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A lattice-filled multicellular square tube features a regular cross-sectional shape, good energy consumption, and good crashworthiness, which is suitable for the design of energy absorbers in various protection fields such as automobiles, aerospace, bridges, etc. Based on the super folding theory, two reference planes are set to refine the energy consumption zone of the super folding element in this study. The energy consumption calculation of convex panel stretching is involved, and the critical crushing force formula is introduced in this study. Meanwhile, the calculation method from a single-cell square tube to a multicellular thin-walled square tube is extended and the structural optimization is investigated, in which the NSGAII algorithm is used to obtain the Pareto front (PF) of the crashworthiness performance index of the square multicellular tubes, the Normal Boundary Intersection (NBI) method is adopted to select knee points, and the influence of different cross-sectional widths on the number, as well as the thickness, of cells are discussed. This study's results indicate that the theoretical value is consistent with that obtained from the numerical simulation, meaning that the improved theoretical model can be applied to predict the crashworthiness of multicellular square cross-sectional tubes. Also, the optimization method and study results proposed in this study can provide a reference for the design of square lattice multicellular tubes. [ABSTRACT FROM AUTHOR]

The positron source is one of the most important parts of the circular electron–positron collider (CEPC) linear accelerator. The design goal is to obtain a 3 nC bunch charge positron beam from a 4 GeV primary electron beam with an intensity of 10 nC/bunch. In this study, an all-solid-state, high-current pulse power system was developed to drive a flux concentrator to capture positrons by generating a magnetic field with a peak value of 6 T. Based on the inductive load topology circuit, the optimized parameters were designed to generate a pulse current with a high peak value and a high rise rate pulse current. In addition, a non-reverse voltage was realized to protect the solid-state switch components. For the characteristics of the long-distance transmission between the pulse power supply and the load in the system, the influences of the cable distribution parameters on the pulse were analyzed, and the design of the damping circuit was proposed to suppress the high-frequency ripples of the peak pulse current. An optimized coaxial discharge structure was designed to reduce the stray parameters in the main circuit. The design was verified through simulations and experiments, and the results demonstrated that the developed prototype successfully generated an ideal half-sinusoidal pulse current with a peak value of 15 kA, and a front pulsewidth of $2.5 ~\mu \text{s}$ at a repetition rate of 50 Hz. The pulse repetition stability is better than 0.1%. The final output was consistent with the theoretical analysis. The system can be applied in the CEPC positron source, which also provides a reference for the subsequent development of a positron source system at research facilities. [ABSTRACT FROM AUTHOR]

Background: Triglyceride glucose-body mass index (TyG-BMI) has been proven to be a reliable substitute for insulin resistance. However, whether a causal association exists between TyG-BMI and new-onset diabetes remains uncertain. The purpose of this study was to investigate the causal association and predictive performance between TyG-BMI and diabetes. Methods: A total of 116,661 subjects who underwent a physical examination were included in this study. The subjects were divided into five equal points according to the quintile of TyG-BMI, and the outcome of interest was the occurrence of diabetic events. TyG-BMI = ln [fasting plasma glucose (mg/dL) × fasting triglycerides (mg/dL)/2] × BMI. Results: During the average follow-up period of 3.1 (0.95) years, 1888 men (1.61 %) and 793 women (0.68 %) were newly diagnosed with diabetes. Multivariate Cox regression analysis showed that TyG-BMI was an independent predictor of new-onset diabetes (HR 1.50 per SD increase, 95 %CI: 1.40 to 1.60, P-trend < 0.00001), and the best TyG-BMI cutoff value for predicting new-onset diabetes was 213.2966 (area under the curve 0.7741, sensitivity 72.51 %, specificity 69.54 %). Additionally, the results of subgroup analysis suggested that the risk of TyG-BMI-related diabetes in young and middle-aged people was significantly higher than that in middle-aged and elderly people, and the risk of TyG-BMI-related diabetes in non-obese people was significantly higher than that in overweight and obese people (P for interaction < 0.05). Conclusions: This cohort study of the Chinese population shows that after excluding other confounding factors, there is a causal association of TyG-BMI with diabetes, and this independent association is more obvious in young, middle-aged and non-obese people. [ABSTRACT FROM AUTHOR]

With the rapid development of network technology and entertainment creation, the types of movies have become more and more diverse, which makes users wonder how to choose the type of movies. In order to improve the selection efficiency, recommend Algorithm came into being. Deep learning is a research field that has received extensive attention from scholars in recent years. Due to the characteristics of its deep architecture, deep learning models can learn more complex structures. Therefore, deep learning algorithms in speech recognition, machine translation, image recognition, and other fields have achieved impressive results. This article mainly introduces the research of personalized movie recommendation methods based on deep learning and intends to provide ideas and directions for the research of personalized movie recommendation under deep learning. This paper proposes a research method of personalized movie recommendation methods based on deep learning, including an overview of personalized recommendation and collaborative filtering recommendation algorithms, which are used to conduct research experiments on personalized movie recommendation methods based on deep learning. The experimental results in this paper show that the accuracy of the training set of the Seq2Seq model based on the LSTM recurrent neural network reaches 96.27% and the accuracy of the test set reaches 95.89%, which can be better for personalized movie recommendation. [ABSTRACT FROM AUTHOR]

The effect of the wave-induced Stokes drift is not taken into account in traditional ocean circulation models used for SST simulations. The spectral parameterization scheme is considered to be the most accurate of the wave-induced Stokes drift calculation schemes. The numerical simulation results of sea surface temperature (SST) with the Stokes drift and SST without the Stokes drift in the North Pacific in 2014 were analyzed. The Stokes drift plays a cooling role in the North Pacific, and the most affected areas are high-latitude sea areas. The following factors are responsible for cooling: the seawater divergence caused by Stokes transport, changes in the sea surface current field caused by the Coriolis-Stokes force and the effects of turbulence caused by Langmuir circulation. The simulation of the vertical temperature profile in the mixed layer is improved when the Stokes drift is accounted for. The simulated results of SST using the Stokes drift approximate parameterization schemes and the spectral parameterization scheme are compared. The results confirm that the spectral parameterization scheme can be used for accurate SST simulation, and the Phillips spectrum approximate parameterization scheme is the best among the approximate parameterization schemes. [ABSTRACT FROM AUTHOR]

This study investigates the characteristics of the heterogeneous carbonate reservoir of Majiagou Formation in Jingxi area, Ordos Basin, China, to explain the diagenetic control and distribution of high‐quality reservoir intervals. The carbonates of the study area mainly consist of silt‐sized crystalline dolomite, microcrystalline dolomite, and microcrystalline limey dolomite. Both dolomite content and dolomite size gradually decrease both from top to bottom and from slope to basin. Intercrystalline pores exist in the silt‐sized crystalline dolomite, and vuggy pores and fractures mainly developed in microcrystalline (limey) dolomite. Furthermore, typical geopetal infills and three stages of calcite cements could be differentiated. Based on petrographical and geochemical analysis, the reservoir is dominantly controlled by seepage reflux dolomitization and telogenetic karstification. Four reservoir evolutions could be differentiated. The reservoir in the first model is dominated by intercrystal porosity occurring in silt‐sized crystalline dolostone. It experienced strong dolomitization, telogenetic karstification, and shallow as well as deep burial cementation. The reservoir in the second model consists of only a small amount of high‐angle dissolution fissures and vertical dissolution cavities in microcrystalline (limey) dolostone. It experienced relatively weak dolomitization, strong telogenetic karstification, and two important calcite cementation events. The reservoir in the third model is marked by many vuggy pores and dissolution fractures, occurring in microcrystalline (limey) dolostone. The strata experienced relatively weak dolomitization, strong telogenetic karstification, and two weak calcite cementation episodes. The reservoir in the fourth model is dominated by fractures and their related dissolution pores, which developed in microcrystalline (limey) dolostone. These dolostones experienced relatively weak dolomitization, telogenetic karstification, and calcite cementation. From a reservoir point of view, the reservoirs represented by the first and third models, which respectively are composed of silt‐sized crystalline dolomite occurring in the top of the whole dolostone succession and the dolomite affected by telogenetic karstification, are the most vital exploration targets. [ABSTRACT FROM AUTHOR]

Reports that Caenorhabditis elegans has a putative sodium channel that could provide the means to mechanosensitivity through an interaction with the extracellular matrix. Connection of channels to the extracellular matrix providing the physical basis by which ions flow; Process as a mechanism of stretch-activated muscle contraction.

The Dongpu Depression, containing huge amounts of hydrocarbons, is a typical petroliferous province in the Bohai Bay Basin, east China. As one set of the main source rocks, the first member of Shahejie Formation (E2s1) shows huge exploration potential with approximately 0.83 × 108 t resources remaining to be discovered. However, the geochemical characteristics and thermal evolution history of E2s1 source rocks have still not been determined. In this study, the sedimentary features were firstly analysed based on the geological data. Then the organic matter abundance, kerogen type, and thermal maturity of E2s1 source rocks in the present day were evaluated according to the Rock‐Eval pyrolysis, micro‐components of kerogen, total organic carbon (TOC), and vitrinite reflectance analysis. Furthermore, the evolution of thermal history and hydrocarbon generation was determined using the PetroMod procedure. The results show that dark mudstones and salt rocks were well developed in E2s1, which are propitious for organic matter to grow and preserve. E2s1 source rocks contain abundant organic matter and moderate to good generative source rock potential. E2s1 source rocks mainly consist of Type II kerogen and have entered early to maturation stage for hydrocarbon generation. Due to the limited buried depth, E2s1 source rocks only attained lower thermal maturity and generated finite hydrocarbons. The initial rapid subsidence and the second rift after uplift erosion resulted in the higher geo‐temperature at the end of E3d and the present day. Corresponding to the geo‐temperature evolution, there are two stages of hydrocarbon generation for E2s1 source rocks: The first stage was in the late E3d period, and the late stage was from the late Neogene to the present day. Moreover, the hydrocarbon generation rate and quantity of the late stage are much higher than the first stage, indicating the major hydrocarbon generation stage. Due to the limited hydrocarbon generation capacity, oils generated from E2s1 source rocks are low maturity; thus, it cannot migrate for a long distance and only accumulated around the sag belts. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the expression of microRNA (miR)-663 and its regulatory effects on the pathogenesis of nasal polyposis in children. Nasal polyp tissue, as well as serum and peripheral blood eosinophils were collected from 35 children diagnosed with nasal polypectomy between August 2013 and August 2015. As a control, the inferior nasal concha, serum and peripheral blood eosinophils were collected from 46 patients with nasal septal deviation complicated by inferior turbinate hypertrophy or patients with simple inferior turbinate hypertrophy who had undergone surgical removal of the inferior nasal concha. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression of miR-663 and transforming growth factor-β1 (TGF-β1) in the nasal polyp tissue, serum and peripheral blood eosinophils of patients with nasal polyposis and controls. Western blotting was used to measure the expression of TGF-β1 protein in nasal tissue and eosinophils and an enzyme-linked immunosorbent assay was used to measure serum level of TGF-β1 protein. A dual luciferase reporter assay was used to determine whether TGF-β1 was a target gene of miR-663. Compared with the control group, levels of TGF-β1 mRNA and protein were significantly increased in all three types of specimens from pediatric patients with nasal polyposis (P<0.05). miR-663 expression was significantly decreased in nasal polyp tissue and peripheral blood eosinophils (P<0.05). The dual luciferase reporter assay confirmed that TGF-β1 was a target gene of miR-663. The current study suggests that the upregulation of TGF-β1 may be associated with the downregulation of miR-663 in nasal polyposis in children. miR-663 may have regulatory effects on the pathogenesis of nasal polyposis by regulating TGF-β1 and may be developed as a genetic marker of nasal polyposis in children. [ABSTRACT FROM AUTHOR]

The southwest vortex (SWV) is a critical weather system in China, but our knowledge of this system remains incomplete. Here, we investigate the cloud properties in the SWV. First, we search for the SWVs with time steps and center locations that are consistent between the SWV yearbook and ERA-Interim reanalysis data. Second, we supplement these SWVs' life spans and movement paths. Third, we relocate the Fengyun (FY) satellite FY-4A cloud retrievals in the 10° × 10° region centered on each SWV and analyze the cloud occurrence frequency (COF), cloud-top height (CTH), and cloud optical thickness (COT). A distribution mode of cloud types is summarized from the COFs, with water clouds, supercooled clouds, mixed clouds, ice clouds, cirrus clouds, and overlap clouds occurring sequentially from west to east. The CTH probability density (PD) distribution features a significant north–south difference. In addition, the COT PD distributions exhibit a common trend: with increasing COT, the PD increases rapidly and then slowly before peaking, whereupon the PD decreases abruptly. From spring to summer, the region with the highest convective COF shifts from the northeast to the northwest, and an east–west gradient of the convective COF appears in autumn and winter. Furthermore, we investigate the cloud properties during SWV-related heavy rainfall. Heavy rain occurs mainly in the west of the SWV, and convective clouds are mainly in the northwest, partly in the southwest and near the SWV center. The average CTH in heavy rainfall is generally higher than 6 km, and the average COT is greater than 20. Significance Statement: The southwest vortex (SWV) is an important weather system in China. However, we do not yet comprehensively know this weather system. The cloud properties can indicate the structures of weather systems and are key parameters in numerical weather prediction (NWP) models. Thus, investigating cloud properties is necessary and meaningful to understand the SWV and accurately predict SWV-related precipitation in NWP models. In this paper, a typical distribution mode of six cloud types in the SWV is summarized from the cloud occurrence frequency, and the distribution features of convective clouds, cloud-top height, and cloud optical thickness in the SWV are analyzed. Furthermore, the cloud properties in SWV-related heavy rain are also studied. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Although the efficacy of teneligliptin, a highly selective dipeptidyl peptidase‐4 inhibitor, has been amply studied for the treatment of type 2 diabetes, no clinical trials of teneligliptin have been carried out in China. We evaluated the efficacy and safety of teneligliptin monotherapy compared with a placebo in Chinese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise. Materials and Methods: This multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study, carried out at 42 sites, enrolled type 2 diabetes patients with glycosylated hemoglobin 7.0 to <10.0% and fasting blood glucose <270 mg/dL. Patients were randomly assigned, in a 1:1 ratio, to treatment with 20 mg teneligliptin or a placebo (n = 127, each) administered orally once daily before breakfast for 24 weeks. Change in glycosylated hemoglobin from baseline to week 24 was the primary efficacy end‐point. Safety was assessed by the incidence of adverse events and adverse drug reactions. Results: The least square mean (LSM) change in glycosylated hemoglobin from baseline to week 24 was −0.95% with teneligliptin versus −0.14% with a placebo, yielding an LSM difference (teneligliptin vs placebo) of −0.80% (P < 0.0001). For the secondary end‐point, from baseline to week 24, the LSM change in fasting blood glucose was −21.9 mg/dL with teneligliptin versus −1.4 mg/dL with a placebo, yielding an LSM difference (teneligliptin vs placebo) of −20.5 mg/dL (P < 0.0001). The adverse event and adverse drug reaction incidence rates, including hypoglycemia, were similar in both groups. Conclusions: At 24 weeks, teneligliptin was generally well tolerated and effective in Chinese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the therapeutic effects of exosomes, which were collected from human neuroepithelial stem cells (HNESCs) treated by miR-29b mimics, on the treatment of spinal cord injury (SCI). Computational analysis, real-time PCR, Western blot analysis and TUNEL assay, a BBB score system, the Nissl staining and IHC assay were conducted to explore the molecular signalling pathway underlying the function of exosomes in SCI. Exosomes isolated from cells treated with HNESC exhibited the strongest inhibitory effect on cell apoptosis while exhibiting the highest level of miR-29b expression and the lowest levels of PTEN and caspase-3 expression. Moreover, PTEN and caspase-3 were identified as the direct target genes of miR-29b. The exosomes isolated from the groups of HNESC and HNESC + miR-29b mimics exhibited in vivo therapeutic effects by restoring the BBB score and apoptosis index of post-SCI neuron cells to those of normal neuron cells, with the exosomes collected from the group of HNESC + miR-29b mimics showing the strongest effect. We suggested that the exosomes derived from the group of HNESC + miR-29b mimics exerted therapeutic effects on SCI by down-regulating the expression of PTEN/caspase-3 and subsequently suppressing the apoptosis of neuron cells. [ABSTRACT FROM AUTHOR]

Highlights • Impacts of fouling and ambient temperature on ASHP's performances were studied. • Increased fouling level and ambient air temperature led to poorer performances. • An equivalent temperature rise due to fouling was proposed and evaluated. • An improved simulated fouling approach was experimentally validated. Abstract Air source heat pumps (ASHPs) have been widely used for providing buildings with heating in winter and cooling in summer. In certain locations, with an increased level of air pollutions, fouling of the outdoor coil in a space cooling ASHP unit may appear, which affects the operating performances of the ASHP unit. Furthermore, the operating performances of an ASHP unit can also be affected by ambient air temperature (T a). In this paper, a field study on the effects of outdoor coil fouling at different T a on the operating performances of a field space cooling ASHP unit is presented. The study results demonstrated that the operating performances of the field ASHP unit were significantly affected by the changes in both T a and percentage of fouled outdoor coil surface (PFOCS). For example, at T a = 30 °C, the variation in PFOCS from 0 to 100% led to a reduction in COP for the field ASHP unit from 2.7 to 2.0. At a fixed PFOCS of 60%, the changes in T a from 26 to 33 °C resulted in a reduction in COP from 2.6 to 2.1. In order to more conveniently investigate the combined impacts of fouling on the operating performances of an ASHP unit at different T a , an equivalent ambient air temperature rise (ETR) was proposed. Based on the measured and evaluated operating parameters of the field ASHP unit at different T a and PFOCS values, ETR values at 0 - 40%, 40 - 60%, 60 - 100% and 0 - 100% PFOCS ranges were evaluated. These ETR values implied that defouling of a fouled outdoor coil may be initiated when PFOCS was at 40 - 60%. With the ETR values for the full PFOCS range of 0 - 100%, the impact of full fouling on the operating performances of an ASHP unit may be evaluated as if it was operated with a clean outdoor coil but at an equivalent ambient air temperature of T a + ETR. [ABSTRACT FROM AUTHOR]

Highlights • The TEPS defrosting initiation strategy was applied to mild and humid regions. • Five short-term and two long-term field test cases were conducted. • The TEPS defrosting initiation strategy was compared to the TT initiation strategy. • The use of TEPS strategy led to more accurate and reliable defrosting initiation. • The use of TEPS strategy led to better operating performances of ASHPs. Abstract A defrosting initiation strategy based on tube-encircled photoelectric sensors (TEPS) was previously proven effective for enhancing the frosting-defrosting performances of air source heat pumps (ASHPs) in cold and dry regions. To verify its applicability to, and evaluate the energy-saving potential when using the TEPS-based strategy in mild and humid regions, field tests were conducted in Guiyang City, China, where the outdoor averaged air temperature and relative humidity were 4.5 °C and 80% in winter, respectively. Two ASHPs of the same-make, one with the TEPS-based strategy and the other with the commonly used temperature-time (TT) strategy, were tested. Totally, seven test cases were organised. Cases 1–5 were for short-term tests to verify the technical feasibility of TEPS-based strategy by comparing the defrosting accuracy of the two strategies. Cases 6–7 were for long-term tests to validate the reliability and effectiveness of the TEPS-based strategy by comparing two ASHPs' operating performances. The test results demonstrated that the use of TEPS-based strategy in mild and humid regions can initiate defrosting more accurately, reliably and efficiently, and thus improve the COP and heating capacity by 11.3% and 12.1%, respectively, compared to the use of the TT strategy. Therefore, it was proven that the TEPS-based strategy was more effective for the ASHPs used in mild and humid regions, for a more accurate defrosting initiation and higher energy efficiency. [ABSTRACT FROM AUTHOR]

Introduction The results of a clinical trial to evaluate the efficacy and safety of initial combination therapy with sitagliptin and metformin in Chinese patients with type 2 diabetes and inadequate glycemic control are reported here. Materials and Methods This was a multicenter, randomized, double-blind, placebo-controlled, parallel group, 24-week clinical trial carried out in China. Patients ( n = 744) with type 2 diabetes and inadequate glycemic control (glycated hemoglobin ≥7.5 and ≤11.0%) who were either drug-naïve or washed out of previous therapy were randomized in equal ratios to sitagliptin 100 mg once daily (q.d.; S100), metformin 500 mg twice daily (b.i.d.; M1000), metformin 850 mg b.i.d. (M1700), sitagliptin 50 mg b.i.d. plus metformin 500 mg b.i.d. (S100/M1000), sitagliptin 50 mg b.i.d. plus metformin 850 mg b.i.d. (S100/M1700), or placebo. Results The mean baseline glycated hemoglobin in randomized patients was 8.7%. Least squares mean changes from baseline in glycated hemoglobin were −0.59% (placebo), −0.99% (S100), −1.29% (M1000), −1.56% (M1700), −1.67% (S100/M1000) and −1.83% (S100/M1700) ( P < 0.05 for each active group vs placebo, for S100/M1700 and S100/M1000 vs S100, and for S100/M1000 vs M1000). All treatments were generally well-tolerated. The overall incidence of hypoglycemia (symptomatic or asymptomatic) was higher in the two co-administration groups (S100/M1700 and S100/M1000) compared with the placebo. The incidence of symptomatic hypoglycemia was low, and similar, across all treatment groups. The incidences of gastrointestinal adverse events were generally higher in high-dose metformin groups than in the placebo group. Conclusions In Chinese patients with type 2 diabetes, initial combination therapy with sitagliptin and metformin was generally well-tolerated, and provided improvement in glycemic control. [ABSTRACT FROM AUTHOR]

The practical applications of lithium sulfur batteries have been greatly restricted by the polysulfide shuttle effect and non-conductivity of sulfur. Here, we report a nickel-catalyzed carbonization method to synthesize three-dimensional (3D) nickel@N-doped carbon-nanotube (CNT) foams for lithium-sulfur batteries. The corresponding carbon/sulfur cathode with a high sulfur loading of 3.71 mg cm−2 possesses a high initial capacity of 855.6 mAh g−1 at 135 mA g−1 and good cyclic stability with a low fading rate of 0.153% per cycle for 100 cycles at 270 mA g−1. The growth of carbon thin layers on the nickel nanoparticles results in the encapsulation of the nanoparticles in the CNTs, which makes the carbon forms highly conductive and prevents the metal nanoparticles from being oxidized by polysulfides. The high conductivity is favorable for the electron transfer between polysulfides and carbon electrode. Moreover, the doped nitrogen atoms on the CNTs have strong chemical adsorption ability for polysulfides, accelerating redox reaction of polysulfides on the carbon electrode (i.e., suppressing the shuttle effect). These unique structural characteristics well explain the excellent electrochemical performance of the assembled batteries. It is believed that the fabricated carbon foam is a promising material for high sulfur-loading lithium-sulfur battery. [Display omitted] • Encapsulates carbon-coated Ni metal nanoparticles in N-doped carbon nanotube. • 3D highly conductive network and strongly chemisorptionto polysulfides. • Stable cycle performance of lithium-sulfur battery under high sulfur loading. [ABSTRACT FROM AUTHOR]

Sparse representation classification, as one of the state-of-the-art classification methods, has been widely studied and successfully applied in face recognition since it was proposed by Wright et al. In this study, we proposed a method to generate virtual available facial images and modified the well-known linear regression classification (LRC) and collaborative representation based classification (CRC) for face recognition. The new method integrates the original and virtual symmetry facial images to form a training sample set of large size. Experimental results show that the proposed method can achieve better performance than most of the competitive face recognition methods, e.g. LRC, CRC, INNC, SRC, RCR, RRC and the method in Xu et al. (2014). This promising performance is mainly attributed to the fact that the sample combination scheme used in the new method can exploit limited original training samples to produce a large number of available training samples and to convey sufficient variations of the original training samples. [ABSTRACT FROM AUTHOR]

Motivation: Reconstruction of gene regulatory networks (GRNs), which explicitly represent the causality of developmental or regulatory process, is of utmost interest and has become a challenging computational problem for understanding the complex regulatory mechanisms in cellular systems. However, all existing methods of inferring GRNs from gene expression profiles have their strengths and weaknesses. In particular, many properties of GRNs, such as topology sparseness and non-linear dependence, are generally in regulation mechanism but seldom are taken into account simultaneously in one computational method.Results: In this work, we present a novel method for inferring GRNs from gene expression data considering the non-linear dependence and topological structure of GRNs by employing path consistency algorithm (PCA) based on conditional mutual information (CMI). In this algorithm, the conditional dependence between a pair of genes is represented by the CMI between them. With the general hypothesis of Gaussian distribution underlying gene expression data, CMI between a pair of genes is computed by a concise formula involving the covariance matrices of the related gene expression profiles. The method is validated on the benchmark GRNs from the DREAM challenge and the widely used SOS DNA repair network in Escherichia coli. The cross-validation results confirmed the effectiveness of our method (PCA-CMI), which outperforms significantly other previous methods. Besides its high accuracy, our method is able to distinguish direct (or causal) interactions from indirect associations.Availability: All the source data and code are available at: http://csb.shu.edu.cn/subweb/grn.htm.Contact: lnchen@sibs.ac.cn; zpliu@sibs.ac.cnSupplementary information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation: Reverse engineering gene regulatory networks, especially large size networks from time series gene expression data, remain a challenge to the systems biology community. In this article, a new hybrid algorithm integrating ordinary differential equation models with dynamic Bayesian network analysis, called Differential Equation-based Local Dynamic Bayesian Network (DELDBN), was proposed and implemented for gene regulatory network inference.Results: The performance of DELDBN was benchmarked with an in vivo dataset from yeast. DELDBN significantly improved the accuracy and sensitivity of network inference compared with other approaches. The local causal discovery algorithm implemented in DELDBN also reduced the complexity of the network inference algorithm and improved its scalability to infer larger networks. We have demonstrated the applicability of the approach to a network containing thousands of genes with a dataset from human HeLa cell time series experiments. The local network around BRCA1 was particularly investigated and validated with independent published studies. BRAC1 network was significantly enriched with the known BRCA1-relevant interactions, indicating that DELDBN can effectively infer large size gene regulatory network from time series data.Availability: The R scripts are provided in File 3 in Supplementary Material.Contact: zheng.li@monsanto.com; jingdong.liu@monsanto.comSupplementary information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

To study systems-level properties of the cell, it is necessary to go beyond individual regulators and target genes to study the regulatory network among transcription factors (TFs). However, it is difficult to directly dissect the TFs mediated genome-wide gene regulatory network (GRN) by experiment. Here, we proposed a hierarchical graphical model to estimate TF activity from mRNA expression by building TF complexes with protein cofactors and inferring TF's downstream regulatory network simultaneously. Then we applied our model on flower development and circadian rhythm processes in Arabidopsis thaliana. The computational results show that the sequence specific bHLH family TF HFR1 recruits the chromatin regulator HAC1 to flower development master regulator TF AG and further activates AG's expression by histone acetylation. Both independent data and experimental results supported this discovery. We also found a flower tissue specific H3K27ac ChIP-seq peak at AG gene body and a HFR1 motif in the center of this H3K27ac peak. Furthermore, we verified that HFR1 physically interacts with HAC1 by yeast two-hybrid experiment. This HFR1–HAC1–AG triplet relationship may imply that flower development and circadian rhythm are bridged by epigenetic regulation and enrich the classical ABC model in flower development. In addition, our TF activity network can serve as a general method to elucidate molecular mechanisms on other complex biological regulatory processes. Network biology: transcription factor activity network reveals novel pathway Transcription factor and its combinatorial regulations are fundamentally important in coordination among complex regulatory processes. An international team of researchers led by Yong Wang and Luonan Chen at Chinese Academy of Sciences proposed a novel hierarchical graphical model to infer TF activity network from its mRNA expression, protein co-factors, and downstream regulations. The TF mediated genome-wide gene regulatory network reveals HFR1-HAC1-AG pathway regulating circadian rhythm and flower development in Arabidopsis thaliana. This HFR1-HAC1-AG pathway may enrich the classical ABC model in flower development and imply epigenetic regulation via circadian rhythm. The TF activity network can serve as a general method to elucidate molecular mechanisms on other complex biological regulatory processes. [ABSTRACT FROM AUTHOR]