Mechanisms of hypoxic up-regulation of versican gene expression in macrophages

Hypoxia is a hallmark of many pathological tissues. Macrophages accumulate in hypoxic sites and up-regulate a range of hypoxia-inducible genes. The matrix proteoglycan versican has been identified as one such gene, but the mechanisms responsible for hypoxic induction are not fully characterised. Here we investigate the up-regulation of versican by hypoxia in primary human monocyte-derived macrophages (HMDM), and, intriguingly, show that versican mRNA is up-regulated much more highly (>600 fold) by long term hypoxia (5 days) than by 1 day of hypoxia (48 fold). We report that versican mRNA decay rates are not affected by hypoxia, demonstrating that hypoxic induction of versican mRNA is mediated by increased transcription. Deletion analysis of the promoter identified two regions required for high level promoter activity of luciferase reporter constructs in human macrophages. The hypoxia-inducible transcription factor HIF-1 has previously been implicated as a key potential regulator of versican expression in hypoxia, however our data suggest that HIF-1 up-regulation is unlikely to be principally responsible for the high levels of induction observed in HMDM. Treatment of HMDM with two distinct specific inhibitors of Phosphoinositide 3-kinase (PI3K), LY290042 and wortmannin, significantly reduced induction of versican mRNA by hypoxia and provides evidence of a role for PI3K in hypoxic up-regulation of versican expression

High-Stress Abrasive Wear Response of 0.2% Carbon Dual Phase Steel: Effects of Microstructural Features and Experimental Conditions.

Effects of heat treatment on the high-stress abrasive wear response of 0.2% carbon steel have been investigated at varying applied loads, abrasive (SiC) sizes and sliding distances. The heat treatment involved intercritical annealing at three different temperatures between Ac1 and Ac3 followed by ice water quenching in order to produce a dual phase microstructure consisting of varying quantities of ferrite plus martensite. The wear rate increased monotonically with applied load irrespective of the heat treatment schedule. Further, the wear rate increased drastically when the abrasive size was increased from 15 to 27 �m; a further increase in the abrasive size led to only a marginal increase in the wear rate. In general, the wear rate decreased with increasing sliding distance and attained a nearly stable value at longer sliding distances.Increasing intercritical annealing temperature resulted into higher martensite content, thereby leading to reduced wear rate. However, the extent of reduction in wear rate with martensite content has been found to change with the applied load and abrasive size. The present investigation clearly suggests that it is quite possible to attain desired combinations of bulk hardness and microstructure (ferrite plus martensite) that could greatly control abrasive wear properties in low carbon steel. The observed wear response of the samples has been explained on the basis of microconstituent–abrasive interaction during the course of abrasive action, degradation of the abrasive particles and the nature of various microconstituents, i.e. mechanical properties

Formation and microstructure of (Ti, V) C-Reinforced iron matrix composites using self propagating high-temperature synthesis.

The combustion synthesis of (Ti, V)C-reinforced iron-matrix composites from elemental powders was examined. Examination using scanning electron microscopy indicated that two types of carbide particles were formed having a different size and composition from each other. These were sub-micron size (Ti, V)C particles and pure TiC or TiC-rich particles of a slightly larger particle size. The development of the microstructure and formation of the two types of carbides were explained through an understanding of the reaction mechanism and the thermodynamics of the carbide phases. Increasing the amount of vanadium in the reactants led to a decrease in the carbide and the iron grain size and to a corresponding increase in microhardness

Cast in situ Cu-TiC composites: Synthesis by SHS route and characterization.

The present investigation discusses observations pertaining to the synthesis of Cu-based composites containing TiC particles in the range of 45–50 volume % by self-propagating high temperature synthesis (SHS) process. A composite with 11–13 volume % TiC dispersion was also synthesized through remelting and dilution. The composites were observed to contain a copper matrix together with a Cu–Ti intermetallic compound, TiC dispersoid particles and partially reacted graphite. The regions showing partially reacted graphite (carbon) became less prominent in the diluted composites. Al addition led to the refinement of TiC particles, higher hardness, reduced density and improved degree of formation and better homogeneity of the distribution of TiC particles. Dilution caused reduced hardness, while the density followed a reverse trend