by Yeung, Sai-mo, Simon. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1989. / Bibliography: leaves 189-207.

by Poon Lit Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (leaves 97-113). / Title page --- p.i / Acknowledgements --- p.ii / Table of contents --- p.iii / List of tables --- p.vii / List of figures --- p.viii / Abbreviations --- p.x / Abstract --- p.xi / Chapter Chapter 1: --- General Introduction --- p.1 / Chapter 1.1 --- Sacral agenesis --- p.2 / Chapter 1.1.1 --- Skeletal anomalies --- p.3 / Chapter 1.1.2 --- Neurological anomalies --- p.4 / Chapter 1.1.3 --- Other anomalies --- p.5 / Chapter 1.1.4 --- Etiology --- p.5 / Chapter 1.1.5 --- Pathogenetic mechanism of SA --- p.7 / Chapter 1.2 --- Retinoids --- p.8 / Chapter 1.2.1 --- RA in embryonic development --- p.9 / Chapter 1.2.2 --- Teratogenic effect of RA in embryonic development --- p.10 / Chapter 1.3 --- Strategy of the thesis --- p.13 / Chapter Chapter 2: --- General Materials and Methods --- p.15 / Chapter 2.1 --- Mouse maintenance and mating method --- p.16 / Chapter 2.2 --- All-trans RA preparation and injection --- p.16 / Chapter 2.3 --- Dissection of embryos --- p.16 / Chapter 2.4 --- Preparation of histological sections --- p.17 / Chapter 2.4.1 --- Dehydration and embedding --- p.17 / Chapter 2.4.2 --- Sectioning --- p.18 / Chapter 2.4.3 --- Haematoxylin and eosin staining --- p.18 / Chapter 2.5 --- Plasmid preparation --- p.19 / Chapter 2.5.1 --- Competent cells preparation --- p.19 / Chapter 2.5.2 --- Bacterial transformation --- p.19 / Chapter 2.5.3 --- Mini-scale preparation of plasmid DNA --- p.20 / Chapter 2.6 --- In situ hybridization --- p.21 / Chapter 2.6.1 --- Sample preparation --- p.21 / Chapter 2.6.2 --- Probe synthesis --- p.21 / Chapter 2.6.3 --- Hybridization --- p.23 / Chapter 2.6.4 --- Post-hybridization wash and antibody labeling --- p.24 / Chapter 2.6.5 --- Post-antibody wash and colour development --- p.25 / Chapter 2.6.6 --- Embryo powder preparation --- p.25 / Chapter Chapter 3: --- Time and Dose Responses to RA --- p.26 / Chapter 3.1 --- Introduction --- p.27 / Chapter 3.1.1 --- Time response --- p.27 / Chapter 3.1.2 --- Dose response --- p.29 / Chapter 3.2 --- Materials and methods --- p.31 / Chapter 3.2.1 --- Dose response --- p.31 / Chapter 3.2.2 --- Time response --- p.31 / Chapter 3.2.3 --- Skeletal preparations and staining --- p.31 / Chapter 3.2.4 --- Early teratogenic responses to RA --- p.32 / Chapter 3.3 --- Results --- p.33 / Chapter 3.3.1 --- Dose response --- p.33 / Chapter 3.3.1.1 --- Tail length --- p.33 / Chapter 3.3.1.2 --- Vertebral pattern --- p.33 / Chapter 3.3.2 --- Time response --- p.36 / Chapter 3.3.2.1 --- Tail length --- p.36 / Chapter 3.3.2.2 --- Vertebral pattern --- p.36 / Chapter 3.3.2.3 --- Other anomalies associated with human SA --- p.40 / Chapter 3.3.3 --- Early teratogenic responses in RA-treated embryos --- p.41 / Chapter 3.4 --- Discussion --- p.44 / Chapter Chapter 4: --- RA-induced Cell Death in Tail Bud --- p.51 / Chapter 4.1. --- Introduction --- p.52 / Chapter 4.1.1 --- Cell death --- p.52 / Chapter 4.1.2 --- Methods in cell death identification --- p.54 / Chapter 4.2 --- Materials and methods --- p.57 / Chapter 4.2.1 --- Histology of tail bud region --- p.57 / Chapter 4.2.2 --- Detection of internucleosomal DNA fragmentation --- p.57 / Chapter 4.2.2.1 --- Sample collection --- p.57 / Chapter 4.2.2.2 --- DNA extraction --- p.58 / Chapter 4.2.2.3 --- Analysis of DNA fragmentation pattern by ethidium bromide staining --- p.59 / Chapter 4.2.2.4 --- Analysis of DNA fragmentation pattern by autoradiography --- p.59 / Chapter 4.2.3 --- TUNEL --- p.61 / Chapter 4.2.3.1 --- Sample collection / Chapter 57 4.2.3.2 --- In situ end-labeling --- p.62 / Chapter 4.2.4 --- In situ hybridization of Wnt-5A --- p.63 / Chapter 4.2.4.1 --- Sample collection --- p.63 / Chapter 4.2.4.2 --- Probe preparation --- p.64 / Chapter 4.3 --- Results --- p.65 / Chapter 4.3.1 --- Histological examination of cell death in tail bud --- p.65 / Chapter 4.3.2 --- Analysis of DNA fragmentation of tail bud cells --- p.66 / Chapter 4.3.3 --- TUNEL --- p.67 / Chapter 4.3.4 --- Wnt-5A gene expression --- p.68 / Chapter 4.4 --- Discussion --- p.71 / Chapter Chapter 5: --- Retinoic Acid Receptors (RARs) --- p.75 / Chapter 5.1 --- Introduction --- p.76 / Chapter 5.1.1 --- RARs and their isoforms --- p.76 / Chapter 5.1.2 --- Expression pattern of RARs during embryogenesis --- p.77 / Chapter 5.1.3 --- RAR mutants and functional redundancy of RARs --- p.78 / Chapter 5.1.4 --- RARs and SA --- p.79 / Chapter 5.2 --- Materials and methods --- p.80 / Chapter 5.2.1 --- In situ hybridization of RAR-α --- p.80 / Chapter 5.2.1.1 --- Sample collection --- p.80 / Chapter 5.2.1.2 --- Probe preparation --- p.80 / Chapter 5.2.2 --- In situ hybridization of RAR-β --- p.81 / Chapter 5.2.2.1 --- Sample collection --- p.81 / Chapter 5.2.2.2 --- Probe preparation --- p.81 / Chapter 5.2.3 --- In situ hybridization of RAR-γ --- p.82 / Chapter 5.2.3.1 --- Sample collection --- p.82 / Chapter 5.2.3.2 --- Probe preparation --- p.82 / Chapter 5.3 --- Results --- p.83 / Chapter 5.3.1 --- RAR-α gene expression --- p.83 / Chapter 5.3.2 --- RAR-β gene expression --- p.84 / Chapter 5.3.3 --- RAR-γ gene expression --- p.86 / Chapter 5.4 --- Discussion --- p.88 / Chapter Chapter 6: --- Conclusion and Future Perspectives --- p.92 / Chapter 6.1 --- Conclusion and future perspectives --- p.93 / References --- p.97 / Appendices --- p.114 / Figures --- p.118

This thesis examines an aspect of embodied relationship that is recognised in colloquial figures of speech but is not theorised, nor even much acknowledged in the psychotherapeutic literature. It argues that when we experience subtle sensations of extending towards another person, as we might when our "heart goes out" to them, and of pulling away, as we might when we "draw back", this seemingly internal experience is snesed by the other. Using a phenomenological-hermeneutic methodology underpinning by Merleau-Ponty, van Manen and Todres, exercised were used to bring such experiences to the awareness of several cohorts of experienced and inexperienced therapists attending a training course. Verbal and written accounts of what was felt during the exercised, and of similar experiences from more naturalistic settings, were collected along with the researchers' own accounts. These accounts are discussed within the framework of a Gadamerian Conversation with a view to making explicit the implication for Person-centred therapy with regard to practice, supervision and training. The conversation speaks of the the impact of these experiences upon whether or not clients perceive therapists as authentic, unconditionally accepting and empathic. Assumptions are uncovered and challenged and an alternative narrative emerges from a consideration of multiple contexts. The conversation also speaks of an unseen dance of closeness and distance that arises as each moves towards and away from the other. Conversation (and silence) is inevitably accompanied and impacted by this dance, which happens in the background of every interaction. The unseen dance impacts not only the relationship, but also each person's organismic state.

Hu, Baoguang. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 121-143). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

伴隨著納米科技的發展，越來越多的納米顆粒系統已經應用於生物醫學领域。其中，二氧化硅納米顆粒因其簡單易操作的表面化學性質和在生理環境中的良好穩定性，已被廣泛認為是最有前途的治療和診斷載體之一。 / 在本論文中，我首先對二氧化硅納米顆粒與人類細胞之間的作用進行了系統研究。這些作用包括了以下主要特點: 胞吞和胞吐被分別確定為納米顆粒主要的進入和離開細胞的主要途徑; 大部份的納米顆粒被發現存在於有膜結構的細胞器里，這些細胞器相當穩定（不易破損），只有很少的一部份納米顆粒被釋放到細胞質里; 納米顆粒和細胞之間的作用是動態的，它們進入細胞內的數量由其在細胞培養液中的數量和形態（聚集的程度）所決定。正是這些特點決定了二氧化硅顆粒在低濃度時的低細胞毒性。 / 緊接著我比較了兩種最常見的二氧化硅納米顆粒（晶體態和無定型態）引入細胞后對細胞所帶來的影響。儘管兩種形態的納米顆粒所造成的細胞毒性都比較低，但是更細緻的分析揭示了它們對細胞及其衍化途徑的不同影響。細胞吞入晶體態的二氧化硅納米顆粒后，其內部的活性氧物質含量顯著提高，這種變化會導致細胞線粒體功能受損（表現為線粒體增生）並且最終將細胞導向死亡。不過只有在p53基因缺失的細胞中才有這種由活性氧物質水平升高導致的細胞損傷，p53正常的細胞卻能抵禦這種來自晶體態二氧化硅納米顆粒的刺激。而無定型態二氧化硅納米顆粒對生物系統無損害，因而有發展為藥物載體的巨大潛力。 / 基於對二氧化硅顆粒細胞毒性研究的理解，我們設計了一種新型納米載體--金核/二氧化硅殼層（Au@SiO₂）納米顆粒用於藥物輸運。在這一體系中，無定形態二氧化硅和金納米顆粒的優勢被整合在一起，同時光敏劑（PS）藥物分子被裝載在二氧化硅殼層內。對比於自由形式的PS，裝載在Au@SiO₂納米顆粒中的PS展示出增強的藥效。需要強調的是，用這種納米顆粒處理的細胞以阻梗壞死為主要的死亡途徑，代替了凋亡這種不太有效的方式。在光照下，金的等離子體效應被發現能促進PS的光響應過程，這使得細胞殺死率得到了大幅度增強。這一效應得益于我們把PS束縛在金核的表面，同時保證金表面等離子體振盪能量和PS吸收能量的配對。此外，把PS裝載在二氧化硅中會引起PS有益的光化學改變。這些作用結合在一起導致了藥效的提高。這些機理能被普遍應用於納米顆粒裝載藥物分子的設計中，為最優化設計提供指導。 / With recent development of nanotechnology, various nanoparticulate systems have been proposed to serve as functional units for biomedical applications in many innovative ways. Among various possible choices, silica nanoparticles (NPs) enjoys easily modifiable surface chemical characteristics and excellent stability in physiological environment. Therefore, it is considered as one of the most promising carrier candidate for therapeutic and diagnostic applications. / A systematic study on the interaction between silica nanoparticles and human cells is first carried out in the present thesis work. Endocytosis and exocytosis are identified as major pathways for NPs entering, and exiting the cells, respectively. Most of the NPs are found to be enclosed in membrane bounded organelles, which are fairly stable (against rupture) as very few NPs are released into the cytoplasma. The nanoparticle-cell interaction is a dynamic process, and the amount of NPs inside the cells is affected by both the amount and morphology (degree of aggregation) of NPs in the medium. These interaction characteristics determine the low cytotoxicity of SiO₂ NPs at low feeding concentration. / Experiments were then designed to compare the the biological consequence of two most common form of SiO₂ nanoparticles, i.e., crystalline and amorphous NPs, when they were introduced to human cells. Although the apparent cytotoxicity of both types of NPs seems to be low, more detailed characterizations disclose the profound difference induced by the crystalline and amorphous ones, resulting in significantly different cell evolution pathways. Crystalline NPs but not amorphous ones are found to drastically increase the recative oxygen species (ROS) level in the cells, which can cause mitochondria dysfunction (being expressed as mitochondria proliferation), and eventually direct the cell into apoptosis. Nonetheless, only p53 deficient cells are subjective to such ROS induced cell damage, while p53 proficient cells can accommodate the stimulation from crystalline SiO₂ NPs. The amorphous SiO₂ NPs are found to be benign in the biological systems, and have great potential to be developed as nanomedicine. / Base on the understanding obtained from the toxicology study of the SiO₂ NPs, we have designed a special nanocarrier system for drug delivery. We have combined advantages of both SiO₂ and Au NPs by constructing Au-core/SiO₂-shell (Au@SiO₂) nanocarriers with the photosensitizer (PS) drug embedded in the SiO₂ shell layer. Compared with free PS, PS loading in the Au@SiO₂ NPs showes a enhanced drug efficacy. In particular, the cells treated with the NP drug take necrosis as a major death path instead of apoptosis, which is a much less effective route. The Au plasmonic effect is found to promote the photo-response of the PS drug under light irradiation, contributing to the largely decreased cell viability. Nevertheless, one shall note that spatial confinement of the drug moledules to the close proximity of the Au core and an energy match between the drug absorption and the Au surface plasmon resonance are critical in manifesting the plasmonic effect. At the same time, embedding the drug in the SiO₂ matrix leads to favorable change in the photochemical process. The combined effects brought by the Au@ SiO₂ NP carrier is responsible for the high drug efficacy. These mechanisms can be generally valid in engineering drug molecule incorporation into NP carriers and also give guidance for the optimum design of the NP drug carrier. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Chu, Zhiqin = 二氧化硅納米顆粒與人類細胞的作用及其在生物醫學方面的應用 / 褚智勤. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 120-137). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Chu, Zhiqin = Er yang hua gui na mi ke li yu ren lei xi bao de zuo yong ji qi zai sheng wu yi xue fang mian de ying yong / Chu Zhiqin. / Table of contents --- p.VIII / List of figures --- p.XIII / List of tables --- p.XIX / Chapter Chapter 1 --- Introduction --- p.1 / Chapter Chapter 2 --- Background --- p.4 / Chapter 2.1 --- Overview of the silica-based nanoparticles for bio-medical applications --- p.4 / Chapter 2.2 --- Health issue on the silica-base nanoparticles --- p.5 / Chapter 2.3 --- Understanding the nano-bio interface --- p.6 / Chapter 2.3.1 --- Nano-bio interface in vitro --- p.7 / Chapter 2.3.2 --- Nano-bio interface in vivo --- p.10 / Chapter 2.4 --- Bio-application of silica-based nanoparticles --- p.11 / Chapter 2.4.1 --- Use of silica nanoparticle as imaging agent --- p.11 / Chapter 2.4.2 --- Use of silica nanoparticle as drug carrier --- p.12 / Chapter 2.4.3 --- Use of silica nanoparticle as coating media --- p.12 / Chapter 2.5 --- Surface plasmon of gold nanostructures and its bio-application --- p.13 / Chapter 2.5.1 --- Introduction to the SPR of gold nanostructures --- p.13 / Chapter 2.5.2 --- Synthesis of gold NRs and their SPR effect --- p.13 / Chapter 2.5.3 --- SPR of gold NRs in bio-application --- p.16 / Chapter Chapter 3 --- Experimental --- p.18 / Chapter 3.1 --- Standard methodologies for nanoparticle preparation and their feeding to the cells --- p.18 / Chapter 3.2 --- Cell sampling for room temperature TEM study --- p.18 / Chapter 3.3 --- Developing methods to distinguish NPs in cell sample under TEM --- p.20 / Chapter 3.4 --- Confocal microscopy study --- p.21 / Chapter 3.4.1 --- Study the photoluminescence of various dye molecules --- p.21 / Chapter 3.4.2 --- Study the two photon luminescence (TPL) of Au NRs --- p.23 / Chapter 3.5 --- UV-Vis-NIR spectrophotometer and fluorescence spectrophotometer --- p.25 / Chapter 3.6 --- Flow-cytometry --- p.26 / Chapter 3.7 --- Western plot --- p.28 / Chapter 3.8 --- Colormetric assays and other biological labels --- p.28 / Chapter 3.8.1 --- 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test --- p.28 / Chapter 3.8.2 --- Mitochondria, lysosome and nucleus staining --- p.30 / Chapter 3.8.3 --- Detection of apoptosis --- p.31 / Chapter 3.8.4 --- Detection of various reactive oxygen species (ROS) --- p.31 / Chapter Chapter 4 --- Silica NPs interact with human cells --- p.34 / Chapter 4.1 --- Introduction --- p.34 / Chapter 4.2 --- Characterization of silica nanoparticles --- p.36 / Chapter 4.3 --- General description of the NPs’ uptaking and excreting process --- p.42 / Chapter 4.4 --- Tracking of NPs inside the cells --- p.53 / Chapter 4.5 --- Factors influencing the NP-cell interaction and exocytosis process --- p.55 / Chapter 4.5.1 --- The effect of serum (in the incubation medium) on cellular uptake --- p.55 / Chapter 4.5.2 --- Crystallinity effectdistribution of amorphous and crystalline SiO₂ NPs in the cells --- p.57 / Chapter 4.5.3 --- Factors affecting the exocytosis process --- p.59 / Chapter 4.6 --- Cytotoxic effect of silica NPs --- p.60 / Chapter 4.7 --- Conclusion --- p.63 / Chapter Chapter 5 --- Genotoxic effect specifically induced by crystalline SiO₂ nanoparticles in p-53 deficient human cells --- p.65 / Chapter 5.1 --- Introduction --- p.65 / Chapter 5.2 --- The difference between crystalline and amorphous silica NPs --- p.66 / Chapter 5.2.1 --- Mitochondria multiplication specially induced by crystalline silica NPs --- p.68 / Chapter 5.2.2 --- DNA fragmentation specially observed in crystalline silica NPs treated cells --- p.71 / Chapter 5.3 --- The cell line sensitive cytotoxicity of crystalline silica NPs --- p.79 / Chapter 5.3.1 --- A general phenomenon of mitochondria increase in p-53 negative cell lines --- p.80 / Chapter 5.3.2 --- General biological consequence of such mitochondria increase --- p.82 / Chapter 5.4 --- Conclusion --- p.83 / Chapter Chapter 6 --- Surface plasmon enhanced drug efficacy for PDT using core shell Au@SiO₂ nanoparticle carrier --- p.84 / Chapter 6.1 --- Introduction --- p.84 / Chapter 6.1.1 --- Brief introduction to the photodynamic therapy (PDT) and photosensitizer (PS) --- p.84 / Chapter 6.1.2 --- Brief introduction to the SPR enhanced generation of ROS --- p.86 / Chapter 6.2 --- Using Au@SiO₂ NPs as drug carrier --- p.88 / Chapter 6.2.1 --- Growth of gold NRs and their controllable oxidation --- p.88 / Chapter 6.2.2 --- Preparation and characterization of Au@(SiO₂-MB) NPs --- p.90 / Chapter 6.2.3 --- Confirmation of MB loading into silica shell --- p.92 / Chapter 6.3 --- Enhanced PDT drug (MB) efficacy when loaded in Au@SiO₂ NPs --- p.95 / Chapter 6.3.1 --- Cellular uptake pathway of free MB and Au@SiO₂ NPs --- p.95 / Chapter 6.3.2 --- Comparing the efficacy of free MB, SiO₂-MB NPs and Au@(SiO₂MB) NPs --- p.98 / Chapter 6.4 --- Studying the behavior of free MB and Au@(SiO₂-MB) NPs as PDT agent --- p.100 / Chapter 6.4.1 --- Comparing the ability of generating ROS by free MB and Au@(SiO₂MB) NPs --- p.100 / Chapter 6.4.2. --- Comparing the types of ROS generated by free MB and Au@(SiO₂MB) NPs --- p.103 / Chapter 6.4.3 --- Comparing the cellular death pathway triggered by free MB and Au@(SiO₂-MB) NPs --- p.105 / Chapter 6.5. --- Discussion on the mechanism for the enhanced efficacy --- p.109 / Chapter 6.5.1 --- Excluding the photothermal effect of Au NRs core --- p.109 / Chapter 6.5.2 --- The role of SiO₂ in the Au@SiO₂ NPs carrier --- p.111 / Chapter 6.5.3 --- Attributing the enhanced efficacy to plasmonic effect of Au NRs core --- p.112 / Chapter 6.6 --- Exploring the potential of using Au@SiO₂ NP carrier in vivo --- p.114 / Chapter 6.7 --- Conclusion --- p.116 / Chapter Chapter 7 --- Conclusion --- p.118 / References --- p.120

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Thesis (M.S.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / 2031-01-01