Search results for: toehold mediated DNA switch

Authors: Shanker Kalakotla, Krishna Mohan Gottumukkala

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Diabetes is a metabolic disorder characterized by hyperglycemia, carbohydrates, altered lipids and proteins metabolism. In recent research nanotechnology is a blazing field for the researchers; latterly there has been prodigious excitement in the nanomedicine and nano pharmacological area for the study of silver nanoparticles synthesis using natural products. Biological methods have been used to synthesize silver nanoparticles in presence of medicinally active antidiabetic plants, and this intention made us assess the biologically synthesized silver nanoparticles from the seed extract of Psoralea corylfolia using 1 mM silver nitrate solution. The synthesized herbal mediated silver nanoparticles (HMSNP’s) then subjected to various characterization techniques such as XRD, SEM, EDX, TEM, DLS, UV and FT-IR respectively. In current study, the silver nanoparticles tested for in-vitro anti-diabetic activity and possible toxic effects in healthy female albino mice by following OECD guidelines-425. Herbal mediated silver nanoparticles were successfully obtained from bioreduction of silver nitrate using Psoralea corylifolia plant extract. Silver nanoparticles have been appropriately characterized and confirmed using different types of equipment viz., UV-vis spectroscopy, XRD, FTIR, DLS, SEM and EDX analysis. From the behavioral observations of the study, the female albino mice did not show sedation, respiratory arrest, and convulsions. Test compounds did not cause any mortality at the dose level tested (i.e., 2000 mg/kg body weight) doses till the end of 14 days of observation and were considered safe. It may be concluded that LD50 of the HMSNPs was 2000mg/kg body weight. Since LD50 of the HMSNPs was 2000mg/kg body weight, so the preferred dose range for HMSNPs falls between the levels of 200 and 400 mg/kg. Further In-vivo pharmacological models and biochemical investigations will clearly elucidate the mechanism of action and will be helpful in projecting the currently synthesized silver nanoparticles as a therapeutic target in treating chronic ailments.

Keywords: herbal mediated silver nanoparticles, HMSNPs, toxicity of silver nanoparticles, PTP1B in-vitro anti-diabetic assay female albino mice, 425 OECD guidelines

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Authors: Heiko Jessen, Laura Tanus, Slobodan Ruzicic

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Objectives: The efficacy of Stribild®, an integrase strand transfer inhibitor (INSTI) -based STR, has been evaluated in randomized clinical trials and it has demonstrated durable capability in terms of achieving sustained suppression of HIV-1 RNA-levels. However, differences in monitoring frequency, existing selection bias and profile of patients enrolled in the trials, may all result in divergent efficacy of this regimen in routine clinical settings. The aim of this study was to assess the virologic outcomes, safety and tolerability profile of Stribild® in a routine clinical setting. Methods: This was a retrospective monocentric analysis on HIV-1-infected patients, who started with or were switched to Stribild®. Virological failure (VF) was defined as confirmed HIV-RNA>50 copies/ml. The minimum time of follow-up was 24 weeks. The percentage of patients remaining free of therapeutic failure was estimated using the time-to-loss-of-virologic-response (TLOVR) algorithm, by intent-to-treat analysis. Results: We analyzed the data of 197 patients (56 ART-naïve and 141 treatment-experienced patients), who fulfilled the inclusion criteria. Majority (95.9%) of patients were male. The median time of HIV-infection at baseline was 2 months in treatment-naïve and 70 months in treatment-experienced patients. Median time [IQR] under ART in treatment-experienced patients was 37 months. Among the treatment-experienced patients 27.0% had already been treated with a regimen consisting of two NRTIs and one INSTI, whereas 18.4% of them experienced a VF. The median time [IQR] of virological suppression prior to therapy with Stribild® in the treatment-experienced patients was 10 months [0-27]. At the end of follow-up (median 33 months), 87.3% (95% CI, 83.5-91.2) of treatment-naïve and 80.3% (95% CI, 75.8-84.8) of treatment-experienced patients remained free of therapeutic failure. Considering only treatment-experienced patients with baseline VL<50 copies/ml, 83.0% (95% CI, 78.5-87.5) remained free of therapeutic failure. A total of 17 patients stopped treatment with Stribild®, 5.4% (3/56) of them were treatment-naïve and 9.9% (14/141) were treatment-experienced patients. The Stribild® therapy was discontinued in 2 (1.0%) because of VF, loss to follow-up in 4 (2.0%), and drug-drug interactions in 2 (1.0%) patients. Adverse events were in 7 (3.6%) patients the reason to switch from therapy with Stribild® and further 2 (1.0%) patients decided personally to switch. The most frequently observed adverse events were gastrointestinal side effects (20.0%), headache (8%), rash events (7%) and dizziness (6%). In two patients we observed an emergence of novel resistances in integrase-gene. The N155H evolved in one patient and resulted in VF. In another patient S119R evolved either during or shortly upon switch from therapy with Stribild®. In one further patient with VF two novel mutations in the RT-gene were observed when compared to historical genotypic test result (V106I/M and M184V), whereby it is not clear whether they evolved during or already before the switch to Stribild®. Conclusions: Effectiveness of Stribild® for treatment-naïve patients was consistent with data obtained in clinical trials. The safety and tolerability profile as well as resistance development confirmed clinical efficacy of Stribild® in a daily practice setting.

Keywords: ART, HIV, integrase inhibitor, stribild

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Authors: Priyanka Sharma, Rajeshwar Nath Srivastava

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Hydrogen has a high level of efficacy in suppressing tumour growth. The role of hydrogen in cancer treatment is unclear. This groundbreaking research will focus on the most effective therapeutic approach for osteosarcoma. Recent data reveals that hydrogen, a naturally occurring gaseous chemical, can protect cells from death. However, little is known about the signalling pathways that regulate cardiac cell death and individual apoptosis signalling by H2 and its downstream targets. According to certain research, the anti-tumor effect of H2 released by magnesium-based biomaterials is mediated by the P53-mediated lysosome-mitochondria apoptosis signalling pathway, bolstering the biomaterial's therapeutic potential as a localised anti-tumor treatment. The role of the H2 molecule in the signalling of apoptotic, autophagic, necroptotic, and pyroptotic cell death in Osteosarcoma is discussed in this paper. Potential Hydrogen-based therapy techniques will broaden the treatment horizon for Osteosarcoma.

Keywords: osteosarcoma, metastasis, hhydrogen, therapeutic

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Authors: John Mambambo

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Debates on the link between Bantu languages are often epitomized by animated theoretical critiques, including the language zoning and groupings. This evaluative, qualitative inquiry hovers above theoretical critiques to offer the sparsely studied ChiShona and isiXhosa code-switching nexus, a yawning gap in scholarship. Using interviews, questionnaires and observations, data germane to the study were collected from a purposively selected group of Shona speakers who had resided in Xhosa-speaking communities for not less than a year. Deploying Myers-Scotton’s Markedness theory, the paper gazes into the pragmatic linguistic affinity that is affirmed through the Shona-Xhosa code-switching in Cape Town. The assorted social variables motivating bilingual speakers to code-switch in Cape Town are also explored in this study. The study unveils that Shona speakers are motivated to code-switch by the linguistic affinity between ChiShona and isiXhosa. Other socio-political justifications also give an impetus to this phenomenon. The Matrix Language Frame Model affirms that ChiShona is the base while isiXhosa is the embedded language during code-switching. This paper is a momentous advancement of the extant literature on code-switching. It is a unique contribution to the nexus between ChiShona and isiXhosa languages, providing fresh insights into the discourse on African language comparison studies.

Keywords: code-switching, chishona, isiXhosa, bilingualism

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Authors: R. Furutani, G. Kikuchi

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Generally, the optical interferometer system is too complicated and difficult to change the measurement items, pitch, yaw, and row, etc. In this article, the optical interferometer system using the transmissive Liquid Crystal Device (LCD) as the switch of the optical path was proposed. At first, the normal optical interferometer, Michelson interferometer, was constructed to measure the pitch angle and the yaw angle. In this optical interferometer, the ball lenses with the refractive indices of 2.0 were used as the retroreflectors. After that, the transmissive LCD was introduced as the switch to select the adequate optical path. In this article, these optical systems were constructed. Pitch measurement interferometer and yaw measurement interferometer were switched by the transmissive LCD. When the LCD was open for the yaw measurement, the yaw was sufficiently measured and optical path for the pitch measurement was blocked. On the other hand, when the LCD was open for the pitch measurement, the pitch was measured and the optical path for the yaw measurement was also blocked. In this article, the results of both of pitch measurement and yaw measurement were shown, and the result of blocked yaw measurement and pitch measurement were shown. As this measurement system was based on Michelson interferometer, the other measuring items, the deviation along the optical axis, the vertical deviation to the optical axis and row angle, could be measured by the additional ball lenses and the additional switching in future work.

Keywords: any direction angle, ball lens, laser interferometer, transmissive liquid crystal device

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Authors: M. Rajasekar, K. Suresh

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Diosmin is a flavonoid, most abundantly found in many citrus fruits. As a flavonoid, it possesses a multitude of biological activities including anti-hyperglycemic, anti-lipid peroxidative, anti-inflammatory, antioxidant, and anti-mutagenic properties. At this point, we established the anti-proliferative and apoptosis-inducing activities of diosmin in Hep-2 and KB cells. Diosmin has cytotoxic effects through inhibiting cellular proliferation of Hep-2 and KB cells, which leads to the induction of apoptosis, as apparent by an increase in the fraction of cells in the sub-G1phase of the cell cycle. Results exposed that inhibition of cell proliferation is associated with regulation of the Interleukins/STAT pathway. In addition, Diosmin treatment with Hep-2 and KB cells actively stimulated reactive oxygen species (ROS) and mitochondrial membrane depolarization. And also an imbalance in the Bax/Bcl-2 ratio triggered the caspase cascade and shifting the balance in favor of apoptosis. These observations conclude that Diosmin induce apoptosis via Interleukins /STAT-mediated pathway.

Keywords: diosmin, apoptosis, antioxidant, STAT pathway

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Authors: Eliana Bergamin

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This philosophical inquiry, influenced by the seminal works of Annemarie Mol and Jeannette Pols, critically examines the transformative impact of artificial intelligence (AI) on emotional caregiving practices within virtual healthcare. Rooted in the traditions of philosophy of care, philosophy of emotions, and applied philosophy, this study seeks to unravel nuanced shifts in the moral and emotional fabric of healthcare mediated by AI-powered technologies. Departing from traditional empirical studies, the approach embraces the foundational principles of care ethics and phenomenology, offering a focused exploration of the ethical and existential dimensions of AI-mediated emotional caregiving. At its core, this research addresses the introduction of AI-powered technologies mediating emotional and care practices in the healthcare sector. By drawing on Mol and Pols' insights, the study offers a focused exploration of the ethical and existential dimensions of AI-mediated emotional caregiving. Anchored in ethnographic research within a pioneering private healthcare company in the Netherlands, this critical philosophical inquiry provides a unique lens into the dynamics of AI-mediated emotional practices. The study employs in-depth, semi-structured interviews with virtual caregivers and care receivers alongside ongoing ethnographic observations spanning approximately two and a half months. Delving into the lived experiences of those at the forefront of this technological evolution, the research aims to unravel subtle shifts in the emotional and moral landscape of healthcare, critically examining the implications of AI in reshaping the philosophy of care and human connection in virtual healthcare. Inspired by Mol and Pols' relational approach, the study prioritizes the lived experiences of individuals within the virtual healthcare landscape, offering a deeper understanding of the intertwining of technology, emotions, and the philosophy of care. In the realm of philosophy of care, the research elucidates how virtual tools, particularly those driven by AI, mediate emotions such as empathy, sympathy, and compassion—the bedrock of caregiving. Focusing on emotional nuances, the study contributes to the broader discourse on the ethics of care in the context of technological mediation. In the philosophy of emotions, the investigation examines how the introduction of AI alters the phenomenology of emotional experiences in caregiving. Exploring the interplay between human emotions and machine-mediated interactions, the nuanced analysis discerns implications for both caregivers and caretakers, contributing to the evolving understanding of emotional practices in a technologically mediated healthcare environment. Within applied philosophy, the study transcends empirical observations, positioning itself as a reflective exploration of the moral implications of AI in healthcare. The findings are intended to inform ethical considerations and policy formulations, bridging the gap between technological advancements and the enduring values of caregiving. In conclusion, this focused philosophical inquiry aims to provide a foundational understanding of the evolving landscape of virtual healthcare, drawing on the works of Mol and Pols to illuminate the essence of human connection, care, and empathy amid technological advancements.

Keywords: applied philosophy, artificial intelligence, healthcare, philosophy of care, philosophy of emotions

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Authors: Siddiq Ahmed

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The current study aimed to investigate the effectiveness of a Peer-Mediated Intervention (PMI) on writing skills for a student with autism spectrum disorders in inclusive classrooms. The participants in this study were two students, one as a tutor and another as a tutee who was diagnosed with autism spectrum disorder (ASD). The target participant struggled with writing skills and was paired with a student with high academic outcomes. The Tutor had a readiness to act as a tutor for his peer and was trained on how to assist his peer and how to identify and guide his peer’s writing mistakes. Multiple baseline design across behaviors was implemented to monitor the student’s progress in writing skills. The results of the present study showed that PMI yielded significant improvements in academic achievements for the target student. This study suggests that further studies should replicate the current study with an intensive focus on other academic skills such as reading comprehension, writing social stories, and math.

Keywords: peer tutoring, writing skills, autism, inclusion

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Authors: James P. Takona

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Most of the global population has never lived through a pandemic, and thus there is so much that remains unknown about students' capacity for resiliency under such environments and circumstances and what a timeline for full recovery will look like. The session will guide participants to focus on misinformation and disinformation in the context of recent crisis events, with specific reference to how information flows across. Particular focus will be given to the flow of information in mediated technology and platforms with particular reference to K-12 and teacher preparation program environments. The paper will draw on theories and responses from the sociology of disaster, the social psychology of rumoring, and published studies on disinformation and misinformation. Applications will be identified and applied in the context of online information-sharing during crisis events. The session will offer the application of the Center for Contagious Diseases' Crisis and Emergency Risk Communication model to understand the themes and evolution of misinformation and disinformation. The paper will invite session participants to suggest and interact with raised challenges on the impact of dis-and misinformation.

Keywords: Sociology of disaster, misinformation, dis-information, Social Psychology of rumors

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Authors: Verd Shomrom, Gilat Trabelsi

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The goal of the study was to examine the effects of Computerized Cognitive Training (CCT) with and without cognitive mediation on Executive Function (EF) (planning and self- regulation) and on psychological resiliency among adolescents with Attention Deficits Hyperactive Disorder (ADHD) with or without Learning Disabilities (LD). Adolescents diagnosed with Attention Deficit Disorder and / or Learning Disabilities have multidimensional impairments that result from neurological damage. This work explored the possibility of influencing cognitive aspects in the field of Executive Functions (specifically: patterns of planning and self-regulation) among adolescents with a diagnosis of Attention Deficit Disorder and / or Learning Disabilities who study for a 10-12 grades. 46 adolescents with ADHD and/or with LD were randomly applied to experimental and control groups. All the participants were tested (BRC- research version, Resiliency quaternaries) before and after the intervention: mediated/ non-mediated Computerized Cognitive Training (MINDRI). The results indicated significant effects of cognitive modification in the experimental group, between pre and post Phases, in comparison to control group, especially in self- regulation (BRC- research version, Resiliency quaternaries), and on process analysis of Computerized Cognitive Training (MINDRI). The main conclusion was that even short- term mediation synchronized with CCT could greatly enhance the performance of executive functions demands. Theoretical implications for the positive effects of MLE in combination with CCT indicate the ability for cognitive change. The practical implication is the awareness and understanding of efficient intervention processes to enhance EF, learning awareness, resiliency and self-esteem of adolescents in their academic and daily routine.

Keywords: attention deficits hyperactive disorder, computerized cognitive training, executive function, mediated learning experience, learning disabilities

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Authors: Jinyoung Park, Eun Joo Song

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Introduction: Deubiquitinating enzymes (DUBs) are proteases that cleave ubiquitin or ubiquitin-like modifications on substrates. Deubiquitination could regulate cellular physiology, such as signal transduction, DNA damage and repair, and cell cycle progression. Although more than 100 DUBs are encoded in the human and the importance of DUBs has been realized, the functions of most DUBs are unknown. This study aims to identify the molecular mechanism by which deubiquitinating enzyme USP35 regulates cell cycle progression for the first time. Methods: USP35 RNAi was mainly used to identify the function of USP35 in cell cycle progression. To find substrates of USP35, we analyzed protein-protein interaction using LC-MS. Several biological methods, such as ubiquitination assay, cell synchronization, immunofluorescence, and immunoprecipitation assay were used to investigate the exact mechanism by which USP35 affects successful completion of mitosis. Results: USP35 knockdown caused not only reduction of mitotic cell number but also induction of mitotic cells with abnormal spindle formation. Actually, cell proliferation was decreased by USP35 knockdown. Interestingly, we found that loss of USP35 decreased the stability and expression of Aurora B, a member of chromosomal passenger complex (CPC), and the phosphorylation of its substrate. Indeed, USP35 interacted with Aurora B and deubiquitinated it. In addition, USP35 knockdown induced abnormal localization of Aurora B in mitotic cells. Finally, CDH1-mediated ubiquitination of Aurora B level was rescued by USP35 overexpression, but not inactive form of USP35, USP35 C450A. Discussion: Our findings suggest that USP35 regulates Aurora B-mediated mitotic spindle assembly and G2-M transition by blocking CDH1-induced degradation of Aurora B.

Keywords: USP35, HSP90, Aurora B, cell cycle progression

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Authors: Abdul Rashid Ahmadi, Samiullah Paracha, Hamidullah Sokout, Mohammad Hanif Gharana

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Conventional educational practices, do not offer all the required skills for teachers to successfully survive in today’s workplace. Due to poor professional training, a big gap exists across the curriculum plan and the teacher practices in the classroom. As such, raising the quality of teaching through ICT-enabled training and professional development of teachers should be an urgent priority. ‘Mobile Learning’, in that vein, is an increasingly growing field of educational research and practice across schools and work places. In this paper, we propose a novel Mobile learning system that allows the users to learn through an intelligent mobile learning in cooperatively every-time and every-where. The system will reduce the training cost and increase consistency, efficiency, and data reliability. To establish that our system will display neither functional nor performance failure, the evaluation strategy is based on formal observation of users interacting with system followed by questionnaires and structured interviews.

Keywords: computer assisted learning, intelligent tutoring system, learner centered design, mobile mediated learning and teacher education

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Authors: Paul Narh Doku

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The relationship between parental HIV/AIDS status or death and child mental health is well known, although the role of child maltreatment as a confounder or mediator in this relationship remains uncertain. This study examined the potential path mechanism through child maltreatment mediating the link between HIV/AIDS family dysfunction trajectories and psychosocial problems. A cross-sectional survey was conducted in the Lower Manya Municipal Assembly of Ghana. A questionnaire which consisted of the Strengths and Difficulties Questionnaire (SDQ), Social and Health Assessment (SAHA), Rosenberg Self-Esteem Scale (RSES), and the Conflict Tactics Scale (CTS) was completed by 291 adolescents. Controlling for relevant sociodemographic confounders, mediation analyses using linear regression were fitted to examine whether the association between family dysfunction and psychosocial problems is mediated by child maltreatment. The results indicate that, among adolescents, child maltreatment fully mediated the association between being orphaned by AIDS and self-esteem, delinquency and risky behaviours, and peer problems. Similarly, child maltreatment fully mediated the association between living with an HIV/AIDS-infected parent and self-esteem, delinquency and risky behaviours, depression/emotional problems, and peer problems. Partial mediation was found for hyperactivity. Child maltreatment mediates the association between the family dysfunction trajectories of parental HIV/AIDS or death and psychosocial problems among adolescents. This implies that efforts to address child maltreatment among families affected by HIV/AIDS may be helpful in the prevention of psychosocial problems among these children, thus enhancing their well-being. The findings, therefore, underscore the need for comprehensive psychosocial interventions that address both the unique negative exposures of HIV/AIDS and maltreatment for children affected by HIV.

Keywords: child maltreatment, child abuse, mental health, psychosocial problems, domestic violence, HIV/AIDS, adolescents

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Authors: Qiaoyue Kuang, Yang Li, Mizuki Endo, Takeaki Ozawa

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G protein-coupled receptors (GPCR) are the largest family of receptor proteins that detect molecules outside the cell and activate cellular responses. Of the GPCRs, dopamine receptors, which recognize extracellular dopamine, are essential to mammals due to their roles in numerous physiological events, including autonomic movement, hormonal regulation, emotions, and the reward system in the brain. To precisely understand the physiological roles of dopamine receptors, it is important to spatiotemporally control the signaling mediated by dopamine receptors, which is strongly dependent on their surface expression. Conventionally, chemical-induced interactions were applied to trigger the endocytosis of cell surface receptors. However, these methods were subjected to diffusion and therefore lacked temporal and special precision. To further understand the receptor-mediated signaling and to control the plasma membrane expression of receptors, an optogenetic tool called E-fragment was developed. The C-terminus of a light-sensitive photosensory protein cyptochrome2 (CRY2) was attached to β-Arrestin, and the E-fragment was generated by fusing the C-terminal peptide of vasopressin receptor (V2R) to CRY2’s binding partner protein CIB. The CRY2-CIB heterodimerization triggered by blue light stimulation brings β-Arrestin to the vicinity of membrane receptors and results in receptor endocytosis. In this study, the E-fragment system was applied to dopamine receptors 1 and 2 (DRD1 and DRD2) to control dopamine signaling. First, confocal fluorescence microscope observation qualitatively confirmed the light-induced endocytosis of E-fragment fused receptors. Second, NanoBiT bioluminescence assay verified quantitatively that the surface amount of E-fragment labeled receptors decreased after light treatment. Finally, GloSensor bioluminescence assay results suggested that the E-fragment-dependent receptor light-induced endocytosis decreased cAMP production in DRD1 signaling and attenuated the inhibition effect of DRD2 on cAMP production. The developed optogenetic tool was able to induce receptor endocytosis by external light, providing opportunities to further understand numerous physiological activities by controlling receptor-mediated signaling spatiotemporally.

Keywords: dopamine receptors, endocytosis, G protein-coupled receptors, optogenetics

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Authors: Soheil Zorofchian Moghadamtousi, Habsah Abdul Kadir, Mohammadjavad Paydar, Elham Rouhollahi, Hamed Karimian

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The present study was designed to evaluate the molecular mechanisms of Annona muricata leaves ethyl acetate extract (AMEAE) against lung cancer A549 cells. Cell viability analysis revealed the selective cytotoxic effect of AMEAE towards A549 cells. Treatment of A549 cells with AMEAE significantly elevated the reactive oxygen species formation, followed by attenuation of mitochondrial membrane potential via upregulation of Bax and downregulation of Bcl-2, accompanied by cytochrome c release to the cytosol. The released cytochrome c triggered the activation of caspase-9 followed by caspase-3. In addition, AMEAE-induced apoptosis was accompanied by cell cycle arrest at G1 phase. Our data showed for the first time that AMEAE inhibited the proliferation of A549 cells, leading to cell cycle arrest and programmed cell death through activation of the mitochondrial-mediated signaling pathway.

Keywords: Annona muricata, lung cancer, apoptosis, mitochondria

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Authors: Hsiao-Chien Tsai, Yu-Pin Chen, Ruei-Ming Chen

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Introduction: Osteoarthritis (OA) is characterized by joint destruction and causes chronic disability. One of the prominent symptoms is pain. Alleviating the pain is necessary and urgent for the therapy of OA patients. However, currently, understanding the mechanisms that drive OA-induced pain remains challenging, which hampers the optimistic management of pain in OA patients. Semaphorin 4D (Sema4D) participates in axon guidance pathway and bone remodeling, thus, may play a role in the regulation of pain in OA. In this study, we have established a rat model of OA to find out the mechanisms of OA-induced pain and to deliberate the roles of Sema4D. Methods: Behavioral changes and the pro-inflammatory cytokines (IL-1β, TNF-α, and IL-17) associated with pain were measured during the development of OA. Sema4D expression in cartilage and synovial membrane at 1, 4, and 12 weeks after inducing OA was analyzed. To assess if Sema4D is related to the neurogenesis in OA as an axon repellant, we analyzed the expression of PGP9.5 as well. Results: Synovitis and cartilage degradation were evident histologically during the development of OA. Mechanical hyperalgesia was most severe at week 1, then persisted thereafter. It was associated with stress coping strategies. Similar to the pain behavioral results, levels of IL-1β and TNF-α in synovial lavage fluid were significantly elevated in the OA group at weeks 1 and 4, respectively. Sema4D expression in cartilage and the synovial membrane was also enhanced in the OA group and was correlated with pain and pro-inflammatory cytokines. The marker of neurogenesis, PGP9.5, was also enhanced during the development of OA. Discussion: OA induced mechanical hyperalgesia, which might be through upregulating IL-1β/TNF-α-mediated Sema4D expressions. If anti-Sema4D treatment could reduce OA-induced mechanical hyperalgesia and prevent the subsequent progression of OA needs to be further investigated. Significance: OA can induce mechanical hyperalgesia through upregulation of IL-1β/TNF-α-mediated Sema4D and PGP9.5 expressions. And the upregulation of Sema4D may indicate the severity or active status of OA and OA-induced pain.

Keywords: traumatic osteoarthritis, mechanical hyperalgesia, Sema4D, inflammatory cytokines

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Authors: Raj Raghupathy

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Recurrent Spontaneous Miscarriage (RSM) is a common form of pregnancy loss, 50% of which are due to ‘unexplained’ causes. Evidence exists to suggest that RSM may be caused by immunologic factors such as cytokines which are critical molecules of the immune system, with an impressive array of capabilities. An association appears to exist between Th2-type reactivity (mediated by Th2 or anti-inflammatory cytokines) and normal, successful pregnancy, and between unexplained RSM and Th1 cytokine dominance. If pro-inflammatory cytokines are indeed associated with pregnancy loss, the suppression of these cytokines, and thus the ‘redirection’ of maternal reactivity, may help prevent cytokine-mediated pregnancy loss. The objective of this study was to explore the possibility of modulating cytokine production using Dydrogesterone (Duphaston®), an orally-administered progestogen. Peripheral blood mononuclear cells from 34 women with a history of at least 3 unexplained recurrent miscarriages were stimulated in vitro with a mitogen (to elicit cytokine production) in the presence and absence of dydrogesterone. Levels of selected pro- and anti-inflammatory cytokines produced by peripheral blood mononuclear cells were measured after exposure to these progestogens. Dydrogesterone down-regulates the production of pro-inflammatory cytokines and up-regulates the production of anti-inflammatory cytokines. The ratios of Th2 to Th1 cytokines are markedly elevated in the presence of dydrogesterone, indicating a shift from potentially harmful maternal Th1 reactivity to a more pregnancy-conducive Th2 profile. We used a progesterone receptor antagonist to show that this cytokine-modulating effect of dydrogesterone is mediated via the progesterone receptor. Dydrogesterone also induces the production of the Progesterone-Induced Blocking Factor (PIBF); lymphocytes exposed to PIBF produce higher levels of Th2 cytokines, affecting a Th1 → Th2 cytokine shift which could be favourable to the success of pregnancy. We conclude that modulation of maternal cytokine production profiles is possible with dydrogesterone which has the merits that it can be administered orally and that it is safe.

Keywords: cytokines, dydrogesterone, progesterone, recurrent spontaneous miscarriage

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Authors: Sungeun Hyun, Sooin Lee, Gyewan Moon

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Work-Family Conflict has been an active research area for the past decades. Work-Family Conflict harms individuals and organizations, it is ultimately expected to bring the cost of losses to the company in the long run. WFC has mainly focused on effects of organizational effectiveness and job attitude such as Job Satisfaction, Organizational Commitment, and Turnover Intention variables. This study is different from consequence variable with previous research. For this purpose, we selected the positive job attitude 'Work Engagement' as a consequence of WFC. This research has its primary research purpose in identifying the negative effects of the Work-Family Conflict, and started out from the recognition of the problem that the research on the direct relationship on the influence of the WFC on Work Engagement is lacking. Based on the COR(Conservation of resource theory) and JD-R(Job Demand- Resource model), the empirical study model to examine the negative effects of WFC with Emotional Exhaustion as the link between WFC and Work Engagement was suggested and validated. Also, it was analyzed how much Positive Psychological Capital may buffer the negative effects arising from WFC within this relationship, and the Mediated Moderation model controlling the indirect effect influencing the Work Engagement by the Positive Psychological Capital mediated by the WFC and Emotional Exhaustion was verified. Data was collected by using questionnaires distributed to 500 employees engaged manufacturing, services, finance, IT industry, education services, and other sectors, of which 389 were used in the statistical analysis. The data are analyzed by statistical package, SPSS 21.0, SPSS macro and AMOS 21.0. The hierarchical regression analysis, SPSS PROCESS macro and Bootstrapping method for hypothesis testing were conducted. Results showed that all hypotheses are supported. First, WFC showed a negative effect on Work Engagement. Specifically, WIF appeared to be on more negative effects than FIW. Second, Emotional exhaustion found to mediate the relationship between WFC and Work Engagement. Third, Positive Psychological Capital showed to moderate the relationship between WFC and Emotional Exhaustion. Fourth, the effect of mediated moderation through the integration verification, Positive Psychological Capital demonstrated to buffer the relationship among WFC, Emotional Exhastion, and Work Engagement. Also, WIF showed a more negative effects than FIW through verification of all hypotheses. Finally, we discussed the theoretical and practical implications on research and management of the WFC, and proposed limitations and future research directions of research.

Keywords: emotional exhaustion, positive psychological capital, work engagement, work-family conflict

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Authors: Busra Nur Ozguler Aktel

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This research aims to understand the factors that affect the ways in which tribes perceive and respond to violent conflicts in fragile states, given that tribes are essential stakeholders in many conflict-ridden fragile states, whether Afghanistan, Iraq, Syria, Libya, Somalia, Nigeria, or Yemen. It explores the primary questions of why some tribes align with extremist groups while others align with states during civil wars and why some tribes switch alignments. It argues that tribes form and switch alignments based on their perception of threats to their traditional tribal structure (internal dynamics) and clientelist relationships (external dynamics). Put differently; threat perceptions lead them to choose either the state or extremist groups that will more likely secure their traditional structure and patronage networks. This study focuses on Iraqi tribes as a case study. It builds a theory of tribal alignment formation based on ethnographic fieldwork in the Middle East, with a particular focus on Iraqi Sunni tribes living in the Kurdish region of Iraq and Jordan. As a result of the interviews with tribal leaders and members, local journalists, researchers, and politicians, it concludes that complex (re)alignments of tribes can determine the course and outcome of the conflicts, either mitigating or escalating violence. This study contributes to the larger body of conflict management and peacebuilding literature by introducing tribes as non-state actors and exploring their interactions with other actors in civil wars.

Keywords: civil wars, tribes, alignment formation, side-switching, Iraq

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Authors: Akshay Patil

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Objective: Mediation analysis identifies causal pathways by testing the relationships between the NCR, the OS, and an intermediate variable that mediates the relationship between the Nimotuzumab-cisplatin-radiation (NCR) and OS. Introduction: In randomized controlled trials, the primary interest is in the mechanisms by which an intervention exerts its effects on the outcomes. Clinicians are often interested in how the intervention works (or why it does not work) through hypothesized causal mechanisms. In this work, we highlight the value of understanding causal mechanisms in randomized trial by applying causal mediation analysis in a randomized trial in oncology. Methods: Data was obtained from a phase III randomized trial (Subgroup of HPVNOCP). NCR is reported to significantly improve the OS of patients locally advanced head and neck cancer patients undergoing definitive chemoradiation. Here, based on trial data, the mediating effect of NCR on patient overall survival was systematically quantified through progression-free survival(PFS), disease free survival (DFS), Loco-regional failure (LRF), and the disease control rate (DCR), Overall response rate (ORR). Effects of potential mediators on the HR for OS with NCR versus cisplatin-radiation (CR) were analyzed by Cox regression models. Statistical analyses were performed using R software Version 3.6.3 (The R Foundation for Statistical Computing) Results: Effects of potential mediator PFS was an association between NCR treatment and OS, with an indirect-effect (IE) 0.76(0.62 – 0.95), which mediated 60.69% of the treatment effect. Taking into account baseline confounders, the overall adjusted hazard ratio of death was 0.64 (95% CI: 0.43 – 0.96; P=0.03). The DFS was also a significant mediator and had an IE 0.77 (95% CI; 0.62-0.93), 58% mediated). Smaller mediation effects (maximum 27%) were observed for LRF with IE 0.88(0.74 – 1.06). Both DCR and ORR mediated 10% and 15%, respectively, of the effect of NCR vs. CR on the OS with IE 0.65 (95% CI; 0.81 – 1.08) and 0.94(95% CI; 0.79 – 1.04). Conclusion: Our findings suggest that PFS and DFS were the most important mediators of the OS with nimotuzumab to weekly cisplatin-radiation in HPVNOCP.

Keywords: mediation analysis, cancer data, survival, NCR, HPV negative oropharyngeal

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Authors: Samar Mohamed Magdy Abdelrahim

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This study is an attempt to investigate the phenomenon of code-switching that takes place between Arabic and English in social discourse among high, well-educated, and young people in Egypt. The study aims at digging deeper to extract the trigger factors of such occurrences, namely when people encounter embarrassing situations in their daily conversations. Nowadays, most young Egyptians tend to use English words in certain situations that might make them feel embarrassed. To disguise their feelings and soften the impact of these words in the context, they code-switch (CS) from Arabic into English. To obtain accurate results, the study utilized a quantitative analysis approach that combines personal observations and a questionnaire to examine the phenomenon appropriately. The questionnaire was designed to categorize different types of embarrassing topics to be evaluated by participants. These topics include certain parts of the human body, types of clothes, taboo words, and specific medical conditions. Many studies have examined the use of CS as a prestigious way of communicating and expressing solidarity between Arabic and English. Other studies have dealt with switches that take place in classrooms. However, not many studies have paid attention to this angle of CS, especially in Egypt. The results conclude that gender and the circumstances that surround the conversation are essential factors of CS since females tend to switch codes more than males in embarrassing situations. According to the study, CS serves the socio-pragmatic function in terms of helping young, well-educated bilinguals express themselves in a second language that would be distressing in the first.

Keywords: code-switching, embarrassment, Arabic, English

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Authors: Hongping Lu, Kelbinur Tursun, Yaru Li, Yu Zhang, Shunai Liu, Ming Han

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Objective: To investigate whether NS5ATP9 is involved in IL-6 mediated autophagy and the relationship between IL-6 and NS5ATP9 in liver cancer cells. Methods: 1. Detect the mRNA and protein levels of Beclin 1 after HepG2 cells were treated with or without recombinant human IL-6 protein. 2. Measure and compare of the changes of autophagy-related genes with their respective control, after IL-6 was silenced or neutralized with monoclonal antibody against human IL-6. 3. HepG2 cells were incubated with 50 ng/ml of IL-6 in the presence or absence of PDTC. The expression of NS5ATP9 was analyzed by Western blot after 48 h. 4. After NS5ATP9-silenced HepG2 cells had been treated with 50 ng/ml recombinant IL-6 protein, we detected the Beclin 1 and LC3B (LC3Ⅱ/Ⅰ) expression. 5. HepG2 cells were transfected with pNS5ATP9, si-NS5ATP9, and their respective control. Total RNA was isolated from cells and analyzed for IL-6. 6. Silence or neutralization of IL-6 in HepG2 cells which has been transfected with NS5ATP9. Beclin 1 and LC3 protein levels were analyzed by Western blot. Result: 1. After HepG2 were treated with recombinant human IL-6 protein, the expression of endogenous Beclin 1 was up-regulated at mRNA and protein level, and the conversion of endogenous LC3-I to LC3-II was also increased. These results indicated that IL-6 could induce autophagy. 2. When HepG2 cells were treated with IL-6 siRNA or monoclonal antibody against human IL-6, the expression of autophagy-related genes were decreased. 3. Exogenous human IL-6 recombinant protein up-regulated NS5ATP9 via NF-κB activation. 4. The expression of Beclin 1 and LC3B was down-regulated after IL-6 treated NS5ATP9-silenced HepG2 cells. 5. NS5ATP9 could reverse regulates IL-6 expression in HepG2 cells. 6. Silence or neutralization of IL-6 attenuates NS5ATP9-induced autophagy slightly. Conclusion: Our results implied that in HCC patients, maybe the higher level of IL-6 in the serum promoted the expression of NS5ATP9 and induced autophagy in cancer cells. And the over-expression of NS5ATP9 which induced by IL-6, in turn, increased IL-6 expression, further, promotes the IL-6/NS5ATP9-mediated autophagy and affects the progression of tumor. Therefore, NS5ATP9 silence might be a potential target for HCC therapy.

Keywords: autophagy, Hepatocellular carcinoma, IL-6, microenvironment, NS5ATP9

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Authors: Ola Hafez

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This study examines the way selected Egyptian digitally mediated memes utilize intertextuality as a means of expression. It is motivated by the emerging digital socio-political humorous practice using various forms of political commentary in Egyptian social media. One of these forms involves the use of memes incorporating (often doctored) video frames taken from Egyptian plays, films and songs, and relocated in a different socio-political context, often with a caption that re-appropriates the frame for the purpose of critical commentary, thus juxtaposing the socio-political phenomena being addressed and the Egyptian artistic and cultural heritage. The paper presents a discourse study of a convenience sample of a recent social media campaign and carries out two levels of analysis. At the micro level, the study pinpoints the various modes of intertextuality employed, including verbal as well as visual intertextuality in the light of the work of social semiotics by Kress and van Leeuwen. At the macro level, the paper sheds light on the socio-political implications of such practice in the light of Political Discourse Analysis.

Keywords: digitally mediated discourse, discourse analysis, Egyptian Arabic, intertextuality, memes, multimodality, political discourse analysis

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Authors: Satya Eswari Jujjavarapu, Swasti Dhagat, Lata Upadhyay, Reecha Sahu

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Silver nanoparticles have a broad range of antimicrobial and antifungal properties ranging from soaps, pastes to sterilization and drug delivery systems. These can be synthesized by physical, chemical and biological methods; biological methods being the most popular owing to their non-toxic nature and reduced energy requirements. Microbial surfactants, produced on the microbial cell surface or excreted extracellularly are an alternative to synthetic surfactants for the production of silver nanoparticles. Hence, they are also called as green molecules. Microbial lipopeptide surfactants (biosurfactant) exhibit anti-tumor and anti-microbial properties and can be used as drug delivery agents. In this study, biosurfactant was synthesized by using a strain of acillus subtilis. The biosurfactant thus produced was analysed by emulsification assay, oil spilling test, and haemolytic test. Biosurfactant-mediated silver nanoparticles were synthesised by microwave irradiation of the culture supernatant and further characterized by UV–vis spectroscopy for a range of 400-600 nm. The UV–vis spectra showed a surface plasmon resonance vibration band at 410 nm corresponding to the peak of silver nanoparticles.

Keywords: biosurfactant, Bacillus subtilis, silver nano particle, lipopeptide

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Authors: Salvador Treviño-Martinez, Christian Reich-Lopez

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This paper investigates the relationship between website appeal and brand value outcomes (brand attraction, brand loyalty, brand relationship, and brand experience), considering the mediating effect of emotional attractiveness. Data were collected from 221 customers of a quick-service restaurant in Culiacan, Mexico, using an online survey distributed via WhatsApp, following the clients' navigation of the restaurant's website. The study employed PLS-SEM to test the proposed hypotheses and performed 5,000 bootstrapping subsamples to obtain results. The findings indicate that consistent image, a key component of website appeal, has a statistically significant direct and mediated effect (through emotional attractiveness) on the aforementioned brand outcomes. The study's limitations include the convenience sampling method and the single company client database used for the sample composition. This research contributes to the branding and website quality literature by testing nine hypotheses using the Stimuli-Organism-Response theoretical approach in an underexplored context: quick-service restaurants in Latin America.

Keywords: website appeal, branding, emotional attractiveness, consistent image, website quality

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Authors: O. S. Ebrahim, K. O. Shawky, M. O. S. Ebrahim, P. K. Jain

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Induction Motor (IM) driving pump is the main consumer of electricity in a typical fluid transportation system (FTS). It was illustrated that changing the connection of the stator windings from delta to star at no load could achieve noticeable active and reactive energy savings. This paper proposes a supervisory hysteresis liquid-level control with three-state energy saving mode (ESM) for IM in FTS including storage tank. The IM pump drive comprises modified star/delta switch and hydromantic coupler. Three-state ESM is defined, along with the normal running, and named analog to computer ESMs as follows: Sleeping mode in which the motor runs at no load with delta stator connection, hibernate mode in which the motor runs at no load with a star connection, and motor shutdown is the third energy saver mode. A logic flow-chart is synthesized to select the motor state at no-load for best energetic cost reduction, considering the motor thermal capacity used. An artificial neural network (ANN) state estimator, based on the recurrent architecture, is constructed and learned in order to provide fault-tolerant capability for the supervisory controller. Sequential test of Wald is used for sensor fault detection. Theoretical analysis, preliminary experimental testing and, computer simulations are performed to show the effectiveness of the proposed control in terms of reliability, power quality and energy/coenergy cost reduction with the suggestion of power factor correction.

Keywords: ANN, ESM, IM, star/delta switch, supervisory control, FT, reliability, power quality

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Authors: Madhu Patial, Dharam Pal, Jagdish Kumar, H. K. Chaudhary

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Doubled haploid breeding serves as a useful technique in wheat improvement by providing instant and complete homozygosity. Of the various techniques employed for haploid production chromosome elimination has a large scale practical application in wheat improvement. Barclay (1975) initiated the technique in wheat by crossing wheat variety Chinese spring with Hordeum bulbosum, but due to presence of the dominant crossability inhibitor genes Kr7 and Kr2 in many wheat varieties, the technique was however genotypic specific. The discovery of wheat X maize system of haploid production being genotype non-specific is quite successful but still maize needs to be grown in greenhouse to coincide flowering with wheat crop. Recently, wheat X Imperate cylindrica has been identified as a new chromosome mediated DH approach for efficient haploid induction. An experiment to use this technique in wheat was set up by crossing six F1s and two three way F1s with Imperata cylindrica. The data was recorded for the three component traits of haploid induction viz., seed formation, embryo formation and regeneration frequency. Variation among wheat F1s was observed and higher frequency for all the traits were recorded in cross HD 2997/2*FL-8/DONSK-POLL and KLE/BER/2*FL-8/DONSK-POLL.

Keywords: wheat, haploid, imperata cylindrica, chromosome elimination technique

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Authors: Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Yung Hyun Choi, Gi-Young Kim

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Camptothecin (CPT) is a quinolone alkaloid which inhibits DNA topoisomerase I that induces cytotoxicity in a variety of cancer cell lines. We previously showed that CPT effectively inhibited invasion of prostate cancer cells and also combined treatment with subtoxic doses of CPT and TNF-related apoptosis-inducing ligand (TRAIL) potentially enhanced apoptosis in a caspase-dependent manner in hepatoma cancer cells. Here, we found that treatment with CPT caused an irreversible cell cycle arrest in the G2/M phase. CPT-induced cell cycle arrest was associated with a decrease in protein levels of cell division cycle 25C (Cdc25C) and increased the level of cyclin B and p21. The CPT-induced decrease in Cdc25C was blocked in the presence of proteasome inhibitor MG132, thus reversed the cell cycle arrest. In addition to that treatment of CPT-increased phosphorylation of Cdc25C was the resulted of activation of checkpoint kinase 2 (Chk2), which was associated with phosphorylation of ataxia telangiectasia-mutated. Interestingly CPT induced G2/M phase of the cell cycle arrest is reactive oxygen species (ROS) dependent where ROS inhibitors NAC and GSH reversed the CPT-induced cell cycle arrest. These results further confirm by using transient knockdown of nuclear factor-erythroid 2-related factor 2 (Nrf2) since it regulates the production of ROS. Our data reveal that treatment of siNrf2 increased the ROS level as well as further increased the CPT induce G2/M phase cell cycle arrest. Our data also indicate CPT-enhanced cell cycle arrest through the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) pathway. Inhibitors of ERK and JNK more decreased the Cdc25C expression and protein expression of p21 and cyclin B. These findings indicate that Chk2-mediated phosphorylation of Cdc25C plays a major role in G2/M arrest by CPT.

Keywords: camptothecin, cell cycle, checkpoint kinase 2, nuclear factor-erythroid 2-related factor 2, reactive oxygen species

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Authors: Ejoke U. P., Smitha Dev., Madwuke Ann, DuPlessis E. D.

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The study examines the relationship between psychological capital (PsyCap) and social well-being among international faculty members in the United Arab Emirates (UAE). The UAE has become a significant destination for global academic talent, yet challenges related to social integration, acceptance, and overall well-being persist among its international faculty. The study focuses on the predictive role of PsyCap, encompassing hope, efficacy, resilience, and optimism, in determining various dimensions of social well-being, including social integration, acceptance, contribution, actualization, and coherence. Additionally, the research investigates the potential moderating or mediating effects of institutional support and Faculty Job-Status position on the relationship between PsyCap and social well-being. Through structural equation modeling, we found that institutional support mediated the positive relationship between PsyCap and SWB and the permanent Faculty job-status position type strengthens the relationship between PsyCap and SWB. Our findings uncover the pathways through which PsyCap influences the social well-being outcomes of international faculty in the UAE. The findings will contribute to the development of tailored interventions and support systems aimed at enhancing the integration experiences and overall well-being of international faculty within the UAE academic community. Thus, fostering a more inclusive and thriving academic environment in the UAE.

Keywords: faculty job-status, institutional-faculty, psychological capital, social well-being, UAE

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Authors: Qazi Mohammed Ahmed, Osman Sadiq Paracha, Iftikhar Hussain

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The study aims to explore the unaddressed relationship between social capital and consumers’ underlying behavioral intentions. The study postulates that this association is mediated by the role of attitudes and peer influence. The research attains evidence from a usable sample of 673 responses. The majority consists of the young and energetic social media users of Pakistan that utilize virtual communities as a way of life. A variance based structural equation modeling has been applied through SmartPLS 3. The results reveal that social capital exerts a statistically supportive association with both attitudes and peer influence. Contrastingly, this predictor variable shows an insignificant linkage with behavioral intentions but this relationship is fully mediated by consumer attitudes and peer influence. The paper enhances marketing literature with respect to an unexplored society of Pakistan. It also provides a lens for the contemporary advertisers, in terms of supporting their social media campaigns with affiliative and cohesive elements. The study also identifies a series of predictor variables that could further be tested with attitudes, subjective norms and behavioral responses.

Keywords: social capital, consumer attitudes, peer influence, behavioral intentions

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