Search results for: mentoring enhanced strategy
Commenced in January 2007
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Edition: International
Paper Count: 6406

Search results for: mentoring enhanced strategy

5206 6-Degree-Of-Freedom Spacecraft Motion Planning via Model Predictive Control and Dual Quaternions

Authors: Omer Burak Iskender, Keck Voon Ling, Vincent Dubanchet, Luca Simonini

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This paper presents Guidance and Control (G&C) strategy to approach and synchronize with potentially rotating targets. The proposed strategy generates and tracks a safe trajectory for space servicing missions, including tasks like approaching, inspecting, and capturing. The main objective of this paper is to validate the G&C laws using a Hardware-In-the-Loop (HIL) setup with realistic rendezvous and docking equipment. Throughout this work, the assumption of full relative state feedback is relaxed by onboard sensors that bring realistic errors and delays and, while the proposed closed loop approach demonstrates the robustness to the above mentioned challenge. Moreover, G&C blocks are unified via the Model Predictive Control (MPC) paradigm, and the coupling between translational motion and rotational motion is addressed via dual quaternion based kinematic description. In this work, G&C is formulated as a convex optimization problem where constraints such as thruster limits and the output constraints are explicitly handled. Furthermore, the Monte-Carlo method is used to evaluate the robustness of the proposed method to the initial condition errors, the uncertainty of the target's motion and attitude, and actuator errors. A capture scenario is tested with the robotic test bench that has onboard sensors which estimate the position and orientation of a drifting satellite through camera imagery. Finally, the approach is compared with currently used robust H-infinity controllers and guidance profile provided by the industrial partner. The HIL experiments demonstrate that the proposed strategy is a potential candidate for future space servicing missions because 1) the algorithm is real-time implementable as convex programming offers deterministic convergence properties and guarantee finite time solution, 2) critical physical and output constraints are respected, 3) robustness to sensor errors and uncertainties in the system is proven, 4) couples translational motion with rotational motion.

Keywords: dual quaternion, model predictive control, real-time experimental test, rendezvous and docking, spacecraft autonomy, space servicing

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5205 Multi-Functional Metal Oxides as Gas Sensors, Photo-Catalysts and Bactericides

Authors: Koyar Rane

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Nano- to submicron size particles of narrow particle size distribution of semi-conducting TiO₂, ZnO, NiO, CuO, Fe₂O₃ have been synthesized by novel hydrazine method and tested for their gas sensing, photocatalytic and bactericidal activities and the behavior found to be enhanced when the oxides in the thin film forms, that obtained in a specially built spray pyrolysis reactor. Hydrazine method is novel in the sense, say, the UV absorption edge of the white pigment grade wide band gap (~3.2eV) TiO₂ and ZnO shifted to the visible region turning into yellowish particles, indicating modification occurring the band structure. The absorption in the visible region makes these oxides visible light sensitive photocatalysis in degrading pollutants, especially the organic dyes which otherwise increase the chemical oxygen demand of the drinking water, enabling the process feasible not under the harsh energetic UV radiation regime. The electromagnetic radiations on irradiation produce electron-hole pairs Semiconductor + hν → e⁻ + h⁺ The electron-hole pairs thus produced form Reactive Oxygen Species, ROS, on the surface of the semiconductors, O₂(adsorbed)+e⁻ → O₂• - superoxide ion OH-(surface)+h⁺ →•OH - Hydroxyl radical The ROS attack the organic material and micro-organisms. Our antibacterial studies indicate the metal oxides control the Biological Oxygen Demand (BOD) of drinking water which had beyond the safe level normally found in the municipal supply. Metal oxides in the thin film form show overall enhanced properties and the films are reusable. The results of the photodegradation and antibactericidal studies are discussed. Gas sensing studies too have been done to find the versatility of the multifunctional metal oxides.

Keywords: hydrazine method, visible light sensitive, photo-degradation of dyes, water/airborne pollutant

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5204 Investigating the Socio-ecological Impacts of Sea Level Rise on Coastal Rural Communities in Ghana

Authors: Benjamin Ankomah-Asare, Richard Adade

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Sea level rise (SLR) poses a significant threat to coastal communities globally. Ghana has over the years implemented protective measures such as the construction of groynes and revetment to serve as barriers to sea waves in major cities and towns to prevent sea erosion and flooding. For vulnerable rural coastal communities, the planned retreat is often proposed; however, relocation costs are often underestimated as losses of future social and cultural value are not always adequately taken into account. Through a mixed-methods approach combining qualitative interviews, surveys, and spatial analysis, the study examined the experiences of coastal rural communities in Ghana and assess the effectiveness of relocation strategies in addressing the socio-economic and environmental challenges posed by sea level rise. The study revealed the devastating consequences of sea level rise on these communities, including increased flooding, erosion, and saltwater intrusion into freshwater sources. Moreover, it highlights the adaptive capacities within these communities and how factors such as infrastructure, economic activities, cultural heritage, and governance structures shape their resilience in the face of environmental change. While relocation can be an effective strategy in reducing the risks associated with sea level rise, the study recommends that proper implementation of this adaptation strategy can be achieved when coupled with community-led planning, participatory decision-making, and targeted support for vulnerable groups.

Keywords: sea level rise, relocation, socio-ecological impacts, rural communities

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5203 Preparedness for Nurses to Adopt the Implementation of Inpatient Medication Order Entry (IPMOE) System at United Christian Hospital (UCH) in Hong Kong

Authors: Yiu K. C. Jacky, Tang S. K. Eric, W. Y. Tsang, C. Y. Li, C. K. Leung

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Objectives : (1) To enhance the competence of nurses on using IPMOE for drug administration; (2) To ensure the transition on implementation of IPMOE in safer and smooth way hospital-wide. Methodology: (1) Well-structured Governance: To make provision for IPMOE implementation, multidisciplinary governance structure at Corporate and Local levels are well established. (2) Staff Engagement: A series of staff engagement events were conducted including Staff Forum, IPMOE Hospital Visit, Kick-off Ceremony and establishment of IPMOE Webpage for familiarizing the forthcoming implementation with frontline staff. (3) Well-organized training program: from Workshop to Workplace Two different IPMOE training programs were tailor-made which aimed at introducing the core features of administration module. Fifty-five identical training classes and six train-the-trainer workshops were organized at 2-3Q 2015. Lending Scheme on IPMOE hardware for hands-on practicing was launched and further extended the training from workshop to workplace. (4) Standard Guidelines and Workflow: the related workflow and guidelines are developed which facilitates users to acquire the competence towards IPMOE and fully familiarize with the standardized contingency plan. (5) Facilities and Equipment: The installations of IPMOE hardware were promptly arranged for rollout. Besides, IPMOE training venue was well-established for staff training. (6) Risk Management Strategy: UCH Medication Safety Forum is organized in December 2015 for sharing “Tricks & Tips” on IPMOE which further disseminate at webpage for arousal of medication safety. Hospital-wide annual audit on drug administration was planned to figure out the compliance and deliberate the rooms for improvement. Results: Through the comprehensive training plan, over 1,000 UCH nurses attended the training program with positive feedback. They agreed that their competence on using IPMOE was enhanced. By the end of November 2015, 28 wards (over 1,000 Inpatient-bed) involving departments of M&G, SUR, O&T and O&G have been successfully rolled out IPMOE in 5-month. A smooth and safe transition of implementation of IPMOE was achieved. Eventually, we all get prepared for embedding IPMOE into daily nursing and work altogether for medication safety at UCH.

Keywords: drug administration, inpatient medication order entry system, medication safety, nursing informatics

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5202 Anti-crisis Public Relations and Aspects of Effective Management in Georgian Companies

Authors: Marine Kobalava

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Introduction. The paper substantiates the crucial role of anti-crisis PR in managing the image and reputation of companies. The critical situation caused by the Covid-19 virus in various countries of the world and the actions taken have had a significant negative impact on the image of companies and public groups. The mentioned circumstance has caused some problems for companies’ products in terms of customer demand. Accordingly, the main goal of PR has become to achieve the optimal relationship between companies and society with effective management. It should also be taken into account that the range of action of PR in crisis situations is much wider than that of advertising. In the paper, Public Relations is evaluated as a determining factor of the companies' prestige, its reliability, which has a decisive effect on the goodwill, trust, and general reputation of the public towards the company. The purpose of the study is to reveal the challenges of anti-crisis PR in Georgian companies and to develop recommendations on effective management mechanisms. Methodologies. Analysis, induction, synthesis, and other methods are used in the paper; Matrix and SWOT analysis are constructed. Ways of establishing and implementing an anti-crisis PR system in companies are proposed. The main aspects of anti-crisis management are identified by using the matrix of the choice of diversification strategy of the companies' activities, the possibilities of making adequate decisions using PR are studied according to the characteristics of the companies' activities and priority directions. Conclusion. The paper draws conclusions on modern problems of anti-crisis PR, offers recommendations on ways to solve it through PR strategies.

Keywords: anti-crisis PR, effective management, company, PR strategy

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5201 Non-Invasive Pre-Implantation Genetic Assessment Using NGS in IVF Clinical Routine

Authors: Katalin Gombos, Bence Gálik, Krisztina Ildikó Kalács, Krisztina Gödöny, Ákos Várnagy, József Bódis, Attila Gyenesei, Gábor L. Kovács

Abstract:

Although non-invasive pre-implantation genetic testing for aneuploidy (NIPGT-A) is potentially appropriate to assess chromosomal ploidy of the embryo, practical application of it in a routine IVF center has not been started in the absence of a recommendation. We developed a comprehensive workflow for a clinically applicable strategy for NIPGT-A based on next-generation sequencing (NGS) technology. We performed MALBAC whole genome amplification and NGS on spent blastocyst culture media of Day 3 embryos fertilized with intra-cytoplasmic sperm injection (ICSI). Spent embryonic culture media of morphologically good quality score embryos were enrolled in further analysis with the blank culture media as background control. Chromosomal abnormalities were identified by an optimized bioinformatics pipeline applying a copy number variation (CNV) detecting algorithm. We demonstrate a comprehensive workflow covering both wet- and dry-lab procedures supporting a clinically applicable strategy for NIPGT-A. It can be carried out within 48 h which is critical for the same-cycle blastocyst transfer, but also suitable for “freeze all” and “elective frozen embryo” strategies. The described integrated approach of non-invasive evaluation of embryonic DNA content of the culture media can potentially supplement existing pre-implantation genetic screening methods.

Keywords: next generation sequencing, in vitro fertilization, embryo assessment, non-invasive pre-implantation genetic testing

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5200 Effect of Fatiguing Hip Muscles on Dynamic Posture Control in Recurrent Ankle Sprain

Authors: Radwa El Shorbagy, Alaa El Din Balbaa, Khaled Ayad, Waleed Reda

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Ankle sprain is a common lower limb injury that is complicated by high recurrence rate. The cause of recurrence is not clear; however, changes in motor control have been postulated.Objective: to determine the contribution of proximal hip strategy to dynamic posture control in patients with recurrent ankle sprain. Methods:Fifteen subjects with recurrent ankle sprain (Group A) and fifteen healthy control subjects (Group B) participated in this study. Abductor-adductor as well as flexor-extensor hip musculature control was abolished by fatigue using the Biodex Isokinatic System. Dynamic posture control was measured before and after fatigue by the Biodex Balance System. Results: Repeated measures MANOVA was used to compare within group differences. In group A fatiguing of hip muscles (flexors-extensors and abductors-adductors) lowered overall stability index (OASI), anteroposterior stability index (APSI) and mediolateral stability index (MLSI) significantly (p=0.00) whereas; in group B fatiguing of hip flexors-extensors lowered significantly OASI and APSI only (p= 0.017, 0.010; respectively) while fatiguing of hip abductors-adductors has no significant effect on these variables. Conclusion: fatiguing of hip muscles has a significant deleterious effect on dynamic posture control in patient with recurrent ankle sprain indicating their increased dependence on hip strategy.

Keywords: ankle sprain, fatigue hip muscles, dynamic balance, ankle sprain

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5199 Integrated Performance Management System a Conceptual Design for PT. XYZ

Authors: Henrie Yunianto, Dermawan Wibisono

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PT. XYZ is a family business (private company) in Indonesia that provide an educational program and consultation services. Since its establishment in 2011, the company has run without any strategic management system implemented. Though the company could survive until now. The management of PT. XYZ sees the business opportunity for such product is huge, even though the targeted market is very specific (niche), the volume is large (due to large population of Indonesia) and numbers of competitors are low (now). It can be said if the product life cycle is in between ‘Introduction stage’ and ‘growth’ stage. It is observed that nowadays the new entrants (competitors) are increasing, thus PT. XYZ consider reacting in facing the intense business rivalry by conducting the business in an appropriate manner. A Performance Management System is important to be implemented in accordance with the business sustainability and growth. The framework of Performance Management System chosen is Integrated Performance Management System (IPMS). IPMS framework has the advantages of its simplicity, linkage between its business variables and indicators where the company can see the connections between all factors measured. IPMS framework consists of perspectives: (1) Business Result, (2) Internal Processes, (3) Resource Availability. Variables and indicators were examined through deep analysis of the business external and internal environments, Strength-Weakness-Opportunity-Threat (SWOT) analysis, Porter’s five forces analysis. Analytical Hierarchy Process (AHP) analysis was then used to quantify the weight of each variable/indicators. AHP is needed since in this study, PT. XYZ, the data of existing performance indicator was not available. Later, where the IPMS is implemented, the real data measured can be examined to determine the weight factor of each indicators using correlation analysis (or other methods). In this study of IPMS design for PT. XYZ, the analysis shows that with current company goals, along with the AHP methodology, the critical indicators for each perspective are: (1) Business results: Customer satisfaction and Employee satisfaction, (2) Internal process: Marketing performance, Supplier quality, Production quality, Continues improvement; (3) Resources Availability: Leadership and company culture & value, Personal Competences, Productivity. Company and/or organization require performance management system to help them in achieving their vision and mission. Company strategy will be effectively defined and addressed by using performance management system. Integrated Performance Management System (IPMS) framework and AHP analysis help us in quantifying the factors which influence the business output expected.

Keywords: analytical hierarchy process, business strategy, differentiation strategy, integrated performance management system

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5198 The Evaluation of Event Sport Tourism on Regional Economic Development

Authors: Huei-Wen Lin, Huei-Fu Lu

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Event sport tourism (EST) has become an especially important economic sector around the world. As the magnitude continues to grow, attracting more tourists, media, and investment for the host community, and many local areas/regions and states have identified the expenditures by visitors as a potential source of economic or employment growth. The main purposes of this study are to investigate stakeholders’ insights into the feature of hosting EST and using them as a regional development strategy. Continuing the focus of previous literature on the regional development and economic benefits by hosting EST, a total of fıve semi-structured interview questions are designed and a thematic analysis is employed to conduct with eight key sport and tourism decision makers in Atlanta during July to August 2016. Through the depth interviews, the study will contribute to a better understanding of stakeholders’ decision-making, identifying benefits and constraints as well as leveraging the impacts of hosting EST. These findings have provided stakeholders’ perspectives of hosting EST and using them as a reference of regional development in emerging sport tourism markets in the US. Additionally, this study examines key considerations and issues that affect and are critical to reliable understanding of the economic impacts of hosting EST on the regional development, and it will be able to benefit future management authorities (i.e. governments and communities) in their sport tourism development endeavors in defining and hosting successful EST. Furthermore, the insights gained from the qualitative analysis could help other cities/regions analyzing the economic impacts of hosting EST and using it as an instrument of city development strategy.

Keywords: economic impacts, event sport tourism, regional economic development, longitudinal analysis

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5197 The Impact of Cooperative Learning on EFL Learners Oral Performance

Authors: Narimen Hamdini

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The mastery of a foreign language often implies adequate speaking competency and communication. However, it has been marked that the Algerian students’ oral performance is affected by the lack of language practice opportunities. The present study aims at investigating the impact of cooperative learning strategies on the learners’ oral performance through integrating some learning strategies in oral expression classes. Thus, a quasi-experimental study with one group pretest-posttest design was conducted. A convenience sample of 27 second-year students from the University of Jijel, Algeria, was taught during three consecutive weeks through cooperative learning activities in conjunction with regular language instruction in oral expression classes. Regarding data collection, the study makes use of students’ questionnaire, a semi-structured interview with the teachers of oral expression, and orally scored pre-posttest. While the students’ questionnaire aims at exploring the learners ‘speaking difficulties and attitudes towards the implementation of the strategy, the semi-structured interview aims at revealing the teachers’ instructional practices and attitudes toward the integration of CL activities. Finally, the oral tests were conducted before and after the intervention to measure the effect of the strategy on the learners’ oral production. The findings showed that the experimental group scored higher in the posttest. Cooperative learning promotes not only the learner’s oral performances, but also motivation and social skills. Consequently, its implementation in the oral expression classes is validated and recommended.

Keywords: cooperative learning, learning, oral performance, teaching

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5196 From Makers to Maker Communities: A Survey on Turkish Makerspaces

Authors: Dogan Can Hatunoglu, Cengiz Hakan Gurkanlı, Hatice Merve Demirci

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Today, the maker movement is regarded as a socio-cultural movement that represents designing and building objects for innovations. In these creativity-based activities of the movement, individuals from different backgrounds such as; inventors, programmers, craftspeople, DIY’ers, tinkerers, engineers, designers, and hackers, form a community and work collaboratively for mutual, open-source innovations. Today, with the accessibility of recently emerged technologies and digital fabrication tools, the Maker Movement is continuously expanding its scope and has evolved into a new experience, and for many, it is now considered as new kind of industrial revolution. In this new experience, makers create new things within their community by using new digital tools and technologies in spots called makerspaces. In these makerspaces, activities of learning, experience sharing, and mentoring are evolved into maker events. Makers who share common interests in making benefit from makerspaces as meeting and working spots. In literature, there are many sources on Maker Movement, maker communities, and their activities, especially in the field of business administration. However, there is a gap in the literature about the maker communities in Turkey. This research aims to be an information source on the dynamics and process design of “making” activities in Turkish maker communities and also aims to provide insights to sustain and enhance local maker communities in the future. Within this aim, semi-structured interviews were conducted with founders and facilitators from selected Turkish maker communities. (1) The perception towards Maker Movement, makers, activity of making, and current situation of maker communities, (2) motivations of individuals who participate the maker communities, and (3) key drivers (collaboration and decision-making in design processes) of maker activities from the perspectives of main actors (founders, facilitators) are all examined deeply with question on personal experiences and perspectives. After a qualitative approached data analysis concerning the maker communities in Turkey, this research reveals that there are two main conclusions regarding (1) the foundation of the Turkish maker mindset and (2) emergence of self-sustaining communities.

Keywords: Maker Movement, maker community, makerspaces, open-source design, sustainability

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5195 Comparative Evaluation on in vitro Bioactivity, Proliferation and Antibacterial Efficiency of Sol-Gel Derived Bioactive Glass Substituted by Li and Mg

Authors: Amirhossein Moghanian, Morteza Elsa, Mehrnaz Aminitabar

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Modified bioactive glass has been considered as a promising multifunctional candidate in bone repair and regeneration due to its attractive properties. The present study mainly aims to evaluate how the individual substitution of lithium (L-BG) and magnesium (M-BG) for calcium can affect the in vitro bioactivity of sol-gel derived substituted 58S bioactive glass (BG); and to present one composition in both of the 60SiO2–(36-x)CaO–4P₂O₅–(x)Li₂O and 60SiO₂ –(36-x)CaO–4P₂O₅–(x)MgO quaternary systems (where x= 0, 5, 10 mol.%) with improved biocompatibility, enhanced alkaline phosphatase (ALP) activity, and the most efficient antibacterial activity against methicillin-resistant staphylococcus aureus bacteria. To address these aims, and study the effect of CaO/Li₂O and CaO/MgO substitution up to 10 mol % in 58S-BGs, the samples were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, inductively coupled plasma atomic emission spectrometry and scanning electron microscopy after immersion in simulated body fluid up to 14 days. Results indicated that substitution of either CaO/ Li₂O and CaO/ MgO had a retarding effect on in vitro hydroxyapatite (HA) formation due to the lower supersaturation degree for nucleation of HA compared with 58s-BG. Meanwhile, magnesium had a more pronounced effect. The 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and alkaline phosphatase (ALP) assays showed that both substitutions of CaO/ Li₂O and CaO/ MgO up to 5mol % in 58s-BGs led to increased biocompatibility and stimulated proliferation of the pre-osteoblast MC3T3 cells with respect to the control. On the other hand, the substitution of either Li or Mg for Ca in the 58s BG composition resulted in improved bactericidal efficiency against MRSA bacteria. Taken together, sample 58s-BG with 5 mol % CaO/Li₂O substitution (BG-5L) was considered as a multifunctional biomaterial in bone repair/regeneration with improved biocompatibility, enhanced ALP activity as well as significant antibacterial activity against methicillin-resistant staphylococcus aureus (MRSA) bacteria.

Keywords: alkaline, alkaline earth, bioactivity, biomedical applications, sol-gel processes

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5194 Freight Time and Cost Optimization in Complex Logistics Networks, Using a Dimensional Reduction Method and K-Means Algorithm

Authors: Egemen Sert, Leila Hedayatifar, Rachel A. Rigg, Amir Akhavan, Olha Buchel, Dominic Elias Saadi, Aabir Abubaker Kar, Alfredo J. Morales, Yaneer Bar-Yam

Abstract:

The complexity of providing timely and cost-effective distribution of finished goods from industrial facilities to customers makes effective operational coordination difficult, yet effectiveness is crucial for maintaining customer service levels and sustaining a business. Logistics planning becomes increasingly complex with growing numbers of customers, varied geographical locations, the uncertainty of future orders, and sometimes extreme competitive pressure to reduce inventory costs. Linear optimization methods become cumbersome or intractable due to a large number of variables and nonlinear dependencies involved. Here we develop a complex systems approach to optimizing logistics networks based upon dimensional reduction methods and apply our approach to a case study of a manufacturing company. In order to characterize the complexity in customer behavior, we define a “customer space” in which individual customer behavior is described by only the two most relevant dimensions: the distance to production facilities over current transportation routes and the customer's demand frequency. These dimensions provide essential insight into the domain of effective strategies for customers; direct and indirect strategies. In the direct strategy, goods are sent to the customer directly from a production facility using box or bulk trucks. In the indirect strategy, in advance of an order by the customer, goods are shipped to an external warehouse near a customer using trains and then "last-mile" shipped by trucks when orders are placed. Each strategy applies to an area of the customer space with an indeterminate boundary between them. Specific company policies determine the location of the boundary generally. We then identify the optimal delivery strategy for each customer by constructing a detailed model of costs of transportation and temporary storage in a set of specified external warehouses. Customer spaces help give an aggregate view of customer behaviors and characteristics. They allow policymakers to compare customers and develop strategies based on the aggregate behavior of the system as a whole. In addition to optimization over existing facilities, using customer logistics and the k-means algorithm, we propose additional warehouse locations. We apply these methods to a medium-sized American manufacturing company with a particular logistics network, consisting of multiple production facilities, external warehouses, and customers along with three types of shipment methods (box truck, bulk truck and train). For the case study, our method forecasts 10.5% savings on yearly transportation costs and an additional 4.6% savings with three new warehouses.

Keywords: logistics network optimization, direct and indirect strategies, K-means algorithm, dimensional reduction

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5193 Design of an Artificial Oil Body-Cyanogen Bromide Technology Platform for the Expression of Small Bioactive Peptide, Mastoparan B

Authors: Tzyy-Rong Jinn, Sheng-Kuo Hsieh, Yi-Ching Chung, Feng-Chia Hsieh

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In this study, we attempted to develop a recombinant oleosin-based fusion expression strategy in Escherichia coli (E. coli) and coupled with the artificial oil bodies (AOB)-cyanogen bromide technology platform to produce bioactive mastoparan B (MP-B). As reported, the oleosin in AOB system plays a carrier (fusion with target protein), since oleosin possess two amphipathic regions (at the N-terminus and C-terminus), which result in the N-terminus and C-terminus of oleosin could be arranged on the surface of AOB. Thus, the target protein fused to the N-terminus or C-terminus of oleosin which also is exposed on the surface of AOB, and this process will greatly facilitate the subsequent separation and purification of target protein from AOB. In addition, oleosin, a unique structural protein of seed oil bodies, has the added advantage of helping the fused MP-B expressed in inclusion bodies, which can protect from proteolytic degradation. In this work, MP-B was fused to the C-terminus of oleosin and then was expressed in E. coli as an insoluble recombinant protein. As a consequence, we successfully developed a reliable recombinant oleosin-based fusion expression strategy in Escherichia coli and coupled with the artificial oil bodies (AOB)-cyanogen bromide technology platform to produce the small peptide, MP-B. Take together, this platform provides an insight into the production of active MP-B, which will facilitate studies and applications of this peptide in the future.

Keywords: artificial oil bodies, Escherichia coli, Oleosin-fusion protein, Mastoparan-B

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5192 Magnetic Single-Walled Carbon Nanotubes (SWCNTs) as Novel Theranostic Nanocarriers: Enhanced Targeting and Noninvasive MRI Tracking

Authors: Achraf Al Faraj, Asma Sultana Shaik, Baraa Al Sayed

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Specific and effective targeting of drug delivery systems (DDS) to cancerous sites remains a major challenge for a better diagnostic and therapy. Recently, SWCNTs with their unique physicochemical properties and the ability to cross the cell membrane show promising in the biomedical field. The purpose of this study was first to develop a biocompatible iron oxide tagged SWCNTs as diagnostic nanoprobes to allow their noninvasive detection using MRI and their preferential targeting in a breast cancer murine model by placing an optimized flexible magnet over the tumor site. Magnetic targeting was associated to specific antibody-conjugated SWCNTs active targeting. The therapeutic efficacy of doxorubicin-conjugated SWCNTs was assessed, and the superiority of diffusion-weighted (DW-) MRI as sensitive imaging biomarker was investigated. Short Polyvinylpyrrolidone (PVP) stabilized water soluble SWCNTs were first developed, tagged with iron oxide nanoparticles and conjugated with Endoglin/CD105 monoclonal antibodies. They were then conjugated with doxorubicin drugs. SWCNTs conjugates were extensively characterized using TEM, UV-Vis spectrophotometer, dynamic light scattering (DLS) zeta potential analysis and electron spin resonance (ESR) spectroscopy. Their MR relaxivities (i.e. r1 and r2*) were measured at 4.7T and their iron content and metal impurities quantified using ICP-MS. SWCNTs biocompatibility and drug efficacy were then evaluated both in vitro and in vivo using a set of immunological assays. Luciferase enhanced bioluminescence 4T1 mouse mammary tumor cells (4T1-Luc2) were injected into the right inguinal mammary fat pad of Balb/c mice. Tumor bearing mice received either free doxorubicin (DOX) drug or SWCNTs with or without either DOX or iron oxide nanoparticles. A multi-pole 10x10mm high-energy flexible magnet was maintained over the tumor site during 2 hours post-injections and their properties and polarity were optimized to allow enhanced magnetic targeting of SWCNTs toward the primary tumor site. Tumor volume was quantified during the follow-up investigation study using a fast spin echo MRI sequence. In order to detect the homing of SWCNTs to the main tumor site, susceptibility-weighted multi-gradient echo (MGE) sequence was used to generate T2* maps. Apparent diffusion coefficient (ADC) measurements were also performed as a sensitive imaging biomarker providing early and better assessment of disease treatment. At several times post-SWCNT injection, histological analysis were performed on tumor extracts and iron-loaded SWCNT were quantified using ICP-MS in tumor sites, liver, spleen, kidneys, and lung. The optimized multi-poles magnet revealed an enhanced targeting of magnetic SWCNTs to the primary tumor site, which was found to be much higher than the active targeting achieved using antibody-conjugated SWCNTs. Iron-loading allowed their sensitive noninvasive tracking after intravenous administration using MRI. The active targeting of doxorubicin through magnetic antibody-conjugated SWCNTs nanoprobes was found to considerably decrease the primary tumor site and may have inhibited the development of metastasis in the tumor-bearing mice lung. ADC measurements in DW-MRI were found to significantly increase in a time-dependent manner after the injection of DOX-conjugated SWCNTs complexes.

Keywords: single-walled carbon nanotubes, nanomedicine, magnetic resonance imaging, cancer diagnosis and therapy

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5191 The Relationship between Procurement Strategies and Sustainability Outcomes: A Systematic Literature Review

Authors: Cathy T. Mpanga Kowet, Aghaegbuna Obinna U. Ozumba

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This study examined and identified the inconsistencies, relationships, gaps and recurring themes in literature regarding the relationship between procurement strategies employed in the construction projects for sustainable buildings and realization of sustainability goals. A systematic literature review of studies on the relationship between various procurement strategies and attainment of sustainability outcomes was conducted. Using specific terms, papers published between 2002 and 2018 were identified and screened according to an inclusion and exclusion criteria. Current findings reveal that, although the attainment of sustainability goals is achievable with both traditional and contemporary procurement strategies, only projects delivered using modern procurement strategies are capable of meeting and exceeding targeted sustainability objectives. However, traditional procurement strategy remains the preferred method for most green building construction projects. The results suggest implications for decision makers in considering the impact of selected procurement strategies on targeted sustainability goals, in the early stages of sustainable building construction projects. The study shows that there is a gap between the reported appropriate procurement strategies and what is being practiced currently. Theoretically, the study expands on the literature on adoption and diffusion of contemporary procurement strategies, by consolidating existing studies to highlight the current gaps. While the study is at the literature review stage, deductions will serve as basis for field work involving empirical data.

Keywords: green buildings construction, procurement method, procurement strategy, sustainability objectives, sustainability outcomes

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5190 The Cleavage of DNA by the Anti-Tumor Drug Bleomycin at the Transcription Start Sites of Human Genes Using Genome-Wide Techniques

Authors: Vincent Murray

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The glycopeptide bleomycin is used in the treatment of testicular cancer, Hodgkin's lymphoma, and squamous cell carcinoma. Bleomycin damages and cleaves DNA in human cells, and this is considered to be the main mode of action for bleomycin's anti-tumor activity. In particular, double-strand breaks are thought to be the main mechanism for the cellular toxicity of bleomycin. Using Illumina next-generation DNA sequencing techniques, the genome-wide sequence specificity of bleomycin-induced double-strand breaks was determined in human cells. The degree of bleomycin cleavage was also assessed at the transcription start sites (TSSs) of actively transcribed genes and compared with non-transcribed genes. It was observed that bleomycin preferentially cleaved at the TSSs of actively transcribed human genes. There was a correlation between the degree of this enhanced cleavage at TSSs and the level of transcriptional activity. Bleomycin cleavage is also affected by chromatin structure and at TSSs, the peaks of bleomycin cleavage were approximately 200 bp apart. This indicated that bleomycin was able to detect phased nucleosomes at the TSSs of actively transcribed human genes. The genome-wide cleavage pattern of the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin was also investigated in human cells. As found for bleomycin, these bleomycin analogues also preferentially cleaved at the TSSs of actively transcribed human genes. The cytotoxicity (IC₅₀ values) of these bleomycin analogues was determined. It was found that the degree of enhanced cleavage at TSSs was inversely correlated with the IC₅₀ values of the bleomycin analogues. This suggested that the level of cleavage at the TSSs of actively transcribed human genes was important for the cytotoxicity of bleomycin and analogues. Hence this study provided a deeper understanding of the cellular processes involved in the cancer chemotherapeutic activity of bleomycin.

Keywords: anti-tumour activity, bleomycin analogues, chromatin structure, genome-wide study, Illumina DNA sequencing

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5189 A Preliminary Literature Review of Digital Transformation Case Studies

Authors: Vesna Bosilj Vukšić, Lucija Ivančić, Dalia Suša Vugec

Abstract:

While struggling to succeed in today’s complex market environment and provide better customer experience and services, enterprises encompass digital transformation as a means for reaching competitiveness and foster value creation. A digital transformation process consists of information technology implementation projects, as well as organizational factors such as top management support, digital transformation strategy, and organizational changes. However, to the best of our knowledge, there is little evidence about digital transformation endeavors in organizations and how they perceive it – is it only about digital technologies adoption or a true organizational shift is needed? In order to address this issue and as the first step in our research project, a literature review is conducted. The analysis included case study papers from Scopus and Web of Science databases. The following attributes are considered for classification and analysis of papers: time component; country of case origin; case industry and; digital transformation concept comprehension, i.e. focus. Research showed that organizations – public, as well as private ones, are aware of change necessity and employ digital transformation projects. Also, the changes concerning digital transformation affect both manufacturing and service-based industries. Furthermore, we discovered that organizations understand that besides technologies implementation, organizational changes must also be adopted. However, with only 29 relevant papers identified, research positioned digital transformation as an unexplored and emerging phenomenon in information systems research. The scarcity of evidence-based papers calls for further examination of this topic on cases from practice.

Keywords: digital strategy, digital technologies, digital transformation, literature review

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5188 Development of a Plug-In Hybrid Powertrain System with Double Continuously Variable Transmissions

Authors: Cheng-Chi Yu, Chi-Shiun Chiou

Abstract:

This study developed a plug-in hybrid powertrain system which consisted of two continuous variable transmissions. By matching between the engine, motor, generator, and dual continuous variable transmissions, this integrated power system can take advantages of the components. The hybrid vehicle can be driven by the internal combustion engine, or electric motor alone, or by these two power sources together when the vehicle is driven in hard acceleration or high load. The energy management of this integrated hybrid system controls the power systems based on rule-based control strategy to achieve better fuel economy. When the vehicle driving power demand is low, the internal combustion engine is operating in the low efficiency region, so the internal combustion engine is shut down, and the vehicle is driven by motor only. When the vehicle driving power demand is high, internal combustion engine would operate in the high efficiency region; then the vehicle could be driven by internal combustion engine. This strategy would operate internal combustion engine only in optimal efficiency region to improve the fuel economy. In this research, the vehicle simulation model was built in MATLAB/ Simulink environment. The analysis results showed that the power coupled efficiency of the hybrid powertrain system with dual continuous variable transmissions was better than that of the Honda hybrid system on the market.

Keywords: plug-in hybrid power system, fuel economy, performance, continuously variable transmission

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5187 Innovative Technology to Sustain Food Security in Qatar

Authors: Sana Abusin

Abstract:

Food security in Qatar is a research priority of Qatar University (2021-2025) and all national strategies, including the Qatar National Vision 2030 and food security strategy (2018-2023). Achieving food security requires three actions: 1) transforming surplus food to those who are insecure; 2) reducing food loss and waste by recycling food into valuable resources such as compost (“green fertilizer”) that can be used in growing food; and, finally, 3) establishing strong enforcement agencies to protect consumers from outdated food and promote healthy food. Currently, these objectives are approached separately and not in a sustainable fashion. Food security in Qatar is a research priority of Qatar University (2021-2025) and all national strategies, including the Qatar National Vision 2030 and food security strategy (2018-2023). The study aims to develop an innovative mobile application that supports a sustainable solution to food insecurity and food waste in Qatar. The application will provide a common solution for many different users. For producers, it will facilitate easy disposal of excess food. For charities, it will notify them about surplus food ready for redistribution. The application will also benefit the second layer of end-users in the form of food recycling companies, who will receive information about available food waste that is unable to be consumed. We will use self-exoplanetary diagrams and digital pictures to show all the steps to the final stage. The aim is to motivate the young generation toward innovation and creation, and to encourage public-private collaboration in this sector.

Keywords: food security, innovative technology, sustainability, food waste, Qatar

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5186 Investigating the Impact of Super Bowl Participation on Local Economy: A Perspective of Stock Market

Authors: Rui Du

Abstract:

This paper attempts to assess the impact of a major sporting event —the Super Bowl on the local economies. The identification strategy is to compare the winning and losing cities at the National Football League (NFL) conference finals under the assumption of similar pre-treatment trends. The stock market performances of companies headquartered in these cities are used to capture the sudden changes in local economic activities during a short time span. The exogenous variations in the football game outcome allow a straightforward difference-in-differences approach to identify the effect. This study finds that the post-event trends in winning and losing cities diverge despite the fact that both cities have economically and statistically similar pre-event trends. Empirical analysis provides suggestive evidence of a positive, significant local economic impact of conference final wins, possibly through city image enhancement. Further empirical evidence shows the presence of heterogeneous effects across industrial sectors, suggesting that city image enhancing the effect of the Super Bowl participation is empirically relevant for the changes in the composition of local industries. Also, this study also adopts a similar strategy to examine the local economic impact of Super Bowl successes, however, finds no statistically significant effect.

Keywords: Super Bowl Participation, local economies, city image enhancement, difference-in-di fferences, industrial sectors

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5185 Fostering Students’ Active Learning in Speaking Class through Project-Based Learning

Authors: Rukminingsih Rukmi

Abstract:

This paper addresses the issue of L2 teaching speaking to ESL students by fostering their active learning through project-based learning. Project-based learning was employed in classrooms where teachers support students by giving sufficient guidance and feedback. The students drive the inquiry, engage in research and discovery, and collaborate effectively with teammates to deliver the final work product. The teacher provides the initial direction and acts as a facilitator along the way. This learning approach is considered helpful for fostering students’ active learning. that the steps in implementing of project-based learning that fosters students’ critical thinking in TEFL class are in the following: (1) Discussing the materials about Speaking Class, (2) Working with the group to construct scenario of ways on speaking practice, (3) Practicing the scenario, (4) Recording the speaking practice into video, and (5) Evaluating the video product. This research is aimed to develop a strategy of teaching speaking by implementing project-based learning to improve speaking skill in the second Semester of English Department of STKIP PGRI Jombang. To achieve the purpose, the researcher conducted action research. The data of the study were gathered through the following instruments: test, observation checklists, and questionnaires. The result was indicated by the increase of students’ average speaking scores from 65 in the preliminary study, 73 in the first cycle, and 82 in the second cycle. Besides, the results of the study showed that project-based learning considered to be appropriate strategy to give students the same amount of chance in practicing their speaking skill and to pay attention in creating a learning situation.

Keywords: active learning, project-based learning, speaking ability, L2 teaching speaking

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5184 Enhanced Ripening Behaviour of Manganese Doped Cadmium Selenide Quantum Dots (Mn-doped CdSe QDs)

Authors: N. A. Hamizi, M. R. Johan, Y. H. Hor, A. N. Sabri, Y. Y. A. Yong

Abstract:

In this research, Mn-doped CdSe QDs is synthesized by using paraffin liquid as the reacting solvent and oleic acid as the ligands for Cd in order to produce Mn-doped CdSe QDs in zinc-blende crystal structure. Characterization studies for synthesized Mn-doped CdSe QDs are carried out using UV-visible and photoluminescence spectroscopy. The absorption wavelengths in UV-vis test and emission wavelengths in PL test were increase with the increases in the ripening temperature and time respectively.

Keywords: semiconductor, chemical synthesis, optical properties, ripening

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5183 Improving the Penalty-free Multi-objective Evolutionary Design Optimization of Water Distribution Systems

Authors: Emily Kambalame

Abstract:

Water distribution networks necessitate many investments for construction, prompting researchers to seek cost reduction and efficient design solutions. Optimization techniques are employed in this regard to address these challenges. In this context, the penalty-free multi-objective evolutionary algorithm (PFMOEA) coupled with pressure-dependent analysis (PDA) was utilized to develop a multi-objective evolutionary search for the optimization of water distribution systems (WDSs). The aim of this research was to find out if the computational efficiency of the PFMOEA for WDS optimization could be enhanced. This was done by applying real coding representation and retaining different percentages of feasible and infeasible solutions close to the Pareto front in the elitism step of the optimization. Two benchmark network problems, namely the Two-looped and Hanoi networks, were utilized in the study. A comparative analysis was then conducted to assess the performance of the real-coded PFMOEA in relation to other approaches described in the literature. The algorithm demonstrated competitive performance for the two benchmark networks by implementing real coding. The real-coded PFMOEA achieved the novel best-known solutions ($419,000 and $6.081 million) and a zero-pressure deficit for the two networks, requiring fewer function evaluations than the binary-coded PFMOEA. In previous PFMOEA studies, elitism applied a default retention of 30% of the least cost-feasible solutions while excluding all infeasible solutions. It was found in this study that by replacing 10% and 15% of the feasible solutions with infeasible ones that are close to the Pareto front with minimal pressure deficit violations, the computational efficiency of the PFMOEA was significantly enhanced. The configuration of 15% feasible and 15% infeasible solutions outperformed other retention allocations by identifying the optimal solution with the fewest function evaluation

Keywords: design optimization, multi-objective evolutionary, penalty-free, water distribution systems

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5182 Effect of Cognitive Rehabilitation in Pediatric Population with Acquired Brain Injury: A Pilot Study

Authors: Carolina Beltran, Carlos De Los Reyes

Abstract:

Acquired brain injury (ABI) is any physical and functional injury secondary to events that affect the brain tissue. It is one of the biggest causes of disability in the world and it has a high annual incidence in the pediatric population. There are several causes of ABI such as traumatic brain injury, central nervous system infection, stroke, hypoxia, tumors and others. The consequences can be cognitive, behavioral, emotional and functional. The cognitive rehabilitation is necessary to achieve the best outcomes for pediatric people with ABI. Cognitive orientation to daily occupational performance (CO-OP) is an individualized client-centered, performance-based, problem-solving approach that focuses on the strategy used to support the acquisition of three client-chosen goals. It has demonstrated improvements in the pediatric population with other neurological disorder but not in Spanish speakers with ABI. Aim: The main objective of this study was to determine the efficacy of cognitive orientation to daily occupational performances (CO-OP) adapted to Spanish speakers, in the level of independence and behavior in a pediatric population with ABI. Methods: Case studies with measure pre/post-treatment were used in three children with ABI, sustained at least before 6 months assessment, in school, aged 8 to 16 years, age ABI after 6 years old and above average intellectual ability. Twelve sessions of CO-OP adapted to Spanish speakers were used and videotaped. The outcomes were based on cognitive, behavior and functional independence measurements such as Child Behavior Checklist (CBCL), Behavior Rating Inventory of Executive Function (BRIEF), The Vineland Adaptive Behavior Scales (VINELAND, Social Support Scale (MOS-SSS) and others neuropsychological measures. This study was approved by the ethics committee of Universidad del Norte in Colombia. Informed parental written consent was obtained for all participants. Results: children were able to identify three goals and use the global strategy ‘goal-plan-do-check’ during each session. Verbal self-instruction was used by all children. CO-OP showed a clinically significant improvement in goals regarding with independence level and behavior according to parents and teachers. Conclusion: The results indicated that CO-OP and the use of a global strategy such as ‘goal-plan-do-check’ can be used in children with ABI in order to improve their specific goals. This is a preliminary version of a big study carrying in Colombia as part of the experimental design.

Keywords: cognitive rehabilitation, acquired brain injury, pediatric population, cognitive orientation to daily occupational performance

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5181 A Systematic Mapping of the Use of Information and Communication Technology (ICT)-Based Remote Agricultural Extension for Women Smallholders

Authors: Busiswa Madikazi

Abstract:

This systematic mapping study explores the underrepresentation of women's contributions to farming in the Global South within the development of Information and Communication Technologies (ICT)-based extension methods. Despite women farmers constituting 70% of the agricultural labour force, their productivity is hindered by various constraints, including illiteracy, household commitments, and limited access to credit and markets. A systematic mapping approach was employed with the aim of identifying evidence gaps in existing ICT extension for women farmers. The data collection protocol follows a structured approach, incorporating key criteria for inclusion, exclusion, search strategy, and coding and the PICO strategy (Population, Intervention, Comparator, and Outcome). The results yielded 119 articles that qualified for inclusion. The findings highlight that mobile phone apps (WhatsApp) and radio/television programming are the primary extension methods employed while integrating ICT with training, field visits, and demonstrations are underutilized. Notably, the study emphasizes the inadequate attention to critical issues such as food security, gender equality, and attracting youth to farming within ICT extension efforts. These findings indicate a significant policy and practice gap, neglecting community-driven approaches that cater to women's specific needs and enhance their agricultural production. Map highlights the importance of refocusing ICT extension efforts to address women farmers’ unique challenges, thereby contributing to their empowerment and improving agricultural practices.

Keywords: agricultural extension, ICT, women farmers, smallholders

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5180 Three Memorizing Strategies Reflective of Individual Students' Learning Modalities Applied to Piano Education

Authors: Olga Guseynova

Abstract:

Being an individual activity, the memorizing process is affected to a greater degree by the individual variables; therefore, one of the decisive factors influencing the memorization is students’ individual characteristics. Based on an extensive literature study in the domains of piano education, psychology, and neuroscience, this comprehensive research was designed in order to develop three memorizing strategies that are reflective of individual students’ learning modalities (visual, kinesthetic and auditory) applied to the piano education. The design of the study required an interdisciplinary approach which incorporated the outcome of neuropsychological and pedagogic experiments. The objectives were to determine the interaction between the process of perception and the process of memorizing music; to systematize the methods of memorizing piano sheet music in accordance with the specifics of perception types; to develop Piano Memorization Inventory (PMI) and the Three Memorizing Strategies (TMS). The following research methods were applied: a method of interdisciplinary analysis and synthesis, a method of non-participant observation. As a result of literature analysis, the following conclusions were made: the majority of piano teachers and piano students participated in the surveys, had not used and usually had not known any memorizing strategy regarding learning styles. As a result, they had used drilling as the main strategy of memorizing. The Piano Memorization Inventory and Three Memorizing Strategies developed by the author of the research were based on the observation and findings of the previous researches and considered the experience of pedagogical and neuropsychological studies.

Keywords: interdisciplinary approach, memorizing strategies, perceptual learning styles, piano memorization inventory

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5179 Biomimetic Architecture from the Inspiration by Nature to the Innovation of the Saharan Architecture

Authors: Yassine Mohammed Benyoucef, Razin Andery Dionisovich

Abstract:

Biomimicry is an old approach, but in the scientific conceptualization is new, as an approach of innovation based on the emulation of Nature, in recent years, this approach brings many potential theories and innovations in the architecture field. Indeed, these innovations have changed our view towards other Natural organisms also to the design processes in architecture, now the use of the biomimicry approach allows the application of a great sustainable development. The Sahara area is heading towards a sustainable policy with the desire to develop this rich context in terms of architecture, because of the rapid evolution of the architectural and urban concepts and the technology acceleration in one side, and under the pressure of the architectural crisis and the accelerated urbanization in the Saharan cities on the other side, the imperatives of sustainable development, ecology, climate adaptation, energy needs, are strongly imposed. Besides that, the new architectural and urban projects in the Saharan cities are not reliable in terms of energy efficiency and design and relationship with the environment. This article discusses the using of biomimetic strategy in the sustainable development of Saharan architecture. The aim of the article is to present a synthesis of biomimicry approach and propose the biomimicry as a solution for the development of Saharan architecture which can use this approach as a sustainable and innovation strategy. The biomimicry is the solution for effective strategies of development and can have a great potential point to meet the current challenges of designing efficient for forms or structures, energy efficiency, and climate issues. Moreover, the Sahara can be a favorable soil for great changes, the use of this approach is the key for the most optimal strategies and sustainable development of the Saharan architecture.

Keywords: biomimicry, Sahara, architecture, nature, innovation, technology

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5178 “Japan’s New Security Outlook: Implications for the US-Japan Alliance”

Authors: Agustin Maciel-Padilla

Abstract:

This paper explores the most significant change to Japan’s security strategy since the end of World War II, in particular Prime Minister Fumio Kishida’s government publication, in late 2022, of 3 policy documents (the National Security Strategy [NSS], the National Defense Strategy and the Defense Buildup Program) that basically propose to expand the country’s military capabilities and to increase military spending over a 5-year period. These policies represent a remarkable transformation of Japan’s defense-oriented policy followed since 1946. These proposals have been under analysis and debate since they were announced, as it was also Japan’s historic ambition to strengthening its deterrence capabilities in the context of a more complex regional security environment. Even though this new defense posture has attracted significant international attention, it is far from representing a done deal because of the fact that there is still a long way to go to implement this vision because of a wide variety of political and economic issues. Japan is currently experiencing the most dangerous security environment since the end of World War II, and this situation led Japan to intensify its dialogue with the United States to reflect a re-evaluation of deterrence in the face of a rapidly worsening security environment, a changing balance of power in East Asia, and the arrival of a new era of “great power competition”. Japan’s new documents, for instance, identify China and North Korea’s as posing, respectively, a strategic challenge and an imminent threat. Japan has also noted that Russia’s invasion of Ukraine has contributed to erode the foundation of the international order. It is considered that Russia’s aggression was possible because Ukraine’s defense capability was not enough for effective deterrence. Moreover, Japan’s call for “counterstrike capabilities” results from a recognition that China and North Korea’s ballistic and cruise missiles could overwhelm Japan’s air and missile defense systems, and therefore there is an urgent need to strengthen deterrence and resilience. In this context, this paper will focus on the impact of these changes on the US-Japan alliance. Adapting this alliance to Tokyo’s new ambitions and capabilities could be critical in terms of updating their traditional protection/access to bases arrangement, interoperability and joint command and control issues, as well as regarding the security–economy nexus. While China is Japan’s largest trading partner, and trade between the two has been growing, US-Japan economic relationship has been slower, notwithstanding the fact that US-Japan security cooperation has strengthened significantly in recent years.

Keywords: us-japan alliance, japan security, great power competition, interoperability

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5177 The Use of Bleomycin and Analogues to Probe the Chromatin Structure of Human Genes

Authors: Vincent Murray

Abstract:

The chromatin structure at the transcription start sites (TSSs) of genes is very important in the control of gene expression. In order for gene expression to occur, the chromatin structure at the TSS has to be altered so that the transcriptional machinery can be assembled and RNA transcripts can be produced. In particular, the nucleosome structure and positioning around the TSS has to be changed. Bleomycin is utilized as an anti-tumor agent to treat Hodgkin's lymphoma, squamous cell carcinoma, and testicular cancer. Bleomycin produces DNA damage in human cells and DNA strand breaks, especially double-strand breaks, are thought to be responsible for the cancer chemotherapeutic activity of bleomycin. Bleomycin is a large glycopeptide with molecular weight of approximately 1500 Daltons and hence its DNA strand cleavage activity can be utilized as a probe of chromatin structure. In this project, Illumina next-generation DNA sequencing technology was used to determine the position of DNA double-strand breaks at the TSSs of genes in intact cells. In this genome-wide study, it was found that bleomycin cleavage preferentially occurred at the TSSs of actively transcribed human genes in comparison with non-transcribed genes. There was a correlation between the level of enhanced bleomycin cleavage at TSSs and the degree of transcriptional activity. In addition, bleomycin was able to determine the position of nucleosomes at the TSSs of human genes. Bleomycin analogues were also utilized as probes of chromatin structure at the TSSs of human genes. In a similar manner to bleomycin, the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin preferentially cleaved at the TSSs of human genes. Interestingly this degree of enhanced TSS cleavage inversely correlated with the cytotoxicity (IC50 values) of BLM analogues. This indicated that the degree of cleavage by bleomycin analogues at the TSSs of human genes was very important in the cytotoxicity of bleomycin and analogues. It also provided a deeper insight into the mechanism of action of this cancer chemotherapeutic agent since actively transcribed genes were preferentially targeted.

Keywords: anti-cancer activity, chromatin structure, cytotoxicity, gene expression, next-generation DNA sequencing

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