Search results for: TGF-β/CD4CD25Foxp3 T regulatory pathway

Authors: David Karasek, Veronika Kubickova, Ondrej Krystynik, Dominika Goldmannova, Lubica Cibickova, Jan Schovanek

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Introduction: Adiponectin, adipocyte-fatty acid-binding protein (A-FABP), and Wnt1 inducible signaling pathway protein-1 (WISP-1) are adipokines particularly associated with insulin resistance. The aim of the study was to compare their levels in women with gestational diabetes (GDM), type 2 diabetes mellitus (T2DM) and healthy controls and determine their relation with metabolic parameters. Methods: Fifty women with GDM, 50 women with T2DM, and 35 healthy women were included in the study. In addition to adipokines, anthropometric, lipid parameters, and markers, insulin resistance, and glucose control were assessed in all participants. Results: Compared to healthy controls only significantly lower levels of adiponectin were detected in women with GDM, whereas lower levels of adiponectin, higher levels of A-FABP and of WISP-1 were present in women with T2DM. Women with T2DM had also lower levels of adiponectin and higher levels of A-FABP compared to women with GDM. In women with GDM or T2DM adiponectin correlated negatively with body mass index (BMI), triglycerides (TG), C-peptide and positively with HDL-cholesterol; A-FABP positively correlated with BMI, TG, waist, and C-peptide. Moreover, there was a positive correlation between WISP-1 and C-peptide in women with T2DM. Conclusion: Adverse adipokines production detecting dysfunctional fat tissue is in women with GDM less presented than in women with T2DM, but more expressed compared to healthy women. Acknowledgment: Supported by AZV NV18-01-00139 and MH CZ DRO (FNOl, 00098892).

Keywords: adiponectin, adipocyte-fatty acid binding protein, wnt1 inducible signaling pathway protein-1, gestational diabetes, type 2 diabetes mellitus

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Authors: Tripta Dixit, Smita Sahu, William Selvamurthy, Sadhana Srivastava

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The translation of healthcare technologies is an expensive, complex affair, current healthcare challenges in Asian countries and their efforts to meet Millennium Development Goals (MDGs), necessitates continuous technology advancement to save countless lives, improve the quality of life and for socio-economic development. India’s consistently improving global innovation index (57) demonstrates its innovation potential, but access to health care is asymmetric and lacks priority in India. Therefore, there is utmost need of a robust translation system for point-of-care (POC) solutions, inexpensive, low-maintenance, reliable, and easy-to-use diagnostic technologies. Few cases of POC technologies viz. Elisa based diagnostic kits for regional viral disease, a device for detection of cancerous lesions were studied to understand the process and challenges involved in their translation. Accordingly, the entire translation ecosystem was summarized proposing a nexus of various actors such as technology developer, technology transferor technology receiver, funding entities, government/regulatory bodies and their effect on translation of different medical technologies. This study highlights the role and concerns pertaining to these actors for POC such as unsystematic and unvalidated research roadmap, low profit preposition, unfocused approach of up-scaling, low market acceptability and multiple window regulatory framework, etc. This provides an opportunity to devise solutions to overcome problem areas in translation path.

Keywords: healthcare technologies, point-of-care solutions, public health, translation

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Authors: Katerina Balounova, Jiri Pacha, Peter Ergang, Martin Vodicka, Pavlina Kvapilova

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MicroRNAs are small non-coding RNAs involved in a wide range of physiological processes. Post-transcriptional regulation of gene expression by microRNAs gives the organism a further level of control of the gene-expression program and the disruption of this microRNA regulatory mechanism seems to increase the risk of various pathophysiological conditions including tumorigenesis. To the present day, microRNAs were shown to participate in the mayor signalization pathways leading to tumorigenesis, including proliferation, cell cycle, apoptosis and metastasis formation. In addition, microRNAs have been found to play important roles in the generation and maintenance of circadian clock. These clocks generate circadian rhythms, which participate in a number of regulatory pathways. Disruption of the circadian signals seems to be associated with the development and the progression of tumours including colorectal cancer. We investigated therefore whether the diurnal profiles of miRNAs linked to tumorigenesis and regulation of circadian clock are changed during tumorigenesis. Based on published data we chose 10 microRNAs linked to tumorigenesis or circadian clock (let-7b-5p, miR 1 3p, miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p, miR 29a 3p, miR 34a 5p and miR 93 5p) and compared their 24-hr expression profiles in healthy and in chemically induces primary colorectal tumours of 52week-old mice. Using RT-qPCR we proved circadian rhythmicity in let-7b-5p, miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p, miR 29a 3p and miR 93 5p in healthy colon but not in tumours. The acrophases of miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p and miR 93 5p were reached around CT 24, the acrophases of let-7b-5p and miR-29a-3p were slightly shifted and reached around CT 21. In summary, our results show that circadian regulation of some colonic microRNAs is greatly affected by neoplastic transformation.

Keywords: circadian rhythm, colon, colorectal cancer, microRNA, tumorigenesis

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Authors: Mateen A. Khan, Elizabeth J. Theil, Dixie J. Goss

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Cellular iron homeostasis is accomplished by the coordinated regulated expression of iron uptake, storage, and export. Iron regulate the translation of ferritin and mitochondrial aconitase iron responsive element (IRE)-mRNA by interaction with an iron regulatory protein (IRPs). Iron increases protein biosynthesis encoded in iron responsive element. The noncoding structure IRE-mRNA, approximately 30-nt, folds into a stem loop to control synthesis of proteins in iron trafficking, cell cycling, and nervous system function. Fluorescence anisotropy measurements showed the presence of one binding site on IRP1 for ferritin and mitochondrial aconitase IRE-mRNA. Scatchard analysis revealed the binding affinity (Kₐ) and average binding sites (n) for ferritin and mitochondrial aconitase IRE-mRNA were 68.7 x 10⁶ M⁻¹ and 9.2 x 10⁶ M⁻¹, respectively. In order to understand the relative importance of equilibrium and stability, we further report the contribution of electrostatic interactions in the overall binding of two IRE-mRNA with IRP1. The fluorescence quenching of IRP1 protein was measured at different ionic strengths. The binding affinity of IRE-mRNA to IRP1 decreases with increasing ionic strength, but the number of binding sites was independent of ionic strength. Such results indicate a differential contribution of electrostatics to the interaction of IRE-mRNA with IRP1, possibly related to helix bending or stem interactions and an overall conformational change. Selective destabilization of ferritin and mitochondrial aconitase RNA/protein complexes as reported here explain in part the quantitative differences in signal response to iron in vivo and indicate possible new regulatory interactions.

Keywords: IRE-mRNA, IRP1, binding, ionic strength

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Authors: Ronald Villamar-Torres, Michael Staudt, Christopher Viot

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Cotton Gossypium hirsutum L. is one of the most important industrial crops, producing the world leading natural textile fiber, but is very prone to arthropod attacks that reduce crop yield and quality. Cotton cultivation, therefore, makes an outstanding use of chemical pesticides. In reaction to herbivorous arthropods, cotton plants nevertheless show natural defense reactions, in particular through volatile organic compounds (VOCs) emissions. These natural defense mechanisms are nowadays underutilized but have a very high potential for cotton cultivation, and elucidating their genetic bases will help to improve their use. Simulating herbivory attacks by mechanical wounding of cotton plants in greenhouse, we studied by qPCR the changes in gene expression for genes of the terpenoids biosynthesis pathway. Differentially expressed genes corresponded to higher levels of the terpenoids biosynthesis pathway and not to enzymes synthesizing particular terpenoids. The genes were mapped on the G. hirsutum L. reference genome; their global relationships inside the general metabolic pathways and the biosynthesis of secondary metabolites were visualized with iPath2. The chromatographic profiles of VOCs emissions indicated first monoterpenes and sesquiterpenes emissions, dominantly four molecules known to be involved in plant reactions to arthropod attacks. As a result, the study permitted to identify potential key genes for the emission of volatile terpenoids by cotton plants in reaction to an arthropod attack, opening possibilities for molecular-assisted cotton breeding in benefit of smallholder cotton growers.

Keywords: biosynthesis pathways, cotton, mechanisms of plant defense, terpenoids, volatile organic compounds

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Authors: D. Bhowmik, Y. Tian, Q. Yin, F. Zhu

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Cyclic GMP-AMP synthase (cGAS), recognises cytoplasmic double-stranded DNA (dsDNA), indicative of bacterial and viral infections, as well as the leakage of self DNA by cellular dysfunction and stresses, to elicit the host's immune responses. Viruses also have developed numerous strategies to antagonize the cGAS-STING pathway. Kaposi's sarcoma-associated herpesvirus (KSHV) is a human DNA tumor virus that is the causative agent of Kaposi’s sarcoma and several other malignancies. To persist in the host, consequently causing diseases, KSHV must overcome the host innate immune responses, including the cGAS-STING DNA sensing pathway. We already found that ORF52 or KicGAS (KSHV inhibitor of cGAS), an abundant and basic gamma herpesvirus-conserved tegument protein, directly inhibits cGAS enzymatic activity. To better understand the mechanism, we have performed the biochemical and structural characterization of full-length KicGAS and various mutants in regarding binding to DNA. We observed that KicGAS is capable of self-association and identified the critical residues involved in the oligomerization process. We also characterized the DNA-binding of KicGAS and found that KicGAS cooperatively oligomerizes along the length of the double stranded DNA, the highly conserved basic residues at the c-terminal disordered region are crucial for DNA recognition. Deficiency in oligomerization also affects DNA binding. Thus DNA binding by KicGAS sequesters DNA and prevents it from being detected by cGAS, consequently inhibiting cGAS activation. KicGAS homologues also inhibit cGAS efficiently, suggesting inhibition of cGAS is evolutionarily conserved mechanism among gamma herpesvirus. These results highlight the important viral strategy to evade this innate immune sensor.

Keywords: Kaposi's sarcoma-associated herpesvirus, KSHV, cGAS, DNA binding, inhibition

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Authors: Eugene Mashapa

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The age of information has witnessed countless unprecedented technological developments, which signal the articulation of succinct technological capabilities that can match these cutting-edge technological trends. These changes have impacted patterns in the production, distribution, and consumption of media content, a space that the Film and Publication Board (FPB) is concerned with. Consequently, the FPB is keen to understand the nature and impact of these technological changes on media content regulation. This exploratory study sought to investigate how content regulators in high and middle-income economies have adapted to the changes in this space, seeking insights into innovations, technological and operational, that facilitate continued relevance during this fast-changing environment. The study is aimed at developing recommendations that could assist and inform the organisation in regulating media content as it evolves. Thus, the overall research strategy in this analysis is applied research, and the analytical model adopted is a mixed research design guided by both qualitative and quantitative research instruments. It was revealed in the study that the FPB was significantly impacted by the unprecedented technological advancements in the media regulation space. Additionally, there exists a need for the FPB to understand the current and future penetrations of 4IR technology in the industry and its impact on media governance and policy implementation. This will range from reskilling officials to align with the technological skills to developing technological innovations as well as adopting co-regulatory or self-regulatory arrangements together with content distributors, where more content is distributed in higher volumes and with increased frequency. Importantly, initiating an interactive learning process for both FPB employees and the general public can assist the regulator and improve FPB’s operational efficiency and effectiveness.

Keywords: media, regulation, technology, film and publications board

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Authors: Igor Sukhotnik

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Objectives: Notch signaling is thought to act to drive cell versification in the lining of the small intestine. When Notch signaling is blocked, proliferation ceases, and epithelial cells become secretory. The purpose of the present study was to evaluate the role of Notch signaling pathway in stem cell differentiation in a rat model of intestinal ischemia-reperfusion (IR). Methods: Male Sprague-Dawley rats were randomly divided into four experimental groups: Sham-24 and Sham-48 rats underwent laparotomy and were killed 24 or 48 h later, respectively; IR-24 and IR-48 rats underwent occlusion of SMA and portal vein for 30 min followed by 24 or 48 h of reperfusion, respectively. Notch-related gene and protein expression were determined using Real Time PCR, Western blotting and immunohistochemistry. Wax histology and immunohistochemistry was used to determine cell differentiation toward absorptive (enterocytes) or secretory progenitors (goblet cells, enteroendocrine cells or Paneth cells). Results: IR-48 rats exhibited a significant decrease in Notch-1 protein expression (Western blot) that was coincided with a significant decrease in the number of Notch-1 positive cells (immunohistochemistry) in jejunum and ileum as well as Hes-1 positive cells in jejunum and ileum compared to Sham-48 rats. A significant down-regulation of Notch signaling related genes and proteins in IR animals was accompanied by a significant increase in the number of goblet and Paneth cells and decreased number of absorptive cells compared to control rats. Conclusions: Forty-eight hours following intestinal IR in rats, inhibited Notch signaling pathway was accompanied by intestinal stem cells differentiation toward secretory progenitors.

Keywords: Intestine, notch, ischemia-reperfusion, cell differentiation, secretory

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Authors: Jessica Ho

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AI has helped government, businesses and industries transform the way they do things. AI is used in automating tasks to improve decision-making and efficiency. AI is embedded in sensors and used in automation to help save time and eliminate human errors in repetitive tasks. Today, we saw the growth in AI using the collection of vast amounts of data to forecast with greater accuracy, inform decision-making, adapt to changing market conditions and offer more personalised service based on consumer habits and preferences. Government around the world share the opportunity to leverage these disruptive technologies to improve productivity while reducing costs. In addition, these intelligent solutions can also help streamline government processes to deliver more seamless and intuitive user experiences for employees and citizens. This is a critical challenge for NSW Government as we are unable to determine the risk that is brought by the unprecedented pace of adoption of AI solutions in government. Government agencies must ensure that their use of AI complies with relevant laws and regulatory requirements, including those related to data privacy and security. Furthermore, there will always be ethical concerns surrounding the use of AI, such as the potential for bias, intellectual property rights and its impact on job security. Within NSW’s public sector, agencies are already testing AI for crowd control, infrastructure management, fraud compliance, public safety, transport, and police surveillance. Citizens are also attracted to the ease of use and accessibility of AI solutions without requiring specialised technical skills. This increased accessibility also comes with balancing a higher risk and exposure to the health and safety of citizens. On the other side, public agencies struggle with keeping up with this pace while minimising risks, but the low entry cost and open-source nature of generative AI led to a rapid increase in the development of AI powered apps organically – “There is an AI for That” in Government. Other challenges include the fact that there appeared to be no legislative provisions that expressly authorise the NSW Government to use an AI to make decision. On the global stage, there were too many actors in the regulatory space, and a sovereign response is needed to minimise multiplicity and regulatory burden. Therefore, traditional corporate risk and governance framework and regulation and legislation frameworks will need to be evaluated for AI unique challenges due to their rapidly evolving nature, ethical considerations, and heightened regulatory scrutiny impacting the safety of consumers and increased risks for Government. Creating an effective, efficient NSW Government’s governance regime, adapted to the range of different approaches to the applications of AI, is not a mere matter of overcoming technical challenges. Technologies have a wide range of social effects on our surroundings and behaviours. There is compelling evidence to show that Australia's sustained social and economic advancement depends on AI's ability to spur economic growth, boost productivity, and address a wide range of societal and political issues. AI may also inflict significant damage. If such harm is not addressed, the public's confidence in this kind of innovation will be weakened. This paper suggests several AI regulatory approaches for consideration that is forward-looking and agile while simultaneously fostering innovation and human rights. The anticipated outcome is to ensure that NSW Government matches the rising levels of innovation in AI technologies with the appropriate and balanced innovation in AI governance.

Keywords: artificial inteligence, machine learning, rules, governance, government

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Authors: Agustyas Tjiptaningrum, Intanri Kurniati, Fadilah Fadilah, Linda Erlina, Tiwuk Susantiningsih

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Coronavirus disease-19 (COVID-19) is still one of the health problems. It can be a severe condition that is caused by a cytokine storm. In a cytokine storm, several proinflammatory cytokines are released massively. It destroys epithelial cells, and subsequently, it can cause death. The anti-inflammatory agent can be used to decrease the number of severe Covid-19 conditions. Melaleuca cajuputi is a plant that has antiviral, antibiotic, antioxidant, and anti-inflammatory activities. This study was carried out to analyze the prediction mechanism of the M. cajuputi extract from Lampung, Indonesia, as an anti-inflammatory agent for COVID-19. This study constructed a database of protein host target that was involved in the inflammation process of COVID-19 using data retrieval from GeneCards with the keyword “SARS-CoV2”, “inflammation,” “cytokine storm,” and “acute respiratory distress syndrome.” Subsequent protein-protein interaction was generated by using Cytoscape version 3.9.1. It can predict the significant target protein. Then the analysis of the Gene Ontology (GO) and KEGG pathways was conducted to generate the genes and components that play a role in COVID-19. The result of this study was 30 nodes representing significant proteins, namely NF-κβ, IL-6, IL-6R, IL-2RA, IL-2, IFN2, C3, TRAF6, IFNAR1, and DOX58. From the KEGG pathway, we obtained the result that NF-κβ has a role in the production of proinflammatory cytokines, which play a role in the COVID-19 cytokine storm. It is an important factor for macrophage transcription; therefore, it will induce inflammatory gene expression that encodes proinflammatory cytokines such as IL-6, TNF-α, and IL-1β. In conclusion, the blocking of NF-κβ is the prediction mechanism of the M. cajuputi extract as an anti-inflammation agent for COVID-19.

Keywords: antiinflammation, COVID-19, cytokine storm, NF-κβ, M. cajuputi

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Authors: Xi Yu, Lili Gu, Huizhu Wang, Xiao Wei, Dandan Sheng, Xiaoyan Jiang, Min Hong

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Introduction: Hypersensitivity disease is difficult to cure completely because of its recurrence, yupingfengsan (YPFS) is used to treat the diseases with the advantage of reducing the recurrence,but the precise mechanism is not clear. Previous studies of our laboratory have shown that the extract of YPFS can inhibit Th2-type allergic contact dermatitis(ACD) induced by FITC.Besides, thymic stromal lymphopoietin(TSLP) have been proved to be a master switch for allergic inflammation. Based on these studies, we want to establish a mouse model of TSLP production based on Th2 cell-mediated allergic inflammation to explore the regulating mechanisms of YPFS on TSLP in Th2 cell-mediated allergic inflammation. Methods: Th2-type ACD mouse model: The mice were topically sensitized on the abdomens (induction phase) and elicited on its ears skin 6 day later (excitation phase) with FITC solution, and the ear swelling was measured to evaluate the allergic inflammation；A mouse model of TSLP production based on Th2 cell-mediated allergic inflammation (TSLP production model): the skin of the ear was sensitized on two consecutive days with FITC solution causing the production of TSLP；Mice were treated with YPFS extract，ELISA、Real-time PCR and Western-blotting were using to examine the mRNA and protein levels of TSLP\TSLPR and TLRs ect. Results: YPFS extract can attenuates Th2-type allergic inflammatory in mice；in TSLP production model, YPFS can inhibit the expression of TSLP、 TSLPR、TLRs and MyD88, So we deduce the possible mechanisms of YPFS to play a role of intervention is through TLRs- MyD88 dependent and independent pathway to reduce TSLP production.

Keywords: YPFS, TSLP, TLRs, Th2-type allergic contact dermatitis

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Authors: Michal Kielbik, Izabela Szulc-Kielbik, Anna Brzostek, Jaroslaw Dziadek, Magdalena Klink

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The goal of many research groups in the world is to find new components that are important for survival of mycobacteria in the host cells. Mycobacterium tuberculosis (Mtb) possesses a number of enzymes degrading cholesterol that are considered to be an important factor for its survival and persistence in host macrophages. One of them - cholesterol oxidase (ChoD), although not being essential for cholesterol degradation, is discussed as a virulence compound, however its involvement in macrophages’ response to Mtb is still not sufficiently determined. The recognition of tubercle bacilli antigens by pathogen recognition receptors is crucial for the initiation of the host innate immune response. An important receptor that has been implicated in the recognition and/or uptake of Mtb is Toll-like receptor type 2 (TLR2). Engagement of TLR2 results in the activation and phosphorylation of intracellular signaling proteins including IRAK-1 and -4, TRAF-6, which in turn leads to the activation of target kinases and transcription factors responsible for bactericidal and pro-inflammatory response of macrophages. The aim of these studies was a detailed clarification of the role of Mtb cholesterol oxidase as a virulence factor affecting the TLR2 signaling pathway in human macrophages. As human macrophages the THP-1 differentiated cells were applied. The virulent wild-type Mtb strain (H37Rv), its mutant lacking a functional copy of gene encoding cholesterol oxidase (∆choD), as well as complimented strain (∆choD–choD) were used. We tested the impact of Mtb strains on the expression of TLR2-depended signaling proteins (mRNA level, cytosolic level and phosphorylation status). The cytokine and bactericidal response of THP-1 derived macrophages infected with Mtb strains in relation to TLR2 signaling pathway dependence was also determined. We found that during the 24-hours of infection process the wild-type and complemented Mtb significantly reduced the cytosolic level and phosphorylation status of IRAK-4 and TRAF-6 proteins in macrophages, that was not observed in the case of ΔchoD mutant. Decreasement of TLR2-dependent signaling proteins, induced by wild-type Mtb, was not dependent on the activity of proteasome. Blocking of TLR2 expression, before infection, effectively prevented the induced by wild-type strain reduction of cytosolic level and phosphorylation of IRAK-4. None of the strains affected the surface expression of TLR2. The mRNA level of IRAK-4 and TRAF-6 genes were significantly increased in macrophages 24 hours post-infection with either of tested strains. However, the impact of wild-type Mtb strain on both examined genes was significantly stronger than its ΔchoD mutant. We also found that wild-type strain stimulated macrophages to release high amount of immunosuppressive IL-10, accompanied by low amount of pro-inflammatory IL-8 and bactericidal nitric oxide in comparison to mutant lacking cholesterol oxidase. The influence of wild-type Mtb on this type of macrophages' response strongly dependent on fully active IRAK-1 and IRAK-4 signaling proteins. In conclusion, Mtb using cholesterol oxidase causes the over-activation of TLR2 signaling proteins leading to the reduction of their cytosolic level and activity resulting in the modulation of macrophages response to allow its intracellular survival. Supported by grant: 2014/15/B/NZ6/01565, National Science Center, Poland

Keywords: Mycobacterium tuberculosis, cholesterol oxidase, macrophages, TLR2-dependent signaling pathway

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Authors: Nasser Alsadoun

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Today's companies in Saudi Arabian capital market must comply with strict criteria and adhere to rigid corporate governance rules and continuous disclosure requirements. Unlike other regulators in the region, decision makers of the Capital Market Authority (hereafter CMA) of Saudi Arabia believes that the announcements of economic sanctions and penalties for non-compliance firms will foster more effective regulatory compliance and hence improve the quality of financial reporting. An implied argument put forward by the opponents, however, states that such penalties are unnecessary and stated to be onerous for non-compliance firms. Over that last years, the CMA has publicly announced several economic fines levied on some listed companies for their failing to comply with corporate governance and continuous disclosure regulation clauses, with the amount of fine levied ranges between 50,000 SR to 100,000 SR for each failing. Economic theory suggests that rational investors make decisions based on a cost-benefit principal. The regulatory intervention made by CMA on the announcement of economic sanctions has been costly to the society (economy) hoping that it improves the transparency of financial statements. It is argued, therefore, that threat of regulators and economic sanctions will provide incentives for firms’ managers to report more relevant and reliable accounting information, and the benefit of such announcements is likely to be reflected in the context of the quality of the financial reports. Yet, the economic consequences of the revealed fines announcement for non-compliance firms in Saudi Arabian market have not been examined. Thus, this study attempts to empirically examine whether market participants are pricing the supposed benefits of rigid governance and disclosure rules in the Saudi market. The study employs an event study methodology to assess the impact of CMA economic sanctions announcements on the market price of non-compliance firms. The study also estimates and examines bid–ask spread behavior of violated firms around the CMA announcements. The findings indicate that the CMA fines announcements for failing to comply with governance and disclosure rules do not appear to play any significant role in securities pricing. In addition, tests of bid-ask behavior does not indicate any significant increases in information asymmetry surrounding these announcements. While the CMA has developed many goals to increase the awareness of listed companies with the best governance and disclosure practices, it seems they have to develop more goals to improve market efficiency and increase investors and public awareness.

Keywords: governance and disclosure violations, financial reporting quality, regulatory intervention, market efficiency

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Authors: Esam El Gohary

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— The companies’ ability to survive and compete in the fierce competition is determined by its competitiveness level. With the spread of information technology use and appearance of online shopping, it became crucial for companies to adopt e-commerce system to increase its competitiveness. This paper was conducted with the purpose of determine how increasing the service value through e-commerce factors (competitive strategy, ICT infrastructures, logistics, security, human resources and innovation) can enhance companies' competitiveness. The problem of this paper is summarized in the absence of the thorough awareness of e-commerce benefits for business owners and customers, as well as how to reduce the intangibility attributes of e-commerce. For this purpose this paper describes the e-commerce in Egypt and its success factors (infrastructures, legal and regulatory environment, human resources and innovation), as well as displays the barriers of such factor, to investigate the significant of these factors on increasing service value and enhance companies' competitiveness. This paper revealed that e-commerce companies have many opportunities to enhance its competitiveness in Egypt, which is enhanced by several factors. The most important factors are “strong ICT infrastructure, qualified and skilled human resources, in addition to the distinctive logistics that distinguish Egypt due to its location, strong legal and regulatory environment and Innovation, as well as the competitive strategy. As well as, companies encounter several threats such as; the lack of infrastructures and logistics in rural areas, the absence of the inclusive understanding and awareness of e-commerce, fear from e-payment transactions and fraud, the ambiguity and burdensome of customs. Through the research findings several recommendations were introduced to both government and companies to overcome threats and exploit opportunities to improve performance and enhance companies' competitiveness.

Keywords: e-commerce competitiveness, e-commerce factors, e-commerce in Egypt, information technology

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Authors: Diab Z., Hamad A., Dixit A., Al-Rikabi M., Keshaverzi F.

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Introduction: According to the NICE guidelines, 2020Prasugrel is the recommended first line treatment in adults with acute coronary syndromes (ACS) in patients with ST-segment-elevation myocardial infarction (STEMI), defined as ST elevation or new left bundle branch block on ECG , that cardiologists intend to treat with primary percutaneous coronary intervention (PCI). The current literature suggests that this is largely due to safety and efficacy, and cost effectiveness. We wanted to do an audit to examine the adherence of the MRI hospital with guidelines in using prasugrel as first-line therapy in patients with STEMI and undergoing PPCI. AIM: To examine the adherence of the MRI hospital with guidelines in using prasugrel as first-line therapy in patients with STEMI and undergoing PPCI Methods: We looked at the patients presented to MRI during1^st of January 2022 to 28th February 2022. We included all the people who were above 18 and were brought to the hospital through the PPCI pathway and diagnosed as ACS and underwent PPCI. We excluded Patients who were brought to the hospital through the PPCI pathway and underwent coronary angiography and their diagnosis was found other than STEMI or if the outcome was death before discharge or they were above age >75 (as per guideline increase bleeding risk of prasugrel in a person aged 75 or older). Results: The total number of patients was 100. There were a total of seventy patients who had STEMI and fit the criteria for inclusion. Out of these, only 72.9% (51) were given Prasugrel as a first line. Seventeen (17) 24.3% STEMI patients were candidates for prasugrel as first-line therapy but were instead offered (clopidogrel/ticagrelor). Two 2 (2.9%) STEMI patients were not given prasugrel as first-line therapy because of C/I (CVA) or the use of anticoagulant Nine 9 (9%) of them died before discharge. Eleven 11 (11%) were above the age of 75. Ten 10 (10%) of patients had a diagnosis other than STEMI. Conclusions and recommendations: Our audit has shown the need to increase awareness amongst staff re: the first line use of Prasugrel as per NICE guidelines. We aim to arrange awareness sessions for staff and increase visibility of the guidelines for the staff to encourage them to adhere to the guideline. Further research is needed to find the optimum treatment in patients above 75.

Keywords: pasurgrel, PCI, NICE, STEMI

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Authors: Matthew I. Bellgard

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The field of bioinformatics has made, and continues to make, substantial progress and contributions to life science research and development. However, this paper contends that a systems approach integrates bioinformatics activities for any project in a defined manner. The application of critical control points in this bioinformatics systems approach may be useful to identify and evaluate points in a pathway where specified activity risk can be reduced, monitored and quality enhanced.

Keywords: bioinformatics, food security, personalized medicine, systems approach

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Authors: Yong Li

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Major cities in China has experienced a shift from production based on manufacturing industry to tertiary industry. How to make a better use of existing obsolete industrial land within urban cores has become a difficult problem for many policymakers. City governments regard old manufacturing industrial land as an important source of land to facilitate the development of the cities. Despite the announcement of policies in promoting that, a large portion of industrial land is still not properly redeveloped and most of them became obsolete. The study uses the project of Xinyi International Club as a case to examine the process of adaptive reuse of obsolete industrial space in Guangzhou, China. It attempts to elucidate the underlying mechanisms by identifying the key forces from both the government and the private sectors in influencing the process. The study found that market forces in transforming industrial space are exerting a strong impact on the existing land use planning system in Chinese cities. Pragmatic relaxation of the formal land use the regulatory framework and government supportive land-use intervention have also been crucial towards achieving successful implementation of the restructuring project and making it a showcase. This study questions whether these extraordinary measures, in particular, the use of temporary land use permit, are sustainable in facilitating the transformation of derelict industrial land, and in informing future industrial land-use restructuring policies. It concludes that, while the land use regulatory system in China is becoming increasingly dynamic and flexible, it remains ill-equipped in responding positively to the market, which is characterized by an increasing bargaining power of the private sector. A comprehensive appraisal of the overall impacts of these adaptive re-uses on society is wanting.

Keywords: China, land alteration, obsolete industrial properties, urban planning

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Authors: Elham Shakerian, Reza Afarin

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The hepatic disease causes approximately 2 million deaths/year worldwide. Liver fibrosis is the last stage of numerous chronic liver diseases, and until now there is no definite cure or drug for it. Activation of hepatic stellate cells (HSCs) is the main reason for fibrosis. Transforming growth factor (TGF-β), as a main profibrogenic cytokine, if increased in these cells, leads to liver fibrosis through smad3 signaling pathways and increasing the expressions of Collagen type I and III, and actin-alpha smooth muscle (αSMA) genes. Curcumin (CUR) is a polyphenolic compound and an active ingredient derived from the rhizome of the turmeric plant that exerts effective antioxidant, anti-inflammatory, and antimicrobial activity. It has been shown that daily consumption of curcumin may have a protective effect on the liver against oxidative stress associated with alcohol consumption. In this study, we investigate the role of Curcumin in decreasing HSC activation and treating liver fibrosis. First, the human HSCs were treated with 2 ng/ml of (TGF-β) for 24 hours to become activated, then with Silibinin for 24 hours. Total RNAs were extracted, reversely transcribed into cDNA, Quantitative Real-time PCR, and western blot were performed. The mRNA expression levels of Collagen type I and III, αSMA genes, and the level of smad3 phosphorylation in TGF-β activated human HSCs treated with Curcumin were significantly reduced compared to human HSCs untreated with Curcumin. Curcumin is effective in reducing the expression of fibrogenic genes in the activated human HSCs treated with TGFB through downregulation of the TGF-β/smad3 signaling pathway. Therefore, Curcumin possesses significant antifibrotic properties in hepatic fibrosis

Keywords: hepatic fibrosis, human HSCs, curcumin, fibrogenic genes

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Authors: Pureun-Haneul Lee, Byeong-Gon Kim, Sun-Hye Lee, An-Soo Jang

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Background: Nanoparticles may pose adverse health effects due to particulate matter inhalation. Nanoparticle exposure induces cell and tissue damage, causing local and systemic inflammatory responses. The inflammasome is a major regulator of inflammation through its activation of pro-caspase-1, which cleaves pro-interleukin-1β (IL-1β) into its mature form and may signal acute and chronic immune responses to nanoparticles. Objective: The aim of the study was to identify whether nanoparticles exaggerates inflammasome pathway leading to airway inflammation and hyperresponsiveness in an allergic mice model of asthma. Methods: Mice were treated with saline (sham), OVA-sensitized and challenged (OVA), or titanium dioxide nanoparticles. Lung interleukin 1 beta (IL-1β), interleukin 18 (IL-18), NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and caspase-1 levels were assessed with Western Blot. Caspase-1 was checked by immunohistochemical staining. Reactive oxygen species were measured for the marker 8-isoprostane and carbonyl by ELISA. Results: Airway inflammation and hyperresponsiveness increased in OVA-sensitized/challenged mice and these responses were exaggerated by TiO2 nanoparticles exposure. TiO2 nanoparticles treatment increased IL-1β and IL-18 protein expression in OVA-sensitized/challenged mice. TiO2 nanoparticles augmented the expression of NLRP3 and caspase-1 leading to the formation of an active caspase-1 in the lung. Lung caspase-1 expression was increased in OVA-sensitized/challenged mice and these responses were exaggerated by TiO2 nanoparticles exposure. Reactive oxygen species was increased in OVA-sensitized/challenged mice and in OVA-sensitized/challenged plus TiO2 exposed mice. Conclusion: Our data demonstrate that inflammasome pathway activates in asthmatic lungs following nanoparticles exposure, suggesting that targeting the inflammasome may help control nanoparticles-induced airway inflammation and responsiveness.

Keywords: bronchial asthma, inflammation, inflammasome, nanoparticles

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Authors: Ejovi Eghwubare Augustine

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This study delved into the traditional mechanisms of conflict resolution in Africa, a pathway to sustainable peace in Nigeria. It deployed the quantitative and qualitative methods of data collection and content analysis. The work adopted the Peace Process theory propounded by John Darby and Roger Macunity. It ascertained that disputes or disagreements are unarguably and necessarily an inevitable part of human existence, flowing directly from communication, interaction, and relationships which can occur at individual and national levels, even at international levels in view of the current trend of globalization. The alternative Dispute Resolution (ADR) mechanism is a basket of procedures outside the traditional process of litigation or strict determination of legal rights. It may also be elucidated as a range of procedures that serve as generally involve the intercession and assistance of a neutral and impartial third party. The traditional mechanisms of conflict resolution in Africa are alien to the Western world; this paper is of utmost importance to the Western world and also enriched their pool of literature. Nigeria is a country that is dominated by various ethnic groups anchored on diverse cultures, customs, and traditions. It is, therefore, not surprising to see conflicts arise, and despite the various attempts at resolving these conflicts through litigation, they still remained unabated. The paper investigated the lessons learned from Traditional Mechanisms of Conflict resolution; it also interrogated its impact and the way forward. In light of the lessons that were learned and the impact of the traditional mechanisms of conflict resolution, suggestions on how to attain a sustainable, peaceful society were proffered. In conclusion, the study crystallized reforms on the alternative dispute resolution introduced through the traditional mechanism, which includes, amongst others, that constitutional recognition should be given to traditional institutions of conflict resolution to enable quick dispensation of matters.

Keywords: traditional, conflict, peace, resolution

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Authors: Ae Ra Han, Seoung Eun Huh, Ji Yeon Kim, Joanne Kwak-Kim, Sung Ki Lee

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Objective: Prevalence of osteoporosis, cardiovascular disorders, and Alzheimer's disease rapidly increase after menopause. Immune activation and inflammation are suggested as an important pathogenesis of these serious diseases. Several pro-inflammatory cytokines are increased in women with surgical or natural menopause. However, the little is known about IL-17 producing T cells and Foxp3+ regulatory T (Treg) cells in post-menopause. Methods: A total of 34 postmenopausal women, who had no active cardiovascular, endocrine and infectious disorders were recruited as study group and healthy premenopausal women participated as controls. Peripheral blood mononuclear cells were isolated. Immuno-morphologic (CD3, CD4, CD8, CD19, CD56/CD16), intracellular cytokine (TNF-alpha, IFN-gamma, IL-10, IL-17), and Treg cell (Foxp3) studies were carried out using flow cytometry. The proportion of peripheral lymphocytes, including IL-17 producing and Foxp3+ Treg cells immune cell in each group were statistically analyzed. Results: The proportion of NK cells was significantly increased in menopausal women as compared to that of controls (P=.005). The ratios of TNF-alpha/IL-10 producing CD3+CD4+ T cells were increased in postmenopausal women. CD3+IL-17+ T cell level was higher in postmenopausal women and CD4+ Foxp3+ Treg cells was lower than that of controls. The ratios of CD3+IL-17+ T cell to CD3+Foxp3+ and to CD4+Foxp3+ Treg cells were significantly increased in postmenopausal women (P=.001). Conclusions: We found enhanced innate immunity and Th1- and Th17-mediated adaptive immunity in postmenopausal women. This may explain increasing prevalence of chronic inflammatory diseases after menopause. Further studies are needed to elucidate what factors contribute to this inflammatory shift in the postmenopause.

Keywords: inflammation, immune cell, menopause, Th17, regulatory T cell

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Authors: Inam Ridha, Christine L. Kuryla, Madhuranga Thilakasiri Madugoda Ralalage Don, Norman J. Kleiman, Yunro Chung, Jin Park, Vel Murugan, Joshua LaBaer

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To date, more than 275 million people worldwide have been diagnosed with COVID-19 and the rapid spread of the omicron variant suggests many millions more will soon become infected. Many infections are asymptomatic, while others result in mild to moderate illness. Unfortunately, some infected individuals exhibit more serious symptoms including respiratory distress, thrombosis, cardiovascular disease, multi-organ failure, cognitive difficulties, and, in roughly 2% of cases, death. Studies indicate other coronaviruses can alter the host cell's epigenetic profile and lead to alterations in the immune response. To better understand the mechanism(s) by which SARS-CoV-2 infection causes serious illness, DNA methylation profiles in peripheral blood mononuclear cells (PBMCs) from 90 hospitalized severely ill COVID-19 patients were compared to profiles from uninfected control subjects. Exploratory epigenome-wide DNA methylation analyses were performed using multiplexed methylated DNA immunoprecipitation (MeDIP) followed by pathway enrichment analysis. The findings demonstrated significant DNA methylation changes in infected individuals as compared to uninfected controls. Pathway analysis indicated that apoptosis, cell cycle control, Toll-like receptors (TLR), cytokine interactions, and T cell differentiation were among the most affected metabolic processes. In addition, changes in specific gene methylation were compared to SARS-CoV-2 induced changes in RNA expression using published RNA-seq data from 3 patients with severe COVID-19. These findings demonstrate significant correlations between differentially methylated and differentially expressed genes in a number of critical pathways.

Keywords: COVID19, epigenetics, DNA mathylation, viral infection

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Authors: L. B. Naves, L. Almeida

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The development of Drugs Delivery System (DDS), has been wildly investigated in the last decades. In this paper, first a general overview of traditional and modern wound dressing is presented. This is followed by a review of what scientist have done in the medical environment, focusing the possibility to develop a new alternative for DDS through transdermal pathway, aiming to treat melanoma skin cancer.

Keywords: cancer therapy, dressing polymers, melanoma, wound healing

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Authors: Evar C. Umeozor, Experience I. Nduagu, Ian D. Gates

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The energy requirements of carbon dioxide utilization (CDU) technologies/processes are diverse, so also are their environmental footprints. This paper explores the energy and environmental impacts of systems for CO₂ conversion to fuels, chemicals, and materials. Energy needs of the technologies and processes deployable in CO₂ conversion systems are met by one or combinations of hydrogen (chemical), electricity, heat, and light. Likewise, the environmental footprint of any CO₂ utilization pathway depends on the systems involved. So far, evaluation of CDU systems has been constrained to particular energy source/type or a subset of the overall system needed to make CDU possible. This introduces limitations to the general understanding of the energy and environmental implications of CDU, which has led to various pitfalls in past studies. A CDU system has an energy source, CO₂ supply, and conversion units. We apply a holistic approach to consider the impacts of all components in the process, including various sources of energy, CO₂ feedstock, and conversion technologies. The electricity sources include nuclear power, renewables (wind and solar PV), gas turbine, and coal. Heat is supplied from either electricity or natural gas, and hydrogen is produced from either steam methane reforming or electrolysis. The CO₂ capture unit uses either direct air capture or post-combustion capture via amine scrubbing, where applicable, integrated configurations of the CDU system are explored. We demonstrate how the overall energy and environmental impacts of each utilization pathway are obtained by aggregating the values for all components involved. Proper accounting of the energy and emission intensities of CDU must incorporate total balances for the utilization process and differences in timescales between alternative conversion pathways. Our results highlight opportunities for the use of clean energy sources, direct air capture, and a number of promising CO₂ conversion pathways for producing methanol, ethanol, synfuel, urea, and polymer materials.

Keywords: carbon dioxide utilization, processes, energy options, environmental impacts

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Authors: Krish Batra

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The advent of open banking has revolutionized the financial services industry by fostering innovation, enhancing customer experience, and promoting competition. However, this paradigm shift towards more open and interconnected banking ecosystems has introduced complex cybersecurity challenges. This research paper delves into the multifaceted cybersecurity landscape of open banking, highlighting the vulnerabilities and threats inherent in sharing financial data across a network of banks and third-party providers. Through a detailed analysis of recent data breaches, phishing attacks, and other cyber incidents, the paper assesses the current state of cybersecurity within the open banking framework. It examines the effectiveness of existing security measures, such as encryption, API security protocols, and authentication mechanisms, in protecting sensitive financial information. Furthermore, the paper explores the regulatory response to these challenges, including the implementation of standards such as PSD2 in Europe and similar initiatives globally. By identifying gaps in current cybersecurity practices, the research aims to propose a set of robust, forward-looking strategies that can enhance the security and resilience of open banking systems. This includes recommendations for banks, third-party providers, regulators, and consumers on how to mitigate risks and ensure a secure open banking environment. The ultimate goal is to provide stakeholders with a comprehensive understanding of the cybersecurity implications of open banking and to outline actionable steps for safeguarding the financial ecosystem in an increasingly interconnected world.

Keywords: open banking, financial services industry, cybersecurity challenges, data breaches, phishing attacks, encryption, API security protocols, authentication mechanisms, regulatory response, PSD2, cybersecurity practices

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Authors: Okafor Joan, Nwodo Uchechukwu

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Klebsiella pneumoniae (K. pneumoniae) is a significant pathogen responsible for opportunistic and nosocomial infection. One of the most significant antibiotic resistance mechanisms in K. pneumoniae isolates is efflux pumps. Our current study identified efflux genes (AcrAB, OqxAB, MacAB, and TolC) and regulatory genes (RamR and RarA) in multidrug-resistant (MDR) K. pneumoniae isolated from hospital effluents and investigated their relationship with antibiotic resistance. The sum of 145 K. pneumoniae isolates was established by PCR and screened for antibiotic susceptibility. PCR detected efflux pump genes, and their link with antibiotic resistance was statistically examined. However, 120 (83%) of the confirmed isolated were multidrug-resistant, with the largest percentage of resistance to ampicillin (88.3%) and the weakest rate of resistance to imipenem (5.5%). Resistance to the other antibiotics ranged from 11% to 76.6%. Molecular distribution tests show that AcrA, AcrB, MacA, oqxB oqxA, TolC, MacB were detected in 96.7%, 85%, 76.7%, 70.8%, 55.8%, 39.1%, and 29.1% respectively. However, 14.3% of the isolates harboured all seven genes screened. Efflux pump system AcrAB (83.2%) was the most commonly detected in K. pneumonia isolated across all the antibiotics class-tested. In addition, the frequencies of RamR and RarA were 46.2% and 31.4%, respectively. AcrAB and OqxAB efflux pump genes were significantly associated with fluoroquinolone, beta-lactam, carbapenem, and tetracycline resistance (p<0.05). The high rate of efflux genes in this study demonstrated that this resistance mechanism is the dominant way in K. pneumoniae isolates. Appropriate treatment must be used to reduce and tackle the burden of resistant Klebsiella pneumonia in hospital wastewater effluents.

Keywords: Klebsiella pneumonia, efflux pumps, regulatory genes, multidrug-resistant, hospital, PCR

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Authors: Jumana Majdi Qutub

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Rationale: Cloud computing has rapidly developed the past few years. Because of the importance of providing protection for personal data used in cloud computing, the role of data protection in promoting trust and confidence in users’ data has become an important policy priority. This research examines key regulatory challenges rose by the growing use and importance of cloud computing with focusing on protection of individuals personal data. Methodology: Describing and analyzing governance challenges facing policymakers and industry in Saudi Arabia, with an account of anticipated governance responses. The aim of the research is to describe and define the regulatory challenges on cloud computing for policy making in Saudi Arabia and comparing it with potential complied issues rose in respect of transported data to EU member state. In addition, it discusses information privacy issues. Finally, the research proposes policy recommendation that would resolve concerns surrounds the privacy and effectiveness of clouds computing frameworks for data protection. Results: There are still no clear regulation in Saudi Arabia specialized in legalizing cloud computing and specialty regulations in transferring data internationally and locally. Decision makers need to review the applicable law in Saudi Arabia that protect information in cloud computing. This should be from an international and a local view in order to identify all requirements surrounding this area. It is important to educate cloud computing users about their information value and rights before putting it in the cloud to avoid further legal complications, such as making an educational program to prevent giving personal information to a bank employee. Therefore, with many kinds of cloud computing services, it is important to have it covered by the law in all aspects.

Keywords: cloud computing, cyber crime, data protection, privacy

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Authors: Ashir Ahmed

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Generally, radicalization happens when a person's thinking and behaviour become significantly different from how most of the members of their society and community view social issues and participate politically. Radicalization often leads to violent extremism that refers to the beliefs and actions of people who support or use violence to achieve ideological, religious or political goals. Studies on radicalization negate the common myths that someone must be in a group to be radicalised or anyone who experiences radical thoughts is a violent extremist. Moreover, it is erroneous to suggest that radicalisation is always linked to religion. Generally, the common motives of radicalization include ideological, issue-based, ethno-nationalist or separatist underpinning. Moreover, there are number of factors that further augments the chances of someone being radicalised and may choose the path of violent extremism and possibly terrorism. Since there are numbers of factors (and sometimes quite different) contributing in radicalization and violent extremism, it is highly unlikely to devise a single solution that could produce effective outcomes to deal with radicalization, violent extremism and terrorism. The pathway to deradicalization, like the pathway to radicalisation, is different for everyone. Considering the need of having customized deradicalization resolution, this study proposes a multi-tier framework, called ‘pyramid of deradicalization’ that first help identifying the stage at which an individual could be on the radicalization pathway and then propose a customize strategy to deal with the respective stage. The first tier (tier 1) addresses broader community and proposes a ‘universal approach’ aiming to offer community-based design and delivery of educational programs to raise awareness and provide general information on possible factors leading to radicalization and their remedies. The second tier focuses on the members of community who are more vulnerable and are disengaged from the rest of the community. This tier proposes a ‘targeted approach’ targeting the vulnerable members of the community through early intervention such as providing anonymous help lines where people feel confident and comfortable in seeking help without fearing the disclosure of their identity. The third tier aims to focus on people having clear evidence of moving toward extremism or getting radicalized. The people falls in this tier are believed to be supported through ‘interventionist approach’. The interventionist approach advocates the community engagement and community-policing, introducing deradicalization programmes to the targeted individuals and looking after their physical and mental health issues. The fourth and the last tier suggests the strategies to deal with people who are actively breaking the law. ‘Enforcement approach’ suggests various approaches such as strong law enforcement, fairness and accuracy in reporting radicalization events, unbiased treatment by law based on gender, race, nationality or religion and strengthen the family connections.It is anticipated that the operationalization of the proposed framework (‘pyramid of deradicalization’) would help in categorising people considering their tendency to become radicalized and then offer an appropriate strategy to make them valuable and peaceful members of the community.

Keywords: deradicalization, framework, terrorism, violent extremism

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Authors: Panadda Rojpibulstit, Suthathip Kittisenachai, Songchan Puthong, Sirikul Manochantr, Pornpen Gamnarai, Sasichai Kangsadalampai, Sittiruk Roytrakul

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Hepatocellular carcinoma (HCC) is the most primary hepatic cancer worldwide. Nowadays a targeted therapy via monoclonal antibodies (mAbs) specific to tumor-associated antigen is continually developed in HCC treatment. In this regard, after establishing and consequently exploring Hep88 mAb’s tumoricidal effect on hepatocellular carcinoma cell line (HepG2 cell line), the Hep88 mAb’s specific Ag from both membrane and cytoplasmic fractions of HepG2 cell line was identified by 2-D gel electrophoresis and western blot analysis. After in-gel digestion and subsequent analysis by liquid chromatography-mass spectrometry (LC-MS), mortalin (HSPA9) and alpha-enolase were identified. The recombinant proteins specific to Hep88 mAb were cloned and expressed in E.coli BL21 (DE3). Moreover, alteration of HepG2 and Chang liver cell line after being induced by Hep88 mAb for 1-3 days was investigated using a transmission electron microscope. The result demonstrated that Hep88 mAb can bind to the recombinant mortalin (HSPA9) andalpha-enolase. In addition, gradual appearance of mitochondria vacuolization and endoplasmic reticulum dilatation were observed. Taken together, paraptosis-like programmed cell death (PCD) of HepG2 is induced by binding of mortalin (HSPA9) and alpha-enolase to Hep88 mAb. Mortalin depletion by formation of Hep88 mAb-mortalin (HSPA9) complex might initiate transcription-independent of p53-mediated apoptosis. Additionally, Hep88 mAb-alpha-enolase complex might initiate HepG2 cells energy exhaustion by glycolysis pathway obstruction. These results imply that Hep88 mAb might be a promising tool for development of an effective treatment of HCC in the next decade.

Keywords: Hepatocellular carcinoma, Monoclonal antibody, Paraptosis-like program cell death, Transmission electron microscopy, mortalin (HSPA9), alpha-enolase

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Authors: Ratneev Kaur, Tajinder Kaur, Anupam Kaur

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Introduction: Polycystic Ovary Syndrome (PCOS) is a heterogenous disorder of endocrine system among women of reproductive age. PCOS is characterized by hyperandrogenism, anovulation, polycystic ovaries, hirsutism, obesity, and hyperinsulinemia. Several pathways are implicated in its etiology including the metabolic pathway of steroid hormone synthesis regulatory pathways. PCOS is an androgen excess disorder, genes operating in steroidogenesis may alter pathogenesis of PCOS. The cytochrome P450scc is a cholesterol side chain cleavage enzyme coded by CYP11A1 gene and catalyzes conversion of cholesterol to pregnenolone, the initial and rate-limiting step in steroid hormone synthesis. It is postulated that polymorphisms in this gene may play an important role in the regulation of CYP11A1 expression and leading to increased or decreased androgen production. The present study will be the first study from north India to best of our knowledge, to analyse the association of CYP11A1 (rs11632698) polymorphism in women suffering from PCOS. Methodology: The present study was approved by ethical committee of Guru Nanak Dev University in consistent with declaration of Helsinki. A total of 300 samples (150 PCOS cases and 150 controls) were recruited from Hartej hospital, for the present study. Venous blood sample (3ml) was withdrawn from women diagnosed with PCOS by doctor, according to Rotterdam 2003 criteria and from healthy age matched controls only after informed consent and detailed filled proforma. For molecular genetics analysis, blood was stored in EDTA vials. After DNA isolation by organic method, PCR-RFLP approach was used for genotyping and association analysis of rs11632698 polymorphism. Statistical analysis was done to check for significance of selected polymorphism with PCOS. Results: In 150 PCOS cases, the frequency of AA, AG and GG genotype was found to be 48%, 35%, and 13% compared to 62%, 27% and 8% in 150 controls. The major allele (A) and minor allele (G) frequency was 68% and 32% in cases and 78% and 22% in controls. Minor allele frequency was higher in cases as compared to controls, as well as the distribution of genotype was observed to be statistically significant (ᵡ²=6.525, p=0.038). Odds ratio in dominant, co-dominant and recessive models observed was 1.81 (p=0.013), 1.54 (p=0.012) and 1.77 (p=0.132) respectively. Conclusion: The present study showed statistically significant association of rs11632698 with PCOS (p=0.038) in North Indian women.

Keywords: polycystic ovary syndrome, CYP11A1, rs11632698, hyperandrogenism

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