Search results for: structural polymorphism
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4540

Search results for: structural polymorphism

3250 Design an Assessment Model of Research and Development Capabilities with the New Product Development Approach: A Case Study of Iran Khodro Company

Authors: Hamid Hanifi, Adel Azar, Alireza Booshehri

Abstract:

In order to know about the capability level of R & D units in automotive industry, it is essential that organizations always compare themselves with standard level and higher than themselves so that to be improved continuously. In this research, with respect to the importance of this issue, we have tried to present an assessment model for R & D capabilities having reviewed on new products development in automotive industry of Iran. Iran Khodro Company was selected for the case study. To this purpose, first, having a review on the literature, about 200 indicators effective in R & D capabilities and new products development were extracted. Then, of these numbers, 29 indicators which were more important were selected by industry and academia experts and the questionnaire was distributed among statistical population. Statistical population was consisted of 410 individuals in Iran Khodro Company. We used the 410 questionnaires for exploratory factor analysis and then used the data of 308 questionnaires from the same population randomly for confirmatory factor analysis. The results of exploratory factor analysis led to categorization of dimensions in 9 secondary dimensions. Naming the dimensions was done according to a literature review and the professors’ opinion. Using structural equation modeling and AMOS software, confirmatory factor analysis was conducted and ultimate model with 9 secondary dimensions was confirmed. Meanwhile, 9 secondary dimensions of this research are as follows: 1) Research and design capability, 2) Customer and market capability, 3) Technology capability, 4) Financial resources capability, 5) Organizational chart, 6) Intellectual capital capability, 7) NPD process capability, 8) Managerial capability and 9) Strategy capability.

Keywords: research and development, new products development, structural equations, exploratory factor analysis, confirmatory factor analysis

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3249 Water Governance Perspectives on the Urmia Lake Restoration Process: Challenges and Achievements

Authors: Jalil Salimi, Mandana Asadi, Naser Fathi

Abstract:

Urmia Lake (UL) has undergone a significant decline in water levels, resulting in severe environmental, socioeconomic, and health-related challenges. This paper examines the restoration process of UL from a water governance perspective. By applying a water governance model, the study evaluates the process based on six selected principles: stakeholder engagement, transparency and accountability, effectiveness, equitable water use, adaptation capacity, and water usage efficiency. The dominance of structural and physicalist approaches to water governance has led to a weak understanding of social and environmental issues, contributing to social crises. Urgent efforts are required to address the water crisis and reform water governance in the country, making water-related issues a top national priority. The UL restoration process has achieved significant milestones, including stakeholder consensus, scientific and participatory planning, environmental vision, intergenerational justice considerations, improved institutional environment for NGOs, investments in water infrastructure, transparency promotion, environmental effectiveness, and local issue resolutions. However, challenges remain, such as power distribution imbalances, bureaucratic administration, weak conflict resolution mechanisms, financial constraints, accountability issues, limited attention to social concerns, overreliance on structural solutions, legislative shortcomings, program inflexibility, and uncertainty management weaknesses. Addressing these weaknesses and challenges is crucial for the successful restoration and sustainable governance of UL.

Keywords: evaluation, restoration process, Urmia Lake, water governance, water resource management

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3248 Trade Openness, Productivity Growth And Economic Growth: Nigeria’s Experience

Authors: S. O. Okoro

Abstract:

Some words become the catch phrase of a particular decade. Globalization, Openness, and Privatization are certainly among the most frequently encapsulation of 1990’s; the market is ‘in’, ‘the state is out’. In the 1970’s, there were many political economists who spoke of autarky as one possible response to global economic forces. Be self-contained, go it alone, put up barriers to trans-nationalities, put in place import-substitution industrialization policy and grow domestic industries. In 1990’s, the emasculation of the state is by no means complete, but there is an acceptance that the state’s power is circumscribed by forces beyond its control and potential leverage. Autarky is no longer as a policy option. Nigeria, since its emergence as an independent nation, has evolved two macroeconomic management regimes of the interventionist and market friendly styles. This paper investigates Nigeria’s growth performance over the periods incorporating these two regimes and finds that there is no structural break in Total Factor Productivity, (TFP) growth and besides, the TFP growth over the entire period of study 1970-2012 is very negligible and hence growth can only be achieved by the unsustainable factor accumulation. Another important finding of this work is that the openness-human capital interaction term has a significant impact on the TFP growth, but the sign of the estimated coefficient does not meet it a theoretical expectation. This is because the negative coefficient on the human capital outweighs the positive openness effect. The poor quality of human capital is considered to have given rise to this. Given these results a massive investment in the education sector is required. The investment should be targeted at reforms that go beyond mere structural reforms to a reform agenda that will improve the quality of human capital in Nigeria.

Keywords: globalization, emasculation, openness and privatization, total factor productivity

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3247 The Quality of Business Relationships in the Tourism System: An Imaginary Organisation Approach

Authors: Armando Luis Vieira, Carlos Costa, Arthur Araújo

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The tourism system is viewable as a network of relationships amongst business partners where the success of each actor will ultimately be determined by the success of the whole network. Especially since the publication of Gümmesson’s (1996) ‘theory of imaginary organisations’, which suggests that organisational effectiveness largely depends on managing relationships and sharing resources and activities, relationship quality (RQ) has been increasingly recognised as a main source of value creation and competitive advantage. However, there is still ambiguity around this topic, and managers and researchers have been recurrently reporting the need to better understand and capitalise on the quality of interactions with business partners. This research aims at testing an RQ model from a relational, imaginary organisation’s approach. Two mail surveys provide the perceptions of 725 hotel representatives about their business relationships with tour operators, and 1,224 corporate client representatives about their business relationships with hotels (21.9 % and 38.8 % response rate, respectively). The analysis contributes to enhance our understanding on the linkages between RQ and its determinants, and identifies the role of their dimensions. Structural equation modelling results highlight trust as the dominant dimension, the crucial role of commitment and satisfaction, and suggest customer orientation as complementary building block. Findings also emphasise problem solving behaviour and selling orientation as the most relevant dimensions of customer orientation. The comparison of the two ‘dyads’ deepens the discussion and enriches the suggested theoretical and managerial guidelines concerning the contribution of quality relationships to business performance.

Keywords: corporate clients, destination competitiveness, hotels, relationship quality, structural equations modelling, tour operators

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3246 Computational Insights Into Allosteric Regulation of Lyn Protein Kinase: Structural Dynamics and Impacts of Cancer-Related Mutations

Authors: Mina Rabipour, Elena Pallaske, Floyd Hassenrück, Rocio Rebollido-Rios

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Protein tyrosine kinases, including Lyn kinase of the Src family kinases (SFK), regulate cell proliferation, survival, and differentiation. Lyn kinase has been implicated in various cancers, positioning it as a promising therapeutic target. However, the conserved ATP-binding pocket across SFKs makes developing selective inhibitors challenging. This study aims to address this limitation by exploring the potential for allosteric modulation of Lyn kinase, focusing on how its structural dynamics and specific oncogenic mutations impact its conformation and function. To achieve this, we combined homology modeling, molecular dynamics simulations, and data science techniques to conduct microsecond-length simulations. Our approach allowed a detailed investigation into the interplay between Lyn’s catalytic and regulatory domains, identifying key conformational states involved in allosteric regulation. Additionally, we evaluated the structural effects of Dasatinib, a competitive inhibitor, and ATP binding on Lyn active conformation. Notably, our simulations show that cancer-related mutations, specifically I364L/N and E290D/K, shift Lyn toward an inactive conformation, contrasting with the active state of the wild-type protein. This may suggest how these mutations contribute to aberrant signaling in cancer cells. We conducted a dynamical network analysis to assess residue-residue interactions and the impact of mutations on the Lyn intramolecular network. This revealed significant disruptions due to mutations, especially in regions distant from the ATP-binding site. These disruptions suggest potential allosteric sites as therapeutic targets, offering an alternative strategy for Lyn inhibition with higher specificity and fewer off-target effects compared to ATP-competitive inhibitors. Our findings provide insights into Lyn kinase regulation and highlight allosteric sites as avenues for selective drug development. Targeting these sites may modulate Lyn activity in cancer cells, reducing toxicity and improving outcomes. Furthermore, our computational strategy offers a scalable approach for analyzing other SFK members or kinases with similar properties, facilitating the discovery of selective allosteric modulators and contributing to precise cancer therapies.

Keywords: lyn tyrosine kinase, mutation analysis, conformational changes, dynamic network analysis, allosteric modulation, targeted inhibition

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3245 Public Debt Shocks and Public Goods Provisioning in Nigeria: Implication for National Development

Authors: Amenawo I. Offiong, Hodo B. Riman

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Public debt profile of Nigeria has continuously been on the increase over the years. The drop in international crude oil prices has further worsened revenue position of the country, thus, necessitating further acquisition of public debt to bridge the gap in revenue deficit. Yet, when we look back at the increasing public sector spending, there are concerns that the government spending do not amount to increase in public goods provided for the country. Using data from 1980 to 2014 the study therefore seeks to investigate the factors responsible for the poor provision of public goods in the face of increasing public debt profile. Using the unrestricted VAR model Governance and Tax revenue were introduced into the model as structural variables. The result suggested that governance and tax revenue were structural determinants of the effectiveness of public goods provisioning in Nigeria. The study therefore identified weak governance as the major reason for the non-provision of public goods in Nigeria. While tax revenue exerted positive influence on the provisions of public goods, weak/poor governance was observed to crowd the benefits from increase tax revenue. The study therefore recommends reappraisal of the governance system in Nigeria. Elected officers in governance should be more transparent and accountable to the electorates they represent. Furthermore, the study advocates for an annual auditing of all government MDAs accounts by external auditors to ensure (a) accountability of public debts utilization, (b) transparent in implementation of program support funds, (c) integrity of agencies responsible for program management, and (d) measuring program effectiveness with amount of funds expended.

Keywords: impulse response function, public debt shocks, governance, public goods, tax revenue, vector auto-regression

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3244 Elements of a Culture of Quality in the Implementation of Quality Assurance Systems of Countries in the European Higher Education Area

Authors: Laura Mion

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The implementation of quality management systems in higher education in different countries is determined by national regulatory choices and supranational indications (such as the European Standard Guidelines for Quality Assurance). The effective functioning and transformative capacity of these quality management systems largely depend on the organizational context in which they are applied and, more specifically, on the culture of quality developed in single universities or in single countries. The University's concept of quality culture integrates the structural dimension of QA (quality management manuals, process definitions, tools) with the value dimension of an organization (principles, skills, and attitudes). Within the EHEA (European Higher Education Area), countries such as Portugal, the Netherlands, the UK, and Norway demonstrate a greater integration of QA principles in the various organizational levels and areas of competence of university institutions or have greater experience in implementation or scientific and political debate on the matter. Therefore, the study, through an integrative literature review, of the quality management systems of these countries is aimed at determining a framework of the culture of quality, helpful in defining the elements which, both in structural-organizational terms and in terms of values and skills and attitudes, have proved to be factors of success in the effective implementation of quality assurance systems in universities and in the countries considered in the research. In order for a QA system to effectively aim for continuous improvement in a complex and dynamic context such as the university one, it must embrace a holistic vision of quality from an integrative perspective, focusing on the objective of transforming the reality being evaluated.

Keywords: higher education, quality assurance, quality culture, Portugal, Norway, Netherlands, United Kingdom

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3243 Structural Equation Modeling Approach: Modeling the Impact of Social Marketing Programs on Combating Female Genital Mutilation in the Sudanese Society

Authors: Nada Abdelsadig Moahamed Saied

Abstract:

Female Genital Mutilation (FGM) and other similar traditional cultural practices pose a significant problem for Sudanese society. Such actions are severe and seriously detrimental to people's health since they are based on false social perceptions. To address these problems, numerous institutions and organizations were compelled to act rapidly. Female circumcision, or FGM, is one of the riskiest practices. It is referred to as the excision of the genitalia. Any surgeries involving the total or partial removal of the external female genitalia for non-medical reasons fall under this category. The results of FGM can vary depending on the kind and degree of the operation. These can be categorized as short-term, mid-term, or long-term issues. Infections, including the Human, blood, discomfort, and difficulty urinating are the immediate effects. FGM is defined by the World Health Organization (WHO) as practices that purposefully damage or modify female genital organs for non-medical purposes. It often takes place between the ages of one and fifteen. The girl's right to decide on important choices affecting her sexual and reproductive health is violated because the act is usually performed without her consent and frequently against her will. UNICEF, the United Nations International Children's Emergency Fund, aggressively combats the issue of FGM in Sudan. Numerous programs were started by NGOs to stop the practice. To our knowledge, no scientific study has been conducted to evaluate the effects of such social marketing techniques on simulating and comprehending society’s feelings surrounding FGM. This study proposes the development of a structural equation model aiming to determine the impact of awareness programs on people’s intentions to adopt the behavior of abandoning FGM based on theoretical models of behavior change. The model incorporates all the relevant factors that contribute to FGM and possible strategic actions to tackle this problem. The theoretical backdrop for FGM is presented in the next section, which also explains the practice's history, justifications, and potential treatments. The methodology section that follows describes the structural equation model. The proposed model, which compiles all the pertinent elements into a single image, is presented in the fourth part. Finally, conclusions are reached, and suggestions for further research are made.

Keywords: social marketing, policy-making, behavioral change, female genital mutilation, culture

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3242 Assets and Health: Examining the Asset-Building Theoretical Framework and Psychological Distress

Authors: Einav Srulovici, Michal Grinstein-Weiss, George Knafl, Linda Beeber, Shawn Kneipp, Barbara Mark

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Background: The asset-building theoretical framework (ABTF) is acknowledged as the most complete framework thus far for depicting the relationships between asset accumulation (the stock of a household’s saved resources available for future investment) and health outcomes. Although the ABTF takes into consideration the reciprocal relationship between asset accumulation and health, no ABTF based study has yet examined this relationship. Therefore, the purpose of this study was to test the ABTF and psychological distress, focusing on the reciprocal relationship between assets accumulation and psychological distress. Methods: The study employed longitudinal data from 6,295 families from the 2001 and 2007 Panel Study of Income Dynamics data sets. Structural equation modeling (SEM) was used to test the reciprocal relationship between asset accumulation and psychological distress. Results: In general, the data displayed a good fit to the model. The longitudinal SEM found that asset accumulation significantly increased with a decreased in psychological distress over time, while psychological distress significantly increased with an increase in asset accumulation over time, confirming the existence of the hypothesized reciprocal relationship. Conclusions: Individuals who are less psychological distressed might have more energy to engage in activities, such as furthering their education or obtaining better jobs that are in turn associated with greater asset accumulation, while those who have greater assets may invest those assets in riskier investments, resulting in increased psychological distress. The confirmation of this reciprocal relationship highlights the importance of conducting longitudinal studies and testing the reciprocal relationship between asset accumulation and other health outcomes.

Keywords: asset-building theoretical framework, psychological distress, structural equation modeling, reciprocal relationship

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3241 Reservoir Potential, Net Pay Zone and 3D Modeling of Cretaceous Clastic Reservoir in Eastern Sulieman Belt Pakistan

Authors: Hadayat Ullah, Pervez Khalid, Saad Ahmed Mashwani, Zaheer Abbasi, Mubashir Mehmood, Muhammad Jahangir, Ehsan ul Haq

Abstract:

The aim of the study is to explore subsurface structures through data that is acquired from the seismic survey to delineate the characteristics of the reservoir through petrophysical analysis. Ghazij Shale of Eocene age is regional seal rock in this field. In this research work, 3D property models of subsurface were prepared by applying Petrel software to identify various lithologies and reservoir fluids distribution throughout the field. The 3D static modeling shows a better distribution of the discrete and continuous properties in the field. This model helped to understand the reservoir properties and enhance production by selecting the best location for future drilling. A complete workflow is proposed for formation evaluation, electrofacies modeling, and structural interpretation of the subsurface geology. Based on the wireline logs, it is interpreted that the thickness of the Pab Sandstone varies from 250 m to 350 m in the entire study area. The sandstone is massive with high porosity and intercalated layers of shales. Faulted anticlinal structures are present in the study area, which are favorable for the accumulation of hydrocarbon. 3D structural models and various seismic attribute models were prepared to analyze the reservoir character of this clastic reservoir. Based on wireline logs and seismic data, clean sand, shaly sand, and shale are marked as dominant facies in the study area. However, clean sand facies are more favorable to act as a potential net pay zone.

Keywords: cretaceous, pab sandstone, petrophysics, electrofacies, hydrocarbon

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3240 Finite Element Analysis of a Glass Facades Supported by Pre-Tensioned Cable Trusses

Authors: Khair Al-Deen Bsisu, Osama Mahmoud Abuzeid

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Significant technological advances have been achieved in the design and building construction of steel and glass in the last two decades. The metal glass support frame has been replaced by further sophisticated technological solutions, for example, the point fixed glazing systems. The minimization of the visual mass has reached extensive possibilities through the evolution of technology in glass production and the better understanding of the structural potential of glass itself, the technological development of bolted fixings, the introduction of the glazing support attachments of the glass suspension systems and the use for structural stabilization of cables that reduce to a minimum the amount of metal used. The variability of solutions of tension structures, allied to the difficulties related to geometric and material non-linear behavior, usually overrules the use of analytical solutions, letting numerical analysis as the only general approach to the design and analysis of tension structures. With the characteristics of low stiffness, lightweight, and small damping, tension structures are obviously geometrically nonlinear. In fact, analysis of cable truss is not only one of the most difficult nonlinear analyses because the analysis path may have rigid-body modes, but also a time consuming procedure. Non-linear theory allowing for large deflections is used. The flexibility of supporting members was observed to influence the stresses in the pane considerably in some cases. No other class of architectural structural systems is as dependent upon the use of digital computers as are tensile structures. Besides complexity, the process of design and analysis of tension structures presents a series of specificities, which usually lead to the use of special purpose programs, instead of general purpose programs (GPPs), such as ANSYS. In a special purpose program, part of the design know how is embedded in program routines. It is very probable that this type of program will be the option of the final user, in design offices. GPPs offer a range of types of analyses and modeling options. Besides, traditional GPPs are constantly being tested by a large number of users, and are updated according to their actual demands. This work discusses the use of ANSYS for the analysis and design of tension structures, such as cable truss structures under wind and gravity loadings. A model to describe the glass panels working in coordination with the cable truss was proposed. Under the proposed model, a FEM model of the glass panels working in coordination with the cable truss was established.

Keywords: Glass Construction material, Facades, Finite Element, Pre-Tensioned Cable Truss

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3239 Moderating and Mediating Effects of Business Model Innovation Barriers during Crises: A Structural Equation Model Tested on German Chemical Start-Ups

Authors: Sarah Mueller-Saegebrecht, André Brendler

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Business model innovation (BMI) as an intentional change of an existing business model (BM) or the design of a new BM is essential to a firm's development in dynamic markets. The relevance of BMI is also evident in the ongoing COVID-19 pandemic, in which start-ups, in particular, are affected by limited access to resources. However, first studies also show that they react faster to the pandemic than established firms. A strategy to successfully handle such threatening dynamic changes represents BMI. Entrepreneurship literature shows how and when firms should utilize BMI in times of crisis and which barriers one can expect during the BMI process. Nevertheless, research merging BMI barriers and crises is still underexplored. Specifically, further knowledge about antecedents and the effect of moderators on the BMI process is necessary for advancing BMI research. The addressed research gap of this study is two-folded: First, foundations to the subject on how different crises impact BM change intention exist, yet their analysis lacks the inclusion of barriers. Especially, entrepreneurship literature lacks knowledge about the individual perception of BMI barriers, which is essential to predict managerial reactions. Moreover, internal BMI barriers have been the focal point of current research, while external BMI barriers remain virtually understudied. Second, to date, BMI research is based on qualitative methodologies. Thus, a lack of quantitative work can specify and confirm these qualitative findings. By focusing on the crisis context, this study contributes to BMI literature by offering a first quantitative attempt to embed BMI barriers into a structural equation model. It measures managers' perception of BMI development and implementation barriers in the BMI process, asking the following research question: How does a manager's perception of BMI barriers influence BMI development and implementation in times of crisis? Two distinct research streams in economic literature explain how individuals react when perceiving a threat. "Prospect Theory" claims that managers demonstrate risk-seeking tendencies when facing a potential loss, and opposing "Threat-Rigidity Theory" suggests that managers demonstrate risk-averse behavior when facing a potential loss. This study quantitively tests which theory can best predict managers' BM reaction to a perceived crisis. Out of three in-depth interviews in the German chemical industry, 60 past BMIs were identified. The participating start-up managers gave insights into their start-up's strategic and operational functioning. After, each interviewee described crises that had already affected their BM. The participants explained how they conducted BMI to overcome these crises, which development and implementation barriers they faced, and how severe they perceived them, assessed on a 5-point Likert scale. In contrast to current research, results reveal that a higher perceived threat level of a crisis harms BM experimentation. Managers seem to conduct less BMI in times of crisis, whereby BMI development barriers dampen this relation. The structural equation model unveils a mediating role of BMI implementation barriers on the link between the intention to change a BM and the concrete BMI implementation. In conclusion, this study confirms the threat-rigidity theory.

Keywords: barrier perception, business model innovation, business model innovation barriers, crises, prospect theory, start-ups, structural equation model, threat-rigidity theory

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3238 The Effect of Jujube Extract and Resistance Training on the Reduction of Complications Caused by the Induction of Anabolic Steroid Boldenone on the Histopathological Changes of Pancreatic Tissue of Male Wistar Rats

Authors: Sayyed-javad Ziaolhagh, Ali-Reza Saadatifar

Abstract:

Introduction: Athletes frequently perform anabolic steroid resistance exercise, but the effects of medical doses and abuse along with resistance exercise on structural damage to the Pancreases and also jujube extract are unknown. The aim of this study was to investigate the effects of resistance training on body weight and hip fractures induced by boldenone injection in male rats. Materials and methods: In this experimental study, 30 male Wistar rats aged 8-12 weeks (weight 202±9.34 g) were randomly divided into five groups: control, boldenone, extract of iujuba+boldenone, boldenone+resistance training and boldenone+resistance training +extract of jujuba. The resistance training program included climbing the ladder for 8 weeks, 3 days a week, 1 session training in a day and each session consisted of the 3 sets and 5 repetitions. Injection was conducted in depth in the hamstring once a week on an appointed day. After anesthesia, autopsy was performed, and the cardiac tissue was isolated. Results: Results showed that boldenone caused tissue damage, congestion, and nuclei unclear and diffuse. In the group "resistance + Boldenone," The Pancreases tissue showed a high degree of hyperemia, and the muscle cells were somewhat abnormal. In boldenone + jujube, the appearance of the tissue was normal, and the rejuvenating effect was visible. Conclusion: Boldenone appears to cause structural damage to the Pancreases tissue. Strength training with Jujube Extract can reduce part of the pancreatic system disorders (necrosis and inflammation) caused by anabolic steroid use.

Keywords: boldenone, Jujube extract, pancreases tissue, resistance training

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3237 Influence of Strengthening with Perforated Steel Plates on the Behavior of Infill Walls and RC Frame

Authors: Eray Ozbek, Ilker Kalkan, S. Oguzhan Akbas, Sabahattin Aykac

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The contribution of the infill walls to the overall earthquake response of a structure is limited and this contribution is generally ignored in the analyses. Strengthening of the infill walls through different techniques has been and is being studied extensively in the literature to increase this limited contribution and the ductilities and energy absorption capacities of the infill walls to create non-structural components where the earthquake-induced energy can be absorbed without damaging the bearing components of the structural frame. The present paper summarizes an extensive research project dedicated to investigate the effects of strengthening the brick infill walls of a reinforced concrete (RC) frame on its lateral earthquake response. Perforated steel plates were used in strengthening due to several reasons, including the ductility and high deformation capacity of these plates, the fire resistant, recyclable and non-cancerogenic nature of mild steel, and the ease of installation and removal of the plates to the wall with the help of anchor bolts only. Furthermore, epoxy, which increases the cost and amount of labor of the strengthening process, is not needed in this technique. The individual behavior of the strengthened walls under monotonic diagonal and lateral reversed cyclic loading was investigated within the scope of the study. Upon achieving brilliant results, RC frames with strengthened infill walls were tested and are being tested to examine the influence of this strengthening technique on the overall behavior of the RC frames. Tests on the wall and frame specimens indicated that the perforated steel plates contribute to the lateral strength, rigidity, ductility and energy absorption capacity of the wall and the infilled frame to a major extent.

Keywords: infill wall, strengthening, external plate, earthquake behavior

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3236 Genome-Wide Identification and Characterization of MLO Family Genes in Pumpkin (Cucurbita maxima Duch.)

Authors: Khin Thanda Win, Chunying Zhang, Sanghyeob Lee

Abstract:

Mildew resistance locus o (Mlo), a plant-specific gene family with seven-transmembrane (TM), plays an important role in plant resistance to powdery mildew (PM). PM caused by Podosphaera xanthii is a widespread plant disease and probably represents the major fungal threat for many Cucurbits. The recent Cucurbita maxima genome sequence data provides an opportunity to identify and characterize the MLO gene family in this species. Total twenty genes (designated CmaMLO1 through CmaMLO20) have been identified by using an in silico cloning method with the MLO gene sequences of Cucumis sativus, Cucumis melo, Citrullus lanatus and Cucurbita pepo as probes. These CmaMLOs were evenly distributed on 15 chromosomes of 20 C. maxima chromosomes without any obvious clustering. Multiple sequence alignment showed that the common structural features of MLO gene family, such as TM domains, a calmodulin-binding domain and 30 important amino acid residues for MLO function, were well conserved. Phylogenetic analysis of the CmaMLO genes and other plant species reveals seven different clades (I through VII) and only clade IV is specific to monocots (rice, barley, and wheat). Phylogenetic and structural analyses provided preliminary evidence that five genes belonged to clade V could be the susceptibility genes which may play the importance role in PM resistance. This study is the first comprehensive report on MLO genes in C. maxima to our knowledge. These findings will facilitate the functional analysis of the MLOs related to PM susceptibility and are valuable resources for the development of disease resistance in pumpkin.

Keywords: Mildew resistance locus o (Mlo), powdery mildew, phylogenetic relationship, susceptibility genes

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3235 Comparing Business Excellence Models Using Quantitative Methods: A First Step

Authors: Mohammed Alanazi, Dimitrios Tsagdis

Abstract:

Established Business Excellence Models (BEMs), like the Malcolm Baldrige National Quality Award (MBNQA) model and the European Foundation for Quality Management (EFQM) model, have been adopted by firms all over the world. They exist alongside more recent country-specific BEMs; e.g. the Australian, Canadian, China, New Zealand, Singapore, and Taiwan quality awards that although not as widespread as MBNQA and EFQM have nonetheless strong national followings. Regardless of any differences in their following or prestige, the emergence and development of all BEMs have been shaped both by their local context (e.g. underlying socio-economic dynamics) as well as by global best practices. Besides such similarities, that render them into objects (i.e. models) of the same class (i.e. BEMs), BEMs exhibit non-trivial differences in their criteria, relations, and emphasis. Given the evolution of BEMs (e.g. the MBNQA underwent seven evolutions since its inception in 1987 while the EFQM five since 1993), it is unsurprising that comparative studies of their validity are few and far in between. This poses challenges for practitioners and policy makers alike; as it is not always clear which BEM is to be preferred or better fitting to a particular context. Especially, in contexts that differ substantially from the original context of BEM development. This paper aims to fill this gap by presenting a research design and measurement model for comparing BEMs using quantitative methods (e.g. structural equations). Three BEMs will be focused upon in particular for illustration purposes; the MBNQA, the EFQM, and the King Abdul Aziz Quality Award (KAQA) model. They have been selected so to reflect the two established and widely spread traditions as well as a more recent context-specific arrival promising a better fit.

Keywords: Baldrige, business excellence, European Foundation for Quality Management, Structural Equation Model, total quality management

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3234 Mechanisms and Regulation of the Bi-directional Motility of Mitotic Kinesin Nano-motors

Authors: Larisa Gheber

Abstract:

Mitosis is an essential process by which duplicated genetic information is transmitted from mother to daughter cells. Incorrect chromosome segregation during mitosis can lead to genetic diseases, chromosome instability and cancer. This process is mediated by a dynamic microtubule-based intracellular structure, the mitotic spindle. One of the major factors that govern the mitotic spindle dynamics are the kinesin-5 biological nano motors that were believed to move unidirectionally on the microtubule filaments, using ATP hydrolysis, thus performing essential functions in mitotic spindle dynamics. Surprisingly, several reports from our and other laboratories have demonstrated that some kinesin-5 motors are bi-directional: they move in minus-end direction on the microtubules as single-molecules and can switch directionality under a number of conditions. These findings broke a twenty-five-years old dogma regarding kinesin directionality (1, 2). The mechanism of this bi-directional motility and its physiological significance remain unclear. To address this unresolved problem, we apply an interdisciplinary approach combining live cell imaging, biophysical single molecule, and structural experiments to examine the activity of these motors and their mutated variants in vivo and in vitro. Our data shows that factors such as protein phosphorylation (3, 4), motor clustering on the microtubules (5, 6) and structural elements (7, 8) regulate the bi-directional motility of kinesin motors. We also show, using Cryo-EM, that bi-directional kinesin motors obtain non-canonical microtubule binding, which is essential to their special motile properties and intracellular functions. We will discuss the implication of these findings to mechanism bi-directional motility and physiological roles in mitosis.

Keywords: mitosis, cancer, kinesin, microtubules, biochemistry, biophysics

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3233 Developing and Shake Table Testing of Semi-Active Hydraulic Damper as Active Interaction Control Device

Authors: Ming-Hsiang Shih, Wen-Pei Sung, Shih-Heng Tung

Abstract:

Semi-active control system for structure under excitation of earthquake provides with the characteristics of being adaptable and requiring low energy. DSHD (Displacement Semi-Active Hydraulic Damper) was developed by our research team. Shake table test results of this DSHD installed in full scale test structure demonstrated that this device brought its energy-dissipating performance into full play for test structure under excitation of earthquake. The objective of this research is to develop a new AIC (Active Interaction Control Device) and apply shake table test to perform its dissipation of energy capability. This new proposed AIC is converting an improved DSHD (Displacement Semi-Active Hydraulic Damper) to AIC with the addition of an accumulator. The main concept of this energy-dissipating AIC is to apply the interaction function of affiliated structure (sub-structure) and protected structure (main structure) to transfer the input seismic force into sub-structure to reduce the structural deformation of main structure. This concept is tested using full-scale multi-degree of freedoms test structure, installed with this proposed AIC subjected to external forces of various magnitudes, for examining the shock absorption influence of predictive control, stiffness of sub-structure, synchronous control, non-synchronous control and insufficient control position. The test results confirm: (1) this developed device is capable of diminishing the structural displacement and acceleration response effectively; (2) the shock absorption of low precision of semi-active control method did twice as much seismic proof efficacy as that of passive control method; (3) active control method may not exert a negative influence of amplifying acceleration response of structure; (4) this AIC comes into being time-delay problem. It is the same problem of ordinary active control method. The proposed predictive control method can overcome this defect; (5) condition switch is an important characteristics of control type. The test results show that synchronism control is very easy to control and avoid stirring high frequency response. This laboratory results confirm that the device developed in this research is capable of applying the mutual interaction between the subordinate structure and the main structure to be protected is capable of transforming the quake energy applied to the main structure to the subordinate structure so that the objective of minimizing the deformation of main structural can be achieved.

Keywords: DSHD (Displacement Semi-Active Hydraulic Damper), AIC (Active Interaction Control Device), shake table test, full scale structure test, sub-structure, main-structure

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3232 Kou Jump Diffusion Model: An Application to the SP 500; Nasdaq 100 and Russell 2000 Index Options

Authors: Wajih Abbassi, Zouhaier Ben Khelifa

Abstract:

The present research points towards the empirical validation of three options valuation models, the ad-hoc Black-Scholes model as proposed by Berkowitz (2001), the constant elasticity of variance model of Cox and Ross (1976) and the Kou jump-diffusion model (2002). Our empirical analysis has been conducted on a sample of 26,974 options written on three indexes, the S&P 500, Nasdaq 100 and the Russell 2000 that were negotiated during the year 2007 just before the sub-prime crisis. We start by presenting the theoretical foundations of the models of interest. Then we use the technique of trust-region-reflective algorithm to estimate the structural parameters of these models from cross-section of option prices. The empirical analysis shows the superiority of the Kou jump-diffusion model. This superiority arises from the ability of this model to portray the behavior of market participants and to be closest to the true distribution that characterizes the evolution of these indices. Indeed the double-exponential distribution covers three interesting properties that are: the leptokurtic feature, the memory less property and the psychological aspect of market participants. Numerous empirical studies have shown that markets tend to have both overreaction and under reaction over good and bad news respectively. Despite of these advantages there are not many empirical studies based on this model partly because probability distribution and option valuation formula are rather complicated. This paper is the first to have used the technique of nonlinear curve-fitting through the trust-region-reflective algorithm and cross-section options to estimate the structural parameters of the Kou jump-diffusion model.

Keywords: jump-diffusion process, Kou model, Leptokurtic feature, trust-region-reflective algorithm, US index options

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3231 Probabilistic Crash Prediction and Prevention of Vehicle Crash

Authors: Lavanya Annadi, Fahimeh Jafari

Abstract:

Transportation brings immense benefits to society, but it also has its costs. Costs include such as the cost of infrastructure, personnel and equipment, but also the loss of life and property in traffic accidents on the road, delays in travel due to traffic congestion and various indirect costs in terms of air transport. More research has been done to identify the various factors that affect road accidents, such as road infrastructure, traffic, sociodemographic characteristics, land use, and the environment. The aim of this research is to predict the probabilistic crash prediction of vehicles using machine learning due to natural and structural reasons by excluding spontaneous reasons like overspeeding etc., in the United States. These factors range from weather factors, like weather conditions, precipitation, visibility, wind speed, wind direction, temperature, pressure, and humidity to human made structures like road structure factors like bump, roundabout, no exit, turning loop, give away, etc. Probabilities are dissected into ten different classes. All the predictions are based on multiclass classification techniques, which are supervised learning. This study considers all crashes that happened in all states collected by the US government. To calculate the probability, multinomial expected value was used and assigned a classification label as the crash probability. We applied three different classification models, including multiclass Logistic Regression, Random Forest and XGBoost. The numerical results show that XGBoost achieved a 75.2% accuracy rate which indicates the part that is being played by natural and structural reasons for the crash. The paper has provided in-deep insights through exploratory data analysis.

Keywords: road safety, crash prediction, exploratory analysis, machine learning

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3230 Modeling and Simulation of Honeycomb Steel Sandwich Panels under Blast Loading

Authors: Sayed M. Soleimani, Nader H. Ghareeb, Nourhan H. Shaker, Muhammad B. Siddiqui

Abstract:

Honeycomb sandwich panels have been widely used as protective structural elements against blast loading. The main advantages of these panels include their light weight due to the presence of voids, as well as their energy absorption capability. Terrorist activities have imposed new challenges to structural engineers to design protective measures for vital structures. Since blast loading is not usually considered in the load combinations during the design process of a structure, researchers around the world have been motivated to study the behavior of potential elements capable of resisting sudden loads imposed by the detonation of explosive materials. One of the best candidates for this objective is the honeycomb sandwich panel. Studying the effects of explosive materials on the panels requires costly and time-consuming experiments. Moreover, these type of experiments need permission from defense organizations which can become a hurdle. As a result, modeling and simulation using an appropriate tool can be considered as a good alternative. In this research work, the finite element package ABAQUS® is used to study the behavior of hexagonal and squared honeycomb steel sandwich panels under the explosive effects of different amounts of trinitrotoluene (TNT). The results of finite element modeling of a specific honeycomb configuration are initially validated by comparing them with the experimental results from literature. Afterwards, several configurations including different geometrical properties of the honeycomb wall are investigated and the results are compared with the original model. Finally, the effectiveness of the core shape and wall thickness are discussed, and conclusions are made.

Keywords: Abaqus, blast loading, finite element modeling, steel honeycomb sandwich panel

Procedia PDF Downloads 353
3229 Non-Linear Load-Deflection Response of Shape Memory Alloys-Reinforced Composite Cylindrical Shells under Uniform Radial Load

Authors: Behrang Tavousi Tehrani, Mohammad-Zaman Kabir

Abstract:

Shape memory alloys (SMA) are often implemented in smart structures as the active components. Their ability to recover large displacements has been used in many applications, including structural stability/response enhancement and active structural acoustic control. SMA wires or fibers can be embedded with composite cylinders to increase their critical buckling load, improve their load-deflection behavior, and reduce the radial deflections under various thermo-mechanical loadings. This paper presents a semi-analytical investigation on the non-linear load-deflection response of SMA-reinforced composite circular cylindrical shells. The cylinder shells are under uniform external pressure load. Based on first-order shear deformation shell theory (FSDT), the equilibrium equations of the structure are derived. One-dimensional simplified Brinson’s model is used for determining the SMA recovery force due to its simplicity and accuracy. Airy stress function and Galerkin technique are used to obtain non-linear load-deflection curves. The results are verified by comparing them with those in the literature. Several parametric studies are conducted in order to investigate the effect of SMA volume fraction, SMA pre-strain value, and SMA activation temperature on the response of the structure. It is shown that suitable usage of SMA wires results in a considerable enhancement in the load-deflection response of the shell due to the generation of the SMA tensile recovery force.

Keywords: airy stress function, cylindrical shell, Galerkin technique, load-deflection curve, recovery stress, shape memory alloy

Procedia PDF Downloads 188
3228 Excited State Structural Dynamics of Retinal Isomerization Revealed by a Femtosecond X-Ray Laser

Authors: Przemyslaw Nogly, Tobias Weinert, Daniel James, Sergio Carbajo, Dmitry Ozerov, Antonia Furrer, Dardan Gashi, Veniamin Borin, Petr Skopintsev, Kathrin Jaeger, Karol Nass, Petra Bath, Robert Bosman, Jason Koglin, Matthew Seaberg, Thomas Lane, Demet Kekilli, Steffen Brünle, Tomoyuki Tanaka, Wenting Wu, Christopher Milne, Thomas A. White, Anton Barty, Uwe Weierstall, Valerie Panneels, Eriko Nango, So Iwata, Mark Hunter, Igor Schapiro, Gebhard Schertler, Richard Neutze, Jörg Standfuss

Abstract:

Ultrafast isomerization of retinal is the primary step in a range of photoresponsive biological functions including vision in humans and ion-transport across bacterial membranes. We studied the sub-picosecond structural dynamics of retinal isomerization in the light-driven proton pump bacteriorhodopsin using an X-ray laser. Twenty snapshots with near-atomic spatial and temporal resolution in the femtosecond regime show how the excited all-trans retinal samples conformational states within the protein binding pocket prior to passing through a highly-twisted geometry and emerging in the 13-cis conformation. The aspartic acid residues and functional water molecules in proximity of the retinal Schiff base respond collectively to formation and decay of the initial excited state and retinal isomerization. These observations reveal how the protein scaffold guides this remarkably efficient photochemical reaction.

Keywords: bacteriorhodopsin, free-electron laser, retinal isomerization mechanism, time-resolved crystallography

Procedia PDF Downloads 248
3227 Dimensionality Reduction in Modal Analysis for Structural Health Monitoring

Authors: Elia Favarelli, Enrico Testi, Andrea Giorgetti

Abstract:

Autonomous structural health monitoring (SHM) of many structures and bridges became a topic of paramount importance for maintenance purposes and safety reasons. This paper proposes a set of machine learning (ML) tools to perform automatic feature selection and detection of anomalies in a bridge from vibrational data and compare different feature extraction schemes to increase the accuracy and reduce the amount of data collected. As a case study, the Z-24 bridge is considered because of the extensive database of accelerometric data in both standard and damaged conditions. The proposed framework starts from the first four fundamental frequencies extracted through operational modal analysis (OMA) and clustering, followed by density-based time-domain filtering (tracking). The fundamental frequencies extracted are then fed to a dimensionality reduction block implemented through two different approaches: feature selection (intelligent multiplexer) that tries to estimate the most reliable frequencies based on the evaluation of some statistical features (i.e., mean value, variance, kurtosis), and feature extraction (auto-associative neural network (ANN)) that combine the fundamental frequencies to extract new damage sensitive features in a low dimensional feature space. Finally, one class classifier (OCC) algorithms perform anomaly detection, trained with standard condition points, and tested with normal and anomaly ones. In particular, a new anomaly detector strategy is proposed, namely one class classifier neural network two (OCCNN2), which exploit the classification capability of standard classifiers in an anomaly detection problem, finding the standard class (the boundary of the features space in normal operating conditions) through a two-step approach: coarse and fine boundary estimation. The coarse estimation uses classics OCC techniques, while the fine estimation is performed through a feedforward neural network (NN) trained that exploits the boundaries estimated in the coarse step. The detection algorithms vare then compared with known methods based on principal component analysis (PCA), kernel principal component analysis (KPCA), and auto-associative neural network (ANN). In many cases, the proposed solution increases the performance with respect to the standard OCC algorithms in terms of F1 score and accuracy. In particular, by evaluating the correct features, the anomaly can be detected with accuracy and an F1 score greater than 96% with the proposed method.

Keywords: anomaly detection, frequencies selection, modal analysis, neural network, sensor network, structural health monitoring, vibration measurement

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3226 Structural Characterization of TIR Domains Interaction

Authors: Sara Przetocka, Krzysztof Żak, Grzegorz Dubin, Tadeusz Holak

Abstract:

Toll-like receptors (TLRs) play central role in the innate immune response and inflammation by recognizing pathogen-associated molecular patterns (PAMPs). A fundamental basis of TLR signalling is dependent upon the recruitment and association of adaptor molecules that contain the structurally conserved Toll/interleukin-1 receptor (TIR) domain. MyD88 (myeloid differentiation primary response gene 88) is the universal adaptor for TLRs and cooperates with Mal (MyD88 adapter-like protein, also known as TIRAP) in TLR4 response which is predominantly used in inflammation, host defence and carcinogenesis. Up to date two possible models of MyD88, Mal and TLR4 interactions have been proposed. The aim of our studies is to confirm or abolish presented models and accomplish the full structural characterisation of TIR domains interaction. Using molecular cloning methods we obtained several construct of MyD88 and Mal TIR domain with GST or 6xHis tag. Gel filtration method as well as pull-down analysis confirmed that recombinant TIR domains from MyD88 and Mal are binding in complexes. To examine whether obtained complexes are homo- or heterodimers we carried out cross-linking reaction of TIR domains with BS3 compound combined with mass spectrometry. To investigate which amino acid residues are involved in this interaction the NMR titration experiments were performed. 15N MyD88-TIR solution was complemented with non-labelled Mal-TIR. The results undoubtedly indicate that MyD88-TIR interact with Mal-TIR. Moreover 2D spectra demonstrated that simultaneously Mal-TIR self-dimerization occurs which is necessary to create proper scaffold for Mal-TIR and MyD88-TIR interaction. Final step of this study will be crystallization of MyD88 and Mal TIR domains complex. This crystal structure and characterisation of its interface will have an impact in understanding the TLR signalling pathway and possibly will be used in development of new anti-cancer treatment.

Keywords: cancer, MyD88, TIR domains, Toll-like receptors

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3225 Condition Assessment of Reinforced Concrete Bridge Deck Using Ground Penetrating Radar

Authors: Azin Shakibabarough, Mojtaba Valinejadshoubi, Ashutosh Bagchi

Abstract:

Catastrophic bridge failure happens due to the lack of inspection, lack of design and extreme events like flooding, an earthquake. Bridge Management System (BMS) is utilized to diminish such an accident with proper design and frequent inspection. Visual inspection cannot detect any subsurface defects, so using Non-Destructive Evaluation (NDE) techniques remove these barriers as far as possible. Among all NDE techniques, Ground Penetrating Radar (GPR) has been proved as a highly effective device for detecting internal defects in a reinforced concrete bridge deck. GPR is used for detecting rebar location and rebar corrosion in the reinforced concrete deck. GPR profile is composed of hyperbola series in which sound hyperbola denotes sound rebar and blur hyperbola or signal attenuation shows corroded rebar. Interpretation of GPR images is implemented by numerical analysis or visualization. Researchers recently found that interpretation through visualization is more precise than interpretation through numerical analysis, but visualization is time-consuming and a highly subjective process. Automating the interpretation of GPR image through visualization can solve these problems. After interpretation of all scans of a bridge, condition assessment is conducted based on the generated corrosion map. However, this such a condition assessment is not objective and precise. Condition assessment based on structural integrity and strength parameters can make it more objective and precise. The main purpose of this study is to present an automated interpretation method of a reinforced concrete bridge deck through a visualization technique. In the end, the combined analysis of the structural condition in a bridge is implemented.

Keywords: bridge condition assessment, ground penetrating radar, GPR, NDE techniques, visualization

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3224 Enhanced Optical Nonlinearity in Bismuth Borate Glass: Effect of Size of Nanoparticles

Authors: Shivani Singla, Om Prakash Pandey, Gopi Sharma

Abstract:

Metallic nanoparticle doped glasses has lead to rapid development in the field of optics. Large third order non-linearity, ultrafast time response, and a wide range of resonant absorption frequencies make these metallic nanoparticles more important in comparison to their bulk material. All these properties are highly dependent upon the size, shape, and surrounding environment of the nanoparticles. In a quest to find a suitable material for optical applications, several efforts have been devoted to improve the properties of such glasses in the past. In the present study, bismuth borate glass doped with different size gold nanoparticles (AuNPs) has been prepared using the conventional melt-quench technique. Synthesized glasses are characterized by X-ray diffraction (XRD) and Fourier Transformation Infrared spectroscopy (FTIR) to observe the structural modification in the glassy matrix with the variation in the size of the AuNPs. Glasses remain purely amorphous in nature even after the addition of AuNPs, whereas FTIR proposes that the main structure contains BO₃ and BO₄ units. Field emission scanning electron microscopy (FESEM) confirms the existence and variation in the size of AuNPs. Differential thermal analysis (DTA) depicts that prepared glasses are thermally stable and are highly suitable for the fabrication of optical fibers. The nonlinear optical parameters (nonlinear absorption coefficient and nonlinear refractive index) are calculated out by using the Z-scan technique with a Ti: sapphire laser at 800 nm. It has been concluded that the size of the nanoparticles highly influences the structural thermal and optical properties system.

Keywords: bismuth borate glass, different size, gold nanoparticles, nonlinearity

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3223 Parametric Optimization of High-Performance Electric Vehicle E-Gear Drive for Radiated Noise Using 1-D System Simulation

Authors: Sanjai Sureshkumar, Sathish G. Kumar, P. V. V. Sathyanarayana

Abstract:

For e-gear drivetrain, the transmission error and the resulting variation in mesh stiffness is one of the main source of excitation in High performance Electric Vehicle. These vibrations are transferred through the shaft to the bearings and then to the e-Gear drive housing eventually radiating noise. A parametrical model developed in 1-D system simulation by optimizing the micro and macro geometry along with bearing properties and oil filtration to achieve least transmission error and high contact ratio. Histogram analysis is performed to condense the actual road load data into condensed duty cycle to find the bearing forces. The structural vibration generated by these forces will be simulated in a nonlinear solver obtaining the normal surface velocity of the housing and the results will be carried forward to Acoustic software wherein a virtual environment of the surrounding (actual testing scenario) with accurate microphone position will be maintained to predict the sound pressure level of radiated noise and directivity plot of the e-Gear Drive. Order analysis will be carried out to find the root cause of the vibration and whine noise. Broadband spectrum will be checked to find the rattle noise source. Further, with the available results, the design will be optimized, and the next loop of simulation will be performed to build a best e-Gear Drive on NVH aspect. Structural analysis will be also carried out to check the robustness of the e-Gear Drive.

Keywords: 1-D system simulation, contact ratio, e-Gear, mesh stiffness, micro and macro geometry, transmission error, radiated noise, NVH

Procedia PDF Downloads 149
3222 Carbon Blacks: A Broad Type of Carbon Materials with Different Electrocatalytic Activity to Produce H₂O₂

Authors: Alvaro Ramírez, Martín Muñoz-Morales, Ester López- Fernández, Javier Llanos, C. Ania

Abstract:

Carbon blacks are value-added materials typically produced through the incomplete combustion or thermal decomposition of hydrocarbons. Traditionally, they have been used as catalysts in many different applications, but in the last decade, their potential in green chemistry has gained significant attention. Among them, the electrochemical production of H₂O₂ has attracted interest because of their properties as high oxidant capacity or their industrial interest as a bleaching agent. Carbon blacks are commonly used in this application in a catalytic ink that is drop-casted on supporting electrodes and acts as catalysts for the electrochemical production of H₂O₂ through oxygen reduction reaction (ORR). However, the different structural and electrochemical behaviors of each type of carbon black influence their applications. In this line, the term ‘carbon black’, has to be considered as a generic name that does not guarantee any physicochemical properties if any further description is mentioned. In fact, different specific surface area (SSA), surface functional groups, porous structure, and electro catalysts effect seem very important for electrochemical applications, and considerable differences were found during the analysis of four types of carbon blacks. Thus, the aim of this work is to evaluate the influence of SSA, porous structure, oxygen functional groups, and structural defects to differentiate among these carbon blacks (e.g. Vulcan XC72, Superior Graphite Co, Printex XE2, and Prolabo) for H₂O₂ production via ORR, using carbon paper as electrode support with improved selectivity and efficiency. Results indicate that the number and size of pores, along with surface functional groups, are key parameters that significantly affect the overall process efficiency.

Keywords: carbon blacks, oxygen reduction reaction, hydrogen peroxide, porosity, surface functional groups

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3221 Genotypic and Allelic Distribution of Polymorphic Variants of Gene SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) and Their Association to the Clinical Response to Metformin in Adult Pakistani T2DM Patients

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

Abstract:

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

Keywords: diabetes, T2DM, SLC47A1, Pakistan, polymorphism

Procedia PDF Downloads 159