8,305 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

    Perfect is the enemy of test oracle

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    Automation of test oracles is one of the most challenging facets of software testing, but remains comparatively less addressed compared to automated test input generation. Test oracles rely on a ground-truth that can distinguish between the correct and buggy behavior to determine whether a test fails (detects a bug) or passes. What makes the oracle problem challenging and undecidable is the assumption that the ground-truth should know the exact expected, correct, or buggy behavior. However, we argue that one can still build an accurate oracle without knowing the exact correct or buggy behavior, but how these two might differ. This paper presents SEER, a learning-based approach that in the absence of test assertions or other types of oracle, can determine whether a unit test passes or fails on a given method under test (MUT). To build the ground-truth, SEER jointly embeds unit tests and the implementation of MUTs into a unified vector space, in such a way that the neural representation of tests are similar to that of MUTs they pass on them, but dissimilar to MUTs they fail on them. The classifier built on top of this vector representation serves as the oracle to generate "fail" labels, when test inputs detect a bug in MUT or "pass" labels, otherwise. Our extensive experiments on applying SEER to more than 5K unit tests from a diverse set of open-source Java projects show that the produced oracle is (1) effective in predicting the fail or pass labels, achieving an overall accuracy, precision, recall, and F1 measure of 93%, 86%, 94%, and 90%, (2) generalizable, predicting the labels for the unit test of projects that were not in training or validation set with negligible performance drop, and (3) efficient, detecting the existence of bugs in only 6.5 milliseconds on average.Comment: Published in ESEC/FSE 202

    QSAR based virtual screening derived identification of a novel hit as a SARS CoV-229E 3CLpro Inhibitor: GA-MLR QSAR modeling supported by molecular Docking, molecular dynamics simulation and MMGBSA calculation approaches

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    Congruous coronavirus drug targets and analogous lead molecules must be identified as quickly as possible to produce antiviral therapeutics against human coronavirus (HCoV SARS 3CLpro) infections. In the present communication, we bear recognized a HIT candidate for HCoV SARS 3CLpro inhibition. Four Parametric GA-MLR primarily based QSAR model (R2:0.84, R2adj:0.82, Q2loo: 0.78) was once promoted using a dataset over 37 structurally diverse molecules along QSAR based virtual screening (QSAR-VS), molecular docking (MD) then molecular dynamic simulation (MDS) analysis and MMGBSA calculations. The QSAR-based virtual screening was utilized to find novel lead molecules from an in-house database of 100 molecules. The QSAR-vS successfully offered a hit molecule with an improved PEC50 value from 5.88 to 6.08. The benzene ring, phenyl ring, amide oxygen and nitrogen, and other important pharmacophoric sites are revealed via MD and MDS studies. Ile164, Pro188, Leu190, Thr25, His41, Asn46, Thr47, Ser49, Asn189, Gln191, Thr47, and Asn141 are among the key amino acid residues in the S1 and S2 pocket. A stable complex of a lead molecule with the HCoV SARS 3CLpro was discovered using MDS. MM-GBSA calculations resulted from MD simulation results well supported with the binding energies calculated from the docking results. The results of this study can be exploited to develop a novel antiviral target, such as an HCoV SARS 3CLpro Inhibitor

    A novel graph-based method for clustering human activities

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    Application of advanced fluorescence microscopy and spectroscopy in live-cell imaging

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    Since its inception, fluorescence microscopy has been a key source of discoveries in cell biology. Advancements in fluorophores, labeling techniques and instrumentation have made fluorescence microscopy a versatile quantitative tool for studying dynamic processes and interactions both in vitro and in live-cells. In this thesis, I apply quantitative fluorescence microscopy techniques in live-cell environments to investigate several biological processes. To study Gag processing in HIV-1 particles, fluorescence lifetime imaging microscopy and single particle tracking are combined to follow nascent HIV-1 virus particles during assembly and release on the plasma membrane of living cells. Proteolytic release of eCFP embedded in the Gag lattice of immature HIV-1 virus particles results in a characteristic increase in its fluorescence lifetime. Gag processing and rearrangement can be detected in individual virus particles using this approach. In another project, a robust method for quantifying Förster resonance energy transfer in live-cells is developed to allow direct comparison of live-cell FRET experiments between laboratories. Finally, I apply image fluctuation spectroscopy to study protein behavior in a variety of cellular environments. Image cross-correlation spectroscopy is used to study the oligomerization of CXCR4, a G-protein coupled receptor on the plasma membrane. With raster image correlation spectroscopy, I measure the diffusion of histones in the nucleoplasm and heterochromatin domains of the nuclei of early mouse embryos. The lower diffusion coefficient of histones in the heterochromatin domain supports the conclusion that heterochromatin forms a liquid phase-separated domain. The wide range of topics covered in this thesis demonstrate that fluorescence microscopy is more than just an imaging tool but also a powerful instrument for the quantification and elucidation of dynamic cellular processes

    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

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    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

    Epilepsy Mortality: Leading Causes of Death, Co-morbidities, Cardiovascular Risk and Prevention

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    a reuptake inhibitor selectively prevents seizure-induced sudden death in the DBA/1 mouse model of sudden unexpected ... Bilateral lesions of the fastigial nucleus prevent the recovery of blood pressure following hypotension induced by ..

    Investigating the mechanism of human beta defensin-2-mediated protection of skin barrier in vitro

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    The human skin barrier is a biological imperative. Chronic inflammatory skin diseases, such as Atopic Dermatitis (AD), are characterised by a reduction in skin barrier function and an increased number of secondary infections. Staphyloccocus aureus (S. aureus) has an increased presence on AD lesional skin and contributes significantly to AD pathology. It was previously demonstrated that the damage induced by a virulence factor of S. aureus, V8 protease, which causes further breakdown in skin barrier function, can be reduced by induction of human β- defensin (HBD)2 (by IL-1β) or exogenous HBD2 application. Induction of this defensin is impaired in AD skin. This thesis examines the mechanism of HBD2-mediated barrier protection in vitro; demonstrating that in this system, HBD2 was not providing protection through direct protease inhibition, nor was it altering keratinocyte proliferation or migration, or exhibiting specific localisation within the monolayer. Proteomics data demonstrated that HBD2 did not induce expression of known antiproteases but suggested that HBD2 stimulation may function by modulating expression of extracellular matrix proteins, specifically collagen- IVα2 and Laminin-β-1. Alternative pathways of protection initiated by IL-1β and TNFα stimulation were also investigated, as well as their influence over generalised wound healing. Finally, novel 3D human skin epidermal models were used to better recapitulate the structure of human epidermis and examine alterations to skin barrier function in a more physiological system. These data validate the barrier-protective properties of HBD2 and extended our knowledge of the consequences of exposure to this peptide in this context

    Socio-endocrinology revisited: New tools to tackle old questions

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    Animals’ social environments impact their health and survival, but the proximate links between sociality and fitness are still not fully understood. In this thesis, I develop and apply new approaches to address an outstanding question within this sociality-fitness link: does grooming (a widely studied, positive social interaction) directly affect glucocorticoid concentrations (GCs; a group of steroid hormones indicating physiological stress) in a wild primate? To date, negative, long-term correlations between grooming and GCs have been found, but the logistical difficulties of studying proximate mechanisms in the wild leave knowledge gaps regarding the short-term, causal mechanisms that underpin this relationship. New technologies, such as collar-mounted tri-axial accelerometers, can provide the continuous behavioural data required to match grooming to non-invasive GC measures (Chapter 1). Using Chacma baboons (Papio ursinus) living on the Cape Peninsula, South Africa as a model system, I identify giving and receiving grooming using tri-axial accelerometers and supervised machine learning methods, with high overall accuracy (~80%) (Chapter 2). I then test what socio-ecological variables predict variation in faecal and urinary GCs (fGCs and uGCs) (Chapter 3). Shorter and rainy days are associated with higher fGCs and uGCs, respectively, suggesting that environmental conditions may impose stressors in the form of temporal bottlenecks. Indeed, I find that short days and days with more rain-hours are associated with reduced giving grooming (Chapter 4), and that this reduction is characterised by fewer and shorter grooming bouts. Finally, I test whether grooming predicts GCs, and find that while there is a long-term negative correlation between grooming and GCs, grooming in the short-term, in particular giving grooming, is associated with higher fGCs and uGCs (Chapter 5). I end with a discussion on how the new tools I applied have enabled me to advance our understanding of sociality and stress in primate social systems (Chapter 6)

    SYSTEMS METHODS FOR ANALYSIS OF HETEROGENEOUS GLIOBLASTOMA DATASETS TOWARDS ELUCIDATION OF INTER-TUMOURAL RESISTANCE PATHWAYS AND NEW THERAPEUTIC TARGETS

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    In this PhD thesis is described an endeavour to compile litterature about Glioblastoma key molecular mechanisms into a directed network followin Disease Maps standards, analyse its topology and compare results with quantitative analysis of multi-omics datasets in order to investigate Glioblastoma resistance mechanisms. The work also integrated implementation of Data Management good practices and procedures
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