Bio-Medical Materials and Engineering - Volume 26, issue s1

Authors: Feng, Yu | Cao, Hui | Zhang, Yanbin

Article Type: Research Article

Abstract: High order partial least squares (HOPLS) is a novel data processing method. It is highly suitable for building prediction model which has tensor input and output. The objective of this study is to build a prediction model of the relationship between sinoatrial node field potential and high glucose using HOPLS. The three sub-signals of the sinoatrial node field potential made up the model’s input. The concentration and the actuation duration of high glucose made up the model’s output. The results showed that on the premise of predicting two dimensional variables, HOPLS had the same predictive ability and a lower dispersion …degree compared with partial least squares (PLS). Show more

Keywords: High order partial least squares, sinoatrial node field potential, prediction model, signal decomposition

DOI: 10.3233/BME-151482

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1805-S1811, 2015

Authors: Ling, Ping | Gao, Dajin | Zhou, Xifeng | Huang, Zhining | Rong, Xiangsheng

Article Type: Research Article

Abstract: Computer-aided diagnosis (CAD) approaches succeed in detecting a number of diseases, however, they are not good at addressing atrial hypertrophy disease due to the lack of training data. Support Vector Machine (SVM) is very popular in few CAD solutions to atrial hypertrophy. Yet the performance of SVM is moderate in atrial hypertrophy detection compared to its success in other classification problems. In this paper we propose a novel CAD algorithm, Local Discriminative SVM (LDSVM), to overcome the above-mentioned difficulty. LDSVM consists of a global SVM that is trained on the training data, and a local kNN that is trained based …on the information of SVM and query. When a query arrives, SVM gives the initial decision. If the initial decision is less confident, local kNN begins to modify the initial decision. LDSVM improves the accuracy of SVM through some contributions: the risk tube, the discriminant information derived from SVM hyperplane, the new metric and the self-tuning size of neighborhood. Empirical evidence on real medical datasets show high performance of LDSVM over the peers in addressing atrial hypertrophy problems. Show more

Keywords: Computer-aided diagnosis, support vector machine, discriminative direction, derivative of hyperplane function

DOI: 10.3233/BME-151483

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1813-S1820, 2015

Authors: Garcia-Chimeno, Yolanda | Garcia-Zapirain, Begonya

Article Type: Research Article

Abstract: The classification of subjects’ pathologies enables a rigorousness to be applied to the treatment of certain pathologies, as doctors on occasions play with so many variables that they can end up confusing some illnesses with others. Thanks to Machine Learning techniques applied to a health-record database, it is possible to make using our algorithm. hClass contains a non-linear classification of either a supervised, non-supervised or semi-supervised type. The machine is configured using other techniques such as validation of the set to be classified (cross-validation), reduction in features (PCA) and committees for assessing the various classifiers. The tool is easy to …use, and the sample matrix and features that one wishes to classify, the number of iterations and the subjects who are going to be used to train the machine all need to be introduced as inputs. As a result, the success rate is shown either via a classifier or via a committee if one has been formed. A 90% success rate is obtained in the ADABoost classifier and 89.7% in the case of a committee (comprising three classifiers) when PCA is applied. This tool can be expanded to allow the user to totally characterise the classifiers by adjusting them to each classification use. Show more

Keywords: Classification, machine learning, PCA, cross-validation, committee

DOI: 10.3233/BME-151484

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1821-S1828, 2015

Authors: Nie, Guoping | Li, Yong | Wang, Feichi | Wang, Siwen | Hu, Xuehai

Article Type: Research Article

Abstract: G-protein-coupled receptors (GPCRs) are seven membrane-spanning proteins and regulate many important physiological processes, such as vision, neurotransmission, immune response and so on. GPCRs-related pathways are the targets of a large number of marketed drugs. Therefore, the design of a reliable computational model for predicting GPCRs from amino acid sequence has long been a significant biomedical problem. Chaos game representation (CGR) reveals the fractal patterns hidden in protein sequences, and then fractal dimension (FD) is an important feature of these highly irregular geometries with concise mathematical expression. Here, in order to extract important features from GPCR protein sequences, CGR algorithm, fractal …dimension and amino acid composition (AAC) are employed to formulate the numerical features of protein samples. Four groups of features are considered, and each group is evaluated by support vector machine (SVM) and 10-fold cross-validation test. To test the performance of the present method, a new non-redundant dataset was built based on latest GPCRDB database. Comparing the results of numerical experiments, the group of combined features with AAC and FD gets the best result, the accuracy is 99.22% and Matthew’s correlation coefficient (MCC) is 0.9845 for identifying GPCRs from non-GPCRs. Moreover, if it is classified as a GPCR, it will be further put into the second level, which will classify a GPCR into one of the five main subfamilies. At this level, the group of combined features with AAC and FD also gets best accuracy 85.73%. Finally, the proposed predictor is also compared with existing methods and shows better performances. Show more

Keywords: GPCR, chaos game representation, support vector machine, fractal dimension

DOI: 10.3233/BME-151485

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1829-S1836, 2015

Authors: Huang, Hai-Hui | Liu, Xiao-Ying | Liang, Yong | Chai, Hua | Xia, Liang-Yong

Article Type: Research Article

Abstract: Tuberculosis (TB), caused by infection with mycobacterium tuberculosis, is still a major threat to human health worldwide. Current diagnostic methods encounter some limitations, such as sample collection problem or unsatisfied sensitivity and specificity issue. Moreover, it is hard to identify TB from some of other lung diseases without invasive biopsy. In this paper, the logistic models with three representative regularization approaches including Lasso (the most popular regularization method), and L 1 / 2 (the method that inclines to achieve more sparse …solution than Lasso) and Elastic Net (the method that encourages a grouping effect of genes in the results) adopted together to select the common gene signatures in microarray data of peripheral blood cells. As the result, 13 common gene signatures were selected, and sequentially the classifier based on them is constructed by the SVM approach, which can accurately distinguish tuberculosis from other pulmonary diseases and healthy controls. In the test and validation datasets of the blood gene expression profiles, the generated classification model achieved 91.86% sensitivity and 93.48% specificity averagely. Its sensitivity is improved 6%, but only 26% gene signatures used compared to recent research results. These 13 gene signatures selected by our methods can be used as the basis of a blood-based test for the detection of TB from other pulmonary diseases and healthy controls. Show more

Keywords: Tuberculosis, feature selection, early diagnostic, regularization, biomarkers

DOI: 10.3233/BME-151486

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1837-S1843, 2015

Authors: Xia, Hong | Li, Ao | Yu, Zhenhua | Liu, Xiaocheng | Feng, Huanqing

Article Type: Research Article

Abstract: Application of the Next generation sequencing (NGS) technology has demonstrated that most tumor samples exhibit intra-tumor heterogeneity. Here we proposed SAPPH (Somatic Aberrations Prediction for Paired Heterogeneous tumor samples), as a new method for estimating tumor somatic copy number aberrations as well as inferring tumor subclone proportions from heterogeneous tumor sequencing data. This method is based on CBS and local proportion clustering strategy. When SAPPH is applied on simulated tumor samples, the agreement between the results analyzed by SAPPH and the sequencing signals suggests that SAPPH can find the solution to best fit the signal distributions. We benchmark the performance …of SAPPH and show that it outperforms existing method in estimating tumor copy number aberrations. Show more

Keywords: Intra-tumor heterogeneity, NGS, copy number aberration, tumor subclone, proportion

DOI: 10.3233/BME-151487

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1845-S1853, 2015

Authors: Cheng, Ke | Chen, Qingfang | Yang, Xibei | Gao, Shang | Yu, Hualong

Article Type: Research Article

Abstract: To address the imbalanced classification problem emerging in Bioinformatics, a boundary movement-based extreme learning machine (ELM) algorithm called BM-ELM was proposed. BM-ELM tries to firstly explore the prior information about data distribution by condensing all training instances into the one-dimensional feature space corresponding to the original output in ELM, and then on the transformed space, to find the optimal moving distance of the classification hyperplane by estimating the probability density distributions of the instances in different classes. Experimental results on four real imbalanced bioinformatics classification data sets indicated that the proposed BM-ELM algorithm outperforms some traditional bias correction algorithms due …to it can greatly improve the sensitivity of the classification results with small loss of specificity as possible. Also, BM-ELM algorithm has presented better performance than the widely used support vector machine (SVM) classifier. The algorithm can be widely popularized in various large-scale bioinformatics applications. Show more

Keywords: Bioinformatics, extreme learning machine, imbalanced classification, kernel density estimation

DOI: 10.3233/BME-151488

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1855-S1862, 2015

Authors: Sun, Lin | Xu, Jiucheng | Yin, Jiaojiao

Article Type: Research Article

Abstract: Fuzzy clustering is an important tool for analyzing microarray data. A major problem in applying fuzzy clustering method to microarray gene expression data is the choice of parameters with cluster number and centers. This paper proposes a new approach to fuzzy kernel clustering analysis (FKCA) that identifies desired cluster number and obtains more steady results for gene expression data. First of all, to optimize characteristic differences and estimate optimal cluster number, Gaussian kernel function is introduced to improve spectrum analysis method (SAM). By combining subtractive clustering with max-min distance mean, maximum distance method (MDM) is proposed to determine cluster centers. …Then, the corresponding steps of improved SAM (ISAM) and MDM are given respectively, whose superiority and stability are illustrated through performing experimental comparisons on gene expression data. Finally, by introducing ISAM and MDM into FKCA, an effective improved FKCA algorithm is proposed. Experimental results from public gene expression data and UCI database show that the proposed algorithms are feasible for cluster analysis, and the clustering accuracy is higher than the other related clustering algorithms. Show more

Keywords: Spectral analysis, maximum distance, fuzzy clustering, gene expression data

DOI: 10.3233/BME-151489

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1863-S1869, 2015

Authors: Zhang, Hui | Wang, Jing | Sun, Ling | Xu, Qiuqin | Hou, Miao | Ding, Yueyue | Huang, Jie | Chen, Ye | Cao, Lei | Zhang, Jianmin | Qian, Weiguo | Lv, Haitao

Article Type: Research Article

Abstract: Obesity has become an increasingly serious health problem and popular research topic. It is associated with many diseases, especially cardiovascular disease (CVD)-related endothelial dysfunction. This study analyzed genes related to endothelial dysfunction and obesity and then summarized their most significant signaling pathways. Genes related to vascular endothelial dysfunction and obesity were extracted from a PubMed database, and analyzed by STRING, DAVID, and Gene-Go Meta-Core software. 142 genes associated with obesity were found to play a role in endothelial dysfunction in PubMed. A significant pathway (Angiotensin system maturation in protein folding and maturation) associated with obesity and endothelial dysfunction was explored. …The genes and the pathway explored may play an important role in obesity. Further studies about preventing vascular endothelial dysfunction obesity should be conducted through targeting these loci and pathways. Show more

Keywords: Pathway, obesity, vascular endothelial function, system biology

DOI: 10.3233/BME-151490

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1871-S1881, 2015

Authors: Guan, Changge | Niu, Xiaohui | Shi, Feng | Yang, Kun | Li, Nana

Article Type: Research Article

Abstract: DNA-binding proteins are involved and play a crucial role in a lot of important biological processes. Hence, the identification of the DNA-binding proteins is a challenging and significant problem. In order to reveal the intrinsic information correlated to DNA-binding, nine classes of candidate features based on different mathematical fields are applied to construct the prediction model with random forest. They are fractal dimension, conjoint triad feature, Hilbert-Huang Transformation, amino acid composition, dipeptide composition, chaos game representation, and the corresponding information entropies. These mathematical expressions are evaluated with 5-fold cross validation test. The results of numerical simulations show that the mathematical …features consisted of amino acid composition, fractal dimension and information entropies of amino acid and chaos game representation achieve the best performance. Its accuracy is 0.8157, and Matthew’s correlation coefficient (MCC) achieves 0.5968 on the benchmark dataset from DNA-Prot. By analyzing the components of top combination of the nine candidate features, the concepts of fractal dimension and information entropy are the effective and vital features, which can provide complementary sequence-order information on the basis of amino acid composition. Show more

Keywords: DNA-binding proteins, random forest, information entropy, fractal dimension, Hilbert-Huang transformation

DOI: 10.3233/BME-151491

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1883-S1889, 2015

Authors: Yan, Chun | Liu, Wei | Qiu, Yiwei | Sun, Haitang

Article Type: Research Article

Abstract: The problem of gene recognition based on the ratio of power spectrum, SNR, and Gabor transform and its implementation of the calculation were discussed. The optimal threshold could guarantee to identify the DNA sequences with the signal-to-noise ratio. It summarized three kinds of traditional ways to determine the threshold, and advanced the optimum entitled method showing the disparate degrees of highlight and the discrimination rate method of the exons or introns as far as possible to improve the rate of their accuracy. To evaluate different determination methods of threshold by using the calculation results of four kinds of DNA sequence. …In order to ensure the analysis of DNA sequence more accurate, it adopted and improved gene identification method of Fourier transformation in a short time which is based on Gabor transformation. By using of the ergodic theory, the fixed percentage of the sequence length of exons in DNA has been improved to be the dynamic percentages which focus on different gene types. The exons of the DNA sequence which have been already discovered were identified by using the improved algorithm. With comparison of the results and the actual endpoint of exons, it confirmed that the improved algorithm can figure out the endpoint of the exons more accurate. Show more

Keywords: The discrete Fourier transform, Gabor transform, gene identification, signal-to-noise ratio, threshold

DOI: 10.3233/BME-151492

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1891-S1901, 2015

Authors: Hua, Lin | Zheng, Weiying | Xia, Hong | Zhou, Ping | An, Li

Article Type: Research Article

Abstract: Currently, the mechanisms underlying chronic obstructive pulmonary disease (COPD) remain unclear. As potential biomarkers, microRNAs (miRNAs), which modulate the levels of specific genes and proteins, are important for enhancing our understanding of the mechanisms behind COPD. Although there have been a number of miRNA expression profiling analyses strategies used to document miRNA expression changes during physiological and pathological processes or used to identify differentially expressed miRNAs in disease or control samples, the study results have been inconsistently replicated using different datasets. For this reason, many findings cannot be well synthesized and interpreted. To address this issue, we used a multiple …co-inertia analysis (MCIA) method to extract potential COPD-related miRNAs using three COPD microarray datasets. The results showed that miR-223, miR-132, and miR-199a-5p are obviously associated with COPD, and these results are consistent with the highly significant differentially-expressed miRNAs that were observed across three microarray datasets. Moreover, when miR-223, miR-132, and miR-199a-5p are taken as predictors to classify the samples of three datasets, the pooled sensitivity and specificity is 0.96 and 0.75, respectively, thereby suggesting that these three miRNAs can effectively distinguish COPD patients and controls. Show more

Keywords: Chronic obstructive pulmonary disease, multiple co-inertia, miRNAs, differentially expressed

DOI: 10.3233/BME-151493

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1903-S1915, 2015

Authors: Lee, Kyung-Eun | Park, Hyun-Seok

Article Type: Research Article

Abstract: Epigenetic computational analyses based on Markov chains can integrate dependencies between regions in the genome that are directly adjacent. In this paper, the BED files of fifteen chromatin states of the Broad Histone Track of the ENCODE project are parsed, and comparative nucleotide frequencies of regional chromatin blocks are thoroughly analyzed to detect the Markov property in them. We perform various tests to examine the Markov property embedded in a frequency domain by checking for the presence of the Markov property in the various chromatin states. We apply these tests to each region of the fifteen chromatin states. The results …of our simulation indicate that some of the chromatin states possess a stronger Markov property than others. We discuss the significance of our findings in statistical models of nucleotide sequences that are necessary for the computational analysis of functional units in noncoding DNA. Show more

Keywords: Chromatin maps, nucleotide frequency patterns, Markov chain, noncoding DNA, computational epigenetics

DOI: 10.3233/BME-151494

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1917-S1927, 2015

Authors: Tian, Xue W. | Lim, Joon S.

Article Type: Research Article

Abstract: Naive Bayesian (NB) network classifier is a simple and well-known type of classifier, which can be easily induced from a DNA microarray data set. However, a strong conditional independence assumption of NB network sometimes can lead to weak classification performance. In this paper, we propose a new approach of interactive naive Bayesian (INB) network to weaken the conditional independence of NB network and classify cancers using DNA microarray data set. We selected the differently expressed genes (DEGs) to reduce the dimension of the microarray data set. Then, an interactive parent which has the biggest influence among all DEGs is searched …for each DEG. And then we calculate a weight to represent the interactive relationship between a DEG and its parent. Finally, the gene-gene interaction network is constructed. We experimentally test the INB network in terms of classification accuracy using leukemia and colon DNA microarray data sets, then we compare it with the NB network. The INB network can get higher classification accuracies than NB network. And INB network can show the gene-gene interactions visually. Show more

Keywords: Gene interaction, naive Bayesian, differently expressed genes (DEGs), leukemia, colon, DNA microarray

DOI: 10.3233/BME-151495

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1929-S1936, 2015

Authors: Belov, Oleg V. | Boyda, Denis L. | Plante, Ianik | Shirmovsky, Sergey Eh.

Article Type: Research Article

Abstract: A computer model to simulate the processes of charge injection and migration through DNA after irradiation by a heavy charged particle was developed. The most probable sites of charge injection were obtained by merging spatial models of short DNA sequence and a single 1 GeV/u iron particle track simulated by the code RITRACKS (Relativistic Ion Tracks). Charge migration was simulated by using a quantum-classical nonlinear model of the DNA–charge system. It was found that charge migration depends on the environmental conditions. The oxidative damage in DNA occurring during hole migration was simulated concurrently, which allowed the determination of probable locations …of radiation-induced DNA lesions. Show more

Keywords: DNA damage, charge migration, radiation

DOI: 10.3233/BME-151496

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1937-S1944, 2015

Authors: Assawinchaichote, Wudhichai

Article Type: Research Article

Abstract: The designing of H ∞ fuzzy controller for HIV/AIDS infected dynamic system has been considered in this paper. With TS fuzzy model and LMIs approach, the proposed controller is obtained for such a system. A set of sufficient conditions of the H ∞ controller is given to ensure the closed-loop system asymptotic stability and the prescribed …H ∞ performance level. Finally, the effectiveness of the fuzzy controller design approach is finally presented through the simulation results. Show more

Keywords: H∞ control, TS fuzzy model, robust control, linear matrix inequalities (LMIs), HIV/AIDS infection system, robust control

DOI: 10.3233/BME-151497

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1945-S1951, 2015

Authors: Xu, Jiucheng | Li, Tao | Sun, Lin

Article Type: Research Article

Abstract: In view of the characteristics of high dimension, small samples, nonlinearity and numeric type in the gene expression profile data, the logistic and the correlation information entropy are introduced into the feature gene selection. At first, the gene variable is screened preliminarily by logistic regression to obtain the genes that have a greater impact on the classification; then, the candidate features set is generated by deleting the unrelated features using Relief algorithm. On the basis of this, delete redundant features by using the correlation information entropy; finally, the feature gene subset is classified by using the classifier of support vector …machine (SVM). Experimental results show that the proposed method can obtain smaller subset of genes and achieve higher recognition rate. Show more

Keywords: Gene chips, logistic, correlation information entropy, feature selection

DOI: 10.3233/BME-151498

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1953-S1959, 2015

Authors: Chen, Tao | Xue, Huifeng | Hong, Zenglin | Cui, Man | Zhao, Hui

Article Type: Research Article

Abstract: Microarray data has small samples and high dimension, and it contains a significant amount of irrelevant and redundant genes. This paper proposes a hybrid ensemble method based on double disturbance to improve classification performance. Firstly, original genes are ranked through reliefF algorithm and part of the genes are selected from the original genes set, and then a new training set is generated from the original training set according to the previously selected genes. Secondly, D bootstrap training subsets are produced from the previously generated training set by bootstrap technology. Thirdly, an attribute reduction method based on neighborhood mutual information …with a different radius is used to reduce genes on each bootstrap training subset to produce new training subsets. Each new training subset is applied to train a base classifier. Finally, a part of the base classifiers are selected based on the teaching-learning-based optimization to build an ensemble by weighted voting. Experimental results on six benchmark cancer microarray datasets showed proposed method decreased ensemble size and obtained higher classification performance compared with Bagging, AdaBoost, and Random Forest. Show more

Keywords: Microarray data, bagging, reliefF, neighborhood mutual information, teaching-learning-based optimization

DOI: 10.3233/BME-151499

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1961-S1968, 2015

Authors: Liu, Xiaoli | Bao, Hang | Zhao, Dazhe | Cao, Peng

Article Type: Research Article

Abstract: Multi-label classification is useful in many bioinformatics tasks such as gene function prediction and protein site localization. This paper presents an improved neural network algorithm, Max Label Distance Back Propagation Algorithm for Multi-Label Classification. The method was formulated by modifying the total error function of the standard BP by adding a penalty term, which was realized by maximizing the distance between the positive and negative labels. Extensive experiments were conducted to compare this method against state-of-the-art multi-label methods on three popular bioinformatic benchmark datasets. The results illustrated that this proposed method is more effective for bioinformatic multi-label classification compared to …commonly used techniques. Show more

Keywords: Multi-label classification, neural networks, max label distance, self-adaptive learning rate

DOI: 10.3233/BME-151500

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1969-S1976, 2015

Authors: Zhang, Xuejuan | Zhao, Haiping | Zhang, Jietao | Han, Di | Zheng, Yu | Guo, Xiaozi | He, Dian | Guo, Jin | Wang, Yingcui

Article Type: Research Article

Abstract: In some GWAs studies, GALNT2 and APOE polymorphisms have been identified to be related to alterations of plasma or serum HDL-C and TG concentrations. The purpose of our study is to assess the contribution of GALNT2 rs4846914, APOE rs429358, rs7412, rs405509 variants, and several environmental factors to the development of hypertension disease in the China Han population. A hospital-based case-control study was conducted. Cases were hypertension (n =211) and controls were normal participants (n =434). The AA, AG, and GG genotype frequencies of GALNT2 rs4846914 were 22.8%, 43.1%, and 34.1% in hypertension subjects, and 35.3%, 44.2%, and 20.5% in controls …(P <0.05), respectively. The OR of the AG genotype adjusted for all risk factors compared to the AA genotype was 1.61 (95%CI: 1.02 to 2.56) and to the GG genotype 2.67 (95%CI: 1.59 to 4.488). There was no significant difference between the APOE rs429358, rs7412, and rs405509 genotype frequencies in hypertension and control subjects. The present work indicates that SNP rs4846914 in GALNT2 gene is related to an increased risk of hypertension in China Han population, but the APOE gene is not. Show more

Keywords: Gene polymorphisms, GALNT2, APOE, hypertension, China

DOI: 10.3233/BME-151501

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1977-S1983, 2015

Authors: Li, Jin | Wang, Ying | Wang, Lei | Liang, Hong | Feng, Weixing | Meng, Xianglian | Cong, Wang | Liu, Yunlong

Article Type: Research Article

Abstract: Rifampin is an important drug used in the treatment of tuberculosis, and it increases the drug metabolism in human hepatocytes. Previous studies have shown that rifampin can indirectly influence drug deposition through the regulation of molecular interactions of miRNA, PXR and other genes. The potential functions of miRNAs associated with rifampin- induced drug disposition are poorly understood. In this study, significantly differentially expressed miRNAs (SDEM) were extracted and used to predict the miRNA-regulated co-expression target genes (MCeTG). Additionally, a miRNA-regulated co-expressed protein interaction network (MCePIN) was constructed for SDEM by extending from the protein interaction network (PIN). The functioning of …the miRNAs were analyzed using GO analysis and KEGG pathway enrichment analysis. A total of 20 miRNAs belonging to SDEM were identified, and 632 miRNA-regulated genes were predicted. The MCePIN was constructed by extending from PIN, and 10 miRNAs and 33 genes that are relevant to 7 functions, including response to wounding, wound healing, response to drug, defense response, inflammatory response, liver development and drug metabolism, were discerned. The results provided by this study offer valuable insights into the effect of rifampin on miRNAs, genes and protein levels. Show more

Keywords: Rifampin, miRNA, gene, hepatocyte, PPI network, P450

DOI: 10.3233/BME-151502

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1985-S1991, 2015

Authors: Kim, Yong-Hyuk | Yoon, Yourim

Article Type: Research Article

Abstract: We present a new genetic filter to identify a predictive gene subset for cancer-type classification on gene expression profiles. This approach pursues to not only maximize correlation between selected genes and cancer types but also minimize inter-correlation among selected genes. The proposed genetic filter was tested on well-known leukemia datasets, and significant improvement over previous work was obtained.

Keywords: Gene selection, filter method, genetic algorithm, cancer classification, gene expression data

DOI: 10.3233/BME-151503

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S1993-S2002, 2015

Authors: Zhao, Qing | Wang, Dong | Chen, Yuehui | Qu, Xumi

Article Type: Research Article

Abstract: Protein subcellular localization prediction is currently receiving much attention in the field of protein research. Many researchers make great efforts to study single-site protein subcellular localization, but the experimental data shows that many proteins can be found in two or more sub-cellular locations, prompting the study of multisite protein sub-cellular localization. This study utilized a Gpos-mPLOC data set and pseudo amino acid compositions, physicochemical properties of amino acid composition, and entropy density as three effective feature extraction methods. Then, these features were then placed in a multi-label k nearest neighbor classifier to predict subcellular protein locations. Experimental results verified that …this approach provides a localization precision of 66.73% through the Jack-knife test. Show more

Keywords: Multisite, pseudo amino acid composition, physicochemical propertiess, entropy density, multi-label k nearest neighbor

DOI: 10.3233/BME-151504

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2003-S2009, 2015

Authors: Sun, Lin | Xu, Jiucheng | Yin, Ying

Article Type: Research Article

Abstract: One of the important problems in microarray gene expression data is tumor classification. This paper proposes a new feature selection method for tumor classification using gene expression data. In this method, three dimensionality reduction methods, including principal component analysis (PCA), factor analysis (FA) and independent component analysis (ICA), are first introduced to extract and select features for tumor classification, and their corresponding specific steps are given respectively. Then, the superiority of three algorithms is demonstrated by performing experimental comparisons on acute leukemia data sets. It is concluded that PCA compared with FA and ICA is the best under feature load …ratio. However, PCA cannot make full use of the category information. To overcome the weak point, Fisher linear discriminant (FLD) is employed as those components of PCA, and a new approach to principal component discriminant analysis (PCDA) is proposed to retain all assets and work better than both PCA and FLD for classification. The further experimental results show that the classification ability of selected feature subsets by means of PCDA is higher than that of the other related dimensionality reduction methods, and the proposed algorithm is efficient and feasible for tumor classification. Show more

Keywords: Feature selection, principal component, discriminant analysis, classification

DOI: 10.3233/BME-151505

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2011-S2017, 2015

Authors: Zhan, Yiling | Guo, Shuyuan

Article Type: Research Article

Abstract: Bacillus thuringiensis (Bt) is capable of producing a chitin-binding protein believed to be functionally important to bacteria during the stationary phase of its growth cycle. In this paper, the chitin-binding domain 3 protein HD73_3189 from B. thuringiensis has been analyzed by computer technology. Primary and secondary structural analyses demonstrated that HD73_3189 is negatively charged and contains several α -helices, aperiodical coils and β -strands. Domain and motif analyses revealed that HD73_3189 contains a signal peptide, an N-terminal chitin binding 3 domains, two copies of a fibronectin-like domain 3 and a C-terminal carbohydrate binding domain classified as CBM_5_12. Moreover, …analysis predicted the protein’s associated localization site to be the cell wall. Ligand site prediction determined that amino acid residues GLU-312, TRP-334, ILE-341 and VAL-382 exposed on the surface of the target protein exhibit polar interactions with the substrate. Show more

Keywords: Bacillus thuringiensis, chitin binding domain 3 protein, 3D structure, functional analysis

DOI: 10.3233/BME-151506

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2019-S2024, 2015

Authors: Huynh, Hieu Trung | Won, Yonggwan | Kim, Jinsul

Article Type: Research Article

Abstract: Hematocrit is a blood test that is defined as the volume percentage of red blood cells in the whole blood. It is one of the important indicators for clinical decision making and the most effective factor in glucose measurement using handheld devices. In this paper, a method for hematocrit estimation that is based upon the transduced current curve and the neural network is presented. The salient points of this method are that (1) the neural network is trained by the online sequential extreme learning machine (OS-ELM) in which the devices can be still trained with new samples during the using …process and (2) the extended features are used to reduce the number of current points which can save the battery power of devices and speed up the measurement process. Show more

Keywords: hematocrit, extreme learning machine, online training, OS-ELM, neural network

DOI: 10.3233/BME-151507

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2025-S2032, 2015

Authors: Xiao, Ting | Zeng, Ou | Luo, Jian | Wu, Zhixiong | Li, Fang | Yang, Jun

Article Type: Research Article

Abstract: In order to explore the effects of hydrogen sulfide (H2 S) on myocardial fibrosis in diabetic rats and its underlying mechanisms, intraperitoneal injections of streptozotocin were used to establish the diabetes models and sodium hydrosulfide (NaHS) was used as an exogenous donor of H2 S. Eight weeks later, Van Gieson staining was used to observe pathological changes, and basic hydrolysis methods were adopted to measure hydroxyproline content, while Western Blot was used to determine the expression of MMP2, MMP7, MMP11, MMP13, MMP16, TIMP1 and TGFβ 1.The results showed that significant myocardial fibrosis, decreased TIMP1 and MMP2 expression and increased MMP7, …MMP11, MMP13, MMP16 expressions occurred in diabetic group, but all these changes were significantly reversed in diabetic rats after NaHS treatment. This suggests that H2 S could attenuate cardiac fibrosis induced by diabetes and its mechanisms may be related to its modulation of MMPs/TIMPs expression and regulation of TGFβ 1. Show more

Keywords: Hydrogen sulfide, diabetic myocardial fibrosis, matrix metalloproteinases, tissue inhibitors of metalloproteinases, transforming growth factor beta1

DOI: 10.3233/BME-151508

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2033-S2039, 2015

Authors: Liu, Junli | Si, Shaoyan | Qin, Yaya | Zhang, Bin | Song, Shujun | Guo, Yanchuan

Article Type: Research Article

Abstract: Our study aimed at investigating the effect of different molecular weight bovine collagen peptides, namely CH878, CH1370, CH2900, and CH7747 on the differentiation of MC3T3-E1 cells. Osteogenic differentiation of MC3T3-E1 cells was assessed by a series of specific assays, after culturing of cells in the presence of collagen peptides. Alkaline phosphatase activity (ALP) was evaluated by NBT/BCIP staining. Osteocalcin expression was determined by a radioimmunology method. Mineralization was quantified by Alizarin Red staining. ALP staining results demonstrated that the ALP staining of cells after culture in the presence of collagen peptides were significantly higher than the control group (P<0.05), indicating …the promotion of ALP activity in MC3T3-E1 cells by these peptides. Radioimmunology results demonstrated that collagen peptides groups were all significantly higher than the control group (P<0.01). Alizarin Red staining results demonstrated that CH1370, CH2900, and CH7747 significantly promoted the formation of mineralized bone matrix. We therefore conclude that CH1370, CH2900, and CH7747 play an active role in the differentiation of MC3T3-E1 cells. Based on the above results, we provide molecular basis for further development of collagens with different molecular weight for the prevention and treatment of osteoporosis. Show more

Keywords: Different molecular weight collagen peptides, MC3T3-E1 cells, differentiation

DOI: 10.3233/BME-151509

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2041-S2047, 2015

Authors: Su, Yan | Han, Lisha | Gao, Lijun | Guo, Jun | Sun, Xiaorong | Li, Jiaxin | Qin, Wenbin

Article Type: Research Article

Abstract: In this paper, the hemoglobin (Hb) re-released from red blood cells (RBCs) and whole blood of 7 carcinoma patients were studied by using electrophoresis release test (ERT), which was established by our lab. Among the 7 carcinoma patients, the re-released Hb was distinctively increased from an intrahepatic bile duct carcinoma patient during one-dimension isotonic ERT. Different from the others, the result of double-dimension Hb re-release of this intrahepatic bile duct carcinoma patient showed that not only HbA but also HbA2 could be re-released from both RBCs and whole blood. The result of isotonic & hypotonic ERT which was performed …at room temperature showed that more Hb could be re-released from both RBCs and whole blood of the intrahepatic bile duct carcinoma patient than that of the normal control. After keeping the samples at 37°C for 1 hour, the re-released Hb from RBCs could still be found more than that of the normal control, but was disappeared completely from the whole blood sample. To our surprise, when the isotonic & hypotonic ERT was repeated 2 days later at 37°C, the re-released Hb from RBCs of the intrahepatic bile duct carcinoma patient was increased only in tube 4-6, and disappeared in the other tube. Further mechanism research work cannot be continued because of the patient’s leave, but ERT is speculated to be a useful and effective technology to observe the physiological or pathological change of RBCs, blood or body in the future. Show more

Keywords: Hemoglobin, red blood cell, electrophoresis release test, intrahepatic bile duct carcinoma

DOI: 10.3233/BME-151510

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2049-S2054, 2015

Authors: Yin, Kun | Zhao, Guihua | Huang, Xiaodan | Gao, Ge | Sun, Hui | Wei, Qingkuan | Liu, Qiaoqiao | Li, Mian | Xu, Chao | Zhu, Song | Ba, Zaihua | Yan, Ge

Article Type: Research Article

Abstract: Tumor necrosis factor-alpha (TNF-α ) has been used as an effective treatment for Hepatocellular Carcinoma, however, inducing tumor cell apoptosis by TNF-α alone is still unsatisfactory. RhoA is highly expressed in hepatocarcinoma cells and can be activated by TNF-α . The activation of RhoA directly leads to a poor prognosis of HCC. Therefore, we propose to investigate the therapeutic effect of TNF-α together with RhoA siRNA. RhoA inhibition was accomplished by constructing a recombinant adenovirus that can efficiently express RhoA siRNA in HepG2 cells. The recombinant adenovirus AdshRNA-RhoA and AdU6-control were generated by adenovirus-mediated siRNA expression system. The …inhibition effects were detected by RT-PCR in addition to immunoblot to quantify the decreased levels of RhoA expression, and the therapeutic effect for HCC was demonstrated by the proliferation and apoptosis ratios of HepG2 cells. The inhibition effects of RhoA by AdshRNA-RhoA were significant at both mRNA and protein levels: the transcription of RhoA mRNA decreased by 74.46%, and the expression of protein decreased by 76.48%. The proliferation rate of HepG2 cells detected by MTT showed that a treatment of AdshRNA-RhoA and TNF-α together could strengthen the suppression ability of TNF-α to HepG2 cells, resulting in approximately 14.2% more than those treated with only TNF-α . FCA and TUNEL assays results revealed that the combined treatment can induce apoptosis in approximately 52.14%-65% of the HepG2 cells, whereas this ratio in the TNF-α -alone group was only 21.91%-32%. Our results showed that AdshRNA-RhoA can efficiently enhance the TNF-α -induced apoptosis of hepatocarcinoma cells. This method might be a useful therapeutic route in HCC and other tumors. Show more

Keywords: RhoA, tumor necrosis factor-alpha, adenovirus-mediated siRNA, hepatocarcinoma cells, apoptosis

DOI: 10.3233/BME-151511

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2055-S2067, 2015

Authors: Zhang, Chunmei | Lin, Linghui | Li, Guirong | Ma, Jianan | Han, Xu | Fei, Rui

Article Type: Research Article

Abstract: Polysaccharides derived from Ginkgo biloba leaf (PGBL) is a kind of active ingredient came out from ginkgo biloba leaf extractions. Previous studies have shown that PGBL has a good anti-inflammatory effect. However, the mechanism is not clear. This study is to investigate the modulated immunity effect of PGBL on RAW264.7 cells. Here we showed that lipopolysaccharide (LPS) induces the expression of tumor necrosis factor-α (TNF-α ) and interleukin-6 (IL-6), and this induction can be repressed by PGBL treatment both in protein level and mRNA level, and PGBL strongly reduced the translocation of nuclear factor (NF)-κ B to the cell …nucleus. These findings demonstrate that PGBL can decrease the sensitivity of monocytes to LPS, and PGBL has applications in systemic inflammation and immune diseases. Show more

Keywords: LPS, PGBL, TNF-α, IL-6, NF–κB

DOI: 10.3233/BME-151512

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2069-S2075, 2015

Authors: Zhang, Yuhong | Zhao, Yongli | Chen, Yafei | Yuan, Changqing | Zhan, Yong

Article Type: Research Article

Abstract: The effects of noise on the calcium oscillations in a cell exposed to electromagnetic fields are described by a dynamic model. Noise is a very important factor to be considered in the dynamic research on the calcium oscillations in a cell exposed to electromagnetic fields. Some meaningful results have been obtained here based on the discussion. The results show that the pattern of intracellular calcium oscillations exposure to electromagnetic fields can be influenced by noise. Furthermore, the intracellular calcium oscillations exposure to electromagnetic fields can also be induced by noise. And the work has also studied the relationships between the …voltage sensitive calcium channel’s open probability and electromagnetic field. The result can provide new insights into constructive roles and potential applications of selecting appropriate electromagnetic field frequency during the research of biological effect of electromagnetic field. Show more

Keywords: Calcium oscillations, noise, electromagnetic fields, open probability

DOI: 10.3233/BME-151513

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2077-S2082, 2015

Authors: Feng, Yi | Wan, Mingxi

Article Type: Research Article

Abstract: To analyze the potential molecular mechanism of ultrasound induced apoptosis in cancer cells, comparative proteomic methods were introduced in the study. After ultrasound exposure at the intensity of 1.2 W/cm2 , the human SMMC-7721 hepatocarcinoma cells were stained by trypan blue to detect the morphologic changes, and then the flow cytometry was used to examine the percentage of early apoptosis via double staining of FITC-labelled Annexin V and Propidium iodide. The proteins were separated by two-dimensional (2D) SDS polyacrylamide gel electrophoresis (PAGE). Among them, the differently expressed proteins were identified by MALDI-TOF mass spectrometry to reveal the key proteins response …to ultrasound exposure. It’s proved early apoptosis of cells were induced by focused ultrasound. After ultrasound exposure, the expressing characteristics of several proteins changed, in which some proteins in HSP family are associated with apoptosis initiation. It is suggested that the focused ultrasound could be applied in the assistant cancer therapy. Moreover, it is proved the comparative proteomic methods could supply information about the protein expression to analyze the metabolic processes related to bio-effects of biomedical ultrasound. Show more

Keywords: Focused ultrasound, apoptosis, comparative proteomic methods, signaling pathway, assistant cancer therapy

DOI: 10.3233/BME-151514

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2083-S2089, 2015

Authors: Xu, Hua | Gu, Dayong | He, Jian’an | Shi, Lei | Yao, Jingyu | Liu, Chunxiao | Zhao, Chunzhong | Xu, Yunqing | Jiang, Shengyang | Long, Jun

Article Type: Research Article

Abstract: In this paper, we report the development of a protein microarray-based biosensor for the detection of the hepatitis B virus (HBV) serological markers using surface plasmon resonance (SPR Printing buffer, protein immobilization time and concentration of the capture protein were optimized systematically to determine the best performance of the biosensor. Under optimal conditions, five hepatitis B markers in 20 μ L human serum can be simultaneously detected within 30 minutes, whereas other methods such as ELISA and PCR can detect only one marker within four hours. This platform has been validated by analysis of 35 patients known to have hepatitis …B, with 85% agreement between the test platform and analysis by commercial enzyme-linked immunosorbent assay (ELISA) kits. The results demonstrate that the protein microarray with SPR displayed a sensitivity of 0.1 ng mL−1 for HBsAg. In addition to high sensitivity, it also shows excellent specificity, reproducibility and stability. This integrated protein microarray technique combined with SPR is a promising candidate for hepatitis B diagnosis with high-throughput. Show more

Keywords: Surface plasmon resonance, protein microarray, hepatitis B virus, label-free, biosensor

DOI: 10.3233/BME-151515

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2091-S2100, 2015

Authors: Yun, Jung Min | Hwang, Sung Jin | Anh, Sung Yong | Lee, Seung Min | Kang, Peter | Lee, Jeong Eun | Yoon, Eun Sil | Choi, Jin Wook | Park, Sung-Hye | Seo, Jung-Wook | Park, Peom

Article Type: Research Article

Abstract: In Korea, there were 224,000 new cases of cancer and 75,334 deaths caused by cancer in 2013, which was three times more than the number of death caused by heart disease, the second leading cause of death. This study proposes a biomarker positivity analysis system based on clinical data, for personalized diagnosis and therapy of cancer. Data of 78,912 cases were obtained from immunopathology and surgical pathology reports. Data on sex, age, organ, diagnosis, and biomarkers were entered into a database. To verify the reliability of the clinical data, an additional 50,450 cases from positivity-related research papers were added. The …proposed biomarker positivity analysis system makes it possible to extract and combine information for searching. The positivity values are in graphical and tabular format for ease of use. With a link to the internal network of the hospital, real-time pathology reports are available. Twenty-five pathology specialists are chosen as subjects to further confirm the reliability of this system; primary assessment results demonstrate a satisfaction level of 4.7 out of 5 and a concordance rate of 79% with positive data under the same conditions as reported in the literature. In the present study, analysis methods and platforms using large volumes of clinical and literature data are developed for cancer prognoses. It is expected that these tools will benefit both healthcare professionals and non-professionals involved in cancer diagnosis and treatment. Show more

Keywords: Cancer, biomarker, clinical data, positive rate

DOI: 10.3233/BME-151516

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2101-S2111, 2015

Authors: Jiang, Donglin | Wang, Xu | Su, Qiang | Jiang, Shengyang | Yuan, Fenglai | Zhang, Caidi | Gong, Fang | Dong, Qiaojing | Shi, Jianping | Chen, Baohua

Article Type: Research Article

Abstract: Milkvetch root as a medicine has been used for more over 2000 years in China, can strengthen immune function, protect liver, promote urination, resist aging and stress, reduce blood pressure and extensively resist bacterium. This study explored the effects of milkvetch root on the immune function of patients with a definitive diagnosis of acute exacerbation of chronic obstructive pulmonary disease (COPD). The patients were randomly assigned to either the experimental or control group. All patients received conventional clinical therapy; those in the experimental group were also administered milkvetch root. The serum levels of cytokines including tumor necrosis factor alpha (TNF-α …), interleukin-8 (IL-8), IL-1β , and IL-32 and immunocytes including T helper (Th), cytotoxic T (Tc), natural killer (NK), regulatory T (Treg) and B cells were measured 1 day before treatment and 7 and 14 days post-treatment. After bronchodilator inhalation, pulmonary function was evaluated at these same time points. The serum TNF-α , IL-8, IL-1β , and IL-32 levels were significantly lower in the experimental group than in the control group 14 days post-treatment. The Th/Tc ratio and NK cell ratio was significantly higher but the Treg cell ratio was significantly lower in the experimental group than in the control group. The forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) were significantly higher in the experimental group than in the control group 14 days post-treatment. These results indicate that milkvetch root can improve the immune function of patients with acute exacerbation of COPD. Show more

Keywords: Chronic obstructive pulmonary disease, milkvetch root, immune function

DOI: 10.3233/BME-151517

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2113-S2121, 2015

Authors: Liu, Juan | Qiu, Hong | Zhu, Zhaorong | Zou, Tangbin

Article Type: Research Article

Abstract: The Yinzhihuang injection, a traditional Chinese medicine, has been the recent target of increasing interest due to its anti-inflammatory properties. The molecular basis by which Yinzhihuang injection could cure Riemerella anatipestifer (RA) serositis in ducks is unclear. This study evaluated the antibacterial, anti-inflammatory and antioxidant effects of Yinzhihuang injection, using disease models of RA-induced infectious serositis in ducks and heptane-induced inflammation in mice and rats. The duck mortality rate was reduced from 60% to 20% and both the inflammatory response and histological damage were ameliorated by treatment with Yinzhihuang injection (0.02 g/kg). Further studies indicated that superoxide dismutase (SOD), …nitric oxide synthase (NOS), and inducible nitric oxide synthase (iNOS) were elevated while malondialdehyde (MDA), nitric oxide (NO) and RA growth were inhibited when the ducks were treated by Yinzhihuang injection. In addition, Yinzhihuang injection (0.04 g/ml) effectively inhibited xylene-induced auricle swelling in mice, (demonstrating an inhibition rate of 35.21%), egg albumen-induced paw metatarsus swelling in rats, (demonstrating an inhibition rate of 22.30%), and agar-induced formation of granulation tissue. These results suggest that Yinzhihuang injection ameliorates RA-induced infectious serositis in ducks by modulation of inflammatory mediators and antioxidation. Show more

Keywords: anti-infective, anti-inflammatory, Yinzhihuang, riemerella anatipestifer

DOI: 10.3233/BME-151518

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2123-S2132, 2015

Authors: Liu, Pengfei | Feng, Yetong | Wang, Yi | Zhou, Yulai | Zhao, Lei

Article Type: Research Article

Abstract: It has been well-known for many years now that vitamin E is an essential nutrient; however, some of the physiological functions of this vitamin are still far from being understood. In recent years, a series of preclinical and clinical studies proposed a protective role of vitamin E on acute kidney injury (AKI), which has a high morbidity rate and mortality rate in clinical investigations. Based on the benefits associated with vitamin E, such as strong antioxidant function, low toxicity, rare side-effects, and low cost, this therapy strategy has garnered an extensive amount of interest in the scientific community for the …development of new therapy modes against AKI. In this review, a concise overview of the application of vitamin E in the treatment of AKI is provided as well as a summary of a series of published data regarding the combination therapy modes and detailed therapy mechanisms of vitamin E-based therapy against AKI. At present, there are critical points of this therapy mode that are still in need of further clarification, meaning the current understanding of the role of vitamin E in the treatment of AKI remains incomplete. However, the development of more reliable pharmacological or biotechnical strategies with vitamin E for the eventual treatment of patients with AKI may guide the next chapter of vitamin E research. Show more

Keywords: Vitamin E, acute kidney injury, antioxidant, kidney repair

DOI: 10.3233/BME-151519

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2133-S2144, 2015

Authors: Wang, Ruinan | Geng, Ning | Zhou, Yuqiao | Zhang, Dunfang | Li, Longjiang | Li, Jing | Ji, Ning | Zhou, Min | Chen, Yu | Chen, Qianming

Article Type: Research Article

Abstract: This study investigates whether Wnt components play a role in carcinogenesis, or the invasion and metastasis of salivary glands, also referred to as adenoid cystic carcinoma (sAdCC). Several sAdCC cell lines with low invasive potential (ACC-2), high metastatic potential (ACC-M), and higher invasive potential (T-ACC-M) were examined to determine whether Wnt components correlate with tumors’ invasive and metastatic behavior. Immunohistochemistry was performed in a sAdCC tissue array. ACC-M expressed higher levels of Wnt-1, beta-catenin and lower WIF-1 compared to ACC-2 (P<0.05). T-ACC-M exhibited increased mRNA of Wnt-1 and beta-catenin, and decreased WIF-1 compared to ACC-2 and ACC-M. Immuno-histochemistry showed up-regulation …of Wnt-1 and down-regulation of WIF-1 in sAdCC compared with normal salivary glands. Beta-catenin was found in the cytoplasm and nuclei of sAdCC. Dislocation of E-cadherin in sAdCC was observed. These results suggest that sAdCC exhibits diverse expressions of Wnt components. It has an important relationship with the invasive phenotype of these cells. Show more

Keywords: Adenoid cystic carcinoma, Wnt-1, WIF-1, Beta-catenin, E-cadherin

DOI: 10.3233/BME-151520

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2145-S2153, 2015

Authors: Kwon, Yuri | Kim, Ji-Won | Kim, Ji-Sun | Koh, Seong-Beom | Eom, Gwang-Moon | Lim, Tae-Hong

Article Type: Research Article

Abstract: The aim of this study was to test the hypothesis in the literature that torque resistance of parkinsonian rigidity is the difference between the independent contributions of stretched and shortened muscles. The hypothesis was tested using muscle-specific stretch-shortening (MSSS) EMG ratio in this study. Nineteen patients with idiopathic Parkinson’s disease (PD) and 18 healthy subjects (the mean age comparable to that of patients) participated in this study. The EMG activity was measured in the four muscles involved in wrist joint movement, i.e. flexor carpi radialis, flexor carpi ulnaris, extensor carpi radialis and extensor carpi ulnaris. The passive flexion-extension movement with …a range of ± 30 ∘ was applied at wrist joint. Root mean squared (RMS) mean was calculated from the envelope of the EMG for each of stretching and shortening phases. MSSS EMG ratio was defined as the ratio of RMS EMG of stretching phase and RMS EMG of shortening phase of a single muscle, and it was calculated for each muscle. MSSS EMG ratios were smaller than one in all muscles. These results indicate that all wrist muscles generate greater mean EMG during shortening than during stretching. Therefore, the torque resistance of parkinsonian rigidity cannot be explained as the simple summation of independent antagonistic torque pair. Show more

Keywords: EMG, parkinsonian rigidity, passive stretching, passive shortening

DOI: 10.3233/BME-151521

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2155-S2163, 2015

Authors: Cui, Yu | Chen, Xiaobei | Liu, Liyan | Xie, Wei | Wu, Yue | Wu, Qunhong | Wang, Decai

Article Type: Research Article

Abstract: As the worldwide elderly population has grown, the incidence and prevalence of Alzheimer’s disease (AD) has steadily increased. The differential lifelong exposure of populations to dietary fatty acids has raised concerns about the potential links between cognitive impairments and nutrition. However, few studies have addressed the levels of free fatty acids (FFAs) in AD patient serum. In this study, gas chromatography–mass spectrometry (GC–MS) was used to determine the levels of 15 serum FFAs in 31 AD patients and 33 healthy controls. The optimized methodology entailed the formation of methyl esters using 10% v/v H2 SO4 /CH3OH at 62°C for 2 …hours. The linear range was 0.55–300 μ g/mL, the range of recovery was 85.1–104.3%, and the detection limit was 0.03–0.08 μ g/mL. Several FFAs in the AD patient significantly decreased when compared to the control, including three saturated fatty acids (C14:0, C16:0, and C18:0) and six unsaturated fatty acids (C16:1, C18:1, C18:2, γ -C18:3, C20:2, and C22:6). The serum level of C18:3 was significantly higher in the AD patients. The FFA profiles of the AD patients differed significantly from those of controls. The method effectively determined the FFA levels and could facilitate future studies regarding the relationship between AD and the metabolism of FFAs. Show more

Keywords: Alzheimer’s disease, fatty acid, GC–MS

DOI: 10.3233/BME-151522

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2165-S2177, 2015

Authors: Tufan, Kadir | Belli, Ahmet Korkut

Article Type: Research Article

Abstract: Injury to the nervous system can lead to irreversible problems as nervous tissues have limited regenerative capability. Therefore it is imperative to find an objective, reliable, cheap, and easy-to-apply method that separates nervous fibers from muscles and blood vessels. The aim of this study is to determine structural differences that can aid in easy and reliable identification of nervous fibers. We analyzed light reflectance from these tissues from 230 nm to 1000 nm and found that in the range of 400 nm-600 nm nervous fibers have higher reflectance in comparison to others. Therefore, we generated distinct features in this range …and utilized support vector machine to automatically classify samples. Classification performance demonstrated that light reflectance is a good candidate feature that can help to classify nervous tissue. Show more

Keywords: Nervous tissue, light reflectance, surgery, support vector machines

DOI: 10.3233/BME-151523

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2179-S2185, 2015

Authors: Zhang, Pengfei | Min, Lequan | Pian, Jianwei

Article Type: Research Article

Abstract: In 1996 Nowak and his colleagues proposed a differential equation virus infection model, which has been widely applied in the study for the dynamics of hepatitis B virus (HBV) infection. Biological dynamics may be described more practically by discrete events rather than continuous ones. Using discrete systems to describe biological dynamics should be reasonable. Based on one revised Nowak et al’s virus infection model, this study introduces a discrete virus infection model (DVIM). Two equilibriums of this model, E 1 and …E 2 , represents infection free and infection persistent, respectively. Similar to the case of the basic virus infection model, this study deduces a basic virus reproductive number R0 independing on the number of total cells of an infected target organ. A proposed theorem proves that if the basic virus reproductive number R 0 < 1 then the virus free equilibrium E 1 is locally stable. The DVIM is more reasonable than an abstract discrete susceptible-infected-recovered model (SIRS) whose basic virus reproductive number R 0 is relevant to the number of total cells of the infected target organ. As an application, this study models the clinic HBV DNA data of a patient who was accepted via anti-HBV infection therapy with drug lamivudine. The results show that the numerical simulation is good in agreement with the clinic data. Show more

Keywords: Hepatitis B virus, modeling, discrete virus infection model, equilibrium stability, numerical simulation

DOI: 10.3233/BME-151524

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2187-S2195, 2015

Authors: Jiang, Jiehui | Duan, Huoqiang | Huang, Zheming | Yu, Zhihua | The Alzheimer’s Disease Neuroimaging Initiative,

Article Type: Research Article

Abstract: One medical challenge in studying the amyloid-β (Aβ ) peptide mechanism for Alzheimer’s disease (AD) is exploring the law of beta toxic oligomers’ diffusion in human brains in vivo . One beneficial means of solving this problem is brain network analysis based on graph theory. In this study, the characteristics of Aβ functional brain networks of Healthy Control (HC), Mild Cognitive Impairment (MCI), and AD groups were compared by applying graph theoretical analyses to Carbon 11-labeled Pittsburgh compound B positron emission tomography (11C PiB-PET) data. 120 groups of PiB-PET images from the ADNI database were analyzed. The results …showed that the small-world property of MCI and AD were lost as compared to HC. Furthermore, the local clustering of networks was higher in both MCI and AD as compared to HC, whereas the path length was similar among the three groups. The results also showed that there could be four potential Aβ toxic oligomer seeds: Frontal_Sup_Medial_L, Parietal_Inf_L, Frontal_Med_Orb_R, and Parietal_Inf_R. These four seeds are corresponding to Regions of Interests referred by physicians to clinically diagnose AD. Show more

Keywords: Alzheimer’s disease, amyloid-β peptide (Aβ), carbon 11-labeled pittsburgh compound B (11C-PiB), positron emission tomography (PET), brain networks

DOI: 10.3233/BME-151525

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2197-S2205, 2015

Authors: Shi, Lei | Sun, Qiuxiang | He, Jian’an | Xu, Hua | Liu, Chunxiao | Zhao, Chunzhong | Xu, Yunqing | Wu, Changlin | Xiang, Junjian | Gu, Dayong | Long, Jun | Lan, Hekui

Article Type: Research Article

Abstract: A surface plasmon resonance (SPR)-based biosensor was developed for specific detection of nine common respiratory virus, including influenza A and influenza B, H1N1, respiratory syncytial virus (RSV), parainfluenza virus 1-3 (PIV1, 2, 3), adenovirus, and severe acute respiratory syndrome coronavirus (SARS). The SPR biosensor was developed by immobilizing nine respiratory virus-specific oligonucleotides in an SPR chip. To increase the biosensor sensitivity, biotin was used to label the PCR primer and further amplify the signal by introducing streptavidin after hybridization. Throat swab specimens representing nine common respiratory viruses were tested by the innovative SPR-based biosensor to evaluate the sensitivity, specificity and …reproducibility of this method. Results suggest that this biosensor has the potential to simultaneously identify common respiratory viruses. Show more

Keywords: SPR, respiratory virus, high throughput, label-free, gene chip

DOI: 10.3233/BME-151526

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2207-S2216, 2015

Authors: Liu, Limei | Sun, Liyuan | Li, Chunhe | Li, Xinyang | Zhang, Yuhong | Yu, Yun | Xia, Wei

Article Type: Research Article

Abstract: The development of carcinoma has been found to be associated with epigenetic modifications. The aim of this study was to estimate the methylation levels of FHIT and BRCA1 promoters using the bisulphite sequencing method (BSP) and high-resolution melting curve analysis (HRM) in the serum of patients with ductal breast carcinoma as a biomarker for the possible application of early diagnosis of breast cancer. The results showed that the methylation levels of both BRCA1 and FHIT promoters were higher in the serum of the breast ductal carcinoma group (BDC group) than those of the breast fibroadenoma group …(BFA group), and the healthy individuals group (HI group). However, the methylation levels of the BRCA1 promoters were very low in all three groups compared to the levels of FHIT . The advanced quantitative detection of the samples with HRM showed that the FHIT promoter methylation level of the cfDNA in each serum was also very high in the BDC group compared to the HI group. The methylation level of FHIT was found to be significantly associated with breast cancer (p < 0.05). In conclusion, the methylation quantitative detection of FHIT promoter in serum may be useful for the early diagnosis of ductal breast carcinoma. Show more

Keywords: FHIT, BRCA1, methylation, breast cancer, cfDNA

DOI: 10.3233/BME-151527

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2217-S2222, 2015

Authors: Zhang, Jiaqiang | Fang, Li-Zhou | Liu, Ling | Zhang, Jianqing | Fu, Weiping | Dai, Luming

Article Type: Research Article

Abstract: To discuss the differences in protein expression among tuberculosis pleural effusion (TBPE), malignant pleural effusion (MPE) and transudative pleural effusion (TSPE). We recruited 50 patients with pleural effusion, including 20 TBPEs, 17 MPEs and 13 TSPEs. Using the two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS), we acquired the peptide mass finger printings (PMFs) of featured proteins. Then, we identified characteristic proteins by searching in the protein databank of the National Center of Biotechnology Information (NCBI) and assessed their diagnostic significance. We found five characteristic proteins: C1-inhibitor (C1-INH), transthyretin (TTR), human complement fragment 3b (C3b), human …ceruloplasmin (CP), and Z34c protein fragment Fc (Z34c-Fc). C1-INH shows a high expression in TBPE and a low expression in MPE while TTR and C3 show low expression in TBPE and high expressions in MPE. Z34c-Fc and CP have a higher expression in TBPE than in TSPE. No common characteristic protein was found between MPE and TSPE. Statistic analysis consisted of paired t-tests and the difference between them is significance ( P < 0.05 ). C1-inhibitor (C1-INH), transthyretin (TTR), human Complement fragment 3b (C3b), human Ceruloplasmin (CP) and Z34c protein fragment Fc (Z34c-Fc) may provide an additional perspective in the differential diagnosis of PE. Show more

Keywords: Tuberculosis pleural effusion, proteomic, 2-DE, MALDI-TOF-MS

DOI: 10.3233/BME-151528

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2223-S2232, 2015

Authors: Wang, Panpan | Yang, Fengyuan | Yang, Hong | Xu, Xiaofei | Liu, Duo | Xue, Weiwei | Zhu, Feng

Article Type: Research Article

Abstract: Selective serotonin reuptake inhibitors (SSRIs) are most adopted therapeutics marketed for major depression, and the efficacy of which are greatly reduced by their delayed onset of action and undesirable side effects. 5-HT1A receptor partial agonist and SERT inhibitor (SPARI) was proposed as a novel strategy to overcome the shortage of efficacy by a negative feedback control of 5-HT1A receptor. However, only one SPARI (vilazodone) has been approved for clinical use, and none is currently in clinical trial, which demonstrates a strong need for searching more novel SPARIs to facilitate antidepressants discovery. This work applied a combinatorial virtual screening method (CVSM) …by integrating multiple tools. Statistic analysis reveals that CVSM surpasses single virtual screening methods in terms of hit rates and enrichment factors. By adopting optimized CVSM, 91 promising dual target leads form 15 scaffolds were identified, and 40% of these scaffolds have already been reported to show antidepressant related therapeutic effects. In sum, CVSM is capable in identifying novel SPARIs from large chemical libraries with extremely low false hit rate. Show more

Keywords: Virtual screening, support vector machines, molecular docking, 5-HT1A receptor agonist, SERT inhibitor

DOI: 10.3233/BME-151529

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2233-S2239, 2015

Authors: Luo, Yunjing | Shi, Jianlong | Li, Jingjing

Article Type: Research Article

Abstract: An increasing number of peroxynitrite-mediated fibrinogen nitrifications have been associated with thrombotic diseases. However, few reports related to priority nitrified fibrinogen injury sites exist. In this paper, an improved method, which simulated the environment in vivo, was used to inspect the structural changes of fibrinogen treated with peroxynitrite and LC-MS/MS in order to investigate the fibrinogen injury sites. The SDS-PAGE results indicated that γ subunits of Fg were vulnerable to oxidative/nitrative modifications induced by peroxynitrite. An in-depth analysis of fibrinogen γ chain (Fg I) nitration site identification and susceptibility to peroxynitrite-utilizing LC-MS/MS strategy was performed. Based on a …large dataset, the results indicated the priority injury sites during database searching were Y96, Y262, Y274, Y348, and Y363; these results could be applied to biomedical studies. Show more

Keywords: Fibrinogen, LC-MS/MS, SDS-PAGE, peroxynitrite, tyrosine nitration

DOI: 10.3233/BME-151530

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2241-S2248, 2015

Authors: Kim, Ji-Won | Kwon, Yuri | Yun, Ju-Seok | Heo, Jae-Hoon | Eom, Gwang-Moon | Tack, Gye-Rae | Lim, Tae-Hong | Koh, Seong-Beom

Article Type: Research Article

Abstract: The aim of this study was to develop regression models for the quantification of parkinsonian bradykinesia. Forty patients with Parkinson’s disease participated in this study. Angular velocity was measured using gyro sensor during finger tapping, forearm-rotation, and toe tapping tasks and the severity of bradykinesia was rated by two independent neurologists. Various characteristic variables were derived from the sensor signal. Stepwise multiple linear regression analysis was performed to develop models predicting the bradykinesia score with the characteristic variables as input. To evaluate the ability of the regression models to discriminate different bradykinesia scores, ANOVA and post hoc test were performed. …Major determinants of the bradykinesia score differed among clinical tasks and between raters. The regression models were better than any single characteristic variable in terms of the ability to differentiate bradykinesia scores. Specifically, the regression models could differentiate all pairs of the bradykinesia scores (p<0.05) except for one pair in the finger tapping task and one pair in the toe tapping task. In contrast, any single characteristic variable was found not sensitive enough to discriminate many of the pairs, especially in case of the toe tapping task. The results suggest that the multiple regression models reflecting these differences would be beneficial for the quantification of bradykinesia because the cardinal features included in the determination of bradykinesia score differ among tasks as well as among the raters. Show more

Keywords: Bradykinesia, quantification, stepwise multiple regression, Parkinson’s disease, clinical rating

DOI: 10.3233/BME-151531

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2249-S2258, 2015

Authors: Zhang, Jing | Zhao, Dali | Xie, Zhongwei | Qi, Yali

Article Type: Research Article

Abstract: Autophagy is an evolutionarily conservation process whereby cytoplasm and cellular organelles are degraded in lysosomes for amino acid and energy recycling. Autophagy concurrent with radiotherapy has emerged as a novel approach in breast cancer treatment. Our studies conclude that autophagy and apoptosis can be induced by radiation and inhibition of autophagy can increase apoptosis. In addition, Akt is a molecule that down-regulates autophagy and apoptosis; blocking Akt can enhance autophagy and apoptosis induced by radiation in MCF-7 cells. Akt could become a new focus in breast cancer radiotherapy.

Keywords: Autophagy, apoptosis, radiation, Akt, breast cancer

DOI: 10.3233/BME-151532

Citation: Bio-Medical Materials and Engineering, vol. 26, no. s1, pp. S2259-S2265, 2015