To what extent has research conducted by the GaWC Research Network aided our understanding of large EU law firm geography?

This thesis explores whether a specific group of large EU law firms exhibited multiple common behaviours regarding their EU geographies between 1998 and 2009. These potentially common behaviours included their preferences for trading in certain EU locations, their usage of law firm alliances, and the specific reasons why they opened or closed EU branch offices. If my hypothesis is confirmed, this may indicate that certain aspects of large law firm geography are predictable – a finding potentially of interest to various stakeholders globally, including legal regulators, academics and law firms. In testing my hypothesis, I have drawn on research conducted by the Globalization and World Cities (GaWC) Research Network to assist me. Between 1999 and 2010, the GaWC published seven research papers exploring the geographies of large US and UK law firms. Several of the GaWC’s observations arising from these studies were evidence-based; others were speculative – including a novel approach for explaining legal practice branch office change, not adopted in research conducted previously or subsequently. By distilling the GaWC’s key observations these papers into a series of “sub-hypotheses”, I been able to test whether the geographical behaviours of my novel cohort of large EU law firms reflect those suggested by the GaWC. The more the GaWC’s suggested behaviours are observed among my cohort, the more my hypothesis will be supported. In conducting this exercise, I will additionally evaluate the extent to which the GaWC’s research has aided our understanding of large EU law firm geography. Ultimately, my findings broadly support most of the GaWC’s observations, notwithstanding our cohort differences and the speculative nature of several of the GaWC’s propositions. My investigation has also allowed me to refine several of the GaWC’s observations regarding commonly-observable large law firm geographical behaviours, while also addressing a key omission from the group’s research output.

The role of acute ambient hypoxia in the regulation of myostatin

When exposed to chronic hypoxia by pathophysiological or environmental causes humans show muscle atrophy, challenging homeostasis and increasing mortality rate. Chronic hypoxia also presents with elevated myostatin peptide, a negative regulator of muscle size. This work induced acute hypoxia in healthy individuals; hypothesizing hypoxia would increase myostatin expression in both muscle and plasma in a concentration- and time-dependent manner. Hypoxia (1 % O2) reduced C2C12 myoblast migration and myotube size in vitro. Myotube atrophy was time-dependent, longer exposures showed greater atrophy. Intracellular myostatin peptide was decreased at every time point measured. Myostatin and downstream signalling pathways in muscle showed a high degree of percentage similarity between mouse and human, when amino acid sequences were directly compared. Healthy males (N = 8) were exposed to 20.9 % O2 or 11.9 % O2 for 2 hours. Following hypoxic exposure myostatin peptide was reduced in muscle but not plasma, relative to control conditions. A second cohort (N = 8) was exposed to 12.5 % O2 for 10 hours. Plasma myostatin was decreased following hypoxia, muscle myostatin trended towards increasing. A third cohort (N = 9; n = 8 lowlander, n = 1 Sherpa) was exposed to 10.7 % or 12.3 % O2 for 2 hours. Plasma myostatin was reduced at both concentrations with no difference between concentrations noted. In response to chronic hypoxia, individuals lose muscle mass. Counter to the hypothesis of an increase in myostatin in both muscle and plasma, here a consistent decrease in plasma myostatin following acute hypoxia is seen. Muscle myostatin shows a variable response, with decreasing intracellular expression seen following a 2 hour hypoxic exposure, and trends towards an increase following 10 hours of hypoxia. Decreases in plasma and muscle myostatin may represent myostatin’s movement towards peripheral compartments in these acute timeframes. Hypoxia alone is capable of altering myostatin in healthy individuals; the effects of hypoxia on myostatin appear to differ between the acute timeframes examined here and chronic exposures in environmental or disease models.