Search results for: TGF-β/CD4+CD25+Foxp3high T regulatory pathway

Authors: Man-Ho Oh

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Membrane localized Leucine-Rich-Repeat Receptor-Like Kinases (LRR-RLKs) play crucial roles in plant growth and abiotic/biotic stress responses in higher plants including Arabidopsis and Brassica species. Among several Receptor-Like Kinases (RLKs), Leucine-Rich-Repeat Receptor-Like-Kinases (LRR-RLKs) are the major group of genes that play crucial roles related to growth, development and stress conditions in plant system. Since it is involved in several functional roles, it seems to be very important to investigate their roles in higher plants. We are particularly interested in brassinosteroid (BR) signaling, which is mediated by the BRASSINOSTEROID INSENSITIVE 1 (BRI1) receptor kinase and its co-receptor, BRI1-ASSOCIATED KINASE 1 (BAK1). Autophosphorylation of receptor kinases is recognized to be an important process in activation of signaling in higher plants. Although the plant receptors are generally classified as Ser/Thr protein kinases, many other receptor kinases including BRI1 and BAK1 are shown to autophosphorylate on Tyr residues in addition to Ser/Thr. As an interesting result, we determined that several 14-3-3 regulatory proteins bind to BRI1-CD and are phosphorylated by several receptor kinases in vitro, suggesting that BRI1 is critical for diverse signaling.

Keywords: autophosphorylation, brassinosteroid, BRASSINOSTEROID INSENSITIVE 1, BRI1-ASSOCIATED KINASE 1, Leucine-Rich-Repeat Receptor-Like Kinases (LRR-RLKs)

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Authors: Waranya Imprasittichai, Patsarawadee Paojinda, Sudaratana R. Krungkrai, Nirianne Marie Q. Palacpac, Toshihiro Horii, Jerapan Krungkrai

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Fusion of the last two enzymes in the pyrimidine biosynthetic pathway in the inversed order by having COOH-terminal orotate phosphoribosyltransferase (OPRT) and NH2-terminal orotidine 5'-monophosphate decarboxylase (OMPDC), as OMPDC-OPRT, are described in many organisms. In this study, we constructed gene fusions of Plasmodium falciparum OMPDC-OPRT (1,836 bp) in pTrcHisA vector and expressed as an 6xHis-tag bifunctional protein in three Escherichia coli strains (BL21, Rosetta, TOP10) at 18 °C, 25 °C and 37 °C. The recombinant bifunctional protein was partially purified by Ni-Nitrilotriacetic acid-affinity chromatography. Specific activities of OPRT and OMPDC domains in the bifunctional enzyme expressed in E. coli TOP10 cells were approximately 3-4-fold higher than those in BL21 cells. There were no enzymatic activities when the construct vector expressed in Rosetta cells. Maximal expression of the fused gene was observed at 18 °C and the bifunctional enzyme had specific activities of OPRT and OMPDC domains in a ratio of 1:2. These results provide greater yields and better catalytic activities of the bifunctional OMPDC-OPRT enzyme for further purification and kinetic study.

Keywords: bifunctional enzyme, orotate phosphoribosyltransferase, orotidine 5'-monophosphate decarboxylase, plasmodium falciparum

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Authors: Fernanda T. Orsati, Julie Causton

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Discursive practices enacted by educators in kindergarten create a blueprint for how the educational trajectories of students with disabilities are constructed. This two-year ethnographic case study critically examine educators’ relationships with students considered to present challenging behaviors in one kindergarten classroom located in a predominantly White middle-class school district in the Northeast of the United States. Focusing on the language and practices used by one special education teacher and three teaching assistants, this paper analyzes how teacher responses to students’ behaviors constructs and positions students over one year of kindergarten education. Using a critical discourse analysis, it shows that educators understand students’ behaviors as a deficit and needing consequences. This study highlights how educators’ responses reflect students' individual characteristics including family background, socioeconomics and ability status. This paper offers in-depth analysis of two students’ stories, which evidenced that the language used by educators amplifies the social positioning of students within the classroom and creates a foundation for who they are constructed to be. Through exploring routine language and practices, this paper demonstrates that educators outlined a blueprint of kindergartners, which positioned students as learners in ways that became the ground for either a limited or a promising educational pathway for them.

Keywords: behavior, early education, special education, critical discourse analysis

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Authors: Leo Byrne, Neil Watts

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In the complex and evolving landscape of global trade, maritime sanctions emerge as a critical tool wielded by the international community to curb illegal activities and alter the behavior of non-compliant states and entities. These sanctions, designed to restrict or prohibit trade by sea with sanctioned jurisdictions, entities, or individuals, face continuous challenges due to the sophisticated evasion tactics employed by countries like North Korea. As the Democratic People's Republic of Korea (DPRK) diverts significant resources to circumvent these measures, understanding the nuances of their methodologies becomes imperative for maintaining the integrity of global trade systems. The DPRK, one of the most sanctioned nations globally, has developed an intricate network to facilitate its trade in illicit goods, ensuring the flow of revenue from designated activities continues unabated. Given its geographic and economic conditions, North Korea predominantly relies on maritime routes, utilizing foreign ports to route its illicit trade. This reliance on the sea is exploited through various sophisticated methods, including the use of front companies, falsification of documentation, commingling of bulk cargos, and physical alterations to vessels. These tactics enable the DPRK to navigate through the gaps in regulatory frameworks and lax oversight, effectively undermining international sanctions regimes Maritime sanctions carry significant implications for global trade, imposing heightened risks in the maritime domain. The deceptive practices employed not only by the DPRK but also by other high-risk jurisdictions, necessitate a comprehensive understanding of UN targeted sanctions. For stakeholders in the maritime sector—including maritime authorities, vessel owners, shipping companies, flag registries, and financial institutions serving the shipping industry—awareness and compliance are paramount. Violations can lead to severe consequences, including reputational damage, sanctions, hefty fines, and even imprisonment. To mitigate risks associated with these deceptive practices, it is crucial for maritime sector stakeholders to employ rigorous due diligence and regulatory compliance screening measures. Effective sanctions compliance serves as a protective shield against legal, financial, and reputational risks, preventing exploitation by international bad actors. This requires not only a deep understanding of the sanctions landscape but also the capability to identify and manage risks through informed decision-making and proactive risk management practices. As the DPRK and other sanctioned entities continue to evolve their sanctions evasion tactics, the international community must enhance its collective efforts to demystify and counter these practices. By leveraging more stringent compliance measures, stakeholders can safeguard against the illicit use of the maritime domain, reinforcing the effectiveness of maritime sanctions as a tool for global security. This paper seeks to dissect North Korea's adaptive strategies in the face of maritime sanctions. By examining up-to-date, geographically, and temporally relevant case studies, it aims to shed light on the primary nodes through which Pyongyang evades sanctions and smuggles goods via third-party ports. The goal is to propose multi-level interaction strategies, ranging from governmental interventions to localized enforcement mechanisms, to counteract these evasion tactics.

Keywords: maritime, maritime sanctions, international sanctions, compliance, risk

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Authors: Matheus Fonseca Durães, Bruno da Silva Pereira, Bruna Stewart

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The concept of Brazil’s water governance has been the topic of discussion and has undergone legal and organizational improvements due to the need to promote a more effective and sustainable relationship with natural resources and stemming from conflicts related to shortcomings in decision-making. The Waters Act has enabled Brazil to create interesting mechanisms for integrated management, but, on the other hand, it has created a challenge that involves the implementation of the principles established in this legal framework. This study aims to evaluate some challenges and opportunities for water governance in two watersheds based on data collection and analysis of concessions, the water use register, and flow data. The elements presented demonstrated, via an analysis of legally instituted criteria, that the level of commitment of water resources is high, especially to public supply, and the adoption of the reference flow constituted one of the main barriers to implementing an efficient system, demonstrating the need for a regulatory policy that considers the hydrological behavior of the watersheds. Finally, the current water management model presents challenges to be addressed to achieve the objectives proposed by the water policy, such as ensuring sustainable, rational, and integrated use of water resources.

Keywords: management, hydrology, public policies, Brazil

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Authors: Dong Il Shim, Geehong Choi, Donghwi Lee, Namkyu Lee, Hyung Hee Cho

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Effective cooling technology is required to secure thermal stability in extreme heat generated systems such as integrated electronic devices and power generated systems. Pool boiling heat transfer is one of the powerful cooling mechanisms using phase change phenomena. Critical heat flux (CHF) and heat transfer coefficient (HTC) are main factors to evaluate the performance of boiling heat transfer. CHF is the limitation of boiling heat transfer before film boiling which occurs thermal failure. Surface wettability is an important surface characteristic of boiling heat transfer. A hydrophilic surface has higher CHF through effective working fluid supply to local hot spots. A hydrophobic surface promotes the onset of nucleate boiling (ONB) to enhance HTC. In this study, superbiphilic surfaces, which is combined with superhydrophillic and superhydrophobic, are applied on boiling experiments to maximize boiling performance. We conducted pool boiling heat transfer using DI water at a saturated temperature and recorded bubble dynamics using a high-speed camera with 2000 fps. As a result, superbiphilic patterned surfaces promote ONB and enhance both CHF and HTC. This study demonstrates the enhanced boiling performance using superbiphilic surfaces by effective nucleation and separation of liquid/vapor pathway. We expect that further enhancement of heat transfer could be achieved in future work using optimized patterned surfaces.

Keywords: boiling heat transfer, wettability, critical heat flux, heat transfer coefficient

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Authors: Mohammed Lawal Danrimi, Ervina Alfan, Mazni Abdullah

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The purpose of this study is to investigate whether the adoption of International Financial Reporting Standards (IFRS) encourages information-based trading and mitigates investors’ herding practice in emerging EU equity markets. Utilizing a modified non-linear model of cross-sectional absolute deviation (CSAD), we find that the hypothesis that mandatory IFRS adoption improves the information set of investors and reduces irrational investment behavior may in some cases be incorrect, and the reverse may be true. For instance, with regard to herding concerns, the new reporting benchmark has rather aggravated investors’ herding practice. However, we also find that mandatory IFRS adoption does not appear to be the only instigator of the observed herding practice; national institutional factors, particularly regulatory quality, political stability and control of corruption, also significantly contribute to investors’ herd formation around the new reporting regime. The findings would be of interest to academics, regulators and policymakers in performing a cost-benefit analysis of the so-called better reporting regime, as well as financial statement users who make decisions based on firms’ fundamental variables, treating them as significant indicators of future market movement.

Keywords: equity markets, herding, IFRS, CSAD

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Authors: Md Mizanur Rahman, M. Aslam Alam, Muhammad Abu Yusuf

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The abundance of Jellyfish across the coasts of the Bay of Bengal is increasing sharply due to marine pollution, increased sea acidification and climate change. Jellyfish draws our attention to address the local and global stressors. This also indicates that something wrong is happening in this bay behind the scenes. This study aimed to investigate how the policy framework governing the sea can be reformed. To do so, this study evaluated the existing policy, regulatory and institutional framework. Empirical data were collected from the middle coastal zone of Bangladesh. The secondary literature on policy, legal documents, and institutional arrangements were reviewed. The causes of poor coordination among different public sectors and non-compliance of laws were identified. The key findings show that despite the existing of Department of Environment, poor coordination with other departments, and lack of logistics and technical staffs have resulted in severe marine pollution and degradation of coastal and marine living resources. The existing policies had no monitoring and evaluation mechanisms. Non-compliance of the existing laws has been fueling the problems. This study provides an integrated policy and a guideline for updating the legal and institutional mechanism to manage coastal and marine living resources sustainably in Bangladesh to achieve Sustainable Development Goal 14.

Keywords: legal, institutional, framework, jellyfish

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Authors: Muna Mohamed Omer Mirghani

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This paper responds to one of the key national development strategies and a typical challenge in the Gash Basin as well as in different parts of Sudan, namely managing water scarcity in view of climate change impacts in minor water systems sustaining over 50% of the Sudan population. While now focusing on the Gash river basin, the ultimate aim is to replicate the same approach in similar water systems in central and west Sudan. The key objective of the paper is the identification of outcome-based water governance interventions in Gash Basin, guided by the global Sustainable Development Goal six (SDG 6 on water and sanitation) and the Sudan water resource policy framework. The paper concluded that improved water resources management of the Gash Basin is a prerequisite for ensuring desired policy outcomes of groundwater use and flood risk management purposes. Analysis of various water governance dimensions in the Gash indicated that the operationalization of a Basin-level institutional reform is critically focused on informed actors and adapted practices through knowledge and technologies along with the technical data and capacity needed to make that. Adapting the devolved Institutional structure at state level is recommended to strengthen the Gash basin regulatory function and improve compliance of groundwater users.

Keywords: water governance, Gash Basin, integrated groundwater management, Sudan

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Authors: Dermot O'Brien, Vasileios Christaras, Georgios Fontaras, Igor Nai Fovino, Ioannis Kounelis

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With the rise of the Internet of Things (IoT), 5G, and blockchain (BC) technologies, vehicles are becoming ever increasingly connected and are already transmitting substantial amounts of data to the original equipment manufacturers (OEMs) servers. This data could be used to help detect mileage fraud and enable more accurate vehicle emissions monitoring. This would not only help regulators but could enable applications such as permitting efficient drivers to pay less tax, geofencing for air quality improvement, as well as pollution tolling and trading platforms for transport-related businesses and EU citizens. Other applications could include traffic management and shared mobility systems. BC enables the transmission of data with additional security and removes single points of failure while maintaining data provenance, identity ownership, and the possibility to retain varying levels of privacy depending on the requirements of the applied use case. This research performs simulations of vehicles interacting with European member state authorities and European Commission BC nodes that are running hyperleger fabric and explores whether the technology is currently feasible for transport applications such as the emission monitoring use-case.

Keywords: future transportation systems, technological innovations, policy approaches for transportation future, economic and regulatory trends, blockchain

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Authors: Maryam Kiani

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In order to enhance the efficiency and stability of an electrocatalyst for formic acid electro-oxidation reaction (FAOR), we developed a method to create Pt/Ni nanoparticles with carbon black. These nanoparticles were prepared using a simple impregnation reduction technique. During the observation, it was found that the nanoparticles had a spherical shape. Additionally, the average particle size remained consistent, falling within the range of about 4 nm. This approach aimed to obtain a loaded Pt-based electrocatalyst that would exhibit improved performance and stability when used in FAOR applications. By utilizing the impregnation reduction method and incorporating Ni nanoparticles along with Pt, we sought to enhance the catalytic properties of the material. By incorporating Ni atoms into the Pt structure, the electronic properties of Pt are modified, resulting in a delay in the chemisorption of harmful CO intermediate species. This modification also promotes the dehydrogenation pathway of the formic acid oxidation reaction (FAOR). Through electrochemical analysis, it has been observed that the Pt3Ni-C catalyst exhibits enhanced performance in FAOR compared to traditional Pt catalysts. This means that the addition of Ni atoms improves the efficiency and effectiveness of the Pt3Ni-C catalyst in facilitating the FAOR process. Overall, the utilization of these alloy nanoparticles as electrocatalysts represents a significant advancement in fuel cell technology.

Keywords: electrocatalyst, impregnation reduction method, formic acid electro-oxidation reaction, fuel cells

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Authors: Muzaffar Iqbal, Essam Ezzeldin, Khalid A. Al-Rashood

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Pomalidomide is a second generation oral immunomodulatory agent, being used for the treatment of multiple myeloma in patients with disease refractory to lenalidomide and bortezomib. In this study, a sensitive UPLC-MS/MS assay was developed and validated for high-throughput determination of pomalidomide in rat plasma using celecoxib as an internal standard (IS). Liquid liquid extraction using dichloromethane as extracting agent was employed to extract pomalidomide and IS from 200 µL of plasma. Chromatographic separation was carried on Acquity BEHTM C18 column (50 × 2.1 mm, 1.7 µm) using an isocratic mobile phase of acetonitrile:10 mM ammonium acetate (80:20, v/v), at a flow rate of 0.250 mL/min. Both pomalidomide and IS were eluted at 0.66 ± 0.03 and 0.80 ± 0.03 min, respectively with a total run time of 1.5 min only. Detection was performed on a triple quadrupole tandem mass spectrometer using electrospray ionization in negative mode. The precursor to product ion transitions of m/z 272.01 → 160.89 for pomalidomide and m/z 380.08 → 316.01 for IS were used to quantify them respectively, using multiple reaction monitoring mode. The developed method was validated according to regulatory guideline for bioanalytical method validation. The linearity in plasma sample was achieved in the concentration range of 0.47–400 ng/mL (r2 ≥ 0.997). The intra and inter-day precision values were ≤ 11.1% (RSD, %) whereas accuracy values ranged from - 6.8 – 8.5% (RE, %). In addition, other validation results were within the acceptance criteria and the method was successfully applied in a pharmacokinetic study of pomalidomide in rats.

Keywords: pomalidomide, pharmacokinetics, LC-MS/MS, celecoxib

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Authors: Peikun Zhang, Chunhua Cui

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Photoelectrochemical (PEC) water splitting provides a promising pathway to convert solar energy into renewable fuels. However, the main and seemingly insurmountable obstacle is that the sluggish kinetics of oxygen evolution reaction (OER) severely jeopardizes the overall efficiency, thus exploring highly active, stable, and appreciable catalysts is urgently requested. Herein a competitive coordination strategy was demonstrated to form a reversible hybrid homo-heterogeneous catalyst for efficient OER in alkaline media. The dynamic process involves an in-situ anchoring of soluble nickel–bipyridine pre-catalyst to a conductive substrate under OER and a re-dissolution course under open circuit potential, induced by the competitive coordination between nickel–bipyridine and nickel-hydroxyls. This catalyst allows to elaborately self-modulate a charge-transfer layer thickness upon the catalytic on-off operation, which affords substantially increased active sites, yet remains light transparency, and sustains the stability of over 200 hours of continuous operation. The integration of this catalyst with exemplified state-of-the-art Ni-sputtered Si photoanode can facilitate a ~250 mV cathodic shift at a current density of 20 mA cm-2. This finding helps the understanding of catalyst from a “dynamic” perspective, which represents a viable alternative to address remaining hurdles toward solar-driven water oxidation.

Keywords: molecular catalyst, oxygen evolution reaction, solar energy, transition metal complex, water splitting

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Authors: Chengcao Sun, Shujun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, Dejia Li

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Recently, the long non-coding RNA (lncRNA) NEAT1 has been identified as an oncogenic gene in multiple cancer types and elevated expression of NEAT1 was tightly linked to tumorigenesis and cancer progression. However, the molecular basis for this observation has not been characterized in progression of non-small cell lung cancer (NSCLC). In our studies, we identified NEAT1 was highly expressed in NSCLC patients and was a novel regulator of NSCLC progression. Patients whose tumors had high NEAT1 expression had a shorter overall survival than patients whose tumors had low NEAT1 expression. Further, NEAT1 significantly accelerates NSCLC cell growth and metastasis in vitro and tumor growth in vivo. Additionally, by using bioinformatics study and RNA pull down combined with luciferase reporter assays, we demonstrated that NEAT1 functioned as a competing endogenous RNA (ceRNA) for has-miR-377-3p, antagonized its functions and led to the de-repression of its endogenous targets E2F3, which was a core oncogene in promoting NSCLC progression. Taken together, these observations imply that the NEAT1 modulated the expression of E2F3 gene by acting as a competing endogenous RNA, which may build up the missing link between the regulatory miRNA network and NSCLC progression.

Keywords: long non-coding RNA NEAT1, hsa-miRNA-377-3p, E2F3, non-small cell lung cancer, tumorigenesis

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Authors: Sean Hall

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Nanosystems for drug delivery are not new; as medicines evolve, so too does the desire to deliver a more targeted, patient-compliant medicine. Though, historically the widespread use of nanosystems for drug delivery has been fouled by non-replicability, scalability, toxicity issues, and economics. Examples include steps of manufacture and thus cost to manufacture, toxicity for nanoparticle scaffolding, autoimmune response, and considerable technical expertise for small non-commercial yields. This, unfortunately, demonstrates the not-so-obvious chasm between science and drug formulation for regulatory approval. Regardless there is a general and global desire to improve the delivery of medicines, reduce potential side effect profiles, promote increased patient compliance, and increase and/or speed public access to medicine availability. In this paper, the author will discuss NanoCelle®, a nano-delivery platform that specifically addresses degradation and solubility issues that expands from fundamental micellar preparations. NanoCelle® has been deployed in several Australian listed medicines and is in use of several drug candidates across small molecules, with research endeavors now extending into large molecules. The author will discuss several research initiatives as they relate to NanoCelle® to demonstrate similarities seen in various drug substances; these examples will include both in vitro and in vivo work.

Keywords: NanoCelle®, micellar, degradation, solubility, toxicity

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Authors: Daruliza Kernain, Shaharum Shamsuddin, See Too Wei Cun

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CTCF is a unique, highly conserved and ubiquitously expressed 11 zinc finger (ZF) transcriptional factor with multiple target sites. It is able to bind to various target sequences to perform different regulatory roles including promoter activation or repression, creating hormone-responsive gene silencing element, and functional block of enhancer-promoter interactions. The binding of CTCF to the essential binding site is through the combination of different ZF domain. On the other hand, BORIS for brother of the regulator of imprinted sites, which expressed only in the testis and certain cancer cell line is homology to CTCF 11 ZF domains. Since both transcriptional factors share the same ZF domains hence there is a possibility for both to bind to the same target sequences. In this study, the interaction of these two proteins to multi-functional Y-box DNA/RNA-binding factor, YB-1 was determined. The protein-protein interaction between CTCF/YB-1 and BORIS/YB-1 were discovered by Co-immuno-precipitation (CO-IP) technique through reciprocal experiment from RGBM total cell lysate. The results showed that both CTCF and BORIS were able to interact with YB-1 in Glioma RGBM cell line. To the best of our knowledge, this is the first findings demonstrating the ability of BORIS and YB-1 to form a complex in vivo.

Keywords: immunoprecipitation, CTCF/BORIS/YB-1, transcription factor, molecular medicine

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Authors: Fern Baedyananda, Arkom Chaiwongkot, Somchai Niruthisard, Nakarin Kitkumthorn, Parvapan Bhattarakosol

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High-risk human papillomavirus (HPV) infections cause transformation of the host cells by down-regulating and inhibiting host regulatory proteins such as p53 and pRb by overexpressing the viral oncoproteins E6 and E7. However, the E1 protein which is the only enzyme encoded by HPV has also been shown to cause DNA instability leading to the integration of the virus into the host genome and triggering carcinogenic events. A 63bp duplication in the E1 helicase region has been detected in European patients. However, the clinical prognosis of these patients is still controversial. This study was performed to determine the presence of the HPV-16 E1 63bp duplication in patient cervical samples in Thai women and determine the sequence of the variant in the Thai population. Detection of the HPV-16 E1 duplication in the helicase region was performed in 90 patient cell samples across normal, cervical intraepithelial neoplasia I-III, and squamous cervical carcinoma stages by PCR. The PCR products were purified and sequenced to determine the presence of duplication variants.The variant form was found in 10% of all CIN 1 patients. In this study, the presence of the 63 bp duplication variant in the Thai population was found to be present and was further characterized. Interestingly, all samples that exhibited the variant form of HPV-16 E1 were classified as CIN I. Presence of the variant, constricted to mild dysplasia signifies the importance of HPV-16 E1 in carcinogenesis.

Keywords: carcinogenesis, cervical cancer, human papillomavirus, HPV-16 E1

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Authors: Qiang Xu, Xingxin Wu, Wenjie Guo, Xingqi Wang, Yang Sun, Renxiang Tan

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The phosphatase SHP-2 is known to exert regulatory activities on cytokine receptor signaling and the dysregulation of SHP-2 has been implicated in the pathogenesis of a variety of diseases. Here we report several small molecule regulators of SHP-2 for the treatment of T cell-mediated diseases. The new cyclodepsipeptide trichomides A, isolated from the fermentation products of Trichothecium roseum, increased the phosphorylation of SHP-2 in activated T cells, and ameliorated contact dermatitis in mice. The trichomides A’s effects were significantly reversed by using the SHP-2-specific inhibitor PHPS1 or T cell-conditional SHP-2 knockout mice. Another compound is a cerebroside Fusaruside isolated from the endophytic fungus Fusarium sp. IFB-121. Fusaruside also triggered the tyrosine phosphorylation of SHP-2, which provided a possible mean of selectively targeting STAT1 for the treatment of Th1 cell-mediated inflammation and led to the discovery of the non-phosphatase-like function of SHP-2. Namely, the Fusaruside-activated pY-SHP-2 selectively sequestrated the cytosolic STAT1 to prevent its recruitment to IFN-R, which contributed to the improvement of experimental colitis in mice. Blocking the pY-SHP-2-STAT1 interaction, with SHP-2 inhibitor NSC-87877 or using T cells from conditional SHP-2 knockout mice, reversed the effects of fusaruside. Furthermore, the fusaruside’s effect is independent of the phosphatase activity of SHP-2, demonstrating a novel role for SHP-2 in regulating STAT1 signaling and Th1-type immune responses.

Keywords: SHP-2, small molecules, T cell, T cell-mediated diseases

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Authors: Hongmeng Su, Luyu Zhao, Yanyan Qian, Hong Fan

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Aim: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors that endanger human health seriously. RNA methylation, especially N6-methyladenosine (m⁶A) and 5-methylcytosine (m⁵C), a crucial epigenetic transcriptional regulatory mechanism, plays an important role in tumorigenesis, progression and prognosis. This research aims to systematically evaluate the prognostic value of m⁶A and m⁵C modulators in HCC patients. Methods: Twenty-four modulators of m⁶A and m⁵C were candidates to analyze their expression level and their contribution to predict the prognosis of HCC. Consensus clustering analysis was applied to classify HCC patients. Cox and LASSO regression were used to construct the risk model. According to the risk score, HCC patients were divided into high-risk and low/medium-risk groups. The clinical pathology factors of HCC patients were analyzed by univariate and multivariate Cox regression analysis. Results: The HCC patients were classified into 2 clusters with significant differences in overall survival and clinical characteristics. Nine-gene risk model was constructed including METTL3, VIRMA, YTHDF1, YTHDF2, NOP2, NSUN4, NSUN5, DNMT3A and ALYREF. It was indicated that the risk score could serve as an independent prognostic factor for patients with HCC. Conclusion: This study constructed a Nine-gene risk model by modulators of m⁶A and m⁵C and investigated its effect on the clinical prognosis of HCC. This model may provide important consideration for the therapeutic strategy and prognosis evaluation analysis of patients with HCC.

Keywords: hepatocellular carcinoma, m⁶A, m⁵C, prognosis, RNA methylation

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Authors: G. Fitzpatrick, S. O. Chonghaile, D. Harmon

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Objective: Chronic pain patients represent a unique challenge in the Emergency Department. Very little literature has been published regarding this group of patients. Our aim was to determine the attitude of patients with chronic pain to the Emergency Department in order to improve and streamline their future visits. Methods: A two-year survey was carried out on Chronic Pain Patients regarding their Emergency Department Attendances. Patients attending the Pain Clinic in Croom Hospital, Co. Limerick were asked to complete a 20-part questionnaire regarding their experiences of visiting the Emergency Department in the preceding year. 46 questionnaires were completed. Results: Unbearable breakthrough pain was the main reason for visiting the Emergency Department. More than half (54%) of those surveyed were not satisfied with the treatment received. Problems indicated included under-treatment of pain (59%), a sense of being under undue suspicion of drug-seeking behaviour (33%) and a perception that the patient themselves understood their condition better than the treating doctor (76%). Paracetamol, NSAIDs, or time off work comprised 72% of the treatments offered – all of which could have been provided by their General Practitioner. Only 4% were offered a nerve block. 67% felt that the creation of personalised Patient Plans, consisting of an agreed plan between the patient, their pain specialist, and the Emergency Department, would expedite their trip through the Emergency Department. Conclusions: Chronic pain patients generally have a negative experience in the ED. Possible future solutions include increasing our empathy and levels of knowledge, provision of nerve blocks in the ED, and use of personalised “Patient Plans” to streamline the treatment pathway for this group of patients.

Keywords: chronic pain, survey, patients, emergency department

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Authors: John Kong Shan Ho

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Senior executives’ remunerations of public companies have aroused much debate and attention in the media. In the aftermath of the Global Financial Crisis (GFC), excessive executive pay arrangements were blamed for contributing to excessive risk-taking, which caused the financial meltdown. Since then, regulators and lawmakers around the world have introduced regulations to strengthen the corporate governance of listed companies. A key aspect of such reform is by strengthening regulatory intervention over executives’ remunerations and increasing the transparency of such information. This article is written against such background and examines the recent proposal by the UK BEIS to ask the FRC to amend the UK Corporate Governance Code (UKCGC) to strengthen clawback provisions for directors’ remuneration in listed companies as part of its audit reform. The article examines the background and debates regarding the possible implementation of such a measure in the UK. Contrary to the BEIS’ proposal, it argues that implementing it through the UKCGC is unlikely to enhance overall corporate governance and audit quality. It argues that the UK should follow the footsteps of its US and Dutch counterparts by enacting legislation to claw back directors’ remunerations. It will also provide some recommendations as to the key factors that need to be considered in drafting such a statutory provision.

Keywords: company law, corporate governance, agency problem, directors' remunerations, clawbacks

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Authors: K. P. Farsana

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Belief in supernatural causation of mental illnesses and resort to religious and faith healing as the method of intervention still continue in many parts of the world. The proposed study intended to find out the belief and causation on health and illness and utilization of religious and faith healing, its implications, and associated socio-cultural and religious factors among Mappila Muslims of Malabar, Kerala, a southern state of India.Thangals are the endogamous community in Kerala, of Yemeni heritage who claim direct descent from the Prophet Mohammed’s family. Because of their sacrosanct status, many Thangal works as religious healers in Malabar, Northern Kerala. Using the case of one Thangal healer as an illustration of the many religious healers in Kerala who engage in the healing practices, it is intended, in this paper to illustrate the religious and ritual healing practices among Mappila Muslims of Malabar. It was found that the majority of the Mappila Muslims believed in supernatural causation on illness, and majority of them consulted religious and faith healers for various health problems before seeking professional help, and a considerable proportion continued to believe in the healing efficiency of the religious and faith healing. A significant proportion of the population found religious and faith healing practices are supportive and more acceptable within the community. Religion and belief system play an important role in the heath seeking behavior of a person.

Keywords: religious and faith healing, mental illness, Mappila Muslims, Malabar

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Authors: Ravi Raghav Sonani, Niraj Kumar Singh, Jitendra Kumar, Datta Madamwar

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Phycobiliproteins (PBPs) are light harvesting proteins showing very strong absorbance and fluorescence in the visible range of the solar spectrum. Phycoerythrin (PE) and phycocyanin (PC) are majorly found PBPs in the cyanobacteria and red algae. In the present study, we have investigated the reactive oxygen species (ROS)-averting capacity of purified PE and PC of cyanobacterial origin. Furthermore, the possibility - whether the ROS-averting potential of PBPs can be explored in the therapeutics of oxidative stress associated physiological anomalies including aging and neurodegenerative diseases. The nematode Caenorhabditis elegans has been used as model organism in this study. PE and PC treatment moderated normal aging and associated physiological functionalities like pharyngeal pumping and locomotion of C. elegans. Moreover, PE-treatment enhanced the stress (oxidative and heat) tolerance upon PE and PC treatment. Specifically, PE treatment was also noted to moderate the progression of Alzheimer’s disease in transgenic C. elegans CL4176. However, PC-treatment curtailed the polyQ aggregation mediated proteotoxicity in C. elegans AM141 (Huntington disease model) under stressed (paraquat stress) as well as normal conditions. The effectiveness of PE and PC in expanding the lifespan of mutant C. elegans knockout for some up- (daf 16) and down- (daf-2 and age-1) stream regulators of insulin/IGF-1 signalling (IIS) shows the independency of their effects from DAF-2–AGE-1–DAF-16 signalling pathway. In conclusion, the present report demonstrates the anti-aging and neuro-protective potential of cyanobacterial PE and PC.

Keywords: phycobiliproteins, aging, alzheimer, huntington, C. elegans

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Authors: Shanaj Parvin Jonaki

Abstract:

After the first wave of the feminist movement, gender has become one of the most important issues to be researched in social science. Many gender theories have been invented and opened a new window to look at. These works showed how gender is a social construct, how gender has been used to oppress, how to rule. While it's the education system’s duty to guide students to understand the concept of gender, it sometimes shows gender-based discrimination. Transgenders exclusion from educational institutes of Bangladesh justifies this very statement. This study aims to figure out how people perceive transgenders’ identity, their inclusion in secondary schools, as well as the underlying barriers in the pathway of inclusion in the context of Bangladesh. A qualitative approach was taken to explore different perspectives towards transgender inclusion from several stakeholders such as students, parents, and teachers of secondary schools and transgenders as well. Data were collected through focus group discussion and interview by convenient sampling. 15 students, 10 parents, and 5 teachers were selected from Bangla Medium school as well as from Madrasha. Collected data were analyzed thematically and were run by experts of gender, education, and psychology to identify the core barriers of inclusion. The study revealed that most of the students, teachers, and parents lacked the knowledge of non-binary gender identities, and they showed unwillingness towards the inclusion of transgender in schools because of the cultural context of Bangladesh. Moreover, this study suggests future initiatives to be taken to ensure the inclusion of transgenders in a secondary school in our country and analyzes it through the lens of feminist theories.

Keywords: education, gender, inclusion, transgender

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Authors: Ivanova B. Natalia, Djambova Т. Svetlana, Hristev S. Ivailo

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The acoustic properties of recycled felt panels have been investigated using various methods. Experimentally, the sound insulation of the panels has been evaluated for frequencies in the range of 600 Hz to 4000 Hz, utilizing a small-sized acoustic chamber. Additionally, the sound absorption coefficient for the frequency range of 63 Hz to 4000 Hz was measured according to the EN ISO 354 standard in a laboratory reverberation room. This research was deemed necessary after conducting reverberation time measurements of a university classroom following the EN ISO 3382-2 standard. The measurements indicated values of 2.86 s at 500 Hz, 3.23 s at 1000 Hz, and 2.53 s at 2000 Hz, which significantly exceeded the requirements set by the national regulatory framework (0.6s) for such premises. For this reason, recycled felt panels have been investigated in the laboratory, showing very good acoustic properties at high frequencies. To enhance performance in the low frequencies, the influence of the distance of the panel spacing was examined. Furthermore, the sound insulation of the panels was studied to expand the possibilities of their application, both for the acoustic treatment of educational and multifunctional halls and for sound insulation purposes (e.g., a suspended ceiling with an air gap passing from room to room). As a conclusion, a theoretical acoustic design of the classroom has been carried out with suggestions for improvements to achieve the necessary acoustic and aesthetic parameters for such rooms.

Keywords: acoustic panels, recycled felt, sound absorption, sound insulation, classroom acoustics

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Authors: Anil Khanal, Ali Osareh, Gary Lebby

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Wind energy offers a significant advantage such as no fuel costs and no emissions from generation. However, wind energy sources are variable and non-dispatchable. The utility grid is able to accommodate the variability of wind in smaller proportion along with the daily load. However, at high penetration levels, the variability can severely impact the utility reserve requirements and the cost associated with it. In this paper, the impact of wind energy is evaluated in detail in formulating the total utility cost. The objective is to minimize the overall cost of generation while ensuring the proper management of the load. Overall cost includes the curtailment cost, reserve cost and the reliability cost as well as any other penalty imposed by the regulatory authority. Different levels of wind penetrations are explored and the cost impacts are evaluated. As the penetration level increases significantly, the reliability becomes a critical question to be answered. Here, we increase the penetration from the wind yet keep the reliability factor within the acceptable limit provided by NERC. This paper uses an economic dispatch (ED) model to incorporate wind generation into the power grid. Power system costs are analyzed at various wind penetration levels using Linear Programming. The goal of this study shows how the increases in wind generation will affect power system economics.

Keywords: wind power generation, wind power penetration, cost analysis, economic dispatch (ED) model

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Authors: Kuladip Jana, Bhaswati Banerjee, Parimal C. Sen

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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems along with carcinogenesis in skin, prostate, ovary, lung and mammary glands. Our study was focused on elucidating the molecular mechanism of B(a)P induced male reproductive toxicity and its prevention with phytochemical like resveratrol. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of Wistar rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased Reactive Oxygen Species (ROS), altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38 mitogen activated protein kinase (p38MAPK), cytosolic translocation of cytochrome-c, upregulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of poly ADP ribose polymerase (PARP) and down regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like steroidogenic acute regulatory protein (StAR), cytochrome P450 IIA1 (CYPIIA1), 3β hydroxy steroid dehydrogenase (3β HSD), 17β hydroxy steroid dehydrogenase (17β HSD) showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis. Next we investigated the role of resveratrol on B(a)P induced male reproductive toxicity. Our study highlighted that resveratrol co-treatment with B(a)P maintained testicular redox potential, increased serum testosterone level and prevented steroidogenic dysfunction with enhanced expression of major testicular steroidogenic proteins (CYPIIA1, StAR, 3β HSD,17β HSD) relative to treatment with B(a)P only. Resveratrol suppressed B(a)P-induced testicular activation of p38 MAPK, ATF2, iNOS and ROS production; cytosolic translocation of Cytochome c and Caspase 3 activation thereby prevented oxidative stress of testis and inhibited apoptosis. Resveratrol co-treatment also decreased B(a)P-induced AhR protein level, its nuclear translocation and subsequent CYP1A1 promoter activation, thereby decreased protein and mRNA levels of testicular cytochrome P4501A1 (CYP1A1) and prevented BPDE-DNA adduct formation. Our findings cumulatively suggest that resveratrol prevents activation of B(a)P by modulating the transcriptional regulation of CYP1A1 and acting as an antioxidant thus prevents B(a)P-induced oxidative stress and testicular apoptosis.

Keywords: benzo(a)pyrene, resveratrol, testis, apoptosis, cytochrome P450 1A1 (CYP1A1), aryl hydrocarbon receptor (AhR), p38 MAPK/ATF2/iNOS

Procedia PDF Downloads 226

Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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One of the major interferences in the Philippines’ tuberculosis control program is the widespread prevalence of Mtb strains that are resistant to known drugs, such as the MDR-TB (Multi Drug Resistant Tuberculosis) and XDR-TB (Extensively Drug Resistant Tuberculosis). Therefore, there is a pressing need to search for novel Mtb drug targets in order to be able to combat these drug resistant strains. The enzyme 7,8-diaminopelargonic acid aminotransferase enzyme, or more commonly known as BioA, is one such ideal target, as it is known that humans do not possess this enzyme. BioA primarily plays a key role in Mtb’s lipid biosynthesis pathway; more specifically in the synthesis of the enzyme cofactor biotin. In this study, structure-based pharmacophore screening, docking, and ADMET evaluation of compounds obtained from the DrugBank chemical database were performed against the MtbBioA enzyme. Results of the screening, docking, ADMET, and TOPKAT calculations revealed that out of the 6,516 compounds in the library, only 7 compounds indicated more favorable binding energies as compared to the enzyme’s known inhibitor, amiclenomycin (ACM), as well as good solubility and toxicity properties. Moreover, out of these 7 compounds, Molecule 6 exhibited the best solubility and toxicity properties. In the future, these lead compounds may then be subjected to bioactivity assays in vitro or in vivo for further evaluation of its therapeutic efficacy.

Keywords: 7, 8-diaminopelargonic acid aminotransferase, BioA, pharmacophore, molecular docking, ADMET, TOPKAT

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Authors: Jinesh Kumar Jain, Faishal Pathan

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The concept of sustainable development and effective environmental regulation has led to the emergence of a new field of study and practise that is the Green Supply Chain Management. GSCM has become a subject of great importance for both the developed and developing countries to achieve the desired and much-awaited goals of the firm within the environmental and sustainable framework. Its merits are comprised of good financial pay off and competitiveness to the firms in a long lasting and sustainable manner. The purpose of the paper is to briefly review the recent literature of the GSCM and also determines the new direction area of this emerging field. A detailed study has helped to enlighten the minute details and develop the research direction of the study. The GSCM has gained popularity with both academic and practitioners. The items for the study were developed based on the extent literature. Here we found that the state of adoption of GSCM practices by Indian Firms was still in its infancy, the awareness of environmental sustainability was quite low among consumers and the regulatory frameworks were also lacking in terms promoting environmental sustainability. The present paper is an attempt to emphasize much attention on the above-mentioned issues and present a conclusive summary to make its use widespread and for reaching.

Keywords: environmental management, environmental performance, financial performance, green supply chain management

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Authors: T. Mahesh, M. K. Samanta

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Antibody dug conjugate (ADC’s) concept is a less explored and more trustable for the treatment of Type 1 diabetes (T1D). T1D is thought to arise from selective immunologically mediated destruction of the insulin- producing β-cells in the pancreatic islets of Langerhans with consequent insulin deficiency. It is evident that type 1 diabetes can be conquered, by 1) to stop immune destruction of βcells, 2) to replace or regenerate β-cells, and 3) to preserve β-cell function and mass. Many studies found that the regulatory T cells (Tregs) are crucial for the maintenance of immunological tolerance. Immune tolerance is liable for the activation of the Th1 response. The important role of Th1 response in pathology of T1D entails the depletion of CD4+ T cells, which initiated the use of anti-CD4 monoclonal antibodies (mAbs) against CD4+ T cells to interfere with induction of T1D.Insulin is regulated by Glucagon-Like Peptide-1 hormone (GLP-1) which also stimulates β-cells proliferation as the half-life of GLP-1 harmone is less due to rapid degradation by DPP-IV enzyme an alternative DPP-IV-inhibitors can increase the half-life of GLP-1 through which it conquers the replacement and reserve β-cells mass. Thus in the present study Anti-CD4 mAb was conjugated with Sitagliptin which is a DPP-IV inhibitor Drug loaded in Nanoparticles through Sulfo-MBS cross-linkers. The above study can be an effective approach for treatment to overcome the Passive subcutaneous insulin therapy.

Keywords: antibody drug conjugates, anti-CD4 Mab, DPP IV inhibitors, GLP-1

Procedia PDF Downloads 384