Search results for: competitive inhibitors
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1650

Search results for: competitive inhibitors

1380 Aza-Flavanones as Small Molecule Inhibitors of MicroRNA-10b in MDA-MB-231 Breast Cancer Cells

Authors: Debasmita Mukhopadhyay, Manika Pal Bhadra

Abstract:

MiRNAs contribute to oncogenesis either as tumor suppressors or oncogenes. Hence, discovery of miRNA-based therapeutics are imperative to ameliorate cancer. Modulation of miRNA maturation is accomplished via several therapeutic agents, including small molecules and oligonucleotides. Due to the attractive pharmacokinetic properties of small molecules over oligonucleotides, we set to identify small molecule inhibitors of a metastasis-inducing microRNA. Cytotoxicity profile of aza-flavanone C1 was analyzed in a panel of breast cancer cells employing the NCI-60 screen protocols. Flow cytometry, immunofluorescence and western blotting of apoptotic or EMT markers were performed to analyze the effect of C1. A dual luciferase assay unequivocally suggested that C1 repressed endogenous miR-10b in MDA-MB-231 cells. A derivative of aza-flavanone C1 is shown as a strong inhibitor miR-10b. Blockade of miR-10b by C1 resulted in decreased expression of miR-10b targets in an aggressive breast cancer cell line model, MDA-MB-231. Abrogation of TWIST1, an EMT-inducing transcription factor also contributed to C1 mediated apoptosis. Moreover C1 exhibited a specific and selective down-regulation of miR-10b and did not function as a general inhibitor of miRNA biogenesis or other oncomiRs of breast carcinoma. Aza-flavanone congener C1 functions as a potent inhibitor of the metastasis-inducing microRNA, miR-10b. Our present study provides evidence for targeting metastasis-inducing microRNA, miR-10b with a derivative of Aza-flavanone. Better pharmacokinetic properties of small molecules place them as attractive agents compared to nucleic acids based therapies to target miRNA. Further work, in generating analogues based on aza-flavanone moieties will significantly improve the affinity of the small molecules to bind miR-10b. Finally, it is imperative to develop small molecules as novel miRNA-therapeutics in the fight against cancer.

Keywords: breast cancer, microRNA, metastasis, EMT

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1379 In-Depth Analysis on Sequence Evolution and Molecular Interaction of Influenza Receptors (Hemagglutinin and Neuraminidase)

Authors: Dong Tran, Thanh Dac Van, Ly Le

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Hemagglutinin (HA) and Neuraminidase (NA) play an important role in host immune evasion across influenza virus evolution process. The correlation between HA and NA evolution in respect to epitopic evolution and drug interaction has yet to be investigated. In this study, combining of sequence to structure evolution and statistical analysis on epitopic/binding site specificity, we identified potential therapeutic features of HA and NA that show specific antibody binding site of HA and specific binding distribution within NA active site of current inhibitors. Our approach introduces the use of sequence variation and molecular interaction to provide an effective strategy in establishing experimental based distributed representations of protein-protein/ligand complexes. The most important advantage of our method is that it does not require complete dataset of complexes but rather directly inferring feature interaction from sequence variation and molecular interaction. Using correlated sequence analysis, we additionally identified co-evolved mutations associated with maintaining HA/NA structural and functional variability toward immunity and therapeutic treatment. Our investigation on the HA binding specificity revealed unique conserved stalk domain interacts with unique loop domain of universal antibodies (CR9114, CT149, CR8043, CR8020, F16v3, CR6261, F10). On the other hand, NA inhibitors (Oseltamivir, Zaninamivir, Laninamivir) showed specific conserved residue contribution and similar to that of NA substrate (sialic acid) which can be exploited for drug design. Our study provides an important insight into rational design and identification of novel therapeutics targeting universally recognized feature of influenza HA/NA.

Keywords: influenza virus, hemagglutinin (HA), neuraminidase (NA), sequence evolution

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1378 A Hybrid ICA-GA Algorithm for Solving Multiobjective Optimization of Production Planning Problems

Authors: Omar Ramzi Jasim, Jalal Sultan Ashour

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Production Planning or Master Production Schedule (MPS) is a key interface between marketing and manufacturing, since it links customer service directly to efficient use of production resources. Mismanagement of the MPS is considered as one of fundamental problems in operation and it can potentially lead to poor customer satisfaction. In this paper, a hybrid evolutionary algorithm (ICA-GA) is presented, which integrates the merits of both imperialist competitive algorithm (ICA) and genetic algorithm (GA) for solving multi-objective MPS problems. In the presented algorithm, the colonies in each empire has be represented a small population and communicate with each other using genetic operators. By testing on 5 production scenarios, the numerical results of ICA-GA algorithm show the efficiency and capabilities of the hybrid algorithm in finding the optimum solutions. The ICA-GA solutions yield the lower inventory level and keep customer satisfaction high and the required overtime is also lower, compared with results of GA and SA in all production scenarios.

Keywords: master production scheduling, genetic algorithm, imperialist competitive algorithm, hybrid algorithm

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1377 Essentiality of Core Strategic Vision in Continuous Cost Reduction Management

Authors: Lai Ving Kam

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Many markets are maturing, consumer buying powers are weakening and customer preferences change rapidly. To survive, many adopt fast paced continuous cost reduction and competitive pricing to remain relevance. Marketers desire to push for more sales to increase revenues have intensified competitions at time cannibalize the product and market. The amazing technologies changes have created both hope and despair to the industries. The pressure to constantly reduce cost, on the one hand, create and market new products in cheaper prices and shorter life cycles, on the other has become a continuous endeavour. The twin trends appear irreconcilable. Can core strategic vision provides and adapts new directions in continuous cost reduction? This study investigates core strategic vision able to meet this need, for firms to survive and stay profitable. Under current uncertainty market, are firms falling back on their core strategic visions to take them out of the unfavourable positions?

Keywords: core strategy vision, continuous cost reduction, fashionable products industry, competitive pricing

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1376 Facing Global Competition through Participation in Global Innovation Networks: The Case of Mechatronics District in the Veneto Region

Authors: Monica Plechero

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Many firms belonging to Italian industrial districts faced a crisis starting from 2000 and upsurging during 2008-2014. To remain competitive in the global market, these firms and their local systems need to renovate their traditional competitive advantages, strengthen their link with global flows of knowledge. This may be particularly relevant in sectors such as the mechatronics, that combine traditional knowledge domain with new knowledge domains (e.g. mechanics, electronics, and informatics). This sector is nowadays one of the key sectors within the so-called ‘smart specialization strategy’ that can lead part of the Italian traditional industry towards new economic developmental opportunities. This paper, by investigating the mechatronics district of the Veneto region, wants to shed new light on how firms of a local system can gain from the globalization of innovation and innovation networks. Methodologically, the paper relies on primary data collected through a survey targeting firms of the local system, as well as on a number of qualitative case studies. The relevant role of medium size companies in the district emerges as evident, as they have wider opportunities to be involved in different processes of globalization of innovation. Indeed, with respect to small companies, the size of medium firms allows them to exploit strategically international markets and globally distributed knowledge. Supporting medium firms’ global innovation strategies, and incentivizing their role as district gatekeepers, may strengthen the competitive capability of the local system and provide new opportunities to positively face global competition.

Keywords: global innovation network, industrial district, internationalization, innovation, mechatronics, Veneto region

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1375 Service Strategy And Innovation In The Food Service Industry: Basis For Designing A Competitive Advantage Model

Authors: Ma. Dina Datiles Jimenez

Abstract:

Service strategy and service Innovation has something to do with the success of the foodservice business. The foodservice business nowadays has become more competitive, and technology driven. This study aimed to determine and investigate the service innovation and strategies of the food service industry and the challenges during the pandemic to serve as the basis for a competitive advantage model. The study used mixed methods, including descriptive quantitative and qualitative methods. The Metro Manila foodservice managers were the target population of the study, which consisted of an estimated 1500 respondents from the selected cities. The assessment of service innovation for the following dimensions: product-related dimension; market-related dimension; process-related dimension; and organization-related dimension, when classified according to profile, was very large for age, gender, and educational attainment. When respondents are classified according to profile, the service strategy in terms of customer service strategy, after-sales service strategy, maintenance service strategy, research and development-oriented service strategy, and operational services strategy were all assessed with a very large extent of implementation. There was a significant difference in all four aspects of service innovation when classified based on age. However, for gender, only the market and process dimensions showed significant differences, while the product and organization conveyed no significant differences. Consequently, the evidence was not enough to prove that educational attainment differs from one another on the four aspects of service innovation. There was sufficient evidence to prove that the ages differ from one another in all aspects of service strategies. While gender and educational attainment showed no significant difference in the assessment of service strategies, Training on the trends in the foodservice industry during the pandemic is offered; technical maintenance is evident; the company allotted budget for outsourcing training; the quality control system; and online customer feedback were revealed as major indicators for service strategy. Fear of viruses, limited customers, a minimal work force, and low revenues were identified as challenges faced by the foodservice industry.

Keywords: foodservice industry, service innovation, service strategy, competitive advantage, sustainability, technology

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1374 The Impact of Information and Communication Technology in Knowledge Fraternization

Authors: Muhammad Aliyu

Abstract:

Significant improvement in Information and Communication Technology (ICT) and the enforced global competition are revolutionizing the way knowledge is managed and the way organizations compete. The emergence of new organizations calls for a new way to fraternize knowledge, which is known as 'knowledge fraternization.' In this modern economy, it is the knowledge if properly managed that can harness the organization's competitive advantage. This competitive advantage is realized through the full utilization of information and data coupled with the harnessing of people’s skills and ideas as well as their commitment and motivations, which can be accomplished through socializing the knowledge management processes. A fraternize network for knowledge management is a web-based system designed using PHP that is Dreamweaver web development tool, with the help of CS4 Adobe Dreamweaver as the PHP code Editor that supports the use of Cascadian Style Sheet (CSS), MySQL with Xamp, Php My Admin (Version 3.4.7) localhost server via TCP/IP for containing the databases of the system to support this in a distributed way, spreading the workload over the whole organization. This paper reviews the technologies and the technology tools to be used in the development of social networks in an organization.

Keywords: Information and Communication Technology (ICT), knowledge, fraternization, social network

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1373 Relations between Human Capital Investments and Business Excellence in Croatian Companies

Authors: Ivana Tadić, Željana Aljinović Barać, Nikolina Plazonić

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Living today in turbulent business environment forces companies to distinguish from each other, securing sustainable competitive growth and competitive advantage. The best possible solution is to invest (effort and financial resources) within companies’ different practices of human resource management (HRM), more specifically in employees’ knowledge, skills and abilities. Applying this approach companies will create enviable level of human capital securing its economic growth. Employees become human capital for their employers at the moment when they contribute with their own knowledge and abilities in creating material and non-material value of the company. The main aim of this research is to explore the relations between human capital investments and business excellence of Croatian companies. Furthermore, the differences in the level of human capital investments with regard to several companies’ characteristics (e.g. size of the company, ownership and type of the industry) are investigated.

Keywords: business excellence, Croatian industries, human capital investments, human resource management

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1372 Development of Immuno-Modulators: Application of Molecular Dynamics Simulation

Authors: Ruqaiya Khalil, Saman Usmani, Zaheer Ul-Haq

Abstract:

The accurate characterization of ligand binding affinity is indispensable for designing molecules with optimized binding affinity. Computational tools help in many directions to predict quantitative correlations between protein-ligand structure and their binding affinities. Molecular dynamics (MD) simulation is a modern state-of-the-art technique to evaluate the underlying basis of ligand-protein interactions by characterizing dynamic and energetic properties during the event. Autoimmune diseases arise from an abnormal immune response of the body against own tissues. The current regimen for the described condition is limited to immune-modulators having compromised pharmacodynamics and pharmacokinetics profiles. One of the key player mediating immunity and tolerance, thus invoking autoimmunity is Interleukin-2; a cytokine influencing the growth of T cells. Molecular dynamics simulation techniques are applied to seek insight into the inhibitory mechanisms of newly synthesized compounds that manifested immunosuppressant potentials during in silico pipeline. In addition to estimation of free energies associated with ligand binding, MD simulation yielded us a great deal of information about ligand-macromolecule interactions to evaluate the pattern of interactions and the molecular basis of inhibition. The present study is a continuum of our efforts to identify interleukin-2 inhibitors of both natural and synthetic origin. Herein, we report molecular dynamics simulation studies of Interluekin-2 complexed with different antagonists previously reported by our group. The study of protein-ligand dynamics enabled us to gain a better understanding of the contribution of different active site residues in ligand binding. The results of the study will be used as the guide to rationalize the fragment based synthesis of drug-like interleukin-2 inhibitors as immune-modulators.

Keywords: immuno-modulators, MD simulation, protein-ligand interaction, structure-based drug design

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1371 Developing an Advanced Algorithm Capable of Classifying News, Articles and Other Textual Documents Using Text Mining Techniques

Authors: R. B. Knudsen, O. T. Rasmussen, R. A. Alphinas

Abstract:

The reason for conducting this research is to develop an algorithm that is capable of classifying news articles from the automobile industry, according to the competitive actions that they entail, with the use of Text Mining (TM) methods. It is needed to test how to properly preprocess the data for this research by preparing pipelines which fits each algorithm the best. The pipelines are tested along with nine different classification algorithms in the realm of regression, support vector machines, and neural networks. Preliminary testing for identifying the optimal pipelines and algorithms resulted in the selection of two algorithms with two different pipelines. The two algorithms are Logistic Regression (LR) and Artificial Neural Network (ANN). These algorithms are optimized further, where several parameters of each algorithm are tested. The best result is achieved with the ANN. The final model yields an accuracy of 0.79, a precision of 0.80, a recall of 0.78, and an F1 score of 0.76. By removing three of the classes that created noise, the final algorithm is capable of reaching an accuracy of 94%.

Keywords: Artificial Neural network, Competitive dynamics, Logistic Regression, Text classification, Text mining

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1370 Intrinsic Contradictions in Entrepreneurship Development and Self-Development

Authors: Revaz Gvelesiani

Abstract:

The problem of compliance between the state economic policy and entrepreneurial policy of businesses is primarily manifested in the contradictions related to the congruence between entrepreneurship development and self-development strategies. Among various types (financial, monetary, social, etc.) of the state economic policy aiming at the development of entrepreneurship, economic order policy is of special importance. Its goal is to set the framework for both public and private economic activities and achieve coherence between the societal value system and the formation of the economic order framework. Economic order policy, in its turn, involves intrinsic contradiction between the social and the competitive order. Competitive order is oriented on the principle of success, while social order _ on the criteria of need satisfaction, which contradicts, at least partly, to the principles of success. Thus within the economic order policy, on the one hand, the state makes efforts to form social order and expand its frontiers, while, on the other hand, market is determined to establish functioning competitive order and ensure its realization. Locating the adequate spaces for and setting the rational border between the state (social order) and the private (competitive order) activities, represents the phenomenon of the decisive importance from the entrepreneurship development strategy standpoint. In the countries where the above mentioned spaces and borders are “set” correctly, entrepreneurship agents (small, medium-sized and large businesses) achieve great success by means of seizing the respective segments and maintaining the leading positions in the internal, the European and the world markets for a long time. As for the entrepreneurship self-development strategy, above all, it involves: •market identification; •interactions with consumers; •continuous innovations; •competition strategy; •relationships with partners; •new management philosophy, etc. The analysis of compliance between the entrepreneurship strategy and entrepreneurship culture should be the reference point for any kind of internationalization in order to avoid shocks of cultural nature and the economic backwardness. Stabilization can be achieved only when the employee actions reflect the existing culture and the new contents of culture (targeted culture) is turned into the implicit consciousness of the personnel. The future leaders should learn how to manage different cultures. Entrepreneurship can be managed successfully if its strategy and culture are coherent. However, not rarely enterprises (organizations) show various forms of violation of both personal and team actions. If personal and team non-observances appear as the form of influence upon the culture, it will lead to global destruction of the system and structure. This is the entrepreneurship culture pathology that complicates to achieve compliance between the entrepreneurship strategy and entrepreneurship culture. Thus, the intrinsic contradictions of entrepreneurship development and self-development strategies complicate the task of reaching compliance between the state economic policy and the company entrepreneurship policy: on the one hand, there is a contradiction between the social and the competitive order within economic order policy and on the other hand, the contradiction exists between entrepreneurship strategy and entrepreneurship culture within entrepreneurship policy.

Keywords: economic order policy, entrepreneurship, development contradictions, self-development contradictions

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1369 Trends and Prospects for the Development of Georgian Wine Market

Authors: E. Kharaishvili, M. Chavleishvili, M. Natsvaladze

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The article presents the trends in Georgian wine market development and evaluates the competitive advantages of Georgia to enter the wine market based on its customs, traditions and historical practices combined with modern technologies. In order to analyze the supply of wine, dynamics of vineyard land area and grape varieties are discussed, trends in wine production are presented, trends in export and import are evaluated, local wine market, its micro and macro environments are studied and analyzed based on the interviews with experts and analysis of initial recording materials. For strengthening its position on the international market, the level of competitiveness of Georgian wine is defined, which is evaluated by “ex-ante” and “ex-post” methods, as well as by four basic and two additional factors of the Porter’s diamond method; potential advantages and disadvantages of Georgian wine are revealed. Conclusions are made by identifying the factors that hinder the development of Georgian wine market. Based on the conclusions, relevant recommendations are developed.

Keywords: Georgian wine market, competitive advantage, bio wine, export-import, Porter's diamond model

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1368 A Location-Allocation-Routing Model for a Home Health Care Supply Chain Problem

Authors: Amir Mohammad Fathollahi Fard, Mostafa Hajiaghaei-Keshteli, Mohammad Mahdi Paydar

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With increasing life expectancy in developed countries, the role of home care services is highlighted by both academia and industrial contributors in Home Health Care Supply Chain (HHCSC) companies. The main decisions in such supply chain systems are the location of pharmacies, the allocation of patients to these pharmacies and also the routing and scheduling decisions of nurses to visit their patients. In this study, for the first time, an integrated model is proposed to consist of all preliminary and necessary decisions in these companies, namely, location-allocation-routing model. This model is a type of NP-hard one. Therefore, an Imperialist Competitive Algorithm (ICA) is utilized to solve the model, especially in large sizes. Results confirm the efficiency of the developed model for HHCSC companies as well as the performance of employed ICA.

Keywords: home health care supply chain, location-allocation-routing problem, imperialist competitive algorithm, optimization

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1367 Investigation into the Role of Leadership in the Management of Digital Transformation for Small and Medium Enterprises

Authors: Francesco Coraci, Abdul-Hadi G. Abulrub

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Digital technology is transforming the landscape of the industrial sector at a precedential level by connecting people, processes, and machines in real-time. It represents the means for a new pathway to achieve innovative, dynamic competitive advantages, deliver unique customers’ values, and sustain critical relationships. Thus, success in a constantly changing environment is governed by the ability of an organization to revolutionize their business models, deliver innovative solutions, and capture values from big data analytics and insights. Businesses need to re-strategize operations and develop extra capabilities to cope with the necessity for additional flexibility and agility. The traditional “command and control” leadership style is structurally and operationally incompatible with the digital era. In this paper, the authors discuss how transformational leaders can act as a glue in the social, organizational context, which is crucial to enable the workforce and develop a psychological attachment to the digital vision.

Keywords: internet of things, strategy, change leadership, dynamic competitive advantage, digital transformation

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1366 Identification of Analogues to EGCG for the Inhibition of HPV E7: A Fundamental Insights through Structural Dynamics Study

Authors: Murali Aarthy, Sanjeev Kumar Singh

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High risk human papillomaviruses are highly associated with the carcinoma of the cervix and the other genital tumors. Cervical cancer develops through the multistep process in which increasingly severe premalignant dysplastic lesions called cervical intraepithelial neoplastic progress to invasive cancer. The oncoprotein E7 of human papillomavirus expressed in the lower epithelial layers drives the cells into S-phase creating an environment conducive for viral genome replication and cell proliferation. The replication of the virus occurs in the terminally differentiating epithelium and requires the activation of cellular DNA replication proteins. To date, no suitable drug molecule is available to treat HPV infection whereas identification of potential drug targets and development of novel anti-HPV chemotherapies with unique mode of actions are expected. Hence, our present study aimed to identify the potential inhibitors analogous to EGCG, a green tea molecule which is considered to be safe to use for mammalian systems. A 3D similarity search on the natural small molecule library from natural product database using EGCG identified 11 potential hits based on their similarity score. The structure based docking strategies were implemented in the potential hits and the key interacting residues of protein with compounds were identified through simulation studies and binding free energy calculations. The conformational changes between the apoprotein and the complex were analyzed with the simulation and the results demonstrated that the dynamical and structural effects observed in the protein were induced by the compounds and indicated the dominance to the oncoprotein. Overall, our study provides the basis for the structural insights of the identified potential hits and EGCG and hence, the analogous compounds identified can be potent inhibitors against the HPV 16 E7 oncoprotein.

Keywords: EGCG, oncoprotein, molecular dynamics simulation, analogues

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1365 Drivers of Digital Product Innovation in Firms: An Empirical Study of Technological, Organizational, and Environmental Factors

Authors: Anne Theresa Eidhoff, Sarah E. Stief, Markus Voeth, Sarah Gundlach

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With digitalization increasingly changing the rules of competition, firms face the need to adapt and assimilate digital technologies in order to remain competitive. Firms can choose from various possibilities to integrate digital technologies including the option to embed digital technologies aiming to innovate products or to develop digital products. However, the question of which specific factors influence a firm’s decision to pursue digital product innovation remains unanswered in research. By adopting the Technology-Organization-Environment (TOE)-framework we have designed a qualitative exploratory study including eleven German practitioners to investigate relevant contingency factors. Our results indicate that the most critical factors for a company’s decision to pursue digital product innovation can be found in the technological and environmental dimensions, namely customers, competitive pressure, technological change, as well as digitalization fit. 

Keywords: digital innovation, digitalization, product innovation, TOE-framework

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1364 Evaluation of Pelargonium Extract and Oil as Eco-Friendly Corrosion Inhibitor for Steel in Acidic Chloride Solutions and Pharmacological Properties

Authors: Ahmed Chetouani

Abstract:

Corrosion is a natural occurring process where it can be defined as the deterioration of materials properties due to its interaction with its environment. Corrosion can lead to failures in plant infrastructure and machines which are usually costly to repair. In terms of loss of contaminated products which will cause environmental damage and possibly costly in terms of human health. The driving force that causes metals to corrode is due to the natural consequence of their temporary existence in metallic form. There is a growing trend in utilizing plant extracts and pharmaceutical compounds as corrosion inhibitors. Exquisite identification of the essential oil of aerial parts of Pelargonium was obtained using hydrodistillation and identification using GC (gas chromatography) and GC/MS (gas chromatography-mass spectrometry). The oil was predominated by Citronellol (22.8%). The inhibitory effect of essential oil and extract of Pelargonium was estimated on the corrosion of mild steel in 1M hydrochloric acid (HCl) using weight loss, Electrochemical Impedance Spectroscopy (EIS) and Tafel polarization curves. Inhibition was found to increase with increasing concentration of the essential oil and extract of Pelargonium. The effect of temperature on the corrosion behaviour of mild steel in 1M HCl with addition of essential oil and extract was also studied and the thermodynamic parameters were determined and discussed. Values of inhibition efficiency were calculated from weight loss, Tafel polarization curves, and EIS. All results are in good agreement. Polarization curves showed that essential oil and extract of Pelargonium behave as mixed type inhibitors in hydrochloric acid. The results obtained showed that the essential oil and extract of Pelargonium could serve as an effective inhibitor of the corrosion of mild steel in Hydrochloric acid solution. To avoid any surprise of toxicity, the majority compounds have been studied by using POM analyses.

Keywords: corrosion inhibition, mild steel, pelargonium oil, extract, electrochemical system, hydrodistillation, side effects, POM Analyses

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1363 Tissue-Specific Distribution of Cytochrome P450 1A1 and 3A in Rainbow Trout (Oncorhynchus mykiss)

Authors: Viktoriia Burkina, Vladimir Zlabek, Galia Zamaratskaia

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Cytochromes P450 (CYP) are important family of enzymes in Phase I metabolism. Environmental pollutants often act as inducers of the gene expression and activities CYP1A1 and CYP3A-like isoforms in fish. The activities are generally measured in the fish liver or gills, and less is known about tissue distribution of expression. In present study, the CYP1A1 and CYP3A-like activities were measured in rainbow trout liver, gill, intestine, heart, brain and gonads. The activities of CYP1A1 and CYP3A-like proteins were estimated as the rates of 7-ethoxyresorufin-O-deethylation (EROD) and benzyloxy-4-trifluoromethylcoumarin-O-debenzyloxylation (BFCOD), respectively. The CYP1A1 and CYP3A-like activities were detectable in all investigated fish tissues, with the highest activity in hepatic tissue followed by heart > brain > gill > intestine > gonads. To confirm the presence of CYP1A1 in different tissues, EROD activity was measured in presence of the selective inhibitors ellipticine (CYP1A1), ketoconazole (CYP3A), 8-methoxypsoralen (human CYP2A) and diallyl sulphide (CYP2E1). It was found that ellipticine, ketoconazole and 8-methoxypsoralen inhibited hepatic EROD activity by 88-98%. Ellipticine inhibited gill, intestine, and gonad EROD activity by 50%. In conclusion, EROD and BFCOD activities were detected in rainbow trout liver, gill, intestine, heart, brain and gonads. Further studies are needed to fully identify all CYP450 isoforms responsible for these activities. Acknowledgement: The study was financially supported by the Ministry of Education, Youth and Sports of the Czech Republic - projects „CENAKVA “(No. CZ.1.05/2.1.00/01.0024), “CENAKVA Center Development “(No. CZ.1.05/2.1.00/19.0380), “CENAKVA II “(No. LO1205 under the NPU I program), and "Development of USB - International mobility (No. CZ.02.2.69/0.0/0.0/16_027/0008364).

Keywords: BFCOD, EROD, fish, phase I metabolism, selective inhibitors

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1362 Research on the Relationship between Localization Strategic Human Resource Management Practices and Firm Performance: A Comparison of Japanese Multinational Enterprise Subsidiaries in Vietnam

Authors: Nana Weng

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Firstly, based on two diamond models and Value-Rarity-Inimitability-Organization framework, this paper analyzes the Country Specific factors of and firm specific factors which influence subsidiaries’ sustainable competitive advantage. Then, according to the main content of Strategic Human Resource Management (SHRM) research that HRM strategy should fit into corporate strategy, we explained what the SHRM practices should be in the context of localization strategies within Multinational Enterprise (MNE) companies. Then we choose two Japanese MNE subsidiaries in the same industry and tested the hypothesis that localization SHRM practices positively impact on subsidiary’s sustainable competitive advantage, further positively affect firm integrated performance (both financial performance and organizational and organizational performance) lever through High Performance Work Practices (HPWPs) of local employees.

Keywords: localization SHRM, firm integrated performance, Japanese MNE subsidiaries, Vietnam

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1361 New Product Development Typologies: An Analysis of Publications and Citations between 1992 and 2012

Authors: Ana Paula Vilas Boas Viveiros Lopes, Marly Monteiro de Carvalho

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The new product development for decades has favored companies that can put their products to market quickly and efficiently, providing sustainable competitive advantage difficult to be achieved by their competitors. This paper presents the outcomes of a systematic review of the literature relating to new product development that was published between 1992 and 2012. A hybrid methodological approach that combines bibliometrics, content analysis and semantic analysis was applied. The review discusses the publication patterns, focusing on aspects related to scientific collaboration. The results show that the main academic journal that discusses this theme is “Journal of Product Innovation Management”. Although the first paper relating to this theme was published in 1992, the number of publications on the subject only began to increase substantially in 1999. Most of the studies reviewed in this paper applied qualitative research methods, indicating that most of the research on the theme is still in an exploratory phase.

Keywords: project type, project typology, new product development, sustainable competitive advantage

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1360 Biological Activities of Protease Inhibitors from Cajanus cajan and Phaseolus limensis

Authors: Tooba N. Shamsi, Romana Perveen, Sadaf Fatima

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Protease Inhibitors (PIs) are widespread in nature, produced by animals, plants and microorganisms. They play vital role in various biological activities by keeping a check on activity of proteases. Present study aims to investigate antioxidant and anti-inflammatory properties of PPI from Cajanus cajan (CCTI) and Phaseolus limensis (LBTI). PPI was purified from C. cajan (PUSA-992) by ammonium sulfate precipitation followed by ion exchange chromatography. The anti-oxidant activity was analyzed by two most common radical scavenging assays of FRAP (ferric reducing antioxidant power) and DPPH (1,1- diphenyl-2-picrylhydrazyl). Also, in-vitro anti-inflammatory activity was evaluated using albumin denaturation assay and membrane stabilization assay at different concentrations. Ascorbic acid and aspirin were used as a standards for antioxidant and anti-inflammatory assays respectively. The PPIs were also checked for antimicrobial activity against a number of bacterial strains. The CCTI and LBTI showed DPPH radical scavenging activity in a concentration–dependent manner with IC50 values 544 µg/ml and 506 µg/ml respectively comparative to ascorbic acid which was 258 µg/ml. Following FRAP assay, it was evaluated that LBTI had 87.5% and CCTI showed 84.4% antioxidant activity, taking value of standard ascorbic acid to be 100%. The PPIs also showed in-vitro anti‐inflammatory activity by inhibiting the heat induced albumin denaturation with IC50 values of 686 µg/ml and 615 µg/ml for CCTI and LBTI respectively compared to the standard (aspirin) which was 70.8 µg/ml. Red blood cells membrane stabilization with IC50 values of 641 µg/ml and 587 µg/ml for CCTI and LBTI respectively against aspirin which showed IC50 value of 70.4 µg/ml. PPIs showed antibacterial activity against 7 known strains while there was apparently no action against fungi.

Keywords: Cajanus cajan, Phaseolus limensis, Lima beans, protein protease inhibitor, antioxidant, anti-inflammatory, antimicrobial activity

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1359 Biochemical Characterization of CTX-M-15 from Enterobacter cloacae and Designing a Novel Non-β-Lactam-β-Lactamase Inhibitor

Authors: Mohammad Faheem, M. Tabish Rehman, Mohd Danishuddin, Asad U. Khan

Abstract:

The worldwide dissemination of CTX-M type β-lactamases is a threat to human health. Previously, we have reported the spread of blaCTX-M-15 gene in different clinical strains of Enterobacteriaceae from the hospital settings of Aligarh in north India. In view of the varying resistance pattern against cephalosporins and other β-lactam antibiotics, we intended to understand the correlation between MICs and catalytic activity of CTX-M-15. In this study, steady-state kinetic parameters and MICs were determined on E. coli DH5α transformed with blaCTX-M-15 gene that was cloned from Enterobacter cloacae (EC-15) strain of clinical background. The effect of conventional β-lactamase inhibitors (clavulanic acid, sulbactam and tazobactam) on CTX-M-15 was also studied. We have found that tazobactam is the best among these inhibitors against CTX-M-15. The inhibition characteristic of tazobactam is defined by its very low IC50 value (6 nM), high affinity (Ki = 0.017 µM) and better acylation efficiency (k+2/K9 = 0.44 µM-1s-1). It forms an acyl-enzyme covalent complex, which is quite stable (k+3 = 0.0057 s-1). Since increasing resistance has been reported against conventional b-lactam antibiotic-inhibitor combinations, we aspire to design a non-b-lactam core containing b-lactamase inhibitor. For this, we screened ZINC database and performed molecular docking to identify a potential non-β-lactam based inhibitor (ZINC03787097). The MICs of cephalosporin antibiotics in combination with this inhibitor gave promising results. Steady-state kinetics and molecular docking studies showed that ZINC03787097 is a reversible inhibitor which binds non-covalently to the active site of the enzyme through hydrogen bonds and hydrophobic interactions. Though, it’s IC50 (180 nM) is much higher than tazobactam, it has good affinity for CTX-M-15 (Ki = 0.388 µM). This study concludes that ZINC03787097 compound can be used as seed molecule to design more efficient non-b-lactam containing b-lactamase inhibitor that could evade pre-existing bacterial resistance mechanisms.

Keywords: ESBL, non-b-lactam-b-lactamase inhibitor, bioinformatics, biomedicine

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1358 Optimization of Production Scheduling through the Lean and Simulation Integration in Automotive Company

Authors: Guilherme Gorgulho, Carlos Roberto Camello Lima

Abstract:

Due to the competitive market in which companies are currently engaged, the constant changes require companies to react quickly regarding the variability of demand and process. The changes are caused by customers, or by demand fluctuations or variations of products, or the need to serve customers within agreed delivery taking into account the continuous search for quality and competitive prices in products. These changes end up influencing directly or indirectly the activities of the Planning and Production Control (PPC), which does business in strategic, tactical and operational levels of production systems. One area of concern for organizations is in the short term (operational level), because this planning stage any error or divergence will cause waste and impact on the delivery of products on time to customers. Thus, this study aims to optimize the efficiency of production scheduling, using different sequencing strategies in an automotive company. Seeking to aim the proposed objective, we used the computer simulation in conjunction with lean manufacturing to build and validate the current model, and subsequently the creation of future scenarios.

Keywords: computational simulation, lean manufacturing, production scheduling, sequencing strategies

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1357 Views and Experiences of Medical Students of Kerman University of Medical Sciences on Facilitators and Inhibitators of Quality of Education in the Clinical Education System in 2021

Authors: Hossein Ghaedamini, Salman Farahbakhsh, Alireza Amirbeigi, Zahra Saghafi, Salman Daneshi, Alireza Ghaedamini

Abstract:

Background: Assessing the challenges of clinical education of medical students is one of the most important and sensitive parts of medical education. The aim of this study was to investigate the views and experiences of Kerman medical students on the factors that facilitate and inhibit the quality of clinical education. Materials and Methods: This research was qualitative and used a phenomenological approach. The study population included medical interns of Kerman University of Medical Sciences in 1400. The method of data collection was in-depth interviews with participants. Data were encoded and analyzed by Claizey stepwise model. Results: First, about 540 primary codes were extracted in the form of two main themes (facilitators and inhibitors) and 10 sub-themes including providing motivational models and creating interest in interns, high scientific level of professors and the appropriate quality of their teaching, the use of technology in the clinical education process, delegating authority and freedom of action and more responsibilities to interns, inappropriate treatment of some officials, professors, assistants and department staff with their interns, inadequate educational programming, lack of necessary cooperation and providing inappropriate treatment by clinical training experts for interns, inadequate evaluation method in clinical training for interns, poor quality mornings, the unefficiency of grand rounds, the inappropriate way of evaluating clinical training for interns, the lack of suitable facilities and conditions with the position of a medical intern, and the hardwork of some departments were categorized. Conclusion: Clinical education is always mixed with special principles and subtleties, and special attention to facilitators and inhibitors in this process has an important role in improving its quality.

Keywords: clinical education, medical students, qualitative study, education

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1356 Evaluation of Forage Yield and Competition Indices for Intercropped Barley and Legumes

Authors: Abdollah Javanmard, Fariborz Shekari

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Barley (Hordeum vulgare L.), vetch (Vicia villosa), and grass pea (Lathyrus sativus L.) monocultures as well as mixtures of barley with each of the above legumes, in three seeding ratios (i.e., barley: legume 75:25, 50:50 and 25:75 based on seed numbers) were used to investigate forage yield and competition indices. The results showed that intercropping reduced the dry matter yield of the three component plants, compared with their respective monocrops. The greatest value of total dry matter yield was obtained from barley25-grasspea75 (5.44 t ha-1) mixture, followed by grass pea sole crop (4.99 t ha-1). The total AYL values were positive and greater than 0 in all mixtures, indicating an advantage from intercropping over sole crops. Intercropped barley had a higher relative crowding coefficient (K=1.64) than intercropped legumes (K=1.20), indicating that barley was more competitive than legumes in mixtures. Furthermore, grass pea was more competitive than vetch in mixtures with barley. The highest LER, SPI and MAI were obtained when barley was mixed at a rate of 25% with 75% seed rate of grass pea. It is concluded that intercropping of barley with grass pea has a good potential to improve the performance of forage with high land-use efficiency.

Keywords: forage, grass pea, intercropping, LER, monetary advantage

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1355 The Importance of Optimization of Halal Tourism: A Study of the Development of Halal Tourism in Indonesia

Authors: Rizqi W. Romadhon, Nur Arifan

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Halal Tourism is a part of tourism industry which is based on Islamic Principle and addressed to the Muslim tourist. The potency of halal tourism is very broad to be developed, because the growth of Muslim populations is rapidly increasing. Indonesia is one of the biggest countries with Majority of its population is Muslim, therefore human resources and natural resources have very good potential to be part of the Halal tourism industry. But the fact is Indonesia can not optimize the potential of human resources and natural resources as well as neighboring countries carried out. This paper will discuss the reasons of the importance of developing Halal tourism, and the factors influencing the success of developing halal tourism in Indonesia, and also the optimization strategies which can be adopted by the government so that the Halal tourism industry in Indonesia has a sustainable competitive advantage. The existence of this research is expected to government, tourism agents and others can optimize the potency of Indonesia’s Human resources and natural resources for developing Halal tourism industry in Indonesia.

Keywords: halal tourism, Islamic principle, optimization, sustainable competitive advantage

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1354 Barriers to Competitive Tenders in Building Conservation Works

Authors: Yoke-Mui Lim, Yahaya Ahmad

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Conservation works in Malaysia that is procured by public organisation usually follow the traditional approach where the works are tendered based on Bills of Quantities (BQ). One of the purposes of tendering is to enable the selection of a competent contractor that offers a competitive price. While competency of the contractors are assessed by their technical knowledge, experience and track records, the assessment of pricing will be dependent on the tender amount. However, the issue currently faced by the conservation works sector is the difficulty in assessing the competitiveness and reasonableness of the tender amount due to the high variance between the tenders amount. Thus, this paper discusses the factors that cause difficulty to the tenderers in pricing competitively in a bidding exercise for conservation tenders. Data on tendering is collected from interviews with conservation works contractors to gain in-depth understanding of the barriers faced in pricing tenders of conservation works. Findings from the study lent support to the contention that the variance of tender amount is very high amongst tenderers. The factors identified in the survey are the format of BQ, hidden works, experience and labour and material costs.

Keywords: building conservation, Malaysia, bill of quantities, tender

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1353 Identification of Nutrient Sensitive Signaling Pathways via Analysis of O-GlcNAcylation

Authors: Michael P. Mannino, Gerald W. Hart

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The majority of glucose metabolism proceeds through glycolytic pathways such as glycolysis or pentose phosphate pathway, however, about 5% is shunted through the hexosamine biosynthetic pathway, producing uridine diphosphate N-acetyl glucosamine (UDP-GlcNAc). This precursor can then be incorporated into complex oligosaccharides decorating the cell surface or remain as an intracellular post-translational-modification (PTM) of serine/threonine residues (O-GlcNAcylation, OGN), which has been identified on over 4,000 cytosolic or nuclear proteins. Intracellular OGN has major implications on cellularprocesses, typically by modulating protein localization, protein-protein interactions, protein degradation, and gene expression. Additionally, OGN is known to have an extensive cross-talk with phosphorylation, be in a competitive or cooperative manner. Unlike other PTMs there are only two cycling enzymes that are capable of adding or removing the GlcNAc moiety, O-linked N-aceytl glucosamine Transferase (OGT) and O-linked N-acetyl glucoamidase (OGA), respectively. The activity of OGT has been shown to be sensitive to cellular UDP-GlcNAc levels, even changing substrate affinity. Owing to this and that the concentration of UDP-GlcNAc is related to the metabolisms of glucose, amino acid, fatty acid, and nucleotides, O-GlcNAc is often referred to as a nutrient sensing rheostat. Indeed OGN is known to regulate several signaling pathways as a result of nutrient levels, such as insulin signaling. Dysregulation of OGN is associated with several disease states such as cancer, diabetes, and neurodegeneration. Improvements in glycomics over the past 10-15 years has significantly increased the OGT substrate pool, suggesting O-GlcNAc’s involvement in a wide variety of signaling pathways. However, O-GlcNAc’s role at the receptor level has only been identified in a case-by-case basis of known pathways. Examining the OGN of the plasma membrane (PM) may better focus our understanding of O-GlcNAc-effected signaling pathways. In this current study, PM fractions were isolated from several cell types via ultracentrifugation, followed by purification and MS/MS analysis in several cell lines. This process was repeated with or without OGT/OGA inhibitors or with increased/decreased glucose levels in media to ascertain the importance of OGN. Various pathways are followed up on in more detailed studies employing methods to localize OGN at the PM specifically.

Keywords: GlcNAc, nutrient sensitive, post-translational-modification, receptor

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1352 The Impact of University League Tables on the Development of Non-Elite Universities. A Case Study of England

Authors: Lois Cheung

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This article examines the impact of League Tables on non-elite universities in the English higher education system. The purpose of this study is to explore the use of rankings in strategic planning by low-ranked universities in this highly competitive higher education market. A sample of non-elite universities was selected for a content analysis based on the measures used by The Guardian rankings. Interestingly, these universities care about their rankings within a single national system. The content analysis appears to be an effective approach to investigating the presence of such influences. It is particularly noteworthy that all sampled universities use these measure terminologies in their strategic plans, missions and news coverage on their institutional web-pages. This analysis may be an example of the key challenges that many low-ranking universities in England are probably facing in the highly competitive and diversified higher education market. These universities use rankings to communicate with their stakeholders, mainly students, in order to fill places to secure their major source of funding. The study concludes with comments on the likely effects of the rankings paradigm in undermining the contributions of non-elite universities.

Keywords: League tables, measures, post-1992 universities, ranking, strategy

Procedia PDF Downloads 152
1351 Molecular Docking Assessment of Pesticides Binding to Bacterial Chitinases

Authors: Diana Larisa Vladoiu, Vasile Ostafe, Adriana Isvoran

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Molecular docking calculations reveal that pesticides provide favorable interactions with the bacterial chitinases. Pesticides interact with both hydrophilic and aromatic residues involved in the active site of the enzymes, their positions partially overlapping the substrate and the inhibitors locations. Molecular docking outcomes, in correlation with experimental literature data, suggest that the pesticides may be degraded or having an inhibitor effect on the activity of these enzymes, depending of the application dose and rate.

Keywords: chitinases, inhibition, molecular docking, pesticides

Procedia PDF Downloads 519