Search results for: brain tumor classification
2449 Reducing Support Structures in Design for Additive Manufacturing: A Neural Networks Approach
Authors: Olivia Borgue, Massimo Panarotto, Ola Isaksson
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This article presents a neural networks-based strategy for reducing the need for support structures when designing for additive manufacturing (AM). Additive manufacturing is a relatively new and immature industrial technology, and the information to make confident decisions when designing for AM is limited. This lack of information impacts especially the early stages of engineering design, for instance, it is difficult to actively consider the support structures needed for manufacturing a part. This difficulty is related to the challenge of designing a product geometry accounting for customer requirements, manufacturing constraints and minimization of support structure. The approach presented in this article proposes an automatized geometry modification technique for reducing the use of the support structures while designing for AM. This strategy starts with a neural network-based strategy for shape recognition to achieve product classification, using an STL file of the product as input. Based on the classification, an automatic part geometry modification based on MATLAB© is implemented. At the end of the process, the strategy presents different geometry modification alternatives depending on the type of product to be designed. The geometry alternatives are then evaluated adopting a QFD-like decision support tool.Keywords: additive manufacturing, engineering design, geometry modification optimization, neural networks
Procedia PDF Downloads 2532448 Human Digital Twin for Personal Conversation Automation Using Supervised Machine Learning Approaches
Authors: Aya Salama
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Digital Twin is an emerging research topic that attracted researchers in the last decade. It is used in many fields, such as smart manufacturing and smart healthcare because it saves time and money. It is usually related to other technologies such as Data Mining, Artificial Intelligence, and Machine Learning. However, Human digital twin (HDT), in specific, is still a novel idea that still needs to prove its feasibility. HDT expands the idea of Digital Twin to human beings, which are living beings and different from the inanimate physical entities. The goal of this research was to create a Human digital twin that is responsible for real-time human replies automation by simulating human behavior. For this reason, clustering, supervised classification, topic extraction, and sentiment analysis were studied in this paper. The feasibility of the HDT for personal replies generation on social messaging applications was proved in this work. The overall accuracy of the proposed approach in this paper was 63% which is a very promising result that can open the way for researchers to expand the idea of HDT. This was achieved by using Random Forest for clustering the question data base and matching new questions. K-nearest neighbor was also applied for sentiment analysis.Keywords: human digital twin, sentiment analysis, topic extraction, supervised machine learning, unsupervised machine learning, classification, clustering
Procedia PDF Downloads 872447 Linguistic Features for Sentence Difficulty Prediction in Aspect-Based Sentiment Analysis
Authors: Adrian-Gabriel Chifu, Sebastien Fournier
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One of the challenges of natural language understanding is to deal with the subjectivity of sentences, which may express opinions and emotions that add layers of complexity and nuance. Sentiment analysis is a field that aims to extract and analyze these subjective elements from text, and it can be applied at different levels of granularity, such as document, paragraph, sentence, or aspect. Aspect-based sentiment analysis is a well-studied topic with many available data sets and models. However, there is no clear definition of what makes a sentence difficult for aspect-based sentiment analysis. In this paper, we explore this question by conducting an experiment with three data sets: ”Laptops”, ”Restaurants”, and ”MTSC” (Multi-Target-dependent Sentiment Classification), and a merged version of these three datasets. We study the impact of domain diversity and syntactic diversity on difficulty. We use a combination of classifiers to identify the most difficult sentences and analyze their characteristics. We employ two ways of defining sentence difficulty. The first one is binary and labels a sentence as difficult if the classifiers fail to correctly predict the sentiment polarity. The second one is a six-level scale based on how many of the top five best-performing classifiers can correctly predict the sentiment polarity. We also define 9 linguistic features that, combined, aim at estimating the difficulty at sentence level.Keywords: sentiment analysis, difficulty, classification, machine learning
Procedia PDF Downloads 892446 Autogenous Diabetic Retinopathy Censor for Ophthalmologists - AKSHI
Authors: Asiri Wijesinghe, N. D. Kodikara, Damitha Sandaruwan
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The Diabetic Retinopathy (DR) is a rapidly growing interrogation around the world which can be annotated by abortive metabolism of glucose that causes long-term infection in human retina. This is one of the preliminary reason of visual impairment and blindness of adults. Information on retinal pathological mutation can be recognized using ocular fundus images. In this research, we are mainly focused on resurrecting an automated diagnosis system to detect DR anomalies such as severity level classification of DR patient (Non-proliferative Diabetic Retinopathy approach) and vessel tortuosity measurement of untwisted vessels to assessment of vessel anomalies (Proliferative Diabetic Retinopathy approach). Severity classification method is obtained better results according to the precision, recall, F-measure and accuracy (exceeds 94%) in all formats of cross validation. In ROC (Receiver Operating Characteristic) curves also visualized the higher AUC (Area Under Curve) percentage (exceeds 95%). User level evaluation of severity capturing is obtained higher accuracy (85%) result and fairly better values for each evaluation measurements. Untwisted vessel detection for tortuosity measurement also carried out the good results with respect to the sensitivity (85%), specificity (89%) and accuracy (87%).Keywords: fundus image, exudates, microaneurisms, hemorrhages, tortuosity, diabetic retinopathy, optic disc, fovea
Procedia PDF Downloads 3412445 Association of Brain-Derived Neurotrophic Factor (BDNF) Gene with Obesity and Metabolic Traits in Malaysian Adults
Authors: Yamunah Devi Apalasamy, Sanjay Rampal, Tin Tin Su, Foong Ming Moy, Hazreen Abdul Majid, Awang Bulgiba, Zahurin Mohamed
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Obesity is a growing global health issue. Obesity results from a combination of environmental and genetics factors. Brain-derived neurotrophic factor (BDNF), a gene encodes the BDNF protein and the BDNF gene have been linked to regulation of body weight and appetite. Genome-wide association studies have identified the BDNF variants to be related to obesity among Caucasians, East Asians, and Filipinos. However, the role of BDNF in other ethnic groups remains inconclusive. This case control study aims to investigate the associations of BDNF gene polymorphisms with obesity and metabolic parameters in Malaysian Malays. BDNF rs4074134, BDNF rs10501087 and BDNF rs6265 were genotyped using Sequenom MassARRAY. Anthropometric, body fat, fasting lipids and glucose levels were measured. A total of 663 subjects (194 obese and 469 non-obese) were included in this study. There were no significant associations association between BDNF SNPs and obesity. The allelic and genotype frequencies of the BDNF SNPs were similar in the obese and non-obese groups. After adjustment for age and sex, the BDNF variants were not associated with obesity, body fat, fasting lipids and glucose levels. Haplotypes at the BDNF gene region, were not significantly associated with obesity. The BDNF rs4074134 was in strong LD with BDNF rs10501087 (D'=0.98) and BDNF rs6265 (D'=0.87). The BDNF rs10501087 was also in strong LD with BDNF rs6265 (D'=0.91). Our findings suggest that the BDNF variants and the haplotypes of BDNF gene were not associated with obesity and metabolic traits in this study population. Further research is needed to explore other BDNF variants with a larger sample size with gene-environment interactions in multi ethnic Malaysian population.Keywords: genomics of obesity, SNP, BMI, haplotypes
Procedia PDF Downloads 4302444 Masquerade and “What Comes Behind Six Is More Than Seven”: Thoughts on Art History and Visual Culture Research Methods
Authors: Osa D Egonwa
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In the 21st century, the disciplinary boundaries of past centuries that we often create through mainstream art historical classification, techniques and sources may have been eroded by visual culture, which seems to provide a more inclusive umbrella for the new ways artists go about the creative process and its resultant commodities. Over the past four decades, artists in Africa have resorted to new materials, techniques and themes which have affected our ways of research on these artists and their art. Frontline artists such as El Anatsui, Yinka Shonibare, Erasmus Onyishi are demonstrating that any material is just suitable for artistic expression. Most of times, these materials come with their own techniques/effects and visual syntax: a combination of materials compounds techniques, formal aesthetic indexes, halo effects, and iconography. This tends to challenge the categories and we lean on to view, think and talk about them. This renders our main stream art historical research methods inadequate, thus suggesting new discursive concepts, terms and theories. This paper proposed the Africanist eclectic methods derived from the dual framework of Masquerade Theory and What Comes Behind Six is More Than Seven. This paper shares thoughts/research on art historical methods, terminological re-alignments on classification/source data, presentational format and interpretation arising from the emergent trends in our subject. The outcome provides useful tools to mediate new thoughts and experiences in recent African art and visual culture.Keywords: art historical methods, classifications, concepts, re-alignment
Procedia PDF Downloads 1102443 Data Mining of Students' Performance Using Artificial Neural Network: Turkish Students as a Case Study
Authors: Samuel Nii Tackie, Oyebade K. Oyedotun, Ebenezer O. Olaniyi, Adnan Khashman
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Artificial neural networks have been used in different fields of artificial intelligence, and more specifically in machine learning. Although, other machine learning options are feasible in most situations, but the ease with which neural networks lend themselves to different problems which include pattern recognition, image compression, classification, computer vision, regression etc. has earned it a remarkable place in the machine learning field. This research exploits neural networks as a data mining tool in predicting the number of times a student repeats a course, considering some attributes relating to the course itself, the teacher, and the particular student. Neural networks were used in this work to map the relationship between some attributes related to students’ course assessment and the number of times a student will possibly repeat a course before he passes. It is the hope that the possibility to predict students’ performance from such complex relationships can help facilitate the fine-tuning of academic systems and policies implemented in learning environments. To validate the power of neural networks in data mining, Turkish students’ performance database has been used; feedforward and radial basis function networks were trained for this task; and the performances obtained from these networks evaluated in consideration of achieved recognition rates and training time.Keywords: artificial neural network, data mining, classification, students’ evaluation
Procedia PDF Downloads 6132442 On the Theory of Persecution
Authors: Aleksander V. Zakharov, Marat R. Bogdanov, Ramil F. Malikov, Irina N. Dumchikova
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Classification of persecution movement laws is proposed. Modes of persecution in number of specific cases were researched. Modes of movement control using GLONASS/GPS are discussed.Keywords: UAV Management, mathematical algorithms of targeting and persecution, GLONASS, GPS
Procedia PDF Downloads 3452441 Transportation Mode Classification Using GPS Coordinates and Recurrent Neural Networks
Authors: Taylor Kolody, Farkhund Iqbal, Rabia Batool, Benjamin Fung, Mohammed Hussaeni, Saiqa Aleem
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The rising threat of climate change has led to an increase in public awareness and care about our collective and individual environmental impact. A key component of this impact is our use of cars and other polluting forms of transportation, but it is often difficult for an individual to know how severe this impact is. While there are applications that offer this feedback, they require manual entry of what transportation mode was used for a given trip, which can be burdensome. In order to alleviate this shortcoming, a data from the 2016 TRIPlab datasets has been used to train a variety of machine learning models to automatically recognize the mode of transportation. The accuracy of 89.6% is achieved using single deep neural network model with Gated Recurrent Unit (GRU) architecture applied directly to trip data points over 4 primary classes, namely walking, public transit, car, and bike. These results are comparable in accuracy to results achieved by others using ensemble methods and require far less computation when classifying new trips. The lack of trip context data, e.g., bus routes, bike paths, etc., and the need for only a single set of weights make this an appropriate methodology for applications hoping to reach a broad demographic and have responsive feedback.Keywords: classification, gated recurrent unit, recurrent neural network, transportation
Procedia PDF Downloads 1372440 Geoinformation Technology of Agricultural Monitoring Using Multi-Temporal Satellite Imagery
Authors: Olena Kavats, Dmitry Khramov, Kateryna Sergieieva, Vladimir Vasyliev, Iurii Kavats
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Geoinformation technologies of space agromonitoring are a means of operative decision making support in the tasks of managing the agricultural sector of the economy. Existing technologies use satellite images in the optical range of electromagnetic spectrum. Time series of optical images often contain gaps due to the presence of clouds and haze. A geoinformation technology is created. It allows to fill gaps in time series of optical images (Sentinel-2, Landsat-8, PROBA-V, MODIS) with radar survey data (Sentinel-1) and use information about agrometeorological conditions of the growing season for individual monitoring years. The technology allows to perform crop classification and mapping for spring-summer (winter and spring crops) and autumn-winter (winter crops) periods of vegetation, monitoring the dynamics of crop state seasonal changes, crop yield forecasting. Crop classification is based on supervised classification algorithms, takes into account the peculiarities of crop growth at different vegetation stages (dates of sowing, emergence, active vegetation, and harvesting) and agriculture land state characteristics (row spacing, seedling density, etc.). A catalog of samples of the main agricultural crops (Ukraine) is created and crop spectral signatures are calculated with the preliminary removal of row spacing, cloud cover, and cloud shadows in order to construct time series of crop growth characteristics. The obtained data is used in grain crop growth tracking and in timely detection of growth trends deviations from reference samples of a given crop for a selected date. Statistical models of crop yield forecast are created in the forms of linear and nonlinear interconnections between crop yield indicators and crop state characteristics (temperature, precipitation, vegetation indices, etc.). Predicted values of grain crop yield are evaluated with an accuracy up to 95%. The developed technology was used for agricultural areas monitoring in a number of Great Britain and Ukraine regions using EOS Crop Monitoring Platform (https://crop-monitoring.eos.com). The obtained results allow to conclude that joint use of Sentinel-1 and Sentinel-2 images improve separation of winter crops (rapeseed, wheat, barley) in the early stages of vegetation (October-December). It allows to separate successfully the soybean, corn, and sunflower sowing areas that are quite similar in their spectral characteristics.Keywords: geoinformation technology, crop classification, crop yield prediction, agricultural monitoring, EOS Crop Monitoring Platform
Procedia PDF Downloads 4562439 Track and Evaluate Cortical Responses Evoked by Electrical Stimulation
Authors: Kyosuke Kamada, Christoph Kapeller, Michael Jordan, Mostafa Mohammadpour, Christy Li, Christoph Guger
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Cortico-cortical evoked potentials (CCEP) refer to responses generated by cortical electrical stimulation at distant brain sites. These responses provide insights into the functional networks associated with language or motor functions, and in the context of epilepsy, they can reveal pathological networks. Locating the origin and spread of seizures within the cortex is crucial for pre-surgical planning. This process can be enhanced by employing cortical stimulation at the seizure onset zone (SOZ), leading to the generation of CCEPs in remote brain regions that may be targeted for disconnection. In the case of a 24-year-old male patient suffering from intractable epilepsy, corpus callosotomy was performed as part of the treatment. DTI-MRI imaging, conducted using a 3T MRI scanner for fiber tracking, along with CCEP, is used as part of an assessment for surgical planning. Stimulation of the SOZ, with alternating monophasic pulses of 300µs duration and 15mA current intensity, resulted in CCEPs on the contralateral frontal cortex, reaching a peak amplitude of 206µV with a latency of 31ms, specifically in the left pars triangularis. The related fiber tracts were identified with a two-tensor unscented Kalman filter (UKF) technique, showing transversal fibers through the corpus callosum. The CCEPs were monitored through the progress of the surgery. Notably, the SOZ-associated CCEPs exhibited a reduction following the resection of the anterior portion of the corpus callosum, reaching the identified connecting fibers. This intervention demonstrated a potential strategy for mitigating the impact of intractable epilepsy through targeted disconnection of identified cortical regions.Keywords: CCEP, SOZ, Corpus callosotomy, DTI
Procedia PDF Downloads 672438 Effect of Renin Angiotensin Pathway Inhibition on the Efficacy of Anti-programmed Cell Death (PD-1/L-1) Inhibitors in Advanced Non-small Cell Lung Cancer Patients- Comparison of Single Hospital Retrospective Assessment to the Published Literature
Authors: Esther Friedlander, Philip Friedlander
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The use of immunotherapy that inhibits programmed death-1 (PD-1) or its ligand PD-L1 confers survival benefits in patients with non-small cell lung cancer (NSCLC). However, approximately 45% of patients experience primary treatment resistance, necessitating the development of strategies to improve efficacy. While the renin-angiotensin system (RAS) has systemic hemodynamic effects, tissue-specific regulation exists along with modulation of immune activity in part through regulation of myeloid cell activity, leading to the hypothesis that RAS inhibition may improve anti-PD-1/L-1 efficacy. A retrospective analysis was conducted that included 173 advanced solid tumor cancer patients treated at Valley Hospital, a community Hospital in New Jersey, USA, who were treated with a PD-1/L-1 inhibitor in a defined time period showing a statistically significant relationship between RAS pathway inhibition (RASi through concomitant treatment with an ACE inhibitor or angiotensin receptor blocker) and positive efficacy to the immunotherapy that was independent of age, gender and cancer type. Subset analysis revealed strong numerical benefit for efficacy in both patients with squamous and nonsquamous NSCLC as determined by documented clinician assessment of efficacy and by duration of therapy. A PUBMED literature search was now conducted to identify studies assessing the effect of RAS pathway inhibition on anti-PD-1/L1 efficacy in advanced solid tumor patients and compare these findings to those seen in the Valley Hospital retrospective study with a focus on NSCLC specifically. A total of 11 articles were identified assessing the effects of RAS pathway inhibition on the efficacy of checkpoint inhibitor immunotherapy in advanced cancer patients. Of the 11 studies, 10 assessed the effect on survival of RASi in the context of treatment with anti-PD-1/PD-L1, while one assessed the effect on CTLA-4 inhibition. Eight of the studies included patients with NSCLC, while the remaining 2 were specific to genitourinary malignancies. Of the 8 studies, two were specific to NSCLC patients, with the remaining 6 studies including a range of cancer types, of which NSCLC was one. Of these 6 studies, only 2 reported specific survival data for the NSCLC subpopulation. Patient characteristics, multivariate analysis data and efficacy data seen in the 2 NSLCLC specific studies and in the 2 basket studies, which provided data on the NSCLC subpopulation, were compared to that seen in the Valley Hospital retrospective study supporting a broader effect of RASi on anti-PD-1/L1 efficacy in advanced NSLCLC with the majority of studies showing statistically significant benefit or strong statistical trends but with one study demonstrating worsened outcomes. This comparison of studies extends published findings to the community hospital setting and supports prospective assessment through randomized clinical trials of efficacy in NSCLC patients with pharmacodynamic components to determine the effect on immune cell activity in tumors and on the composition of the tumor microenvironment.Keywords: immunotherapy, cancer, angiotensin, efficacy, PD-1, lung cancer, NSCLC
Procedia PDF Downloads 692437 Examining the Relationship between Concussion and Neurodegenerative Disorders: A Review on Amyotrophic Lateral Sclerosis and Alzheimer’s Disease
Authors: Edward Poluyi, Eghosa Morgan, Charles Poluyi, Chibuikem Ikwuegbuenyi, Grace Imaguezegie
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Background: Current epidemiological studies have examined the associations between moderate and severe traumatic brain injury (TBI) and their risks of developing neurodegenerative diseases. Concussion, also known as mild TBI (mTBI), is however quite distinct from moderate or severe TBIs. Only few studies in this burgeoning area have examined concussion—especially repetitive episodes—and neurodegenerative diseases. Thus, no definite relationship has been established between them. Objectives : This review will discuss the available literature linking concussion and amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD). Materials and Methods: Given the complexity of this subject, a realistic review methodology was selected which includes clarifying the scope and developing a theoretical framework, developing a search strategy, selection and appraisal, data extraction, and synthesis. A detailed literature matrix was set out in order to get relevant and recent findings on this topic. Results: Presently, there is no objective clinical test for the diagnosis of concussion because the features are less obvious on physical examination. Absence of an objective test in diagnosing concussion sometimes leads to skepticism when confirming the presence or absence of concussion. Intriguingly, several possible explanations have been proposed in the pathological mechanisms that lead to the development of some neurodegenerative disorders (such as ALS and AD) and concussion but the two major events are deposition of tau proteins (abnormal microtubule proteins) and neuroinflammation, which ranges from glutamate excitotoxicity pathways and inflammatory pathways (which leads to a rise in the metabolic demands of microglia cells and neurons), to mitochondrial function via the oxidative pathways.Keywords: amyotrophic lateral sclerosis, Alzheimer's disease, mild traumatic brain injury, neurodegeneration
Procedia PDF Downloads 892436 TP53 Mutations in Molecular Subtypes of Breast Cancer in Young Pakistani Patients
Authors: Nadia Naseem, Farwa Batool, Nasir Mehmood, AbdulHannan Nagi
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Background: The incidence and mortality of breast cancer vary significantly in geographically distinct populations. In Pakistan, breast cancer has shown an increase in incidence in young females and is characterized by more aggressive behavior. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. This study investigated the TP53 mutations in molecular subtypes of both nodes negative and positive breast cancer in young Pakistani patients. Material and Methods: p53, Estrogen Receptor (ER), Progesterone Receptor (PR), Her-2 neu and Ki 67 expressions were analyzed immunohistochemically in a series of 75 node negative (A) and 75 node positive (B) young (aged: 19-40 years) breast cancer patients diagnosed between 2014 to 2017 at two leading hospitals of Punjab, Pakistan. Tumor tissue specimens and peripheral blood samples were examined for TP53 mutations by direct sequencing of the gene (exons 4-9). The relation of TP53 mutations to these markers and clinicopathological data was investigated. Results: Mean age of the patients was 32.4 + 9.1 SD. Invasive breast carcinoma was the most frequent histological variant (A=92%, B=94.6%). Grade 3 carcinoma was the commonest grade (A=72%, B=81.3%). Triple negative cases (ER-, PR-, Her-2) formed most of the molecular subtypes (A=44%, B=50.6%). A total of 17.2% (A: 6.6%, B: 10.6%) patients showed TP53 mutations. Mutations were significantly more frequent in triple negative cases (A: 74.8%, B: 62.2%) compared to HER2-positive patients (P < 0.0001). In the multivariate analysis of the whole patient group, the independent prognosticator were triple negative cases (P=0.021), TP53 overexpression by IHC (P=0.001) and advanced-stage disease (P=0.007). No statistically significant correlation between TP53 mutations and clinicopathological parameters was found (P < 0.05). Conclusions: It is concluded that TP53 mutations are infrequently present in breast carcinoma of young Pakistani population and there was no significant correlation between p53 mutation and early onset disease. Immunohistochemically detected TP53 expression in our resource-constrained to set up can be beneficial in predicting mutations at the younger age in our population.Keywords: immunohistochemistry (IHC), invasive breast carcinoma (IBC), Pakistan, TP53
Procedia PDF Downloads 1582435 The Optimum Mel-Frequency Cepstral Coefficients (MFCCs) Contribution to Iranian Traditional Music Genre Classification by Instrumental Features
Authors: M. Abbasi Layegh, S. Haghipour, K. Athari, R. Khosravi, M. Tafkikialamdari
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An approach to find the optimum mel-frequency cepstral coefficients (MFCCs) for the Radif of Mirzâ Ábdollâh, which is the principal emblem and the heart of Persian music, performed by most famous Iranian masters on two Iranian stringed instruments ‘Tar’ and ‘Setar’ is proposed. While investigating the variance of MFCC for each record in themusic database of 1500 gushe of the repertoire belonging to 12 modal systems (dastgâh and âvâz), we have applied the Fuzzy C-Mean clustering algorithm on each of the 12 coefficient and different combinations of those coefficients. We have applied the same experiment while increasing the number of coefficients but the clustering accuracy remained the same. Therefore, we can conclude that the first 7 MFCCs (V-7MFCC) are enough for classification of The Radif of Mirzâ Ábdollâh. Classical machine learning algorithms such as MLP neural networks, K-Nearest Neighbors (KNN), Gaussian Mixture Model (GMM), Hidden Markov Model (HMM) and Support Vector Machine (SVM) have been employed. Finally, it can be realized that SVM shows a better performance in this study.Keywords: radif of Mirzâ Ábdollâh, Gushe, mel frequency cepstral coefficients, fuzzy c-mean clustering algorithm, k-nearest neighbors (KNN), gaussian mixture model (GMM), hidden markov model (HMM), support vector machine (SVM)
Procedia PDF Downloads 4462434 Performance Analysis of Traffic Classification with Machine Learning
Authors: Htay Htay Yi, Zin May Aye
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Network security is role of the ICT environment because malicious users are continually growing that realm of education, business, and then related with ICT. The network security contravention is typically described and examined centrally based on a security event management system. The firewalls, Intrusion Detection System (IDS), and Intrusion Prevention System are becoming essential to monitor or prevent of potential violations, incidents attack, and imminent threats. In this system, the firewall rules are set only for where the system policies are needed. Dataset deployed in this system are derived from the testbed environment. The traffic as in DoS and PortScan traffics are applied in the testbed with firewall and IDS implementation. The network traffics are classified as normal or attacks in the existing testbed environment based on six machine learning classification methods applied in the system. It is required to be tested to get datasets and applied for DoS and PortScan. The dataset is based on CICIDS2017 and some features have been added. This system tested 26 features from the applied dataset. The system is to reduce false positive rates and to improve accuracy in the implemented testbed design. The system also proves good performance by selecting important features and comparing existing a dataset by machine learning classifiers.Keywords: false negative rate, intrusion detection system, machine learning methods, performance
Procedia PDF Downloads 1182433 Construction of Ovarian Cancer-on-Chip Model by 3D Bioprinting and Microfluidic Techniques
Authors: Zakaria Baka, Halima Alem
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Cancer is a major worldwide health problem that has caused around ten million deaths in 2020. In addition, efforts to develop new anti-cancer drugs still face a high failure rate. This is partly due to the lack of preclinical models that recapitulate in-vivo drug responses. Indeed conventional cell culture approach (known as 2D cell culture) is far from reproducing the complex, dynamic and three-dimensional environment of tumors. To set up more in-vivo-like cancer models, 3D bioprinting seems to be a promising technology due to its ability to achieve 3D scaffolds containing different cell types with controlled distribution and precise architecture. Moreover, the introduction of microfluidic technology makes it possible to simulate in-vivo dynamic conditions through the so-called “cancer-on-chip” platforms. Whereas several cancer types have been modeled through the cancer-on-chip approach, such as lung cancer and breast cancer, only a few works describing ovarian cancer models have been described. The aim of this work is to combine 3D bioprinting and microfluidic technics with setting up a 3D dynamic model of ovarian cancer. In the first phase, alginate-gelatin hydrogel containing SKOV3 cells was used to achieve tumor-like structures through an extrusion-based bioprinter. The desired form of the tumor-like mass was first designed on 3D CAD software. The hydrogel composition was then optimized for ensuring good and reproducible printability. Cell viability in the bioprinted structures was assessed using Live/Dead assay and WST1 assay. In the second phase, these bioprinted structures will be included in a microfluidic device that allows simultaneous testing of different drug concentrations. This microfluidic dispositive was first designed through computational fluid dynamics (CFD) simulations for fixing its precise dimensions. It was then be manufactured through a molding method based on a 3D printed template. To confirm the results of CFD simulations, doxorubicin (DOX) solutions were perfused through the dispositive and DOX concentration in each culture chamber was determined. Once completely characterized, this model will be used to assess the efficacy of anti-cancer nanoparticles developed in the Jean Lamour institute.Keywords: 3D bioprinting, ovarian cancer, cancer-on-chip models, microfluidic techniques
Procedia PDF Downloads 1962432 Germline Mutations of Mitogen-Activated Protein Kinases Pathway Signaling Pathway Genes in Children
Authors: Nouha Bouayed Abdelmoula, Rim Louati, Nawel Abdellaoui, Balkiss Abdelmoula, Oldez Kaabi, Walid Smaoui, Samir Aloulou
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Background and Aims: Cardiofaciocutaneous syndrome (CFC) is an autosomal dominant disorder with the vast majority of cases arising by a new mutation of BRAF, MEK1, MEK2, or rarely, KRAS genes. Here, we report a rare Tunisian case of CFC syndrome for whom we identify SOS1 mutation. Methods: Genomic DNA was obtained from peripheral blood collected in an EDTA tube and extracted from leukocytes using the phenol/chloroform method according to standard protocols. High resolution melting (HRM) analysis for screening of mutations in the entire coding sequence of PTPN11 was conducted first. Then, HRM assays to look for hot spot mutations coding regions of the other genes of the RAS-MAPK pathway (RAt Sarcoma viral oncogene homolog Mitogen-Activated Protein Kinases Pathway): SOS1, SHOC2, KRAS, RAF1, KRAS, NRAS, CBL, BRAF, MEK1, MEK2, HRAS, and RIT1, were applied. Results: Heterozygous SOS1 point mutation clustered in exon 10, which encodes for the PH domain of SOS1, was identified: c.1655 G > A. The patient was a 9-year-old female born from a consanguineous couple. She exhibited pulmonic valvular stenosis as congenital heart disease. She had facial features and other malformations of Noonan syndrome, including macrocephaly, hypertelorism, ptosis, downslanting palpebral fissures, sparse eyebrows, a short and broad nose with upturned tip, low-set ears, high forehead commonly associated with bitemporal narrowing and prominent supraorbital ridges, short and/or webbed neck and short stature. However, the phenotype is also suggestive of CFC syndrome with the presence of more severe ectodermal abnormalities, including curly hair, keloid scars, hyperkeratotic skin, deep plantar creases, and delayed permanent dentition with agenesis of the right maxillary first molar. Moreover, the familial history of the patient revealed recurrent brain malignancies in the paternal family and epileptic disease in the maternal family. Conclusions: This case report of an overlapping RASopathy associated with SOS1 mutation and familial history of brain tumorigenesis is exceptional. The evidence suggests that RASopathies are truly cancer-prone syndromes, but the magnitude of the cancer risk and the types of cancer partially overlap.Keywords: cardiofaciocutaneous syndrome, CFC, SOS1, brain cancer, germline mutation
Procedia PDF Downloads 1532431 Action Potential of Lateral Geniculate Neurons at Low Threshold Currents: Simulation Study
Authors: Faris Tarlochan, Siva Mahesh Tangutooru
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Lateral Geniculate Nucleus (LGN) is the relay center in the visual pathway as it receives most of the input information from retinal ganglion cells (RGC) and sends to visual cortex. Low threshold calcium currents (IT) at the membrane are the unique indicator to characterize this firing functionality of the LGN neurons gained by the RGC input. According to the LGN functional requirements such as functional mapping of RGC to LGN, the morphologies of the LGN neurons were developed. During the neurological disorders like glaucoma, the mapping between RGC and LGN is disconnected and hence stimulating LGN electrically using deep brain electrodes can restore the functionalities of LGN. A computational model was developed for simulating the LGN neurons with three predominant morphologies, each representing different functional mapping of RGC to LGN. The firings of action potentials at LGN neuron due to IT were characterized by varying the stimulation parameters, morphological parameters and orientation. A wide range of stimulation parameters (stimulus amplitude, duration and frequency) represents the various strengths of the electrical stimulation with different morphological parameters (soma size, dendrites size and structure). The orientation (0-1800) of LGN neuron with respect to the stimulating electrode represents the angle at which the extracellular deep brain stimulation towards LGN neuron is performed. A reduced dendrite structure was used in the model using Bush–Sejnowski algorithm to decrease the computational time while conserving its input resistance and total surface area. The major finding is that an input potential of 0.4 V is required to produce the action potential in the LGN neuron which is placed at 100 µm distance from the electrode. From this study, it can be concluded that the neuroprostheses under design would need to consider the capability of inducing at least 0.4V to produce action potentials in LGN.Keywords: Lateral Geniculate Nucleus, visual cortex, finite element, glaucoma, neuroprostheses
Procedia PDF Downloads 2782430 Applying the Eye Tracking Technique for the Evaluation of Oculomotor System in Patients Survived after Cerebellar Tumors
Authors: Marina Shurupova, Victor Anisimov, Alexander Latanov
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Background: The cerebellar lesions inevitably provoke oculomotor impairments in patients of different age. Symptoms of subtentorial tumors, particularly medulloblastomas, include static and dynamic coordination disorders (ataxia, asynergia, imbalance), hypo-muscle tonus, disruption of the cranial nerves, and within the oculomotor system - nystagmus (fine or gross). Subtentorial tumors can also affect the areas of cerebellum that control the oculomotor system. The noninvasive eye-tracking technology allows obtaining multiple oculomotor characteristics such as the number of fixations and their duration, amplitude, latency and velocity of saccades, trajectory and scan path of gaze during the process of the visual field navigation. Eye tracking could be very useful in clinical studies serving as convenient and effective tool for diagnostics. The aim: We studied the dynamics of oculomotor system functioning in patients undergoing remission from cerebellar tumors removal surgeries and following neurocognitive rehabilitation. Methods: 38 children (23 boys, 15 girls, 9-17 years old) that have recovered from the cerebellar tumor-removal surgeries, radiation therapy and chemotherapy and were undergoing course of neurocognitive rehabilitation participated in the study. Two tests were carried out to evaluate oculomotor performance - gaze stability test and counting test. The monocular eye movements were recorded with eye tracker ArringtonResearch (60 Hz). Two experimental sessions with both tests were conducted before and after rehabilitation courses. Results: Within the final session of both tests we observed remarkable improvement in oculomotor performance: 1) in the gaze stability test the spread of gaze positions significantly declined compared to the first session, and 2) the visual path in counting test significantly shortened both compared to the first session. Thus, neurocognitive rehabilitation improved the functioning of the oculomotor system in patients following the cerebellar tumor removal surgeries and subsequent therapy. Conclusions: The experimental data support the effectiveness of the utilization of the eye tracking technique as diagnostic tool in the field of neurooncology.Keywords: eye tracking, rehabilitation, cerebellar tumors, oculomotor system
Procedia PDF Downloads 1612429 Reliability of Using Standard Penetration Test (SPT) in Evaluation of Soil Properties
Authors: Hossein Alimohammadi, Mohsen Amirmojahedi, Mehrdad Rowhani
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Soil properties are used by geotechnical engineers to evaluate and analyze site conditions for designing purposes. Although basic soil classification tests are easy to perform and provide useful information to determine the properties of soils, it may take time to get the result and add some costs to the projects. Standard Penetration Test (SPT) provides an opportunity to evaluate soil parameters without performing laboratory tests. In addition to its simplicity and cheapness, the results become available immediately. This research provides a guideline on the application of the SPT test method, reliability of adapting the SPT test results in evaluating soil physical and mechanical properties such as Atterberg limits, shear strength, and compressive strength compressibility parameters. A total of 70 boreholes were investigated in this study by taking soil samples between depths of 1.2 to 15.25 meters. The project site was located in Morrow County, Ohio. A regression-based formula was proposed based on Tobit regression with a stepwise variable selection analysis conducted between SPT and other typical soil properties obtained from soil tests. The results of the research illustrated that the shear strength and physical properties of the soil affect the SPT number. The proposed correlation can help engineers to use SPT test results in their design with higher accuracy.Keywords: standard penetration test, soil properties, soil classification, regression method
Procedia PDF Downloads 1882428 Solid Oral Leiomyoma: Clinical Case Report
Authors: Hurtado Zuñiga Yonel Marcos, Ferreira Joao Tiago
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Introduction: Leiomyoma is a benign smooth muscle tumor. It is predominantly found between 40-49 years with a small prevalence in men. It is commonly found in the uterus, stomach, and in areas with smooth muscle. It presents as nodular, solitary, variable size, slow growing, and asymptomatic. It is classified into solid, vascular, and epithelioid leiomyoma. Vascular leiomyoma is the most common in the oral cavity. Oral leiomyomas are very rare because a smooth muscle in the oral cavity isn’t common. The most frequent areas of this pathologyaretongue, lip, buccal mucosa, and palate. It may be derived from the vascular walls or excretory ducts of the salivary glands. The diagnosis is made by histologically analysis. The treatment of choice is complete excision. Recurrence is rare. Objective: To report the case of a solid leiomyoma on the dorsum of the tongue and review the literature. Case description: A 78-year-old female patient presented a nodular (ovoid) elevation of 8x6mm, brownish color, with irregular limits and firm consistency located in the dorsal part of the tongue with slight symptoms. An excisional biopsy was performed, photographic record, and 3 weeks post-surgical follow-up. Result: The surgical specimen was submitted to an anatomopathological analysis, resulting in a benign nodule with defined limits compatible with solid leiomyoma of the tongue. Discussion: It is a pathology that presents in a solitary, nodular, well-defined, asymptomatic form; in the oral cavity, leiomyomas are found in the tongue, lip, buccal mucosa, and palate; as in our patient, it was nodular and, in the tongue, with a difference only in the symptomatology. The most prevalent age is 40-49 years and with small predominance in men, unlike our female patient with 78 years. Conclusions: Oral leiomyoma is a rare benign lesion that presents as a solitary nodular nodule; for its diagnosis, an anatomopathological analysis should be performed, and the treatment of choice is total excision with little recurrence.Keywords: tongue, bening tumor, oral leiomyoma, leiomyoma
Procedia PDF Downloads 2172427 Detecting Venomous Files in IDS Using an Approach Based on Data Mining Algorithm
Authors: Sukhleen Kaur
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In security groundwork, Intrusion Detection System (IDS) has become an important component. The IDS has received increasing attention in recent years. IDS is one of the effective way to detect different kinds of attacks and malicious codes in a network and help us to secure the network. Data mining techniques can be implemented to IDS, which analyses the large amount of data and gives better results. Data mining can contribute to improving intrusion detection by adding a level of focus to anomaly detection. So far the study has been carried out on finding the attacks but this paper detects the malicious files. Some intruders do not attack directly, but they hide some harmful code inside the files or may corrupt those file and attack the system. These files are detected according to some defined parameters which will form two lists of files as normal files and harmful files. After that data mining will be performed. In this paper a hybrid classifier has been used via Naive Bayes and Ripper classification methods. The results show how the uploaded file in the database will be tested against the parameters and then it is characterised as either normal or harmful file and after that the mining is performed. Moreover, when a user tries to mine on harmful file it will generate an exception that mining cannot be made on corrupted or harmful files.Keywords: data mining, association, classification, clustering, decision tree, intrusion detection system, misuse detection, anomaly detection, naive Bayes, ripper
Procedia PDF Downloads 4142426 QSAR Modeling of Germination Activity of a Series of 5-(4-Substituent-Phenoxy)-3-Methylfuran-2(5H)-One Derivatives with Potential of Strigolactone Mimics toward Striga hermonthica
Authors: Strahinja Kovačević, Sanja Podunavac-Kuzmanović, Lidija Jevrić, Cristina Prandi, Piermichele Kobauri
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The present study is based on molecular modeling of a series of twelve 5-(4-substituent-phenoxy)-3-methylfuran-2(5H)-one derivatives which have potential of strigolactones mimics toward Striga hermonthica. The first step of the analysis included the calculation of molecular descriptors which numerically describe the structures of the analyzed compounds. The descriptors ALOGP (lipophilicity), AClogS (water solubility) and BBB (blood-brain barrier penetration), served as the input variables in multiple linear regression (MLR) modeling of germination activity toward S. hermonthica. Two MLR models were obtained. The first MLR model contains ALOGP and AClogS descriptors, while the second one is based on these two descriptors plus BBB descriptor. Despite the braking Topliss-Costello rule in the second MLR model, it has much better statistical and cross-validation characteristics than the first one. The ALOGP and AClogS descriptors are often very suitable predictors of the biological activity of many compounds. They are very important descriptors of the biological behavior and availability of a compound in any biological system (i.e. the ability to pass through the cell membranes). BBB descriptor defines the ability of a molecule to pass through the blood-brain barrier. Besides the lipophilicity of a compound, this descriptor carries the information of the molecular bulkiness (its value strongly depends on molecular bulkiness). According to the obtained results of MLR modeling, these three descriptors are considered as very good predictors of germination activity of the analyzed compounds toward S. hermonthica seeds. This article is based upon work from COST Action (FA1206), supported by COST (European Cooperation in Science and Technology).Keywords: chemometrics, germination activity, molecular modeling, QSAR analysis, strigolactones
Procedia PDF Downloads 2862425 Classification of Foliar Nitrogen in Common Bean (Phaseolus Vulgaris L.) Using Deep Learning Models and Images
Authors: Marcos Silva Tavares, Jamile Raquel Regazzo, Edson José de Souza Sardinha, Murilo Mesquita Baesso
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Common beans are a widely cultivated and consumed legume globally, serving as a staple food for humans, especially in developing countries, due to their nutritional characteristics. Nitrogen (N) is the most limiting nutrient for productivity, and foliar analysis is crucial to ensure balanced nitrogen fertilization. Excessive N applications can cause, either isolated or cumulatively, soil and water contamination, plant toxicity, and increase their susceptibility to diseases and pests. However, the quantification of N using conventional methods is time-consuming and costly, demanding new technologies to optimize the adequate supply of N to plants. Thus, it becomes necessary to establish constant monitoring of the foliar content of this macronutrient in plants, mainly at the V4 stage, aiming at precision management of nitrogen fertilization. In this work, the objective was to evaluate the performance of a deep learning model, Resnet-50, in the classification of foliar nitrogen in common beans using RGB images. The BRS Estilo cultivar was sown in a greenhouse in a completely randomized design with four nitrogen doses (T1 = 0 kg N ha-1, T2 = 25 kg N ha-1, T3 = 75 kg N ha-1, and T4 = 100 kg N ha-1) and 12 replications. Pots with 5L capacity were used with a substrate composed of 43% soil (Neossolo Quartzarênico), 28.5% crushed sugarcane bagasse, and 28.5% cured bovine manure. The water supply of the plants was done with 5mm of water per day. The application of urea (45% N) and the acquisition of images occurred 14 and 32 days after sowing, respectively. A code developed in Matlab© R2022b was used to cut the original images into smaller blocks, originating an image bank composed of 4 folders representing the four classes and labeled as T1, T2, T3, and T4, each containing 500 images of 224x224 pixels obtained from plants cultivated under different N doses. The Matlab© R2022b software was used for the implementation and performance analysis of the model. The evaluation of the efficiency was done by a set of metrics, including accuracy (AC), F1-score (F1), specificity (SP), area under the curve (AUC), and precision (P). The ResNet-50 showed high performance in the classification of foliar N levels in common beans, with AC values of 85.6%. The F1 for classes T1, T2, T3, and T4 was 76, 72, 74, and 77%, respectively. This study revealed that the use of RGB images combined with deep learning can be a promising alternative to slow laboratory analyses, capable of optimizing the estimation of foliar N. This can allow rapid intervention by the producer to achieve higher productivity and less fertilizer waste. Future approaches are encouraged to develop mobile devices capable of handling images using deep learning for the classification of the nutritional status of plants in situ.Keywords: convolutional neural network, residual network 50, nutritional status, artificial intelligence
Procedia PDF Downloads 192424 Conformance to Spatial Planning between the Kampala Physical Development Plan of 2012 and the Existing Land Use in 2021
Authors: Brendah Nagula, Omolo Fredrick Okalebo, Ronald Ssengendo, Ivan Bamweyana
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The Kampala Physical Development Plan (KPDP) was developed in 2012 and projected both long term and short term developments within the City .The purpose of the plan was to not only shape the city into a spatially planned area but also to control the urban sprawl trends that had expanded with pronounced instances of informal settlements. This plan was approved by the National Physical Planning Board and a signature was appended by the Minister in 2013. Much as the KPDP plan has been implemented using different approaches such as detailed planning, development control, subdivision planning, carrying out construction inspections, greening and beautification, there is still limited knowledge on the level of conformance towards this plan. Therefore, it is yet to be determined whether it has been effective in shaping the City into an ideal spatially planned area. Attaining a clear picture of the level of conformance towards the KPDP 2012 through evaluation between the planned and the existing land use in Kampala City was performed. Methods such as Supervised Classification and Post Classification Change Detection were adopted to perform this evaluation. Scrutiny of findings revealed Central Division registered the lowest level of conformance to the planning standards specified in the KPDP 2012 followed by Nakawa, Rubaga, Kawempe, and Makindye. Furthermore, mixed-use development was identified as the land use with the highest level of non-conformity of 25.11% and institutional land use registered the highest level of conformance of 84.45 %. The results show that the aspect of location was not carefully considered while allocating uses in the KPDP whereby areas located near the Central Business District have higher land rents and hence require uses that ensure profit maximization. Also, the prominence of development towards mixed-use denotes an increased demand for land towards compact development that was not catered for in the plan. Therefore in order to transform Kampala city into a spatially planned area, there is need to carefully develop detailed plans especially for all the Central Division planning precincts indicating considerations for land use densification.Keywords: spatial plan, post classification change detection, Kampala city, landuse
Procedia PDF Downloads 922423 Efficacy of Phonological Awareness Intervention for People with Language Impairment
Authors: I. Wardana Ketut, I. Suparwa Nyoman
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This study investigated the form and characteristic of speech sound produced by three Balinese subjects who have recovered from aphasia as well as intervened their language impairment on side of linguistic and neuronal aspects of views. The failure of judging the speech sound was caused by impairment of motor cortex that indicated there were lesions in left hemispheric language zone. Sound articulation phenomena were in the forms of phonemes deletion, replacement or assimilation in individual words and meaning building for anomic aphasia. Therefore, the Balinese sound patterns were stimulated by showing pictures to the subjects and recorded to recognize what individual consonants or vowels they unclearly produced and to find out how the sound disorder occurred. The physiology of sound production by subject’s speech organs could not only show the accuracy of articulation but also any level of severity the lesion they suffered from. The subjects’ speech sounds were investigated, classified and analyzed to know how poor the lingual units were and observed to clarify weaknesses of sound characters occurred either for place or manner of articulation. Many fricative and stopped consonants were replaced by glottal or palatal sounds because the cranial nerve, such as facial, trigeminal, and hypoglossal underwent impairment after the stroke. The phonological intervention was applied through a technique called phonemic articulation drill and the examination was conducted to know any change has been obtained. The finding informed that some weak articulation turned into clearer sound and simple meaning of language has been conveyed. The hierarchy of functional parts of brain played important role of language formulation and processing. From this finding, it can be clearly emphasized that this study supports the role of right hemisphere in recovery from aphasia is associated with functional brain reorganization.Keywords: aphasia, intervention, phonology, stroke
Procedia PDF Downloads 1962422 High-Resolution ECG Automated Analysis and Diagnosis
Authors: Ayad Dalloo, Sulaf Dalloo
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Electrocardiogram (ECG) recording is prone to complications, on analysis by physicians, due to noise and artifacts, thus creating ambiguity leading to possible error of diagnosis. Such drawbacks may be overcome with the advent of high resolution Methods, such as Discrete Wavelet Analysis and Digital Signal Processing (DSP) techniques. This ECG signal analysis is implemented in three stages: ECG preprocessing, features extraction and classification with the aim of realizing high resolution ECG diagnosis and improved detection of abnormal conditions in the heart. The preprocessing stage involves removing spurious artifacts (noise), due to such factors as muscle contraction, motion, respiration, etc. ECG features are extracted by applying DSP and suggested sloping method techniques. These measured features represent peak amplitude values and intervals of P, Q, R, S, R’, and T waves on ECG, and other features such as ST elevation, QRS width, heart rate, electrical axis, QR and QT intervals. The classification is preformed using these extracted features and the criteria for cardiovascular diseases. The ECG diagnostic system is successfully applied to 12-lead ECG recordings for 12 cases. The system is provided with information to enable it diagnoses 15 different diseases. Physician’s and computer’s diagnoses are compared with 90% agreement, with respect to physician diagnosis, and the time taken for diagnosis is 2 seconds. All of these operations are programmed in Matlab environment.Keywords: ECG diagnostic system, QRS detection, ECG baseline removal, cardiovascular diseases
Procedia PDF Downloads 2972421 The Mitigation of Quercetin on Lead-Induced Neuroinflammation in a Rat Model: Changes in Neuroinflammatory Markers and Memory
Authors: Iliyasu Musa Omoyine, Musa Sunday Abraham, Oladele Sunday Blessing, Iliya Ibrahim Abdullahi, Ibegbu Augustine Oseloka, Nuhu Nana-Hawau, Animoku Abdulrazaq Amoto, Yusuf Abdullateef Onoruoiza, Sambo Sohnap James, Akpulu Steven Peter, Ajayi Abayomi
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The neuroprotective role of inflammation from detrimental intrinsic and extrinsic factors has been reported. However, the overactivation of astrocytes and microglia due to lead toxicity produce excessive pro-inflammatory cytokines, mediating neurodegenerative diseases. The present study investigated the mitigatory effects of quercetin on neuroinflammation, correlating with memory function in lead-exposed rats. In this study, Wistar rats were administered orally with Quercetin (Q: 60 mg/kg) and Succimer as a standard drug (S: 10 mg/kg) for 21 days after lead exposure (Pb: 125 mg/kg) of 21 days or in combination with Pb, once daily for 42 days. Working and reference memory was assessed using an Eight-arm radial water maze (8-ARWM). The changes in brain lead level, the neuronal nitric oxide synthase (nNOS) activity, and the level of neuroinflammatory markers such as tumour necrosis factor-alpha (TNF-α) and Interleukin 1 Beta (IL-1β) were determined. Immunohistochemically, astrocyte expression was evaluated. The results showed that the brain level of lead was increased significantly in lead-exposed rats. The expression of astrocytes increased in the CA3 and CA1 regions of the hippocampus, and the levels of brain TNF-α and IL-1β increased in lead-exposed rats. Lead impaired reference and working memory by increasing reference memory errors and working memory incorrect errors in lead-exposed rats. However, quercetin treatment effectively improved memory and inhibited neuroinflammation by reducing astrocytes’ expression and the levels of TNF-α and IL-1β. The expression of astrocytes and the levels of TNF-α and IL-1β correlated with memory function. The possible explanation for quercetin’s anti-neuroinflammatory effect is that it modulates the activity of cellular proteins involved in the inflammatory response; inhibits the transcription factor of nuclear factor-kappa B (NF-κB), which regulates the expression of proinflammatory molecules; inhibits kinases required for the synthesis of Glial fibrillary acidic protein (GFAP) and modifies the phosphorylation of some proteins, which affect the structure and function of intermediate filament proteins; and, lastly, induces Cyclic-AMP Response Element Binding (CREB) activation and neurogenesis as a compensatory mechanism for memory deficits and neuronal cell death. In conclusion, the levels of neuroinflammatory markers negatively correlated with memory function. Thus, quercetin may be a promising therapy in neuroinflammation and memory dysfunction in populations prone to lead exposure.Keywords: lead, quercetin, neuroinflammation, memory
Procedia PDF Downloads 542420 Identification of Potential Small Molecule Inhibitors Against β-hCG for Cancer Therapy: An In-Silico Study
Authors: Shreya Sara Ittycheria, K. C. Sivakumar, Shijulal Nelson Sathi, Priya Srinivas
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hCG, a heterodimer composed of α and β subunits, is a peptide hormone having numerous biological functions. Although hCG is expressed by placenta during pregnancy, ectopic β-hCG secretion is observed in many non-trophoblastic tumors including that of breast. In-vitro and in-vivo studies done in the lab, have proved that BRCA1 defective cancers express β-hCG and when β-hCG is expressed or supplemented, it promotes tumor progression and exhibits resistance to carboplatin and ABT888, in such cancers but not in BRCA1 wild type cancers. In cancer cells, instead of binding to its regular receptor, LH-CGR, β-hCG binds with Transforming Growth Factor Receptor 2 (TGFβRII) and phosphorylates it resulting in faster tumor progression through the Smad signaling pathway. Targeting β-hCG could be a potential therapeutic strategy for managing BRCA1 defective cancers. Here, molecular docking and dynamic simulation studies were done to identify potential small molecule inhibitors against β-hCG as there are currently no such inhibitors reported. The binding sites of TGFβRII on β-hCG were identified from the top 10 predicted complexes from Z Dock. Virtual screening of selected commercially available small molecules from various libraries such as ZINC, NCI and Life Chemicals amounting to a total of 50,025 molecules were done. Four potential small molecule inhibitors were identified, RgcbPs-1, RgcbPs-2, RgcbPs-3 and RgcbPs-4 with binding affinities -60.778 kcal/mol, -45.447 kcal/mol, -65.2268 kcal/mol and -82.040 kcal/mol respectively. Further, 100ns Molecular Dynamics (MD) simulation showed that these molecules form stable complexes with β-hCG. RgcbPs-1 maintains hydrogen bonds with Q54, L52, Q46, C100, G36, C57, C38 residues, RgcbPs-2 maintains hydrogen bonds with A83 residue, RgcbPs-3 maintains hydrogen bonds with C57, Y58, R94, G101 residues and RgcbPs-4 maintains hydrogen bonds with G36, C38, T40, C57, D99, C100, G101 and L104 residues of β-hCG all of which coincide with the TGFβRII binding site on β-hCG. These results show that these two inhibitors could be used either singly or in combination for inhibiting β-hCG from binding to TGFβRII and thereby directly inhibiting the tumorigenesis pathway.Keywords: β-hCG, breast cancer, dynamic simulations, molecular docking, small molecule inhibitors, virtual screening.
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