Environmental features which limit organization and industry viability:a study of the footwear industry

This thesis proposes a conceptual framework for the analysis of organizational environments. Three primary segments of the task environment - the transaction environment, the industrial environment and the ecotone are delineated. The interrelationships between the organization and these three environmental segments are examined. It is suggested that the task environment i) defines the nature of the task confronting the organization and the economic, political and social position of the organization within this network; ii) influences the way organizations and industries are organized; iii) prevents recognition of the need for adaptation and change; and iv) limits the alternatives available to the organization should changes in the environment render existing technology, behaviour and structures obsolete. The British Footwear Industry provides an example of how this framework might be used to investigate the problem of industry decline and organization viability. It is argued that the explanations usually put forth to explain organization failure and industrial decline have not taken into consideration the environmental factors which affect organization and industry viability. The shift from national markets to global markets has altered the composition of the task environment and has changed the nature of competition from firm versus firm to environment versus environment. Organizations do not compete in the market, their products do. These products are often produced by organizations embedded in environments which are significantly different from the one in which the focal organization and industry are embedded.

Regulation of beta-cell viability and gene expression by distinct agonist fragments of adiponectin

Obesity is an established risk factor for type 2 diabetes. Activation of the adiponectin receptors has a clear role in improving insulin resistance although conflicting evidence exists for its effects on pancreatic beta-cells. Previous reports have identified both adiponectin receptors (ADR-1 and ADR-2) in the beta-cell. Recent evidence has suggested that two distinct regions of the adiponectin molecule, the globular domain and a small N-terminal region, have agonist properties. This study investigates the effects of two agonist regions of adiponectin on insulin secretion, gene expression, cell viability and cell signalling in the rat beta-cell line BRIN-BD11, as well as investigating the expression levels of adiponectin receptors (ADRs) in these cells. Cells were treated with globular adiponectin and adiponectin (15-36) +/-leptin to investigate cell viability, expression of key beta-cell genes and ERK1/2 activation. Both globular adiponectin and adiponectin (15-36) caused significant ERK1/2 dependent increases in cell viability. Leptin co-incubation attenuated adiponectin (15-36) but not globular adiponectin induced cell viability. Globular adiponectin, but not adiponectin (15-36), caused a significant 450% increase in PDX-1 expression and a 45% decrease in LPL expression. ADR-1 was expressed at a higher level than ADR-2, and ADR mRNA levels were differentially regulated by non-esterified fatty acids and peroxisome-proliferator-activated receptor agonists. These data provide evidence of roles for two distinct adiponectin agonist domains in the beta-cell and confirm the potentially important role of adiponectin receptor agonism in maintaining beta-cell mass.

Resistin down-regulates insulin receptor expression, and modulates cell viability in rodent pancreatic beta-cells

The adipokine resistin is known to induce insulin resistance in rodent tissues. Increases in adipose tissue mass are known to have a negative effect on pancreatic beta-cell function, although the mechanisms are poorly understood. This study investigated the effects of resistin on insulin secretion, insulin receptor expression and cell viability in pancreatic beta-cells. BTC-6 or BRIN-BD11 cells were treated for 24h with resistin, and insulin receptor expression, insulin secretion and cell viability were measured. Incubation with 40ng/ml resistin caused significant decreases in insulin receptor mRNA and protein expression, but did not affect insulin secretion. At low concentrations, resistin caused significant increases in cell viability. These data implicate resistin as a factor that may regulate beta-cell function/viability, and suggests a potential mechanism by which increased adiposity causes beta-cell dysfunction.

Luminescent techniques for studying free radical production and cell viability in relation to cardiovascular disease and HRT

Epidemiological studies have suggested that hormone replacement therapy (HRT) offers protection from atherosclerosis, a precursor of cardiovascular disease (CVD), in postmenopausal women. There is good evidence that oxidation of low-density lipoprotein (LDL) by leucocyte-derived reactive oxygen species plays a key role in development of an atherosclerotic plaque. Therefore we have investigated whether the possible protection against CVD by HRT could be due to immunomodulation, specifically of free radical production. The study involves 2 approaches: I) analysing the production of free radicals by leucocytes from women on HRT, 2) investigating the effect of I7p-oestradiol and progesterone on cultured myeloid cells (HL60 and U937). Free radical production by leucocytes was determined using a recently developed bioluminescent assay. In the assay, Pholasin® emits light in the presence of free radicals produced by the NADPH oxidase system of leucocytes stimulated with PMA or fMLP. Cell viability was also investigated using a bioluminescent assay (Cell Titer-Glo®) in which cytosolic ATP levels were measured by the production of luminescence in the presence of Luciferin/Luciferase reagent. Studies of leucocytes from HRT patients showed considerable variation in free radical production, which appeared to be dependent on HRT regime. Studies on the cultured cells showed that there was no cell proliferation at low hormone concentrations, while high concentrations caused cytotoxicity. The effect of hormones on free radical production in this in vitro model system is currently being investigated. The results show that the effects of the hormones on cells of the immune system are very dose dependent, and that both beneficial and adverse effects may occur. In conclusion, luminescent techniques offer a valuable and sensitive approach to studying inflammatory and oxidative processes both in vivo and in vitro.

Viability Kernels of Higher Order

AMS subject classification: Primary 34A60, Secondary 49K24.

Time-Dependent Differential Inclusions and Viability

AMS subject classification: Primary 34A60, Secondary 49J52.

Viability, Optimality and Stability of Dynamical Systems and Estimation of Convergence of Numerical Schemes

AMS subject classification: 49N35,49N55,65Lxx.

Nicotine exposure reduces cell viability but induces anti-inflammatory effects in human cystic fibrosis bronchial epithelial cells

Background: Mouse models of cystic fibrosis (CF) fail to truly represent the respiratory pathology. We have consequently developed human airways cell culture models to address this. The impact of cigarette smoke within the CF population is well documented, with exposure being known to worsen lung function. As nicotine is often perceived to be a less harmful component of tobacco smoke, this research aimed to identify its effects upon viability and inflammatory responses of CF (IB3-1) and CF phenotype corrected (C38) bronchial epithelial cells. Methods: IB3-1 and C38 cell lines were exposed to increasing concentrations of nicotine (0.55-75μM) for 24 hours. Cell viability was assessed via Cell Titre Blue and the inflammatory response with IL-6 and IL-8 ELISA. Results: CF cells were more sensitive; nicotine significantly (P<0.05) reduced cell viability at all concentrations tested, but failed to have a marked effect on C38 viability. Whilst nicotine induced anti-inflammatory effects in CF cells with a significant reduction in IL-6 and IL-8 release, it had no effect on chemokine release by C38 cells. Conclusion: CF cells may be more vulnerable to inhaled toxicants than non-CF cells. As mice lack a number of human nicotinic receptor subunits and fail to mimic the characteristic pathology of CF, these data emphasise the importance of employing relevant human cell lines to study a human-specific disease.

Viability Theory and Economic Modeling

A brief introduction into the theory of differential inclusions, viability theory and selections of set valued mappings is presented. As an application the implicit scheme of the Leontief dynamic input-output model is considered.

Population viability analyses of Chamaecrista keyensis (Leguminosae: Caesalpinioideae), a narrowly endemic herb of the lower Florida Keys: Effects of seasonal timing of fires and the urban -wildland interface

This research first evaluated the effects of urban wildland interface on reproductive biology of the Big Pine Partridge Pea, Chamaecrista keyensis, an understory herb that is endemic to Big Pine Key, Florida. I found that C. keyensis was self-compatible, but depended on bees for seed set. Furthermore, individuals of C. keyensis in urban habitats suffered higher seed predation and therefore set fewer seeds than forest interior plants. ^ I then focused on the effects of fire at different times of the year, summer (wet) and winter (dry), on the population dynamics and population viability of C. keyensis. I found that C. keyensis population recovered faster after winter burns and early summer burns (May–June) than after late summer burns (July–September) due to better survival and seedling recruitment following former fires. Fire intensity had positive effects on reproduction of C. keyensis. In contrast, no significant fire intensity effects were found on survival, growth, and seedling recruitment. This indicated that better survival and seedling recruitment following winter and early summer burns (compared with late summer burns) were due to the reproductive phenology of the plant in relation to fires rather than differences in fire intensity. Deterministic population modeling showed that time since fire significantly affected the finite population growth rates (λ). Particularly, recently burned plots had the largest λ. In addition, effects of timing of fires on λ were most pronounced the year of burn, but not the subsequent years. The elasticity analyses suggested that maximizing survival is an effective way to minimize the reduction in finite population growth rate the year of burn. Early summer fires or dry-season fires may achieve this objective. Finally, stochastic simulations indicated that the C. keyensis population had lower extinction risk and population decline probability if burned in the winter than in the late summer. A fire frequency of approximately 7 years would create the lowest extinction probability for C. keyensis. A fire management regime including a wide range of burning seasons may be essential for the continued existence of C. keyensis and other endemic species of pine rockland on Big Pine Key. ^

Coevolutionary Feedbacks between Female Mating Interval and Male Allocation to Competing Sperm Traits Can Drive Evolution of Costly Polyandry

Acknowledgments We thank A. B. Duthie, S. Losdat, and M. E. Wolak for useful discussions and comments and the European Research Council for funding. We also thank the two reviewers, whose suggestions greatly improved the manuscript.

Coevolutionary Feedbacks between Female Mating Interval and Male Allocation to Competing Sperm Traits Can Drive Evolution of Costly Polyandry

Acknowledgments We thank A. B. Duthie, S. Losdat, and M. E. Wolak for useful discussions and comments and the European Research Council for funding. We also thank the two reviewers, whose suggestions greatly improved the manuscript.

The effect of Me2SO overexposure during cryopreservation on HOS TE85 and hMSC viability, growth and quality

With the cell therapy industry continuing to grow, the ability to preserve clinical grade cells, including mesenchymal stem cells (MSCs), whilst retaining cell viability and function remains critical for the generation of off-the-shelf therapies. Cryopreservation of MSCs, using slow freezing, is an established process at lab scale. However, the cytotoxicity of cryoprotectants, like Me2SO, raises questions about the impact of prolonged cell exposure to cryoprotectant at temperatures >0 °C during processing of large cell batches for allogenic therapies prior to rapid cooling in a controlled rate freezer or in the clinic prior to administration. Here we show that exposure of human bone marrow derived MSCs to Me2SO for ≥1 h before freezing, or after thawing, degrades membrane integrity, short-term cell attachment efficiency and alters cell immunophenotype. After 2 h's exposure to Me2SO at 37 °C post-thaw, membrane integrity dropped to ∼70% and only ∼50% of cells retained the ability to adhere to tissue culture plastic. Furthermore, only 70% of the recovered MSCs retained an immunophenotype consistent with the ISCT minimal criteria after exposure. We also saw a similar loss of membrane integrity and attachment efficiency after exposing osteoblast (HOS TE85) cells to Me2SO before, and after, cryopreservation. Overall, these results show that freezing medium exposure is a critical determinant of product quality as process scale increases. Defining and reporting cell sensitivity to freezing medium exposure, both before and after cryopreservation, enables a fair judgement of how scalable a particular cryopreservation process can be, and consequently whether the therapy has commercial feasibility.

Seawater carbonate chemistry and sperm swimming speed of the polychaete Galeolaria caespitosa in lab experiment

The rapidity of ocean acidification intensifies selection pressure for resilient phenotypes, particularly during sensitive early life stages. The scope for selection is greater in species with greater within-species variation in responses to changing environments, thus enhancing the potential for adaptation. We investigated among-male variation in sperm swimming responses (percent motility and swimming speeds) of the serpulid polychaete Galeolaria caespitosa to near- (delta pH 0.3) and far-future ocean acidification (delta pH 0.5). Responses of sperm swimming to acidification varied significantly among males and were overall negative. Robust sperm swimming behavior under near-future ocean acidification in some males may ameliorate climate change impacts, if traits associated with robustness are heritable, and thereby enhance the potential for adaptation to far-future conditions. Reduced sperm swimming in the majority of male G. caespitosa may decrease their fertilization success in a high CO2 future ocean. Resultant changes in offspring production could affect recruitment success and population fitness downstream.