133 research outputs found
Transitioning to Online Teaching and Learning: A Discussion of Barriers Faced by Educators and Students in Higher Education during a Global Pandemic
The Coronavirus pandemic and the resulting interruption of global education systems in more than 195 nations affected almost 1.8 billion students at all education levels. Strict measures including immediate lockdown and social- and self-distancing measures and policies were implemented. This sudden move has had a devastating and direct impact on schools, colleges and higher education institutions (HEIs), which led to closures (Huang et al., 2020), resulting in a 95% move from face-to-face teaching to online teaching and learning (Adnan & Anwar, 2020). This paper highlights some of the early educational barriers resulting from the Covid-19 pandemic by exploring them through Scholssberg et al. (1984) transition theory of 'moving in', 'moving through' and 'moving out' of a situation, which is, in this case, the pandemic
Connectivity in One-Dimensional Soft Random Geometric Graphs
In this paper, we study the connectivity of a one-dimensional soft random
geometric graph (RGG). The graph is generated by placing points at random on a
bounded line segment and connecting pairs of points with a probability that
depends on the distance between them. We derive bounds on the probability that
the graph is fully connected by analysing key modes of disconnection. In
particular, analytic expressions are given for the mean and variance of the
number of isolated nodes, and a sharp threshold established for their
occurrence. Bounds are also derived for uncrossed gaps, and it is shown
analytically that uncrossed gaps have negligible probability in the scaling at
which isolated nodes appear. This is in stark contrast to the hard RGG in which
uncrossed gaps are the most important factor when considering network
connectivity
Morphology, histochemistry and glycosylation of the placenta and associated tissues in the European hedgehog (Erinaceus europaeus)
Cytochrome P450 CYP1 metabolism of hydroxylated flavones and flavonols: Selective bioactivation of luteolin in breast cancer cells.
The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Natural flavonoids with methoxy substitutions are metabolized by CYP1 enzymes to yield the corresponding demethylated products. The present study aimed to characterize the metabolism and further antiproliferative activity of the hydroxylated flavonoids apigenin, luteolin, scutellarein, kaempferol and quercetin in CYP1 recombinant enzymes and in the CYP1 expressing cell lines MCF7 and MDA–MB–468, respectively. Apigenin was converted to luteolin and scutellarein, whereas kaempferol was metabolized only to quercetin by recombinant CYP1 enzymes. Luteolin metabolism yielded 6 hydroxyluteolin only by recombinant CYP1B1, whereas CYP1A1 and CYP1A2 were not capable of metabolizing this compound. Molecular modeling demonstrated that CYP1B1 favored the A ring orientation of apigenin and luteolin to the heme group compared with CYP1A1. The IC50 of the compounds luteolin, scutellarein and 6 hydroxyluteolin was significantly lower in MDA–MB–468, MCF7 and MCF10A cells compared with that of apigenin. Similarly, the IC50 of quercetin in MDA–MB–468 cells was significantly lower compared with that of kaempferol. The most potent compound was luteolin in MDA–MB–468 cells (IC50= 2±0.3 μM). In the presence of the CYP1-inhibitors α-napthoflavone and/or acacetin, luteolin activation was lessened. Taken collectively, the data demonstrate that the metabolism of hydroxylated flavonoids by cytochrome P450 CYP1 enzymes, notably CYP1A1 and CYP1B1, can enhance their antiproliferative activity in breast cancer cells. In addition, this antiproliferative activity is attributed to the combined action of the parent compound and the corresponding CYP1 metabolites
Effect of exogenous surfactants on viability and DNA synthesis in A549, immortalized mouse type II and isolated rat alveolar type II cells
<p>Abstract</p> <p>Background</p> <p>In mechanically ventilated preterm infants with respiratory distress syndrome (RDS), exogenous surfactant application has been demonstrated both to decrease DNA-synthesis but also and paradoxically to increase epithelial cell proliferation. However, the effect of exogenous surfactant has not been studied directly on alveolar type II cells (ATII cells), a key cell type responsible for alveolar function and repair.</p> <p>Objective</p> <p>The aim of this study was to investigate the effects of two commercially available surfactant preparations on ATII cell viability and DNA synthesis.</p> <p>Methods</p> <p>Curosurf<sup>® </sup>and Alveofact<sup>® </sup>were applied to two ATII cell lines (human A549 and mouse iMATII cells) and to primary rat ATII cells for periods of up to 24 h. Cell viability was measured using the redox indicator resazurin and DNA synthesis was measured using BrdU incorporation.</p> <p>Results</p> <p>Curosurf<sup>® </sup>resulted in slightly decreased cell viability in all cell culture models. However, DNA synthesis was increased in A549 and rat ATII cells but decreased in iMATII cells. Alveofact<sup>® </sup>exhibited the opposite effects on A549 cells and had very mild effects on the other two cell models.</p> <p>Conclusion</p> <p>This study showed that commercially available exogenous surfactants used to treat preterm infants with RDS can have profound effects on cell viability and DNA synthesis.</p
The synthesis of chalcones as anticancer prodrugs and their bioactivation in CYP1 expressing breast cancer cells
The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI linkAbstract: Background: Although the expression levels of many P450s differ between tumour and
corresponding normal tissue, CYP1B1 is one of the few CYP subfamilies which is significantly
and consistently overexpressed in tumours. CYP1B1 has been shown to be active within tumours
and is capable of metabolising a structurally diverse range of anticancer drugs. Because of this,
and its role in the activation of procarcinogens, CYP1B1 is seen as an important target for anticancer
drug development.
Objectives: To synthesise a series of chalcone derivatives based on the chemopreventative agent
DMU-135 and investigate their antiproliferative activities in human breast cancer cell lines which
express CYP1B1 and CYP1A1.
Method: A series of chalcones were synthesised in yields of 43-94% using the Claisen-Schmidt
condensation reaction. These were screened using a MTT assay against a panel of breast cancer
cell lines which have been characterised for CYP1 expression.
Results: A number of derivatives showed promising antiproliferative activities in human breast
cancer cell lines which express CYP1B1 and CYP1A1, while showing significantly lower toxicity
towards a non-tumour breast cell line with no CYP expression. Experiments using the CYP1 inhibitors
acacetin and -naphthoflavone provided supporting evidence for the involvement of CYP1
enzymes in the bioactivation of these compounds.
Conclusions: Chalcones show promise as anticancer agents with evidence suggesting that CYP1
activation of these compounds may be involved
Epidemiology of Exertional Rhabdomyolysis Susceptibility in Standardbred Horses Reveals Associated Risk Factors and Underlying Enhanced Performance
BACKGROUND: Exertional rhabdomyolysis syndrome is recognised in many athletic horse breeds and in recent years specific forms of the syndrome have been identified. However, although Standardbred horses are used worldwide for racing, there is a paucity of information about the epidemiological and performance-related aspects of the syndrome in this breed. The objectives of this study therefore were to determine the incidence, risk factors and performance effects of exertional rhabdomyolysis syndrome in Standardbred trotters and to compare the epidemiology and genetics of the syndrome with that in other breeds. METHODOLOGY/PRINCIPAL FINDINGS: A questionnaire-based case-control study (with analysis of online race records) was conducted following identification of horses that were determined susceptible to exertional rhabdomyolysis (based on serum biochemistry) from a total of 683 horses in 22 yards. Thirty six exertional rhabdomyolysis-susceptible horses were subsequently genotyped for the skeletal muscle glycogen synthase (GYS1) mutation responsible for type 1 polysaccharide storage myopathy. A total of 44 susceptible horses was reported, resulting in an annual incidence of 6.4 (95% CI 4.6-8.2%) per 100 horses. Female horses were at significantly greater risk than males (odds ratio 7.1; 95% CI 2.1-23.4; p = 0.001) and nervous horses were at a greater risk than horses with calm or average temperaments (odds ratio 7.9; 95% CI 2.3-27.0; p = 0.001). Rhabdomyolysis-susceptible cases performed better from standstill starts (p = 0.04) than controls and had a higher percentage of wins (p = 0.006). All exertional rhabdomyolysis-susceptible horses tested were negative for the R309H GYS1 mutation. CONCLUSIONS/SIGNIFICANCE: Exertional rhabdomyolysis syndrome in Standardbred horses has a similar incidence and risk factors to the syndrome in Thoroughbred horses. If the disorder has a genetic basis in Standardbreds, improved performance in susceptible animals may be responsible for maintenance of the disorder in the population
Pharmacokinetics in mice and growth-inhibitory properties of the putative cancer chemopreventive agent resveratrol and the synthetic analogue trans 3,4,5,4′-tetramethoxystilbene
Service planning and delivery outcomes of home adaptations for ageing in the UK
In response to the impact of demographic change on the healthcare system, ‘ageing in place’ was introduced as a national policy to support elderly people living independently in their homes. Housing adaptation is essential for successful independent living and has been given increased political priority. However, adaptation policies and practice vary regionally, reflecting statutory limits, policy choices and local planning. This study investigated the current status of adaptation provision in different regions in the UK and assessed the effectiveness of local service planning and management. A mixed-methods sequential explanatory research strategy was employed. In the first quantitative phase, a questionnaire survey was carried out involving all 378 local authorities in England, Scotland and Wales. This was followed by a second qualitative phase involving individual interviews with five professionals and two clients and a focus group meeting with six key stakeholders. The study found that the current number of adaptations was relatively small compared with potential demands in most local areas, as was funding for adaptations. On the operational side, the adaptation process was fragmented, involving different service groups in many local authorities. There were disconnections between these groups, which often caused inefficiencies and poor effectiveness. Moving forward, local authorities need to have a clear vision of the overall need for adaptations and allocate sufficient resources. Practical guidelines are also needed for better integrated working and performance management
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