Exploring passenger rail markets using new station catchment size and shape metrics

This paper presents a novel spatial market segmentation method to determine key user groups of a train station (such as gender, age and access mode), based on the size and shape of the station catchment area of each group. Two new indices–area ratio and composite ratio–are developed to quantify the importance of user groups for a train station. This method is applied to identify key user groups at seven train stations in Perth, Western Australia. The study offers a new way to explore the travel behaviour of train users and provides insights for rail transport planning and marketing

Recovery of renal function in end-stage renal failure: comparison between peritoneal dialysis and haemodialysis

© The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.Background. Recovery of dialysis-independent renal function in long-term dialysis patients has not been studied extensively. The aim of this study was to investigate the effect of dialysis modality on the likelihood, timing and durability of recovery of dialysis-independent renal function. Methods. The study reviewed all patients in Australia and New Zealand who commenced dialysis for treatment of end-stage renal disease (ESRD) between 1963 and 2006. Dialysis modality was assigned at 90 days. A supplementary analysis was also conducted using a contemporary cohort that included data on comorbidities, smoking and eGFR at dialysis onset. Results. During the study period, 15 912 individuals received peritoneal dialysis (PD) and 23 658 received haemodialysis (HD). Renal recovery occurred in 176 (1.1%) PD and 244 (1.0%) HD patients. Using multivariate Cox proportional hazards regression analyses, dialysis modality was not independently predictive of time to renal recovery (HR 0.92, 95% CI 0.76–1.13, P = 0.4). Recovery was significantly more likely in patients with higher baseline eGFR, with no hypertension or peripheral vascular disease, and with certain causes of kidney failure (autoimmune renal disease, haemolytic uraemic syndrome, interstitial nephritis, obstructive uropathy, paraproteinaemia and renovascular nephrosclerosis). Recovery was less likely in Maori/Pacific Islanders and polycystic kidney disease. Among patients who recovered, 328 (78%) subsequently experienced renal death, mostly within the first year. The duration of renal recovery was not associated with initial dialysis modality (OR 0.82, 95% CI 0.50– 1.32). Conclusions. Dialysis modality is not associated with the likelihood, timing or durability of spontaneous recovery of dialysis-independent renal function in patients thought to have ESRD.James A. Macdonald, Stephen P. McDonald, Carmel M. Hawley, Johan Rosman, Fiona Brown, Kathryn J. Wiggins, Kym Bannister, and David W. Johnso

Magnetic nanoparticle-based isolation of endocytic vesicles reveals a role of the heat shock protein GRP75 in macromolecular delivery.

An increased understanding of cellular uptake mechanisms of macromolecules remains an important challenge in cell biology with implications for viral infection and macromolecular drug delivery. Here, we report a strategy based on antibody-conjugated magnetic nanoparticles for the isolation of endocytic vesicles induced by heparan sulfate proteoglycans (HSPGs), key cell-surface receptors of macromolecular delivery. We provide evidence for a role of the glucose-regulated protein (GRP)75/PBP74/mtHSP70/mortalin (hereafter termed "GRP75") in HSPG-mediated endocytosis of macromolecules. GRP75 was found to be a functional constituent of intracellular vesicles of a nonclathrin-, noncaveolin- dependent pathway that was sensitive to membrane cholesterol depletion and that showed colocalization with the membrane raft marker cholera toxin subunit B. We further demonstrate a functional role of the RhoA GTPase family member CDC42 in this transport pathway; however, the small GTPase dynamin appeared not to be involved. Interestingly, we provide evidence of a functional role of GRP75 using RNAi-mediated down-regulation of GRP75 and GRP75-blocking antibodies, both of which inhibited macromolecular endocytosis. We conclude that GRP75, a chaperone protein classically found in the endoplasmic reticulum and mitochondria, is a functional constituent of noncaveolar, membrane raft-associated endocytic vesicles. Our data provide proof of principle of a strategy that should be generally applicable in the molecular characterization of selected endocytic pathways involved in macromolecular uptake by mammalian cells

Visualizing odorant receptor trafficking in living cells down to the single-molecule level

Despite the importance of trafficking for regulating G protein-coupled receptor signaling, for many members of the seven transmembrane helix protein family, such as odorant receptors, little is known about this process in live cells. Here, the complete life cycle of the human odorant receptor OR17-40 was directly monitored in living cells by ensemble and single-molecule imaging, using a double-labeling strategy. While the overall, intracellular trafficking of the receptor was visualized continuously by using a GFP tag, selective imaging of cell surface receptors was achieved by pulse-labeling an acyl carrier protein tag. We found that OR17-40 efficiently translocated to the plasma membrane only at low expression, whereas at higher biosynthesis the receptor accumulated in intracellular compartments. Receptors in the plasma membrane showed high turnover resulting from constitutive internalization along the clathrin pathway, even in the absence of ligand. Single-molecule microscopy allowed monitoring of the early, dynamic processes in odorant receptor signaling. Although mobile receptors initially diffused either freely or within domains of various sizes, binding of an agonist or an antagonist increased partitioning of receptors into small domains of ≈190 nm, which likely are precursors of clathrin-coated pits. The binding of a ligand, therefore, resulted in modulation of the continuous, constitutive internalization. After endocytosis, receptors were directed to early endosomes for recycling. This unique mechanism of continuous internalization and recycling of OR17-40 might be instrumental in allowing rapid recovery of odor perception

Chronic and Acute Effects of Coal Tar Pitch Exposure and Cardiopulmonary Mortality Among Aluminum Smelter Workers

Air pollution causes several adverse cardiovascular and respiratory effects. In occupational studies, where levels of particulate matter and polycyclic aromatic hydrocarbons (PAHs) are higher, the evidence is inconsistent. The effects of acute and chronic PAH exposure on cardiopulmonary mortality were examined within a Kitimat, Canada, aluminum smelter cohort (n = 7,026) linked to a national mortality database (1957–1999). No standardized mortality ratio was significantly elevated compared with the province's population. Smoking-adjusted internal comparisons were conducted using Cox regression for male subjects (n = 6,423). Ischemic heart disease (IHD) mortality (n = 281) was associated with cumulative benzo[a]pyrene (B(a)P) exposure (hazard ratio = 1.62, 95% confidence interval: 1.06, 2.46) in the highest category. A monotonic but nonsignificant trend was observed with chronic B(a)P exposure and acute myocardial infarction (n = 184). When follow-up was restricted to active employment, the hazard ratio for IHD was 2.39 (95% confidence interval: 0.95, 6.05) in the highest cumulative B(a)P category. The stronger associations observed during employment suggest that risk may not persist after exposure cessation. No associations with recent or current exposure were observed. IHD was associated with chronic (but not current) PAH exposure in a high-exposure occupational setting. Given the widespread workplace exposure to PAHs and heart disease's high prevalence, even modest associations produce a high burden