Monitoring Slope Failure at Kadoorie Agricultural Research Centre with a 3D Laser Scanner

A loosely compacted fill slope with an angle of 33° was constructed at the Kadoorie Agricultural Research Centre of The University of Hong Kong. The height and width were 4.75 m and 9 m respectively. It was constructed by end-tipping method and resulted in a loose state with an initial dry density of 70% of the maximum dry density. Two rows of grouted nails were installed at a grid of 1.5 m x 1.5 m at an inclination of 20° from the horizontal. The slope was brought to failure by subjecting it to surcharge at the slope crest in combination with induced rise in groundwater table and precipitation. Heavy instrumentation comprised in-place inclinometer, vibrating wire piezometers, vibrating wire extensometer, earth pressure cell, tensiometer and strain gauges along soil nails and they had been monitored throughout the test. Surface movement was monitored using a GPS system and a 3D laser scanner. This paper focuses on the use of 3D laser scanner in capturing the formation of cracks and surface movement during the failure. It is found that by overlapping the point clouds generated from the scanner at different time intervals, the surface movement of the slope can be accurately recorded without the need of physically accessing the slope surface. When the slope reaches failure, the use of laser scanning can safely and quickly record the movement and dimension of washout and cracks, providing advantages over conventional survey method. This study shows that the movement obtained from the scanner agrees very well with that from conventional inclinometer reading at the surface. The travel distance of the surcharge block can be easily measured and point cloud can be easily modeled into geometrical shape for further rendering.published_or_final_versio

Reclamation Ground Settlement Monitoring by Using GPS and Other Positioning Technologies at ShenZhen Airport.

Hong Kong is a small territory of about 1070 km2 . There is an ever-increasing demand for land to cope with her increasing development. Typical geology in Hong Kong under the seabed comprises a layer of soft marine deposit of variable thickness of up to 20 m, overlying alluvium, residual soil, decomposed rock and bedrock. However, the marine deposit is too soft to support any structures. Conventional reclamation practice in Hong Kong is to dredge the marine deposit, build the seawalls and fill the enclosed space by sand. This conventional approach has many shortcomings. A research project was undertaken by The University of Hong Kong to develop a vacuum preloading technique that is environmentally safe to improve the engineering properties of the thick layer of soft marine deposits so that they can be kept in place during land reclamation. As a result, the environmental problems relating to dredging can be completely eliminated. A vacuum preloading test near the Shenzhen Airport was carried out as part of a very large research program. Sub-surface field instrumentation comprised piezometers, inclinometers, extensometers and pressure cells to monitor the performance of the vacuum system and the physical changes of the marine deposit during vacuum preloading. Surface settlement was monitored using 3 units of high precision GPS equipment throughout the test for checking against the sub-surface monitored movement. It is necessary to use a fully automatic system like GPS for replacing conventional survey because the test was carried out over water, which was difficult to access and the test was carried out over a very long period of 4 months. This paper reports the use of GPS for reclamation ground settlement monitoring and demonstrates cm-level positioning results through experimental trials. The results also agree very well with the sub-surface settlement readings.published_or_final_versio

TCGA whole-transcriptome sequencing data reveals significantly dysregulated genes and signaling pathways in hepatocellular carcinoma

This study systematically evaluates the TCGA whole-transcriptome sequencing data of hepatocellular carcinoma (HCC) by comparing the global gene expression profiles between tumors and their corresponding nontumorous liver tissue. Based on the differential gene expression analysis, we identified a number of novel dysregulated genes, in addition to those previously reported. Top-listing upregulated (CENPF and FOXM1) and downregulated (CLEC4G, CRHBP, and CLEC1B) genes were successfully validated using qPCR on our cohort of 65 pairs of human HCCs. Further examination for the mechanistic overview by subjecting significantly upregulated and downregulated genes to gene set enrichment analysis showed that different cellular pathways were involved. This study provides useful information on the transcriptomic landscape and molecular mechanism of hepatocarcinogenesis for development of new biomarkers and further in-depth characterization

Pim1 is upregulated by hypoxia in hepatocellular carcinoma and promotes tumor progression

Poster Session - Molecular pathogenesis, molecular pathology, cell biology and translational research: no. P-022INTRODUCTION: Hepatocellular carcinoma (HCC) is the second/third most common fatal cancer in Hong Kong and Southeast Asia associated with frequent tumor recurrence and metastasis. Apart from surgical intervention, tumor control at cellular and molecular levels can possibly improve clinical outcome. HCC is characteristically one of the most rapidly proliferating tumors which often outpace functional blood supply, leading to a regional oxygen deprivation. Therefore, molecular changes induced by hypoxia are attractive therapeutic targets. Overexpression of PIM1, a serine/threonine kinase, has been identified in recent years in solid cancers such as prostate cancer, gastric cancer, and pancreatic cancer. In the latter, PIM1 was upregulated by hypoxia. In this study, we aim at investigating the expression, functional role, and regulatory mechanism of PIM1 in HCC, which have …published_or_final_versio

Sox9 confers stemness properties in hepatocellular carcinoma through Frizzled-7 mediated Wnt/β-catenin signaling

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Down-regulation of TIMP2 by HIF-1α/miR-210/HIF-3α regulatory feedback circuit enhances cancer metastasis in hepatocellular carcinoma

Cancer metastasis is a multistep process that involves a series of tumor-stromal interaction, including extracellular matrix (ECM) remodeling, which requires a concerted action of multiple proteolytic enzymes and their endogenous inhibitors. This study investigated the role of tissue inhibitor of metalloproteinases (TIMP) 2 in the context of hepatocellular carcinoma (HCC) metastasis. We found that TIMP2 was the most significantly down-regulated member among the TIMP family in human HCCs. Moreover, TIMP2 underexpression was frequent (41.8%; 23 of 55) in human HCCs and was significantly associated with liver invasion and poorer survival outcomes of HCC patients. Furthermore, stable silencing of TIMP2 in HCC cell lines enhanced cell invasive ability and ECM degradation associated with formation of invadopodia-like feature, suggesting that TIMP2 is a negative regulator of HCC metastasis. Using an orthotopic tumor xenograft model, we demonstrated that ectopic expression of TIMP2 open reading frame in the highly metastatic HCC cell line, MHCC-97L, significantly reduced HCC progression as well as pulmonary metastasis. Mechanistically, TIMP2 suppression, in a hypoxic environment, was induced through a regulatory feedback circuit consisting of hypoxia-inducible factor (HIF) 1 alpha, microRNA-210 (miR-210), and HIF-3alpha. CONCLUSION: TIMP2 is frequently down-regulated in human HCCs and its down-regulation is associated with aggressive tumor behavior and poorer patient outcome. Its suppression is under the regulation of a novel feedback circuit consisting of HIF-1alpha/miR-210/HIF-3alpha. TIMP2 is an important regulator of ECM degradation and HCC metastasis. (Hepatology 2016;64:473-487).published_or_final_versio

PIM1 regulates glycolysis and promotes tumor progression in hepatocellular carcinoma

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NF-κB p65 Subunit Is Modulated by Latent Transforming Growth Factor-β Binding Protein 2 (LTBP2) in Nasopharyngeal Carcinoma HONE1 and HK1 Cells

NF-kappa B is a well-characterized transcription factor, widely known as a key player in tumor-derived inflammation and cancer development. Herein, we present the functional and molecular relevance of the canonical NF-kappa B p65 subunit in nasopharyngeal carcinoma (NPC). Loss-and gain-of-function approaches were utilized to reveal the functional characteristics of p65 in propagating tumor growth, tumor-associated angiogenesis, and epithelial-to-mesenchymal transition in NPC cells. Extracellular inflammatory stimuli are critical factors that trigger the NF-kappa B p65 signaling; hence, we investigated the components of the tumor microenvironment that might potentially influence the p65 signaling pathway. This led to the identification of an extracellular matrix (ECM) protein that was previously reported as a candidate tumor suppressor in NPC. Our studies on the Latent Transforming Growth Factor-beta Binding Protein 2 (LTBP2) protein provides substantial evidence that it can modulate the p65 transcriptional activity. Re-expression of LTBP2 elicits tumor suppressive effects that parallel the inactivation of p65 in NPC cells. LTBP2 was able to reduce phosphorylation of p65 at Serine 536, inhibit nuclear localization of active phosphorylated p65, and impair the p65 DNA-binding ability. This results in a consequential down-regulation of p65-related gene expression. Therefore, the data suggest that the overall up-regulation of p65 expression and the loss of this candidate ECM tumor suppressor are milestone events contributing to NPC development.published_or_final_versio

SENP1 promotes hypoxia-induced cancer stemness by HIF-1α deSUMOylation and SENP1/HIF-1α positive feedback loop

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CCR5 antagonist TD-0680 uses a novel mechanism for enhanced potency against HIV-1 entry, cell-mediated infection, and a resistant variant

Regardless of the route of transmission, R5-tropic HIV-1 predominates early in infection, rendering C-C chemokine receptor type 5 (CCR5) antagonists as attractive agents not only for antiretroviral therapy but also for prevention. Here, we report the specificity, potency, and underlying mechanism of action of a novel small molecule CCR5 antagonist, TD-0680. TD-0680 displayed the greatest potency against a diverse group of R5-tropic HIV-1 and SIV strains when compared with its prodrug, TD-0232, the Food and Drug Administration-approved CCR5 antagonist Maraviroc, and TAK-779, with EC 50 values in the subnanomolar range (0.09-2.29 nM). Importantly, TD-0680 was equally potent at blocking envelope-mediated cell-cell fusion and cell-mediated viral transmission as well as the replication of a TAK-779/Maraviroc-resistant HIV-1 variant. Interestingly, TD-0232 and TD-0680 functioned differently despite binding to a similar transmembrane pocket of CCR5. Site-directed mutagenesis, drug combination, and antibody blocking assays identified a novel mechanism of action of TD-0680. In addition to binding to the transmembrane pocket, the unique exo configuration of this molecule protrudes and sterically blocks access to the extracellular loop 2 (ECL2) region of CCR5, thereby interrupting the interaction between virus and its co-receptor more effectively. This mechanism of action was supported by the observations of similar TD-0680 potency against CD4-dependent and -independent SIV strains and by molecular docking analysis using a CCR5 model. TD-0680, therefore, merits development as an anti-HIV-1 agent for therapeutic purposes and/or as a topical microbicide for the prevention of sexual transmission of R5-tropic HIV-1. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.link_to_OA_fulltex