Search results for: multiple sequence alignment
5928 Clastic Sequence Stratigraphy of Late Jurassic to Early Cretaceous Formations of Jaisalmer Basin, Rajasthan
Authors: Himanshu Kumar Gupta
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The Jaisalmer Basin is one of the parts of the Rajasthan basin in northwestern India. The presence of five major unconformities/hiatuses of varying span i.e. at the top of Archean basement, Cambrian, Jurassic, Cretaceous, and Eocene have created the foundation for constructing a sequence stratigraphic framework. Based on basin formative tectonic events and their impact on sedimentation processes three first-order sequences have been identified in Rajasthan Basin. These are Proterozoic-Early Cambrian rift sequence, Permian to Middle-Late Eocene shelf sequence and Pleistocene - Recent sequence related to Himalayan Orogeny. The Permian to Middle Eocene I order sequence is further subdivided into three-second order sequences i.e. Permian to Late Jurassic II order sequence, Early to Late Cretaceous II order sequence and Paleocene to Middle-Late Eocene II order sequence. In this study, Late Jurassic to Early Cretaceous sequence was identified and log-based interpretation of smaller order T-R cycles have been carried out. A log profile from eastern margin to western margin (up to Shahgarh depression) has been taken. The depositional environment penetrated by the wells interpreted from log signatures gave three major facies association. The blocky and coarsening upward (funnel shape), the blocky and fining upward (bell shape) and the erratic (zig-zag) facies representing distributary mouth bar, distributary channel and marine mud facies respectively. Late Jurassic Formation (Baisakhi-Bhadasar) and Early Cretaceous Formation (Pariwar) shows a lesser number of T-R cycles in shallower and higher number of T-R cycles in deeper bathymetry. Shallowest well has 3 T-R cycles in Baisakhi-Bhadasar and 2 T-R cycles in Pariwar, whereas deeper well has 4 T-R cycles in Baisakhi-Bhadasar and 8 T-R cycles in Pariwar Formation. The Maximum Flooding surfaces observed from the stratigraphy analysis indicate major shale break (high shale content). The study area is dominated by the alternation of shale and sand lithologies, which occurs in an approximate ratio of 70:30. A seismo-geological cross section has been prepared to understand the stratigraphic thickness variation and structural disposition of the strata. The formations are quite thick to the west, the thickness of which reduces as we traverse towards the east. The folded and the faulted strata indicated the compressional tectonics followed by the extensional tectonics. Our interpretation is supported with seismic up to second order sequence indicates - Late Jurassic sequence is a Highstand Systems Tract (Baisakhi - Bhadasar formations), and the Early Cretaceous sequence is Regressive to Lowstand System Tract (Pariwar Formation).Keywords: Jaisalmer Basin, sequence stratigraphy, system tract, T-R cycle
Procedia PDF Downloads 1305927 An Unbiased Profiling of Immune Repertoire via Sequencing and Analyzing T-Cell Receptor Genes
Authors: Yi-Lin Chen, Sheng-Jou Hung, Tsunglin Liu
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Adaptive immune system recognizes a wide range of antigens via expressing a large number of structurally distinct T cell and B cell receptor genes. The distinct receptor genes arise from complex rearrangements called V(D)J recombination, and constitute the immune repertoire. A common method of profiling immune repertoire is via amplifying recombined receptor genes using multiple primers and high-throughput sequencing. This multiplex-PCR approach is efficient; however, the resulting repertoire can be distorted because of primer bias. To eliminate primer bias, 5’ RACE is an alternative amplification approach. However, the application of RACE approach is limited by its low efficiency (i.e., the majority of data are non-regular receptor sequences, e.g., containing intronic segments) and lack of the convenient tool for analysis. We propose a computational tool that can correctly identify non-regular receptor sequences in RACE data via aligning receptor sequences against the whole gene instead of only the exon regions as done in all other tools. Using our tool, the remaining regular data allow for an accurate profiling of immune repertoire. In addition, a RACE approach is improved to yield a higher fraction of regular T-cell receptor sequences. Finally, we quantify the degree of primer bias of a multiplex-PCR approach via comparing it to the RACE approach. The results reveal significant differences in frequency of VJ combination by the two approaches. Together, we provide a new experimental and computation pipeline for an unbiased profiling of immune repertoire. As immune repertoire profiling has many applications, e.g., tracing bacterial and viral infection, detection of T cell lymphoma and minimal residual disease, monitoring cancer immunotherapy, etc., our work should benefit scientists who are interested in the applications.Keywords: immune repertoire, T-cell receptor, 5' RACE, high-throughput sequencing, sequence alignment
Procedia PDF Downloads 1895926 Reliability of Movement Assessment Battery for Children-2 Age Band 3 Using Multiple Testers
Authors: Jernice S. Y. Tan
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Introduction: Reliability within and between testers is vital to ensure the accuracy of any motor assessment instrument. However, reliability checks of the Movement Assessment Battery for Children-2 (MABC-2) age band 3 using multiple testers assigned to different MABC-2 tasks for the same group of participants are uncommon. Multiple testers were not stated as a choice in the MABC-2 manual. Therefore, the purpose of this study was to determine the inter- and intra-tester reliability for using multiple testers to administer the test protocols of MABC-2 age band 3. Methods: Thirty volunteered adolescents (n = 30; 15 males, 15 females; age range: 13 – 16 years) performed the eight tasks in a randomised sequence at three different test stations for the MABC-2 task components (Manual Dexterity, Aiming and Catching, Balance). Ethics approval and parental consent were obtained. The participants were videotaped while performing the test protocols of MABC-2 age band 3. Five testers were involved in the data collection process. They were Sports Science graduating students doing their final year project and were supervised by experienced motor assessor. Inter- and intra-tester reliability checks using intra-class coefficient (ICC) were carried out using the videotaped data. Results: The inter-tester reliability between the five testers for the eight tasks ranged from rᵢcc = 0.705 to rᵢcc = 0.995. This suggests that the average agreement between them was considered good to excellent. With the exception of one tester who had rᵢcc = 0.687 for one of the eight tasks (i.e. zip-zap hopping), the intra-tester reliability within each tester ranged from rᵢcc = 0.728 to rᵢcc = 1.000, and this also suggested good to excellent consistency within testers. Discussion: The use of multiple testers with good intra-tester reliability for different test stations is feasible. This method allows several participants to be assessed concurrently at different test stations and saves overall data collection time. Therefore, it is recommended that the administering of MABC-2 with multiple testers should be extended to other age bands ensuring the feasibility of such method for other age bands.Keywords: adolescents, MABC, motor assessment, motor skills, reliability
Procedia PDF Downloads 3185925 Current Epizootic Situation of Q Fever in Polish Cattle
Authors: Monika Szymańska-Czerwińska, Agnieszka Jodełko, Krzysztof Niemczuk
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Q fever (coxiellosis) is an infectious disease of animals and humans causes by C. burnetii and widely distributed throughout the world. Cattle and small ruminants are commonly known as shedders of C. burnetii. The aims of this study were the evaluation of seroprevalence and shedding of C. burnetii in cattle. Genotypes of the pathogen present in the tested specimens were also identified using MLVA (Multiple Locus Variable-Number Tandem Repeat Analysis) and MST (multispacer sequence typing) methods. Sampling was conducted in different regions of Poland in 2018-2021. In total, 2180 bovine serum samples from 801 cattle herds were tested by ELISA (enzyme-linked immunosorbent assay). 489 specimens from 157 cattle herds such as: individual milk samples (n=407), bulk tank milk (n=58), vaginal swabs (n=20), placenta (n=3) and feces (n=1) were subjected to C. burnetii specific qPCR. The qPCR (IS1111 transposon-like repetitive region) was performed using Adiavet COX RealTime PCR kit. Genotypic characterization of the strains was conducted utilizing MLVA and MST methods. MLVA was performed using 6 variable loci. The overall herd-level seroprevalence of C. burnetii infection was 36.74% (801/2180). Shedders were detected in 29.3% (46/157) cattle herds in all tested regions. ST 61 sequence type was identified in 10 out of 18 genotyped strains. Interestingly one strain represents sequence type which has never been recorded previously. MLVA method identified three previously known genotypes: most common was J but also I and BE were recognized. Moreover, a one genotype has never been described previously. Seroprevalence and shedding of C. burnetii in cattle is common and strains are genetically diverse.Keywords: Coxiella burnetii, cattle, MST, MLVA, Q fever
Procedia PDF Downloads 815924 In-Vitro Dextran Synthesis and Characterization of an Intracellular Glucosyltransferase from Leuconostoc Mesenteroides AA1
Authors: Afsheen Aman, Shah Ali Ul Qader
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Dextransucrase [EC 2.4.1.5] is a glucosyltransferase that catalysis the biosynthesis of a natural biopolymer called dextran. It can catalyze the transfer of D-glucopyranosyl residues from sucrose to the main chain of dextran. This unique biopolymer has multiple applications in several industries and the key utilization of dextran lies on its molecular weight and the type of branching. Extracellular dextransucrase from Leuconostoc mesenteroides is most extensively studied and characterized. Limited data is available regarding cell-bound or intracellular dextransucrase and on the characterization of dextran produced by in-vitro reaction of intracellular dextransucrase. L. mesenteroides AA1 is reported to produce extracellular dextransucrase that catalyzes biosynthesis of a high molecular weight dextran with only α-(1→6) linkage. Current study deals with the characterization of an intracellular dextransucrase and in vitro biosynthesis of low molecular weight dextran from L. mesenteroides AA1. Intracellular dextransucrase was extracted from cytoplasm and purified to homogeneity for characterization. Kinetic constants, molecular weight and N-terminal sequence analysis of intracellular dextransucrase reveal unique variation with previously reported extracellular dextransucrase from the same strain. In vitro synthesized biopolymer was characterized using NMR spectroscopic techniques. Intracellular dextransucrase exhibited Vmax and Km values of 130.8 DSU ml-1 hr-1 and 221.3 mM, respectively. Optimum catalytic activity was detected at 35°C in 0.15 M citrate phosphate buffer (pH-5.5) in 05 minutes. Molecular mass of purified intracellular dextransucrase is approximately 220.0 kDa on SDS-PAGE. N-terminal sequence of the intracellular enzyme is: GLPGYFGVN that showed no homology with previously reported sequence for the extracellular dextransucrase. This intracellular dextransucrase is capable of in vitro synthesis of dextran under specific conditions. This intracellular dextransucrase is capable of in vitro synthesis of dextran under specific conditions and this biopolymer can be hydrolyzed into different molecular weight fractions for various applications.Keywords: characterization, dextran, dextransucrase, leuconostoc mesenteroides
Procedia PDF Downloads 3915923 Quality Management in Construction Project
Authors: Harsh Panchal, Saurabh Amrutkar
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Quality management is an essential part of any project that has directly related to the performance of a project. Quality management is depended on multiple factors at different stages in a project, right from time management to construction logistics. A project is a mixture of various components that include iternary management, health and safety, crew productivity, and many more. From the survey conducted, we came to the conclusion that advancement in technology and indigenous approach to any project will result in maximum quality standards and better project performance. In this paper, we discuss various components of the factors above that lead to compromise the quality of a project and how it can be controlled in order to achieve maximum quality assurance using quality planning and total quality management. The paper also focuses on limitations and problems faced in each factor responsible for quality management and to tackle them using techniques and processes based on activities and identifying the sequence, approaching critical path, and duration. The project management concept that deals with the sequence of scope cost time give us an overview regarding the ongoing quality management, in a nutshell, giving us hints to regulate the current procedure for maximum achievable quality. It also deals with the problems faced by engineers that make the mundane work process slow, reducing the quality outcome drastically.Keywords: management, performance, project, quality
Procedia PDF Downloads 1585922 Perceptual Organization within Temporal Displacement
Authors: Michele Sinico
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The psychological present has an actual extension. When a sequence of instantaneous stimuli falls in this short interval of time, observers perceive a compresence of events in succession and the temporal order depends on the qualitative relationships between the perceptual properties of the events. Two experiments were carried out to study the influence of perceptual grouping, with and without temporal displacement, on the duration of auditory sequences. The psychophysical method of adjustment was adopted. The first experiment investigated the effect of temporal displacement of a white noise on sequence duration. The second experiment investigated the effect of temporal displacement, along the pitch dimension, on temporal shortening of sequence. The results suggest that the temporal order of sounds, in the case of temporal displacement, is organized along the pitch dimension.Keywords: time perception, perceptual present, temporal displacement, Gestalt laws of perceptual organization
Procedia PDF Downloads 2475921 Identification of Promiscuous Epitopes for Cellular Immune Responses in the Major Antigenic Protein Rv3873 Encoded by Region of Difference 1 of Mycobacterium tuberculosis
Authors: Abu Salim Mustafa
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Rv3873 is a relatively large size protein (371 amino acids in length) and its gene is located in the immunodominant genomic region of difference (RD)1 that is present in the genome of Mycobacterium tuberculosis but deleted from the genomes of all the vaccine strains of Bacillus Calmette Guerin (BCG) and most other mycobacteria. However, when tested for cellular immune responses using peripheral blood mononuclear cells from tuberculosis patients and BCG-vaccinated healthy subjects, this protein was found to be a major stimulator of cell mediated immune responses in both groups of subjects. In order to further identify the sequence of immunodominant epitopes and explore their Human Leukocyte Antigen (HLA)-restriction for epitope recognition, 24 peptides (25-mers overlapping with the neighboring peptides by 10 residues) covering the sequence of Rv3873 were synthesized chemically using fluorenylmethyloxycarbonyl chemistry and tested in cell mediated immune responses. The results of these experiments helped in the identification of an immunodominant peptide P9 that was recognized by people expressing varying HLA-DR types. Furthermore, it was also predicted to be a promiscuous binder with multiple epitopes for binding to HLA-DR, HLA-DP and HLA-DQ alleles of HLA-class II molecules that present antigens to T helper cells, and to HLA-class I molecules that present antigens to T cytotoxic cells. In addition, the evaluation of peptide P9 using an immunogenicity predictor server yielded a high score (0.94), which indicated a greater probability of this peptide to elicit a protective cellular immune response. In conclusion, P9, a peptide with multiple epitopes and ability to bind several HLA class I and class II molecules for presentation to cells of the cellular immune response, may be useful as a peptide-based vaccine against tuberculosis.Keywords: mycobacterium tuberculosis, PPE68, peptides, vaccine
Procedia PDF Downloads 1275920 Formulation of Optimal Shifting Sequence for Multi-Speed Automatic Transmission
Authors: Sireesha Tamada, Debraj Bhattacharjee, Pranab K. Dan, Prabha Bhola
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The most important component in an automotive transmission system is the gearbox which controls the speed of the vehicle. In an automatic transmission, the right positioning of actuators ensures efficient transmission mechanism embodiment, wherein the challenge lies in formulating the number of actuators associated with modelling a gearbox. Data with respect to actuation and gear shifting sequence has been retrieved from the available literature, including patent documents, and has been used in this proposed heuristics based methodology for modelling actuation sequence in a gear box. This paper presents a methodological approach in designing a gearbox for the purpose of obtaining an optimal shifting sequence. The computational model considers factors namely, the number of stages and gear teeth as input parameters since these two are the determinants of the gear ratios in an epicyclic gear train. The proposed transmission schematic or stick diagram aids in developing the gearbox layout design. The number of iterations and development time required to design a gearbox layout is reduced by using this approach.Keywords: automatic transmission, gear-shifting, multi-stage planetary gearbox, rank ordered clustering
Procedia PDF Downloads 3195919 Effect of Weave Structure and Picking Sequence on the Comfort Properties of Woven Fabrics
Authors: Muhammad Umair, Tanveer Hussain, Khubab Shaker, Yasir Nawab, Muhammad Maqsood, Madeha Jabbar
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The term comfort is defined as 'the absence of unpleasantness or discomfort' or 'a neutral state compared to the more active state'. Comfort mainly is of three types: sensorial (tactile) comfort, psychological comfort and thermo-physiological comfort. Thermophysiological comfort is determined by the air permeability and moisture management properties of the garment. The aim of this study was to investigate the effect of weave structure and picking sequence on the comfort properties of woven fabrics. Six woven fabrics with two different weave structures i.e. 1/1 plain and 3/1 twill and three different picking sequences: (SPI, DPI, 3PI) were taken as input variables whereas air permeability, wetting time, wicking behavior and overall moisture management capability (OMMC) of fabrics were taken as response variables and a comparison is made of the effect of weave structure and picking sequence on the response variables. It was found that fabrics woven in twill weave design and with simultaneous triple pick insertion (3PI) give significantly better air permeability, shorter wetting time and better water spreading rate, as compared to plain woven fabrics and those with double pick insertion (DPI) or single pick insertion (SPI). It could be concluded that the thermophysiological comfort of woven fabrics may be significantly improved simply by selecting a suitable weave design and picking sequence.Keywords: air permeability, picking sequence, thermophysiological comfort, weave design
Procedia PDF Downloads 4105918 PMEL Marker Identification of Dark and Light Feather Colours in Local Canary
Authors: Mudawamah Mudawamah, Muhammad Z. Fadli, Gatot Ciptadi, Aulanni’am
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Canary breeders have spread throughout Indonesian regions for the low-middle society and become an income source for them. The interesting phenomenon of the canary market is the feather colours become one of determining factor for the price. The advantages of this research were contributed to the molecular database as a base of selection and mating for the Indonesia canary breeder. The research method was experiment with the genome obtained from canary blood isolation. The genome did the PCR amplification with PMEL marker followed by sequencing. Canaries were used 24 heads of light and dark colour feathers. Research data analyses used BioEdit and Network 4.6.0.0 software. The results showed that all samples were amplification with PMEL gene with 500 bp fragment length. In base sequence of 40 was found Cytosine(C) in the light colour canaries, while the dark colour canaries was obtained Thymine (T) in same base sequence. Sequence results had 286-415 bp fragment and 10 haplotypes. The conclusions were the PMEL gene (gene of white pigment) was likely to be used PMEL gene to detect molecular genetic variation of dark and light colour feather.Keywords: canary, haplotype, PMEL, sequence
Procedia PDF Downloads 2285917 Co-Movement between Financial Assets: An Empirical Study on Effects of the Depreciation of Yen on Asia Markets
Authors: Yih-Wenn Laih
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In recent times, the dependence and co-movement among international financial markets have become stronger than in the past, as evidenced by commentaries in the news media and the financial sections of newspapers. Studying the co-movement between returns in financial markets is an important issue for portfolio management and risk management. The realization of co-movement helps investors to identify the opportunities for international portfolio management in terms of asset allocation and pricing. Since the election of the new Prime Minister, Shinzo Abe, in November 2012, the yen has weakened against the US dollar from the 80 to the 120 level. The policies, known as “Abenomics,” are to encourage private investment through a more aggressive mix of monetary and fiscal policy. Given the close economic relations and competitions among Asia markets, it is interesting to discover the co-movement relations, affected by the depreciation of yen, between stock market of Japan and 5 major Asia stock markets, including China, Hong Kong, Korea, Singapore, and Taiwan. Specifically, we devote ourselves to measure the co-movement of stock markets between Japan and each one of the 5 Asia stock markets in terms of rank correlation coefficients. To compute the coefficients, return series of each stock market is first fitted by a skewed-t GARCH (generalized autoregressive conditional heteroscedasticity) model. Secondly, to measure the dependence structure between matched stock markets, we employ the symmetrized Joe-Clayton (SJC) copula to calculate the probability density function of paired skewed-t distributions. The joint probability density function is then utilized as the scoring scheme to optimize the sequence alignment by dynamic programming method. Finally, we compute the rank correlation coefficients (Kendall's and Spearman's ) between matched stock markets based on their aligned sequences. We collect empirical data of 6 stock indexes from Taiwan Economic Journal. The data is sampled at a daily frequency covering the period from January 1, 2013 to July 31, 2015. The empirical distributions of returns indicate fatter tails than the normal distribution. Therefore, the skewed-t distribution and SJC copula are appropriate for characterizing the data. According to the computed Kendall’s τ, Korea has the strongest co-movement relation with Japan, followed by Taiwan, China, and Singapore; the weakest is Hong Kong. On the other hand, the Spearman’s ρ reveals that the strength of co-movement between markets with Japan in decreasing order are Korea, China, Taiwan, Singapore, and Hong Kong. We explore the effects of “Abenomics” on Asia stock markets by measuring the co-movement relation between Japan and five major Asia stock markets in terms of rank correlation coefficients. The matched markets are aligned by a hybrid method consisting of GARCH, copula and sequence alignment. Empirical experiments indicate that Korea has the strongest co-movement relation with Japan. The strength of China and Taiwan are better than Singapore. The Hong Kong market has the weakest co-movement relation with Japan.Keywords: co-movement, depreciation of Yen, rank correlation, stock market
Procedia PDF Downloads 2285916 Phenotype Prediction of DNA Sequence Data: A Machine and Statistical Learning Approach
Authors: Mpho Mokoatle, Darlington Mapiye, James Mashiyane, Stephanie Muller, Gciniwe Dlamini
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Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on $k$-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0%, 80.5%, 80.5%, 63.6%, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms.Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing
Procedia PDF Downloads 1615915 Phenotype Prediction of DNA Sequence Data: A Machine and Statistical Learning Approach
Authors: Darlington Mapiye, Mpho Mokoatle, James Mashiyane, Stephanie Muller, Gciniwe Dlamini
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Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on k-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0 %, 80.5 %, 80.5 %, 63.6 %, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanismsKeywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing
Procedia PDF Downloads 1475914 Tectonics of Out-of-Sequence Thrusting in Higher Himalaya- Example from Jhakri-Chaura-Sarahan Region, Himachal Pradesh
Authors: Rajkumar Ghosh
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The Out-of-Sequence Thrust (OOST) is a common phenomenon in collisional tectonic settings like the Himalayas. These OOSTs are activated in different locations at different time frames. These OOST are linked with the multiple Himalayan Thrusts. Apart from minimal documentation in geological mapping for OOST, there exists a lack of field data to establish OOST in the field. This work has considered three thrusts from NW Himalaya in Himachal Pradesh with published data from other sources, allowing a re-examination for correlation of OOST. For the Sutlej section, the approach has been to do fieldwork and microstructural studies. The information related to the cross-cut signature of S/C- and relative time relation could help to predict the nature of OOST. The activation timing, along with the basis of identification of OOST in Higher Himalayan, was documented in various literature. Compilation of the Grain Boundary Migration (GBM) associated temperature range (400–750 °C) was documented from microstructural studies along the Jhakri-Chaura section. No such significant temperature variation across thrusts was observed. Strain variation paths using S Ʌ C angle measurement were carried out along the Jeori-Wangtu transect to distinguish overprinting structures for OOSTs. Near the Chaura Thrust (CT), angular variation of S Ʌ C was documented, and it varies within a range of 15° - 28 °. Along the NH22 (National Highway, 22), all tectonic units of the orogen are exposed in NW Himalaya, INDIA. But there are inherent difficulties in finding field evidence of OOST, largely due to the lack of adequate surface morphology, including topography and drainage pattern.Keywords: out-of-sequence thrust (OOST), main central thrust (MCT), south tibetan detachment system (STDS), jhakri thrust (JT), sarahan thrust (ST), chaura thrust (CT), higher himalaya (HH), greater himalayan crystalline (GHC)
Procedia PDF Downloads 765913 Automatic Method for Classification of Informative and Noninformative Images in Colonoscopy Video
Authors: Nidhal K. Azawi, John M. Gauch
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Colorectal cancer is one of the leading causes of cancer death in the US and the world, which is why millions of colonoscopy examinations are performed annually. Unfortunately, noise, specular highlights, and motion artifacts corrupt many images in a typical colonoscopy exam. The goal of our research is to produce automated techniques to detect and correct or remove these noninformative images from colonoscopy videos, so physicians can focus their attention on informative images. In this research, we first automatically extract features from images. Then we use machine learning and deep neural network to classify colonoscopy images as either informative or noninformative. Our results show that we achieve image classification accuracy between 92-98%. We also show how the removal of noninformative images together with image alignment can aid in the creation of image panoramas and other visualizations of colonoscopy images.Keywords: colonoscopy classification, feature extraction, image alignment, machine learning
Procedia PDF Downloads 2465912 DNpro: A Deep Learning Network Approach to Predicting Protein Stability Changes Induced by Single-Site Mutations
Authors: Xiao Zhou, Jianlin Cheng
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A single amino acid mutation can have a significant impact on the stability of protein structure. Thus, the prediction of protein stability change induced by single site mutations is critical and useful for studying protein function and structure. Here, we presented a deep learning network with the dropout technique for predicting protein stability changes upon single amino acid substitution. While using only protein sequence as input, the overall prediction accuracy of the method on a standard benchmark is >85%, which is higher than existing sequence-based methods and is comparable to the methods that use not only protein sequence but also tertiary structure, pH value and temperature. The results demonstrate that deep learning is a promising technique for protein stability prediction. The good performance of this sequence-based method makes it a valuable tool for predicting the impact of mutations on most proteins whose experimental structures are not available. Both the downloadable software package and the user-friendly web server (DNpro) that implement the method for predicting protein stability changes induced by amino acid mutations are freely available for the community to use.Keywords: bioinformatics, deep learning, protein stability prediction, biological data mining
Procedia PDF Downloads 4545911 In-Depth Analysis on Sequence Evolution and Molecular Interaction of Influenza Receptors (Hemagglutinin and Neuraminidase)
Authors: Dong Tran, Thanh Dac Van, Ly Le
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Hemagglutinin (HA) and Neuraminidase (NA) play an important role in host immune evasion across influenza virus evolution process. The correlation between HA and NA evolution in respect to epitopic evolution and drug interaction has yet to be investigated. In this study, combining of sequence to structure evolution and statistical analysis on epitopic/binding site specificity, we identified potential therapeutic features of HA and NA that show specific antibody binding site of HA and specific binding distribution within NA active site of current inhibitors. Our approach introduces the use of sequence variation and molecular interaction to provide an effective strategy in establishing experimental based distributed representations of protein-protein/ligand complexes. The most important advantage of our method is that it does not require complete dataset of complexes but rather directly inferring feature interaction from sequence variation and molecular interaction. Using correlated sequence analysis, we additionally identified co-evolved mutations associated with maintaining HA/NA structural and functional variability toward immunity and therapeutic treatment. Our investigation on the HA binding specificity revealed unique conserved stalk domain interacts with unique loop domain of universal antibodies (CR9114, CT149, CR8043, CR8020, F16v3, CR6261, F10). On the other hand, NA inhibitors (Oseltamivir, Zaninamivir, Laninamivir) showed specific conserved residue contribution and similar to that of NA substrate (sialic acid) which can be exploited for drug design. Our study provides an important insight into rational design and identification of novel therapeutics targeting universally recognized feature of influenza HA/NA.Keywords: influenza virus, hemagglutinin (HA), neuraminidase (NA), sequence evolution
Procedia PDF Downloads 1525910 Cloning and Expression of Human Interleukin 15: A Promising Candidate for Cytokine Immunotherapy
Authors: Sadaf Ilyas
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Recombinant cytokines have been employed successfully as potential therapeutic agent. Some cytokine therapies are already used as a part of clinical practice, ranging from early exploratory trials to well established therapies that have already received approval. Interleukin 15 is a pleiotropic cytokine having multiple roles in peripheral innate and adaptive immune cell function. It regulates the activation, proliferation and maturation of NK cells, T-cells, monocytes/macrophages and granulocytes, and the interactions between them thus acting as a bridge between innate and adaptive immune responses. Unraveling the biology of IL-15 has revealed some interesting surprises that may point toward some of the first therapeutic applications for this cytokine. In this study, the human interleukin 15 gene was isolated, amplified and ligated to a TA vector which was then transfected to a bacterial host, E. coli Top10F’. The sequence of cloned gene was confirmed and it showed 100% homology with the reported sequence. The confirmed gene was then subcloned in pET Expression system to study the IPTG induced expression of IL-15 gene. Positive expression was obtained for number of clones that showed 15 kd band of IL-15 in SDS-PAGE analysis, indicating the successful strain development that can be studied further to assess the potential therapeutic intervention of this cytokine in relevance to human diseases.Keywords: Interleukin 15, pET expression system, immune therapy, protein purification
Procedia PDF Downloads 4075909 A Conflict of Relations in Toni Morrison’s New World Fiction
Authors: Rajeswar Pal
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Toni Morrison’s novels belong to present day relations of Africans with the White peoples and tangible man-woman relations. Her literary criticism can be seen as a contribution to the debate over the revision of the canon that dominated much of the scholarship of the 1980s and 1990s. New Criticism began to give way to theories of cultural studies, feminist scholarship, postcolonial revisions and investigations of race and ethnicity. Morrison is concerned with the definition of the American literature whether it reflects an eternal, universal or transcending paradigm – a paradigm that separates it clearly and unequivocally Chicano or African-American or Asian-American or Native American literature. She sees evidence on an incursion of third world or so-called minority literature into a Eurocentric stronghold, which threatens power structures and leads to an upheaval of existing norms. We see women more aligned, cross-culturally, with nature; however, the very critical distinction is that within a white world, the alignment seems to lead towards individuation for women yet separation from white male culture, and within a black world the alignment leads towards individuation and connection to a ownership of a racial consciousness. Whether externally or internally, the characters of Morrison are marked with a sense of incompleteness and mutual conflict, which drives them towards some force of wholeness. Present study fucusses to elucidate and enunciate the man-woman relations and an individual cataclysmic conflict in their minds.Keywords: tangible, postcolonial, ethnicity, paradigm, upheaval, alignment, elucidate, cataclysmic
Procedia PDF Downloads 4415908 Exploring Simple Sequence Repeats within Conserved microRNA Precursors Identified from Tea Expressed Sequence Tag (EST) Database
Authors: Anjan Hazra, Nirjhar Dasgupta, Chandan Sengupta, Sauren Das
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Tea (Camellia sinensis) has received substantial attention from the scientific world time to time, not only for its commercial importance, but also for its demand to the health-conscious people across the world for its extensive use as potential sources of antioxidant supplement. These health-benefit traits primarily rely on some regulatory networks of different metabolic pathways. Development of microsatellite markers from the conserved genomic regions is being worthwhile for studying the genetic diversity of closely related species or self-pollinated species. Although several SSR markers have been reported, in tea the trait-specific Simple Sequence Repeats (SSRs) are yet to be identified, which can be used for marker assisted breeding technique. MicroRNAs are endogenous, noncoding, short RNAs directly involved in regulating gene expressions at the post-transcriptional level. It has been found that diversity in miRNA gene interferes the formation of its characteristic hair pin structure and the subsequent function. In the present study, the precursors of small regulatory RNAs (microRNAs) has been fished out from tea Expressed Sequence Tag (EST) database. Furthermore, the simple sequence repeat motifs within the putative miRNA precursor genes are also identified in order to experimentally validate their existence and function. It is already known that genic-SSR markers are very adept and breeder-friendly source for genetic diversity analysis. So, the potential outcome of this in-silico study would provide some novel clues in understanding the miRNA-triggered polymorphic genic expression controlling specific metabolic pathways, accountable for tea quality.Keywords: micro RNA, simple sequence repeats, tea quality, trait specific marker
Procedia PDF Downloads 3065907 Genetic Polymorphism and Insilico Study Epitope Block 2 MSP1 Gene of Plasmodium falciparum Isolate Endemic Jayapura
Authors: Arsyam Mawardi, Sony Suhandono, Azzania Fibriani, Fifi Fitriyah Masduki
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Malaria is an infectious disease caused by Plasmodium sp. This disease has a high prevalence in Indonesia, especially in Jayapura. The vaccine that is currently being developed has not been effective in overcoming malaria. This is due to the high polymorphism in the Plasmodium genome especially in areas that encode Plasmodium surface proteins. Merozoite Surface Protein 1 (MSP1) Plasmodium falciparum is a surface protein that plays a role in the invasion process in human erythrocytes through the interaction of Glycophorin A protein receptors and sialic acid in erythrocytes with Reticulocyte Binding Proteins (RBP) and Duffy Adhesion Protein (DAP) ligands in merozoites. MSP1 can be targeted to be a specific antigen and predicted epitope area which will be used for the development of diagnostic and malaria vaccine therapy. MSP1 consists of 17 blocks, each block is dimorphic, and has been marked as the K1 and MAD20 alleles. Exceptions only in block 2, because it has 3 alleles, among others K1, MAD20 and RO33. These polymorphisms cause allelic variations and implicate the severity of patients infected P. falciparum. In addition, polymorphism of MSP1 in Jayapura isolates has not been reported so it is interesting to be further identified and projected as a specific antigen. Therefore, in this study, we analyzed the allele polymorphism as well as detected the MSP1 epitope antigen candidate on block 2 P. falciparum. Clinical samples of selected malaria patients followed the consecutive sampling method, examining malaria parasites with blood preparations on glass objects observed through a microscope. Plasmodium DNA was isolated from the blood of malarial positive patients. The block 2 MSP1 gene was amplified using PCR method and cloned using the pGEM-T easy vector then transformed to TOP'10 E.coli. Positive colonies selection was performed with blue-white screening. The existence of target DNA was confirmed by PCR colonies and DNA sequencing methods. Furthermore, DNA sequence analysis was done through alignment and formation of a phylogenetic tree using MEGA 6 software and insilico analysis using IEDB software to predict epitope candidate for P. falciparum. A total of 15 patient samples have been isolated from Plasmodium DNA. PCR amplification results show the target gene size about ± 1049 bp. The results of MSP1 nucleotide alignment analysis reveal that block 2 MSP1 genes derived from the sample of malarial patients were distributed in four different allele family groups, K1 (7), MAD20 (1), RO33 (0) and MSP1_Jayapura (10) alleles. The most commonly appears of the detected allele is MSP1_Jayapura single allele. There was no significant association between sex variables, age, the density of parasitemia and alel variation (Mann Whitney, U > 0.05), while symptomatic signs have a significant difference as a trigger of detectable allele variation (U < 0.05). In this research, insilico study shows that there is a new epitope antigen candidate from the MSP1_Jayapura allele and it is predicted to be recognized by B cells with 17 amino acid lengths in the amino acid sequence 187 to 203.Keywords: epitope candidate, insilico analysis, MSP1 P. falciparum, polymorphism
Procedia PDF Downloads 1735906 Prediction and Identification of a Permissive Epitope Insertion Site for St Toxoid in cfaB from Enterotoxigenic Escherichia coli
Authors: N. Zeinalzadeh, Mahdi Sadeghi
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Enterotoxigenic Escherichia coli (ETEC) is the most common cause of non-inflammatory diarrhea in the developing countries, resulting in approximately 20% of all diarrheal episodes in children in these areas. ST is one of the most important virulence factors and CFA/I is one of the frequent colonization factors that help to process of ETEC infection. ST and CfaB (CFA/I subunit) are among vaccine candidates against ETEC. So, ST because of its small size is not a good immunogenic in the natural form. However to increase its immunogenic potential, here we explored candidate positions for ST insertion in CfaB sequence. After bioinformatics analysis, one of the candidate positions was selected and the chimeric gene (cfaB*st) sequence was synthesized and expressed in E. coli BL21 (DE3). The chimeric recombinant protein was purified with Ni-NTA columns and characterized with western blot analysis. The residue 74-75 of CfaB sequence could be a good candidate position for ST and other epitopes insertion.Keywords: bioinformatics, CFA/I, enterotoxigenic E. coli, ST toxoid
Procedia PDF Downloads 4435905 Design and Tooth Contact Analysis of Face Gear Drive with Modified Tooth Surface in Helicopter Transmission
Authors: Kazumasa Kawasaki, Isamu Tsuji, Hiroshi Gunbara
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A face gear drive is actually composed of a spur or helical pinion that is in mesh with a face gear and transfers power and motion between intersecting or skew axes. Due to the peculiarity of the face gear drive in shunt and confluence drive, it shows potential advantages in the application in the helicopter transmission. The advantages of such applications are the possibility of the split of the torque that appears to be significant where a pinion drives two face gears to provide an accurate division of power and motion. This mechanism greatly reduces the weight and cost compared to conventional design. Therefore, this has been led to revived interest and the face gear drive has been utilized in substitution for bevel and hypoid gears in limited cases. The face gear drive with a spur or a helical pinion is newly designed in order to determine an effective meshing area under the design parameters and specific design dimensions. The face gear has two unique dimensions which control the face width of the tooth, and the outside and inside diameters of the face gear. On the other hand, it is necessary to modify the tooth surfaces of face gear drive in order to avoid the influences of alignment errors on the tooth contact patterns in practical use. In this case, the pinion tooth surfaces are usually modified in the conventional method. However, it is hard to control the tooth contact pattern intentionally and adjust the position of the pinion axis in meshing of the gear pair. Therefore, a method of the modification of the tooth surfaces of the face gear is proposed. Moreover, based on tooth contact analysis, the tooth contact pattern and transmission errors of the designed face gear drive are analyzed, and the influences of alignment errors on the tooth contact patterns and transmission errors are investigated. These results showed that the tooth contact patterns and transmission errors were controllable and the face gear drive which is insensitive to alignment errors can be obtained.Keywords: alignment error, face gear, gear design, helicopter transmission, tooth contact analysis
Procedia PDF Downloads 4295904 Fabrication of Cylindrical Silicon Nanowire-Embedded Field Effect Transistor Using Al2O3 Transfer Layer
Authors: Sang Hoon Lee, Tae Il Lee, Su Jeong Lee, Jae Min Myoung
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In order to manufacture short gap single Si nanowire (NW) field effect transistor (FET) by imprinting and transferring method, we introduce the method using Al2O3 sacrificial layer. The diameters of cylindrical Si NW addressed between Au electrodes by dielectrophoretic (DEP) alignment method are controlled to 106, 128, and 148 nm. After imprinting and transfer process, cylindrical Si NW is embedded in PVP adhesive and dielectric layer. By curing transferred cylindrical Si NW and Au electrodes on PVP-coated p++ Si substrate with 200nm-thick SiO2, 3μm gap Si NW FET fabrication was completed. As the diameter of embedded Si NW increases, the mobility of FET increases from 80.51 to 121.24 cm2/V•s and the threshold voltage moves from –7.17 to –2.44 V because the ratio of surface to volume gets reduced.Keywords: Al2O3 sacrificial transfer layer, cylindrical silicon nanowires, dielectrophorestic alignment, field effect transistor
Procedia PDF Downloads 4505903 Nucleotide Based Validation of the Endangered Plant Diospyros mespiliformis (Ebenaceae) by Evaluating Short Sequence Region of Plastid rbcL Gene
Authors: Abdullah Alaklabi, Ibrahim A. Arif, Sameera O. Bafeel, Ahmad H. Alfarhan, Anis Ahamed, Jacob Thomas, Mohammad A. Bakir
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Diospyros mespiliformis (Hochst. ex A.DC.; Ebenaceae) is a large deciduous medicinal plant. This plant species is currently listed as endangered in Saudi Arabia. Molecular identification of this plant species based on short sequence regions (571 and 664 bp) of plastid rbcL (ribulose-1, 5-biphosphate carboxylase) gene was investigated in this study. The endangered plant specimens were collected from Al-Baha, Saudi Arabia (GPS coordinate: 19.8543987, 41.3059349). Phylogenetic tree inferred from the rbcL gene sequences showed that this species is very closely related with D. brandisiana. The close relationship was also observed among D. bejaudii, D. Philippinensis and D. releyi (≥99.7% sequence homology). The partial rbcL gene sequence region (571 bp) that was amplified by rbcL primer-pair rbcLaF-rbcLaR failed to discriminate D. mespiliformis from the closely related plant species, D. brandisiana. In contrast, primer-pair rbcL1F-rbcL724R yielded longer amplicon, discriminated the species from D. brandisiana and demonstrated nucleotide variations in 3 different sites (645G>T; 663A>C; 710C>G). Although D. mespiliformis (EU980712) and D. brandisiana (EU980656) are very closely related species (99.4%); however, studied specimen showed 100% sequence homology with D. mespiliformis and 99.6% with D. brandisiana. The present findings showed that rbcL short sequence region (664 bp) of plastid rbcL gene, amplified by primer-pair rbcL1F-rbcL724R, can be used for authenticating samples of D. mespiliforformis and may provide help in authentic identification and management process of this medicinally valuable endangered plant species.Keywords: Diospyros mespiliformis, endangered plant, identification partial rbcL
Procedia PDF Downloads 4225902 Unveiling the Chaura Thrust: Insights into a Blind Out-of-Sequence Thrust in Himachal Pradesh, India
Authors: Rajkumar Ghosh
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The Chaura Thrust, located in Himachal Pradesh, India, is a prominent geological feature that exhibits characteristics of an out-of-sequence thrust fault. This paper explores the geological setting of Himachal Pradesh, focusing on the Chaura Thrust's unique characteristics, its classification as an out-of-sequence thrust, and the implications of its presence in the region. The introduction provides background information on thrust faults and out-of-sequence thrusts, emphasizing their significance in understanding the tectonic history and deformation patterns of an area. It also outlines the objectives of the paper, which include examining the Chaura Thrust's geological features, discussing its classification as an out-of-sequence thrust, and assessing its implications for the region. The paper delves into the geological setting of Himachal Pradesh, describing the tectonic framework and providing insights into the formation of thrust faults in the region. Special attention is given to the Chaura Thrust, including its location, extent, and geometry, along with an overview of the associated rock formations and structural characteristics. The concept of out-of-sequence thrusts is introduced, defining their distinctive behavior and highlighting their importance in the understanding of geological processes. The Chaura Thrust is then analyzed in the context of an out-of-sequence thrust, examining the evidence and characteristics that support this classification. Factors contributing to the out-of-sequence behavior of the Chaura Thrust, such as stress interactions and fault interactions, are discussed. The geological implications and significance of the Chaura Thrust are explored, addressing its impact on the regional geology, tectonic evolution, and seismic hazard assessment. The paper also discusses the potential geological hazards associated with the Chaura Thrust and the need for effective mitigation strategies in the region. Future research directions and recommendations are provided, highlighting areas that warrant further investigation, such as detailed structural analyses, geodetic measurements, and geophysical surveys. The importance of continued research in understanding and managing geological hazards related to the Chaura Thrust is emphasized. In conclusion, the Chaura Thrust in Himachal Pradesh represents an out-of-sequence thrust fault that has significant implications for the region's geology and tectonic evolution. By studying the unique characteristics and behavior of the Chaura Thrust, researchers can gain valuable insights into the geological processes occurring in Himachal Pradesh and contribute to a better understanding and mitigation of seismic hazards in the area.Keywords: chaura thrust, out-of-sequence thrust, himachal pradesh, geological setting, tectonic framework, rock formations, structural characteristics, stress interactions, fault interactions, geological implications, seismic hazard assessment, geological hazards, future research, mitigation strategies.
Procedia PDF Downloads 725901 Neural Machine Translation for Low-Resource African Languages: Benchmarking State-of-the-Art Transformer for Wolof
Authors: Cheikh Bamba Dione, Alla Lo, Elhadji Mamadou Nguer, Siley O. Ba
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In this paper, we propose two neural machine translation (NMT) systems (French-to-Wolof and Wolof-to-French) based on sequence-to-sequence with attention and transformer architectures. We trained our models on a parallel French-Wolof corpus of about 83k sentence pairs. Because of the low-resource setting, we experimented with advanced methods for handling data sparsity, including subword segmentation, back translation, and the copied corpus method. We evaluate the models using the BLEU score and find that transformer outperforms the classic seq2seq model in all settings, in addition to being less sensitive to noise. In general, the best scores are achieved when training the models on word-level-based units. For subword-level models, using back translation proves to be slightly beneficial in low-resource (WO) to high-resource (FR) language translation for the transformer (but not for the seq2seq) models. A slight improvement can also be observed when injecting copied monolingual text in the target language. Moreover, combining the copied method data with back translation leads to a substantial improvement of the translation quality.Keywords: backtranslation, low-resource language, neural machine translation, sequence-to-sequence, transformer, Wolof
Procedia PDF Downloads 1415900 Opaque Mineralogy of the Late Precambrian Ophiolites from Bou Azzer Area, Anti-atlas, Morrocco
Authors: Yaser Maher Abdelaziz Hawa
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The Basic-ultrabasic rocks of Bou Azzer ophiolite complex in the Anti-atlas , Morrocco enclose some oxide and sulfide minerals as dissiminated traces. The oxide minerals show a wide variation in composition ranging from Cr-free. Titanomagnetite and ilmenite in the chilled margin gabbro of the upper part of the ophiolite sequence to Al-rich chromian spinel and pure magnetite enclosed in the serpentinized peridotite in the lower part of the sequence. Five mineral assemblages have been distinguished depending on the rock type of the ophiolite sequence. 1-Gersodorfite + Chalcopyrite + Al-Mg rich chromian spinel + pure magnetite, hosted by serpentinized peridotite. 2- Pyrite + Chalcopyrite, enclosed in metagabbro and overlying the ultrabasic cumulates. 3- Al-Fe rich Chromian spinel with rims of Al –rich chromian magnetite enclosed in wherlite. 4- Titanomagnetite replaced by sphene enclosed in marginal Gabbro. 5- Pyrrhotite exsolving Pentlandite + ilmenite + Ilmenite + Al- rich Chromian spinel + magnetite enclosed in fresh olivine olivine in the upper part of the ophiolite sequence.Keywords: opaques, ophiolites, anti-atlas, morrocco
Procedia PDF Downloads 995899 HIV-1 Nef Mediates Host Invasion by Differential Expression of Alpha-Enolase
Authors: Reshu Saxena, R. K. Tripathi
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HIV-1 transmission and spread involves significant host-virus interaction. Potential targets for prevention of HIV-1 lies at the site of mucosal barriers. Thus a better understanding of how HIV-1 infects target cells at such sites and lead their invasion is required, with prime focus on the host determinants regulating HIV-1 spread. HIV-1 Nef is important for viral infectivity and pathogenicity. It promotes HIV-1 replication, facilitating immune evasion by interacting with various host factors and altering cellular pathways via multiple protein-protein interactions. In this study nef was sequenced from HIV-1 patients, and showed specific mutations revealing sequence variability in nef. To explore the difference in Nef functionality based on sequence variability we have studied the effects of HIV-1 Nef in human SupT1 T cell line and (THP-1) monocyte-macrophage cell lines through proteomics approach. 2D-Gel Electrophoresis in control and Nef-transfected SupT1 cells demonstrated several differentially expressed proteins with significant modulation of alpha-enolase. Through further studies, effects of Nef on alpha-enolase regulation were found to be cell lineage-specific, being stimulatory in macrophages/monocytes, inhibitory in T cells and without effect in HEK-293 cells. Cell migration and invasion studies were employed to determine biological function affected by Nef mediated regulation of alpha-enolase. Cell invasion was enhanced in THP-1 cells but was inhibited in SupT1 cells by wildtype nef. In addition, the modulation of enolase and cell invasion remained unaffected by a unique nef variant. These results indicated that regulation of alpha-enolase expression and invasive property of host cells by Nef is sequence specific, suggesting involvement of a particular motif of Nef. To precisely determine this site, we designed a heptapeptide including the suggested alpha-enolase regulating sequence of nef and a nef mutant with deletion of this site. Macrophages/monocytes being the major cells affected by HIV-1 at mucosal barriers, were particularly investigated by the nef mutant and peptide. Both the nef mutant and heptapeptide led to inhibition of enhanced enolase expression and increased invasiveness in THP-1 cells. Together, these findings suggest a possible mechanism of host invasion by HIV-1 through Nef mediated regulation of alpha-enolase and identifies a potential therapeutic target for HIV-1 entry at mucosal barriers.Keywords: HIV-1 Nef, nef variants, host-virus interaction, tissue invasion
Procedia PDF Downloads 401