Al-Qallaf, Danah A. A. A. Q., Tomlinson, Darren, Bell, Sandra, and McPherson, Michael
Abstract
Biomarkers are molecules present in the patients' samples. They are used to detect the presence of a disease or an infection. An array of laboratory tools is used to monitor changes in the biomarker levels for diagnostic and prognostic purposes. Affimers are relatively new tools, which can be used in similar ways to commonly used antibodies with many advantages over the later. The work described in this PhD thesis has focused on a number of methodologies for the generation of Affimers against purified proteins and cell-surface molecules, with the intention of using these to detect biomarkers in cancer. To ensure the development of functional Affimer reagents against different membrane target molecules, EGFR, HER2, and HER3 were used as models to optimise the process of Affimers isolation and selection using phage display technology. In vitro production of Affimers using bacterial cells was assessed and optimised. Following optimisation, a range of Affimers that bound to EGFR, HER2, and HER3 were generated and partially characterised by different molecular applications, including immunofluorescence, immunohistochemistry, and pull-down assay. Upon characterisation, the developed reagents were not only able to identify their targets on cells and to precipitate them down from cell lysates, but also exhibited a complete inhibition of the downstream signalling activation of both EGFR and HER3. In addition, this thesis provides clear evidence of the potential of Affimers in biomarker discovery studies. After multiple rounds on non-tumourigenic (HB2) and cancerous (MDA-MB-453) breast-cell lines, eight novel anti-breast-cancer Affimers were successfully isolated and characterised. Following pull-down assay and mass spectrometry analysis, the target proteins to which these Affimers were found to bind was identified as CK18 and 19. Upon identification, the specificity of Affimers was further validated on a panel of breast cells, tissues, and on multiple breast-tissue microarrays (TMAs). There is a need to develop the knowledge to utilise this new Affimers-based technology to encourage adoption of this useful tool. With the aid of such technology, several novel detection reagents were generated, partially validated and proved to be promising tools for biomarker detection in different conventional assays.
Childhood obesity has reached epidemic proportions globally, and poses a considerable burden on a child’s short- and long-term health. Most obesity presents in the early (preschool) years, and once established tracks into later life. Therefore, identification of risk factors in the preschool period is considered critical for prevention of long-term obesity. In the United Arab Emirate (UAE), the rising prevalence of childhood obesity is of great public health concern. However, no previous study has explored risk factors for obesity in preschool children. This PhD aimed to: (i) identify risk factors for preschool obesity in the UAE (Study 1); (ii) describe dietary intake and patterns of preschool children, and explore their associations with risk of obesity (Study 2); and (iii) in a randomised controlled trial investigate the effectiveness of the ‘Eat Right Emirates’ (ERE) tool, a simple leaflet intervention designed to encourage a healthy lifestyle and prevent preschool obesity (Study 3). Study 1 showed that a longer duration of breastfeeding, and later introduction of complementary foods were associated with lower BMI z-score. Study 2 found that, compared with UK dietary guidelines, preschool children in the UAE exceeded intakes of protein, but did not meet recommended intakes for fibre. A high carbohydrate intake as a percentage of energy was associated with lower BMI z-score, whereas a high fat intake was associated with higher BMI z-score. A priori derived diet score found diets of preschool children were suboptimal, and principal component analysis identified three dietary patterns (‘traditional/health-conscious’, ‘processed/western’ and ‘convenience/snack’), which were not associated with BMI z-score. Study 3 found that the ERE tool was effective in reducing obesity risk compared to controls at 6-month follow-up. These findings, and the high compliance rate, suggest that the simple intervention is a promising approach for prevention of obesity in the UAE.
This research considers the possibility of a locally-centric design education curricula in Amman, Jordan by investigating the philosophies, theories, practices and models of curriculum and pedagogy most appropriate for design education. It describes perceptions of design and examines the possibilities for shifting these perceptions to move towards transforming design education. Jordan is a neopatriarchal society, and education re-enacts the dominant structures of the state within curriculum and pedagogy centred on the authority of the educator. This thesis argues for a decolonised design education based on a student-centred pedagogy drawn from the process and praxis curriculum models - a design education and design otherwise. Working with a range of designers, students and educators, it investigates the potential of these actors to contribute to the development of a pedagogy for design education in Jordan that is relevant to the milieu and locality. It poses the following questions: What philosophies, theories, practices, models of curriculum, and pedagogy are appropriate?; What potential shifts could this require and create?; How do we shift perceptions? This qualitative research uses interviews, focus groups, and design charrettes for data collection. Through participation and engagement with people that have most at stake in design education - designers, design educators and design students - I argue for an emancipatory design education that reflects on design beyond its traditional service-provider definition. Drawing on scholarship from design and education studies, and literature from fields such as history, decolonial studies, architecture and urbanism, political science, economics and philosophy, I argue for a curriculum model and student-centred pedagogy that considers design's role in society. Literature on Arab higher education is preoccupied with reforms to help the Arab region build a knowledge-society without considering the role of curriculum models and pedagogy nor addressing power structures. In addition, within design, little literature exists on the Arab region or Jordan, leaving its design culture(s) largely undocumented. My thesis investigates design education in higher education in Jordan by concentrating on models of pedagogy and curriculum and provides an overview of Jordan's contemporary design culture.
Canadian Journal of Physiology and Pharmacology. Oct, 2017, Vol. 95 Issue 10, p1091, 9 p.
Subjects
Fibrosis -- Physiological aspects, Fibrosis -- Care and treatment, Heart diseases -- Physiological aspects, Heart diseases -- Care and treatment, and Cardiac patients -- Physiological aspects
Abstract
Cardiac fibrosis is a significant global health problem that is closely associated with multiple forms of cardiovascular disease, including myocardial infarction, dilated cardiomyopathy, and diabetes. Fibrosis increases myocardial wall stiffness due to excessive extracellular matrix deposition, causing impaired systolic and diastolic function, and facilitating arrhythmogenesis. As a result, patient morbidity and mortality are often dramatically elevated compared with those with cardiovascular disease but without overt fibrosis, demonstrating that fibrosis itself is both a pathologic response to existing disease and a significant risk factor for exacerbation of the underlying condition. The lack of any specific treatment for cardiac fibrosis in patients suffering from cardiovascular disease is a critical gap in our ability to care for these individuals. Here we provide an overview of the development of cardiac fibrosis, and discuss new research directions that have recently emerged and that may lead to the creation of novel treatments for patients with cardiovascular diseases. Such treatments would, ideally, complement existing therapy by specifically focusing on amelioration of fibrosis. Key words: cardiac fibrosis, extracellular matrix, fibrosis therapy, fibroblast, myofibroblast. A l'echelle mondiale, la fibrose cardiaque est un important probleme de sante etroitement lie a diverses formes de maladies cardiaques, y compris l'infarctus du myocarde, la cardiomyopathie dilatee et le diabete. La fibrose entraine une augmentation de la rigidite de la paroi myocardique en raison du depot d'un exces de matrice extracellulaire, ce qui affecte les fonctions systolique et diastolique et qui favorise l'arythmogenese. En consequence, les taux de morbidite et de mortalite des patients sont souvent considerablement plus eleves qu'en absence de fibrose manifeste, ce qui montre que la fibrose elle-meme est a la fois une reaction pathologique a une maladie existante et un important facteur de risque de l'exacerbation de l'affection sous-jacente. Le manque de tout traitement specifique de la fibrose cardiaque chez les patients atteints de maladie cardiovasculaire constitue une lacune cruciale dans notre capacite de soigner ces personnes. Nous presentons ici un apercu de la formation de fibrose cardiaque, et nous discutons de nouvelles avenues de recherche emergentes qui pourraient mener au developpement de nouveaux traitements pour les patients atteints de maladies cardiovasculaires. Idealement, de tels traitements pourraient apporter un complement aux traitements existants en se centrant specifiquement sur des ameliorations en matiere de fibrose. [Traduit par la Redaction] Mots-cles: fibrose cardiaque, matrice extracellulaire, traitement de la fibrose, fibroblaste, myofibroblaste.
Al-Shamary, Danah S., Al-Alshaikh, Monirah A., Kheder, Nabila Abdelshafy, Mabkhot, Yahia Nasser, and Badshah, Syed Lal
Chemistry Central Journal. May 31, 2017, Vol. 11 Issue 1
Subjects
Organic compounds -- Research, Cancer -- Care and treatment, and Cancer -- Research
Abstract
Background The quinazoline are an important class of medicinal compounds that possess a number of biological activities like anticancer, anticonvulsant and antioxidant etc. Results We evaluated the previously synthesized quinazoline derivatives 1-3 for their anticancer activities against three cancer cell lines (HepG2, MCF-7, and HCT-116). Among the tested compounds, quinazolines 1 and 3 were found to be more potent than the standard drug Vinblastine against HepG2 and MCF-7 cell lines. All the tested compounds had less antioxidant activity and did not exhibit any anticonvulsant activity. Also, molecular docking studies were performed to get an insight into the binding modes of the compounds with human cyclin-dependent kinase 2, butyrylcholinesterase enzyme, human gamma-aminobutyric acid receptor. These compounds showed better docking properties with the CDK2 as compared to the other two enzymes. Conclusions The overall study showed that thioxoquinazolines are suitable antitumor agents and they should be explored for other biological activities. Modification in the available lot of quinazoline and synthesis of its novel derivatives is essential to explore the potential of this class of compounds. The increase in the threat and with the emergence of drug resistance, it is important to explore and develop more efficacious drugs. Keywords: Thioxoquinazolin-4(3H)-one, Anticancer activity, Antioxidant activity, Anticonvulsant activity, Molecular docking
Market trend/market analysis, Bullying -- Prevention, and Bullying -- Social aspects
Abstract
THE suicide of Jamey Rodemeyer, the 14-year-old boy from western New York who killed himself last Sunday after being tormented by his classmates for being gay, is appalling. His story [...]
Privacy issue, Company Web site/Web page, Company business management, Computer services industry, Web sites -- Safety and security measures, Computer services industry -- Safety and security measures, Computer services industry -- Management, and Privacy -- Reports
Abstract
Each time Facebook's privacy settings change or a technology makes personal information available to new audiences, people scream foul. Each time, their cries seem to fall on deaf ears. [...]
I FOUND THE images for February's 'Are You With the Right Mate?' demeaning to men. I've grown tired of media making fun of men or depicting them as less than [...]
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