Search results for: relative gene support
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 10452

Search results for: relative gene support

9552 The Cellular Internalization Mechanisms of Cationic Niosomes/DNA Complex in HeLa Cells

Authors: Orapan Paecharoenchai, Tanasait Ngawhirunpat, Theerasak Rojanarata, Auayporn Apirakaramwong, Praneet Opanasopit

Abstract:

Cationic niosomes formulated with Span20, cholesterol and novel synthesized spermine-cationic lipids (2-hydrocarbon tail and 4- hydrocarbon tail) in a molar ratio of 2.5:2.5:1 can mediate high gene transfection in vitro. However, the uptake mechanisms of these systems are not well clarified. In the present study, effect of endocytic inhibitors on the transfection efficiency of niosomes/DNA complexes was determined on a human cervical carcinoma cell line (HeLa cells) using the inhibitors of macropinocytosis (wortmannin), clathrin- and caveolae-mediated endocytosis (methyl-β-cyclodextrin), clathrin-mediated endocytosis (chlorpromazine), caveolae-mediated endocytosis (genistein and filipin), cytosolic transfer (ammonium chloride) and microtubules polymerization (nocodazole). The transfection of niosomes with 2-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride and filipin, respectively, whereas, the transfection of niosomes with 4-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride, methyl-β-cyclodextrin and filipin, respectively. It can be concluded that these niosomes/DNA complexes were internalized predominantly by endocytosis via clathrin and caveolae-independent pathway.

Keywords: cellular internalization, cationic niosomes, gene carriers, spermine-cationic lipids

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9551 Predicting Susceptibility to Coronary Artery Disease using Single Nucleotide Polymorphisms with a Large-Scale Data Extraction from PubMed and Validation in an Asian Population Subset

Authors: K. H. Reeta, Bhavana Prasher, Mitali Mukerji, Dhwani Dholakia, Sangeeta Khanna, Archana Vats, Shivam Pandey, Sandeep Seth, Subir Kumar Maulik

Abstract:

Introduction Research has demonstrated a connection between coronary artery disease (CAD) and genetics. We did a deep literature mining using both bioinformatics and manual efforts to identify the susceptible polymorphisms in coronary artery disease. Further, the study sought to validate these findings in an Asian population. Methodology In first phase, we used an automated pipeline which organizes and presents structured information on SNPs, Population and Diseases. The information was obtained by applying Natural Language Processing (NLP) techniques to approximately 28 million PubMed abstracts. To accomplish this, we utilized Python scripts to extract and curate disease-related data, filter out false positives, and categorize them into 24 hierarchical groups using named Entity Recognition (NER) algorithms. From the extensive research conducted, a total of 466 unique PubMed Identifiers (PMIDs) and 694 Single Nucleotide Polymorphisms (SNPs) related to coronary artery disease (CAD) were identified. To refine the selection process, a thorough manual examination of all the studies was carried out. Specifically, SNPs that demonstrated susceptibility to CAD and exhibited a positive Odds Ratio (OR) were selected, and a final pool of 324 SNPs was compiled. The next phase involved validating the identified SNPs in DNA samples of 96 CAD patients and 37 healthy controls from Indian population using Global Screening Array. ResultsThe results exhibited out of 324, only 108 SNPs were expressed, further 4 SNPs showed significant difference of minor allele frequency in cases and controls. These were rs187238 of IL-18 gene, rs731236 of VDR gene, rs11556218 of IL16 gene and rs5882 of CETP gene. Prior researches have reported association of these SNPs with various pathways like endothelial damage, susceptibility of vitamin D receptor (VDR) polymorphisms, and reduction of HDL-cholesterol levels, ultimately leading to the development of CAD. Among these, only rs731236 had been studied in Indian population and that too in diabetes and vitamin D deficiency. For the first time, these SNPs were reported to be associated with CAD in Indian population. Conclusion: This pool of 324 SNP s is a unique kind of resource that can help to uncover risk associations in CAD. Here, we validated in Indian population. Further, validation in different populations may offer valuable insights and contribute to the development of a screening tool and may help in enabling the implementation of primary prevention strategies targeted at the vulnerable population.

Keywords: coronary artery disease, single nucleotide polymorphism, susceptible SNP, bioinformatics

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9550 The Effects of Metformin And PCL-sorafenib Nanoparticles Co-treatment on MCF-7 Cell Culture Model of Breast Cancer

Authors: Emad Heydarnia, Aref Sepasi, Nika Asefi, Sara Khakshournia, Javad Mohammadnejad

Abstract:

Background: Despite breakthrough therapeutics in breast cancer, it is one of the main causes of mortality among women worldwide. Thus, drug therapies for treating breast cancer have recently been developed by scientists. Metformin and Sorafenib are well-known therapeutic in breast cancer. In the present study, we combined Sorafenib and PCL-sorafenib with metformin to improve drug absorption and promote therapeutic efficiency. Methods: The MCF-7 cells were treated with Metformin, Sorafenib, or PCL-sorafenib. The growth inhibitory effect of these drugs and cell viability were assessed using MTT and flow cytometry assays, respectively. The expression of targeted genes involved in cell proliferation, signaling, and the cell cycle was measured by Real-time PCR. Results: The results showed that MCF-7 cells treated with Metformin/Sorafenib and PCL-sorafenib/Metformin co-treatment contributed to 50% viability compared to untreated group. Moreover, PI and Annexin V staining tests showed that the cells viability for Metformin/Sorafenib and PCL-sorafenib/Metformin was 38% and 17%, respectively. Furthermore, Sorafenib/Metformin and PCL-sorafenib/Metformin leads to p53 gene expression increase by which they can increase ROS, thereby decreasing GPX4 gene expression. In addition, they affected the expression of BCL2, and BAX genes and altered the cell cycle. Conclusion: Together, the combination of PCL-sorafenib/Metformin and Sorafenib/Metformin increased Sorafenib absorption at lower doses and also leads to apoptosis and oxidative stress increases in MCF-7 cells.

Keywords: breast cancer, metformin, nanotechnology, sorafenib

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9549 Insect Inducible Methanol Production in Plants for Insect Resistance

Authors: Gourav Jain, Sameer Dixit, Surjeet Kumar Arya, Praveen C. Verma

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Plant cell wall plays a major role in defence mechanism against biotic and abiotic stress as it constitutes the physical barrier between the microenvironment and internal component of the cell. It is a complex structure composed of mostly carbohydrates among which cellulose and hemicelluloses are most abundant that is embedded in a matrix of pectins and proteins. Multiple enzymes have been reported which plays a vital role in cell wall modification, Pectin Methylesterase (PME) is one of them which catalyses the demethylesterification of homogalacturonans component of pectin which releases acidic pectin and methanol. As emitted methanol is toxic to the insect pest, we use PME gene for the better methanol production. In the current study we showed overexpression of PME gene isolated from Withania somnifera under the insect inducible promoter causes enhancement of methanol production at the time of insect feeds to plants, and that provides better insect resistance property. We found that the 85-90% mortality causes by transgenic tobacco in both chewing (Spodoptera litura larvae and Helicoverpa armigera) and sap-sucking (Aphid, mealybug, and whitefly) pest. The methanol content and emission level were also enhanced by 10-15 folds at different inducible time point interval (15min, 30min, 45min, 60min) which would be analysed by Purpald/Alcohol Oxidase method.

Keywords: methanol, Pectin methylesterase, inducible promoters, Purpald/Alcohol oxidase

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9548 Analysis of Extracellular Vesicles Interactomes of two Isoforms of Tau Protein via SHSY-5Y Cell Lines

Authors: Mohammad Aladwan

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Alzheimer’s disease (AD) is a widespread dementing illness with a complex and poorly understood etiology. An important role in improving our understanding of the AD process is the modeling of disease-associated changes in tau protein phosphorylation, a protein known to mediate events essential to the onset and progression of AD. A main feature of AD is the abnormal phosphorylation of tau protein and the presence of neurofibrillary tangles. In order to evaluate the respective roles of the microtubule-binding region (MTBR) and alternatively spliced exons in the N-terminal projection domains in AD, we have constructed SHSY-5Y cell lines that stably overexpress four different species of tau protein (4R2N, 4R0N, N(E-2), N(E+2)). Since the toxicity and spreading of tau lesions in AD depends on the interactions of tau with other proteins, we have performed a proteomic analysis of exosome-fraction interactomes for cell lysates and media samples that were isolated from SHSY-5Y cell lines. Functional analysis of tau interactomes based on gene ontology (GO) terms was performed using the String 10.5 database program. The highest number of exosomes proteomes and tau associated proteins were found with 4R2N isoform (2771 and 159) in cell lysate and they have a high strength of connectivity (78%) between proteins, while N(E-2) isoform in the media proteomes has the highest number of proteins and tau associated protein (1829 and 205). Moreover, known AD markers were significantly enriched in secreted interactomes relative to lysate interactomes in the SHSY-5Y cells of tau isoforms lacking exons 2 and 3 in the N-terminal. The lack of exon 2 (E-2) from tau protein can be mediated by tau secretion and spreading to different cells. Enriched functions in the secreted E-2 interactome include signaling and developmental pathways that have been linked to a) tau misprocessing and lesion development and b) tau secretion and which, therefore, could play novel roles in AD pathogenesis.

Keywords: Alzheimer's disease, dementia, tau protein, neurodegenration disease

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9547 The Evaluation of Occupational Exposure of Chrome in Welders of Stainless Steels

Authors: L. Musak, J. Valachova, T. Vasicko, O. Osina

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Introduction: Stainless steel is resistant to electrochemical corrosion by passivation. Welders are greatly exposed to welding fumes of toxic metals, which added to this steel. The content of chromium (Cr) in steel was above 11.5%, Ni and Mo from 2 to 6.5%. The aim of the study was the evaluation of occupational exposure to Cr, chromosome analysis and valuation of individual susceptibility polymorphism of gene CCND1 c.870 G>A. Materials and Methods: The exposed group was consisted from 117 welders of stainless steels. The average age was 38.43 years and average exposure time 7.14 years. Smokers represented 40.17%. The control group consisted of 123 non-exposed workers with an average age of 39.74 years and time employment 16.67 years. Smokers accounted for 22.76%. Analysis of Cr in blood and urine was performed by atomic absorption spectrophotometry (AAS Varian SpectraAA 30P) with electrothermal decomposition of the sample in the graphite furnace. For the evaluation of chromosomal aberrations (CA) was used cytogenetic analysis of peripheral blood lymphocytes, gene polymorphism was determined by PCR-RFLP reaction using appropriate primers and restriction enzymes. For statistical analysis was used the Mann-Whitney U-test. Results: The mean Cr level in exposed group was 0.095 mmol/l (0.019 min-max 0.504). No value does exceed the average normal value. The average value Cr in urine was 7.9 mmol/mol creatinine (min 0.026 to max 19.26). The total number of CA was 1.86% in compared to 1.70% controls. (CTA-type 0.90% vs 0.80% and CSA-type 0.96% vs 0.90%). In the number of total CA was observed statistical difference between smokers and non-smokers of exposed group (S-1.57% vs. NS-2.04%, P<0.05). In CCND1 gene polymorphisms was observed the increasing of the total CA with wild-type allele (WT) via heterozygous to the VAR genotype (1.44%<1.82%<2.13%). There was observed a statistically higher incidence of CTA-type aberrations in variant genotypes between exposed and control groups (1.22% vs. 0.59%, P<0.05). Discussion and conclusions: The work place is usually higher source of exposure to harmful factors. Workers need consistently and checked frequently health control. In assessing the risk of adverse effects of metals is important to consider their persistence, behavior and bioavailability. Prolonged exposure to carcinogens may not manifest symptoms of poisoning, but delayed effects may occur, which resulted in a higher incidence of malignant tumors.

Keywords: genotoxicity, chromium, stainless steels, welders

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9546 Load-Settlement Behaviour of Geogrid-Reinforced Sand Bed over Granular Piles

Authors: Sateesh Kumar Pisini, Swetha Priya Darshini Thammadi, Sanjay Kumar Shukla

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Granular piles are a popular ground improvement technique in soft cohesive soils as well as for loose non-cohesive soils. The present experimental study has been carried out on granular piles in loose (Relative density = 30%) and medium dense (Relative density = 60%) sands with geogrid reinforcement within the sand bed over the granular piles. A group of five piles were installed in the sand at different spacing, s = 2d, 3d and 4d, d being the diameter of the pile. The length (L = 0.4 m) and diameter (d = 50 mm) of the piles were kept constant for all the series of experiments. The load-settlement behavior of reinforced sand bed and granular piles system was studied by applying the load on a square footing. The results show that the effect of reinforcement increases the load bearing capacity of the piles. It is also found that an increase in spacing between piles decreases the settlement for both loose and medium dense soil.

Keywords: granular pile, load-carrying capacity, settlement, geogrid reinforcement, sand

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9545 Effects of Environmental and Genetic Factors on Growth Performance, Fertility Traits and Milk Yield/Composition in Saanen Goats

Authors: Deniz Dincel, Sena Ardicli, Hale Samli, Mustafa Ogan, Faruk Balci

Abstract:

The aim of the study was to determine the effects of some environmental and genetic factors on growth, fertility traits, milk yield and composition in Saanen goats. For this purpose, the total of 173 Saanen goats and kids were investigated for growth, fertility and milk traits in Marmara Region of Turkey. Fertility parameters (n=70) were evaluated during two years. Milk samples were collected during the lactation and the milk yield/components (n=59) of each goat were calculated. In terms of CSN3 and AGPAT6 gene; the genotypes were defined by PCR-RFLP. Saanen kids (n=86-112) were measured from birth to 6 months of life. The birth, weaning, 60ᵗʰ, 90ᵗʰ, 120ᵗʰ and 180tᵗʰ days of average live weights were calculated. The effects of maternal age on pregnancy rate (p < 0.05), birth rate (p < 0.05), infertility rate (p < 0.05), single born kidding (p < 0.001), twinning rate (p < 0.05), triplet rate (p < 0.05), survival rate of kids until weaning (p < 0.05), number of kids per parturition (p < 0.01) and number of kids per mating (p < 0.01) were found significant. The impacts of year on birth rate (p < 0.05), abortion rate (p < 0.001), single born kidding (p < 0.01), survival rate of kids until weaning (p < 0.01), number of kids per mating (p < 0.01) were found significant for fertility traits. The impacts of lactation length on all milk yield parameters (lactation milk, protein, fat, totally solid, solid not fat, casein and lactose yield) (p < 0.001) were found significant. The effects of age on all milk yield parameters (lactation milk, protein, fat, total solid, solid not fat, casein and lactose yield) (p < 0.001), protein rate (p < 0.05), fat rate (p < 0.05), total solid rate (p < 0.01), solid not fat rate (p < 0.05), casein rate (p < 0.05) and lactation length (p < 0.01), were found significant too. However, the effect of AGPAT6 gene on milk yield and composition was not found significant in Saanen goats. The herd was found monomorphic (FF) for CSN3 gene. The effects of sex on live weights until 90ᵗʰ days of life (birth, weaning and 60ᵗʰ day of average weight) were found significant statistically (p < 0.001). The maternal age affected only birth weight (p < 0,001). The effects month at birth on all of the investigated day [the birth, 120ᵗʰ, 180ᵗʰ days (p < 0.05); the weaning, 60ᵗʰ, 90ᵗʰ days (p < 0,001)] were found significant. The birth type was found significant on the birth (p < 0,001), weaning (p < 0,01), 60ᵗʰ (p < 0,01) and 90ᵗʰ (p < 0,01) days of average live weights. As a result, screening the other regions of CSN3, AGPAT6 gene and also investigation the phenotypic association of them should be useful to clarify the efficiency of target genes. Environmental factors such as maternal age, year, sex and birth type were found significant on some growth, fertility and milk traits in Saanen goats. So consideration of these factors could be used as selection criteria in dairy goat breeding.

Keywords: fertility, growth, milk yield, Saanen goats

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9544 Genetic Divergence and Morphogenic Analysis of Sugarcane Red Rot Pathogen Colletotrichum falcatum under South Gujarat Condition

Authors: Prittesh Patel, Ramar Krishnamurthy

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In the present study, nine strains of C. falcatum obtained from different places and cultivars were characterized for sporulation, growth rate, and 18S rRNA gene sequence. All isolates had characteristic fast-growing sparse and fleecy aerial mycelia on potato dextrose agar with sickle shape conidia (length x width: varied from 20.0 X 3.89 to 25.52 X 5.34 μm) and blackish to orange acervuli with setae (length x width: varied from 112.37X 2.78 to 167.66 X 6.73 μm). They could be divided into two groups on the base of morphology; P1, dense mycelia with concentric growth and P2, sparse mycelia with uneven growth. Genomic DNA isolation followed by PCR amplification with ITS1 and ITS4 primer produced ~550bp amplicons for all isolates. Phylogeny generated by 18S rRNA gene sequence confirmed the variation in isolates and mainly grouped into two clusters; cluster 1 contained CoC671 isolates (cfNAV and cfPAR) and Co86002 isolate (cfTIM). Other isolates cfMAD, cfKAM, and cfMAR were grouped into cluster 2. Remaining isolates did not fall into any cluster. Isolate cfGAN, collected from Co86032 was found highly diverse of all the nine isolates. In a nutshell, we found considerable genetic divergence and morphological variation within C. falcatum accessions collected from different areas of south Gujarat, India and these can be used for the breeding program.

Keywords: Colletotrichum falcatum, ITS, morphology, red rot, sugarcane

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9543 Antimicrobial Resistance of Acinetobacter baumannii in Veterinary Settings: A One Health Perspective from Punjab, Pakistan

Authors: Minhas Alam, Muhammad Hidayat Rasool, Mohsin Khurshid, Bilal Aslam

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The genus Acinetobacter has emerged as a significant concern in hospital-acquired infections, particularly due to the versatility of Acinetobacter baumannii in causing nosocomial infections. The organism's remarkable metabolic adaptability allows it to thrive in various environments, including the environment, animals, and humans. However, the extent of antimicrobial resistance in Acinetobacter species from veterinary settings, especially in developing countries like Pakistan, remains unclear. This study aimed to isolate and characterize Acinetobacter spp. from veterinary settings in Punjab, Pakistan. A total of 2,230 specimens were collected, including 1,960 samples from veterinary settings (nasal and rectal swabs from dairy and beef cattle), 200 from the environment, and 70 from human clinical settings. Isolates were identified using routine microbiological procedures and confirmed by polymerase chain reaction (PCR). Antimicrobial susceptibility was determined by the disc diffusion method, and minimum inhibitory concentration (MIC) was measured by the micro broth dilution method. Molecular techniques, such as PCR and DNA sequencing, were used to screen for antimicrobial-resistant determinants. Genetic diversity was assessed using standard techniques. The results showed that the overall prevalence of A. baumannii in cattle was 6.63% (65/980). However, among cattle, a higher prevalence of A. baumannii was observed in dairy cattle, 7.38% (54/731), followed by beef cattle, 4.41% (11/249). Out of 65 A. baumannii isolates, the carbapenem resistance was found in 18 strains, i.e. 27.7%. The prevalence of A. baumannii in nasopharyngeal swabs was higher, i.e., 87.7% (57/65), as compared to rectal swabs, 12.3% (8/65). Class D β-lactamases genes blaOXA-23 and blaOXA-51 were present in all the CRAB from cattle. Among carbapenem-resistant isolates, 94.4% (17/18) were positive for class B β-lactamases gene blaIMP, whereas the blaNDM-1 gene was detected in only one isolate of A. baumannii. Among 70 clinical isolates of A. baumannii, 58/70 (82.9%) were positive for the blaOXA-23-like gene, and 87.1% (61/70) were CRAB isolates. Among all clinical isolates of A. baumannii, blaOXA-51-like gene was present. Hence, the co-existence of blaOXA-23 and blaOXA-51 was found in 82.85% of clinical isolates. From the environmental settings, a total of 18 A. baumannii isolates were recovered; among these, 38.88% (7/18) strains showed carbapenem resistance. All environmental isolates of A. baumannii harbored class D β-lactamases genes, i.e., blaOXA-51 and blaOXA-23 were detected in 38.9% (7/18) isolates. Hence, the co-existence of blaOXA-23 and blaOXA-51 was found in 38.88% of isolates. From environmental settings, 18 A. baumannii isolates were recovered, with 38.88% showing carbapenem resistance. All environmental isolates harbored blaOXA-51 and blaOXA-23 genes, with co-existence in 38.88% of isolates. MLST results showed ten different sequence types (ST) in clinical isolates, with ST 589 being the most common in carbapenem-resistant isolates. In veterinary isolates, ST2 was most common in CRAB isolates from cattle. Immediate control measures are needed to prevent the transmission of CRAB isolates among animals, the environment, and humans. Further studies are warranted to understand the mechanisms of antibiotic resistance spread and implement effective disease control programs.

Keywords: Acinetobacter baumannii, carbapenemases, drug resistance, MSLT

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9542 Buckling of Plates on Foundation with Different Types of Sides Support

Authors: Ali N. Suri, Ahmad A. Al-Makhlufi

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In this paper the problem of buckling of plates on foundation of finite length and with different side support is studied. The Finite Strip Method is used as tool for the analysis. This method uses finite strip elastic, foundation, and geometric matrices to build the assembly matrices for the whole structure, then after introducing boundary conditions at supports, the resulting reduced matrices is transformed into a standard Eigenvalue-Eigenvector problem. The solution of this problem will enable the determination of the buckling load, the associated buckling modes and the buckling wave length. To carry out the buckling analysis starting from the elastic, foundation, and geometric stiffness matrices for each strip a computer program FORTRAN list is developed. Since stiffness matrices are function of wave length of buckling, the computer program used an iteration procedure to find the critical buckling stress for each value of foundation modulus and for each boundary condition. The results showed the use of elastic medium to support plates subject to axial load increase a great deal the buckling load, the results found are very close with those obtained by other analytical methods and experimental work. The results also showed that foundation compensates the effect of the weakness of some types of constraint of side support and maximum benefit found for plate with one side simply supported the other free.

Keywords: buckling, finite strip, different sides support, plates on foundation

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9541 Network Mobility Support in Content-Centric Internet

Authors: Zhiwei Yan, Jong-Hyouk Lee, Yong-Jin Park, Xiaodong Lee

Abstract:

In this paper, we analyze NEtwork MObility (NEMO) supporting problems in Content-Centric Networking (CCN), and propose the CCN-NEMO which can well support the deployment of the content-centric paradigm in large-scale mobile Internet. The CCN-NEMO extends the signaling message of the basic CCN protocol, to support the mobility discovery and fast trigger of Interest re-issuing during the network mobility. Besides, the Mobile Router (MR) is extended to optimize the content searching and relaying in the local subnet. These features can be employed by the nested NEMO to maximize the advantages of content retrieving with CCN. Based on the analysis, we compare the performance on handover latency between the basic CCN and our proposed CCN-NEMO. The results show that our scheme can facilitate the content-retrieving in the NEMO scenario with improved performance.

Keywords: NEMO, CCN, mobility, handover latency

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9540 A Decision Support System for Flight Disruptions Management

Authors: Burak Erkayman, Emin Gundogar, Hayrettin Evirgen, Murat Sarı

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With the increasing competition in recent years, airline companies tend to manage their operations aiming fewer losses in a robust manner. Airline operations are complex operations and have the necessity of being performed just in time and more knock-on relevant elements in the event of a disruption. In this study a knowledge based decision support system is suggested and software is developed. The developed software includes knowledge bases which are based on expert experience and government regulations, model bases and data bases. The results of the suggested approach are presented and improvable aspects of the approach are discussed.

Keywords: knowledge based systems, irregular operations, decision support systems, flight disruptions management

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9539 An Intelligent Decision Support System Approach for New Product Development by Using QFD and Its Application in Metal Plating Industry

Authors: Ufuk Cebeci, Onur Doğan

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New product becomes critical in competitive environment shortening a product's lifecycle due to the rapidly changing technology and increasing consumer requirements. Quality Function Deployment is one of the first steps of NPD process. The study presents an intelligent QFD application in metal plating industry. For application, an intelligent decision support system was developed. By intelligent system, house of quality was drawn and some calculations were shown. According to the results, some recommendations are given to end user. One of the purposes of this system is to give some advices to firms which do not know technical details of QFD and guide them about first steps of the new product development process.

Keywords: intelligent decision support systems, metal plating, quality function deployment, QFD software, new product development

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9538 Effect of Family-Based DOTS Support Program on Adherence to Health Behaviors among Patients with Pulmonary Tuberculosis in Bandung, Indonesia

Authors: D. I. Yani, S. Isaramalai, C. Kritpracha

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Adherence to health behaviors is essential to achieve successful TB treatment. This study aimed to examine the effect of a family-based DOTS support program on adherence to health behaviors in patients with pulmonary TB. Sixty TB patients and their families were selected using cluster randomization of community health centers. The subjects were assigned into a control group, who received the routine care, and an experimental group, who received both routine care and care from the family-based DOTS support program. Paired t-test and the independent t-test were applied. The total score of adherence to health behaviors in the experimental group was significantly higher after receiving care from the family-based DOTS support program than the pretest score (t = -10.34, p < .001). Suggestions were made to expand the application of this program in various contexts and to extend knowledge for nursing practices and research.

Keywords: self-care deficit nursing theory, family-based DOTS program, pulmonary tuberculosis, adherence, health behaviors

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9537 Application of Support Vector Machines in Forecasting Non-Residential

Authors: Wiwat Kittinaraporn, Napat Harnpornchai, Sutja Boonyachut

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This paper deals with the application of a novel neural network technique, so-called Support Vector Machine (SVM). The objective of this study is to explore the variable and parameter of forecasting factors in the construction industry to build up forecasting model for construction quantity in Thailand. The scope of the research is to study the non-residential construction quantity in Thailand. There are 44 sets of yearly data available, ranging from 1965 to 2009. The correlation between economic indicators and construction demand with the lag of one year was developed by Apichat Buakla. The selected variables are used to develop SVM models to forecast the non-residential construction quantity in Thailand. The parameters are selected by using ten-fold cross-validation method. The results are indicated in term of Mean Absolute Percentage Error (MAPE). The MAPE value for the non-residential construction quantity predicted by Epsilon-SVR in corporation with Radial Basis Function (RBF) of kernel function type is 5.90. Analysis of the experimental results show that the support vector machine modelling technique can be applied to forecast construction quantity time series which is useful for decision planning and management purpose.

Keywords: forecasting, non-residential, construction, support vector machines

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9536 Genetic Variations of CYP2C9 in Thai Patients Taking Medical Cannabis

Authors: Naso Isaiah Thanavisuth

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Medical cannabis can be used for treatment including pain, multiple sclerosis, Parkinson's disease, and cancer. However, medical cannabis leads to adverse effects (AEs), which is delta-9-tetrahydrocannabinol (THC). In previous studies, the major of THC metabolism enzymes are CYP2C9. Especially, the variation of CYP2C9 gene consist of CYP2C9*2 on exon 3 and CYP2C9*3 on exon 7 to decrease enzyme activity. Notwithstanding, there is no data describing whether the variant of CYP2C9 genes are apharmacogenetics marker for the prediction of THC-induced AEs in Thai patients. We want to investigate the association between CYP2C9 gene and THC-induced AEs in Thai patients. We enrolled 39 Thai patients with medical cannabis treatment who were classified by clinical data. The CYP2C9*2 and *3 genotyping were conducted using the TaqMan real time PCR assay. All Thai patients who received the medical cannabis consist of twenty-four (61.54%) patients were female, and fifteen (38.46%) were male, with age range 27- 87 years. Moreover, the most AEs in Thai patients who were treated with medical cannabis between cases and controls were tachycardia, arrhythmia, dry mouth, and nausea. Particularly, thirteen (72.22%) medical cannabis-induced AEs were female and age range 33 – 69 years. In this study, none of the medical cannabis groups carried CYP2C9*2 variants in Thai patients. The CYP2C9*3 variants (*1/*3, intermediate metabolizer, IM) and (*3/*3, poor metabolizer, PM) were found, three of thirty-nine (7.69%) and one of thirty-nine (2.56%), respectively. Although, our results indicate that there is no found the CYP2C9*2. However, the variation of CYP2C9 allele might serve as a pharmacogenetics marker for screening before initiating the therapy with medical cannabis for the prevention of medical cannabis-induced AEs.

Keywords: CYP2C9, medical cannabis, adverse effects, THC, P450

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9535 An Examination of the Relationship between Organizational Justice and Trust in the Supervisor: The Mediating Role of Perceived Supervisor Support

Authors: Michel Zaitouni, Mohamed Nassar

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The purpose of this study is first, to explore the effect of employees’ perception of justice on trust in the supervisor in the context of performance appraisal; Second, to assess the role of perceived supervisor support as a mediator between organizational justice and trust in the supervisor in a non-western society such as Kuwait.The survey data consisted of 415 employees working at different hierarchical levels in three major banks in Kuwait. Hierarchical regression analysis was used to test the research hypotheses. Results supported hypothesized relationships between distributive, informational and interpersonal justice and trust in the supervisor but failed to support that procedural justice positively and significantly relate to trust in the supervisor. Moreover, results found that this relationship is partially mediated by perceived supervisor support. A potential limitation of this study is that data were obtained from the same industry which limits the generalizability of this study to other industries. Moreover, a longitudinal research will be helpful to strengthen the mediating relationship. The findings provide valuable information for the development of common perspectives regarding the perception of justice in the context of performance appraisal between the western and non-western societies. The paper has the privilege to explore additional relationships related to justice perceptions in the Kuwaiti banking sector, whereas previous research focused mainly on procedural and distributive justice as predictors of trust in the supervisor.

Keywords: Kuwait, organizational justice, perceived supervisor support, trust in the supervisor

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9534 Decision Support System Based On GIS and MCDM to Identify Land Suitability for Agriculture

Authors: Abdelkader Mendas

Abstract:

The integration of MultiCriteria Decision Making (MCDM) approaches in a Geographical Information System (GIS) provides a powerful spatial decision support system which offers the opportunity to efficiently produce the land suitability maps for agriculture. Indeed, GIS is a powerful tool for analyzing spatial data and establishing a process for decision support. Because of their spatial aggregation functions, MCDM methods can facilitate decision making in situations where several solutions are available, various criteria have to be taken into account and decision-makers are in conflict. The parameters and the classification system used in this work are inspired from the FAO (Food and Agriculture Organization) approach dedicated to a sustainable agriculture. A spatial decision support system has been developed for establishing the land suitability map for agriculture. It incorporates the multicriteria analysis method ELECTRE Tri (ELimitation Et Choix Traduisant la REalité) in a GIS within the GIS program package environment. The main purpose of this research is to propose a conceptual and methodological framework for the combination of GIS and multicriteria methods in a single coherent system that takes into account the whole process from the acquisition of spatially referenced data to decision-making. In this context, a spatial decision support system for developing land suitability maps for agriculture has been developed. The algorithm of ELECTRE Tri is incorporated into a GIS environment and added to the other analysis functions of GIS. This approach has been tested on an area in Algeria. A land suitability map for durum wheat has been produced. Through the obtained results, it appears that ELECTRE Tri method, integrated into a GIS, is better suited to the problem of land suitability for agriculture. The coherence of the obtained maps confirms the system effectiveness.

Keywords: multicriteria decision analysis, decision support system, geographical information system, land suitability for agriculture

Procedia PDF Downloads 633
9533 Analysis of Mutation Associated with Male Infertility in Patients and Healthy Males in the Russian Population

Authors: Svetlana Zhikrivetskaya, Nataliya Shirokova, Roman Bikanov, Elizaveta Musatova, Yana Kovaleva, Nataliya Vetrova, Ekaterina Pomerantseva

Abstract:

Nowadays there is a growing number of couples with conceiving problems due to male or female infertility. Genetic abnormalities are responsible for about 31% of all cases of male infertility. These abnormalities include both chromosomal aberrations or aneuploidies and mutations in certain genes. Chromosomal abnormalities can be easily identified, thus the development of screening panels able to reveal genetic reasons of male infertility on gene level is of current interest. There are approximately 2,000 genes involved in male fertility that is the reason why it is very important to determine the most clinically relevant in certain population and ethnic conditions. An infertility screening panel containing 48 mutations in genes AMHR2, CFTR, DNAI1, HFE, KAL1, TSSK2 and AZF locus which are the most clinically relevant for the European population according to databases NCBI and ClinVar was designed. The aim of this research was to confirm clinic relevance of these mutations in the Russian population. Genotyping was performed in 220 patients with different types of male infertility and in 57 healthy males with normozoospermia. Mutations were identified by end-point PCR with TaqMan probes in microfluidic plates. The frequency of 5 mutations in healthy males and 13 mutations in patients with infertility was revealed and estimated. The frequency of mutation c.187C>G in HFE gene was significantly lower for healthy males (8.8%) compared with patients (17.7%) and the values for the European population according to ExAc database (13.7%) and dbSNP (17.2%). Analysis of c.3454G>C, and c.1545_1546delTA mutations in the CFTR gene revealed increased frequency (0.9 and 0.2%, respectively) in patients with infertility compared with data for the European population (0.04%, respectively (ExAc, European (Non-Finnish) and for the Aggregated Populations (0.002% (ExAc), because there is no data for European population for c.1545_1546delTA mutation. The frequency of del508 mutation (CFTR) in patients (1.59%) were lower comparing with male infertility Europeans (3.34-6.25% depending on nationality) and at the same level with healthy Europeans (1.06%, ExAc, European (Non-Finnish). Analysis of c.845G>A (HFE) mutation resulted in decreased frequency in patients (1.8%) in contrast with the European population data (5.1%, respectively, ExAc, European (Non-Finnish). Moreover, obtained data revealed no statistically significant frequency difference for c.845G>A mutation (HFE) between healthy males in the Russian and the European populations. Allele frequencies of mutations c.350G>A (CFTR), c.193A>T (HFE), c.774C>T, and c.80A>G (gene TSSK2) showed no significantly difference among patients with infertility, healthy males and Europeans. Analysis of AZF locus revealed increased frequency for AZFc microdeletion in patients with male infertility. Thereby, the new data of the allele frequencies in infertility patients in the Russian population was obtained. As well as the frequency differences of mutations associated with male infertility among patients, healthy males in the Russian population and the European one were estimated. The revealed differences showed that for high effectiveness of screening panel detecting genetically caused male infertility it is very important to consider ethnic and population characteristics of patients which will be screened.

Keywords: allele frequency, azoospermia, male infertility, mutation, population

Procedia PDF Downloads 388
9532 A Biophysical Model of CRISPR/Cas9 on- and off-Target Binding for Rational Design of Guide RNAs

Authors: Iman Farasat, Howard M. Salis

Abstract:

The CRISPR/Cas9 system has revolutionized genome engineering by enabling site-directed and high-throughput genome editing, genome insertion, and gene knockdowns in several species, including bacteria, yeast, flies, worms, and human cell lines. This technology has the potential to enable human gene therapy to treat genetic diseases and cancer at the molecular level; however, the current CRISPR/Cas9 system suffers from seemingly sporadic off-target genome mutagenesis that prevents its use in gene therapy. A comprehensive mechanistic model that explains how the CRISPR/Cas9 functions would enable the rational design of the guide-RNAs responsible for target site selection while minimizing unexpected genome mutagenesis. Here, we present the first quantitative model of the CRISPR/Cas9 genome mutagenesis system that predicts how guide-RNA sequences (crRNAs) control target site selection and cleavage activity. We used statistical thermodynamics and law of mass action to develop a five-step biophysical model of cas9 cleavage, and examined it in vivo and in vitro. To predict a crRNA's binding specificities and cleavage rates, we then compiled a nearest neighbor (NN) energy model that accounts for all possible base pairings and mismatches between the crRNA and the possible genomic DNA sites. These calculations correctly predicted crRNA specificity across 5518 sites. Our analysis reveals that cas9 activity and specificity are anti-correlated, and, the trade-off between them is the determining factor in performing an RNA-mediated cleavage with minimal off-targets. To find an optimal solution, we first created a scheme of safe-design criteria for Cas9 target selection by systematic analysis of available high throughput measurements. We then used our biophysical model to determine the optimal Cas9 expression levels and timing that maximizes on-target cleavage and minimizes off-target activity. We successfully applied this approach in bacterial and mammalian cell lines to reduce off-target activity to near background mutagenesis level while maintaining high on-target cleavage rate.

Keywords: biophysical model, CRISPR, Cas9, genome editing

Procedia PDF Downloads 400
9531 The Diversity of DRB1 Locus of Exon 2 of MHC Molecule of Sudanese Indigenous Desert Sheep

Authors: Muna A. Eissawi, Safaa Abed Elfataah, Haytham Hago, Fatima E Abukunna, Ibtisam Amin Goreish, Nahid Gornas

Abstract:

The study examined and analyzed the genetic diversity of DRB1locus of exon 2 of major histocompatibility complex of Sudanese desert sheep using PCR-RFLP and DNA sequencing. Five hundred samples belonging to five ecotypes of Desert Sudanese sheep (Abrag (Ab), Ashgar (Ash), Hamari (H), Kabashi (K) and Watish (W) were included. Amplification of exon 2 of the DRB1 gene yielded (300bp) amplified product in different ecotypes. Nine different digestion patterns corresponding to Five distinct alleles were observed with Rsa1 digestion. Genotype (ag) was the most common among all ecotypes, with a percentage comprised (40.4 %). The Hardy-Weinberg equilibrium (HWE) test showed that the studied ecotypes have significantly deviated from the theoretical proportions of Rsa1 patterns; probability values of the Chi-square test for HWE for MHC-DRB1 gene in SDS were 0.00 in all ecotypes. The constructed phylogenetic tree revealed the relation of 22 Sudanese isolates with each other and showed the shared sequences with 47 published foreign sequences randomly selected from different geographic regions. The results of this study highlight the effect of heterozygosity of MHC genes of the Desert sheep of Sudan which may clarify some of genetic back ground of their disease resistance and adaptation to environment.

Keywords: desert sheep, MHC, Ovar-DRB1, polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP)

Procedia PDF Downloads 70
9530 Fuzzy Decision Support System for Human-Realistic Overtaking in Railway Traffic Simulations

Authors: Tomáš Vyčítal

Abstract:

In a simulation model of a railway system it is important, besides other crucial algorithms, to have correct behaviour of train overtaking in stochastic conditions. This problem is being addressed in many simulation tools focused on railway traffic, however these are not very human-realistic. The goal of this paper is to create a more human-realistic overtaking decision support system for the use in railway traffic simulations. A fuzzy system has been chosen for this task as fuzzy systems are well-suited for human-like decision making. The fuzzy system designed takes into account timetables, train positions, delays and buffer times as inputs and provides an instruction to overtake or not overtake.

Keywords: decision-making support, fuzzy systems, simulation, railway, transport

Procedia PDF Downloads 135
9529 Effects of Lateness Gene on Yield and Related Traits in Indica Rice

Authors: B. B. Rana, M. Yokota, Y. Shimizu, Y. Koide, I. Takamure, T. Kawano, M. Murai

Abstract:

Various genes which control or affect heading time have been found in rice. Out of them, Se1 and E1 loci play important roles in determining heading time by controlling photosensitivity. An isogenic-line pair of late and early lines were developed from progenies of the F1 from Suweon 258 × 36U. A lateness gene tentatively designated as “Ex” was found to control the difference in heading time between the early and late lines mentioned above. The present study was conducted to examine the effect of Ex on yield and related traits. Indica-type variety Suweon 258 was crossed with 36U, which is an Ur1 (Undulate rachis-1) isogenic line of IR36. In the F2 population, comparatively early-heading, late-heading and intermediate-heading plants were segregated. Segregation similar to that by the three types of heading was observed in the F3 and later generations. A late-heading plant and an early-heading plant were selected in the F8 population from an intermediate-heading F7 plant, for developing L and E of the isogenic-line pair, respectively. Experiments for L and E were conducted by randomized block design with three replications. Transplanting was conducted on May 3 at a planting distance of 30 cm × 15 cm with two seedlings per hill to an experimental field of the Faculty of Agriculture, Kochi University. Chemical fertilizers containing N, P2O5 and K2O were applied at the nitrogen levels of 4 g/m2, 9 g/m2 and 18 g/m2 in total being denoted by "N4", "N9" and "N18", respectively. Yield, yield components and other traits were measured. Ex delayed 80%-heading by 17 or 18 days in L as compared with E. In total brown rice yield (g/m2), L was 635, 606 and 590, and E was 577, 548 and 501, respectively, at N18, N9 and N4, indicating that Ex increased this trait by 10% to 18%. Ex increased yield-1.5 mm sieve (g/m2) b 9% to 15% at the three fertilizer levels. Ex increased the spikelet number per panicle by 16% to 22%. As a result, the spikelet number per m2 was increased by 11% to 18% at the three fertilizer levels. Ex decreased 1000-grain weight (g) by 2 to 4%. L was not significantly different from E in ripened-grain percentage, fertilized-spikelet percentage and percentage of ripened grains to fertilized spikelets. Hence, it is inferred that Ex increased yield by increasing spikelet number per panicle. Hence, Ex could be utilized to develop high yielding varieties for warmer districts.

Keywords: heading time, lateness gene, photosensitivity, yield, yield components

Procedia PDF Downloads 194
9528 Application of Particle Image Velocimetry in the Analysis of Scale Effects in Granular Soil

Authors: Zuhair Kadhim Jahanger, S. Joseph Antony

Abstract:

The available studies in the literature which dealt with the scale effects of strip footings on different sand packing systematically still remain scarce. In this research, the variation of ultimate bearing capacity and deformation pattern of soil beneath strip footings of different widths under plane-strain condition on the surface of loose, medium-dense and dense sand have been systematically studied using experimental and noninvasive methods for measuring microscopic deformations. The presented analyses are based on model scale compression test analysed using Particle Image Velocimetry (PIV) technique. Upper bound analysis of the current study shows that the maximum vertical displacement of the sand under the ultimate load increases for an increase in the width of footing, but at a decreasing rate with relative density of sand, whereas the relative vertical displacement in the sand decreases for an increase in the width of the footing. A well agreement is observed between experimental results for different footing widths and relative densities. The experimental analyses have shown that there exists pronounced scale effect for strip surface footing. The bearing capacity factors rapidly decrease up to footing widths B=0.25 m, 0.35 m, and 0.65 m for loose, medium-dense and dense sand respectively, after that there is no significant decrease in . The deformation modes of the soil as well as the ultimate bearing capacity values have been affected by the footing widths. The obtained results could be used to improve settlement calculation of the foundation interacting with granular soil.

Keywords: DPIV, granular mechanics, scale effect, upper bound analysis

Procedia PDF Downloads 150
9527 Efficient Hydrogen Separation through Pd-Pt Membrane

Authors: Lawan Muhammad Adam, Abduljabar Hilal Alsayoud

Abstract:

One of the most promising techniques to produce pure hydrogen is through a palladium-based membrane (Pd-membrane). Density functional theory (DFT) is employed in this work to examine how the physical and chemical adsorption properties of hydrogen on the surface of Pd-Pt can be mutated in the presence of contaminating gases, CH₄, CO, and CO₂. The main target is to survey the energy topology related to hydrogen adsorption while adjusting the stages of freedom in both the structure and composition. The adsorption sites, crystal plane of the slab, and relative orientation of the adsorbed molecules on its surface, as well as various arrangements of adsorbed species, have been considered in this study. The dependency of hydrogen adsorption on surface coverage is studied. The study demonstrated the physical adsorption energies of the molecules on the surface concerning the different coverages of hydrogen atoms. The most stable combinations of the adsorption sites (Top, Hollow, and Bridge) with various orientations of gaseous molecules on the Pd-Pt surface were identified according to their calculated energies. When the binding of contaminating gaseous species to the Pd-Pt surface and their impact on the physical adsorption energies of the H₂ are examined, it is observed that the most poisonous gas relative to all other gases modifies the energetics of the adsorption process of hydrogen on the surface.

Keywords: DFT, Pd-Pt-membrane, H₂, CO, CO₂

Procedia PDF Downloads 67
9526 Selecting a Foreign Country to Build a Naval Base Using a Fuzzy Hybrid Decision Support System

Authors: Latif Yanar, Muammer Kaçan

Abstract:

Decision support systems are getting more important in many fields of science and technology and used effectively especially when the problems to be solved are complicated with many criteria. In this kind of problems one of the main challenges for the decision makers are that sometimes they cannot produce a countable data for evaluating the criteria but the knowledge and sense of experts. In recent years, fuzzy set theory and fuzzy logic based decision models gaining more place in literature. In this study, a decision support model to determine a country to build naval base is proposed and the application of the model is performed, considering Turkish Navy by the evaluations of Turkish Navy officers and academicians of international relations departments of various Universities located in Istanbul. The results achieved from the evaluations made by the experts in our model are calculated by a decision support tool named DESTEC 1.0, which is developed by the authors using C Sharp programming language. The tool gives advices to the decision maker using Analytic Hierarchy Process, Analytic Network Process, Fuzzy Analytic Hierarchy Process and Fuzzy Analytic Network Process all at once. The calculated results for five foreign countries are shown in the conclusion.

Keywords: decision support system, analytic hierarchy process, fuzzy analytic hierarchy process, analytic network process, fuzzy analytic network process, naval base, country selection, international relations

Procedia PDF Downloads 587
9525 Ethanol Chlorobenzene Dosimetr Usage for Measuring Dose of the Intraoperative Linear Electron Accelerator System

Authors: Mojtaba Barzegar, Alireza Shirazi, Saied Rabi Mahdavi

Abstract:

Intraoperative radiation therapy (IORT) is an innovative treatment modality that the delivery of a large single dose of radiation to the tumor bed during the surgery. The radiotherapy success depends on the absorbed dose delivered to the tumor. The achievement better accuracy in patient treatment depends upon the measured dose by standard dosimeter such as ionization chamber, but because of the high density of electric charge/pulse produced by the accelerator in the ionization chamber volume, the standard correction factor for ion recombination Ksat calculated with the classic two-voltage method is overestimated so the use of dose/pulse independent dosimeters such as chemical Fricke and ethanol chlorobenzene (ECB) dosimeters have been suggested. Dose measurement is usually calculated and calibrated in the Zmax. Ksat calculated by comparison of ion chamber response and ECB dosimeter at each applicator degree, size, and dose. The relative output factors for IORT applicators have been calculated and compared with experimentally determined values and the results simulated by Monte Carlo software. The absorbed doses have been calculated and measured with statistical uncertainties less than 0.7% and 2.5% consecutively. The relative differences between calculated and measured OF’s were up to 2.5%, for major OF’s the agreement was better. In these conditions, together with the relative absorbed dose calculations, the OF’s could be considered as an indication that the IORT electron beams have been well simulated. These investigations demonstrate the utility of the full Monte Carlo simulation of accelerator head with ECB dosimeter allow us to obtain detailed information of clinical IORT beams.

Keywords: intra operative radiotherapy, ethanol chlorobenzene, ksat, output factor, monte carlo simulation

Procedia PDF Downloads 475
9524 The Role of Formal and Informal Social Support in Predicting the Involvement of Mothers and Fathers of Young Children with Autism Spectrum Disorder

Authors: Adi Sharabi, Dafna Marom-Golan

Abstract:

Parents’ involvement in the care of their children with Autism Spectrum Disorder (ASD) and its beneficial effect on the children’s developmental and educational outcomes is well documented. At the same time, parents of children with ASD tend to experience greater psychological distress than parents of children with other developmental disabilities or with typical development. Positive social support is an important resource used by parents to reduce their psychological distress. The goal of the current research was to examine the contribution of formal and informal social support in explaining mothers’ and fathers’ involvement with their young children with ASD. The sample consisted of 107 parents who live in Israel (61 mothers and 46 fathers) of children aged between 2 and 7, all diagnosed with ASD and attending special kindergartens or special day care for children with ASD. Parental involvement and social support perception were assessed. Initial analysis focused on the relations between involvement, support, and demographic variables. In addition, analysis of variance (ANOVA) was conducted to test differences between mothers and fathers. Two hierarchical multiple regression analyses were performed to examine the predicted factors in the involvement model while controlling for group (mothers/fathers). Results indicate that mothers reported significantly higher levels of parenting involvement than fathers. Mothers reported higher levels of general involvement and all sub-types of involvement. For example, mothers reported that they were more interested in and have higher levels of attendance in their child’s educational program. They were also more collaborative in their child’s educational therapeutic program, and socialized with other parents of children from their child’s kindergarten than fathers. Mothers’ involvement was found to be related to their informal support (non-formal relatives). Findings also reveal significant differences between mothers and fathers on the formal support subscale measure of specializes services. Fathers, more than mothers, reported more specializes services support such as social workers or professional therapists. Separate hierarchical multiple regression analyses revealed a unique gender difference in the factors that explained parental involvement. Specifically, informal support only had a unique positive contribution in explaining mothers’, but not fathers’ involvement. This study highlights the central role of mothers in maintaining constant contact with the educational system and the professionals who help care for their child with ASD. At the same time, this research emphasizes the crucial role of both mothers and fathers in their child's development and well-being at every development stage, particularly in early development. Further, different kinds of social support seem to relate to the different kinds of parental involvement. It is in the best interest of educators and family therapists who work with families with children with ASD to support the cohesiveness of the family and the collaboration of the parents by understanding and respecting the way each member addresses the responsibilities of parenting a child with ASD, and her or his need for different types of social support.

Keywords: parental differences, parental involvement, social support, specialized support services

Procedia PDF Downloads 245
9523 VHL, PBRM1, and SETD2 Genes in Kidney Cancer: A Molecular Investigation

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

Abstract:

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

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

Procedia PDF Downloads 455