Volume 22, Issue 2
New Insights in Routine Procedure for Mathematical Evaluation of in vitro Cytotoxicity Data from Cancer Cell Lines87-106
Maya M. Zaharieva, Antonios Trochopoulos, Lyudmila Dimitrova, Martin R. Berger, Hristo Najdenski, Spiro Konstantinov, Alexander D. Kroumov
doi: 10.7546/ijba.2018.22.2.87-106
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Maya M. Zaharieva, Antonios Trochopoulos, Lyudmila Dimitrova, Martin R. Berger, Hristo Najdenski, Spiro Konstantinov, Alexander D. Kroumov (2018) New Insights in Routine Procedure for Mathematical Evaluation of in vitro Cytotoxicity Data from Cancer Cell Lines, Int J Bioautomation, 22 (2), 87-106, doi: 10.7546/ijba.2018.22.2.87-106
Abstract: In oncopharmacology, the common procedure to evaluate median-effect concentrations (IC50) on experimental data is based on the use of well-established kinetic models representing inhibition effects of drugs on human cancer cell lines. Several widespread software programs, such as GraphPad Prism and CompuSyn offer possibilities for calculation of IC50 through the model of Chou. In recent study, we analyzed the results from those two software programs and compared them with the non-linear programming procedure written by us in the MAPLE symbolic software. The last evaluated IC50 more precisely and the correlation coefficient R value was better in all trails. We demonstrated the efficiency of non-linear programming procedures in examples of two cancer cell lines treated with three different drugs. The response surface analysis showed the potential of the applied kinetic model. As a result, we were able to define better the IC50 values and to use them in planning further experiments in human cancer cell lines related to single drug influence and drug-drug interference.

Keywords: Non-linear programming, Kinetics models, Drugs, in vitro cytotoxicity, Human cancer cell lines
Application of a Microfluidic Chip with Mechanical Stimuli for Culturing Mouse Embryos in vitro107-116
Jingchun Li, Qi Li, Guosheng Wei, Shengjun Liu, Jiabao Zhang, Yanbing Li
doi: 10.7546/ijba.2018.22.2.107-116
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Jingchun Li, Qi Li, Guosheng Wei, Shengjun Liu, Jiabao Zhang, Yanbing Li (2018) Application of a Microfluidic Chip with Mechanical Stimuli for Culturing Mouse Embryos in vitro, Int J Bioautomation, 22 (2), 107-116, doi: 10.7546/ijba.2018.22.2.107-116
Abstract: In order to solve some problems of lower blastocyst rate of early embryos in vitro and poor quality of blastocyst, application of a microfluidic chip with mechanical stimuli (MS) to imitate microenvironment of fallopian tube, to investigate the effect of a microfluidic chip with mechanical stimuli on the early embryo development in mammalian. We designed and made a novel and simple system to apply MS similar to those generated inside the oviduct to cultured mammalian embryos by using poly(dimethylsiloxiane). Using this microfluidic chip embryo culture device to culture 2-cell stage mouse embryo from in vitro fertilization. There were large differences in development rates of > 4-cell stage, development rates of morula (63.1 ± 12.5% vs. 80.6 ± 17.9%) and blastocyst (58.6 ± 2.3% vs. 73.2 ± 2.8%) between control and microfluidic chip group (p < 0.05). meanwhile, there was large differences in cell numbers of inner cell mass in blastocyst between control and microfluidic chip group (p < 0.05). These results suggested that the culture device can significantly improve blastocyst development rate of embryo in vitro and the quality of the blastocyst in mice, this novel and simple system was feasible to generate and apply MS similar to those generated inside the oviduct to cultured mammalian embryos

Keywords: Microfluidic chip, Mechanical stimuli, Embryo culture, Mouse
Backstepping Glycemic Control of Type 1 Diabetes for Implementation on an Embedded System117-132
Mounir Djouima, Said Drid, Driss Mehdi
doi: 10.7546/ijba.2018.22.2.117-132
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Mounir Djouima, Said Drid, Driss Mehdi (2018) Backstepping Glycemic Control of Type 1 Diabetes for Implementation on an Embedded System, Int J Bioautomation, 22 (2), 117-132, doi: 10.7546/ijba.2018.22.2.117-132
Abstract: In this paper a nonlinear control intended for Blood glucose regulation for Type 1 Diabetes patients is considered. The control law is designed using the Lyapunov theory associated with a Kalman filter to estimate the system states. The asymptotic stability of the overall system is theoretically proven. The proposed control scheme will be implemented in a low cost embedded system. The simulation results confirm the effectiveness of the proposed control.

Keywords: Type 1 Diabetes, Blood glucose, Nonlinear control, Lyapunov method, Kalman filter, Backsteeping control
A Novel Classification Method for Class-imbalanced Data and Its Application in microRNA Recognition133-146
Xia Geng, Yu-Quan Zhu, Zhi Yang
doi: 10.7546/ijba.2018.22.2.133-146
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Xia Geng, Yu-Quan Zhu, Zhi Yang (2018) A Novel Classification Method for Class-imbalanced Data and Its Application in microRNA Recognition, Int J Bioautomation, 22 (2), 133-146, doi: 10.7546/ijba.2018.22.2.133-146
Abstract: For non-coding RNA gene mining, especially microRNA mining, there are many challenges in the classification of imbalanced data. A novel classification method based on the Adaboost algorithm is proposed to handle the imbalance of positive and negative cases. Unstable-Adaboost is improved with respect to the initial weight assignment, the base classifier selection, the weight adjustment mechanism and other aspects. Furthermore, the Stable-Adaboost algorithm is proposed, which adjusts the weight of the sample set to rapidly achieve a more balanced training set. In addition, the Stable-Adaboost algorithm can ensure that the follow-up training set is maintained in a balanced state by optimizing the weight adjustment mechanism of incorrectly classified samples and stabilizing the classification performance. Experimental results show the superiority of Unstable-Adaboost and Stable-Adaboost in imbalance classification.

Keywords: Non-coding RNA, Class imbalance, Ensemble learning, Adaboost algorithm
Subtraction Procedure for Power-line Interference Removal from ECG signals with High Sampling Rate147-158
Georgy Mihov
doi: 10.7546/ijba.2018.22.2.147-158
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Georgy Mihov (2018) Subtraction Procedure for Power-line Interference Removal from ECG signals with High Sampling Rate, Int J Bioautomation, 22 (2), 147-158, doi: 10.7546/ijba.2018.22.2.147-158
Abstract: The paper deals with some aspects of the subtraction procedure applied for power-line interference removing from high sampling rated ECG signals. Here high sampling rated ECG signal stands for signal with sampling rate-to-mains frequency ratio of about 15. Appropriate changes in the main stages of the subtraction procedure are introduced to ensure effective power-line interference removal. An adequate methodology is proposed to compensate the frequency deviation of the mains frequency. Besides, a specifically developed algorithm accelerates the initial procedure adaptation, as well as its work in case of abrupt changes of the mains frequency. Finally, program implementation of the modified subtraction procedure is elaborated and the results of simulated tests with 16 kHz sampling rated ECG signals are presented.

Keywords: ECG signals, Power-line interference removal, Subtraction procedure
Nuclear Factor Erythroid 2 Activation Mediated by PRKCA in Increasing Ca2+ Intracellular in Diabetic Condition159-168
Shahdevi Nandar Kurniawan, Didik Huswo Utomo, Achmad Rudijanto, Masruroh Rahayu, Aulanni’am Aulanni’am
doi: 10.7546/ijba.2018.22.2.159-168
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Shahdevi Nandar Kurniawan, Didik Huswo Utomo, Achmad Rudijanto, Masruroh Rahayu, Aulanni’am Aulanni’am (2018) Nuclear Factor Erythroid 2 Activation Mediated by PRKCA in Increasing Ca2+ Intracellular in Diabetic Condition, Int J Bioautomation, 22 (2), 159-168, doi: 10.7546/ijba.2018.22.2.159-168
Abstract: Diabetes increases in the worldwide by prevalence and numbers of complications related to it. The most common risk factor for foot ulcers in diabetic is peripheral neuropathy. In diabetic condition, Ca2+ concentration intracellular increases. NRF2 (Nuclear Factor Erythroid 2) acts as a bridging link in various inflammatory and apoptotic pathways impacting progress of diabetic neuropathy. The aim of this study is to predict the pathway of NRF2 activation that is mediated by the increased of intracellular Ca2+. Data interaction between Ca2+ and NRF2 were retrieved from STITCH (Search Tool for Interacting Chemicals) which were experimentally and prediction, then were analyzed computationally. Pathway analysis used Cytoscape software. The functional analysis was evaluated using STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) database. The consequence of increased intracellular Ca2+ content is the increases of oxidative stress, ROS (Reactive Oxygen Species) and the translocation of the protein kinase Cα (PKRCA) to the plasma membrane as the initial step of their activations. This study reveals that activation NRF2 by Ca2+ intracellular which increases in diabetic condition through PRKCA, PRKCA phosphorylate NRF2 in its Neh2 domain at Ser-40.

Keywords: Nuclear factor erythroid 2, Ca2+, PRKCA, Diabetes, Neuropathy
Characterization of a Novel Lytic Bacteriophage φEC14 that Infects Enterobacter cloacae Clinical Isolates169-178
Hongyan Shi, Jinghua Li, Yuchong Hao, Yanbo Sun
doi: 10.7546/ijba.2018.22.2.169-178
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Hongyan Shi, Jinghua Li, Yuchong Hao, Yanbo Sun (2018) Characterization of a Novel Lytic Bacteriophage φEC14 that Infects Enterobacter cloacae Clinical Isolates, Int J Bioautomation, 22 (2), 169-178, doi: 10.7546/ijba.2018.22.2.169-178
Abstract: Enterobacter cloacae, an important agent associated with nosocomial infection, usually involves expanded-spectrum cephalosporin resistance. The therapeutic potential of bacteriophage is a possibly alternative chemotherapy against bacterial infection. In this study, we have characterized one newly isolated bacteriophage φEC14, which is lytic to E. cloacae specifically. Transmission electron microscopy revealed that phage φEC14 had an icosahedral head and long contractile tail, morphologically similar to phages belonging to family Siphoviridae. Pulsed-Field Gel Electrophoresis (PFGE) showed that the size of φEC14 virion DNA was in rang of 23.0-48.5 kb. Restriction analysis showed that lytic phage φEC14 was a double-stranded DNA virus, which might be cut by some restriction endonucleases. SDS-PAGE of phage proteins exhibited one major band and six minor bands with molecular weight ranging from 6.5 to 66.4 kilo-Dalton. In one-step experiment, phage φEC14 had a short latent period of 10 minutes and a burst size of 50 PFU/cell. The best understanding of the biological features of lytic bacteriophage φEC14 would facilitate the development of an alternative agent to control the spread of multidrug-resistant E. cloacae.

Keywords: Phage therapy, Enterobacter cloacae, Antibiotic resistance
Research on Human Body Movement Posture Based on Inertial Sensor179-186
Lijuan Zhang
doi: 10.7546/ijba.2018.22.2.179-186
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Lijuan Zhang (2018) Research on Human Body Movement Posture Based on Inertial Sensor, Int J Bioautomation, 22 (2), 179-186, doi: 10.7546/ijba.2018.22.2.179-186
Abstract: Human movement refers to the various actions completed by the human body with flexibility and diversity which cannot be found in actions completed by robots. This paper proposed to use inertial sensors to collect the information about body movements and apply the collected information to analyze and identify human movements. It was found through the experiment that the inertial sensor could well identify the human body movement postures, which provided theoretical basis for its application in the field of human motion posture recognition.

Keywords: Inertial sensor, Human motion recognition, Biomechanical characteristics
The Effect of Co-activation of Antagonist Muscles on Motor Cortex Excitability: A Transcranial Magnetic Stimulation Study187-194
Kapka Mancheva, Diana I. Stephanova, Werner Wolf, Andon Kossev
doi: 10.7546/ijba.2018.22.2.187-194
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Kapka Mancheva, Diana I. Stephanova, Werner Wolf, Andon Kossev (2018) The Effect of Co-activation of Antagonist Muscles on Motor Cortex Excitability: A Transcranial Magnetic Stimulation Study, Int J Bioautomation, 22 (2), 187-194, doi: 10.7546/ijba.2018.22.2.187-194
Abstract: The effect of unilateral tonic muscle activity with and without co-activation of the antagonists on motor cortex excitability has been studied in seven right handed healthy volunteers. Contralateral motor evoked potentials (MEPs) were recorded from the first dorsal interosseous muscles of right hands in response to transcranial magnetic stimulation (TMS) during relax, isometric index finger abduction and antagonistic co-activation. The intracortical facilitation (ICF), short- and long-latency intracortical inhibition (SICI and LICI) were investigated by paired-pulse TMS. The unilateral tonic activation of the right hand facilitated MEPs in response to single-pulse TMS. The increase of MEP amplitudes was significantly greater during isometric index finger abduction compared to co-activation of antagonist muscles. During paired-pulse TMS with short interstimulus intervals, the SICI (interstimulus interval of 3 ms) was not influenced by the unilateral tonic activity while ICF (interstimulus interval of 13 ms) was suppressed. During paired-pulse TMS with longer interstimulus interval (100 ms) the LICI was not influenced during isometric index finger abduction while during antagonistic co-activation the LICI was significantly less pronounced. The decreased LICI is assumed to reflect mechanisms underlying the co-activation of antagonists.

Keywords: Transcranial magnetic stimulation, Motor evoked potential, Intracortical facilitation, Short-latency intracortical inhibition, Long-latency intracortical inhibition, Co-activation

Sponsored by National Science Fund of Bulgaria, Grant No DNP 06-18/2017

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