Limited proteolysis in the investigation of beta2-microglobulin amyloidogenic and fibrillar states.

Amyloid fibrils of patients treated with regular haemodialysis essentially consists of β2-microglobulin (β2-m) and its truncated species ΔN6β2-m lacking six residues at the amino terminus. The truncated fragment shows a higher propensity to self-aggregate and constitutes an excellent candidate for the analysis of a protein in the amyloidogenic conformation. The surface topology and the conformational analysis of native β2-m and the truncated ΔN6β2-m species both in the soluble and in the fibrillar forms were investigated by the limited proteolysis/mass spectrometry strategy. The conformation in solution of a further truncated mutant ΔN3β2-m lacking three residues at the N-terminus was also examined. This approach appeared particularly suited to investigate the regions that are solvent-exposed, or flexible enough to be accessible to protein-protein interactions and to describe the conformation of transient intermediates. Moreover, proteolysis experiments can also be tailored to investigate amyloid fibrils by discriminating the protein regions constituting the unaccessible core of the fibrils and those still flexible and exposed to the solvent. Although native β2-m and ΔN3β2-m shared essentially the same conformation, significative structural differences exist between the native and the ΔN6β2-m proteins in solution with major differences located at the end moiety of strand V and subsequent loop with strand VI and at both the N- and C-termini of the proteins. On the contrary, an identical distribution of preferential proteolytic sites was observed in both proteins in the fibrillar state, which was nearly superimposible to that observed for the soluble form of ΔN6β2-m. These data revealed that synthetic fibrils essentially consists of an unaccessible core comprising residues 20-87 of the β2-m protein with exposed and flexible N- and C-terminal ends. Moreover, proteolytic cleavages observed in vitro at Lys 6 and Lys 19 reproduce specific cleavages that have to take place in vivo to generate the truncated forms of β2-m occurring in natural fibrils. On the basis of these results, a molecular mechanism for fibril formation has been propose

The value relevance of effective investor relations

In this study, we test formally the market value of investor relations (IR) activity employing the annual Investor Relations Magazine Best Overall IR Awards data from 2000 to 2002 to proxy for the quality of firm investor relations. We find firms perceived by survey respondents to have effective IR strategies have significantly higher market value, and, also, earn superior abnormal returns, both before and after the award nominations. We also find that, not surprisingly, higher analyst following is associated with more nominations, suggesting analysts tend to favor the stocks they follow, although being nominated for best overall IR is also consistent with a significant increase in analyst following in the following year. Finally, in line with effective IR leading to lower information risk, liquidity of nominated firms, measured by stock turnover, increases in the year subsequent to the award nominations. Overall, our evidence is consistent with good IR successfully reducing the risk to investors associated with high information asymmetry, as predicted by information risk and agency theories

A Bayesian Networks Approach to Operational Risk

A system for Operational Risk management based on the computational paradigm of Bayesian Networks is presented. The algorithm allows the construction of a Bayesian Network targeted for each bank using only internal loss data, and takes into account in a simple and realistic way the correlations among different processes of the bank. The internal losses are averaged over a variable time horizon, so that the correlations at different times are removed, while the correlations at the same time are kept: the averaged losses are thus suitable to perform the learning of the network topology and parameters. The algorithm has been validated on synthetic time series. It should be stressed that the practical implementation of the proposed algorithm has a small impact on the organizational structure of a bank and requires an investment in human resources limited to the computational area

Universality of three-body systems in 2D: parametrization of the bound states energies

Universal properties of mass-imbalanced three-body systems in 2D are studied using zero-range interactions in momentum space. The dependence of the three-particle binding energy on the parameters (masses and two-body energies) is highly non-trivial even in the simplest case of two identical particles and a distinct one. This dependence is parametrized for ground and excited states in terms of {\itshape supercircles} functions in the most general case of three distinguishable particles.Comment: 3 pages, 1 figure, published versio

Nucleon decay and atmospheric neutrinos in the Mont Blanc experiment

In the NUSEX experiment, during 2.8 years of operation, 31 fully contained events have been collected; 3 among them are nucleon decay candidates, while the others have been attributed to upsilon interactions. Limits on nucleon lifetime and determinations of upsilon interaction rates are presented