Smooth muscle (SM) tissue is found in many parts of the body, primarily in sheets or bundles surrounding hollow organs. The main function of the tissue is the regulation of organ tone via its contractile state. Dysfunction of SM in diseases such as asthma and atherosclerosis affect millions worldwide. Current methods for studying SM primarily rely on ex vivo animal tissues or 2D in vitro models. Animal models do not accurately recreate human disease states and 2D models are cultured on stiff surfaces lacking the elastic properties and 3D morphology found in natural extracellular matrix in vivo. Therefore it is desirable to develop both an in vitro model of SM that possesses the ability to contract and a method in which this contraction can be measured. In order to achieve this, primary rat aortic SM cells and primary human airway SM cells were cultured in collagen hydrogels; both free floating in the form of collagen disks and under uniaxial tension in order to generate aligned SM collagen constructs. When stimulated with contractile agonists, these constructs contract in a uniaxial fashion. The design of the constructs allows them to be attached to a force transducer allowing the physical force of contraction to be measured. The force of contraction was dependant on the agonist concentration and could be antagonised by the presence of an L-type calcium channel blocker. In order to improve the alignment and uniformity of the smooth muscle population a range of aligned electrospun scaffolds were produced from polyethylene terephthalate (PET), cross-linked gelatin and cross-linked gelatin methacrylate (GelMa). The average fibre diameter of the scaffolds ranged from approximately 200 nm to several micrometres. Additionally the Young’s moduli of the scaffolds ranged from around 1x105 to 1x108 Pa. In all cases, scaffolds were highly aligned; alignment was achieved by using a rapidly rotating collector mandrel. Culture of primary SM cells upon these scaffolds showed that the cells readily adhered to and proliferated upon the scaffolds over a 10 day culture period. The cells formed a highly aligned population following the topographical cues of the aligned fibrous scaffolds. Additionally, the cells stained positive for SM markers in all cases, indicative of a contractile phenotype. When stimulated with 100 µM UTP, the SM cells were able to contract the gelatin and GelMa scaffolds but not the PET scaffolds. SM seeded GelMa scaffolds were cultured for 10 days prior to attachment to the previously mentioned force transducer apparatus. Upon stimulation the seeded scaffolds contracted generating forces greater than those achieved by the hydrogel model, and was reproducible over several experiments.

Business models integrating the internet into their value propositions have demonstrated varying levels of viability. In particular, firms offering information-based products via the internet commonly are unable to generate sufficient revenue and, consequently, experience financial losses. Researchers continue to examine factors which motivate individuals' willingness-to-pay for online content. One factor from the marketing literature which has been argued to affect consumer behavior is social influence. The purpose of this research is to investigate the effect of the three levels of social influence, micro-, meso-, and macro-, on both willingness-to-pay for online content and each other. This is accomplished by examining social influence in the context of online gaming, which has proven to be one of the most successful industries in integrating the internet as a delivery channel for information-based goods. Our results suggested that all levels of social influence play a considerable role in the product valuation process. While micro-level influences, such as attitude, arguably serve as the best predictors of WTP, we found that macro-level social influence, in the form of reputation, played the greatest role in affecting the formation of individual attitudes and behaviors. This was due not only to its direct effect on WTP, but also a consequence of several significant indirect effects. Our hypothesis that an interaction effect occurs between social influences such that their effect on WTP would be "greater than the sum of their parts" was not supported. Nonetheless, our study demonstrates social influence's ability to affect an individual is not a straight forward process. Only examining the relationships between constructs occurring at different levels of social structure does the magnitude of interaction which occurs between them becomes apparent.

Translocation of wild Asian elephants (Elephas maximus) is used extensively to mitigate human-elephant conflict (HEC) in Peninsular Malaysia since 1974. Very little is known about the fate of translocated elephants after relocation due to challenges in observing elephants in the dense rainforest. Advances in wildlife endocrinology suggest that faecal glucocorticoid metabolites (fGCM) can be used to study adrenal activity remotely, to assess the Hypothalamic-Pituitary-Adrenal (HPA) axis response towards stressors. The aim is to assess the impact of translocation on wild Asian elephants in Peninsular Malaysia using faecal endocrinology and GPS technology. The specific objectives are: (i) adapting hormone sampling methods for use under tropical field conditions, (ii) comparing fGCM concentrations between translocated and local resident elephants using enzyme immunoassay, and (iii) quantifying gastrointestinal parasite eggs and microflora ciliates in faecal samples to detect signs of immunosuppression. We found that Asian elephant’s fGCM (80 dungpiles, 685 subsamples) are stable up to eight hours in the field. From the monitoring of wild elephants at the release sites, between two months up to a year, translocated elephants (N=5) had lower fGCM concentrations in comparison to local resident elephants (N=4; Linear Mixed Models: t=-2.77, df=7.09, P=0.027). There were no differences in gastrointestinal parasite egg counts (P > 0.05) or microflora ciliate counts (P > 0.05) between translocated and local resident elephants. In conclusion, translocation does affect elephant physiology but this is in the opposite direction from that expected – a prolonged decrease rather than increase of adrenal activity. It is unknown if these conditions could cause immunosuppression, but it could adversely affect stress response and health of the elephant (e.g. adrenal insufficiency, chronic fatigue or Post-Traumatic Stress Disorder). When assessing HEC mitigation, conservation authorities and other stakeholders need to consider that translocation may not be the best solution for HEC, as it will have long-term consequences on elephants’ health.

The skin is the most extensive and accessible organ in the human body. It efficiently provides a barrier to an external hostile environment whilst maintaining and regulating fundamental physiological functions. The sophisticated and complex nature of this natural barrier requires continued analytical advancement to offer further insight into both its biological mechanisms and how to target the delivery of compounds through it. This work presents the use of a recently emerging technique in the field of skin research, time of flight - secondary ion mass spectrometry (ToF-SIMS), to investigate the presence of both native and exogenous compounds in skin tissue from samples collected both in vivo and ex vivo. Subtle changes to the stratum corneum lipid composition have been shown to exert significant effects on the barrier properties of the skin and are associated with numerous skin disorders. The analysis of these lipid species and factors affecting their composition, both internal and external, is therefore a vital area of research. Using ToF-SIMS, this work has conducted an examination of changes to this lipid composition that have resulted from aging of the skin. This has been achieved by undertaking extensive development of a recently proposed surface analysis method to analyse sequential tape strips of stratum corneum. This study was unprecedented in demonstrating that ToF-SIMS could obtain information on human skin from samples collected in vivo. Changes in the levels of both cholesterol sulfate and long chain fatty acids were observed as a consequence of both intrinsic and extrinsic aging, offering confirmatory evidence to previously theorised skin aging mechanisms. Research relating to the effective permeation of compounds across this skin barrier is also of upmost importance, both to the pharmaceutical and cosmetic industries, to enable the design of new topical formulations for skin delivery. Currently employed methods to assess the permeation of a compound are heavily focused on dermal delivery, with limited information obtained on the effectiveness of a compound to permeate into the upper layers of the skin. This research has therefore pioneered a dynamic SIMS method to conduct depth profile analysis of ex vivo porcine skin tissue, enabling the permeation of exogenous compounds to be monitored as a function of skin depth. This work is novel in successfully producing 3D spatially resolved chemical profiles of exogenous compounds within biological tissue using ToF-SIMS. The permeation of four different vitamin C related compounds, popular ingredients in anti-aging cosmetic formulations, were assessed using this method, highlighting a significant difference in permeation efficiency between them. An investigation into the delivery of ascorbic acid to the skin from various different formulations was also achieved, highlighting a permeation enhancing effect from delivery via a novel supramolecular gel formulation. The method developed for surface analysis was also successfully applied to monitor the permeation of ascorbic acid through human stratum corneum following in vivo application of an ‘off-the-shelf’ cosmetic product.

No description available.

Research during the past decade has highlighted the functional role of perivascular adipose tissue (PVAT) in regulating the contractility of the underlying vascular smooth muscle cell layer. However, the mechanisms underlying these observations are poorly understood. As a sexual dimorphism has been identified in the regulation of vascular tone, the aim of this thesis was to determine whether there are sex differences in PVAT-mediated regulation of the porcine coronary arterial (PCA) tone. In the presence of adherent PVAT, which was stored overnight at 4Co, contractions to the thromboxane mimetic U46619 and endothelin-1 were significantly reduced in PCAs from females, but not PCAs from males. In PCAs pre-contracted with U46619, re-addition of PVAT caused relaxation in PCAs from females, but not PCAs from males. This relaxant response in coronary arteries derived from females was inhibited by a combination of both NO synthase inhibitor (L-NAME) and the cyclooxygenase inhibitor indomethacin. Pre-incubation with an anti-adiponectin antibody abolished the relaxant effects of PVAT, indicating that adiponectin is likely to be the mediator released from the fat. There was no difference in either expression or release of adiponectin from PVAT between sexes. On the other hand, the adiponectin receptor agonist adipoRon produced greater relaxation in PCAs from females compared to PCAs derived from males. No adiponectin receptor 1 expression was detected in PCAs whilst adiponectin receptor 2 and adiponectin binding protein (APPL1) were expressed equally in PCAs from both sexes. Pre-incubation with the hydrogen sulphide enzyme inhibitors 4-propargylglycine (PPG) and 2-(aminooxy)-acetic acid (AOAA) did not reduce the anticontractile responses to PVAT. Cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3MPST) are expressed in PVAT from both sexes equally, with a relatively low activity, whilst no cystathionine γ-lyase (CSE) expression has been identified in PVAT from both sexes. These data indicate a clear sex difference in the regulation of coronary artery tone in response to adiponectin receptor stimulation, which may underlie the anticontractile effects of PVAT in females. Although H2S synthesizing enzymes are expressed in PVAT, they have no functional role in PVAT-induced vasorelaxation. In arteries from both male and female pigs, addition of fresh PVAT caused a contraction, which was partially inhibited by the cyclooxygenase inhibitors indomethacin and flurbiprofen. The PGF2α receptor (FP) antagonist AL8810 attenuated the PVAT-induced contractions in arteries from males, whereas the TXA2 receptor (TP) antagonist GR32191B inhibited the PVAT-induced contractions in arteries from females. Although there was no difference in PGF2α levels in PVAT between females and males, PGF2α produced a larger contraction in arteries from males, correlating with a higher FP receptor expression detected by immunoblotting. In contrast, the release of TXB2 from PVAT from females was greater than the release from males PVAT, but there was no difference in the contraction by the TXA2 agonist U46619. Furthermore, there was no difference in the role of extracellular Ca2+ and Rho kinase pathway (intracellular Ca2+) in the action of U46619, or TP receptor expression in arteries from different sexes. Pre-incubation with the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC), a non-selective NADPH oxidase (Nox) inhibitor (DPI), a selective Nox1 inhibitor (ML171), a selective Nox2 inhibitor Phox-I2 and selective Nox1 and Nox4 inhibitor (GKT137831) significantly reduced PVAT-induced vasoconstriction in PCAs from both females and males. Nox1, Nox2 and Nox4 were expressed equally in PVAT from male and females. However, in PCAs, Nox1 expression was greater in females whilst Nox4 was higher in males. Nox2 was expressed equally in PCAs from different sexes. ML171 and phox-I2 reduced superoxide anion (O2-) production in PVAT and PCAs from both sexes. GKT137831 inhibited H2O2 production in PCAs, but not PVAT, from both sexes. Both U46619 and PGF2α had similar effects on ROS production in that they did not increase O2- production in PVAT while they enhanced O2- production in PCA from females only. Functional studies showed that Nox inhibitors could inhibit the PCAs response to both U46619 and PGF2α in females only. The adipose-derived compound chemerin-9 caused a significantly higher vasoconstriction in PCAs from females in comparison with males PCAs. Similarly, chemerin-9 enhanced Nox activity in females PCAs but not in males PCAs. Chemerin mRNA was expressed in the PVAT, and the chemerin receptor ChemR23 was expressed in PCAs, although there were no sex differences. The anti-chemerin antibody can abolish the PVAT-induced contractions in both sexes. The sexual dimorphism in the contraction to chemerin could be explained by differences in the signalling downstream of the chemerin receptor in PCAs rather than the expression of chemerin or its receptor in PVAT and PCA, respectively. In conclusion, this thesis has demonstrated clear sex differences in the regulation of coronary artery tone by PVAT, with a dual effect of PVAT on the contractility of the PCA. PVAT stored overnight enhanced vasorelaxation in PCAs from females only due to the increased adiponectin activity compared to the males PCAs. In contrast, fresh PVAT augments vasoconstriction in PCAs from both sexes. Prostanoids have an important role in PVAT-induced vasoconstriction in which PGF2α and TXA2 are responsible for vasoconstriction in male and female PCAs, respectively. In addition, chemerin may have a role as a PVAT-derived contractile agent in female PCA only, while Nox-derived ROS regulates PVAT-induced contraction in the PCAs from both sexes. This study highlighted the importance of considering potential sex differences in the responses to PVAT and that sex-specific drug treatment may represent a potential strategy in the treatment of cardiovascular diseases.

Concerted efforts to debunk popular myths about the Great War have resulted in cant attention being paid to the purpose and value of the lost generation myth within British society, particularly during times of further conflict such as the Second World War. This thesis reveals the benefits of reflecting on the previous conflict in ways connected with the concept of a lost generation during the years 1939-45. These benefits boiled down to the fact that myths exist for their utility as means of comprehending both past and present. This applied to the myth in its strictest sense as an explanatory narrative used to interpret demographic issues as well as psychological, spiritual and material ones. Notions of a missing generation and visions of the living lost are therefore used to demonstrate how the concept of a lost generation was used to make sense of the world. Also examined are the myth's wider discursive effects. Other handy devices used to understand the past and to approach the present were powerful symbols and commemorative narratives closely connected to visions of a lost generation. Analysis of the myth-making power of major poets demonstrates how engagement with the iconic status and visions of Rupert Brooke, Wilfred Owen and Siegfried Sasoon was used to outline contemporary concerns. A detailed examination of the language surrounding the British Legion's Poppy Appeal and the observance of Armistice Day also shows how these rituals were used not only to frame loss but also to understand and explain the renewal of international conflict. By exposing the utility of these related discourses and practices, as well as of the myth in its own right, this thesis ultimately illuminates a crucial phase in the myth's endurance as a popular definition of what happened between 1914 and 1918.

Made available in DSpace on 2016-01-13T13:27:38Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-05-29. Added 1 bitstream(s) on 2016-01-13T13:33:08Z : No. of bitstreams: 1 000846229.pdf: 1248733 bytes, checksum: df15fbfc30cdb5ef027a3e94d3e3e22b (MD5) / O objetivo desta pesquisa consiste em analisar as relações de influência entre as práticas de colaboração proposta pela abordagem de Open Innovation, com aspectos da cultura organizacional e estrutura organizacional. Além disso, pretende-se analisar as influências da colaboração para inovação com desempenho operacional, desempenho inovador e desempenho de mercado. Foi adotada uma pesquisa quantitativa tipo survey, com uma amostra de 116 empresas pertencentes a setores considerados dinâmicos em termos tecnológicos. Dentre os resultados obtidos, há a indicação de que os clientes são a principal fonte de colaboração para a inovação das empresas, que empresas que recebem incentivos governamentais para inovação são menos propensas à utilização de prática de colaboração para inovação; há a preponderância em empresas de grande porte no desenvolvimento de inovações radicais; as relações de colaboração propostas pela abordagem da Open Innovation com clientes, fornecedores, funcionários, universidades e outros, exercem influências positivas tanto no desempenho inovador quanto no de mercado das firmas, porém não apresenta influência positiva no desempenho organizacional / The objective of this research is to analyze the relationships of influence between collaborative practices proposed by the Open Innovation approach, with aspects of organizational culture and organizational structure. In addition, we intend to analyze the influences of collaboration for innovations with operational performance, innovative performance and market performance. A quantitative survey was adopted, with a sample of 116 firms in sectors considered dynamics in terms of technology. Some of the results presented that customers are the main source of collaboration for innovation companies; those companies that receive govermnment incentives for innovation are less prone to the use of collaborative innovation practices; there is a preponderance of large companies in the development of radical innovations; collaborative relations proposed by Open Innovation approach with customers, suppliers, employees, universities and others, exert positive influences both innovative performance as the market firms, but has no positive influence on operating performance

Circadian rhythms are present in all living organisms; daily oscillations of biological process from the expression of a gene to the number of times that an animal displays a given behaviour. The light/dark cycle is the primary cue that entrains these rhythms and the suprachiasmatic nuclei, within the hypothalamus are the central pacemaker which synchronises peripheral body clocks. Mice are useful circadian biology models and two peripheral circadian outputs were studied, locomotor activity and the rhythm of body temperature in a common inbred strain, the C57BL/6 mouse. The use of individually ventilated cages to house mice increases biocontainment, enabling the maintenance of high health status colonies and reducing the risk of allergies for laboratory personnel. The effect of these sealed units on ambient light levels was examined, using locomotor activity as a marker of entrainment to the light/dark cycle. Mice housed closer to the overhead light source experienced greater levels of illumination than those at the lower levels, yet all entrained to the light/dark cycle. Mice housed lower on the rack showed more activity during light hours when they normally rest and the onset of activity was advanced in relation to the time the lights turned off. Individually ventilated cages do not therefore compromise circadian entrainment but cage position may alter the distribution of rest and activity in relation to the light cycle. Measuring the rhythm of body temperature of animals is often confounded by the stress associated with immobilisation and restraint. A novel non-invasive method, a thermal imaging camera was trialled against an indwelling intraperitoneal implant, to compare the relationship between peripheral and core body temperature under different light cycles. A stable relationship was found between the two methods (average R² value = 0.92) and this persisted in conditions of constant darkness, where lack of light cues resulted in free-running of the rhythm, assuming a shorter period length of oscillation. This novel method has potential for use in circadian phenotyping studies and to improve welfare, following experimental interventions where the mouse, a small, metabolically active animal is at risk of hypothermia.

The present study investigated the impact of a number of assessor characteristics upon the relative contribution of individual assessor ratings to the final assessment centre decision. Berger, Cohen and Zelditch (1966) have suggested that status characteristics such as gender can affect the influence hierarchy of the group in that women are seen to be of a lower status than men and as such are allowed less influence over the group task. It was therefore proposed that male assessors would have more influence over the final assessment centre decision than female assessors. It has also been suggested that personality characteristics may affect the amount of influence that an individual is allowed over a group discussion. Previous literature has proposed that individuals who demonstrate high dominance and masculinity and low femininity may be allowed more influence over a group decision. The present study also proposes therefore that assessors who show high dominance or masculinity and low femininity will have more influence over the consensus discussion in an assessment centre. These hypotheses were investigated using two alternate studies. The first of these consisted of a laboratory-based simulation of an assessment centre. The results showed that sex, dominance and masculinity did not have an impact on influence, whereas femininity had a negative effect in that assessors who were less feminine had more influence over the consensus discussion. The second study was designed to assess the external validity of the findings of the first study using information that from archive records of candidates who participated in a real life assessment centre. The results demonstrated an effect of sex but not of femininity upon influence therefore contradicting the findings of study one. These findings are discussed with regard to the literature on sex and personality differences in group-decision-making.