61 research outputs found
Notch Signaling: Mechanistic And Functional Studies In Intestinal Stem Cells And Colorectal Cancer Cells
No full text: 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
Simulation of a mixed wave and definition of nonlinearity parameter with diffraction correction
No full textThe 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
Nai duo yao fei jie he de CT biao xian
No full textM.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
A design framework for product families implemented with additive manufactured variable platforms
No full textChallenges 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
No full textGABAergic 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 (>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 (<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
Plasma IL-37 Elevated in Patients with Chronic Heart Failure and Predicted Major Adverse Cardiac Events: A 1-Year Follow-Up Study
No full textA great number of basic and clinical studies have demonstrated that inflammatory cytokines play an important role in the development and progression of chronic heart failure (CHF). However, there is limited information about the role of novel cytokine interleukin-37 (IL-37) in heart failure. We measured plasma IL-37 levels by enzyme-linked immunosorbent assay (ELISA) in 158 patients with chronic heart failure and 30 control subjects. Our results showed that plasma IL-37 levels were significantly elevated in patients with CHF compared with healthy controls (143.73 ± 26.83 pg/ml versus 45.2 ± 11.56 pg/ml,P<0.001). Furthermore, plasma IL-37 levels were positively correlated with hs-CRP, hs-TnT, and NT-proBNP and negatively correlated with left ventricular ejection function (LVEF). 11 patients died of cardiovascular cause, and 27 HF patients were rehospitalized for worsening HF within 12 months. Multivariate Cox regression analysis showed that plasma IL-37 is an independent predictor of major adverse cardiac events (MACE). Furthermore, CHF patients with >99 pg/ml plasma IL-37 had significantly higher incidences of MACE within 12 months. Our data suggest that plasma IL-37 may play a role in the pathogenesis of CHF and may be a novel predictor of poor prognosis in HF patients.</jats:p
Dynamic rolling horizon scheduling of waterborne AGVs for inter terminal transport
No full textThe demand for transport between terminals within port areas, known as inter terminal transport (ITT), is increasing. This paper proposes a dynamic rolling horizon scheduling strategy for ITT using waterborne Autonomous Guided Vessels (waterborne AGVs). The strategy is dynamic in that it can handle the dynamically arriving ITT requests and adapt transport schedules accordingly in real time. Specifically, every certain period of time, we formulate and solve a pick-up and delivery problem considering the dynamic vessel states, waterway network topology, and ITT requests over a future time horizon. In the dynamic setting, waterborne AGVs are allowed to divert from the previously scheduled destination. Moreover, the distances between terminals are not calculated simply as the Euclidean metric but based on the complex port waterway network, which complicates the dynamic problem even more. Time windows of ITT requests, capacity constraints of waterborne AGVs and load/unload service times at terminals are also taken into account. A waterborne ITT transport network in the Port of Rotterdam is constructed. Simulation results demonstrate the effectiveness of the proposed dynamic scheduling strategy.Accepted Author ManuscriptTransport Engineering and Logistic
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