Transglutaminase inhibition ameliorates experimental diabetic nephropathy

Diabetic nephropathy is characterized by excessive extracellular matrix accumulation resulting in renal scarring and end-stage renal disease. Previous studies have suggested that transglutaminase type 2, by formation of its protein crosslink product epsilon-(gamma-glutamyl)lysine, alters extracellular matrix homeostasis, causing basement membrane thickening and expansion of the mesangium and interstitium. To determine whether transglutaminase inhibition can slow the progression of chronic experimental diabetic nephropathy over an extended treatment period, the inhibitor NTU281 was given to uninephrectomized streptozotocin-induced diabetic rats for up to 8 months. Effective transglutaminase inhibition significantly reversed the increased serum creatinine and albuminuria in the diabetic rats. These improvements were accompanied by a fivefold decrease in glomerulosclerosis and a sixfold reduction in tubulointerstitial scarring. This was associated with reductions in collagen IV accumulation by 4 months, along with reductions in collagens I and III by 8 months. This inhibition also decreased the number of myofibroblasts, suggesting that tissue transglutaminase may play a role in myofibroblast transformation. Our study suggests that transglutaminase inhibition ameliorates the progression of experimental diabetic nephropathy and can be considered for clinical application.

Oxidational wear of low alloy steel in gases other than air

A pin on disc wear machine has been used to study the oxidational wear of low alloy steel in a series of experiments which were carried out under dry wear sliding conditions at range of loads from 11.28 to 49.05 N and three sliding speeds of 2 m/s, 3.5 m/s and 5 m/s, in atmosphere of air, Ar, CO2, 100% O2, 20% O2-80% Ar and 2% O2-98% Ar. Also, the experiments were conducted to study frictional force, surface and contact temperatures and surface parameters of the wearing pins. The wear debris was examined using x-ray diffraction technique for the identification of compounds produced by the wear process. Scanning electron microscopy was employed to study the topographical features of worn pins and to measure the thickness of the oxide films. Microhardness tests were carried out to investigate the influence of the sub-surface microhardness in tribological conditions. Under all loads, speeds and atmospheres parabolic oxidation growth was observed on worn surfaces, although such growth is dependent on the concentration of oxygen in the atmospheres employed. These atmospheres are shown to influence wear rate and coefficient of friction with change in applied load. The nature of the atmosphere also has influence on surface and contact temperatures as determined from heat flow analysis. Unlubricated wear debris was found to be a mixture of αFe2O3, Fe3O4 and FeO oxide. A model has been proposed for tribo-oxide growth demonstrating the importance of diffusion rate and oxygen partial pressure, in the oxidation processes and thus in determination of wear rates.

Transglutaminase inhibition reduces fibrosis and preserves function in experimental chronic kidney disease

Progressive tissue fibrosis is involved in debilitating diseases that affect organs including the lungs, liver, heart, skin, and kidneys. Recent evidence suggests that tissue transglutaminase, an enzyme that crosslinks proteins, may be involved in tissue fibrosis by crosslinking and stabilizing the extracellular matrix or by recruiting and activating the large latent transforming growth factor (TGF)-β1 complex. We treated rats that had undergone 5/6-nephrectomy with two different irreversible inhibitors of transglutaminase and found that both prevented a decline in kidney function and reduced the development of glomerulosclerosis and tubulointerstitial fibrosis by up to 77% and 92%, respectively. Treatment reduced the accumulation of collagen I and collagen III, with the primary mechanism of action being direct interference with the crosslinking of extracellular matrix rather than altered regulation of TGFβ1. We conclude that inhibition of transglutaminase offers a potential therapeutic option for chronic kidney disease and other conditions that result from tissue fibrosis. Copyright © 2007 by the American Society of Nephrology.

Marketing strategy and new product development in the UK credit card industry

The development of new products in today's marketing environment is generally accepted as a requirement for the continual growth and prosperity of organisations. The literature is consequently rich with information on the development of various aspects of good products. In the case of service industries, it can be argued that new service product development is of as least equal importance as it is to organisations that produce tangible goods products. Unlike the new goods product literature, the literature on service marketing practices, and in particular, new service product development, is relatively sparse. The main purpose of this thesis is to examine a number of aspects of new service product development practice with respect to financial services and specifically, credit card financial services. The empirical investigation utilises both a case study and a survey approach, to examine aspects of new service product development industry practice relating specifically to gaps and deficiencies in the literature with respect to the financial service industry. The findings of the empirical work are subsequently examined in the context in which they provide guidance and support for a new normative new service product development model. The study examines the UK credit card financial service product sector as an industry case study and perspective. The findings of the field work reveal that the new service product development process is still evolving, and that in the case of credit card financial services can be seen as a well-structured and well-documented process. New product development can also be seen as an incremental, complex, interactive and continuous process which has been applied in a variety of ways. A number of inferences are subsequently presented.

Nitrogen implantation of tool steels and engineering coatings

Ion implantation modifies the surface composition and properties of materials by bombardment with high energy ions. The low temperature of the process ensures the avoidance of distortion and degradation of the surface or bulk mechanical properties of components. In the present work nitrogen ion implantation at 90 keV and doses above 1017 ions/cm2 has been carried out on AISI M2, D2 and 420 steels and engineering coatings such as hard chromium, electroless Ni-P and a brush plated Co-W alloy. Evaluation of wear and frictional properties of these materials was performed with a lubricated Falex wear test at high loads up to 900 N and a dry pin-on-disc apparatus at loads up to 40 N. It was found that nitrogen implantation reduced the wear of AISI 420 stainless steel by a factor of 2.5 under high load lubricated conditions and by a factor of 5.5 in low load dry testing. Lower but significant reductions in wear were achieved for AISI M2 and D2 steels. Wear resistance of coating materials was improved by up to 4 times in lubricated wear of hard Cr coatings implanted at the optimum dose but lower improvements were obtained for the Co-W alloy coating. However, hardened electroless Ni-P coatings showed no enhancement in wear properties. The benefits obtained in wear behaviour for the above materials were generally accompanied by a significant decrease in the running-in friction. Nitrogen implantation hardened the surface of steels and Cr and Co-W coatings. An ultra-microhardness technique showed that the true hardness of implanted layers was greater than the values obtained by conventional micro-hardness methods, which often result in penetration below the implanted depth. Scanning electron microscopy revealed that implantation reduced the ploughing effect during wear and a change in wear mechanism from an abrasive-adhesive type to a mild oxidative mode was evident. Retention of nitrogen after implantation was studied by Nuclear Reaction Analysis and Auger Electron Spectroscopy. It was shown that maximum nitrogen retention occurs in hard Cr coatings and AISI 420 stainless steel, which explains the improvements obtained in wear resistance and hardness. X-ray photoelectron spectroscopy on these materials revealed that nitrogen is almost entirely bound to Cr, forming chromium nitrides. It was concluded that nitrogen implantation at 90 keV and doses above 3x1017 ions/cm2 produced the most significant improvements in mechanical properties in materials containing nitride formers by precipitation strengthening, improving the load bearing capacity of the surface and changing the wear mechanism from adhesive-abrasive to oxidative.

Microstructural analysis of surface and interface zones in concrete

Several of OPC paste and concrete specimens, with different mix proportions, were cast against CPF and impermeable formwork (IF) and the profiles of pore structure, microhardness and scratch hardness of the cover zone were established. The chloride ingress and the depth of carbonation of the surface zone of concrete cast against CPF and IF were investigated. The main mechanisms controlling the ECR processes and the factors affecting such treatment were critically reviewed. Subsequently, as a means of restoring passivation of steel embedded in carbonated concrete, such HCP specimens were subjected to ECR. The influence of ECR on the chemistry of the pore solution and the microstructure of the surface and the steel/cement past interface zones were also studied. The main findings of this investigation were as follows: (a) The thickness of the microstructure gradient of cover concrete is significantly decreased with increasing period of water curing but is relatively unaffected by curing temperature, w/e ratio and the use of cement replacement materials. (b) The scratch hardness technique was shown to be potentially useful for characterising the microstructure and microhardness gradients of the surface zone. (c) A relationship between the microstructure gradient and mass transport properties of the surface zone was established. (d) The use of CPF resulted in a significant reduction in porosity of both the cement paste matrix and the aggregate/cement paste transition zone, and a marked improvement in the resistance of the surface zone to carbonation and the ingress of chloride ions. (e) The ECR treatment resulted in a marked densification of the pore structure and in changes to the pore solution chemistry and the cement phases of near-surface and steel/cement paste transition zones. This effect was more pronounced with current density, period of treatment and particularly with the use of sodium phosphate as an electrolyte.

Abrasion resistance of fibre reinforced concrete floors

This thesis focuses on the investigation of the abrasion resistance of fibre reinforced concrete floors at both the macro and micro levels. A literature review of the available literature concerning subjects allied to the current project is included. This highlights themes relevant to wear mechanisms and the factors influencing it: factors that affect the abrasion resistance of concrete and several test methods for assessing it; and the historical development of fibres and the properties of different fibre types and their influence on concrete. Three accelerated abrasion testers were compared and critically discussed for their suitability for assessing the abrasion resistance of concrete floors. Based on the experimental findings one accelerated abrasion apparatus was selected as more appropriate to be used for carrying out the main investigations. The laboratory programme that followed was undertaken to investigate the influence of various material and construction factors on abrasion resistance. These included mix variations (w/c ratio), fibre reinforcement, geometry, type and volume, curing method and superplasticizing agents. The results clearly show that these factors significantly affected abrasion resistance and several mechanisms were presumed to explain and better understand these observations. To verify and understand these mechanisms that are accountable for the breakdown of concrete slabs, the same concrete specimens that were used for the macro-study, were also subjected to microstructutural investigations using techniques such as Microhardness examination, Mercury intrusion porosimetry and Petrographic examination. It has been found that the abrasion resistance of concrete is primarily dependent on the microstructure and porosity of the concrete nearest to the surface. The feasibility of predicting the abrasion resistance of fibre reinforced concrete floors by indirect and non-destructive methods was investigated using five methods that have frequently been used for assessing the quality of concrete. They included the initial surface absorption test, the impact test, ball cratering, the scratch test and the base hardness test. The impact resistance (BRE screed tester) and scratch resistance (Base hardness tester) were found to be the most sensitive to factors affecting abrasion resistance and hence are considered to be the most appropriate testing techniques. In an attempt to develop an appropriate method for assessing the abrasion resistance of heavy-duty industrial concrete floors, it was found that the presence of curing/sealing compound on the concrete surface at the time of accelerated abrasion testing produces inappropriate results. A preliminary investigation in the direction of modifying the Aston accelerated abrasion tester has been carried out and a more aggressive head has been developed and is pending future research towards standardisation.

Electrochemical chloride extraction to halt corrosion of reinforcement

This thesis presents results of experiments designed to study the effect of applying electrochemical chloride extraction (ECE) to a range of different hardened cement pastes. Rectangular prism specimens of hydrated cement paste containing sodium chloride at different concentrations were subjected to electrolysis between the embedded steel cathodes and external anodes of activated titanium mesh. The cathodic current density used was in the range of 1 to 5 A/m2 with treatment periods of 4 to 12 weeks. After treatment, the specimens were cut into sections which were subjected to pore-solution expression and analysis in order to determine changes in the distribution of free and total ionic species. The effect of the ECE treatment on the physical and microstructural properties of the cements was studied by using microhardness and MIP techniques. XRD was employed to look at the possibility of ettringite redistribution as a result of the accumulation of soluble sulphate ions in the cement matrix near the cathode during ECE. Remigration of chloride which remains after the ECE treatment and distribution of other ions were studied by analysing specimens which had been stored for several months, after undergoing ECE treatment. The potentials of the steel cathodes were also monitored over the period to detect any changes in their corrosion state. The main findings of this research were as follows: 1, ECE, as applied in this investigation, was capable of removing both free and bound chloride. The removal process occurred relatively quickly and an equilibrium between free and bound chlorides in the specimens was maintained throughout. At the same time, alkali concentrations in the pore solution near the steel cathode increased. The soluble sulphate ionic concentration near the cathode also increased due to the local increase in the pH of the pore solution. 2, ECE caused some changes in physical and microstructural of the cement matrix. However these changes were minimal and in the case of microhardness, the results were highly scattered. Ettringite in the bulk material well away from the cathode was found not to increase significantly with the increase in charge passed.3, Remigration of chloride and other ionic species occurred slowly after cessation of ECE with a resultant gradual increase in the Cl-/OH- ratio around the steel.4, The removal of chloride from blended cements was slower than that from OPC.

Abrasion resistance of concrete

This thesis describes an experimental study of the abrasion resistance of concrete at both the macro and micro levels. This is preceded by a review related to friction and wear, methods of test for assessing abrasion resistance, and factors influencing the abrasion resistance of concrete. A versatile test apparatus was developed to assess the abrasion resistance of concrete. This could be operated in three modes and a standardised procedure was established for all tests. A laboratory programme was undertaken to investigate the influence, on abrasion resistance, of three major factors - finishing techniques, curing regimes and surface treatments. The results clearly show that abrasion resistance was significantly affected by these factors, and tentative mechanisms were postulated to explain these observations. To substantiate these mechanisms, the concrete specimens from the macro-study were subjected to micro-structural investigation, using such techniques as 'Mercury Intrusion Forosimetry, Microhardness, Scanning Electron Microscopy, Petrography and Differential Thermal Analysis. The results of this programme clearly demonstrated that the abrasion resistance of concrete is primarily dependent on the microstructure of the concrete nearest to the surface. The viability of indirectly assessing the abrasion resistance was investigated using three non-destructive techniques - Ultrasonic Pulse Velocity, Schmidt Rebound Hardness, and the Initial Surface Absorption Test. The Initial Surface Absorption was found to be most sensitive to factors which were shown to have influenced the abrasion resistance of concrete. An extensive field investigation was also undertaken. The results were used to compare site and laboratorypractices, and the performance in the accelerated abrasion test with the service wear. From this study, criteria were developed for assessing the quality of concrete floor slabs in terms of abrasion resistance.

Wear of abrasion resisting materials

The wear behaviour of a series of chromium containing white irons has been investigated under conditions of high stress grinding abrasion using a specimen on track abrasion testing machine. The measured abrasion resistance of the irons has been explained in terms of microstructure and hardness and with respect to the wear damage observed at and beneath abraded surfaces. During abrasion material removal occurred by cracking and detachment from the matrix of eutectic carbides as well as by penetration and micromachining effects of the abrasive grits being crushed at the wearing surface. Under the particular test conditions used martensitic matrix structures gave higher resistance to abrasion than austenitic or pearlitic. However, no simple relationship was found between general hardness or matrix microhardness at wear surfaces and abrasion resistance, and the test yielded pessimistic results for austenitic irons. The fine structures of the 15% Cr and 30% Cr alloys were studied by thin foil transmission electron microscopy. It was found that both the matrix and carbide constituents could be thinned for examination at 100 Kv using conventional dishing followed by ion beam thinning. Flany of the rodlike eutectic N7C3 carbides were seen to consist of clusters of scalier rods with individual 117C3 crystals quite often containing central cores of matrix constituent. 3oth eutectic and secondary N7C3 carbides were found to contain stacking faults on planes normal to the basal plane. In the eutectic carbides in the 30A Cr iron there was evidence of an in-situ PI7C3 C. transition which had taken place during the hardening heat treatment of this alloy. In the as-cast austenitic matrix iron strain induced martensite was produced at the wear surface contributing to work hardening. The significance of these findings have been discussed in relation to wear performance.

Structure and thermal properties of yttrium alumino-phosphate glasses

The structure and thermal properties of yttrium alumino-phosphate glasses, of nominal composition (Y2O3)(0.31-z)(Al2O3)(z)(P2O5)(0.69) with 0 less than or similar to z less than or similar to 0.31, were studied by using a combination of neutron diffraction, Al-27 and P-31 magic angle spinning nuclear magnetic resonance, differential scanning calorimetry and thermal gravimetric analysis methods. The Vickers hardness of the glasses was also measured. The data are compared to those obtained for pseudo-binary Al2O3-P2O5 glasses and the structure of all these materials is rationalized in terms of a generic model for vitreous phosphate materials in which Y3+ and Al3+ act as modifying cations that bind only to the terminal (non-bridging) oxygen atoms of PO4 tetrahedra. The results are used to help elucidate the phenomenon of rare-earth clustering in phosphate glasses which can be reduced by substituting Al3+ ions for rare-earth R3+ ions at fixed modifier content.

Fracture toughness of SIC, Si3N4, and sialon ceramics using controlled surface flaws

Knoop and Vickers indentation cracks have frequently been used as model 'precracks' in ceramic bend specimens for fracture toughness (K1c) determination. Indentation residual stress reduces the measured K1c but can be removed or accounted for by grinding, annealing, or modelling. Values of K1c are obtained for four materials using Vickers indentations and an improved stress intensity factor. Methods for residual stress removal or incorporation are compared, and the most reliable stress removal alternative is identified for each material. © 1996 The Institute of Materials.