Search results for: nef variants

Authors: Rindra Rantoson, Hichem Nouira, Nabil Anwer, Charyar Mehdi-Souzani

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Multiple measurements by means of various data acquisition systems are generally required to measure the shape of freeform workpieces for accuracy, reliability and holisticity. The obtained data are aligned and fused into a common coordinate system within a registration technique involving coarse and fine registrations. Standardized iterative methods have been established for fine registration such as Iterative Closest Points (ICP) and its variants. For coarse registration, no conventional method has been adopted yet despite a significant number of techniques which have been developed in the literature to supply an automatic rough matching between data sets. Two main issues are addressed in this paper: the coarse registration and the fine registration. For coarse registration, two novel automated methods based on the exploitation of discrete curvatures are presented: an enhanced Hough Transformation (HT) and an improved Ransac Transformation. The use of curvature features in both methods aims to reduce computational cost. For fine registration, a new variant of ICP method is proposed in order to reduce registration error using curvature parameters. A specific distance considering the curvature similarity has been combined with Euclidean distance to define the distance criterion used for correspondences searching. Additionally, the objective function has been improved by combining the point-to-point (P-P) minimization and the point-to-plane (P-Pl) minimization with automatic weights. These ones are determined from the preliminary calculated curvature features at each point of the workpiece surface. The algorithms are applied on simulated and real data performed by a computer tomography (CT) system. The obtained results reveal the benefit of the proposed novel curvature-based registration methods.

Keywords: discrete curvature, RANSAC transformation, hough transformation, coarse registration, ICP variant, point-to-point and point-to-plane minimization combination, computer tomography

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Authors: Weaam Aldeeban, Majd Aljamali, Lama A. Youssef

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Background & Objective: Warfarin is considered a problematic drug due to its narrow therapeutic window and wide inter-individual response variations, which are attributed to demographic, environmental, and genetic factors, particularly single nucleotide polymorphism (SNPs) in the genes encoding VKORC1 and CYP2C9 involved in warfarin's mechanism of action and metabolism, respectively. CYP2C9*2rs1799853 and CYP2C9*3rs1057910 alleles are linked to reduced enzyme activity, as carriers of either or both alleles are classified as moderate or slow metabolizers, and therefore exhibit higher sensitivity of warfarin compared with wild type (CYP2C9*1*1). Our study aimed to assess the frequency of *1, *2, and *3 alleles in the CYP2C9 gene in a cohort of Syrian patients receiving a maintenance dose of warfarin for different indications, the impact of genotypes on warfarin dosing, and the frequency of adverse effects (i.e., bleedings). Subjects & Methods: This retrospective cohort study encompassed 94 patients treated with warfarin. Patients’ genotypes were identified by sequencing the polymerase chain reaction (PCR) specific products of the gene encoding CYP2C9, and the effects on warfarin therapeutic outcomes were investigated. Results: Sequencing revealed that 43.6% of the study population has the *2 and/or *3 SNPs. The mean weekly maintenance dose of warfarin was 37.42 ± 15.5 mg for patients with the wild-type allele (CYP2C9*1*1), whereas patients with one or both variants (*2 and/or *3) demanded a significantly lower dose (28.59 ±11.58 mg) of warfarin, (P= 0.015). A higher percentage (40.7%) of patients with allele *2 and/or *3 experienced hemorrhagic accidents compared with only 17.9% of patients with the wild type *1*1, (P = 0.04). Conclusions: Our study proves an association between *2 and *3 genotypes and higher sensitivity to warfarin and a tendency to bleed, which necessitates lowering the dose. These findings emphasize the significance of CYP2C9 genotyping prior to commencing warfarin therapy in order to achieve optimal and faster dose control and to ensure effectiveness and safety.

Keywords: warfarin, CYP2C9, polymorphisms, Syrian, hemorrhage

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Authors: Tomasz Komornicki

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The primary aim of the presentation is to try to model border traffic and, at the same time to explain on which economic variables the intensity of border traffic depended in the long term. For this purpose, long series of traffic data on the Polish borders were used. Models were estimated for three variants of explanatory variables: a) for total arrivals and departures (total movement of Poles and foreigners), b) for arrivals and departures of Poles, and c) for arrivals and departures of foreigners. Each of the defined explanatory variables in the models appeared as the logarithm of the natural number of persons. Data from 1994-2017 were used for modeling (for internal Schengen borders for the years 1994-2007). Information on the number of people arriving in and leaving Poland was collected for a total of 303 border crossings. On the basis of the analyses carried out, it was found that one of the main factors determining border traffic is generally differences in the level of economic development (GDP) and the condition of the economy (level of unemployment) and the degree of border permeability. Also statistically significant for border traffic are differences in the prices of goods (fuels, tobacco, and alcohol products) and services (mainly basic ones, e.g., hairdressing services). Such a relationship exists mainly on the eastern border (border traffic determined largely by differences in the prices of goods) and on the border with Germany (in the first analysed period, border traffic was determined mainly by the prices of goods, later - after Poland's accession to the EU and the Schengen area - also by the prices of services). The models also confirmed differences in the set of factors shaping the volume and structure of border traffic on the Polish borders resulting from general geopolitical conditions, with the year 2007 being an important caesura, after which the classical population mobility factors became visible. The results obtained were additionally related to changes in traffic that occurred as a result of the CPOVID-19 pandemic and as a result of the Russian aggression against Ukraine.

Keywords: border, modal structure, transport, Ukraine

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Authors: Mehrdad Sheikhvatan, Mohammad Ali Boroumand, Mehrdad Behmanesh, Shayan Ziaee

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Contradictory results have been obtained regarding the role of integrin, beta 3 (ITGB3) gene polymorphisms in occurrence of acute myocardial infarction (MI) in patients with coronary artery disease (CAD). Hence, we aimed to assess the association between 1565C/T polymorphism of ITGB3 gene and increased risk for acute MI in patients who suffered premature CAD in Iranian population. Our prospective study included 1000 patients (492 men and 508 women aged 21 to 55 years) referred to Tehran Heart center during a period of four years from 2008 to 2011 with the final diagnosis of premature CAD and classified into two groups with history of MI (n = 461) and without of MI (n = 539). The polymorphism variants were determined by PCR-RFLP technique by entering 10% of randomized samples and then genotyping of the polymorphism was also conducted by High Resolution Melting (HRM) method. Among study samples, 640 were followed with a median follow-up time 45.74 months for determining association of long-term major adverse cardiac events (MACE) and genotypes of polymorphisms. There was no significant difference in the frequency of 1565C/T polymorphism between the MI and non-MI groups. The frequency of wild genotype was 69.2% and 72.2%, the frequency of homozygous genotype was 21.3% and 18.4%, and the frequency of mutant genotype was 9.5% and 9.5%, respectively (p=0.505). Results were also similar when adjusted for covariates in a multivariate logistic regression model. No significant difference was also found in total-MACE free survival rate between the patients with different genotypes of 1565C/T polymorphism in both MI and non-MI group. The carriage of the 1565C/T polymorphism of ITGB3 gene seems unlikely to be a significant risk factor for the development of MI in Iranian patients with premature CAD. The presence of this ITGB3 gene polymorphism may not also predict long-term cardiac events.

Keywords: coronary artery disease, myocardial infarction, gene, integrin, beta 3, polymorphism

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Authors: Saad Mahmud Khan, Sarah El Hajj Chehadeh, Mehera Abdulrahman, Wael Osman, Habiba Al Safar

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Obesity is a non-communicable disease that is widely prevalent with approximately 600 million people classified as obese worldwide. Its etiology is multifactorial and involves a complex interplay between genes and the environment. Over the past few decades, obesity rates among the Emirati population have been increasing. The aim of this study was to investigate the association of candidate gene single nucleotide polymorphisms (SNPs), namely the fat mass and obesity associated (FTO) gene SNP rs9939609 and Vitamin D Receptor (VDR) gene SNP rs1544410, with obesity in the UAE population. Methods: This is a case-control study in which 414 individuals were enrolled during their routine visit to endocrinology clinics in Abu Dhabi, United Arab Emirates between the period of June 2012 and December 2013. Several biochemical tests and clinical assessments along with a lifestyle questionnaire for each participant were completed at the clinic. Genomic DNA was extracted from saliva samples of 201 obese, 114 overweight and 99 normal subjects. Genotyping for the variants was performed using TaqMan assay. Results: The mean Body Mass Index (BMI) ± SD for the obese, overweight, and normal subjects was 35.76 ± 4.54, 27.53 ± 1.45 and 22.69 ± 1.84 kg/m2, respectively. Increasing BMI values were associated with an increase in values for systolic blood pressure, diastolic blood pressure, HbA1c, and triglycerides. The SNP rs9939609 in the FTO gene was found to be significantly associated with the BMI (p=0.028), with the minor allele A having a clear additive effect on BMI values. No significant association was detected between BMI and rs1544410 of the VDR gene. Conclusions: Our study findings indicate that the minor allele A of the rs9939609 has a significant association with increasing BMI values. In addition, our findings support the fact that increasing BMI is associated with increasing risks of other comorbidities such as higher blood pressure, poorer glycemic control and higher triglycerides.

Keywords: body mass index, FTO gene, obesity, rs9939609, United Arab Emirates

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Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias

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Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.

Keywords: cancer vaccines, safety, toxicology, rats, non human primates

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Authors: Prabesh Karki, Shyam Thapa Chettri, Bajarang Prasad Sah, Manoj Bhattarai, Sudeep Mishra

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Introduction: Frontal sinus is frequently described as the most difficult sinus to access surgically due to its proximity to the cribriform plate, orbit, and anterior ethmoid artery. Frontal sinus surgery requires a detailed understanding of the cellular structure and FSDP unique to each patient, making high-resolution CT scans an indispensable tool to assess the difficulty of planned sinus surgery. International Frontal Sinus Anatomy Classification (IFAC) was developed to provide a more precise nomenclature for cells in the frontal recess, classifying cells based on their anatomic origin. Objectives: To assess the proportion of frontal cell variants defined by IFAC, variation with respect to age and gender. Methods: 54 cases were enrolled after a detailed clinical history, thorough general and physical examinations, and CT a report ordered in a film. Assessment and tabulation of the presence of frontal cells according to the IFAC analyzed. The prevalence of each cell type was calculated, and data were entered in MS Excel and analyzed using Statistical Package for the Social Sciences (SPSS). Descriptive statistics and frequencies were defined for categorical and numerical variables. Frequency, percentage, the mean and standard deviation were calculated. Result: Among 54 patients, 30 (55.6%) were male and 24 (44.4%) were female. The patient enrolled ranged from 18 to 78 years. Majority33.3% (n=18) were in age group of >50 years.According to IFAC, Agger nasi cells (92.6%) were most common, whereas supraorbital ethmoidal cells were least common 16 (29.6%). Prevalence of other frontoethmoidal cells was SAC- 57.4%, SAFC- 38.9%, SBC- 74.1%, SBFC- 33.3%, FSC- 38.9% of 54 cases. Conclusion: IFAC is an international consensus document that describes an anatomically precise nomenclature for classifying frontoethmoidal cells' anatomy. This study has defined the prevalence, symmetry and reliability of frontoethmoidal cells as established by the IFAC system as in other parts of the world.

Keywords: frontal sinus, frontoethmoidal cells, international frontal sinus anatomy classification

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Authors: Afsaneh Mohammadnejad, Marianne Nygaard, Jan Baumbach, Shuxia Li, Weilong Li, Jesper Lund, Jacob v. B. Hjelmborg, Lene Christensen, Qihua Tan

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Cognitive impairment in the elderly is a key issue affecting the quality of life. Despite a strong genetic background in cognition, only a limited number of single nucleotide polymorphisms (SNPs) have been found. These explain a small proportion of the genetic component of cognitive function, thus leaving a large proportion unaccounted for. We hypothesize that one reason for this missing heritability is the misspecified modeling in data analysis concerning phenotype distribution as well as the relationship between SNP dosage and the phenotype of interest. In an attempt to overcome these issues, we introduced a model-free method based on the generalized correlation coefficient (GCC) in a genome-wide association study (GWAS) of cognitive function in twin samples and compared its performance with two popular linear regression models. The GCC-based GWAS identified two genome-wide significant (P-value < 5e-8) SNPs; rs2904650 near ZDHHC2 on chromosome 8 and rs111256489 near CD6 on chromosome 11. The kinship model also detected two genome-wide significant SNPs, rs112169253 on chromosome 4 and rs17417920 on chromosome 7, whereas no genome-wide significant SNPs were found by the linear mixed model (LME). Compared to the linear models, more meaningful biological pathways like GABA receptor activation, ion channel transport, neuroactive ligand-receptor interaction, and the renin-angiotensin system were found to be enriched by SNPs from GCC. The GCC model outperformed the linear regression models by identifying more genome-wide significant genetic variants and more meaningful biological pathways related to cognitive function. Moreover, GCC-based GWAS was robust in handling genetically related twin samples, which is an important feature in handling genetic confounding in association studies.

Keywords: cognition, generalized correlation coefficient, GWAS, twins

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Authors: L. Kiefer, C. Richter, G. Reinhart

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The uprising complexity in production systems due to an increasing amount of variants up to customer innovated products leads to requirements that hierarchical control systems are not able to fulfil. Therefore, factory planners can install autonomous manufacturing systems. The fundamental requirement for an autonomous control is the identification of objects within production systems. In this approach an attribute-based identification is focused for avoiding dose-dependent identification costs. Instead of using an identification mark (ID) like a radio frequency identification (RFID)-Tag, an object type is directly identified by its attributes. To facilitate that it’s recommended to include the identification and the corresponding sensors within handling processes, which connect all manufacturing processes and therefore ensure a high identification rate and reduce blind spots. The presented methodology reduces the individual effort to integrate identification processes in handling systems. First, suitable object attributes and sensor systems for object identification in a production environment are defined. By categorising these sensor systems as well as handling systems, it is possible to match them universal within a compatibility matrix. Based on that compatibility further requirements like identification time are analysed, which decide whether the combination of handling and sensor system is well suited for parallel handling and identification within an autonomous control. By analysing a list of more than thousand possible attributes, first investigations have shown, that five main characteristics (weight, form, colour, amount, and position of subattributes as drillings) are sufficient for an integrable identification. This knowledge limits the variety of identification systems and leads to a manageable complexity within the selection process. Besides the procedure, several tools, as an example a sensor pool are presented. These tools include the generated specific expert knowledge and simplify the selection. The primary tool is a pool of preconfigured identification processes depending on the chosen combination of sensor and handling device. By following the defined procedure and using the created tools, even laypeople out of other scientific fields can choose an appropriate combination of handling devices and sensors which enable parallel handling and identification.

Keywords: agent systems, autonomous control, handling systems, identification

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Authors: Nicole Ramlachan, Samuel Mark West

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Lung cancer is the leading cause of cancer-associated deaths in North America, with the vast majority being non-small cell lung cancer (NSCLC), with a five-year survival rate of only 24%. Non-invasive discovery of biomarkers associated with early-diagnosis of NSCLC can enable precision oncology efforts using liquid biopsy-based multiomics profiling of plasma. Although tissue biopsies are currently the gold standard for tumor profiling, this method presents many limitations since these are invasive, risky, and sometimes hard to obtain as well as only giving a limited tumor profile. Blood-based tests provides a less-invasive, more robust approach to interrogate both tumor- and non-tumor-derived signals. We intend to examine 30 stage III-IV NSCLC patients pre-surgery and collect plasma samples.Cell-free DNA (cfDNA) will be extracted from plasma, and next-generation sequencing (NGS) performed. Through the analysis of tumor-specific alterations, including single nucleotide variants (SNVs), insertions, deletions, copy number variations (CNVs), and methylation alterations, we intend to identify tumor-derived DNA—ctDNA among the total pool of cfDNA. This would generate data to be used as an accurate form of cancer genotyping for diagnostic purposes. Using liquid biopsies offer opportunities to improve the surveillance of cancer patients during treatment and would supplement current diagnosis and tumor profiling strategies previously not readily available in Trinidad and Tobago. It would be useful and advantageous to use this in diagnosis and tumour profiling as well as to monitor cancer patients, providing early information regarding disease evolution and treatment efficacy, and reorient treatment strategies in, timethereby improving clinical oncology outcomes.

Keywords: genomics, multiomics, clinical genetics, genotyping, oncology, diagnostics

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Authors: Timothy Kayode Samson, Adedoyin Isola Lawal

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The past five years have shown a sharp increase in public interest in the crypto market, with its market capitalization growing from $100 billion in June 2017 to $2158.42 billion on April 5, 2022. Despite the outrageous nature of the volatility of cryptocurrencies, the use of skewed error innovation distributions in modelling the volatility behaviour of these digital currencies has not been given much research attention. Hence, this study models the volatility of 5 largest cryptocurrencies by market capitalization (Bitcoin, Ethereum, Tether, Binance coin, and USD Coin) using four variants of GARCH models (GJR-GARCH, sGARCH, EGARCH, and APARCH) estimated using three skewed error innovation distributions (skewed normal, skewed student- t and skewed generalized error innovation distributions). Daily closing prices of these currencies were obtained from Yahoo Finance website. Finding reveals that the Binance coin reported higher mean returns compared to other digital currencies, while the skewness indicates that the Binance coin, Tether, and USD coin increased more than they decreased in values within the period of study. For both Bitcoin and Ethereum, negative skewness was obtained, meaning that within the period of study, the returns of these currencies decreased more than they increased in value. Returns from these cryptocurrencies were found to be stationary but not normality distributed with evidence of the ARCH effect. The skewness parameters in all best forecasting models were all significant (p<.05), justifying of use of skewed error innovation distributions with a fatter tail than normal, Student-t, and generalized error innovation distributions. For Binance coin, EGARCH-sstd outperformed other volatility models, while for Bitcoin, Ethereum, Tether, and USD coin, the best forecasting models were EGARCH-sstd, APARCH-sstd, EGARCH-sged, and GJR-GARCH-sstd, respectively. This suggests the superiority of skewed Student t- distribution and skewed generalized error distribution over the skewed normal distribution.

Keywords: skewed generalized error distribution, skewed normal distribution, skewed student t- distribution, APARCH, EGARCH, sGARCH, GJR-GARCH

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Authors: Reema K. AlEssa, Sahar Alshomer, Abdullah Alfaleh, Sultan ALkhenaizan, Mohammed Albalwi

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Ichthyosis is a disorder of abnormal keratinization, characterized by excessive scaling, and consists of more than twenty subtypes varied in severity, mode of inheritance, and the genes involved. There is insufficient data in the literature about the epidemiology and characteristics of ichthyosis locally. Our aim is to identify the histopathological features and genetic profile of ichthyosis. Method: It is an observational retrospective case series study conducted in March 2020, included all patients who were diagnosed with Ichthyosis and confirmed by histological and molecular findings over the last 20 years in King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. Molecular analysis was performed by testing genomic DNA and checking genetic variations using the AmpliSeq panel. All disease-causing variants were checked against HGMD, ClinVar, Genome Aggregation Database (gnomAD), and Exome Aggregation Consortium (ExAC) databases. Result: A total of 60 cases of Ichthyosis were identified with a mean age of 13 ± 9.2. There is an almost equal distribution between female patients 29 (48%) and males 31 (52%). The majority of them were Saudis, 94%. More than half of patients presented with general scaling 33 (55%), followed by dryness and coarse skin 19 (31.6%) and hyperlinearity 5 (8.33%). Family history and history of consanguinity were seen in 26 (43.3% ), 13 (22%), respectively. History of colloidal babies was found in 6 (10%) cases of ichthyosis. The most frequent genes were ALOX12B, ALOXE3, CERS3, CYP4F22, DOLK, FLG2, GJB2, PNPLA1, SLC27A4, SPINK5, STS, SUMF1, TGM1, TGM5, VPS33B. Most frequent variations were detected in CYP4F22 in 16 cases (26.6%) followed by ALOXE3 6 (10%) and STS 6 (10%) then TGM1 5 (8.3) and ALOX12B 5 (8.3). The analysis of molecular genetic identified 23 different genetic variations in the genes of ichthyosis, of which 13 were novel mutations. Homozygous mutations were detected in the majority of ichthyosis cases, 54 (90%), and only 1 case was heterozygous. Few cases, 4 (6.6%) had an unknown type of ichthyosis with a negative genetic result. Conclusion: 13 novel mutations were discovered. Also, about half of ichthyosis patients had a positive history of consanguinity.

Keywords: ichthyosis, genetic profile, molecular characterization, congenital ichthyosis

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Authors: Sadam Elayah, Yang Li, Bing Shi

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Background: The impact of relaxing incisions on maxillofacial growth during palatoplasty remains a topic of debate, and further research is needed to understand its effects fully. Thus, the current study is the first long-term study that aimed to assess the maxillofacial growth of patients with isolated cleft palate following the Sommerlad-Furlow modified (S.F) technique and to estimate the impact of relaxing incisions on maxillofacial growth following S.F technique in patients with isolated cleft palate. Methods: A total of 85 participants, 55 patients with non-syndromic isolated soft and hard cleft palate underwent primary palatoplasty with our technique (30 patients received the Sommerlad-Furlow modified technique without relaxing incision (S.F+RI group), and 25 received Sommerlad-Furlow modified technique without relaxing (S.F-RI group) with no significant difference found between them regarding the cleft type, cleft width, and age at repair. While the other 30 were normal participants with skeletal class I pattern (C group). The control group was matched with the study group in number, age, and sex. All the study variables were measured using stable landmarks, including 12 linear and 10 angular variants. Results: The mean ages at collection of cephalograms were 6.03±0.80 in the S.F+RI group, 5.96±0.76 in the S.F-RI group, and 5.91±0.87 in the C group. Regarding cranial base, the results showed no statistically significant differences between the three groups in S-N and S-N-Ba. The S.F+R.I group had a significantly shorter S-Ba than the S.F-R.I & C groups (P= 0.01). However, there was no statistically significant difference between the S.F-R.I & C groups (P=0.80). Regarding the skeletal maxilla, there was no significant difference between the S.F+R.I and S.F-R.I groups in all linear measurements (N-ANS, S- PM & SN-PP ) except Co-A, the S.F+R.I group had significantly shorter Co-A than the S.F-R.I & C groups (P= <0.01). While the angular measurement, S.F+R.I group had significantly less SNA angle than the S.F-R.I & C groups (P= <0.01). Regarding mandibular bone, there were no statistically significant differences in all linear and angular mandibular measurements between the S.F+R.I and S.F-R.I groups. Regarding intermaxillary relation, the S.F+R.I group had significant differences in Co-Gn - Co-A and ANB compared to the S.F-R.I & C groups (P= <0.01). There was no statistically significant difference in PP-MP among the three groups. Conclusion: As a preliminary report, the Sommerlad-Furlow modified technique without relaxing incisions was found to have good maxillary positioning in the face and a satisfactory intermaxillary relationship compared to the Sommerlad-Furlow modified technique with relaxing incisions.

Keywords: relaxing incisions, cleft palate, palatoplasty, maxillofacial growth

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Authors: Yutong Wan, John N. Wood

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

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

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Authors: William Marquis, Fang Dong

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There has been a growing concern in recent years over the economic and social effects of adult video gaming. It has been estimated that the number of people who played video games during the COVID-19 pandemic is close to three billion, and there is evidence that this form of entertainment is here to stay. Many people are concerned that this growing use of time could crowd out time that could be spent on alternative forms of entertainment with family, friends, sports, and other social activities that build community. For example, recent studies of children suggest that playing videogames crowds out time that could be spent on homework, watching TV, or in other social activities. Similar studies of adults have shown that video gaming is negatively associated with earnings, time spent at work, and socializing with others. The primary objective of this paper is to examine how time adults spend on video gaming could displace time they could spend working and on activities that enhance their health and well-being. We use data from the American Time Use Survey (ATUS), maintained by the Bureau of Labor Statistics, to analyze the effects of time-use decisions on three measures of well-being. We pool the ATUS Well-being Module for multiple years, 2010, 2012, 2013, and 2021, along with the ATUS Activity and Who files for these years. This pooled data set provides three broad measures of well-being, e.g., health, life satisfaction, and emotional well-being. Seven variants of each are used as a dependent variable in different multivariate regressions. We add to the existing literature in the following ways. First, we investigate whether the time adults spend in video gaming crowds out time spent working or in social activities that promote health and life satisfaction. Second, we investigate the relationship between adult gaming and their emotional well-being, also known as negative or positive affect, a factor that is related to depression, health, and labor market productivity. The results of this study suggest that the time adult gamers spend on video gaming has no effect on their supply of labor, a negligible effect on their time spent socializing and studying, and mixed effects on their emotional well-being, such as increasing feelings of pain and reducing feelings of happiness and stress.

Keywords: online gaming, health, social capital, emotional wellbeing

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Authors: H. Scholz, P. Kuehne, G. Heckenberger

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Problems during the calving period (December until May) often are results in a high body condition score (BCS) at this time. At the end of the grazing period (frequently after early weaning), however, an increase of BCS can often be observed under German conditions. In the last eight weeks before calving, the body condition should be reduced or at least not increased. Rations with a higher amount of crude fiber can be used (rations with straw or late mowed grass silage). Fermentative digestion of fiber is slow and incomplete; that’s why the fermentative process in the rumen can be reduced over a long feeding time. Viewed in this context, feed intake of suckler cows (8 weeks before calving) in different rations and fermentation in the rumen should be checked by taking rumen fluid. Eight suckler cows (Charolais) were feeding a Total Mixed Ration (TMR) in the last eight weeks before calving and grass silage after calving. By the addition of straw (30 % [TMR1] vs. 60 % [TMR2] of dry matter) was varied the amount of crude fiber in the TMR (grass silage, straw, mineral) before calving. After calving of the cow's grass, silage [GS] was fed ad libitum, and the last measurement of rumen fluid took place on the pasture [PS]. Rumen fluid, plasma, body weight, and backfat thickness were collected. Rumen fluid pH was assessed using an electronic pH meter. Volatile fatty acids (VFA), sedimentation, methylene-blue, and amount of infusorians were measured. From these 4 parameters, an “index of rumen fermentation” [IRF] in the rumen was formed. Fixed effects of treatment (TMR1, TMR2, GS, and PS) and a number of lactations (3-7 lactations) were analyzed by ANOVA using SPSS Version 25.0 (significant by p ≤ 5 %). Rumen fluid pH was significantly influenced by variants (TMR 1 by 6.6; TMR 2 by 6.9; GS by 6.6 and PS by 6.9) but was not affected by other effects. The IRF showed disturbed fermentation in the rumen by feeding the TMR 1+2 with a high amount of crude fiber (Score: > 10.0 points) and a very good environment for fermentation during grazing the pasture (Score: 6.9 points). Furthermore, significant differences were found for VFA, methylene blue, and the number of infusorians. The use of rations with a high amount of crude fiber from weaning to calving may cause deviations from undisturbed fermentation in the rumen and adversely affect the utilization of the feed in the rumen.

Keywords: rumen fermentation, suckler cow, digestibility organic matter, crude fiber

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Authors: Farahnaz Sadat Golestan Hashemi, Mohd Razi Ismail, Mohd Y. Rafii

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A huge revolution has emerged in genome engineering by the discovery of CRISPR (clustered regularly interspaced palindromic repeats) and CRISPR-associated system genes (Cas) in bacteria. The function of type II Streptococcus pyogenes (Sp) CRISPR/Cas9 system has been confirmed in various species. Other S. thermophilus (St) CRISPR-Cas systems, CRISPR1-Cas and CRISPR3-Cas, have been also reported for preventing phage infection. The CRISPR1-Cas system interferes by cleaving foreign dsDNA entering the cell in a length-specific and orientation-dependant manner. The S. thermophilus CRISPR3-Cas system also acts by cleaving phage dsDNA genomes at the same specific position inside the targeted protospacer as observed in the CRISPR1-Cas system. It is worth mentioning, for the effective DNA cleavage activity, RNA-guided Cas9 orthologs require their own specific PAM (protospacer adjacent motif) sequences. Activity levels are based on the sequence of the protospacer and specific combinations of favorable PAM bases. Therefore, based on the specific length and sequence of PAM followed by a constant length of target site for the three orthogonals of Cas9 protein, a well-organized procedure will be required for high-throughput and accurate mining of possible target sites in a large genomic dataset. Consequently, we created a reliable procedure to explore potential gRNA sequences for type I (Streptococcus thermophiles), II (Streptococcus pyogenes), and III (Streptococcus thermophiles) CRISPR/Cas systems. To mine CRISPR target sites, four different searching modes of sgRNA binding to target DNA strand were applied. These searching modes are as follows: i) coding strand searching, ii) anti-coding strand searching, iii) both strand searching, and iv) paired-gRNA searching. The output of such procedure highlights the power of comparative genome mining for different CRISPR/Cas systems. This could yield a repertoire of Cas9 variants with expanded capabilities of gRNA design, and will pave the way for further advance genome and epigenome engineering.

Keywords: CRISPR/Cas systems, gRNA mining, Streptococcus pyogenes, Streptococcus thermophiles

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Authors: Mitesh Rathod, Jungho Ahn, Noo Li Jeon, Junghoon Lee

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Endothelial cells respond to cues from both biochemical as well as micro mechanical environment. Significant effort has been directed to understand the effects of biochemical signaling, however, relatively little is known about regulation of endothelial cell biology by the micro mechanical environment. Numerous studies have been performed to understand how physical forces regulate endothelial cell behavior. In this regard, past studies have majorly focused on exploring how fluid shear stress governs endothelial cell behavior. Parallel plate flow chambers and rectangular microchannels are routinely employed for applying fluid shear force on endothelial cells. However, these studies fall short in mimicking the in vivo like micro environment from topological aspects. Few studies have only used circular microchannels to replicate in vivo like condition. Seldom efforts have been directed to elucidate the combined effect of topology, substrate rigidity and fluid shear stress on endothelial cell response. In this regard, we demonstrate a facile fabrication process to develop a hybrid polydimethylsiloxane microfluidic platform to study endothelial cell biology. On a single chip microchannels with different cross sections i.e., circular, rectangular and square have been fabricated. In addition, our fabrication approach allows variation in the substrate rigidity along the channel length. Two different variants of polydimethylsiloxane, namely Sylgard 184 and Sylgard 527, were utilized to achieve the variation in rigidity. Moreover, our approach also enables in creating Y bifurcation circular microchannels. Our microfluidic platform thus facilitates for conducting studies pertaining to endothelial cell morphology with respect to change in topology, substrate rigidity and fluid flow on a single chip. The hybrid platform was tested by culturing Human Umbilical Vein Endothelial Cells in circular microchannels with varying substrate rigidity, and exposed to fluid shear stress of 12 dynes/cm² and static conditions. Results indicate the cell area response to flow induced shear stress was governed by the underlying substrate mechanics.

Keywords: hybrid, microfluidic platform, PDMS, shear flow, substrate rigidity

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Authors: Zbigniew Czyż, Adam Majczak, Lukasz Grabowski

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The paper presents a description of geometric models, computational algorithms, and results of numerical analyses of charge exchange in a two-stroke opposed-piston engine. The research engine was a newly designed internal Diesel engine. The unit is characterized by three cylinders in which three pairs of opposed-pistons operate. The engine will generate a power output equal to 100 kW at a crankshaft rotation speed of 3800-4000 rpm. The numerical investigations were carried out using ANSYS FLUENT solver. Numerical research, in contrast to experimental research, allows us to validate project assumptions and avoid costly prototype preparation for experimental tests. This makes it possible to optimize the geometrical model in countless variants with no production costs. The geometrical model includes an intake manifold, a cylinder, and an outlet manifold. The study was conducted for a series of modifications of manifolds and intake and exhaust ports to optimize the charge exchange process in the engine. The calculations specified a swirl coefficient obtained under stationary conditions for a full opening of intake and exhaust ports as well as a CA value of 280° for all cylinders. In addition, mass flow rates were identified separately in all of the intake and exhaust ports to achieve the best possible uniformity of flow in the individual cylinders. For the models under consideration, velocity, pressure and streamline contours were generated in important cross sections. The developed models are designed primarily to minimize the flow drag through the intake and exhaust ports while the mass flow rate increases. Firstly, in order to calculate the swirl ratio [-], tangential velocity v [m/s] and then angular velocity ω [rad / s] with respect to the charge as the mean of each element were calculated. The paper contains comparative analyses of all the intake and exhaust manifolds of the designed engine. Acknowledgement: This work has been realized in the cooperation with The Construction Office of WSK "PZL-KALISZ" S.A." and is part of Grant Agreement No. POIR.01.02.00-00-0002/15 financed by the Polish National Centre for Research and Development.

Keywords: computational fluid dynamics, engine swirl, fluid mechanics, mass flow rates, numerical analysis, opposed-piston engine

Procedia PDF Downloads 177

Authors: Evgeni Baratashvili, Giorgi Sulashvili, Malkhaz Sulashvili, Bela Khotenashvili, Irma Makharashvili

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The most investment decision-making principle of regional travel firm's management and its partner is the formulation of the aims of investment programs. The investments can be targeted in order to reduce the firm's production costs and to purchase good transport equipment. In attractive region, in order to develop firm’s activities, the investment program can be targeted for increasing of provided services. That is the case where the sales already have been used in the market. The investment can be directed to establish the affiliate firms, branches, to construct new hotels, to create food and trade enterprises, to develop entertainment enterprises, etc. Economic development is of great importance to regional development. International experience shows that inclusive economic growth largely depends on not only the national, but also regional development planning and implementation of a strong and competitive regions. Regional development is considered as the key factor in achieving national success. Establishing a modern institute separate entities if the pilot centers will constitute a promotion, international best practice-based public-private partnership to encourage the use of models. Regional policy directions and strategies adopted in accordance with the successful implementation of major importance in the near future specific action plans for inclusive development and implementation, which will be provided in accordance with the effective monitoring and evaluation tools and measurable indicators combined. All of these above-mentioned investments are characterized by different levels, which are related to the following fact: How successful tourism marketing service is, whether it is able to determine the proper market's reaction according to the particular firm's actions. In the sphere of regional tourism industry and in the investment decision possible variants it can be developed the some specter of models. Each of the models can be modified and specified according to the situation, and characteristic skills of the existing problem that must be solved. Besides, while choosing the proper model, the process is affected by the regulation system of economic processes. Also, it is influenced by liberalization quality and by the level of state participation.

Keywords: net income of travel firm, economic growth, Investment profitability, regional development, tourist product, tourism development

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Authors: Reshu Saxena, R. K. Tripathi

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HIV-1 transmission and spread involves significant host-virus interaction. Potential targets for prevention of HIV-1 lies at the site of mucosal barriers. Thus a better understanding of how HIV-1 infects target cells at such sites and lead their invasion is required, with prime focus on the host determinants regulating HIV-1 spread. HIV-1 Nef is important for viral infectivity and pathogenicity. It promotes HIV-1 replication, facilitating immune evasion by interacting with various host factors and altering cellular pathways via multiple protein-protein interactions. In this study nef was sequenced from HIV-1 patients, and showed specific mutations revealing sequence variability in nef. To explore the difference in Nef functionality based on sequence variability we have studied the effects of HIV-1 Nef in human SupT1 T cell line and (THP-1) monocyte-macrophage cell lines through proteomics approach. 2D-Gel Electrophoresis in control and Nef-transfected SupT1 cells demonstrated several differentially expressed proteins with significant modulation of alpha-enolase. Through further studies, effects of Nef on alpha-enolase regulation were found to be cell lineage-specific, being stimulatory in macrophages/monocytes, inhibitory in T cells and without effect in HEK-293 cells. Cell migration and invasion studies were employed to determine biological function affected by Nef mediated regulation of alpha-enolase. Cell invasion was enhanced in THP-1 cells but was inhibited in SupT1 cells by wildtype nef. In addition, the modulation of enolase and cell invasion remained unaffected by a unique nef variant. These results indicated that regulation of alpha-enolase expression and invasive property of host cells by Nef is sequence specific, suggesting involvement of a particular motif of Nef. To precisely determine this site, we designed a heptapeptide including the suggested alpha-enolase regulating sequence of nef and a nef mutant with deletion of this site. Macrophages/monocytes being the major cells affected by HIV-1 at mucosal barriers, were particularly investigated by the nef mutant and peptide. Both the nef mutant and heptapeptide led to inhibition of enhanced enolase expression and increased invasiveness in THP-1 cells. Together, these findings suggest a possible mechanism of host invasion by HIV-1 through Nef mediated regulation of alpha-enolase and identifies a potential therapeutic target for HIV-1 entry at mucosal barriers.

Keywords: HIV-1 Nef, nef variants, host-virus interaction, tissue invasion

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Authors: Scholz Heiko, Kuhne Petra, Heckenberger Gerd

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Problems during the calving period (December to May) often result in a high body condition score (BCS) at this time. At the end of the grazing period (frequently after early weaning), however, an increase of BCS can often be observed under German conditions. In the last eight weeks before calving, the body condition should be reduced or at least not increased. Rations with a higher amount of crude fiber can be used (rations with straw or late mowed grass silage). Fermentative digestion of fiber is slow and incomplete; that’s why the fermentative process in the rumen can be reduced over a long feeding time. Viewed in this context, feed intake of suckler cows (8 weeks before calving) in different rations and fermentation in the rumen should be checked by taking rumen fluid. Eight suckler cows (Charolais) were feeding a Total Mixed Ration (TMR) in the last eight weeks before calving and grass silage after calving. By the addition of straw (30 % [TMR1] vs. 60 % [TMR2] of dry matter) was varied the amount of crude fiber in the TMR (grass silage, straw, mineral) before calving. After calving of the cow's grass, silage [GS] was fed ad libitum, and the last measurement of rumen fluid took place on the pasture [PS]. Rumen fluid, plasma, body weight, and backfat thickness were collected. Rumen fluid pH was assessed using an electronic pH meter. Volatile fatty acids (VFA), sedimentation, methylene-blue and amount of infusorians were measured. From these 4 parameters, an “index of rumen fermentation” [IRF] in the rumen was formed. Fixed effects of treatment (TMR1, TMR2, GS and PS) and a number of lactations (3-7 lactations) were analyzed by ANOVA using SPSS Version 25.0 (significant by p ≤ 5 %). Rumen fluid pH was significant influenced by variants (TMR 1 by 6.6; TMR 2 by 6.9; GS by 6.6 and PS by 6.9) but was not affected by other effects. The IRF showed disturbed fermentation in the rumen by feeding the TMR 1+2 with a high amount of crude fiber (Score: > 10.0 points) and a very good environment for fermentation during grazing the pasture (Score: 6.9 points). Furthermore, significant differences were found for VFA, methylene blue and the number of infusorians. The use of rations with the high amount of crude fiber from weaning to calving may cause deviations from undisturbed fermentation in the rumen and adversely affect the utilization of the feed in the rumen.

Keywords: suckler cow, feeding systems, crude fiber, digestibilty of organic matter

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Authors: Omar Youssef, Aija Knuuttila, Paivi Piirilä, Virinder Sarhadi, Sakari Knuutila

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Exhaled breath condensate (EBC) is a unique sample that allows studying different genetic changes in lung carcinoma through a non-invasive way. With the aid of next generation sequencing (NGS) technology, analysis of genetic mutations has been more efficient with increased sensitivity for detection of genetic variants. In order to investigate the possibility of applying this method for cancer diagnostics, mutations in EBC DNA from lung cancer patients and healthy individuals were studied by using NGS. The key aim is to assess the feasibility of using this approach to detect clinically important mutations in EBC. EBC was collected from 20 healthy individuals and 9 lung cancer patients (four lung adenocarcinomas, four 8 squamous cell carcinoma, and one case of mesothelioma). Mutations in hotpot regions of 22 genes were studied by using Ampliseq Colon and Lung cancer panel and sequenced on Ion PGM. Results demonstrated that all nine patients showed a total of 19 cosmic mutations in APC, BRAF, EGFR, ERBB4, FBXW7, FGFR1, KRAS, MAP2K1, NRAS, PIK3CA, PTEN, RET, SMAD4, and TP53. In controls, 15 individuals showed 35 cosmic mutations in BRAF, CTNNB1, DDR2, EGFR, ERBB2, FBXW7, FGFR3, KRAS, MET, NOTCH1, NRAS, PIK3CA, PTEN, SMAD4, and TP53. Additionally, 45 novel mutations not reported previously were also seen in patients’ samples, and 106 novel mutations were seen in controls’ specimens. KRAS exon 2 mutations G12D was identified in one control specimen with mutant allele fraction of 6.8%, while KRAS G13D mutation seen in one patient sample showed mutant allele fraction of 17%. These findings illustrate that hotspot mutations are present in DNA from EBC of both cancer patients and healthy controls. As some of the cosmic mutations were seen in controls too, no firm conclusion can be drawn on the clinical importance of cosmic mutations in patients. Mutations reported in controls could represent early neoplastic changes or normal homeostatic process of apoptosis occurring in lung tissue to get rid of mutant cells. At the same time, mutations detected in patients might represent a non-invasive easily accessible way for early cancer detection. Follow up of individuals with important cancer mutations is necessary to clarify the significance of these mutations in both healthy individuals and cancer patients.

Keywords: exhaled breath condensate, lung cancer, mutations, next generation sequencing

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Authors: Debamitra Chakravorty, Pratap K. Parida

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Cold-adapted proteases enhance wash performance in low-temperature laundry resulting in a reduction in energy consumption and wear of textiles and are also used in the dehairing process in leather industries. Unfortunately, the possible drawbacks of using cold-adapted proteases are their instability at higher temperatures. Therefore, proteases with broad temperature stability are required. Unfortunately, wild-type cold-adapted proteases exhibit instability at higher temperatures and thus have low shelf lives. Therefore, attempts to engineer cold-adapted proteases by protein engineering were made previously by directed evolution and random mutagenesis. The lacuna is the time, capital, and labour involved to obtain these variants are very demanding and challenging. Therefore, rational engineering for cold stability without compromising an enzyme's optimum pH and temperature for activity is the current requirement. In this work, mutations were rationally designed with the aid of high throughput computational methodology of network analysis, evolutionary conservation scores, and molecular dynamics simulations for Savinase from Bacillus lentus with the intention of rendering the mutants cold stable without affecting their temperature and pH optimum for activity. Further, an attempt was made to incorporate a mutation in the most stable mutant rationally obtained by this method to introduce oxidative stability in the mutant. Such enzymes are desired in detergents with bleaching agents. In silico analysis by performing 300 ns molecular dynamics simulations at 5 different temperatures revealed that these three mutants were found to be better in cold stability compared to the wild type Savinase from Bacillus lentus. Conclusively, this work shows that cold adaptation without losing optimum temperature and pH stability and additionally stability from oxidative damage can be rationally designed by in silico enzyme engineering. The key findings of this work were first, the in silico data of H5 (cold stable savinase) used as a control in this work, corroborated with its reported wet lab temperature stability data. Secondly, three cold stable mutants of Savinase from Bacillus lentus were rationally identified. Lastly, a mutation which will stabilize savinase against oxidative damage was additionally identified.

Keywords: cold stability, molecular dynamics simulations, protein engineering, rational design

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Authors: P. Fucik, J. Vymazal, M. Seres

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Pollution from agricultural drainage is a severe issue for water quality, and it is a major reason for the failure in accomplishment of 'good chemical status' according to Water Framework Directive, especially due to high nitrogen and pesticide burden of receiving waters. Constructed wetlands were proposed as a suitable measure for removal of nitrogen from agricultural drainage in the early 1990s. Until now, the vast majority of constructed wetlands designed to treat tile drainage were free-surface constructed wetlands. In 2018, three small experimental constructed wetlands with horizontal subsurface flow were built in Czech Highlands to treat tile drainage from 15.73 ha watershed. The wetlands have a surface area of 79, 90 and 98 m² and were planted with Phalaris arundinacea and Glyceria maxima in parallel bands. The substrate in the first two wetlands is gravel (4-8 mm) mixed with birch woodchips (10:1 volume ratio). In one of those wetlands, the water level is kept 10 cm above the surface; in the second one, the water is kept below the surface. The third wetland has 20 cm layer of birch woodchips on top of gravel. The drainage outlet, as well as wetland outlets, are equipped with automatic discharge-gauging devices, temperature probes, as well as automatic water samplers (Teledyne ISCO). During the monitored period (2018-2019), the flows were unexpectedly low due to a drop of the shallow ground water level, being the main source of water for the monitored drainage system, as experienced at many areas of the Czech Republic. The mean water residence time was analyzed in the wetlands (KBr), which was 16, 9 and 27 days, respectively. The mean total nitrogen concentration eliminations during one-year period were 61.2%, 62.6%, and 70.9% for wetlands 1, 2, and 3, respectively. The average load removals amounted to 0.516, 0.323, and 0.399 g N m-2 d-1 or 1885, 1180 and 1457 kg ha-1 yr-1 in wetlands 1, 2 and 3, respectively. The plant uptake and nitrogen sequestration in aboveground biomass contributed only marginally to the overall nitrogen removal. Among the three variants, the one with shallow water on the surface was revealed to be the most effective for removal of nitrogen from drainage water. In August 2019, herbicide Metazachlor was experimentally poured in time of 2 hours at drainage outlet in a concentration of 250 ug/l to find out the removal rates of the aforementioned wetlands. Water samples were taken the first day every six hours, and for the next nine days, every day one water sample was taken. The removal rates were as follows 94, 69 and 99%; when the most effective wetland was the one with the longest water residence time and the birch woodchip-layer on top of gravel.

Keywords: constructed wetlands, metazachlor, nitrogen, tile drainage

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Authors: Sanjay Rathee, Arti Kashyap

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Extraction of useful information from large datasets is one of the most important research problems. Association rule mining is one of the best methods for this purpose. Finding possible associations between items in large transaction based datasets (finding frequent patterns) is most important part of the association rule mining. There exist many algorithms to find frequent patterns but Apriori algorithm always remains a preferred choice due to its ease of implementation and natural tendency to be parallelized. Many single-machine based Apriori variants exist but massive amount of data available these days is above capacity of a single machine. Therefore, to meet the demands of this ever-growing huge data, there is a need of multiple machines based Apriori algorithm. For these types of distributed applications, MapReduce is a popular fault-tolerant framework. Hadoop is one of the best open-source software frameworks with MapReduce approach for distributed storage and distributed processing of huge datasets using clusters built from commodity hardware. However, heavy disk I/O operation at each iteration of a highly iterative algorithm like Apriori makes Hadoop inefficient. A number of MapReduce-based platforms are being developed for parallel computing in recent years. Among them, two platforms, namely, Spark and Flink have attracted a lot of attention because of their inbuilt support to distributed computations. Earlier we proposed a reduced- Apriori algorithm on Spark platform which outperforms parallel Apriori, one because of use of Spark and secondly because of the improvement we proposed in standard Apriori. Therefore, this work is a natural sequel of our work and targets on implementing, testing and benchmarking Apriori and Reduced-Apriori and our new algorithm ReducedAll-Apriori on Apache Flink and compares it with Spark implementation. Flink, a streaming dataflow engine, overcomes disk I/O bottlenecks in MapReduce, providing an ideal platform for distributed Apriori. Flink's pipelining based structure allows starting a next iteration as soon as partial results of earlier iteration are available. Therefore, there is no need to wait for all reducers result to start a next iteration. We conduct in-depth experiments to gain insight into the effectiveness, efficiency and scalability of the Apriori and RA-Apriori algorithm on Flink.

Keywords: apriori, apache flink, Mapreduce, spark, Hadoop, R-Apriori, frequent itemset mining

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Authors: Mohamad Ammar Ayass, Natalya Griko, Victor Pashkov, Wanying Cao, Kevin Zhu, Jin Zhang, Lina Abi Mosleh

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Respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for coronavirus disease 2019 (COVID-19). Early evidence pointed at the angiotensin-converting enzyme 2 (ACE-2) expressed on the epithelial cells of the lung as the main entry point of SARS-CoV-2 into the cells. The viral entry is mediated by the binding of the Receptor Binding Domain (RBD) of the spike protein that is expressed on the surface of the virus to the ACE-2 receptor. As the number of SARS-CoV-2 variants continues to increase, mutations arising in the RBD of SARS-CoV-2 may lead to the ineffectiveness of RBD targeted neutralizing antibodies. To address this limitation, the objective of this study is to develop a combination of aptamers that target different regions of the RBD, preventing the binding of the spike protein to ACE-2 receptor and subsequent viral entry and replication. A safe and innovative biomedical tool was developed to inhibit viral infection and reduce the harms of COVID-19. In the present study, DNA aptamers were developed against a recombinant trimer S protein using the Systematic Evolution of Ligands by Exponential enrichment (SELEX). Negative selection was introduced at round number 7 to select for aptamers that bind specifically to the RBD domain. A series of 9 aptamers (ADI2010, ADI2011, ADI201L, ADI203L, ADI205L, ADIR68, ADIR74, ADIR80, ADIR83) were selected and characterized with high binding affinity and specificity to the RBD of the spike protein. Aptamers (ADI25, ADI2009, ADI203L) were able to bind and pull down endogenous spike protein expressed on the surface of SARS-CoV-2 virus in COVID-19 positive patient samples and determined by liquid chromatography- tandem mass spectrometry analysis (LC-MS/MS). LC-MS/MS data confirmed that aptamers can bind to the RBD of the spike protein. Furthermore, results indicated that the combination of the 9 best aptamers inhibited the binding of the purified trimer spike protein to the ACE-2 receptor found on the surface of Vero E6 cells. In the same experiment, the combined aptamers displayed a better neutralizing effect than antibodies. The data suggests that the selected aptamers could be used in therapy to neutralize the effect of the SARS-CoV-2 virus by inhibiting the interaction between the RBD and ACE-2 receptor, preventing viral entry into target cells and therefore blocking viral replication.

Keywords: aptamer, ACE-2 receptor, binding inhibitor, COVID-19, spike protein, SARS-CoV-2, treatment

Procedia PDF Downloads 158

Authors: Aasaithambi Kalaiselvi, Michael Gabriel Paulraj, Ekambaram Nakkeeran

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Emergences of mosquito vector-borne diseases are considered as a perpetual problem globally in tropical countries. The outbreak of several diseases such as chikungunya, zika virus infection and dengue fever has created a massive threat towards the living population. Frequent usage of synthetic insecticides like Dichloro Diphenyl Trichloroethane (DDT) eventually had its adverse harmful effects on humans as well as the environment. Since there are no perennial vaccines, prevention, treatment or drugs available for these pathogenic vectors, WHO is more concerned in eradicating their breeding sites effectively without any side effects on humans and environment by approaching plant-derived natural eco-friendly bio-insecticides. The aim of this study is to investigate the larvicidal potency of Cinnamomum verum essential oil (CEO) loaded niosomes. Cholesterol and surfactant variants of Span 20, 60 and 80 were used in synthesizing CEO loaded niosomes using Transmembrane pH gradient method. The synthesized CEO loaded niosomes were characterized by Zeta potential, particle size, Fourier Transform Infrared Spectroscopy (FT-IR), GC-MS and SEM analysis to evaluate charge, size, functional properties, the composition of secondary metabolites and morphology. The Z-average size of the formed niosomes was 1870.84 nm and had good stability with zeta potential -85.3 meV. The entrapment efficiency of the CEO loaded niosomes was determined by UV-Visible Spectrophotometry. The bio-potency of CEO loaded niosomes was treated and assessed against gram-positive (Bacillus subtilis) and gram-negative (Escherichia coli) bacteria and fungi (Aspergillus fumigatus and Candida albicans) at various concentrations. The larvicidal activity was evaluated against II to IV instar larvae of Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus at various concentrations for 24 h. The mortality rate of LC₅₀ and LC₉₀ values were calculated. The results exhibited that CEO loaded niosomes have greater efficiency against mosquito larvicidal activity. The results suggest that niosomes could be used in various applications of biotechnology and drug delivery systems with greater stability by altering the drug of interest.

Keywords: Cinnamomum verum, niosomes, entrapment efficiency, bactericidal and fungicidal, mosquito larvicidal activity

Procedia PDF Downloads 127

Authors: Dorcas Ropo Abejide, Olamide Ahmed Falusi, Oladipupo Abdulazeez Yusuf Daudu, Bolaji Zuluqurineen Salihu, Muhammad Liman Muhammad

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This study evaluated the morpho-agronomic response of twenty-four (24) Nigerian Bambara groundnut landraces to water stress and genetic diversity of some selected accessions using SSR markers. The studies were carried out in the botanical garden of the Department of Plant Biology, Federal University of Technology, Minna, Niger State, Nigeria in a randomized complete block design using three replicates. Molecular analysis using SSR primers was carried out at the International Institute of Tropical Agriculture (IITA) Ibadan in order to characterize ten selected accessions comprising the seven most drought tolerant and three most susceptible accessions from the 24 accessions evaluated. Results revealed that water stress decreased morpho-agronomic traits such as plant height, leaf area, number of leaves per plant, seed yield, etc. A total of 22 alleles were detected by the SSR markers used with a mean number of 4 allelles. SSR markers MBamCO₃₃, Primer 65, and G358B2-D15 each detected 4 allelles, while Primer 3FR and 4FR detected 5 allelles each. The study revealed significantly high polymorphisms in 10 Loci. The mean value of polymorpic information content was 0.6997, implying the usefulness of the primers used in identifying genetic similarities and differences among the Bambara groundnut genotypes. The SSR analysis revealed a comparable pattern between genetic diversity and drought tolerance of the genotypes. The UPGMA dendrogram showed that at a genetic distance of 0.1, the accessions were grouped into three groups according to their level of tolerance to drought. The two most drought-tolerant accessions were grouped together, and the 5th and 6th most drought-tolerant accessions were also grouped together. This suggests that the genotypes grouped together may be genetically close, may possess similar genes, or have a common origin. The degree of genetic variants obtained from this profiling could be useful in Bambara groundnut breeding for drought tolerance. The identified drought tolerant Bambara groundnut landraces are important genetic resources for drought stress tolerance breeding programme of Bambara groundnut. The genotypes are also useful for germplasm conservation and global implications.

Keywords: Bambara groundnut, genetic diversity, germplasm, SSR markers, water stress

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Authors: Chen Guo, Heng Tang, Ben Niu

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Clustering splits objects into different groups based on similarity, making the objects have higher similarity in the same group and lower similarity in different groups. Thus, clustering can be treated as an optimization problem to maximize the intra-cluster similarity or inter-cluster dissimilarity. In real-world applications, the datasets often have some complex characteristics: sparse, overlap, high dimensionality, etc. When facing these datasets, simultaneously optimizing two or more objectives can obtain better clustering results than optimizing one objective. However, except for the objectives weighting methods, traditional clustering approaches have difficulty in solving multi-objective data clustering problems. Due to this, evolutionary multi-objective optimization algorithms are investigated by researchers to optimize multiple clustering objectives. In this paper, the Data Clustering algorithm based on Multi-objective Periodic Bacterial Foraging Optimization with two Learning Archives (DC-MPBFOLA) is proposed. Specifically, first, to reduce the high computing complexity of the original BFO, periodic BFO is employed as the basic algorithmic framework. Then transfer the periodic BFO into a multi-objective type. Second, two learning strategies are proposed based on the two learning archives to guide the bacterial swarm to move in a better direction. On the one hand, the global best is selected from the global learning archive according to the convergence index and diversity index. On the other hand, the personal best is selected from the personal learning archive according to the sum of weighted objectives. According to the aforementioned learning strategies, a chemotaxis operation is designed. Third, an elite learning strategy is designed to provide fresh power to the objects in two learning archives. When the objects in these two archives do not change for two consecutive times, randomly initializing one dimension of objects can prevent the proposed algorithm from falling into local optima. Fourth, to validate the performance of the proposed algorithm, DC-MPBFOLA is compared with four state-of-art evolutionary multi-objective optimization algorithms and one classical clustering algorithm on evaluation indexes of datasets. To further verify the effectiveness and feasibility of designed strategies in DC-MPBFOLA, variants of DC-MPBFOLA are also proposed. Experimental results demonstrate that DC-MPBFOLA outperforms its competitors regarding all evaluation indexes and clustering partitions. These results also indicate that the designed strategies positively influence the performance improvement of the original BFO.

Keywords: data clustering, multi-objective optimization, bacterial foraging optimization, learning archives

Procedia PDF Downloads 110