54 research outputs found

    Different cis-regulatory DNA elements mediate developmental stage- and tissue-specific expression of the human COL2A1 gene in transgenic mice

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    Expression of the type II collagen gene (human COL2A1, mouse Col2a1) heralds the differentiation of chondrocytes. It is also expressed in progenitor cells of some nonchondrogenic tissues during embryogenesis. DNA sequences in the 5' flanking region and intron 1 are known to control tissue- specific expression in vitro, but the regulation of COL2A1 expression in vivo is not clearly understood. We have tested the regulatory activity of DNA sequences from COL2A1 on the expression of a lacZ reporter gene in transgenic mice. We have found that type II collagen characteristic expression of the transgene requires the enhancer activity of a 309-bp fragment (+2,388 to +2,696) in intron 1 in conjunction with 6.1-kb 5' sequences. Different regulatory elements were found in the 1.6-kb region (+701 to +2,387) of intron 1 which only needs 90-bp 5' sequences for tissue-specific expression in different components of the developing cartilaginous skeleton. Distinct positive and negative regulatory elements act together to control tissue- specific transgene expression in the developing midbrain neuroepithelium. Positive elements affecting expression in the midbrain were found in the region from -90 to -1,500 and from +701 to +2,387, whereas negatively acting elements were detected in the regions from -1,500 to -6,100 and +2,388 to +2,855.published_or_final_versio

    A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

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    dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

    Emission-aware adjustable robust flight path planning with respect to fuel and contrail cost

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    202208 bckwNot applicableRGCOthersThe Hong Kong Polytechnic Universit

    Aircraft scheduling considering discrete airborne delay and holding pattern in the near terminal area

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    13th International Conference on Intelligent Computing, ICIC 2017, 7 - 10 August 20172017-2018 > Academic research: refereed > Refereed conference paper201802 bcrcAccepted ManuscriptSelf-fundedPublishe

    Makespan minimization in aircraft landing problem under congested traffic situation using modified artificial bee colony algorithm

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    2016 International Conference on Industrial Engineering and Engineering Management, IEEM 2016, Indonesia, 4-7 December 20162016-2017 > Academic research: refereed > Refereed conference paper201803_a bcwhAccepted ManuscriptOthersRU8HPublishe

    A modified variable neighborhood search for aircraft landing problem

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    2016 IEEE International Conference on Management of Innovation and Technology, ICMIT 2016, Thailand, 19-22 September 2016Accepted ManuscriptOthersRU8HPublishe

    Robust parallel machine scheduling problem with uncertainties and sequence-dependent setup time

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    Version of RecordRGCOthersRGC: 14YZ111,QD2015041Others: RUF1,RU8H,71201099Publishe

    A robust optimisation approach to the aircraft sequencing and scheduling problem with runway configuration planning

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    2017-2018 > Academic research: refereed > Refereed conference paper201809 bcmaAccepted ManuscriptOthersRU8H, G-UA4F, 1-ZE3BPublishe
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