Perimeter Control Method of Road Traffic Regions Based on MFD-DDPG.

As urban areas continue to expand, traffic congestion has emerged as a significant challenge impacting urban governance and economic development. Frequent regional traffic congestion has become a primary factor hindering urban economic growth and social activities, necessitating improved regional traffic management. Addressing regional traffic optimization and control methods based on the characteristics of regional congestion has become a crucial and complex issue in the field of traffic management and control research. This paper focuses on the macroscopic fundamental diagram (MFD) and aims to tackle the control problem without relying on traffic determination information. To address this, we introduce the Q-learning (QL) algorithm in reinforcement learning and the Deep Deterministic Policy Gradient (DDPG) algorithm in deep reinforcement learning. Subsequently, we propose the MFD-QL perimeter control model and the MFD-DDPG perimeter control model. We conduct numerical analysis and simulation experiments to verify the effectiveness of the MFD-QL and MFD-DDPG algorithms. The experimental results show that the algorithms converge rapidly to a stable state and achieve superior control effects in optimizing regional perimeter control.

Locating the Human Cardiac Conduction System Using a 3D Model of Its Nutritious Arteries.

It is difficult for anatomists to dissect the human cardiac conduction system (CCS) on specimens as well as for cardiovascular clinicians to locate the CCS during cardiac operations. Here, we demonstrate a new method for locating the CCS using a 3D model of its nutritious arteries. First, we perfused the coronary arteries with contrast material and then acquired a set of data of thin computer tomography (CT) scans. Then, we generated a 3D model of the coronary artery and distinguished the arteries that supply the CCS. We then located the CCS on the 3D model via its nutritious arteries and dissected the CCS. Finally, the structures that were dissected were removed for histological and immunofluorescent staining. The results of histological and immunofluorescence examination proved the structure to be the CCS. Thus, we successfully located the CCS using a 3D model of its nutritious arteries. We suggest that with this new method, cardiac surgeons can locate a patient's CCS during cardiac surgeries such as transcatheter aortic valve implantation (TAVI) or radiofrequency catheter ablation (RFCA).

Hepatitis B virus X protein activates Notch signaling by its effects on Notch1 and Notch4 in human hepatocellular carcinoma.

Deregulated expression of Notch receptors and abnormal activity of Notch signaling have been observed in a growing number of malignant tumors, however, the expression and activity of Notch in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and their relationship with HBV X protein (HBx) are still not fully elucidated. To address this, we examined the overall expression of Notch receptors in HBV-associated HCC tissues, analyzed their relationship with HBx, and further investigated the role of Notch signaling in HBx stable transfected HepG2 cells (HepG2X). The results showed that Notch signaling could be activated by HBx in HepG2 cells. The expression of cytoplasmic Notch1 or nuclear Notch4 was correlated with the expression of HBx in HBV-associated HCC tissues. The expression of cytoplasmic Notch1 or nuclear Notch4 could also be upregulated by HBx in HepG2X cells. The upregulation of Notch1 by HBx was through p38 MAPK pathway. Moreover, HBx was found to directly interact with Notch1, whereas, not with Notch4 in HepG2X cells. Suppression of Notch signaling by γ-secretase inhibitor (GSI) decreased cell growth, blocked cell cycle progression and induced cell apoptosis in HepG2X cells. The present study indicates that HBx activates Notch signaling by its effects on Notch1 and Notch4, and therefore, recruits Notch signaling as a downstream pathway contributing to its carcinogenic role in HBV-associated HCC.

Analysis of DNA methylation patterns associated with the gastric cancer genome.

The objective of the current study was to investigate the characteristics of DNA methylation patterns associated with the gastric cancer genome and to identify clinically useful diagnostic markers and therapeutic targets for gastric cancer. The Infinium 450K methylation microarray was used to compare differential DNA methylation sites of gastric cancer tissue with that of normal gastric tissue. The results of the DNA microarray analysis were confirmed by pyrosequencing. Functional analysis of the differential genes was performed using the GO software. The effect of candidate site methylation on gene expression was monitored using quantitative polymerase chain reaction analysis. Of the 2,645 differential methylation sites identified in gastric cancer tissues, 2,016 were hypermethylated sites, 629 were hypomethylated sites, 826 were located in promoter regions and 1,024 were located within genes. These differential sites were associated with 1,352 genes. In total, five sites were selected and pyrosequencing verified the results of the microarray analysis in five of the sites. Change in gastric cancer DNA methylation pattern was a common occurrence. Differential methylation sites appeared more often in non-promoter regions. The associated genes were involved in multiple signaling pathways, and hypermethylated and hypomethylated sites were involved in roughly the same signaling pathways. Methylation of the genome promoted gene expression. TRIM15, ITGAM, MSX2 and FAM38A may be candidate genes for diagnosing gastric cancer.

A two-microRNA signature as a potential biomarker for early gastric cancer.

Gastric cancer (GC) is one of the most common malignant tumors worldwide. No fundamental improvements in the five-year survival rates of patients with GC have been reported due to a low early diagnosis rate. Therefore, the identification of novel biomarkers is urgently required for an early diagnosis of GC. A total of 86 patients were selected for the present study, including 44 patients with early stage GC (T1-T2 according to TNM staging criteria) and 42 normal gastric mucosa samples from non-cancer patients as controls. A total of 18 samples were used for the microRNA (miRNA) microarray experiments, including nine early GC and nine normal gastric mucosa samples. Bioinformatics algorithms, significant analysis of microarray (SAM), top scoring pair (TSP) and statistical receiver operating characteristic curves were used to identify the best signatures. Finally, quantitative PCR was used to validate the candidate biomarkers for early gastric cancer in the test samples (35 cancer and 33 normal samples). Using the SAM algorithm, 14 differential miRNAs were selected as candidate biomarkers. Using the TSP algorithm, hsa-miR-196a and hsa-miR-148a were obtained as a signature to differentiate between the early GC and normal samples. A coincidental result was observed in the test samples. hsa-miR-196a was upregulated and hsa-miR-148a was downregulated in the early GC samples. hsa-miR-196a and hsa-miR-148a have the potential to serve as candidate biomarkers for early GC.

Unsedated versus sedated gastrointestinal endoscopy: a questionnaire investigation in Wuhan, central China.

National data show that in China mainland unsedated gastrointestinal (GI) endoscopy has been applied in most hospitals for clinical examination, while sedated GI endoscopy is only performed in some hospitals. The purpose of this study was to compare sedated versus unsedated GI endoscopy regarding cost, safety, degree of comfort, tolerance level and overall satisfaction of patients over a 6-month period investigation. From March to September 2011, a questionnaire survey was performed on 1800 patients and 30 physicians at Zhongnan Hospital of Wuhan University and Wuhan General Hospital of Guangzhou Military Command. The patients fell into two groups according to their own decisions: the unsedated group (n=1000) and the sedated group (n=800). After examination, the patients and the physicians were required to fill in a questionnaire form. All the data were analyzed statistically. The results showed that the main factors the patients took for consideration between sedated and unsedated procedures included economy, comfort and safety. The income levels between the sedated and unsedated groups showed significant difference (P<0.01). Most patients in the unsedated group had lower income and were covered by less medical insurance. The tolerance rate was 92.4% vs. 65.5% between the sedated and unsedated group, respectively. 95.5% patients in the sedated group and 72.1% patients in the unsedated group chose the same endoscopy procedure for repeat examination. The survey data from endoscopists suggested the sedated procedure was more comfortable but less safe than the unsedated procedure (P<0.01). In China, unsedated GI endoscopy is now widely accepted by the majority of patients due to low cost and safety. Compared to unsedated GI endoscopy, sedated GI endoscopy is less painful, but more expensive and less safe. With the rapid improvement of people's living standard and the reliability of sedation technology, we expect sedated GI endoscopy will be gradually accepted by more patients.

Highly accurate two-gene signature for gastric cancer.

Large amount of expression data were generated by high-throughput experimental techniques such as microarray. Single algorithm cannot be widely accepted as suitable method for mining of gene expression data. Therefore, integration of different algorithms and extraction of more useful information from the expression data are the key problems for identification of biomarkers. Here, we used three machine learning algorithms to select feature genes based on gene profiling data of gastric cancer (GC). Then, a common divisor was extracted as candidate feature genes aggregation for Tree Building and Tree Pruning analysis by Decision Tree (DT) algorithm. Real-time quantitative PCR and immunohistochemistry (IHC) staining were used to validate the relative expression levels of the candidate feature genes. Receiver operating characteristic curves were used to analyse the classification sensitivity and specificity of the feature genes. A total of 174, 202, 149 feature genes were selected by Class Information Index, Information Gain Index and Relief algorithms, with a common divisor consisting of 32 genes. Using a DT algorithm to contribute to the classification rule sets, we identified COL2A1 and ATP4B as candidate biomarkers of GC. The expression levels of these two genes were validated by real-time PCR and IHC with high sensitivity (>90 %) and specificity (>90 %) in both training and test samples. We first introduced an integral and systematic data-mining model for identification of biomarkers based on gene expression data. The two-gene signature obtained by our predictive model could be used for recognizing the biological characteristic of GC.

Identification of recurrence-related genes by integrating microRNA and gene expression profiling of gastric cancer.

We previously analyzed the microRNA (miRNA) expression pattern in gastric cancer with and without recurrence and obtained 17 differentially expressed miRNAs with potential to predict recurrence risk for GC patients. In the present study, we aimed to investigate recurrence-related genes which may be regulated by the differentially expressed miRNAs identified in our prior research. Three different miRNA target gene databases (miRanda, TargetScan and PicTar) were used for searching the potential genes regulated by miRNAs. A combination was performed between miRNA target genes and recurrence-related gene expression profiling. Three bioinformatics algorithms (PAM, SVM and RF) were used to feature recurrence-related gene selection. In addition, we validated the expression levels of the genes in GC patients using real-time PCR. A total of 3,263 genes were identified as potential targets of 17 miRNAs. We identified 2,736 differential expressed genes using the SAM method based on 22K oligo microarray data which included 7 recurrence and 4 without recurrence GC samples. Combining the target genes regulated by miRNAs and the differentially expressed genes between recurrence and non-recurrence groups, we identified 228 differential genes for further study. Finally, we identified HNRPA0 and PRDM4 as risk biomarkers of GC patients, which were regulated by hsa-miR­194 and hsa-miR-373, respectively. Our data indicated that HNRPA0 and PRDM4 may be involved in the recurrence process of GC and have potential to act as new prognostic biomarkers in predicting recurrence risk for gastric cancer patients.

Notch1 activation contributes to tumor cell growth and proliferation in human hepatocellular carcinoma HepG2 and SMMC7721 cells.

Notch signaling controls cellular differentiation and proliferation. Recent studies have shown that Notch signaling plays an important role in the carcinogenesis and progression of a growing number of malignant tumors. We investigated the effect of Notch1 activation on human hepatocellular carcinoma (HCC). In five human HCC cell lines, it was found that SMMC7721 had relatively high while HepG2 relatively low expression of Notch1 and the activity of Notch signaling. Notch1 activation by transfection of active intracellular region of Notch1 (ICN1) into HCC HepG2 cells enhanced cell growth and proliferation, including in vitro single cell colony formation, anchorage-independent proliferation, and in vivo tumorigenicity. Notch1 activation also promoted HepG2 cell cycle progression. Suppression of Notch1 activation by RNAi of Notch1 or by γ-secretase inhibitor (GSI) in HCC SMMC7721 cells decreased cell growth capability and blocked cell cycle progression. Moreover, it was found that suppression of Notch1 activation induced SMMC7721 cell apoptosis, as demonstrated by apoptosis assays. These findings indicate that Notch1 activation promotes human HCC cell growth and proliferation, which may contribute to the progression of this type of malignant carcinoma.

Identification of hsa-miR-335 as a prognostic signature in gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common malignancy and primary cause of death in Chinese cancer patients. Recurrence is a major factor leading to treatment failure and low level of 5-year survival rate in GC patients following surgical resection. Therefore, identification of biomarkers with potential in predicting recurrence risk is the key problem of the prognosis in GC patients. PATIENTS AND METHODS: A total of 74 GC patients were selected for systematic analysis, consisting of 31 patients with recurrence and 43 patients without recurrence. Firstly, miRNAs microarray and bioinformatics methods were used to characterize differential expressed miRNAs from primary tumor samples. Following, we used a ROC method to select signature with best sensitivity and specificity. Finally, we validated the signature in GC samples (frozen fresh and blood samples) using quantitative PCR. RESULTS: We have identified 12 differential miRNAs including 7 up-regulated and 5 down-regulated miRNAs in recurrence group. Using ROC method, we further ascertained hsa-miR-335 as a signature to recognize recurrence and non-recurrence cases in the training samples. Moreover, we validated this signature using quantitative PCR method in 64 test samples with consistent result with training set. A high frequency recurrence and poor survival were observed in GC cases with high level of hsa-miR-335 (P<0.001). In addition, we evaluated that hsa-miR-335 were involved in regulating target genes in several oncogenic signal-pathways, such as p53, MAPK, TGF-ß, Wnt, ERbB, mTOR, Toll-like receptor and focal adhesion. CONCLUSION: Our results indicate that the hsa-miR-335 has the potential to recognize the recurrence risk and relate to the prognosis of GC patients.

Identification of candidate colon cancer biomarkers by applying a random forest approach on microarray data.

Colon cancer is the third most common cancer and one of the leading causes of cancer-related death in the world. Therefore, identification of biomarkers with potential in recognizing the biological characteristics is a key problem for early diagnosis of colon cancer patients. In this study, we used a random forest approach to discover biomarkers based on a set of oligonucleotide microarray data of colon cancer. Real-time PCR was used to validate the related expression levels of biomarkers selected by our approach. Furthermore, ROC curves were used to analyze the sensitivity and specificity of each biomarker in both training and test sample sets. Finally, we analyzed the clinical significance of each biomarker based on their differential expression. A single classifier consisting of 4 genes (IL8, WDR77, MYL9 and VIP) was selected by random forests with an average sensitivity and specificity of 83.75 and 76.15%. The differential expression levels of each biomarker was validated by real-time PCR in 48 test colon cancer samples compared to the matched normal tissues. Patients with high expression of IL8 and WDR77, and low expression of MYL9 and VIP had a significantly reduced median survival rate compared to colon cancer patients. The results indicate that our approach can be employed for biomarker identification based on microarray data. These 4 genes identified by our approach have the potential to act as clinical biomarkers for the early diagnosis of colon cancer.

RUNX3 directly interacts with intracellular domain of Notch1 and suppresses Notch signaling in hepatocellular carcinoma cells.

RUNX3 takes a strong suppressive effect in many tumors including hepatocellular carcinoma (HCC). HES-1, a downstream target of Notch signaling, is shown to be decreased in human HCC cell line SMMC7721 with RUNX3 gene transfection. Since Notch signaling is oncogenic in HCC, RUNX3 might exert its inhibitory effect in HCC partly through the suppression on Notch signaling. To investigate the possible mechanism of the down-regulation of HES-1 by RUNX3, we performed Western blot and reporter assay and found that RUNX3 suppressed intracellular domain of Notch1 (ICN1)-mediated transactivation of Notch signaling while it did not alter the expression of ICN1 and recombination signal binding protein-J kappa (RBP-J) in SMMC7721 cells. Besides, confocal microscopy, co-immunoprecipitation and GST pull-down assays showed that RUNX3 could co-localize with ICN1 and RBP-J, forming a complex with these two molecules in nucleus of SMMC7721 cells by its direct interaction with ICN1. Furthermore, RUNX3 was recruited to RBP-J recognition motif of HES-1 promoter, which was identified by chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA). Taken together, these findings indicate that RUNX3 suppresses Notch signaling in HCC SMMC7721 cells by its interaction with ICN1 and thus recruitment to the RBP-J recognition motif of downstream genes of Notch signaling.

Construction and expression of a eukaryotic expression vector containing a fusion gene of the Hantaan virus S gene and hsp70 gene.

Hantavirus (HV) infection leads to a kind of severe systematic syndrome, hemorrhagic fever with renal syndrome (HFRS). Heat shock proteins (HSPs) can be used as adjuvants assisting soluble antigens to produce specific targets which can be attacked by cytotoxic T lymphocytes. For further research on HFRS vaccine, this study aimed to express Hantaan virus nucleocapsid protein (HTNV NP)-HSP70 fusion protein in COS-7 cells. First, an HTNV S gene encoding NP was amplified by PCR with a mutated termination code and cloned into eukaryotic expression vector pCDNA3.1(+), into which the full-length hsp70 gene had already been inserted, to form the S-hsp70 fusion expression vector pCDNA3.1(+)/S-hsp70. Then this recombinant plasmid was transfected into COS-7 cells by liposome, and eukaryotic expression of NP-HSP70 fusion protein was detected by immunocytochemistry and western blot. The results show that the eukaryotic expression vector pCDNA3.1(+)/S-hsp70 was successfully constructed and the NP-HSP70 fusion protein was effectively expressed in COS-7 cells. This study demonstrates that the NP-HSP70 fusion protein was expressed effectively from the pCDNA3.1(+)/S-hsp70 vector in a eukaryotic system and thus provides a basis for using this plasmid as a new DNA vaccine against HV infection.

(R)-(+)-3-Hydr-oxy-2-methoxy-carbonyl-8-methyl-8-azoniabicyclo-[3.2.1]octane l-bitartrate.

(RS)-(±)-2-Methoxy-carbonyl-3-tropinone is an important inter-mediate for the preparation of cocaine and its derivatives. The molecule in the title compound, C(10)H(16)NO(3) (+)·C(4)H(5)O(6) (-), is present as the enol tautomer. The six-membered ring adopts a half boat conformation, and the five-membered ring a slightly distorted envelope conformation. There are intra- and inter-molecular hydrogen bonds involving the hydroxyl, carboxyl groups and quaternary ammonium groups.

9-(cycloheptatrienylidene)-fluorene derivative: remarkable ratiometric pH sensor and computing switch with NOR logic gate.

2,7-Bis(4-dimethylaminophenyl)-9-(cycloheptatrienylidene)fluorene (1) was synthesized and characterized. 1 could be used as a fluorescent sensor either for pH or for pyridinium halide. Integrated with the ratiometric method and an NOR logic gate, a tunable two-input/multi-output system was presented on the basis of this single molecule. [structure: see text]