Principles of microRNA regulation of a human cellular signaling network

MicroRNAs (miRNAs) are endogenous 22-nucleotide RNAs, which suppress gene expression by selectively binding to the 3-noncoding region of specific message RNAs through base-pairing. Given the diversity and abundance of miRNA targets, miRNAs appear to functionally interact with various components of many cellular networks. By analyzing the interactions between miRNAs and a human cellular signaling network, we found that miRNAs predominantly target positive regulatory motifs, highly connected scaffolds and most downstream network components such as signaling transcription factors, but less frequently target negative regulatory motifs, common components of basic cellular machines and most upstream network components such as ligands. In addition, when an adaptor has potential to recruit more downstream components, these components are more frequently targeted by miRNAs. This work uncovers the principles of miRNA regulation of signal transduction networks and implies a potential function of miRNAs for facilitating robust transitions of cellular response to extracellular signals and maintaining cellular homeostasis

Shear Resistance Capacity of Interface of Plate-Studs Connection between CFST Column and RC Beam

The combination of a concrete-filled steel tube (CFST) column and reinforced concrete (RC) beam produces a composite structural system that affords good structural performance, functionality, and workability. The effective transmission of moments and shear forces from the beam to the column is key to the full exploitation of the structural performance. The studs of the composite beam transfer the interfacial shear force between the steel beam and the concrete slab, with the web bearing most of the vertical shear force of the steel beam. In this study, the studs and vertical steel plate were welded to facilitate the transfer of the interfacial shear force between the RC beam and CFST column. Six groups of a total of 18 specimens were used to investigate the shear transfer mechanism and failure mode of the plate-studs connection, which was confirmed to effectively transmit the shear forces between the beam and column. The results of theoretical calculations were also observed to be in good agreement with the experimental measurements

MicroRNAs preferentially target the genes with high transcriptional regulation complexity

Over the past few years, microRNAs (miRNAs) have emerged as a new prominent class of gene regulatory factors that negatively regulate expression of approximately one-third of the genes in animal genomes at post-transcriptional level. However, it is still unclear why some genes are regulated by miRNAs but others are not, i.e. what principles govern miRNA regulation in animal genomes. In this study, we systematically analyzed the relationship between transcription factors (TFs) and miRNAs in gene regulation. We found that the genes with more TF-binding sites have a higher probability of being targeted by miRNAs and have more miRNA-binding sites on average. This observation reveals that the genes with higher cis-regulation complexity are more coordinately regulated by TFs at the transcriptional level and by miRNAs at the post-transcriptional level. This is a potentially novel discovery of mechanism for coordinated regulation of gene expression. Gene ontology analysis further demonstrated that such coordinated regulation is more popular in the developmental genes.Comment: supplementary data available at http://www.bri.nrc.ca/wan

Global analysis of microRNA target gene expression reveals that miRNA targets are lower expressed in mature mouse and Drosophila tissues than in the embryos

MicroRNAs (miRNAs) are non-coding small RNAs of ∼22 nt that regulate the gene expression by base pairing with target mRNAs, leading to mRNA cleavage or translational repression. It is currently estimated that miRNAs account for ∼1% of predicted genes in higher eukaryotic genomes and that up to 30% of genes might be regulated by miRNAs. However, only very few miRNAs have been functionally characterized and the general functions of miRNAs are not globally studied. In this study, we systematically analyzed the expression patterns of miRNA targets using several public microarray profiles. We found that the expression levels of miRNA targets are lower in all mouse and Drosophila tissues than in the embryos. We also found miRNAs more preferentially target ubiquitously expressed genes than tissue-specifically expressed genes. These results support the current suggestion that miRNAs are likely to be largely involved in embryo development and maintaining of tissue identity

Aberrant allele frequencies of the SNPs located in microRNA target sites are potentially associated with human cancers

MicroRNAs (miRNAs) are a class of noncoding small RNAs that regulate gene expression by base pairing with target mRNAs at the 3′-terminal untranslated regions (3′-UTRs), leading to mRNA cleavage or translational repression. Single-nucleotide polymorphisms (SNPs) located at miRNA-binding sites (miRNA-binding SNPs) are likely to affect the expression of the miRNA target and may contribute to the susceptibility of humans to common diseases. We herein performed a genome-wide analysis of SNPs located in the miRNA-binding sites of the 3′-UTR of various human genes. We found that miRNA-binding SNPs are negatively selected in respect to SNP distribution between the miRNA-binding ‘seed’ sequence and the entire 3′-UTR sequence. Furthermore, we comprehensively defined the expression of each miRNA-binding SNP in cancers versus normal tissues through mining EST databases. Interestingly, we found that some miRNA-binding SNPs exhibit significant different allele frequencies between the human cancer EST libraries and the dbSNP database. More importantly, using human cancer specimens against the dbSNP database for case-control association studies, we found that twelve miRNA-binding SNPs indeed display an aberrant allele frequency in human cancers. Hence, SNPs located in miRNA-binding sites affect miRNA target expression and function, and are potentially associated with cancers

Recombinant Human Endostatin Endostar Inhibits Tumor Growth and Metastasis in a Mouse Xenograft Model of Colon Cancer

To investigate the effects of recombinant human endostatin Endostar on metastasis and angiogenesis and lymphangiogenesis of colorectal cancer cells in a mouse xenograft model. Colon cancer cells SW620 were injected subcutaneously into the left hind flank of nude mice to establish mouse xenograft models. The mice were treated with normal saline or Endostar subcutaneously every other day. The growth and lymph node metastasis of tumor cells, angiogenesis and lymphangiogenesis in tumor tissue were detected. Apoptosis and cell cycle distribution were studied by flow cytometry. The expression of VEGF-A, -C, or -D in SW620 cells was determined by immunoblotting assays. Endostar inhibited tumor growth and the rate of lymph node metastasis (P < 0.01). The density of blood vessels in or around the tumor area was 12.27 ± 1.21 and 22.25 ± 2.69 per field in Endostar-treated mice and controls (P < 0.05), respectively. Endostar also decreased the density of lymphatic vessels in tumor tissues (7.84 ± 0.81 vs. 13.83 ± 1.08, P < 0.05). Endostar suppresses angiogenesis and lymphangiogenesis in the lymph nodes with metastases, simultaneously. The expression of VEGF-A, -C and -D in SW620 cells treated with Endostar was substantially lower than that of controls. Endostar inhibited growth and lymph node metastasis of colon cancer cells by inhibiting angiogenesis and lymphangiogenesis in a mouse xenograft model of colon cancer

Development of Location Method for Urban Public Transit Networks Based on Hub-and-Spoke Network Structure

A location method is presented for an urban public transit (PT) network based on the hub-and-spoke network structure model. The proposed method integrates the PT lines with transfer hubs. PT lines fall into four major service levels: subway, bus rapid transport, bus, and feeder bus. The transfer hubs fall into three major categories: intermodal terminals, transfer centers, and transfer stations. Every level of PT line is located by connecting the different classes of transfer hubs. The optimization objectives, constraints, and procedures for PT line locations are present, and they vary by level of PT service. The design and implementation of the proposed method are illustrated by a case study for the city of Fuzhou, China. The proposed allocation method offers a new approach for increasing the PT level of service of a high-density city. The procedure for allocating PT lines is practical and maneuverable

Optimization of Matching on Torque Converter with Engine Based on Improved Radar Chart Method

In order to comprehensively evaluate the performance of matching between engine and torque converter, a series of matching evaluation indexes were developed according to the ideal matching principle and a standardized treatment for every index was put forward. Considering the different importance of each indexes in different applications, weight of each index was given by using comprehensive method, The evaluation method of the hydraulic torque converter and engine matching was established based on the improved radar map method. The objective function was constructed based on the sum of each evaluation index and the perimeter of radar map. With a hydraulic torque converter of ZL50 loader as an example, the effective diameter of circular circle on hydraulic torque converter was optimized in view of the shovel loading cycle condition. The original size of torque converter effective diameter was 0.340 m. After optimization, the effective diameter of hydraulic torque converter was 0.350 m, and the matching performance of engine and torque converter was increased by 7.4%. The results show that the optimal matching scheme can be improved by using the improved radar map method

A route-planning method for long-distance commuter express bus service based on OD estimation from mobile phone location data: the case of the Changping Corridor in Beijing

With the background of hyperurbanization and a jobs–housing imbalance in Beijing and other megacities in China, this study aims at developing a systematic toolkit of demand estimation and route planning for long-distance commuter bus lines. Taking the express bus services (EBS) in the Changping Corridor in Beijing as an example, this paper presents the use of a route-planning algorithm. Mobile phone location (MPL) data serves as a valid instrument for the origin–destination (OD) estimation, which provides a new perspective to identify the locations of homes and jobs. The OD distribution matrices are specified via geocoded MPL data. To minimize the aggregated travel time and attract potential passengers, this study subsamples long-distance commuting trips among the OD matrices by determining the operation distance threshold. The threshold can be solved by comparing the aggregated travel time of EBS to the travel time of local buses and private cars. Using the distance threshold and other operational parameters, we process an iterative computation to determine the length of routes, number of lines, and stop spacing and location. Compared to local buses and private cars, the planned EBS lines could reduce aggregated travel time by at least 20%. The results demonstrate that the method presented in this study is applicable and flexible. This paper may lead to new research directions for route planning of long-distance commuter buses. The limitations of this study and the future research agenda are also discussed

Control Of The Thermal Conductivity Of Sic By Modifying The Polymer Precursor

Compared to other methods, the fabrication of SiC from precursors allows designing the microstructure and thus the properties of the ceramic material by adjusting the microstructure of the precursor materials. In this study, we used a divinylbenzene (DVB) isomer mixture to modify the polycarbosilane (PCS) precursor via the chemical modification method. The ceramics derived from the modified precursors showed different thermal conductivities. The SiC prepared from PCS without DVB exhibited a very low thermal conductivity at low and at high temperatures. A proper doping with DVB led to clean SiC grain boundaries, resulting in the typical thermal conductivity behaviour of coarse SiC ceramics. An excess doping with DVB led to the precipitation of free carbon around the SiC grains, resulting in a still suitable thermal conductivity which was between the other two values. The results clearly demonstrate that adjusting the thermal properties by modifying the microstructure is a promising approach