487 research outputs found
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The mediating role of individual readiness for change
This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel UniversityThis study investigates the mediating role of Individual Readiness for Change (IRFC) in the relationship between Organisational Culture (OC) and Total Quality Management (TQM) implementation. Despite the substantial body of literature examining the influence of OC on TQM implementation, there has been limited research investigating the mechanics of the link between OC and TQM implementation. In particular, an extensive review of the literature revealed that a contribution to knowledge would be derived from the investigation of the role of IRFC as one possible mechanism through which an organisationâs culture comes to have an impact on TQM implementation. However, there is a gap in the TQM literature in not investigating the mediating role of IRFC on the relationship between OC and TQM implementation. The aim of this research study is to examine the influence of OC on TQM implementation and the mediating role of IRFC in the OC-TQM implementation relationship in Syrian Manufacturing Organisations (SMOs). The research methodology began with conducting a systematic review of the relevant literature, which led to the development of a theoretical framework. In the present study, an integrative framework was developed to combine the direct effect of OC on TQM implementation and the mediating role of IRFC in the OC-TQM relationship within a single framework. To validate this framework, empirical research was conducted. The empirical study was carried out in a new cultural context: Syria, and more specifically amongst SMOs. Following a hypothetico- deductive approach, primary data was collected through questionnaires from 350 middle managers in SMOs. The findings of this study indicate that the characteristics and values of group culture and adhocracy culture positively affect the implementation of TQM, however, IRFC was found to act as a mediator and possible mechanism to attenuate these positive relationships. This in turn highlights the critical role of IRFC in the formation of OC-TQM implementation link. Therefore, this study provides a refined and deeper understanding of the relationships between OC types and TQM implementation. With an improved comprehension of the relationship between OC and TQM, organisational leaders and managers can implement TQM more effectively and efficiently in their organisations. Consequently, this would assist SMOs in achieving higher levels of global marketing effectiveness. This research contributes to knowledge in several ways. Most importantly, it extends the existing literature on the link between OC and TQM implementation. Unlike previous studies about the direct influence of OC on TQM implementation, this research is one of the few empirical studies that examine the mediating role of IRFC as one of the mechanisms through which an organisationâs culture comes to have an impact on TQM implementation. This research makes a further innovative contribution by providing empirical evidence leading to advancement of the understanding of the relationship between all four OC types of the Competing Values Framework (CVF) and IRFC. Furthermore, this research study adds value via its contextual originality. It is believed that this study is one of the few studies that examine the Syrian cultural context empirically. Hence, it contributes to the scarce body of literature on the relationship between OC, IRFC, and TQM implementation specifically in developing countries
Watch Your Mouth: Navigating the English language
Interesting words with different meanings that you may have been unaware of from around the world.
Also includes Don\u27t Be the Person Who
Lipotoxicity in diabetic cardiomyopathy
Le diabĂšte est en croissance Ă un rythme alarmant. Sa fatalitĂ© la plus importante provient de ses effets sur le systĂšme cardiovasculaire. Effectivement, le diabĂšte est un facteur de risque majeur pour la maladie coronarienne et lâhypertension artĂ©rielle. En plus, les diabĂ©tiques courent le risque de dĂ©velopper une cardiomyopathie diabĂ©tique (DCM) qui est prĂ©sente indĂ©pendamment de lâathĂ©rosclĂ©rose et de lâhypertension. Les causes exactes de cette maladie cardiaque ne sont pas encore dĂ©finies complĂštement mais une anomalie du mĂ©tabolisme lipidique a Ă©mergĂ© comme Ă©tant un facteur contributeur clĂ©. Il est intĂ©ressant de noter quâune caractĂ©ristique commune de la DCM est lâaccumulation des lipides intracellulaires ce qui est connu comme la stĂ©atose cardiaque. Cette derniĂšre est probablement causĂ©e par un dĂ©sĂ©quilibre entre lâabsorption et la clairance cellulaires des lipides. En tant que tel, nous nous sommes concentrĂ© nos Ă©tudes sur lâĂ©lucidation des mĂ©canismes de lipotoxicitĂ© dans le contexte de la DCM. Nous avons donc investiguĂ© le rĂŽle du mĂ©tabolisme lipidique sur des voies de signalisation reliĂ©es Ă la DCM telles que le stress du rĂ©ticulum endoplasmique (ERS), lâactivitĂ© du RĂ©cepteur activĂ© par les prolifĂ©rateurs de peroxysomes (PPAR), lâinflammation et la dysfonction mitochondriale avec un intĂ©rĂȘt spĂ©cifique sur lâoxydation des acides gras.
Nous avons caractĂ©risĂ© lâERS et lâapoptose induits par les lipides; nous avons confirmĂ© que le palmitate, un acide gras lipotoxique, induit lâERS et la mort des cardiomyocytes primaires. Ensuite, on a dĂ©montrĂ© que la lipotoxicitĂ© mĂ©diĂ©e par cet acide gras est associĂ©e Ă un degrĂ© dâinflammation significatif qui peut ĂȘtre dĂ» Ă une rĂ©gulation Ă la baisse des rĂ©cepteurs de PPAR.
La stĂ©atose cardiaque et la lipotoxicitĂ© peuvent altĂ©rer des voies de signalisation ce qui conduit Ă la dysfonction mitochondriale. On a dĂ©couvert que la toxicitĂ© du palmitate est associĂ©e Ă une dĂ©ficience de lâoxydation complĂšte des acides gras (FAO). SpĂ©cifiquement, le palmitate attĂ©nue la ÎČ-oxydation et le cycle de lâacide citrique sans toucher Ă lâactivitĂ© de Cpt1b qui est lâĂ©tape cinĂ©tiquement dĂ©terminante dans la FAO. Il est intĂ©ressant de noter que lâaugmentation de la FAO attĂ©nue les effets toxiques du palmitate, alors que lâattĂ©nuation de la FAO de lâolĂ©ate, qui est normalement un acide gras non toxique, induit la mort cellulaire. Ces rĂ©sultats suggĂšrent que lâaugmentation de la FAO peut avoir des effets cliniques utiles comme ĂȘtre une cible pour le traitement de la DCM.
Nous avons Ă©galement cherchĂ© Ă savoir si la dĂ©ficience en FAO contribue Ă la DCM in vivo. Des Ă©tudes prĂ©cĂ©dentes ont dĂ©montrĂ© que la FAO augmente chez les souris diabĂ©tiques. Cependant, les souris diabĂ©tiques montrent une absorption Ă©levĂ©e des acides gras ce qui pourrait contribuer significativement Ă lâaugmentation de la FAO dans leurs tissus cardiaques. Par la suite, nous avons tentĂ© dâĂ©valuer la FAO directement des mitochondries au lieu des tissus cardiaques complets afin dâĂ©viter le facteur de confusion, qui est lâaugmentation de lâabsorption des acides gras. Nous avons dĂ©montrĂ© alors que les souris atteintes de diabĂšte chronique prĂ©sentent une dĂ©ficience en FAO accompagnĂ©e dâune dysfonction cardiaque. En revanche, les souris atteintes de diabĂšte aigu possĂ©daient des fonctions cardiaques normales associĂ©es de taux normaux de FAO.
Ensemble, ces Ă©tudes ont amĂ©liorĂ© notre comprĂ©hension des mĂ©canismes de lipotoxicitĂ© associĂ©e Ă la DCM et ils soulignent lâimportance de lâERS, de lâinflammation et de la dysfonction mitochondriale comme des facteurs clefs dans la promotion de la lipotoxicitĂ© dans la DCM.Diabetes is growing at an alarming rate in North America. The biggest killer of patients with diabetes is heart disease. Indeed, diabetes is a major risk factor for both coronary artery disease and hypertension. However, patients with diabetes are also at risk for developing diabetic cardiomyopathy (DCM), which is characterized as heart disease in the absence of atherosclerosis and hypertension. The exact causes of this diabetic heart disease has not been completely elucidated but abnormal lipid metabolism has emerged as a key contributing factor. Interestingly, a common characteristic of DCM is the accumulation of intra cellular lipids otherwise known as cardiac steatosis. Cardiac steatosis is likely caused by a mismatch between lipid uptake and lipid clearance from the cells. As such, we focused on elucidating the mechanisms of lipotoxicity in the context of diabetic cardiomyopathy. To this end, we investigated the role of lipid metabolism on key pathways related to diabetic cardiomyopathy including Endoplasmic Reticulum (ER) stress, Peroxisome proliferator-activated receptors (PPARs) activity, inflammation, and mitochondrial dysfunction with a specific focus on fatty acid oxidation.
We characterized lipid induced ER stress and apoptosis in vitro, using primary neonatal cardiomyocytes. We were able to confirm that palmitate, a lipotoxic fatty acid, induces ER stress and cell death in primary cardiomyocytes. We also demonstrated that palmitate mediated lipotoxicity is associated with a significant degree of inflammation which may be due to down-regulation of PPAR receptors.
Cardiac steatosis and lipotoxicity can alter metabolic signaling pathways leading to mitochondrial dysfunction. We discovered that palmitate toxicity is associated with an impairment of complete fatty acid oxidation (FAO). Specifically, palmitate impairs ÎČ-oxidation and citric acid cycle simultaneously with no effect on Cpt1b activity, the rate limiting step in FAO. Interestingly enhancing FAO attenuated the toxic effects of palmitate while inhibiting FAO caused oleate, which is normally non-toxic, to induce cell death. These results suggest that enhancing FAO might have some clinical utility as a therapeutic target for the treatment of diabetic cardiomyopathy.
As such, we have investigated whether impaired fatty acid oxidation might contribute to DCM pathology in vivo. Previous studies have shown that FAO is actually increased in diabetic mice. However, diabetic mice also exhibit elevated fatty acid uptake which could significantly contribute to the elevated FAO rates in these hearts. Therefore, we aimed to assess FAO rates directly from isolated mitochondria instead of whole hearts to exclude the potentially confounding factor of enhanced fatty acid uptake. We found that older (chronic) diabetic mice exhibited impaired fatty acid oxidation rates and this was associated with ER stress and impaired cardiac function. In contrast, acutely diabetic mice had normal cardiac functions which was associated with normal FAO rates.
Taken together, these studies have furthered our understanding of lipotoxic mechanisms in the context of diabetic cardiomyopathy and they accentuated the importance of ER stress, inflammation, and impaired mitochondrial function as key factors promoting lipotoxicity in diabetic cardiomyopathy
Design of a Statistics Lecture for Multidisciplinary Postgraduate Students Using a Range of Tools and Techniques
Teaching statistics is a critical and challenging issue especially to students from multidisciplinary and diverse postgraduate backgrounds. Postgraduate research students require statistics not only for the design of experiments; but also for data analysis. Students often perceive statistics as a complex and technical subject; thus, they leave data analysis to the last moment. The lecture needs to be simple and inclusive at the same time to make it comprehendible and address the learning needs of each student. Therefore, the aim of this work was to design a simple and comprehendible statistics lecture to postgraduate research students regarding âResearch plan, design and data collectionâ. The lecture adopted the constructive alignment learning theory which facilitated the learning environments for the students. The learning environment utilized a student-centered approach and used interactive learning environment with in-class discussion, handouts and electronic voting system handsets. For evaluation of the lecture, formative assessment was made with in-class discussions and poll questions which were introduced during and after the lecture. The whole approach showed to be effective in creating a learning environment to the students who were able to apply the concepts addressed to their individual research projects
Football Returns Home
On March 7, 2003, the Federation Internationale de Football Association (FIFA) announced that one of the greatest spectacles on the globe would be on the soil of a country that lives, breathes and ultimately loves the beautiful game of football (soccer)âBrazil. Every four years, more than 200 nations strive to reach the finals, and only 32 teams get to compete on the big stage known simply as the World Cup. The players have the opportunity to display their abilities while at the same time, represent their respective homes. This summer marks the 20th FIFA World Cup
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Glucocorticoid-regulated localization of cell surface glycoproteins in rat hepatoma cells is mediated within the Golgi complex.
Glucocorticoid hormones regulate the post-translational maturation and sorting of cell surface and extracellular mouse mammary tumor virus (MMTV) glycoproteins in M1.54 cells, a stably infected rat hepatoma cell line. Exposure to monensin significantly reduced the proteolytic maturation and externalization of viral glycoproteins resulting in a stable cellular accumulation of a single 70,000-Mr glycosylated polyprotein (designated gp70). Cell surface- and intracellular-specific immunoprecipitations of monensin-treated cells revealed that gp70 can be localized to the cell surface only in the presence of 1 microM dexamethasone, while in uninduced cells gp70 is irreversibly sequestered in an intracellular compartment. Analysis of oligosaccharide processing kinetics demonstrated that gp70 acquired resistance to endoglycosidase H with a half-time of 65 min in the presence or absence of hormone. In contrast, gp70 was inefficiently galactosylated after a 60-min lag in uninduced cells while rapidly acquiring this carbohydrate modification in the presence of dexamethasone. Furthermore, in the absence or presence of monensin, MMTV glycoproteins failed to be galactosylated in hormone-induced CR4 cells, a complement-selected sorting variant defective in the glucocorticoid-regulated compartmentalization of viral glycoproteins to the cell surface. Since dexamethasone had no apparent global effects on organelle morphology or production of total cell surface-galactosylated species, we conclude that glucocorticoids induce the localization of cell surface MMTV glycoproteins by regulating a highly selective step within the Golgi apparatus after the acquisition of endoglycosidase H-resistant oligosaccharide side chains but before or at the site of galactose attachment
Who Do You Think You Are? Vonnie
The beginning of then six-year-old JaâVon âVonnieâ Latimore\u27s immense fascination with the insect world all started with the accidental squashing of her sisterâs ladybug. She couldnât resist the temptation to take a stick from the yard, poke the bug apart and examine its part
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