288 research outputs found
Cong nü xue sheng dao wu si shi qi Tianjin nü quan yun dong xian feng: yi nü xing yan shuo yu jing yan wei zhong xin de yan jiu.
李淨昉.Thesis (Ph.D.)--Chinese University of Hong Kong, 2009.Includes bibliographical references (leaves 205-219)Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.Abstracts in Chinese and English.Li Jingfang
Shi tou ji suo yin /
Fu: Qian Jingfang Hong lou meng kao, ji Dong Xiaowan kao.Mode of access: Internet
Abstract 5443: Developing a novel miR-15a mimic as a potential therapeutic molecule to eliminate resistant colorectal cancer stem cells
Abstract
In the last 15 years, it has become well established that microRNA play important roles in cancer biology. Due to their ability to regulate the expression of important target genes, aberrant expression of miRNAs has been linked to cancer development and progression. Based on these important functions, there is great interest in developing miRNA based therapeutics. In colorectal cancer, treatment using 5-flurouracil (5-FU) based chemotherapy has improved patient outcomes. However, there remain challenges associated with chemoresistance and recurrence for patients with advanced stage colorectal cancer. miRNA based therapeutics may represent an potential novel therapeutic option for colorectal cancer therapy either alone or in combination with 5-FU based chemotherapy. miR-15a was of the first miRNAs identified to be associated with cancer, and has been shown to have important roles in several tumor types. miR-15a is downregulated in colon cancer and associated with poor patient prognosis. We have identified several important cancer related targets of miR-15a in colon cancer, including YAP1, DCLK1, BMI1 and BCL2. Through the regulation of these targets, miR-15a expression can be used as a potent inhibitor to reduce colon cancer cell proliferation, invasion and improve sensitivity to 5-FU, as well as decreasing tumor growth in vivo mouse colon tumor models using colon cancer stem cells. In the interest of developing miR-15a based colon cancer therapeutics, we have made a modified miR-15a mimic that shows enhanced abilities to disrupt resistant colon cancer cell proliferation and induction of cell cycle arrest when compared to unmodified miR-15a. Following transfection with miR-15a mimic, cell number was reduced by 84% compared to control and 66% compared to miR-15a precursor. Cell cycle analysis showed that G1/S ratio was increased from 1.07 for control to 2.87 for precursor miR-15a and 7.07 for miR-15a mimic. This miR-15a mimic also maintains its ability to regulate these important target genes in colon cancer stem cells. In mouse models using colon cancer stem cells, miR-15a mimic has demonstrated therapeutic potential by reducing tumor growth. Based on these findings, there is potential that modified miR-15a could be adapted for treatment of patients to improve survival of advanced stage colorectal cancer patients.
Citation Format: Andrew T. Fesler, Hua Liu, Ning Wu, Jingfang Ju. Developing a novel miR-15a mimic as a potential therapeutic molecule to eliminate resistant colorectal cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5443. doi:10.1158/1538-7445.AM2017-5443</jats:p
Abstract 2141: Development of a novel miR-129 mimic with enhanced therapeutic potential for treatment of resistant colorectal cancer
Abstract
Treatment of advanced stage colorectal cancer remains a clinical challenge associated with resistance to fluoropyrimidine based chemotherapy. There is an urgent need to discover and develop new strategies to enhance treatment efficacy in order to improve outcomes for these patients. Non-coding microRNAs (miRNAs) have important functions as oncogenes or tumor suppressor genes in the regulation of cancer development and progression. Recently, miRNAs have emerged as potential therapeutic options. We have previously identified miR-129 as a tumor suppressor miRNA and potential therapeutic candidate in colorectal cancer. The expression of miR-129 is progressively lost in colorectal cancer patients and is an important regulator of apoptosis through the targeting of genes such as BCL-2. miR-129 was also found to enhance 5-flurouracil (5-FU) cytotoxicity in vitro and in vivo. To further developing miR-129 based novel therapeutics in colorectal cancer, we have designed a modified version of miR-129 to enhance stability and efficacy. The miR-129 mimic is significantly more potent in inhibiting proliferation of a panel of colon cancer cell lines than the native miR-129 precursor, with 79% reduction by miR-129 mimic compared to 38% for native precursor. The miR-129 mimic induces profound cell cycle arrest at the G1/S checkpoint. The G1/S ratio increased 3.8 fold compared to control when cells were transfected with miR-129 mimic. We also demonstrated that the miR-129 mimic retains its target specificity to BCL-2, TS and E2F3. The therapeutic potential of miR-129 mimic was demonstrated in vivo mouse colon tumor models as a potent inhibitor of tumor growth and metastasis. As a result, miR-129 mimic has a great potential to be further developed as a novel therapeutic drug for treatment of advanced colorectal cancer.
Citation Format: Andrew T. Fesler, Ning Wu, Hua Liu, Jingfang Ju. Development of a novel miR-129 mimic with enhanced therapeutic potential for treatment of resistant colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2141. doi:10.1158/1538-7445.AM2017-2141</jats:p
UNVEILING RELATIONS: STATISTICAL INDEPENDENCE TEST AND LOW-DIMENSIONAL MANIFOLD LEARNING
Determining dependence between two continuous random vectors in high dimensions (d>>1) from noisy observations is a fundamental problem in scientific research. Inspired by the recent work on non-parametric tests of independence using Hadamard matrices (Walsh wavelets) in search of dependencies between random variables of a noisy sample, we present a frequency domain analysis-based framework and design a class of non-parametric tests of independence. This dissertation first expands the Walsh wavelets to other basis function choices. We found that the polynomial-based basis choices often perform better when the underlying relations can be approximatedby polynomial equation-based relations. When the Legendre polynomial basisfunctions are used, we apply the canonical component analysis (CCA) to find an optimal algebraic variety (zeros of a polynomial equation) on which data may be located. Rigorous mathematical analysis is performed to justify the optimization problem and its CCA-based solution. Numerical experiments were performed to understand the stability of this low-dimensional manifold learning algorithm. To address high-dimensional challenges, we explored hierarchical tree-based Haar wavelet basis and corresponding fast transforms, randomized algorithms, and k-nearest neighbors based sensor functions. Extensive numerical experiments were performed in 2+1 dimensionsto understand the mathematical and statistical properties of different approaches.Finally, out of curiosity, we study the application of modern deep neural network (DNN)approaches for independence tests. We discovered that the convolutional neural network (CNN) architecture can effectively distinguish between different distributions, however, in its current training settings and with the current feature inputs, it is unable to handle independence testing for arbitrary distributions in high dimensions.Doctor of Philosoph
Financial informatization: A comparative study of industry adaptation
Abstract onlyThis qualitative case study explored the industry adaptation on financial informatization of the financial industry within a specific region in China. The aim of this study was to understand the extent and experiences of financial information technology within the insurance and securities companies, the strategies that harness IT to gain competitive advantage and the challenges and opportunities that influence the adoption of financial informatization. Results of interviews with participants indicated some common and diverse ideas about the financial technology in insurance and securities entities. Financial informatization has bolstered competitiveness through improved efficiency and decision-making capabilities, yet raised data security concerns. There were four themes that emerged from this study namely, digital transformation in financial information technology, technological innovation and service differentiation, data protection and risk management, and financial innovation and business cooperation. The study concluded that data protection strategies differ, with larger entities often having the edge due to greater resources and innovation capabilities. It recommends sustained investment in technology, management system optimization, staff training, and innovation and exploration. Regulators are urged to improve standards and supervision and to promote industry self-regulation. The study calls for enhanced cooperation and innovation within the financial sector to bolster its image.Includes bibliographical referencesMaster in Business Administratio
Research and Software Development of Active Learning Mode for College Students Based on Computer Network
With the development of information technology, especially the fast development of Internet technology, the network technology has expanded to all walks of life. Using Internet to acquire knowledge has become an important means for us. The paper sums up the current status of foreign active learning modes and the problems existing in computer network environment by referring to the relevant literature. What is more, it also further clarifies the basic concepts and connotations of active learning in the computer network environment and active learning itself by researching on its relevant theoretical basis and influential factors as well. “A new active learning mode in computer network environment” is constructed based on the analysis of the relevant factors of active learning in the computer network environment, taking college students as the studying object and the college English course as an example. According to this model, the active learning platform of college English network is designed and developed. The research conclusion is not only theoretically based, but also founded on the concrete practice and the application. Therefore, it is endowed with maneuverability so as to provide a research example for the general teachers
The location of lymphangiogenesis is an independent prognostic factor in rectal cancers with or without preoperative radiotherapy
Background: Lymphangiogenesis and angiogenesis are essential for tumour development and progression. The lymphatic vessel density (LVD) and blood vessel density (BVD) and their relationship to outcome have been studied extensively, however the clinical significance of the location of LVD/BVD in tumour is not known. In the present study, the location and degree of LVD/BVD and their relationship to preoperative radiotherapy (RT), clinicopathological, histopathological and biological factors were studied in rectal cancer patients participating in a Swedish clinical trial of preoperative RT. Patients and methods: The location and degree of LVD/BVD were analysed in primary tumours (n = 138/140) and in their subgroups of non-RT (n = 74) and RT (n = 64/66). Further, the degree of LVD/BVD was examined in the corresponding distant normal mucosa (n = 35/31) and adjacent normal mucosa (n = 72/91). All sections were immunohistochemically examined by using D2-40 and CD34 antibodies. Results: In the whole series of the patients, a higher LVD at the periphery was related to negative p53 expression (P = 0.03) and favourable survival independent of tumour-node-metastasis stage, differentiation and p53 expression (P = 0.03). LVD was increased in p53-negative tumours after RT (P = 0.01). Conclusion: LVD at the periphery of the tumour was an independent prognostic factor in rectal cancer patients.This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Annals of Oncology following peer review. The definitive publisher-authenticated version:A Holmqvist, Jingfang Gao, Gunnar Adell, John Carstensen and Xiao-Feng Sun, The location of lymphangiogenesis is an independent prognostic factor in rectal cancers with or without preoperative radiotherapy, 2010, ANNALS OF ONCOLOGY, (21), 3, 512-517.is available at: http://dx.doi.org/10.1093/annonc/mdp486Copyright: Oxford University Presshttp://www.oxfordjournals.org
IDENTIFICATION AND SYNTHESIS OF MODULAR GLUCOSIDES, A NEW FAMILY OF SECONDARY METABOLITES FROM C. ELEGANS
465 pagesSmall molecules with highly diverse structures are produced by all animals and play essential functions in nearly all facets of their biology, including development, lifespan, reproduction, as well as interactions with other species. Identification of small molecule metabolites can reveal new biosynthetic and signaling pathways, with broad implications for medicine, human nutrition, but also agriculture. While great efforts over the past few decades have led to impressive discoveries in the field of metabolomics, the vast majority of metabolites still remain unknown and uncharacterized. Given the significance of metabolites and their biological functions, the development of new approaches toward a systematic structural and functional annotation of animal metabolomes is an important goal. In this dissertation, the author explores two highly conserved metabolic pathways with demonstrated relevance for human health and identifies diverse novel metabolites using the nematode Caenorhabditis elegans, a highly tractable model animal for biomedical research. Chapters 1–2 uncover new aspects of neurotransmitter metabolism of C. elegans, with a specific focus on serotonin metabolism. We uncovered a parallel pathway for serotonin biosynthesis and identified modular glucosides as novel down-stream metabolites of serotonin in C. elegans, and further investigated their biological activities. In chapter 3, the author investigates the metabolomes of C. elegans mitochondrial mutants, which revealed distinctive metabolic signatures in long-lived mutants, suggesting that amino acid metabolism and mitochondria-related longevity are linked. In chapter 4, the author developed selective synthetic strategies that allow to access structurally diverse modular glucosides, providing authentic samples for confirmation of proposed structures studying their biological functions
Dinghu Shan zhi
丁易總修 ; 釋成鷲纂述.In 1 case.框19.3x13.8公分, 9行19字, 白口, 左右雙邊, 單白魚尾, 版心上鐫"鼎湖山志", 中鐫卷次, 下鐫葉次.前有趙弘燦序, 康熙56年[1717]陳元龍序, 吳柯序, 康熙56年宋志益序, 王炳序, 王經方等序.Ding Yi zong xiu ; Shi Chengjiu zuan shu.Kuang 19.3x13.8 gong fen, 9 hang 19 zi, bai kou, zuo you shuang bian, dan bai yu wei, ban xin shang juan "Dinghu Shan zhi", zhong juan juan ci, xia juan ye ci.Qian you Zhao Hongcan xu, Kangxi 56 nian [1717] Chen Yuanlong xu, Wu Ke xu, Kangxi 56 nian Song Zhiyi xu, Wang Bing xu, Wang Jingfang deng xu
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