12,388 research outputs found

    The Metaverse: Survey, Trends, Novel Pipeline Ecosystem & Future Directions

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    The Metaverse offers a second world beyond reality, where boundaries are non-existent, and possibilities are endless through engagement and immersive experiences using the virtual reality (VR) technology. Many disciplines can benefit from the advancement of the Metaverse when accurately developed, including the fields of technology, gaming, education, art, and culture. Nevertheless, developing the Metaverse environment to its full potential is an ambiguous task that needs proper guidance and directions. Existing surveys on the Metaverse focus only on a specific aspect and discipline of the Metaverse and lack a holistic view of the entire process. To this end, a more holistic, multi-disciplinary, in-depth, and academic and industry-oriented review is required to provide a thorough study of the Metaverse development pipeline. To address these issues, we present in this survey a novel multi-layered pipeline ecosystem composed of (1) the Metaverse computing, networking, communications and hardware infrastructure, (2) environment digitization, and (3) user interactions. For every layer, we discuss the components that detail the steps of its development. Also, for each of these components, we examine the impact of a set of enabling technologies and empowering domains (e.g., Artificial Intelligence, Security & Privacy, Blockchain, Business, Ethics, and Social) on its advancement. In addition, we explain the importance of these technologies to support decentralization, interoperability, user experiences, interactions, and monetization. Our presented study highlights the existing challenges for each component, followed by research directions and potential solutions. To the best of our knowledge, this survey is the most comprehensive and allows users, scholars, and entrepreneurs to get an in-depth understanding of the Metaverse ecosystem to find their opportunities and potentials for contribution

    Examples of works to practice staccato technique in clarinet instrument

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    Klarnetin staccato tekniğini güçlendirme aşamaları eser çalışmalarıyla uygulanmıştır. Staccato geçişlerini hızlandıracak ritim ve nüans çalışmalarına yer verilmiştir. Çalışmanın en önemli amacı sadece staccato çalışması değil parmak-dilin eş zamanlı uyumunun hassasiyeti üzerinde de durulmasıdır. Staccato çalışmalarını daha verimli hale getirmek için eser çalışmasının içinde etüt çalışmasına da yer verilmiştir. Çalışmaların üzerinde titizlikle durulması staccato çalışmasının ilham verici etkisi ile müzikal kimliğe yeni bir boyut kazandırmıştır. Sekiz özgün eser çalışmasının her aşaması anlatılmıştır. Her aşamanın bir sonraki performans ve tekniği güçlendirmesi esas alınmıştır. Bu çalışmada staccato tekniğinin hangi alanlarda kullanıldığı, nasıl sonuçlar elde edildiği bilgisine yer verilmiştir. Notaların parmak ve dil uyumu ile nasıl şekilleneceği ve nasıl bir çalışma disiplini içinde gerçekleşeceği planlanmıştır. Kamış-nota-diyafram-parmak-dil-nüans ve disiplin kavramlarının staccato tekniğinde ayrılmaz bir bütün olduğu saptanmıştır. Araştırmada literatür taraması yapılarak staccato ile ilgili çalışmalar taranmıştır. Tarama sonucunda klarnet tekniğin de kullanılan staccato eser çalışmasının az olduğu tespit edilmiştir. Metot taramasında da etüt çalışmasının daha çok olduğu saptanmıştır. Böylelikle klarnetin staccato tekniğini hızlandırma ve güçlendirme çalışmaları sunulmuştur. Staccato etüt çalışmaları yapılırken, araya eser çalışmasının girmesi beyni rahatlattığı ve istekliliği daha arttırdığı gözlemlenmiştir. Staccato çalışmasını yaparken doğru bir kamış seçimi üzerinde de durulmuştur. Staccato tekniğini doğru çalışmak için doğru bir kamışın dil hızını arttırdığı saptanmıştır. Doğru bir kamış seçimi kamıştan rahat ses çıkmasına bağlıdır. Kamış, dil atma gücünü vermiyorsa daha doğru bir kamış seçiminin yapılması gerekliliği vurgulanmıştır. Staccato çalışmalarında baştan sona bir eseri yorumlamak zor olabilir. Bu açıdan çalışma, verilen müzikal nüanslara uymanın, dil atış performansını rahatlattığını ortaya koymuştur. Gelecek nesillere edinilen bilgi ve birikimlerin aktarılması ve geliştirici olması teşvik edilmiştir. Çıkacak eserlerin nasıl çözüleceği, staccato tekniğinin nasıl üstesinden gelinebileceği anlatılmıştır. Staccato tekniğinin daha kısa sürede çözüme kavuşturulması amaç edinilmiştir. Parmakların yerlerini öğrettiğimiz kadar belleğimize de çalışmaların kaydedilmesi önemlidir. Gösterilen azmin ve sabrın sonucu olarak ortaya çıkan yapıt başarıyı daha da yukarı seviyelere çıkaracaktır

    Bridging technology and educational psychology: an exploration of individual differences in technology-assisted language learning within an Algerian EFL setting

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    The implementation of technology in language learning and teaching has a great influence onthe teaching and learning process as a whole and its impact on the learners’ psychological state seems of paramount significance, since it could be either an aid or a barrier to students’ academic performance. This thesis therefore explores individual learner differences in technology-assisted language learning (TALL) and when using educational technologies in higher education within an Algerian English as a Foreign Language (EFL) setting. Although I initially intended to investigate the relationship between TALL and certain affective variables mainly motivation, anxiety, self-confidence, and learning styles inside the classroom, the collection and analysis of data shifted my focus to a holistic view of individual learner differences in TALL environments and when using educational technologies within and beyond the classroom. In an attempt to bridge technology and educational psychology, this ethnographic case study considers the nature of the impact of technology integration in language teaching and learning on the psychology of individual language learners inside and outside the classroom. The study considers the reality constructed by participants and reveals multiple and distinctive views about the relationship between the use of educational technologies in higher education and individual learner differences. It took place in a university in the north-west of Algeria and involved 27 main and secondary student and teacher participants. It consisted of focus-group discussions, follow-up discussions, teachers’ interviews, learners’ diaries, observation, and field notes. It was initially conducted within the classroom but gradually expanded to other settings outside the classroom depending on the availability of participants, their actions, and activities. The study indicates that the impact of technology integration in EFL learning on individual learner differences is both complex and dynamic. It is complex in the sense that it is shown in multiple aspects and reflected on the students and their differences. In addition to various positive and different negative influences of different technology uses and the different psychological reactions among students to the same technology scenario, the study reveals the unrecognised different manifestations of similar psychological traits in the same ELT technology scenario. It is also dynamic since it is characterised by constant change according to contextual approaches to and practical realities of technology integration in language teaching and learning in the setting, including discrepancies between students’ attitudes and teacher’ actions, mismatches between technological experiences inside and outside the classroom, local concerns and generalised beliefs about TALL in the context, and the rapid and unplanned shift to online educational delivery during the Covid-19 pandemic situation. The study may therefore be of interest, not only to Algerian teachers and students, but also to academics and institutions in other contexts through considering the complex and dynamic impact of TALL and technology integration at higher education on individual differences, and to academics in similar low-resource contexts by undertaking a context approach to technology integration

    In vitro investigation of the effect of disulfiram on hypoxia induced NFκB, epithelial to mesenchymal transition and cancer stem cells in glioblastoma cell lines

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    A thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of Philosophy.Glioblastoma multiforme (GBM) is one of the most aggressive and lethal cancers with a poor prognosis. Advances in the treatment of GBM are limited due to several resistance mechanisms and limited drug delivery into the central nervous system (CNS) compartment by the blood-brain barrier (BBB) and by actions of the normal brain to counteract tumour-targeting medications. Hypoxia is common in malignant brain tumours such as GBM and plays a significant role in tumour pathobiology. It is widely accepted that hypoxia is a major driver of GBM malignancy. Although it has been confirmed that hypoxia induces GBM stem-like-cells (GSCs), which are highly invasive and resistant to all chemotherapeutic agents, the detailed molecular pathways linking hypoxia, GSC traits and chemoresistance remain obscure. Evidence shows that hypoxia induces cancer stem cell phenotypes via epithelial-to-mesenchymal transition (EMT), promoting therapeutic resistance in most cancers, including GBM. This study demonstrated that spheroid cultured GBM cells consist of a large population of hypoxic cells with CSC and EMT characteristics. GSCs are chemo-resistant and displayed increased levels of HIFs and NFκB activity. Similarly, the hypoxia cultured GBM cells manifested GSC traits, chemoresistance and invasiveness. These results suggest that hypoxia is responsible for GBM stemness, chemoresistance and invasiveness. GBM cells transfected with nuclear factor kappa B-p65 (NFκB-p65) subunit exhibited CSC and EMT markers indicating the essential role of NFκB in maintaining GSC phenotypes. The study also highlighted the significance of NFκB in driving chemoresistance, invasiveness, and the potential role of NFκB as the central regulator of hypoxia-induced stemness in GBM cells. GSC population has the ability of self-renewal, cancer initiation and development of secondary heterogeneous cancer. The very poor prognosis of GBM could largely be attributed to the existence of GSCs, which promote tumour propagation, maintenance, radio- and chemoresistance and local infiltration. In this study, we used Disulfiram (DS), a drug used for more than 65 years in alcoholism clinics, in combination with copper (Cu) to target the NFκB pathway, reverse chemoresistance and block invasion in GSCs. The obtained results showed that DS/Cu is highly cytotoxic to GBM cells and completely eradicated the resistant CSC population at low dose levels in vitro. DS/Cu inhibited the migration and invasion of hypoxia-induced CSC and EMT like GBM cells at low nanomolar concentrations. DS is an FDA approved drug with low toxicity to normal tissues and can pass through the BBB. Further research may lead to the quick translation of DS into cancer clinics and provide new therapeutic options to improve treatment outcomes in GBM patients

    Estudo da remodelagem reversa miocárdica através da análise proteómica do miocárdio e do líquido pericárdico

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    Valve replacement remains as the standard therapeutic option for aortic stenosis patients, aiming at abolishing pressure overload and triggering myocardial reverse remodeling. However, despite the instant hemodynamic benefit, not all patients show complete regression of myocardial hypertrophy, being at higher risk for adverse outcomes, such as heart failure. The current comprehension of the biological mechanisms underlying an incomplete reverse remodeling is far from complete. Furthermore, definitive prognostic tools and ancillary therapies to improve the outcome of the patients undergoing valve replacement are missing. To help abridge these gaps, a combined myocardial (phospho)proteomics and pericardial fluid proteomics approach was followed, taking advantage of human biopsies and pericardial fluid collected during surgery and whose origin anticipated a wealth of molecular information contained therein. From over 1800 and 750 proteins identified, respectively, in the myocardium and in the pericardial fluid of aortic stenosis patients, a total of 90 dysregulated proteins were detected. Gene annotation and pathway enrichment analyses, together with discriminant analysis, are compatible with a scenario of increased pro-hypertrophic gene expression and protein synthesis, defective ubiquitinproteasome system activity, proclivity to cell death (potentially fed by complement activity and other extrinsic factors, such as death receptor activators), acute-phase response, immune system activation and fibrosis. Specific validation of some targets through immunoblot techniques and correlation with clinical data pointed to complement C3 β chain, Muscle Ring Finger protein 1 (MuRF1) and the dual-specificity Tyr-phosphorylation regulated kinase 1A (DYRK1A) as potential markers of an incomplete response. In addition, kinase prediction from phosphoproteome data suggests that the modulation of casein kinase 2, the family of IκB kinases, glycogen synthase kinase 3 and DYRK1A may help improve the outcome of patients undergoing valve replacement. Particularly, functional studies with DYRK1A+/- cardiomyocytes show that this kinase may be an important target to treat cardiac dysfunction, provided that mutant cells presented a different response to stretch and reduced ability to develop force (active tension). This study opens many avenues in post-aortic valve replacement reverse remodeling research. In the future, gain-of-function and/or loss-of-function studies with isolated cardiomyocytes or with animal models of aortic bandingdebanding will help disclose the efficacy of targeting the surrogate therapeutic targets. Besides, clinical studies in larger cohorts will bring definitive proof of complement C3, MuRF1 and DYRK1A prognostic value.A substituição da válvula aórtica continua a ser a opção terapêutica de referência para doentes com estenose aórtica e visa a eliminação da sobrecarga de pressão, desencadeando a remodelagem reversa miocárdica. Contudo, apesar do benefício hemodinâmico imediato, nem todos os pacientes apresentam regressão completa da hipertrofia do miocárdio, ficando com maior risco de eventos adversos, como a insuficiência cardíaca. Atualmente, os mecanismos biológicos subjacentes a uma remodelagem reversa incompleta ainda não são claros. Além disso, não dispomos de ferramentas de prognóstico definitivos nem de terapias auxiliares para melhorar a condição dos pacientes indicados para substituição da válvula. Para ajudar a resolver estas lacunas, uma abordagem combinada de (fosfo)proteómica e proteómica para a caracterização, respetivamente, do miocárdio e do líquido pericárdico foi seguida, tomando partido de biópsias e líquidos pericárdicos recolhidos em ambiente cirúrgico. Das mais de 1800 e 750 proteínas identificadas, respetivamente, no miocárdio e no líquido pericárdico dos pacientes com estenose aórtica, um total de 90 proteínas desreguladas foram detetadas. As análises de anotação de genes, de enriquecimento de vias celulares e discriminativa corroboram um cenário de aumento da expressão de genes pro-hipertróficos e de síntese proteica, um sistema ubiquitina-proteassoma ineficiente, uma tendência para morte celular (potencialmente acelerada pela atividade do complemento e por outros fatores extrínsecos que ativam death receptors), com ativação da resposta de fase aguda e do sistema imune, assim como da fibrose. A validação de alguns alvos específicos através de immunoblot e correlação com dados clínicos apontou para a cadeia β do complemento C3, a Muscle Ring Finger protein 1 (MuRF1) e a dual-specificity Tyr-phosphoylation regulated kinase 1A (DYRK1A) como potenciais marcadores de uma resposta incompleta. Por outro lado, a predição de cinases a partir do fosfoproteoma, sugere que a modulação da caseína cinase 2, a família de cinases do IκB, a glicogénio sintase cinase 3 e da DYRK1A pode ajudar a melhorar a condição dos pacientes indicados para intervenção. Em particular, a avaliação funcional de cardiomiócitos DYRK1A+/- mostraram que esta cinase pode ser um alvo importante para tratar a disfunção cardíaca, uma vez que os miócitos mutantes responderam de forma diferente ao estiramento e mostraram uma menor capacidade para desenvolver força (tensão ativa). Este estudo levanta várias hipóteses na investigação da remodelagem reversa. No futuro, estudos de ganho e/ou perda de função realizados em cardiomiócitos isolados ou em modelos animais de banding-debanding da aorta ajudarão a testar a eficácia de modular os potenciais alvos terapêuticos encontrados. Além disso, estudos clínicos em coortes de maior dimensão trarão conclusões definitivas quanto ao valor de prognóstico do complemento C3, MuRF1 e DYRK1A.Programa Doutoral em Biomedicin

    On the Mechanism of Building Core Competencies: a Study of Chinese Multinational Port Enterprises

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    This study aims to explore how Chinese multinational port enterprises (MNPEs) build their core competencies. Core competencies are firms’special capabilities and sources to gain sustainable competitive advantage (SCA) in marketplace, and the concept led to extensive research and debates. However, few studies include inquiries about the mechanisms of building core competencies in the context of Chinese MNPEs. Accordingly, answers were sought to three research questions: 1. What are the core competencies of the Chinese MNPEs? 2. What are the mechanisms that the Chinese MNPEs use to build their core competencies? 3. What are the paths that the Chinese MNPEs pursue to build their resources bases? The study adopted a multiple-case study design, focusing on building mechanism of core competencies with RBV. It selected purposively five Chinese leading MNPEs and three industry associations as Case Companies. The study revealed three main findings. First, it identified three generic core competencies possessed by Case Companies, i.e., innovation in business models and operations, utilisation of technologies, and acquisition of strategic resources. Second, it developed the conceptual framework of the Mechanism of Building Core Competencies (MBCC), which is a process of change of collective learning in effective and efficient utilization of resources of a firm in response to critical events. Third, it proposed three paths to build core competencies, i.e., enhancing collective learning, selecting sustainable processes, and building resource base. The study contributes to the knowledge of core competencies and RBV in three ways: (1) presenting three generic core competencies of the Chinese MNPEs, (2) proposing a new conceptual framework to explain how Chinese MNPEs build their core competencies, (3) suggesting a solid anchor point (MBCC) to explain the links among resources, core competencies, and SCA. The findings set benchmarks for Chinese logistics industry and provide guidelines to build core competencies

    Transformation of the business model to establish sustainable value in the consumer durables super store industry of Sri Lanka

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    The business model of an organization, operates as the fundamental blue print of the planning process, which shapes the nature of the strategies executed during the course of operation. These strategies in turn are responsible for the value creation or value erosion that takes place during the operation of the organization determining its sustainability, and in a broader context the sustainability of the industry. The research is done for the Consumer Durables Super Store (CDSS) industry of Sri Lanka concerning the existing business model, the value erosion occurring as a result of it and the risk it carries to the sustainability of the industry. The theoretical aspect of the research to develop a relationship based business model was anchored on the understanding of existing frameworks relating to sustainable value and extracting relevant areas of each of these frameworks (alignment of value, transforming current strategies and service offerings to create sustainable value) to develop a suitable hybrid framework with modifications to the literature to suite the research context.Ten in-depth interviews with CDSS organizational representatives holding leadership, sales and marketing management positions, and two focus group sessions with fifty selected customers were conducted in a virtual environment due to the prevailing pandemic situation. The data collected were analyzed with NVIVO 12, with themes relevant to the research utilized as codes, giving a clear understanding over the buyer and seller purview on the themes of the research. The findings surfaced the value erosion caused due to the financially driven strategies originated from the transactional orientation of the existing business model. The theories adopted to construct the relationship oriented business model to rectify the value erosion taking place, based on sustainable value, value alignment and service offerings, were modified to incorporate ‘quality of trade’ to bridge the gap, leading towards the creation and delivery of sustainable value to the buyer-seller eco system of the industry

    The determinants of value addition: a crtitical analysis of global software engineering industry in Sri Lanka

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    It was evident through the literature that the perceived value delivery of the global software engineering industry is low due to various facts. Therefore, this research concerns global software product companies in Sri Lanka to explore the software engineering methods and practices in increasing the value addition. The overall aim of the study is to identify the key determinants for value addition in the global software engineering industry and critically evaluate the impact of them for the software product companies to help maximise the value addition to ultimately assure the sustainability of the industry. An exploratory research approach was used initially since findings would emerge while the study unfolds. Mixed method was employed as the literature itself was inadequate to investigate the problem effectively to formulate the research framework. Twenty-three face-to-face online interviews were conducted with the subject matter experts covering all the disciplines from the targeted organisations which was combined with the literature findings as well as the outcomes of the market research outcomes conducted by both government and nongovernment institutes. Data from the interviews were analysed using NVivo 12. The findings of the existing literature were verified through the exploratory study and the outcomes were used to formulate the questionnaire for the public survey. 371 responses were considered after cleansing the total responses received for the data analysis through SPSS 21 with alpha level 0.05. Internal consistency test was done before the descriptive analysis. After assuring the reliability of the dataset, the correlation test, multiple regression test and analysis of variance (ANOVA) test were carried out to fulfil the requirements of meeting the research objectives. Five determinants for value addition were identified along with the key themes for each area. They are staffing, delivery process, use of tools, governance, and technology infrastructure. The cross-functional and self-organised teams built around the value streams, employing a properly interconnected software delivery process with the right governance in the delivery pipelines, selection of tools and providing the right infrastructure increases the value delivery. Moreover, the constraints for value addition are poor interconnection in the internal processes, rigid functional hierarchies, inaccurate selections and uses of tools, inflexible team arrangements and inadequate focus for the technology infrastructure. The findings add to the existing body of knowledge on increasing the value addition by employing effective processes, practices and tools and the impacts of inaccurate applications the same in the global software engineering industry
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