Search results for: genetic differentiation
523 Design of an Improved Distributed Framework for Intrusion Detection System Based on Artificial Immune System and Neural Network
Authors: Yulin Rao, Zhixuan Li, Burra Venkata Durga Kumar
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Intrusion detection refers to monitoring the actions of internal and external intruders on the system and detecting the behaviours that violate security policies in real-time. In intrusion detection, there has been much discussion about the application of neural network technology and artificial immune system (AIS). However, many solutions use static methods (signature-based and stateful protocol analysis) or centralized intrusion detection systems (CIDS), which are unsuitable for real-time intrusion detection systems that need to process large amounts of data and detect unknown intrusions. This article proposes a framework for a distributed intrusion detection system (DIDS) with multi-agents based on the concept of AIS and neural network technology to detect anomalies and intrusions. In this framework, multiple agents are assigned to each host and work together, improving the system's detection efficiency and robustness. The trainer agent in the central server of the framework uses the artificial neural network (ANN) rather than the negative selection algorithm of AIS to generate mature detectors. Mature detectors can distinguish between self-files and non-self-files after learning. Our analyzer agents use genetic algorithms to generate memory cell detectors. This kind of detector will effectively reduce false positive and false negative errors and act quickly on known intrusions.Keywords: artificial immune system, distributed artificial intelligence, multi-agent, intrusion detection system, neural network
Procedia PDF Downloads 107522 Molecular Detection of E. coli in Treated Wastewater and Well Water Samples Collected from Al Riyadh Governorate, Saudi Arabia
Authors: Hanouf A. S. Al Nuwaysir, Nadine Moubayed, Abir Ben Bacha, Islem Abid
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Consumption of waste water continues to cause significant problems for human health in both developed and developing countries. Many regulations have been implied by different world authorities controlling water quality for the presence of coliforms used as standard indicators of water quality deterioration and historically leading health protection concept. In this study, the European directive for the detection of Escherichia coli, ISO 9308-1, was applied to examine and monitor coliforms in water samples collected from Wadi Hanifa and neighboring wells, Riyadh governorate, kingdom of Saudi Arabia, which is used for irrigation and industrial purposes. Samples were taken from different locations for 8 months consecutively, chlorine concentration ranging from 0.1- 0.4 mg/l, was determined using the DPD FREE CHLORINE HACH kit. Water samples were then analyzed following the ISO protocol which relies on the membrane filtration technique (0.45µm, pore size membrane filter) and a chromogenic medium TTC, a lactose based medium used for the detection and enumeration of total coliforms and E.coli. Data showed that the number of bacterial isolates ranged from 60 to 300 colonies/100ml for well and surface water samples respectively; where higher numbers were attributed to the surface samples. Organisms which apparently ferment lactose on TTC agar plates, appearing as orange colonies, were selected and additionally cultured on EMB and MacConkey agar for a further differentiation among E.coli and coliform bacteria. Two additional biochemical tests (Cytochrome oxidase and indole from tryptophan) were also investigated to detect and differentiate the presence of E.coli from other coliforms, E. coli was identified in an average of 5 to 7colonies among 25 selected colonies.On the other hand, a more rapid, specific and sensitive analytical molecular detection namely single colony PCR was also performed targeting hha gene to sensitively detect E.coli, giving more accurate and time consuming identification of colonies considered presumptively as E.coli. Comparative methodologies, such as ultrafiltration and direct DNA extraction from membrane filters (MoBio, Grermany) were also applied; however, results were not as accurate as the membrane filtration, making it a technique of choice for the detection and enumeration of water coliforms, followed by sufficiently specific enzymatic confirmatory stage.Keywords: coliform, cytochrome oxidase, hha primer, membrane filtration, single colony PCR
Procedia PDF Downloads 317521 Effects of Chemicals in Elderly
Authors: Ali Kuzu
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There are about 800 thousand chemicals in our environment and the number is increasing more than a thousand every year. While most of these chemicals are used as components in various consumer products, some are faced as industrial waste in the environment. Unfortunately, many of these chemicals are hazardous and affect humans. According to the “International Program on Chemical Safety” of World Health Organization; Among the chronic health effects of chemicals, cancer is of major concern. Many substances have found in recent years to be carcinogenic in one or more species of laboratory animals. Especially with respect to long-term effects, the response to a chemical may vary, quantitatively or qualitatively, in different groups of individuals depending on predisposing conditions, such as nutritional status, disease status, current infection, climatic extremes, and genetic features, sex and age of the individuals. Understanding the response of such specific risk groups is an important area of toxicology research. People with age 65+ is defined as “aged (or elderly)”. The elderly population in the world is about 600 million, which corresponds to ~8 percent of the world population. While every 1 of each 4 people is aged in Japan, the elderly population is quite close to 20 percent in many developed countries. And elderly population in these countries is growing more rapidly than the total population. The negative effects of chemicals on elderly take an important place in health-care related issues in last decades. The aged population is more susceptible to the harmful effects of environmental chemicals. According to the poor health of the organ systems in elderly, the ability of their body to eliminate the harmful effects and chemical substances from their body is also poor. With the increasing life expectancy, more and more people will face problems associated with chemical residues.Keywords: elderly, chemicals’ effects, aged care, care need
Procedia PDF Downloads 454520 Apolipoprotein A1 -75 G to a Substitution and Its Relationship with Serum ApoA1 Levels among Indian Punjabi Population
Authors: Savjot Kaur, Mridula Mahajan, AJS Bhanwer, Santokh Singh, Kawaljit Matharoo
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Background: Disorders of lipid metabolism and genetic predisposition are CAD risk factors. ApoA1 is the apolipoprotein component of anti-atherogenic high density lipoprotein (HDL) particles. The protective action of HDL and ApoA1 is attributed to their central role in reverse cholesterol transport (RCT). Aim: This study was aimed at identifying sequence variations in ApoA1 (-75G>A) and its association with serum ApoA1 levels. Methods: A total of 300 CAD patients and 300 Normal individuals (controls) were analyzed. PCR-RFLP method was used to determine the DNA polymorphism in the ApoA1 gene, PCR products digested with restriction enzyme MspI, followed by Agarose Gel Electrophoresis. Serum apolipoprotein A1 concentration was estimated with immunoturbidimetric method. Results: Deviation from Hardy- Weinberg Equilibrium (HWE) was observed for this gene variant. The A- allele frequency was higher among Coronary Artery disease patients (53.8) compared to controls (45.5), p= 0.004, O.R= 1.38(1.11-1.75). Under recessive model analysis (AA vs. GG+GA) AA genotype of ApoA1 G>A substitution conferred ~1 fold increased risk towards CAD susceptibility (p= 0.002, OR= 1.72(1.2-2.43). With serum ApoA1 levels < 107 A allele frequency was higher among CAD cases (50) as compared to controls (43.4) [p=0.23, OR= 1.2(0.84-2)] and there was zero % occurrence of A allele frequency in individuals with ApoA1 levels > 177. Conclusion: Serum ApoA1 levels were associated with ApoA1 promoter region variation and influence CAD risk. The individuals with the APOA1 -75 A allele confer excess hazard of developing CAD as a result of its effect on low serum concentrations of ApoA1.Keywords: apolipoprotein A1 (G>A) gene polymorphism, coronary artery disease (CAD), reverse cholesterol transport (RCT)
Procedia PDF Downloads 313519 Distributed System Computing Resource Scheduling Algorithm Based on Deep Reinforcement Learning
Authors: Yitao Lei, Xingxiang Zhai, Burra Venkata Durga Kumar
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As the quantity and complexity of computing in large-scale software systems increase, distributed system computing becomes increasingly important. The distributed system realizes high-performance computing by collaboration between different computing resources. If there are no efficient resource scheduling resources, the abuse of distributed computing may cause resource waste and high costs. However, resource scheduling is usually an NP-hard problem, so we cannot find a general solution. However, some optimization algorithms exist like genetic algorithm, ant colony optimization, etc. The large scale of distributed systems makes this traditional optimization algorithm challenging to work with. Heuristic and machine learning algorithms are usually applied in this situation to ease the computing load. As a result, we do a review of traditional resource scheduling optimization algorithms and try to introduce a deep reinforcement learning method that utilizes the perceptual ability of neural networks and the decision-making ability of reinforcement learning. Using the machine learning method, we try to find important factors that influence the performance of distributed system computing and help the distributed system do an efficient computing resource scheduling. This paper surveys the application of deep reinforcement learning on distributed system computing resource scheduling proposes a deep reinforcement learning method that uses a recurrent neural network to optimize the resource scheduling, and proposes the challenges and improvement directions for DRL-based resource scheduling algorithms.Keywords: resource scheduling, deep reinforcement learning, distributed system, artificial intelligence
Procedia PDF Downloads 110518 Consumption and Diffusion Based Model of Tissue Organoid Development
Authors: Elena Petersen, Inna Kornienko, Svetlana Guryeva, Sergey Simakov
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In vitro organoid cultivation requires the simultaneous provision of necessary vascularization and nutrients perfusion of cells during organoid development. However, many aspects of this problem are still unsolved. The functionality of vascular network intergrowth is limited during early stages of organoid development since a function of the vascular network initiated on final stages of in vitro organoid cultivation. Therefore, a microchannel network should be created in early stages of organoid cultivation in hydrogel matrix aimed to conduct and maintain minimally required the level of nutrients perfusion for all cells in the expanding organoid. The network configuration should be designed properly in order to exclude hypoxic and necrotic zones in expanding organoid at all stages of its cultivation. In vitro vascularization is currently the main issue within the field of tissue engineering. As perfusion and oxygen transport have direct effects on cell viability and differentiation, researchers are currently limited only to tissues of few millimeters in thickness. These limitations are imposed by mass transfer and are defined by the balance between the metabolic demand of the cellular components in the system and the size of the scaffold. Current approaches include growth factor delivery, channeled scaffolds, perfusion bioreactors, microfluidics, cell co-cultures, cell functionalization, modular assembly, and in vivo systems. These approaches may improve cell viability or generate capillary-like structures within a tissue construct. Thus, there is a fundamental disconnect between defining the metabolic needs of tissue through quantitative measurements of oxygen and nutrient diffusion and the potential ease of integration into host vasculature for future in vivo implantation. A model is proposed for growth prognosis of the organoid perfusion based on joint simulations of general nutrient diffusion, nutrient diffusion to the hydrogel matrix through the contact surfaces and microchannels walls, nutrient consumption by the cells of expanding organoid, including biomatrix contraction during tissue development, which is associated with changed consumption rate of growing organoid cells. The model allows computing effective microchannel network design giving minimally required the level of nutrients concentration in all parts of growing organoid. It can be used for preliminary planning of microchannel network design and simulations of nutrients supply rate depending on the stage of organoid development.Keywords: 3D model, consumption model, diffusion, spheroid, tissue organoid
Procedia PDF Downloads 307517 Inherited Eye Diseases in Africa: A Scoping Review and Strategy for an African Longitudinal Eye Study
Authors: Bawa Yusuf Muhammad, Musa Abubakar Kana, Aminatu Abdulrahman, Kerry Goetz
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Background: Inherited eye diseases are disorders that affect globally, 1 in 1000 people. The six main world populations have created databases containing information on eye genotypes. Aim: The aim of the scoping review was to mine and present the available information to date on the genetics of inherited eye diseases within the African continent. Method: Literature Search Strategy was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed and Google Scholar searched for articles on inherited eye diseases from inception to 20th June 2022. Both Original and review articles that report on inherited, genetic or developmental/congenital eye diseases within the African Continent were included in the research. Results: A total of 1162 citations were obtained, but only 37 articles were reviewed based on the inclusion and exclusion criteria. The highest output of publications on inherited eye diseases comes from South Africa and Tunisia (about 43%), followed by Morocco and Egypt (27%), then Sub-Saharan Africa and North Africa (13.50%), while the remaining articles (16.5%) originated from Nigeria, Ghana, Mauritania Cameroon, Zimbabwe and combined article between Zimbabwe and Cameroon. Glaucoma and inherited retinal disorders represent the most studied diseases, followed by Albinism and congenital cataracts, respectively. Conclusion: Despite the growing research from Tunisia, Morocco, Egypt and South Africa, Sub-Saharan Africa remains almost a virgin region to explore the genetics of eye diseases.Keywords: inherited eye diseases, Africa, scoping review, longitudinal eye study
Procedia PDF Downloads 55516 Salicylic Acid Signalling in Relation to Root Colonization in Rice
Authors: Seema Garcha, Sheetal Chopra, Navraj Sarao
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Plant hormones play a role in internal colonization by beneficial microbes and also systemic acquired resistance. They define qualitative and quantitative nature of root microbiome and also influence dynamics of root rhizospheric soil. The present study is an attempt to relate salicylic acid (signal molecule) content and qualitative nature of root endophytes at various stages in the growth of rice varieties of commercial value- Parmal 121 and Basmati 1121. Root seedlings of these varieties were raised using tissue culture techniques and then they were transplanted in the fields. Cultivation was done using conventional methods in agriculture. Field soil contained 0.39% N, 75.12 Kg/hectare of phosphorus and 163.0 Kg/hectare of potassium. Microfloral profiling of the root tissue was done using the selective microbiological medium. The salicylic acid content was estimated using HPLC-Agilent 1100 HPLC Series. Salicylic acid level of Basmati 1121 remained relatively low at the time of transplant and 90 days after transplant. It increased marginally at 60 days. A similar trend was observed with Parmal 121 as well. However, Parmal variety recorded 0.935 ug/g of salicylic acid at 60 days after transplant. Salicylic acid content decreased after 90 days as both the rice varieties remained disease free. The endophytic root microflora was established by 60 days after transplant in both the varieties after which their population became constant. Rhizobium spp dominated over Azotobacter spp. Genetic profiling of endophytes for nitrogen-fixing ability is underway.Keywords: plant-microbe interaction, rice, root microbiome, salicylic acid
Procedia PDF Downloads 200515 Budget Optimization for Maintenance of Bridges in Egypt
Authors: Hesham Abd Elkhalek, Sherif M. Hafez, Yasser M. El Fahham
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Allocating limited budget to maintain bridge networks and selecting effective maintenance strategies for each bridge represent challenging tasks for maintenance managers and decision makers. In Egypt, bridges are continuously deteriorating. In many cases, maintenance works are performed due to user complaints. The objective of this paper is to develop a practical and reliable framework to manage the maintenance, repair, and rehabilitation (MR&R) activities of Bridges network considering performance and budget limits. The model solves an optimization problem that maximizes the average condition of the entire network given the limited available budget using Genetic Algorithm (GA). The framework contains bridge inventory, condition assessment, repair cost calculation, deterioration prediction, and maintenance optimization. The developed model takes into account multiple parameters including serviceability requirements, budget allocation, element importance on structural safety and serviceability, bridge impact on network, and traffic. A questionnaire is conducted to complete the research scope. The proposed model is implemented in software, which provides a friendly user interface. The framework provides a multi-year maintenance plan for the entire network for up to five years. A case study of ten bridges is presented to validate and test the proposed model with data collected from Transportation Authorities in Egypt. Different scenarios are presented. The results are reasonable, feasible and within acceptable domain.Keywords: bridge management systems (BMS), cost optimization condition assessment, fund allocation, Markov chain
Procedia PDF Downloads 291514 Effect of Feed Additive on Cryopreservation of Barki Ram Semen
Authors: Abdurzag Kerban, Mostfa M. Abou-Ahmed, Abdelrof M. Ghallab, Mona H. Shaker
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Preservation of semen had a major impact on sheep genetic breeding. The aim of this study was to evaluate the effect of protected fat, probiotic and zinc-enriched diets on semen freezability. Twenty two Barki rams were randomly assigned into four groups; Group I (n=5) was fed the basal diet enriched with 3.7% of dry fat/kg concentration/day, Group II (n=5) was fed a basal diet-enriched with 10gm of probiotic /head/day, Group III (n=6) was fed on the basal diet enriched with 100 ppm of 10% zinc chelated with methionine/kg dry matter/day and Group IV (n=6) was served as control. A pool of three to four ejaculates were pooled from rams within a period of ten weeks. Semen was diluted in egg yolk-Tris diluent and processed in 0.25 ml straw. Motility was evaluated after dilution, before freezing and post-thawing at 0, 1, 2 and 3 hour incubation. Viability index, acrosome integrity and leakage of intracellular enzymes (Aspartat aminotransferase and Alkline phosphatase) were also evaluated. Spermatozoa exhibited highly significant (P<0.01) percentages of motility at 0, 1, 2, and 3 hours incubation after thawing, viability index and acrosome integrity in rams fed a diet enriched with protected fat and zinc groups as compared with probiotic and control groups. Also, the mean value of extracellular leakage of AST was significantly lower in fat and zinc group as compared with probiotic and control groups. In conclusion, semen freezability was improved in animals fed a diet fortified with fat and zinc with no significant improvement in animals fed the probiotic-enriched diet.Keywords: Barki ram semen, freezing, straw, feed additives
Procedia PDF Downloads 782513 A Prediction Model for Dynamic Responses of Building from Earthquake Based on Evolutionary Learning
Authors: Kyu Jin Kim, Byung Kwan Oh, Hyo Seon Park
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The seismic responses-based structural health monitoring system has been performed to prevent seismic damage. Structural seismic damage of building is caused by the instantaneous stress concentration which is related with dynamic characteristic of earthquake. Meanwhile, seismic response analysis to estimate the dynamic responses of building demands significantly high computational cost. To prevent the failure of structural members from the characteristic of the earthquake and the significantly high computational cost for seismic response analysis, this paper presents an artificial neural network (ANN) based prediction model for dynamic responses of building considering specific time length. Through the measured dynamic responses, input and output node of the ANN are formed by the length of specific time, and adopted for the training. In the model, evolutionary radial basis function neural network (ERBFNN), that radial basis function network (RBFN) is integrated with evolutionary optimization algorithm to find variables in RBF, is implemented. The effectiveness of the proposed model is verified through an analytical study applying responses from dynamic analysis for multi-degree of freedom system to training data in ERBFNN.Keywords: structural health monitoring, dynamic response, artificial neural network, radial basis function network, genetic algorithm
Procedia PDF Downloads 300512 Susceptibility Assessment and Genetic Diversity of Iranian and CIMMYT Wheat Genotypes to Common Root Rot Disease Bipolaris sorokiniana
Authors: Mehdi Nasr Esfahani, Abdal-Rasool Gholamalian, Abdelfattah A. Dababat
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Wheat, Triticum aestivum L. is one of the most important and strategic crops in the human diet. Several diseases threaten this particular crop. Common root rot disease of wheat by a fungal agent, Bipolaris sorokiniana is one of the important diseases, causing considerable losses worldwide. Resistant sources are the only feasible and effective method of control for managing diseases. In this study, the response of 33 domestic and exotic wheat genotypes, including cultivars and promising lines were screened to B. sorokiniana at greenhouse and field conditions, based on five scoring scale indexes of 0 to 100 severity percentage. The screening was continued on resistant wheat genotypes and repeated several times to confirm the greenhouse and field results. Statistical and cluster analysis of data was performed using SAS and SPSS software, respectively. The results showed that, the response of wheat genotypes to the disease in the greenhouse and field conditions was highly significant. The highest rate of common root rot disease infection, B. sorokiniana in the greenhouse and field, was of CVS. Karkheh and Beck Cross-Roshan with 60.83% and 59.16% disease severity respectively, and the lowest one were in cv. Alvand with 18.33%, followed by cv. Baharan with 19.16% disease severity, with a highly significant difference respectively. The remaining wheat genotypes were located in between these two highest and lowest infected groups to B. sorokiniana significantly. There was a high correlation coefficient between the related statistical groups and cluster analysis.Keywords: wheat, rot, root, crown, fungus, genotype, resistance
Procedia PDF Downloads 133511 Comparision of Neospora caninum Experimental Infection in Pigeons and Chickens Embryonated Eggs
Authors: S. Bahrami, A. Rezaie, Z. Boroumand, S. Ghavami
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Neospora caninum is protozoan parasite which can cause a serious disease in dogs and cattle. It has been shown that birds may be a permissive intermediate host for N. caninum since parasite DNA has been detected in tissues from birds. It is showed that embryonated chicken egg can be used as an animal model for experimental infection. The aim of present study was to compare experimental infection of Neospora in chicken and pigeons embryonated eggs. An infection with N. caninum Nc1 isolate was conducted in chicken and pigeons embryonated eggs to evaluate LD50. After calculation of LD50, 2LD50 of tachyzoites were injected to eggs. Macroscopic changes of each embryo were noticed and to investigate the parasite distribution in tissues immunohistochemistry (IHC) and molecular methods were used. In the present study, histopathological changes were considered and sections to those used for histopathological examination including heart, liver, brain and chorioallantoic (CA) membrane were subjected to IHC, too. For PCR procedure, primer pair Np21/Np6 was used for amplification of the Nc5 gene. Pigeon's embryo showed more macroscopic changes than chicken embryo. A hemorrhage of the CA was the main grass lesion. All the infected tissues had histopathological changes. Microscopic examination of tissues revealed acute neosporosis due to hemorrhage, necrosis and infiltration of mononuclear inflammatory cells. Based on IHC and molecular results, the parasite aggregation in the heart was more predominant than in the other tissues. These results reinforce that there is genetic susceptibility to N. caninum in pigeons embryonated eggs like chickens embryonated eggs and provide new insights to research an inexpensive and available animal model for N. caninum.Keywords: immunohistochemistry, Neospora caninum, PCR, pigeon embryonated egg
Procedia PDF Downloads 343510 Molecular Characterization and Phylogenetic Analysis of Capripoxviruses from Outbreak in Iran 2021
Authors: Maryam Torabi, Habibi, Abdolahi, Mohammadi, Hassanzadeh, Darban Maghami, Baghi
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Sheeppox Virus (SPPV) and goatpox virus (GTPV) are considerable diseases of sheep, and goats, caused by viruses of the Capripoxvirus (CaPV) genus. They are responsible for economic losses. Animal mortality, morbidity, cost of vaccinations, and restrictions in animal products’ trade are the reasons of economic losses. Control and eradication of CaPV depend on early detection of outbreaks so that molecular detection and genetic analysis could be effective to this aim. This study was undertaken to molecularly characterize SPPV and GTPV strains that have been circulating in Iran. 120 skin papules and nodule biopsies were collected from different regions of Iran and were examined for SPPV, GTPV viruses using TaqMan Real -Time PCR. Some of these amplified genes were sequenced, and phylogenetic trees were constructed. Out of the 120 samples analysed, 98 were positive for CaPV by Real- Time PCR (81.6%), and most of them wereSPPV. then 10 positive samples were sequenced and characterized by amplifying the ORF 103CaPV gene. sequencing and phylogenetic analysis for these positive samples revealed a high percentage of identity with SPPV isolated from different countries in Middle East. In conclusions, molecular characterization revealed nearly complete identity with all recent SPPVs strains in local countries that requires further studies to monitor the virus evolution and transmission pathways to better understand the virus pathobiology that will help for SPPV control.Keywords: molecular epidemiology, Real-Time PCR, phylogenetic analysis, capripoxviruses
Procedia PDF Downloads 147509 Thrombophilic Mutations in Tunisian Patients with Recurrent Pregnancy Loss
Authors: Frikha Rim, Abdelmoula Bouayed Nouha, Rebai Tarek
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Pregnancy is a hypercoagulable state which causing a defective maternal haemostatic response and leading to thrombosis of the uteroplacental vasculature, that might cause pregnancy complications as recurrent pregnancy loss (RPL). Since heritable Thrombophilic defects are associated with increased thrombosis, their prevalence was evaluated in patients with special emphasis on combinations of the above pathologies. Especially, Factor V Leiden (FVL) G1691A, methylene tetra hydro folate reductase (MTHFR) C677T, and factor II (FII) G20210A mutations are three important causes of thrombophilia, which might be related to recurrent pregnancy loss (RPL). In this study we evaluated the presence of these three mutations [factor V Leiden (FVL), prothrombin G20210A (PTG) and methylenetetrahydrofolate reductase (MTHFR) C677T] amongst 35 Tunisian women with more than 2 miscarriages, referred to our genetic counseling. DNA was extracted from peripheral blood samples and PCR-RFLP was performed for the molecular diagnosis of each mutation. Factor V Leiden and Prothrombin mutation were detected respectively in 5.7% and 2.9% of women with particular history of early fetal loss and thrombotic events. Despites the luck of strength of this study, we insist that testing for the most inherited thrombophilia (FVL and FII mutation) should be performed in women with RPL in the context of thrombotic events. Multi-centre collaboration is necessary to clarify the real impact of thrombotic molecular defects on the pregnancy outcome, to ascertain the effect of thrombophilia on recurrent pregnancy loss and then to evaluate the appropriate therapeutic approach.Keywords: thrombophilia, recurrent pregnancy loss, factor V Leiden, prothrombin G20210A, methylene tetra hydro folate reductase
Procedia PDF Downloads 454508 Sequence Polymorphism and Haplogroup Distribution of Mitochondrial DNA Control Regions HVS1 and HVS2 in a Southwestern Nigerian Population
Authors: Ogbonnaya O. Iroanya, Samson T. Fakorede, Osamudiamen J. Edosa, Hadiat A. Azeez
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The human mitochondrial DNA (mtDNA) is about 17 kbp circular DNA fragments found within the mitochondria together with smaller fragments of 1200 bp known as the control region. Knowledge of variation within populations has been employed in forensic and molecular anthropology studies. The study was aimed at investigating the polymorphic nature of the two hypervariable segments (HVS) of the mtDNA, i.e., HVS1 and HVS2, and to determine the haplogroup distribution among individuals resident in Lagos, Southwestern Nigeria. Peripheral blood samples were obtained from sixty individuals who are not related maternally, followed by DNA extraction and amplification of the extracted DNA using primers specific for the regions under investigation. DNA amplicons were sequenced, and sequenced data were aligned and compared to the revised Cambridge Reference Sequence (rCRS) GenBank Accession number: NC_012920.1) using BioEdit software. Results obtained showed 61 and 52 polymorphic nucleotide positions for HVS1 and HVS2, respectively. While a total of three indels mutation were recorded for HVS1, there were seven for HVS2. Also, transition mutations predominate nucleotide change observed in the study. Genetic diversity (GD) values for HVS1 and HVS2 were estimated to be 84.21 and 90.4%, respectively, while random match probability was 0.17% for HVS1 and 0.89% for HVS2. The study also revealed mixed haplogroups specific to the African (L1-L3) and the Eurasians (U and H) lineages. New polymorphic sites obtained from the study are promising for human identification purposes.Keywords: hypervariable region, indels, mitochondrial DNA, polymorphism, random match probability
Procedia PDF Downloads 112507 Chemical Composition and Biological Investigation of Halpophyllum tuberculatum A. Juss (Rutaceae) Essential Oils Growing in Libya
Authors: O. M. M. Sabry, Abeer M. El Sayed
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The essential oils from the aerial parts and flowers of Haplophyllum tuberculatum (Forsskal) Adr. Juss (Rutaceae) growing in Libya were obtained separately by hydro-distillation using a Clevenger-type apparatus. The essential oils yield were (0.4, 1.5w/w%) respectively based on the dry weight of the plant. The oils were analyzed by GC-MS. Twenty four constituents, amounting to 96.6%, were identified in the oil of the aerial parts. The predominant compounds were among the non oxygenated terpenoids (82.4%) as monoterpene hydrocarbons, represented by sabinen (26.4 %), δ-terpinen (26 %), β-phellandrene (10.4%) and 3-carene (3.86%). Zingiberine (0.4%) and β-sesquiphellandrene (0.12%) were the major sesquiterpene hydrocarbons identified. Oxygenated monoterpenes were represented by eucalyptol (5.5%) and piperitone (5.55%). Twenty six constituents, equivalent to 99.5%, were identified in the oil of the flowers. The dominance of monoterpene hydrocarbons in the flowers oil can be attributed to the high percentage of γ-terpinen (38.44%), β-phellandrene (10.0%), α- phellandrene (2.33%), 3,4-dimethyl-1,5-cyclooctadiene (6.67%), β-myrecene (6.04%), 3-carene (5.43%) and α-pinene (1.3%).While the oxygenated monoterpenes can be contributed to the trans-piperitol (4.67%) and piperitone (2.07%). Sesquiterpene hydrocarbons were not identified in the oil of the flower of H. tuberculatum. Variation in constitution between oils of Libyan H. tuberculatum and that obtained from other countries can be due to both environmental and genetic factors. The essential oils have demonstrated variable antimicrobial activities against certain micro-organisms. Also have revealed marked in vitro cytotoxicity against lung (H1299), liver (HEPG2) carcinoma cell line and variably effective as anti-inflammatory and antioxidant.Keywords: Halpophyllum tuberculatum, rutaceae, essential oil, antimicrobial, anti-inflammatory, antitumor, antioxidant, Libya
Procedia PDF Downloads 477506 Effects of Plumage Colour on Measurable Attributes of Indigenous Chickens in North Central Nigeria
Authors: Joseph J. Okoh, Samuel T. Mbap, Tahir Ibrahim, Yusuf P. Mancha
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The influence of plumage colour on measurable attributes of 6176 adult indigenous chickens of mixed-sex from four states of the North Central Zone of Nigeria namely; Nasarawa, Niger, Benue, Kogi and the Federal Capital Territory (FCT) Abuja were assessed. The overall average body weight of the chickens was 1.95 ± 0.03kg. The body weights of black, white, black/white, brown, black/brown, grey and mottled chicken however were 1.87 ± 0.04, 1.94 ± 0.04, 1.95 ± 0.03, 1.93 ± 0.03, 2.01 ± 0.04, 1.96 ± 0.04 and 1.94±0.14kg respectively. Only body length did not vary by plumage colour. The others; body weight and width, shank, comb and breast length, breast height (p < 0.001), beak and wing lengths (p < 0.001) varied significantly. Generally, no colour was outrightly superior to others in all body measurements. However, body weight and breast height were both highest in black/brown chickens which also had the second highest breast length. Body width, shank, beak, comb and wing lengths were highest in grey chickens but lowest in those with white colour and combinations. Egg quality was on the other hand mostly lowest in grey chickens. In selection for genetic improvement in body measurements, black/brown and grey chickens should be favoured. However, in view of the known negative relationship between body weight and egg attributes, selection in favour of grey plumage may result in chickens of poor egg attributes. Therefore, grey chickens should be selected against egg quality.Keywords: body weight, indigenous chicken, measurements, plumage colour
Procedia PDF Downloads 126505 Study of seum Tumor Necrosis Factor Alpha in Pediatric Patients with Hemophilia A
Authors: Sara Mohammad Atef Sabaika
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Background: The development of factor VIII (FVIII) inhibitor and hemophilic arthropathy in patients with hemophilia A (PWHA) are a great challenge for hemophilia care. Both genetic and environmental factors led to complications in PWHA. The development of inhibitory antibodies is usually induced by the immune response. Tumor necrosis factor α (TNF-α), one of the cytokines, might contribute to its polymorphism. Aim: Study the association between tumor necrosis alpha level and genotypes in pediatric patients with hemophilia A and its relation to inhibitor development and joint status. Methods: A cross-sectional study was conducted among a sufficient number of PWHA attending the Pediatric Hematology and Oncology Unit, Pediatric department in Menoufia University hospital. The clinical parameters, FVIII, FVIII inhibitor, and serum TNF-α level were assessed. The genotyping of −380G > A TNF-α gene polymorphism was performed using real time polymerase chain reaction. Results: Among the 50 PWHA, 28 (56%) were identified as severe PWHA. The FVIII inhibitor was identified in 6/28 (21.5%) of severe PWHA. There was a significant correlation between serum TNF-α level and the development of inhibitor (p = 0:043). There was significant correlation between polymorphisms of −380G > A TNF-α gene and hemophilic arthropathy development (p = 0:645). Conclusion: The prevalence of FVIII inhibitor in severe PWHA in Menoufia was 21.5%. The frequency of replacement therapy is a risk factor for inhibitor development. Serum TNF-α level and its gene polymorphism might be used to predict inhibitor development and joint status in pediatric patients with hemophilia A.Keywords: hemophilic arthropathy, TNF alpha., patients witb hemophilia A PWHA, inhibitor
Procedia PDF Downloads 92504 Multi-Point Dieless Forming Product Defect Reduction Using Reliability-Based Robust Process Optimization
Authors: Misganaw Abebe Baye, Ji-Woo Park, Beom-Soo Kang
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The product quality of multi-point dieless forming (MDF) is identified to be dependent on the process parameters. Moreover, a certain variation of friction and material properties may have a substantially worse influence on the final product quality. This study proposed on how to compensate the MDF product defects by minimizing the sensitivity of noise parameter variations. This can be attained by reliability-based robust optimization (RRO) technique to obtain the optimal process setting of the controllable parameters. Initially two MDF Finite Element (FE) simulations of AA3003-H14 saddle shape showed a substantial amount of dimpling, wrinkling, and shape error. FE analyses are consequently applied on ABAQUS commercial software to obtain the correlation between the control process setting and noise variation with regard to the product defects. The best prediction models are chosen from the family of metamodels to swap the computational expensive FE simulation. Genetic algorithm (GA) is applied to determine the optimal process settings of the control parameters. Monte Carlo Analysis (MCA) is executed to determine how the noise parameter variation affects the final product quality. Finally, the RRO FE simulation and the experimental result show that the amendment of the control parameters in the final forming process leads to a considerably better-quality product.Keywords: dimpling, multi-point dieless forming, reliability-based robust optimization, shape error, variation, wrinkling
Procedia PDF Downloads 252503 Variability for Nodulation and Yield Traits in Biofertilizer Treated and Untreated Pea (Pisum sativum L.) Varieties
Authors: Areej Javaid, Nishat Fatima, Mehwish Naseer
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There is a tremendous use of biofertilizers in agriculture to increase crop productivity. Pakistan spends a huge amount on the purchase of synthetic fertilizers every year. The use of natural compounds to harness crop productivity is the major area of interest nowadays due to being safe for human health and the environment as well. Legumes have the intrinsic quality to enrich the nutrient status of soil because of the presence of nitrogen fixation bacteria on nodules. This research determined the effect of biofertilizer on nodulation attributes and yield of the pea plant. Seeds of pea varieties were treated with a slurry of biofertilizer prepared in a 10% sugar solution just before seed sowing. The impact of biofertilizer on different parameters of growth, yield and nodulation was observed. Analysis of variance showed that plant height, days to flowering, number of nodes, days to first pod, root length and plant height exhibited significant genetic variation. All the yield parameters, including the number of pods per plant, number of seeds per pod, seed fresh and dry weight showed significant results under treatment. Among nodulation parameters, nodule number responded positively to biofertilizer treatment. Genotypes 2001-40 showed better performance followed by 2001-20 and LINA-PAK in all the parameters, whereas 2001-40 and 2001-20 performed well in nodulation and yield parameters. Consequently, seed treatment with biofertilizer before sowing is recommended to obtain higher crop yield.Keywords: biological nitrogen fixation, correlation analysis, quantitative inheritance, varietal responses
Procedia PDF Downloads 151502 A Content Analysis of the Introduction to the Philosophy of Religion Literature Published in the West between 1950-2010 in Terms of Definition, Method and Subjects
Authors: Fatih Topaloğlu
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Although philosophy is inherently a theoretical and intellectual activity, it should not be denied that environmental conditions influence the formation and shaping of philosophical thought. In this context, it should be noted that the Philosophy of Religion has been influential in the debates in the West, especially since the beginning of the 20th century, and that this influence has dimensions that cannot be limited to academic or intellectual fields. The issues and problems that fall within the field of interest of Philosophy of Religion are followed with interest by a significant proportion of society through popular publications. Philosophy of Religion has its share in many social, economic, cultural, scientific, political and ethical developments. Philosophy of Religion, in the most general sense, can be defined as a philosophical approach to religion or a philosophical way of thinking and discussing religion. Philosophy of Religion tries to explain the epistemological foundations of concepts such as belief and faith that shape religious life by revealing their meaning for the individual. Thus, Philosophy of Religion tries to evaluate the effect of beliefs on the individual's values, judgments and behaviours with a comprehensive and critical eye. The Philosophy of Religion, which tries to create new solutions and perspectives by applying the methods of philosophy to religious problems, tries to solve these problems not by referring to the holy book or religious teachings but by logical proofs obtained through the possibilities of reason and evidence filtered through the filter of criticism. Although there is no standard method for doing Philosophy of Religion, it can be said that an approach that can be expressed as thinking about religion in a rational, objective, and consistent way is generally accepted. The evaluations made within the scope of Philosophy of Religion have two stages. The first is the definition stage, and the second is the evaluation stage. In the first stage, the data of different scientific disciplines, especially other religious sciences, are utilized to define the issues objectively. In the second stage, philosophical evaluations are made based on this foundation. During these evaluations, the issue of how the relationship between religion and philosophy should be established is extremely sensitive. The main thesis of this paper is that the Philosophy of Religion, as a branch of philosophy, has been affected by the conditions caused by the historical experience through which it has passed and has differentiated its subjects and the methods it uses to realize its philosophical acts over time under the influence of these conditions. This study will attempt to evaluate the validity of this study based on the "Introduction to Philosophy of Religion" literature, which we assume reflects this differentiation. As a result of this examination will aim to reach some factual conclusions about the nature of both philosophical and religious thought, to determine the phases that the Philosophy of Religion as a discipline has gone through since the day it emerged, and to investigate the possibilities of a holistic view of the field.Keywords: content analysis, culture, history, philosophy of religion, method
Procedia PDF Downloads 55501 Application of Mesenchymal Stem Cells in Diabetic Therapy
Authors: K. J. Keerthi, Vasundhara Kamineni, A. Ravi Shanker, T. Rammurthy, A. Vijaya Lakshmi, Q. Hasan
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Pancreatic β-cells are the predominant insulin-producing cell types within the Islets of Langerhans and insulin is the primary hormone which regulates carbohydrate and fat metabolism. Apoptosis of β-cells or insufficient insulin production leads to Diabetes Mellitus (DM). Current therapy for diabetes includes either medical management or insulin replacement and regular monitoring. Replacement of β- cells is an attractive treatment option for both Type-1 and Type-2 DM in view of the recent paper which indicates that β-cells apoptosis is the common underlying cause for both the Types of DM. With the development of Edmonton protocol, pancreatic β-cells allo-transplantation became possible, but this is still not considered as standard of care due to subsequent requirement of lifelong immunosuppression and the scarcity of suitable healthy organs to retrieve pancreatic β-cell. Fetal pancreatic cells from abortuses were developed as a possible therapeutic option for Diabetes, however, this posed several ethical issues. Hence, in the present study Mesenchymal stem cells (MSCs) were differentiated into insulin producing cells which were isolated from Human Umbilical cord (HUC) tissue. MSCs have already made their mark in the growing field of regenerative medicine, and their therapeutic worth has already been validated for a number of conditions. HUC samples were collected with prior informed consent as approved by the Institutional ethical committee. HUC (n=26) were processed using a combination of both mechanical and enzymatic (collagenase-II, 100 U/ml, Gibco ) methods to obtain MSCs which were cultured in-vitro in L-DMEM (Low glucose Dulbecco's Modified Eagle's Medium, Sigma, 4.5 mM glucose/L), 10% FBS in 5% CO2 incubator at 37°C. After reaching 80-90% confluency, MSCs were characterized with Flowcytometry and Immunocytochemistry for specific cell surface antigens. Cells expressed CD90+, CD73+, CD105+, CD34-, CD45-, HLA-DR-/Low and Vimentin+. These cells were differentiated to β-cells by using H-DMEM (High glucose Dulbecco's Modified Eagle's Medium,25 mM glucose/L, Gibco), β-Mercaptoethanol (0.1mM, Hi-Media), basic Fibroblast growth factor (10 µg /L,Gibco), and Nicotinamide (10 mmol/L, Hi-Media). Pancreatic β-cells were confirmed by positive Dithizone staining and were found to be functionally active as they released 8 IU/ml insulin on glucose stimulation. Isolating MSCs from usually discarded, abundantly available HUC tissue, expanding and differentiating to β-cells may be the most feasible cell therapy option for the millions of people suffering from DM globally.Keywords: diabetes mellitus, human umbilical cord, mesenchymal stem cells, differentiation
Procedia PDF Downloads 258500 Polymorphisms of Calpastatin Gene and Its Association with Growth Traits in Indonesian Thin Tail Sheep
Authors: Muhammad Ihsan Andi Dagong, Cece Sumantri, Ronny Rachman Noor, Rachmat Herman, Mohamad Yamin
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Calpastatin involved in various physiological processes in the body such as the protein turnover, growth, fusion and mioblast migration. Thus, allegedly Calpastatin gene diversity (CAST) have an association with growth and potential use as candidate genes for growth trait. This study aims to identify the association between the genetic diversity of CAST gene with some growth properties such as body dimention (morphometric), body weight and daily weight gain in sheep. A total of 157 heads of Thin Tail Sheep (TTS) reared intensively for fattening purposes in the uniform environmental conditions. Overall sheep used were male, and maintained for 3 months. The parameters of growth properties were measured among others: body weight gain (ADG) (g/head / day), body weight (kg), body length (cm), chest circumference (cm), height (cm). All the sheep were genotyped by using PCR-SSCP (single strand conformational polymorphism) methods. CAST gene in locus fragment intron 5 - exon 6 were amplified with a predicted length of about 254 bp PCR products. Then the sheep were stratified based on their CAST genotypes. The result of this research showed that no association were found between the CAST gene variations with morphometric body weight, but there was a significant association with daily body weight gain (ADG) in sheep observed. CAST-23 and CAST-33 genotypes has higher average daily gain than other genotypes. CAST-23 and CAST-33 genotypes that carrying the CAST-2 and CAST-3 alleles potential to be used in the selection of the nature of the growth trait of the TTS sheep.Keywords: body weight, calpastatin, genotype, growth trait, thin tail sheep
Procedia PDF Downloads 319499 Parameter Identification Analysis in the Design of Rock Fill Dams
Authors: G. Shahzadi, A. Soulaimani
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This research work aims to identify the physical parameters of the constitutive soil model in the design of a rockfill dam by inverse analysis. The best parameters of the constitutive soil model, are those that minimize the objective function, defined as the difference between the measured and numerical results. The Finite Element code (Plaxis) has been utilized for numerical simulation. Polynomial and neural network-based response surfaces have been generated to analyze the relationship between soil parameters and displacements. The performance of surrogate models has been analyzed and compared by evaluating the root mean square error. A comparative study has been done based on objective functions and optimization techniques. Objective functions are categorized by considering measured data with and without uncertainty in instruments, defined by the least square method, which estimates the norm between the predicted displacements and the measured values. Hydro Quebec provided data sets for the measured values of the Romaine-2 dam. Stochastic optimization, an approach that can overcome local minima, and solve non-convex and non-differentiable problems with ease, is used to obtain an optimum value. Genetic Algorithm (GA), Particle Swarm Optimization (PSO) and Differential Evolution (DE) are compared for the minimization problem, although all these techniques take time to converge to an optimum value; however, PSO provided the better convergence and best soil parameters. Overall, parameter identification analysis could be effectively used for the rockfill dam application and has the potential to become a valuable tool for geotechnical engineers for assessing dam performance and dam safety.Keywords: Rockfill dam, parameter identification, stochastic analysis, regression, PLAXIS
Procedia PDF Downloads 145498 Update on Genetic Diversity for Lamotrigine Induced Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
Authors: Natida Thongsima, Patompong Satapornpong
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Introduction: Lamotrigine is widely used in the treatment of epilepsy and bipolar disorder. However, lamotrigine leads to adverse drug reactions (ADRs) consist of severe cutaneous adverse reactions (SCARs) include Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug rash with eosinophilia and systemic symptoms (DRESS). Moreover, lamotrigine-induced SCARs are usually manifested between 2 and 8 weeks after treatment initiation. According to a previous study, the association between HLA-B*15:02 and lamotrigine-induced cutaneous adverse drug reactions in the Thai population (odds ratio 4.89; 95% CI 1.28–18.66; p-value = 0.014) was found. Therefore, the distribution of pharmacogenetics markers a major role in predicting the culprit drugs for SCARs in many populations. Objective: In this study, we want to investigate the prevalence of HLA-B allele, which correlates with lamotrigine-induced SCARs in the healthy Thai population. Materials and Methods: We enrolled 350 healthy Thai individuals and were approved by the ethics committee of Rangsit University. HLA-B alleles were genotyped by the Lifecodes HLA SSO typing kits (Immucor, West Avenue, Stamford, USA). Results: The results presented HLA-B allele frequency in healthy Thai population were 14.71% (HLA-B*46:01), 8.57% (HLA-B*15:02), 6.71% (HLA-B*40:01), 5.86% (HLA-B*13:01), 5.71% (HLA-B*58:01), 5.14% (HLA-B*38:02), 4.86% (HLA-B*18:01), 4.86% (HLA-B*51:01), 3.86% (HLA-B*44:03) and 2.71% (HLA-B*07:05). Especially, HLA-B*15:02 allele was the high frequency in the Thais (8.57%), Han Chinese (7.30%), Vietnamese (13.50%), Malaysian (6.06%) and Indonesian (11.60%). Nevertheless, this allele was much lower in other populations, namely, Africans, Caucasians, and Japanese. Conclusions: Although the sample size of the healthy Thai population in this research was limited, there were found the frequency of the HLA-B*15:02 allele could predispose them toward to lamotrigine-induced SCARs in Thailand.Keywords: lamotrigine, cutaneous adverse drug reactions, HLA-B, Thai population
Procedia PDF Downloads 189497 Membrane-Localized Mutations as Predictors of Checkpoint Blockade Efficacy in Cancer
Authors: Zoe Goldberger, Priscilla S. Briquez, Jeffrey A. Hubbell
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Tumor cells have mutations resulting from genetic instability that the immune system can actively recognize. Immune checkpoint immunotherapy (ICI) is commonly used in the clinic to re-activate immune reactions against mutated proteins, called neoantigens, resulting in tumor remission in cancer patients. However, only around 20% of patients show durable response to ICI. While tumor mutational burden (TMB) has been approved by the Food and Drug Administration (FDA) as a criterion for ICI therapy, the relevance of the subcellular localizations of the mutated proteins within the tumor cell has not been investigated. Here, we hypothesized that localization of mutations impacts the effect of immune responsiveness to ICI. We analyzed publicly available tumor mutation sequencing data of ICI treated patients from 3 independent datasets. We extracted the subcellular localization from the UniProtKB/Swiss-Prot database and quantified the proportion of membrane, cytoplasmic, nuclear, or secreted mutations per patient. We analyzed this information in relation to response to ICI treatment and overall survival of patients showing with 1722 ICI-treated patients that high mutational burden localized at the membrane (mTMB), correlate with ICI responsiveness, and improved overall survival in multiple cancer types. We anticipate that our results will ameliorate predictability of cancer patient response to ICI with potential implications in clinical guidelines to tailor ICI treatment. This would not only increase patient survival for those receiving ICI, but also patients’ quality of life by reducing the number of patients enduring non-effective ICI treatments.Keywords: cancer, immunotherapy, membrane neoantigens, efficacy prediction, biomarkers
Procedia PDF Downloads 108496 Transforming Healthcare with Immersive Visualization: An Analysis of Virtual and Holographic Health Information Platforms
Authors: Hossein Miri, Zhou YongQi, Chan Bormei-Suy
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The development of advanced technologies and innovative solutions has opened up exciting new possibilities for revolutionizing healthcare systems. One such emerging concept is the use of virtual and holographic health information platforms that aim to provide interactive and personalized medical information to users. This paper provides a review of notable virtual and holographic health information platforms. It begins by highlighting the need for information visualization and 3D representation in healthcare. It then proceeds to provide background knowledge on information visualization and historical developments in 3D visualization technology. Additional domain knowledge concerning holography, holographic computing, and mixed reality is then introduced, followed by highlighting some of their common applications and use cases. After setting the scene and defining the context, the need and importance of virtual and holographic visualization in medicine are discussed. Subsequently, some of the current research areas and applications of digital holography and holographic technology are explored, alongside the importance and role of virtual and holographic visualization in genetics and genomics. An analysis of the key principles and concepts underlying virtual and holographic health information systems is presented, as well as their potential implications for healthcare are pointed out. The paper concludes by examining the most notable existing mixed-reality applications and systems that help doctors visualize diagnostic and genetic data and assist in patient education and communication. This paper is intended to be a valuable resource for researchers, developers, and healthcare professionals who are interested in the use of virtual and holographic technologies to improve healthcare.Keywords: virtual, holographic, health information platform, personalized interactive medical information
Procedia PDF Downloads 86495 Characteristic and Prevalence of Cleft Lip and Palate Patient in Bandung Cleft Lip and Palate Center: A Descriptive Study
Authors: Kusmayadi Ita Nursita, Sundoro Ali
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Cleft lip and palate are one of the most common congenital abnormalities in the face. It could happen to anyone, but mostly affect Asian population including Indonesia. Factors that influence the occurrence of cleft lip and palate vary from genetic to environmental factors. Children with cleft lip and palate will often have various problems such as airway disorders, eating disorders, speech and language developmental disorders, hearing disorders and psycho-social disorders, one of which is caused by appearance disorders. During his life, the child will experience multidisciplinary surgery and non-surgical treatment and can be accompanied by a psychological and financial burden on himself and his family. In Indonesia, there are no detailed scientific data on the prevalence and characteristic of cleft lip and palate patients. It was mainly caused by the absence of a national level organization, differences in geographical location, and the absence of national guidelines. This study aimed to describe the characteristic and prevalence of cleft lip and palate patients in Bandung Cleft Lip and Palate Center from 1 January 2016 to 31 December 2017. A total of 560 patients were included in the study. The highest percentage of cases are left unilateral cleft lip and palate with higher number of female patient and labioplasty as the most often surgical procedure to be conducted in Bandung Cleft Lip and Palate Center. In order to improve quality of life in patients with cleft lip and palate, early recognition and early treatment based on actual comprehensive data should be conducted. The data from Bandung Cleft Lip and Palate Center as one of the largest center of cleft lip and palate in West Java Indonesia hopefully could provide a big step of further comprehensive data collection in Indonesia and for the better overall management of cleft lip and palate in the future.Keywords: cleft lip, cleft palate, characteristic, prevalence
Procedia PDF Downloads 136494 Computational Insights Into Allosteric Regulation of Lyn Protein Kinase: Structural Dynamics and Impacts of Cancer-Related Mutations
Authors: Mina Rabipour, Elena Pallaske, Floyd Hassenrück, Rocio Rebollido-Rios
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Protein tyrosine kinases, including Lyn kinase of the Src family kinases (SFK), regulate cell proliferation, survival, and differentiation. Lyn kinase has been implicated in various cancers, positioning it as a promising therapeutic target. However, the conserved ATP-binding pocket across SFKs makes developing selective inhibitors challenging. This study aims to address this limitation by exploring the potential for allosteric modulation of Lyn kinase, focusing on how its structural dynamics and specific oncogenic mutations impact its conformation and function. To achieve this, we combined homology modeling, molecular dynamics simulations, and data science techniques to conduct microsecond-length simulations. Our approach allowed a detailed investigation into the interplay between Lyn’s catalytic and regulatory domains, identifying key conformational states involved in allosteric regulation. Additionally, we evaluated the structural effects of Dasatinib, a competitive inhibitor, and ATP binding on Lyn active conformation. Notably, our simulations show that cancer-related mutations, specifically I364L/N and E290D/K, shift Lyn toward an inactive conformation, contrasting with the active state of the wild-type protein. This may suggest how these mutations contribute to aberrant signaling in cancer cells. We conducted a dynamical network analysis to assess residue-residue interactions and the impact of mutations on the Lyn intramolecular network. This revealed significant disruptions due to mutations, especially in regions distant from the ATP-binding site. These disruptions suggest potential allosteric sites as therapeutic targets, offering an alternative strategy for Lyn inhibition with higher specificity and fewer off-target effects compared to ATP-competitive inhibitors. Our findings provide insights into Lyn kinase regulation and highlight allosteric sites as avenues for selective drug development. Targeting these sites may modulate Lyn activity in cancer cells, reducing toxicity and improving outcomes. Furthermore, our computational strategy offers a scalable approach for analyzing other SFK members or kinases with similar properties, facilitating the discovery of selective allosteric modulators and contributing to precise cancer therapies.Keywords: lyn tyrosine kinase, mutation analysis, conformational changes, dynamic network analysis, allosteric modulation, targeted inhibition
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