Search results for: gene concordance factor confidence
6421 Electrochemical APEX for Genotyping MYH7 Gene: A Low Cost Strategy for Minisequencing of Disease Causing Mutations
Authors: Ahmed M. Debela, Mayreli Ortiz , Ciara K. O´Sullivan
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The completion of the human genome Project (HGP) has paved the way for mapping the diversity in the overall genome sequence which helps to understand the genetic causes of inherited diseases and susceptibility to drugs or environmental toxins. Arrayed primer extension (APEX) is a microarray based minisequencing strategy for screening disease causing mutations. It is derived from Sanger DNA sequencing and uses fluorescently dideoxynucleotides (ddNTPs) for termination of a growing DNA strand from a primer with its 3´- end designed immediately upstream of a site where single nucleotide polymorphism (SNP) occurs. The use of DNA polymerase offers a very high accuracy and specificity to APEX which in turn happens to be a method of choice for multiplex SNP detection. Coupling the high specificity of this method with the high sensitivity, low cost and compatibility for miniaturization of electrochemical techniques would offer an excellent platform for detection of mutation as well as sequencing of DNA templates. We are developing an electrochemical APEX for the analysis of SNPs found in the MYH7 gene for group of cardiomyopathy patients. ddNTPs were labeled with four different redox active compounds with four distinct potentials. Thiolated oligonucleotide probes were immobilised on gold and glassy carbon substrates which are followed by hybridisation with complementary target DNA just adjacent to the base to be extended by polymerase. Electrochemical interrogation was performed after the incorporation of the redox labelled dedioxynucleotide. The work involved the synthesis and characterisation of the redox labelled ddNTPs, optimisation and characterisation of surface functionalisation strategies and the nucleotide incorporation assays.Keywords: array based primer extension, labelled ddNTPs, electrochemical, mutations
Procedia PDF Downloads 2466420 Molecular Characterization of Cysticercus tenuicolis of Slaughtered Livestock in Upper-Egypt Governorates
Authors: Mosaab A. Omara, Layla O. Elmajdoubb, Mohammad Saleh Al-Aboodyc, Ahmed ElSifyd, Ahmed O. Elkhtamd
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The aim of this study is to present the molecular characterization of cysticercus tenuicolis of Taenia hydatigena from livestock isolates in Egypt, using the amplification of sequencing of the mt-CO1 gene. We introduce a detailed image of the Cysticercus tenuicolis infection in ruminant animals in Upper Egypt. Cysticercus tenuicolis inhabits such organs in ruminants as the omentum, viscera, and liver. In the present study, the infection rate of Cysticercus tenuicolis was found to be 16% and 19% in sheep and goat sample respectively. Firstly we report one larval stage of Taenia hydatigena detected in the camel liver in Egypt. Cysticercus tenuicolis infection manifested a higher prevalence in females than in males. Those above 2 years of age manifested a higher infection rate than younger animals. The preferred site for the infection was the omentum: a 70% preference in sheep and a 68% preference in goat samples. The molecular characterization using the mitochondrial cytochrome c oxidase subunit 1 (CO1) gene of isolates from sheep, goats and camels corresponded to T. hydatigena. For this study, molecular characterizations of T. hydatigena were done for the first time in Egypt. Molecular tools are of great assistance in characterizing the Cysticercus tenuicolis parasite especially when the morphological character cannot be detected because the metacestodes are frequently confused with infection by the Hydatid cyst, especially when these occur in the visceral organs. In the present study, Cysticercus tenuicolis manifested high identity in the goat and sheep samples, while differences were found more frequently in the camel samples (10 pairbase). Clearly molecular diagnosis for Cysticercus tenuicolis infection significantly helps to differentiate it from such other metacestodes.Keywords: cysticercus tenuicolis, its2, genetic, qena, molecular and taenia hydatigena
Procedia PDF Downloads 5236419 Assessing Significance of Correlation with Binomial Distribution
Authors: Vijay Kumar Singh, Pooja Kushwaha, Prabhat Ranjan, Krishna Kumar Ojha, Jitendra Kumar
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Present day high-throughput genomic technologies, NGS/microarrays, are producing large volume of data that require improved analysis methods to make sense of the data. The correlation between genes and samples has been regularly used to gain insight into many biological phenomena including, but not limited to, co-expression/co-regulation, gene regulatory networks, clustering and pattern identification. However, presence of outliers and violation of assumptions underlying Pearson correlation is frequent and may distort the actual correlation between the genes and lead to spurious conclusions. Here, we report a method to measure the strength of association between genes. The method assumes that the expression values of a gene are Bernoulli random variables whose outcome depends on the sample being probed. The method considers the two genes as uncorrelated if the number of sample with same outcome for both the genes (Ns) is equal to certainly expected number (Es). The extent of correlation depends on how far Ns can deviate from the Es. The method does not assume normality for the parent population, fairly unaffected by the presence of outliers, can be applied to qualitative data and it uses the binomial distribution to assess the significance of association. At this stage, we would not claim about the superiority of the method over other existing correlation methods, but our method could be another way of calculating correlation in addition to existing methods. The method uses binomial distribution, which has not been used until yet, to assess the significance of association between two variables. We are evaluating the performance of our method on NGS/microarray data, which is noisy and pierce by the outliers, to see if our method can differentiate between spurious and actual correlation. While working with the method, it has not escaped our notice that the method could also be generalized to measure the association of more than two variables which has been proven difficult with the existing methods.Keywords: binomial distribution, correlation, microarray, outliers, transcriptome
Procedia PDF Downloads 4156418 Assessment of the Impact of Regular Pilates Exercises on Static Balance in Healthy Adult Women: Preliminary Report
Authors: Anna Słupik, Krzysztof Jaworski, Anna Mosiołek, Dariusz Białoszewski
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Background: Maintaining the correct body balance is essential in the prevention of falls in the elderly, which is especially important for women because of postmenopausal osteoporosis and the serious consequences of falls. One of the exercise methods which is very popular among adults, and which may affect body balance in a positive way is the pilates method. The aim of the study was to evaluate the effect of regular pilates exercises on the ability to maintain body balance in static conditions in adult healthy women. Material and methods: The study group consisted of 20 healthy women attending pilates twice a week for at least 1 year. The control group consisted of 20 healthy women physically inactive. Women in the age range from 35 to 50 years old without pain in musculoskeletal system or other pain were only qualified to the groups. Body balance was assessed using MatScan VersaTek platform with Sway Analysis Module based on Matscan Clinical 6.7 software. The balance was evaluated under the following conditions: standing on both feet with eyes open, standing on both feet with eyes closed, one-leg standing (separately on the right and left foot) with eyes open. Each test lasted 30 seconds. The following parameters were calculated: estimated size of the ellipse of 95% confidence, the distance covered by the Center of Gravity (COG), the size of the maximum shift in the sagittal and frontal planes and load distribution between the left and right foot, as well as between rear- and forefoot. Results: It was found that there is significant difference between the groups in favor of the study group in the size of the confidence ellipse and maximum shifts of COG in the sagittal plane during standing on both feet, both with the eyes open and closed (p < 0.05). While standing on one leg both on the right and left leg, with eyes opened there was a significant difference in favor of the study group, in terms of the size of confidence ellipse, the size of the maximum shifts in the sagittal and in the frontal plane (p < 0.05). There were no differences between the distribution of load between the right and left foot (standing with both feet), nor between fore- and rear foot (in standing with both feet or one-leg). Conclusions: 1. Static balance in women exercising regularly by pilates method is better than in inactive women, which may in the future prevent falls and their consequences. 2. The observed differences in maintaining balance in frontal plane in one-leg standing may indicate a positive impact of pilates exercises on the ability to maintain global balance in terms of the reduced support surface. 3. Pilates method can be used as a form preventive therapy for all people who are expected to have problems with body balance in the future, for example in chronic neurological disorders or vestibular problems. 4. The results have shown that further prospective randomized research on a larger and more representative group is needed.Keywords: balance exercises, body balance, pilates, pressure distribution, women
Procedia PDF Downloads 3186417 Numerical Investigation on Optimizing Fatigue Life in a Lap Joint Structure
Authors: P. Zamani, S. Mohajerzadeh, R. Masoudinejad, K. Farhangdoost
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The riveting process is one of the important ways to keep fastening the lap joints in aircraft structures. Failure of aircraft lap joints directly depends on the stress field in the joint. An important application of riveting process is in the construction of aircraft fuselage structures. In this paper, a 3D finite element method is carried out in order to optimize residual stress field in a riveted lap joint and also to estimate its fatigue life. In continue, a number of experiments are designed and analyzed using design of experiments (DOE). Then, Taguchi method is used to select an optimized case between different levels of each factor. Besides that, the factor which affects the most on residual stress field is investigated. Such optimized case provides the maximum residual stress field. Fatigue life of the optimized joint is estimated by Paris-Erdogan law. Stress intensity factors (SIFs) are calculated using both finite element analysis and experimental formula. In addition, the effect of residual stress field, geometry, and secondary bending are considered in SIF calculation. A good agreement is found between results of such methods. Comparison between optimized fatigue life and fatigue life of other joints has shown an improvement in the joint’s life.Keywords: fatigue life, residual stress, riveting process, stress intensity factor, Taguchi method
Procedia PDF Downloads 4526416 Spatial Temporal Rainfall Trends in Australia
Authors: Bright E. Owusu, Nittaya McNeil
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Rainfall is one of the most essential quantities in meteorology and hydrology. It has important impacts on people’s daily life and excess or inadequate of it could bring tremendous losses in economy and cause fatalities. Population increase around the globe tends to have a corresponding increase in settlement and industrialization. Some countries are affected by flood and drought occasionally due to climate change, which disrupt most of the daily activities. Knowledge of trends in spatial and temporal rainfall variability and their physical explanations would be beneficial in climate change assessment and to determine erosivity. This study describes the spatial-temporal variability of daily rainfall in Australia and their corresponding long-term trend during 1950-2013. The spatial patterns were investigated by using exploratory factor analysis and the long term trend in rainfall time series were determined by linear regression, Mann-Kendall rank statistics and the Sen’s slope test. The exploratory factor analysis explained most of the variations in the data and grouped Australia into eight distinct rainfall regions with different rainfall patterns. Significant increasing trends in annual rainfall were observed in the northern regions of Australia. However, the northeastern part was the wettest of all the eight rainfall regions.Keywords: climate change, explanatory factor analysis, Mann-Kendall and Sen’s slope test, rainfall.
Procedia PDF Downloads 3526415 Cognitive Function and Coping Behavior in the Elderly: A Population-Based Cross-Sectional Study
Authors: Ryo Shikimoto, Hidehito Niimura, Hisashi Kida, Kota Suzuki, Yukiko Miyasaka, Masaru Mimura
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Introduction: In Japan, the most aged country in the world, it is important to explore predictive factors of cognitive function among the elderly. Coping behavior relieves chronic stress and improves lifestyle, and consequently may reduce the risk of cognitive impairment. One of the most widely investigated frameworks evaluated in previous studies is approach-oriented and avoidance-oriented coping strategies. The purpose of this study is to investigate the relationship between cognitive function and coping strategies among elderly residents in urban areas of Japan. Method: This is a part of the cross-sectional Arakawa geriatric cohort study for 1,099 residents (aged 65 to 86 years; mean [SD] = 72.9 [5.2]). Participants were assessed for cognitive function using the Mini-Mental State Examination (MMSE) and diagnosed by psychiatrists in face-to-face interviews. They were then investigated for their each coping behaviors and coping strategies (approach- and avoidance-oriented coping) using stress and coping inventory. A multiple regression analysis was used to investigate the relationship between MMSE score and each coping strategy. Results: Of the 1,099 patients, the mean MMSE score of the study participants was 27.2 (SD = 2.7), and the numbers of the diagnosis of normal, mild cognitive impairment (MCI), and dementia were 815 (74.2%), 248 (22.6%), and 14 (1.3%), respectively. Approach-oriented coping score was significantly associated with MMSE score (B [partial regression coefficient] = 0.12, 95% confidence interval = 0.05 to 0.19) after adjusting for confounding factors including age, sex, and education. Avoidance-oriented coping did not show a significant association with MMSE score (B [partial regression coefficient] = -0.02, 95% confidence interval = -0.09 to 0.06). Conclusion: Approach-oriented coping was clearly associated with neurocognitive function in the Japanese population. A future longitudinal trial is warranted to investigate the protective effects of coping behavior on cognitive function.Keywords: approach-oriented coping, cognitive impairment, coping behavior, dementia
Procedia PDF Downloads 1296414 Women Executives' Career Success in the Office of the Basic Education
Authors: Nipon Sasithornsaowapa
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This research aims to study the impact of personality and family status on women executives’ career success of the primary education department of Thailand. The independent variable includes three factors, namely family status, personality, and knowledge-skill-experience, while the dependent variable is the career success. The population of this study includes 2,179 female management officials in the department of primary education. A total of 400 female managers is interviewed and utilized as a sample group. A questionnaire is developed and used as a research tool for data collection. Content analysis is performed to get the quantitative data. Descriptive statistics in this research is conducted by SPSS program. The findings revealed that personality and family status of samples have an influence on the overall career success of women executives in terms of their objective career success. However, in terms of specific factors of personality or family status, it is found that there is no relevance of each factor on the women executives’ career success. It can be concluded that the factor affecting the women executives’ career success is subjective career success including the happiness and enjoyment with the job not factor concerning materials. Their success is the result of each individual working experience. However, their personal characteristics do not affect their success.Keywords: career success, women executives, primary education, knowledge-skill-experience
Procedia PDF Downloads 4816413 Reverse Impact of Temperature as Climate Factor on Milk Production in ChaharMahal and Bakhtiari
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When long-term changes in normal weather patterns happen in a certain area, it generally could be identified as climate change. Concentration of principal's greenhouse gases such as carbon dioxide, nitrous oxide, methane, ozone, and water vapor will cause climate change and perhaps climate variability. Main climate factors are temperature, precipitation, air pressure, and humidity. Extreme events may be the result of the changing of carbon dioxide concentration levels in the atmosphere which cause a change in temperature. Extreme events in some ways will affect the productivity of crop and dairy livestock. In this research, the correlation of milk production and temperature as the main climate factor in ChaharMahal and Bakhtiari province in Iran has been considered. The methodology employed for this study consists, collect reports and published national and provincial data, available recorded data on climate factors and analyzing collected data using statistical software. Milk production in ChaharMahal and Bakhtiari province is in the same pattern as national milk production in Iran. According to the current study results, there is a significant negative correlation between milk production in ChaharMahal and Bakhtiari provinces and temperature as the main climate change factor.Keywords: Chaharmahal and Bakhtiari, climate change, impacts, Iran, milk production
Procedia PDF Downloads 1666412 Role of Micro-Patterning on Stem Cell-Material Interaction Modulation and Cell Fate
Authors: Lay Poh Tan, Chor Yong Tay, Haiyang Yu
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Micro-contact printing is a form of soft lithography that uses the relief patterns on a master polydimethylsiloxane (PDMS) stamp to form patterns of self-assembled monolayers (SAMs) of ink on the surface of a substrate through conformal contact technique. Here, we adopt this method to print proteins of different dimensions on our biodegradable polymer substrates. We started off with printing 20-500 μm scale lanes of fibronectin to engineer the shape of bone marrow derived human mesenchymal stem cell (hMSCs). After 8 hours of culture, the hMSCs adopted elongated shapes, and upon analysis of the gene expressions, genes commonly associated with myogenesis (GATA-4, MyoD1, cTnT and β-MHC) and neurogenesis (NeuroD, Nestin, GFAP, and MAP2) were up-regulated but gene expression associated to osteogenesis (ALPL, RUNX2, and SPARC) were either down modulated or remained at the nominal level. This is the first evidence that cellular morphology control via micropatterning could be used to modulate stem cell fate without external biochemical stimuli. We further our studies to modulate the focal adhesion (FA) instead of the macro shape of cells. Micro-contact printed islands of different smaller dimensions were investigated. We successfully regulated the FAs into dense FAs and elongated FAs by micropatterning. Additionally, the combined effects of hard (40.4 kPa), and intermediate (10.6 kPa) PA gel and FAs patterning on hMSCs differentiation were studied. Results showed that FA and matrix compliance plays an important role in hMSCs differentiation, and there is a cross-talk between different physical stimulants and the significance of these stimuli can only be realized if they are combined at the optimum level.Keywords: micro-contact printing, polymer substrate, cell-material interaction, stem cell differentiation
Procedia PDF Downloads 1726411 Trade Policy Incentives and Economic Growth in Nigeria
Authors: Emmanuel Dele Balogun
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This paper analyzes, using descriptive statistics and econometrics data which span the period 1981 to 2014 to gauge the effects of trade policy incentives on economic growth in Nigeria. It argues that the provided incentives penalize economic growth during pre-trade liberalization eras, but stimulated a rapid increase in total factor productivity during the post-liberalization period of 2000 to 2014. The trend analysis shows that Nigeria maintained high tariff walls in economic regulation eras which became low in post liberalization era. The protections were in favor of infant industries, which were mainly appendages of multinationals but against imports of competing food and finished consumer products. The trade openness index confirms the undue exposure of Nigeria’s economy to the vagaries of international market shocks; while banking sector recapitalization and new listing of telecommunications companies deepened the financial markets in post-liberalization era. The structure of economic incentives was biased in favor of construction, trade and services, but against the real sector despite protectionist policies. Total Factor Productivity (TFP) estimates show that the Nigerian economy suffered stagnation in pre-liberalization eras, but experienced rapid growth rates in post-liberalization eras. The regression results relating trade policy incentives to TFP growth rate yielded a significant but negative intercept suggesting that a non-interventionist policy could be detrimental to economic progress, while protective tariff which limits imports of competing products could spur productivity gains in domestic import substitutes beyond factor growth with market liberalization. The main constraint to the effectiveness of trade policy incentives is the failure of benefiting industries to leverage on the domestic factor endowments of the nation. This paper concludes that there is the need to review the current economic transformation strategies urgently with a view to provide policymakers with a better understanding of the most viable options that could make for rapid success.Keywords: economic growth, macroeconomic incentives, total factor productivity, trade policies
Procedia PDF Downloads 3226410 Improving Security Features of Traditional Automated Teller Machines-Based Banking Services via Fingerprint Biometrics Scheme
Authors: Anthony I. Otuonye, Juliet N. Odii, Perpetual N. Ibe
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The obvious challenges faced by most commercial bank customers while using the services of ATMs (Automated Teller Machines) across developing countries have triggered the need for an improved system with better security features. Current ATM systems are password-based, and research has proved the vulnerabilities of these systems to heinous attacks and manipulations. We have discovered by research that the security of current ATM-assisted banking services in most developing countries of the world is easily broken and maneuvered by fraudsters, majorly because it is quite difficult for these systems to identify an impostor with privileged access as against the authentic bank account owner. Again, PIN (Personal Identification Number) code passwords are easily guessed, just to mention a few of such obvious limitations of traditional ATM operations. In this research work also, we have developed a system of fingerprint biometrics with PIN code Authentication that seeks to improve the security features of traditional ATM installations as well as other Banking Services. The aim is to ensure better security at all ATM installations and raise the confidence of bank customers. It is hoped that our system will overcome most of the challenges of the current password-based ATM operation if properly applied. The researchers made use of the OOADM (Object-Oriented Analysis and Design Methodology), a software development methodology that assures proper system design using modern design diagrams. Implementation and coding were carried out using Visual Studio 2010 together with other software tools. Results obtained show a working system that provides two levels of security at the client’s side using a fingerprint biometric scheme combined with the existing 4-digit PIN code to guarantee the confidence of bank customers across developing countries.Keywords: fingerprint biometrics, banking operations, verification, ATMs, PIN code
Procedia PDF Downloads 426409 Optimized Algorithm for Particle Swarm Optimization
Authors: Fuzhang Zhao
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Particle swarm optimization (PSO) is becoming one of the most important swarm intelligent paradigms for solving global optimization problems. Although some progress has been made to improve PSO algorithms over the last two decades, additional work is still needed to balance parameters to achieve better numerical properties of accuracy, efficiency, and stability. In the optimal PSO algorithm, the optimal weightings of (√ 5 − 1)/2 and (3 − √5)/2 are used for the cognitive factor and the social factor, respectively. By the same token, the same optimal weightings have been applied for intensification searches and diversification searches, respectively. Perturbation and constriction effects are optimally balanced. Simulations of the de Jong, the Rosenbrock, and the Griewank functions show that the optimal PSO algorithm indeed achieves better numerical properties and outperforms the canonical PSO algorithm.Keywords: diversification search, intensification search, optimal weighting, particle swarm optimization
Procedia PDF Downloads 5826408 Asset Pricing Model: A Quality Paradigm
Authors: Urmi Khatri
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Capital asset pricing model (CAPM) draws a direct relationship between the risk and the expected rate of return. There was a criticism on the beta and the assumptions of CAPM, as they are not applicable in the real world. Fama French Three Factor Model and Fama French Five Factor Model have given different factors, which have an impact on the return of any asset like size, value, investment and profitability. This study proposes to see Capital Asset pricing Model through the lenses of the quality aspect. In the study, the six factors are studied. The Fama French Five Factor Model and addition of the quality dimension are studied. Here, Graham’s seven quality and quantity criteria are measured to determine the score of the sample firms. Thus, this study tries to check the model fit. The beta coefficient of the quality dimension and the R square value is seen to determine validity of the proposed model. The sample is drawn from the firms listed on Indian Stock Exchange (BSE). For the study, only nonfinancial firms are been selected. The time period of the study is from January 1999 to December 2019. Hence, the primary objective of the study is to check how robust the model becomes after giving the quality dimension to the capital asset pricing model in addition to the size, value, profitability and investment.Keywords: asset pricing model, CAPM, Graham’s score, G-score, multifactor model, quality
Procedia PDF Downloads 1586407 Women Entrepreneuship in Croatia: Issues and Policies
Authors: Marko Kolakovic, Mihaela Mikic, Martina Taborin
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Women entrepreneurship is often regarded as the unused economical potential in many countries, including Republic of Croatia. Although women represent a majority in the population, they are still a minority in the field of entrepreneurship and face many challenges in fulfilling their entrepreneurship potential. The reasons are often hided in historical distorted perceptions about value, credibility, competitiveness, responsibility and knowledge which women have, or can have. This is significant for at least two reasons. First, in terms of global economic crisis, the economy needs more quality, more skilled and educated people willing to face entrepreneurial challenges and create new jobs, new opportunities and higher living standards. Second, in the entrepreneurial activity, women finally have a chance to highlight their own abilities, such as knowledge, relentless work, organizational skills, communication and negotiation skills, responsibility, flexibility, etc., in order to insure their economic independence, for a better social position, and to increase confidence and faith in their own abilities. This paper empirically analyses characteristics of women entrepreneurship in Croatia and conducted policies for it improvement. An empirical research was conducted with the goal of discovering real life experiences and attitudes of Croatian women entrepreneurs. Results show that Croatian women entrepreneurs are usually highly educated, have previous work experience and operate in service sector, due to lower need for start-up capital. The biggest obstacle on their entrepreneurial path represents government bureaucracy. Although the number of women entrepreneurs is rising today and the gap between male and women entrepreneurs in Croatia, as well as women entrepreneurship levels lower than the European average, we believe that there is still a long way to reach potential and successful women entrepreneurship development. Research showed that by breaking down the barriers as access to finance, education investments, knowledge, skills and confidence development, women will be able to accomplish more significant and more efficient entrepreneurial outcome.Keywords: Croatia, policy, SMEs, women entrepreneurial strategy, women entrepreneurship
Procedia PDF Downloads 3236406 Digital Sustainable Human Resource Management Model Innovation Based on Dynamic Capabilities
Authors: Mohammad Kargar Shouraki, Naji Yazdi, Mohsen Emami
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The environmental and social challenges have caused the organizations to put further attention and emphasis on sustainable growth and developing strategies for sustainability. Since human is both the target of development and the agent of development at the same time, one of the most important factors in the development of the sustainability strategy in organizations is the human factor. In addition, organizations have been facing the new challenge of digital transformation which impacts the human factor, meanwhile, undeniably, the human factor contributes to such transformation. Therefore, organizations are facing the challenge of digital human resource management (HRM). Thus, the present study aims to investigate how an HRM model should be so that it not only can help the consideration and of the business sustainability requirements but also can make the highest and the most appropriate positive, not destructive, utilization of the digital transformations. Furthermore, the success of the HRM regarding the two sustainability and digital transformation challenges requires dynamic human competencies, which are addressed as digital/sustainable human dynamic capabilities in this paper. The present study is conducted using a hybrid methodology consisting of the qualitative methods of meta-synthesis and content analysis and the quantitative method of interpretive-structural model (ISM). Finally, a rotatory model, including 3 approaches, 3 perspectives, and 9 dimensions, is presented.Keywords: sustainable human resource management, digital human resource management, digital/sustainable human dynamic capabilities, talent management
Procedia PDF Downloads 1186405 Genetic Structuring of Four Tectona grandis L. F. Seed Production Areas in Southern India
Authors: P. M. Sreekanth
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Teak (Tectona grandis L. f.) is a tree species indigenous to India and other Southeastern countries. It produces high-value timber and is easily established in plantations. Reforestation requires a constant supply of high quality seeds. Seed Production Areas (SPA) of teak are improved stands used for collection of open-pollinated quality seeds in large quantities. Information on the genetic diversity of major teak SPAs in India is scanty. The genetic structure of four important seed production areas of Kerala State in Southern India was analyzed employing amplified fragment length polymorphism markers using ten selective primer combinations on 80 samples (4 populations X 20 trees). The study revealed that the gene diversity of the SPAs varied from 0.169 (Konni SPA) to 0.203 (Wayanad SPA). The percentage of polymorphic loci ranged from 74.42 (Parambikulam SPA) to 84.06 (Konni SPA). The mean total gene diversity index (HT) of all the four SPAs was 0.2296 ±0.02. A high proportion of genetic diversity was observed within the populations (83%) while diversity between populations was lower (17%) (GST = 0.17). Principal coordinate analysis and STRUCTURE analysis of the genotypes indicated that the pattern of clustering was in accordance with the origin and geographic location of SPAs, indicating specific identity of each population. A UPGMA dendrogram was prepared and showed that all the twenty samples from each of Konni and Parambikulam SPAs clustered into two separate groups, respectively. However, five Nilambur genotypes and one Wayanad genotype intruded into the Konni cluster. The higher gene flow estimated (Nm = 2.4) reflected the inclusion of Konni origin planting stock in the Nilambur and Wayanad plantations. Evidence for population structure investigated using 3D Principal Coordinate Analysis of FAMD software 1.30 indicated that the pattern of clustering was in accordance with the origin of SPAs. The present study showed that assessment of genetic diversity in seed production plantations can be achieved using AFLP markers. The AFLP fingerprinting was also capable of identifying the geographical origin of planting stock and there by revealing the occurrence of the errors in genotype labeling. Molecular marker-based selective culling of genetically similar trees from a stand so as to increase the genetic base of seed production areas could be a new proposition to improve quality of seeds required for raising commercial plantations of teak. The technique can also be used to assess the genetic diversity status of plus trees within provenances during their selection for raising clonal seed orchards for assuring the quality of seeds available for raising future plantations.Keywords: AFLP, genetic structure, spa, teak
Procedia PDF Downloads 3086404 Design and Validation of the 'Teachers' Resilience Scale' for Assessing Protective Factors
Authors: Athena Daniilidou, Maria Platsidou
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Resilience is considered to greatly affect the personal and occupational wellbeing and efficacy of individuals; therefore, it has been widely studied in the social and behavioral sciences. Given its significance, several scales have been created to assess resilience of children and adults. However, most of these scales focus on examining only the internal protective or risk factors that affect the levels of resilience. The aim of the present study is to create a reliable scale that assesses both the internal and the external protective factors that affect Greek teachers’ levels of resilience. Participants were 136 secondary school teachers (89 females, 47 males) from urban areas of Greece. Connor-Davidson Resilience Scale (CD-Risc) and Resilience Scale for Adults (RSA) were used to collect the data. First, exploratory factor analysis was employed to investigate the inner structure of each scale. For both scales, the analyses revealed a differentiated factor solution compared to the ones proposed by the creators. That prompt us to create a scale that would combine the best fitting subscales of the CD-Risc and the RSA. To this end, the items of the four factors with the best fit and highest reliability were used to create the ‘Teachers' resilience scale’. Exploratory factor analysis revealed that the scale assesses the following protective/risk factors: Personal Competence and Strength (9 items, α=.83), Family Cohesion Spiritual Influences (7 items, α=.80), Social Competence and Peers Support (7 items, α=.78) and Spiritual Influence (3 items, α=.58). This four-factor model explained 49,50% of the total variance. In the next step, a confirmatory factor analysis was performed on the 26 items of the derived scale to test the above factor solution. The fit of the model to the data was good (χ2/292 = 1.245, CFI = .921, GFI = .829, SRMR = .074, CI90% = .026-,056, RMSEA = 0.43), indicating that the proposed scale can validly measure the aforementioned four aspects of teachers' resilience and thus confirmed its factorial validity. Finally, analyses of variance were performed to check for individual differences in the levels of teachers' resilience in relation to their gender, age, marital status, level of studies, and teaching specialty. Results were consistent to previous findings, thus providing an indication of discriminant validity for the instrument. This scale has the advantage of assessing both the internal and the external protective factors of resilience in a brief yet comprehensive way, since it consists 26 items instead of the total of 58 of the CD-Risc and RSA scales. Its factorial inner structure is supported by the relevant literature on resilience, as it captures the major protective factors of resilience identified in previous studies.Keywords: protective factors, resilience, scale development, teachers
Procedia PDF Downloads 2976403 Association between Polygenic Risk of Alzheimer's Dementia, Brain MRI and Cognition in UK Biobank
Authors: Rachana Tank, Donald. M. Lyall, Kristin Flegal, Joey Ward, Jonathan Cavanagh
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Alzheimer’s research UK estimates by 2050, 2 million individuals will be living with Late Onset Alzheimer’s disease (LOAD). However, individuals experience considerable cognitive deficits and brain pathology over decades before reaching clinically diagnosable LOAD and studies have utilised gene candidate studies such as genome wide association studies (GWAS) and polygenic risk (PGR) scores to identify high risk individuals and potential pathways. This investigation aims to determine whether high genetic risk of LOAD is associated with worse brain MRI and cognitive performance in healthy older adults within the UK Biobank cohort. Previous studies investigating associations of PGR for LOAD and measures of MRI or cognitive functioning have focused on specific aspects of hippocampal structure, in relatively small sample sizes and with poor ‘controlling’ for confounders such as smoking. Both the sample size of this study and the discovery GWAS sample are bigger than previous studies to our knowledge. Genetic interaction between loci showing largest effects in GWAS have not been extensively studied and it is known that APOE e4 poses the largest genetic risk of LOAD with potential gene-gene and gene-environment interactions of e4, for this reason we also analyse genetic interactions of PGR with the APOE e4 genotype. High genetic loading based on a polygenic risk score of 21 SNPs for LOAD is associated with worse brain MRI and cognitive outcomes in healthy individuals within the UK Biobank cohort. Summary statistics from Kunkle et al., GWAS meta-analyses (case: n=30,344, control: n=52,427) will be used to create polygenic risk scores based on 21 SNPs and analyses will be carried out in N=37,000 participants in the UK Biobank. This will be the largest study to date investigating PGR of LOAD in relation to MRI. MRI outcome measures include WM tracts, structural volumes. Cognitive function measures include reaction time, pairs matching, trail making, digit symbol substitution and prospective memory. Interaction of the APOE e4 alleles and PGR will be analysed by including APOE status as an interaction term coded as either 0, 1 or 2 e4 alleles. Models will be adjusted partially for adjusted for age, BMI, sex, genotyping chip, smoking, depression and social deprivation. Preliminary results suggest PGR score for LOAD is associated with decreased hippocampal volumes including hippocampal body (standardised beta = -0.04, P = 0.022) and tail (standardised beta = -0.037, P = 0.030), but not with hippocampal head. There were also associations of genetic risk with decreased cognitive performance including fluid intelligence (standardised beta = -0.08, P<0.01) and reaction time (standardised beta = 2.04, P<0.01). No genetic interactions were found between APOE e4 dose and PGR score for MRI or cognitive measures. The generalisability of these results is limited by selection bias within the UK Biobank as participants are less likely to be obese, smoke, be socioeconomically deprived and have fewer self-reported health conditions when compared to the general population. Lack of a unified approach or standardised method for calculating genetic risk scores may also be a limitation of these analyses. Further discussion and results are pending.Keywords: Alzheimer's dementia, cognition, polygenic risk, MRI
Procedia PDF Downloads 1136402 Evaluation of Hepatic Metabolite Changes for Differentiation Between Non-Alcoholic Steatohepatitis and Simple Hepatic Steatosis Using Long Echo-Time Proton Magnetic Resonance Spectroscopy
Authors: Tae-Hoon Kim, Kwon-Ha Yoon, Hong Young Jun, Ki-Jong Kim, Young Hwan Lee, Myeung Su Lee, Keum Ha Choi, Ki Jung Yun, Eun Young Cho, Yong-Yeon Jeong, Chung-Hwan Jun
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Purpose: To assess the changes of hepatic metabolite for differentiation between non-alcoholic steatohepatitis (NASH) and simple steatosis on proton magnetic resonance spectroscopy (1H-MRS) in both humans and animal model. Methods: The local institutional review board approved this study and subjects gave written informed consent. 1H-MRS measurements were performed on a localized voxel of the liver using a point-resolved spectroscopy (PRESS) sequence and hepatic metabolites of alanine (Ala), lactate/triglyceride (Lac/TG), and TG were analyzed in NASH, simple steatosis and control groups. The group difference was tested with the ANOVA and Tukey’s post-hoc tests, and diagnostic accuracy was tested by calculating the area under the receiver operating characteristics (ROC) curve. The associations between metabolic concentration and pathologic grades or non-alcoholic fatty liver disease(NAFLD) activity scores were assessed by the Pearson’s correlation. Results: Patient with NASH showed the elevated Ala(p<0.001), Lac/TG(p < 0.001), TG(p < 0.05) concentration when compared with patients who had simple steatosis and healthy controls. The NASH patients were higher levels in Ala(mean±SEM, 52.5±8.3 vs 2.0±0.9; p < 0.001), Lac/TG(824.0±168.2 vs 394.1±89.8; p < 0.05) than simple steatosis. The area under the ROC curve to distinguish NASH from simple steatosis was 1.00 (95% confidence interval; 1.00, 1.00) with Ala and 0.782 (95% confidence interval; 0.61, 0.96) with Lac/TG. The Ala and Lac/TG levels were well correlated with steatosis grade, lobular inflammation, and NAFLD activity scores. The metabolic changes in human were reproducible to a mice model induced by streptozotocin injection and a high-fat diet. Conclusion: 1H-MRS would be useful for differentiation of patients with NASH and simple hepatic steatosis.Keywords: non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, 1H MR spectroscopy, hepatic metabolites
Procedia PDF Downloads 3266401 Effect of Slope Angle on Gougerd Landslide Stability in Northwest of Iran
Authors: Akbar Khodavirdizadeh
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Gougerd village landslide with area about 150 hectares is located in southwest of Khoy city in northwest of the Iran. This Landslide was commenced more than 21 years and caused some damages in houses like some fissures on walls and some cracks on ground and foundations. The main mechanism of landslide is rotational with the high different of top and foot is about 230 m. The thickness of slide mass based on geoelectrical investigation is about 16m obtained. The upper layer of slope is silty sand and the lower layer of clayey gravel. In this paper, the stability of landslide are analyzed based in static analysis under different groundwater surface conditions and at slope angle changes with limit eqlibrium method and the simplified Bishop method. The results of the 72 stability analysis showed that the slope stability of Gougerd landslide increased with increasing of the groundwater surface depth of slope crown. And especially when decreased of slope angle, the safety facter more than in previous state is increased. The required of safety factor for stability in groundwater surface depth from slope crown equal 14 m and with decreased of slope angle to 3 degree at decrease of groundwater surface depth from slope crown equal 6.5 m obtained. The safety factor in critical conditions under groundwater surface depth from slope crown equal 3.5 m and at decreased of slope angle to 3 degree equal 0.5 m obtained. At groudwater surface depth from slope crown of 3 m, 7 m and 10 m respectively equal to 0.97, 1.19 and 1.33 obtained. At groudwater surface depth from slope crown of 3 m, 7 m and 10 m with decreased of slope angle to 3 degree, respectively equal to 1.27, 1.54 and 1.72 obtained. According to the results of this study, for 1 m of groundwater level decrease, the safety factor increased by 5%, and for 1 degree of reduction of the slope angle, safety factor increased by 15%. And the effect of slope angle on Gougerd landslide stability was felt more than groundwater effect.Keywords: Gougerd landslide, stability analysis, slope angle, groundwater, Khoy
Procedia PDF Downloads 1696400 Interpersonal Variation of Salivary Microbiota Using Denaturing Gradient Gel Electrophoresis
Authors: Manjula Weerasekera, Chris Sissons, Lisa Wong, Sally Anderson, Ann Holmes, Richard Cannon
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The aim of this study was to characterize bacterial population and yeasts in saliva by Polymerase chain reaction followed by denaturing gradient gel electrophoresis (PCR-DGGE) and measure yeast levels by culture. PCR-DGGE was performed to identify oral bacteria and yeasts in 24 saliva samples. DNA was extracted and used to generate DNA amplicons of the V2–V3 hypervariable region of the bacterial 16S rDNA gene using PCR. Further universal primers targeting the large subunit rDNA gene (25S-28S) of fungi were used to amplify yeasts present in human saliva. Resulting PCR products were subjected to denaturing gradient gel electrophoresis using Universal mutation detection system. DGGE bands were extracted and sequenced using Sanger method. A potential relationship was evaluated between groups of bacteria identified by cluster analysis of DGGE fingerprints with the yeast levels and with their diversity. Significant interpersonal variation of salivary microbiome was observed. Cluster and principal component analysis of the bacterial DGGE patterns yielded three significant major clusters, and outliers. Seventeen of the 24 (71%) saliva samples were yeast positive going up to 10³ cfu/mL. Predominately, C. albicans, and six other species of yeast were detected. The presence, amount and species of yeast showed no clear relationship to the bacterial clusters. Microbial community in saliva showed a significant variation between individuals. A lack of association between yeasts and the bacterial fingerprints in saliva suggests the significant ecological person-specific independence in highly complex oral biofilm systems under normal oral conditions.Keywords: bacteria, denaturing gradient gel electrophoresis, oral biofilm, yeasts
Procedia PDF Downloads 2226399 Genomics Approach for Excavation of NAS Genes from Nutri Rich Minor Millet Crops: Transforming Perspective from Orphan Plants to Future Food Crops
Authors: Mahima Dubey, Girish Chandel
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Minor millets are highly nutritious and climate resilient cereal crops. These features make them ideal candidates to excavate the physiology of the underlying mechanism. In an attempt to understand the basis of mineral nutrition in minor millets, a set of five Barnyard millet genotypes were analyzed for grain Fe and Zn content under contrasting Fe-Zn supply to identify genotypes proficient in tolerating mineral deficiency. This resulted in the identification of Melghat-1 genotype to be nutritionally superior with better ability to withstand deficiency. Expression analysis of several Nicotianamine synthase (NAS) genes showed that HvNAS1 and OsNAS2 genes were prominent in positively mediating mineral deficiency response in Barnyard millet. Further, strategic efforts were employed for fast-track identification of more effective orthologous NAS genes from Barnyard millet. This resulted in the identification of two genes namely EfNAS1 (orthologous to HvNAS1 of barley) and EfNAS2 (orthologous to OsNAS2 gene of rice). Sequencing and thorough characterization of these sequences revealed the presence of intact NAS domain and signature tyrosine and di-leucine motifs in their predicted proteins and thus established their candidature as functional NAS genes in Barnyard millet. Moreover, EfNAS1 showed structural superiority over previously known NAS genes and is anticipated to have role in more efficient metal transport. Findings of the study provide insight into Fe-Zn deficiency response and mineral nutrition in millets. This provides millets with a physiological edge over micronutrient deficient staple cereals such as rice in withstanding Fe-Zn deficiency and subsequently accumulating higher levels of Fe and Zn in millet grains.Keywords: gene expression, micronutrient, millet, ortholog
Procedia PDF Downloads 2326398 Multilocus Phylogenetic Approach Reveals Informative DNA Barcodes for Studying Evolution and Taxonomy of Fusarium Fungi
Authors: Alexander A. Stakheev, Larisa V. Samokhvalova, Sergey K. Zavriev
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Fusarium fungi are among the most devastating plant pathogens distributed all over the world. Significant reduction of grain yield and quality caused by Fusarium leads to multi-billion dollar annual losses to the world agricultural production. These organisms can also cause infections in immunocompromised persons and produce the wide range of mycotoxins, such as trichothecenes, fumonisins, and zearalenone, which are hazardous to human and animal health. Identification of Fusarium fungi based on the morphology of spores and spore-forming structures, colony color and appearance on specific culture media is often very complicated due to the high similarity of these features for closely related species. Modern Fusarium taxonomy increasingly uses data of crossing experiments (biological species concept) and genetic polymorphism analysis (phylogenetic species concept). A number of novel Fusarium sibling species has been established using DNA barcoding techniques. Species recognition is best made with the combined phylogeny of intron-rich protein coding genes and ribosomal DNA sequences. However, the internal transcribed spacer of (ITS), which is considered to be universal DNA barcode for Fungi, is not suitable for genus Fusarium, because of its insufficient variability between closely related species and the presence of non-orthologous copies in the genome. Nowadays, the translation elongation factor 1 alpha (TEF1α) gene is the “gold standard” of Fusarium taxonomy, but the search for novel informative markers is still needed. In this study, we used two novel DNA markers, frataxin (FXN) and heat shock protein 90 (HSP90) to discover phylogenetic relationships between Fusarium species. Multilocus phylogenetic analysis based on partial sequences of TEF1α, FXN, HSP90, as well as intergenic spacer of ribosomal DNA (IGS), beta-tubulin (β-TUB) and phosphate permease (PHO) genes has been conducted for 120 isolates of 19 Fusarium species from different climatic zones of Russia and neighboring countries using maximum likelihood (ML) and maximum parsimony (MP) algorithms. Our analyses revealed that FXN and HSP90 genes could be considered as informative phylogenetic markers, suitable for evolutionary and taxonomic studies of Fusarium genus. It has been shown that PHO gene possesses more variable (22 %) and parsimony informative (19 %) characters than other markers, including TEF1α (12 % and 9 %, correspondingly) when used for elucidating phylogenetic relationships between F. avenaceum and its closest relatives – F. tricinctum, F. acuminatum, F. torulosum. Application of novel DNA barcodes confirmed the fact that F. arthrosporioides do not represent a separate species but only a subspecies of F. avenaceum. Phylogeny based on partial PHO and FXN sequences revealed the presence of separate cluster of four F. avenaceum strains which were closer to F. torulosum than to major F. avenaceum clade. The strain F-846 from Moldova, morphologically identified as F. poae, formed a separate lineage in all the constructed dendrograms, and could potentially be considered as a separate species, but more information is needed to confirm this conclusion. Variable sites in PHO sequences were used for the first-time development of specific qPCR-based diagnostic assays for F. acuminatum and F. torulosum. This work was supported by Russian Foundation for Basic Research (grant № 15-29-02527).Keywords: DNA barcode, fusarium, identification, phylogenetics, taxonomy
Procedia PDF Downloads 3246397 Association between G2677T/A MDR1 Polymorphism with the Clinical Response to Disease Modifying Anti-Rheumatic Drugs in Rheumatoid Arthritis
Authors: Alan Ruiz-Padilla, Brando Villalobos-Villalobos, Yeniley Ruiz-Noa, Claudia Mendoza-Macías, Claudia Palafox-Sánchez, Miguel Marín-Rosales, Álvaro Cruz, Rubén Rangel-Salazar
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Introduction: In patients with rheumatoid arthritis, resistance or poor response to disease modifying antirheumatic drugs (DMARD) may be a reflection of the increase in g-P. The expression of g-P may be important in mediating the effluence of DMARD from the cell. In addition, P-glycoprotein is involved in the transport of cytokines, IL-1, IL-2 and IL-4, from normal lymphocytes activated to the surrounding extracellular matrix, thus influencing the activity of RA. The involvement of P-glycoprotein in the transmembrane transport of cytokines can serve as a modulator of the efficacy of DMARD. It was shown that a number of lymphocytes with glycoprotein P activity is increased in patients with RA; therefore, P-glycoprotein expression could be related to the activity of RA and could be a predictor of poor response to therapy. Objective: To evaluate in RA patients, if the G2677T/A MDR1 polymorphisms is associated with differences in the rate of therapeutic response to disease-modifying antirheumatic agents in patients with rheumatoid arthritis. Material and Methods: A prospective cohort study was conducted. Fifty seven patients with RA were included. They had an active disease according to DAS-28 (score >3.2). We excluded patients receiving biological agents. All the patients were followed during 6 months in order to identify the rate of therapeutic response according to the American College of Rheumatology (ACR) criteria. At the baseline peripheral blood samples were taken in order to identify the G2677T/A MDR1 polymorphisms using PCR- Specific allele. The fragment was identified by electrophoresis in polyacrylamide gels stained with ethidium bromide. For statistical analysis, the genotypic and allelic frequencies of MDR1 gene polymorphism between responders and non-responders were determined. Chi-square tests as well as, relative risks with 95% confidence intervals (95%CI) were computed to identify differences in the risk for achieving therapeutic response. Results: RA patients had a mean age of 47.33 ± 12.52 years, 87.7% were women with a mean for DAS-28 score of 6.45 ± 1.12. At the 6 months, the rate of therapeutic response was 68.7 %. The observed genotype frequencies were: for G/G 40%, T/T 32%, A/A 19%, G/T 7% and for A/A genotype 2%. Patients with G allele developed at 6 months of treatment, higher rate for therapeutic response assessed by ACR20 compared to patients with others alleles (p=0.039). Conclusions: Patients with G allele of the - G2677T/A MDR1 polymorphisms had a higher rate of therapeutic response at 6 months with DMARD. These preliminary data support the requirement for a deep evaluation of these and other genotypes as factors that may influence the therapeutic response in RA.Keywords: pharmacogenetics, MDR1, P-glycoprotein, therapeutic response, rheumatoid arthritis
Procedia PDF Downloads 2086396 Study Protocol: Impact of a Sustained Health Promoting Workplace on Stock Price Performance and Beta - A Singapore Case
Authors: Wee Tong Liaw, Elaine Wong Yee Sing
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Since 2001, many companies in Singapore have voluntarily participated in the bi-annual Singapore HEALTH Award initiated by the Health Promotion Board of Singapore (HPB). The Singapore HEALTH Award (SHA), is an industry wide award and assessment process. SHA assesses and recognizes employers in Singapore for implementing a comprehensive and sustainable health promotion programme at their workplaces. The rationale for implementing a sustained health promoting workplace and participating in SHA is obvious when company management is convinced that healthier employees, business productivity, and profitability are positively correlated. However, performing research or empirical studies on the impact of a sustained health promoting workplace on stock returns are not likely to yield any interests in the absence of a systematic and independent assessment on the comprehensiveness and sustainability of a health promoting workplace in most developed economies. The principles of diversification and mean-variance efficient portfolio in Modern Portfolio Theory developed by Markowitz (1952) laid the foundation for the works of many financial economists and researchers, and among others, the development of the Capital Asset Pricing Model from the work of Sharpe (1964), Lintner (1965) and Mossin (1966), and the Fama-French Three-Factor Model of Fama and French (1992). This research seeks to support the rationale by studying whether there is a significant relationship or impact of a sustained health promoting workplace on the performance of companies listed on the SGX. The research shall form and test hypotheses pertaining to the impact of a sustained health promoting workplace on company’s performances, including stock returns, of companies that participated in the SHA and companies that did not participate in the SHA. In doing so, the research would be able to determine whether corporate and fund manager should consider the significance of a sustained health promoting workplace as a risk factor to explain the stock returns of companies listed on the SGX. With respect to Singapore’s stock market, this research will test the significance and relevance of a health promoting workplace using the Singapore Health Award as a proxy for non-diversifiable risk factor to explain stock returns. This study will examine the significance of a health promoting workplace on a company’s performance and study its impact on stock price performance and beta and examine if it has higher explanatory power than the traditional single factor asset pricing model CAPM (Capital Asset Pricing Model). To study the significance there are three key questions pertinent to the research study. I) Given a choice, would an investor be better off investing in a listed company with a sustained health promoting workplace i.e. a Singapore Health Award’s recipient? II) The Singapore Health Award has four levels of award starting from Bronze, Silver, Gold to Platinum. Would an investor be indifferent to the level of award when investing in a listed company who is a Singapore Health Award’s recipient? III) Would an asset pricing model combining FAMA-French Three Factor Model and ‘Singapore Health Award’ factor be more accurate than single factor Capital Asset Pricing Model and the Three Factor Model itself?Keywords: asset pricing model, company's performance, stock prices, sustained health promoting workplace
Procedia PDF Downloads 3696395 High-Risk Gene Variant Profiling Models Ethnic Disparities in Diabetes Vulnerability
Authors: Jianhua Zhang, Weiping Chen, Guanjie Chen, Jason Flannick, Emma Fikse, Glenda Smerin, Yanqin Yang, Yulong Li, John A. Hanover, William F. Simonds
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Ethnic disparities in many diseases are well recognized and reflect the consequences of genetic, behavior, and environmental factors. However, direct scientific evidence connecting the ethnic genetic variations and the disease disparities has been elusive, which may have led to the ethnic inequalities in large scale genetic studies. Through the genome-wide analysis of data representing 185,934 subjects, including 14,955 from our own studies of the African America Diabetes Mellitus, we discovered sets of genetic variants either unique to or conserved in all ethnicities. We further developed a quantitative gene function-based high-risk variant index (hrVI) of 20,428 genes to establish profiles that strongly correlate with the subjects' self-identified ethnicities. With respect to the ability to detect human essential and pathogenic genes, the hrVI analysis method is both comparable with and complementary to the well-known genetic analysis methods, pLI and VIRlof. Application of the ethnicity-specific hrVI analysis to the type 2 diabetes mellitus (T2DM) national repository, containing 20,791 cases and 24,440 controls, identified 114 candidate T2DM-associated genes, 8.8-fold greater than that of ethnicity-blind analysis. All the genes identified are defined as either pathogenic or likely-pathogenic in ClinVar database, with 33.3% diabetes-associated and 54.4% obesity-associated genes. These results demonstrate the utility of hrVI analysis and provide the first genetic evidence by clustering patterns of how genetic variations among ethnicities may impede the discovery of diabetes and foreseeably other disease-associated genes.Keywords: diabetes-associated genes, ethnic health disparities, high-risk variant index, hrVI, T2DM
Procedia PDF Downloads 1376394 Neurotoxic Effects Assessment of Metformin in Danio rerio
Authors: Gustavo Axel Elizalde-Velázquez
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Metformin is the first line of oral therapy to treat type II diabetes and is also employed as a treatment for other indications, such as polycystic ovary syndrome, cancer, and COVID-19. Recent data suggest it is the aspirin of the 21st century due to its antioxidant and anti-aging effects. However, increasingly current articles indicate its long-term consumption generates mitochondrial impairment. Up to date, it is known metformin increases the biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription, but further information related to brain damage after its consumption is missing. Bearing in mind the above, this work aimed to establish whether or not chronic exposure to metformin may alter swimming behavior and induce neurotoxicity in Danio rerio adults. For this purpose, 250 Danio rerio grown-ups were assigned to six tanks of 50 L of capacity. Four of the six systems contained 50 fish, while the remaining two had 25 fish (≈1 male:1 female ratio). Every system with 50 fish was allocated one of the three metformin treatment concentrations (1, 20, and 40 μg/L), with one system as the control treatment. Systems with 25 fish, on the other hand, were used as positive controls for acetylcholinesterase (10 μg/L of Atrazine) and oxidative stress (3 μg/L of Atrazine). After four months of exposure, a mean of 32 fish (S.D. ± 2) per group of MET treatment survived, which were used for the evaluation of behavior with the Novel Tank test. Moreover, after the behavioral assessment, we aimed to collect the blood and brains of all fish from all treatment groups. For blood collection, fish were anesthetized with an MS-222 solution (150 mg/L), while for brain gathering, fish were euthanized using the hypothermic shock method (2–4 °C). Blood was employed to determine CASP3 activity and the percentage of apoptotic cells with the TUNEL assay, and brains were used to evaluate acetylcholinesterase activity, oxidative damage, and gene expression. After chronic exposure, MET-exposed fish exhibited less swimming activity when compared to control fish. Moreover, compared with the control group, MET significantly inhibited the activity of AChE and induced oxidative damage in the brain of fish. Concerning gene expression, MET significantly upregulated the expression of Nrf1, Nrf2, BAX, p53, BACE1, APP, PSEN1, and downregulated CASP3 and CASP9. Although MET did not overexpress the CASP3 gene, we saw a meaningful rise in the activity of this enzyme in the blood of fish exposed to MET compared to the control group, which we then confirmed by a high number of apoptotic cells in the TUNEL assay. To the best of our understanding, this is the first study that delivers evidence of oxidative impairment, apoptosis, AChE alteration, and overexpression of B- amyloid-related genes in the brain of fish exposed to metformin.Keywords: AChE inhibition, CASP3 activity, NovelTank test, oxidative damage, TUNEL assay
Procedia PDF Downloads 866393 Validity of Clinical Disease Activity Index (CDAI) to Evaluate the Disease Activity of Rheumatoid Arthritis Patients in Sri Lanka: A Prospective Follow up Study Based on Newly Diagnosed Patients
Authors: Keerthie Dissanayake, Chandrika Jayasinghe, Priyani Wanigasekara, Jayampathy Dissanayake, Ajith Sominanda
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The routine use of Disease Activity Score-28 (DAS28) to assess the disease activity in rheumatoid arthritis (RA) is limited due to its dependency on laboratory investigations and the complex calculations involved. In contrast, the clinical disease activity index (CDAI) is simple to calculate, which makes the "treat to target" strategy for the management of RA more practical. We aimed to assess the validity of CDAI compared to DAS28 in RA patients in Sri Lanka. A total of 103 newly diagnosed RA patients were recruited, and their disease activity was calculated using DAS 28 and CDAI during the first visit to the clinic (0 months) and re-assessed at 4 and 9 months of the follow-up visits. The validity of the CDAI, compared to DAS 28, was evaluated. Patients had a female preponderance (6:1) and a short symptom duration (mean = 6.33 months). The construct validity of CDAI, as assessed by Cronbach's α test, was 0.868. Convergent validity was assessed by correlation and Kappa statistics. Strong positive correlations were observed between CDAI and DAS 28 at the baseline (0 months), 4, and 9 months of evaluation (Spearman's r = 0.9357, 0.9354, 0.9106, respectively). Moderate-good inter-rater agreements between the DAS-28 and CDAI were observed (Weighted kappa of 0.660, 0.519, and 0.741 at 0, 4, and 9 months respectively). Discriminant validity, as assessed by ROC curves at 0, 4th, and 9th months of the evaluation, showed the area under the curve (AUC) of 0.958, 0.985, and 0.914, respectively. The suggested cut-off points for different CDAI disease activity categories according to ROC curves were ≤ 2 (Remission), >2 to ≤ 5 (low), >5 to ≤ 18 (moderate), > 18 (high). These findings indicate that the CDAI has good concordance with DAS 28 in assessing the disease activity in RA patients in this study sample.Keywords: rheumatoid arthritis, CDAI, disease activity, Sri Lanka, validation
Procedia PDF Downloads 1546392 Improving Sample Analysis and Interpretation Using QIAGENs Latest Investigator STR Multiplex PCR Assays with a Novel Quality Sensor
Authors: Daniel Mueller, Melanie Breitbach, Stefan Cornelius, Sarah Pakulla-Dickel, Margaretha Koenig, Anke Prochnow, Mario Scherer
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The European STR standard set (ESS) of loci as well as the new expanded CODIS core loci set as recommended by the CODIS Core Loci Working Group, has led to a higher standardization and harmonization in STR analysis across borders. Various multiplex PCRs assays have since been developed for the analysis of these 17 ESS or 23 CODIS expansion STR markers that all meet high technical demands. However, forensic analysts are often faced with difficult STR results and the questions thereupon. What is the reason that no peaks are visible in the electropherogram? Did the PCR fail? Was the DNA concentration too low? QIAGEN’s newest Investigator STR kits contain a novel Quality Sensor (QS) that acts as internal performance control and gives useful information for evaluating the amplification efficiency of the PCR. QS indicates if the reaction has worked in general and furthermore allows discriminating between the presence of inhibitors or DNA degradation as a cause for the typical ski slope effect observed in STR profiles of such challenging samples. This information can be used to choose the most appropriate rework strategy.Based on the latest PCR chemistry called FRM 2.0, QIAGEN now provides the next technological generation for STR analysis, the Investigator ESSplex SE QS and Investigator 24plex QS Kits. The new PCR chemistry ensures robust and fast PCR amplification with improved inhibitor resistance and easy handling for a manual or automated setup. The short cycling time of 60 min reduces the duration of the total PCR analysis to make a whole workflow analysis in one day more likely. To facilitate the interpretation of STR results a smart primer design was applied for best possible marker distribution, highest concordance rates and a robust gender typing.Keywords: PCR, QIAGEN, quality sensor, STR
Procedia PDF Downloads 495