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Evaluation of Minor Groove Binders (MGBs) as novel anti-mycobacterial agents, and the effect of using non-ionic surfactant vesicles as a delivery system to improve their efficacy
Get PDFObjectives: The slow development of major advances in drug discovery for the treatment of
Mycobacterium tuberculosis (Mtb) infection have led to a compelling need for evaluation of
more effective drug therapies against tuberculosis. New classes of drugs are constantly being evaluated for anti-mycobacterial activity with currently a very limited number of new drugs approved for TB treatment. Minor Groove Binders (MGBs) have previously revealed promising anti-microbial activity against various infectious agents; however have not yet been screened against Mtb.
Methods: Mycobactericidal activity of MGB compounds against Mtb was determined using H37Rv-GFP microplate assay. MGB hits were screened for their intracellular mycobactericidal efficacy against clinical Beijing Mtb strain HN878 in bone marrow-derived
macrophages using standard colony-forming unit counting. Cell viability was assessed by
CellTiter-Blue assays. Selected MGB were encapsulated into non-ionic surfactant vesicles
(NIVs) for drug delivery system evaluation.
Results: H37Rv-GFP screening yielded a hitlist of 7 compounds at an MIC99 between 0.39
and 1.56 μM. MGB-362 and MGB-364 displayed intracellular mycobactericidal activity
against Mtb HN878 at MIC50 of 4.09 μM and 4.19 μM respectively, whilst being non-toxic.
Subsequent encapsulation into NIVs demonstrated a 1.6 and 2.1-fold increased intracellular
mycobacterial activity, similar to that of rifampicin when compared to MGB alone formulation
Conclusions: MGBs anti-mycobacterial activities together with non-toxic properties indicate
that MGB compounds constitute an important new class of drug/chemical entity, which holds
promise in future anti-TB therapy. Furthermore, NIVs ability to better deliver entrapped MGB
compounds to an intracellular Mtb infection has provided merit for further preclinical
evaluation
During early to mid adolescence, moderate to vigorous physical activity is associated with restoring sleep, psychological functioning, mental toughness and male gender
No full textNumerous studies showed that regular physical activity (PA) is associated with both favourable and restorative sleep and improved psychological functioning (PF). However, there is little research on the topic covering the early to mid-adolescence period. Moreover, curiosity and exploratory behaviour (CEB) and mental toughness (MT) as a result of PA remains thus far uninvestigated, as do possible gender differences. The aim of the present study was to explore the associations between PA, subjective sleep (sS), PF, CEB, and MT during early to mid-adolescence. A total of 1361 participants (mean age = 13.37 years; range: 11–16 years; 51.2% female) took part in the study. They completed questionnaires covering PA, sS, PF, CEB, and MT. Greater PA was related to improved PF, better sS, and increased CEB and MT. Compared to male participants, females reported less PA, poorer sS, and had lower PF and MT scores. The present pattern of results suggests that during early and mid-adolescence greater PA was associated with more favourable sS and better PF, including CEB and MT, and that female participants reported lower scores in PA, sS, and PF. Accordingly, if PA has a favourable impact on sleep and psychological functioning, then data suggest that sports participation should be more tailored to increase motivation among female adolescents
Looking at men and masculinities through Information and Communication Technologies, and Vice Versa
No full textThe lecture series that led to this paper, “Gender-Effects: How Women create Technology of Tomorrow”, has an explicit focus on women. However, in this article in keeping with a relational approach to gender, we focus on men and masculinities, seen within the context of and gender power relations, and the diverse interrelations of men and masculinities with information and communication technologies (ICTs). This includes addressing to some of the shortcomings of contemporary studies of men and masculinities that neglect ICTs; the different kinds of social relations of men and masculinities to ICTS, in work, organizations, and social change more generally; and the implications of ICTs for sexualities and sexual violences, ending with the current case of online revenge pornography. As such, we seek to bring two areas of scholarship, critical studies on men and masculinities (CSMM) and studies of ICTs, into closer dialogue. We begin with a brief overview of academic debates in studies on men and masculinities without ICTs, followed by an examination of some aspects of the relations of men, masculinities and ICTs, with a final short discussion of the case of ICTs, sexualities, sexual violences and revenge pornography
A quantitative analysis of nozzle surface-bound fuel for diesel injectors
No full textIn a fuel injector at the end of the injection, the needle descent and the rapid pressure drop in the nozzle leads to discharge of large, slow-moving liquid structures. This unwanted discharge is often referred as fuel ‘dribble’ and results in near-nozzle surface wetting, creating fuel-rich regions that are believed to contribute to unburnt hydrocarbon emissions. Subsequent fluid overspill occurs during the pressure drop in the expansion stroke when
residual fluid inside the nozzle is displaced by the expansion of trapped gases as the pressure through the orifices is equalised, leading to further surface wetting. There have been several recent advancements in the
characterisation of these near nozzle fluid processes, yet there is a lack of quantitative data relating the operating conditions and hardware parameters to the quantity of overspill and surface-bound fuel. In this study, methods for quantifying nozzle tip wetting after the end of injection were developed, to gain a better understanding of the underlying processes and to study the influence of engine operating conditions. A high-speed camera with a longdistance
microscope was used to visualise fluid behaviour at the microscopic scale during, and after, the end of injection. In order to measure the nozzle tip temperature, a production injector was used which was instrumented with a type K thermocouple near one of the orifices. Image post-processing techniques were developed to track both the initial fuel coverage area on the nozzle surface, as well as the temporal evolution and spreading rate of surface-bound fluid. The conclusion presents an analysis of the area of fuel coverage and the rate of spreading and
how these depend on injection pressure, in-cylinder pressure and in-cylinder temperature. It was observed that for this VCO injector, the rate of spreading correlates with the initial area of fuel coverage measured after the end of
injection, suggesting that the main mechanism for nozzle wetting is through the impingement of dribble onto the nozzle. However, occasional observations of the expansion of orifice-trapped gas were made that lead to a
significant increase in nozzle wetting
Carbonation of Hydrous Materials at the Molecular Level: A Time of Flight-Secondary Ion Mass Spectrometry, Raman and Density Functional Theory Study
Get PDFCarbonation of hydrous minerals such as calcium hydroxide (Ca(OH)2) is an important process in environmental and industrial applications for the construction industry, geological disposal repositories for nuclear waste, and green technologies for carbon capture. Although the role of ions during the carbonation mechanism of Ca(OH)2 is still unclear, we identified the exchange of ions during the dissolution and precipitation process, by determining the change in isotopic composition of carbonation products using time-of-flight-secondary ion mass spectrometry. Our samples of pure Ca(18OH)2 carbonated in air were characterized using scanning electron microscopy and Raman spectroscopy, aided by density functional theory calculations. Our results show that the carbonation process at high pH is a two-stage mechanism. The first stage occurs in a short time after Ca(18OH)2 is exposed to air and involved the dissolution of surface Ca ions and hydroxyl 18OH groups, which reacts directly with dissolved CO2, leading to 1/3 of 18O in the oxygen content of carbonate phases. The second stage occurs within 24 h of exposure allowing a rebalance of the oxygen isotopic composition of the carbonate phases with a higher content of 16O
Book Review: 'Assessment and autonomy in language learning', Carol J. Everhard, Linda Murphy (Eds.). Palgrave Macmillan, Basingstoke (2015), 238pp
No full textFamilies beyond boundaries: Conceptualising kinship in gay and lesbian adoption and fostering
Get PDFThis paper discusses some key findings taken from a qualitative study conducted with gay and lesbian adopters and foster carers in England and Wales. The study examined the experiences of 24 self-identified lesbians and gay men, who had been involved in adoption or fostering processes since the introduction of the Adoption and Children Act, 2002. This article will explore why participants chose to adopt or foster and their approach to relationships generated through these routes. Findings indicate that gay and lesbian applicants troubled dominant conceptualisations of family and kinship and revealed both heteronormative and nuclear constructions of parenting within adoption and fostering social work. In contrast, participants often demonstrated a reflexive and creative approach to caring for looked after children. This paper will therefore consider how professionals can recognise nuanced or complex relationships, situated beyond traditional frameworks, through drawing upon wider concepts within sociological literature
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