Search results for: copy number variant

Authors: Michael Zimba

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A duplicated image region may be subjected to a number of attacks such as noise addition, compression, reflection, rotation, and scaling with the intention of either merely mating it to its targeted neighborhood or preventing its detection. In this paper, we present an effective and robust method of detecting duplicated regions inclusive of those affected by the various attacks. In order to reduce the dimension of the image, the proposed algorithm firstly performs discrete wavelet transform, DWT, of a suspicious image. However, unlike most existing copy move image forgery (CMIF) detection algorithms operating in the DWT domain which extract only the low frequency sub-band of the DWT of the suspicious image thereby leaving valuable information in the other three sub-bands, the proposed algorithm simultaneously extracts features from all the four sub-bands. The extracted features are not only more accurate representation of image regions but also robust to additive noise, JPEG compression, and affine transformation. Furthermore, principal component analysis-eigenvalue decomposition, PCA-EVD, is applied to reduce the dimension of the features. The extracted features are then sorted using the more computationally efficient Radix Sort algorithm. Finally, same affine transformation selection, SATS, a duplication verification method, is applied to detect duplicated regions. The proposed algorithm is not only fast but also more robust to attacks compared to the related CMIF detection algorithms. The experimental results show high detection rates.

Keywords: affine transformation, discrete wavelet transform, radix sort, SATS

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Authors: Jade Edey, Andrew Bennett, Gareth Hathway

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Nuclear receptor-related 1 protein (also known as Nurr1 or NR4A2) is an orphan nuclear receptor which plays a vital role in the development, survival and maintenance of dopaminergic (DA) neurons particularly in the substantia nigra (SN). Increasing research has investigated Nurr1’s additional role within microglia and astrocytes where it has been suggested to act as a negative regulator of inflammation; potentially offering neuroprotection. Considering both DA neurodegeneration and neuroinflammation are commonly accepted constituents of Parkinson’s Disease (PD), understanding the mechanisms by which Nurr1 regulates inflammatory processes could provide an attractive therapeutic target. Nurr1 regulates inflammation via a transrepressive mechanism possibly dependent upon SUMOylation. In addition, Nurr1 can transactivate numerous genes involved in DA synthesis, such as Tyrosine Hydroxylase (TH). A C-terminal splice variant of Nurr1, Nurr-1a, has been reported in both neuronal and glial cells. However, research into its transcriptional activity is minimal. We employed in vitro methods such as SUMO-Pulldown experiments alongside Luciferase reporter assays to investigate the SUMOylation status and transactivation capabilities of Nurr1 and Nurr-1a respectively. The SUMO-Pulldown assay demonstrated Nurr-1a undergoes significantly more SUMO modification than its full-length variant. Consequently, despite having less transcriptional activation than Nurr1, Nurr1a may play a more prominent role in repression of microglial inflammation. Contrary to published literature we also identified that SUMOylation enhances transcriptional activation by Nurr1 and Nurr1a. SUMOylation-dependent increases in Nurr1 and Nurr1a transcriptional activation were only evident in neuronal SHSY5Y cells but not in HEK293 cells. This research provides novel insight into the regulation of Nurr-1a and indicates differential effects of SUMOylation dependent regulation in neuronal and inflammatory cells.

Keywords: nuclear receptors, Parkinson’s disease, inflammation, transcriptional regulation

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Authors: Amel Tayari, Atef Eljerry, Mourad Magherbi

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The paper reports a numerical investigation of the entropy generation analysis due to mixed convection in laminar flow through a channel filled with porous media. The second law of thermodynamics is applied to investigate the entropy generation rate. The Darcy-Brinkman Model is employed. The entropy generation due to heat transfer and friction dissipations has been determined in mixed convection by solving numerically the continuity, momentum and energy equations, using a control volume finite element method. The effects of Darcy number, modified Brinkman number and the Rayleigh number on averaged entropy generation and averaged Nusselt number are investigated. The Rayleigh number varied between 103 ≤ Ra ≤ 105 and the modified Brinkman number ranges between 10-5 ≤ Br≤ 10-1 with fixed values of porosity and Reynolds number at 0.5 and 10 respectively. The Darcy number varied between 10-6 ≤ Da ≤10.

Keywords: entropy generation, porous media, heat transfer, mixed convection, numerical methods, darcy, brinkman

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Authors: Amer A. Hasan, Mehri Igci, Ersin Borazan, Rozhgar A. Khailany, Emine Bayraktar, Ahmet Arslan

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Gastric cancer (GC) has high morbidity and fatality rate in various countries and is still one of the most frequent and deadly diseases. Novel mitogenic and motogenic Gastrokine1 (GKN1) and Gastrokine 2 (GKN2) genes that are highly expressed in the normal stomach epithelium and plays an important role in maintaining the integrity and homeostasis of stomach mucosal epithelial cells. Significant loss of copy number and mRNA transcript of GKN1 and GKN2 gene expression were frequently observed in all types of gastric cancer. In this study, 47 paired samples that were grouped according to the types of gastric cancer and the clinical characteristics of the patients, including gender and average of age were investigated with gene expression analysis and mutation screening by monetering RT-PCR, SSCP and nucleotide sequencing techniques. Both GKN1 and GKN2 genes were observed significantly reduced found by (Wilcoxon signed rank test; p<0.05). As a result of gene screening, no mutation (no different genotype) was detected. It is considered that gene mutations are not the cause of inactivation of gastrokines. In conclusion, the mRNA expression level of GKN1 and GKN2 genes statistically was decreased regardless the gender, age or cancer type of patients. Reduced of gastrokine genes seems to occur at the initial steps of cancer development. In order to understand the investigation between gastric cancer and diagnostic biomarker; further analysis is necessary.

Keywords: gastric cancer, diagnostic biomarker, nucleotide sequencing, semi-quantitative RT-PCR

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Authors: Thomas Wetere

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Background: The coronavirus disease 2019 (COVID-19) pandemic (COVID-19) virus infection is a severe infectious disease with the highly transmissible variant, which become the global public health treat now. It has taken the life of more than 4 million people so far. What makes the disease the worst of all is no specific effective treatment available, its dynamics is not much researched and understood. Methodology: To end the global COVID-19 pandemic, implementation of multiple population-wide strategies, including vaccination, environmental factors, Government action, testing, and contact tracing, is required. In this article, a new mathematical model incorporating both temperature and government action to study the dynamics of the COVID-19 pandemic has been developed and comprehensively analysed. The model considers eight stages of infection: susceptible (S), infected Asymptomatic and Undetected(IAU ), infected Asymptomatic and detected(IAD), infected symptomatic and Undetected(ISU ), infected Symptomatic and detected(ISD), Hospitalized or threatened(H), Recovered(R) and Died(D). Results: The existence as well as non-negativity of the solution to the model is also verified, and the basic reproduction number is calculated. Besides, stability conditions are also checked, and finally, simulation results are compared with real data. The results demonstrates that effective government action will need to be combined with vaccination to end the ongoing COVID-19 pandemic. Conclusion: Vaccination and Government action are highly the crucial measures to control the COVID-19 pandemic. Besides, as the cost of vaccination might be high, we recommend an optimal control to reduce the cost and number of infected individuals. Moreover, in order to prevent COVID-19 pandemic, through the analysis of the model, the government must strictly manage the policy on COVID-19 and carry it out. This, in turn, helps for health campaigning and raising health literacy which plays a role to control the quick spread of the disease. We finally strongly believe that our study will play its own role in the current effort of controlling the pandemic.

Keywords: modeling, COVID-19, MCMC, stability

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Authors: Marielle Leijten, Catherine Meulemans, Sven De Maeyer, Luuk Van Waes

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For the diagnosis of Alzheimer's disease (AD), a large variety of neuropsychological tests are available. In some of these tests, linguistic processing - both oral and written - is an important factor. Language disturbances might serve as a strong indicator for an underlying neurodegenerative disorder like AD. However, the current diagnostic instruments for language assessment mainly focus on product measures, such as text length or number of errors, ignoring the importance of the process that leads to written or spoken language production. In this study, it is our aim to describe and test differences between cognitive and impaired elderly on the basis of a selection of writing process variables (inter- and intrapersonal characteristics). These process variables are mainly related to pause times, because the number, length, and location of pauses have proven to be an important indicator of the cognitive complexity of a process. Method: Participants that were enrolled in our research were chosen on the basis of a number of basic criteria necessary to collect reliable writing process data. Furthermore, we opted to match the thirteen cognitively impaired patients (8 MCI and 5 AD) with thirteen cognitively healthy elderly. At the start of the experiment, participants were each given a number of tests, such as the Mini-Mental State Examination test (MMSE), the Geriatric Depression Scale (GDS), the forward and backward digit span and the Edinburgh Handedness Inventory (EHI). Also, a questionnaire was used to collect socio-demographic information (age, gender, eduction) of the subjects as well as more details on their level of computer literacy. The tests and questionnaire were followed by two typing tasks and two picture description tasks. For the typing tasks participants had to copy (type) characters, words and sentences from a screen, whereas the picture description tasks each consisted of an image they had to describe in a few sentences. Both the typing and the picture description tasks were logged with Inputlog, a keystroke logging tool that allows us to log and time stamp keystroke activity to reconstruct and describe text production processes. The main rationale behind keystroke logging is that writing fluency and flow reveal traces of the underlying cognitive processes. This explains the analytical focus on pause (length, number, distribution, location, etc.) and revision (number, type, operation, embeddedness, location, etc.) characteristics. As in speech, pause times are seen as indexical of cognitive effort. Results. Preliminary analysis already showed some promising results concerning pause times before, within and after words. For all variables, mixed effects models were used that included participants as a random effect and MMSE scores, GDS scores and word categories (such as determiners and nouns) as a fixed effect. For pause times before and after words cognitively impaired patients paused longer than healthy elderly. These variables did not show an interaction effect between the group participants (cognitively impaired or healthy elderly) belonged to and word categories. However, pause times within words did show an interaction effect, which indicates pause times within certain word categories differ significantly between patients and healthy elderly.

Keywords: Alzheimer's disease, keystroke logging, matching, writing process

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Authors: Kelsi Hagerty, Ami Rosen, Aaliyah Heyward, Nadia Ali, Emily Brown, Erin Demo, Yue Guan, Modele Ogunniyi, Brianna McDaniels, Alanna Morris, Kunal Bhatt

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Hereditary transthyretin amyloidosis (hATTR) is a progressive, multi-systemic, and life-threatening disease caused by a disruption in the TTR protein that delivers thyroxine and retinol to the liver. This disruption causes the protein to misfold into amyloid fibrils, leading to the accumulation of the amyloid fibrils in the heart, nerves, and GI tract. Over 130 variants in the TTR gene are known to cause hATTR. The Val122Ile variant is the most common in the United States and is seen almost exclusively in people of African descent. TTR variants are inherited in an autosomal dominant fashion and have incomplete penetrance and variable expressivity. Individuals with hATTR may exhibit symptoms from as early as 30 years to as late as 80 years of age. hATTR is characterized by a wide range of clinical symptoms such as cardiomyopathy, neuropathy, carpal tunnel syndrome, and GI complications. Without treatment, hATTR leads to progressive disease and can ultimately lead to heart failure. hATTR disproportionately affects individuals of African descent; the estimated prevalence of hATTR among Black individuals in the US is 3.4%. Unfortunately, hATTR is often underdiagnosed and misdiagnosed because many symptoms of the disease overlap with other cardiac conditions. Due to the progressive nature of the disease, multi-systemic manifestations that can lead to a shortened lifespan, and the availability of free genetic testing and promising FDA-approved therapies that enhance treatability, early identification of individuals with a pathogenic hATTR variant is important, as this can significantly impact medical management for patients and their relatives. Furthermore, recent literature suggests that TTR genetic testing should be performed in all patients with suspicion of TTR-related cardiomyopathy, regardless of age, and that follow-up with genetic counseling services is recommended. Relatives of patients with hATTR benefit from genetic testing because testing can identify carriers early and allow relatives to receive regular screening and management. Despite the striking prevalence of hATTR among Black individuals, hATTR remains underdiagnosed in this patient population, and germline genetic testing for hATTR in Black individuals seems to be underrepresented, though the reasons for this have not yet been brought to light. Historically, Black patients experience a number of barriers to seeking healthcare that has been hypothesized to perpetuate the underdiagnosis of hATTR, such as lack of access and mistrust of healthcare professionals. Prior research has described a myriad of factors that shape an individual’s decision about whether to pursue presymptomatic genetic testing for a familial pathogenic variant, such as family closeness and communication, family dynamics, and a desire to inform other family members about potential health risks. This study explores these factors through 10 in-depth interviews with patients with hATTR about what factors may be contributing to the underdiagnosis of hATTR in the Black population. Participants were selected from the Emory University Amyloidosis clinic based on having a molecular diagnosis of hATTR. Interviews were recorded and transcribed verbatim, then coded using MAXQDA software. Thematic analysis was completed to draw commonalities between participants. Upon preliminary analysis, several themes have emerged. Barriers identified include i) Misdiagnosis and a prolonged diagnostic odyssey, ii) Family communication and dynamics surrounding health issues, iii) Perceptions of healthcare and one’s own health risks, and iv) The need for more intimate provider-patient relationships and communication. Overall, this study gleaned valuable insight from members of the Black community about possible factors contributing to the underdiagnosis of hATTR, as well as potential solutions to go about resolving this issue.

Keywords: cardiac amyloidosis, heart failure, TTR, genetic testing

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Authors: Mohammad Mirzaei

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This article proposes literary criticism as a source of insight into consumer behavior, provides an extensive overview of literary criticism, provides concrete illustrative analysis, and offers suggestions for further research. To do, a literary analysis of advertising copy identifies elements that provide additional information to consumer researchers and discusses the contribution of literary criticism to consumer research. Important post-war critical schools of thought are reviewed, and relevant theoretical concepts are summarized. Ivory Flakes' advertisements are analyzed using a variety of concepts drawn from literary schools, primarily sociocultural and reader responses. Suggestions for further research on content analysis, image analysis, and consumption history are presented.

Keywords: consumer behaviour, consumer research, consumption history, criticism

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Authors: Salem Ben Said

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In recent times the decimal number system to which we are accustomed has received serious competition from the binary number system. In this note, an approach is suggested to teaching and learning the binary number system using examples from the real world. More precisely, we will demonstrate the utility of the binary system in describing the optimal strategy to win the Chinese Nim game, and in telegraphy by decoding the hidden message on Perseverance’s Mars parachute written in the language of binary system. Finally, we will answer the question, “why do modern computers prefer the ternary number system instead of the binary system?”. All materials are provided in a format that is conductive to classroom presentation and discussion.

Keywords: binary number system, Nim game, telegraphy, computers prefer the ternary system

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Authors: Pei-Chen Wu

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Both preexisting cross-sectional and longitudinal studies of personality-depression relationship have suffered from one main limitation: they ignored the stability of the construct of interest (e.g., personality and depression) can be expected to influence the estimate of the association between personality and depression. To address this limitation, the Trait-State-Occasion (TSO) modeling was adopted to analyze the sources of variance of the focused constructs. A TSO modeling was operated by partitioning a state variance into time-invariant (trait) and time-variant (occasion) components. Within a TSO framework, it is possible to predict change on the part of construct that really changes (i.e., time-variant variance), when controlling the trait variances. 750 high school students were followed for 4 waves over six-month intervals. The baseline data (T1) were collected from the senior high schools (aged 14 to 15 years). Participants were given Beck Depression Inventory and Big Five Inventory at each assessment. TSO modeling revealed that 70~78% of the variance in personality (five constructs) was stable over follow-up period; however, 57~61% of the variance in depression was stable. For personality construct, there were 7.6% to 8.4% of the total variance from the autoregressive occasion factors; for depression construct there were 15.2% to 18.1% of the total variance from the autoregressive occasion factors. Additionally, results showed that when controlling initial symptom severity, the time-invariant components of all five dimensions of personality were predictive of change in depression (Extraversion: B= .32, Openness: B = -.21, Agreeableness: B = -.27, Conscientious: B = -.36, Neuroticism: B = .39). Because five dimensions of personality shared some variance, the models in which all five dimensions of personality were simultaneous to predict change in depression were investigated. The time-invariant components of five dimensions were still significant predictors for change in depression (Extraversion: B = .30, Openness: B = -.24, Agreeableness: B = -.28, Conscientious: B = -.35, Neuroticism: B = .42). In sum, the majority of the variability of personality was stable over 2 years. Individuals with the greater tendency of Extraversion and Neuroticism have higher degrees of depression; individuals with the greater tendency of Openness, Agreeableness and Conscientious have lower degrees of depression.

Keywords: assessment, depression, personality, trait-state-occasion model

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Authors: Saurav Sharma, Deepshikha Sharma, Pratibha Sharma

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This paper includes fast fashion verses sustainable fashion or slow fashion Indian based consumers. The expression ‘Fast fashion’ is generally referred to low-cost clothing collections that considered first hand copy of luxury brands, sometime interchangeably used with ‘mass fashion’. Whereas slow fashion or limited fashion which are consider to be more organic or eco-friendly. "Sustainable fashion is ethical fashion and here the consumer is just not design conscious but also social-environment conscious". Paper will deal with desire of young Indian consumer towards such luxury brands present in India, and their understanding of sustainable fashion, how to maintain the equilibrium between never newer fashion, style, and fashion sustainability.

Keywords: fast fashion, sustainable fashion, sustainability, India

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Authors: Ladislav Kristoufek, Helen Susannah Moat, Tobias Preis

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Data on the number of people who have committed suicide tends to be reported with a substantial time lag of around two years. We examine whether online activity measured by Google searches can help us improve estimates of the number of suicide occurrences in England before official figures are released. Specifically, we analyse how data on the number of Google searches for the terms “depression” and “suicide” relate to the number of suicides between 2004 and 2013. We find that estimates drawing on Google data are significantly better than estimates using previous suicide data alone. We show that a greater number of searches for the term “depression” is related to fewer suicides, whereas a greater number of searches for the term “suicide” is related to more suicides. Data on suicide related search behaviour can be used to improve current estimates of the number of suicide occurrences.

Keywords: nowcasting, search data, Google Trends, official statistics

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Authors: Tomas Barnak, Libor Matejka

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The aim of this study is to create a standard application using multi-criteria evaluation in the field of forensic engineering. This situation can occur in the professional assessment in several cases such as when it is necessary to consider more criteria variant of the structural subsystems, more variants according to several criteria based on a court claim, which requires expert advice. A problematic situation arises when it is necessary to clearly determine the ranking of the options according to established criteria, and reduce subjective evaluation. For the procurement in the field of construction which is based on the prepared text of the law not only economic criteria but also technical, technological and environmental criteria will be determined. This fact substantially changes the style of evaluation of individual bids. For the above-mentioned needs of procurement, the unification of expert’s decisions and the use of multi-criteria assessment seem to be a reasonable option. In the case of experimental verification when using multi-criteria evaluation of alternatives construction subsystem the economic, technical, technological and environmental criteria will be compared. The core of the solution is to compare a selected number of set criteria, application methods and evaluation weighting based on the weighted values assigned to each of the criteria to use multi-criteria evaluation methods. The sequence of individual variations is determined by the evaluation of the importance of the values of corresponding criteria concerning expertise in the problematic of outside wall constructional subsystems.

Keywords: criteria, expertise, multi-criteria evaluation, outside wall subsystems

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Authors: Belmiloud Mohamed Amine, Sad Chemloul Nord-Eddine

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In this study we investigated numerically heat transfer by mixed convection coupled to radiation in a square cavity; the upper horizontal wall is movable. The purpose of this study is to see the influence of the emissivity and the varying of the Richardson number on the variation of the average Nusselt number. The vertical walls of the cavity are differentially heated, the left wall is maintained at a uniform temperature higher than the right wall, and the two horizontal walls are adiabatic. The finite volume method is used for solving the dimensionless governing equations. Emissivity values used in this study are ranged between 0 and 1, the Richardson number in the range 0.1 to10. The Rayleigh number is fixed to Ra = 10000 and the Prandtl number is maintained constant Pr = 0.71. Streamlines, isothermal lines and the average Nusselt number are presented according to the surface emissivity. The results of this study show that the Richardson number and emissivity affect the average Nusselt number.

Keywords: mixed convection, square cavity, wall emissivity, lid-driven, numerical study

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Authors: Omaima N. Ahmad AL-Allaf

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Over communication networks, images can be easily copied and distributed in an illegal way. The copyright protection for authors and owners is necessary. Therefore, the digital watermarking techniques play an important role as a valid solution for authority problems. Digital image watermarking techniques are used to hide watermarks into images to achieve copyright protection and prevent its illegal copy. Watermarks need to be robust to attacks and maintain data quality. Therefore, we discussed in this paper two approaches for image watermarking, first is based on Particle Swarm Optimization (PSO) and the second approach is based on Genetic Algorithm (GA). Discrete wavelet transformation (DWT) is used with the two approaches separately for embedding process to cover image transformation. Each of PSO and GA is based on co-relation coefficient to detect the high energy coefficient watermark bit in the original image and then hide the watermark in original image. Many experiments were conducted for the two approaches with different values of PSO and GA parameters. From experiments, PSO approach got better results with PSNR equal 53, MSE equal 0.0039. Whereas GA approach got PSNR equal 50.5 and MSE equal 0.0048 when using population size equal to 100, number of iterations equal to 150 and 3×3 block. According to the results, we can note that small block size can affect the quality of image watermarking based PSO/GA because small block size can increase the search area of the watermarking image. Better PSO results were obtained when using swarm size equal to 100.

Keywords: image watermarking, genetic algorithm, particle swarm optimization, discrete wavelet transform

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Authors: Housein Deli, Loui Al-Shrouf, Hammoud Al Joumaa, Mohieddine Jelali

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When forming metallic materials, fluctuations in material properties, process conditions, and wear lead to deviations in the component geometry. Several hundred features sometimes need to be measured, especially in the case of functional and safety-relevant components. These can only be measured offline due to the large number of features and the accuracy requirements. The risk of producing components outside the tolerances is minimized but not eliminated by the statistical evaluation of process capability and control measurements. The inspection intervals are based on the acceptable risk and are at the expense of productivity but remain reactive and, in some cases, considerably delayed. Due to the considerable progress made in the field of condition monitoring and measurement technology, permanently installed sensor systems in combination with machine learning and artificial intelligence, in particular, offer the potential to independently derive forecasts for component geometry and thus eliminate the risk of defective products - actively and preventively. The reliability of forecasts depends on the quality, completeness, and timeliness of the data. Measuring all geometric characteristics is neither sensible nor technically possible. This paper, therefore, uses the example of car seat rail production to discuss the necessary first step of feature selection and reduction by correlation analysis, as otherwise, it would not be possible to forecast components in real-time and inline. Four different car seat rails with an average of 130 features were selected and measured using a coordinate measuring machine (CMM). The run of such measuring programs alone takes up to 20 minutes. In practice, this results in the risk of faulty production of at least 2000 components that have to be sorted or scrapped if the measurement results are negative. Over a period of 2 months, all measurement data (> 200 measurements/ variant) was collected and evaluated using correlation analysis. As part of this study, the number of characteristics to be measured for all 6 car seat rail variants was reduced by over 80%. Specifically, direct correlations for almost 100 characteristics were proven for an average of 125 characteristics for 4 different products. A further 10 features correlate via indirect relationships so that the number of features required for a prediction could be reduced to less than 20. A correlation factor >0.8 was assumed for all correlations.

Keywords: long-term SHM, condition monitoring, machine learning, correlation analysis, component prediction, wear prediction, regressions analysis

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Authors: Lamis Naddaf, Yuval Tabach

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We identified missense genetic variants with the potential to enhance resistance against cancer. Such a field has not been widely explored as researchers tend to investigate the mutations that cause diseases, in response to the suffering of patients, rather than those mutations that protect from them. In conjunction with the genomic revolution and the advances in genetic engineering and synthetic biology, identifying the protective variants will increase the power of genotype-phenotype predictions and have significant implications for improved risk estimation, diagnostics, prognosis, and even personalized therapy and drug discovery. To approach our goal, we systematically investigated the sites of the coding genomes and selected the alleles that showed a correlation with the species’ cancer resistance. Interestingly, we found several amino acids that are more generally preferred (like the Proline) or avoided (like the Cysteine) by the resistant species. Furthermore, Cancer resistance in mammals and reptiles is significantly predicted by the number of the predicted protecting variants (PVs) a species has. Moreover, PVs-enriched-genes are enriched in pathways relevant to tumor suppression. For example, they are enriched in the Hedgehog signaling and silencing pathways, which its improper activation is associated with the most common form of cancer malignancy. We also showed that the PVs are mostly more abundant in healthy people compared to cancer patients within different human races.

Keywords: cancer resistance, protecting variant, naked mole rat, comparative genomics

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Authors: Kazuyoshi Mori

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In this paper, we consider the number of parameters for the parametrization of stabilizing controllers for RHinf systems with size 2 × 2. Fortunately, any plant of this model can admit doubly coprime factorization. Thus we can use the Youla parameterization to parametrize the stabilizing contollers . However, Youla parameterization does not give itself the minimal number of parameters. This paper shows that the minimal number of parameters is four. As a result, we show that the Youla parametrization naturally gives the parameterization of stabilizing controllers with minimal numbers.

Keywords: RHinfo, parameterization, number of parameters, multi-input, multi-output systems

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Authors: Zarine Avetisyan

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The paradigm of Modern Linguistics incorporates disciplines which allow to analyze both language and discourse units and to demonstrate the multi-layeredness of lingo-cultural consciousness. By implementing lingo-cognitive approach to discourse and communication studies, the present paper tries to create the integral linguistic picture of the concept of joy and to analyze the lexico-semantic groups and relevant lexico-semantic variants of its realization in the context of Modern English fiction.

Keywords: concept of joy, lexico-semantic variant, semantic sign, cognition

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Authors: Sadegh Lotfieblisofla, Arash Khodabakhshi

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Tissue plasminogen activator (tPA) as a serine protease plays an important role in the fibrinolytic system and the dissolution of fibrin clots in human body. The production of this drug in plants such as tobacco could reduce its production costs. In this study, expression of tPA gene and protein targeting to different plant cell compartments, using various signal peptides has been investigated. For high level of expression, Kozak sequence was used after CaMV35S in the beginning of the gene. In order to design the final construction, Extensin, KDEL (amino acid sequence including Lys-Asp-Glu-Leu) and SP (γ-zein signal peptide coding sequence) were used as leader signals to conduct this protein into apoplast, endoplasmic reticulum and cytosol spaces, respectively. Cloned human tPA gene under the CaMV (Cauliflower mosaic virus) 35S promoter and NOS (Nopaline Synthase) terminator into pBI121 plasmid was transferred into tobacco explants by Agrobacterium tumefaciens strain LBA₄₄₀₄. The presence and copy number of genes in transgenic tobacco was proved by Southern blotting. Enzymatic activity of the rt-PA protein in transgenic plants compared to non-transgenic plants was confirmed by Zymography assay. The presence and amount of rt-PA recombinant protein in plants was estimated by ELISA analysis on crude protein extract of transgenic tobacco using a specific antibody. The yield of recombinant tPA in transgenic tobacco for SP, KDEL, Extensin signals were counted 0.50, 0.68, 0.69 microgram per milligram of total soluble proteins.

Keywords: tPA, recombinant, transgenic, tobacco

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Authors: Tanakrit Doltanakarn

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Introduction: These days, cannabis is being accepted in many countries due to the fact that cannabis could be use in medical. The medical cannabis is used to treat and reduce the pain many diseases. For example, neuropathic pain, Parkinson, autism disorders, cancer pain reduce the adverse effect of chemotherapy, diabetes, and migraine. Active ingredients in cannabis that modulate patients' perceptions of their conditions include Δ9‐tetrahydrocannabinol (THC), cannabidiol (CBD), flavonoids, and terpenes. However, there is an adverse effect of cannabis, cardiovascular effects, psychosis, schizophrenia, mood disorder, and cognitive alternation. These effects are from the THC and CBD ingredients in the cannabis. The metabolize processes of delta-9 THC to 11-OH-delta 9 -THC (inactive form), THC were cause of adverse effects. Interestingly, the distributions of CYP2C9 gene (CYP2C9*2 and CYP2C9*3, poor metabolizer) that might affect incidences of adverse effects in patients who treated with medical cannabis. Objective: The aim of this study we want to investigate the association between genetic polymorphism of CYP2C9 frequency and Thai patients who treated with medical cannabis. Materials and Methods:We recruited sixty-five unrelated Thai patients from the College of Pharmacy, Rangsit University. DNA were extracted using Genomic DNA Mini Kit. Genotyping of CYP2C9*2 (430C>T, rs1799853) and CYP2C9*3 (1075A>C, rs1057910) were genotyped by the TaqMan Real-time PCR assay. Results: Among these 31 medicals cannabis-induced ADRs patients, they were diagnosed with 22 (33.85%) tachycardia and 3 (4.62%) arrhythmia. There were 34 (52.31%) medical cannabis-tolerant controls who were included in this study.40 (61.53%) Thai patients were female, and 25 (38.46%) were male, with median age of 57 (range 27 – 87) years. In this study, we found none of the medical cannabis-induced ADRs carried CYP2C9*2 variant along with medical cannabis-tolerant control group. CYP2C9*3 variant (intermediate metabolizer, IM) was found just only one of thirty-one (3.23%) in the medical cannabis-induced ADRs and two of thirty-fourth (5.88%) in the tolerant controls. Conclusions: Thus, the distribution of CYP2C9 alleles offer a comprehensive view of pharmacogenomics marker in Thai population that could be used as a reference for worldwide to investigate the pharmacogenomics application.

Keywords: medical cannabis, adverse effect, CYP2C9, thai patients

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Authors: B. Grygalewicz, R. Woroniecka, J. Rygier, K. Borkowska, A. Labak, B. Nowakowska, B. Pienkowska-Grela

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Introduction: Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western world. Hemizygous and or homozygous loss at 13q14 occur in more than half of cases and constitute the most frequent chromosomal abnormality in CLL. It is believed that deletions 13q14 play a role in CLL pathogenesis. Two microRNA genes miR-15a and miR- 16-1 are targets of 13q14 deletions and plays a tumor suppressor role by targeting antiapoptotic BCL2 gene. Deletion size, as a single change detected in FISH analysis, has haprognostic significance. Patients with small deletions, without RB1 gene involvement, have the best prognosis and the longest overall survival time (OS 133 months). In patients with bigger deletion region, containing RB1 gene, prognosis drops to intermediate, like in patients with normal karyotype and without changes in FISH with overall survival 111 months. Aim: Precise delineation of 13q14 deletions regions in two groups of CLL patients, with mono- and biallelic deletions and qualifications of their prognostic significance. Methods: Detection of 13q14 deletions was performed by FISH analysis with CLL probe panel (D13S319, LAMP1, TP53, ATM, CEP-12). Accurate deletion size detection was performed by CGH Haematological Cancer and SNP array (8x60K). Results: Our investigated group of CLL patients with the 13q14 deletion, detected by FISH analysis, comprised two groups: 18 patients with monoallelic deletions and 18 patients with biallelic deletions. In FISH analysis, in the monoallelic group the range of cells with deletion, was 43% to 97%, while in biallelic group deletion was detected in 11% to 94% of cells. Microarray analysis revealed precise deletion regions. In the monoallelic group, the range of size was 348,12 Kb to 34,82 Mb, with median deletion size 7,93 Mb. In biallelic group discrepancy of total deletions, size was 135,27 Kb to 33,33 Mb, with median deletion size 2,52 Mb. The median size of smaller deletion regions on one copy chromosome 13 was 1,08 Mb while the average region of bigger deletion on the second chromosome 13 was 4,04 Mb. In the monoallelic group, in 8/18 deletion region covered RB1 gene. In the biallelic group, in 4/18 cases, revealed deletion on one copy of biallelic deletion and in 2/18 showed deletion of RB1 gene on both deleted 13q14 regions. All minimal deleted regions included miR-15a and miR-16-1 genes. Genetic results will be correlated with clinical data. Conclusions: Application of CGH microarrays technique in CLL allows accurately delineate the size of 13q14 deletion regions, what have a prognostic value. All deleted regions included miR15a and miR-16-1, what confirms the essential role of these genes in CLL pathogenesis. In our investigated groups of CLL patients with mono- and biallelic 13q14 deletions, patients with biallelic deletion presented smaller deletion sizes (2,52 Mb vs 7,93 Mb), what is connected with better prognosis.

Keywords: CLL, deletion 13q14, CGH microarrays, SNP array

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Authors: Yuyan Yi, Jingyi Zheng, Nedret Billor

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Independent component analysis (ICA) is one of the most commonly used blind source separation (BSS) techniques for signal pre-processing, such as noise reduction and feature extraction. The main parameter in the ICA method is the number of independent components (IC). Although there have been several methods for the determination of the number of ICs, it has not been given sufficient attentionto this important parameter. In this study, wereview the mostused methods fordetermining the number of ICs and providetheir advantages and disadvantages. Further, wepropose an improved version of column-wise ICAByBlock method for the determination of the number of ICs.To assess the performance of the proposed method, we compare the column-wise ICAbyBlock with several existing methods through different ICA methods by using simulated and real signal data. Results show that the proposed column-wise ICAbyBlock is an effective and stable method for determining the optimal number of components in ICA. This method is simple, and results can be demonstrated intuitively with good visualizations.

Keywords: independent component analysis, optimal number, column-wise, correlation coefficient, cross-validation, ICAByblock

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

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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) is 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. 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) cytogenetic analysis of peripheral blood lymphocytes was used. Gene polymorphism was determined by PCR-RFLP reaction using appropriate primers and restriction enzymes. For statistic analysis the Mann-Whitney U-test was used. The mean Cr level in blood of exposed group was 0.095 µmol/l (0.019 min - max 0.504). No value exceeds the average normal value. The mean value Cr in urine was 7.9 µmol/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 statistical difference was observed 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%). A statistically higher incidence of CTA-type aberrations in variant genotypes between exposed and control groups was observed (1.22% vs. 0.59%, P <0.05). The work place is usually higher source of exposure to harmful factors. Workers need consistent and frequent health control. In assessing the risk of adverse effects of metals it 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: CCND1, genotoxicity, polymorphism, stainless steel, welders

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Authors: Seema Ahlawat, Parul Saxena, Malik Zainul Abdin

Abstract:

Malaria is a major health problem in many developing countries. The parasite responsible for the vast majority of fatal malaria infections is Plasmodium falciparum. Unfortunately, most Plasmodium strains including P. falciparum have become resistant to most of the antimalarials including chloroquine, mefloquine, etc. To combat this problem, WHO has recommended the use of artemisinin and its derivatives in artemisinin based combination therapy (ACT). Due to its current use in artemisinin based-combination therapy (ACT), its global demand is increasing continuously. But, the relatively low yield of artemisinin in A. annua L. plants and unavailability of economically viable synthetic protocols are the major bottlenecks for its commercial production and clinical use. Chemical synthesis of artemisinin is also very complex and uneconomical. The hairy root system, using the Agrobacterium rhizogenes LBA 9402 strain to enhance the production of artemisinin in A. annua L., is developed in our laboratory. The transgenic nature of hairy root lines and the copy number of trans gene (rol B) were confirmed using PCR and Southern Blot analyses, respectively. The effect of different concentrations of Piriformospora indica on artemisinin production in hairy root cultures were evaluated. 3% P. indica has resulted 1.97 times increase in artemisinin production in comparison to control cultures. The effects of P. indica on artemisinin production was positively correlated with regulatory genes of MVA, MEP and artemisinin biosynthetic pathways, viz. hmgr, ads, cyp71av1, aldh1, dxs, dxr and dbr2 in hairy root cultures of A. annua L. Mass scale cultivation of A. annua L. hairy roots by plant tissue culture technology may be an alternative route for production of artemisinin. A comprehensive investigation of the hairy root system of A. annua L. would help in developing a viable process for the production of artemisinin. The efficiency of the scaling up systems still needs optimization before industrial exploitation becomes viable.

Keywords: A. annua L., artemisinin, hairy root cultures, malaria

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Authors: Sadaf Moeez, Madiha Khalid, Zoya Khalid, Sania Shaheen, Sumbul Khalid

Abstract:

Background: Inter-individual variation in response to metformin, which has been considered as a first line therapy for T2DM treatment is considerable. In the current study, it was aimed to investigate the impact of two genetic variants Leu125Phe (rs77474263) and Gly64Asp (rs77630697) in gene SLC47A1 on the clinical efficacy of metformin in T2DM Pakistani patients. Methods: The study included 800 T2DM patients (400 metformin responders and 400 metformin non-responders) along with 400 ethnically matched healthy individuals. The genotypes were determined by allele-specific polymerase chain reaction. In-silico analysis was done to confirm the effect of the two SNPs on the structure of genes. Association was statistically determined using SPSS software. Results: Minor allele frequency for rs77474263 and rs77630697 was 0.13 and 0.12. For SLC47A1 rs77474263 the homozygotes of one mutant allele ‘T’ (CT) of rs77474263 variant were fewer in metformin responders than metformin non-responders (29.2% vs. 35.5 %). Likewise, the efficacy was further reduced (7.2% vs. 4.0 %) in homozygotes of two copies of ‘T’ allele (TT). Remarkably, T2DM cases with two copies of allele ‘C’ (CC) had 2.11 times more probability to respond towards metformin monotherapy. For SLC47A1 rs77630697 the homozygotes of one mutant allele ‘A’ (GA) of rs77630697 variant were fewer in metformin responders than metformin non-responders (33.5% vs. 43.0 %). Likewise, the efficacy was further reduced (8.5% vs. 4.5%) in homozygotes of two copies of ‘A’ allele (AA). Remarkably, T2DM cases with two copies of allele ‘G’ (GG) had 2.41 times more probability to respond towards metformin monotherapy. In-silico analysis revealed that these two variants affect the structure and stability of their corresponding proteins. Conclusion: The present data suggest that SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) polymorphisms were associated with the therapeutic response of metformin in T2DM patients of Pakistan.

Keywords: diabetes, T2DM, SLC47A1, Pakistan, polymorphism

Procedia PDF Downloads 160

Authors: Njabulo Ncube, Elena Kulinskaya, Nicholas Steel, Dmitry Pshezhetskiy

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Life expectancy in the United Kingdom (UK) has been near constant since 2010, particularly for the individuals of 65 years and older. This trend has been also noted in several other countries. This slowdown in the increase of life expectancy was concurrent with the increase in the number of deaths caused by non-communicable diseases. Of particular concern is the world-wide exponential increase in the number of diabetes related deaths. Previous studies have reported increased mortality hazards among diabetics compared to non-diabetics, and on the differing effects of antidiabetic drugs on mortality hazards. This study aimed to estimate the all-cause mortality hazards and related life expectancies among type 2 diabetes (T2DM) patients in the UK using the time-variant Gompertz-Cox model with frailty. The study also aimed to understand the major causes of the change in life expectancy growth in the last decade. A total of 221 182 (30.8% T2DM, 57.6% Males) individuals aged 50 years and above, born between 1930 and 1960, inclusive, and diagnosed between 2000 and 2016, were selected from The Health Improvement Network (THIN) database of the UK primary care data and followed up to 31 December 2016. About 13.4% of participants died during the follow-up period. The overall all-cause mortality hazard ratio of T2DM compared to non-diabetic controls was 1.467 (1.381-1.558) and 1.38 (1.307-1.457) when diagnosed between 50 to 59 years and 60 to 74 years, respectively. The estimated life expectancies among T2DM individuals without further comorbidities diagnosed at the age of 60 years were 2.43 (1930-1939 birth cohort), 2.53 (1940-1949 birth cohort) and 3.28 (1950-1960 birth cohort) years less than those of non-diabetic controls. However, the 1950-1960 birth cohort had a steeper hazard function compared to the 1940-1949 birth cohort for both T2DM and non-diabetic individuals. In conclusion, mortality hazards for people with T2DM continue to be higher than for non-diabetics. The steeper mortality hazard slope for the 1950-1960 birth cohort might indicate the sub-population contributing to a slowdown in the growth of the life expectancy.

Keywords: T2DM, Gompetz-Cox model with frailty, all-cause mortality, life expectancy

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Authors: K. S. Suganya, R. Nedunchezhian

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In recent years, blockchain technology has been found to be the most significant discovery in this digital era, after the discovery of the Internet and Cloud Computing. Blockchain is a simple, distributed public ledger that contains all the user’s transaction details in a block. The global copy of the block is then shared among all its peer-peer network users after validation by the Blockchain miners. Once a block is validated and accepted, it cannot be altered by any users making it a trust-free transaction. It also resolves the problem of double-spending by using traditional cryptographic methods. Since the advent of bitcoin, blockchain has been the backbone for all its transactions. But in recent years, it has found its roots and uses in many fields like Smart Contracts, Smart City management, healthcare, etc. Identity management against digital identity theft has become a major concern among financial and other organizations. To solve this digital identity theft, blockchain technology can be employed with existing identity management systems, which maintain a distributed public ledger containing details of an individual’s identity containing information such as Digital birth certificates, Citizenship number, Bank details, voter details, driving license in the form of blocks verified on the blockchain becomes time-stamped, unforgeable and publicly visible for any legitimate users. The main challenge in using blockchain technology to prevent digital identity theft is ensuring the pseudo-anonymity and privacy of the users. This survey paper will exert to study the blockchain concepts, consensus protocols, and various blockchain-based Digital Identity Management systems with their research scope. This paper also discusses the role of Blockchain in COVID-19 pandemic management by self-sovereign identity and supply chain management.

Keywords: blockchain, consensus protocols, bitcoin, identity theft, digital identity management, pandemic, COVID-19, self-sovereign identity

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Authors: Abdullah Salameh, Jamil Renno, Khaled Ali

Abstract:

This paper investigates how fatigue life is influenced by increasing the number and size of bolts under several wind speed averages. The study determined that increasing the size or number of bolts can notably improve the fatigue life of bolted flange connections. Additionally, the curves derived from the assessment data demonstrated a steeper slope for a greater number of bolts, indicating that the percentage increase of adding bolts is not consistent for each additional bolt. Instead, the percentage increment rises exponentially when increasing the number of bolts. However, selecting the most suitable design improvement strategy depends on the specific circumstances. In the majority of cases, the study observed that increasing the number of bolts resulted in significant improvements in fatigue life, regardless of the size of the bolts used.

Keywords: wind turbine tower, flanged connection, number of bolts, size of bolts, fatigue life

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Authors: Anil Ranjitbhai Patel, Clement John Shaji, Peter Liggesmeyer

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Safety and security of autonomous vehicles (AVs) is a growing concern, first, due to the increased number of safety-critical functions taken over by automotive embedded systems; second, due to the increased exposure of the software-intensive systems to potential attackers; third, due to dynamic interaction in an uncertain and unknown environment at runtime which results in changed functional and non-functional properties of the system. Frequently occurring environmental uncertainties, random component failures, and compromise security of the AVs might result in hazardous events, sometimes even in an accident, if left undetected. Beyond these technical issues, we argue that the safety and security of AVs against accidental and deliberate faults are poorly understood and rarely implemented. One possible way to overcome this is through a well-known diversity approach. As an effective approach to increase safety and security, diversity has been widely used in the aviation, railway, and aerospace industries. Thus, the paper proposes fault-tolerance by diversity model takes into consideration the mitigation of accidental and deliberate faults by application of structure and variant redundancy. The model can be used to design the AVs with various types of diversity in hardware and software-based multi-version system. The paper evaluates the presented approach by employing an example from adaptive cruise control, followed by discussing the case study with initial findings.

Keywords: autonomous vehicles, diversity, fault-tolerance, adaptive cruise control, safety, security

Procedia PDF Downloads 129