Search results for: variant prioritization
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 399

Search results for: variant prioritization

399 The Development of an Automated Computational Workflow to Prioritize Potential Resistance Variants in HIV Integrase Subtype C

Authors: Keaghan Brown

Abstract:

The prioritization of drug resistance mutations impacting protein folding or protein-drug and protein-DNA interactions within macromolecular systems is critical to the success of treatment regimens. With a continual increase in computational tools to assess these impacts, the need for scalability and reproducibility became an essential component of computational analysis and experimental research. Here it introduce a bioinformatics pipeline that combines several structural analysis tools in a simplified workflow, by optimizing the present computational hardware and software to automatically ease the flow of data transformations. Utilizing preestablished software tools, it was possible to develop a pipeline with a set of pre-defined functions that will automate mutation introduction into the HIV-1 Integrase protein structure, calculate the gain and loss of polar interactions and calculate the change in energy of protein fold. Additionally, an automated molecular dynamics analysis was implemented which reduces the constant need for user input and output management. The resulting pipeline, Automated Mutation Introduction and Analysis (AMIA) is an open source set of scripts designed to introduce and analyse the effects of mutations on the static protein structure as well as the results of the multi-conformational states from molecular dynamic simulations. The workflow allows the user to visualize all outputs in a user friendly manner thereby successfully enabling the prioritization of variant systems for experimental validation.

Keywords: automated workflow, variant prioritization, drug resistance, HIV Integrase

Procedia PDF Downloads 56
398 Prioritization in Modern Portfolio Management - An Action Design Research Approach to Method Development for Scaled Agility

Authors: Jan-Philipp Schiele, Karsten Schlinkmeier

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Allocation of scarce resources is a core process of traditional project portfolio management. However, with the popularity of agile methodology, established concepts and methods of portfolio management are reaching their limits and need to be adapted. Consequently, the question arises of how the process of resource allocation can be managed appropriately in scaled agile environments. The prevailing framework SAFe offers Weightest Shortest Job First (WSJF) as a prioritization technique, butestablished companies are still looking for methodical adaptions to apply WSJF for prioritization in portfolios in a more goal-oriented way and aligned for their needs in practice. In this paper, the relevant problem of prioritization in portfolios is conceptualized from the perspective of coordination and related mechanisms to support resource allocation. Further, an Action Design Research (ADR) project with case studies in a finance company is outlined to develop a practically applicable yet scientifically sound prioritization method based on coordination theory. The ADR project will be flanked by consortium research with various practitioners from the financial and insurance industry. Preliminary design requirements indicate that the use of a feedback loop leads to better team and executive level coordination in the prioritization process.

Keywords: scaled agility, portfolio management, prioritization, business-IT alignment

Procedia PDF Downloads 175
397 A Hybrid Data-Handler Module Based Approach for Prioritization in Quality Function Deployment

Authors: P. Venu, Joeju M. Issac

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Quality Function Deployment (QFD) is a systematic technique that creates a platform where the customer responses can be positively converted to design attributes. The accuracy of a QFD process heavily depends on the data that it is handling which is captured from customers or QFD team members. Customized computer programs that perform Quality Function Deployment within a stipulated time have been used by various companies across the globe. These programs heavily rely on storage and retrieval of the data on a common database. This database must act as a perfect source with minimum missing values or error values in order perform actual prioritization. This paper introduces a missing/error data handler module which uses Genetic Algorithm and Fuzzy numbers. The prioritization of customer requirements of sesame oil is illustrated and a comparison is made between proposed data handler module-based deployment and manual deployment.

Keywords: hybrid data handler, QFD, prioritization, module-based deployment

Procedia PDF Downloads 279
396 A Novel Approach towards Test Case Prioritization Technique

Authors: Kamna Solanki, Yudhvir Singh, Sandeep Dalal

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Software testing is a time and cost intensive process. A scrutiny of the code and rigorous testing is required to identify and rectify the putative bugs. The process of bug identification and its consequent correction is continuous in nature and often some of the bugs are removed after the software has been launched in the market. This process of code validation of the altered software during the maintenance phase is termed as Regression testing. Regression testing ubiquitously considers resource constraints; therefore, the deduction of an appropriate set of test cases, from the ensemble of the entire gamut of test cases, is a critical issue for regression test planning. This paper presents a novel method for designing a suitable prioritization process to optimize fault detection rate and performance of regression test on predefined constraints. The proposed method for test case prioritization m-ACO alters the food source selection criteria of natural ants and is basically a modified version of Ant Colony Optimization (ACO). The proposed m-ACO approach has been coded in 'Perl' language and results are validated using three examples by computation of Average Percentage of Faults Detected (APFD) metric.

Keywords: regression testing, software testing, test case prioritization, test suite optimization

Procedia PDF Downloads 313
395 Web-GIS Technology: A Tool for Farm-to-Market Road Project Profiling and Proposal Prioritization of the Philippines’ Department of Agriculture

Authors: Elbert S. Moyon, Edsel Matt O. Morales, Jaymer M. Jayoma, Kent C. Espejon, Jayson C. Dollete, Mark Phil B. Pacot

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This research paper focuses on the potential of using Web-GIS technology in prioritizing farm-to-market road projects by the Philippines’ Department of Agriculture (DA). The study aimed to explore the benefits of Web-GIS in addressing the limitations faced by the DA in terms of Farm to Market Road profiling and project prioritization, which include a lack of access to updated data, limited spatial analysis capabilities, and difficulties in sharing information between stakeholders. The research methodology involves a comprehensive literature review and a case study of a Web-GIS application developed for the DA, which was used to profile and prioritize farm-to-market road projects in the Philippines. The results showed that the Web-GIS technology provides the DA with an effective tool for analyzing and visualizing data, which can help in profiling and prioritizing road projects based on various criteria such as economic, social, and environmental impacts. The study also showed that Web-GIS technology could help in reducing the time and effort required for road project prioritization and improve communication between stakeholders.

Keywords: GIS, web application, farm-to-market road, FMR prioritization, Django, GeoServer

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394 Prioritization of Mutation Test Generation with Centrality Measure

Authors: Supachai Supmak, Yachai Limpiyakorn

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Mutation testing can be applied for the quality assessment of test cases. Prioritization of mutation test generation has been a critical element of the industry practice that would contribute to the evaluation of test cases. The industry generally delivers the product under the condition of time to the market and thus, inevitably sacrifices software testing tasks, even though many test cases are required for software verification. This paper presents an approach of applying a social network centrality measure, PageRank, to prioritize mutation test generation. The source code with the highest values of PageRank will be focused first when developing their test cases as these modules are vulnerable to defects or anomalies which may cause the consequent defects in many other associated modules. Moreover, the approach would help identify the reducible test cases in the test suite, still maintaining the same criteria as the original number of test cases.

Keywords: software testing, mutation test, network centrality measure, test case prioritization

Procedia PDF Downloads 87
393 The Impact of P108L Genetic Variant on Calcium Release and Malignant Hyperthermia Susceptibility

Authors: Mohammed Althobiti, Patrick Booms, Dorota Fiszer, Philip Hopkins

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Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. MH results from anaesthetics induced breakdown of calcium homeostasis. RYR1 and CACN1AS mutations represent the aetiology in ~70% of the MH population. Previous studies indicate that up to 25% of MH patients carry no variants in these genes. Therefore, the aim of this study is to investigate the relationships between MH susceptibility and genes encoding skeletal muscle Ca2+ channels as well as accessory proteins. The JSRP, encoding JP-45, was previously sequenced and novel genetic variants were identified. The variant p.P108L (c.323C > T) was identified in exon 4 and encodes a change from a proline at amino acid 108 to leucine residue. The variant P108L was detected in two patients out of 50 with 4% frequency in the sample population. The alignment of DNA sequences in different species indicates highly conserved proline sequences involved in the substitution of the P108L variant. In this study, the variant P108L co-segregates with the SNP p.V92A (c.275T > C) at the same exon, both variants being inherited in the same two patients only. This indicates that the two variants may represent a haplotype. Therefore, a set of single nucleotide polymorphisms and statistical analysis will be used to investigate the effects of haplotypes on MH susceptibility. Furthermore, investigating the effect of the P108L variant in combination with RYR1 mutations or other genetic variants in other genes as a combination of two or more genetic variants, haplotypes may then provide stronger genetic evidence indicating that JSRP1 is associated with MH susceptibility. In conclusion, these preliminary results lend a potential modifier role of the variant P108L in JSRP1 in MH susceptibility and further investigations are suggested to confirm these results.

Keywords: JSRP1, malignant hyperthermia, RyR1, skeletal muscle

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392 Performance Analysis of Proprietary and Non-Proprietary Tools for Regression Testing Using Genetic Algorithm

Authors: K. Hema Shankari, R. Thirumalaiselvi, N. V. Balasubramanian

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The present paper addresses to the research in the area of regression testing with emphasis on automated tools as well as prioritization of test cases. The uniqueness of regression testing and its cyclic nature is pointed out. The difference in approach between industry, with business model as basis, and academia, with focus on data mining, is highlighted. Test Metrics are discussed as a prelude to our formula for prioritization; a case study is further discussed to illustrate this methodology. An industrial case study is also described in the paper, where the number of test cases is so large that they have to be grouped as Test Suites. In such situations, a genetic algorithm proposed by us can be used to reconfigure these Test Suites in each cycle of regression testing. The comparison is made between a proprietary tool and an open source tool using the above-mentioned metrics. Our approach is clarified through several tables.

Keywords: APFD metric, genetic algorithm, regression testing, RFT tool, test case prioritization, selenium tool

Procedia PDF Downloads 408
391 The Association Between COL4A3 Variant RS55703767 With the Susceptibility to Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus: Results from the Cohort Study

Authors: Zi-Han Li, Zi-Jun Sun, Dong-Yuan Chang, Li Zhu, Min Chen, Ming-Hui Zhao

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Aims: A genome-wide association study (GWAS) reported that patients with the rs55703767 minor allele in collagen type IV α3 chain encoding gene COL4A3 showed protection against diabetic kidney disease (DKD) in type 1 diabetes mellitus (T1DM). However, the role of rs55703767 in type 2 DKD has not been elucidated. The aim of the current study was to investigate the association between COL4A3 variant rs55703767 and DKD risk in Chinese patients with type 2 diabetes mellitus (T2DM). Methods: This nested case-control study was performed on 1311 patients who had T2DM for at least 10 years, including 580 with DKD and 731 without DKD. We detected the genotypes of all patients by TaqMan SNP Genotyping Assay and analyzed the association between COL4A3 variant rs55703767 and DKD risk. Results: Genetic analysis revealed that there was no significant difference between T2DM patients with DKD and those without DKD regarding allele or genotype frequencies of rs55703767, and the effect of this variant was not hyperglycemia specific. Conclusion: Our findings suggested that there was no detectable association between the COL4A3 variant rs55703767 and the susceptibility to DKD in the Chinese T2DM population.

Keywords: collagen type IV α3 chain, gene polymorphism, type 2 diabetes, diabetic kidney disease

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390 Sequence Analysis of the Effect of HPV-16 E1 Variation on Cervical Carcinogenesis

Authors: Fern Baedyananda, Arkom Chaiwongkot, Somchai Niruthisard, Nakarin Kitkumthorn, Parvapan Bhattarakosol

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High-risk human papillomavirus (HPV) infections cause transformation of the host cells by down-regulating and inhibiting host regulatory proteins such as p53 and pRb by overexpressing the viral oncoproteins E6 and E7. However, the E1 protein which is the only enzyme encoded by HPV has also been shown to cause DNA instability leading to the integration of the virus into the host genome and triggering carcinogenic events. A 63bp duplication in the E1 helicase region has been detected in European patients. However, the clinical prognosis of these patients is still controversial. This study was performed to determine the presence of the HPV-16 E1 63bp duplication in patient cervical samples in Thai women and determine the sequence of the variant in the Thai population. Detection of the HPV-16 E1 duplication in the helicase region was performed in 90 patient cell samples across normal, cervical intraepithelial neoplasia I-III, and squamous cervical carcinoma stages by PCR. The PCR products were purified and sequenced to determine the presence of duplication variants.The variant form was found in 10% of all CIN 1 patients. In this study, the presence of the 63 bp duplication variant in the Thai population was found to be present and was further characterized. Interestingly, all samples that exhibited the variant form of HPV-16 E1 were classified as CIN I. Presence of the variant, constricted to mild dysplasia signifies the importance of HPV-16 E1 in carcinogenesis.

Keywords: carcinogenesis, cervical cancer, human papillomavirus, HPV-16 E1

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389 Prevalence of Methylenetetrahydrofolate Reductase A1298C Variant in Tunisian Childhood Acute Lymphoblastic Leukemia

Authors: Rim Frikha, Maha Ben Jema, Moez Elloumi, Tarek Rebai

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Background: Acute lymphoblastic leukemia (ALL); a common blood cancer characterized by the interaction between genetic and environmental factors. Methylenetetrahydrofolate reductase (MTHFR) is an essential folate metabolic enzyme in the processes of DNA synthesis and methylation. A common functional variant of the MTHFR gene, the A1298C, which induces disturbances in folate metabolism, may affect susceptibility to ALL. Objective: The present study aimed to assess the prevalence of MTHFR polymorphism A1298 > C in Tunisian children with ALL. Materials and Methods: A total of 28 Tunisian ALL children were enrolled in this study. Genomic DNA was extracted from whole venous blood collected in ethylenediaminetetraacetic acid (EDTA). Genotyping was carried out with restriction fragment length polymorphism (RFLP) using MboII restriction enzyme. Genotype distribution and allele frequency of MTHFR A1298C was calculated in ALL patients. Results: The A1298C variant of MTHFR was found in 11(19.6%) heterozygous and one homozygous patient (3.5%). Conclusions: This result highlights that A1298C polymorphism of MTHFR is common in Tunisian childhood ALL and suggests that this variant may have a potential role in leukemogenesis. Genotyping of large samples and different ethnicities are required to validate these findings.

Keywords: methylenetetrahydrofolate reductase, acute lymphoblastic leukemia, A1298C variant, prevalence

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388 Multi-Sectoral Prioritization of Zoonotic Diseases in Uganda, 2017: The Perspective of One Health Experts

Authors: Musa Sekamatte

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Background: Zoonotic diseases continue to be a public health burden in countries around the world. Uganda is especially vulnerable due to its location, biodiversity, and population. Given these concerns, the Ugandan government in collaboration with the Global Health Security Agenda conducted a zoonotic disease prioritization workshop to identify zoonotic diseases of concern to multiple Ugandan ministries. Materials and Methods: The One Health Zoonotic Disease Prioritization tool, developed by the U.S. Centers for Disease Control and Prevention (CDC), was used for prioritization of zoonotic diseases in Uganda. Workshop participants included voting members representing human, animal, and environmental health ministries as well as key partners who observed the workshop. Over 100 articles describing characteristics of these zoonotic diseases were reviewed for the workshop. During the workshop, criteria for prioritization were selected, and questions and weights relevant to each criterion were determined. Next steps for multi-sectoral engagement for the prioritized zoonoses were then discussed. Results: 48 zoonotic diseases were considered during the workshop. Criteria selected to prioritize zoonotic diseases in order of importance were (1) severity of disease in humans in Uganda, (2) availability of effective control strategies, (3) potential to cause an epidemic or pandemic in humans or animals, (4) social and economic impacts, and (5) bioterrorism potential. Seven zoonotic diseases were identified as priorities for Uganda: anthrax, zoonotic influenza viruses, viral hemorrhagic fevers, brucellosis, African trypanosomiasis, plague, and rabies. Discussion: One Health approaches and multi-sectoral collaborations are crucial in the surveillance, prevention, and control strategies for zoonotic diseases. Uganda used such an approach to identify zoonotic diseases of national concern. Identifying these priority diseases enables the National One Health Platform and the Zoonotic Disease Coordinating Office to address the diseases in the future.

Keywords: national one health platform, zoonotic diseases, multi-sectoral, severity

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387 Prioritization of Sub-Watersheds in Semi Arid Region: A Case Study of Shevgaon and Pathardi Tahsils in Maharashtra

Authors: Dadasaheb R. Jawre, Maya G. Unde

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Prioritization of sub-watershed plays important role in watershed management. It shows the requirement of watershed to give a treatment for the green growth of the region and conservation of the sub-watersheds. There is a number of factors like topography of the region, climatic characteristics like rainfall and runoff, land-use land-cover, social factors which are related to the development of watershed for agricultural uses and domestic purposes in the region. The present research is throwing a focus on how morphometric parameters in association with GIS analysis will help in identifying the ranking of the sub-watersheds for further development which help of suggested watershed structures. Shevgaon and Pathardi tahsils are drought prone tahsils of Ahmednagar district in Maharashtra. These tahsils come under the semi-arid region. Sub-watershed prioritization is necessary for proper planning and management of natural resources for sustainable development of the study area. Less rainfall and increasing population pressure on the land as well as water resources lead to scarcity of the water in the region. Hence, researcher has selected Shevgaon and Pathardi tahsils for sub-watershed prioritization. There are seven sub-watersheds which selected for the present research paper. In the morphological analysis linear aspects, aerial aspects and relief aspects are considered for the prioritization. The largest sub-watershed is Erdha which is located at Karanji in Pathardi tahsil having an area of 145.06 km2 and smallest sub-watershed is Erandgaon which is located in Shevgaon tahsil having an area of 40.143 km2. For all seven sub-watersheds, seven morphometric parameters were considered for calculating the compound parameter values. Finally, compound parameter values are grouped into three groups such as, high priority (below 4.0), moderate priority (4.0 to 5.0) and low priority (above 5.0) according to the compound value Erandgaon, Chapadgaon and Tarak sub-watersheds comes under high priority group, Erdha and Domeshwar sub-watersheds come under moderate priority group and Chandani and Kasichi sub-watershed come under low priority group. Both the tahsils falls in drought prone area, after getting the watershed structure overall development of the region will take place.

Keywords: sub-watersheds, GIS and remote sensing, morphometric analysis, compound parameter value, prioritization

Procedia PDF Downloads 133
386 Design an Development of an Agorithm for Prioritizing the Test Cases Using Neural Network as Classifier

Authors: Amit Verma, Simranjeet Kaur, Sandeep Kaur

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Test Case Prioritization (TCP) has gained wide spread acceptance as it often results in good quality software free from defects. Due to the increase in rate of faults in software traditional techniques for prioritization results in increased cost and time. Main challenge in TCP is difficulty in manually validate the priorities of different test cases due to large size of test suites and no more emphasis are made to make the TCP process automate. The objective of this paper is to detect the priorities of different test cases using an artificial neural network which helps to predict the correct priorities with the help of back propagation algorithm. In our proposed work one such method is implemented in which priorities are assigned to different test cases based on their frequency. After assigning the priorities ANN predicts whether correct priority is assigned to every test case or not otherwise it generates the interrupt when wrong priority is assigned. In order to classify the different priority test cases classifiers are used. Proposed algorithm is very effective as it reduces the complexity with robust efficiency and makes the process automated to prioritize the test cases.

Keywords: test case prioritization, classification, artificial neural networks, TF-IDF

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385 WebGIS Development Framework With Prioritized Usability Elements

Authors: Ezekiel Mwangi, Stephen Kimani, Agnes Mindila

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Usability is one of the key factors that determine the success or failure of any WebGIS (technology normally applied on the internet to analyze and present spatial data on the Internet). However, not all the usability attributes have the same impact on usability. It is, therefore, necessary to prioritize WebGIS usability elements and determine the ones that are more crucial to the success of the WebGIS. This research aims to identify the main elements of WebGIS usability, investigate the order of importance and priority of the usability elements of WebGIS, and propose a WebGIS development framework that incorporates the prioritization of the usability elements. This will be achieved through a literature review. The outcome of this research will help usability specialists and WebGIS developers in determining specific usability elements that should be accorded more emphasis during the design and development of WebGIS.

Keywords: framework, prioritization, usability, WebGIS

Procedia PDF Downloads 133
384 Manual to Automated Testing: An Effort-Based Approach for Determining the Priority of Software Test Automation

Authors: Peter Sabev, Katalina Grigorova

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Test automation allows performing difficult and time consuming manual software testing tasks efficiently, quickly and repeatedly. However, development and maintenance of automated tests is expensive, so it needs a proper prioritization what to automate first. This paper describes a simple yet efficient approach for such prioritization of test cases based on the effort needed for both manual execution and software test automation. The suggested approach is very flexible because it allows working with a variety of assessment methods, and adding or removing new candidates at any time. The theoretical ideas presented in this article have been successfully applied in real world situations in several software companies by the authors and their colleagues including testing of real estate websites, cryptographic and authentication solutions, OSGi-based middleware framework that has been applied in various systems for smart homes, connected cars, production plants, sensors, home appliances, car head units and engine control units (ECU), vending machines, medical devices, industry equipment and other devices that either contain or are connected to an embedded service gateway.

Keywords: automated testing, manual testing, test automation, software testing, test prioritization

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383 Inhibition of Variant Surface Glycoproteins Translation to Define the Essential Features of the Variant Surface Glycoprotein in Trypanosoma brucei

Authors: Isobel Hambleton, Mark Carrington

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Trypanosoma brucei, the causal agent of a range of diseases in humans and livestock, evades the mammalian immune system through a population survival strategy based on the expression of a series of antigenically distinct variant surface glycoproteins (VSGs). RNAi mediated knockdown of the active VSG gene triggers a precytokinesis cell cycle arrest. To determine whether this phenotype is the result of reduced VSG transcript or depleted VSG protein, we used morpholino antisense oligonucleotides to block translation of VSG mRNA. The same precytokinesis cell cycle arrest was observed, suggesting that VSG protein abundance is monitored closely throughout the cell cycle. An inducible expression system has been developed to test various GPI-anchored proteins for their ability to rescue this cell cycle arrest. This system has been used to demonstrate that wild-type VSG expressed from a T7 promoter rescues this phenotype. This indicates that VSG expression from one of the specialised bloodstream expression sites (BES) is not essential for cell division. The same approach has been used to define the minimum essential features of a VSG necessary for function.

Keywords: bloodstream expression site, morpholino, precytokinesis cell cycle arrest, variant surface glycoprotein

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382 Peculiar Implications of Self Perceived Identity as Policy Tool for Transgender Recognition in Pakistan

Authors: Hamza Iftikhar

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The research study focuses on the transgender community's gender recognition challenges. It is one of the issues for the transgender community, interacting directly with the difficulties of gender identity and the lives of these people who are facing gender disapproval from society. This study investigates the major flaws of the transgender act. The study's goal is to look into the strange implications of self-perceived identity as a policy tool for transgender recognition. This policy tool jeopardises the rights of Pakistan's indigenous gender-variant people as well as the country's legal and social framework. Qualitative research using semi structured interviews will be carried out. This study proposes developing a scheme for mainstreaming gender-variant people on the basis of the Pakistani Constitution, Supreme Court guidelines, and internationally recognised principles of law. This would necessitate a thorough review of current law using a new approach and reference point.

Keywords: transgender act, self perceived identity, gender variant, policy tool

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381 An Approximation Technique to Automate Tron

Authors: P. Jayashree, S. Rajkumar

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With the trend of virtual and augmented reality environments booming to provide a life like experience, gaming is a major tool in supporting such learning environments. In this work, a variant of Voronoi heuristics, employing supervised learning for the TRON game is proposed. The paper discusses the features that would be really useful when a machine learning bot is to be used as an opponent against a human player. Various game scenarios, nature of the bot and the experimental results are provided for the proposed variant to prove that the approach is better than those that are currently followed.

Keywords: artificial Intelligence, automation, machine learning, TRON game, Voronoi heuristics

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380 Erosion Susceptibility Zoning and Prioritization of Micro-Watersheds: A Remote Sensing-Gis Based Study of Asan River Basin, Western Doon Valley, India

Authors: Pijush Roy, Vinay Kumar Rai

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The present study highlights the estimation of soil loss and identification of critical area for implementation of best management practice is central to the success of soil conservation programme. The quantification of morphometric and Universal Soil Loss Equation (USLE) factors using remote sensing and GIS for prioritization of micro-watersheds in Asan River catchment, western Doon valley at foothills of Siwalik ranges in the Dehradun districts of Uttarakhand, India. The watershed has classified as a dendritic pattern with sixth order stream. The area is classified into very high, high, moderately high, medium and low susceptibility zones. High to very high erosion zone exists in the urban area and agricultural land. Average annual soil loss of 64 tons/ha/year has been estimated for the watershed. The optimum management practices proposed for micro-watersheds of Asan River basin are; afforestation, contour bunding suitable sites for water harvesting structure as check dam and soil conservation, agronomical measure and bench terrace.

Keywords: erosion susceptibility zones, morphometric characteristics, prioritization, remote sensing and GIS, universal soil loss equation

Procedia PDF Downloads 285
379 Ultra-Fast pH-Gradient Ion Exchange Chromatography for the Separation of Monoclonal Antibody Charge Variants

Authors: Robert van Ling, Alexander Schwahn, Shanhua Lin, Ken Cook, Frank Steiner, Rowan Moore, Mauro de Pra

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Purpose: Demonstration of fast high resolution charge variant analysis for monoclonal antibody (mAb) therapeutics within 5 minutes. Methods: Three commercially available mAbs were used for all experiments. The charge variants of therapeutic mAbs (Bevacizumab, Cetuximab, Infliximab, and Trastuzumab) are analyzed on a strong cation exchange column with a linear pH gradient separation method. The linear gradient from pH 5.6 to pH 10.2 is generated over time by running a linear pump gradient from 100% Thermo Scientific™ CX-1 pH Gradient Buffer A (pH 5.6) to 100% CX-1 pH Gradient Buffer B (pH 10.2), using the Thermo Scientific™ Vanquish™ UHPLC system. Results: The pH gradient method is generally applicable to monoclonal antibody charge variant analysis. In conjunction with state-of-the-art column and UHPLC technology, ultra fast high-resolution separations are consistently achieved in under 5 minutes for all mAbs analyzed. Conclusion: The linear pH gradient method is a platform method for mAb charge variant analysis. The linear pH gradient method can be easily optimized to improve separations and shorten cycle times. Ultra-fast charge variant separation is facilitated with UHPLC that complements, and in some instances outperforms CE approaches in terms of both resolution and throughput.

Keywords: charge variants, ion exchange chromatography, monoclonal antibody, UHPLC

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378 Scoring Approach to Identify High-Risk Corridors for Winter Safety Measures ‎in the Iranian Roads Network

Authors: M. Mokhber, J. Hedayati

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From the managerial perspective, it is important to devise an operational plan based on top priorities due to limited resources, diversity of measures and high costs needed to improve safety in infrastructure. Dealing with the high-risk corridors across Iran, this study prioritized the corridors according to statistical data on accidents involving fatalities, injury or damage over three consecutive years. In collaboration with the Iranian Police Department, data were collected and modified. Then, the prioritization criteria were specified based on the expertise opinions and international standards. In this study, the prioritization criteria included accident severity and accident density. Finally, the criteria were standardized and weighted (equal weights) to score each high-risk corridor. The prioritization phase involved the scoring and weighting procedure. The high-risk corridors were divided into twelve groups out of 50. The results of data analysis for a three-year span suggested that the first three groups (150 corridors) along with a quarter of Iranian road network length account for nearly 60% of traffic accidents. In the next step, according to variables including weather conditions particular roads for the purpose of winter safety measures were extracted from the abovementioned categories. According to the results ranking, ‎‏9‏‎ roads with the overall ‎length of about ‎‎‏1000‏‎ Km of high-risk corridors are considered as preferences of ‎safety measures‎.

Keywords: high-risk corridors, HRCs, road safety rating, road scoring, winter safety measures

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377 Risk Assessment on Construction Management with “Fuzzy Logy“

Authors: Mehrdad Abkenari, Orod Zarrinkafsh, Mohsen Ramezan Shirazi

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Construction projects initiate in complicated dynamic environments and, due to the close relationships between project parameters and the unknown outer environment, they are faced with several uncertainties and risks. Success in time, cost and quality in large scale construction projects is uncertain in consequence of technological constraints, large number of stakeholders, too much time required, great capital requirements and poor definition of the extent and scope of the project. Projects that are faced with such environments and uncertainties can be well managed through utilization of the concept of risk management in project’s life cycle. Although the concept of risk is dependent on the opinion and idea of management, it suggests the risks of not achieving the project objectives as well. Furthermore, project’s risk analysis discusses the risks of development of inappropriate reactions. Since evaluation and prioritization of construction projects has been a difficult task, the network structure is considered to be an appropriate approach to analyze complex systems; therefore, we have used this structure for analyzing and modeling the issue. On the other hand, we face inadequacy of data in deterministic circumstances, and additionally the expert’s opinions are usually mathematically vague and are introduced in the form of linguistic variables instead of numerical expression. Owing to the fact that fuzzy logic is used for expressing the vagueness and uncertainty, formulation of expert’s opinion in the form of fuzzy numbers can be an appropriate approach. In other words, the evaluation and prioritization of construction projects on the basis of risk factors in real world is a complicated issue with lots of ambiguous qualitative characteristics. In this study, evaluated and prioritization the risk parameters and factors with fuzzy logy method by combination of three method DEMATEL (Decision Making Trial and Evaluation), ANP (Analytic Network Process) and TOPSIS (Technique for Order-Preference by Similarity Ideal Solution) on Construction Management.

Keywords: fuzzy logy, risk, prioritization, assessment

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376 Changes in Physical Soil Properties and Crop Status on Soil Enriched With Treated Manure

Authors: Vaclav Novak, Katerina Krizova, Petr Sarec

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Modern agriculture has to face many issues from which soil degradation and lack of organic matter in the soil are only a few of them. Apart from Climate Change, human utilization of landscape is the cause of a majority part of these problems. Cattle production in Czechia has been reduced by more than half in recent 30 years. However, cattle manure is considered as staple organic fertilizer, and its role in attempts for sustainable agriculture is irreplaceable. This study aims to describe the impact of so-called activators of biological manure transformation (Z´fix, Olmix Group) mainly on physical soil properties but also on crop status. The experiment has been established in 2017; nevertheless, initial measurements of implement draft have been performed before the treated manure application. In 2018, the physical soil properties and crop status (sugar beet) has been determined and compared with the untreated manure and control variant. Significant results have been observed already in the first year, where the implement draft decreased by 9.2 % within the treated manure variant in comparison with the control variant.

Keywords: field experiment, implement draft, vegetation index, sugar beet

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375 Prioritization Ranking for Managing Moisture Problems in a Building

Authors: Sai Amulya Gollapalli, Dilip A. Patel, Parth Patel K., Lukman E. Mansuri

Abstract:

Accumulation of moisture is one of the most worrisome aspects of a building. Architects and engineers tend to ignore its vitality during the designing and construction stage. Major fatalities in buildings can be caused by it. People avoid spending a lot of money on waterproofing. If the same mistake is repeated, no deep thinking is done. The quality of workmanship and construction is depleting due to negligence. It is important to do an analysis of the water maintenance issues happening in the current buildings and give a database for all the factors that are causing the defect. In this research, surveys are done with two waterproofing consultants, two client engineers, and two project managers. The survey was based on a matrix that was based on the causes of water maintenance issues. There were around 100 causes that were identified. The causes were categorized into six, namely, manpower, finance, method, management, environment, and material. In the matrices, the causes on the x-direction matched with the causes on the y-direction. 3 Likert scale was used to make a pairwise comparison between causes on each cell. Matrices were evaluated for the main categories and for each category separately. A final ranking was done by the weights achieved, and ‘cracks arriving from various construction joints’ was the highest with 0.57 relative significance, and ‘usage of the material’ was the lowest with 0.03 relative significance. Twelve defects due to water leakage were identified, and interviewees were asked to make a pairwise comparison of them, too, to understand the priorities. When the list of causes is achieved, the prioritization as per the stratification analysis is done. This will be beneficial to the consultants and contractors as they will get a primary idea of which causes to focus on.

Keywords: water leakage, survey, causes, matrices, prioritization

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374 In silico Analysis of a Causative Mutation in Cadherin-23 Gene Identified in an Omani Family with Hearing Loss

Authors: Mohammed N. Al Kindi, Mazin Al Khabouri, Khalsa Al Lamki, Tommasso Pappuci, Giovani Romeo, Nadia Al Wardy

Abstract:

Hereditary hearing loss is a heterogeneous group of complex disorders with an overall incidence of one in every five hundred newborns presented as syndromic and non-syndromic forms. Cadherin-related 23 (CDH23) is one of the listed deafness causative genes. CDH23 is found to be expressed in the stereocilia of hair cells and the retina photoreceptor cells. Defective CDH23 has been associated mostly with prelingual severe-to-profound sensorineural hearing loss (SNHL) in either syndromic (USH1D) or non-syndromic SNHL (DFNB12). An Omani family diagnosed clinically with severe-profound sensorineural hearing loss was genetically analysed by whole exome sequencing technique. A novel homozygous missense variant, c.A7451C (p.D2484A), in exon 53 of CDH23 was detected. One hundred and thirty control samples were analysed where all were negative for the detected variant. The variant was analysed in silico for pathogenicity verification using several mutation prediction software. The variant proved to be a pathogenic mutation and is reported for the first time in Oman and worldwide. It is concluded that in silico mutation prediction analysis might be used as a useful molecular diagnostics tool benefiting both genetic counseling and mutation verification. The aspartic acid 2484 alanine missense substitution might be the main disease-causing mutation that damages CDH23 function and could be used as a genetic hearing loss marker for this particular Omani family.

Keywords: Cdh23, d2484a, in silico, Oman

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373 Method for Selecting and Prioritising Smart Services in Manufacturing Companies

Authors: Till Gramberg, Max Kellner, Erwin Gross

Abstract:

This paper presents a comprehensive investigation into the topic of smart services and IIoT-Platforms, focusing on their selection and prioritization in manufacturing organizations. First, a literature review is conducted to provide a basic understanding of the current state of research in the area of smart services. Based on discussed and established definitions, a definition approach for this paper is developed. In addition, value propositions for smart services are identified based on the literature and expert interviews. Furthermore, the general requirements for the provision of smart services are presented. Subsequently, existing approaches for the selection and development of smart services are identified and described. In order to determine the requirements for the selection of smart services, expert opinions from successful companies that have already implemented smart services are collected through semi-structured interviews. Based on the results, criteria for the evaluation of existing methods are derived. The existing methods are then evaluated according to the identified criteria. Furthermore, a novel method for the selection of smart services in manufacturing companies is developed, taking into account the identified criteria and the existing approaches. The developed concept for the method is verified in expert interviews. The method includes a collection of relevant smart services identified in the literature. The actual relevance of the use cases in the industrial environment was validated in an online survey. The required data and sensors are assigned to the smart service use cases. The value proposition of the use cases is evaluated in an expert workshop using different indicators. Based on this, a comparison is made between the identified value proposition and the required data, leading to a prioritization process. The prioritization process follows an established procedure for evaluating technical decision-making processes. In addition to the technical requirements, the prioritization process includes other evaluation criteria such as the economic benefit, the conformity of the new service offering with the company strategy, or the customer retention enabled by the smart service. Finally, the method is applied and validated in an industrial environment. The results of these experiments are critically reflected upon and an outlook on future developments in the area of smart services is given. This research contributes to a deeper understanding of the selection and prioritization process as well as the technical considerations associated with smart service implementation in manufacturing organizations. The proposed method serves as a valuable guide for decision makers, helping them to effectively select the most appropriate smart services for their specific organizational needs.

Keywords: smart services, IIoT, industrie 4.0, IIoT-platform, big data

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372 A CD40 Variant is Associated with Systemic Bone Loss Among Patients with Rheumatoid Arthritis

Authors: Rim Sghiri, Samia Al Shouli, Hana Benhassine, Nejla Elamri, Zahid Shakoor, Foued Slama, Adel Almogren, Hala Zeglaoui, Elyes Bouajina, Ramzi Zemni

Abstract:

Objectives: Little is known about genes predisposing to systemic bone loss (SBL) in rheumatoid arthritis (RA). Therefore, we examined the association between SBL and a variant of CD40 gene, which is known to play a critical role in both immune response and bone homeostasis among patients with RA. Methods: CD40 rs48104850 was genotyped in 176 adult RA patients. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA). Results: Low BMD was observed in 116 (65.9%) patients. Among them, 60 (34.1%) had low femoral neck (FN) Z score, 72 (40.9%) had low total femur (TF) Z score, and 105 (59.6%) had low lumbar spine (LS) Z score. CD40 rs4810485 was found to be associated with reduced TF Z score with the CD40 rs4810485 T allele protecting against reduced TF Z score (OR = 0.40, 95% CI = 0.23-0.68, p = 0.0005). This association was confirmed in the multivariate logistic regression analysis (OR=0.31, 95% CI= 0.16-0.59, p=3.84 x 10₋₄). Moreover, median FN BMD was reduced among RA patients with CD40 rs4810485 GG genotype compared to RA patients harbouring CD40 rs4810485 TT and GT genotypes (0.788± 0.136 versus 0.826± 0.146g/cm², p=0.001). Conclusion: This study, for the first time ever, demonstrated an association between a CD40 genetic variant and SBL among patients with RA.

Keywords: rheumatoid arthritis, CD40 gene, bone mineral density, systemic bone loss, rs48104850

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371 Variant Selection and Pre-transformation Phase Reconstruction for Deformation-Induced Transformation in AISI 304 Austenitic Stainless Steel

Authors: Manendra Singh Parihar, Sandip Ghosh Chowdhury

Abstract:

Austenitic stainless steels are widely used and give a good combination of properties. When this steel is plastically deformed, a phase transformation of the metastable Face Centred Cubic Austenite to the stable Body Centred Cubic (α’) or to the Hexagonal close packed (ԑ) martensite may occur, leading to the enhancement in the mechanical properties like strength. The work was based on variant selection and corresponding texture analysis for the strain induced martensitic transformation during deformation of the parent austenite FCC phase to form the product HCP and the BCC martensite phases separately, obeying their respective orientation relationships. The automated method for reconstruction of the parent phase orientation using the EBSD data of the product phase orientation is done using the MATLAB and TSL-OIM software. The method of triplets was used which involves the formation of a triplet of neighboring product grains having a common variant and linking them using a misorientation-based criterion. This led to the proper reconstruction of the pre-transformation phase orientation data and thus to its micro structure and texture. The computational speed of current method is better compared to the previously used methods of reconstruction. The reconstruction of austenite from ԑ and α’ martensite was carried out for multiple samples and their IPF images, pole figures, inverse pole figures and ODFs were compared. Similar type of results was observed for all samples. The comparison gives the idea for estimating the correct sequence of the transformation i.e. γ → ε → α’ or γ → α’, during deformation of AISI 304 austenitic stainless steel.

Keywords: variant selection, reconstruction, EBSD, austenitic stainless steel, martensitic transformation

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370 Risk Prioritization in Tunneling Construction Projects

Authors: David Nantes, George Gilbert

Abstract:

There are a lot of risks that might crop up as a tunneling project develops, and it's crucial to be aware of them. Due to the unexpected nature of tunneling projects and the interconnectedness of risk occurrences, the risk assessment approach presents a significant challenge. The purpose of this study is to provide a hybrid FDEMATEL-ANP model to help prioritize risks during tunnel construction projects. The ambiguity in expert judgments and the relative severity of interdependencies across risk occurrences are both taken into consideration by this model, thanks to the Fuzzy Decision-Making Trial and Evaluation Laboratory (FDEMATEL). The Analytic Network Process (ANP) method is used to rank priorities and assess project risks. The authors provide a case study of a subway tunneling construction project to back up the validity of their methodology. The results showed that the proposed method successfully isolated key risk factors and elucidated their interplay in the case study. The proposed method has the potential to become a helpful resource for evaluating dangers associated with tunnel construction projects.

Keywords: risk, prioritization, FDEMATEL, ANP, tunneling construction projects

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