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RISS 인기검색어
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- 저자 : Singh, Vishwakarma (검색결과 387 건)
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Querying Patterns in High-Dimensional Heterogenous Datasets
Singh, Vishwakarma University of California, Santa Barbara 2012 해외박사(DDOD)
소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.
The recent technological advancements have led to the availability of a plethora of heterogenous datasets, e.g., images tagged with geo-location and descriptive keywords. An object in these datasets is described by a set of high-dimensional feature vectors. For example, a keyword-tagged image is represented by a color-histogram and a word-histogram. Analyzing these datasets gives better insights into the processes generating the datasets, opens new frontiers of scientific research, and fuels development of life-changing products. An effective mechanism for exploring these heterogenous datasets is querying. One such kind of query is a pattern query. Given a heterogenous dataset and a query, the task here is to find a set of objects which are constrained by a relationship and satisfy the query. For example, given a dataset of keyword-tagged objects, a useful pattern query is to find a set of similar objects that contains a given set of keywords. Querying patterns in high-dimensional heterogenous datasets brings about a new set of computational challenges. High performance algorithms to efficiently and accurately query patterns are presented in this thesis. First, a scalable algorithm, SIMP, is described for accurately querying near neighbors in a high-dimensional dataset. SIMP significantly outperforms the state-of-the-art techniques. Next, a novel algorithm, ProMiSH, is proposed for efficiently querying patterns by keywords. ProMiSH has a speed-up of more than four orders over the state-of-the-art techniques. Then, an algorithm, QUIP, is described for querying patterns by example in a spatial dataset, e.g., geographical maps. QUIP offers an improvement of 87% in running time over the baseline approach. Next, an algorithm for querying patterns by example in a temporal dataset is described. It specifically solves the problem of finding duplicate videos. The proposed algorithm yields a practical query time for video duplicate detection. Finally, a scalable method to compute statistical significance of results of a multi-object query is discussed. Statistical significance or p-value provides a more useful criterion for ranking the results of a query.
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Singh, Rohit Kangwon National Univ. 2014 국내박사
위암에서 HER2의 과 발현은 나쁜 결과(poor outcome)와 관련이 있으며, 그리고 항암화학요법과 함께 조합된 anti-HER2 항체 trastuzumab이 말기위암환자 치료를 위해 승인된 바 있다. 위암에서 VEGF의 발현도 재발(recurrence) 그리고 나쁜 예후(poor prognosis)와 관련이 있지만, anti-VEGF 항체 bevacizumab은 임상시험에서 위암에 대하여 제한된 효능을 보여 왔다. 본 연구에서는 이종이식모델에서 trastuzumab, 그리고 VEGF-A, VEGF-B, PlGF에 결합하는 VEGF-Trap의 단독 치료와 비교하여, trastuzumab과 VEGF-Trap 병합치료에 의한 항암효과를 평가하였다. 결과에서, Trastuzumab 또는 VEGF-Trap은 종양의 성장을 중간 정도로 억제하였지만, 두 물질을 조합한 조건은 각각의 물질에 비하여 더 높은 억제 효과를 보였다. 면역조직화학적 분석은 종양 성장의 감소가 종양 세포의 증식 저하 그리고 감소한 종양혈관의 밀도와 연관되어 있음을 보여주었다. 병합치료(combined treatment)는 trastuzumab 또는 VEGF-Trap의 단독치료와 비교했을 때, 더 적게 증식하는 종양세포와 더 많은 사멸세포, 그리고 더 적은 종양혈관밀도의 결과를 가져왔으며, trastuzumab과 VEGF-Trap의 병합치료가 위암 이종이식의 종양 성장과 혈관생성에 대한 부가적 억제효능을 가지고 있음을 나타내었다. 이 결과는 VEGF-Trap과 결합한 trastuzumab이 HER2를 과 발현 하는 위암 치료에서 있어서 효과적인 접근이 될 수 있음을 시사한다. 한편, 본 연구진은 항종양(anti-tumor), 항 혈관신생(anti-angiogenic) 활성을 모두 갖는 이중특이성단백질을 만들어냈다. 즉, anti-HER2 단일클론항체인 trastuzumab의 단일사슬항체조각을 VEGF-Trap에 융합함으로, HER2와 VEGF 모두에 결합하는 이중특이성단백질(4D5-VT)을 제작하였다. 본 재조합단백질, 4D5-VT는 HER2에 결합하여 in vitro에서 HER2를 과 발현하는 유방암세포의 증식을 억제시켰다. 4D5-VT는 trastuzumab과 같이 효과적으로 HER2 하류영역 신호전달을 억제시켰고, in vitro 분석에서 HER2 인터널리제이션(internalization)을 유도하였다. 4D5-VT는 VEGF-Trap과 같이, VEGF-A, VEGF-B, 그리고 PlGF에 결합하여 VEGF-A에 매개된 HUVEC의 증식 그리고 트랜스웰 이동을 억제하였다. 본 이중특이성단백질은 유방암 이종이식모델에서 trastuzumab에 비해 더 효과적인 종양 억제를 보였다. 추가적 연구를 통해, 체내(in vivo) 효능과 4D5-VT 작용 메커니즘 평가가 요구된다. The HER2 overexpression in Gastric cancer is correlated with poor outcome, and anti-HER2 antibody trastuzumab in combination with chemotherapy has been approved for the treatment of advanced gastric cancer. VEGF expression in gastric cancer is also correlated with recurrence and1 poor prognosis, but anti-VEGF antibody bevacizumab has shown limited efficacy against gastric cancer in clinical trial. We have evaluated the antitumor effects of trastuzumab, VEGF-Trap binding to VEGF-A, VEGF-B, and placental growth factor (PlGF), and combination of trastuzumab and VEGF-Trap in gastric cancer xenograft model. Trastuzumab or VEGF-Trap moderately inhibited tumor growth, but combination of the both agents exerted greater inhibition compared with either agent. Immunohistochemical analyses indicated that the reduction in tumor growth was associated with decreased proliferation of tumor cells and decreased tumor vascular density. The combined treatment resulted in less proliferating tumor cells, more apoptotic cells, and less tumor vascular density compared with treatment with trastuzumab or VEGF-Trap, indicating that trastuzumab and VEGF-Trap had additive inhibitory effects on the tumor growth and angiogenesis of the gastric cancer xenografts. The data suggest that trastuzumab in combination with VEGF-Trap may represent an effective approach in treating HER2 overexpressing gastric cancer. In addition, we generated a bispecific protein, that exerts both anti-tumor and anti-angiogenic activities. We constructed a bispecific protein (4D5-VT) binding HER2 and VEGF by fusing a single chain antibody fragment of anti-HER monoclonal antibody trastuzumab to the amino-terminus of VEGF-Trap. The recombinant protein, 4D5-VT binds to HER2 and inhibited in vitro proliferation of HER2-overexpressing breast cancer cells. 4D5-VT inhibited HER2 downstream signaling as effectively as trastuzumab and induced HER2 internalization in in vitro assay. 4D5-VT binds to VEGF-A, VEGF-B, and PlGF as VEGF-Trap and inhibited VEGF-A mediated HUVEC proliferation and transwell migration. This bispecific protein exhibited more effective tumor inhibition in a breast cancer xenograft model compared with trastuzumab. Additional studies are warranted to evaluate the in vivo efficacy and mechanism of action of 4D5-VT.
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