12,735 research outputs found
The Metaverse: Survey, Trends, Novel Pipeline Ecosystem & Future Directions
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
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Ensuring Access to Safe and Nutritious Food for All Through the Transformation of Food Systems
A Design Science Research Approach to Smart and Collaborative Urban Supply Networks
Urban supply networks are facing increasing demands and challenges and thus constitute a relevant field for research and practical development. Supply chain management holds enormous potential and relevance for society and everyday life as the flow of goods and information are important economic functions. Being a heterogeneous field, the literature base of supply chain management research is difficult to manage and navigate. Disruptive digital technologies and the implementation of cross-network information analysis and sharing drive the need for new organisational and technological approaches. Practical issues are manifold and include mega trends such as digital transformation, urbanisation, and environmental awareness.
A promising approach to solving these problems is the realisation of smart and collaborative supply networks. The growth of artificial intelligence applications in recent years has led to a wide range of applications in a variety of domains. However, the potential of artificial intelligence utilisation in supply chain management has not yet been fully exploited. Similarly, value creation increasingly takes place in networked value creation cycles that have become continuously more collaborative, complex, and dynamic as interactions in business processes involving information technologies have become more intense.
Following a design science research approach this cumulative thesis comprises the development and discussion of four artefacts for the analysis and advancement of smart and collaborative urban supply networks. This thesis aims to highlight the potential of artificial intelligence-based supply networks, to advance data-driven inter-organisational collaboration, and to improve last mile supply network sustainability. Based on thorough machine learning and systematic literature reviews, reference and system dynamics modelling, simulation, and qualitative empirical research, the artefacts provide a valuable contribution to research and practice
Subsidiary Entrepreneurial Alertness: Antecedents and Outcomes
This thesis brings together concepts from both international business and entrepreneurship to develop a framework of the facilitators of subsidiary innovation and performance. This study proposes that Subsidiary Entrepreneurial Alertness (SEA) facilitates the recognition of opportunities (the origin of subsidiary initiatives). First introduced by Kirzner (1979) in the context of the individual, entrepreneurial alertness (EA) is the ability to notice an opportunity without actively searching. Similarly, to entrepreneurial alertness at the individual level, this study argues that SEA enables the subsidiary to best select opportunities based on resources available. The research further develops our conceptualisation of SEA by drawing on work by Tang et al. (2012) identifying three distinct activities of EA: scanning and search (identifying opportunities unseen by others due to their awareness gaps), association and connection of information, and evaluation and judgement to interpret or anticipate future viability of opportunities. This study then hypothesises that SEA leads to opportunity recognition at the subsidiary level and further hypothesises innovation and performance as outcomes of opportunity recognition. This research brings these arguments together to develop and test a comprehensive theoretical model.
The theoretical model is tested through a mail survey of the CEOs/MDs of foreign subsidiaries within the Republic of Ireland (an innovative hub for foreign subsidiaries). This method was selected as the best method to reach the targeted respondent, and due to the depth of knowledge the target respondent holds, the survey can answer the desired question more substantially. The results were examined using partial least squares structural equation modelling (PLS-SEM). The study’s findings confirm two critical aspects of subsidiary context, subsidiary brokerage and subsidiary credibility are positively related to SEA. The study establishes a positive link between SEA and both the generation of innovation and the subsidiary’s performance. This thesis makes three significant contributions to the subsidiary literature as it 1) introduces and develops the concept of SEA, 2) identifies the antecedents of SEA, and 3) demonstrates the impact of SEA on subsidiary opportunity recognition. Implications for subsidiaries, headquarters and policy makers are discussed along with the limitations of the study
Central-provincial Politics and Industrial Policy-making in the Electric Power Sector in China
In addition to the studies that provide meaningful insights into the complexity of technical and economic issues, increasing studies have focused on the political process of market transition in network industries such as the electric power sector. This dissertation studies the central–provincial interactions in industrial policy-making and implementation, and attempts to evaluate the roles of Chinese provinces in the market reform process of the electric power sector. Market reforms of this sector are used as an illustrative case because the new round of market reforms had achieved some significant breakthroughs in areas such as pricing reform and wholesale market trading. Other policy measures, such as the liberalization of the distribution market and cross-regional market-building, are still at a nascent stage and have only scored moderate progress. It is important to investigate why some policy areas make greater progress in market reforms than others. It is also interesting to examine the impacts of Chinese central-provincial politics on producing the different market reform outcomes. Guangdong and Xinjiang are two provinces being analyzed in this dissertation. The progress of market reforms in these two provinces showed similarities although the provinces are very different in terms of local conditions such as the stages of their economic development and energy structures. The actual reform can be understood as the outcomes of certain modes of interactions between the central and provincial actors in the context of their particular capabilities and preferences in different policy areas. This dissertation argues that market reform is more successful in policy areas where the central and provincial authorities are able to engage mainly in integrative negotiations than in areas where they engage mainly in distributive negotiations
Consent and the Construction of the Volunteer: Institutional Settings of Experimental Research on Human Beings in Britain during the Cold War
This study challenges the primacy of consent in the history of human experimentation and argues that privileging the cultural frameworks adds nuance to our understanding of the construction of the volunteer in the period 1945 to 1970. Historians and bio-ethicists have argued that medical ethics codes have marked out the parameters of using people as subjects in medical scientific research and that the consent of the subjects was fundamental to their status as volunteers. However, the temporality of the creation of medical ethics codes means that they need to be understood within their historical context. That medical ethics codes arose from a specific historical context rather than a concerted and conscious determination to safeguard the well-being of subjects needs to be acknowledged. The British context of human experimentation is under-researched and there has been even less focus on the cultural frameworks within which experiments took place. This study demonstrates, through a close analysis of the Medical Research Council's Common Cold Research Unit (CCRU) and the government's military research facility, the Chemical Defence Experimental Establishment, Porton Down (Porton), that the `volunteer' in human experiments was a subjective entity whose identity was specific to the institution which recruited and made use of the subject. By examining representations of volunteers in the British press, the rhetoric of the government's collectivist agenda becomes evident and this fed into the institutional construction of the volunteer at the CCRU. In contrast, discussions between Porton scientists, staff members, and government officials demonstrate that the use of military personnel in secret chemical warfare experiments was far more complex. Conflicting interests of the military, the government and the scientific imperative affected how the military volunteer was perceived
Characterising the role of the Amyloid Precursor Protein and Glucagon-like peptide-1 analogues in Age-Related Macular Degeneration
Age-related macular degeneration (AMD) is a progressive retinal neurodegenerative disorder characterised, in some forms of the disease, by the loss of photoreceptors and the underlying retinal pigment epithelium (RPE) in the macula due to the accumulation of extracellular deposits known as “drusen”. A major component of drusen deposits is the Alzheimer’s disease (AD)-related amyloid beta (Aβ)-peptide, a 4kDa peptide derived from the larger amyloid precursor protein (APP) through sequential cleavage by enzymes known as β- and γ-secretases. Alternatively, in the ‘non-amyloidogenic’ pathway, APP can be processed by a third enzyme, α-secretase, which cleaves within the Aβ region of the protein thereby preventing the production of toxic peptides as well as producing a larger soluble fragment, sAPPα, known for its neuroprotective and neurotrophic properties. The current project aims to characterise the role played by APP and its proteolytic fragments in AMD using human retinal pigment epithelial cells (ARPE-19) and UV-A light (a known AMD risk factor) as the stressor. In addition, a group of diabetes drugs known as Glucagon Like Peptide-1 (GLP-1) analogues that have previously been purported to reduce neuronal death in AD and Parkinson’s Disease (PD) have been tested for their ability to protect ARPE-19 cells against stress-inducing reagents relative to AMD (UV-A light, hydrogen peroxide and Aβ-peptides). The results of the current study demonstrate that endogenous cell-associated full-length APP expression was depleted in ARPE-19 cells following UV-A irradiation. Furthermore, β-secretase but not α-secretase processing of the protein was reduced. Small interfering RNA-mediated depletion of endogenous APP or γ-secretase (but not α- or β-secretase) inhibition ablated the detrimental effect of UV-A on cell viability. In contrast, α-secretase and, possibly, γ-secretase but not β-secretase activity appeared to promote the longer-term proliferation of ARPE-19 cells in the absence of UV-A irradiation. Furthermore, two of the GLP-1 analogues tested, liraglutide and lixisenatide, were able to restore cell viability after UV-A exposure. Collectively, these data indicate clear links between the expression/proteolysis of APP and the proliferation and resistance of ARPE-19 cells to UV-A irradiation. Whilst these effects are clearly differential, the data warrant further investigation of the role played by APP in AMD. Furthermore, the protective effects against UV-A shown by liraglutide and lixisenatide warrant further investigation of the molecular mechanisms involved with a view to identifying new drug targets for the prevention or treatment of retinal neurodegenerative diseases such as AMD
Embodying entrepreneurship: everyday practices, processes and routines in a technology incubator
The growing interest in the processes and practices of entrepreneurship has
been dominated by a consideration of temporality. Through a thirty-six-month
ethnography of a technology incubator, this thesis contributes to extant
understanding by exploring the effect of space. The first paper explores how
class structures from the surrounding city have appropriated entrepreneurship
within the incubator. The second paper adopts a more explicitly spatial analysis
to reveal how the use of space influences a common understanding of
entrepreneurship. The final paper looks more closely at the entrepreneurs within
the incubator and how they use visual symbols to develop their identity. Taken
together, the three papers reject the notion of entrepreneurship as a primarily
economic endeavour as articulated through commonly understood language and
propose entrepreneuring as an enigmatic attractor that is accessed through the
ambiguity of the non-verbal to develop the ‘new’. The thesis therefore contributes
to the understanding of entrepreneurship and proposes a distinct role for the non-verbal in that understanding
RNA pull-down-confocal nanoscanning (RP-CONA), a novel method for studying RNA/protein interactions in cell extracts that detected potential drugs for Parkinson’s disease targeting RNA/HuR complexes
MicroRNAs (miRNAs, miRs) are a class of small non-coding RNAs that regulate gene expression through specific base-pair targeting. The functional mature miRNAs usually undergo a two-step cleavage from primary miRNAs (pri-miRs), then precursor miRNAs (pre-miRs). The biogenesis of miRNAs is tightly controlled by different RNA-binding proteins (RBPs). The dysregulation of miRNAs is closely related to a plethora of diseases. Targeting miRNA biogenesis is becoming a promising therapeutic strategy.
HuR and MSI2 are both RBPs. MiR-7 is post-transcriptionally inhibited by the HuR/MSI2 complex, through a direct interaction between HuR and the conserved terminal loop (CTL) of pri-miR-7-1. Small molecules dissociating pri-miR-7/HuR interaction may induce miR-7 production. Importantly, the miR-7 levels are negatively correlated with Parkinson’s disease (PD).
PD is a common, incurable neurodegenerative disease causing serious motor deficits. A hallmark of PD is the presence of Lewy bodies in the human brain, which are inclusion bodies mainly composed of an aberrantly aggregated protein named α-synuclein (α-syn). Decreasing α-syn levels or preventing α-syn aggregation are under investigation as PD treatments. Notably, α-syn is negatively regulated by several miRNAs, including miR-7, miR-153, miR-133b and others. One hypothesis is that elevating these miRNA levels can inhibit α-syn expression and ameliorate PD pathologies.
In this project, we identified miR-7 as the most effective α-syn inhibitor, among the miRNAs that are downregulated in PD, and with α-syn targeting potentials. We also observed potential post-transcriptional inhibition on miR-153 biogenesis in neuroblastoma, which may help to uncover novel therapeutic targets towards PD.
To identify miR-7 inducers that benefit PD treatment by repressing α-syn expression, we developed a novel technique RNA Pull-down Confocal Nanoscaning (RP-CONA) to monitor the binding events between pri-miR-7 and HuR. By attaching FITC-pri-miR-7-1-CTL-biotin to streptavidin-coated agarose beads and incubating them in human cultured cell lysates containing overexpressed mCherry-HuR, the bound RNA and protein can be visualised as quantifiable fluorescent rings in corresponding channels in a confocal high-content image system. A pri-miR-7/HuR inhibitor can decrease the relative mCherry/FITC intensity ratio in RP-CONA. With this technique, we performed several small-scale screenings and identified that a bioflavonoid, quercetin can largely dissociate the pri-miR-7/HuR interaction. Further studies proved that quercetin was an effective miR-7 inducer as well as α-syn inhibitor in HeLa cells.
To understand the mechanism of quercetin mediated α-syn inhibition, we tested the effects of quercetin treatment with miR-7-1 and HuR knockout HeLa cells. We found that HuR was essential in this pathway, while miR-7 hardly contributed to the α-syn inhibition. HuR can directly bind an AU-rich element (ARE) at the 3’ untranslated region (3’-UTR) of α-syn mRNA and promote translation. We believe quercetin mainly disrupts the ARE/HuR interaction and disables the HuR-induced α-syn expression.
In conclusion, we developed and optimised RP-CONA, an on-bead, lysate-based technique detecting RNA/protein interactions, as well as identifying RNA/protein modulators. With RP-CONA, we found quercetin inducing miR-7 biogenesis, and inhibiting α-syn expression. With these beneficial effects, quercetin has great potential to be applied in the clinic of PD treatment. Finally, RP-CONA can be used in many other RNA/protein interactions studies
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