How Industrial Distributors View Distributor-Supplier Partnership Arrangements

This nationwide survey reports distributors\u27 perspectives of their relationship with a core supplier. The survey reports on elements of partnership, expectations, outcomes, and satisfaction relating to the relationship\u27s position on a continuum between arm\u27s length and close partnership styles

How Industrial Distributors View Distributor-Supplier Partnership Arrangements

This nationwide survey reports distributors\u27 perspectives of their relationship with a core supplier. The survey reports on elements of partnership, expectations, outcomes, and satisfaction relating to the relationship\u27s position on a continuum between arm\u27s length and close partnership styles

Cellular and molecular pathology of age-related macular degeneration: Potential role for proteoglycans

Age-related macular degeneration (AMD) is a retinal disease evident after the age of 50 that damages the macula in the centre of retina. It leads to a loss of central vision with retained peripheral vision but eventual blindness occurs in many cases. The initiation site of AMD development is Bruch's membrane (BM) where multiple changes occur including the deposition of plasma derived lipids, accumulation of extracellular debris, changes in cell morphology, and viability and the formation of drusen. AMD manifests as early and late stage; the latter involves cell proliferation and neovascularization in wet AMD. Current therapies target the later hyperproliferative and invasive wet stage whilst none target early developmental stages of AMD. In the lipid deposition disease atherosclerosis modified proteoglycans bind and retain apolipoproteins in the artery wall. Chemically modified trapped lipids are immunogenic and can initiate a chronic inflammatory process manifesting as atherosclerotic plaques and subsequent artery blockages, heart attacks, or strokes. As plasma derived lipoprotein deposits are found in BM in early AMD, it is possible that they arise by a similar process within the macula. In this review we consider aspects of the pathological processes underlying AMD with a focus on the potential role of modifications to secreted proteoglycans being a cause and therefore a target for the treatment of early AMD

Platelet-derived growth factor-stimulated versican synthesis but not glycosaminoglycan elongation in vascular smooth muscle is mediated via Akt phosphorylation

Proteoglycans are associated with the initiation of atherosclerosis due to their binding of apolipoproteins on lipid particles leading to retention in the vessel wall. The signaling pathways through which growth factors regulate the synthesis and structure of proteoglycans are potential therapeutic targets. Platelet-derived growth factor (PDGF) is present in atherosclerotic plaques and activates phosphorylation of the serine/threonine kinase Akt. We have investigated the role of Akt in the signaling pathways for proteoglycan core protein expression and elongation of glycosaminoglycan chains on proteoglycans secreted by human vascular smooth muscle cells. The pharmacological inhibitor of Akt phosphorylation, SN30978, blocked PDGF stimulated phosphorylation of Akt. SN30978 caused concentration dependent inhibition of PDGF stimulated radiosulfate incorporation into secreted proteoglycans and the response was blocked by the PDGF receptor antagonists Ki11502 and imatinib. Analysis of the size of the biglycan molecules by SDS-PAGE showed that PDGF increased the apparent size of biglycan but this effect on glycosaminoglycan chain elongation was blocked by Ki11502 but not by SN30978. PDGF also stimulated total protein core protein synthesis assessed as 35S-methionine/cysteine incorporation and specifically the expression of versican mRNA. Both of these responses were blocked by SN30978. This data shows that PDGF-stimulated proteoglycan core protein synthesis but not glycosaminoglycan chain elongation is mediated via Akt phosphorylation. These data identify potential pathways for the development of agents which can pharmacologically regulate individual components of the synthesis of proteoglycans

Seasonal increases in fish trophic niche plasticity within a flood-pulse river ecosystem (Tonle Sap Lake, Cambodia)

Species' responses to seasonal environmental variation can influence trophic interactions and food web structure within an ecosystem. However, our ability to predict how species' interactions will vary spatially and temporally in response to seasonal variation unfortunately remains inadequate within most ecosystems. Fish assemblages in the Tonle Sap Lake (TSL) of Cambodia-a dynamic flood-pulse ecosystem-were studied for five years (2010-2014) using stable isotope and Bayesian statistical approaches to explore both within-and among-species isotopic niche variation associated with seasonal flooding. Roughly 600 individual fish specimens were collected during 19 sampling events within the lake. We found that fishes within the same species tended to have a broader isotopic niche during the wet season, likely reflecting assimilation of resources from either a wider range of isotopically distinct prey items or a variety of habitats, or both. Furthermore, among-species isotopic niches tended to overlap and range more broadly during the wet season, suggesting that floodplain inundation promotes exploitation of more diverse and similar resources by different species in the fish community. Our study highlights that the flood-pulse dynamic that is typical of tropical aquatic ecosystems may be an essential element supporting freshwater fish community structure and the fish diversity that underpins the TSL food web. This flow regime is currently threatened by regional dam development, which may in turn impact the natural function and structure of the fishery food web

Trends in breast cancer incidence in Hong Kong between 1973 and 1999: an age-period-cohort analysis

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Effects of thermal stress on morality in the older population of Hong Kong

BACKGROUND AND AIMS: A wide body of epidemiological evidence demonstrated consistent associations between temperature and daily mortality mainly from ecological time series studies. But few studies have examined these associations in a cohort. METHODS: We used a matched case-control design with time-dependent covariates to assess short-term effects of apparent temperature (AT) on mortality in a cohort of 66,820 persons aged 65 years or older, with a total of 14,446 deaths after about 10 years of follow up. The cases and controls were matched by duration of exposure with adjustment for particulate matter of aero-diameter …postprin

Spatial analytical methods for deriving a historical map of physiological equivalent temperature of Hong Kong

Physiological Equivalent Temperature (PET) has been widely used as an indicator for impacts of climate change on thermal comfort of humans. The effects of thermal stress are often examined using longitudinal observational studies over many years. A major problem in retrospective versus prospective studies is that it is not feasible to go back in time to measure historical data not collected in the past. These data must be reconstructed for the baseline period to enable comparative analysis of change and its human impact. This paper describes a systematic method for constructing a PET map using spatial analytical procedures. The procedures involve estimating PET values (based on the RayMan model and four key parameters of temperature, relative humidity, wind velocity, and mean radiant temperature) at a spatially disaggregated level comprising of a grid of 100 m × 100 m cells. The method can be applied to other geographic locations pending availability of basic meteorological and morphological data of the locations.postprin

Biophysical and Functional Characterization of Rhesus Macaque IgG Subclasses

Antibodies raised in Indian rhesus macaques [Macaca mulatta (MM)] in many preclinical vaccine studies are often evaluated in vitro for titer, antigen-recognition breadth, neu- tralization potency, and/or effector function, and in vivo for potential associations with protection. However, despite reliance on this key animal model in translation of promising candidate vaccines for evaluation in first in man studies, little is known about the proper- ties of MM immunoglobulin G (IgG) subclasses and how they may compare to human IgG subclasses. Here, we evaluate the binding of MM IgG1, IgG2, IgG3, and IgG4 to human Fc gamma receptors (FcγR) and their ability to elicit the effector functions of human FcγR-bearing cells, and unlike in humans, find a notable absence of subclasses with dramatically silent Fc regions. Biophysical, in vitro, and in vivo characterization revealed MM IgG1 exhibited the greatest effector function activity followed by IgG2 and then IgG3/4. These findings in rhesus are in contrast with the canonical understanding that IgG1 and IgG3 dominate effector function in humans, indicating that subclass-switching profiles observed in rhesus studies may not strictly recapitulate those observed in human vaccine studies