106 research outputs found

    Notch Signaling: Mechanistic And Functional Studies In Intestinal Stem Cells And Colorectal Cancer Cells

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    : The study of stem cell regulation in intestinal and colonic tissues is an area of significant focus within the scientific community, providing mechanistic insight into biological process and offering translational clinical potential. In this thesis we address the contribution of NOTCH signaling in maintaining the stem cell niche by modulating the mode of stem cell division and receptor-ligand interactions for cell-cell communication. Furthermore, we examine NOTCHmediated spatiotemporal recovery of the intestinal stem cell (ISC) niche following single cell ablation. Finally, we demonstrate that elevated NOTCH signaling exists under conditions of physiological stress and in colon cancer initiating cells (CCICs), promoting tumorigenic potential of the intestinal epithelium. Overall, our research highlights the underlying complexities of NOTCH signaling as an essential pathway to maintain intestinal homeostasis and may inspire development of novel CRC therapeutic strategies. Research efforts and findings during my graduate study have been consolidated into the following peer-reviewed publications, of which the four first co-author manuscripts are described in detail in this dissertation. 1. Srinivasan, Tara; Walters, Jewell; Bu, Pengcheng; Than, Elaine B.; Tung, Kuei-Ling; Chen, Kai-Yuan; Panarelli, Nicole; Milsom, Jeff; Augenlicht, Leonard; Lipkin, Steven M; Shen, Xiling. "NOTCH Signaling Regulates Asymmetric Division of Fast- and Slow-Cycling Colon Cancer Initiating Cells." Cancer Research, 2016. (in press) 2. Srinivasan, Tara; Than, Elaine B.; Bu, Pengcheng; Tung, Kuei-Ling; Chen, Kai-Yuan; Augenlicht, Leonard; Lipkin, Steven M.; Shen, Xiling. "NOTCH Signaling Regulates Fast- and Slow-Cycling Intestinal Stem Cells." Scientific Reports, 2016. (in press) 3. Chen, Kai-Yuan*; Srinivasan, Tara*; Choi, Jiahn*; Bu, Pengcheng; Tung, Kuei-Ling; Nishimura, Nozomi; Shen, Xiling. "Dynamic regulation of intestinal stem cell niche recovery in real-time." Cell Systems, 2015. (in review) 4. Murthy, Preetish KL*; Srinivasan, Tara*; Bochter, Skye; Bu, Pengcheng; Cole, Susan; Shen, Xiling. "FRINGE-dependent modification of NOTCH Ligands in Intestinal Stem Cells." 2016. (in preparation) 5. Rothschild, Daniel; Srinivasan, Tara; Aponte-Santiago, Linette; Shen, Xiling; Irving, Allen. "The Ex Vivo Culture and Pattern Recognition Receptor Stimulation of Mouse Intestinal Organoids." JoVE, 2015. (in press) 6. Bu, Pengcheng*; Wang, Lihua*; Chen, Kai-Yuan; Srinivasan, Tara; Lakshminarasimha, Preetish; Tung, Kuei-Ling; Varanko, Anastasia; Ai, Yiwei; Lipkin, Steven; Shen, Xiling. "miR34a and Numb synergize for asymmetric cell fate determination." Cell Stem Cell, 2016 Feb 4;18(2):189-202. 7. Crespo, Miguel; Tsai, Su-Yi; Srinivasan, Tara; Pipalia, Nina; Maxfield, Nina; Lipkin, Steven M; Evans, Todd; Chen, Shuibing. "Colonic Organoids Derived from Human Pluripotent Stem Cells for Modeling Colorectal Cancer and Drug Testing." Nature Medicine, 2015. (in review) 8. Wang, Lihua*; Bu, Pengcheng*; Ai, Yiwel; Srinivasan, Tara; Lipkin, Steven M; Shen, Xiling. "A Long Non-Coding RNA Targets MicroRNA miR-34a to Regulate Colon Cancer Stem Cell Asymmetric Division." eLife, 2016. (in press

    Kang zhan: du mu xin ju xuan.

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    在烽火中 / 沈西苓 -- 重逢 / 丁玲 -- 爭取最後勝利 / 塞克 -- 游擊隊的開始 / 張克 -- 我們打沖鋒 / 尤兢 -- 漢奸末路 / 姚時曉 -- 榮譽大隊 / 趙明, 呂復 -- 夜之歌 / 凌鶴 -- 我們放開恩怨 / 石靈 -- 舞女淚 / 集體創作.[沈西苓 ... [et al.]著] ; 戰時劇社編.[Shen Xiling ... [et al.] zhu] ; Zhan shi ju she bian.Zai feng huo zhong / Shen Xiling -- Chong feng / Ding Ling -- Zheng qu zui hou sheng li / Sai Ke -- You ji dui de kai shi / Zhang Ke -- Wo men da chong feng / You Jing -- Han jian mo lu / Yao Shixiao -- Rong yu da dui / Zhao Ming, Lü Fu -- Yan zhi ge / Ling He -- Mo men fang kai en yuan / Shi Ling -- Wu nü lei / Ji ti chuang zuo

    Nai duo yao fei jie he de CT biao xian

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    M.Phil.Pulmonary tuberculosis (TB) is the ninth leading cause of death worldwide and the leading cause from a single infectious agent, ranking above HIV/AIDS . Multidrug resistant tuberculosis ( MDR-TB ) refers to TB infection resistant to at least two most powerful anti TB drugs, isoniazid and rifampincin. Extensively drug resistant TB ( XDR-TB ) has resistance to rifampin and isoniazid, as well as to any member of the quinolone family and at least one of the second line injectable drugs: kanamycin, amikacin and capreomycin. DS-TB (Drug sensitive tuberculosis) is defined as pulmonary TB infection with sputum culture showing M. tb and where drug sensitivity test revealed drug sensitivity to all four first-line anti TB drugs . XDR-TB accounts for 4 20% of MDR-TB . Early detection and targeted treatment are priorities for MDR-TB/XDR-TB control. The suspicion of pulmonary MDR-TB/XDR-TB by specific CT features shall suggest intensive diagnostic testing for pulmonary MDR-TB/XDR-TB . However, study in this field with more than 50 MDR-TB cases with DS-TB as control is limitedThis study aims to compare CT features of pulmonary MDR-TB and DS-TB patients (including the number , measurement, and range of some CT signs ) and attempts to find differentiators for separating DS-TB vs MDR-TB/XDR-TB cases.In the first study , we collected a large number of MDR-TB patients (287 in and compare d the CT characteristics with DS-TB patients (68 in This study showed that MDR-TB patients had more large nodules, larger inner diameter of cavity, and more lobes involved in tree in bud sign and bronchiectasis. The most specific CT features indicating MDR-TB were: three or more nodules with diameter ≥ 10mm; the largest internal diameter of cavity≥4cm and bronchiectasis involving five or more lung lobes.In the second study , we aimed to figure out the CT feature of MDR-TB (287 patients) by observing the CT characteristics of XDR-TB 94 patients as an extreme performance. This study showed that The incidence of nodule with diameter≥6mm in XDR-TB group was higher than that in MDR-TB group, and MDR-TB patients could not have more than 10 such nodules in this study . Although not statistically significant, the cavities in XDR-TB were larger and the wall was thicker.In the third study , considering the low incidence of MDR-TB, we built a model based on the epidemiological proportion of MDR-TB and DS-TB. T his model was set to explore the imaging effect on indicating MDR-TB in ordinary hospital . This study showed that when a TB patient had tree in bud sign ≥ three lung lobes along with nodule≥6mm in diameter presence on CT, this patient was likely to have MDR-TB with accuracy of 85.85%In conclusion , CT plays an important role in suggesting MDR-TB . The suspicion of pulmonary MDR-TB/XDR-TB by specific CT features shall suggest intensive diagnostic testing for pulmonary MDR-TB/XDR-TB肺結核(TB )是全球第九大死亡原因,也是單壹傳染源的主要死因,僅次於 HIV/AIDS 。耐多藥結核病( MDR-TB )是指至少對兩種最有效的抗結核藥物異煙肼和利福平耐藥的結核病感染。廣 泛耐藥結核病( XDR-TB )對利福平和異煙肼、喹諾酮類藥物以及至少壹種二線可註射藥物卡那黴素、阿米卡星和卷曲黴素具有耐藥性。藥敏肺結核( DS-TB )是指痰培養呈結核分枝桿菌的肺結核感染,藥敏試驗顯示對四種壹線抗結核藥物均敏感。 XDR-TB 占 MDR-TB 的4-20% 。早期發現和靶向治療是控制 MDR-TB/ XDR-TB 的優先事項。通過胸部影像提示疑似 MDR/XDR-TB 應指示肺部強化診斷試驗。然而,以 50 多例 MDR-TB 病例並包含為對照的這壹領域的研究是有限的。本研究旨在比較肺部MDR-TB 和 DS-TB 患 者的 CT 表現(包括CT 征象的數目、測量值和範圍),並試圖尋找區分 DS-TB 與MDR-TB/XDR-TB 病例的方法。在第壹項研究中,我們收集了大量MDR-TB 患者,並將其 CT特征與 DS-TB 患者進行了比較。結果表明, MDR-TB 患者肺部結節較多,空洞內徑較大,累及樹芽征和支氣管擴張累及多肺葉。指示MDR-TB 的最具體 CT 特征是: 3 個或 3 個以上直徑≥ 10mm 的結節、最大空洞內徑≥ 4cm 、累及 5 個或 5 個以上肺葉的支氣管擴張為特征。在第二項研究中,我們的目的是通過觀察XDR-TB 的 CT 表現來了解 MDR-TB 的 CT 特征。研究表明, XDR-TB 組直徑≥ 6mm 的結節發生率高於 MDR-TB 組,且 在我們的實驗中, MDR-TB 組的 結節數不超過 10 個。盡管沒有統計學意義, XDR-TB 的空洞更大,壁更厚。在第三項研究中,考慮到MDR-TB 的低發病率,我們根據MDR-TB 和 DS-TB 的流行病學比例建立了壹個模型。本模型旨在探討影像學在普通醫院中對診斷 MDR-TB 的影響。研究表明,肺結核患者 CT 上有樹芽征≥ 3 個肺葉,並且結節直徑≥ 6mm 時,其發生MDR-TB 的準確 率為 85.85% 。總之,CT 在提示 MDR-TB 中起著重要作用。根據特定 CT 特征提示疑似 MDR/XDR-TB 應指示肺部強化診斷試驗。Huang, Xiling.Thesis M.Phil. Chinese University of Hong Kong 2020.Includes bibliographical references (leaves 130-146).Abstracts also in Chinese.Title from PDF title page (viewed on March 29, 2022).Huang, Xiling

    Design and implementation of a human tracking and following capability for a robotic avatar

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    In this project, the human-following capability has been implemented on a mobile platform (MAVEN-II) which was also called a robotic avatar. The design and implementation of human-following capability was part of the research project under the general topic of Telepresence, which aimed at developing remotely controllable robots that can interact with humans in social scenarios (conference, eldercare etc.). Previous designs had used RGB cameras and laser range finders to detect and track humans, with Mean Shift, Histogram of Oriented Gradient (HOG), and Background-Foreground Model as the commonly used algorithms. However, these methods were not able to re-identify the targeted person among a crowd when he/she came back to the scene after being occluded or being out of the sensor’s field of view. In this project, the Kinect sensor was used to detect the person and to track his/her position in 3D space. In each frame of the sensor reading, the histogram in HSV color space was calculated for the targeted person’s clothes, while the person’s position was updated and stored until he/she was in a situation (being occluded or away from the field of view) where he/she could not be detected by the Kinect sensor. From then on, for every person detectable by the sensor, his/her current color histogram and 3D position was compared with that of the originally targeted person with a Matching Level calculated. Hence if the targeted person re-enter the field of view, he/she would generate the best Matching Level and then he/she would be recognized as the target. Based on the relative position from the robot to the targeted person, the robot’s linear and rotational travelling speed was calculated, and it was able to follow the person when he/she was walking around. During the human-following process, the robot tried to maintain a constant distance to the targeted person. In addition to the mode of human-following at the person’s back, which had been implemented in previous research, the Side-by-side Following mode was implemented in this project, which enabled the robot to accompany the targeted person by his/her side when he/she was walking around. Obstacle avoidance function was also implemented using the Virtual Potential Field concept. Experiment result showed that the Back-Following function was satisfactorily robust; while the robot movement in the Side-by-side Following mode was unstable.Bachelor of Engineering (Mechanical Engineering

    Simulation of a mixed wave and definition of nonlinearity parameter with diffraction correction

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    The acoustic nonlinearity parameter has been frequently measured for early detection of micro damage in various materials. The technique typically employs a toneburst signal of single frequency and measures the second harmonic generation during its propagation in through-transmission mode. In this work, we propose a two wave mixing technique and the use of difference frequency components in determining the nonlinearity parameter. One important advantage of this technique is to use difference frequency components apart from higher harmonics including the second harmonic, therefore effects of source nonlinearity can be minimized and low attenuating nonlinear signal can be acquired. Beam fields radiated from various configurations of radiating transducers are simulated. The fundamental and difference frequency waves are calculated using the multi-Gaussian beam model based on the quasilinear solution for the Westervelt equation. Explicit expressions for diffraction and attenuation corrections are derived, and the nonlinearity parameter is newly defined with these corrections included.</p

    Yanbo Lin's landscape fan painting - 林彥博山水扇面畫

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    Yanbo Lin, born in Hebei, China, excelled in finger paintings. He learned from Xiling Liu (a renowned finger painter in the late Qing dynasty) and published several books regarding technique of finger painting.林彥博,字嵩堃,河北人。擅指画,曾為聾道人(劉錫玲,晚清指畫家)學生。著有「指畫著」、「續指頭畫说」。Postscript: dedication to Runxiang; Signature: Yanbo Pian Hen.款識: 潤庠先生雅正, 彥博片痕.Gongbo公

    A design framework for product families implemented with additive manufactured variable platforms

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    Challenges exist in developing new product family design methodologies that can utilize the additive manufacturing (AM) advantages to improve the product family competitiveness in a cost efficient way. In this research, the author attempts to compensate the performance compromise in conventional product families by proposing the novel concept of an additive manufactured variable platform (VP); and the major objective of this thesis is to develop a design framework that helps designers implement additive manufactured VP modules within product families. During the development of the design framework, the following methodologies have been proposed: 1) a representative mathematical model to formulated the VP-based product family configuration; 2) a hybrid machine learning approach to select appropriate AM design features for addtive manufactured VP modules; 3) a fuzzy time-driven activity-based costing method to predict the AM production cost variation as a function of VP design adjustments, 4) a novel evaluation metric for VP-based product family designs, and 5) a multiobjective design optimization technique to identify the modular configuration and engineering design parameters of a product family. A case study of an R/C racing car family design is used throughout this thesis to demonstrate the usefulness of the proposed methodology. The implementation of additive manufactured VP modules shows a significant improvement in a product family’s performance at the price of a slight decrease in design commonality. As the major contribution of this research, the proposed design framework provides designers and enterprises with a guideline in developing high-performance and cost-efficient product families by utilizing AM-enabled design flexibility. The two previously separate research domains, i.e. AM and product family design, are integrated using the proposed framework and the constituent methodologies.Doctor of Philosophy (MAE

    Physiological and morphological characterization of GABAergic neurons in the medial amygdala

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    GABAergic neurons in the medial amygdala (MeA) have been indicated in information processing in reproductive behavior and fear/anxiety. However, basic knowledge of their physiological and morphological properties is still very limited, probably due to the technical challenge to selectively record the GABAergic neurons. In this study, I characterized properties of the MeA GABAergic neurons by performing whole-cell patch clamp recordings from brain slices of adult knock-in mice selectively expressing green fluorescence protein (GFP) in GABAergic neurons. The majority (73%) of GABAergic neurons exhibiting low threshold calcium spike were classified as type I neurons, with morphological properties of being bitufted or stellate, and dendrites either aspiny or covered by various shapes of spines. Axonal collaterals of some neurons were observed near somata as well as in other amygdaloid nuclei. Neurons incapable of generate low threshold calcium spikes were divided into two types. Type II neurons (11%) exhibited hyperpolarization-activated sag and higher input resistance (&gt;400 M Omega). Most Type II neurons exhibited asymmetric dendritic trees extending towards the superficial layer covered with long neck dendritic spines. The axons of type II neurons formed large collaterals and projected to other amygdaloid nuclei. Type III neurons (16%) lack prominent hyperpolarization-activated sag and possessed lower input resistance (&lt;400 M Omega). These neurons were local interneurons with smooth multipolar dendritic trees. Since both MeA and nearby amygdaloid nuclei are involved in fear/anxiety processing, two types of MeA GABAergic projection neurons and a third type of interneurons that might participate in anxiety-related behavior were revealed by my present study. (C) 2013 Elsevier B.V. All rights reserved.NeurosciencesSCI(E)PubMed2ARTICLE8-19150

    Regional ecological security evaluation with subjective and objective weights model based on multi remote sensing observations

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    With the rapid development of economy and urban construction, urban ecological security protection has become a prominent issue in the development process. Territorial spatial planning and urban ecological monitoring urgently need the support of a scientific evaluation system of urban ecological security status. To respond the demand of ecological assessment, this study considers a variety of key ecological factors. A generalized assessment framework for ecological security is constructed. According to the data accessibility of the indicators and their representativeness. The 23 indicators centered on the elements of ecological environment change of water, soil, air, forest and grassland were divided into four tasks for detailed review: ecological health, ecological space, ecological economy and ecological life. As for weight allocation, to avoid the irrationality of the weights from the single method, we use a weight integration approach to integrate the subjective weights of the analytic hierarchy process (AHP) and the objective weights of the entropy weight method (EWM). Combining the above, the ecological security comprehensive index (ESCI) for evaluation was finally developed. The method was applied to assess the ecological security of Yichang (YC) in 2021. It was found that Xiling District, the core of the YC, had the highest ESCI, while Xiaoting and Zhijiang have the lowest. However, even Xiling still has room for improvement in terms of ecological space and ecological environment. All other cities also suffer from one or more lagging tasks. This framework reveals the general trend of the need to strengthen spatial and environmental construction in the developed areas, and the need to strengthen living and economic construction in the backward areas in YC. It can provide a comprehensive decision-making basis for ecological restoration decision-making and ecosystem management
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