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.

Relaxin stimulates leukocyte adhesion and migration through a relaxin receptor LGR7-dependent mechanism

Leukocytes are critical effectors of inflammation and tumor biology. Chemokine-like factors produced by such inflammatory sites are key mediators of tumor growth that activate leukocytic recruitment and tumor infiltration and suppress immune surveillance. Here we report that the endocrine peptide hormone, relaxin, is a regulator of leukocyte biology with properties important in recruitment to sites of inflammation. This study uses the human monocytic cell line THP-1 and normal human peripheral blood mononuclear cells to define a novel role for relaxin in regulation of leukocyte adhesion and migration. Our studies indicate that relaxin promotes adenylate cyclase activation, substrate adhesion, and migratory capacity of mononuclear leukocytes through a relaxin receptor LGR7-dependent mechanism. Relaxin-stimulated cAMP accumulation was observed to occur primarily in non-adherent cells. Relaxin stimulation results in increased substrate adhesion and increased migratory activity of leukocytes. In addition, relaxin-stimulated substrate adhesion resulted in enhanced chemotaxis to monocyte chemoattractant protein-1. These responses in THP-1 and peripheral blood mononuclear cells are relaxin dose-dependent and proportional to cAMP accumulation. We further demonstrate that LGR7 is critical for mediating these biological responses by use of RNA interference lentiviral short hairpin constructs. In summary, we provide evidence that relaxin is a novel leukocyte stimulatory agent with properties affecting adhesion and chemomigration

The aftermath of the Lehman Brothers collapse in Hong Kong : the saga, regulatory deficiencies and government responses

The paper examines the fallout of the Lehman Brothers collapse in Hong Kong. As an international financial hub in Asia, Hong Kong was profoundly affected by the collapse of this company. As a result, it impacted negatively on the public’s confidence in the Hong Kong’s banking sector. Furthermore, this event has exposed a number of regulatory deficiencies in Hong Kong. In response to this financial crisis, the Hong Kong government had made an unprecedented move to negotiate with local banks to refund the investors. In addition, the government has also sought public consultation on proposal to enhance the regulation of the sale of financial products. This paper argues that there needs to be amendments to the prevailing laws and the inclusions of legal rules to back up those proposed measures so that the disclosed information from the financial institution will not mislead the investors or misrepresent the products offered.

Thomas Young's contribution to visual optics : the Bakerian lecture "On the mechanism of the eye"

Thomas Young (1773-1829) carried out major pioneering work in many different subjects. In 1800 he gave the Bakerian Lecture of the Royal Society on the topic of the “mechanism of the eye”: this was published in the following year (Young, 1801). Young used his own design of optometer to measure refraction and accommodation, and discovered his own astigmatism. He considered the different possible origins of accommodation and confirmed that it was due to change in shape of the lens rather than to change in shape of the cornea or an increase in axial length. However, the paper also dealt with many other aspects of visual and ophthalmic optics, such as biometric parameters, peripheral refraction, longitudinal chromatic aberration, depth-of-focus and instrument myopia. These aspects of the paper have previously received little attention. We now give detailed consideration to these and other less-familiar features of Young’s work and conclude that his studies remain relevant to many of the topics which currently engage visual scientists.

A regulatory on-board mass monitoring application for heavy vehicles in Australia

This paper reports on the development of specifications for an on-board mass monitoring (OBM) application for regulatory requirements in Australia. An earlier paper reported on feasibility study and pilot testing program prior to the specification development [1]. Learnings from the pilot were used to refine this testing process and a full scale testing program was conducted from July to October 2008. The results from the full scale test and evidentiary implications are presented in this report. The draft specification for an evidentiary on-board mass monitoring application is currently under development.

Franchisor failure : an assessment of the adequacy of regulatory response

Franchisor failure is one of the most problematic areas of the franchise relationship. It impacts negatively on landlords and other suppliers, but the contracting parties that are currently without legal rights to respond when a franchisor fails, and thus without consumer protection, are its franchisees. In this thesis I explore the current contractual, regulatory and commercial environment that franchisees inhabit, within the context of franchisor failure. I conclude that ex ante there are opportunities to level the playing field through consumer protection legislation. I also conclude that the task is not one solely for the consumer protection legislation; the problem should also be addressed ex post through the Corporations Act.

Mechanism of Resistance to Rice Tungro Spherical Virus (RTSV)

RTSV is one of two viruses that cause tungro disease. RTSV is independently transmitted, whereas the other virus, rice tungro bacilliform virus (RTBV), is dependent on RTSV for its transmission by the green leafhopper (GLH), Nephotettix virescens. The occurrence and spread of tungro disease therefore depend on the presence of RTSV in the field. Resistance to RTSV infection would slow down the spread of the disease.

Public regulatory reform and management earnings forecasts in a low private litigation environment

We examine the impact of continuous disclosure regulatory reform on the likelihood, frequency and qualitative characteristics of management earnings forecasts issued in New Zealand’s low private litigation environment. Using a sample of 720 earnings forecasts issued by 94 firms listed on the New Zealand Exchange before and after the reform (1999–2005), we provide strong evidence of significant changes in forecasting behaviour in the post-reform period. Specifically, firms were more likely to issue earnings forecasts to pre-empt earnings announcements and, in contrast to findings in other legal settings, those earnings forecasts exhibited higher frequency and improved qualitative characteristics (better precision and accuracy). An important implication of our findings is that public regulatory reforms may have a greater benefit in a low private litigation environment and thus add to the global debate about the effectiveness of alternative public regulatory reforms of corporate requirements.

An intelligent building model of sustainable architecture in a mechanism of open systems evolution

This paper argues a model of open systems evolution based on evolutionary thermodynamics and complex system science, as a design paradigm for sustainable architecture. The mechanism of open system evolution is specified in mathematical simulations and theoretical discourses. According to the mechanism, the authors propose an intelligent building model of sustainable design by a holistic information system of the end-users, the building and nature. This information system is used to control the consumption of energy and material resources in building system at microscopic scale, to adapt the environmental performance of the building system to the natural environment at macroscopic scale, for an evolutionary emergence of sustainable performance of buildings.

Optimal voltage support mechanism in distribution networks

Optimal scheduling of voltage regulators (VRs), fixed and switched capacitors and voltage on customer side of transformer (VCT) along with the optimal allocaton of VRs and capacitors are performed using a hybrid optimisation method based on discrete particle swarm optimisation and genetic algorithm. Direct optimisation of the tap position is not appropriate since in general the high voltage (HV) side voltage is not known. Therefore, the tap setting can be determined give the optimal VCT once the HV side voltage is known. The objective function is composed of the distribution line loss cost, the peak power loss cost and capacitors' and VRs' capital, operation and maintenance costs. The constraints are limits on bus voltage and feeder current along with VR taps. The bus voltage should be maintained within the standard level and the feeder current should not exceed the feeder-rated current. The taps are to adjust the output voltage of VRs between 90 and 110% of their input voltages. For validation of the proposed method, the 18-bus IEEE system is used. The results are compared with prior publications to illustrate the benefit of the employed technique. The results also show that the lowest cost planning for voltage profile will be achieved if a combination of capacitors, VRs and VCTs is considered.