Search results for: Hoek-Brown failure criterion

Authors: Talal Asif, Maya Kosinska, Lucas Georger, Krish Sardesai, Muhammad Shah Miran

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This article presents a case review and literature review focused on the challenges of managing subaortic membranes (SAM) in young adult patients with mild aortic regurgitation (AR) or aortic stenosis (AS). The study aims to discuss the diagnosis of SAM, imaging studies used for assessment, management strategies in young patients, the risk of valvular damage, and the controversy surrounding prophylactic resection in mild AR. The management of SAM in adults poses challenges due to limited treatment options and potential complications, necessitating further investigation into the progression of AS and AR in asymptomatic SAM patients. The case presentation describes a 40-year-old male with muscular dystrophy who presented with symptoms and was diagnosed with SAM. Various imaging techniques, including CT chest, transthoracic echocardiogram (TTE), and transesophageal echocardiogram (TEE), were used to confirm the presence and severity of SAM. Based on the patient's clinical profile and the absence of surgical indications, medical therapy was initiated, and regular outpatient follow-up was recommended to monitor disease progression. The discussion highlights the challenges in diagnosing SAM, the importance of imaging studies, and the potential complications associated with SAM in young patients. The article also explores the management options for SAM, emphasizing surgical resection as the definitive treatment while acknowledging the limited success rates of alternative approaches. Close monitoring and prompt intervention for complications are crucial in the management of SAM. The concluding statement emphasizes the need for further research to explore alternative treatments for SAM in young patients.

Keywords: subaortic membrane, management, case report, literature review, aortic regurgitation, aortic stenosis, left ventricular outflow obstruction, guidelines, heart failure

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Authors: Shadreck Muchaku, Grey Magaiza, Jerit Dube

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The high insolvency rate of female-led emerging enterprises in the Southern African mountain region reflects the various vulnerabilities that exist. Although this is the case, there is a limited understanding of how these vulnerabilities influence entrepreneurship failure. This paper focuses on female entrepreneurs because of their role in economic development. Emerging female entrepreneurs in this region often operate in uncertain environments, which makes it difficult for them to thrive. The form and nature of entrepreneurial opportunities rural women of the Afro Montane region engage in are largely unsustainable as a lot of women struggle with confidence, and they need help with understanding their skills. However, there is still a gap in the existing literature on women entrepreneurship resilience and vulnerability reduction in the Afromontane. Furthermore, a major problem is the lack of empirical studies on this matter and limited studies indicating a general profile of emerging female entrepreneurs in this region. This systematic literature review attempts to fill in the gap of knowledge on entrepreneurship resilience and vulnerability reduction of emerging female entrepreneurs in the Afromontane regions and other similar precarious environments. In this review, we focus much on highlighting the nexus between entrepreneurship resilience and vulnerability reduction of emerging female entrepreneurs in academic literature through a chronological dispersal of publications in developing countries. This review adopts an ATLAS ti.22 software-based thematic analysis to analyze results obtained from reviewed academic journal articles. As research on entrepreneurship resilience and vulnerability reduction is still developing in the Sothern African mountain region, the results of this review will contribute to the body of literature and provide recommendations and a foundation for future research. This systematic review paper provides valuable insights and methodological approaches to scholarship in a nascent area of emerging female entrepreneurs in the Afromontane.

Keywords: entrepreneurship resiliency, vulnerability reduction, female entrepreneurs, mountain regions

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Authors: Nosratollah Hedayatpour, Hamid Reza Taheri, Mehrdad Fathi

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Introduction: Quadriceps femoris muscle is frequently involved in various movements e.g., jumping, landing) during sport and/or daily activities. During ballistic movement when individuals are faced with unexpected knee perturbation, fast twitch muscle fibers contribute to force production to stabilize knee joint. Fast twitch muscle fiber is more susceptible to fatigue and therefor may reduce the ability of the quadriceps muscle to stabilize knee joint during fast perturbation. Aim: The aim of this study was to investigate the effect of fatigue on postural response of the knee extensor muscles to fast and slow perturbations. Methods: Fatigue was induced to the quadriceps muscle using a KinCom Isokinetic Dynamometer (Chattanooga, TN). Bipolar surface electromyography (EMG) signals were simultaneously recorded from quadriceps components (vastus medialis, rectus femoris, and vastus lateralis) during pre- and post-fatigue postural perturbation performed at two different velocities of 120 ms and 250 mes. Results: One-way ANOVA showed that maximal voluntary knee extension force and time to task failure, and associated EMG activities were significantly reduced after fatiguing knee exercise (P< 0.05). Two-ways ANOVA also showed that ARV of EMG during backward direction was significantly larger than forward direction (P< 0.05), and during fast-perturbation it was significantly higher than slow-perturbation (P< 0.05). Moreover, ARV of EMG was significantly reduced during post fatigue perturbation, with the largest reduction identified for fast-perturbation compared with slow perturbation (P< 0.05). Conclusion: A larger reduction in muscle activity of the quadriceps muscle was observed during post fatigue fast-perturbation to stabilize knee joint, most likely due to preferential recruitment of fast twitch muscle fiber which are more susceptible to fatigue. This may partly explain that why knee injuries is common after fast ballistic movement.

Keywords: electromyography, fast-slow perturbations, fatigue, quadriceps femoris muscle

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Authors: B. Yermekbayeva, A. Gulyayaev, T. Nurgozhin, C. Bektur

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Cytisine aminophosphonate under the name "Cytafat" was approved for clinical trials in Republic of Kazakhstan as a putative liver protecting drug for the treatment of acute toxic hepatitis. A method of conducting the clinical trial is a double blind study. Total number of patients -71, aged from 16 to 56 years. Research on healthy volunteers determined the maximal tolerable doze of "Cytafat" as 200 mg/kg. Side effects when administered at high dozes (100-200 mg/kg) are tachycardia and increase of arterial blood pressure. The drug is tested in the treatment of 28 patients with a syndrome of hepatocellular failure (a poisoning with substitutes of alcohol, rat poison, or medical products). "Cytafat" was intravenously administered at a dose of 10 mg/kg in 200 ml of 5 % glucose solution once daily. The number of administrations: 1-3. In the comparison group, 23 patients were treated intravenously once a day with “Essenciale H” at a dose of 10 ml. 20 patients received a placebo (10 ml of glucose intravenously). In all cases of toxic hepatopathology the significant positive clinical effect of the testing drug distinguishable from placebo and surpassing the alternative was observed. Within a day after administration a sharp reduction of cytolitic syndrome parameters (ALT, AST, alkaline phosphatase, thymol turbidity test, GGT) was registered, a reduction of the severity of cholestatic syndrome (bilirubin decreased) was recorded, significantly decreased indices of lipid peroxidation. The following day, in all cases the positive dynamics was determined with ultrasound study (reduction of diffuse changes and events of reactive pancreatitis), hepatomegaly disappeared. Normalization of all parameters occurred in 2-3 times faster, than when using the drug "Essenciale H" and placebo. Average term of elimination of toxic hepatopathy when using the drug "Cytafat" -2,8 days, "Essenciale H" -7,2 days, and placebo -10,6 days. The new drug "Cytafat" has expressed cytoprotective properties.

Keywords: cytisine, cytoprotection, hepatopathy, hepatoprotection

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Authors: Akshay Patil

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Objective: Mediation analysis identifies causal pathways by testing the relationships between the NCR, the OS, and an intermediate variable that mediates the relationship between the Nimotuzumab-cisplatin-radiation (NCR) and OS. Introduction: In randomized controlled trials, the primary interest is in the mechanisms by which an intervention exerts its effects on the outcomes. Clinicians are often interested in how the intervention works (or why it does not work) through hypothesized causal mechanisms. In this work, we highlight the value of understanding causal mechanisms in randomized trial by applying causal mediation analysis in a randomized trial in oncology. Methods: Data was obtained from a phase III randomized trial (Subgroup of HPVNOCP). NCR is reported to significantly improve the OS of patients locally advanced head and neck cancer patients undergoing definitive chemoradiation. Here, based on trial data, the mediating effect of NCR on patient overall survival was systematically quantified through progression-free survival(PFS), disease free survival (DFS), Loco-regional failure (LRF), and the disease control rate (DCR), Overall response rate (ORR). Effects of potential mediators on the HR for OS with NCR versus cisplatin-radiation (CR) were analyzed by Cox regression models. Statistical analyses were performed using R software Version 3.6.3 (The R Foundation for Statistical Computing) Results: Effects of potential mediator PFS was an association between NCR treatment and OS, with an indirect-effect (IE) 0.76(0.62 – 0.95), which mediated 60.69% of the treatment effect. Taking into account baseline confounders, the overall adjusted hazard ratio of death was 0.64 (95% CI: 0.43 – 0.96; P=0.03). The DFS was also a significant mediator and had an IE 0.77 (95% CI; 0.62-0.93), 58% mediated). Smaller mediation effects (maximum 27%) were observed for LRF with IE 0.88(0.74 – 1.06). Both DCR and ORR mediated 10% and 15%, respectively, of the effect of NCR vs. CR on the OS with IE 0.65 (95% CI; 0.81 – 1.08) and 0.94(95% CI; 0.79 – 1.04). Conclusion: Our findings suggest that PFS and DFS were the most important mediators of the OS with nimotuzumab to weekly cisplatin-radiation in HPVNOCP.

Keywords: mediation analysis, cancer data, survival, NCR, HPV negative oropharyngeal

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Authors: Laith K. Abbas, Xiaoting Rui, Pier Marzocca

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Aerospace systems, generally speaking, are inherently nonlinear. These nonlinearities may modify the behavior of the system. However, nonlinearities in an aeroelastic system can be divided into structural and aerodynamic. Structural nonlinearities can be subdivided into distributed and concentrated ones. Distributed nonlinearities are spread over the whole structure representing the characteristic of materials and large motions. Concentrated nonlinearities act locally, representing loose of attachments, worn hinges of control surfaces, and the presence of external stores. The concentrated nonlinearities can be approximated by one of the classical structural nonlinearities, namely, cubic, free-play and hysteresis, or by a combination of these, for example, a free-play and a cubic one. Compressibility, aerodynamic heating, separated flows and turbulence effects are important aspects that result in nonlinear aerodynamic behavior. An issue related to the low-speed flutter and its catastrophic/benign character represented by Limit Cycle Oscillation (LCO) of all-movable fin, as well to their control is addressed in the present work. To the approach of this issue: (1) Quasi-Steady (QS) Theory and Computational Fluid Dynamics (CFD) of subsonic flow are implemented, (2) Flutter motion equations of a two-dimensional typical section with cubic nonlinear stiffness in the pitching direction and free play gap are established, (3) Uncoupled bending/torsion frequencies of the selected fin are computed using recently developed Transfer Matrix Method of Multibody System Dynamics (MSTMM), and (4) Time simulations are carried out to study the bifurcation behavior of the aeroelastic system. The main objective of this study is to investigate how the LCO and chaotic behavior are influenced by the coupled aeroelastic nonlinearities and intend to implement a control capability enabling one to control both the flutter boundary and its character. By this way, it may expand the operational envelop of the aerospace vehicle without failure.

Keywords: aeroelasticity, CFD, MSTMM, flutter, freeplay, fin

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Authors: Boshra Mozaffar, Arash Ardavani, Iskandar Idris

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Food taste and flavor affect food choice and acceptance, which are essential to maintain good health and quality of life. Reduced circulating zinc levels have been shown to adversely affect taste which can result in reduced appetite, weight loss and psychological problems, but the efficacy of Zinc supplementation to treat disorders of taste remains unclear. In this systematic review and meta-analysis, we aimed to examine the efficacy of zinc supplementation in the treatment of taste disorders. We searched four electronic bibliographical databases; Ovid MEDLINE, Ovid Embase, Ovid AMAD and PubMed. Article bibliographies were also searched, which yielded additional relevant studies. To facilitate the collection and identification of all available and relevant articles published before 7 December 2020, there were no restrictions on the publication date. We performed a systematic review and meta-analysis according to the PRISMA Statement. This review was registered at PROSPERO and given the identification number CRD42021228461. In total, we included 12 randomized controlled trials with 938 subjects. Intervention includes zinc (sulfate, gluconate, picolinate, polaprezinc and acetate); the pooled results of the meta-analysis indicate that improvements in taste disorder occurred more frequently in the intervention group compared to the control group (RR = 1.8; 95% CI:1.27 -2.57, p=0.009). The doses are equivalent to 17 mg- 86.7 mg of elemental zin for three to six months. Zinc supplementation is an effective treatment for taste disorders in patients with zinc deficiency or idiopathic taste disorders when given in high doses ranging from 68–86.7 mg/d for up to three months. However, we did not find sufficient evidence to determine the effectiveness of zinc supplementation in patients with taste disorders induced by chronic renal failure.

Keywords: taste change, taste disorder, zinc, zinc sulfate or Zn, deficiency, supplementation.

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Authors: Laheeb M. Ibrahim, Ibrahim A. Salih

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Biometrics is a technology that has been widely used in many official and commercial identification applications. The increased concerns in security during recent years (especially during the last decades) have essentially resulted in more attention being given to biometric-based verification techniques. Here, a novel fusion approach of palmprint, dental traits has been suggested. These traits which are authentication techniques have been employed in a range of biometric applications that can identify any postmortem PM person and antemortem AM. Besides improving the accuracy, the fusion of biometrics has several advantages such as increasing, deterring spoofing activities and reducing enrolment failure. In this paper, a first unimodel biometric system has been made by using (palmprint and dental) traits, for each one classification applying an artificial neural network and a hybrid technique that combines swarm intelligence and neural network together, then attempt has been made to combine palmprint and dental biometrics. Principally, the fusion of palmprint and dental biometrics and their potential application has been explored as biometric identifiers. To address this issue, investigations have been carried out about the relative performance of several statistical data fusion techniques for integrating the information in both unimodal and multimodal biometrics. Also the results of the multimodal approach have been compared with each one of these two traits authentication approaches. This paper studies the features and decision fusion levels in multimodal biometrics. To determine the accuracy of GAR to parallel system decision-fusion including (AND, OR, Majority fating) has been used. The backpropagation method has been used for classification and has come out with result (92%, 99%, 97%) respectively for GAR, while the GAR) for this algorithm using hybrid technique for classification (95%, 99%, 98%) respectively. To determine the accuracy of the multibiometric system for feature level fusion has been used, while the same preceding methods have been used for classification. The results have been (98%, 99%) respectively while to determine the GAR of feature level different methods have been used and have come out with (98%).

Keywords: back propagation neural network BP ANN, multibiometric system, parallel system decision-fusion, practical swarm intelligent PSO

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Authors: Marianna Maiaru, Gregory M. Odegard

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During the processing of high-performance thermoset polymer matrix composites, chemical reactions occur during elevated pressure and temperature cycles, causing the constituent monomers to crosslink and form a molecular network that gradually can sustain stress. As the crosslinking process progresses, the material naturally experiences a gradual shrinkage due to the increase in covalent bonds in the network. Once the cured composite completes the cure cycle and is brought to room temperature, the thermal expansion mismatch of the fibers and matrix cause additional residual stresses to form. These compounded residual stresses can compromise the reliability of the composite material and affect the composite strength. Composite process modeling is greatly complicated by the multiscale nature of the composite architecture. At the molecular level, the degree of cure controls the local shrinkage and thermal-mechanical properties of the thermoset. At the microscopic level, the local fiber architecture and packing affect the magnitudes and locations of residual stress concentrations. At the macroscopic level, the layup sequence controls the nature of crack initiation and propagation due to residual stresses. The goal of this research is use molecular dynamics (MD) and finite element analysis (FEA) to predict the residual stresses in composite laminates and the corresponding effect on composite failure. MD is used to predict the polymer shrinkage and thermomechanical properties as a function of degree of cure. This information is used as input into FEA to predict the residual stresses on the microscopic level resulting from the complete cure process. Virtual testing is subsequently conducted to predict strength allowables. Experimental characterization is used to validate the modeling.

Keywords: molecular dynamics, finite element analysis, processing modeling, multiscale modeling

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Authors: V. Manjunath, C. V. Chandrashekara

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Ecosystem authority calls for the use of lubricants with less effect on the nature in terms of exhaust emission, while engine user demands more mileage per liter of fuel without any compromise on engine durability. From this viewpoint, engine manufacturers require the optimum combination of materials and lubricant additive package to minimize friction and wear in the engine components like piston, crankshaft and valve train etc. The demands are placed for requirements to operate at higher speeds, loads, temperature and for extended replacement intervals of engine oil. Besides, it is necessary to accurately predict the lubricant life or the replacement interval to prevent lubrication and valve-train components failure. Experimental tribology evaluation of new engine oils requires large amount of time and energy. Hence low cost bench test is necessary for industries and original equipment manufacturing companies (OEM) to study the performance of lubricants. The present work outlines the procedure for the design and development of a valve train wear rig (MCR) to simulate the ASTMD-6891 and to develop new engine test for Indian automobile sector to evaluate lubricants for Indian automobile market. In order to improve the lubrication between cam and follower of internal combustion engine, the influence of materials or oils viscosity and additives on the friction and wear characteristics are examined with test rig by increasing the contact load at two different revolution speed. From the experimentation following results are made obvious. Temperature, Torque, speed and wear plots are used to validate the data obtained from the newly developed multi-cam cam rig (MCR) with follower against a cast iron camshaft. Camshaft lobe wear is measured at seven different locations on cam profile. Tribofilm formed using 5W-30 oil is evaluated and correlated with the standard test results.

Keywords: ASTMD-6891, multi-cam rig (MCR), 5W-30, cam-profile

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Authors: Al-Amin, Huanjun Jiang, Anayat Ali

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Reinforced concrete frames (RC), especially Ordinary RC frames, are prone to structural failures/collapse during seismic events, leading to a large proportion of debris from the structures, which obstructs adjacent areas, including streets. These blocked areas severely impede post-earthquake resilience. This study uses computational simulation (FEM) to investigate the amount of debris generated by the seismic collapse of an ordinary reinforced concrete moment frame building and its effects on the adjacent pedestrian and road network. A three-story ordinary reinforced concrete frame building, primarily designed for gravity load and earthquake resistance, was selected for analysis. Sixteen different ground motions were applied and scaled up until the total collapse of the tested building to evaluate the failure mode under various seismic events. Four types of collapse direction were identified through the analysis, namely aligned (positive and negative) and skewed (positive and negative), with aligned collapse being more predominant than skewed cases. The amount and distribution of debris around the collapsed building were assessed to investigate the interaction between collapsed buildings and adjacent street networks. An interaction was established between a building that collapsed in an aligned direction and the adjacent pedestrian walkway and narrow street located in an unplanned old city. The FEM model was validated against an existing shaking table test. The presented results can be utilized to simulate the interdependency between the debris generated from the collapse of seismic-prone buildings and the resilience of street networks. These findings provide insights for better disaster planning and resilient infrastructure development in earthquake-prone regions.

Keywords: building collapse, earthquake-induced debris, ORC moment resisting frame, street network

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Authors: Serena Salvi

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Ageistic stereotypes and practices have become a normal and therefore pervasive phenomenon in various aspects of everyday life. Over the past years, renewed awareness towards self-directed age stereotyping in older adults has given rise to a line of research focused on the potential role of attitudes towards ageing on seniors’ health and functioning. This set of studies has showed how a negative internalisation of ageistic stereotypes would discourage older adults in seeking medical advice, in addition to be associated to negative subjective health evaluation. An important dimension of mental health that is often affected in older adults is represented by sleep quality. Self-reported sleep quality among older adults has shown to be often unreliable when compared to their objective sleep measures. Investigations focused on self-reported sleep quality among older adults have suggested how this portion of the population would tend to accept disrupted sleep if believed to be up to standard for their age. On the other hand, unrealistic expectations, and dysfunctional beliefs towards sleep in ageing, might prompt older adults to report sleep disruption even in the absence of objective disrupted sleep. Objective of this study is to examine an association between personal attitudes towards ageing in adults aged 60+ and dysfunctional sleep related cognition. More in detail, this study aims to investigate a potential association between personal attitudes towards ageing, sleep locus of control and dysfunctional beliefs towards sleep among this portion of the population. Data in this study were statistically analysed in SPSS software. Participants were recruited through the online participants recruitment system Prolific. Inclusion of attention check questions throughout the questionnaire and consistency of responses were looked at. Prior to the commencement of this study, Ethical Approval was granted (ref. 39396). Descriptive statistics were used to determine the frequency, mean, and SDs of the variables. Pearson coefficient was used for interval variables, independent T-test for comparing means between two independent groups, analysis of variance (ANOVA) test for comparing the means in several independent groups, and hierarchical linear regression models for predicting criterion variables based on predictor variables. In this study self-perceptions of ageing were assessed using APQ-B’s subscales, while dysfunctional sleep related cognition was operationalised using the SLOC and the DBAS16 scales. Of the final subscales taken in consideration in the brief version of the APQ questionnaire, Emotional Representations (ER), Control Positive (PC) and Control and Consequences Negative (NC) have shown to be of particularly relevance for the remits of this study. Regression analysis show how an increase in the APQ-B subscale Emotional Representations (ER) predicts an increase in dysfunctional beliefs and attitudes towards sleep in this sample, after controlling for subjective sleep quality, level of depression and chronological age. A second regression analysis showed that APQ-B subscales Control Positive (PC) and Control and Consequences Negative (NC) were significant predictors in the change of variance of SLOC, after controlling for subjective sleep quality, level of depression and dysfunctional beliefs about sleep.

Keywords: sleep-related cognition, perceptions of aging, older adults, sleep quality

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Authors: Mohd Aslam Aslam

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Chronic renal failure is a debilitating condition responsible for high morbidity and mortality. Because of its costs and the complexity of its treatment, proper care is available to very few patients in India. According to researchers, the number of adults aged 30 or older who have chronic kidney disease is projected to increase from 13.2 percent currently, to 14.4 percent in 2020 and 16.7 percent in 2030. The aerial part of Aerva lanata (Busehri booti) have been used in kidney disorders by the Unani physicians. In the present study, the effect of extract of Aerva lanata was investigated on cisplatin-induced nephrotoxicity in rats. The renal effects of this drug was evaluated by monitoring levels of blood urea nitrogen (BUN), serum creatinine, serum uric acid in blood and histopathological examination of kidney. Aerva lanata was evaluated at two different doses (1400 mg/kg and 2800 mg/kg). The effect of higher dose was more pronounced in terms of inhibition in the rise of BUN, serum creatinine and uric acid. Higher dose show greater prevention in the rise of BUN, serum creatinine, and uric acid. The histopathological examination of the kidney tissue of the rats treated with aqueous methanolic extract of Aerva lanata (Higher dose-2800 mg/kg) showed marked inhibition of glomerular congestion, tubular casts, peritubular congestion, epithelial desquamation, blood vessel congestion, interstitial edema and inflammatory cells produced by the cisplatin-induced nephrotoxicity. This finding clearly indicates the protective role of Aerva lanata at higher dose. Present investigation validates the use of Aerva lanata in kidney disorders by Unani physicians.

Keywords: Aerva lanata, Busehri booti, nephroprotective, unani medicine

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Authors: Mohammad Aljuhani, Yasamina Aljuhani

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The Mining Engineering Department at College of Engineering in NBU is under establishment. It is essential to establish such department in NBU. This is because, it is the only university in the region. Moreover, the mining industry is very active in the northern borders region. However, there is no mining engineering department in KSA except one in King Abdulziz University, which is 1400 km from the mining industry in the northern borders. As a result, department graduates from KAU find difficulties to get suitable jobs in their specialization in spite of their few numbers graduated per year and the presence of many jobs vacancies at the local mining sector. Therefore, the objectives of this research are to identify, measure and analyze the above mentioned problem from educational point of view. One more objective is to add a contribution towards solving such vital, society affecting problem. For achieving the first task of the research, that is problem size identification and analyses, a questionnaire was designed. The questionnaire was directed towards experienced engineers, in the mining and related industries, including the ministry of petroleum and minerals, Saudi Geological Survey, and Ma’aden Company as being prospective employers for the mining sector. The questionnaire target was to evaluate the Saudi mining engineers from an industrial point of view and to detect the main reasons behind their failure to find jobs. In addition, the study focuses in the demand of mining engineers in the northern borders region. Moreover, the study plan of the suggested department is designed based on the requirements of the mining industry. The feedback received from the industry reflected major educational shortcomings. In order to overcome the revealed defects, the second objective of the research was achieved where a suggested study plan “curriculum” has been prepared to take into consideration all the points of weakness so as to improve the graduates’ quality to fit the local mining work market.

Keywords: mining engineering, labor market, qualifications, curriculum, mining industry, mining engineers

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Authors: Farhat Imtiaz, Umar Farooq

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In this work, we developed a computational model to predict ply level failure in impacted composite laminates. Data obtained from physical testing from flat and round nose impacts of 8-, 16-, 24-ply laminates were considered. Routine inspections of the tested laminates were carried out to approximate ply by ply inflicted damage incurred. Plots consisting of load–time, load–deflection, and energy–time history were drawn to approximate the inflicted damages. Impact test generated unwanted data logged due to restrictions on testing and logging systems were also filtered. Conventional filters (built-in, statistical, and numerical) reliably predicted load thresholds for relatively thin laminates such as eight and sixteen ply panels. However, for relatively thick laminates such as twenty-four ply laminates impacted by flat nose impact generated clipped data which can just be de-noised using oscillatory algorithms. The literature search reveals that modern oscillatory data filtering and extrapolation algorithms have scarcely been utilized. This investigation reports applications of filtering and extrapolation of the clipped data utilising fast Fourier Convolution algorithm to predict load thresholds. Some of the results were related to the impact-induced damage areas identified with Ultrasonic C-scans and found to be in acceptable agreement. Based on consistent findings, utilizing of modern data filtering and extrapolation algorithms to data logged by the existing machines has efficiently enhanced data interpretations without resorting to extra resources. The algorithms could be useful for impact-induced damage approximations of similar cases.

Keywords: fibre reinforced laminates, fast Fourier algorithms, mechanical testing, data filtering and extrapolation

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Authors: Anusree Ghosh, Nahid Morshed, Tapas Ranjan Chakraborty, Moniruzzaman Khan, Liakath Ali

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To establish the Bangabandhu Sheikh Mujib Shilpa Nagar in Mirsarai, Chattogram land was reclaimed from the river mouth of the Feni River in the Bay of Bangle. The sandy land has a salinity of 9.5 EC ds/m, and the water of the adjacent Bay was 13.2 EC ds/m during winter, i.e., it has moderate salinity. The selection of plant species for the plantation was following the local practices. Mangrove plantation in a such landscape is not common in the country, and some actions towards the plantation seem ineffective and could be accomplished differently. The aim of this paper is to analyze the trial and develop a strategy for mangrove afforestation in reclaimed land where the tidal effect does not occur year-round. Though the Keora (Sonneratia apetala) is the priority species in a typical mangrove plantation, the success rate is comparatively high for the Baen (Avcennia officinalis) and Sada Baen (Avicennia alba). The natural growth was recorded for Keora, Goran (Ceriops decandra), Lal Jhau (Tamarix dioica) and Baen. Though there was the natural growth of Durba grass (Cynodon dactylon) and Motha Gash (Cyperus rotundus), no growth of climber was reported at the early stage of the natural growth. The transplanted growth of Keora, Gewa (Excoecaria agallocha), and Baen was found not suitable for plantation. The saplings growing from the viviparous germinated bean show no germination failure. Since the plantation site remains dry for 5 months, there was irrigation from the river; though it resulted in an increase in land salinity. To increase fertility, cow dung was used, and green manuring by planting Doincha (Sesbania bispinosa) shows a very insignificant contribution. The plantation of, only one and a half years old, is now a habitat of more than 100 species. The learning from the mangrove plantation from August 2021 to February 2023 assumes that in reclaimed land where there is inundation during monsoon only and salinity is moderate, the plantation from viviparous germinated Baen is better.

Keywords: mangrove plantation, reclaimed land, climate change, habitat restoration

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Authors: Shadi Fathi, Moura Mehravar, Mujib Rahman

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The railwaytransportation network in the UK is over 100 years old and is known as one of the oldest mass transit systems in the world. This aged track network requires frequent closure for maintenance. One of the main reasons for closure is inadequate drainage due to the leakage in the buried drainage pipes. The leaking water can cause localised subgrade weakness, which subsequently can lead to major ground/substructure failure.Different condition assessment methods are available to assess the railway substructure. However, the existing condition assessment methods are not able to detect any local ground weakness/damageand provide details of the damage (e.g. size and location). To tackle this issue, a hybrid back-analysis technique based on artificial neural network (ANN) and genetic algorithm (GA) has been developed to predict the substructurelayers’ moduli and identify any soil weaknesses. At first, afinite element (FE) model of a railway track section under Falling Weight Deflection (FWD) testing was developed and validated against field trial. Then a drainage pipe and various scenarios of the local defect/ soil weakness around the buried pipe with various geometriesand physical properties were modelled. The impact of the soil local weaknesson the track surface deflection wasalso studied. The FE simulations results were used to generate a database for ANN training, and then a GA wasemployed as an optimisation tool to optimise and back-calculate layers’ moduli and soil weakness moduli (ANN’s input). The hybrid ANN-GA back-analysis technique is a computationally efficient method with no dependency on seed modulus values. The modelcan estimate substructures’ layer moduli and the presence of any localised foundation weakness.

Keywords: finite element (FE) model, drainage defect, falling weight deflectometer (FWD), hybrid ANN-GA

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Authors: Sachin Pawar, Suman Patra, Goutam Mukhopadhyay

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The primary function of a shaft is to transfer power. The shaft can be cast or forged and then machined to the final shape. Manufacturing of ~5 m length and 0.6 m diameter shaft is very critical. More difficult is to maintain its straightness during heat treatment and machining operations, which involve thermal and mechanical loads, respectively. During the machining operation of a such forged mandrel shaft, a deflection of 3-4mm was observed. To remove this deflection shaft was pressed at both ends which led to the development of cracks in it. To investigate the root cause of the deflection and cracking, the sample was cut from the failed shaft. Possible causes were identified with the help of a cause and effect diagram. Chemical composition analysis, microstructural analysis, and hardness measurement were done to confirm whether the shaft meets the required specifications or not. Chemical composition analysis confirmed that the material grade was 42CrMo4. Microstructural analysis revealed the presence of untempered martensite, indicating improper heat treatment. Due to this, ductility and impact toughness values were considerably lower than the specification of the mentioned grade. Residual stress measurement of one more bent shaft manufactured by a similar route was done by portable X-ray diffraction(XRD) technique. For better understanding, measurements were done at twelve different locations along the length of the shaft. The occurrence of a high amount of undesirable tensile residual stresses close to the Ultimate Tensile Strength(UTS) of the material was observed. Untempered martensitic structure, lower ductility, lower impact strength, and presence of a high amount of residual stresses all confirmed the improper tempering heat treatment of the shaft. Tempering relieves the residual stresses. Based on the findings of this study, stress-relieving heat treatment was done to remove the residual stresses and deflection in the shaft successfully.

Keywords: residual stress, mandrel shaft, untempered martensite, portable XRD

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Authors: N. P. Bhandary, R. C. Tiwari, R. Yatabe

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The research employs finite element method to evaluate the stability of roadside settlements slopes from Barpak to Yamagaon through Laprak village of Gorkha, Nepal after the 7.8Mw 2015 Barpak, Gorkha, Nepal earthquake. It includes three major villages of Gorkha, i.e., Barpak, Laprak and Yamagaun that were devastated by 2015 Gorkhas’ earthquake. The road head distance from the Barpak to Laprak and Laprak to Yamagaun are about 14 and 29km respectively. The epicentral distance of main shock of magnitude 7.8 and aftershock of magnitude 6.6 were respectively 7 and 11 kilometers (South-East) far from the Barpak village nearer to Laprak and Yamagaon. It is also believed that the epicenter of the main shock as said until now was not in the Barpak village, it was somewhere near to the Yamagaun village. The chaos that they had experienced during the earthquake in the Yamagaun was much more higher than the Barpak. In this context, we have carried out a detailed study to investigate the stability of Yamagaun settlements slope as a case study, where ground fissures, ground settlement, multiple cracks and toe failures are the most severe. In this regard, the stability issues of existing settlements and proposed road alignment, on the Yamagaon village slope are addressed, which is surrounded by many newly activated landslides. Looking at the importance of this issue, field survey is carried out to understand the behavior of ground fissures and multiple failure characteristics of the slopes. The results suggest that the Yamgaun slope in Profile 2-2, 3-3 and 4-4 are not safe enough for infrastructure development even in the normal soil slope conditions as per 2, 3 and 4 material models; however, the slope seems quite safe for at Profile 1-1 for all 4 material models. The result also indicates that the first three profiles are marginally safe for 2, 3 and 4 material models respectively. The Profile 4-4 is not safe enough for all 4 material models. Thus, Profile 4-4 needs a special care to make the slope stable.

Keywords: earthquake, finite element method, landslide, stability

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Authors: Ghadeer Mohammad Said El-Sheikh, Samer Mohamad Shalhoob

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Medical equipment operation state is a valid reflection of health care organizations' performance, where such equipment highly contributes to the quality of healthcare services on several levels in which quality improvement has become an intrinsic part of the discourse and activities of health care services. In healthcare organizations, clinical and biomedical engineering departments play an essential role in maintaining the safety and efficiency of such equipment. One of the most challenging topics when it comes to such sophisticated equipment is the lifespan of medical equipment, where many factors will impact such characteristics of medical equipment through its life cycle. So far, many attempts have been made in order to address this issue where most of the approaches are kind of arbitrary approaches and one of the criticisms of existing approaches trying to estimate and understand the lifetime of a medical equipment lies under the inquiry of what are the environmental factors that can play into such a critical characteristic of a medical equipment. In an attempt to address this shortcoming, the purpose of our study rises where in addition to the standard technical factors taken into consideration through the decision-making process by a clinical engineer in case of medical equipment failure, the dimension of environmental factors shall be added. The investigations, researches and studies applied for the purpose of supporting the decision making process by a clinical engineers and assessing the lifespan of healthcare equipment’s in the Lebanese society was highly dependent on the identification of technical criteria’s that impacts the lifespan of a medical equipment where the affecting environmental factors didn’t receive the proper attention. The objective of our study is based on the need for introducing a new well-designed plan for evaluating medical equipment depending on two dimensions. According to this approach, the equipment that should be replaced or repaired will be classified based on a systematic method taking into account two essential criteria; the standard identified technical criteria and the added environmental criteria.

Keywords: technical, environmental, healthcare, characteristic of medical equipment

Procedia PDF Downloads 154

Authors: Hakim Herbane

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Efforts to achieve sustainability in architecture must prove their effectiveness despite various methods attempted. Biomimicry, which looks to successful natural models to promote sustainability and innovation, faces obstacles in implementing sustainability despite its restorative approach to the relationship between humans and nature. In Nunavik, Inuit communities are exploring a sustainable production system that aligns with their aspirations and meets their demands of human, technological, technical, economic, and ecological factors. Biomimicry holds promise in line with Inuit philosophy, but its failure to implement sustainability requires further investigations to remedy its deficiencies. Our literature review underscores the importance of involving the community in defining sustainability and determining the best methods for its implementation. Additionally, vernacular architecture shows valuable orientations for achieving sustainability. Moreover, reintegrating Inuit communities and their traditional architectural practices, which have successfully balanced their built environment's diverse needs and constraints, could pave the way for a sustainable Inuit-built environment in Nunavik and advance architectural biomimicry principles simultaneously. This research aims at establishing a sustainability monitoring tool for Nordic architectural process by analyzing Inuit vernacular and biomimetic architecture, in addition to the input of stakeholders involved in Inuit architecture production in Nunavik, especially Inuit. The goal is to create a practical tool (an index) to aid in designing sustainable architecture, taking into account environmental, social, and economic perspectives. Furthermore, the study seeks to authenticate strong, sustainable design principles of vernacular and biomimetic architectures. The literature review uncovered challenges and identified new opportunities. The forthcoming discourse will focus on the careful and considerate incorporation of Inuit communities’ perceptions and indigenous building practices into our methodology and the latest findings of our research.

Keywords: sustainability, biomimicry, vernacular architecture, community involvement

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Authors: Sharon Waichman, Shahaf Froim, Ido Zukerman, Shmuel Barzilai, Shmual Hayun, Avi Raveh

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Boron carbide is a ceramic material with superior properties such as high chemical and thermal stability, high hardness and high wear resistance. Moreover, it has a big cross section for neutron absorption and therefore can be employed in nuclear based applications. However, an efficient attachment of boron carbide to a metal such as aluminum can be very challenging, mainly because of the formation of aluminum-carbon bonds that are unstable in humid environment, the affinity of oxygen to the metal and the different thermal expansion coefficients of the two materials that may cause internal stresses and a subsequent failure of the bond. Here, we aimed to achieving a strong and a durable attachment between the boron carbide coating and the aluminum substrate. For this purpose, we applied Ti as a thin intermediate layer that provides a gradual change in the thermal expansion coefficients of the configured layers. This layer is continuous and therefore prevents the formation of aluminum-carbon bonds. Boron carbide coatings with a thickness of 1-5 µm were deposited on the aluminum substrate by pulse-DC magnetron sputtering. Prior to the deposition of the boron carbide layer, the surface was pretreated by energetic ion plasma followed by deposition of the Ti intermediate adhesive layer in a continuous process. The properties of the Ti intermediate layer were adjusted by the bias applied to the substrate. The boron carbide/aluminum bond was evaluated by various methods and complementary techniques, such as SEM/EDS, XRD, XPS, FTIR spectroscopy and Glow Discharge Spectroscopy (GDS), in order to explore the structure, composition and the properties of the layers and to study the adherence mechanism of the boron carbide/aluminum contact. Based on the interfacial bond characteristics, we propose a desirable solution for improved adhesion of boron carbide to aluminum using a highly efficient intermediate adhesive layer.

Keywords: adhesion, boron carbide coatings, ceramic/metal bond, intermediate layer, pulsed-DC magnetron sputtering

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Authors: Dineshsingh Thakur, S. Nagesh, J. Basha

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A lightweight High Speed Flexible Coupling (HSFC) is used to connect the Engine Gear Box (EGB) with an Accessory Gear Box (AGB) of the combat aircraft. The HSFC transmits the power at high speeds ranging from 10000 to 18000 rpm from the EGB to AGB. The HSFC is also accommodates larger misalignments resulting from thermal expansion of the aircraft engine and mounting arrangement. The HSFC has the series of metallic contoured annular thin cross-sectioned flexible plates to accommodate the misalignments. The flexible plates are accommodating the misalignment by the elastic material flexure. As the HSFC operates at higher speed, the flexural and axial resonance frequencies are to be kept away from the operating speed and proper prediction is required to prevent failure in the transmission line of a single engine fighter aircraft. To study the influence of flexible plate’s contour on the lateral critical speed (LCS) of HSFC, a mathematical model of HSFC as a elven rotor system is developed. The flexible plate being the bending member of the system, its bending stiffness which results from the contoured governs the LCS. Using transfer matrix method, Influence of various flexible plate contours on critical speed is analyzed. In the above analysis, the support bearing flexibility on critical speed prediction is also considered. Based on the study, a model is built with the optimum contour of flexible plate, for validation by experimental modal analysis. A good correlation between the theoretical prediction and model behavior is observed. From the study, it is found that the flexible plate’s contour is playing vital role in modification of system’s dynamic behavior and the present model can be extended for the development of similar type of flexible couplings for its computational simplicity and reliability.

Keywords: flexible rotor, critical speed, experimental modal analysis, high speed flexible coupling (HSFC), misalignment

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Authors: Sherif D. El Wakil, John Rice

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The aim of the current work was to employ the finite element method to model a slab, with a small hole across its width, undergoing plastic plane strain deformation. The computational model had, however, to be validated by comparing its results with those obtained experimentally. Since they were in good agreement, the finite element method can therefore be considered a reliable tool that can help gain better understanding of the mechanism of ductile failure in structural members having stress raisers. The finite element software used was ANSYS, and the PLANE183 element was utilized. It is a higher order 2-D, 8-node or 6-node element with quadratic displacement behavior. A bilinear stress-strain relationship was used to define the material properties, with constants similar to those of the material used in the experimental study. The model was run for several tensile loads in order to observe the progression of the plastic deformation region, and the stress concentration factor was determined in each case. The experimental study involved employing the visioplasticity technique, where a circular mesh (each circle was 0.5 mm in diameter, with 0.05 mm line thickness) was initially printed on the side of an aluminum slab having a small hole across its width. Tensile loading was then applied to produce a small increment of plastic deformation. Circles in the plastic region became ellipses, where the directions of the principal strains and stresses coincided with the major and minor axes of the ellipses. Next, we were able to determine the directions of the maximum and minimum shear stresses at the center of each ellipse, and the slip-line field was then constructed. We were then able to determine the stress at any point in the plastic deformation zone, and hence the stress concentration factor. The experimental results were found to be in good agreement with the analytical ones.

Keywords: finite element method to model a slab, slab undergoing plastic deformation, stress distribution around a circular hole, visioplasticity

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Authors: Marcin Zieliński, Marcin Dębowski, Mirosław Krzemieniewski

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The anaerobic degradation of substrates is limited especially by the rate and effectiveness of the first (hydrolytic) stage of fermentation. This stage may be intensified through pre-treatment of substrate aimed at disintegration of the solid phase and destruction of substrate tissues and cells. The most frequently applied criterion of disintegration outcomes evaluation is the increase in biogas recovery owing to the possibility of its use for energetic purposes and, simultaneously, recovery of input energy consumed for the pre-treatment of substrate before fermentation. Hydrodynamic cavitation is one of the methods for organic substrate disintegration that has a high implementation potential. Cavitation is explained as the phenomenon of the formation of discontinuity cavities filled with vapor or gas in a liquid induced by pressure drop to the critical value. It is induced by a varying field of pressures. A void needs to occur in the flow in which the pressure first drops to the value close to the pressure of saturated vapor and then increases. The process of cavitation conducted under controlled conditions was found to significantly improve the effectiveness of anaerobic conversion of organic substrates having various characteristics. This phenomenon allows effective damage and disintegration of cellular and tissue structures. Disintegration of structures and release of organic compounds to the dissolved phase has a direct effect on the intensification of biogas production in the process of anaerobic fermentation, on reduced dry matter content in the post-fermentation sludge as well as a high degree of its hygienization and its increased susceptibility to dehydration. A device the efficiency of which was confirmed both in laboratory conditions and in systems operating in the technical scale is a hydrodynamic generator of cavitation. Cavitators, agitators and emulsifiers constructed and tested worldwide so far have been characterized by low efficiency and high energy demand. Many of them proved effective under laboratory conditions but failed under industrial ones. The only task successfully realized by these appliances and utilized on a wider scale is the heating of liquids. For this reason, their usability was limited to the function of heating installations. Design of the presented cavitation generator allows achieving satisfactory energy efficiency and enables its use under industrial conditions in depolymerization processes of biomass with various characteristics. Investigations conducted on the laboratory and industrial scale confirmed the effectiveness of applying cavitation in the process of biomass destruction. The use of the cavitation generator in laboratory studies for disintegration of sewage sludge allowed increasing biogas production by ca. 30% and shortening the treatment process by ca. 20 - 25%. The shortening of the technological process and increase of wastewater treatment plant effectiveness may delay investments aimed at increasing system output. The use of a mechanical cavitator and application of repeated cavitation process (4-6 times) enables significant acceleration of the biogassing process. In addition, mechanical cavitation accelerates increases in COD and VFA levels.

Keywords: hydrodynamic cavitation, pretreatment, biomass, methane fermentation, Virginia fanpetals

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Authors: Thomas Heffernan, Nick Neave, Colin Hamilton, Gill Case

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Hoarding is the acquisition of and failure to discard possessions, leading to excessive clutter and significant psychological/emotional distress. From a cognitive-behavioural approach, excessive hoarding arises from information-processing deficits, as well as from problems with emotional attachment to possessions and beliefs about the nature of possessions. In terms of information processing, hoarders have shown deficits in executive functions, including working memory, planning, inhibitory control, and cognitive flexibility. However, this previous research is often confounded by co-morbid factors such as anxiety, depression, or obsessive-compulsive disorder. The current study adopted a cognitive-behavioural approach, specifically assessing executive deficits and working memory in a non-clinical sample of hoarders, compared with non-hoarders. In this study, a non-clinical sample of 40 hoarders and 73 non-hoarders (defined by The Savings Inventory-Revised) completed the Adult Executive Functioning Inventory, which measures working memory and inhibition, Dysexecutive Questionnaire-Revised, which measures general executive function and the Hospital Anxiety and Depression Scale, which measures mood. The participant sample was made up of unpaid young adult volunteers who were undergraduate students and who completed the questionnaires on a university campus. The results revealed that, after observing no differences between hoarders and non-hoarders on age, sex, and mood, hoarders reported significantly more deficits in inhibitory control and general executive function when compared with non-hoarders. There was no between-group difference on general working memory. This suggests that non-clinical hoarders have a specific difficulty with inhibition-control, which enables you to resist repeated, unwanted urges. This might explain the hoarder’s inability to resist urges to buy and keep items that are no longer of any practical use. These deficits may be underpinned by general executive function deficiencies.

Keywords: hoarding, memory, executive, deficits

Procedia PDF Downloads 191

Authors: Eki Farlen, Akas

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Condition assessment of oil-paper-insulated power transformers, particularly of water content, is becoming increasingly important for aged transformers. As insulation ages, it can produce water, which reduces its dielectric strength, accelerates the cellulose ageing process, and causes gas bubbles to form at high temperatures. This paper mainly assesses the life condition of oil-paper insulation system of Inter Bus Transformer (IBT) 30 MVA, 150/30 kV in PT PLN-Substation Jelok that has been operating for 41 years, since 1974. Valuable information about the condition of high voltage insulation may be obtained by measuring its dielectric response. This paper describes in detail the interpretation of Dielectric Response Analysis (DIRANA) measurements and the test result compared to other insulation tests to get deep information for diagnostic, such as Tan delta test, oil characteristic test and Dissolve Gas Analysis (DGA) test. This paper mainly discusses the parameter relationship between moisture content, water content, acidity, oil conductivity and dissipation factor. The result and analysis show that IBT 30 MVA Jelok phase U and W had just been ageing due to high acidity level (>0.2 mgKOH/g) which cause high moisture in cellulose/paper (%) are in wet category about 4.7% and 5% and water content in oil (ppm) about 3.13 ppm and 3.33 ppm at temperature 20°C. High acidity level can make oxidation process and produce water in paper and particle which can decrease the value of Interfacial Tension (IFT) below 22 mN/m (poor category) for both phase U and W. Even if paper insulation of transformer are in wet condition, dissipation factor and capacitance at the same frequency (50 Hz) from both measurement DIRANA test and Tangent delta test give the same result (almost), the results are 0.69% and 0.71% (<1%), it may be acceptable and should not be investigated. The DGA results show that TDCG are in level one (1) condition and there are no found a Key Gases, it means that transformers had no failure during operation like arching, partial discharge and thermal in oil or cellulose.

Keywords: diagnostic, inter-bus transformer, oil-paper insulation, moisture, dissipation factor

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Authors: Aathira Peedikaparambil Somasundaran

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The beginning of the 20th century marked the perios when a new generation of Lebanese radicals sowed the seeds for the second phase of Levant literary modernism, situated in the Levant. Beirut, during this era popularly fit every radical writer’s criterion owing to its weakened censorship and political control, despite the absence of a protective womb for the development of literary modernism, caused by the natively prevalent political unsettlement. The third stage of literary modernization, in which scholars used Western-inspired critical techniques to better understand their own cultures, coincides with the time period examined in this paper, which involved the international-inspired critical analysis of native cultural stimulants, which raised questions among Arab freethinking intellectuals. Locals who ventured outside recognised the difference between the West's progress and their own nations' stagnation. The awareness of such ‘gap of success’ aroused an ambition from journalists, authors, and proletarian revolutionaries who had studied in Europe, and finally developed enlightened ideas. Some Middle Eastern authors and artists only adopted current social and political frameworks after discovering western modernity. After learning about the upheavals that were happening in the West, these thinkers aspired to bring about equally broad drastic developments in their own country's social, political, and cultural milieu. These occurrences illustrate the increased power of migration to alter the cultural and literary scene in the Levant. The paper intends to discuss the different effects of migration that contributed to Levant literary modernism. The exploration of these factors as causes begins with addressing the politically influenced activism, that has always been a relevant part of Beirut, and then diving into the psychological effects of migration in the individuals of the society, which might have induced an accommodability to alien thoughts and ideas over time, as a coping mechanism. Nature or environmental stimuli, a common trigger for any creative output, often having the highest influence during travel will be identified and analysed to inspect the extent of its impact on the exchange of ideas that resulted in Levant modernism. The efficiency of both the stimulating component of travel and the diaspora of the indigenous, a by-product of travel in catalysing modernism in the Levant has to be proven in order to understand how migration indirectly affected the transmission and adoption of ideas in Levant literature. The paper will revisit the events revolving around these key players and platforms like Shir, to understand how the Lebanese literature, tied down in poetry drastically mutated under the leadership of Adonis, Yusuf et Khal, and other pioneers of Levant literary modernism. The conclision will identify the triggers that helped authors overcome personal and geographical barriers to unite the West and the Levant, and investigate the extent to which the bi-directional migration prompted a transformation in the local poetry. Consequently, the paper aims to shed light into the unique factor that provoked the shift in the literary scene of Twentieth century in the Middle East.

Keywords: literature, modernism, Middle East, levant, Beirut

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Authors: Vrushali Guhe, Shailza Singh

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Cutaneous leishmaniasis is neglected tropical disease present worldwide caused by the protozoan parasite Leishmania major, the therapeutic armamentarium for leishmaniasis are showing several limitations as drugs are showing toxic effects with increasing resistance by a parasite. Thus identification of novel therapeutic targets is of paramount importance. Previous studies have shown that autophagy, a cellular process, can either facilitate infection or aid in the elimination of the parasite, depending on the specific parasite species and host background in leishmaniasis. In the present study, our objective was to target the essential autophagy protein ATG8, which plays a crucial role in the survival, infection dynamics, and differentiation of the Leishmania parasite. ATG8 in Leishmania major and its homologue, LC3, in Homo sapiens, act as autophagic markers. Present study manifested the crucial role of ATG8 protein as a potential target for combating Leishmania major infection. Through bioinformatics analysis, we identified non-conserved motifs within the ATG8 protein of Leishmania major, which are not present in LC3 of Homo sapiens. Against these two non-conserved motifs, we generated a peptide library of 60 peptides on the basis of physicochemical properties. These peptides underwent a filtering process based on various parameters, including feasibility of synthesis and purification, compatibility with Selective Reaction Monitoring (SRM)/Multiple reaction monitoring (MRM), hydrophobicity, hydropathy index, average molecular weight (Mw average), monoisotopic molecular weight (Mw monoisotopic), theoretical isoelectric point (pI), and half-life. Further filtering criterion shortlisted three peptides by using molecular docking and molecular dynamics simulations. The direct interaction between ATG8 and the shortlisted peptides was confirmed through Surface Plasmon Resonance (SPR) experiments. Notably, these peptides exhibited the remarkable ability to penetrate the parasite membrane and exert profound effects on Leishmania major. The treatment with these peptides significantly impacted parasite survival, leading to alterations in the cell cycle and morphology. Furthermore, the peptides were found to modulate autophagosome formation, particularly under starved conditions, suggesting their involvement in disrupting the regulation of autophagy within Leishmania major. In vitro, studies demonstrated that the selected peptides effectively reduced the parasite load within infected host cells. Encouragingly, these findings were corroborated by in vivo experiments, which showed a reduction in parasite burden upon peptide administration. Additionally, the peptides were observed to affect the levels of LC3II within host cells. In conclusion, our findings highlight the efficacy of these novel peptides in targeting Leishmania major’s ATG8 and disrupting parasite survival. These results provide valuable insights into the development of innovative therapeutic strategies against leishmaniasis via targeting autophagy protein ATG8 of Leishmania major.

Keywords: ATG8, leishmaniasis, surface plasmon resonance, MD simulation, molecular docking, peptide designing, therapeutics

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Authors: Xiaomin Zhong, Alexander Pate, Ya-Ting Yang, Ali Fahmi, Darren M. Ashcroft, Ben Goldacre, Brian Mackenna, Amir Mehrkar, Sebastian C. J. Bacon, Jon Massey, Louis Fisher, Peter Inglesby, Kieran Hand, Tjeerd van Staa, Victoria Palin

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Background: This study aimed to predict risks of potentially inappropriate antibiotic type and repeat prescribing and assess changes during COVID-19. Methods: With the approval of NHS England, we used the OpenSAFELY platform to access the TPP SystmOne electronic health record (EHR) system and selected patients prescribed antibiotics from 2019 to 2021. Multinomial logistic regression models predicted the patient’s probability of receiving an inappropriate antibiotic type or repeating the antibiotic course for each common infection. Findings: The population included 9.1 million patients with 29.2 million antibiotic prescriptions. 29.1% of prescriptions were identified as repeat prescribing. Those with same-day incident infection coded in the EHR had considerably lower rates of repeat prescribing (18.0%), and 8.6% had a potentially inappropriate type. No major changes in the rates of repeat antibiotic prescribing during COVID-19 were found. In the ten risk prediction models, good levels of calibration and moderate levels of discrimination were found. Important predictors included age, prior antibiotic prescribing, and region. Patients varied in their predicted risks. For sore throat, the range from 2.5 to 97.5th percentile was 2.7 to 23.5% (inappropriate type) and 6.0 to 27.2% (repeat prescription). For otitis externa, these numbers were 25.9 to 63.9% and 8.5 to 37.1%, respectively. Interpretation: Our study found no evidence of changes in the level of inappropriate or repeat antibiotic prescribing after the start of COVID-19. Repeat antibiotic prescribing was frequent and varied according to regional and patient characteristics. There is a need for treatment guidelines to be developed around antibiotic failure and clinicians provided with individualised patient information.

Keywords: antibiotics, infection, COVID-19 pandemic, antibiotic stewardship, primary care

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