京都大学 / 新制・課程博士 / 博士(医学) / 甲第23104号 / 医博第4731号 / 新制||医||1050(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 渡邉 大, 教授 林 康紀, 教授 村井 俊哉 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Semiconducting material CdTe/CdZnTe has a huge application potential in spectroscopic room temperature radiation detection due to its properties. Such detectors can be used in medical applications, homeland security and for monitoring of nuclear facilities. However, the final device quality is influenced by many parameters. One crucial stage in detector fabrication is the proper surface treatment. The detailed study of surface treatments and their effect on final detector device is reported. Another crucial fact is the polarization of the detector caused by high radiation fluxes which negatively affects the use of such devices. The polarization occurs by capturing the photogenerated holes at the deep levels inside the semiconductor. The possible detector depolarization by infrared illumination during the detector operation has been experimentally verified and the obtained results are shown in this thesis. For optimal technology of preparation, it is also necessary to develop the fast characterization method for prepared detectors. The last aim of the thesis is to study the resulting quality of prepared planar and co-planar detectors by transient-current-technique (TCT). TCT is an electro-optical method allowing to determine variety of transport properties of radiation detectors, such as internal electric...

The diagnostic technique, polarization and depolarization current (PDC) is useful for insulation testing. It requires applying a DC step voltage to the test sample and measuring the current. To measure fast PDC phenomena a fast step is needed. One way of applying a fast high voltage step is to use power electronic switches. Series connection can be used to increase the voltage limit, but this result in unequal voltage sharing unless equipped with voltage balancing. In this work a high voltage vacuum reed switch is investigated as a simple and low-cost alternative to power electronic switches, handling up to 10 kV with a single device. The switch turn on and off behavior was studied. It was found that the initial turn-on is good, in the range of nanoseconds, but there is a problem with the vacuum recovering its insulating properties at low currents before the contacts fully close. The required output voltage level is therefore obtained only after a further settling time that increases with increased input voltage and is much longer than the initial breakdown, e.g. 20 µs for the case of 4.5 kV input voltage. Other limitations of the fast high voltage PDC were also studied. The output voltage was measured across the test sample without adding an intentional resistor in the circuit. There were large oscillations for 1 µs but these oscillations are damped due to inherent resistance of the connecting leads, series resistance of the capacitors and resistance of the reed switch. A comparison is made between the measured and the simulated results using MATLAB to see the effect of parasitic inductance. A damping resistor was added in the circuit and the output results were again compared. With the addition of the damping resistor, the number of oscillations were reduced and their time scale was limited to 0.1 µs . An analysis is made at the end which describes the limitation occurring in determining the high frequency component of PDC. The current during the step is many orders of magnitude higher than the polarization current even at 1 µs , so measurement of the current and protection of the apparatus is not trivial.

付記する学位プログラム名: 充実した健康長寿社会を築く総合医療開発リーダー育成プログラム / 京都大学 / 新制・課程博士 / 博士(医科学) / 甲第23816号 / 医科博第137号 / 新制||医科||9(附属図書館) / 京都大学大学院医学研究科医科学専攻 / (主査)教授 伊佐 正, 教授 林 康紀, 教授 村井 俊哉 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Complex samples containing nanoscale or larger materials exhibit light scattering, a universal property of matter. However, the influence of scattering-induced cascading optical processes on quantifying sample scattering intensity and depolarization has not been thoroughly evaluated. This study uses polystyrene nanoparticles (PSNPs) as a model analyte for systematic experimental and computational investigation. It aims to elucidate the effects of cascading optical processes on scattering cross-section, molar coefficients, depolarization, and intensities. A theoretical model is introduced to show how the Beer-Lambert law is complicated by forward-scattered light interference in UV-Vis measurements. The dependence of scattering intensity on concentration and particle size is complex due to light scattering depolarization and inner filter effects (IFEs). Scattering depolarization increases with PSNP scattering extinction but levels off before unity, influenced by light polarization. Insights from this work enhance understanding of material characterization and nanoparticle quantification and clarify light scattering effects on absorption and fluorescence measurements.

Light absorption and scattering are fundamental properties of matter, particularly significant in nanoscale materials. This study explores how cascading optical processes affect the experimental measurement of absorption and scattering intensities, along with scattering depolarization, in samples containing absorbers and scatterers. The experimental UV–vis spectrum results from the combination of absorption and scattering extinction spectra. However, the maximum measurable extinction may be limited by forward scattered light. Light absorption decreases the intensity of scattered light and influences scattering depolarization. While scattering can reduce absorption along the optical path to the detector, sufficient absorption of the scattered light may counterbalance this effect, leading to minimal overall impact (less than 10%). This research supports the use of the integrating-sphere-assisted resonance synchronous spectroscopic method for accurately quantifying absorption and scattering contributions in UV–vis extinction spectra, providing guidelines to improve the reliability of optical characterization for materials exhibiting absorption and scattering properties.

Ametistas naturais brasileiras foram estudadas através das técnicas de Absorção Óptica (AO), Ressonância Paramagnética Eletrônica (RPE) e Corrente de Despolarização Termicamente Estimulada (CDTE).O espectro de AO apresentou três picos principais na região espectral do visível (10500, 18600 e 28200cm POT.-1) e um enorme pico na região do ultravioleta (45000cm POT.-1) atribuídos ao ferro em diferentes estados de valência. A presença de centros OH POT.- foi observada na região do infravermelho através das bandas em 3440 e 3580cm POT.-1. O espectro de RPE, operando na banda X, exibe um conjunto de linhas centrado em 2000G, um pico intenso em 3000G e quatro picos pequenos em 4000, 5000, 6000 e 7000G, quando o campo magnético encontra-se paralelo a um dos eixos cristalograficamente equivalentes. Quando o campo magnético encontra-se paralelo ao eixo c do cristal, o espectro de RPE revela um conjunto de linhas centrado em 2000G, dois picos intensos próximos a 5000G e um pico pequeno em 6800G. Amostras em pó apresentam uma banda larga centrada em 3400G. Tratamentos térmicos mostram uma redução gradativa desta banda com o aumento do tempo de tratamento térmico e uma redução mais rápida para temperaturas maiores. Sabe-se que os centros de cor nas ametistas são produzidos pela ação de radiação ionizante natural sobre os centros precursores que surgem da substituição do Si POT.4+ pelo Fe POT.3+ na estrutura do quartzo-alfa. Esses centros de Fe POT.3+ não se distribuem igualmente entre os sítios equivalentes no cristal natural e são responsáveis pelas características dominantes do espectro de RPE. O espectro de CDTE obtido da polarização de uma amostra em 1000V apresenta uma banda em 215K, que vem a ser a composição de três bandas de menor intensidade (185, 200 e 214K) e uma banda única em 260K. Foi confirmado o caráter dipolar dessas bandas. Tratamentos térmicos efetuados a diferentes temperaturas mostram ) um decaimento de área total e uma redução da intensidade das bandas mais acentuadas para temperaturas maiores. Iluminação ultravioleta restaura parcialmente o espectro de CDTE e demonstra o crescimento de uma banda na região da temperatura ambiente. Devido ao comportamento semelhante dos espectros de CDTE e de RPE, o sendo Fe POT.3+ um elemento presente em grande quantidade nas amostras estudadas, acredita-se que o centro de dipolo responsável pelas bandas de CDTE observadas, seja do Fe POT.3+ substituindo um Si POT.4+ próximo a um O POT.- ou a um OH POT.-, e que as diferentes posições dos picos devem-se à população desigual do Fe POT.3+ substitucional nos sítios cristalograficamente equivalentes do cristal. / Brazilian natural amethyst samples have been studied through Optical Absorption (AO), Electron Paramagnetic Resonance (EPR) and Thermally Stimulated Depolarization Current (TSDC) Techniques.The AO spectrum shows three main peaks in the visible region (10500, 18600 e 28200cm POT.-1) and a huge peak in the ultraviolet region (45000cm POT.-1). All these peaks were attributed to iron in different valence states. The presence of centros OH POT.- centres have been observed through the bands at 3440 e 3580cm POT.-1in the infrared.The EPR spectrum shows a set of lines centered at 2000G, an intense peak at 3000G and four small peaks at 4000, 5000, 6000 and 7000G, when the magnetic field is parallel to one of crystallographically equivalents sites. When the magnetic field is parallel to the crystal c-axis, the EPR spectrum shows a set of lines centered at 2000G, two high peaks near 5000G and a small peak at 6800G. Powder samples presents a broad band centered in 3400G. Thermal treatments reduce this band for increasing thermal treatments time intervals. The reduction increases for high temperatures. It is well known that colour centres in amethysts are produced after natural ionizing radiation and that the centres are provided with the substitution of Fe POT.3+ for Si POT.4+ in quartzo-alfa structure. The Fe POT.3+ centres are not equally distributed among the equivalent sites of the natural crystal and are responsible for the dominant features of the EPR spectra. The obtained TSDC spectrum for polarization at 1000V shows a broad band at 215K, resulting from the superposition of three bands at 185, 200 and 214k and another band at 260K. The dipole origin of these bands has been confirmed. Thermal treatments at different temperatures produce a decay of the total area and a reduction of the bands intensities. Thermal reduction increases for higher temperatures. Ultraviolet illumination partially restores the TSDC spectrum. A new band appears at room temperature. Due to the similar behavior of the TSDC and EPR spectra and taking into account that the Fe POT.3+ is the most prominent impurity in the studied samples, we believe that the dipoles are substitutional Fe POT.3+ near O POT.- or an OH POT.- and that the different position of the peaks, very near, but not the same, are in crystallographically equivalent sites.

V této teoretické práci se zabýváme kvantově mechanickými jevy, jež jsou spjaté s vodi- vostními elektrony uzavřenými v kvantových tečkách. Nejprve je odvozen model nanokrys- talu jakožto potenciálové jámy. Při tom se ukazuje, že pouze objem, ne tvar, je významným parametrem modelu pro účely terahertzové spektroskopie. Studované geometrie jsou tak vzájemně zaměnitelné a výběr mezi nimi m·že zjednodušit dané úlohy. Pro zkoumání depo- larizačních efekt·, které jsou zahrnuty v depolarizačním faktoru v Maxwell Garnettově teorii efektivního prostředí, je zvolena sférická symetrie. V rámci poruchy prvního řádu je vyřešena Poissonova rovnice pro elektrony rozmístěné uvnitř koule podle vlnové funkce a je určen depo- larizační faktor. Zatímco v klasické limitě tento nabývá p·vodní hodnoty, pro nanokrystaly se zvyšuje a maxima je dosaženo v ne-degenerovaném režimu, kdy je obsazen pouze základní stav. Navýšení depolarizačního faktoru posouvá plasmonovou rezonanci směrem k vyšším frekvencím. 1

<p>Communication between neuronal and non-neuronal is called volume transmission when the released neurotransmitter (NT) acts via diffusion and affects several target cells. Both the neurosecretory and postsynaptic cell responses are linked to [Ca²⁺]_i elevations. </p><p>In the present thesis the role of pre-and postsynaptic Ca²⁺ elevations has been investigated in the reconstituted "synapse" model comprised of NGF-differentiated PC12 and HEL cells as well as in SH-SY5Y neuroblastoma cells. In PC12 cells, both 70mM K⁺ and nicotine triggered NT release, which could be detected as a secondary [Ca²⁺]_i increase in surrounding HEL cells. Both secretagogues shared the same voltage-dependent Ca²⁺ influx pathway as judged from the pharmacological profile blockers of voltage-gated Ca²⁺ channels. The coupling of electrical responses to the activation of Ca²⁺ signaling via muscarinic receptors in SH-SY5Y cells was also studied. These data revealed that depolarization caused a considerable potentiation of the muscarinic Ca²⁺ response. The potentiated Ca²⁺ increase was mainly dependent on the enhanced Ca²⁺ influx and to a lesser extent on [Ca²⁺]_i release from intracellular stores. A phospholipase C (PLC) activator, m-3M3FBS was used to further study the role of G-protein coupled receptor (GPCR)-coupled Ca²⁺ signaling. However, it was found that m-3M3FBS instead triggered [Ca²⁺]_i elevations independently of PLC activation. </p><p>In conclusion, the results indicate that the magnitude of NT release from PC12 cells is sufficient to cause a robust activation of neighboring target cells. Postsynaptic muscarinic signaling is amplified due to integration of electrical excitation and GPCR signaling. The PLC activator, m-3M3FBS is not suitable for studies of PLC-mediated signals in intact cells.</p>

Hyperthermia damages both developing and adult brains, especially when it occurs after ischemia or stroke. Work presented in this dissertation used in vitro models of these stresses to investigate mechanisms underlying damage to immature neurons and neural precursors cultured from embryonic rat brain. Studies described in Chapter 2 investigated the effects of a brief, intense hyperthermic stress (30-45 min at 43ºC). This stress produced a selective depletion of nestin-immunoreactive neural precursor cells, and reduced proliferation, as evidenced by reduced BrdU incorporation into young Tuj1-immunoreactive neurons. The stress activated caspase 3, and produced multiple signs of nuclear damage as well as early and persisting mitochondrial depolarization. Cycloheximide, an inhibitor of protein synthesis, reduced cell death. All these findings suggest an apoptotic death process. Studies described in Chapter 3 used a combination of oxygen-glucose deprivation (OGD, 2 h) followed by mild 41ºC hyperthermia for 90 min (T). The combined OGDT stress reduced both survival in monolayer cultures and colony-forming ability in neurospheres. Cell death occurred gradually over 2 days, and was accompanied by caspase activation that began within 6 h post-stress. Post-stress application of cycloheximide or a general caspase inhibitor (especially qVD-OPH) reduced cell death, but specific inhibitors of caspases 2, 3, 8 or 9 were ineffective. OGDT led to upregulation of the pro-apoptotic protein Bim as well as redistribution of Bax from cytoplasm to mitochondria within 6 h. Persisting mitochondrial depolarization began within 3 h following the combined OGDT stress, but not following individual OGD or T stresses alone. These findings suggest that OGD sensitizes neural precursor cells to hyperthermia-induced damage, and that the combined OGDT stress kills neural precursors via apoptotic mechanisms that include activation of mitochondrial death pathways. Results of these studies suggest that immature neurons and neural precursors are especially vulnerable to hyperthermia-induced damage via apoptotic mechanisms. Pan-caspase inhibitors may be a promising therapeutic strategy to preserve viability of these cells following stroke with hyperthermia.