Search results for: autosomal recessive point mutation

Authors: Wafa’ Alma'Aitah, Khaled Almakadmeh

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this study presents an information retrieval system of using genetic algorithm to increase information retrieval efficiency. Using vector space model, information retrieval is based on the similarity measurement between query and documents. Documents with high similarity to query are judge more relevant to the query and should be retrieved first. Using genetic algorithms, each query is represented by a chromosome; these chromosomes are fed into genetic operator process: selection, crossover, and mutation until an optimized query chromosome is obtained for document retrieval. Results show that information retrieval with adaptive crossover probability and single point type crossover and roulette wheel as selection type give the highest recall. The proposed approach is verified using (242) proceedings abstracts collected from the Saudi Arabian national conference.

Keywords: genetic algorithm, information retrieval, optimal queries, crossover

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Authors: D. S. Palimkar

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Random fixed point theory has received much attention in recent years, and it is needed for the study of various classes of random equations. The study of random fixed point theorems was initiated by the Prague school of probabilistic in the 1950s. The existence and uniqueness of fixed points for the self-maps of a metric space by altering distances between the points with the use of a control function is an interesting aspect in the classical fixed point theory. In a new category of fixed point problems for a single self-map with the help of a control function that alters the distance between two points in a metric space which they called an altering distance function. In this paper, we prove the results of existence of random common fixed point and its uniqueness for a pair of random mappings under weakly contractive condition for generalizing alter distance function in polish spaces using Random Common Fixed Point Theorem for Generalized Weakly Contractions.

Keywords: Polish space, random common fixed point theorem, weakly contractive mapping, altering function

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Authors: Pakkinee Chitsakul

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In this article, we would like to show that there is no cut point of any point in a plane, but there exists the cut locus of a point in a flat torus. By the results, we would like to determine the structure of cut locus of a flat torus.

Keywords: cut locus, flat torus, geodesics

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Authors: Arunima Verma, Padmabati Mondal

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Serotonin-receptor binding plays a key role in several neurological and biological processes, including mood, sleep, hunger, cognition, learning, and memory. In this article, we performed molecular dynamics simulation to examine the key residues that play an essential role in the binding of serotonin to the G-protein-coupled 5-HT₁ᴮ receptor (5-HT₁ᴮ R) via electrostatic interactions. An end-point free energy calculation method (MM-PBSA) determines the stability of the 5-HT1B R due to serotonin binding. The single-point mutation of the polar or charged amino acid residues (Asp129, Thr134) on the binding sites and the calculation of binding free energy validate the importance of these residues in the stability of the serotonin-receptor complex. Principal component analysis indicates the serotonin-bound 5-HT1BR is more stabilized than the apo-receptor in terms of dynamical changes. The difference dynamic cross-correlations map shows the correlation between the transmembrane and mini-Go, which indicates signal transduction happening between mini-Go and the receptor. Allosteric communication reveals the key nodes for signal transduction in 5-HT1BR. These results provide useful insights into the signal transduction pathways and mutagenesis study to regulate the functionality of the complex. The developed protocols can be applied to study local non-covalent interactions and long-range allosteric communications in any protein-ligand system for computer-aided drug design.

Keywords: allostery, CADD, MD simulations, MM-PBSA

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Authors: Zhipeng Yan, Janice Wing-Tung Kwong, Ching-Lung Lai

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Background: Advanced melanoma accounts for the majority of skin cancer death due to its poor prognosis. Nivolumab and ipilimumab are monoclonal antibodies targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocytes antigen 4 (CTLA-4). Nivolumab and ipilimumab combination therapy has been proven to be effective for advanced melanoma. This systematic review and meta-analysis are to evaluate its clinical efficacy and adverse events. Method: A systematic search was done on databases (Pubmed, Embase, Medline, Cochrane) on 21 June 2020. Search keywords were nivolumab, ipilimumab, melanoma, and randomised controlled trials. Clinical trials fulfilling the inclusion criteria were selected to evaluate the efficacy of combination therapy in terms of prolongation of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The odd ratios and distributions of grade 3 or above adverse events were documented. Subgroup analysis was performed based on PD-L1 expression-status and BRAF-mutation status. Results: Compared with nivolumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR in combination therapy were 0.64 (95% CI, 0.48-0.85; p=0.002), 0.84 (95% CI, 0.74-0.95; p=0.007) and 1.76 (95% CI, 1.51-2.06; p < 0.001), respectively. Compared with ipilimumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR were 0.46 (95% CI, 0.37-0.57; p < 0.001), 0.54 (95% CI, 0.48-0.61; p < 0.001) and 6.18 (95% CI, 5.19-7.36; p < 0.001), respectively. In combination therapy, the odds ratios of grade 3 or above adverse events were 4.71 (95% CI, 3.57-6.22; p < 0.001) compared with nivolumab monotherapy, and 3.44 (95% CI, 2.49-4.74; p < 0.001) compared with ipilimumab monotherapy, respectively. High PD-L1 expression level and BRAF mutation were associated with better clinical outcomes in patients receiving combination therapy. Conclusion: Combination therapy is effective for the treatment of advanced melanoma. Adverse events were common but manageable. Better clinical outcomes were observed in patients with high PD-L1 expression levels and positive BRAF-mutation.

Keywords: nivolumab, ipilimumab, advanced melanoma, systematic review, meta-analysis

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Authors: Yi Yu, Vu Xuan Nguyen, Gaoxi Xiao

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Opinion formation in complex social networks may exhibit complex system dynamics even when based on some simplest system evolution models. An interesting and important issue is the effects of the initial state on the final steady-state opinion distribution. By carrying out extensive simulations and providing necessary discussions, we show that, while different initial opinion distributions certainly make differences to opinion evolution in social systems without noises, in systems with noises, given enough time, different initial states basically do not contribute to making any significant differences in the final steady state. Instead, it is the basal distribution of the preferred opinions that contributes to deciding the final state of the systems. We briefly explain the reasons leading to the observed conclusions. Such an observation contradicts with a long-term belief on the roles of system initial state in opinion formation, demonstrating the dominating role that opinion mutation can play in opinion formation given enough time. The observation may help to better understand certain observations of opinion evolution dynamics in real-life social networks.

Keywords: opinion formation, Deffuant model, opinion mutation, consensus making

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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Authors: Daria Zabolotnaya, Svetlana Degtyareva, Veronika Kanestri, Danila Konnov

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An adequate choice of the initial antiretroviral treatment determines the treatment efficacy. In the clinical guidelines in Russia non-nucleoside reverse transcriptase inhibitors (NNRTIs) are still considered to be an option for first-line treatment while pretreatment drug resistance (PDR) testing is not routinely performed. We conducted a cohort retrospective study in HIV-positive treatment naïve patients of the H-clinic (Moscow, Russia) who performed PDR testing from July 2017 to November 2021. All the information was obtained from the medical records anonymously. We analyzed the mutations in reverse transcriptase and protease genes. RT-sequences were obtained by AmpliSens HIV-Resist-Seq kit. Drug resistance was defined using the HIVdb Program v. 8.9-1. PDR was estimated using the Stanford algorithm. Descriptive statistics were performed in Excel (Microsoft Office, 2019). A total of 261 HIV-1 infected patients were enrolled in the study including 197 (75.5%) male and 64 (24.5%) female. The mean age was 34.6±8.3 years. The median CD4 count – 521 cells/µl (IQR 367-687 cells/µl). Data on risk factors of HIV-infection were scarce. The total quantity of strains containing mutations in the reverse transcriptase gene was 75 (28.7%). From these 5 (1.9%) mutations were associated with PDR to nucleoside reverse transcriptase inhibitors (NRTIs) and 30 (11.5%) – with PDR to NNRTIs. The number of strains with mutations in protease gene was 43 (16.5%), from these only 3 (1.1%) mutations were associated with resistance to protease inhibitors. For NNRTIs the most prevalent PDR mutations were E138A, V106I. Most of the HIV variants exhibited a single PDR mutation, 2 were found in 3 samples. Most of HIV variants with PDR mutation displayed a single drug class resistance mutation. 2/37 (5.4%) strains had both NRTIs and NNRTIs mutations. There were no strains identified with PDR mutations to all three drug classes. Though earlier data demonstrated a lower level of PDR in HIV treatment naïve population in Russia and our cohort can be not fully representative as it is taken from the private clinic, it reflects the trend of increasing PDR especially to NNRTIs. Therefore, we consider either pretreatment testing or giving the priority to other drugs as first-line treatment necessary.

Keywords: HIV, resistance, mutations, treatment

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Authors: Paula I. Buonfiglio, Carlos David Bruque, Lucia Salatino, Vanesa Lotersztein, Sebastián Menazzi, Paola Plazas, Ana Belén Elgoyhen, Viviana Dalamón

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Hearing loss (HL) is the most prevalent sensorineural disorder affecting about 10% of the global population, with more than half due to genetic causes. About 1 in 500-1000 newborns present congenital HL. Most of the patients are non-syndromic with an autosomal recessive mode of inheritance. To date, more than 100 genes are related to HL. Therefore, the Whole-exome sequencing (WES) technique has become a cost-effective alternative approach for molecular diagnosis. Nevertheless, new challenges arise from the detection of novel variants, in particular missense changes, which can lead to a spectrum of genotype-to-phenotype correlations, which is not always straightforward. In this work, we aimed to identify the genetic causes of HL in isolated and familial cases by designing a multistep approach to analyze target genes related to hearing impairment. Moreover, we performed in silico and in vivo analyses in order to further study the effect of some of the novel variants identified in the hair cell function using the zebrafish model. A total of 650 patients were studied by Sanger Sequencing and Gap-PCR in GJB2 and GJB6 genes, respectively, diagnosing 15.5% of sporadic cases and 36% of familial ones. Overall, 50 different sequence variants were detected. Fifty of the undiagnosed patients with moderate HL were tested for deletions in STRC gene by Multiplex ligation-dependent probe amplification technique (MLPA), leading to 6% of diagnosis. After this initial screening, 50 families were selected to be analyzed by WES, achieving diagnosis in 44% of them. Half of the identified variants were novel. A missense variant in MYO6 gene detected in a family with postlingual HL was selected to be further analyzed. A protein modeling with AlphaFold2 software was performed, proving its pathogenic effect. In order to functionally validate this novel variant, a knockdown phenotype rescue assay in zebrafish was carried out. Injection of wild-type MYO6 mRNA in embryos rescued the phenotype, whereas using the mutant MYO6 mRNA (carrying c.2782C>A variant) had no effect. These results strongly suggest the deleterious effect of this variant on the mobility of stereocilia in zebrafish neuromasts, and hence on the auditory system. In the present work, we demonstrated that our algorithm is suitable for the sequential multigenic approach to HL in our cohort. These results highlight the importance of a combined strategy in order to identify candidate variants as well as the in silico and in vivo studies to analyze and prove their pathogenicity and accomplish a better understanding of the mechanisms underlying the physiopathology of the hearing impairment.

Keywords: diagnosis, genetics, hearing loss, in silico analysis, in vivo analysis, WES, zebrafish

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Authors: Shiamaa Eltantawy, Gihan Sobhy, Alif Alaam

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Wilson disease, or hepatolenticular degeneration, is an autosomal recessive disease that results in excess copper buildup in the body. It primarily affects the liver and basal ganglia of the brain, but it can affect other organ systems. Musculoskeletal abnormalities, including premature osteoarthritis, skeletal deformity, and pathological bone fractures, can occasionally be found in WD patients with a hepatic or neurologic type. The aim was to assess the prevalence of osteoporosis and osteopenia in Wilson’s disease patients. This case-control study was conducted on ninety children recruited from the inpatient ward and outpatient clinic of the Paediatric Hepatology, Gastroenterology, and Nutrition department of the National Liver Institute at Menofia University, aged from 1 to 18 years. Males were 49, and females were 41. Children were divided into three groups: (Group I) consisted of thirty patients with WD; (Group II) consisted of thirty patients with chronic liver disease other than WD; (Group III) consisted of thirty age- and sex-matched healthy The exclusion criteria were patients with hyperparathyroidism, hyperthyroidism, renal failure, Cushing's syndrome, and patients on certain drugs such as chemotherapy, anticonvulsants, or steroids. All patients were subjected to the following: 1- Full history-taking and clinical examination. 2-Laboratory investigations: (FBC,ALT,AST,serum albumin, total protein, total serum bilirubin,direct bilirubin,alkaline phosphatase, prothrombin time, serum critine,parathyroid hormone, serum calcium, serum phosphrus). 3-Bone mineral density (BMD, gm/cm2) values were measured by dual-energy X-ray absorptiometry (DEXA). The results revealed that there was a highly statistically significant difference between the three groups regarding the DEXA scan, and there was no statistically significant difference between groups I and II, but the WD group had the lowest bone mineral density. The WD group had a large number of cases of osteopenia and osteoporosis, but there was no statistically significant difference with the group II mean, while a high statistically significant difference was found when compared to group III. In the WD group, there were 20 patients with osteopenia, 4 patients with osteoporosis, and 6 patients who were normal. The percentages were 66.7%, 13.3%, and 20%, respectively. Therefore, the largest number of cases in the WD group had osteopenia. There was no statistically significant difference found between WD patients on different treatment regimens regarding DEXA scan results (Z-Score). There was no statistically significant difference found between patients in the WD group (normal, osteopenic, or osteoporotic) regarding phosphorus (mg/dL), but there was a highly statistically significant difference found between them regarding ionised Ca (mmol/L). Therefore, there was a decrease in bone mineral density when the Ca level was decreased. In summary, Wilson disease is associated with bone demineralization. The largest number of cases in the WD group in our study had osteopenia (66.7%). Different treatment regimens (zinc monotherapy, Artamin, and zinc) as well as different laboratory parameters have no effect on bone mineralization in WD cases. Decreased ionised Ca is associated with low BMD in WD patients. Children with WD should be investigated for BMD.

Keywords: wilson disease, Bone mineral density, liver disease, osteoporosis

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Authors: Danilo Habermann, Aleksander Medella, Carla Cremon, Yusef Caceres

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This paper aims to analyze the ability of 2d point clouds features to classify different models of helicopters using radars. This method does not need to estimate the blade length, the number of blades of helicopters, and the period of their micro-Doppler signatures. It is also not necessary to generate spectrograms (or any other image based on time and frequency domain). This work transforms a radar return signal into a 2D point cloud and extracts features of it. Three classifiers are used to distinguish 9 different helicopter models in order to analyze the performance of the features used in this work. The high accuracy obtained with each of the classifiers demonstrates that the 2D point clouds features are very useful for classifying helicopters from radar signal.

Keywords: helicopter classification, point clouds features, radar, supervised classifiers

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Authors: Ali M. EL-Soll

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Physical properties of Sarir waxy crude oil was investigated, pour-point was determined using ASTM D-79 procedure, paraffin content and carbon number distribution of the paraffin was determined using gas liquid Chromatography(GLC), polymeric additives were prepared and their structures were confirmed using IR spectrophotometer. The molecular weight and molecular weigh distribution of these additives were determined by gel permeation chromatography (GPC). the performance of the synthesized additives as pour-point depressants was evaluated, for the mentioned crude oil.

Keywords: sarir, waxy, crude, pour point, depressants

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Authors: Tanushree Jaitly, Shailendra Gupta, Leila Taher, Gerold Schuler, Julio Vera

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Genomics-based personalized medicine is a promising approach to fight aggressive tumors based on patient's specific tumor mutation and expression profiles. A remarkable case is, dendritic cell-based immunotherapy, in which tumor epitopes targeting patient's specific mutations are used to design a vaccine that helps in stimulating cytotoxic T cell mediated anticancer immunity. Here we present a computational pipeline for epitope-based personalized cancer vaccines using patient-specific haplotype and cancer mutation profiles. In the workflow proposed, we analyze Whole Exome Sequencing and RNA Sequencing patient data to detect patient-specific mutations and their expression level. Epitopes including the tumor mutations are computationally predicted using patient's haplotype and filtered based on their expression level, binding affinity, and immunogenicity. We calculate binding energy for each filtered major histocompatibility complex (MHC)-peptide complex using docking studies, and use this feature to select good epitope candidates further.

Keywords: cancer immunotherapy, epitope prediction, NGS data, personalized medicine

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Authors: Jingyuan Hu, Zhandong Liu

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CRISPR genome editing technology has transformed molecular biology by accurately targeting and altering an organism’s DNA. Despite the state-of-art precision of CRISPR genome editing, the imprecise mutation outcome and off-target effects present considerable risk, potentially leading to unintended genetic changes. Targeted deep sequencing, combined with bioinformatics sequence alignment, can detect such unwanted mutations. Nevertheless, the classical method, Needleman-Wunsch (NW) algorithm may produce false alignment outcomes, resulting in inaccurate mutation identification. The key to precisely identifying CRISPR-induced mutations lies in determining optimal parameters for the sequence alignment algorithm. Hidden Markov models (HMM) are ideally suited for this task, offering flexibility across CRISPR systems by leveraging forward-backward algorithms for parameter estimation. In this study, we introduce CRISPR-HMM, a statistical software to precisely call CRISPR-induced mutations. We demonstrate that the software significantly improves precision in identifying CRISPR-induced mutations compared to NW-based alignment, thereby enhancing the overall understanding of the CRISPR gene-editing process.

Keywords: CRISPR, HMM, sequence alignment, gene editing

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Authors: Boumesbah Asma, Chergui Mohamed El-amine

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Since it has been shown that the multi-objective minimum spanning tree problem (MOST) is NP-hard even with two criteria, we propose in this study a hybrid NSGA-II algorithm with an exact mutation operator, which is only used with low probability, to find an approximation to the Pareto front of the problem. In a connected graph G, a spanning tree T of G being a connected and cycle-free graph, if k edges of G\T are added to T, we obtain a partial graph H of G inducing a reduced size multi-objective spanning tree problem compared to the initial one. With a weak probability for the mutation operator, an exact method for solving the reduced MOST problem considering the graph H is then used to give birth to several mutated solutions from a spanning tree T. Then, the selection operator of NSGA-II is activated to obtain the Pareto front approximation. Finally, an adaptation of the VNS metaheuristic is called for further improvements on this front. It allows finding good individuals to counterbalance the diversification and the intensification during the optimization search process. Experimental comparison studies with an exact method show promising results and indicate that the proposed algorithm is efficient.

Keywords: minimum spanning tree, multiple objective linear optimization, combinatorial optimization, non-sorting genetic algorithm, variable neighborhood search

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Authors: Mohammad Jalali Varnamkhasti

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The genetic algorithms have been very successful in handling difficult optimization problems. The fundamental problem in genetic algorithms is premature convergence. This paper, present a new fuzzy genetic algorithm based on chaotic values instead of the random values in genetic algorithm processes. In this algorithm, for initial population is used chaotic sequences and then a new sexual selection proposed for selection mechanism. In this technique, the population is divided such that the male and female would be selected in an alternate way. The layout of the male and female chromosomes in each generation is different. A female chromosome is selected by tournament selection size from the female group. Then, the male chromosome is selected, in order of preference based on the maximum Hamming distance between the male chromosome and the female chromosome or The highest fitness value of male chromosome (if more than one male chromosome is having the maximum Hamming distance existed), or Random selection. The selections of crossover and mutation operators are achieved by running the fuzzy logic controllers, the crossover and mutation probabilities are varied on the basis of the phenotype and genotype characteristics of the chromosome population. Computational experiments are conducted on the proposed techniques and the results are compared with some other operators, heuristic and local search algorithms commonly used for solving p-median problems published in the literature.

Keywords: genetic algorithm, fuzzy system, chaos, sexual selection

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Authors: Natalia Koltovaya, Nadezhda Zhuchkina, Ksenia Lyubimova

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We study the biological effects induced by ionizing radiation in view of therapeutic exposure and the idea of space flights beyond Earth's magnetosphere. In particular, we examine the differences between base pair substitution induction by ionizing radiation in model haploid and diploid yeast Saccharomyces cerevisiae cells. Such mutations are difficult to study in higher eukaryotic systems. In our research, we have used a collection of six isogenic trp5-strains and 14 isogenic haploid and diploid cyc1-strains that are specific markers of all possible base-pair substitutions. These strains differ from each other only in single base substitutions within codon-50 of the trp5 gene or codon-22 of the cyc1 gene. Different mutation spectra for two different haploid genetic trp5- and cyc1-assays and different mutation spectra for the same genetic cyc1-system in cells with different ploidy — haploid and diploid — have been obtained. It was linear function for dose-dependence in haploid and exponential in diploid cells. We suggest that the differences between haploid yeast strains reflect the dependence on the sequence context, while the differences between haploid and diploid strains reflect the different molecular mechanisms of mutations.

Keywords: base pair substitutions, γ-rays, haploid and diploid cells, yeast Saccharomyces cerevisiae

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Authors: Abdelhadi Adel, Kadri Ouahab

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This paper proposes an improved approach based on MAS Architecture and Heuristic Algorithm for systematic maintenance to minimize makespan. We have implemented a problem-solving approach for optimizing the processing time, methods based on metaheuristics. The proposed approach is inspired by the behavior of the human body. This hybridization is between a multi-agent system and inspirations of the human body, especially genetics. The effectiveness of our approach has been demonstrated repeatedly in this paper. To solve such a complex problem, we proposed an approach which we have used advanced operators such as uniform crossover set and single point mutation. The proposed approach is applied to three preventive maintenance policies. These policies are intended to maximize the availability or to maintain a minimum level of reliability during the production chain. The results show that our algorithm outperforms existing algorithms. We assumed that the machines might be unavailable periodically during the production scheduling.

Keywords: multi-agent systems, emergence, genetic algorithm, makespan, systematic maintenance, scheduling, hybrid flow shop scheduling

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Authors: Faisal Zaman, Ya Ping Wong, Boon Yian Ng

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Point cloud source data for surface reconstruction is usually contaminated with noise and outliers. To overcome this, we present a novel approach using modified kernel density estimation (KDE) technique with bilateral filtering to remove noisy points and outliers. First we present a method for estimating optimal bandwidth of multivariate KDE using particle swarm optimization technique which ensures the robust performance of density estimation. Then we use mean-shift algorithm to find the local maxima of the density estimation which gives the centroid of the clusters. Then we compute the distance of a certain point from the centroid. Points belong to outliers then removed by automatic thresholding scheme which yields an accurate and economical point surface. The experimental results show that our approach comparably robust and efficient.

Keywords: point preprocessing, outlier removal, surface reconstruction, kernel density estimation

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Authors: M. Dezvarei, S. Morovati

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In recent years, increasing usage of electrical energy provides a widespread field for investigating new methods to produce clean electricity with high reliability and cost management. Fuel cells are new clean generations to make electricity and thermal energy together with high performance and no environmental pollution. According to the expansion of fuel cell usage in different industrial networks, the identification and optimization of its parameters is really significant. This paper presents optimization of a proton exchange membrane fuel cell (PEMFC) parameters based on modified particle swarm optimization with real valued mutation (RVM) and clonal algorithms. Mathematical equations of this type of fuel cell are presented as the main model structure in the optimization process. Optimized parameters based on clonal and RVM algorithms are compared with the desired values in the presence and absence of measurement noise. This paper shows that these methods can improve the performance of traditional optimization methods. Simulation results are employed to analyze and compare the performance of these methodologies in order to optimize the proton exchange membrane fuel cell parameters.

Keywords: clonal algorithm, proton exchange membrane fuel cell (PEMFC), particle swarm optimization (PSO), real-valued mutation (RVM)

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Authors: Atitallah Sofien, Bouyahia Olfa, Attar Souleima, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

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Introduction: Ciliopathies are a spectrum of diseases that have in common a defect in the synthesis of ciliary proteins. It is a rare cause of neonatal cholestasis. Clinical presentation varies extremely, and the main affected organs are the kidneys, liver, and pancreas. Methodology: This is a descriptive case report of a newborn who was admitted for exploration of neonatal cholestasis in the Paediatric Department C at the Children’s Hospital of Tunis, where the investigations concluded with a rare genetic mutation. Results: This is the case of a newborn male with no family history of hepatic and renal diseases, born to consanguineous parents, and from a well-monitored uneventful pregnancy. He developed jaundice on the second day of life, for which he received conventional phototherapy in the neonatal intensive care unit. He was admitted at 15 days for mild bronchiolitis. On clinical examination, intense jaundice was noted with normal stool and urine colour. Initial blood work showed an elevation in conjugated bilirubin and a high gamma-glutamyl transferase level. Transaminases and prothrombin time were normal. Abdominal sonography revealed hepatomegaly, splenomegaly, and undifferentiated renal cortex with bilateral medullar micro-cysts. Kidney function tests were normal. The infant received ursodeoxycholic acid and vitamin therapy. Genetic testing showed a homozygous mutation in the DCDC2 gene that hadn’t been documented before confirming the diagnosis of renal-hepatic ciliopathy. The patient has regular follow-ups, and his conjugated bilirubin and gamma-glutamyl transferase levels have been decreasing. Conclusion: Genetic testing has revolutionized the approach to etiological diagnosis in pediatric cholestasis. It enables personalised treatment strategies to better enhance the quality of life of patients and prevent potential complications following adequate long-term monitoring.

Keywords: cholestasis, newborn, ciliopathy, DCDC2, genetic

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Authors: Jumanah S. Alawfi

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Polycystic ovary syndrome (PCOS) is a common endocrinopathy among females in their reproductive years. The incidence cases are nearly 1.55 million among females across the globe, with 0.43 million associated disability-adjusted life-years (DALYs). This syndrome is associated with intricate mechanisms typically characterized by insulin resistance (IR), infertility, overweight and/or obesity. Lifestyle interventions are often prescribed as an adjective treatment. Nonetheless, obesity is a complex disease that encompasses multiple dimensions, such as excessive energy intake and genetics. The melanocortin 4 receptor mutation (MC4R) is an important mediator in appetite. There is emerging evidence that suggests its role in the Body Mass Index (BMI) among PCOS subjects, which poses the question of obesity and/or overweight among the PCOS patients who carry the MC4R variants may be caused by overconsumption. Thereby, using other satiety techniques may be beneficial as a part of personalized nutrition. Therefore, the aim of the current mini-review is to discuss the effect of the vegan low glycemic diet on reducing appetite among PCOS patients. The review shows that there is a gap in the knowledge of the effect of the vegan diet on PCOS patients who carry MC4R variants which need further research.

Keywords: polycystic ovarian syndrome (PCOS), Appetite, Melanocortin 4 Receptor Mutation (MC4R)., Obesity

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Authors: M. Altekin, R. F. Yükseler

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Geometrically nonlinear axisymmetric bending of a shallow spherical shell with a point support at the apex under linearly varying axisymmetric load was investigated numerically. The edge of the shell was assumed to be simply supported or clamped. The solution was obtained by the finite difference and the Newton-Raphson methods. The thickness of the shell was considered to be uniform and the material was assumed to be homogeneous and isotropic. Sensitivity analysis was made for two geometrical parameters. The accuracy of the algorithm was checked by comparing the deflection with the solution of point supported circular plates and good agreement was obtained.

Keywords: Bending, Nonlinear, Plate, Point support, Shell.

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Authors: Rozhgar A. Khailany, Mehri Igci, Emine Bayraktar, Sakip Erturhan, Metin Karakok, Ahmet Arslan

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Kidney cancer is the most lethal urological cancer accounting for 3% of adult malignancies. VHL, a tumor-suppressor gene, is best known to be associated with renal cell carcinoma (RCC). The VHL functions as negative regulator of hypoxia inducible factors. Recent sequencing efforts have identified several novel frequent mutations of histone modifying and chromatin remodeling genes in ccRCC (clear cell RCC) including PBRM1 and SETD2. The PBRM1 gene encodes the BAF180 protein, which involved in transcriptional activation and repression of selected genes. SETD2 encodes a histone methyltransferase, which may play a role in suppressing tumor development. In this study, RNAs of 30 paired tumor and normal samples that were grouped according to the types of kidney cancer and clinical characteristics of patients, including gender and average age were examined by RT-PCR, SSCP and sequencing techniques. VHL, PBRM1 and SETD2 expressions were relatively down-regulated. However, statistically no significance was found (Wilcoxon signed rank test, p > 0.05). Interestingly, no mutation was observed on the contrary of previous studies. Understanding the molecular mechanisms involved in the pathogenesis of RCC has aided the development of molecular-targeted drugs for kidney cancer. Further analysis is required to identify the responsible genes rather than VHL, PBRM1 and SETD2 in kidney cancer.

Keywords: kidney cancer, molecular biomarker, expression analysis, mutation screening

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Authors: Ahmed E. Hodaib, Mohamed A. Hashem

Abstract:

In engineering applications, a design has to be as fully perfect as possible in some defined case. The designer has to overcome many challenges in order to reach the optimal solution to a specific problem. This process is called optimization. Generally, there is always a function called “objective function” that is required to be maximized or minimized by choosing input parameters called “degrees of freedom” within an allowed domain called “search space” and computing the values of the objective function for these input values. It becomes more complex when we have more than one objective for our design. As an example for Multi-Objective Optimization Problem (MOP): A structural design that aims to minimize weight and maximize strength. In such case, the Pareto Optimal Frontier (POF) is used, which is a curve plotting two objective functions for the best cases. At this point, a designer should make a decision to choose the point on the curve. Engineers use algorithms or iterative methods for optimization. In this paper, we will discuss the Evolutionary Algorithms (EA) which are widely used with Multi-objective Optimization Problems due to their robustness, simplicity, suitability to be coupled and to be parallelized. Evolutionary algorithms are developed to guarantee the convergence to an optimal solution. An EA uses mechanisms inspired by Darwinian evolution principles. Technically, they belong to the family of trial and error problem solvers and can be considered global optimization methods with a stochastic optimization character. The optimization is initialized by picking random solutions from the search space and then the solution progresses towards the optimal point by using operators such as Selection, Combination, Cross-over and/or Mutation. These operators are applied to the old solutions “parents” so that new sets of design variables called “children” appear. The process is repeated until the optimal solution to the problem is reached. Reliable and robust computational fluid dynamics solvers are nowadays commonly utilized in the design and analyses of various engineering systems, such as aircraft, turbo-machinery, and auto-motives. Coupling of Computational Fluid Dynamics “CFD” and Multi-Objective Evolutionary Algorithms “MOEA” has become substantial in aerospace engineering applications, such as in aerodynamic shape optimization and advanced turbo-machinery design.

Keywords: mathematical optimization, multi-objective evolutionary algorithms "MOEA", computational fluid dynamics "CFD", aerodynamic shape optimization

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Authors: Mengistu G. Woldu, Hani Y. Zaki, Areeg Faggad, Badreldin E. Abdalla

Abstract:

Background: Type 2 diabetes mellitus (T2DM) is a complex, degenerative, and multi-factorial disease, which is culpable for huge mortality and morbidity worldwide. Even though relatively significant numbers of studies are conducted on the genetics domain of this disease in the developed world, there is huge information gap in the sub-Saharan Africa region in general and in Eritrea in particular. Objective: The principal aim of this study was to investigate the association of common variants of the Insulin Receptor Substrate 1 (IRS1) and Transcription Factor 7-Like 2 (TCF7L2) genes with T2DM in the Eritrean population. Method: In this cross-sectional case control study 200 T2DM patients and 112 non-diabetes subjects were participated and genotyping of the IRS1 (rs13431179, rs16822615, 16822644rs, rs1801123) and TCF7L2 (rs7092484) tag SNPs were carries out using PCR-RFLP method of analysis. Haplotype analyses were carried out using Plink version 1.07, and Haploview 4.2 software. Linkage disequilibrium (LD), and Hardy-Weinberg equilibrium (HWE) analyses were performed using the Plink software. All descriptive statistical data analyses were carried out using SPSS (Version-20) software. Throughout the analysis p-value ≤0.05 was considered statistically significant. Result: Significant association was found between rs13431179 SNP of the IRS1 gene and T2DM under the recessive model of inheritance (OR=9.00, 95%CI=1.17-69.07, p=0.035), and marginally significant association found in the genotypic model (OR=7.50, 95%CI=0.94-60.06, p=0.058). The rs7092484 SNP of the TCF7L2 gene also showed markedly significant association with T2DM in the recessive (OR=3.61, 95%CI=1.70-7.67, p=0.001); and allelic (OR=1.80, 95%CI=1.23-2.62, p=0.002) models. Moreover, eight haplotypes of the IRS1 gene found to have significant association withT2DM (p=0.013 to 0.049). Assessments made on the interactions of genotypes of the rs13431179 and rs7092484 SNPs with various parameters demonstrated that high density lipoprotein (HDL), low density lipoprotein (LDL), waist circumference (WC), and systolic blood pressure (SBP) are the best T2DM onset predicting models. Furthermore, genotypes of the rs7092484 SNP showed significant association with various atherogenic indexes (Atherogenic index of plasma, LDL/HDL, and CHLO/HDL); and Eritreans carrying the GG or GA genotypes were predicted to be more susceptible to cardiovascular diseases onset. Conclusions: Results of this study suggest that IRS1 (rs13431179) and TCF7L2 (rs7092484) gene polymorphisms are associated with increased risk of T2DM in Eritreans.

Keywords: IRS1, SNP, TCF7L2, type 2 diabetes

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Authors: Filipe Cardoso de Oliveira, Lino Marcos da Silva, Ademar Nogueira do Nascimento, Cristiano Hora de Oliveira Fontes

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This article presents a mathematical formulation for the production Break-Even Point problem in a non-homogeneous system. The optimization problem aims to obtain the composition of the best product mix in a non-homogeneous industrial plant, with the lowest cost until the breakeven point is reached. The problem constraints represent real limitations of a generic non-homogeneous industrial plant for n different products. The proposed model is able to solve the equilibrium point problem simultaneously for all products, unlike the existing approaches that propose a resolution in a sequential way, considering each product in isolation and providing a sub-optimal solution to the problem. The results indicate that the product mix found through the proposed model has economical advantages over the traditional approach used.

Keywords: branch and bound, break-even point, non-homogeneous production system, integer linear programming, management accounting

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Authors: Mohit Kumar, Beklashwar Salona, Shiv Murti, Mukesh Singh

Abstract:

We report here a case of five-months old male baby, born as second child of non-consanguineous parents with no considerable history of genetic abnormality which was referred to our cytogenetic laboratory for chromosomal analysis. Physical dysmorphic facial features including mongoloid face, cleft palate, simian crease, and developmental delay were observed. We present this case with unique balanced autosomal translocation of t(3;10)(p21;p13). The risk of phenotypic abnormalities based on de novo balanced translocation was estimated to be 7%. The association of balanced chromosomal rearrangement with Down syndrome features such as multiple congenital anomalies, facial dysmorphism and congenital heart anomalies are very rare in a 5-months old male child. Trisomy-21 is not uncommon in chromosomal abnormality with the birth defect and balanced translocations are frequently observed in patients with secondary infertility or recurrent spontaneous abortion (RSA). Two ml heparinized peripheral blood cells cultured in RPMI-1640 for 72 hours supplemented with 20% fetal bovine serum, phytohemagglutinin (PHA), and antibiotics were used for chromosomal analysis. A total 30 metaphases images were captured using Olympus-BX51 microscope and analyzed using Bio-view karyotyping software through GTG-banding (G bands by trypsin and Giemsa) according to International System for Human Cytogenetic Nomenclature 2016. The results showed balanced translocation between short arm of chromosome # 3 and short arm of chromosome # 10. The karyotype of the child was found to be 46,XY,t(3;10)(p21; p13). Chromosomal abnormalities are one of the major causes of birth defect in new born babies. Also, balanced translocations are frequently observed in patients with secondary infertility or recurrent spontaneous abortion. The index case presented with dysmorphic facial features and had a balanced translocation 46,XY,t(3;10)(p21;p13). This translocation with break points at (p21; p13) has not been reported in the literature in a child with facial dysmorphism. To the best of our knowledge, this is the first report of novel balanced translocation t(3;10) with break points in a child with dysmorphic features. We found balanced chromosomal translocation instead of any trisomy or unbalanced aberrations along with some phenotypic abnormalities. Therefore, we suggest that such novel balanced translocation with abnormal phenotype should be reported in order to enable the pathologist, pediatrician, and gynecologist to have a better insight into the intricacies of chromosomal abnormalities and their associated phenotypic features. We hypothesized that dysmorphic features as seen in this case may be the result of change in the pattern of genes located at the breakpoint area in balanced translocations or may be due to deletion or mutation of genes located on the p-arm of chromosome # 3 and p-arm of chromosome # 10.

Keywords: balanced translocation, karyotyping, phenotypic abnormalities, facial dimorphisms

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Authors: Mohamed Houas, Maamar Benbachir

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In this paper, under weak assumptions, we study the existence and uniqueness of solutions for a nonlinear fractional boundary value problem. New existence and uniqueness results are established using Banach contraction principle. Other existence results are obtained using scheafer and krasnoselskii's fixed point theorem. At the end, some illustrative examples are presented.

Keywords: caputo derivative, boundary value problem, fixed point theorem, local conditions

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Authors: Noora Al Muftah, Reda Rawi, Richard Thompson, Halima Bensmail

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Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers of response to targeted agents. There is an urgent need to identify biomarkers that predict which patients with are most likely to respond to treatment. Systematic efforts to correlate tumor mutational data with biologic dependencies may facilitate the translation of somatic mutation catalogs into meaningful biomarkers for patient stratification. To identify genomic features associated with drug sensitivity and uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we have screened and integrated a panel of several hundred cancer cell lines from different databases, mutation, DNA copy number, and gene expression data for hundreds of cell lines with their responses to targeted and cytotoxic therapies with drugs under clinical and preclinical investigation. We found mutated cancer genes were associated with cellular response to most currently available Glioma cancer drugs and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Keywords: cancer, gene network, Lasso, penalized regression, P-values, unbiased estimator

Procedia PDF Downloads 380