17 research outputs found

    The effect of location of post drilled web opening on the strength of reinforced concrete beam

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    The construction of modern buildings requires many pipes and ducts in order to accommodate essential services such as electricity, air conditioning, telephone, and network cables. Web openings in Reinforced Concrete (RC) beams enable the installation of these services under lower floor to floor height without compromising any architectural headroom. However, the requirement of opening often reaches the engineers and contractors after the beam has been constructed. As such, there is a need to reassess the new strength of the beam with the newly added opening without the placement of trimmer reinforcement bar. Methods to assess the reduced strength of the RC beams due to post drilling these opening are often complicated. To overcome this, a research has been carried out with the aim to provide simple guidance to engineers to access the new strength of the RC beams due to small post drilled transverse circular web openings at different location of the beam. RC beams with a series of opening at different location were analysed using LUSAS, by conducting nonlinear analysis to determine the new strength of the RC beam. A graph of relative load bearing capacity of an RC beam with respect to location of post drilled web opening is proposed to aid design engineers to assess the beam capacity without a need for detail calculation

    Differentiation of Club Cells to Alveolar Epithelial Cells In Vitro

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    Club cells are known to function as regional progenitor cells to repair the bronchiolar epithelium in response to lung damage. By lineage tracing in mice, we have shown recently that club cells also give rise to alveolar type 2 cells (AT2s) and alveolar type 1 cells (AT1s) during the repair of the damaged alveolar epithelium. Here, we show that when highly purified, anatomically and phenotypically confirmed club cells are seeded in 3-dimensional culture either in bulk or individually, they proliferate and differentiate into both AT2- and AT1-like cells and form alveolar-like structures. This differentiation was further confirmed by transcriptomic analysis of freshly isolated club cells and their cultured progeny. Freshly isolated club cells express Sca-1 and integrin α6, markers commonly used to characterize lung stem/progenitor cells. Together, current study for the first time isolated highly purified club cells for in vitro study and demonstrated club cells’ capacity to differentiate into alveolar epithelial cells at the single-cell level.National Cancer Institute (U.S.) (P30-CA14051

    Super-enhancers promote transcriptional dysregulation in nasopharyngeal carcinoma

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    Nasopharyngeal carcinoma (NPC) is an invasive cancer with particularly high incidence in Southeast Asia and Southern China. The pathogenic mechanisms of NPC, particularly those involving epigenetic dysregulation, remain largely elusive, hampering clinical management of this malignancy. To identify novel druggable targets, we carried out an unbiased high-throughput chemical screening and observed that NPC cells were highly sensitive to inhibitors of cyclin-dependent kinases (CDK), especially THZ1, a covalent inhibitor of CDK7. THZ1 demonstrated pronounced antineoplastic activities both in vitro and in vivo An integrative analysis using both whole-transcriptome sequencing and chromatin immunoprecipitation sequencing pinpointed oncogenic transcriptional amplification mediated by super-enhancers (SE) as a key mechanism underlying the vulnerability of NPC cells to THZ1 treatment. Further characterization of SE-mediated networks identified many novel SE-associated oncogenic transcripts, such as BCAR1, F3, LDLR, TBC1D2, and the long noncoding RNA TP53TG1. These transcripts were highly and specifically expressed in NPC and functionally promoted NPC malignant phenotypes. Moreover, DNA-binding motif analysis within the SE segments suggest that several transcription factors (including ETS2, MAFK, and TEAD1) may help establish and maintain SE activity across the genome. Taken together, our data establish the landscape of SE-associated oncogenic transcriptional network in NPC, which can be exploited for the development of more effective therapeutic regimens for this disease. Cancer Res; 77(23); 6614-26. ©2017 AACR
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