Search results for: roughness progression
264 A Historical Analysis of The Concept of Equivalence from Different Theoretical Perspectives in Translation Studies
Authors: Amenador Kate Benedicta, Wang Zhiwei
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Since the later parts of the 20th century, the notion of equivalence continues to be a central and critical concept in the development of translation theory. After decades of arguments over word-for-word and free translations methods, scholars attempting to develop more systematic and efficient translation theories began to focus on fundamental translation concepts such as equivalence. Although the concept of equivalence has piqued the interest of many scholars, its definition, scope, and applicability have sparked contentious arguments within the discipline. As a result, several distinct theories and explanations on the concept of equivalence have been put forward over the last half-century. Thus, this study explores and discusses the evolution of the critical concept of equivalence in translation studies through a bibliometric method of investigation of manual and digital books and articles by analyzing different scholars' key contributions and limitations on equivalence from various theoretical perspectives. While analyzing them, emphasis is placed on the innovations that each theory has brought to the comprehension of equivalence. In order to achieve the aim of the study, the article began by discussing the contributions of linguistically motivated theories to the notion of equivalence in translation, followed by functionalist-oriented contributions, before moving on to more recent advancements in translation studies on the concept. Because equivalence is such a broad notion, it is impossible to discuss each researcher in depth. As a result, the most well-known names and their equivalent theories are compared and contrasted in this research. The study emphasizes the developmental progression in our comprehension of the equivalence concept and equivalent effect. It concluded that the various theoretical perspective's contributions to the notion of equivalence rather complement and make up for the limitations of each other. The study also highlighted how troublesome the equivalent concept might become in terms of identifying the nature of translation and how central and unavoidable the concept is in every translation action, despite its limitations. The significance of the study lies in its synthesis of the different contributions and limitations of the various theories offered by scholars on the notion of equivalence, lending literature to both student and scholars in the field, and providing insight on future theoretical developmentKeywords: equivalence, functionalist translation theories, linguistic translation approaches, translation theories, Skopos
Procedia PDF Downloads 113263 Clinical Efficacy of Nivolumab and Ipilimumab Combination Therapy for the Treatment of Advanced Melanoma: A Systematic Review and Meta-Analysis of Clinical Trials
Authors: Zhipeng Yan, Janice Wing-Tung Kwong, Ching-Lung Lai
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Background: Advanced melanoma accounts for the majority of skin cancer death due to its poor prognosis. Nivolumab and ipilimumab are monoclonal antibodies targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocytes antigen 4 (CTLA-4). Nivolumab and ipilimumab combination therapy has been proven to be effective for advanced melanoma. This systematic review and meta-analysis are to evaluate its clinical efficacy and adverse events. Method: A systematic search was done on databases (Pubmed, Embase, Medline, Cochrane) on 21 June 2020. Search keywords were nivolumab, ipilimumab, melanoma, and randomised controlled trials. Clinical trials fulfilling the inclusion criteria were selected to evaluate the efficacy of combination therapy in terms of prolongation of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The odd ratios and distributions of grade 3 or above adverse events were documented. Subgroup analysis was performed based on PD-L1 expression-status and BRAF-mutation status. Results: Compared with nivolumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR in combination therapy were 0.64 (95% CI, 0.48-0.85; p=0.002), 0.84 (95% CI, 0.74-0.95; p=0.007) and 1.76 (95% CI, 1.51-2.06; p < 0.001), respectively. Compared with ipilimumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR were 0.46 (95% CI, 0.37-0.57; p < 0.001), 0.54 (95% CI, 0.48-0.61; p < 0.001) and 6.18 (95% CI, 5.19-7.36; p < 0.001), respectively. In combination therapy, the odds ratios of grade 3 or above adverse events were 4.71 (95% CI, 3.57-6.22; p < 0.001) compared with nivolumab monotherapy, and 3.44 (95% CI, 2.49-4.74; p < 0.001) compared with ipilimumab monotherapy, respectively. High PD-L1 expression level and BRAF mutation were associated with better clinical outcomes in patients receiving combination therapy. Conclusion: Combination therapy is effective for the treatment of advanced melanoma. Adverse events were common but manageable. Better clinical outcomes were observed in patients with high PD-L1 expression levels and positive BRAF-mutation.Keywords: nivolumab, ipilimumab, advanced melanoma, systematic review, meta-analysis
Procedia PDF Downloads 136262 Modelling Tyre Rubber Materials for High Frequency FE Analysis
Authors: Bharath Anantharamaiah, Tomas Bouda, Elke Deckers, Stijn Jonckheere, Wim Desmet, Juan J. Garcia
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Automotive tyres are gaining importance recently in terms of their noise emission, not only with respect to reduction in noise, but also their perception and detection. Tyres exhibit a mechanical noise generation mechanism up to 1 kHz. However, owing to the fact that tyre is a composite of several materials, it has been difficult to model it using finite elements to predict noise at high frequencies. The currently available FE models have a reliability of about 500 Hz, the limit which, however, is not enough to perceive the roughness or sharpness of noise from tyre. These noise components are important in order to alert pedestrians on the street about passing by slow, especially electric vehicles. In order to model tyre noise behaviour up to 1 kHz, its dynamic behaviour must be accurately developed up to a 1 kHz limit using finite elements. Materials play a vital role in modelling the dynamic tyre behaviour precisely. Since tyre is a composition of several components, their precise definition in finite element simulations is necessary. However, during the tyre manufacturing process, these components are subjected to various pressures and temperatures, due to which these properties could change. Hence, material definitions are better described based on the tyre responses. In this work, the hyperelasticity of tyre component rubbers is calibrated, using the design of experiments technique from the tyre characteristic responses that are measured on a stiffness measurement machine. The viscoelasticity of rubbers are defined by the Prony series for rubbers, which are determined from the loss factor relationship between the loss and storage moduli, assuming that the rubbers are excited within the linear viscoelasticity ranges. These values of loss factor are measured and theoretically expressed as a function of rubber shore hardness or hyperelasticities. From the results of the work, there exists a good correlation between test and simulation vibrational transfer function up to 1 kHz. The model also allows flexibility, i.e., the frequency limit can also be extended, if required, by calibrating the Prony parameters of rubbers corresponding to the frequency of interest. As future work, these tyre models are used for noise generation at high frequencies and thus for tyre noise perception.Keywords: tyre dynamics, rubber materials, prony series, hyperelasticity
Procedia PDF Downloads 193261 Patient-Reported Adverse Drug Reactions, Medication Adherence and Clinical Outcomes among major depression disorder Patients in Ethiopia: A Prospective Hospital Based Study.
Authors: Tadesse Melaku Abegaz
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Background: there was paucity of data on the self-reported adverse drug reactions (ADRs), level of adherence and clinical outcomes with antidepressants among major depressive disorder (MDD) patients in Ethiopia. Hence, the present study sought to determine the level of adherence for and clinical outcome with antidepressants and the magnitude of ADRs. Methods: A prospective cross-sectional study was employed on MDD patients from September 2016 to January 2017 at Gondar university hospital psychiatry clinic. All patients who were available during the study period were included under the study population. The Naranjo adverse drug reaction probability scale was employed to assess the adverse drug reaction. The rate of medication adherence was determined using morisky medication adherence measurement scale eight. Clinical Outcome of patients was measured by using patient health questionnaire. Multivariable logistic carried out to determine factors for adherence and patient outcome. Results: two hundred seventy patients were participated in the study. More than half of the respondents were males 122(56.2%). The mean age of the participants was 30.94 ± 8.853. More than one-half of the subjects had low adherence to their medications 124(57.1%). About 186(85.7%) of patients encountered ADR. The most common ADR was weight gain 29(13.2). Around 198(92.2%) ADRs were probable and 19(8.8%) were possible. Patients with long standing MDD had high risk of non-adherence COR: 2.458[4.413-4.227], AOR: 2.424[1.185-4.961]. More than one-half 125(57.6) of respondents showed improved outcome. Optimal level of medication adherence was found to be associated with reduced risk of progression of the diseases COR: 0.37[0.110-5.379] and AOR: 0.432[0.201-0.909]. Conclusion: Patient reported adverse drug reactions were more prevalent in major depressive disorder patients. Adherence to medications was very poor in the setup. However, the clinical outcome was relatively higher. Long standing depression was associated with non-adherence. In addition, clinical outcome of patients were affected by non-adherence. Therefore, adherence enhancing interventions should be provided to improve medication adherence and patient outcome.Keywords: adverse drug reactions, clinical outcomes, Ethiopia, prospective study, medication adherence
Procedia PDF Downloads 247260 Application of Host Factors as Biomarker in Early Diagnosis of Pulmonary Tuberculosis
Authors: Ambrish Tiwari, Sudhasini Panda, Archana Singh, Kalpana Luthra, S. K. Sharma
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Introduction: On the basis of available literature we know that various host factors play a role in outcome of Tuberculosis (TB) infection by modulating innate immunity. One such factor is Inducible Nitric Oxide Synthase enzyme (iNOS) which help in the production of Nitric Oxide (NO), an antimicrobial agent. Expression of iNOS is in control of various host factors in which Vitamin D along with its nuclear receptor Vitamin D receptor (VDR) is one of them. Vitamin D along with its receptor also produces cathelicidin (antimicrobicidal agent). With this background, we attempted to investigate the levels of Vitamin D and NO along with their associated molecules in tuberculosis patients and household contacts as compared to healthy controls and assess the implication of these findings in susceptibility to tuberculosis (TB). Study subjects and methods: 100 active TB patients, 75 household contacts, and 70 healthy controls were taken. VDR and iNOS mRNA levels were studied using real-time PCR. Serum VDR, cathelicidin, iNOS levels were measured using ELISA. Serum Vitamin D levels were measured in serum samples using chemiluminescence based immunoassay. NO was measured using colorimetry based kit. Results: VDR and iNOS mRNA levels were found to be lower in active TB group compared to household contacts and healthy controls (P=0.0001 and 0.005 respectively). The serum levels of Vitamin D were also found to be lower in active TB group as compared to healthy controls (P =0.001). Levels of cathelicidin and NO was higher in patient group as compared to other groups (p=0.01 and 0.5 respectively). However, the expression of VDR and iNOS and levels of vitamin D was significantly (P < 0.05) higher in household contacts compared to both active TB and healthy control groups. Inference: Higher levels of Vitamin D along with VDR and iNOS expression in household contacts as compared to patients suggest that vitamin D might have a protective role against TB which prevents activation of the disease. From our data, we can conclude that decreased vitamin D levels could be implicated in disease progression and we can use cathelicidin and NO as a biomarker for early diagnosis of pulmonary tuberculosis.Keywords: vitamin D, VDR, iNOS, tuberculosis
Procedia PDF Downloads 303259 Breast Cancer in Very Young (Less Than 25 Yeras) Women: An Institutional Analysis from Developing Country
Authors: Ajay Gogia, Svs Deo, Dn Sharma, Atul Batra, Ashutash Mishra
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Background and Aims: Breast cancer in women aged less than 25 years (defined as very young breast cancer, VYBC) is rare and accounts for 0.25% of all breast cancer in the West. There is no data available on VYBC from developing countries. The aim of this study was to analyze the clinical, pathological, and prognostic factors and outcomes in VYBC. Methods: This retrospective analysis was performed on 80 patients aged 25 years or less (screened 8000 files of female BC) who were registered at All India Institute of Medical Sciences (AIIMS), New Delhi, India, over a 15-year period between 2011 and 2023. Results: The median age was 21.5 years (range 16-25). A positive family history (siblings and parents) was elicited in 30% of cases, and breast cancer gene (BRCA1/2) mutation was found in 33% of cases patients. Ten patients (12.5%) patients have pregnancy-associated breast cancer (BC detected during pregnancy or 1 year after postpartum period). The TNM stage distribution was Stage I was 0, stage II -30%, stage III –60% and Stage IV -10 %patients. Seventy percent of tumors were high grade, and 90% had pathological node-positive disease. Estrogen, Progesterone, and human epidermal growth factor receptor 2 (HER2)/neu positivity were 25%,25% and 35%, respectively. Triple-negative breast cancer constituted 40% of patients. With a median follow-up of 42 months, 3 years, relapse-free survival (nonmetastatic disease), progression-free survival (metastatic disease) and overall survival were 30%, 15% and 50%, respectively. Conclusions: Very young women constituted 1% of all breast cancer cases. Advanced disease at presentation and high-risk pathological features result in poor outcomes. One-third of VYBCs are associated with BRCA mutation, which requires genetic counseling and risk reduction surgery if required. Due to the aggressive behavior of BC in this age group, need early diagnosis and prompt treatmentKeywords: very young, breast cancer, outcome, developing country, India
Procedia PDF Downloads 28258 Study the Difference Between the Mohr-Coulomb and the Barton-Bandis Joint Constitutive Models: A Case Study from the Iron Open Pit Mine, Canada
Authors: Abbas Kamalibandpey, Alain Beland, Joseph Mukendi Kabuya
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Since a rock mass is a discontinuum medium, its behaviour is governed by discontinuities such as faults, joint sets, lithologic contact, and bedding planes. Thus, rock slope stability analysis in jointed rock masses is largely dependent upon discontinuities constitutive equations. This paper studies the difference between the Mohr-Coulomb (MC) and the Barton-Bandis (BB) joint constitutive numerical models for lithological contacts and joint sets. For the rock in these models, generalized Hoek-Brown criteria have been considered. The joint roughness coefficient (JRC) and the joint wall compressive strength (JCS) are vital parameters in the BB model. The numerical models are applied to the rock slope stability analysis in the Mont-Wright (MW) mine. The Mont-Wright mine is owned and operated by ArcelorMittal Mining Canada (AMMC), one of the largest iron-ore open pit operations in Canada. In this regard, one of the high walls of the mine has been selected to undergo slope stability analysis with RS2D software, finite element method. Three piezometers have been installed in this zone to record pore water pressure and it is monitored by radar. In this zone, the AMP-IF and QRMS-IF contacts and very persistent and altered joint sets in IF control the rock slope behaviour. The height of the slope is more than 250 m and consists of different lithologies such as AMP, IF, GN, QRMS, and QR. To apply the B-B model, the joint sets and geological contacts have been scanned by Maptek, and their JRC has been calculated by different methods. The numerical studies reveal that the JRC of geological contacts, AMP-IF and QRMS-IF, and joint sets in IF had a significant influence on the safety factor. After evaluating the results of rock slope stability analysis and the radar data, the B-B constitutive equation for discontinuities has shown acceptable results to the real condition in the mine. It should be noted that the difference in safety factors in MC and BB joint constitutive models in some cases is more than 30%.Keywords: barton-Bandis criterion, Hoek-brown and Mohr-Coulomb criteria, open pit, slope stability
Procedia PDF Downloads 105257 Rate of Force Development, Net Impulse and Modified Reactive Strength as Predictors of Volleyball Spike Jump Height among Young Elite Players
Authors: Javad Sarvestan, Zdenek Svoboda
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Force-time (F-T) curvature characteristics are globally referenced as the main indicators of athletic jump performance. Nevertheless, to the best of authors’ knowledge, no investigation tried to deeply study the relationship between F-T curve variables and real-game jump performance among elite volleyball players. To this end, this study was designated to investigate the association between F-T curve variables, including movement timings, force, velocity, power, rate of force development (RFD), modified reactive strength index (RSImod), and net impulse with spike jump height during real-game circumstances. Twelve young elite volleyball players performed 3 countermovement jump (CMJ) and 3 spike jump in real-game circumstances with 1-minute rest intervals to prevent fatigue. Shapiro-Wilk statistical test illustrated the normality of data distribution, and Pearson’s product correlation test portrayed a significant correlation between CMJ height and peak RFD (0.85), average RFD (r=0.81), RSImod (r=0.88) and concentric net impulse (r=0.98), and also significant correlation between spike jump height and peak RFD (0.73), average RFD (r=0.80), RSImod (r=0.62) and concentric net impulse (r=0.71). Multiple regression analysis also reported that these factors have a strong contribution in predicting of CMJ (98%) and spike jump (77%) heights. Outcomes of this study confirm that the RFD, concentric net impulse, and RSImod values could precisely monitor and track the volleyball attackers’ explosive strength, muscular stretch-shortening cycle function efficiency, and ultimate spike jump height. To this effect, volleyball coaches and trainers are advised to have an in-depth focus on their athletes’ progression or the impacts of strength trainings by observing and chasing the F-T curve variables such as RFD, net impulse, and RSImod.Keywords: net impulse, reactive strength index, rate of force development, stretch-shortening cycle
Procedia PDF Downloads 135256 Management of Autoimmune Diseases with Ayurveda
Authors: Simmi Chopra
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In the last few years, there has been a surge of Autoimmune diseases that have become more like an epidemic all over the world. The reasons vary from stress, insufficient sleep, smoking, genetics, environmental pollution, adulterated foods, and a diet full of “the deadly white,” which is white sugar and white flour. Most of the people diagnosed with these diseases are given steroids, opioids, supplements, or elimination diets to manage their lives, but most of them continue suffering to varying degrees. On the other hand, Ayurveda can help manage autoimmune problems effectively. Ayurveda is a 5000 years old holistic medical system from India that has an individualistic approach where health problems are looked at from the lens of balancing body and mind and by targeting the root cause of the problem. A combination of diet and lifestyle according to Ayurvedic principles, Ayurvedic herbal formulations and Ayurvedic therapies can help in the management of autoimmune and other chronic diseases. Panchkarma, which is an intense six weeks detox method, helps balance our body and mind, and has been very effective in managing autoimmune problems. The paper will introduce the basic concepts of Ayurveda and describe the terminologies- doshas, agni and ama. The paper will discuss the importance of diet and lifestyle according to the individual’s imbalance in the three functional parameters - doshas, which govern every aspect of our body and mind, our cells and tissues. The significance of agni, which can be correlated to digestive strength and ama, which can be correlated to toxins that are formed in our body leading to health problems, will be outlined. The Ayurvedic pathophysiology of autoimmune diseases will be discussed with emphasis on Rheumatoid arthritis, Multiple sclerosis and Psoriasis. Ayurvedic management will be discussed for these autoimmune conditions. As Ayurveda is an individualistic system, one protocol will not work for everyone. Therefore, case studies with Ayurvedic protocols for the above autoimmune disease will be presented. Conclusion: Ayurveda can help in managing as well as arresting the progression of autoimmune problems. Ayurveda is an ancient medical system, is much more needed today than ever. It is a tried and tested holistic system which has been practiced for the past many generations in India.Keywords: ayurveda, autoimmune, diseases, nutrition
Procedia PDF Downloads 66255 The Psychosis Prodrome: Biomarkers of the Glutamatergic System and Their Potential Role in Prediction and Treatment
Authors: Peter David Reiss
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The concept of the psychosis prodrome has allowed for the identification of adolescent and young adult patients who have a significantly elevated risk of developing schizophrenia spectrum disorders. A number of different interventions have been tested in order to prevent or delay progression of symptoms. To date, there has been no consistent meta-analytical evidence to support efficacy of antipsychotic treatment for patients in the prodromal state, and their use remains therefore inconclusive. Although antipsychotics may manage symptoms transiently, they have not been found to prevent or delay onset of psychotic disorders. Furthermore, pharmacological intervention in high-risk individuals remains controversial, because of the antipsychotic side effect profile in a population in which only about 20 to 35 percent will eventually convert to psychosis over a two-year period, with even after two years conversion rates not exceeding 30 to 40 percent. This general estimate is additionally problematic, in that it ignores the fact that there is significant variation in individual risk among clinical high-risk cases. The current lack of reliable tests for at-risk patients makes it difficult to justify individual treatment decisions. Preventive treatment should ideally be dictated by an individual’s risk while minimizing potentially harmful medication exposure. This requires more accurate predictive assessments by using valid and accessible prognostic markers. The following will compare prediction and risk modification potential of behavioral biomarkers such as disturbances of basic sense of self and emotion awareness, neurocognitive biomarkers such as attention, working and declarative memory, and neurophysiological biomarkers such as glutamatergic abnormalities and NMDA receptor dysfunction. Identification of robust biomarkers could therefore not only provide more reliable means of psychosis prediction, but also help test and develop new clinical interventions targeted at the prodromal state.Keywords: at-risk mental state, biomarkers, glutamatergic system, NMDA receptor, psychosis prodrome, schizophrenia
Procedia PDF Downloads 195254 Endoscopic Pituitary Surgery: Learning Curve and Nasal Quality of Life
Authors: Martin Dupuy, Solange Grunenwald, Pierre-Louis Colombo, Laurence Mahieu, Pomone Richard, Philippe Bartoli
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Endonasal endoscopic trans-sphenoidal surgery for pituitary tumours has become a mainstay of treatment over the last two decades. Although it is generally accepted that there is no significant difference between endoscopic versus microscopic approach for surgical outcomes (endocrine and ophthalmologic status), nasal morbidity seems to the benefit of endoscopic procedures. Minimally invasive endoscopic surgery needs an operative learning curve to achieve surgeon’s efficiency. This learning curve is now well known for surgical outcomes and complications rate, however, few data are available for nasal morbidity. The aim of our series is to document operative experience and nasal quality of life after (NQOL) endoscopic trans-sphenoidal surgery. The prospective pituitary surgical cohort consisted of 525 consecutives patients referred to our Skull Base Diseases Department. Endoscopic procedures were performed by a single neurosurgeon using an uninostril approach. NQOL was evaluated using the Sino-Nasal Test (SNOT-22), the Anterior Base Nasal Inventory (ASBNI) and the Skull Base Inventory Score (SBIS). Data were collected before surgery during hospital stay and 3 months after the surgery. The seventy first patients were compared to the latest 70 patients. There was no significant difference between comparison score before versus after surgery for SNOT-22, ASBNI and SBIS during the single surgeon’s learning curve. Our series demonstrates that in our institution there is no statistically significant learning curve for NQOL after uninostril endoscopic pituitary surgery. A careful progression through sinonasal structures with very limited mucosal incision is associated with minimal morbidity and preserves nasal function. Conservative and minimal invasive approach could be achieved early during learning curve.Keywords: pituitary surgery, quality of life, minimal invasive surgery, learning curve, pituitary tumours, skull base surgery, endoscopic surgery
Procedia PDF Downloads 124253 Seismic Active Earth Pressure on Retaining Walls with Reinforced Backfill
Authors: Jagdish Prasad Sahoo
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The increase in active earth pressure during the event of an earthquake results sliding, overturning and tilting of earth retaining structures. In order to improve upon the stability of structures, the soil mass is often reinforced with various types of reinforcements such as metal strips, geotextiles, and geogrids etc. The stresses generated in the soil mass are transferred to the reinforcements through the interface friction between the earth and the reinforcement, which in turn reduces the lateral earth pressure on the retaining walls. Hence, the evaluation of earth pressure in the presence of seismic forces with an inclusion of reinforcements is important for the design retaining walls in the seismically active zones. In the present analysis, the effect of reinforcing horizontal layers of reinforcements in the form of sheets (Geotextiles and Geogrids) in sand used as backfill, on reducing the active earth pressure due to earthquake body forces has been studied. For carrying out the analysis, pseudo-static approach has been adopted by employing upper bound theorem of limit analysis in combination with finite elements and linear optimization. The computations have been performed with and out reinforcements for different internal friction angle of sand varying from 30 ° to 45 °. The effectiveness of the reinforcement in reducing the active earth pressure on the retaining walls is examined in terms of active earth pressure coefficient for presenting the solutions in a non-dimensional form. The active earth pressure coefficient is expressed as functions of internal friction angle of sand, interface friction angle between sand and reinforcement, soil-wall interface roughness conditions, and coefficient of horizontal seismic acceleration. It has been found that (i) there always exists a certain optimum depth of the reinforcement layers corresponding to which the value of active earth pressure coefficient becomes always the minimum, and (ii) the active earth pressure coefficient decreases significantly with an increase in length of reinforcements only up to a certain length beyond which a further increase in length hardly causes any reduction in the values active earth pressure. The optimum depth of the reinforcement layers and the required length of reinforcements corresponding to the optimum depth of reinforcements have been established. The numerical results developed in this analysis are expected to be useful for purpose of design of retaining walls.Keywords: active, finite elements, limit analysis, presudo-static, reinforcement
Procedia PDF Downloads 365252 Effect of Madecassoside on the Antioxidant Status of Streptozotocin-Nicotinamide Induced Diabetes in Sprague-Dawley Rats
Authors: C. Mayuren, C. K. Paul Wang, K. Purushotham, C. Dinesh Kumar
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Diabetes Mellitus (DM) is one of the most common non-communicable diseases globally. Although significant advances have led to better understanding of the condition and the development of effective therapies and preventive strategies, the pathway to cure remains elusive and DM prevails as a serious medical challenge in the 21st century. Oxidative stress has been suggested to contribute to the progression and pathophysiological conditions of diabetes. Madecassoside (MA) a major pentacyclic triterpenoid, has been demonstrated to possess various biological activities. However, no attempt has been made to study the antioxidant activity in diabetic rats. Therefore, the present study is aimed to evaluate the antioxidant effect of MA on streptozotocin-nicotinamide induced type-2 diabetes in Sprague-Dawley rats. The study protocol was approved by the institutional ethical committee prior to the conduct of research. Adult male Sprague-Dawley rats weighing 250-300 g were used in the study. The animals were rendered diabetic with a single intraperitoneal dose of streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg). The diabetic animals after a stabilisation period of 14 days received various treatments (Madecassoside 50 mg/kg; Glimepiride 2.5 mg/kg) suspended in 0.5% carboxymethyl cellulose orally, for a period of 28 days. The animals fasted overnight after the last treatment were sacrificed and the pancreas, liver and kidneys were isolated. The weighted quantity of the samples of various treatments were homogenised in ice-cold condition and were subjected to lipid peroxidation, catalase and superoxide dismutase assay. The data’s obtained were subjected to statistical analysis. Diabetic rats showed significant increase in lipid peroxidation and decrease in enzymatic antioxidant levels. All the treated groups had significantly higher SOD, CAT and reduced LPO activity in the pancreas, liver and kidney. Results suggest madecassoside to have potential antioxidant effect against the diabetic model. However further investigations are necessary to study the mechanism at the cellular level.Keywords: antioxidant, diabetes, madecassoside, nicotinamide, streptozotocin
Procedia PDF Downloads 379251 Environmental Performance Improvement of Additive Manufacturing Processes with Part Quality Point of View
Authors: Mazyar Yosofi, Olivier Kerbrat, Pascal Mognol
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Life cycle assessment of additive manufacturing processes has evolved significantly since these past years. A lot of existing studies mainly focused on energy consumption. Nowadays, new methodologies of life cycle inventory acquisition came through the literature and help manufacturers to take into account all the input and output flows during the manufacturing step of the life cycle of products. Indeed, the environmental analysis of the phenomena that occur during the manufacturing step of additive manufacturing processes is going to be well known. Now it becomes possible to count and measure accurately all the inventory data during the manufacturing step. Optimization of the environmental performances of processes can now be considered. Environmental performance improvement can be made by varying process parameters. However, a lot of these parameters (such as manufacturing speed, the power of the energy source, quantity of support materials) affect directly the mechanical properties, surface finish and the dimensional accuracy of a functional part. This study aims to improve the environmental performance of an additive manufacturing process without deterioration of the part quality. For that purpose, the authors have developed a generic method that has been applied on multiple parts made by additive manufacturing processes. First, a complete analysis of the process parameters is made in order to identify which parameters affect only the environmental performances of the process. Then, multiple parts are manufactured by varying the identified parameters. The aim of the second step is to find the optimum value of the parameters that decrease significantly the environmental impact of the process and keep the part quality as desired. Finally, a comparison between the part made by initials parameters and changed parameters is made. In this study, the major finding claims by authors is to reduce the environmental impact of an additive manufacturing process while respecting the three quality criterion of parts, mechanical properties, dimensional accuracy and surface roughness. Now that additive manufacturing processes can be seen as mature from a technical point of view, environmental improvement of these processes can be considered while respecting the part properties. The first part of this study presents the methodology applied to multiple academic parts. Then, the validity of the methodology is demonstrated on functional parts.Keywords: additive manufacturing, environmental impact, environmental improvement, mechanical properties
Procedia PDF Downloads 288250 Cyclic Etching Process Using Inductively Coupled Plasma for Polycrystalline Diamond on AlGaN/GaN Heterostructure
Authors: Haolun Sun, Ping Wang, Mei Wu, Meng Zhang, Bin Hou, Ling Yang, Xiaohua Ma, Yue Hao
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Gallium nitride (GaN) is an attractive material for next-generation power devices. It is noted that the performance of GaN-based high electron mobility transistors (HEMTs) is always limited by the self-heating effect. In response to the problem, integrating devices with polycrystalline diamond (PCD) has been demonstrated to be an efficient way to alleviate the self-heating issue of the GaN-based HEMTs. Among all the heat-spreading schemes, using PCD to cap the epitaxial layer before the HEMTs process is one of the most effective schemes. Now, the mainstream method of fabricating the PCD-capped HEMTs is to deposit the diamond heat-spreading layer on the AlGaN surface, which is covered by a thin nucleation dielectric/passivation layer. To achieve the pattern etching of the diamond heat spreader and device preparation, we selected SiN as the hard mask for diamond etching, which was deposited by plasma-enhanced chemical vapor deposition (PECVD). The conventional diamond etching method first uses F-based etching to remove the SiN from the special window region, followed by using O₂/Ar plasma to etch the diamond. However, the results of the scanning electron microscope (SEM) and focused ion beam microscopy (FIB) show that there are lots of diamond pillars on the etched diamond surface. Through our study, we found that it was caused by the high roughness of the diamond surface and the existence of the overlap between the diamond grains, which makes the etching of the SiN hard mask insufficient and leaves micro-masks on the diamond surface. Thus, a cyclic etching method was proposed to solve the problem of the residual SiN, which was left in the F-based etching. We used F-based etching during the first step to remove the SiN hard mask in the specific region; then, the O₂/Ar plasma was introduced to etch the diamond in the corresponding region. These two etching steps were set as one cycle. After the first cycle, we further used cyclic etching to clear the pillars, in which the F-based etching was used to remove the residual SiN, and then the O₂/Ar plasma was used to etch the diamond. Whether to take the next cyclic etching depends on whether there are still SiN micro-masks left. By using this method, we eventually achieved the self-terminated etching of the diamond and the smooth surface after the etching. These results demonstrate that the cyclic etching method can be successfully applied to the integrated preparation of polycrystalline diamond thin films and GaN HEMTs.Keywords: AlGaN/GaN heterojunction, O₂/Ar plasma, cyclic etching, polycrystalline diamond
Procedia PDF Downloads 134249 Patients' Quality of Life and Caregivers' Burden of Parkinson's Disease
Authors: Kingston Rajiah, Mari Kannan Maharajan, Si Jen Yeen, Sara Lew
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Parkinson’s disease (PD) is a progressive neurodegenerative disorder with evolving layers of complexity. Both motor and non-motor symptoms of PD may affect patients’ quality of life (QoL). Life expectancy for an individual with Parkinson’s disease depends on the level of care the individual has access to, can have a direct impact on length of life. Therefore, improvement of the QoL is a significant part of therapeutic plans. Patients with PD, especially those who are in advanced stages, are in great need of assistance, mostly from their family members or caregivers in terms of medical, emotional, and social support. The role of a caregiver becomes increasingly important with the progression of PD, the severity of motor impairment and increasing age of the patient. The nature and symptoms associated with PD can place significant stresses on the caregivers’ burden. As the prevalence of PD is estimated to more than double by 2030, it is important to recognize and alleviate the burden experienced by caregivers. This study focused on the impact of the clinical features on the QoL of PD patients, and of their caregivers. This study included PD patients along with their caregivers and was undertaken at the Malaysian Parkinson's Disease Association from June 2016 to November 2016. Clinical features of PD patients were assessed using the Movement Disorder Society revised Unified Parkinson Disease Rating Scale (MDS-UPDRS); the Hoehn and Yahr Staging of Parkinson's Disease were used to assess the severity and Parkinson's disease activities of daily living scale were used to assess the disability of Parkinson’s disease patients. QoL of PD patients was measured using the Parkinson's Disease Questionnaire-39 (PDQ-39). The revised version of the Zarit Burden Interview assessed caregiver burden. At least one of the clinical features affected PD patients’ QoL, and at least one of the QoL domains affected the caregivers’ burden. Clinical features ‘Saliva and Drooling’, and ‘Dyskinesia’ explained 29% of variance in QoL of PD patients. The QoL domains ‘stigma’, along with ‘emotional wellbeing’ explained 48.6% of variance in caregivers’ burden. Clinical features such as saliva, drooling and dyskinesia affected the QoL of PD patients. The PD patients’ QoL domains such as ‘stigma’ and ‘emotional well-being’ influenced their caregivers’ burden.Keywords: carers, quality of life, clinical features, Malaysia
Procedia PDF Downloads 244248 Clinical and Structural Differences in Knee Osteoarthritis with/without Synovial Hypertrophy
Authors: Gi-Young Park, Dong Rak Kwon, Sung Cheol Cho
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Objective: The synovium is known to be involved in many pathological characteristic processes. Also, synovitis is common in advanced osteoarthritis. We aimed to evaluate the clinical, radiographic, and ultrasound findings in patients with knee osteoarthritis and to compare the clinical and imaging findings between knee osteoarthritis with and without synovial hypertrophy confirmed by ultrasound. Methods: One hundred knees (54 left, 46 right) in 95 patients (64 women, 31 men; mean age, 65.9 years; range, 43-85 years) with knee osteoarthritis were recruited. The Visual Analogue Scale (VAS) was used to assess the intensity of knee pain. The severity of knee osteoarthritis was classified according to Kellgren and Lawrence's (K-L) grade on a radiograph. Ultrasound examination was performed by a physiatrist who had 24 years of experience in musculoskeletal ultrasound. Ultrasound findings, including the thickness of joint effusion in the suprapatellar pouch, synovial hypertrophy, infrapatellar tendinosis, meniscal tear or extrusion, and Baker cyst, were measured and detected. The thickness of knee joint effusion was measured at the maximal anterior-posterior diameter of fluid collection in the suprapatellar pouch. Synovial hypertrophy was identified as the soft tissue of variable echogenicity, which is poorly compressible and nondisplaceable by compression of an ultrasound transducer. The knees were divided into two groups according to the presence of synovial hypertrophy. The differences in clinical and imaging findings between the two groups were evaluated by independent t-test and chi-square test. Results: Synovial hypertrophy was detected in 48 knees of 100 knees on ultrasound. There were no significant differences in demographic parameters and VAS score except in sex between the two groups (P<0.05). Medial meniscal extrusion and tear were significantly more frequent in knees with synovial hypertrophy than those in knees without synovial hypertrophy. K-L grade and joint effusion thickness were greater in patients with synovial hypertrophy than those in patients without synovial hypertrophy (P<0.05). Conclusion: Synovial hypertrophy in knee osteoarthritis was associated with greater suprapatellar joint effusion and higher K-L grade and maybe a characteristic ultrasound feature of late knee osteoarthritis. These results suggest that synovial hypertrophy on ultrasound can be regarded as a predictor of rapid progression in patients with knee osteoarthritis.Keywords: knee osteoarthritis, synovial hypertrophy, ultrasound, K-L grade
Procedia PDF Downloads 75247 Tribological Behavior Of 17-4PH Steel Produced Via Binder Jetting And Low Energy High Current Pulsed Electron Beam Surface Treated
Authors: Lorenza Fabiocchi, Marco Mariani, Andrea Lucchini Huspek, Matteo Pozzi, Massimiliano Bestetti, Serena Graziosi, Nora Lecis
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Additive manufacturing of stainless steels is rapidly developing thanks to the ability to achieve complex designs effortlessly. Stainless steel 17-4PH is valued for its high strength and corrosion resistance, however intricate geometries are challenging to obtain due to rapid tool wear when machined. Binder jetting additive manufacturing was used to produce 17–4PH samples and pulsed electron beam surface treatment was investigated to enhance surface properties of components. The aim is to improve the tribological performance compared to the as-sintered condition and the H900 aging process, which optimizes hardness and wear resistance. Printed samples were sintered in a reducing atmosphere and superficially treated with an electron beam by varying the voltage (20 - 25 - 30 kV) and pulse count (20 – 40 pulses). Then, the surface was characterized from a microstructural and mechanical standpoint. Scratch tests were performed, and a reciprocating linear pin-on-disk wear test was conducted at 2 N and 10 Hz. Results showed that the voltage affects the roughness and thickness of the treated layer, whilst the number of pulses influences the hardening of the microstructure and consequently the wear resistance. Treated samples exhibited lower coefficients of friction compared to as-printed surfaces, though the values approached those of aged samples after the abrasion of the melted layer, indicating a deeper heat-affected zone formation. Different amounts of residual stress in the heat effected zone were individuated through the scratch tests. Still, the friction remained lower than that of as-printed specimens. This study demonstrates that optimizing electron beam parameters is vital for achieving surface performance comparable to bulk aging treatments, with significant implications for long-term wear resistance.Keywords: low energy high current pulsed electron beam, tribology, binder jetting 3D printing, 17-4PH stainless steel
Procedia PDF Downloads 9246 Liver Transplantation after Downstaging with Electrochemotherapy of Large Hepatocellular Carcinoma and Portal Vein Tumor Thrombosis: A Case Report
Authors: Luciano Tarantino, Emanuele Balzano, Aurelio Nasto
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S.R. 53 years. January 2009: HCV-related cirrhosis, Child-Pugh A5 class, EGDS no aesophageal Varices. No important comorbidities. Treated with PEG-IFN+Ribavirin (march-november 2009) with subsequent sustained virologic response. HCVRNA absent overtime. October 2016 :CT detected small HCC nodule in the VIII segment (diam.=12 mm). Treated with US guided RF-ablation. November 2016 CT: complete necrosis. Unfortunately, the patient dropped out US and CT follow-up controls.September 2018: asthenia and weight loss. CT showed a large tumor infiltrating V-VII-VI segments and complete PVTT of right portal vein and its branches . Surgical Consultation excluded indication to Liver resection and OLT . 23 october 2018: ECT of a large peri-hilar area of the tumor including the PVTT. 1 and 3 months post-treatment CT showed complete necrosis and retraction of the thrombus and residual viable tumor in the peripheral portion of the right lobe . Therefor, the patient was reevaluated for OLT and considered eligible in waiting list . March 2019: CT showed no perihilar or portal vein recurrence and distant progression in the right lobe . March 2019 : Trans-arterial-Radio-therapy (TARE) of the right lobe. Post-treatment CT demonstrated no perihilar or portal vein recurrence and extensive necrosis of the residual tumor . December 2019: CT demonstrated several recurrences of HCC infiltrating the VI and VII segment . Howewer no recurrence was observed at hepatic hilum and in portal vessels . Therefore, on February 2020 the patient received OLT. At 44 months follow-up, no complication or recurrence or liver disfunction have been observed.Keywords: hepatocellular carcinoma, portal vein tumor thrombosis, interventional ultrasound, liver tumor ablation, liver transplantation
Procedia PDF Downloads 67245 Involvement of Nrf2 in Kolaviron-Mediated Attenuation of Behavioural Incompetence and Neurodegeneration in a Murine Model of Parkinson's Disease
Authors: Yusuf E. Mustapha, Inioluwa A Akindoyeni, Oluwatoyin G. Ezekiel, Ifeoluwa O. Awogbindin, Ebenezer O. Farombi
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Background: Parkinson's disease (PD) is the most prevalent motor disorder. Available therapies are palliative with no effect on disease progression. Kolaviron (KV), a natural anti-inflammatory and antioxidant agent, has been reported to possess neuroprotective effects in Parkinsonian flies and rats. Objective: The present study investigates the neuroprotective effect of KV, focusing on the DJ1/Nrf2 signaling pathway. Methodology: All-trans retinoic acid (ATRA, 10 mg/kg, i.p.) was used to inhibit Nrf2. Murine model of PD was established with four doses of MPTP (20 mg/kg i.p.) at 2 hours interval. MPTP mice were pre-treated with either KV (200 mg/kg/day p.o), ATRA, or both conditions for seven days before PD induction. Motor behaviour was evaluated, and markers of oxidative stress/damage and its regulators were assessed with immunofluorescence and ELISA techniques. Results: MPTP-treated mice covered less distance with reduced numbers of anticlockwise rotations, heightened freezing, and prolonged immobility when compared to control. However, KV significantly attenuated these deficits. Pretreatment of MPTP mice with KV upregulated Nrf2 expression beyond MPTP level with a remarkable reduction in Keap1 expression and marked elevation of DJ-1 level, whereas co-administration with ATRA abrogated these effects. KV treatment restored MPTP-mediated depletion of endogenous antioxidant, striatal oxidative stress, oxidative damage, and inhibition of acetylcholinesterase activity. However, ATRA treatment potentiated acetylcholinesterase inhibition and attenuated the protective effect of KV on the level of nitric oxide and activities of catalase and superoxide dismutase. Conclusion: Kolaviron protects Parkinsonian mice by stabilizing and activating the Nrf2 signaling pathway. Thus, kolaviron can be explored as a pharmacological lead in PD management.Keywords: Garcinia kola, Kolaviron, Parkinson Disease, Nrf2, behavioral incompetence, neurodegeneration
Procedia PDF Downloads 101244 Targeting Mre11 Nuclease Overcomes Platinum Resistance and Induces Synthetic Lethality in Platinum Sensitive XRCC1 Deficient Epithelial Ovarian Cancers
Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan
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Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality
Procedia PDF Downloads 129243 Human Par14 and Par17 Isomerases Bind Hepatitis B Virus Components Inside and Out
Authors: Umar Saeed
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Peptidyl-prolyl cis/trans isomerases Par14 and Par17 in humans play crucial roles in diverse cellular processes, including protein folding, chromatin remodeling, DNA binding, ribosome biogenesis, and cell cycle progression. However, the effects of Par14 and Par17 on viral replication have been explored to a limited extent. We first time discovered their influential roles in promoting Hepatitis B Virus replication. In this study, we observed that in the presence of HBx, either Par14 or Par17 could upregulate HBV replication. However, in the absence of HBx, neither Par14 nor Par17 had any effect on replication. Their mechanism of action involves binding to specific motifs within HBc and HBx proteins. Notably, they target the conserved 133Arg-Pro134 (RP) motif of HBc and the 19RP20-28RP29 motifs of HBx. This interaction is fundamental for the stability of HBx, core particles, and HBc. Par14 and Par17 exhibit versatility by binding both outside and inside core particles, thereby facilitating core particle assembly through their participation in HBc dimer-dimer interactions. NAGE and immunoblotting analyses unveiled the binding of Par14/Par17 to core particles. Co-immunoprecipitation experiments further demonstrated the interaction of Par14/Par17 with core particle assembly-defective and dimer-positive HBc-Y132A. It's essential to emphasize that R133 is the key residue in the HBc RP motif that governs their interaction with Par14/Par17. Chromatin immunoprecipitation conducted on HBV-infected cells elucidated the participation of residues S19 and E46/D74 in Par14 and S44 and E71/D99 in Par17 in the recruitment of 133RP134 motif-containing HBc into cccDNA. Depleting PIN4 in liver cell lines results in a significant reduction in cccDNA levels, pgRNA, sgRNAs, HBc, core particle assembly, and HBV DNA synthesis. Notably, parvulin inhibitors like juglone and PiB have proven to be effective in substantially reducing HBV replication. These inhibitors weaken the interaction between HBV core particles and Par14/Par17, underscoring the dynamic nature of this interaction. It's also worth noting that specific Par14/Par17 inhibitors hold promise as potential therapeutic options for chronic hepatitis B.Keywords: Par14Par17, HBx, HBc, cccDNA, HBV
Procedia PDF Downloads 66242 Magnetoelastically Induced Perpendicular Magnetic Anisotropy and Perpendicular Exchange Bias of CoO/CoPt Multilayer Films
Authors: Guo Lei, Wang Yue, Nakamura Yoshio, Shi Ji
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Recently, perpendicular exchange bias (PEB) is introduced as an active topic attracting continuous efforts. Since its discovery, extrinsic control of PEB has been proposed, due to its scientific significance in spintronic devices and potential application in high density magnetic random access memory with perpendicular magnetic tunneling junction (p-MTJ). To our knowledge, the researches aiming to controlling PEB so far are focused mainly on enhancing the interfacial exchange coupling by adjusting the FM/AFM interface roughness, or optimizing the crystalline structures of FM or AFM layer by employing different seed layers. In present work, the effects of magnetoelastically induced PMA on PEB have been explored in [CoO5nm/CoPt5nm]5 multilayer films. We find the PMA strength of FM layer also plays an important role on PEB at the FM/AFM interface and it is effective to control PEB of [CoO5nm/CoPt5nm]5 multilayer films by changing the magnetoelastically induced PMA of CoPt layer. [CoO5nm/CoPt5nm]5 multilayer films were deposited by magnetron sputtering on fused quartz substrate at room temperature, then annealed at 100°C, 250°C, 300°C and 375°C for 3h, respectively. XRD results reveal that all the samples are well crystallized with preferred fcc CoPt (111) orientation. The continuous multilayer structure with sharp component transition at the CoO5nm/CoPt5nm interface are identified clearly by transmission electron microscopy (TEM), x-ray reflectivity (XRR) and atomic force microscope (AFM). CoPt layer in-plane tensile stress is calculated by sin2φ method, and we find it increases gradually upon annealing from 0.99 GPa (as-deposited) up to 3.02 GPa (300oC-annealed). As to the magnetic property, significant enhancement of PMA is achieved in [CoO5nm/CoPt5nm]5 multilayer films after annealing due to the increase of CoPt layer in-plane tensile stress. With the enhancement of magnetoelastically induced PMA, great improvement of PEB is also achieved in [CoO5nm/CoPt5nm]5 multilayer films, which increases from 130 Oe (as-deposited) up to 1060 Oe (300oC-annealed), showing the same change tendency as PMA and the strong correlation with CoPt layer in-plane tensile stress. We consider it is the increase of CoPt layer in-plane tensile stress that leads to the enhancement of PMA, and thus the enhancement of magnetoelastically induced PMA results in the improvement of PEB in [CoO5nm/CoPt5nm]5 multilayer films.Keywords: perpendicular exchange bias, magnetoelastically induced perpendicular magnetic anisotropy, CoO5nm/CoPt5nm]5 multilayer film with in-plane stress, perpendicular magnetic tunneling junction
Procedia PDF Downloads 462241 Experimental Evaluation of Contact Interface Stiffness and Damping to Sustain Transients and Resonances
Authors: Krystof Kryniski, Asa Kassman Rudolphi, Su Zhao, Per Lindholm
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ABB offers range of turbochargers from 500 kW to 80+ MW diesel and gas engines. Those operate on ships, power stations, generator-sets, diesel locomotives and large, off-highway vehicles. The units need to sustain harsh operating conditions, exposure to high speeds, temperatures and varying loads. They are expected to work at over-critical speeds damping effectively any transients and encountered resonances. Components are often connected via friction joints. Designs of those interfaces need to account for surface roughness, texture, pre-stress, etc. to sustain against fretting fatigue. The experience from field contributed with valuable input on components performance in hash sea environment and their exposure to high temperature, speed and load conditions. Study of tribological interactions of oxide formations provided an insight into dynamic activities occurring between the surfaces. Oxidation was recognized as the dominant factor of a wear. Microscopic inspections of fatigue cracks on turbine indicated insufficient damping and unrestrained structural stress leading to catastrophic failure, if not prevented in time. The contact interface exhibits strongly non-linear mechanism and to describe it the piecewise approach was used. Set of samples representing the combinations of materials, texture, surface and heat treatment were tested on a friction rig under range of loads, frequencies and excitation amplitudes. Developed numerical technique extracted the friction coefficient, tangential contact stiffness and damping. Vast amount of experimental data was processed with the multi-harmonics balance (MHB) method to categorize the components subjected to the periodic excitations. At the pre-defined excitation level both force and displacement formed semi-elliptical hysteresis curves having the same area and secant as the actual ones. By cross-correlating the terms remaining in the phase and out of the phase, respectively it was possible to separate an elastic energy from dissipation and derive the stiffness and damping characteristics.Keywords: contact interface, fatigue, rotor-dynamics, torsional resonances
Procedia PDF Downloads 375240 Constraint-Based Computational Modelling of Bioenergetic Pathway Switching in Synaptic Mitochondria from Parkinson's Disease Patients
Authors: Diana C. El Assal, Fatima Monteiro, Caroline May, Peter Barbuti, Silvia Bolognin, Averina Nicolae, Hulda Haraldsdottir, Lemmer R. P. El Assal, Swagatika Sahoo, Longfei Mao, Jens Schwamborn, Rejko Kruger, Ines Thiele, Kathrin Marcus, Ronan M. T. Fleming
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Degeneration of substantia nigra pars compacta dopaminergic neurons is one of the hallmarks of Parkinson's disease. These neurons have a highly complex axonal arborisation and a high energy demand, so any reduction in ATP synthesis could lead to an imbalance between supply and demand, thereby impeding normal neuronal bioenergetic requirements. Synaptic mitochondria exhibit increased vulnerability to dysfunction in Parkinson's disease. After biogenesis in and transport from the cell body, synaptic mitochondria become highly dependent upon oxidative phosphorylation. We applied a systems biochemistry approach to identify the metabolic pathways used by neuronal mitochondria for energy generation. The mitochondrial component of an existing manual reconstruction of human metabolism was extended with manual curation of the biochemical literature and specialised using omics data from Parkinson's disease patients and controls, to generate reconstructions of synaptic and somal mitochondrial metabolism. These reconstructions were converted into stoichiometrically- and fluxconsistent constraint-based computational models. These models predict that Parkinson's disease is accompanied by an increase in the rate of glycolysis and a decrease in the rate of oxidative phosphorylation within synaptic mitochondria. This is consistent with independent experimental reports of a compensatory switching of bioenergetic pathways in the putamen of post-mortem Parkinson's disease patients. Ongoing work, in the context of the SysMedPD project is aimed at computational prediction of mitochondrial drug targets to slow the progression of neurodegeneration in the subset of Parkinson's disease patients with overt mitochondrial dysfunction.Keywords: bioenergetics, mitochondria, Parkinson's disease, systems biochemistry
Procedia PDF Downloads 294239 Health Economics in the Cost-Benefit Analysis of Transport Schemes
Authors: Henry Kelly, Helena Shaw
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This paper will seek how innovative methods from Health Economics and, to a lesser extent, wellbeing analysis can be applied in the Cost-Benefit Analysis (CBA) of transport infrastructure and policy interventions. The context for this will focus on the framework articulated by the UK Treasury (finance department) and the English Department for Transport. Both have well-established methods for undertaking CBA, but there is increased policy interest, particularly at a regional level of exploring broader strategic goals beyond those traditionally associated with transport user benefits, productivity gains, and labour market access. Links to different CBA approaches internationally, such as New Zealand, France, and Wales will be referenced. By exploring a complementary method of accessing the impacts of policies through the quantification of health impacts is a fruitful line to explore. In a previous piece of work, 14 impact pathways were identified, mapping the relationship between transport and health. These are wide-ranging, from improved employment prospects, the stress of unreliable journey times, and air quality to isolation and loneliness. Importantly, we will consider these different measures of health from an intersectional point of view to ensure that the basis that remains in the health industry does not get translated across to this work. The objective is to explore how a CBA based on these pathways may, through quantifying forecast impacts in terms of Quality-Adjusted Life Years may, produce different findings than a standard approach. Of particular interest is how a health-based approach may have different distributional impacts on socio-economic groups and may favour distinct types of interventions. Consideration will be given to the degree this approach may double-count impacts or if it is possible to identify additional benefits to the established CBA approach. The investigation will explore a range of schemes, from a high-speed rail link, highway improvements, rural mobility hubs, and coach services to cycle lanes. The conclusions should aid the progression of methods concerning the assessment of publicly funded infrastructure projects.Keywords: cost-benefit analysis, health, QALYs transport
Procedia PDF Downloads 80238 Study of Variation of Winds Behavior on Micro Urban Environment with Use of Fuzzy Logic for Wind Power Generation: Case Study in the Cities of Arraial do Cabo and São Pedro da Aldeia, State of Rio de Janeiro, Brazil
Authors: Roberto Rosenhaim, Marcos Antonio Crus Moreira, Robson da Cunha, Gerson Gomes Cunha
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This work provides details on the wind speed behavior within cities of Arraial do Cabo and São Pedro da Aldeia located in the Lakes Region of the State of Rio de Janeiro, Brazil. This region has one of the best potentials for wind power generation. In interurban layer, wind conditions are very complex and depend on physical geography, size and orientation of buildings and constructions around, population density, and land use. In the same context, the fundamental surface parameter that governs the production of flow turbulence in urban canyons is the surface roughness. Such factors can influence the potential for power generation from the wind within the cities. Moreover, the use of wind on a small scale is not fully utilized due to complexity of wind flow measurement inside the cities. It is difficult to accurately predict this type of resource. This study demonstrates how fuzzy logic can facilitate the assessment of the complexity of the wind potential inside the cities. It presents a decision support tool and its ability to deal with inaccurate information using linguistic variables created by the heuristic method. It relies on the already published studies about the variables that influence the wind speed in the urban environment. These variables were turned into the verbal expressions that are used in computer system, which facilitated the establishment of rules for fuzzy inference and integration with an application for smartphones used in the research. In the first part of the study, challenges of the sustainable development which are described are followed by incentive policies to the use of renewable energy in Brazil. The next chapter follows the study area characteristics and the concepts of fuzzy logic. Data were collected in field experiment by using qualitative and quantitative methods for assessment. As a result, a map of the various points is presented within the cities studied with its wind viability evaluated by a system of decision support using the method multivariate classification based on fuzzy logic.Keywords: behavior of winds, wind power, fuzzy logic, sustainable development
Procedia PDF Downloads 293237 Cadmium Telluride Quantum Dots (CdTe QDs)-Thymine Conjugate Based Fluorescence Biosensor for Sensitive Determination of Nucleobases/Nucleosides
Authors: Lucja Rodzik, Joanna Lewandowska-Lancucka, Michal Szuwarzynski, Krzysztof Szczubialka, Maria Nowakowska
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The analysis of nucleobases is of great importance for bioscience since their abnormal concentration in body fluids suggests the deficiency and mutation of the immune system, and it is considered to be an important parameter for diagnosis of various diseases. The presented conjugate meets the need for development of the effective, selective and highly sensitive sensor for nucleobase/nucleoside detection. The novel, highly fluorescent cadmium telluride quantum dots (CdTe QDs) functionalized with thymine and stabilized with thioglycolic acid (TGA) conjugates has been developed and thoroughly characterized. Successful formation of the material was confirmed by elemental analysis, and UV–Vis fluorescence and FTIR spectroscopies. The crystalline structure of the obtained product was characterized with X-ray diffraction (XRD) method. The composition of CdTe QDs and their thymine conjugate was also examined using X-ray photoelectron spectroscopy (XPS). The size of the CdTe-thymine was 3-6 nm as demonstrated using atomic force microscopy (AFM) and high resolution transmission electron microscopy (HRTEM) imaging. The plasmon resonance fluorescence band at 540 nm on excitation at 351 nm was observed for these nanoparticles. The intensity of this band increased with the increase in the amount of conjugated thymine with no shift in its position. Based on the fluorescence measurements, it was found that the CdTe-thymine conjugate interacted efficiently and selectively not only with adenine, a nucleobase complementary to thymine, but also with nucleosides and adenine-containing modified nucleosides, i.e., 5′-deoxy-5′-(methylthio)adenosine (MTA) and 2’-O-methyladenosine, the urinary tumor markers which allow monitoring of the disease progression. The applicability of the CdTe-thymine sensor for the real sample analysis was also investigated in simulated urine conditions. High sensitivity and selectivity of CdTe-thymine fluorescence towards adenine, adenosine and modified adenosine suggest that obtained conjugate can be potentially useful for development of the biosensor for complementary nucleobase/nucleoside detection.Keywords: CdTe quantum dots, conjugate, sensor, thymine
Procedia PDF Downloads 412236 Antioxidant Efficacy of Lovi (Flacourtia inermis) Peel Extract in Edible Oils during Storage
Authors: Sasini U. G. Nanayakkara, Nishala E. Wedamulla, W. A. J. P. Wijesinghe
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Lovi (Flacourtia inermis) is an underutilized fruit crop grown in Sri Lanka with promising antioxidant properties; thus, exhibits the great potential to use as a natural antioxidant. With the concern of synthetic antioxidants, there is a growing trend towards the addition of a natural antioxidant to retard the rancidity of edible oils. Hence, in this backdrop, extract obtained from the peel of F. inermis fruit was used to retard the rancidity of selected edible oils. Free fatty acid (FFA) content and peroxide value (PV) of sunflower oil (SO) and virgin coconut oil (VCO) were measured at 3-day intervals for 21 days at 65 ± 5°C after addition of extract at 500, 1000, 2000 ppm levels and α-tocopherol at 500 ppm level was used as positive control. SO and VCO without added extract was used as the control. The extract was prepared with 70% ethanol using ultrasound-assisted extraction, and antioxidant efficacy and total phenolic content (TPC) of the extract were measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity and Folin-Ciocalteu method respectively. Antioxidant activity (IC50) and TPC of the extract were 227.14 ± 4.12 µgmL⁻¹ and 4.87 ± 0.01 mg GAE per gram, respectively. During the storage period, FFA content and PV of both oils were increased with time. However, SO showed comparatively high PV than that of VCO and thereby indicate the progression of lipid oxidation as PV is a good indicator of the extent of primary oxidative products formed in oils. The most effective extract concentration was 2000 ppm. After 21 days of storage, VCO (control) sample exhibited significantly (p < 0.05) high FFA (0.36%) and PV (1.93 meq kg⁻¹) than that of VCO with 1000 ppm (FFA: 0.35%; PV: 1.72 meq kg⁻¹) and 2000 ppm (FFA: 0.28%; PV: 1.19 meq kg-1) levels of extract. Thus, demonstrates the efficacy of lovi peel extract in retardation of lipid oxidation of edible oils during storage at higher concentrations of the extract addition. Moreover, FFA and PV of SO (FFA: 0.10%; PV: 12.38 meq kg⁻¹) and VCO (FFA: 0.28%; PV: 1.19 meq kg⁻¹) at 2000 ppm level of extract were significantly (p < 0.05) lower than that of positive control: SO with α-tocopherol (FFA: 0.22%, PV: 17.94 meq kg⁻¹) and VCO with α-tocopherol (FFA: 0.29%, PV: 1.39 meq kg⁻¹) after 21 days. Accordingly, lovi peel extract at 2000 ppm level was more effective than α-tocopherol in retardation of lipid oxidation of edible oils. In conclusion, lovi peel extract has strong antioxidant properties and can be used as a natural antioxidant to inhibit deteriorative oxidation of edible oils.Keywords: antioxidant, Flacourtia inermis, peroxide value, virgin coconut oil
Procedia PDF Downloads 127235 Transcranial Electric Field Treatments on Redox-Toxic Iron Deposits in Transgenic Alzheimer’s Disease Mouse Models: The Electroceutical Targeting of Alzheimer’s Disease
Authors: Choi Younshick, Lee Wonseok, Lee Jaemeun, Park Sun-Hyun, Kim Sunwoung, Park Sua, Kim Eun Ho, Kim Jong-Ki
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Iron accumulation in the brain accelerates Alzheimer’s disease progression. To cure iron toxicity, we assessed the therapeutic effects of noncontact transcranial electric field stimulation to the brain on toxic iron deposits in either the Aβ-fibril structure or the Aβ plaque in a mouse model of Alzheimer’s disease (AD). A capacitive electrode-based alternating electric field (AEF) was applied to a suspension of magnetite (Fe₃O₄) to measure the field-sensitized electro-Fenton effect and resultant reactive oxygen species (ROS) generation. The increase in ROS generation compared to the untreated control was both exposure-time and AEF-frequency dependent. The frequency-specific exposure of AEF to 0.7–1.4 V/cm on a magnetite-bound Aβ-fibril or a transgenic Alzheimer’s disease (AD) mouse model revealed the removal of intraplaque ferrous magnetite iron deposit and Aβ-plaque burden together at the same time compared to the untreated control. The results of the behavioral tests show an improvement in impaired cognitive function following AEF treatment on the AD mouse model. Western blot assay found some disease-modifying biological responses, including down-regulating ferroptosis, neuroinflammation and reactive astrocytes that eventually made cognitive improvement feasible. Tissue clearing and 3D-imaging analysis revealed no induced damage to the neuronal structures of normal brain tissue following AEF treatment. In conclusion, our results suggest that the effective degradation of magnetite-bound amyloid fibrils or plaques in the AD brain by the electro-Fenton effect from electric field-sensitized magnetite offers a potential electroceutical treatment option for AD.Keywords: electroceutical, intraplaque magnetite, alzheimer’s disease, transcranial electric field, electro-fenton effect
Procedia PDF Downloads 71