Search results for: somatic sequence mutations
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1429

Search results for: somatic sequence mutations

1159 A Critical Look on Clustered Regularly Interspaced Short Palindromic Repeats Method Based on Different Mechanisms

Authors: R. Sulakshana, R. Lakshmi

Abstract:

Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR associate (CRISPR/Cas) is an adaptive immunity system found in bacteria and archaea. It has been modified to serve as a potent gene editing tool. Moreover, it has found widespread use in the field of genome research because of its accessibility and low cost. Several bioinformatics methods have been created to aid in the construction of specific single guide RNA (sgRNA), which is highly active and crucial to CRISPR/Cas performance. Various Cas proteins, including Cas1, Cas2, Cas9, and Cas12, have been used to create genome engineering tools because of their programmable sequence specificity. Class 1 and 2 CRISPR/Cas systems, as well as the processes of all known Cas proteins (including Cas9 and Cas12), are discussed in this review paper. In addition, the various CRISPR methodologies and their tools so far discovered are discussed. Finally, the challenges and issues in the CRISPR system along with future works, are presented.

Keywords: gene editing tool, Cas proteins, CRISPR, guideRNA, programmable sequence

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1158 Characteristics of Tremella fuciformis and Annulohypoxylon stygium for Optimal Cultivation Conditions

Authors: Eun-Ji Lee, Hye-Sung Park, Chan-Jung Lee, Won-Sik Kong

Abstract:

We analyzed the DNA sequence of the ITS (Internal Transcribed Spacer) region of the 18S ribosomal gene and compared it with the gene sequence of T. fuciformis and Hypoxylon sp. in the BLAST database. The sequences of collected T. fuciformis and Hypoxylon sp. have over 99% homology in the T. fuciformis and Hypoxylon sp. sequence BLAST database. In order to select the optimal medium for T. fuciformis, five kinds of a medium such as Potato Dextrose Agar (PDA), Mushroom Complete Medium (MCM), Malt Extract Agar (MEA), Yeast extract (YM), and Compost Extract Dextrose Agar (CDA) were used. T. fuciformis showed the best growth on PDA medium, and Hypoxylon sp. showed the best growth on MCM. So as to investigate the optimum pH and temperature, the pH range was set to pH4 to pH8 and the temperature range was set to 15℃ to 35℃ (5℃ degree intervals). Optimum culture conditions for the T. fuciformis growth were pH5 at 25℃. Hypoxylon sp. were pH6 at 25°C. In order to confirm the most suitable carbon source, we used fructose, galactose, saccharose, soluble starch, inositol, glycerol, xylose, dextrose, lactose, dextrin, Na-CMC, adonitol. Mannitol, mannose, maltose, raffinose, cellobiose, ethanol, salicine, glucose, arabinose. In the optimum carbon source, T. fuciformis is xylose and Hypoxylon sp. is arabinose. Using the column test, we confirmed sawdust a suitable for T. fuciformis, since the composition of sawdust affects the growth of fruiting bodies of T. fuciformis. The sawdust we used is oak tree, pine tree, poplar, birch, cottonseed meal, cottonseed hull. In artificial cultivation of T. fuciformis with sawdust medium, T. fuciformis and Hypoxylon sp. showed fast mycelial growth on mixture of oak tree sawdust, cottonseed hull, and wheat bran.

Keywords: cultivation, optimal condition, tremella fuciformis, nutritional source

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1157 Assessment of Neurodevelopmental Needs in Duchenne Muscular Dystrophy

Authors: Mathula Thangarajh

Abstract:

Duchenne muscular dystrophy (DMD) is a severe form of X-linked muscular dystrophy caused by mutations in the dystrophin gene resulting in progressive skeletal muscle weakness. Boys with DMD also have significant cognitive disabilities. The intelligence quotient of boys with DMD, compared to peers, is approximately one standard deviation below average. Detailed neuropsychological testing has demonstrated that boys with DMD have a global developmental impairment, with verbal memory and visuospatial skills most significantly affected. Furthermore, the total brain volume and gray matter volume are lower in children with DMD compared to age-matched controls. These results are suggestive of a significant structural and functional compromise to the developing brain as a result of absent dystrophin protein expression. There is also some genetic evidence to suggest that mutations in the 3’ end of the DMD gene are associated with more severe neurocognitive problems. Our working hypothesis is that (i) boys with DMD do not make gains in neurodevelopmental skills compared to typically developing children and (ii) women carriers of DMD mutations may have subclinical cognitive deficits. We also hypothesize that there may be an intergenerational vulnerability of cognition, with boys of DMD-carrier mothers being more affected cognitively than boys of non-DMD-carrier mothers. The objectives of this study are: 1. Assess the neurodevelopment in boys with DMD at 4-time points and perform baseline neuroradiological assessment, 2. Assess cognition in biological mothers of DMD participants at baseline, 3. Assess possible correlation between DMD mutation and cognitive measures. This study also explores functional brain abnormalities in people with DMD by exploring how regional and global connectivity of the brain underlies executive function deficits in DMD. Such research can contribute to a better holistic understanding of the cognition alterations due to DMD and could potentially allow clinicians to create better-tailored treatment plans for the DMD population. There are four study visits for each participant (baseline, 2-4 weeks, 1 year, 18 months). At each visit, the participant completes the NIH Toolbox Cognition Battery, a validated psychometric measure that is recommended by NIH Common Data Elements for use in DMD. Visits 1, 3, and 4 also involve the administration of the BRIEF-2, ABAS-3, PROMIS/NeuroQoL, PedsQL Neuromuscular module 3.0, Draw a Clock Test, and an optional fMRI scan with the N-back matching task. We expect to enroll 52 children with DMD, 52 mothers of children with DMD, and 30 healthy control boys. This study began in 2020 during the height of the COVID-19 pandemic. Due to this, there were subsequent delays in recruitment because of travel restrictions. However, we have persevered and continued to recruit new participants for the study. We partnered with the Muscular Dystrophy Association (MDA) and helped advertise the study to interested families. Since then, we have had families from across the country contact us about their interest in the study. We plan to continue to enroll a diverse population of DMD participants to contribute toward a better understanding of Duchenne Muscular Dystrophy.

Keywords: neurology, Duchenne muscular dystrophy, muscular dystrophy, cognition, neurodevelopment, x-linked disorder, DMD, DMD gene

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1156 Highly-Sensitive Nanopore-Based Sensors for Point-Of-Care Medical Diagnostics

Authors: Leyla Esfandiari

Abstract:

Rapid, sensitive detection of nucleic acid (NA) molecules of specific sequence is of interest for a range of diverse health-related applications such as screening for genetic diseases, detecting pathogenic microbes in food and water, and identifying biological warfare agents in homeland security. Sequence-specific nucleic acid detection platforms rely on base pairing interaction between two complementary single stranded NAs, which can be detected by the optical, mechanical, or electrochemical readout. However, many of the existing platforms require amplification by polymerase chain reaction (PCR), fluorescent or enzymatic labels, and expensive or bulky instrumentation. In an effort to address these shortcomings, our research is focused on utilizing the cutting edge nanotechnology and microfluidics along with resistive pulse electrical measurements to design and develop a cost-effective, handheld and highly-sensitive nanopore-based sensor for point-of-care medical diagnostics.

Keywords: diagnostics, nanopore, nucleic acids, sensor

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1155 A Hybrid System of Hidden Markov Models and Recurrent Neural Networks for Learning Deterministic Finite State Automata

Authors: Pavan K. Rallabandi, Kailash C. Patidar

Abstract:

In this paper, we present an optimization technique or a learning algorithm using the hybrid architecture by combining the most popular sequence recognition models such as Recurrent Neural Networks (RNNs) and Hidden Markov models (HMMs). In order to improve the sequence or pattern recognition/ classification performance by applying a hybrid/neural symbolic approach, a gradient descent learning algorithm is developed using the Real Time Recurrent Learning of Recurrent Neural Network for processing the knowledge represented in trained Hidden Markov Models. The developed hybrid algorithm is implemented on automata theory as a sample test beds and the performance of the designed algorithm is demonstrated and evaluated on learning the deterministic finite state automata.

Keywords: hybrid systems, hidden markov models, recurrent neural networks, deterministic finite state automata

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1154 Molecular Characterization of Chicken B Cell Marker (ChB6) in Native Chicken of Poonch Region from International Borders of India and Pakistan

Authors: Mandeep Singh Azad.Dibyendu Chakraborty, Vikas Vohra

Abstract:

Introduction: Poonch is one of the remotest districts of the Jammu and Kashmir (UT) and situated on international borders. This native poultry population in these areas is quite hardy and thrives well in adverse climatic conditions. Till date, no local breed from this area (Jammu Province) has been characterized thus present study was undertaken with the main objectives of molecular characterization of ChB6 gene in local native chicken of Poonch region located at international borders between India and Pakistan. The chicken B-cell marker (ChB6) gene has been proposed as a candidate gene in regulating B-cell development. Material and Method: RNA was isolated by Blood RNA Purification Kit (HiPura) and Trizol method from whole blood samples. Positive PCR products with size 1110 bp were selected for further purification, sequencing and analysis. The amplified PCR product was sequenced by Sangers dideoxy chain termination method. The obtained sequence of ChB6 gene of Poonchi chicken were compared by MEGAX software. BioEdit software was used to construct phylogenic tree, and Neighbor Joining method was used to infer evolutionary history. In order to compute evolutionary distance Maximum Composite Likelihood method was used. Results: The positively amplified samples of ChB6 genes were then subjected to Sanger sequencing with “Primer Walking. The sequences were then analyzed using MEGA X and BioEdit software. The sequence results were compared with other reported sequence from different breed of chicken and with other species obtained from the NCBI (National Center for Biotechnology Information). ClustalW method using MEGA X software was used for multiple sequence alignment. The sequence results of ChB6 gene of Poonchi chicken was compared with Centrocercus urophasianus, G. gallus mRNA for B6.1 protein, G. gallus mRNA for B6.2, G. gallus mRNA for B6.3, Gallus gallus B6.1, Halichoeres bivittatus, Miniopterus fuliginosus Ferringtonia patagonica, Tympanuchus phasianellus. The genetic distances were 0.2720, 0.0000, 0.0245, 0.0212, 0.0147, 1.6461, 2.2394, 2.0070 and 0.2363 for ChB6 gene of Poonchi chicken sequence with other sequences in the present study respectively. Sequencing results showed variations between different species. It was observed that AT content were higher then GC content for ChB6 gene. The lower AT content suggests less thermostable. It was observed that there was no sequence difference within the Poonchi population for ChB6 gene. The high homology within chicken population indicates the conservation of ChB6 gene. The maximum difference was observed with Miniopterus fuliginosus (Eastern bent-wing bat) followed by Ferringtonia patagonica and Halichoeres bivittatus. Conclusion: Genetic variation is the essential component for genetic improvement. The results of immune related gene Chb6 shows between population genetic variability. Therefore, further association studies of this gene with some prevalent diseases in large population would be helpful to identify disease resistant/ susceptible genotypes in the indigenous chicken population.

Keywords: ChB6, sequencing, ClustalW, genetic distance, poonchi chicken, SNP

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1153 Tectonics of Out-of-Sequence Thrusting in Higher Himalaya- Example from Jhakri-Chaura-Sarahan Region, Himachal Pradesh

Authors: Rajkumar Ghosh

Abstract:

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)

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1152 Relative Entropy Used to Determine the Divergence of Cells in Single Cell RNA Sequence Data Analysis

Authors: An Chengrui, Yin Zi, Wu Bingbing, Ma Yuanzhu, Jin Kaixiu, Chen Xiao, Ouyang Hongwei

Abstract:

Single cell RNA sequence (scRNA-seq) is one of the effective tools to study transcriptomics of biological processes. Recently, similarity measurement of cells is Euclidian distance or its derivatives. However, the process of scRNA-seq is a multi-variate Bernoulli event model, thus we hypothesize that it would be more efficient when the divergence between cells is valued with relative entropy than Euclidian distance. In this study, we compared the performances of Euclidian distance, Spearman correlation distance and Relative Entropy using scRNA-seq data of the early, medial and late stage of limb development generated in our lab. Relative Entropy is better than other methods according to cluster potential test. Furthermore, we developed KL-SNE, an algorithm modifying t-SNE whose definition of divergence between cells Euclidian distance to Kullback–Leibler divergence. Results showed that KL-SNE was more effective to dissect cell heterogeneity than t-SNE, indicating the better performance of relative entropy than Euclidian distance. Specifically, the chondrocyte expressing Comp was clustered together with KL-SNE but not with t-SNE. Surprisingly, cells in early stage were surrounded by cells in medial stage in the processing of KL-SNE while medial cells neighbored to late stage with the process of t-SNE. This results parallel to Heatmap which showed cells in medial stage were more heterogenic than cells in other stages. In addition, we also found that results of KL-SNE tend to follow Gaussian distribution compared with those of the t-SNE, which could also be verified with the analysis of scRNA-seq data from another study on human embryo development. Therefore, it is also an effective way to convert non-Gaussian distribution to Gaussian distribution and facilitate the subsequent statistic possesses. Thus, relative entropy is potentially a better way to determine the divergence of cells in scRNA-seq data analysis.

Keywords: Single cell RNA sequence, Similarity measurement, Relative Entropy, KL-SNE, t-SNE

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1151 Magnetophotonics 3D MEMS/NEMS System for Quantitative Mitochondrial DNA Defect Profiling

Authors: Dar-Bin Shieh, Gwo-Bin Lee, Chen-Ming Chang, Chen Sheng Yeh, Chih-Chia Huang, Tsung-Ju Li

Abstract:

Mitochondrial defects have a significant impact in many human diseases and aging associated phenotypes. The pathogenic mitochondrial DNA (mtDNA) mutations are diverse and usually present as heteroplasmic. mtDNA 4977bps deletion is one of the common mtDNA defects, and the ratio of mutated versus normal copy is significantly associated with clinical symptoms thus their quantitative detection has become an important unmet needs for advanced disease diagnosis and therapeutic guidelines. This study revealed a Micro-electro-mechanical-system (MEMS) enabled automatic microfluidic chip that only required minimal sample. The system integrated multiple laboratory operation steps into a Lab-on-a-Chip for high-sensitive and prompt measurement. The entire process including magnetic nanoparticle based mtDNA extraction in chip, mutation selective photonic DNA cleavage, and nanoparticle accelerated photonic quantitative polymerase chain reaction (qPCR). All subsystems were packed inside a miniature three-dimensional micro structured system and operated in an automatic manner. Integration of magnetic beads with microfluidic transportation could promptly extract and enrich the specific mtDNA. The near infrared responsive magnetic nanoparticles enabled micro-PCR to be operated by pulse-width-modulation controlled laser pulsing to amplify the desired mtDNA while quantified by fluorescence intensity captured by a complementary metal oxide system array detector. The proportions of pathogenic mtDNA in total DNA were thus obtained. Micro capillary electrophoresis module was used to analyze the amplicone products. In conclusion, this study demonstrated a new magnetophotonic based qPCR MEMS system that successfully detects and quantify specific disease related DNA mutations thus provides a promising future for rapid diagnosis of mitochondria diseases.

Keywords: mitochondrial DNA, micro-electro-mechanical-system, magnetophotonics, PCR

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1150 Efficient Motion Estimation by Fast Three Step Search Algorithm

Authors: S. M. Kulkarni, D. S. Bormane, S. L. Nalbalwar

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The rapid development in the technology have dramatic impact on the medical health care field. Medical data base obtained with latest machines like CT Machine, MRI scanner requires large amount of memory storage and also it requires large bandwidth for transmission of data in telemedicine applications. Thus, there is need for video compression. As the database of medical images contain number of frames (slices), hence while coding of these images there is need of motion estimation. Motion estimation finds out movement of objects in an image sequence and gets motion vectors which represents estimated motion of object in the frame. In order to reduce temporal redundancy between successive frames of video sequence, motion compensation is preformed. In this paper three step search (TSS) block matching algorithm is implemented on different types of video sequences. It is shown that three step search algorithm produces better quality performance and less computational time compared with exhaustive full search algorithm.

Keywords: block matching, exhaustive search motion estimation, three step search, video compression

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1149 From Primer Generation to Chromosome Identification: A Primer Generation Genotyping Method for Bacterial Identification and Typing

Authors: Wisam H. Benamer, Ehab A. Elfallah, Mohamed A. Elshaari, Farag A. Elshaari

Abstract:

A challenge for laboratories is to provide bacterial identification and antibiotic sensitivity results within a short time. Hence, advancement in the required technology is desirable to improve timing, accuracy and quality. Even with the current advances in methods used for both phenotypic and genotypic identification of bacteria the need is there to develop method(s) that enhance the outcome of bacteriology laboratories in accuracy and time. The hypothesis introduced here is based on the assumption that the chromosome of any bacteria contains unique sequences that can be used for its identification and typing. The outcome of a pilot study designed to test this hypothesis is reported in this manuscript. Methods: The complete chromosome sequences of several bacterial species were downloaded to use as search targets for unique sequences. Visual basic and SQL server (2014) were used to generate a complete set of 18-base long primers, a process started with reverse translation of randomly chosen 6 amino acids to limit the number of the generated primers. In addition, the software used to scan the downloaded chromosomes using the generated primers for similarities was designed, and the resulting hits were classified according to the number of similar chromosomal sequences, i.e., unique or otherwise. Results: All primers that had identical/similar sequences in the selected genome sequence(s) were classified according to the number of hits in the chromosomes search. Those that were identical to a single site on a single bacterial chromosome were referred to as unique. On the other hand, most generated primers sequences were identical to multiple sites on a single or multiple chromosomes. Following scanning, the generated primers were classified based on ability to differentiate between medically important bacterial and the initial results looks promising. Conclusion: A simple strategy that started by generating primers was introduced; the primers were used to screen bacterial genomes for match. Primer(s) that were uniquely identical to specific DNA sequence on a specific bacterial chromosome were selected. The identified unique sequence can be used in different molecular diagnostic techniques, possibly to identify bacteria. In addition, a single primer that can identify multiple sites in a single chromosome can be exploited for region or genome identification. Although genomes sequences draft of isolates of organism DNA enable high throughput primer design using alignment strategy, and this enhances diagnostic performance in comparison to traditional molecular assays. In this method the generated primers can be used to identify an organism before the draft sequence is completed. In addition, the generated primers can be used to build a bank for easy access of the primers that can be used to identify bacteria.

Keywords: bacteria chromosome, bacterial identification, sequence, primer generation

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1148 Comparison between Radiocarbon and Dendrochronology Ages Obtained on a 700 Years Tree-Ring Sequence from Northern Romania

Authors: G. Sava, I. Popa, T. Sava, A. Ion, M. Ilie, C. Manailescu, A. Robu

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At the RoAMS laboratory in Bucharest we have looked for a head-to-head meeting between AMS radiocarbon dating and dendrochronology dating, aiming to point out and explain any differences or similarities that might appear between their output results. As a subject of this investigation, we have fixed our attention on a sequence of tree rings spanning on a period of 700 years, starting with 1000 AD. The samples were collected from the northern Romanian territory within Moldavia region, and were provided by the ‘Marin Dracea - National Institute for Research and Development in Forestry’. All the 23 single ring wood samples were radiocarbon dated using alpha-cellulose extraction, followed by graphitization in an AGE3 installation. A wiggle matching procedure was applied to reduce the radiocarbon uncertainties for the calibrated ages. The results showed a good agreement on 3 out of 4 wood cores, the age-shifting of one of the wood cores being interpreted as an uncertain dendrochronology matching, which was further corrected.

Keywords: wiggle matching, tree-ring radiocarbon dating, dendrochronology, AMS radiocarbon dating, radiocarbon dating in Romania

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1147 Corpus-Based Model of Key Concepts Selection for the Master English Language Course "Government Relations"

Authors: Elena Pozdnyakova

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“Government Relations” is a field of knowledge presently taught at the majority of universities around the globe. English as the default language can become the language of teaching since the issues discussed are both global and national in character. However for this field of knowledge key concepts and their word representations in English don’t often coincide with those in other languages. International master’s degree students abroad as well as students, taught the course in English at their national universities, are exposed to difficulties, connected with correct conceptualizing of terminology of GR in British and American academic traditions. The study was carried out during the GR English language course elaboration (pilot research: 2013 -2015) at Moscow State Institute of Foreign Relations (University), Russian Federation. Within this period, English language instructors designed and elaborated the three-semester course of GR. Methodologically the course design was based on elaboration model with the special focus on conceptual elaboration sequence and theoretical elaboration sequence. The course designers faced difficulties in concept selection and theoretical elaboration sequence. To improve the results and eliminate the problems with concept selection, a new, corpus-based approach was worked out. The computer-based tool WordSmith 6.0 was used with the aim to build a model of key concept selection. The corpus of GR English texts consisted of 1 million words (the study corpus). The approach was based on measuring effect size, i.e. the percent difference of the frequency of a word in the study corpus when compared to that in the reference corpus. The results obtained proved significant improvement in the process of concept selection. The corpus-based model also facilitated theoretical elaboration of teaching materials.

Keywords: corpus-based study, English as the default language, key concepts, measuring effect size, model of key concept selection

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1146 Personalize E-Learning System Based on Clustering and Sequence Pattern Mining Approach

Authors: H. S. Saini, K. Vijayalakshmi, Rishi Sayal

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Network-based education has been growing rapidly in size and quality. Knowledge clustering becomes more important in personalized information retrieval for web-learning. A personalized-Learning service after the learners’ knowledge has been classified with clustering. Through automatic analysis of learners’ behaviors, their partition with similar data level and interests may be discovered so as to produce learners with contents that best match educational needs for collaborative learning. We present a specific mining tool and a recommender engine that we have integrated in the online learning in order to help the teacher to carry out the whole e-learning process. We propose to use sequential pattern mining algorithms to discover the most used path by the students and from this information can recommend links to the new students automatically meanwhile they browse in the course. We have Developed a specific author tool in order to help the teacher to apply all the data mining process. We tend to report on many experiments with real knowledge so as to indicate the quality of using both clustering and sequential pattern mining algorithms together for discovering personalized e-learning systems.

Keywords: e-learning, cluster, personalization, sequence, pattern

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1145 Chinese Sentence Level Lip Recognition

Authors: Peng Wang, Tigang Jiang

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The computer based lip reading method of different languages cannot be universal. At present, for the research of Chinese lip reading, whether the work on data sets or recognition algorithms, is far from mature. In this paper, we study the Chinese lipreading method based on machine learning, and propose a Chinese Sentence-level lip-reading network (CNLipNet) model which consists of spatio-temporal convolutional neural network(CNN), recurrent neural network(RNN) and Connectionist Temporal Classification (CTC) loss function. This model can map variable-length sequence of video frames to Chinese Pinyin sequence and is trained end-to-end. More over, We create CNLRS, a Chinese Lipreading Dataset, which contains 5948 samples and can be shared through github. The evaluation of CNLipNet on this dataset yielded a 41% word correct rate and a 70.6% character correct rate. This evaluation result is far superior to the professional human lip readers, indicating that CNLipNet performs well in lipreading.

Keywords: lipreading, machine learning, spatio-temporal, convolutional neural network, recurrent neural network

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1144 Is Sodium Channel Nav1.7 an Ideal Therapeutically Analgesic Target? A Systematic Review

Authors: Yutong Wan, John N. Wood

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Introduction: SCN9A encoded Nav1.7 is an ideal therapeutic target with minimal side effects for the pharmaceutical industry because SCN9A variants can cause both human gains of function pain-related mutations and loss of function pain-free mutations. This study reviews the clinical effectiveness of existing Nav1.7 inhibitors, which theoretically should be powerful analgesics. Methods: A systematic review is conducted on the effectiveness of current Nav1.7 blockers undergoing clinical trials. Studies were mainly extracted from PubMed, U.S. National Library of Medicine Clinical Trials, World Health Organization International Clinical Trials Registry, ISRCTN registry platform, and Integrated Research Approval System by NHS. Only studies with full text available and those conducted using double-blinded, placebo controlled, and randomised designs and reporting at least one analgesic measurement were included. Results: Overall, 61 trials were screened, and eight studies covering PF 05089771 (Pfizer), TV 45070 (Teva & Xenon), and BIIB074 (Biogen) met the inclusion criteria. Most studies were excluded because results were not published. All three compounds demonstrated insignificant analgesic effects, and the comparison between PF 05089771 and pregabalin/ibuprofen showed that PF 05089771 was a much weaker analgesic. All three drug candidates only have mild side effects, indicating the potentials for further investigation of Nav1.7 antagonists. Discussion: The failure of current Nav1.7 small molecule inhibitors might attribute to ignorance of the key role of endogenous systems in Nav1.7 null mutants, the lack of selectivity and blocking potency, and central impermeability. The synergistic combination of analgesic drugs, a recent UCL patent, combining a small dose of Nav1.7 blockers and opioids or enkephalinase inhibitors dramatically enhanced the analgesic effects. Conclusion: The current clinical testing Nav1.7 blockers are generally disappointing. However, the newer generation of Nav1.7 targeting analgesics has overcome the major constraints of its predecessors.

Keywords: chronic pain, Nav1.7 blockers, SCN9A, systematic review

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1143 Identification and Differentiation of Fagonia Arabica and Fagonia Indica by Using DNA Barcode Region Matk

Authors: Noshaba Dilbar, Aisha Tahir, Amer Jamil

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During the last decade, DNA barcoding proved to be an authentic tool for discovery and identification of plants. In the present study, DNA barcoding of two species, Fagonia arabica and Fagonia indica was done for differentiation by using matK region. matK gene is considered as a universal barcode because of its easy alignment and high discrimination ability. In this study, matK yielded 100% sequencing results. The sequences from both plants were aligned at clustal W and observed that there is no nucleotide variation and polymorphism among both sequences. This was further analysed by BLAST which showed the similar sequences from different plants belonging to same family but didn’t find sequence of both species. Considering this, the resulted sequence was submitted by the name of Fagonia arabica with accession number KM276890. In the end, we analysed the results from BOLD which gave us the final conclusion that both plants are same as their matK sequences are 100% identical. In literature, both Fagonia indica and Fagonia arabica names are used for this plant but there is no clear differentiation has been observed in these plants. Results evaluate that Fagonia indica and Fagonia arabica are the alternative names of same plant.

Keywords: DNA barcoding, Fagonia arabica, Fagonia indica, matK

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1142 Evaluation Methods for Question Decomposition Formalism

Authors: Aviv Yaniv, Ron Ben Arosh, Nadav Gasner, Michael Konviser, Arbel Yaniv

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This paper introduces two methods for the evaluation of Question Decomposition Meaning Representation (QDMR) as predicted by sequence-to-sequence model and COPYNET parser for natural language questions processing, motivated by the fact that previous evaluation metrics used for this task do not take into account some characteristics of the representation, such as partial ordering structure. To this end, several heuristics to extract such partial dependencies are formulated, followed by the hereby proposed evaluation methods denoted as Proportional Graph Matcher (PGM) and Conversion to Normal String Representation (Nor-Str), designed to better capture the accuracy level of QDMR predictions. Experiments are conducted to demonstrate the efficacy of the proposed evaluation methods and show the added value suggested by one of them- the Nor-Str, for better distinguishing between high and low-quality QDMR when predicted by models such as COPYNET. This work represents an important step forward in the development of better evaluation methods for QDMR predictions, which will be critical for improving the accuracy and reliability of natural language question-answering systems.

Keywords: NLP, question answering, question decomposition meaning representation, QDMR evaluation metrics

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1141 Non-Population Search Algorithms for Capacitated Material Requirement Planning in Multi-Stage Assembly Flow Shop with Alternative Machines

Authors: Watcharapan Sukkerd, Teeradej Wuttipornpun

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This paper aims to present non-population search algorithms called tabu search (TS), simulated annealing (SA) and variable neighborhood search (VNS) to minimize the total cost of capacitated MRP problem in multi-stage assembly flow shop with two alternative machines. There are three main steps for the algorithm. Firstly, an initial sequence of orders is constructed by a simple due date-based dispatching rule. Secondly, the sequence of orders is repeatedly improved to reduce the total cost by applying TS, SA and VNS separately. Finally, the total cost is further reduced by optimizing the start time of each operation using the linear programming (LP) model. Parameters of the algorithm are tuned by using real data from automotive companies. The result shows that VNS significantly outperforms TS, SA and the existing algorithm.

Keywords: capacitated MRP, tabu search, simulated annealing, variable neighborhood search, linear programming, assembly flow shop, application in industry

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1140 Quantifying Late Cenozoic Out‐of‐Sequence Thrusting at Chaura, Sutlej Valley, Himachal Pradesh, India

Authors: Rajkumar Ghosh

Abstract:

Out-of-sequence thrusts (OOST) are reported at different geographic locations with various local names along Siwalik Himalaya (SH), Lesser Himalaya (LH), Higher Himalaya (HH) from Bhutan, India, Nepal, and Pakistan Himalayan range. Most of OOSTs have been identified within the upper LH, and the lower HH based on geochronological age jump across. These thrusts activated from Late Miocene to recent. The Chaura Thrust (CT) was deciphered from age jump of Apatite Fission Track (AFT) and considered as blind thrust base on variable exhumation rates in Chaura region, Satluj river valley, Himachal Pradesh. CT is located north of Jhakri Thrust (JhT) and is also differently identified as Sarahan thrust (ST). Structural documentation from the rocks near the OOST in Chaura was not so far done. Detail structural study of the Jeori Group of rocks was carried out in this study to understand the manifestation of the Chaura thrust and associated structures in meso- to micro-scale. Box fold, scar fold, kink fold, crenulation cleavages, and boudins are developed in the Chaura region. These structures usually do not indicate shear sense. When studied under an optical microscope, the Chaura samples reveal that the mica fish are usually lenticular with aspect ratio (R) varying from 6–11 and inclination angle (α) from 15–40°. According to ‘R’ and ‘α’, elongated sigmoid shaped mica fish and parallelogram shaped mica fish were also documented. Asymmetric mica fish demonstrate top-to-S/SW ductile shear, which is similar as that of Chaura thrust. Grain boundary migration (GBM) structures in quartzo-feldspathic grains from Jeori Group of rocks indicate deformation temperature ranging from 400 to 650°C. This can indicate that the OOST at Chaura, i.e., the Chaura Thrust, underwent thrusting in the ductile regime.

Keywords: out-of-sequence thrust, chaura thrust, sarahan thrust, jakhri thrust, higher himalaya, s/c- fabric

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1139 The Convolution Recurrent Network of Using Residual LSTM to Process the Output of the Downsampling for Monaural Speech Enhancement

Authors: Shibo Wei, Ting Jiang

Abstract:

Convolutional-recurrent neural networks (CRN) have achieved much success recently in the speech enhancement field. The common processing method is to use the convolution layer to compress the feature space by multiple upsampling and then model the compressed features with the LSTM layer. At last, the enhanced speech is obtained by deconvolution operation to integrate the global information of the speech sequence. However, the feature space compression process may cause the loss of information, so we propose to model the upsampling result of each step with the residual LSTM layer, then join it with the output of the deconvolution layer and input them to the next deconvolution layer, by this way, we want to integrate the global information of speech sequence better. The experimental results show the network model (RES-CRN) we introduce can achieve better performance than LSTM without residual and overlaying LSTM simply in the original CRN in terms of scale-invariant signal-to-distortion ratio (SI-SNR), speech quality (PESQ), and intelligibility (STOI).

Keywords: convolutional-recurrent neural networks, speech enhancement, residual LSTM, SI-SNR

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1138 Integration of an Evidence-Based Medicine Curriculum into Physician Assistant Education: Teaching for Today and the Future

Authors: Martina I. Reinhold, Theresa Bacon-Baguley

Abstract:

Background: Medical knowledge continuously evolves and to help health care providers to stay up-to-date, evidence-based medicine (EBM) has emerged as a model. The practice of EBM requires new skills of the health care provider, including directed literature searches, the critical evaluation of research studies, and the direct application of the findings to patient care. This paper describes the integration and evaluation of an evidence-based medicine course sequence into a Physician Assistant curriculum. This course sequence teaches students to manage and use the best clinical research evidence to competently practice medicine. A survey was developed to assess the outcomes of the EBM course sequence. Methodology: The cornerstone of the three-semester sequence of EBM are interactive small group discussions that are designed to introduce students to the most clinically applicable skills to identify, manage and use the best clinical research evidence to improve the health of their patients. During the three-semester sequence, the students are assigned each semester to participate in small group discussions that are facilitated by faculty with varying background and expertise. Prior to the start of the first EBM course in the winter semester, PA students complete a knowledge-based survey that was developed by the authors to assess the effectiveness of the course series. The survey consists of 53 Likert scale questions that address the nine objectives for the course series. At the end of the three semester course series, the same survey was given to all students in the program and the results from before, and after the sequence of EBM courses are compared. Specific attention is paid to overall performance of students in the nine course objectives. Results: We find that students from the Class of 2016 and 2017 consistently improve (as measured by percent correct responses on the survey tool) after the EBM course series (Class of 2016: Pre- 62% Post- 75%; Class of 2017: Pre- 61 % Post-70%). The biggest increase in knowledge was observed in the areas of finding and evaluating the evidence, with asking concise clinical questions (Class of 2016: Pre- 61% Post- 81%; Class of 2017: Pre- 61 % Post-75%) and searching the medical database (Class of 2016: Pre- 24% Post- 65%; Class of 2017: Pre- 35 % Post-66 %). Questions requiring students to analyze, evaluate and report on the available clinical evidence regarding diagnosis showed improvement, but to a lesser extend (Class of 2016: Pre- 56% Post- 77%; Class of 2017: Pre- 56 % Post-61%). Conclusions: Outcomes identified that students did gain skills which will allow them to apply EBM principles. In addition, the outcomes of the knowledge-based survey allowed the faculty to focus on areas needing improvement, specifically the translation of best evidence into patient care. To address this area, the clinical faculty developed case scenarios that were incorporated into the lecture and discussion sessions, allowing students to better connect the research studies with patient care. Students commented that ‘class discussion and case examples’ contributed most to their learning and that ‘it was helpful to learn how to develop research questions and how to analyze studies and their significance to a potential client’. As evident by the outcomes, the EBM courses achieved the goals of the course and were well received by the students. 

Keywords: evidence-based medicine, clinical education, assessment tool, physician assistant

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1137 The Golden Ratio as a Common ‘Topos’ of Architectural, Musical and Stochastic Research of Iannis Xenakis

Authors: Nikolaos Mamalis

Abstract:

The work of the eminent architect and composer has undoubtedly been influenced both by his architecture and collaboration with Le Corbusier and by the conquests of the musical avant-garde of the 20th century (Schoenberg, Messian, Bartock, electroacoustic music). It is known that the golden mean and the Fibonacci sequence played a momentous role in the Architectural Avant-garde (Modulor) and expanded on musical pursuits. Especially in the 50s (serialism), it was a structural tool for composition. Xenakis' architectural and musical work (Sacrifice, Metastasis, Rebonds, etc.) received the influence of the Golden Section, as has been repeatedly demonstrated. However, the idea of this retrospective sequence and the reflection raised by the search for new proportions, both in the architectural and the musical work of Xenakis, was not limited to constituting a step, a workable formula that acted unifyingly with regard to the other parameters of the musical work, or as an aesthetic model that makes sense - philosophically and poetically - an anthropocentric dimension as in other composers (see Luigi Nono) ̇ triggered a qualitative leap, an opening of the composer to the assimilation of mathematical concepts and scientific types in music and the consolidation of new sound horizons of stochastic music.

Keywords: golden ratio, music, space, stochastic music

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1136 Charge Transport in Biological Molecules

Authors: E. L. Albuquerque, U. L. Fulco, G. S. Ourique

Abstract:

The focus of this work is on the numerical investigation of the charge transport properties of the de novo-designed alpha3 polypeptide, as well as in its variants, all of them probed by gene engineering. The theoretical framework makes use of a tight-binding model Hamiltonian, together with ab-initio calculations within quantum chemistry simulation. The alpha3 polypeptide is a 21-residue with three repeats of the seven-residue amino acid sequence Leu-Glu-Thr-Leu-Ala-Lys-Ala, forming an alpha–helical bundle structure. Its variants are obtained by Ala→Gln substitution at the e (5th) and g (7th) position, respectively, of the alpha3 polypeptide amino acid sequence. Using transmission electron microscopy and atomic force microscopy, it was observed that the alpha3 polypeptide and one of its variant do have the ability to form fibrous assemblies, while the other does not. Our main aim is to investigate whether or not the biased alpha3 polypeptide and its variants can be also identified by quantum charge transport measurements through current-voltage (IxV) curves as a pattern to characterize their fibrous assemblies. It was observed that each peptide has a characteristic current pattern, which may be distinguished by charge transport measurements, suggesting that it might be a useful tool for the development of biosensors.

Keywords: charge transport properties, electronic transmittance, current-voltage characteristics, biological sensor

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1135 Optimal Design of Composite Patch for a Cracked Pipe by Utilizing Genetic Algorithm and Finite Element Method

Authors: Mahdi Fakoor, Seyed Mohammad Navid Ghoreishi

Abstract:

Composite patching is a common way for reinforcing the cracked pipes and cylinders. The effects of composite patch reinforcement on fracture parameters of a cracked pipe depend on a variety of parameters such as number of layers, angle, thickness, and material of each layer. Therefore, stacking sequence optimization of composite patch becomes crucial for the applications of cracked pipes. In this study, in order to obtain the optimal stacking sequence for a composite patch that has minimum weight and maximum resistance in propagation of cracks, a coupled Multi-Objective Genetic Algorithm (MOGA) and Finite Element Method (FEM) process is proposed. This optimization process has done for longitudinal and transverse semi-elliptical cracks and optimal stacking sequences and Pareto’s front for each kind of cracks are presented. The proposed algorithm is validated against collected results from the existing literature.

Keywords: multi objective optimization, pareto front, composite patch, cracked pipe

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1134 Negative Sequence-Based Protection Techniques for Microgrid Connected Power Systems

Authors: Isabelle Snyder, Travis Smith

Abstract:

Microgrid protection presents challenges to conventional protection techniques due to the low-induced fault current. Protection relays present in microgrid applications require a combination of settings groups to adjust based on the architecture of the microgrid in islanded and grid-connected modes. In a radial system where the microgrid is at the other end of the feeder, directional elements can be used to identify the direction of the fault current and switch settings groups accordingly (grid-connected or microgrid-connected). However, with multiple microgrid connections, this concept becomes more challenging, and the direction of the current alone is not sufficient to identify the source of the fault current contribution. ORNL has previously developed adaptive relaying schemes through other DOE-funded research projects that will be evaluated and used as a baseline for this research. The four protection techniques in this study are labeled as follows: (1) Adaptive Current only Protection System (ACPS), Intentional (2) Unbalanced Control for Protection Control (IUCPC), (3) Adaptive Protection System with Communication Controller (APSCC) (4) Adaptive Model-Driven Protective Relay (AMDPR).

Keywords: adaptive relaying, microgrid protection, sequence components, islanding detection

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1133 The Use of Medical Biotechnology to Treat Genetic Disease

Authors: Rachel Matar, Maxime Merheb

Abstract:

Chemical drugs have been used for many centuries as the only way to cure diseases until the novel gene therapy has been created in 1960. Gene therapy is based on the insertion, correction, or inactivation of genes to treat people with genetic illness (1). Gene therapy has made wonders in Parkison’s, Alzheimer and multiple sclerosis. In addition to great promises in the healing of deadly diseases like many types of cancer and autoimmune diseases (2). This method implies the use of recombinant DNA technology with the help of different viral and non-viral vectors (3). It is nowadays used in somatic cells as well as embryos and gametes. Beside all the benefits of gene therapy, this technique is deemed by some opponents as an ethically unacceptable treatment as it implies playing with the genes of living organisms.

Keywords: gene therapy, genetic disease, cancer, multiple sclerosis

Procedia PDF Downloads 503
1132 Performance Analysis and Comparison of Various 1-D and 2-D Prime Codes for OCDMA Systems

Authors: Gurjit Kaur, Shashank Johri, Arpit Mehrotra

Abstract:

In this paper we have analyzed and compared the performance of various coding schemes. The basic ID prime sequence codes are unique in only dimension i.e. time slots whereas 2D coding techniques are not unique by their time slots but with their wavelengths also. In this research we have evaluated and compared the performance of 1D and 2D coding techniques constructed using prime sequence coding pattern for OCDMA system on a single platform. Results shows that 1D Extended Prime Code (EPC) can support more number of active users compared to other codes but at the expense of larger code length which further increases the complexity of the code. Modified Prime Code (MPC) supports lesser number of active users at λc=2 but it has a lesser code length as compared to 1D prime code. Analysis shows that 2D prime code supports lesser number of active users than 1D codes but they are having large code family and are the most secure codes compared to other codes. The performance of all these codes is analyzed on basis of number of active users supported at a Bit Error Rate (BER) of 10-9.

Keywords: CDMA, OCDMA, BER, OOC, PC, EPC, MPC, 2-D PC/PC, λc, λa

Procedia PDF Downloads 479
1131 Unsupervised Classification of DNA Barcodes Species Using Multi-Library Wavelet Networks

Authors: Abdesselem Dakhli, Wajdi Bellil, Chokri Ben Amar

Abstract:

DNA Barcode, a short mitochondrial DNA fragment, made up of three subunits; a phosphate group, sugar and nucleic bases (A, T, C, and G). They provide good sources of information needed to classify living species. Such intuition has been confirmed by many experimental results. Species classification with DNA Barcode sequences has been studied by several researchers. The classification problem assigns unknown species to known ones by analyzing their Barcode. This task has to be supported with reliable methods and algorithms. To analyze species regions or entire genomes, it becomes necessary to use similarity sequence methods. A large set of sequences can be simultaneously compared using Multiple Sequence Alignment which is known to be NP-complete. To make this type of analysis feasible, heuristics, like progressive alignment, have been developed. Another tool for similarity search against a database of sequences is BLAST, which outputs shorter regions of high similarity between a query sequence and matched sequences in the database. However, all these methods are still computationally very expensive and require significant computational infrastructure. Our goal is to build predictive models that are highly accurate and interpretable. This method permits to avoid the complex problem of form and structure in different classes of organisms. On empirical data and their classification performances are compared with other methods. Our system consists of three phases. The first is called transformation, which is composed of three steps; Electron-Ion Interaction Pseudopotential (EIIP) for the codification of DNA Barcodes, Fourier Transform and Power Spectrum Signal Processing. The second is called approximation, which is empowered by the use of Multi Llibrary Wavelet Neural Networks (MLWNN).The third is called the classification of DNA Barcodes, which is realized by applying the algorithm of hierarchical classification.

Keywords: DNA barcode, electron-ion interaction pseudopotential, Multi Library Wavelet Neural Networks (MLWNN)

Procedia PDF Downloads 287
1130 Investigations of Protein Aggregation Using Sequence and Structure Based Features

Authors: M. Michael Gromiha, A. Mary Thangakani, Sandeep Kumar, D. Velmurugan

Abstract:

The main cause of several neurodegenerative diseases such as Alzhemier, Parkinson, and spongiform encephalopathies is formation of amyloid fibrils and plaques in proteins. We have analyzed different sets of proteins and peptides to understand the influence of sequence-based features on protein aggregation process. The comparison of 373 pairs of homologous mesophilic and thermophilic proteins showed that aggregation-prone regions (APRs) are present in both. But, the thermophilic protein monomers show greater ability to ‘stow away’ the APRs in their hydrophobic cores and protect them from solvent exposure. The comparison of amyloid forming and amorphous b-aggregating hexapeptides suggested distinct preferences for specific residues at the six positions as well as all possible combinations of nine residue pairs. The compositions of residues at different positions and residue pairs have been converted into energy potentials and utilized for distinguishing between amyloid forming and amorphous b-aggregating peptides. Our method could correctly identify the amyloid forming peptides at an accuracy of 95-100% in different datasets of peptides.

Keywords: aggregation, amyloids, thermophilic proteins, amino acid residues, machine learning techniques

Procedia PDF Downloads 583