On democracy

If one clear argument emerged from my doctoral thesis in political science, it is that there is no agreement as to what democracy is. There are over 40 different varieties of democracy ranging from those in the mainstream with subtle or minute differences to those playing by themselves in the corner. And many of these various types of democracy are very well argued, empirically supported, and highly relevant to certain polities. The irony is that the thing which all of these democratic varieties or the ‘basic democracy’ that all other forms of democracy stem from, is elusive. There is no international agreement in the literature or in political practice as to what ‘basic democracy’ is and that is problematic as many of us use the word ‘democracy’ every day and it is a concept of tremendous importance internationally. I am still uncertain as to why this problem has not been resolved before by far greater minds than my own, and it may have something to do with the recent growth in democratic theory this past decade and the innovative areas of thought my thesis required, but I think I’ve got the answer. By listing each type of democracy and filling the column next to this list with the literature associated with these various styles of democracy, I amassed a large and comprehensive body of textual data. My research intended to find out what these various styles of democracy had in common and to create a taxonomy (like the ‘tree of life’ in biology) of democracy to attempt at showing how various styles of democracy have ‘evolved’ over the past 5000 years.ii I then ran a word frequency analysis program or a piece of software that counts the 100 most commonly used words in the texts. This is where my logic came in as I had to make sense of these words. How did they answer what the most fundamental commonalities are between 40 different styles of democracy? I used a grounded theory analysis which required that I argue my way through these words to form a ‘theory’ or plausible explanation as to why these particular words and not others are the important ones for answering the question. It came down to the argument that all 40 styles of democracy analysed have the following in common 1) A concept of a citizenry. 2) A concept of sovereignty. 3) A concept of equality. 4) A concept of law. 5) A concept of communication. 6) And a concept of selecting officials. Thus, democracy is a defined citizenry with its own concept of sovereignty which it exercises through the institutions which support the citizenry’s understandings of equality, law, communication, and the selection of officials. Once any of these 6 concepts are defined in a particular way it creates a style of democracy. From this, we can also see that there can be more than one style of democracy active in a particular government as a citizenry is composed of many different aggregates with their own understandings of the six concepts.

The mechanism of maturation of insulin-like growth factor-1

This study, to elucidate the role of des(1-3)IGF-I in the maturation of IGF-I,used two strategies. The first was to detect the presence of enzymes in tissues, which would act on IGF-I to produce des(1-3)IGF-I, and the second was to detect the potential products of such enzymic activity, namely Gly-Pro-Glu(GPE), Gly-Pro(GP) and des(l- 3)IGF-I. No neutral tripeptidyl peptidase (TPP II), which would release the tripeptide GPE from IGF-I, was detected in brain, urine nor in red or white blood cells. The TPPlike activity which was detected, was attributed to a combined action of a dipeptidyl peptidase (DPP N) and an aminopeptidase (AP A). A true TPP II was, however, detected in platelets. Two purified TPP II enzymes were investigated but they did not release GPE from IGF-I under a variety of conditions. Consequently, TPP II seemed unlikely to participate in the formation of des(1-3)IGF-I. In contrast, an acidic tripeptidyl peptidase activity (TPP I) was detected in brain and colostrum, the former with a pH optimum of 4.5 and the latter 3.8. It seems likely that such an enzyme would participate in the formation of des( 1-3 )IGF-I in these tissues in vitro, ie. that des(1-3)IGF-I may have been produced as an artifact in the isolation of IGF-I from brain and colostrum in acidic conditions. This contrasts with suggestions of an in vivo role for des(1-3)IGF-I, as reported by others. The activity of a dipeptidyl peptidase N (DPP N) from urine, which should release the dipeptide GP from IGF-I, was assessed under a variety of conditions and with a variety of additives and potential enzyme stimulants, but there was no release of GP. The DPP N also exhibited a transferase activity with synthetic substrates in the presence of dipeptides, at lower concentrations than previously reported for other acceptors or other proteolytic enzymes. In addition, a low concentration of a product,possibly the tetrapeptide Gly-Pro-Gly-Leu, was detected with the action of the enzyme on IGF-I in the presence of the dipeptide Gly-Leu. As part of attempts to detect tissue production of des(1-3)IGF-I, a monoclonal antibody (MAb ), directed towards the GPE- end ofiGF-I was produced by immunisation with a 10-mer covalently attached to a carrier protein. By the use of indirect ELISA and inhibitor studies, the MAb was shown to selectively recognise peptides with anNterminal GPE- sequence, and applied to the indirect detection of des(1-3)IGF-I. The concentration of GPE in brain, measured by mass spectrometry ( MS), was low, and the concentration of total IGF-I (measured by ELISA with a commercial polyclonal antibody [P Ab]) was 40 times higher at 50 nmol/kg. This also, was not consistent with the action of a tripeptidyl peptidase in brain that converted all IGF-I to des(1-3)IGF-I plus GPE. Contrasting ELISA results, using the MAb prepared in this study, suggest an even higher concentration of intact IGF-I of 150 nmollkg. This would argue against the presence of any des( 1-3 )IGF-I in brain, but in turn, this indicates either the presence of other substances containing a GPE amino-terminus or other cross reacting epitope. Although the results of the specificity studies reported in Chapter 5 would make this latter possibility seem unlikely, it cannot be completely excluded. No GP was detected in brain by MS. No GPE was detected in colostrum by capillary electrophoresis (CE) but the interference from extraneous substances reduced the detectability of GPE by CE and this approach would require further, prior, purification and concentration steps. A molecule, with a migration time equal to that of the peptide GP, was detected in colostrum by CE, but the concentration (~ 10 11mo/L) was much higher than the IGF-I concentration measured by radio-immunoassay using a PAb (80 nmol/L) or using a Mab (300-400 nmolL). A DPP IV enzyme was detected in colostrum and this could account for the GP, derived from substrates other than IGF-1. Based on the differential results of the two antibody assays, there was no indication of the presence of des(1-3)IGF-I in brain or colostrum. In the absence of any enzyme activity directed towards the amino terminus of IGF-I and the absence any potential products, IGF-I, therefore, does not appear to "mature" via des(1-3)IGF-I in the brain, nor in the neutral colostrum. In spite of these results which indicate the absence of an enzymic attack on IGF-I and the absence of the expected products in tissues, the possibility that the conversion of IGF-I may occur in neutral conditions in limited amounts, cannot be ruled out. It remains possible that in the extracellular environment of the membrane, a complex interaction of IGF-I, binding protein, aminopeptidase(s) and receptor, produces des(1- 3)IGF-I as a transient product which is bound to the receptor and internalised.