Natural and engineered kallikrein inhibitors: an emerging pharmacopoeia

The kallikreins and kallikrein-related peptidases are serine proteases that control a plethora of developmental and homeostatic phenomena, ranging from semen liquefaction to skin desquamation and blood pressure. The diversity of roles played by kallikreins has stimulated considerable interest in these enzymes from the perspective of diagnostics and drug design. Kallikreins already have well-established credentials as targets for therapeutic intervention and there is increasing appreciation of their potential both as biomarkers and as targets for inhibitor design. Here, we explore the current status of naturally occurring kallikrein protease-inhibitor complexes and illustrate how this knowledge can interface with strategies for rational re-engineering of bioscaffolds and design of small-molecule inhibitors.

Living well with diabetes: a randomized controlled trial of a telephone-delivered intervention for maintenance of weight loss, physical activity and glycaemic control in adults with type 2 diabetes

Background By 2025, it is estimated that approximately 1.8 million Australian adults (approximately 8.4% of the adult population) will have diabetes, with the majority having type 2 diabetes. Weight management via improved physical activity and diet is the cornerstone of type 2 diabetes management. However, the majority of weight loss trials in diabetes have evaluated short-term, intensive clinic-based interventions that, while producing short-term outcomes, have failed to address issues of maintenance and broad population reach. Telephone-delivered interventions have the potential to address these gaps. Methods/Design Using a two-arm randomised controlled design, this study will evaluate an 18-month, telephone-delivered, behavioural weight loss intervention focussing on physical activity, diet and behavioural therapy, versus usual care, with follow-up at 24 months. Three-hundred adult participants, aged 20-75 years, with type 2 diabetes, will be recruited from 10 general practices via electronic medical records search. The Social-Cognitive Theory driven intervention involves a six-month intensive phase (4 weekly calls and 11 fortnightly calls) and a 12-month maintenance phase (one call per month). Primary outcomes, assessed at 6, 18 and 24 months, are: weight loss, physical activity, and glycaemic control (HbA1c), with weight loss and physical activity also measured at 12 months. Incremental cost-effectiveness will also be examined. Study recruitment began in February 2009, with final data collection expected by February 2013. Discussion This is the first study to evaluate the telephone as the primary method of delivering a behavioural weight loss intervention in type 2 diabetes. The evaluation of maintenance outcomes (6 months following the end of intervention), the use of accelerometers to objectively measure physical activity, and the inclusion of a cost-effectiveness analysis will advance the science of broad reach approaches to weight control and health behaviour change, and will build the evidence base needed to advocate for the translation of this work into population health practice.

Measuring transit service reliability using data from web-based transit user survey : a case study at Brisbane, Australia

This paper reports an empirical study on measuring transit service reliability using the data from a Web-based passenger survey on a major transit corridor in Brisbane, Australia. After an introduction of transit service reliability measures, the paper presents the results from the case study including study area, data collection, and reliability measures obtained. This includes data exploration of boarding/arrival lateness, in-vehicle time variation, waiting time variation, and headway adherence. Impacts of peak-period effects and separate operation on service reliability are examined. Relationships between transit service characteristics and passenger waiting time are also discussed. A summary of key findings and an agenda of future research are offered in conclusions.

Critical gap estimation by numerical and statistical highest likelihood search

Many traffic situations require drivers to cross or merge into a stream having higher priority. Gap acceptance theory enables us to model such processes to analyse traffic operation. This discussion demonstrated that numerical search fine tuned by statistical analysis can be used to determine the most likely critical gap for a sample of drivers, based on their largest rejected gap and accepted gap. This method shares some common features with the Maximum Likelihood Estimation technique (Troutbeck 1992) but lends itself well to contemporary analysis tools such as spreadsheet and is particularly analytically transparent. This method is considered not to bias estimation of critical gap due to very small rejected gaps or very large rejected gaps. However, it requires a sufficiently large sample that there is reasonable representation of largest rejected gap/accepted gap pairs within a fairly narrow highest likelihood search band.

Raman microscopy study of tyrolite : a multi-anion arsenate mineral

The Raman spectrum of tyrolite, CaCu5(AsO4)2(CO3)(OH) 4.6H2O, from Brixlegg, Tyrol, Austria, is reported. Comparison with copper hydroxy-arsenate and basic carbonates was used to achieve assignments of the observed bands. The AsO43- group is characterized by two υ4 modes around 433 and 480 cm-1 plus a broad band around 840 cm-1 as the υ overlapping with the υ. The υ3 mode is observed as a single band around 355 cm -1. The CO32- υ1 mode is observed around 1035 and 1088 cm-1, although this assignment is difficult because of the in-plane OH bending vibrations at similar frequencies. Two υ4 modes are assigned to the 717 and 755 cm-1 bands. The υ3 mode is present as three bands at 1431, 1463, and 1498 cm-1. A large split caused by bridging carbonates may explain the band at 1370 cm -1. The H2O bending region shows two bands at 1635 and 1667 cm-1 together with stretching modes around 3204 and 3303 cm-1, the first associated with adsorbed H2O, while the second indicates more strongly bonded H2O. Three bands around 3534, 3438, and 3379 cm -1 are assigned to OH stretching modes of the OH groups in the crystal structure. The 202, 262, 301, 524, and 534 cm-1 bands are assigned to Cu-OH bending and stretching modes, whereas the bands around 179, 202, and 217 cm-1 are ascribed to O-(Ca, Cu)-O(H) with the O(H) at much greater distance from the cation. The bands around 503, 570, and 598 cm-1 are ascribed to the Cu-O stretching modes.

Empirical evaluation of an autonomous vehicle in an urban environment

Operation in urban environments creates unique challenges for research in autonomous ground vehicles. Due to the presence of tall trees and buildings in close proximity to traversable areas, GPS outage is likely to be frequent and physical hazards pose real threats to autonomous systems. In this paper, we describe a novel autonomous platform developed by the Sydney-Berkeley Driving Team for entry into the 2007 DARPA Urban Challenge competition. We report empirical results analyzing the performance of the vehicle while navigating a 560-meter test loop multiple times in an actual urban setting with severe GPS outage. We show that our system is robust against failure of global position estimates and can reliably traverse standard two-lane road networks using vision for localization. Finally, we discuss ongoing efforts in fusing vision data with other sensing modalities.