Search results for: suppressing QD charging

Authors: Benjamin Arazi

Abstract:

Blockchain is the technology behind cryptocurrencies like Bitcoin. It revolutionizes the meaning of trust in the sense of offering total reliability without relying on any central entity that controls or supervises the system. The Wall Street Journal states: “Blockchain Marks the Next Step in the Internet’s Evolution”. Blockchain was listed as #1 in Linkedin – The Learning Blog “most in-demand hard skills needed in 2020”. As stated there: “Blockchain’s novel way to store, validate, authorize, and move data across the internet has evolved to securely store and send any digital asset”. GSMA, a leading Telco organization of mobile communications operators, declared that “Blockchain has the potential to be for value what the Internet has been for information”. Motivated by these seminal observations, this paper presents the foundations of a Blockchain-based “Internet of Assets” academic program that joins under one roof leading application areas that are characterized by the transfer of assets over communication lines. Two such areas, which are pillars of our economy, are Fintech – Financial Technology and mobile communications services. The next application in line is Healthcare. These challenges are met based on available extensive professional literature. Blockchain-based assets communication is based on extending the principle of Bitcoin, starting with the basic question: If digital money that travels across the universe can ‘prove its own validity’, can this principle be applied to digital content. A groundbreaking positive answer here led to the concept of “smart contract” and consequently to DLT - Distributed Ledger Technology, where the word ‘distributed’ relates to the non-existence of reliable central entities or trusted third parties. The terms Blockchain and DLT are frequently used interchangeably in various application areas. The World Bank Group compiled comprehensive reports, analyzing the contribution of DLT/Blockchain to Fintech. The European Central Bank and Bank of Japan are engaged in Project Stella, “Balancing confidentiality and auditability in a distributed ledger environment”. 130 DLT/Blockchain focused Fintech startups are now operating in Switzerland. Blockchain impact on mobile communications services is treated in detail by leading organizations. The TM Forum is a global industry association in the telecom industry, with over 850 member companies, mainly mobile operators, that generate US$2 trillion in revenue and serve five billion customers across 180 countries. From their perspective: “Blockchain is considered one of the digital economy’s most disruptive technologies”. Samples of Blockchain contributions to Fintech (taken from a World Bank document): Decentralization and disintermediation; Greater transparency and easier auditability; Automation & programmability; Immutability & verifiability; Gains in speed and efficiency; Cost reductions; Enhanced cyber security resilience. Samples of Blockchain contributions to the Telco industry. Establishing identity verification; Record of transactions for easy cost settlement; Automatic triggering of roaming contract which enables near-instantaneous charging and reduction in roaming fraud; Decentralized roaming agreements; Settling accounts per costs incurred in accordance with agreement tariffs. This clearly demonstrates an academic education structure where fundamental technologies are studied in classes together with these two application areas. Advanced courses, treating specific implementations then follow separately. All are under the roof of “Internet of Assets”.

Keywords: blockchain, education, financial technology, mobile telecommunications services

Procedia PDF Downloads 163

Authors: Hosein Maghsoudi

Abstract:

Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

Procedia PDF Downloads 369