Search results for: target cell load
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 8373

Search results for: target cell load

8313 Efficient Pre-Processing of Single-Cell Assay for Transposase Accessible Chromatin with High-Throughput Sequencing Data

Authors: Fan Gao, Lior Pachter

Abstract:

The primary tool currently used to pre-process 10X Chromium single-cell ATAC-seq data is Cell Ranger, which can take very long to run on standard datasets. To facilitate rapid pre-processing that enables reproducible workflows, we present a suite of tools called scATAK for pre-processing single-cell ATAC-seq data that is 15 to 18 times faster than Cell Ranger on mouse and human samples. Our tool can also calculate chromatin interaction potential matrices, and generate open chromatin signal and interaction traces for cell groups. We use scATAK tool to explore the chromatin regulatory landscape of a healthy adult human brain and unveil cell-type specific features, and show that it provides a convenient and computational efficient approach for pre-processing single-cell ATAC-seq data.

Keywords: single-cell, ATAC-seq, bioinformatics, open chromatin landscape, chromatin interactome

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8312 Inhibitory Effect of P2Y1R Agonist 1-Indolinoalkyl 2-Phenolic Derivative on Prostate Cancer Cell Proliferation via the MAPK Signalling

Authors: Hien Thi Thu Le, Nuno Rafael Candeias, Olli Yli-Harja, Meenakshisundaram Kandhavelu

Abstract:

Purinergic receptor 1 (P2Y1R) is the potential therapeutic target for inducing prostate cancer (PCa) cell death. Recently, 1-indolinoalkyl 2-phenolic derivative, HIC, was identified as a P2Y1R agonist that increases apoptosis and inhibits cell proliferation of PCa. However, the biological effects of HIC have not been extensively studied at the molecular level. In the present study, we have investigated the anticancer effects of HIC and the molecular mechanisms underlying in PCa cells. Half maximal inhibitory concentration (IC₅₀) of HIC was measured as 15.98 μM and 15.64 μM for DU145 and PC3 cells, respectively. In addition, we found that HIC inhibited cell growth and metastasis of PC3 and DU145 cells colonies, spheroid areas, and migrated cells. RNA seq analysis revealed significant changes of over 3000 genes (p value < 0.05) upon HIC treatment in PC3 and DU145 cells. Genes involved in DNA damage, apoptosis, cell cycle arrest at G1/S phase were modulated by HIC treatment. MAPK and NF-κB protein array revealed the increased expression of ERK1/2, JNK1/2, p53 phosphorylation, and p53 protein. ERK1/2 and JNK1/2 activations are known to increase the stabilization of p53, a tumor suppressor protein, which is required to arrest the cell cycle at G1/S phase and cause cell death of PCa cells. Overall, our results suggest that HIC can serve as a multi-dimensional chemotherapeutic agent possessing strong cytotoxic, anti-cancer, and anti-metastasis against PCa growth.

Keywords: prostate cancer, P2Y1 receptor, apoptosis, metastasis

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8311 Redox-labeled Electrochemical Aptasensor Array for Single-cell Detection

Authors: Shuo Li, Yannick Coffinier, Chann Lagadec, Fabrizio Cleri, Katsuhiko Nishiguchi, Akira Fujiwara, Soo Hyeon Kim, Nicolas Clément

Abstract:

The need for single cell detection and analysis techniques has increased in the past decades because of the heterogeneity of individual living cells, which increases the complexity of the pathogenesis of malignant tumors. In the search for early cancer detection, high-precision medicine and therapy, the technologies most used today for sensitive detection of target analytes and monitoring the variation of these species are mainly including two types. One is based on the identification of molecular differences at the single-cell level, such as flow cytometry, fluorescence-activated cell sorting, next generation proteomics, lipidomic studies, another is based on capturing or detecting single tumor cells from fresh or fixed primary tumors and metastatic tissues, and rare circulating tumors cells (CTCs) from blood or bone marrow, for example, dielectrophoresis technique, microfluidic based microposts chip, electrochemical (EC) approach. Compared to other methods, EC sensors have the merits of easy operation, high sensitivity, and portability. However, despite various demonstrations of low limits of detection (LOD), including aptamer sensors, arrayed EC sensors for detecting single-cell have not been demonstrated. In this work, a new technique based on 20-nm-thick nanopillars array to support cells and keep them at ideal recognition distance for redox-labeled aptamers grafted on the surface. The key advantages of this technology are not only to suppress the false positive signal arising from the pressure exerted by all (including non-target) cells pushing on the aptamers by downward force but also to stabilize the aptamer at the ideal hairpin configuration thanks to a confinement effect. With the first implementation of this technique, a LOD of 13 cells (with5.4 μL of cell suspension) was estimated. In further, the nanosupported cell technology using redox-labeled aptasensors has been pushed forward and fully integrated into a single-cell electrochemical aptasensor array. To reach this goal, the LOD has been reduced by more than one order of magnitude by suppressing parasitic capacitive electrochemical signals by minimizing the sensor area and localizing the cells. Statistical analysis at the single-cell level is demonstrated for the recognition of cancer cells. The future of this technology is discussed, and the potential for scaling over millions of electrodes, thus pushing further integration at sub-cellular level, is highlighted. Despite several demonstrations of electrochemical devices with LOD of 1 cell/mL, the implementation of single-cell bioelectrochemical sensor arrays has remained elusive due to their challenging implementation at a large scale. Here, the introduced nanopillar array technology combined with redox-labeled aptamers targeting epithelial cell adhesion molecule (EpCAM) is perfectly suited for such implementation. Combining nanopillar arrays with microwells determined for single cell trapping directly on the sensor surface, single target cells are successfully detected and analyzed. This first implementation of a single-cell electrochemical aptasensor array based on Brownian-fluctuating redox species opens new opportunities for large-scale implementation and statistical analysis of early cancer diagnosis and cancer therapy in clinical settings.

Keywords: bioelectrochemistry, aptasensors, single-cell, nanopillars

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8310 Fast and Scale-Adaptive Target Tracking via PCA-SIFT

Authors: Yawen Wang, Hongchang Chen, Shaomei Li, Chao Gao, Jiangpeng Zhang

Abstract:

As the main challenge for target tracking is accounting for target scale change and real-time, we combine Mean-Shift and PCA-SIFT algorithm together to solve the problem. We introduce similarity comparison method to determine how the target scale changes, and taking different strategies according to different situation. For target scale getting larger will cause location error, we employ backward tracking to reduce the error. Mean-Shift algorithm has poor performance when tracking scale-changing target due to the fixed bandwidth of its kernel function. In order to overcome this problem, we introduce PCA-SIFT matching. Through key point matching between target and template, that adjusting the scale of tracking window adaptively can be achieved. Because this algorithm is sensitive to wrong match, we introduce RANSAC to reduce mismatch as far as possible. Furthermore target relocating will trigger when number of match is too small. In addition we take comprehensive consideration about target deformation and error accumulation to put forward a new template update method. Experiments on five image sequences and comparison with 6 kinds of other algorithm demonstrate favorable performance of the proposed tracking algorithm.

Keywords: target tracking, PCA-SIFT, mean-shift, scale-adaptive

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8309 A Criterion for Evaluating Plastic Loads: Plastic Work-Tangent Criterion

Authors: Ying Zhang

Abstract:

In ASME Boiler and Pressure Vessel Code, the plastic load is defined by applying the twice elastic slope (TES) criterion of plastic collapse to a characteristic load-deformation curve for the vessel. Several other plastic criterion such as tangent intersection (TI) criterion, plastic work (PW) criterion have been proposed in the literature, but all exhibit a practical limitation: difficult to define the load parameter for vessels subject to several combined loads. An alternative criterion: plastic work-tangent (PWT) criterion for evaluating plastic load in pressure vessel design by analysis is presented in this paper. According to the plastic work-load curve, when the tangent variation is less than a given value in the plastic phase, the corresponding load is the plastic load. Application of the proposed criterion is illustrated by considering the elastic-plastic response of the lower head of reactor pressure vessel (RPV) and nozzle intersection of (RPV). It is proposed that this is because the PWT criterion more fully represents the constraining effect of material strain hardening on the spread of plastic deformation and more efficiently ton evaluating the plastic load.

Keywords: plastic load, plastic work, strain hardening, plastic work-tangent criterion

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8308 SOCS3 Reverses Multidrug Resistance by Inhibiting MDR1 in Mammary Cell Carcinoma

Authors: S. Pradhan, D. Pradhan, G. Tripathy, T. Dasmohapatra

Abstract:

Suppressors of cytokine signalling (SOCS3), a newly indentified anti-apoptotic molecule is a downstream effecter of the receptor tyrosine kinase-Ras signalling pathway. Current study has uncovered that SOCS3 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS3 on MDR, we analyzed the expression of P-gp and SOCS3 by immune-histochemistry and found there was positive correlation between them. At that point we effectively interfered with RNA translation by the contamination of siRNA of SOCS3 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flowcytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS3 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: SOCS3gene, breast cancer, multidrug resistance, MDR1 gene, RNA interference

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8307 OFDM Radar for Detecting a Rayleigh Fluctuating Target in Gaussian Noise

Authors: Mahboobeh Eghtesad, Reza Mohseni

Abstract:

We develop methods for detecting a target for orthogonal frequency division multiplexing (OFDM) based radars. As a preliminary step we introduce the target and Gaussian noise models in discrete–time form. Then, resorting to match filter (MF) we derive a detector for two different scenarios: a non-fluctuating target and a Rayleigh fluctuating target. It will be shown that a MF is not suitable for Rayleigh fluctuating targets. In this paper we propose a reduced-complexity method based on fast Fourier transfrom (FFT) for such a situation. The proposed method has better detection performance.

Keywords: constant false alarm rate (CFAR), match filter (MF), fast Fourier transform (FFT), OFDM radars, Rayleigh fluctuating target

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8306 Biophysical Consideration in the Interaction of Biological Cell Membranes with Virus Nanofilaments

Authors: Samaneh Farokhirad, Fatemeh Ahmadpoor

Abstract:

Biological membranes are constantly in contact with various filamentous soft nanostructures that either reside on their surface or are being transported between the cell and its environment. In particular, viral infections are determined by the interaction of viruses (such as filovirus) with cell membranes, membrane protein organization (such as cytoskeletal proteins and actin filament bundles) has been proposed to influence the mechanical properties of lipid membranes, and the adhesion of filamentous nanoparticles influence their delivery yield into target cells or tissues. The goal of this research is to integrate the rapidly increasing but still fragmented experimental observations on the adhesion and self-assembly of nanofilaments (including filoviruses, actin filaments, as well as natural and synthetic nanofilaments) on cell membranes into a general, rigorous, and unified knowledge framework. The global outbreak of the coronavirus disease in 2020, which has persisted for over three years, highlights the crucial role that nanofilamentbased delivery systems play in human health. This work will unravel the role of a unique property of all cell membranes, namely flexoelectricity, and the significance of nanofilaments’ flexibility in the adhesion and self-assembly of nanofilaments on cell membranes. This will be achieved utilizing a set of continuum mechanics, statistical mechanics, and molecular dynamics and Monte Carlo simulations. The findings will help address the societal needs to understand biophysical principles that govern the attachment of filoviruses and flexible nanofilaments onto the living cells and provide guidance on the development of nanofilament-based vaccines for a range of diseases, including infectious diseases and cancer.

Keywords: virus nanofilaments, cell mechanics, computational biophysics, statistical mechanics

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8305 Short Term Distribution Load Forecasting Using Wavelet Transform and Artificial Neural Networks

Authors: S. Neelima, P. S. Subramanyam

Abstract:

The major tool for distribution planning is load forecasting, which is the anticipation of the load in advance. Artificial neural networks have found wide applications in load forecasting to obtain an efficient strategy for planning and management. In this paper, the application of neural networks to study the design of short term load forecasting (STLF) Systems was explored. Our work presents a pragmatic methodology for short term load forecasting (STLF) using proposed two-stage model of wavelet transform (WT) and artificial neural network (ANN). It is a two-stage prediction system which involves wavelet decomposition of input data at the first stage and the decomposed data with another input is trained using a separate neural network to forecast the load. The forecasted load is obtained by reconstruction of the decomposed data. The hybrid model has been trained and validated using load data from Telangana State Electricity Board.

Keywords: electrical distribution systems, wavelet transform (WT), short term load forecasting (STLF), artificial neural network (ANN)

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8304 Non-Linear Control in Positioning of PMLSM by Estimates of the Load Force by MRAS Method

Authors: Maamar Yahiaoui, Abdelrrahmene Kechich, Ismail Elkhallile Bousserhene

Abstract:

This article presents a study in simulation by means of MATLAB/Simulink software of the nonlinear control in positioning of a linear synchronous machine with the esteemed force of load, to have effective control in the estimator in all tests the wished trajectory follows and the disturbance of load start. The results of simulation prove clearly that the control proposed can detect the reference of positioning the value estimates of load force equal to the actual value.

Keywords: mathematical model, Matlab, PMLSM, control, linearization, estimator, force, load, current

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8303 In-silico Target Identification and Molecular Docking of Withaferin A and Withanolide D to Understand their Anticancer Therapeutic Potential

Authors: Devinder Kaur Sugga, Ekamdeep Kaur, Jaspreet Kaur, C. Rajesh, Preeti Rajesh, Harsimran Kaur

Abstract:

Withanolides are steroidal lactones and are highly oxygenated phytoconstituents that can be developed as potential anti-carcinogenic agents. The two main withanolides, namely Withaferin A and Withanolides D, have been extensively studied for their pharmacological activities. Both these withanolides are present in the Withania somnifera (WS) leaves belonging to the family Solanaceae, also known as “Indian ginseng .”In this study effects of WS leaf extract on the MCF7 breast cancer cell line were investigated by performing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effects and in vitro wound-healing assay to study the effect on cancer cell migration. Our data suggest WS extracts have cytotoxic effects and are effective anti-migrating agents and thus can be a source of potential candidates for the development of potential agents against metastasis. Thus, it can be a source of potential candidates for the development of potential agents against metastasis. Insight into these results, the in-silico approach to identify the possible protein targets interacting with withanolides was taken. Protein kinase C alpha (PKCα) was among the selected 5 top-ranked target proteins identified by the Swiss Target Prediction tool. PKCα is known to promote the growth and invasion of cancer cells and is being evaluated as a prognostic biomarker and therapeutic target in clinically aggressive tumors. Molecular docking of Withaferin A and Withanolides D was performed using AutoDock Vina. Both the bioactive compounds interacted with PKCα. The targets predicted using this approach will serve as leads for the possible therapeutic potential of withanolides, the bioactive ingredients of WS extracts, as anti-cancer drugs.

Keywords: withania somnifera, withaferin A, withanolides D, PKCα

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8302 Behavior of A Vertical Pile Under the Effect of an Inclined Load in Loose Sand

Authors: Fathi Mohamed Abdrabbo, Khaled Esayed Gaaver, Musab Musa Eldooma

Abstract:

This paper presents an attempt made to investigate the behavior of a single vertical steel hollow pile embedded in sand subjected to compressive inclined load at various inclination angles α through FEM package MIDAS GTS/NX 2019. The effect of the inclination angle and slenderness ratio on the performance of the pile was investigated. Inclined load caring capacity and pile stiffness, as well as lateral deformation profiles along with the pile, were presented. The global, vertical, and horizontal load displacements of pile head, as well as the deformation profiles along the pile and the pile stiffness, are significantly affected by α. It was observed that the P-Y curves of the pile-soil system are independent of α. Also, the slenderness ratios are markedly affecting the behavior of the pile. In addition, there was a noticeable effect of the horizontal load component of the applied load on the vertical behavior of the pile, whereas there was no influence of the presence of vertical load on the horizontal behavior of the pile.

Keywords: deep foundation, piles, inclined load, pile deformations

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8301 Preparation of Gramine Nanosuspension and Protective Effect of Gramine on Human Oral Cell Lines by Induction of Apoptosis

Authors: K. Suresh, R. Arunkumar

Abstract:

The objective of this study is to investigate the preparation of gramine nano suspension and protective effect of Gramine on the apoptosis of laryngeal cancer cells cell line (HEp-2 and KB). The growth inhibition rate of Hep-2 and KB cells in vitro were measured by MTT assay and apoptosis by, levels of reactive oxygen species, mitochondrial membrane potential, morphological changes and flowcytometry. Based on the results, we determined the effective doses of gramine as 127.23µm/ml for 24 hr and 119.81 µm/ml for 48hr in hep-2 cell line and 147.58 µm ml for 24 hr and 123.74µm µm/ml for 48hr in KB cell line. cytotoxicity effects of gramine were confirmed by treatment of HEp-2 cell and KB cell with IC50 concentration of gramine resulted in sequences of events marked by the enhance the apoptosis accompanied by loss of cell viability, modulation of reactive oxygen species and cell cycle arrest through the induction of G0/G1 phase arrest on HEp-2 cells. Our study suggests that the nanosuspension of gramine possesses the more cytotoxic effect of cancer cells and a novel candidate for cancer chemoprevention.

Keywords: apoptosis, HEp-2 cell line, KB cell line mitochondria, gramine, nanosuspension

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8300 SOCS1 Inhibits MDR1 in Mammary Cell Carcinoma Reverses Multidrug Resistance

Authors: Debasish Pradhan, Shaktiprasad Pradhan, Rakesh Kumar Pradhan, Gitanjali Tripathy

Abstract:

Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. The current study has uncovered that SOCS1 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS1 on MDR, we analyzed the expression of P-gp and SOCS1 by immunohistochemistry and found there was a positive correlation between them. At that point, we effectively interfered with RNA translation by the contamination of siRNA of SOCS1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi, the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise, the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flow cytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS1 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: breast cancer, multidrug resistance, SOCS1 gene, MDR1 gene, RNA interference

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8299 Target Drug Delivery of Pamidronate Nanoparticles for Enhancing Osteoblastic Activity in Osteoporosis

Authors: Purnima Rawat, Divya Vohora, Sarika Gupta, Farhan J. Ahmad, Sushama Talegaonkar

Abstract:

Nanoparticles (NPs) that target bone tissue were developed using PLGA–mPEG (poly(lactic-co-glycolic-acid)–polyethylene glycol) diblock copolymers by using pamidronate as a bone-targeting moieties. These NPs are expected to enable the transport of hydrophilic drugs. The NP was prepared by in situ polymerization method, and their in- vitro characteristics were evaluated using dynamic light scattering, transmission electron microscopy (TEM) and in phosphate-buffered solution. The bone targeting potential of the NP was also evaluated on in-vitro pre-osteoblast MCT3E1 cell line using ALP activity, degree of mineralization and RT-PCR assay. The average particle size of the NP was 101.6 ± 3.7nm, zeta potential values were negative (-25±0.34mV) of the formulations and the entrapment efficiency was 93± 3.1 % obtained. The moiety of the PLGA–mPEG–pamidronate NPs exhibited the best apatite mineral binding ability in-vitro MCT3E1 pre-osteoblast cell line. Our results suggested that the developed nanoparticles may use as a delivery system for Pamidronate in bone repair and regeneration, warranting further evaluation of the treatment of bone disease.

Keywords: nanoparticle, pamidronate, in-situ polymerization, osteoblast

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8298 Compilation of Load Spectrum of Loader Drive Axle

Authors: Wei Yongxiang, Zhu Haoyue, Tang Heng, Yuan Qunwei

Abstract:

In order to study the preparation method of gear fatigue load spectrum for loaders, the load signal of four typical working conditions of loader is collected. The signal that reflects the law of load change is obtained by preprocessing the original signal. The torque of the drive axle is calculated by using the rain flow counting method. According to the operating time ratio of each working condition, the two-dimensional load spectrum based on the real working conditions of the drive axle of loader is established by the cycle extrapolation and synthesis method. The two-dimensional load spectrum is converted into one-dimensional load spectrum by means of the mean of torque equal damage method. Torque amplification includes the maximum load torque of the main reduction gear. Based on the theory of equal damage, the accelerated cycles are calculated. In this way, the load spectrum of the loading condition of the drive axle is prepared to reflect loading condition of the loader. The load spectrum can provide reference for fatigue life test and life prediction of loader drive axle.

Keywords: load spectrum, axle, torque, rain-flow counting method, extrapolation

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8297 Investigation of Different Control Stratgies for UPFC Decoupled Model and the Impact of Location on Control Parameters

Authors: S. A. Al-Qallaf, S. A. Al-Mawsawi, A. Haider

Abstract:

In order to evaluate the performance of a unified power flow controller (UPFC), mathematical models for steady state and dynamic analysis are to be developed. The steady state model is mainly concerned with the incorporation of the UPFC in load flow studies. Several load flow models for UPFC have been introduced in literature, and one of the most reliable models is the decoupled UPFC model. In spite of UPFC decoupled load flow model simplicity, it is more robust compared to other UPFC load flow models and it contains unique capabilities. Some shortcoming such as additional set of nonlinear equations are to be solved separately after the load flow solution is obtained. The aim of this study is to investigate the different control strategies that can be realized in the decoupled load flow model (individual control and combined control), and the impact of the location of the UPFC in the network on its control parameters.

Keywords: UPFC, decoupled model, load flow, control parameters

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8296 Biologically Inspired Small Infrared Target Detection Using Local Contrast Mechanisms

Authors: Tian Xia, Yuan Yan Tang

Abstract:

In order to obtain higher small target detection accuracy, this paper presents an effective algorithm inspired by the local contrast mechanism. The proposed method can enhance target signal and suppress background clutter simultaneously. In the first stage, a enhanced image is obtained using the proposed Weighted Laplacian of Gaussian. In the second stage, an adaptive threshold is adopted to segment the target. Experimental results on two changeling image sequences show that the proposed method can detect the bright and dark targets simultaneously, and is not sensitive to sea-sky line of the infrared image. So it is fit for IR small infrared target detection.

Keywords: small target detection, local contrast, human vision system, Laplacian of Gaussian

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8295 CRISPR-DT: Designing gRNAs for the CRISPR-Cpf1 System with Improved Target Efficiency and Specificity

Authors: Houxiang Zhu, Chun Liang

Abstract:

The CRISPR-Cpf1 system has been successfully applied in genome editing. However, target efficiency of the CRISPR-Cpf1 system varies among different gRNA sequences. The published CRISPR-Cpf1 gRNA data was reanalyzed. Many sequences and structural features of gRNAs (e.g., the position-specific nucleotide composition, position-nonspecific nucleotide composition, GC content, minimum free energy, and melting temperature) correlated with target efficiency were found. Using machine learning technology, a support vector machine (SVM) model was created to predict target efficiency for any given gRNAs. The first web service application, CRISPR-DT (CRISPR DNA Targeting), has been developed to help users design optimal gRNAs for the CRISPR-Cpf1 system by considering both target efficiency and specificity. CRISPR-DT will empower researchers in genome editing.

Keywords: CRISPR-Cpf1, genome editing, target efficiency, target specificity

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8294 In Silico Analysis of Salivary miRNAs to Identify the Diagnostic Biomarkers for Oral Cancer

Authors: Andleeb Zahra, Itrat Rubab, Sumaira Malik, Amina Khan, Muhammad Jawad Khan, M. Qaiser Fatmi

Abstract:

Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. Recent studies have highlighted the role of miRNA in disease pathology, indicating its potential use in an early diagnostic tool. miRNAs are small, double stranded, non-coding RNAs that regulate gene expression by deregulating mRNAs. miRNAs play important roles in modifying various cellular processes such as cell growth, differentiation, apoptosis, and immune response. Dis-regulated expression of miRNAs is known to affect the cell growth, and this may function as tumor suppressors or oncogenes in various cancers. Objectives: The main objectives of this study were to characterize the extracellular miRNAs involved in oral cancer (OC) to assist early detection of cancer as well as to propose a list of genes that can potentially be used as biomarkers of OC. We used gene expression data by microarrays already available in literature. Materials and Methods: In the first step, a total of 318 miRNAs involved in oral carcinoma were shortlisted followed by the prediction of their target genes. Simultaneously, the differentially expressed genes (DEGs) of oral carcinoma from all experiments were identified. The common genes between lists of DEGs of OC based on experimentally proven data and target genes of each miRNA were identified. These common genes are the targets of specific miRNA, which is involved in OC. Finally, a list of genes was generated which may be used as biomarker of OC. Results and Conclusion: In results, we included some of pathways in cancer to show the change in gene expression under the control of specific miRNA. Ingenuity pathway analysis (IPA) provided a list of major biomarkers like CDH2, CDK7 and functional enrichment analysis identified the role of miRNA in major pathways like cell adhesion molecules pathway affected by cancer. We observed that at least 25 genes are regulated by maximum number of miRNAs, and thereby, they can be used as biomarkers of OC. To better understand the role of miRNA with respect to their target genes further experiments are required, and our study provides a platform to better understand the miRNA-OC relationship at genomics level.

Keywords: biomarkers, gene expression, miRNA, oral carcinoma

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8293 Scheduling Nodes Activity and Data Communication for Target Tracking in Wireless Sensor Networks

Authors: AmirHossein Mohajerzadeh, Mohammad Alishahi, Saeed Aslishahi, Mohsen Zabihi

Abstract:

In this paper, we consider sensor nodes with the capability of measuring the bearings (relative angle to the target). We use geometric methods to select a set of observer nodes which are responsible for collecting data from the target. Considering the characteristics of target tracking applications, it is clear that significant numbers of sensor nodes are usually inactive. Therefore, in order to minimize the total network energy consumption, a set of sensor nodes, called sentinel, is periodically selected for monitoring, controlling the environment and transmitting data through the network. The other nodes are inactive. Furthermore, the proposed algorithm provides a joint scheduling and routing algorithm to transmit data between network nodes and the fusion center (FC) in which not only provides an efficient way to estimate the target position but also provides an efficient target tracking. Performance evaluation confirms the superiority of the proposed algorithm.

Keywords: coverage, routing, scheduling, target tracking, wireless sensor networks

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8292 BRG1 and Ep300 as a Transcriptional Regulators of Breast Cancer Growth

Authors: Maciej Sobczak, Julita Pietrzak, Tomasz Płoszaj, Agnieszka Robaszkiewicz

Abstract:

Brg1, a member of SWI/SNF complex, plays a role in chromatin remodeling, therefore, regulates expression of many genes. Brg1 is an ATPase of SWI/SNF complex, thus its activity requires ATP. Through its bromodomain recognizes acetylated histone residues and evicts them, thus promoting transcriptionally active state of chromatin. One of the enzymes that is responsible for acetylation of histone residues is Ep300. It was previously shown in the literature that cooperation of Brg1 and Ep300 occurs at the promoter regions that have binding sites for E2F-family transcription factors as well as CpG islands. According to literature, approximately 20% of human cancer possess mutation in Brg1 or any other crucial SWI/SNF subunit. That phenomenon makes Brg1-Ep300 a very promising target for anti-cancer therapy. Therefore in our study, we investigated if physical interaction between Brg1 and Ep300 exists and what impact those two proteins have on key for breast cancer cells processes such as DNA damage repair and cell proliferation. Bioinformatical analysis pointed out, that genes involved in cell proliferation and DNA damage repair are overexpressed in MCF7 and MDA-MB-231 cells. Moreover, promoter regions of these genes are highly acetylated, which suggests high transcriptional activity of those sites. Notably, many of those gene possess within their promoters an E2F, Brg1 motives, as well as CpG islands and acetylated histones. Our data show that Brg1 physically interacts with Ep300, and together they regulate expression of genes involved in DNA damage repair and cell proliferation. Upon inhibiting Brg1 or Ep300, expression of vital for cancer cell survival genes such as CDK2/4, BRCA1/2, PCNA, and XRCC1 is decreased in MDA-MB-231 and MCF7 cells. Moreover, inhibition or silencing of either Brg1 or Ep300 leads to cell cycle arrest in G1. After inhibition of BRG1 or Ep300 on tested gene promoters, the repressor complex including Rb, HDAC1, and EZH2 is formed, which inhibits gene expression. These results highlight potentially significant target for targeted anticancer therapy to be introduced as a supportive therapy.

Keywords: brg1, ep300, breast cancer, epigenetics

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8291 Ring FingerPortein 2 (RNF2) Targeting by miRNAs in Breast Cancer Cell Lines

Authors: Ceyda Okudu, Secil Eroglu, Khandakar A. S. M. Saadat, Sibel O. Balci

Abstract:

Ring Finger Protein 2 (RNF2) is a member of polycomb repressive complex 1 (PRC1), which is one of the epigenetic regulators in the genome. When RNF2 combines with other PRC1 members, it mediates the mono-ubiquitination of Histon2A (H2A). In breast cancer, RNF2 is commonly overexpressed, and also it promotes metastasis and invasion in other aggressive tumors like melanoma, prostate, and hepatocarcinoma. The role of RNF2 in the metastasis and invasion of breast cancer has not yet been elucidated. Our aim is to observe the role of RNF2 in metastasis and invasion in this study by miRNA mediated RNF2 gene silencing in breast cancer cell lines. We selected miRNAs, targeting to RNF2 by searching online databases. miR-17-5p, miR20a-5p, and miR-106b-5p were transfected to breast cancer cell lines (MCF-7, MDA-MB-231, SK-BR-3, and ZR-75-1), and also we used normal breast epithelial cell line (hTERT-HME1) to compare RNF2 gene expression level. After 48-72 hours post-transfection, mRNAs were isolated from the cells, and gene expressions were measured by RT-qPCR after from cDNA syntheses. We observed that RNF2 was highly expressed in SK-BR-3 and MDA-MB-231 cell lines opposite to MCF-7 and ZR-75-1 cell lines. RNF2 was downregulated 5, 5 and 7 fold by miR17-5p, miR20a-5p and miR106b-5p respectively in MCF-7. However, in SK-BR-3 and ZR-75-1 cell lines, miRNAs did not affect significantly RNF2 gene expression level. miR20a-5p decreased RNF2 3 fold and miR17-5p and miR106b-5p did not affect MDA-MB-231. After gene expression analysis, we performed metastasis and invasion assay in MCF-7 cells. For metastasis, we used both wound healing assay and Transwell Cell Migration Assay, and we used Transwell Cell Invasion Assay for invasion. The data of this assay showed that miR17-5p and miR20a-5p decreased both invasion and metastasis level, but miR106b-5p has no effect. We would like to conclude that RNF2 can be targeted by miR17-5p, miR20a-5p and miR106b-5p in MCF-7 cells and also RNF2, which is one of the upregulated genes in aggressive tumor, can be decreased by using these miRNAs. In future, we would like to confirm these results at the protein level and also whether these miRNAs are direct target of RNF2 or not.

Keywords: breast cancer, epigenetic, microRNAs, RNF2

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8290 Clutter Suppression Based on Singular Value Decomposition and Fast Wavelet Algorithm

Authors: Ruomeng Xiao, Zhulin Zong, Longfa Yang

Abstract:

Aiming at the problem that the target signal is difficult to detect under the strong ground clutter environment, this paper proposes a clutter suppression algorithm based on the combination of singular value decomposition and the Mallat fast wavelet algorithm. The method first carries out singular value decomposition on the radar echo data matrix, realizes the initial separation of target and clutter through the threshold processing of singular value, and then carries out wavelet decomposition on the echo data to find out the target location, and adopts the discard method to select the appropriate decomposition layer to reconstruct the target signal, which ensures the minimum loss of target information while suppressing the clutter. After the verification of the measured data, the method has a significant effect on the target extraction under low SCR, and the target reconstruction can be realized without the prior position information of the target and the method also has a certain enhancement on the output SCR compared with the traditional single wavelet processing method.

Keywords: clutter suppression, singular value decomposition, wavelet transform, Mallat algorithm, low SCR

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8289 Forced Vibration of an Auxetic Cylindrical Shell Containing Fluid Under the Influence of Shock Load

Authors: Korosh Khorshidi

Abstract:

Due to the increasing use of different materials, such as auxetic structures, it is necessary to investigate mechanical phenomena, such as vibration, in structures made of these types of materials. This paper examines the forced vibrations of a three-layer cylindrical shell containing inviscid fluid under shock load. All three layers are made of aluminum, and the central layer is made of a re-entrant honeycomb cell structure. Using high-order shear deformation theories (HSDT) and Hamilton’s principle, the governing equations of the system have been extracted and solved by the Galerkin weighted residual method. The outputs of the Abaqus finite element software are used to validate the results. The system is investigated with both simple and clamped support conditions. Finally, this study investigates the influence of the geometrical parameters of the shell and the auxetic structure, as well as the type, intensity, duration, and location of the load, and the effect of the fluid on the dynamic and time responses.

Keywords: force vibration, cylindrical shell, auxetic structure, inviscid fluid

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8288 Optimal Feedback Linearization Control of PEM Fuel Cell

Authors: E. Shahsavari, R. Ghasemi, A. Akramizadeh

Abstract:

This paper presents a new method to design nonlinear feedback linearization controller for polymer electrolyte membrane fuel cells (PEMFCs). A nonlinear controller is designed based on nonlinear model to prolong the stack life of PEM fuel cells. Since it is known that large deviations between hydrogen and oxygen partial pressures can cause severe membrane damage in the fuel cell, feedback linearization is applied to the PEM fuel cell system so that the deviation can be kept as small as possible during disturbances or load variations. To obtain an accurate feedback linearization controller, tuning the linear parameters are always important. So in proposed study NSGA_II method was used to tune the designed controller in aim to decrease the controller tracking error. The simulation result showed that the proposed method tuned the controller efficiently.

Keywords: nonlinear dynamic model, polymer electrolyte membrane fuel cells, feedback linearization, optimal control, NSGA_II

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8287 Seismic Assessment of Passive Control Steel Structure with Modified Parameter of Oil Damper

Authors: Ahmad Naqi

Abstract:

Today, the passively controlled buildings are extensively becoming popular due to its excellent lateral load resistance circumstance. Typically, these buildings are enhanced with a damping device that has high market demand. Some manufacturer falsified the damping device parameter during the production to achieve the market demand. Therefore, this paper evaluates the seismic performance of buildings equipped with damping devices, which their parameter modified to simulate the falsified devices, intentionally. For this purpose, three benchmark buildings of 4-, 10-, and 20-story were selected from JSSI (Japan Society of Seismic Isolation) manual. The buildings are special moment resisting steel frame with oil damper in the longitudinal direction only. For each benchmark buildings, two types of structural elements are designed to resist the lateral load with and without damping devices (hereafter, known as Trimmed & Conventional Building). The target building was modeled using STERA-3D, a finite element based software coded for study purpose. Practicing the software one can develop either three-dimensional Model (3DM) or Lumped Mass model (LMM). Firstly, the seismic performance of 3DM and LMM models was evaluated and found excellent coincide for the target buildings. The simplified model of LMM used in this study to produce 66 cases for both of the buildings. Then, the device parameters were modified by ± 40% and ±20% to predict many possible conditions of falsification. It is verified that the building which is design to sustain the lateral load with support of damping device (Trimmed Building) are much more under threat as a result of device falsification than those building strengthen by damping device (Conventional Building).

Keywords: passive control system, oil damper, seismic assessment, lumped mass model

Procedia PDF Downloads 83
8286 Study of Magnetic Nanoparticles’ Endocytosis in a Single Cell Level

Authors: Jefunnie Matahum, Yu-Chi Kuo, Chao-Ming Su, Tzong-Rong Ger

Abstract:

Magnetic cell labeling is of great importance in various applications in biomedical fields such as cell separation and cell sorting. Since analytical methods for quantification of cell uptake of magnetic nanoparticles (MNPs) are already well established, image analysis on single cell level still needs more characterization. This study reports an alternative non-destructive quantification methods of single-cell uptake of positively charged MNPs. Magnetophoresis experiments were performed to calculate the number of MNPs in a single cell. Mobility of magnetic cells and the area of intracellular MNP stained by Prussian blue were quantified by image processing software. ICP-MS experiments were also performed to confirm the internalization of MNPs to cells. Initial results showed that the magnetic cells incubated at 100 µg and 50 µg MNPs/mL concentration move at 18.3 and 16.7 µm/sec, respectively. There is also an increasing trend in the number and area of intracellular MNP with increasing concentration. These results could be useful in assessing the nanoparticle uptake in a single cell level.

Keywords: magnetic nanoparticles, single cell, magnetophoresis, image analysis

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8285 HIV-1 Nef Mediates Host Invasion by Differential Expression of Alpha-Enolase

Authors: Reshu Saxena, R. K. Tripathi

Abstract:

HIV-1 transmission and spread involves significant host-virus interaction. Potential targets for prevention of HIV-1 lies at the site of mucosal barriers. Thus a better understanding of how HIV-1 infects target cells at such sites and lead their invasion is required, with prime focus on the host determinants regulating HIV-1 spread. HIV-1 Nef is important for viral infectivity and pathogenicity. It promotes HIV-1 replication, facilitating immune evasion by interacting with various host factors and altering cellular pathways via multiple protein-protein interactions. In this study nef was sequenced from HIV-1 patients, and showed specific mutations revealing sequence variability in nef. To explore the difference in Nef functionality based on sequence variability we have studied the effects of HIV-1 Nef in human SupT1 T cell line and (THP-1) monocyte-macrophage cell lines through proteomics approach. 2D-Gel Electrophoresis in control and Nef-transfected SupT1 cells demonstrated several differentially expressed proteins with significant modulation of alpha-enolase. Through further studies, effects of Nef on alpha-enolase regulation were found to be cell lineage-specific, being stimulatory in macrophages/monocytes, inhibitory in T cells and without effect in HEK-293 cells. Cell migration and invasion studies were employed to determine biological function affected by Nef mediated regulation of alpha-enolase. Cell invasion was enhanced in THP-1 cells but was inhibited in SupT1 cells by wildtype nef. In addition, the modulation of enolase and cell invasion remained unaffected by a unique nef variant. These results indicated that regulation of alpha-enolase expression and invasive property of host cells by Nef is sequence specific, suggesting involvement of a particular motif of Nef. To precisely determine this site, we designed a heptapeptide including the suggested alpha-enolase regulating sequence of nef and a nef mutant with deletion of this site. Macrophages/monocytes being the major cells affected by HIV-1 at mucosal barriers, were particularly investigated by the nef mutant and peptide. Both the nef mutant and heptapeptide led to inhibition of enhanced enolase expression and increased invasiveness in THP-1 cells. Together, these findings suggest a possible mechanism of host invasion by HIV-1 through Nef mediated regulation of alpha-enolase and identifies a potential therapeutic target for HIV-1 entry at mucosal barriers.

Keywords: HIV-1 Nef, nef variants, host-virus interaction, tissue invasion

Procedia PDF Downloads 384
8284 In-Situ Quasistatic Compression and Microstructural Characterization of Aluminium Foams of Different Cell Topology

Authors: M. A. Islam, P. J. Hazell, J. P. Escobedo, M. Saadatfar

Abstract:

Quasistatic compression and micro structural characterization of closed cell aluminium foams of different pore size and cell distributions has been carried out. Metallic foams have good potential for lightweight structures for impact and blast mitigation and therefore it is important to find out the optimized foam structure (i.e. cell size, shape, relative density, and distribution) to maximize energy absorption. In this paper, we present results for two different aluminium metal foams of density 0.5 g/cc and 0.7 g/cc respectively that have been tested in quasi-static compression. The influence of cell geometry and cell topology on quasistatic compression behavior has been investigated using computed tomography (micro-CT) analysis. The compression behavior and micro structural characterization will be presented.

Keywords: metal foams, micro-CT, cell topology, quasistatic compression

Procedia PDF Downloads 427