36 research outputs found

    Review of Crowdfunding Regulations across Countries: A Systematic Review Study

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    In recent years, the financial industry is seeing rapid implementation of an increasing number of new technologies. In crowdfunding campaigns, borrowers, potential investors, and platform providers may face some issues in terms of information disclosures, selecting an appropriate threshold, and platform insolvency. However, there is insufficient research to provide a cohesive view of the regulatory framework for crowdfunding platforms. This research offers comparative and comprehensive insights through a systematic literature review (SLR) in analyzing the existing regulatory environment across countries. The results suggest the fundamental regulatory framework in supporting startups, early-stage companies, innovation and entrepreneurs, and balancing investor protections and support for businesses seeking to raise funds, particularly in protecting client’s fund, crowdfunding advertising law, fundraising and investment limit, authorization and disclosure obligations. This study contributes to providing a comprehensive understanding of crowdfunding regulatory frameworks and informing governments or policymakers in the future development or reform of crowdfunding regulation frameworks

    The Viral Macrodomain Counters Host Antiviral ADP-Ribosylation

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    This work is licensed under a Creative Commons Attribution 4.0 International License.Macrodomains, enzymes that remove ADP-ribose from proteins, are encoded by several families of RNA viruses and have recently been shown to counter innate immune responses to virus infection. ADP-ribose is covalently attached to target proteins by poly-ADP-ribose polymerases (PARPs), using nicotinamide adenine dinucleotide (NAD+) as a substrate. This modification can have a wide variety of effects on proteins including alteration of enzyme activity, protein–protein interactions, and protein stability. Several PARPs are induced by interferon (IFN) and are known to have antiviral properties, implicating ADP-ribosylation in the host defense response and suggesting that viral macrodomains may counter this response. Recent studies have demonstrated that viral macrodomains do counter the innate immune response by interfering with PARP-mediated antiviral defenses, stress granule formation, and pro-inflammatory cytokine production. Here, we will describe the known functions of the viral macrodomains and review recent literature demonstrating their roles in countering PARP-mediated antiviral responses

    Protein disulfide isomerase A1 regulates breast cancer cell immunorecognition in a manner dependent on redox state

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    Oxidoreductase protein disulphide isomerases (PDI) are involved in the regulation of a variety of biological processes including the modulation of endoplasmic reticulum (ER) stress, unfolded protein response (UPR), ER‑mitochondria communication and the balance between pro‑survival and pro‑death pathways. In the current study the role of the PDIA1 family member in breast carcinogenesis was investigated by measuring ROS generation, mitochondrial membrane disruption, ATP production and HLA‑G protein levels on the surface of the cellular membrane in the presence or absence of PDIA1. The results showed that this enzyme exerted pro‑apoptotic effects in estrogen receptor (ERα)‑positive breast cancer MCF‑7 and pro‑survival in triple negative breast cancer (TNBC) MDA‑MB‑231 cells. ATP generation was upregulated in PDIA1‑silenced MCF‑7 cells and downregulated in PDIA1‑silenced MDA‑MB‑231 cells in a manner dependent on the cellular redox status. Furthermore, MCF‑7 and MDA‑MB‑231 cells in the presence of PDIA1 expressed higher surface levels of the non‑classical human leukocyte antigen (HLA‑G) under oxidative stress conditions. Evaluation of the METABRIC datasets showed that low PDIA1 and high HLA‑G mRNA expression levels correlated with longer survival in both ERα‑positive and ERα‑negative stage 2 breast cancer patients. In addition, analysis of the PDIA1 vs. the HLA‑G mRNA ratio in the subgroup of the living stage 2 breast cancer patients exhibiting low PDIA1 and high HLA‑G mRNA levels revealed that the longer the survival time of the ratio was high PDIA1 and low HLA‑G mRNA and occurred predominantly in ERα‑positive breast cancer patients whereas in the same subgroup of the ERα‑negative breast cancer mainly this ratio was low PDIA1 and high HLA‑G mRNA. Taken together these results provide evidence supporting the view that PDIA1 is linked to several hallmarks of breast cancer pathways including the process of antigen processing and presentation and tumor immunorecognition

    The reliability of lower limb 3D gait analysis variables during a change of direction to 90- and 135-degree manoeuvres in recreational soccer players

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    Several biomechanical outcomes are being used to monitor the risk of injuries; therefore, their reliability and measurement errors need to be known. To measure the reliability and measurement error in lower limb 3D gait analysis outcomes during a 90∘ and 135∘ change of direction (COD) manoeuvre. A test re-test reliability study for ten healthy recreational players was conducted at seven-day intervals. Kinematics (Hip flexion, adduction, internal rotation angles and knee flexion abduction angles) and kinetics (Knee abduction moment and vertical ground reaction force) data during cutting 90∘ and 135∘ were collected using 3D gait analysis and force platform. Five trials for each task and leg were collected. Standard error of measurement (SEM) and the intraclass correlation coefficient (ICC) were calculated form the randomised leg. The ICC values of the kinematics, kinetics, and vertical ground reaction force (VGRF) outcomes (90∘ and 135∘) ranged from 0.85 to 0.95, showing good to excellent reliability. The SEM for joint angles was less than 1.69∘. The VGRV showed a higher ICC value than the other outcomes. The current study results support the use of kinematics, kinetics, and VGRF outcomes for the assessment of knee ACL risk in clinic or research. However, the hip internal rotation angle should be treated with caution since the standard measurement error exceeded 10% compared to the mean value. The measurement errors provided in the current study are valuable for future studies

    Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity

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    Poly(ADP-ribose) polymerase (PARP) superfamily members covalently link either a single ADP-ribose (ADPR) or a chain of ADPR units to proteins using NAD as the source of ADPR. Although the well-known poly(ADP-ribosylating) (PARylating) PARPs primarily function in the DNA damage response, many noncanonical mono(ADP-ribosylating) (MARylating) PARPs are associated with cellular antiviral responses. We recently demonstrated robust up-regulation of several PARPs following infection with murine hepatitis virus (MHV), a model coronavirus. Here we show that SARS-CoV-2 infection strikingly up-regulates MARylating PARPs and induces the expression of genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR), while down-regulating other NAD biosynthetic pathways. We show that overexpression of PARP10 is sufficient to depress cellular NAD and that the activities of the transcriptionally induced enzymes PARP7, PARP10, PARP12 and PARP14 are limited by cellular NAD and can be enhanced by pharmacological activation of NAD synthesis. We further demonstrate that infection with MHV induces a severe attack on host cell NAD+ and NADP+. Finally, we show that NAMPT activation, NAM, and NR dramatically decrease the replication of an MHV that is sensitive to PARP activity. These data suggest that the antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses

    CleanET: enabling timing validation for complex automotive systems

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    Timing validation for automotive systems occurs in late integration stages when it is hard to control how the instances of software tasks overlap in time. To make things worse, in complex software systems, like those for autonomous driving, tasks schedule has a strong event-driven nature, which further complicates relating those task-overlapping scenarios (TOS) captured during the software timing budgeting and those observed during validation phases. This paper proposes CleanET, an approach to derive the dilation factor r caused due to the simultaneous execution of multiple tasks. To that end, CleanET builds on the captured TOS during testing and predicts how tasks execution time react under untested TOS (e.g. full overlap), hence acting as a mean of robust testing. CleanET also provides additional evidence for certification about the derived timing budgets for every task. We apply CleanET to a commercial autonomous driving framework, Apollo, where task measurements can only be reasonably collected under 'arbitrary' TOS. Our results show that CleanET successfully derives the dilation factor and allows assessing whether execution times for the different tasks adhere to their respective deadlines for unobserved scenarios.This work has been partially supported by the Spanish Ministry of Economy and Competitiveness (MINECO) under grant TIN2015- 65316-P, the SuPerCom European Research Council (ERC) project under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 772773), and the HiPEAC Network of Excellence. MINECO partially supported Jaume Abella under Ramon y Cajal postdoctoral fellowship (RYC-2013-14717).Peer ReviewedPostprint (author's final draft

    Context Relevant Persuasive Interaction and Design: Consideration of Human Factors Influencing B2C Persuasive Interaction

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    Accepted Version Alhammad, M., M. and Gulliver, S. R
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