Search

Mutations within the β-amyloid peptide (Aβ) sequence that cause early onset familial Alzheimer's disease (FAD) have been shown to promote Aβ aggregation. How these FAD-related mutants increase the aggregative ability of Aβ is not fully understood. Here, we characterized the effect of the Arctic variant (E22G) on the conformational stability of Aβ using various forms of spectroscopy and kinetic analyses, including nuclear magnetic resonance (NMR), circular dichroism (CD) spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy and transmission electron microscopy (TEM). The E22G mutation in the Arctic variant reduced the α-helical propensity and conformational stability of Aβ on residues 15-25. This mutation also caused an increase in both α-helix-to-β-strand conversion and fibril nucleation rates. Our results suggest that the α-helical propensity of residues 15-25 may play a determinant role in the aggregative ability of Aβ. This may provide a structural basis for understanding the molecular mechanism of Aβ aggregation. [ABSTRACT FROM AUTHOR]

This study develops a series of models for designing an air cargo network, including flight frequencies, aircraft types and routes, that minimises the total logistics cost. The time value of cargo, economies of scale, and route distance are considered in the hub-and-spoke network design. We calculate the boundaries of the type of aircraft to be used and the route selection, thereby providing airlines with efficient decision-making tools to respond to variations in both the cargo flow and the distance of a route. In addition, this study analyses how fluctuations in demand affect the optimal network design, and evaluates its reliability. The evaluation results show that due to flow consolidation of a hub-and-spoke system, the impact of demand fluctuations can be intensified. Airlines adopting a hub-and-spoke system ought to plan their routes and flights with sufficient flexibility in order to respond to sudden events. [ABSTRACT FROM AUTHOR]

Background: There are few reports of Pseudomonas aeruginosa liver abscess (PALA) in the literature, and clinical information regarding its risk factors, route of transmission, and clinical course remains limited. Methods: The medical records of 1076 patients with pyogenic liver abscess treated at Chang Gung Memorial Hospital were reviewed. Results: Twenty of the patients whose records were analyzed had PALA. Mortality was 20%. Five patients with PALA, diagnosed immediately following an intra-abdominal surgical or endoscopic procedure, were classified as group A. The latent phase for the development of PALA in this group was less than 3 weeks. The remaining 15 patients were further subgrouped into group B ( n = 8), with a traceable intra-abdominal procedure, and group C ( n = 7), with no history of an invasive intra-abdominal procedure. The latent period in patients in group B varied from 6 weeks to 3.7 y. The absence of multidrug resistance in P. aeruginosa isolates from group C suggests the community-acquired nature of the infection in this group. Risk factor analysis showed that the incidence of hepatobiliary co-morbidities was high in all the groups (100%, 88%, and 71% in groups A, B, and C, respectively). The rates of co-infection with human gastrointestinal tract flora were 20%, 50%, and 71% in groups A, B, and C, respectively. Conclusions: PALA may be found in subjects without conventional risk factors for P. aeruginosa infection. In addition to patients with a preceding contaminated procedure, those with hepatobiliary co-morbidities form another high-risk group for this condition. [ABSTRACT FROM AUTHOR]