The binding of glycosaminoglycans to peptides : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Biochemistry at Massey University

The overall aim this study was to examine the possibility of using immobilised polypeptide chains to fractionate/separate Glycosaminoglycans (GAG's) from mixtures. Initially individual samples of three GAG classes (chondroitin sulphate, dermatan sulphate and heparin) were characterised to establish purity and provide basic information. Once these samples had been characterised the samples were treated as standards. Three short poly-l-lysine (PLL) chains with defined length and orientation were synthesized. As a control a PLL chain with 633 residues was immobilised. The interaction of the GAG standards with these resins did not replicate published solution binding behaviour of longer PLL chains. This suggested a different mode of binding. The interaction of two lengths of PLL (126 and 633 residues) and the K8G peptide with the GAG standards in solution was investigated. These studies demonstrated that the mode of binding of GAG's to short PLL chains was radically different to the earlier reported solution binding studies. β-Strand dominates with the short PLL chains instead of α-helix established in the published solution binding studies. The interaction of two peptides PCI (264-283) and thrombospondin peptide with the GAG standards was studied using circular dichroism spectroscopy. In the case of the PCI peptide, each GAG induced different secondary structures. Chondroitin sulphate and heparin induced an α-helix, whereas dermatan sulphate gave β-strands. Heparin and dermatan sulphate induced double the amount of secondary structure compared to chondroitin sulphate. The strength of the interaction of GAG's with the peptide was also measured by the concentration of salt required to dissociate 50% of the complex. The figures for dermatan sulphate and heparin were found to be 0.1 and 0.3 M salt respectively. The binding of the GAG standards to the thrombospondin peptide did not elicit any detectable change in conformation of the peptide. Critical examination of published material on the interaction of GAG's (principally heparin) with short peptides, prompted the writer to propose two new complementary models. The first model examines binding in terms of the conformation of the peptide induced by binding to the GAG. It is composed of three components, the periodicity of polar and nonpolar residues within the peptide sequence, the spacing of pairs of basic residues and the spacing of pairs of acidic and basic residues. This model is successfully able to rationalise the binding behaviour of a number of GAG/peptide interactions in terms of the dominant secondary structure and the biological activity. The model is able to make a number of specific predictions. The second model examines the strength of the interaction between heparin and peptides containing the proposed consensus sequences for GAG binding sites. A significant correlation between the binding strength and an attribute derived from the sequence of the peptide was found using only one assumption. The assumption was that the peptides in the correlation bound to heparin with significant levels of β-strand. For the first time it is possible to rationalise the behaviour of GAG/peptide interactions in a coherent manner. The design of peptides that are capable of binding to specific GAG's now seems possible

New constraints on the tau neutrino mass and fourth generation mixing

We present new constraints on the mass $m_{\nu_\tau}$ of the tau neutrino and its mixing with a fourth generation neutrino. From an analysis of the partial widths of tau lepton decays we obtain the following bounds at the 90% confidence level: $m_{\nu_\tau} < 32$ MeV and $\sin^2\theta < 0.007$, where $\theta$ describes the Cabibbo-like mixing of the third and fourth generation neutrinos.Comment: 2 pages, no figures. Submitted to Phys. Rev.

Anger and assaultiveness of male forensic patients with developmental disabilities : links to volatile parents

This study with 107 male forensic patients with developmental disabilities investigated whether exposure to parental anger and aggression was related to anger and assaultiveness in a hospital, controlling for background variables. Patient anger and aggression were assessed by self-report, staff-ratings, and archival records. Exposure to parental anger/aggression, assessed by a clinical interview, was significantly related to patient self-reported anger, staff-rated anger and aggression, and physical assaults in hospital, controlling for age, intelligence quotient, length of hospital stay, violent offense history, and childhood physical abuse. Results are consonant with previous findings concerning detrimental effects of witnessing parental violence and with the theory on acquisition of cognitive scripts for aggression. Implications for clinical assessment and cognitive restructuring in anger treatment are discussed

The Lack Of An Empirical Rationale For A Revival Of Discretionary Fiscal Policy

Finanzpolitik; Diskretionäre Politik; Kritik; Steuerbegünstigung; USA

The Robustness and Efficiency of Monetary Policy Rules as Guidelines for Interest Rate Setting by the European Central Bank

This paper examines the implications of recent research on monetary policy rules for practical monetary policy making, with special emphasis on strategies for setting interest rates by the new European Central Bank (ECB). The paper draws on recent research and new simulations of a large open economy model to assess the efficiency of a simple benchmark rule in comparison with other proposed rules. The paper stresses new results on the robustness of monetary policy rules in which each rule that is optimal or good according to one model or researcher is tested for robustness by other researchers using different models. Because of the large increase in the number of economists focussing on econometric evaluation of monetary policy rules for the interest rate instrument and because of the parallel increase in the variety of models being developed for this purpose, much more evidence is becoming available on the robustness of simle monetary policy rules for the interest rate than ever before.monetary policy rules; interest rate; efficiency; robustness; European Central Bank;

Low Inflation, Deflation, and Policies for Future Price Stability

The effects of three different inflationary environments--high inflation, low inflation, and negative inflation--on real output stability are examined by looking at the experiences of Japan and the United States during the last 30 years. I begin by going back to see how things looked from the vantage point of the 1987 international conference at the Bank of Japan. Next I trace out how economic performance has evolved since then. Economic performance appears to have been better with low inflation than with either high inflation or negative inflation. I also look at some of the reasons for the different inflationary environments. I take both an interest rate policy rule approach and a quantity theory of money approach. Both approaches suggest that monetary policy has been the key factor in generating the different inflationary experiences.