Search results for: real-valued mutation (RVM)

Authors: Hyeon Su Kim, Sungjin Park, Hae Ryung Chang, Hae Rim Jung, Young Zoo Ahn, Yon Hui Kim, Seungyoon Nam

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Ependymoma, one of the most common parenchymal spinal cord tumor, represents 3-6% of all CNS tumor. Especially intracranial ependymomas, which are more frequent in childhood, have a more poor prognosis and more malignant than spinal ependymomas. Although there are growing needs to understand pathogenesis, detailed molecular understanding of pathogenesis remains to be explored. A cancer cell is composed of complex signaling pathway networks, and identifying interaction between genes and/or proteins are crucial for understanding these pathways. Therefore, we explored each ependymoma in terms of differential expressed genes and signaling networks. We used Microsoft Excel™ to manipulate microarray data gathered from NCBI’s GEO Database. To analyze and visualize signaling network, we used web-based PATHOME algorithm and Cytoscape. We show HOX family and NEFL are down-regulated but SCL family is up-regulated in cerebrum and posterior fossa cancers over a spinal cancer, and JAK/STAT signaling pathway and Chemokine signaling pathway are significantly different in the both intracranial ependymoma comparing to spinal ependymoma. We are considering there may be an age-dependent mechanism under different histological pathogenesis. We annotated mutation data of each gene subsequently in order to find potential target genes.

Keywords: systems biology, ependymoma, deg, network analysis

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Authors: Xueying Zhao, Ke Ma, Hui Li, Yu Cao, Fan Yang, Qingwen Xu, Wenbin Liu

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Massively parallel sequencing (MPS) technologies allow high-throughput sequencing analyses with a relatively affordable price and have gradually been applied to forensic casework. MPS technology identifies short tandem repeat (STR) loci based on sequence so that repeat motif variation within STRs can be detected, which may help one to infer the origin of the mutation in some cases. Here, we report on one case with one three-step mismatch (D18S51) in family trios based on both capillary electrophoresis (CE) and MPS typing. The alleles of the alleged father (AF) are [AGAA]₁₇AGAG[AGAA]₃ and [AGAA]₁₅. The mother’s alleles are [AGAA]₁₉ and [AGAA]₉AGGA[AGAA]₃. The questioned child’s (QC) alleles are [AGAA]₁₉ and [AGAA]₁₂. Given that the sequence variants in repeat regions of AF and mother are not observed in QC’s alleles, the QC’s allele [AGAA]₁₂ was likely inherited from the AF’s allele [AGAA]₁₅ by loss of three repeat [AGAA]. Besides, two new alleles of D18S51 in this study, [AGAA]₁₇AGAG[AGAA]₃ and [AGAA]₉AGGA[AGAA]₃, have not been reported before. All the results in this study were verified using Sanger-type sequencing. In summary, the MPS typing method can offer valuable information for forensic genetics research and play a promising role in paternity testing.

Keywords: family trios analysis, forensic casework, ion torrent personal genome machine (PGM), massively parallel sequencing (MPS)

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Authors: K. Ali, M. F. Qamar, M. A. Zaman, M. Younus, I. Khan, S. Ehtisham-ul-Haque, R. Tamkeen, M. I. Rashid, Q. Ali

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This study centers on molecular identification of Haemonchus contortus and isolation of Benz-imidazoles (BZ) resistant strains. Different abattoirs’ of two geographic regions of Punjab (Pakistan) were frequently visited for the collection of worms. Out of 1500 (n=1500) samples that were morphologically confirmed as H. contortus, 30 worms were subjected to molecular procedures for isolation of resistant strains. Resistant worms (n=8) were further subjected to DNA gene sequencing. Bio edit sequence alignment editor software was used to detect the possible mutation, deletion, replacement of nucleotides. Genetic diversity was noticed and genetic variation existing in β-tubulin isotype 1 of the H. contortus population of small ruminants of different regions considered in this study. H. contortus showed three different type of genetic sequences. 75%, 37.5%, 25% and 12.5% of the studied samples showed 100% query cover and identity with isolates and clones of China, UK, Australia and other countries, respectively. Interestingly the neighbor countries such as India and Iran haven’t many similarities with the Pakistani isolates. Thus, it suggests that population density of same genetic makeup H. contortus is scattered worldwide rather than clustering in a single region.

Keywords: Haemonchus contortus, Benzimidazole resistant, β-tubulin-1 gene, abattoirs

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Authors: Guangyuan Zhao, Nan Huang, Xuesong Han, Xu Huang

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In order to solve the problem of sample dilution in the traditional particle filter algorithm and achieve accurate state estimation in a nonlinear system, a particle filter method based on an improved artificial bee colony (ABC) algorithm was proposed. The algorithm simulated the process of bee foraging and optimization and made the high likelihood region of the backward probability of particles moving to improve the rationality of particle distribution. The opposition-based learning (OBL) strategy is introduced to optimize the initial population of the artificial bee colony algorithm. The convergence factor is introduced into the neighborhood search strategy to limit the search range and improve the convergence speed. Finally, the crossover and mutation operations of the genetic algorithm are introduced into the search mechanism of the following bee, which makes the algorithm jump out of the local extreme value quickly and continue to search the global extreme value to improve its optimization ability. The simulation results show that the improved method can improve the estimation accuracy of particle filters, ensure the diversity of particles, and improve the rationality of particle distribution.

Keywords: particle filter, impoverishment, state estimation, artificial bee colony algorithm

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Authors: Maryam Vaezjalali, Koroush Rahimian, Maryam Asli, Tahmineh Kandelouei, Foad Davoodbeglou, Amir H. Kashi

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Objectives: The present study was conducted to assess the HBV molecular profiles including genotypes, subgenotypes, subtypes & mutations in hepatitis B genes. Materials/Patients and Methods: This study was conducted on 229 intravenous drug users who referred to three Drop- in-Centers and a hospital in Tehran. HBV DNA was extracted from HBsAg positive serum samples and amplified by Nested PCR. HBV genotype, subgenotypes, subtype and genes mutation were determined by direct sequencing. Phylogenetic tree was constructed using neighbor- joining (NJ) method. Statistical analyses were carried out by SPSS 20. Results: HBV DNA was found in 3 HBsAg positive cases. Phylogenetic tree of derived HBV DNAs showed the existence of genotype D (subgenotype D1, subtype ayw2). Also immune escape mutations were determined in S gene. Conclusion: There were a few variations and genotypes and subtypes among infected intravenous drug users. This study showed the predominance of genotype D among intravenous drug users. Our study concurs with other reports from Iran, that all showing currently only genotype D is the only detectable genotype in Iran.

Keywords: drug users, genotype, HBV, phylogenetic tree

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Authors: Tofigh Hamidavi, Sepehr Abrishami, Pasquale Ponterosso, David Begg

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Structural design and analysis is an important and time-consuming process, particularly at the conceptual design stage. Decisions made at this stage can have an enormous effect on the entire project, as it becomes ever costlier and more difficult to alter the choices made early on in the construction process. Hence, optimisation of the early stages of structural design can provide important efficiencies in terms of cost and time. This paper suggests a structural design optimisation (SDO) framework in which Genetic Algorithms (GAs) may be used to semi-automate the production and optimisation of early structural design alternatives. This framework has the potential to leverage conceptual structural design innovation in Architecture, Engineering and Construction (AEC) projects. Moreover, this framework improves the collaboration between the architectural stage and the structural stage. It will be shown that this SDO framework can make this achievable by generating the structural model based on the extracted data from the architectural model. At the moment, the proposed SDO framework is in the process of validation, involving the distribution of an online questionnaire among structural engineers in the UK.

Keywords: building information, modelling, BIM, genetic algorithm, GA, architecture-engineering-construction, AEC, optimisation, structure, design, population, generation, selection, mutation, crossover, offspring

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Authors: L. K. Davis

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The effects of the evolution force are observable in nature at all structural levels ranging from small molecular systems to conversely enormous biospheric systems. However, the evolution force and work associated with formation of biological structures has yet to be described mathematically or theoretically. In addressing the conundrum, we consider evolution from a unique perspective and in doing so we introduce the “Fundamental Theory of the Evolution Force: FTEF”. We utilized synthetic evolution artificial intelligence (SYN-AI) to identify genomic building blocks and to engineer 14-3-3 ζ docking proteins by transforming gene sequences into time-based DNA codes derived from protein hierarchical structural levels. The aforementioned served as templates for random DNA hybridizations and genetic assembly. The application of hierarchical DNA codes allowed us to fast forward evolution, while dampening the effect of point mutations. Natural selection was performed at each hierarchical structural level and mutations screened using Blosum 80 mutation frequency-based algorithms. Notably, SYN-AI engineered a set of three architecturally conserved docking proteins that retained motion and vibrational dynamics of native Bos taurus 14-3-3 ζ.

Keywords: 14-3-3 docking genes, synthetic protein design, time-based DNA codes, writing DNA code from scratch

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Authors: Mohsen Rezaei Aghdam

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Recombinant DNA technology has meaningfully augmented the conventional crop improvement and has a great possibility to contribution plant breeders to encounter the augmented food request foretold for the 21st century. Predictable changes in weather and its erraticism, chiefly extreme fevers and vicissitudes in rainfall are expected to brand crop upgrading even more vital for food manufacture. Tissue attitude has been downtrodden to create genetic erraticism from which harvest plants can be better, to improve the state of health of the recognized physical and to upsurge the number of wanted germplasms obtainable to the plant breeder. This appraisal delivers an impression of the chances obtainable by the integration of vegetable biotechnology into plant development efforts and increases some of the social subjects that need to be considered in their application. Public-private companies offer chances to catalyze new approaches and investment while accelerating integrated research and development and commercial supply chain-based solutions. Novel varieties derivative by encouraged mutatgenesis are used commonly: rice in Thailand. These paper combinations obtainable data about the influence of change breeding-derived crop changes around the world, traveler magnetism the possibility of mutation upbringing as a flexible and feasible approach appropriate to any crop if that suitable objectives and selection approaches are used.

Keywords: crop, improve, genetic, agricultural

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Authors: Asiri Wijesinghe, N. D. Kodikara, Damitha Sandaruwan

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The Diabetic Retinopathy (DR) is a rapidly growing interrogation around the world which can be annotated by abortive metabolism of glucose that causes long-term infection in human retina. This is one of the preliminary reason of visual impairment and blindness of adults. Information on retinal pathological mutation can be recognized using ocular fundus images. In this research, we are mainly focused on resurrecting an automated diagnosis system to detect DR anomalies such as severity level classification of DR patient (Non-proliferative Diabetic Retinopathy approach) and vessel tortuosity measurement of untwisted vessels to assessment of vessel anomalies (Proliferative Diabetic Retinopathy approach). Severity classification method is obtained better results according to the precision, recall, F-measure and accuracy (exceeds 94%) in all formats of cross validation. In ROC (Receiver Operating Characteristic) curves also visualized the higher AUC (Area Under Curve) percentage (exceeds 95%). User level evaluation of severity capturing is obtained higher accuracy (85%) result and fairly better values for each evaluation measurements. Untwisted vessel detection for tortuosity measurement also carried out the good results with respect to the sensitivity (85%), specificity (89%) and accuracy (87%).

Keywords: fundus image, exudates, microaneurisms, hemorrhages, tortuosity, diabetic retinopathy, optic disc, fovea

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Authors: Caroline Kim

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The designation autism spectrum disorder (ASD) groups complex disorders in the development of the brain. Autism is defined essentially as a condition in which an individual lacks a theory of mind. The theory of mind, in this sense, explains the ability of an individual to attribute feelings, emotions, or thoughts to another person. An autistic patient is characteristically unable to determine what an interlocutor is feeling, or to understand the beliefs of others. However, it is possible that autism cannot plausibly characterized as the lack of theory of mind in an individual. Genes, the bran, and its interplay with environmental factors may also cause autism. A mutation in a gene may be hereditary, or instigated by diseases such as mumps. Though an autistic patient may experience abnormalities in the cerebellum and the cortical regions, these are in fact only possible theories as to a biochemical explanation behind the disability. The prevailing theory identifying autism with lacking the theory of mind is supported by behavioral observation, but this form of observation is itself determined by socially constructed standards, limiting the possibility for empirical verification. The theory of mind infers that the beliefs and emotions of people are causally based on their behavior. This paper demonstrates the fallacy of this inference, critiquing its basis in socially constructed values, and arguing instead for a biochemical approach free from the conceptual apparatus of language and social expectation.

Keywords: autism spectrum disorder, sociology of psychology, social construction, the theory of mind

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Authors: Melliti Rihab, Zaeid Sonia, Khechine Wiem, Daldoul Amira

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Introduction: Lung cancer is the leading cause of cancer death. Its incidence is increasing, and its prognosis remains pejorative. We present the clinical, pathological, and therapeutic characteristics of bronchopulmonary cancer (BPC) in Tunisia. Methods: Retrospective study including patients followed in the oncology department of the University Hospital of Monastir between April 2014 and December 2021 suffering from lung cancer. Results: These are 117 patients, including 86.3% men and 13.7% women (sex ratio 6.3). The average age was 64 years ± 9 (37-83), with 95.7% being over 50 years old. Patients were smokers in 82% of cases. The clinical signs were dominated by chest pain (27.5%) and dyspnea in 21.1% of cases. In 6 patients, an episode of COVID-19 infection revealed the diagnosis. Half of the patients had a PS between 0 and 1. Small cell lung cancer was present in 18 patients (15.4%). The majority of non small cell lung cancer was of the adenocarcinoma type (68.7%). The diagnosis was late (stage IV) in 62.4% of cases. BPC was metastatic to bone (52%), contralateral lung (25.9%), and brain (27.3%). Patients were oligometastatic in 26% of cases. Surgery and radiotherapy were performed respectively in 14.5% and 23.1% of cases. Three-quarters of the patients had had nutrition (75.2%). The ROS1 mutation was present in 1 patient. PDL-1 expression was >40% in 2 patients. Survival was mean eight months ± 7.4. Conclusion: Lung cancer is diagnosed at a late stage in Tunisia. The lack of molecular study for non-small cell PBC and the lack of marketing authorization for tyrosine kinase inhibitors in Tunisia make the management incomplete.

Keywords: SCLC, NCSLC, ROS1, PDL1

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Authors: Ashish Kumar Agrahari, Amit Kumar

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Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal blood disorder that manifests with hemolytic anemia, thrombosis, and peripheral blood cytopenias. The disease is caused by the deficiency of two glycosylphosphatidylinositols (GPI)-anchored proteins (CD55 and CD59) in the hemopoietic stem cells. The deficiency of GPI-anchored proteins has been associated with the somatic mutations in phosphatidylinositol glycan class A (PIGA). However, the mutations that do not cause PNH is associated with the multiple congenital anomalies-hypotonia-seizures syndrome 2 (MCAHS2). To best of our knowledge, no computational study has been performed to explore the atomistic level impact of PIGA mutations on the structure and dynamics of the protein. In the current work, we are mainly interested to get insights into the molecular mechanism of PIGA mutations. In the initial step, we screened the most pathogenic mutations from the pool of publicly available mutations. Further, to get a better understanding, pathogenic mutations were mapped to the modeled structure and subjected to 50ns molecular dynamics simulation. Our computational study suggests that four mutations are highly vulnerable to altering the structural conformation and stability of the PIGA protein, which illustrates its association with PNH and MCAHS2 phenotype.

Keywords: homology modeling, molecular dynamics simulation, missense mutations PNH, MCAHS2, PIGA

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Authors: Tan Zhang, Zhongjian Wang, Jack Xin, Zhiwen Zhang

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We aim to efficiently compute the spreading speeds of reaction-diffusion-advection (RDA) fronts in divergence-free random flows under the Kolmogorov-Petrovsky-Piskunov (KPP) nonlinearity. We study a stochastic interacting particle method (IPM) for the reduced principal eigenvalue (Lyapunov exponent) problem of an associated linear advection-diffusion operator with spatially random coefficients. The Fourier representation of the random advection field and the Feynman-Kac (FK) formula of the principal eigenvalue (Lyapunov exponent) form the foundation of our method implemented as a genetic evolution algorithm. The particles undergo advection-diffusion and mutation/selection through a fitness function originated in the FK semigroup. We analyze the convergence of the algorithm based on operator splitting and present numerical results on representative flows such as 2D cellular flow and 3D Arnold-Beltrami-Childress (ABC) flow under random perturbations. The 2D examples serve as a consistency check with semi-Lagrangian computation. The 3D results demonstrate that IPM, being mesh-free and self-adaptive, is simple to implement and efficient for computing front spreading speeds in the advection-dominated regime for high-dimensional random flows on unbounded domains where no truncation is needed.

Keywords: KPP front speeds, random flows, Feynman-Kac semigroups, interacting particle method, convergence analysis

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Authors: Nicolae Bold, Daniel Nijloveanu

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The idea of cropping-system is a method used by farmers. It is an environmentally-friendly method, protecting the natural resources (soil, water, air, nutritive substances) and increase the production at the same time, taking into account some crop particularities. The combination of this powerful method with the concepts of genetic algorithms results into a possibility of generating sequences of crops in order to form a rotation. The usage of this type of algorithms has been efficient in solving problems related to optimization and their polynomial complexity allows them to be used at solving more difficult and various problems. In our case, the optimization consists in finding the most profitable rotation of cultures. One of the expected results is to optimize the usage of the resources, in order to minimize the costs and maximize the profit. In order to achieve these goals, a genetic algorithm was designed. This algorithm ensures the finding of several optimized solutions of cropping-systems possibilities which have the highest profit and, thus, which minimize the costs. The algorithm uses genetic-based methods (mutation, crossover) and structures (genes, chromosomes). A cropping-system possibility will be considered a chromosome and a crop within the rotation is a gene within a chromosome. Results about the efficiency of this method will be presented in a special section. The implementation of this method would bring benefits into the activity of the farmers by giving them hints and helping them to use the resources efficiently.

Keywords: chromosomes, cropping, genetic algorithm, genes

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Authors: Alvaro Javier Ortega

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A large number of companies face the challenge of matching highly-skilled professionals to high-end positions by human resource deployment professionals. However, when the professional list and tasks to be matched are larger than a few dozens, this process result is far from optimal and takes a long time to be made. Therefore, an automated assignment algorithm for this workforce management problem is needed. The majority of companies are divided into several sectors or departments, where trained employees with different experience levels deal with a large number of tasks daily. Also, the execution order of all tasks is of mater consequence, due to some of these tasks just can be run it if the result of another task is provided. Thus, a wrong execution order leads to large waiting times between consecutive tasks. The desired goal is, therefore, creating accurate matches and a near-optimal execution order that maximizes the number of tasks performed and minimizes the idle time of the expensive skilled employees. The problem described before can be model as a mixed-integer non-linear programming (MINLP) as it will be shown in detail through this paper. A large number of MINLP algorithms have been proposed in the literature. Here, genetic algorithm solutions are considered and a comparison between two different mutation approaches is presented. The simulated results considering different complexity levels of assignment decisions show the appropriateness of the proposed model.

Keywords: employees, genetic algorithm, industry management, workforce

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Authors: S. Salah, S. A. El-Masry, H. F. Sheba, R. A. El-Banna, W. Saad

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Background: Familial Mediterranean fever (FMF) has episodic or subclinical inflammation that may lead to a decrease in bone mineral density (BMD). Objective: To assess BMD in Egyptian children with FMF on genetic basis. Subjects and Methods: A cross sectional study included 45 FMF patients and 25 control children of both sexes, with age range between 3-16 years old. The patients were reclassified into 2 groups: Group I (A) 23 cases used colchicines for 1 month or less, and Group I (B) 22 cases used colchicines for more than 6 months. For both patients and control, MEFV mutations were defined using molecular genetics technique and BMD was measured by DXA at 2 sites: proximal femur and the lumber spines. Results: four frequent gene mutations were found in the patient group: E148Q (35.6%), V726A (33.3%), M680I (28.9.0%) and M694V (2.2%). There were also 4 heterozygous gene mutations in 40% of control children. Patients received colchicines treatment for less than 1 month had highly significant lower values of BMD at femur and lumber spines than control children (p<0.05). Patients received colchicines treatment for more than 6 months had improved values of BMD at femur compared to control, but there were still significant differences between them at lumbar spine (p>0.05). There are insignificant effect of type of gene mutation on BMD and the risk of osteopenia among the patients. Conclusion: FMF had significant effect on BMD. However, regular use of colchicines treatment improves this effect mainly at femur.

Keywords: familial mediterranean fever, bone mineral density, genes, children

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Authors: Rueyhung Weng, Chia-En Huang, Jung-Chi-Liao

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The transition zone (TZ) serves as a diffusion barrier to regulate the ins and outs of the proteins recruited to the primary cilia. TCTN2 is one of the TZ proteins and its mutation causes Joubert syndrome, a serious multi-organ disease. Despite its important medical relevance, the functions of TCTN2 remain elusive. Here we created a TCTN2 gene deleted retinal pigment epithelial cells (RPE1) using CRISPR/Cas9-based genome editing technique and used this knockout line to reveal roles of TCTN2. TCTN2 knockout RPE1 cells displayed a significantly reduced ciliogenesis or a shortened primary cilium length in the cilium-remaining population. Intraflagellar transport protein IFT88 aberrantly accumulated at the tip of TCTN2 deficient cells. Guanine nucleotide exchange factor Arl13B was mostly absent from the ciliary compartment, with a small population localizing at the ciliary tip. The deficient TZ was corroborated with the mislocalization of two other TZ proteins TMEM67 and MKS1. In addition, TCTN2 deficiency induced TZ impairment led to the suppression of Sonic hedgehog signaling in response to Smoothened (Smo) agonist. Together, depletion of TCTN2 destabilizes other TZ proteins and considerably alters the localization of key transport and signaling-associated proteins, including IFT88, Arl13B, and Smo.

Keywords: CRISPR/Cas9, primary cilia, Sonic hedgehog signaling, transition zone

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Authors: Shryas Bhurat, Aryan Vashistha, Sampreet Dinakar Nayak, Ayush Gupta

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As the technology is advancing more towards high computational resources, there is a paradigm shift in the usage of these resources to optimize the design process. This paper discusses the usage of ‘Generative Design using Artificial Intelligence’ to build better models that adapt the operations like selection, mutation, and crossover to generate results. The human mind thinks of the simplest approach while designing an object, but the intelligence learns from the past & designs the complex optimized CAD Models. Generative Design takes the boundary conditions and comes up with multiple solutions with iterations to come up with a sturdy design with the most optimal parameter that is given, saving huge amounts of time & resources. The new production techniques that are at our disposal allow us to use additive manufacturing, 3D printing, and other innovative manufacturing techniques to save resources and design artistically engineered CAD Models. Also, this paper discusses the Genetic Algorithm, the Non-Domination technique to choose the right results using biomimicry that has evolved for current habitation for millions of years. The computer uses parametric models to generate newer models using an iterative approach & uses cloud computing to store these iterative designs. The later part of the paper compares the topology optimization technology with Generative Design that is previously being used to generate CAD Models. Finally, this paper shows the performance of algorithms and how these algorithms help in designing resource-efficient models.

Keywords: genetic algorithm, bio mimicry, generative modeling, non-dominant techniques

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Authors: M. Moaeen-ud-Din, G. Bilal, M. Yaqoob

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Identification of genes of importance regarding production traits in buffalo is impaired by a paucity of genomic resources. Choice to fill this gap is to exploit data available for cow. The cross-species application of comparative genomics tools is potential gear to investigate the buffalo genome. However, this is dependent on nucleotide sequences similarity. In this study gene diversity between buffalo and cattle was determined by using 86 gene orthologues. There was about 3% difference in all genes in term of nucleotide diversity; and 0.267±0.134 in amino acids indicating the possibility for successfully using cross-species strategies for genomic studies. There were significantly higher non synonymous substitutions both in cattle and buffalo however, there was similar difference in term of dN – dS (4.414 vs 4.745) in buffalo and cattle respectively. Higher rate of non-synonymous substitutions at similar level in buffalo and cattle indicated a similar positive selection pressure. Results for relative rate test were assessed with the chi-squared test. There was no significance difference on unique mutations between cattle and buffalo lineages at synonymous sites. However, there was a significance difference on unique mutations for non synonymous sites indicating ongoing mutagenic process that generates substitutional mutation at approximately the same rate at silent sites. Moreover, despite of common ancestry, our results indicate a different divergent time among genes of cattle and buffalo. This is the first demonstration that variable rates of molecular evolution may be present within the family Bovidae.

Keywords: buffalo, cattle, gene diversity, molecular evolution

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Authors: Rim Frikha, Nouha Bouayed, Afifa Sellami, Nozha Chakroun, Salima Daoud, Leila Keskes, Tarek Rebai

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Introduction: Recurrent pregnancy loss (RPL) defined as two or more pregnancy losses, is a serious clinical problem. Methylene-tetrahydro-folate-reductase (MTHFR) polymorphisms, commonly the variant C677T is recognized as an inherited thrombophilia which might affect embryonic development and pregnancy success and cause pregnancy complications as RPL. Material and Methods DNA was extracted from peripheral blood samples and PCR-RFLP was performed for the molecular diagnosis of the C677T MTHFR polymorphism among 70 patients (35 couples) with more than 2 fetal losses. Aims and Objective: The aim of this study is to determine the frequency of MTHFR C677T among Tunisian couples with RPL and to critically analyze the available literature on the importance of MTHFR polymorphism testing in the management of RPL. Result and comments: No C677T mutation was detected in the carriers of RPL. This result would be related to sample size and to different criteria (number of abortion), - The association between MTHFR polymorphisms and pregnancy complications has been reported but with controversial results. - A lack of evidence for MTHFR polymorphism testing previously recommended by ACMG (American College of Medical medicine). Our study highlights the importance of screening of MTHFR polymorphism since the real impact of such thrombotic molecular defect on the pregnancy outcome is evident. - Folic supplementation of these patients during pregnancy can prevent such complications and lead to a successful pregnancy outcome.

Keywords: methylenetetrahydrofolate reductase, C677T, recurrent pregnancy loss, genetic testing

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Authors: W. Abu Rayyan, A. Singh, A. M. Al-Jaafreh, W. Abu Dayyih, M. Bustami, S. Salem, N. Seder, K. Schröppel

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Hyphal growth and the transcriptional regulation to the host environment are key issues during the pathogenesis of C. albicans. Tec1p is the C. albicans homolog of a TEA transcription factor family, which share a conserved DNA-binding TEA domain in their N-terminal. In order to define a structure-function relationship of the C. albicans Tec1p protein, we constructed several mutations on the N terminal, C terminal or in the TEA binding domain itself by homologous recombination technology. The modifications in the open reading frame of TEC1 were tested for reconstitution of the morphogenetic development of the tec1/tec1 mutant strain CaAS12. Mutation in the TEA consensus sequence did not confer transition to hyphae whereas the reconstitution of the full-length Tec1p has reconstituted hyphal development. A deletion in one of glutamine-rich regions either in the Tec1p N-terminal or the C-terminal in regions of 53-212 or 637–744 aa, respectively, did not restore morphological development in mutant CaAS12 strain. Whereas, the reconstitution with Tec1p mutants other than the glutamate-rich region has restored the morphogenetic switch. Additionally, the deletion of the glutamine-rich region has attenuated the invasive growth and the heat shock resistance of C. albicans. In conclusion, we show that a glutamine-rich region of Tec1p is essential for the hyphal development and mediating adaptation to the host environment of C. albicans.

Keywords: Candida albicans, morphogenetic development, TEA domain, hyphal formation, TEC1

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Authors: Susanta Kumar Gachhayat, S. K. Dash

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Multi objective non-convex economic dispatch problems of a thermal power plant are of grave concern for deciding the cost of generation and reduction of emission level for diminishing the global warming level for improving green-house effect. This paper deals with ramp rate constraints for achieving better inequality constraints so as to incorporate valve point loading for cost of generation in thermal power plant through ramp rate biogeography based optimization involving mutation and migration. Through 50 out of 100 trials, the cost function and emission objective function were found to have outperformed other classical methods such as lambda iteration method, quadratic programming method and many heuristic methods like particle swarm optimization method, weight improved particle swarm optimization method, constriction factor based particle swarm optimization method, moderate random particle swarm optimization method etc. Ramp rate biogeography based optimization applications prove quite advantageous in solving non convex multi objective economic dispatch problems subjected to nonlinear loads that pollute the source giving rise to third harmonic distortions and other such disturbances.

Keywords: economic load dispatch, ELD, biogeography-based optimization, BBO, ramp rate biogeography-based optimization, RRBBO, valve-point loading, VPL

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Authors: Selena Ferrian, Erin Mccaffrey, Toshie Saito, Aiqin Cao, Noah Greenwald, Mark Robert Nicolls, Trevor Bruce, Roham T. Zamanian, Patricia Del Rosario, Marlene Rabinovitch, Michael Angelo

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Recent experimental and clinical observations are advancing immunotherapies to clinical trials in pulmonary arterial hypertension (PAH). However, comprehensive mapping of the immune landscape in pulmonary arteries (PAs) is necessary to understand how immune cell subsets interact to induce pulmonary vascular pathology. We used multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to interrogate the immune landscape in PAs from idiopathic (IPAH) and hereditary (HPAH) PAH patients. Massive immune infiltration in I/HPAH was observed with intramural infiltration linked to PA occlusive changes. The spatial context of CD11c+DCs expressing SAMHD1, TIM-3 and IDO-1 within immune-enriched microenvironments and neutrophils were associated with greater immune activation in HPAH. Furthermore, CD11c-DC3s (mo-DC-like cells) within a smooth muscle cell (SMC) enriched microenvironment were linked to vessel score, proliferating SMCs, and inflamed endothelial cells. Experimental data in cultured cells reinforced a causal relationship between neutrophils and mo-DCs in mediating pulmonary arterial SMC proliferation. These findings merit consideration in developing effective immunotherapies for PAH.

Keywords: pulmonary arterial hypertension, vascular remodeling, indoleamine 2-3-dioxygenase 1 (IDO-1), neutrophils, monocyte-derived dendritic cells, BMPR2 mutation, interferon gamma (IFN-γ)

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Authors: Elena K. Schneider, Johnny X. Huang, Vincenzo Carbone, Mark Baker, Mohammad A. K. Azad, Matthew A. Cooper, Jian Li, Tony Velkov

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Ivacaftor is a novel CF trans-membrane conductance regulator (CFTR) potentiator that improves the pulmonary function for cystic fibrosis patients bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs that compete for the same plasma protein binding sites and impact the free drug concentration. This in turn could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes. This study compares the binding affinity of ivacaftor and co-administered CF drugs for human serum albumin (HSA) and α1-acid glycoprotein (AGP) using surface plasmon resonance and fluorimetric binding assays that measure the displacement of site selective probes. Due to their high plasma protein binding affinities, drug-drug interactions between ivacaftor are to be expected with ducosate, montelukast, ibuprofen, dicloxacillin, omeprazole and loratadine. The significance of these drug-drug interactions is interpreted in terms of the pharmacodynamic/pharmacokinetic parameters and molecular docking simulations. The translational outcomes of the data are presented as recommendations for a staggered treatment regimen for future clinical trials which aims to maximize the effective free drug concentration and clinical efficacy of ivacaftor.

Keywords: human α-1-acid glycoprotein, binding affinity, human serum albumin, ivacaftor, cystic fibrosis

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Authors: T. Toathom, M. Munlin, P. Sugunnasil

Abstract:

The traveling salesman problem (TSP) is one of the best-known problems in optimization problem. There are many research regarding the TSP. One of the most usage tool for this problem is the genetic algorithm (GA). The chromosome of the GA for TSP is normally encoded by the order of the visited city. However, the traditional chromosome encoding scheme has some limitations which are twofold: the large solution space and the inability to encapsulate some information. The number of solution for a certain problem is exponentially grow by the number of city. Moreover, the traditional chromosome encoding scheme fails to recognize the misplaced correct relation. It implies that the tradition method focuses only on exact solution. In this work, we relax some of the concept in the GA for TSP which is the exactness of the solution. The proposed work exploits the relation between cities in order to reduce the solution space in the chromosome encoding. In this paper, a second order GA is proposed to solve the TSP. The term second order refers to how the solution is encoded into chromosome. The chromosome is divided into 2 types: the high order chromosome and the low order chromosome. The high order chromosome is the chromosome that focus on the relation between cities such as the city A should be visited before city B. On the other hand, the low order chromosome is a type of chromosome that is derived from a high order chromosome. In other word, low order chromosome is encoded by the traditional chromosome encoding scheme. The genetic operation, mutation and crossover, will be performed on the high order chromosome. Then, the high order chromosome will be mapped to a group of low order chromosomes whose characteristics are satisfied with the high order chromosome. From the mapped set of chromosomes, the champion chromosome will be selected based on the fitness value which will be later used as a representative for the high order chromosome. The experiment is performed on the city data from TSPLIB.

Keywords: genetic algorithm, traveling salesman problem, initial population, chromosomes encoding

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Authors: Mahawish Masud, Muhammad Iqbal, M. U. Khan, Farooque Azam

Abstract:

Manual writing of test cases from functional requirements is a time-consuming task. Such test cases are not only difficult to write but are also challenging to maintain. Test cases can be drawn from the functional requirements that are expressed in natural language. However, manual test case generation is inefficient and subject to errors.  In this paper, we have presented a systematic procedure that could automatically derive test cases from user stories. The user stories are specified in a restricted natural language using a well-defined template.  We have also presented a detailed methodology for writing our test ready user stories. Our tool “Test-o-Matic” automatically generates the test cases by processing the restricted user stories. The generated test cases are executed by using open source Selenium IDE.  We evaluate our approach on a case study, which is an open source web based application. Effectiveness of our approach is evaluated by seeding faults in the open source case study using known mutation operators.  Results show that the test case generation from restricted user stories is a viable approach for automated testing of web applications.

Keywords: automated testing, natural language, restricted user story modeling, software engineering, software testing, test case specification, transformation and automation, user story, web application testing

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Authors: Shuo Mu, Guangzhi Jiang, Jinsa Chen

Abstract:

The analysis of Indel for RNA sequencing of clinical samples is easily affected by sequencing experiment errors and software selection. In order to improve the efficiency and accuracy of analysis, we developed an automatic reporting system for Indel recognition and annotation based on image snapshot of transcriptome reads alignment. This system includes sequence local-assembly and realignment, target point snapshot, and image-based recognition processes. We integrated high-confidence Indel dataset from several known databases as a training set to improve the accuracy of image processing and added a bioinformatical processing module to annotate and filter Indel artifacts. Subsequently, the system will automatically generate data, including data quality levels and images results report. Sanger sequencing verification of the reference Indel mutation of cell line NA12878 showed that the process can achieve 83% sensitivity and 96% specificity. Analysis of the collected clinical samples showed that the interpretation accuracy of the process was equivalent to that of manual inspection, and the processing efficiency showed a significant improvement. This work shows the feasibility of accurate Indel analysis of clinical next-generation sequencing (NGS) transcriptome. This result may be useful for RNA study for clinical samples with microsatellite instability in immunotherapy in the future.

Keywords: automatic reporting, indel, next-generation sequencing, NGS, transcriptome

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Authors: Zerrin Orbak, Busra Demir

Abstract:

Osteopetrosis is a rare genetic disease characterized by impaired bone resorption and increased bone sclerosis. Clinical presentation is very different in osteopetrosis. It can be asymptomatic or can be seen with typical symptoms. Here, a case of osteopetrosis was presented when evaluated for nystagmus. She was 10 months old. Parents were second-degree relatives. On physical examination, pigeon chest deformity and horizontal nystagmus were observed. There was a failure of thrive but no fracture. The cardiovascular examination was normal. Cranial, vertebral and long bone roentgenograms revealed characteristic deformities of osteopetrosis and diffuse sclerosis. The diagnosis was confirmed by genetic testing. A Homozygous mutation was detected in the TNFRSF11A gene (c.508A>G p.(Arg170Gly)). RANKL is encoded by the tumor necrosis factor ligand superfamily member 11 (TNFSF11) gene, and the binding to its receptor RANK, encoded by the TNFRSF11A gene, determines the activation of the downstream pathway that drives osteoclast differentiation and activation (51). The complete absence of osteoclasts is the key feature of the osteoclast-poor form of osteopetrosis (46). Patients are characterized by the absence of TRAP-positive osteoclasts in bone biopsies. The osteoclast-poor subtype of osteopetrosis caused by mutations in TNFSF11 gene is ultra-rare in humans. Clinical presentation is usually severe, with onset in early infancy or in fetal life. But here, a case was presented with horizontal nystagmus. A case presented with horizontal nystagmus, which was evaluated by neurology and diagnosed incidentally, was shared.

Keywords: osteopetrosis, nystagmus, bone, osteoclast-poor

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Authors: D. J. Kalita

Abstract:

Cancer is one of the prime causes of early death worldwide. Mutation of the gene involve in DNA repair and damage, like BRCA2 (Breast cancer gene two) genes, can be detected efficiently by PCR-RFLP to early breast cancer diagnosis and adopt the suitable method of treatment. Host Defense Peptide can be used as blueprint for the design and synthesis of novel anticancer drugs to avoid the side effect of conventional chemotherapy and chemo resistance. The change at nucleotide position 392 of a -› c in the cancer sample of dog mammary tumour at BRCA2 (exon 7) gene lead the creation of a new restriction site for SsiI restriction enzyme. This SNP may be a marker for detection of canine mammary tumour. Support vector machine (SVM) algorithm was used to design and predict the anticancer peptide from the mature functional peptide. MTT assay of MCF-7 cell line after 48 hours of post treatment showed an increase in the number of rounded cells when compared with untreated control cells. The ability of the synthesized peptide to induce apoptosis in MCF-7 cells was further investigated by staining the cells with the fluorescent dye Hoechst stain solution, which allows the evaluation of the nuclear morphology. Numerous cells with dense, pyknotic nuclei (the brighter fluorescence) were observed in treated but not in control MCF-7 cells when viewed using an inverted phase-contrast microscope. Thus, PCR-RFLP is one of the attractive approach for early diagnosis, and synthetic cationic peptide can be used for the treatment of canine mammary tumour.

Keywords: cancer, cationic peptide, host defense peptides, Breast cancer genes

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Authors: Arunima Verma, Padmabati Mondal

Abstract:

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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