutions were prepared in the experiments. In the vast majority of tests, it was plasma-activated tap water – PAW. Depending on the test organism, dilution water was further processed, namely dilution water for Thamnocephalus platyurus and Daphnia magna. In this master‘s thesis the ecotoxicological effects were assessed through aquatic ecotoxicity tests with an aquatic plant Lemna minor, on a crustaceans T. platyurus and D. magna and on agricultural crops Lactuca sativa and Allium cepa L. . Crustaceans are fresh-water organisms on which the water contamination can be quickly and quite easily assessed. These plasma-activated solutions were also tested for acute ecotoxicity of soil organisms by ecotoxicological contact tests with Eisenia fetida, springtails Folsomia candida and seeds of L. sativa. Tests on T. platyurus and D. magna were performed in time intervals and a change in mortality was observed depending on PAW concentration. If the test results allowed, the LC50, IC50, A and NR escapism values were calculated. When the measured and calculated values did not allow such a calculation, the overall effect of PAW on organisms was assessed and a significant difference was calculated for the L.sativa root growth inhibition test. The final results showed that PAW has an ecotoxic effect on aquatic organisms, while it has rather beneficial effects on terrestrial organisms.

Ceramic membranes (CM) are robust membranes attributed with high production, long life span and stability against critical conditions. While capital costs are high, these are partially offset by lower operation and maintenance costs compared to polymeric membranes. Like any other low-pressure membrane (LPM), CM faces problems of fouling, low removal of organic matter and poor removal of trace organic compounds (TOrCs). Current pretreatment approaches that are mainly based on coagulation and adsorption can remove some organic matter but with a low removal of the biopolymers component which is responsible for fouling. Powdered activated carbon (PAC) accompanied with a LPM maintains good removal of TOrCs. However, enhanced removal of TOrCs to higher level is required. Submicron powdered activated carbon (SPAC), obtained after crushing commercial activated carbon into very fine particle, and novel activated carbon (KCU 6) which is characterized with larger pores and high surface area were employed. A pre-coating approach, which provides intimated contact between PAC and contaminants, was adopted for wastewater and (high DOC) surface water treatment. For seawater, in-line coagulation with iron III chloride was adopted. Both SPAC and KCU 6 showed good removal of biopolymers at a dose of 30 mg/L with > 85 % and 90 %, respectively. A dose of 40 mg/L of SPAC and 30 mg/L KCU 6 pre-coats were successful used in controlling membrane fouling. SPAC is suggested to remove biopolymers by physical means and adsorption while KCU 6 removed biopolymers through adsorption. Both KCU 6 and SPAC attained high removal of TOrCs whereas KCU 6 showed outstanding performance. Out of 29 TOrCs investigated, KCU 6 showed > 87 % TOrCs rejection for 28 compounds. In seawater pretreatment, transparent exopolymer particles (TEP) were found to be an important foulant. TEP promoted both reversible and irreversible fouling. TEP are highly electronegative while alumina CM is positively charged which support strong TEP–alumina binding. The influence of TEP fouling was minimized with a low dose of 0.5 – 1 mg/l Fe coagulant. Bacteria were almost completely removed; Silt Density Index (SDI) value was maintained to 2 % per minute and a constant permeate turbidity of 0.05 NTU was achieved.

No description available.

Activated carbons are one of the most used adsorbents with lots of applications in many sectors. Activated carbons can be produced from lignocellulosic materials with a large content of carbon. Coffee is the second trade most consumed all over the world; hence their residues can be treated in order to give a value. In order to evaluate the viability of using coffee residues as precursor have been carried out experiments by chemical and physical activation. The chosen chemical was phosphoric acid, a dehydrating chemical widely used in production of activated carbons while steam was selected for a physical activation. In this study have been studied the temperature activation and the concentration of chemical as the main factors. One of the advantages of using a chemical is the lower activation temperature; in this study were selected 500ºC, 600ºC and 700ºC while samples treated by steam were 600ºC, 700ºC and 800ºC. Water is a reactive agent that removes volatile compounds and makes wide pores whereas chemicals create linkages with the carbon and volatile compounds enhancing their porosity. Hence, have been studied the following impregnation concentrations 30%, 40% and 50% in order to evaluate their properties as adsorbents. Isotherms were analysed to determine their surface area and pore size distribution. Also were determined the pore size and pore volume for all samples.

This thesis explores potential seeding techiniques to limit harmful effects of preemergent herbicide on a seeded species while simultaneously reducing abudance of annual invasive grasses. The first chapter examines the use of activated carbon seed coatings and furrows to limit herbicide effect on seeds of a perrenial bunchgrass. We found that both carbon coatings and furrows mitigated some of the herbicide effects, but that only when the two techniques were combined did we observe unaffected seedling emergence, plant density, and aboveground growth. Therefore, we suggest to management that use of carbon coatings and furrows after herbicide application can likely be used to reduce invasive annual grasses while simultaneously establishing a native bunchgrass. In chapter 2, we examine the effects of a novel preemergent herbicide indaziflam, on native seeds and compare it against a common preemergent herbicide, imazapic. We found that indaziflam provides superior long-term control of annual invasive grasses than imazapic, but that it is also more detrimental to native seeds. Our results suggest that indaziflam is best suited for control purposes only, and is hard to incorporate in restoration seeding efforts due to its strong effects on native seed.

Background: Peroxisome proliferator-activated receptor δ (PPARδ) is a versatile regulator of distinct biological processes and overexpression of PPARδ in cancer may be partially related to its suppression of its own co-regulators. Aims: To determine whether recruited suppressor proteins bind to and regulate PPARδ expression, activity and PPARδ-dependent cholangiocarcinoma proliferation. Methods: Yeast two-hybrid assays were done using murine PPARδ as bait. PPARδ mRNA expression was determined by qPCR. Protein expression was measured by western blot. Immunohistochemistry and fluorescence microscopy were used to determine PPARδ expression and co-localization with NDP Kinase alpha (NM23-H2). Cell proliferation assays were performed to determine cell numbers. Results: Yeast two-hybrid screening identified NM23-H2 as a PPARδ binding protein and their interaction was confirmed. Overexpressed PPARδ or treatment with the agonist GW501516 resulted in increased cell proliferation. NM23-H2 siRNA activated PPARδ luciferase promoter activity, upregulated PPARδ RNA and protein expression and increased GW501516-stimulated CCA growth. Overexpression of NM23-H2 inhibited PPARδ luciferase promoter activity, downregulated PPARδ expression and AKT phosphorylation and reduced GW501516-stimulated CCA growth. Conclusions: We report the novel association of NM23-H2 with PPARδ and the negative regulation of PPARδ expression by NM23-H2 binding to the C-terminal region of PPARδ. These findings provide evidence that the metastasis suppressor NM23-H2 is involved in the regulation of PPARδ-mediated proliferation.

Apoptosis is a complex process essential for normal tissue development and cellular homeostasis. While biochemical events that occur late in the apoptotic process are better characterized, early physiological changes that initiate the progression of cell death remain poorly understood. Previously, we observed that lymphocytes, undergoing apoptosis in response to growth factor withdrawal, experienced a rapid and transient rise in cytosolic pH. We found that the protein responsible was the pH-regulating, plasma membrane protein Na +/H+ exchanger isoform 1 (NHE1), and that its activity was impeded by inhibition of the stress-activated kinase, p38 MAP kinase. In the current study, we examined how NHE1 is activated during apoptosis. We identified the phosphorylation sites on NHE1 that regulate its alkalinizing activity in response to a cell death stimulus. Performing targeted mutagenesis, we observed that substitution of Ser726 and Ser729 for alanines produced a mutant form of NHE1 that did not alkalinize in response to an apoptotic stimulus, and expression of which protected cells from serum withdrawal- induced death. In contrast, substitution of Ser726 and Ser729 for glutamic acids raised the basal pH and induced susceptibility to death. Analysis of serine phosphorylation showed that phosphorylation of NHE1 during apoptosis decreased upon mutation of Ser726 and Ser729. Our findings thus confirm a necessary function for NHE1 during apoptosis and reveal the critical regulatory sites that when phosphorylated mediate the alkalinizing activity of NHE1 in the early stages of a cell death response.

Doxorubicin (Dox) is a chemotherapeutic agent that causes significant cardiotoxicity. We showed previously that Dox activates p53 and induces apoptosis in mouse hearts. This study was designed to elucidate the molecular events that lead to p53 stabilization, to examine the pathways involved in Dox-induced apoptosis, and to evaluate the effectiveness of pifithrin-α (PFT-α), a p53 inhibitor, in blocking apoptosis of rat H9c2 myoblasts. H9c2 cells that were exposed to 5 μM Dox had elevated levels of p53 and phosphorylated p53 at Ser15. Dox also triggered a transient activation of p38, p42/p44ERK, and p46/p54JNK MAP kinases. Caspase activity assays and Western blot analysis showed that H9c2 cells treated with Dox for 16 h had marked increase in the levels of caspases-2, -3, -8, -9, -12, Fas, and cleaved poly(ADP ribose) polymerase (PARP). There was a concomitant increase in p53 binding activity, cytochrome c release, and apoptosis. These results suggest that Dox can trigger intrinsic, extrinsic, and endoplasmic reticulum-associated apoptotic pathways. Pretreatment of cells with PFT-α followed by Dox administration attenuated Dox-induced increases in p53 levels and p53 binding activity and partially blocked the activation of p46/p54JNK and p42/p44ERK. PFT-α also led to decreased levels of caspases-2, -3, -8, -9, -12, Fas, PARP, cytochrome c release, and apoptosis. Our results suggest that p53 stabilization is a focal point of Dox-induced apoptosis and that PFT-α interferes with multiple steps of Dox-induced apoptosis.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第22430号 / 工博第4691号 / 新制||工||1732(附属図書館) / 京都大学大学院工学研究科都市環境工学専攻 / (主査)教授 高岡 昌輝, 教授 米田 稔, 准教授 大下 和徹 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM