17,862 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

    Circadian variations in aortic stiffness, sympathetic vasoconstriction, and post-ischemic vasodilation in adults with and without type 2 diabetes.

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    The current literature reveals a lack of information on the circadian variations of some important cardiovascular risk factors related to the work of the heart or the capacity to provide blood and oxygen to various tissues. These factors include aortic stiffness, peripheral vasoconstrictor responsiveness, and post-ischemic vasodilation capacity. Furthermore, it is not clear whether the impact of an external stressor capable of activating the sympathetic nervous system could have greater repercussions on the cardiovascular system in the morning than in the evening. Given the higher incidence of acute cardiovascular events in the morning than in the evening, the studies undertaken in this thesis aim to investigate the circadian variations of these factors that are linked to cardiovascular risk, both at rest and during acute activation of the sympathetic nervous system. Type 2 diabetes (T2DM) is a condition that induces deleterious changes in cardiovascular function, impacting cardiovascular mortality and morbidity. Thus, the impact of diabetes will be evaluated. As a secondary purpose, considering the sex differences in the incidence and prognosis of cardiovascular disease, the effect of sex will be evaluated. Aortic stiffness proved not to be increased in the morning compared to the evening at specific times when the cardiovascular risk is significantly different, both at rest and during sympathetic activation. However, while healthy older women show similar aortic stiffness values compared to their male counterparts during acute stress, older women with T2DM reported greater aortic stiffness compared to men with T2DM. The post-ischemic forearm vasodilation is blunted in the morning compared to the evening in healthy elderly and such an attenuated vasodilation capacity impairs blood flow supply towards the ischemic area. The presence of T2DM does not affect vasodilation capacity and reactive hyperemia, but induces circadian variations in arterial pressure. The peripheral vasoconstriction triggered by a standardized sympathetic stressor is similar between morning and evening, regardless of the presence of T2DM and reduced baseline vascular conductance values in the morning. However, the peripheral vasoconstriction responsiveness is blunted in individuals with T2DM than in healthy ones as sympathetic activation induces vasodilation on the contralateral forearm in individuals with T2DM and vasoconstriction in healthy age-matched subjects. This finding highlights a neurovascular response to an external stressor altered by T2DM. Taken together, our findings suggest that the baseline state of constriction of the peripheral vascular tissue is greater in the morning than in the evening, but this fact is not due to greater sympathetic vasoconstriction responsiveness in the morning. Higher morning vasoconstriction at baseline however affects the capacity of a vascular tissue to dilate and, in turn, to supply blood to an ischemic tissue. Similar sympathetic vasoconstriction responsiveness between morning and evening is a likely factor explaining similar or lower values of central artery stiffness in the morning than in the evening, not only at rest but also during sympathetic excitation. Paradoxically, adults with T2DM report an increase in sympathetic-mediated dilatation capacity on the vascular tissue, which might be a defense mechanism that allows to reduce the central pressor response during sympathetic excitation

    Integrative multi-omics analysis for the effect of genetic alterations in cancer xenograft and organoid models

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    Department of Biomedical EngineeringDNA damage is a well-recognized factor in the development and progression of cancer. Numerous studies on genetic changes associated with cancer or the DNA repair pathway have been conducted, however, there is still a need for additional research on their function. The establishment of patient-derived xenografts or organoids for the purpose of testing functional genomic approaches is the subject of ongoing research. According to model-specific characteristics, it is not fully understood how these attempts to simulate patient cancer differ from original cancer. To comprehend the distinction between genuine patient cancer and these patient-derived disease models in more depth, multi-omics analysis is required to comprehend the overall genotypes, phenotypes, and environmental variables. Depending on the characteristics of each disease model, distinct omics analysis approaches and factors must be considered. In addition, care must be taken to avoid technical errors when integrating omics data generated by different sequencing equipment. There is currently no golden rule for data integration, but several approaches are being developed. It is crucial to determine the function of genes linked with the DNA repair pathway because these genes contribute to the induction or prevention of cancer. In chapter 1, I identified the interaction between MRE11 and TRIP13 through proximity labeling combined with the SILAC method which is quantitative proteomics using metabolic labeling. TRIP13 depletion doesn???t affect the nuclease activity and conformation of the MRN complex but directly inhibits the interaction of MDC1 with MRN complex and MDC1 recruitment on the DNA damage site. TRIP13 degradation with mirin treatment shows additive effects on ATM signaling activation. In conclusion, TRIP13 regulates immediate-early DNA damage sensing through MRE11 and ATM signaling independently of mirin. When assessing the functional genomic approach using patient-derived disease models, it is essential to determine which aspects of the models' correlation to actual cancer should be properly considered. In chapter 2, I found there are a few overlapped deleterious somatic mutations of the PDX model and their original tumor. I suspected novel mutagen exposure during PDX establishment or sample contamination. However, germline mutations of PDX models are well conserved from original tumors, and their mutational signatures of PDX also mimic that of their tumor. Though the number of overlapped mutations between the PDX model and their tumor was few, brain tumor-specific mutations are found in PDX samples. Especially, histone methylation- and cilia-related gene mutations are enriched in PDX samples. While it suggested these mutated genes are needed for maintaining the stemness of brain tumor PDX model or PDX model would be more appropriate for the samples with high heterogeneity, I have presented precautions and considerations in PDX model genome analysis. Multi-omics analysis that takes into consideration genetic, expressive, and clinical aspects can provide important information for the study of diseases with complicated etiologies, such as cancer, and can contribute to the development of diagnosis and treatment. To utilize colorectal cancer organoids for Companion Diagnostics (CDx), in chapter 3, I characterized patient-derived colorectal cancer (CRC) organoids through well-known genomic markers such as Tumor mutation burden (TMB), Microsatellite instability (MSI) and propose a novel grouping method using sharing same mutation site. The classification of CRC patients was more detailed combined with consensus molecular subtype (CMS) classifications. Additionally, I extract the expression features of the patients who experience recurrence or metastasis after first-line chemotherapy treatment with reference to clinical data. Drug response of CRC organoids by patient group and knockdown of the extracted features in the selected organoids would be validated in further study. In summary, with this dissertation, I conducted functional research on the DNA repair pathway of cancer-related genes, as well as the genetic analysis between patient-derived xenograft and original tumors, and introduced a novel perspective on the diagnosis and treatment of colorectal cancer patients using patient-derived organoids through multi-omics analysis.ope

    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

    Nitrite and insulin lower the oxygen cost of ATP synthesis in skeletal muscle cells by pleiotropic stimulation of glycolysis

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    Dietary nitrate lowers the oxygen cost of submaximal exercise, but precise mechanistic insight into how this occurs is lacking. Research suggests that dietary nitrate may render oxidative ATP synthesis more efficient, but evidence is inconclusive at present. This thesis aimed to establish how nitrite (a reduced form of nitrate) affects the bioenergetics of cultured skeletal muscle cells. Comparison between the acute effects of nitrite and insulin, a hormonal regulator of muscle function that increases mitochondrial efficiency, was explored to assess possible mechanistic overlap. Calculation of real-time intracellular ATP synthesis rates from simultaneous oxygen consumption and medium acidification measurements revealed the effects of sodium nitrite and insulin on intact rat (L6) myoblasts and myotubes. These extracellular flux data were also used to determine how mitochondrial and glycolytic ATP supply is used to fuel ATP-demanding processes. The data presented in this thesis revealed that both nitrite and insulin acutely stimulate glycolytic ATP synthesis. This stimulation occurs without significant mitochondrial ATP supply changes, thus increasing the glycolytic index of myocytes. Consequently, nitrite and insulin lower the oxygen cost of cellular ATP supply. Notably, insulin lowers oxygen consumption linked to mitochondrial proton leak, thus increasing mitochondrial efficiency. Nitrite does not improve coupling efficiency in myoblasts or myotubes. Further investigations revealed that stimulation of glycolytic ATP supply is not secondary to increased glucose availability. In myotubes, glycolytic stimulation persists in the presence of a mitochondrial uncoupler, suggesting that glycolysis is increased directly. In myoblasts, stimulation is annulled by uncoupler, suggesting that glycolysis increases indirectly, via increased ATP consumption. The molecular targets of nitrite and insulin remain unclear, but the data exclude stimulation of protein synthesis. Together, the data demonstrate that nitrite and insulin lower the oxygen cost of ATP synthesis in skeletal muscle cells by pleiotropic stimulation of glycolysis. The data inform the ongoing debate regarding the mechanism by which dietary nitrate lowers the oxygen cost of exercise, suggesting a push toward a more glycolytic phenotype. Such mechanistic insight is crucial for achieving the full translational potential of dietary nitrate

    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

    Interview with Wolfgang Knauss

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    An oral history in four sessions (September 2019–January 2020) with Wolfgang Knauss, von Kármán Professor of Aeronautics and Applied Mechanics, Emeritus. Born in Germany in 1933, he speaks about his early life and experiences under the Nazi regime, his teenage years in Siegen and Heidelberg during the Allied occupation, and his move to Pasadena, California, in 1954 under the sponsorship of a local minister and his family. He enrolled in Caltech as an undergraduate in 1957, commencing a more than half-century affiliation with the Institute and GALCIT (today the Graduate Aerospace Laboratories of Caltech). He recalls the roots of his interest in aeronautics, his PhD solid mechanics studies with his advisor, M. Williams, and the GALCIT environment in the late 1950s and 1960s at the dawn of the Space Age, including the impact of Sputnik and classes with NASA astronauts. He discusses his experimental and theoretical work on materials deformation, dynamic fracture, and crack propagation, including his solid-propellant fuels research for NASA and the US Army, wide-ranging programs with the US Navy, and his pioneering micromechanics investigations and work on the time-dependent fracture of polymers in the 1990s. He offers his perspective on GALCIT’s academic culture, its solid mechanics and fluid mechanics programs, and its evolving administrative directions over the course of five decades, as well as its impact and reputation both within and beyond Caltech. He describes his work with Caltech’s undergraduate admissions committee and his scientific collaborations with numerous graduate students and postdocs and shares his recollections of GALCIT and other Caltech colleagues, including C. Babcock, D. Coles, R.P. Feynman, Y.C. Fung, G. Neugebauer, G. Housner, D. Hudson, H. Liepmann, A. Klein, G. Ravichandran, A. Rosakis, A. Roshko, and E. Sechler. Six appendices contributed by Dr. Knauss, offering further insight into his life and career, also form part of this oral history and are cross-referenced in the main text

    Wildlife trade in Latin America: people, economy and conservation

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    Wildlife trade is among the main threats to biodiversity conservation and may pose a risk to human health because of the spread of zoonotic diseases. To avoid social, economic and environmental consequences of illegal trade, it is crucial to understand the factors influencing the wildlife market and the effectiveness of policies already in place. I aim to unveil the biological and socioeconomic factors driving wildlife trade, the health risks imposed by the activity, and the effectiveness of certified captive-breeding as a strategy to curb the illegal market in Latin America through a multidisciplinary approach. I assess socioeconomic correlates of the emerging international trade in wild cat species from Latin America using a dataset of >1,000 seized cats, showing that high levels of corruption and Chinese private investment and low income per capita were related to higher numbers of jaguar seizures. I assess the effectiveness of primate captive-breeding programmes as an intervention to curb wildlife trafficking. Illegal sources held >70% of the primate market share. Legal primates are more expensive, and the production is not sufficiently high to fulfil the demand. I assess the scale of the illegal trade and ownership of venomous snakes in Brazil. Venomous snake taxa responsible for higher numbers of snakebites were those most often kept as pets. I uncover how online wildlife pet traders and consumers responded to campaigns associating the origin of the COVID-19 pandemic. Of 20,000 posts on Facebook groups, only 0.44% mentioned COVID-19 and several stimulated the trade in wild species during lockdown. Despite the existence of international and national wildlife trade regulations, I conclude that illegal wildlife trade is still an issue that needs further addressing in Latin America. I identify knowledge gaps and candidate interventions to amend the current loopholes to reduce wildlife trafficking. My aspiration with this thesis is to provide useful information that can inform better strategies to tackle illegal wildlife trade in Latin America

    Gamification in E-Learning: game factors to strengthen specific English pronunciation features in undergraduate students at UPTC Sogamoso

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    Appendix A Characterization survey (104), Appendix B. EFL Students’ questionnaire (109), Appendix C. Characterization survey: data treatment question (113), Appendix D. Informed consent letter, English version (114), Appendix E. Carta de consentimiento informado, versión en español (117), Appendix F. Time Schedule (120), Appendix G. Sample Challenges at Moodle (126), Appendix H. Participants’ questionnaire results (128).La gamificación es un término que suele denotar el uso de componentes del juego en situaciones no relacionadas con el juego en sí para crear experiencias de aprendizaje agradables, divertidas y motivadoras para los estudiantes (Werbach y Hunter, 2012). Por lo tanto, el análisis de los factores básicos de los juegos se convierte en algo esencial a la hora de definir y utilizar la gamificación como estrategia de mediación del inglés como lengua extranjera para fortalecer rasgos específicos de pronunciación en los estudiantes de pregrado de la UPTC Sogamoso. El procedimiento de estudio se basa en la investigación acción mediante la implementación de la estrategia de gamificación para la mediación en la pronunciación del inglés, orientada a treinta estudiantes de diferentes programas de ingeniería, administración y tecnología con niveles heterogéneos de dominio del inglés. Las actividades se centran principalmente en la producción de sonidos, el ritmo, el acento y la entonación, los rasgos de pronunciación segmental y suprasegmental. Los resultados arrojaron una evidente mejora en las características segméntales y suprasegmentales de la percepción en la pronunciación de los participantes así como la contribución del objetivo de los juegos a la instrucción fonética y fonológica, la sensación en el juego a la motivación para mejorar la pronunciación, el reto establecido en los juegos a la actitud positiva de los participantes, y la sociabilidad a la exposición practica de la pronunciación inglesa.Gamification is a relatively new term that often denotes the use of game components in situations unrelated to the game itself to create enjoyable, fun, and motivating learning experiences for students (Werbach and Hunter, 2012). Therefore, analyzing the games' basic factors becomes essential when defining and using gamification as a strategy for English as Foreign Language mediation to strengthen specific pronunciation features in UPTC Sogamoso undergraduate students. The study procedure is based on action research by implementing the gamification strategy for mediation in English pronunciation, oriented to thirty students from different engineering, management, and technology programs at heterogeneous levels of English proficiency. The activities mainly focus on sound production, rhythm, stress, and intonation, segmental and suprasegmental pronunciation features. The results showed an evident improvement in the segmental and suprasegmental features of the participants' pronunciation perception as well as the contribution of game goals to phonetics and phonological instruction, the game sensation to the motivation for pronunciation improvement, the game challenge to the participants' positive attitude, and the sociality to the English pronunciation exposure practice
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