Search results for: somatic sequence mutations

Authors: Nouha Bouayed Abdelmoula, Rim Louati, Nawel Abdellaoui, Balkiss Abdelmoula, Oldez Kaabi, Walid Smaoui, Samir Aloulou

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Background and Aims: Cardiofaciocutaneous syndrome (CFC) is an autosomal dominant disorder with the vast majority of cases arising by a new mutation of BRAF, MEK1, MEK2, or rarely, KRAS genes. Here, we report a rare Tunisian case of CFC syndrome for whom we identify SOS1 mutation. Methods: Genomic DNA was obtained from peripheral blood collected in an EDTA tube and extracted from leukocytes using the phenol/chloroform method according to standard protocols. High resolution melting (HRM) analysis for screening of mutations in the entire coding sequence of PTPN11 was conducted first. Then, HRM assays to look for hot spot mutations coding regions of the other genes of the RAS-MAPK pathway (RAt Sarcoma viral oncogene homolog Mitogen-Activated Protein Kinases Pathway): SOS1, SHOC2, KRAS, RAF1, KRAS, NRAS, CBL, BRAF, MEK1, MEK2, HRAS, and RIT1, were applied. Results: Heterozygous SOS1 point mutation clustered in exon 10, which encodes for the PH domain of SOS1, was identified: c.1655 G > A. The patient was a 9-year-old female born from a consanguineous couple. She exhibited pulmonic valvular stenosis as congenital heart disease. She had facial features and other malformations of Noonan syndrome, including macrocephaly, hypertelorism, ptosis, downslanting palpebral fissures, sparse eyebrows, a short and broad nose with upturned tip, low-set ears, high forehead commonly associated with bitemporal narrowing and prominent supraorbital ridges, short and/or webbed neck and short stature. However, the phenotype is also suggestive of CFC syndrome with the presence of more severe ectodermal abnormalities, including curly hair, keloid scars, hyperkeratotic skin, deep plantar creases, and delayed permanent dentition with agenesis of the right maxillary first molar. Moreover, the familial history of the patient revealed recurrent brain malignancies in the paternal family and epileptic disease in the maternal family. Conclusions: This case report of an overlapping RASopathy associated with SOS1 mutation and familial history of brain tumorigenesis is exceptional. The evidence suggests that RASopathies are truly cancer-prone syndromes, but the magnitude of the cancer risk and the types of cancer partially overlap.

Keywords: cardiofaciocutaneous syndrome, CFC, SOS1, brain cancer, germline mutation

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Authors: Ernesto Linan, Linda Cruz, Lucero Becerra

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In this paper, a new hybridized algorithm based on Chemical Reaction Optimization and Simulated Annealing is proposed to solve the alignment sequence Problem. The Chemical Reaction Optimization is a population-based meta-heuristic algorithm based on the principles of a chemical reaction. Simulated Annealing is applied to solve a large number of combinatorial optimization problems of general-purpose. In this paper, we propose hybridization between Chemical Reaction Optimization algorithm and Simulated Annealing in order to solve the Sequence Alignment Problem. An initial population of molecules is defined at beginning of the proposed algorithm, where each molecule represents a sequence alignment problem. In order to simulate inter-molecule collisions, the process of Chemical Reaction is placed inside the Metropolis Cycle at certain values of temperature. Inside this cycle, change of molecules is done due to collisions; some molecules are accepted by applying Boltzmann probability. The results with the hybrid scheme are better than the results obtained separately.

Keywords: chemical reaction optimization, sequence alignment problem, simulated annealing algorithm, metaheuristics

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Authors: Nishal Parbhoo, John B. Dewar, Samantha Gildenhuys

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Rotavirus is the major cause of severe gastroenteritis worldwide in children aged 5 and younger. Death rates are high particularly in developing countries. The mature rotavirus is a non-enveloped triple-layered nucleocapsid containing 11 double-stranded RNA segments. Here a global view on the sequence and structure of the three main capsid proteins, VP7, VP6, and VP2 is taken by generating a consensus sequence for each of these rotavirus proteins, for each species obtained from published data of representative rotavirus genotypes from across the world and across species. The degree of conservation between species was represented on homology models for each of the proteins. VP7 shows the highest level of variation with 14 - 45 amino acids showing conservation of less than 60%. These changes are localized to the outer surface which is exposed to antibodies alluding to a possible mechanism in evading the immune system. The middle layer, VP6 shows lower variability with only 14-32 sites having lower than 70% conservation. The inner structural layer made up of VP2 showed the lowest variability with only 1-16 sites having less than 70% conservation across species. The results correlate with proteins’ multiple structural roles. Although the nucleotide sequences vary due to an error-prone replication and lack of proofreading, the corresponding amino acid sequence of VP2, 6 and 7 remains conserved. Sequence conservation maintained for the virus results in stable protein structures, fit for function. This can be exploited in drug design, molecular studies and biotechnological applications.

Keywords: amino acid sequence conservation, capsid protein, protein structure, vaccine candidate

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Authors: Yakup Ulusu, Numan Eczacıoğlu, İsa Gökçe, Helen Waller, Jeremy H. Lakey

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Besides having the appropriate amino acid sequence to perform the function of proteins, it is important to have correct conformation after this sequence to process. To consist of this conformation depends on the amino acid sequence at the primary structure, hydrophobic interaction, chaperones and enzymes in charge of folding etc. Misfolded proteins are not functional and tend to be aggregated. Cysteine originating disulfide cross-links make stable this conformation of functional proteins. When two of the cysteine amino acids come side by side, disulfide bond is established that forms a cystine bridge. Due to this feature cysteine plays an important role on the formation of three-dimensional structure of many proteins. There are two cysteine amino acids (C44, C69) in the Tol-A-III protein. Unlike protein disulfide bonds from within his own, any non-specific cystine bridge causes a change in the three dimensional structure of the protein. Proteins can be expressed in various host cells as directly or fusion (chimeric). As a result of overproduction of the recombinant proteins, aggregation of insoluble proteins in the host cell can occur by forming a crystal structure called inclusion body. In general fusion proteins are produced for provide affinity tags to make proteins more soluble and production of some toxic proteins via fusion protein expression system like pTolT. Proteins can be modified by using a site-directed mutagenesis. By this way, creation of non-specific disulfide crosslinks can be prevented at fusion protein expression system via the present cysteine replaced by another amino acid such as serine, glycine or etc. To do this, we need; a DNA molecule that contains the gene that encodes for the target protein, required primers for mutation to be designed according to site directed mutagenesis reaction. This study was aimed to be replaced cysteine encoding codon TGT with serine encoding codon AGT. For this sense and reverse primers designed (given below) and used site-directed mutagenesis reaction. Several new copy of the template plasmid DNA has been formed with above mentioned mutagenic primers via polymerase chain reaction (PCR). PCR product consists of both the master template DNA (wild type) and the new DNA sequences containing mutations. Dpn-l endonuclease restriction enzyme which is specific for methylated DNA and cuts them to the elimination of the master template DNA. E. coli cells obtained after transformation were incubated LB medium with antibiotic. After purification of plasmid DNA from E. coli, the presence of the mutation was determined by DNA sequence analysis. Developed this new plasmid is called PtolT-δ.

Keywords: site directed mutagenesis, Escherichia coli, pTolT, protein expression

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Authors: Adam Rosiński

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This paper discusses an experiment conducted with two groups of participants, composed of musicians and non-musicians, in order to investigate the impact of the speed of a sound sequence and the order of sounds on the grouping of sounds into sequences of six tones. Significant differences were observed between musicians and non-musicians with respect to the threshold sequence speed at which the sequence was split into two streams. The differences in the results for the two groups suggest that the musical education of the participating listeners may be a vital factor. The criterion of musical education should be taken into account during experiments so that the results obtained are reliable, uniform, and free from interpretive errors.

Keywords: auditory scene analysis, education, hearing, psychoacoustics

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Authors: T. Padma, Jayashree S. Pillai

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Random entities are an essential component in any cryptographic application. The suitability of a number theory based novel pseudorandom sequence called Pseudorandom Partial Quotient Sequence (PPQS) generated from the continued fraction expansion of irrational numbers, in cryptographic applications, is analyzed in this paper. An approach to build the algorithm around a hard mathematical problem has been considered. The PQ sequence is tested for randomness and its suitability as a cryptographic key by performing randomness analysis, key sensitivity and key space analysis, precision analysis and evaluating the correlation properties is established.

Keywords: pseudorandom sequences, key sensitivity, correlation, security analysis, randomness analysis, sensitivity analysis

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Authors: Hongmin Deng, Qionghua Wang

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A modified two dimensional (2D) logistic map based on cross feedback control is proposed. This 2D map exhibits more random chaotic dynamical properties than the classic one dimensional (1D) logistic map in the statistical characteristics analysis. So it is utilized as the pseudo-random (PN) sequence generator, where the obtained real-valued PN sequence is quantized at first, then applied to radio frequency identification (RFID) communication system in this paper. This system is experimentally validated on a cortex-M₀ development board, which shows the effectiveness in key generation, the size of key space and security. At last, further cryptanalysis is studied through the test suite in the National Institute of Standards and Technology (NIST).

Keywords: chaos encryption, logistic map, pseudo-random sequence, RFID

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Authors: Jung Ho Yang, Yong Soo Kim

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Electrical units are operated by electrical and electronic components. An environmental test sequence is useful for testing electrical units to reduce reliability issues. This study introduces test sequence guidelines based on relevant principles and considerations for electronic testing according to international standard IEC-60068-1 and the United States military standard MIL-STD-810G. Then, test sequences were proposed based on the descriptions for each test. Finally, General Motors (GM) specification GMW3172 was interpreted and compared to IEC-60068-1 and MIL-STD-810G.

Keywords: reliability, environmental test sequence, electrical units, IEC 60068-1, MIL-STD-810G

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Authors: G. Tamilpavai, C. Vishnuppriya

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Bioinformatics is an active research area which combines biological matter as well as computer science research. The longest common subsequence (LCSS) is one of the major challenges in various bioinformatics applications. The computation of the LCSS plays a vital role in biomedicine and also it is an essential task in DNA sequence analysis in genetics. It includes wide range of disease diagnosing steps. The objective of this proposed system is to find the longest common subsequence which presents in a normal and various disease affected human DNA sequence using Self Organizing Map (SOM) and LCSS. The human DNA sequence is collected from National Center for Biotechnology Information (NCBI) database. Initially, the human DNA sequence is separated as k-mer using k-mer separation rule. Mean and median values are calculated from each separated k-mer. These calculated values are fed as input to the Self Organizing Map for the purpose of clustering. Then obtained clusters are given to the Longest Common Sub Sequence (LCSS) algorithm for finding common subsequence which presents in every clusters. It returns nx(n-1)/2 subsequence for each cluster where n is number of k-mer in a specific cluster. Experimental outcomes of this proposed system produce the possible number of longest common subsequence of normal and disease affected DNA data. Thus the proposed system will be a good initiative aid for finding disease causing sequence. Finally, performance analysis is carried out for different DNA sequences. The obtained values show that the retrieval of LCSS is done in a shorter time than the existing system.

Keywords: clustering, k-mers, longest common subsequence, SOM

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Authors: Frikha Rim, Abdelmoula Bouayed Nouha, Rebai Tarek

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Pregnancy is a hypercoagulable state which causing a defective maternal haemostatic response and leading to thrombosis of the uteroplacental vasculature, that might cause pregnancy complications as recurrent pregnancy loss (RPL). Since heritable Thrombophilic defects are associated with increased thrombosis, their prevalence was evaluated in patients with special emphasis on combinations of the above pathologies. Especially, Factor V Leiden (FVL) G1691A, methylene tetra hydro folate reductase (MTHFR) C677T, and factor II (FII) G20210A mutations are three important causes of thrombophilia, which might be related to recurrent pregnancy loss (RPL). In this study we evaluated the presence of these three mutations [factor V Leiden (FVL), prothrombin G20210A (PTG) and methylenetetrahydrofolate reductase (MTHFR) C677T] amongst 35 Tunisian women with more than 2 miscarriages, referred to our genetic counseling. DNA was extracted from peripheral blood samples and PCR-RFLP was performed for the molecular diagnosis of each mutation. Factor V Leiden and Prothrombin mutation were detected respectively in 5.7% and 2.9% of women with particular history of early fetal loss and thrombotic events. Despites the luck of strength of this study, we insist that testing for the most inherited thrombophilia (FVL and FII mutation) should be performed in women with RPL in the context of thrombotic events. Multi-centre collaboration is necessary to clarify the real impact of thrombotic molecular defects on the pregnancy outcome, to ascertain the effect of thrombophilia on recurrent pregnancy loss and then to evaluate the appropriate therapeutic approach.

Keywords: thrombophilia, recurrent pregnancy loss, factor V Leiden, prothrombin G20210A, methylene tetra hydro folate reductase

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Authors: Kyung Jin Kim, Jiwon Kwak, Jae-Hoon Lee, Soo Suk Lee

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We describe an innovative method for highly specific detection of miRNAs using a specially modified method of poly(A) adaptor RT-qPCR. We use uniquely designed specific extension sequence, which plays important role in providing an opportunity to affect high specificity of miRNA detection. This method involves two steps of reactions as like previously reported and which are poly(A) tailing and reverse-transcription followed by real-time PCR. Firstly, miRNAs are extended by a poly(A) tailing reaction and then converted into cDNA. Here, we remarkably reduced the reaction time by the application of short length of poly(T) adaptor. Next, cDNA is hybridized to the 3’-end of a specific extension sequence which contains miRNA sequence and results in producing a novel PCR template. Thereafter, the SYBR Green-based RT-qPCR progresses with a universal poly(T) adaptor forward primer and a universal reverse primer. The target miRNA, miR-106b in human brain total RNA, could be detected quantitatively in the range of seven orders of magnitude, which demonstrate that the assay displays a dynamic range of at least 7 logs. In addition, the better specificity of this novel extension-based assay against well known poly(A) tailing method for miRNA detection was confirmed by melt curve analysis of real-time PCR product, clear gel electrophoresis and sequence chromatogram images of amplified DNAs.

Keywords: microRNA(miRNA), specific extension sequence, RT-qPCR, poly(A) tailing assay, reverse transcription

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Authors: Vidhu Mitha Goutham, Ruma Mukherjee

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The low availability of well-trained, unlimited, dynamic-access models for specific languages makes it hard for corporate users to adopt quick translation techniques and incorporate them into product solutions. As translation tasks increasingly require a dynamic sequence learning curve; stable, cost-free opensource models are scarce. We survey and compare current translation techniques and propose a modified sequence to sequence model repurposed with attention techniques. Sequence learning using an encoder-decoder model is now paving the path for higher precision levels in translation. Using a Convolutional Neural Network (CNN) encoder and a Recurrent Neural Network (RNN) decoder background, we use Fairseq tools to produce an end-to-end bilingually trained Spanish-English machine translation model including source language detection. We acquire competitive results using a duo-lingo-corpus trained model to provide for prospective, ready-made plug-in use for compound sentences and document translations. Our model serves a decent system for large, organizational data translation needs. While acknowledging its shortcomings and future scope, it also identifies itself as a well-optimized deep neural network model and solution.

Keywords: attention, encoder-decoder, Fairseq, Seq2Seq, Spanish, translation

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Authors: Negin Parsamanesh, Saman Ameri-Mahabadi, Ali Nikfar, Mojdeh Mansouri, Hossein Chiti, Gita Fatemi Abhari

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Duchenne muscular dystrophy (DMD) is a severe progressive X-linked neuromuscular illness that affects movement through mutations in dystrophin gene. The mutation leads to insufficient, lack of or dysfunction of dystrophin. The cause of DMD was determined in an Iranian family. Exome sequencing was carried out along with a complete physical examination of the family. In silico methods were applied to find the alteration in the protein structure. The homozygous variant in DMD gene (NM-004006.2) was defined as c.2732-2733delTT (p.Phe911CysfsX8) in exon 21. In addition, phylogenetic conservation study of the human dystrophin protein sequence revealed that phenylalanine 911 is one of the evolutionarily conserved amino acids. In conclusion, our study indicated a new deletion in the DMD gene in the affected family. This deletion with an X-linked inheritance pattern is new in Iran. These findings could facilitate genetic counseling for this family and other patients in the future.

Keywords: duchenne muscular dystrophy, whole exome sequencing, iran, metabolic syndrome

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Authors: Nahed Al-Hajeri

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There are several reasons which lead to a delay in project completion, out of all, one main reason is the delay in deliverable processing, i.e. submission and review of documents. Most of the project cycles start with a list of deliverables but without a sequence of submission of the same, means without a direction to move, leading to overlapping of activities and more interdependencies. Hence Project Design Deliverables (PDD) is developed as a solution to Organize Transmittals (Documents/Drawings) received from contractors/consultants during different phases of an EPC (Engineering, Procurement, and Construction) projects, which gives proper direction to the stakeholders from the beginning, to reduce inter-discipline dependency, avoid overlapping of activities, provide a list of deliverables, sequence of activities, etc. PDD attempts to provide a list and sequencing of the engineering documents/drawings required during different phases of a Project which will benefit both client and Contractor in performing planned activities through timely submission and review of deliverables. This helps in ensuring improved quality and completion of Project in time. The successful implementation begins with a detailed understanding the specific challenges and requirements of the project. PDD will help to learn about vendor document submissions including general workflow, sequence and monitor the submission and review of the deliverables from the early stages of Project. This will provide an overview for the Submission of deliverables by the concerned during the projects in proper sequence. The goal of PDD is also to hold responsible and accountability of all stakeholders during complete project cycle. We believe that successful implementation of PDD with a detailed list of documents and their sequence will help organizations to achieve the project target.

Keywords: EPC (Engineering, Procurement, and Construction), project design deliverables (PDD), econometrics sciences, management sciences

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Authors: Anthony John Walker, Glen Bright

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The challenge faced by manufactures, when producing custom products, is that each product needs exact components. This can cause work-in-process instability due to component matching constraints imposed on assembly cells. Clearing type flow control policies have been used extensively in mediating server access between multiple arrival processes. Although the stability and performance of clearing policies has been well formulated and studied in the literature, the growth in arrival to departure sequence disorder for each arriving job, across a serving resource, is still an area for further analysis. In this paper, a closed form industrial model has been formulated that characterizes arrival-to-departure sequence disorder through stable manufacturing systems under clearing type flow control policy. Specifically addressed are the effects of sequence disorder imposed on a downstream assembly cell in terms of work-in-process instability induced through component matching constraints. Results from a simulated manufacturing system show that steady state average sequence disorder in parallel upstream processing cells can be balanced in order to decrease downstream assembly system instability. Simulation results also show that the closed form model accurately describes the growth and limiting behavior of average sequence disorder between parts arriving and departing from a manufacturing system flow controlled via clearing policy.

Keywords: assembly system constraint, custom products, discrete sequence disorder, flow control

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Authors: Sarwan Dhir, Suma Basak, Dipika Parajulee

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Alfalfa is renowned for its nutritional and biopharmaceutical value as a perennial forage legume. However, establishing a rapid plant regeneration protocol using somatic embryogenesis and efficient transformation frequency are the crucial prerequisites for gene editing in alfalfa. This study was undertaken to establish and improve the protocol for somatic embryogenesis and subsequent plant regeneration. The experiments were conducted in response to natural sensitivity using various antibiotics such as cefotaxime, carbenicillin, gentamycin, hygromycin, and kanamycin. Using 3-week-old leaf tissue, somatic embryogenesis was initiated on Gamborg’s B5 basal (B5H) medium supplemented with 3% maltose, 0.9µM Kinetin, and 4.5µM 2,4-D. Embryogenic callus (EC) obtained from the B5H medium exhibited a high rate of somatic embryo formation (97.9%) after 3 weeks when the cultures were placed in the dark. Different developmental stages of somatic embryos and cotyledonary stages were then transferred to Murashige and Skoog’s (MS) basal medium under light, resulting in a 94% regeneration rate of plantlets. Our results indicate that leaf segments can grow (tolerate) up to 450 mg/L of cefotaxime and 400 mg/L of carbenicillin in the culture medium. However, the survival threshold for hygromycin at 12.5 mg/L, kanamycin at 250 mg/L, gentamycin at 50 mg/L, and timentin (300 mg/L). The experiment to improve the protocol for achieving efficient transient gene expression in alfalfa through genetic transformation with the Agrobacterium tumefaciens pCAMBIA1304 vector was also conducted. The vector contains two reporter genes such as β-glucuronidase (GUS) and green fluorescent protein (GFP), along with a selectable hygromycin B phosphotransferase gene (HPT), all driven under the CaMV 35s promoter. Various transformation parameters were optimized using 3-week-old in vitro-grown plantlets. The different parameters such as types of explant, leaf ages, preculture days, segment sizes, wounding types, bacterial concentrations, infection periods, co-cultivation periods, different concentrations of acetosyringone, silver nitrate, and calcium chloride were optimized for transient gene expression. The transient gene expression was confirmed via histochemical GUS and GFP visualization under fluorescent microscopy. The data were analyzed based on the semi-quantitative observation of the percentage and number of blue GUS spots on different days of agro-infection. The highest percentage of GUS positivity (76.2%) was observed in 3-week-old leaf segments wounded using a scalpel blade of 11 size- after 3 days of post-incubation at a bacterial concentration of 0.6, with 2 days of preculture, 30 min of bacterial-leaf segment co-cultivation, with the addition of 150 µM acetosyringone, 4 mM calcium chloride, and 75 µM silver nitrate. Our results suggest that various factors influence T-DNA delivery in the Agrobacterium-mediated transformation of alfalfa. The stable gene expression in the putative transgenic tissue was confirmed using PCR amplification of both marker genes, indicating that gene expression in explants was not solely due to Agrobacterium, but also from transformed cells. The improved protocol could be used for generating transgenic alfalfa plants using genome editing techniques such as CRISPR/Cas9.

Keywords: Medicago sativa l. (Alfalfa), agrobacterium tumefaciens, β-glucuronidase, green fluorescent protein, transient gene

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Authors: Eirini Konstanta, Cedric Gouedard, Aggeliki Delimitsou, Stefania Patera, Samuel Murray

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Introduction: Quality reference DNA standards (QRS) for molecular testing by next-generation sequencing (NGS) are essential for accurate quantitation of copy number variations (CNV) for germline and variant allelic frequencies (VAF) for somatic analyses. Objectives: Presently, several molecular analytics for oncology patients are reliant upon quantitative metrics. Test validation and standardisation are also reliant upon the availability of surrogate control materials allowing for understanding test LOD (limit of detection), sensitivity, specificity. We have developed a dual calibration platform allowing for QRS pairs to be included in analysed DNA samples, allowing for accurate quantitation of CNV and VAF metrics within and between patient samples. Methods: QRS™ blocks up to 500nt were designed for common NGS panel targets incorporating ≥ 2 identification tags (IDTDNA.com). These were analysed upon spiking into gDNA, somatic, and ctDNA using a proprietary CalSuite™ platform adaptable to common LIMS. Results: We demonstrate QRS™ calibration reproducibility spiked to 5–25% at ± 2.5% in gDNA and ctDNA. Furthermore, we demonstrate CNV and VAF within and between samples (gDNA and ctDNA) with the same reproducibility (± 2.5%) in a clinical sample of lung cancer and HBOC (EGFR and BRCA1, respectively). CNV analytics was performed with similar accuracy using a single pair of QRS calibrators when using multiple single targeted sequencing controls. Conclusion: Dual paired QRS™ calibrators allow for accurate and reproducible quantitative analyses of CNV, VAF, intrinsic sample allele measurement, inter and intra-sample measure not only simplifying NGS analytics but allowing for monitoring clinically relevant biomarker VAF across patient ctDNA samples with improved accuracy.

Keywords: calibrator, CNV, gene copy number, VAF

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Authors: Chen Wang, Chun Liang

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Microsatellite instability (MSI) is characterized by high degree of polymorphism in microsatellite (MS) length due to a deficiency in mismatch repair (MMR) system. MSI is associated with several tumor types and its status can be considered as an important indicator for tumor prognostic. Conventional clinical diagnosis of MSI examines PCR products of a panel of MS markers using electrophoresis (MSI-PCR) which is laborious, time consuming, and less reliable. MSIpred, a python 2 package for automatic classification of MSI was released by this study. It computes important somatic mutation features from files in mutation annotation format (MAF) generated from paired tumor-normal exome sequencing data, subsequently using these to predict tumor MSI status with a support vector machine (SVM) classifier trained by MAF files of 1074 tumors belonging to four types. Evaluation of MSIpred on an independent 358-tumor test set achieved overall accuracy of over 98% and area under receiver operating characteristic (ROC) curve of 0.967. These results indicated that MSIpred is a robust pan-cancer MSI classification tool and can serve as a complementary diagnostic to MSI-PCR in MSI diagnosis.

Keywords: microsatellite instability, pan-cancer classification, somatic mutation, support vector machine

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Authors: Peri Harish Kumar, Rafique Umer Harvitkar

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Background: The emergency department mandates maximum efficacy in the utilization of the available resources. Non-urgent patient visits pose a serious concern to the treatment, patient triage, and resources available. Aims and Objectives: We conducted a retrospective case-control study of the emergency department patient list from October 2019 to November 2022. A total of 839 patients formed part of the study. Somatic complaints, vital signs, diagnostic test results, admission to the hospital, etc., were some of the criteria used for the categorization of patients. Results: The proportion of non-urgent visits varied from 7.2% to 43%, with a median of 21%. Somatic complaints were the least associated with further hospital admissions (n=28%), while diagnostic test results were the most significant indicator of further hospital admissions (n=74%). Effective triage helped minimize emergency department admissions by 36%. Conclusion: Our study shows that effective triaging, patient counselling, and round-the-clock consumable monitoring helped in the effective management of patients admitted and also significantly helped provide treatment to the patients most in need.

Keywords: urgent visits, non-urgent visits, traiging, emergency department admissions

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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

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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

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Authors: Caleb B. Sagwa, Tobias O. Okeno, Alexander K. Kahi

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Dairy cattle production plays an important role in the Kenyan economy. However, high incidences of mastitis is a major setback to the productivity in this industry. The current dairy cattle breeding objective in Kenya does not include mastitis resistance, mainly because the economic value of mastitis resistance has not been determined. Therefore this study aimed at estimating the economic value of mastitis resistance in dairy cattle in Kenya. Initial input parameters were obtained from literature on dairy cattle production systems in the tropics. Selection index methodology was used to derive the economic value of mastitis resistance. Somatic cell count (SCC) was used an indicator trait for mastitis resistance. The economic value was estimated relative to milk yield (MY). Economic values were assigned to SCC in a selection index such that the overall gain in the breeding goal trait was maximized. The option of estimating the economic value for SCC by equating the response in the trait of interest to its index response was considered. The economic value of mastitis resistance was US $23.64 while maximum response to selection for MY was US $66.01. The findings of this study provide vital information that is a pre-requisite for the inclusion of mastitis resistance in the current dairy cattle breeding goal in Kenya.

Keywords: somatic cell count, milk quality, payment system, breeding goal

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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

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Authors: Shahid Hussain Abro, Siamak Zohari, Lena H. M. Renström, Désirée S. Jansson, Faruk Otman, Karin Ullman, Claudia Baule

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Infectious bronchitis is an acute, highly contagious respiratory, nephropathogenic and reproductive disease of poultry that is caused by infectious bronchitis virus (IBV). The present study used a large data set of structural gene sequences, including newly generated ones and sequences available in the GenBank database to further analyze the diversity and to identify selective pressures and recombination spots. There were some deletions or insertions in the analyzed regions in isolates of the Italy-02 and D274 genotypes. Whereas, there were no insertions or deletions observed in the isolates of the Massachusetts and 4/91 genotype. The hypervariable nucleotide sequence regions spanned positions 152–239, 554–582, 686–737 and 802–912 in the S1 sub-unit of the all analyzed genotypes. The nucleotide sequence data of the E gene showed that this gene was comparatively unstable and subjected to a high frequency of mutations. The M gene showed substitutions consistently distributed except for a region between nucleotide positions 250–680 that remained conserved. The lowest variation in the nucleotide sequences of ORF5a was observed in the isolates of the D274 genotype. While, ORF5b and N gene sequences showed highly conserved regions and were less subjected to variation. Genes ORF3a, ORF3b, M, ORF5a, ORF5b and N presented negative selective pressure among the analyzed isolates. However, some regions of the ORFs showed favorable selective pressure(s). The S1 and E proteins were subjected to a high rate of mutational substitutions and non-synonymous amino acids. Strong signals of recombination breakpoints and ending break point were observed in the S and N genes. Overall, the results of this study revealed that very likely the strong selective pressures in E, M and the high frequency of substitutions in the S gene can probably be considered the main determinants in the evolution of IBV.

Keywords: IBV, avian infectious bronchitis, structural genes, genotypes, genetic diversity

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Authors: Muhammad Umair, Tanveer Hussain, Khubab Shaker, Yasir Nawab, Muhammad Maqsood, Madeha Jabbar

Abstract:

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

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Authors: Mudawamah Mudawamah, Muhammad Z. Fadli, Gatot Ciptadi, Aulanni’am

Abstract:

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

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Authors: Mpho Mokoatle, Darlington Mapiye, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

Abstract:

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

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Authors: Darlington Mapiye, Mpho Mokoatle, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

Abstract:

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 159

Authors: Sungsoo Na, Chanho Park

Abstract:

Lung cancer is one of the most common severe diseases driving to the death of a human. Lung cancer can be divided into two cases of small-cell lung cancer (SCLC) and non-SCLC (NSCLC), and about 80% of lung cancers belong to the case of NSCLC. From several studies, the correlation between epidermal growth factor receptor (EGFR) and NSCLCs has been investigated. Therefore, EGFR inhibitor drugs such as gefitinib and erlotinib have been used as lung cancer treatments. However, the treatments result showed low response (10~20%) in clinical trials due to EGFR mutations that cause the drug resistance. Patients with resistance to EGFR inhibitor drugs usually are positive to KRAS mutation. Therefore, assessment of EGFR and KRAS mutation is essential for target therapies of NSCLC patient. In order to overcome the limitation of conventional therapies, overall EGFR and KRAS mutations have to be monitored. In this work, the only detection of EGFR will be presented. A variety of techniques has been presented for the detection of EGFR mutations. The standard detection method of EGFR mutation in ctDNA relies on real-time polymerase chain reaction (PCR). Real-time PCR method provides high sensitive detection performance. However, as the amplification step increases cost effect and complexity increase as well. Other types of technology such as BEAMing, next generation sequencing (NGS), an electrochemical sensor and silicon nanowire field-effect transistor have been presented. However, those technologies have limitations of low sensitivity, high cost and complexity of data analyzation. In this report, we propose a label-free and high-sensitive detection method of lung cancer using quartz crystal microbalance based platform. The proposed platform is able to sense lung cancer mutant DNA with a limit of detection of 1nM.

Keywords: cancer DNA, resonance frequency, quartz crystal microbalance, lung cancer

Procedia PDF Downloads 233

Authors: Mahmoud M. S. Farrag, Alaa A. K. Elhaweet, El-Sayed Kh. A. Akel, Mohsen A. Moustafa

Abstract:

The present work aimed to study the reproductive strategy of the common lessepsian puffer fish Lagocephalus sceleratus (Gmelin, 1879) from the Egyptian Mediterranean Waters. It is a famous migratory species plays an important role in the field of fisheries and ecology of aquatic ecosystem. The specimens were collected monthly from the landing centers along the Egyptian Mediterranean coast during 2012. Six maturity stages were recorded: (I) Thread like stage, (II) Immature stage (Virgin stage), (III) Maturing stage (Developing Virgin and recovering spent), (IV) Nearly ripe stage, (V) Fully ripe, (VI) Spawning stage, (VII) Spent stage. According to sex ratio, males exhibited higher number than females representing 52.44 % of the total fishes with sex ratio 1: 0.91. Fish length corresponding to 50% maturation was 38.5 cm for males and 41 cm for females. The corresponding ages (age at first maturity) are equal to 2.14 and 2.27 years for male and female respectively. The ova diameter ranged from 0.02mm to 0.85mm, the mature ova ranged from 0.16mm to 0.85mm and showed progressive increase from April towards September. Also, the presences of ova diameter in one peak of mature and ripe eggs in the ovaries were observed during spawning period. The relationship between gutted weight and absolute fecundity indicated that that fecundity increased as the fish grew in weight. The absolute fecundity ranged from 260288 to 2372931 for fish weight ranged from 698 to 3285 cm with an average of 1449522±720975. The relative fecundity ranged from 373 to 722 for fish weight ranged from 698 to 3285 cm with an average of 776±231. The spawning season of L. sceleratus was investigated from the data of gonado-somatic index and monthly distribution of maturity stages along the year as well as sequence of ova diameter for mature stages and exhibited a relatively prolong spawning season extending from April for both sexes and ends in August for male while ends in September for female. Fish releases its ripe ova in one batch during the spawning season. Histologically, the ovarian cycle of L. sceleratus was classified into six stages and the testicular cycle into five stages. Histological characters of gonads of L. sceleratus during the year of study had confirmed the previous results of distribution of maturity stages, gonado-somatic index and ova diameter, indicating this fish species has prolonged spawning season from April to September. This species is considered totally or uni spawner with synchronous group as it contained one to two developmental stages at the same gonad.

Keywords: Lagocephalus sceleratus, reproductive biology, oogenesis, histology

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