京都大学 / 新制・課程博士 / 博士(情報学) / 甲第25438号 / 情博第876号 / 新制||情||147(附属図書館) / 京都大学大学院情報学研究科数理工学専攻 / (主査)教授 梅野 健, 教授 辻本 諭, 教授 田口 智清 / 学位規則第4条第1項該当 / Doctor of Informatics / Kyoto University / DFAM

付記する学位プログラム名: 京都大学卓越大学院プログラム「先端光・電子デバイス創成学」 / 京都大学 / 新制・課程博士 / 博士(情報学) / 甲第25445号 / 情博第883号 / 新制||情||148(附属図書館) / 京都大学大学院情報学研究科通信情報システム専攻 / (主査)教授 大木 英司, 教授 原田 博司, 教授 岡部 寿男 / 学位規則第4条第1項該当 / Doctor of Informatics / Kyoto University / DFAM

This thesis assessed the readability of CRT displays viewed under ambient lighting conditions and then evaluated the findings with respect to the ISO 9241-7 standard. More specifically, two phases of work were conducted in this thesis. In Phase 1, seven monitors were evaluated photometrically according to the ISO 9241-7 standard to determine whether they were Class I, II, or III in positive and negative polarity. Additionally, six filters were attached to each of the monitors and their ISO Class also was assessed. All monitor/filter combinations yielded either Class I or II in positive polarity and Class II, III or failed in negative polarity. In Phase 2, fourteen participants were asked to read Tinker passages from seven display/filter combinations (tested in Phase 1) under five lighting conditions and two screen polarities. The purpose of the Phase 2 was to determine if people perform differently for Class I, II, or III monitor/filter combinations. The dependent measures were the time to read the Tinker passage (reading time) and the ability to identify the out of context word in each passage (accuracy). An Analysis of Variance was used to determine the significant effects of reading time and accuracy. The ANOVA results indicate that specular glare interferes significantly more with reading time than does diffuse glare. Diffuse (200 lux) and Specular reading times also were correlated against two ISO metrics: screen image luminance ratio (Diffuse, 200 lux) and specular reflection luminance ratio. Reading times did not correlate with the screen image luminance ratio, but they did correlate with one of the ISO specular reflection luminance ratios. The results of this thesis indicate that the ISO standard should not equally weight the screen image and the specular reflection luminance ratios. Additionally, the results indicate that it is not necessary to have separate ISO Classes for positive and negative polarity. Furthermore, people did not read differently for Class I, II, or III monitor/filter combinations. Finally, the data of this investigation provide an initial human factors database for use in assessing the validity of ISO 9241-7. / Master of Science

This thesis evaluates the ISO 9241 Part 7, Ergonomic requirements for office work with visual display terminals (VDTs) - Part 7: Requirements for display with reflections. The thesis involved two phases of effort that evaluated the photometric measurements required in the ISO standard in terms of subjective image quality judgments. In phase one, seven monitors were evaluated photometrically according to the ISO 9241-7 standard to determine whether they were Class I, II, or III. Additionally, glare filters were attached to monitors to see if they change the ISO classification of the monitor. The results of phase one indicated that positive polarity always yielded either Class I or Class II because the Large Source, Screen Image Luminance Ratio (LR BDS/FDS) and the Specular Reflection Luminance Ratio (LR BDS/BD) always passed. Conversely, negative polarity always produced Class II or Class III because the Small Source, Specular Reflection Luminance Ratio (LR BDS/BD) failed every time. Also, the AF 150 and HF 300 were the best filters for reducing glare on monitors. The BF 10 and AF 100 or AF 200 ,on the other hand, were the worst because they intensified screen reflections. In phase two, human image quality judgments were collected to determine if people rated Class I, II, or III monitor-filter combinations differently under different lighting and different screen polarity conditions. Specifically, phase two assessed the effects of seven monitor/add-on glare filter combinations, five ambient lighting conditions, and two screen polarities on subjective image quality ratings. Each participant provided subjective image quality judgments by viewing alphanumeric text on the CRT screens. Subjective scale values also were correlated with ISO classifications and two ISO metrics: screen image luminance ratio (Diffuse, 200 lux) and specular reflection image luminance ratio. The ANOVA findings indicated that specular glare significantly degrades image quality ratings more than diffuse glare. The author contends that this finding is the result of an experimental context effect. In other words, the specular glare was so influential on subjective ratings of image quality that subjects paid little or no attention to reductions in contrast from the diffuse lighting conditions. The correlation analysis showed that the specular reflection luminance ratio and the negative polarity classifications did index subjective quality ratings. Finally, this thesis establishes a human factors basis to justify the measurement requirements in the ISO 9241-7 standard. Specifically, the findings show that it underemphasizes the contribution of the specular reflection luminance ratio' and overemphasizes the contribution of the screen image luminance ratio to compliance classification calculations, because the procedure gives equal weight to both ratios. / Master of Science

Slo2, a large conductance potassium channel in the nervous system is important for regulating neuronal function and excitability. Mutations in the gene that encodes the Slo2 channel are associated with neurological disorders, including epilepsy and intellectual disabilities in humans. However, much remains unknown about the genes and proteins that regulate Slo2 channel activity in the physiological system. This study investigates regulation of SLO-2, a homologue of mammalian Slo2 in C. elegans, by thoc-7 in an RNA editing-dependent pathway. Prior research has shown that adr-1, the gene important for RNA editing, promotes SLO-2 function by RNA editing of scyl-1 that encodes a regulator of SLO-2. To gain a better understanding of the regulation of SLO-2, this study employed a forward genetic approach to screen for mutants with a specific phenotype. Through SNP mapping and whole genome sequencing, we identified the gene thoc-7, which is predicted to be involved in mRNA export from nucleus, from the isolated mutants. The identification was further confirmed by CRISPR/Cas9-mediated gene knock-out, which showed a similar phenotype to the mutant strain. Results of electrophysiological recordings suggest that thoc-7 likely contributes to SLO-2 function in a common pathway with scyl-1. A reporter gene revealed strong expression of thoc-7 in most of the cells of C. elegans, particularly muscular and digestive system. Translational fusion with GFP showed the primary localization of the THOC-7 protein in cytoplasm, with some weak expression in the nucleus. RT-qPCR analysis suggests that thoc-7 regulates scyl-1 by through a post-transcriptional mechanism, possibly involving the transport of mRNA from cytoplasm to nucleus. This study highlights thoc-7 as a potential key regulator recruited by adr-1 to control SLO-2 via scyl-1 expression.

No / Cryptolepine (5-methyl-10H-indolo [3, 2-b] quinoline), an indoloquinoline alkaloid (1) isolated from a medicinal plant traditionally used in Western Africa for treatment of malaria, has been shown to possess broad spectrum biological activity in addition to its antiplasmodial effect. Here, the antileishmanial properties of 11 synthetic derivatives of cryptolepine against Leishmania donovani parasites have been evaluated for the first time. 2,7-Dibromocryptolepine (8; IC50 0.5 ± 0.1 μM) was found to be the most active analogue against the promastigote form of a classical L. donovani strain (AG83) in comparison to the natural alkaloid, cryptolepine (1; IC50 1.6 ± 0.1 μM). Further, 8 was found to substantially inhibit the intracellular amastigote forms of two clinical isolates, one of them being an SbV-resistant strain of L. donovani. Moreover, the toxicity of 8 against normal mouse peritoneal macrophage cells was markedly lower than that of 1 (IC50 values: 9.0 ± 1.2 and 1.1 ± 0.3 μM, respectively), indicating 8 to be a prospective “lead” towards novel antileishmanial therapy. This was supported by studies on the mechanism of cytotoxicity induced by 8 in L. donovani promastigotes (AG83), which revealed the cytoplasmic and nuclear features of metazoan apoptosis. Light microscopic observation demonstrated a gradual decline in the motility, cell volume, and survival of the treated parasites with increasing incubation time. Flow cytometric analysis of phosphatidylserine externalization and distribution of cells in different phases of cell cycle confirmed the presence of a substantial percentage of cells in early apoptotic stage. Disruption of mitochondrial membrane integrity in terms of depolarization of membrane potential, and finally degradation of chromosomal DNA into oligonucleosomal fragments—the hallmark event of apoptosis—characterized the mode of cell death in L. donovani promastigotes.

The expression of CCR7 was evaluated in different cancer cell lines by using flow cytometry, western blot, Immunofluorescence and immunohistochemistry. We showed for the selected cell lines that the expression is maintained in cells grown as spheroids, and xenoplanted in mice. Furthermore, we showed the expression of CCR7 correlates with stage of the disease in patient derived head and neck cancer tissue. We also showed that expression of CCR7 in cancer cell lines correlates with migratory aptitude towards CCL21 in a scratch assay, Boyden chamber assay and spheroid invasion assay. We then showed that the expression of CCR7 is elevated under serum starvation and under hypoxia in cancer cell lines grown as monolayers and as spheroids; and that there is a correlation between hypoxia and CCR7 expression in spheroids, xenografted cells and clinical cancer tissue. However, we found that in cell line OSC-19, the increase in the expression of CCR7 did not correlate to increased migration. Our investigations following this observation showed that whilst hypoxia increases the expression of CCR7, it concurrently causes a decrease in reactive oxygen species (ROS) which strongly abrogates migratory aptitude in OSC-19, resulting in an overall loss of migration in OSC-19 cells. In addition, we characterised OSC-19 as a suitable model to evaluate small molecule CCR7 antagonists using a number of different assays. In particular, we showed that ICT13069 antagonised response of this cell line across a number of drivers of malignancy such as migration, invasion in 2D and 3D models. / Zarqa University / The full text was made available at the end of the embargo, 3rd December 2019

L’estrogène le plus actif, soit l’œstradiol (E2), stimule la prolifération des cellules du cancer du sein, alors que la dihydrotestostérone (DHT), qui est l’androgène le plus actif, prévient la croissance des cellules du cancer du sein hormonodépendant dans certaines concentrations et conditions physiologiques. Il a été rapporté que la 17β-hydroxystéroïde déshydrogénase de type 7 (17β-HSD7) détient deux activités enzymatiques. La première activité est la réduction de l’E1 en E2 et la seconde activité est l’inactivation de la DHT en 3β-diol qui pourrait permettre de jouer un rôle dans la cancérogenèse des cellules tumorales du cancer du sein hormonodépendants. À ce jour, très peu d’informations sont disponibles à propos des activités catalytiques de cette protéine et aucune structure tridimensionnelle n’est disponible pour mieux comprendre l’implication et les mécanismes enzymatiques de la 17β-HSD7 dans la stéroïdogenèse. Dans cette étude, nous avons développé un protocole permettant l’expression et la purification de la 17β-HSD7 active et stable à partir d’un système bactérien. Nous avons aussi déterminé les paramètres de cinétique enzymatique à l’état stationnaire et nous avons obtenu des conditions de cristallisation qui ont permis d’obtenir des cristaux préliminaires. Les résultats de cinétique enzymatique ont démontré que la 17β-HSD7 réduit l’E1 en E2 et la DHT en 3β-diol à des vitesses de conversion et des spécificités de même ordre. De plus, nous avons confirmé que l’inhibition de la 17β-HSD7 avait un impact aussi important dans la diminution de la vitesse de conversion de l’E1 en E2 que l’inhibition de la 17β-HSD1 dans des lignées cellulaires de tumeurs du sein hormonodépendant. Aussi, la 17β-HSD7 est beaucoup plus spécifique pour la réduction de la DHT que la 17β-HSD1 a une activité réductrice de la DHT. Ces résultats mettent en évidence le rôle de la 17β-HSD7 dans la carcinogenèse du cancer du sein. / The most potent estrogen, estradiol (E2), stimulates proliferation, while the dihydrotestosterone (DHT) prevents it in estrogen dependent breast cancer cells. It brought reported that 17ß-HSD7 has two major reduction activities which can reduce E1 to E2 and inactivate the DHT to 3ß-diol. To this day, the detailed kinetic parameters and crystalline structure of the 17ß-HSD7 are unknown and theses knowledge allow a better understand of is implication in steroidogenesis. In this study, a purification protocol was developed to obtain pure 17ß-HSD7 in bacterial system to determine the steady state kinetic parameters of the 17ß-HSD7, and also its crystallization condition. Firstly, we were able to express and purify the 17ß-HSD7 in E. coli at purity over 95%. Secondly, the results of enzymatic kinetics demonstrated that the 17ß-HSD7 reduced both steroids at similar rates. Finally, the crystallization conditions were determined to growth some preliminary crystals of the 17ß-HSD7. Furthermore, we were able to confirm that the inhibition of the 17ß-HSD7 had a higher impact in to decrease the conversion of E1 in E2 than the inhibition of the 17ß-HSD1 in breast cancer cell lines. At the same time the 17ß-HSD7 demonstrates an effect on DHT reduction much more important than the 17ß-HSD1. These results highlight the role of the 17ß-HSD7 in the carcinogenesis of the breast cancer.

I denna uppsats studeras hur Matt 7:24-30 har kommit att tolkats i modern tid av feministiska exegeter. Först ur en västerländsk kontext för att sedan övergå till en postkolonial kontext i Indien och södra Asien. I och med detta undersöks frågan: Hur har feministiska exegeter från olika kulturella kontexter förhållit sig till frågan om etnicitet, kön och tolkningen av de grekiska begreppen för barn respektive hundar i Mark 7:24-30?

Twelve halloysites from different sources in Slovakia, Turkey, China, New Zealand and U.S.A. have been characterized by combination of analytical methods together with the commercial sample of halloysite supplied by Sigma-Aldrich. The aim of this work was to select suitable candidates for to be used as carriers of porphyrine photoactive molecules. In nature, the formation of halloysite is related to the weathering of magmatic rocks or to the hydrothermal alteration of volcanic rocks, frequently in the contact with limestones. Halloysite belong to the kaolinite group, but, contrarily to kaolinite, it contains molecules of water in the interlayer space. It occurs in two forms: hydrated halloysite (10 ?) and dehydrated halloysite (7 ?).Dehydrated halloysites contain more admixtures than hydrated ones ? typically kaolinite, quartz, cristobalite, alunite, gibbsite and in one case also potassium mica. In samples containing both dehydrated halloysite and kaolinite their 001 diffractions overlap. Interaction with formamide was used in these cases to increase the interlayer space of halloysite and thus shift its basal diffraction to lower angles. The basal 001 diffraction of kaolinite after this treatment remains on 7 ?. Silver thiourea method (AgTU) was used to measure the cationic exchange capacity (CEC). Silver...