MicroRNA let-7a suppresses breast cancer cell migration and invasion through downregulation of C-C chemokine receptor type 7.

INTRODUCTION: C-C chemokine receptor type 7 (CCR7) plays an important role in chemotactic and metastatic responses in various cancers, including breast cancer. In the present study, the authors demonstrated that microRNA (miRNA) let-7a downregulates CCR7 expression and directly influences the migration and invasion of breast cancer cells. METHODS: The expression of CCR7, its ligand CCL21, and let-7a was detected in breast cancer cell lines and in breast cancer patient tissues. Synthetic let-7a and an inhibitor of let-7a were transfected into MDA-MB-231 and MCF-7 breast cancer cells, respectively, and cell proliferation, cell migration, and invasion assays were performed. To confirm the fact that 3'UTR of CCR7 is a direct target of let-7a, a luciferase assay for the reporter gene expressing the let-7a binding sites of CCR7 3'UTR was used. An in vivo invasion animal model system using transparent zebrafish embryos was also established to determine the let-7a effect on breast cancer cell invasion. RESULTS: First, a higher expression of both CCR7 and CCL21 in malignant tissues than in their normal counterparts from breast cancer patients was observed. In addition, a reverse correlation in the expression of CCR7 and let-7a in breast cancer cell lines and breast cancer patient tissues was detected. Synthetic let-7a decreased breast cancer cell proliferation, migration, and invasion, as well as CCR7 protein expression in MDA-MB-231 cells. The let-7a inhibitor reversed the let-7a effects on the MCF-7 cells. The 3'UTR of CCR7 was confirmed as a direct target of let-7a by using the luciferase assay for the reporter gene expressing let-7a CCR7 3'UTR binding sites. Notably, when analyzing in vivo invasion, MDA-MB 231 cells after synthetic let-7a transfection were unable to invade the vessels in zebrafish embryos. CONCLUSIONS: The results from the present study suggest that targeting of CCL21-CCR7 signaling is a valid approach for breast cancer therapy and that let-7a directly binds to the 3'UTR of CCR7 and blocks its protein expression, thereby suppressing migration and invasion of human breast cancer cells. Furthermore, the present study underscores the therapeutic potential of let-7a as an antitumor and antimetastatic manager in breast cancer patients.ope

복수 체인의 건설적 선택 학습 신경망을 통한 앙상블 머신의 구축

학위논문(석사)--서울대학교 대학원 :컴퓨터공학과,2000.Maste

(A)Research on the inclination for traditions demonstrated in th modern Korean poetry

학위논문(박사)--서울대학교 대학원 :국어국문학과 국문학전공,2005.Docto

자율 관리 SSD 아키텍쳐

학위논문 (박사)-- 서울대학교 대학원 : 공과대학 컴퓨터공학부, 2018. 2. 민상렬.From small mobile devices to large-scale storage arrays, flash memory-based storage systems have gained a lot of popularity in recent years thanks to flash memory’s low latency and collectively massive parallelism. However, despite their apparent advantages, achieving predictable performance for flash storages has been difficult. User experiences and large-scale deployments show that the performance of flash storages not only degrades over time, but also exhibits substantial variations and instabilities. This performance unpredictability is caused by the uncoordinated use of resources by competing tasks in the flash translation layer (FTL)—an abstraction layer that hides the quirks of flash memory. As more FTL tasks are added to address the limitations of flash memory, guaranteeing performance will become increasingly difficult. In this dissertation, we present an autonomic SSD architecture that self-manages FTL tasks to maintain a high-level of QoS performance. In this architecture, each FTL task is given an illusion of a dedicated flash memory subsystem of its own through virtualization. This resource virtualization allows each FTL task to be implemented oblivious to others and makes it easy to integrate new tasks to handle future flash memory quirks. Furthermore, each task is allocated a share that represents its relative importance, and its utilization is enforced by a simple and effective scheduling scheme that limits the number of outstanding flash memory requests for each task. The shares are dynamically adjusted through feedback control by monitoring key system states and reacting to their changes to coordinate the progress of FTL tasks. We demonstrate the effectiveness of the autonomic architecture by implementing a flash storage system with multiple FTL tasks such as garbage collection, mapping management, and read scrubbing. The autonomic SSD provides stable performance across diverse workloads, reducing the average response time by 16.2% and the six nines QoS by 67.8% on average for QoS-sensitive small reads.I. Introduction 1 1.1 Advent of flash memory-based storage systems 1 1.2 Research motivation 2 1.3 SSD design challenges 3 1.4 Dissertation contributions 4 1.5 Dissertation layout 6 II. Background 7 2.1 Flash memory 7 2.1.1 Flash memory organization 7 2.1.2 Flash memory operations 8 2.1.3 Error characteristics of flash memory 10 2.2 Flash translation layer 11 III. Architecture of the autonomic SSD 14 3.1 Virtualization of the flash memory subsystem 14 3.2 Scheduling mechanisms for share enforcement 16 3.2.1 Fair queueing scheduler 18 3.2.2 Debit scheduler 21 3.2.3 Preemptive schedulers 23 3.3 Scheduling policy based on feedback control 25 3.3.1 Proportional control 26 3.3.2 Proportional-integral control 27 IV. Evaluation methodology 29 4.1 Flash memory subsystem 29 4.2 Scheduling subsystem 30 4.3 Share controller 31 4.4 Flash translation layer 32 4.4.1 Mapping 32 4.4.2 Host request handling 33 4.4.3 Garbage collection 34 4.4.4 Read scrubbing 34 4.5 Workload and test settings 35 V. Experiment results 37 5.1 Micro-benchmark results 37 5.2 I/O trace results 41 5.3 I/O trace results with scaled intensity 48 5.4 I/O trace results with collocated workloads 57 5.5 Sensitivity analysis with I/O trace workloads 58 5.5.1 Debit scheduler parameters 60 5.5.2 Share controller parameters 62 5.5.3 Read scrubbing thresholds 67 VI. Related work 70 6.1 Real-time FTL 70 6.2 Scheduling techniques inside the SSD 72 6.3 Scheduling at the host system for SSD performance 74 6.4 Performance isolation of SSDs 78 6.5 Scheduling in shared disk-based storages 79 VII. Conclusion 82 7.1 Summary 82 7.2 Future work and directions 83 Bibliography 86 초록 95Docto