Search results for: cardiovascular disease policy model
21822 A Computational Investigation of Potential Drugs for Cholesterol Regulation to Treat Alzheimer’s Disease
Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang
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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation
Procedia PDF Downloads 7721821 GABARAPL1 (GEC1) mRNA Expression Levels in Patients with Alzheimer's Disease
Authors: Ali Bayram, Burak Uz, Ilhan Dolasik, Remzi Yiğiter
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The GABARAP (GABAA-receptor-associated protein) family consists of GABARAP, GABARAPL1 (GABARAP-like 1) and GABARAPL2 (GABARAP-like 2). GABARAPL1, like GABARAP, was described to interact with both GABAA receptor and tubulin, and to be involved in intracellular GABAA receptor trafficking and promoting tubulin polymerization. In addition, GABARAPL1 is thought to be involved in various physiological (autophagosome closure, regulation of circadian rhythms) and/or pathological mechanisms (cancer, neurodegeneration). Alzheimer’s disease (AD) is a progressive neuro degenerative disorder characterized with impaired cognitive functions. Disruption of the GABAergic neuro transmission as well as cholinergic and glutamatergic interactions, may also be involved in the pathogenesis of AD. GABARAPL1 presents a regulated tissue expression and is the most expressed gene among the GABARAP family members in the central nervous system. We, herein, conducted a study to investigate the GABARAPL1 mRNA expression levels in patients with AD. 50 patients with AD and 49 control patients were enrolled to the present study. Messenger RNA expression levels of GABARAPL1 were detected by real-time polymerase chain reaction. GABARAPL1 mRNA expression in AD / control patients was 0,495 (95% confidence interval: 0,404-0,607), p= 0,00000002646. Reduced activity of GABARAPL1 gene might play a role, at least partly, in the pathophysiology of AD.Keywords: Alzheimer’s disease, GABARAPL1, mRNA expression, RT-PCR
Procedia PDF Downloads 45921820 In vitro Control of Mycosphaerella arachidis Deighton the Early Leaf Spot Disease Pathogen of Groundnut by the Extracts from Six Medicinal Plants
Authors: Matthew Omoniyi Adebola, Jude E Amadi
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Ground nut (Arachis hypogaea) is one of the most popular commercial crops in Nigeria. Its suc-cessful production has been drastically affected by early leaf spot disease caused by Mycosphae-rella arachidis Deighton. In vitro control of the pathogen by six medicinal plants (Entada afri-cana, Vitex doniana, Lawsonia inermis, Azadirachta indica, Acalypha hispida and Nuaclea lati-folia) was assessed in this study. The extracts of the plants were prepared using cold and hot wa-ter and alcohol. The pathogen was isolated from ground nut infected with early leaf spot disease. The results revealed a great significant difference (P<0.05) in yield of extracts between cold water, hot water, and alcohol extracts. A significant difference (P<0.05) was observed in percentage concentrations of the various phytochemical constituents present in the extracts. Flavonoids per-centage concentration was the highest (0.68 - 1.95%) followed by saponnin(0.09-1.53%) in N. latifolia extracts. Steroiods had the least percentage concentrations (0.00- 0.09%)followed by terpenoids(0.02–0.71%) and proanthocyannin (0.05 – 0.86%). N. latifolia extracts produced the highest percentage concentrations (0.07–1.95%) of all the phytochemicals followed by A. indi-ca(0.05–1.64%)and least concentrations were obtained in A. hispidia(0.09 – 0.87%)and V. do-niana (0.00–0.88%). The extracts inhibited spore germination and growth of M. arachidis. The inhibition by alcohol extracts was high and significantly different (P>0.05) from cold and hot water extracts. Alcohol extract of L. inermis gave 100% spore germination inhibition followed by N. latifolia and A.indica with 97.75% and 85.60% inhibition respectively. Therefore, field trials of these six medicinal plants on the control of early leaf spot disease of ground nut are rec-ommended.Keywords: groundnut, phytochemicals, medicinal plants, extracts, inhibition
Procedia PDF Downloads 30021819 Technical Efficiency and Challenges of Smallholder Horticultural Farmers in Ghana: A Wake-Up Call for Policy Implementers
Authors: Freda E. Asem, R. D. Osei, D. B. Sarpong, J. K. Kuwornu
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While market access remains important, Ghana’s major handicap is her inability to sustain export growth on the open market. The causes of these could be attributed to inefficiency, lack of competitiveness and supply-side constraints. This study examined the challenges faced by smallholder horticultural farmers and how it relates to their technical efficiency. The study employed mixed methods to address the problem. Using the Millennium Development Account (MiDA) Farmer Based Organization survey data on farm households in 23 districts in Ghana, the study assessed the technical efficiency of smallholder horticultural farmers (taking into account production risks). Focus group discussions (FGDs) and in-depth interviews were also conducted on smallholder mango, pineapple, and chilli pepper farmers selected districts in Ghana. Results revealed the constraints faced by smallholder horticultural farmers to be marketing, training, funding, accessibility, and affordability of inputs, land, access to credit, and the disconnect between themselves and policy makers and implementers.Keywords: productivity, gender, policy, efficiency, constraints
Procedia PDF Downloads 48621818 Examining Macroeconomics Determinants of Inflation Rate in Somalia
Authors: Farhia Hassan Mohamed
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This study examined the macroeconomic factors that affect the inflation Rate in Somalia using quarterly time series data from 1991q1 to 2017q4 retired from World Development Indicators and SESRIC. It employed the vector error correction model (VECM) and Granger Causality method to measure the long-run and short-run causality of the GDP, inflation exchange rate, and unemployment. The study confirmed that there is one cointegration equation between GDP, exchange rate, inflation, and unemployment in Somalia. However, the VECM model's result indicates a long-run relationship among variables. The VEC Granger causality/Block Exogeneity Wald test result confirmed that all covariates are statistically significant at 5% and are Granger's cause of inflation in the short term. Finally, the impulse response result showed that inflation responds negatively to the shocks from the exchange rate and unemployment rate and positively to GDP and itself. Drawing from the empirical findings, the study makes several policy recommendations for both the monetary and Government sides.Keywords: CPI, OP, exchange rate, inflation ADF, Johansen, PP, VECM, impulse, ECT
Procedia PDF Downloads 5121817 Model of MSD Risk Assessment at Workplace
Authors: K. Sekulová, M. Šimon
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This article focuses on upper-extremity musculoskeletal disorders risk assessment model at workplace. In this model are used risk factors that are responsible for musculoskeletal system damage. Based on statistic calculations the model is able to define what risk of MSD threatens workers who are under risk factors. The model is also able to say how MSD risk would decrease if these risk factors are eliminated.Keywords: ergonomics, musculoskeletal disorders, occupational diseases, risk factors
Procedia PDF Downloads 55221816 Application of Bundle Care to Reduce Invasive Catheter-Associated Infection in High Risk Units at a Medical Center
Authors: Hsin-Hsin Chang, Jann-Tay Wang, Wang-Huei Sheng
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Background: Hospital-associated infections (HAIs) have significant medical and social resource consumption. In view of medical technology change rapidly and the prolonged average life expectancy, the patients' chances of receiving invasive medical devices have also increased. As well as the potential disease of the patients, the aging, and immune dysfunction makes the disease more serious, raising the risk of HAIs. In our adult intensive care units, catheter-associated urinary tract infections (CAUTIs) have an average of 4.6% in 2014, which is much higher than that of the National Healthcare Safety Network (NHSN). Therefore, we started the intervention of CAUTI bundle care. Methods: This 3-year intervention was conducted in adults’ intensive care units (ICUs) during January 2015 to December 2017. The implementation of CAUTI bundle care in order to reduce invasive catheter-associated infections were built on evidence-based infection control measures. Prospective surveillance was performed on all patients admitted to hospital. The four major directions are 'Leader Engagement', 'Educate Personnel', 'Executive Multidisciplinary Teamwork', 'Innovation and Improvement of Tools'. Results: During the intervention period, there were 167,024 patient-days with a total of 508 episodes of CAUTIs in the entire adult ICUs identified. The incidence of CAUTIs in adult ICU was significantly decreased in the intervention period (from 2015 to 2017), from 4.6 to 3.6 per 1000 catheter days (p=0.05). Conclusion: The necessity for the implementation of CAUTI bundle care in the health care system plays an important role in the quality and policy of infection control. Multidisciplinary teamwork, education, a comprehensive checklist and from time to time audit feedback to improve healthcare workers’ compliance are the keys to success.Keywords: bundle care, hospital-associated infections, leader engagement, multidisciplinary team work
Procedia PDF Downloads 15521815 Role of Pro-Inflammatory and Regulatory Cytokines in Pathogenesis of Graves’ Disease in Association with Autoantibody Thyroid and Regulatory FoxP3 T-Cells
Authors: Dwitya Elvira, Eryati Darwin
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Background: Graves’ disease (GD) is an autoimmune thyroid disease. Imbalance of Th1/Th2 cells and T-regulatory (Treg)/Th17 cells was thought to play pivotal role in the pathogenesis of GD. Treg FoxP3 produced TGF-β to maintain regulatory function, and Th17 cells produced IL-17 as cytokines that were thought in mediating several autoimmune diseases. The aim of this study is to assess the role of IL-17 and TGF-β in the pathogenesis of GD and to investigate its correlation with Thyroid Stimulating Hormone Receptor Antibody (TRAb) and Treg FoxP3 expression. Method: 30 GD patients and 27 age and sex-matched controls were enrolled in this study. Diagnosis of GD was based on clinical and biochemical of GD. Serum IL-17, TGF-β, TRAb, and FoxP3 were measured by enzyme-linked immunosorbent assay (ELISA). Data were analyzed by using SPSS 21.0 (SPSS Inc.). Spearman rank correlation test was used for assessment of correlation. The statistical significance was accepted as P<0.05. Result: There was no significant correlation between IL-17 and TGF-β serum with expression of FoxP3 level in GD, but there was significant correlation between TGF-β and TRAb serum level (P<0.05). Serum levels of IL-17 and TGF-β were found to be elevated in patient group compared to control, where mean values of IL-17 were 14.43±2.15 pg/mL and TGF-β were 10.44±3.19 pg/mL in patients group; and in control group, level of IL-17 were 7.1±1.45 pg/mL and TGF-β were 4.95±1.35 pg/mL. Conclusion: Serum Il-17 and TGF-β were elevated in GD patients that reflect the role of inflammatory and regulatory cytokines activation in pathogenesis of GD. There was significant correlation between TGF-β and TRAb, revealing that Treg cytokines may play a role in pathogenesis of GD.Keywords: IL-17, TGF-B, FoxP3, TRAb, Graves’ disease
Procedia PDF Downloads 28821814 Mutation Analysis of the ATP7B Gene in 43 Vietnamese Wilson’s Disease Patients
Authors: Huong M. T. Nguyen, Hoa A. P. Nguyen, Mai P. T. Nguyen, Ngoc D. Ngo, Van T. Ta, Hai T. Le, Chi V. Phan
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Wilson’s disease (WD) is an autosomal recessive disorder of the copper metabolism, which is caused by a mutation in the copper-transporting P-type ATPase (ATP7B). The mechanism of this disease is the failure of hepatic excretion of copper to bile, and leads to copper deposits in the liver and other organs. The ATP7B gene is located on the long arm of chromosome 13 (13q14.3). This study aimed to investigate the gene mutation in the Vietnamese patients with WD, and make a presymptomatic diagnosis for their familial members. Forty-three WD patients and their 65 siblings were identified as having ATP7B gene mutations. Genomic DNA was extracted from peripheral blood samples; 21 exons and exon-intron boundaries of the ATP7B gene were analyzed by direct sequencing. We recognized four mutations ([R723=; H724Tfs*34], V1042Cfs*79, D1027H, and IVS6+3A>G) in the sum of 20 detectable mutations, accounting for 87.2% of the total. Mutation S105* was determined to have a high rate (32.6%) in this study. The hotspot regions of ATP7B were found at exons 2, 16, and 8, and intron 14, in 39.6 %, 11.6 %, 9.3%, and 7 % of patients, respectively. Among nine homozygote/compound heterozygote siblings of the patients with WD, three individuals were determined as asymptomatic by screening mutations of the probands. They would begin treatment after diagnosis. In conclusion, 20 different mutations were detected in 43 WD patients. Of this number, four novel mutations were explored, including [R723=; H724Tfs*34], V1042Cfs*79, D1027H, and IVS6+3A>G. The mutation S105* is the most prevalent and has been considered as a biomarker that can be used in a rapid detection assay for diagnosis of WD patients. Exons 2, 8, and 16, and intron 14 should be screened initially for WD patients in Vietnam. Based on risk profile for WD, genetic testing for presymptomatic patients is also useful in diagnosis and treatment.Keywords: ATP7B gene, mutation detection, presymptomatic diagnosis, Vietnamese Wilson’s disease
Procedia PDF Downloads 38321813 The Effectiveness of National Fiscal Rules in the Asia-Pacific Countries
Authors: Chiung-Ju Huang, Yuan-Hong Ho
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This study utilizes the International Monetary Fund (IMF) Fiscal Rules Dataset focusing on four specific fiscal rules such as expenditure rule, revenue rule, budget balance rule, and debt rule and five main characteristics of each fiscal rule those are monitoring, enforcement, coverage, legal basis, and escape clause to construct the Fiscal Rule Index for nine countries in the Asia-Pacific region from 1996 to 2015. After constructing the fiscal rule index for each country, we utilize the Panel Generalized Method of Moments (Panel GMM) by using the constructed fiscal rule index to examine the effectiveness of fiscal rules in reducing procyclicality. Empirical results show that national fiscal rules have a significantly negative impact on procyclicality of government expenditure. Additionally, stricter fiscal rules combined with high government effectiveness are effective in reducing procyclicality of government expenditure. Results of this study indicate that for nine Asia-Pacific countries, policymakers’ use of fiscal rules and government effectiveness to reducing procyclicality of fiscal policy are effective.Keywords: counter-cyclical policy, fiscal rules, government efficiency, procyclical policy
Procedia PDF Downloads 28321812 Identification of Classes of Bilinear Time Series Models
Authors: Anthony Usoro
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In this paper, two classes of bilinear time series model are obtained under certain conditions from the general bilinear autoregressive moving average model. Bilinear Autoregressive (BAR) and Bilinear Moving Average (BMA) Models have been identified. From the general bilinear model, BAR and BMA models have been proved to exist for q = Q = 0, => j = 0, and p = P = 0, => i = 0 respectively. These models are found useful in modelling most of the economic and financial data.Keywords: autoregressive model, bilinear autoregressive model, bilinear moving average model, moving average model
Procedia PDF Downloads 41221811 Dividend Policy in Family Controlling Firms from a Governance Perspective: Empirical Evidence in Thailand
Authors: Tanapond S.
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Typically, most of the controlling firms are relate to family firms which are widespread and important for economic growth particularly in Asian Pacific region. The unique characteristics of the controlling families tend to play an important role in determining the corporate policies such as dividend policy. Given the complexity of the family business phenomenon, the empirical evidence has been unclear on how the families behind business groups influence dividend policy in Asian markets with the prevalent existence of cross-shareholdings and pyramidal structure. Dividend policy as one of an important determinant of firm value could also be implemented in order to examine the effect of the controlling families behind business groups on strategic decisions-making in terms of a governance perspective and agency problems. The purpose of this paper is to investigate the impact of ownership structure and concentration which are influential internal corporate governance mechanisms in family firms on dividend decision-making. Using panel data and constructing a unique dataset of family ownership and control through hand-collecting information from the nonfinancial companies listed in Stock Exchange of Thailand (SET) between 2000 and 2015, the study finds that family firms with large stakes distribute higher dividends than family firms with small stakes. Family ownership can mitigate the agency problems and the expropriation of minority investors in family firms. To provide insight into the distinguish between ownership rights and control rights, this study examines specific firm characteristics including the degrees of concentration of controlling shareholders by classifying family ownership in different categories. The results show that controlling families with large deviation between voting rights and cash flow rights have more power and affect lower dividend payment. These situations become worse when second blockholders are families. To the best knowledge of the researcher, this study is the first to examine the association between family firms’ characteristics and dividend policy from the corporate governance perspectives in Thailand with weak investor protection environment and high ownership concentration. This research also underscores the importance of family control especially in a context in which family business groups and pyramidal structure are prevalent. As a result, academics and policy makers can develop markets and corporate policies to eliminate agency problem.Keywords: agency theory, dividend policy, family control, Thailand
Procedia PDF Downloads 29221810 Towards the Development of Uncertainties Resilient Business Model for Driving the Solar Panel Industry in Nigeria Power Sector
Authors: Balarabe Z. Ahmad, Anne-Lorène Vernay
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The emergence of electricity in Nigeria was dated back to 1896. The power plants have the potential to generate 12,522 MW of electric power. Whereas current dispatch is about 4,000 MW, access to electrification is about 60%, with consumption at 0.14 MWh/capita. The government embarked on energy reforms to mitigate energy poverty. The reform targeted the provision of electricity access to 75% of the population by 2020 and 90% by 2030. Growth of total electricity demand by a factor of 5 by 2035 had been projected. This means that Nigeria will require almost 530 TWh of electricity which can be delivered through generators with a capacity of 65 GW. Analogously, the geographical location of Nigeria has placed it in an advantageous position as the source of solar energy; the availability of a high sunshine belt is obvious in the country. The implication is that the far North, where energy poverty is high, equally has about twice the solar radiation as against southern Nigeria. Hence, the chance of generating solar electricity is 66% possible at 11850 x 103 GWh per year, which is one hundred times the current electricity consumption rate in the country. Harvesting these huge potentials may be a mirage if the entrepreneurs in the solar panel business are left with the conventional business models that are not uncertainty resilient. Currently, business entities in RE in Nigeria are uncertain of; accessing the national grid, purchasing potentials of cooperating organizations, currency fluctuation and interest rate increases. Uncertainties such as the security of projects and government policy are issues entrepreneurs must navigate to remain sustainable in the solar panel industry in Nigeria. The aim of this paper is to identify how entrepreneurial firms consider uncertainties in developing workable business models for commercializing solar energy projects in Nigeria. In an attempt to develop a novel business model, the paper investigated how entrepreneurial firms assess and navigate uncertainties. The roles of key stakeholders in helping entrepreneurs to manage uncertainties in the Nigeria RE sector were probed in the ongoing study. The study explored empirical uncertainties that are peculiar to RE entrepreneurs in Nigeria. A mixed-mode of research was embraced using qualitative data from face-to-face interviews conducted on the Solar Energy Entrepreneurs and the experts drawn from key stakeholders. Content analysis of the interview was done using Atlas. It is a nine qualitative tool. The result suggested that all stakeholders are required to synergize in developing an uncertainty resilient business model. It was opined that the RE entrepreneurs need modifications in the business recommendations encapsulated in the energy policy in Nigeria to strengthen their capability in delivering solar energy solutions to the yawning Nigerians.Keywords: uncertainties, entrepreneurial, business model, solar-panel
Procedia PDF Downloads 15221809 Transformation of Antitrust Policy against Collusion in Russia and Transition Economies
Authors: Andrey Makarov
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This article will focus on the development of antitrust policy in transition economies in the context of preventing explicit and tacit collusion. Experience of BRICS, CIS (Ukraine, Kazakhstan) and CEE countries (Bulgaria, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, Slovenia, Czech Republic, Estonia) in the creation of antitrust institutions was analyzed, including both legislation and enforcement practice. Most of these countries in the early 90th were forced to develop completely new legislation in the field of protection of competition and it is important to compare different ways of building antitrust institutions and policy results. The article proposes a special approach to evaluation of preventing collusion mechanisms. This approach takes into account such enforcement problems as: classification problems (tacit vs explicit collusion, vertical vs horizontal agreements), flexibility of prohibitions (the balance between “per se” vs “rule of reason” approaches de jure and in practice), design of sanctions, private enforcement challenge, leniency program mechanisms, the role of antitrust authorities etc. The analysis is conducted using both official data, published by competition authorities, and expert assessments. The paper will show how the integration process within the EU predetermined some aspects of the development of antitrust policy in CEE countries, including the trend of the use of "rule of reason" approach. Simultaneously was analyzed the experience of CEE countries in special mechanisms of government intervention. CIS countries in the development of antitrust policy followed more or less original ways, without such a great impact from the European Union, more attention will be given to Russian experience in this field, including the analysis of judicial decisions in antitrust cases. Main problems and challenges for transition economies in this field will be shown, including: Legal uncertainty problem; Problem of rigidity of prohibitions; Enforcement priorities of the regulator; Interaction of administrative and criminal law, limited effectiveness of criminal sanctions in the antitrust field; The effectiveness of leniency program design; Private enforcement challenge.Keywords: collusion, antitrust policy, leniency program, transition economies, Russia, CEE
Procedia PDF Downloads 44721808 Frequency of Gastrointestinal Manifestations in Systemic Sclerosis and Impact of Rituximab Treatment
Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova
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Objectives. Gastrointestinal involvement is one of the most common manifestations of systemic sclerosis (SSc). The aim of our study was to assess the frequency of gastrointestinal manifestations in SSc patients (pts) with interstitial lung disease (ILD) and their changes to rituximab (RTX) therapy. Methods. There were 103 pts with SSc in this study. The mean follow-up period was 12.6±10.7 months. The mean age was 47±12.9 years, females - 87 pts (84%), and the diffuse cutaneous subset of the disease 55 pts (53%). The mean disease duration was 6.2±5.5 years. All pts had ILD and were positive for ANA. 67% of them were positive for anti-topoisomerase-1. All patients received prednisolone at a dose of 11.3±4.5 mg/day, and immunosuppressants at inclusion received 47% of them. Pts received RTX due to the ineffectiveness of previous therapy for ILD. The cumulative mean dose of RTX was 1.7±0.6 grams. 90% of pts received omeprazole at a dose of 20-40 mg/day. Results. At inclusion, dysphagia was observed in 76 pts (74%), early satiety or vomiting in 32 pts (31%), and diarrhea in 20 pts (19%). We didn't observe any changes in gastrointestinal manifestation during RTX therapy. There was a decrease in the number of pts with dysphagia from 76 (74%) to 66 (64%), but it was insignificant. The number of pts with early satiety or vomiting and diarrhea didn't change. Conclusion. In our study, gastrointestinal involvement was observed in most of the pts with SSc-ILD. We didn't find any significant changes in gastrointestinal manifestations during RTX therapy. RXT does not worsen gastrointestinal manifestations in SSc-ILD.Keywords: systemic sclerosis, dysphagia, rituximab, gastrointestinal manifestations
Procedia PDF Downloads 8521807 Corporate Governance Mechanisms, Whistle-Blowing Policy and Earnings Management Practices of Firms in Malaysia
Authors: Mujeeb Saif Mohsen Al-Absy, Ku Nor Izah Ku Ismail, Sitraselvi Chandren
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This study examines whether corporate governance (CG) mechanisms in firms that have a whistle-blowing policy (WHBLP) are more effective in constraining earnings management (EM), than those without. A sample of 288 Malaysian firms for the years 2013 to 2015, amounting to 864 firm-years were grouped into firms with and without WHBLP. Results show that for firms without WHBLP, the board chairman tenure would minimize EM activities. Meanwhile, for firms with WHBLP, board chairman independence, board chairman tenure, audit committee size, audit committee meeting and women in the audit committees are found to be associated with less EM activities. Further, it is found that ownership concentration and Big 4 auditing firms help to reduce EM activities in firms with WHBLP, while not in firms without WHBLP. Hence, functional and effective governance can be achieved by having a WHBLP, which is in line with agency and resource dependent theories. Therefore, this study suggests that firms should have a WHBLP in place, and policymakers should come up with enhanced criteria to strengthen the mechanisms of WHBLP.Keywords: corporate governance, earnings management, whistle-blowing policy, audit committee, board of directors
Procedia PDF Downloads 13721806 The Impact Of Türki̇ye’s Decision-making Mechanism On The Transformation In Türkiye-syria Relations (2002-2024)
Authors: Ibrahim Akkan
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This study analyses the transformation of Türkiye's Syria policy between 2002 and 2024 and the impact of domestic political dynamics in this process. Since the collapse of the Ottoman Empire, Türkiye and Syria have had a tense relationship for a long time due to reasons such as border issues, water sharing, security concerns and the activities of terrorist organizations. However, the process that started with the Adana Agreement in 1998 gained momentum with the Justice and Development Party (Ak Party) coming to power in 2002 and a historical period of rapprochement began between the two countries. During this period, Türkiye adopted the concept of “zero problems with neighbors” in its foreign policy and deepened its strategic partnerships in the region. Turkish-Syrian relations also developed within this framework, the trade volume between the two countries increased and cooperation was strengthened through mutual visits and diplomatic agreements. However, the Arab Spring that started in 2011 was a sharp turning point in Turkish-Syrian relations. The harsh stance of the Bashar Assad administration against the popular uprisings in Syria caused Türkiye to take a stance against Assad and support opposition groups. This process led to the severing of diplomatic ties between the two countries and the gradual deterioration of relations until 2024. Türkiye directly intervened in the civil war in Syria after the Arab Spring and conducted military operations in northern Syria that highlighted security policies. The main purpose of this study is to examine the transformation in Türkiye's Syria policies between 2002 and 2024 and to analyze the role of domestic political dynamics in Türkiye in this transformation. The main research question of the study is how domestic political actors in Türkiye, especially decision-makers (leaders, governments, political parties), shape foreign policy. In this context, the extent to which the leadership of the Ak Party government is decisive in decision-making processes and how the impact of domestic dynamics on foreign policy emerges will be studied. In this study, how both the pressures of the international system and domestic political dynamics shape foreign policy will be analyzed using the theoretical framework of neoclassical realism. How decision-making processes are decisive in foreign policy will be examined through a case study specific to Türkiye-Syria relations. In addition, the strategic preferences of leaders such as Recep Tayyip Erdoğan and Ahmet Davutoğlu in foreign policy and how these preferences overlap with developments in domestic politics will be evaluated using the discourse analysis method. This study aims to make a new contribution to the literature by providing a comprehensive analysis of how domestic dynamics shape foreign policy in Türkiye-Syria relations.Keywords: decision-making mechanisms, foreign policy analysis, neoclassical realism, syria, türkiye
Procedia PDF Downloads 1721805 Effects of Transit Fare Discount Programs on Passenger Volumes and Transferring Behaviors
Authors: Guan-Ying Chen, Han-Tsung Liou, Shou-Ren Hu
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To address traffic congestion problems and encourage the use of public transportation systems in the Taipei metropolitan area, the Taipei City Government and the New Taipei City Government implemented a monthly ticket policy on April 16, 2018. This policy offers unlimited rides on the Taipei MRT, Taipei City Bus, New Taipei City Bus, Danhai Light Rail, and Public Bike (YouBike) on a monthly basis. Additionally, both city governments replaced the smart card discount policy with a new frequent flyer discount program (referred to as the loyal customer program) on February 1, 2020, introducing a differential pricing policy. Specifically, the more frequently the Taipei MRT system is used, the greater the discounts users receive. To analyze the impact of the Taipei public transport monthly ticket policy and the frequent user discount program on the passenger volume of the Taipei MRT system and the transferring behaviors of MRT users, this study conducts a trip-chain analysis using transaction data from Taipei MRT smart cards between September 2017 and December 2020. To achieve these objectives, the study employs four indicators: 1) number of passengers, 2) average number of rides, 3) average trip distance, and 4) instances of multiple consecutive rides. The study applies the t-test and Mann-Kendall trend test to investigate whether the proposed indicators have changed over time due to the implementation of the discount policy. Furthermore, the study examines the travel behaviors of passengers who use monthly tickets. The empirical results of the study indicate that the implementation of the Taipei public transport monthly ticket policy has led to an increase in the average number of passengers and a reduction in the average trip distance. Moreover, there has been a significant increase in instances of multiple consecutive rides, attributable to the unlimited rides offered by the monthly tickets. The impact of the frequent user discount program on changes in MRT passengers is not as pronounced as that of the Taipei public transportation monthly ticket policy. This is partly due to the fact that the frequent user discount program is only applicable to the Taipei MRT system, and the passenger volume was greatly affected by the COVID-19 pandemic. The findings of this research can serve as a reference for Taipei MRT Corporation in formulating its fare strategy and can also provide guidance for the Taipei and New Taipei City Governments in evaluating differential pricing policies for public transportation systems.Keywords: frequent user discount program, mass rapid transit, monthly ticket, smart card
Procedia PDF Downloads 8721804 Identification of Disease Causing DNA Motifs in Human DNA Using Clustering Approach
Authors: G. Tamilpavai, C. Vishnuppriya
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Studying DNA (deoxyribonucleic acid) sequence is useful in biological processes and it is applied in the fields such as diagnostic and forensic research. DNA is the hereditary information in human and almost all other organisms. It is passed to their generations. Earlier stage detection of defective DNA sequence may lead to many developments in the field of Bioinformatics. Nowadays various tedious techniques are used to identify defective DNA. The proposed work is to analyze and identify the cancer-causing DNA motif in a given sequence. Initially the human DNA sequence is separated as k-mers using k-mer separation rule. The separated k-mers are clustered using Self Organizing Map (SOM). Using Levenshtein distance measure, cancer associated DNA motif is identified from the k-mer clusters. Experimental results of this work indicate the presence or absence of cancer causing DNA motif. If the cancer associated DNA motif is found in DNA, it is declared as the cancer disease causing DNA sequence. Otherwise the input human DNA is declared as normal sequence. Finally, elapsed time is calculated for finding the presence of cancer causing DNA motif using clustering formation. It is compared with normal process of finding cancer causing DNA motif. Locating cancer associated motif is easier in cluster formation process than the other one. The proposed work will be an initiative aid for finding genetic disease related research.Keywords: bioinformatics, cancer motif, DNA, k-mers, Levenshtein distance, SOM
Procedia PDF Downloads 19121803 The Effect of SIAH1 on PINK1 Homeostasis in Parkinson Disease
Authors: Fatimah Abd Elghani, Raymonde Szargel, Vered Shani, Hazem Safory, Haya Hamza, Mor Savyon, Ruth Rott, Rina Bandopadhyay, Simone Engelender
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Background: PINK1 is a mitochondrial kinase mutated in some familial cases of Parkinson’s disease. Down regulation of PINK1 results in abnormal mitochondrial morphology and altered membrane potential. Although PINK1 has a predicted mitochondrial import sequence, it’s cellular, and submitochondrial localization remains unclear, in part because it is rapidly degraded. In this work, we investigated the mechanisms involved in PINK1 degradation and how this may affect PINK1 stability and function, with implications for mitochondrial function in PD. In addition, pharmacological inhibition of proteasome activity was shown to lead to PINK1 accumulation, indicating that PINK1 degradation depends on the ubiquitin-proteasome system (UPS). Methods: Using co-immunoprecipitation assays, we identified E3 ubiquitin ligase SIAH1 as a PINK1-interacting protein in HEK293 cells as well as on rat brain tissues. In addition, we determined the effect of SIAH 1, SIAH2 and Parkin on PINK1 steady-state levels by Western blot analysis, and checked their possibility to ubiquitinate and mediate PINK1 degradation through the proteasome carried out in vivo ubiquitination experiments. Results: We have obtained results showing that SIAH-1 interacts with and ubiquitinates PINK1. The ubiquitination promoted by SIAH-1 leads to the proteasomal degradation of PINK1. We confirmed these findings by knocking down SIAH-1 and observing important accumulation of PINK1 in cells. Besides, we found that SIAH-1 decreases PINK1 steady-state levels but not the E3 ligase Parkin. We also investigated the interaction of SIAH-1 with PINK1 disease mutants and its ability to promote their ubiquitination and degradation. Although, no clear difference in the ability of SIAH-1 to promote the degradation of PINK1 disease mutants was observed. It is possible that dysfunction of proteasomal activity in the disease may lead to the accumulation and aggregation of ubiquitinated PINK1 in patients with PINK1 mutations, with possible implications to the pathogenesis of PD. Conclusions: Here, we demonstrated that SIAH-1 ubiquitinates and promotes the degradation of PINK1. In addition, SIAH-1 represents now a target that may help the improvement of mitophagy in PD. Further investigations needed to understand how mitophagy is regulated by PINK1-SIAH-1 axis to provide targets for future therapeutics.Keywords: PD, Parkinson's disease, PINK1, PTEN-induced kinase1, SIAH, seven in absentia homolog, SN, substantia nigra
Procedia PDF Downloads 14621802 Qualitative Risk Assessment of Rift Valley Fever Vaccine Production
Authors: Mohammed E. Mansour, Tamador M. A. Elhassan, Nahid A. Ibrahim, Awatif A. Ahmed, Manal A. Abdalla
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Rift valley fever (RVF) is mosquito-borne disease. RVF is transboundary zoonotic disease. It has socioeconomic and public health importance. This paper describes qualitative risk of the RVF vaccine production. RVF is endemic in the Sudan. It has been reported in Sudan due to abundance of Ades Eqytie. Thus, there is huge effort to control it. Vaccination practices had significant role to control and manage RVF. The risk assessment explains the likelihood of a risk as likely. Thus, insecticides and repellents synergize the effort of the vaccination.Keywords: qualitative analysis, risk assessment, rift valley fever vaccine, quality control
Procedia PDF Downloads 51621801 Between a Rock and a Hard Place: The Impact of Inflation on Global Supply Chains
Authors: Elad Harison
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The paper identifies the complex links between post-COVID-19 inflationary pressures and global supply chains. Throughout the COVID-19 lockdowns and long periods after the termination of social distancing policies, consumers, notably in the U.S., have confronted and still face disruptions in the supply of goods. The study analyzes the monetary policy in the U.S. that led to the significant shift in consumer demand during a limited supply period, hence resulting in shortages and emphasizing inflationary dynamics. We argue that the monetary guidelines applied by the U.S. government further elevated the scope of supply chain disruptions.Keywords: consumer demand, COVID-19, inflation, monetary policy, supply chain
Procedia PDF Downloads 9521800 Why is the Recurrence Rate of Residual or Recurrent Disease Following Endoscopic Mucosal Resection (EMR) of the Oesophageal Dysplasia’s and T1 Tumours Higher in the Greater Midlands Cancer Network?
Authors: Harshadkumar Rajgor, Jeff Butterworth
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Background: Barretts oesophagus increases the risk of developing oesophageal adenocarcinoma. Over the last 40 years, there has been a 6 fold increase in the incidence of oesophageal adenocarcinoma in the western world and the incidence rates are increasing at a greater rate than cancers of the colon, breast and lung. Endoscopic mucosal resection (EMR) is a relatively new technique being used by 2 centres in the greater midlands cancer network. EMR can be used for curative or staging purposes, for high-grade dysplasia’s and T1 tumours of the oesophagus. EMR is also suitable for those who are deemed high risk for oesophagectomy. EMR has a recurrence rate of 21% according to the Wiesbaden data. Method: A retrospective study of prospectively collected data was carried out involving 24 patients who had EMR for curative or staging purposes. Complications of residual or recurrent disease following EMR that required further treatment were investigated. Results: In 54% of cases residual or recurrent disease was suspected. 96% of patients were given clear and concise information regarding their diagnosis of high-grade dysplasia or T1 tumours. All 24 patients consulted the same specialist healthcare team. Conclusion: EMR is a safe and effective treatment for patients who have high-grade dysplasia and T1NO tumours. In 54% of cases residual or recurrent disease was suspected. Initially, only single resections were undertaken. Multiple resections are now being carried out to reduce the risk of recurrence. Complications from EMR remain low in this series and consisted of a single episode of post procedural bleeding.Keywords: endoscopic mucosal resection, oesophageal dysplasia, T1 tumours, cancer network
Procedia PDF Downloads 32021799 Deep Reinforcement Learning Model Using Parameterised Quantum Circuits
Authors: Lokes Parvatha Kumaran S., Sakthi Jay Mahenthar C., Sathyaprakash P., Jayakumar V., Shobanadevi A.
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With the evolution of technology, the need to solve complex computational problems like machine learning and deep learning has shot up. But even the most powerful classical supercomputers find it difficult to execute these tasks. With the recent development of quantum computing, researchers and tech-giants strive for new quantum circuits for machine learning tasks, as present works on Quantum Machine Learning (QML) ensure less memory consumption and reduced model parameters. But it is strenuous to simulate classical deep learning models on existing quantum computing platforms due to the inflexibility of deep quantum circuits. As a consequence, it is essential to design viable quantum algorithms for QML for noisy intermediate-scale quantum (NISQ) devices. The proposed work aims to explore Variational Quantum Circuits (VQC) for Deep Reinforcement Learning by remodeling the experience replay and target network into a representation of VQC. In addition, to reduce the number of model parameters, quantum information encoding schemes are used to achieve better results than the classical neural networks. VQCs are employed to approximate the deep Q-value function for decision-making and policy-selection reinforcement learning with experience replay and the target network.Keywords: quantum computing, quantum machine learning, variational quantum circuit, deep reinforcement learning, quantum information encoding scheme
Procedia PDF Downloads 13721798 A Nonlinear Visco-Hyper Elastic Constitutive Model for Modelling Behavior of Polyurea at Large Deformations
Authors: Shank Kulkarni, Alireza Tabarraei
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The fantastic properties of polyurea such as flexibility, durability, and chemical resistance have brought it a wide range of application in various industries. Effective prediction of the response of polyurea under different loading and environmental conditions necessitates the development of an accurate constitutive model. Similar to most polymers, the behavior of polyurea depends on both strain and strain rate. Therefore, the constitutive model should be able to capture both these effects on the response of polyurea. To achieve this objective, in this paper, a nonlinear hyper-viscoelastic constitutive model is developed by the superposition of a hyperelastic and a viscoelastic model. The proposed constitutive model can capture the behavior of polyurea under compressive loading conditions at various strain rates. Four parameter Ogden model and Mooney Rivlin model are used to modeling the hyperelastic behavior of polyurea. The viscoelastic behavior is modeled using both a three-parameter standard linear solid (SLS) model and a K-BKZ model. Comparison of the modeling results with experiments shows that Odgen and SLS model can more accurately predict the behavior of polyurea. The material parameters of the model are found by curve fitting of the proposed model to the uniaxial compression test data. The proposed model can closely reproduce the stress-strain behavior of polyurea for strain rates up to 6500 /s.Keywords: constitutive modelling, ogden model, polyurea, SLS model, uniaxial compression test
Procedia PDF Downloads 24721797 A Clinical Study of Tracheobronchopathia Osteochondroplastica: Findings from a Large Chinese Cohort
Authors: Ying Zhu, Ning Wu, Hai-Dong Huang, Yu-Chao Dong, Qin-Ying Sun, Wei Zhang, Qin Wang, Qiang Li
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Background and study aims: Tracheobronchopathia osteochondroplastica (TO) is an uncommon disease of the tracheobronchial system that leads to narrowing of the airway lumen from cartilaginous and/or osseous submucosal nodules. The aim of this study is to perform a detailed review of this rare disease in a large cohort of patients with TO proven by fiberoptic bronchoscopy from China. Patients and Methods: Retrospective chart review was performed on 41,600 patients who underwent bronchoscopy in the Department of Respiratory Medicine of Changhai Hospital between January 2005 and December 2012. Cases of TO were identified based on characteristic features during bronchoscopic examination. Results: 22 cases of bronchoscopic TO were identified. Among whom one-half were male and the mean age was 47.45 ±10.91 years old. The most frequent symptoms at presentation were chronic cough (n=14) and increased sputum production (n=10). Radiographic abnormalities were observed in 3/18 patients and findings on computed tomography consistent with TO such as beaded intraluminal calcifications and/or increased luminal thickenings were observed in 18/22 patients. Patients were classified into the following categories based on the severity of bronchoscopic findings: Stage I (n=2), Stage II (n=6) and Stage III(n=14). The result that bronchoscopic improvement was observed in 2 patients administered with inhaled corticosteroids suggested that resolution of this disease is possible. Conclusions: TO is a benign disease with slow progression, which could be roughly divided into 3 stages on the basis of the characteristic endoscopic features and histopathologic findings. Chronic inflammation was thought to be more important than the other existing plausible hypotheses in the course of TO. Inhaled corticosteroids might have some impact on patients at Stage I/II.Keywords: airway obstruction, bronchoscopy, etiology, Tracheobronchopathia osteochondroplastica (TO), treatment
Procedia PDF Downloads 46621796 The Association Between COL4A3 Variant RS55703767 With the Susceptibility to Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus: Results from the Cohort Study
Authors: Zi-Han Li, Zi-Jun Sun, Dong-Yuan Chang, Li Zhu, Min Chen, Ming-Hui Zhao
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Aims: A genome-wide association study (GWAS) reported that patients with the rs55703767 minor allele in collagen type IV α3 chain encoding gene COL4A3 showed protection against diabetic kidney disease (DKD) in type 1 diabetes mellitus (T1DM). However, the role of rs55703767 in type 2 DKD has not been elucidated. The aim of the current study was to investigate the association between COL4A3 variant rs55703767 and DKD risk in Chinese patients with type 2 diabetes mellitus (T2DM). Methods: This nested case-control study was performed on 1311 patients who had T2DM for at least 10 years, including 580 with DKD and 731 without DKD. We detected the genotypes of all patients by TaqMan SNP Genotyping Assay and analyzed the association between COL4A3 variant rs55703767 and DKD risk. Results: Genetic analysis revealed that there was no significant difference between T2DM patients with DKD and those without DKD regarding allele or genotype frequencies of rs55703767, and the effect of this variant was not hyperglycemia specific. Conclusion: Our findings suggested that there was no detectable association between the COL4A3 variant rs55703767 and the susceptibility to DKD in the Chinese T2DM population.Keywords: collagen type IV α3 chain, gene polymorphism, type 2 diabetes, diabetic kidney disease
Procedia PDF Downloads 11621795 Experiences of Patients Living with Peritoneal Dialysis: A Qualitative Study
Authors: Xuzhen Yang, Yan Shan, Yabo Ding, Keke DIao, Yanjun Zhang, Yijia Huang
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Purpose: Our aim is to understand the unique experiences of patients with peritoneal dialysis and how they deal with issues brought on by disease and dialysis. Patients and Methods: Semi-structured interview was designed to collect information, and inpatients with peritoneal dialysis in a university-based tertiary hospital in the central province of China were purposively chosen as interviewees. The content analysis method was used to analyze the data. Results: Nine patients participated in the study, and three themes and eight subthemes were generated. Conclusion: Patients using peritoneal dialysis encounter numerous challenges and problems in the process of disease and dialysis, and they took attempt to cope with them well to adapt to living with peritoneal dialysis.Keywords: peritoneal dialysis, experience, patient, coping strategy
Procedia PDF Downloads 10121794 Design of a Lumbar Interspinous Process Fixation Device for Minimizing Soft Tissue Removal and Operation Time
Authors: Minhyuk Heo, Jihwan Yun, Seonghun Park
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It has been reported that intervertebral fusion surgery, which removes most of the ligaments and muscles of the spine, increases the degenerative disease in adjacent spinal segments. Therefore, it is required to develop a lumbar interspinous process fixation device that minimizes the risks and side effects from the surgery. The objective of the current study is to design an interspinous process fixation device with simple structures in order to minimize soft tissue removal and operation time during intervertebral fusion surgery. For the design concepts of a lumbar fixation device, the principle of the ratchet was first applied on the joining parts of the device in order to shorten the operation time. The coil spring structure was selected for connecting parts between the spinous processes so that a normal range of motion in spinal segments is preserved and degenerative spinal diseases are not developed in the adjacent spinal segments. The stiffness of the spring was determined not to interrupt the motion of a lumbar spine. The designed value of the spring stiffness allows the upper part of the spring to move ~10° which is higher than the range of flexion and extension for normal lumbar spine (6°-8°), when a moment of 10Nm is applied on the upper face of L1. A finite element (FE) model composed of L1 to L5 lumbar spines was generated to verify the mechanical integrity and the dynamic stability of the designed lumbar fixation device and to further optimize the lumbar fixation device. The FE model generated above produced the same pressure value on intervertebral disc and dynamic behavior as the normal intact model reported in the literature. The consistent results from this comparison validates the accuracy in the modeling of the current FE model. Currently, we are trying to generate an abnormal model with defects in one or more components of the normal FE model above. Then, the mechanical integrity and the dynamic stability of the designed lumbar fixation device will be analyzed after being installed in the abnormal model and then the lumbar fixation device will be further optimized.Keywords: lumbar interspinous process fixation device, finite element method, lumbar spine, kinematics
Procedia PDF Downloads 23021793 OmniDrive Model of a Holonomic Mobile Robot
Authors: Hussein Altartouri
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In this paper the kinematic and kinetic models of an omnidirectional holonomic mobile robot is presented. The kinematic and kinetic models form the OmniDrive model. Therefore, a mathematical model for the robot equipped with three- omnidirectional wheels is derived. This model which takes into consideration the kinematics and kinetics of the robot, is developed to state space representation. Relative analysis of the velocities and displacements is used for the kinematics of the robot. Lagrange’s approach is considered in this study for deriving the equation of motion. The drive train and the mechanical assembly only of the Festo Robotino® is considered in this model. Mainly the model is developed for motion control. Furthermore, the model can be used for simulation purposes in different virtual environments not only Robotino® View. Further use of the model is in the mechatronics research fields with the aim of teaching and learning the advanced control theories.Keywords: mobile robot, omni-direction wheel, mathematical model, holonomic mobile robot
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