Search results for: Osiris Terry

Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

Abstract:

Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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Authors: Agatha Bebbington, Terry Tetley, Kathryn Hadler

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Background: Astronauts will set foot on the Moon later this decade, and are at high risk of lunar dust inhalation. Freshly-fractured lunar dust produces reactive oxygen species in solution, which are known to cause cellular damage and inflammation. Cytotoxicity and inflammatory mediator release was measured in pulmonary alveolar epithelial cells (cells that line the gas-exchange zone of the lung) exposed to a lunar dust simulant, LMS-1. It was hypothesised that freshly-fractured LMS-1 would result in increased cytotoxicity and inflammatory mediator release, owing to the angular morphology and high reactivity of fractured particles. Methods: A human alveolar epithelial type 1-like cell line (TT1) and a human macrophage-like cell line (THP-1) were exposed to 0-200μg/ml of unground, aged-ground, and freshly-ground LMS-1 (screened at <22μm). Cell viability, cytotoxicity, and inflammatory mediator release (IL-6, IL-8) were assessed using MMT, LDH, and ELISA assays, respectively. LMS-1 particles were characterised for their size, surface area, and morphology before and after grinding. Results: Exposure to LMS-1 particles did not result in overt cytotoxicity in either TT1 epithelial cells or THP-1 macrophage-like cells. A dose-dependent increase in IL-8 release was observed in TT1 cells, whereas THP-1 cell exposure, even at low particle concentrations, resulted in increased IL-8 release. Both cytotoxic and pro-inflammatory responses were most marked and significantly greater in TT1 and THP-1 cells exposed to freshly-fractured LMS-1. Discussion: LMS-1 is a novel lunar dust simulant; this is the first study to determine its toxicological effects on respiratory cells in vitro. An increased inflammatory response in TT1 and THP-1 cells exposed to ground LMS-1 suggests that low particle size, increased surface area, and angularity likely contribute to toxicity. Conclusions: Evenlow levels of exposure to LMS-1 could result in alveolar inflammation. This may have pathological consequences for astronauts exposed to lunar dust on future long-duration missions. Future research should test the effect of low-dose, intermittent lunar dust exposure on the respiratory system.

Keywords: lunar dust, LMS-1, lunar dust simulant, long-duration space travel, lunar dust toxicity

Procedia PDF Downloads 175

Authors: Peter Clutterbuck, Terry Rowlands, Owen Seamons

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In this paper we describe one critical research program within a complex, ongoing multi-year project (2010 to 2014 inclusive) with the overall goal to improve the learning outcomes for first year undergraduate commerce/business students within an Information Systems (IS) subject with very large enrolment. The single research program described in this paper is the analysis of student attitudes and decision making in relation to the availability of formative assessment feedback via Web-based real time conferencing and document exchange software (Adobe Connect). The formative assessment feedback between teaching staff and students is in respect of an authentic problem-based, team-completed assignment. The analysis of student attitudes and decision making is investigated via both qualitative (firstly) and quantitative (secondly) application of the Theory of Planned Behavior (TPB) with a two statistically-significant and separate trial samples of the enrolled students. The initial qualitative TPB investigation revealed that perceived self-efficacy, improved time-management, and lecturer-student relationship building were the major factors in shaping an overall favorable student attitude to online feedback, whilst some students expressed valid concerns with perceived control limitations identified within the online feedback protocols. The subsequent quantitative TPB investigation then confirmed that attitude towards usage, subjective norms surrounding usage, and perceived behavioral control of usage were all significant in shaping student intention to use the online feedback protocol, with these three variables explaining 63 percent of the variance in the behavioral intention to use the online feedback protocol. The identification in this research of perceived behavioral control as a significant determinant in student usage of a specific technology component within a virtual learning environment (VLE) suggests that VLEs could now be viewed not as a single, atomic entity, but as a spectrum of technology offerings ranging from the mature and simple (e.g., email, Web downloads) to the cutting-edge and challenging (e.g., Web conferencing and real-time document exchange). That is, that all VLEs should not be considered the same. The results of this research suggest that tertiary students have the technological sophistication to assess a VLE in this more selective manner.

Keywords: formative assessment feedback, virtual learning environment, theory of planned behavior, perceived behavioral control

Procedia PDF Downloads 364

Authors: Shulamit Sternin, Raymond M. McKie, Carter Winberg, Robb N. Travers, Terry P. Humphreys, Elke D. Reissing

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Issues surrounding sexual consent negotiation have become a major topic of societal concern. The majority of current research focuses on the complexities of sexual consent negotiations and the multitude of nuanced issues that surround the consent obtainment of heterosexual adults in post-secondary educational institutions. To date, the only study that has addressed sexual consent negotiation behaviour in same-sex relationships focused on the extent to which individuals used a variety of different verbal and nonverbal sexual consent behaviours to initiate or respond to sexual activity. The results were consistent with trends found within heterosexual individuals; thus, suggesting that the current understanding of sexual consent negotiation, which is grounded in heterosexual research, can serve as a strong foundation for further exploration of sexual consent negotiation within same-sex relationships populations. The current study quantitatively investigated the differences between heterosexual men and gay and bisexual men (GBM) in their understanding of sexual consent negotiation. Exploring how the perceptions of GBM differ from heterosexual males provides insight into some of the unique challenges faced by GBM. Data were collected from a sample of 252 heterosexual men and 314 GBM from Canada, the United States, and Western Europe. Participants responded to the question, 'do you think sexual consent and sex negotiation is different for heterosexual men compared to gay men? If so, how?' by completed an online survey. Responses were analysed following Braun & Clarke’s (2006) six phase thematic analysis guidelines. Inter-rater coding was validated using Cohen’s Kappa value and was calculated at (ϰ = 0.84), indicating a very strong level of agreement between raters. The final thematic structure yielded four major themes: understanding of sexual interaction, unique challenges, scripted role, and universal consent. Respondents spoke to their understanding of sexual interaction, believing GBM sexual consent negotiation to be faster and more immediate. This was linked to perceptions of emotional attachment and the idea that sexual interaction and emotional involvement were distinct and separate processes in GBM sexual consent negotiation, not believed to be the case in heterosexual interactions. Unique challenges such as different protection concerns, role declaration, and sexualization of spaces were understood to hold differing levels of consideration for heterosexual men and GBM. The perception of a clearly defined sexual script for GBM was suggested as a factor that may create ambiguity surrounding sexual consent negotiation, which in turn holds significant implications on unwanted sexual experiences for GBM. Broadening the scope of the current understanding of sexual consent negotiation by focusing on heterosexual and GBM population, the current study has revealed variations in perception of sexual consent negotiation between these two populations. These differences may be understood within the context of sexual scripting theory and masculinity gender role theory. We suggest that sexual consent negotiation is a health risk factor for GBM that has not yet been adequately understood and addressed. Awareness of the perceptions that surround the sexual consent negotiation of both GBM and heterosexual men holds implications on public knowledge, which in turn can better inform policy making, education, future research, and clinical treatment.

Keywords: sexual consent, negotiation, heterosexual men, GBM, sexual script

Procedia PDF Downloads 169

Authors: Yi Wang, Greg Hearn, Terry Flew

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In order to understand how cultural innovation occurs, this paper explores the interaction in Shenzhen of China between universities, creative industries, and government in creative economic using the Triple Helix framework. During the past two decades, Triple Helix has been recognized as a new theory of innovation to inform and guide policy-making in national and regional development. Universities and governments around the world, especially in developing countries, have taken actions to strengthen connections with creative industries to develop regional economies. To date research based on the Triple Helix model has focused primarily on Science and Technology collaborations, largely ignoring other fields. Hence, there is an opportunity for work to be done in seeking to better understand how the Triple Helix framework might apply in the field of creative industries and what knowledge might be gleaned from such an undertaking. Since the late 1990s, the concept of ‘creative industries’ has been introduced as policy and academic discourse. The development of creative industries policy by city agencies has improved city wealth creation and economic capital. It claims to generate a ‘new economy’ of enterprise dynamics and activities for urban renewal through the arts and digital media, via knowledge transfer in knowledge-based economies. Creative industries also involve commercial inputs to the creative economy, to dynamically reshape the city into an innovative culture. In particular, this paper will concentrate on creative spaces (incubators, digital tech parks, maker spaces, art hubs) where academic, industry and government interact. China has sought to enhance the brand of their manufacturing industry in cultural policy. It aims to transfer the image of ‘Made in China’ to ‘Created in China’ as well as to give Chinese brands more international competitiveness in a global economy. Shenzhen is a notable example in China as an international knowledge-based city following this path. In 2009, the Shenzhen Municipal Government proposed the city slogan ‘Build a Leading Cultural City”’ to show the ambition of government’s strong will to develop Shenzhen’s cultural capacity and creativity. The vision of Shenzhen is to become a cultural innovation center, a regional cultural center and an international cultural city. However, there has been a lack of attention to the triple helix interactions in the creative industries in China. In particular, there is limited knowledge about how interactions in creative spaces co-location within triple helix networks significantly influence city based innovation. That is, the roles of participating institutions need to be better understood. Thus, this paper discusses the interplay between university, creative industries and government in Shenzhen. Secondary analysis and documentary analysis will be used as methods in an effort to practically ground and illustrate this theoretical framework. Furthermore, this paper explores how are creative spaces being used to implement Triple Helix in creative industries. In particular, the new combination of resources generated from the synthesized consolidation and interactions through the institutions. This study will thus provide an innovative lens to understand the components, relationships and functions that exist within creative spaces by applying Triple Helix framework to the creative industries.

Keywords: cultural policy, creative industries, creative city, triple Helix

Procedia PDF Downloads 173