Search results for: miRNA:mRNA target prediction

Authors: Sagir M. Yusuf, Chris Baber

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In this paper, we describe how Bayesian inferential reasoning will contributes in obtaining a well-satisfied prediction for Distributed Constraint Optimization Problems (DCOPs) with uncertainties. We also demonstrate how DCOPs could be merged to multi-agent knowledge understand and prediction (i.e. Situation Awareness). The DCOPs functions were merged with Bayesian Belief Network (BBN) in the form of situation, awareness, and utility nodes. We describe how the uncertainties can be represented to the BBN and make an effective prediction using the expectation-maximization algorithm or conjugate gradient descent algorithm. The idea of variable prediction using Bayesian inference may reduce the number of variables in agents’ sampling domain and also allow missing variables estimations. Experiment results proved that the BBN perform compelling predictions with samples containing uncertainties than the perfect samples. That is, Bayesian inference can help in handling uncertainties and dynamism of DCOPs, which is the current issue in the DCOPs community. We show how Bayesian inference could be formalized with Distributed Situation Awareness (DSA) using uncertain and missing agents’ data. The whole framework was tested on multi-UAV mission for forest fire searching. Future work focuses on augmenting existing architecture to deal with dynamic DCOPs algorithms and multi-agent information merging.

Keywords: DCOP, multi-agent reasoning, Bayesian reasoning, swarm intelligence

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Authors: Mikhail Gritskevich, Sebastian Hohenstein

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The paper presents the results of a detailed assessment of several modern Reynolds Averaged Navier-Stokes (RANS) turbulence models for prediction of C3X vane film cooling at various injection regimes. Three models are considered, namely the Shear Stress Transport (SST) model, the modification of the SST model accounting for the streamlines curvature (SST-CC), and the Explicit Algebraic Reynolds Stress Model (EARSM). It is shown that all the considered models face with a problem in prediction of the adiabatic effectiveness in the vicinity of the cooling holes; however, accounting for the Reynolds stress anisotropy within the EARSM model noticeably increases the solution accuracy. On the other hand, further downstream all the models provide a reasonable agreement with the experimental data for the adiabatic effectiveness and among the considered models the most accurate results are obtained with the use EARMS.

Keywords: discrete holes film cooling, Reynolds Averaged Navier-Stokes (RANS), Reynolds stress tensor anisotropy, turbulent heat transfer

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Authors: Pooja Rani, G. S. Mahapatra, S. K. Pandey

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In this paper, we propose a novel approach of Neural Network and Particle Swarm Optimization methods for software reliability prediction. We first explain how to apply compound function in neural network so that we can derive a Flexible Logistic (S-shaped) Growth Curve (FLGC) model. This model mathematically represents software failure as a random process and can be used to evaluate software development status during testing. To avoid trapping in local minima, we have applied Particle Swarm Optimization method to train proposed model using failure test data sets. We drive our proposed model using computational based intelligence modeling. Thus, proposed model becomes Neuro-Particle Swarm Optimization (NPSO) model. We do test result with different inertia weight to update particle and update velocity. We obtain result based on best inertia weight compare along with Personal based oriented PSO (pPSO) help to choose local best in network neighborhood. The applicability of proposed model is demonstrated through real time test data failure set. The results obtained from experiments show that the proposed model has a fairly accurate prediction capability in software reliability.

Keywords: software reliability, flexible logistic growth curve model, software cumulative failure prediction, neural network, particle swarm optimization

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Authors: Andri Ottesen, Sam Toglaw, Mirna Safa

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Entrepreneurial companies on their developing path from an idea to a corporation go through a similar six-step process. Each of these six development steps is supported by a distinctive financing path. This paper explores the Kuwait model for Entrepreneurial Finance and Development through in-depth interviews with ten successful Kuwaiti entrepreneurs. This paper offers insight into the development and financing of entrepreneurial companies in this oil-rich, predominantly Islamic country that are in many ways different from the steps. Western entrepreneurial companies go through. This model could be used to understand the commonalities and the difference between entrepreneurial development and financing and could be used to bridge the gap.

Keywords: entrepreneurial-financing, entrepreneurial-developing, Kuwait, Vancouver school

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Authors: Michael Ayomoh, Adriaan Roux, Oyindamola Omotuyi

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This paper presents an efficient robot navigation model in a multi-target domain amidst static and dynamic workspace obstacles. The problem is that of developing an optimal algorithm to minimize the total travel time of a robot as it visits all target points within its task domain amidst unknown workspace obstacles and finally return to its initial position. In solving this problem, a classical algorithm was first developed to compute the optimal number of paths to be travelled by the robot amidst the network of paths. The principle of shortest distance between robot and targets was used to compute the target point visitation order amidst workspace obstacles. Algorithm premised on the standard polar coordinate system was developed to determine the length of obstacles encountered by the robot hence giving room for a geometrical estimation of the total surface area occupied by the obstacle especially when classified as a relevant obstacle i.e. obstacle that lies in between a robot and its potential visitation point. A stochastic model was developed and used to estimate the likelihood of a dynamic obstacle bumping into the robot’s navigation path and finally, the navigation/obstacle avoidance algorithm was hinged on the hybrid virtual force field (HVFF) method. Significant modelling constraints herein include the choice of navigation path to selected target points, the possible presence of static obstacles along a desired navigation path and the likelihood of encountering a dynamic obstacle along the robot’s path and the chances of it remaining at this position as a static obstacle hence resulting in a case of re-routing after routing. The proposed algorithm demonstrated a high potential for optimal solution in terms of efficiency and effectiveness.

Keywords: multi-target, mobile robot, optimal path, static obstacles, dynamic obstacles

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Authors: A. Hakimiyan, H. Namazi

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Human behavior is defined as a range of behaviors exhibited by humans who are influenced by different internal or external sources. Human behavior is the subject of much research in different areas of psychology and neuroscience. Despite some advances in studies related to forecasting of human behavior, there are not many researches which consider the effect of the time delay between the presence of stimulus and the related human response. Analysis of EEG signal as a fractal time series is one of the major tools for studying the human behavior. In the other words, the human brain activity is reflected in his EEG signal. Artificial Neural Network has been proved useful in forecasting of different systems’ behavior especially in engineering areas. In this research, a time delay neural network is trained and tested in order to forecast the human EEG signal and subsequently human behavior. This neural network, by introducing a time delay, takes care of the lagging time between the occurrence of the stimulus and the rise of the subsequent action potential. The results of this study are useful not only for the fundamental understanding of human behavior forecasting, but shall be very useful in different areas of brain research such as seizure prediction.

Keywords: human behavior, EEG signal, time delay neural network, prediction, lagging time

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Authors: Anika Chebrolu

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Mono-targeted drugs can be of limited efficacy against complex diseases. Recently, multi-target drug design has been approached as a promising tool to fight against these challenging diseases. However, the scope of current computational approaches for multi-target drug design is limited. DeepLig presents a de-novo drug discovery platform that uses reinforcement learning to generate and optimize novel, potent, and multitargeted drug candidates against protein targets. DeepLig’s model consists of two networks in interplay: a generative network and a predictive network. The generative network, a Stack- Augmented Recurrent Neural Network, utilizes a stack memory unit to remember and recognize molecular patterns when generating novel ligands from scratch. The generative network passes each newly created ligand to the predictive network, which then uses multiple Graph Attention Networks simultaneously to forecast the average binding affinity of the generated ligand towards multiple target proteins. With each iteration, given feedback from the predictive network, the generative network learns to optimize itself to create molecules with a higher average binding affinity towards multiple proteins. DeepLig was evaluated based on its ability to generate multi-target ligands against two distinct proteins, multi-target ligands against three distinct proteins, and multi-target ligands against two distinct binding pockets on the same protein. With each test case, DeepLig was able to create a library of valid, synthetically accessible, and novel molecules with optimal and equipotent binding energies. We propose that DeepLig provides an effective approach to design multi-targeted drug therapies that can potentially show higher success rates during in-vitro trials.

Keywords: drug design, multitargeticity, de-novo, reinforcement learning

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Authors: Petra Borilova Linhartova, Michaela Ruckova, Sabina Sevcikova, Natalie Mlcuchova, Jan Bohm, Katerina Zukalova, Monika Vlachova, Jiri Dolina, Lumir Kunovsky, Radek Kroupa, Zdenek Pavlovsky, Zdenek Danek, Tereza Deissova, Lydie Izakovicova Holla, Ondrej Slaby, Zdenek Kala

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Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy that frequently develops from Barrett's esophagus (BE), a premalignant pathologic change occurring in the lower end of the esophagus. Specific microRNAs (miRNAs), small non-coding RNAs that function as posttranscriptional regulators of gene expression, were repeatedly proved to play key roles in the pathogenesis of these diseases. This pilot study aimed to analyze four selected miRNAs in esophageal tissues from healthy controls (HC) and patients with reflux esophagitis (RE)/BE/EAC, as well as to compare expression at the site of Barrett's mucosa/adenocarcinoma and healthy esophageal tissue outside the area of the main pathology in patients with BE/EAC. In this pilot study, 22 individuals (3 HC, 8 RE, 5 BE, 6 EAC) were included and endoscopically examined. RNA was isolated from the fresh-frozen esophageal tissue (stored in the RNAlater™ Stabilization Solution −70°C) using the AllPrep DNA/RNA/miRNA Universal Kit. Subsequent RT-qPCR analysis was performed using selected TaqMan MicroRNA Assays for miR-21, miR-34a, miR-196a, miR-196b, and endogenous control (RNU44). While the expression of miR-21 in the esophageal tissue with the main pathology was decreased in BE and EAC patients in comparison to the group of HC and RE patients (p=0.01), the expression of miR-196a was increased in the BE and EAC patients (p<0.01). Correlations between those miRNAs expression in tissue and severity of diagnosis were observed (p<0.05). In addition, miR-196a was significantly more expressed at the site with the main pathology than in paired adjacent esophageal tissue in BE and EAC patients (p<0.01). In conclusion, our pilot results showed that miR-196a, which regulates the proliferation, invasion, and migration (and was previously associated with esophageal squamous cell carcinoma and marked as a potential therapeutic target), could be a diagnostic tissue biomarker for BE and EAC as well.

Keywords: microRNA, barrett´s esophagus, esophageal adenocarcinoma, biomarker

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Authors: Heramb Somthankar, Anujoy Chakraborty

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This paper presents a classification study on yield prediction in semiconductor production using machine learning approaches. A complicated semiconductor production process is generally monitored continuously by signals acquired from sensors and measurement sites. A monitoring system contains a variety of signals, all of which contain useful information, irrelevant information, and noise. In the case of each signal being considered a feature, "Feature Selection" is used to find the most relevant signals. The open-source UCI SECOM Dataset provides 1567 such samples, out of which 104 fail in quality assurance. Feature extraction and selection are performed on the dataset, and useful signals were considered for further study. Afterward, common machine learning algorithms were employed to predict whether the signal yields pass or fail. The most relevant algorithm is selected for prediction based on the accuracy and loss of the ML model.

Keywords: deep learning, feature extraction, feature selection, machine learning classification algorithms, semiconductor production monitoring, signal processing, time-series analysis

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Authors: Bao Thach Nguyen, Abbas Mohajerani

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The California bearing ratio (CBR) has been acknowledged as an important parameter to characterize the bearing capacity of earth structures, such as earth dams, road embankments, airport runways, bridge abutments, and pavements. Technically, the CBR test can be carried out in the laboratory or in the field. The CBR test is time-consuming and is infrequently performed due to the equipment needed and the fact that the field moisture content keeps changing over time. Over the years, many correlations have been developed for the prediction of CBR by various researchers, including the dynamic cone penetrometer, undrained shear strength, and Clegg impact hammer. This paper reports and discusses some of the results from a study on the prediction of CBR. In the current study, the CBR test was performed in the laboratory on some fine-grained subgrade soils collected from various locations in Victoria. Based on the test results, a satisfactory empirical correlation was found between the CBR and the physical properties of the experimental soils.

Keywords: California bearing ratio, fine-grained soils, soil physical properties, pavement, soil test

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Authors: Yousif Mohamed Y. Abdallah

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This is an experimental study deals with detection, measurement and analysis of the periodic physiological organ motion during external beam radiotherapy; to improve the accuracy of the radiation field placement, and to reduce the exposure of healthy tissue during radiation treatments. The importance of this study is to detect the maximum path of the mobile structures during radiotherapy delivery, to define the planning target volume (PTV) and irradiated volume during both inspiration and expiration period and to verify the target volume. In addition to its role to highlight the importance of the application of Intense Guided Radiotherapy (IGRT) methods in the field of radiotherapy. The results showed (body contour was equally (3.17 + 0.23 mm), for left lung displacement reading (2.56 + 0.99 mm) and right lung is (2.42 + 0.77 mm) which the radiation oncologist to take suitable countermeasures in case of significant errors. In addition, the use of the image registration technique for automatic position control is predicted potential motion. The motion ranged between 2.13 mm and 12.2 mm (low and high). In conclusion, individualized assessment of tumor mobility can improve the accuracy of target areas definition in patients undergo Sterostatic RT for stage I, II and III lung cancer (NSCLC). Definition of the target volume based on a single CT scan with a margin of 10 mm is clearly inappropriate.

Keywords: respiratory motion, external beam radiotherapy, image processing, lung

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Authors: Ann Ying-An Chen, Yi-Lun Tsai, Hso-Chi Chaung

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An understanding of pathogens and the immune system has played an utmost important role in agricultural research for the development of vaccinations. The immunological synapse, cell to cell interaction play a crucial role in triggering the body's immune system, such as activation between antigen-presenting cells (APCs) and different subsets of T-cell. If these interactions are regulated appropriately, the host has the ability to defend itself against a wide spectrum of infectious pathogens. The aim of this study is to establish and to characterize a porcine immune synapse system by co-culturing T cell/APC. In this study, blood samples were collected from specific-pathogen-free piglets, and peripheral blood mononuclear cells (PBMC) were separated by using Ficoll-Pague. The PBMC were then stained with CD4 (FITC) and CD25 (PE) antibodies. Different subsets of T cells sorted by fluorescence-activated cell sorting flow cytometer were co-cultured for 24 hrs with alveolar macrophages, and the profiles of cytokine secretion and mRNA transcription levels of Toll-like receptors were examined after. Results showed that the three stages of immune synapse were clearly visible and identified under both transmission and scanning electron microscope (TEM and SEM). The significant interaction differences in toll-like receptor expressions within the co-cultured cell system were observed. The TLR7 mRNA expressions in CD4+CD25- cells were lower than those in CD4+CD25+ and CD4 -CD25+. Interestingly, the IL-10 production levels in CD4+CD25- cells (7.732 pg/mL) were significantly higher than those of CD4+CD25+ (2.636 pg/mL) and CD4 -CD25+ (2.48 pg/mL). These findings demonstrated that a clear understanding of the porcine immune synapse system can contribute greatly for further investigations on the mechanism of T-cell activation, which can benefit in the discovery of potential adjuvant candidate or effective antigen epitopes in the development of vaccinations with high efficacy.

Keywords: antigen-presenting cells, immune synapse, pig, T subsets, toll-like receptor

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Authors: Clotilde Guyon, Nada Jmari, Yen-Chin Li, Jean Denoyel, Noriyuki Fujikado, Christophe Blanchet, David Root, Matthieu Giraud

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Aire induces ectopic expression of a large repertoire of tissue-specific antigen (TSA) genes in thymic medullary epithelial cells (MECs), driving immunological self-tolerance in maturing T cells. Although important mechanisms of Aire-induced transcription have recently been disclosed through the identification and the study of Aire’s partners, the fine transcriptional functions underlied by a number of them and conferred to Aire are still unknown. Alternative cleavage and polyadenylation (APA) is an essential mRNA processing step regulated by the termination complex consisting of 85 proteins, 10 of them have been related to Aire. We evaluated APA in MECs in vivo by microarray analysis with mRNA-spanning probes and RNA deep sequencing. We uncovered the preference of Aire-dependent transcripts for short-3’UTR isoforms and for proximal poly(A) site selection marked by the increased binding of the cleavage factor Cstf-64. RNA interference of the 10 Aire-related proteins revealed that Clp1, a member of the core termination complex, exerts a profound effect on short 3’UTR isoform preference. Clp1 is also significantly upregulated in the MECs compared to 25 mouse tissues in which we found that TSA expression is associated with longer 3’UTR isoforms. Aire-dependent transcripts escape a global 3’UTR lengthening associated with MEC differentiation, thereby potentiating the repressive effect of microRNAs that are globally upregulated in mature MECs. Consistent with these findings, RNA deep sequencing of actinomycinD-treated MECs revealed the increased stability of short 3’UTR Aire-induced transcripts, resulting in TSA transcripts accumulation and contributing for their enrichment in the MECs.

Keywords: Aire, central tolerance, miRNAs, transcription termination

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Authors: Nipun Manirajan, Heeralal Gargama, Sushil Guhe, Manoj Prabhakaran

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In railway industry, train sets are designed based on contractual requirements (mission profile), where reliability targets are measured in terms of mean distance between failures (MDBF). However, during the beginning of revenue services, trains do not achieve the designed mission profile distance (mileage) within the timeframe due to infrastructure constraints, scarcity of commuters or other operational challenges thereby not respecting the original design inputs. Since trains do not run sufficiently and do not achieve the designed mileage within the specified time, car builder has a risk of not achieving the contractual MDBF target. This paper proposes a constant failure rate based model to deal with the situations where mileage accumulation is not a part of the design mission profile. The model provides appropriate MDBF target to be demonstrated based on actual accumulated mileage. A case study of rolling stock running in the field is undertaken to analyze the failure data and MDBF target demonstration during low mileage accumulation. The results of case study prove that with the proposed method, reliability targets are achieved under low mileage accumulation.

Keywords: mean distance between failures, mileage-based reliability, reliability target appropriations, rolling stock reliability

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Authors: M. R. Akbari, M. Sadeghi, R. Faghihi, M. A. Mosleh-Shirazi, A. R. Khorrami-Moghadam

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Proton radiotherapy (PRT) is becoming an established treatment modality for cancer. The localized tumors, the same as undifferentiated thyroid tumors are insufficiently handled by conventional radiotherapy, while protons would propose the prospect of increasing the tumor dose without exceeding the tolerance of the surrounding healthy tissues. In spite of relatively high advantages in giving localized radiation dose to the tumor region, in proton therapy, secondary neutron production can have significant contribution on integral dose and lessen advantages of this modality contrast to conventional radiotherapy techniques. Furthermore, neutrons have high quality factor, therefore, even a small physical dose can cause considerable biological effects. Measuring of this neutron dose is a very critical step in prediction of secondary cancer incidence. It has been found that FLUKA Monte Carlo code simulations have been used to evaluate dose due to secondaries in proton therapy. In this study, first, by validating simulated proton beam range in water phantom with CSDA range from NIST for the studied proton energy range (34-54 MeV), a proton therapy in thyroid gland cancer was simulated using FLUKA code. Secondary neutron dose equivalent of some organs and tissues after the target volume caused by 34 and 54 MeV proton interactions were calculated in order to evaluate secondary cancer incidence. A multilayer cylindrical neck phantom considering all the layers of neck tissues and a proton beam impinging normally on the phantom were also simulated. Trachea (accompanied by Larynx) had the greatest dose equivalent (1.24×10-1 and 1.45 pSv per primary 34 and 54 MeV protons, respectively) among the simulated tissues after the target volume in the neck region.

Keywords: FLUKA code, neutron dose equivalent, proton therapy, thyroid gland

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Authors: Deba Kumar Sarma, Sanjib Kr. Rajbongshi

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Surface finish is an important product quality in machining. At first, experiments were carried out to investigate the effect of the cutting tool nose radius (considering 1mm and 0.65mm) in prediction of surface finish with process parameters of cutting speed, feed and depth of cut. For all possible cutting conditions, full factorial design was considered as two levels four parameters. Commercial Mild Steel bar and High Speed Steel (HSS) material were considered as work-piece and cutting tool material respectively. In order to obtain functional relationship between process parameters and surface roughness, neural network was used which was found to be capable for the prediction of surface roughness within a reasonable degree of accuracy. It was observed that tool nose radius of 1mm provides better surface finish in comparison to 0.65 mm. Also, it was observed that feed rate has a significant influence on surface finish.

Keywords: full factorial design, neural network, nose radius, surface finish

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Authors: Maaly Jarrah

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Oral fluency in the target language is what many second language learners hope to achieve by living abroad. Research in the past has demonstrated the role informal environments play in improving L2 learners' oral fluency. However, living in the target country and being part of its community does not ensure the development of oral fluency skills. L2 learners' desire to communicate and access to speaking opportunities in the host community are key in achieving oral fluency in the target language. This study attempts to identify differences in oral fluency, specifically speech rate, between learners who communicate in the L2 outside the classroom and those who do not. In addition, as the desire to communicate is a crucial factor in developing oral fluency, this study investigates whether or not learners' desire to speak the L2 outside the classroom plays a role in their frequency of L2 use outside the classroom. Finally, given the importance of the availability of speaking opportunities for L2 learners in order to practice their speaking skills, this study reports on the participants' perceptions of the speaking opportunities accessible to them in the target community while probing whether or not their perceptions differed based on their oral fluency level and their desire to communicate. The results suggest that exposure to the target language and daily communication with the native speakers is strongly related to the development of learners' oral fluency. Moreover, the findings suggest that learners' desire to communicate affects their frequency of communication in their L2 outside the classroom. At the same time, all participants, regardless of their oral fluency level and their desire to communicate, asserted that speaking opportunities beyond the classroom are very limited. Finally, the study finds there are marked differences in the perceptions learners have regarding opportunities for learning offered by the same language program. After reporting these results, the study concludes with recommendations for ESL programs that serve international students.

Keywords: ESL programs, L2 Learners, oral fluency, second language

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Authors: Qiming Zhang, Youda Ye, Qinxue Jiang

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Accurate prediction of external flowfield and aero-heating at the wall of hypersonic vehicle is very crucial for the design of aircrafts. Unstructured/hybrid meshes have more powerful advantages than structured meshes in terms of pre-processing, parallel computing and mesh adaptation, so it is imperative to develop high-resolution numerical methods for the calculation of aerothermal environment on unstructured/hybrid meshes. The inviscid flux scheme is one of the most important factors affecting the accuracy of unstructured/ hybrid mesh heat flux calculation. Here, a new hybrid flux scheme is developed and the approach of interface type selection is proposed: i.e. 1) using the exact Riemann scheme solution to calculate the flux on the faces parallel to the wall; 2) employing Sterger-Warming (S-W) scheme to improve the stability of the numerical scheme in other interfaces. The results of the heat flux fit the one observed experimentally and have little dependence on grids, which show great application prospect in unstructured/ hybrid mesh.

Keywords: aero-heating prediction, computational fluid dynamics, hybrid meshes, hybrid schemes

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Authors: Rehan Waheed, Abdul Shakoor

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Distortion produced during welding of thin metal plates is a problem in many industries. The purpose of this research was to study distortion produced during welding in 2mm Mild Steel plate by simulating the welding process using Finite Element Analysis. Simulation of welding process requires a couple field transient analyses. At first a transient thermal analysis is performed and the temperature obtained from thermal analysis is used as input in structural analysis to find distortion. An actual weld sample is prepared and the weld distortion produced is measured. The simulated and actual results were in quite agreement with each other and it has been found that there is profound deflection at center of plate. Temperature dependent material properties play significant role in prediction of weld distortion. The results of this research can be used for prediction and control of weld distortion in large steel structures by changing different weld parameters.

Keywords: welding simulation, FEA, welding distortion, temperature dependent mechanical properties

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Authors: Hyunchul Ahn, William X. S. Wong

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Corporate credit rating prediction is one of the most important topics, which has been studied by researchers in the last decade. Over the last decade, researchers are pushing the limit to enhance the exactness of the corporate credit rating prediction model by applying several data-driven tools including statistical and artificial intelligence methods. Among them, multiclass support vector machine (MSVM) has been widely applied due to its good predictability. However, heuristics, for example, parameters of a kernel function, appropriate feature and instance subset, has become the main reason for the critics on MSVM, as they have dictate the MSVM architectural variables. This study presents a hybrid MSVM model that is intended to optimize all the parameter such as feature selection, instance selection, and kernel parameter. Our model adopts genetic algorithm (GA) to simultaneously optimize multiple heterogeneous design factors of MSVM.

Keywords: corporate credit rating prediction, Feature selection, genetic algorithms, instance selection, multiclass support vector machines

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Authors: Abdelkader Hocine, Abdelhakim Maizia

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The exponential growth of reinforced fibers composite materials use has prompted researchers to step up their work on the prediction of their reliability. Owing to differences between the properties of the materials used for the composite, the manufacturing processes, the load combinations and types of environment, the prediction of the reliability of composite materials has become a primary task. Through failure criteria, TSAI-WU and the maximum stress, the reliability of multilayer tubular structures under pressure is the subject of this paper, where the failure probability of is estimated by the method of Monte Carlo.

Keywords: composite, design, monte carlo, tubular structure, reliability

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Authors: Abul B. M. M. K. Islam, Mandar Dave, Roderick V. Jensen, Ashok R. Amin

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A systems approach was applied to characterize differentially expressed transcripts, bioinformatics pathways, and proteins and prostaglandins (PGs) from lung fibroblasts procured from wild-type (WT), COX-1-/- and COX-2-/- mice to understand system level control mechanism. Bioinformatics analysis of COX-2 and COX-1 ablated cells induced COX-1 and COX-2 specific signature respectively, which significantly overlapped with an 'IL-1β induced inflammatory signature'. This defined novel cross-talk signals that orchestrated coordinated activation of pathways of sterile inflammation sensed by cellular stress. The overlapping signals showed significant over-representation of shared pathways for interferon y and immune responses, T cell functions, NOD, and toll-like receptor signaling. Gene Ontology Biological Process (GOBP) and pathway enrichment analysis specifically showed an increase in mRNA expression associated with: (a) organ development and homeostasis in COX-1-/- cells and (b) oxidative stress and response, spliceosomes and proteasomes activity, mTOR and p53 signaling in COX-2-/- cells. COX-1 and COX-2 showed signs of functional pathways committed to cell cycle and DNA replication at the genomics level. As compared to WT, metabolomics analysis revealed a significant increase in COX-1 mRNA and synthesis of basal levels of eicosanoids (PGE2, PGD2, TXB2, LTB4, PGF1α, and PGF2α) in COX-2 ablated cells and increase in synthesis of PGE2, and PGF1α in COX-1 null cells. There was a compensation of PGE2 and PGF1α in COX-1-/- and COX-2-/- cells. Collectively, these results support a broader, differential and collaborative regulation of both COX-1 and COX-2 pathways at the metabolic, signaling, and genomics levels in cellular homeostasis and sterile inflammation induced by cellular stress.

Keywords: cyclooxygenases, inflammation, lung fibroblasts, systemic

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Authors: Bingqing Xu, Wenxing Shuai

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This study investigates the priming effects of different Chinese compound words by native Mandarin speakers. There are lots of homonym, polysemy, and synonym in Chinese. However, it is unclear which kind of words have the biggest priming effect. Native Mandarin speakers were tested in a visual-word lexical decision experiment. The stimuli, which are all two-character compound words, consisted of two parts: primes and targets. Five types of relationships were used in all stimuli: morphologically related condition, in which the prime and the target contain the same morpheme; orthographically related condition, in which the target and the prime contain the different morpheme with the same form; phonologically related condition, in which the target and the prime contain the different morpheme with the same phonology; semantically related condition, in which the target and the prime contain the different morpheme with similar meanings; totally unrelated condition. The time since participants saw the target to respond was recorded. Analyses on reaction time showed that the average reaction time of morphologically related targets was much shorter than others, suggesting the morphological priming effect is the biggest. However, the reaction time of the phonologically related conditions was the longest, even longer than unrelated conditions. According to scatter plots analyses, 86.7% of participants had priming effects in morphologically related conditions, only 20% of participants had priming effects in phonologically related conditions. These results suggested that morphologically related conditions had the biggest priming effect. The orthographically and semantically related conditions also had priming effects, whereas the phonologically related conditions had few priming effects.

Keywords: priming effect, morphology, phonology, semantics, orthography

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Authors: Güldane Zengin

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Advertisers often make use of humorous elements in advertisements they create. Advertisements that contain such elements play a great role in creating awareness and attaining positive attitudes. Caricature, which is an element of humour, is interesting, eye catching, entertaining and memorable by its very nature. Because of these characteristics of caricatures, they are being used for advertising purposes. Advertisements with caricatures are spreading rapidly and embraced by consumers easily. Especially in the last ten years, companies in different sectors use advertisements with caricatures to publicize their products and services. These companies have different target audiences with different characteristics. They all have differences in opinions, attitudes, perceptions and buying behaviours. Target audiences’ brand choices depend on many different factors. Advertising is an important factor in brand choice. Using attention grabbing methods like advertising with caricatures affects their buying behaviours. This study examines the use of caricatures in Sütaş advertisements. Target audiences’ opinions, perceptions and attitudes about advertisements with caricatures are examined in this descriptive study.

Keywords: advertising, advertisements with caricatures, caricature, communication, humour, Sütaş caricatures

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Authors: Michal Kielbik, Izabela Szulc-Kielbik, Anna Brzostek, Jaroslaw Dziadek, Magdalena Klink

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The goal of many research groups in the world is to find new components that are important for survival of mycobacteria in the host cells. Mycobacterium tuberculosis (Mtb) possesses a number of enzymes degrading cholesterol that are considered to be an important factor for its survival and persistence in host macrophages. One of them - cholesterol oxidase (ChoD), although not being essential for cholesterol degradation, is discussed as a virulence compound, however its involvement in macrophages’ response to Mtb is still not sufficiently determined. The recognition of tubercle bacilli antigens by pathogen recognition receptors is crucial for the initiation of the host innate immune response. An important receptor that has been implicated in the recognition and/or uptake of Mtb is Toll-like receptor type 2 (TLR2). Engagement of TLR2 results in the activation and phosphorylation of intracellular signaling proteins including IRAK-1 and -4, TRAF-6, which in turn leads to the activation of target kinases and transcription factors responsible for bactericidal and pro-inflammatory response of macrophages. The aim of these studies was a detailed clarification of the role of Mtb cholesterol oxidase as a virulence factor affecting the TLR2 signaling pathway in human macrophages. As human macrophages the THP-1 differentiated cells were applied. The virulent wild-type Mtb strain (H37Rv), its mutant lacking a functional copy of gene encoding cholesterol oxidase (∆choD), as well as complimented strain (∆choD–choD) were used. We tested the impact of Mtb strains on the expression of TLR2-depended signaling proteins (mRNA level, cytosolic level and phosphorylation status). The cytokine and bactericidal response of THP-1 derived macrophages infected with Mtb strains in relation to TLR2 signaling pathway dependence was also determined. We found that during the 24-hours of infection process the wild-type and complemented Mtb significantly reduced the cytosolic level and phosphorylation status of IRAK-4 and TRAF-6 proteins in macrophages, that was not observed in the case of ΔchoD mutant. Decreasement of TLR2-dependent signaling proteins, induced by wild-type Mtb, was not dependent on the activity of proteasome. Blocking of TLR2 expression, before infection, effectively prevented the induced by wild-type strain reduction of cytosolic level and phosphorylation of IRAK-4. None of the strains affected the surface expression of TLR2. The mRNA level of IRAK-4 and TRAF-6 genes were significantly increased in macrophages 24 hours post-infection with either of tested strains. However, the impact of wild-type Mtb strain on both examined genes was significantly stronger than its ΔchoD mutant. We also found that wild-type strain stimulated macrophages to release high amount of immunosuppressive IL-10, accompanied by low amount of pro-inflammatory IL-8 and bactericidal nitric oxide in comparison to mutant lacking cholesterol oxidase. The influence of wild-type Mtb on this type of macrophages' response strongly dependent on fully active IRAK-1 and IRAK-4 signaling proteins. In conclusion, Mtb using cholesterol oxidase causes the over-activation of TLR2 signaling proteins leading to the reduction of their cytosolic level and activity resulting in the modulation of macrophages response to allow its intracellular survival. Supported by grant: 2014/15/B/NZ6/01565, National Science Center, Poland

Keywords: Mycobacterium tuberculosis, cholesterol oxidase, macrophages, TLR2-dependent signaling pathway

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Authors: Yaqing Hu

Abstract:

This paper puts forward a syntactic analysis involving multidominance and rightward movement in Chinese bi-comparatives, as in 'Yuehan bi Mali gao (John is taller than Mary).' It is argued here that the predicate of comparison is a shared constituent in two small clauses, namely one for the target and one for the standard; and then it moves rightward to form a degree phrase with the comparative morpheme. This proposal comes from four aspects. First, the example above can also be expressed in this way, 'A: Yuehan he Mali, shui gao? (John and Mary, who is taller?) B: Yuehan gao./Yuehan geng gao. (John is taller).' This shows that the gradable adjective is predicated of the target. In addition, according to a constraint on Chinese bi-comparatives, namely the target and the standard must be arguments of the predicate simultaneously, it is not unreasonable to assume that the gradable adjective may also be predicated of the standard. Second, subcomparatives are totally disallowed in Chinese, as in '*zhe-zhang zhuozi bi zhe-zhang yizi kuan chang. (This table is longer than this chair is wide.)' In order to save it from ungrammaticality, the target and the standard should be compared along the same dimension denoted by the gradable adjective. It may follow that in Chinese comparatives, having equal roles in the same eventuality, the target and the standard bear the same thematic relationship with the predicate of comparison. Third, verb-copy can appear in Chinese bi-comparatives, as in 'Yuehan qi ma bi Mali qi ma qi de kuai. (John rides horses faster than Mary does.)' The predicate qi seems to form a small clause with both the target and the standard. This might be supporting evidence that both the target and the standard share the predicate of comparison. Fourth, Chinese comparatives do have comparative morphemes, as in 'Yuehan bi Mali geng gao. (John is taller than Mary)', which is semantically equivalent to the first example above. Thus, it follows that one feature of Chinese comparative morphemes is that they can remain overt or covert in the syntax, which will not affect semantics. This further shows that comparative morphemes in bi-comparatives may not be able to saturate the degree argument denoted by the predicate of comparison due to its optionality in the structure. These four aspects present a challenge to the Direct Analysis used in Chinese comparatives since this approach would presume that the target and the standard somehow show independency with the predicate in the syntax. Meanwhile, this study also rejects the previous analysis of multidomiance in bi-comparatives in which the degree phrase comprised of the comparative morpheme and the gradable adjective may be shared by the standard when the comparative morpheme is covert. This syntactic analysis proposed in this study will therefore offer a different perspective of how to treat degree phrase in Chinese comparatives and may offer evidence to argue whether there is degree phrase movement in bi-comparatives as in its English counterparts.

Keywords: Chinese comparatives, degree phrase, movement, multidominance, syntactic analysis

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Authors: Uzma Saqib, Mirza S. Baig

Abstract:

Myeloid differentiation primary response protein 88 (MYD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MYD88 and Nur77 at the same time. Since both MYD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MYD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MYD88 and Nur77 targets.

Keywords: drug design, Nur77, MYD88, inflammation

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Authors: Zhen Cheng, Xinyu Dai, Shujian Huang, Jiajun Chen

Abstract:

Recently, explanatory natural language inference has attracted much attention for the interpretability of logic relationship prediction, which is also known as explanation generation for Natural Language Inference (NLI). Existing explanation generators based on discriminative Encoder-Decoder architecture have achieved noticeable results. However, we find that these discriminative generators usually generate explanations with correct evidence but incorrect logic semantic. It is due to that logic information is implicitly encoded in the premise-hypothesis pairs and difficult to model. Actually, logic information identically exists between premise-hypothesis pair and explanation. And it is easy to extract logic information that is explicitly contained in the target explanation. Hence we assume that there exists a latent space of logic information while generating explanations. Specifically, we propose a generative model called Variational Explanation Generator (VariationalEG) with a latent variable to model this space. Training with the guide of explicit logic information in target explanations, latent variable in VariationalEG could capture the implicit logic information in premise-hypothesis pairs effectively. Additionally, to tackle the problem of posterior collapse while training VariaztionalEG, we propose a simple yet effective approach called Logic Supervision on the latent variable to force it to encode logic information. Experiments on explanation generation benchmark—explanation-Stanford Natural Language Inference (e-SNLI) demonstrate that the proposed VariationalEG achieves significant improvement compared to previous studies and yields a state-of-the-art result. Furthermore, we perform the analysis of generated explanations to demonstrate the effect of the latent variable.

Keywords: natural language inference, explanation generation, variational auto-encoder, generative model

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Authors: Liang Ning, Chung Hau Yin

Abstract:

Angiogenesis is the process of new blood vessel development. It has been recognized as a therapeutic target for blocking cancer growth four decades ago. Vascular sprouting is initiated by pro-angiogenic factors. Vascular endothelial cell growth factor (VEGF) plays a central role in angiogenic initiation, many patients with cancer or ocular neovascularization have been benefited from anti-VEGF therapy. Emerging approaches impacting in the later stages of vessel remodeling and maturation are expected to improve clinical efficacy. TIE receptor as well as the corresponding angiopoietin ligands, were identified as another endothelial cell specific receptor tyrosine kinase signaling system. Much efforts were made to reduce the activity of angiopoietin-TIE receptor axis. Two eudesmane-type sesquiterpenes from laggera alata, namely, 15-dihydrocostic acid and ilicic acid were found with strong anti-angiogenic properties in zebrafish model. Meanwhile, the mRNA expression levels of VEGFR2 and TIE2 pathway related genes were down-regulated in the sesquiterpenes treated zebrafish embryos. Besides, in human umbilical vein endothelial cells (HUVECs), the sesquiterpenes have the ability to inhibit VEGF-induced HUVECs proliferation and migration at non-toxic concentration. Moreover, angiopoietin-2 induced TIE2 phosphorylation was inhibited by the sesquiterpenes, the inhibitory effect was detected in angiopoietin-1 induced HUVECs proliferation as well. Thus, we hypothesized the anti-angiogenic activity of the compounds may via the inhibition of VEGF and TIE2 related pathways. How the compounds come into play as the pathways inhibitors need to be evaluated in the future.

Keywords: Laggera alata, eudesmane-type sesquiterpene, anti-angiogenesis, VEGF, angiopoietin, TIE2

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Authors: R. Stalin, D. Karthick, H. Haseena Banu, T. P. Sachidanandam, P. Shanthi

Abstract:

Background: Breast cancer is emerging as one of the leading cause of cancer related deaths and hence there arises the need to look out for drugs which are more targets specific with minimal side effects. In recent times, there is a shift towards alternative medicine due to low cost and less side effects. Siddha system of medicine is one the oldest system of medicine practiced against various ailments. Tridham (TD) is a herbal formulation prepared in our laboratory consisting of Terminalia chebula, Elaeocarpus ganitrus and Prosopis cineraria in a definite ratio (TD) and its anticancer potential is evaluated in terms of induction of apoptosis. Objective: The present study was designed to investigate the anti proliferative effect of TD and 1,2,3,4,6-penta-O-galloyl-b-D-glucose (PGG), a pure compound isolated from TD on human mammary carcinoma cell line (MCF-7). Materials and Methods: Cell viability was studied using MTT analysis and trypan blue staining. Mitochondrial membrane potential was studied using DAPI staining. The protein and mRNA expressions of pro-apoptotic and anti- apoptotic markers namely Bax, Bad, Bcl-2 and caspases were also assessed by Western Blotting and RT PCR. Results: Viability studies of TD and PGG treated MCF-7 cells showed an inhibition in cell growth in time and dose dependent manner. The alteration in mitochondrial membrane potential was restored through treatment with TD and PGG which was confirmed by DAPI staining. The protein and mRNA expression of pro-apoptotic markers was found to be significantly increased in TD and PGG treated cells with a concomitant decrease in anti-apoptotic markers. Conclusion: The results of the study suggest that TD and PGG exhibit their anticancer effect through its membrane stabilizing property and activation of apoptotic cascade in MCF-7 cells.

Keywords: apoptosis, mammary carcinoma, MCF-7, penta galloyl glucose, Tridham

Procedia PDF Downloads 289