Synthesis and biological evaluation of nonpeptide mimetics of co-conotoxin GVIA

A benzothiazole-derived compound (4a) designed to mimic the C-alpha-C-beta bond vectors and terminal functionalities of Lys2, TyrI3 and Arg17 in omega-conotoxin GVIA was synthesised, together with analogues (4b-d), which had each side-chain mimic systematically truncated or eliminated. The affinity of these compounds for rat brain N-type and P/Q-type voltage gated calcium channels (VGCCs) was determined. In terms of N-type channel affinity and selectivity, two of these compounds (4a and 4d) were found to be highly promising, first generation mimetics of omega-conotoxin. The fully functionalised mimetic (4a) showed low PM binding affinity to N-type VGCCs (IC50 = 1.9 muM) and greater than 20-fold selectivity for this channel sub-type over P/Q-type VGCCs, whereas the mimetic in which the guanidine-type side chain was truncated back to an amine (4d, IC50 = 4.1 muM) showed a greater than 25-fold selectivity for the N-type channel. (C) 2004 Elsevier Ltd. All rights reserved.

Perceptions of organisational subculture and their significance for organisational commitment

This paper investigates the relationship between perceptions of organisational culture, organisational subculture, leadership style, and commitment. The impact of culture and leadership style on commitment has been previously noted, but there is a lack of detail regarding how different types of culture and leadership styles relate to commitment. The paper particularly addresses the notion of organisational subcultures and how the perception of those cultures relates to commitment, subculture being a neglected variable in the commitment literature. These issues were addressed in a survey of 258 nurses drawn from a range of hospital settings and wards within the Sydney metropolitan region. Results indicate that perceived organisational subculture has a strong relationship with commitment. Furthermore, the results identify the relative strength of specific types of leadership style and specific types of subculture with commitment. Both innovative and supportive subcultures have a clear positive relationship, while bureaucratic subcultures have a negative relationship. In terms of leadership style, a consideration style had a stronger relationship with commitment than a structuring style. Regression analysis was used to investigate the possible role of subculture as a mediator for the influence of leadership on commitment. Both direct and indirect effects of leadership on commitment were found. Implications for practice and for further research are discussed.

Finding temporal features of event-oriented patterns

A major task of traditional temporal event sequence mining is to predict the occurrences of a special type of event (called target event) in a long temporal sequence. Our previous work has defined a new type of pattern, called event-oriented pattern, which can potentially predict the target event within a certain period of time. However, in the event-oriented pattern discovery, because the size of interval for prediction is pre-defined, the mining results could be inaccurate and carry misleading information. In this paper, we introduce a new concept, called temporal feature, to rectify this shortcoming. Generally, for any event-oriented pattern discovered under the pre-given size of interval, the temporal feature is the minimal size of interval that makes the pattern interesting. Thus, by further investigating the temporal features of discovered event-oriented patterns, we can refine the knowledge for the target event prediction.