Mouse models of neurodegenerative disease: preclinical imaging and neurovascular component.

Neurodegenerative diseases represent great challenges for basic science and clinical medicine because of their prevalence, pathologies, lack of mechanism-based treatments, and impacts on individuals. Translational research might contribute to the study of neurodegenerative diseases. The mouse has become a key model for studying disease mechanisms that might recapitulate in part some aspects of the corresponding human diseases. Neurode- generative disorders are very complicated and multifacto- rial. This has to be taken in account when testing drugs. Most of the drugs screening in mice are very di cult to be interpretated and often useless. Mouse models could be condiderated a ‘pathway models’, rather than as models for the whole complicated construct that makes a human disease. Non-invasive in vivo imaging in mice has gained increasing interest in preclinical research in the last years thanks to the availability of high-resolution single-photon emission computed tomography (SPECT), positron emission tomography (PET), high eld Magnetic resonance, Optical Imaging scanners and of highly speci c contrast agents. Behavioral test are useful tool to characterize di erent ani- mal models of neurodegenerative pathology. Furthermore, many authors have observed vascular pathological features associated to the di erent neurodegenerative disorders. Aim of this review is to focus on the di erent existing animal models of neurodegenerative disorders, describe behavioral tests and preclinical imaging techniques used for diagnose and describe the vascular pathological features associated to these diseases

Large arc voltage fluctuations and droplet formation in electric arc wire spraying

The diameter of droplets in electric arc wire spraying is critical in determining the microstructure, porosity and oxide content of the resulting sprayed coatings. Droplet diameter controls dynamic and thermal behaviour in the spray, and the splashing and spreading behaviour of droplets at deposition. In electric arc wire spraying, the droplet diameter is determined by a combination of the melting behaviour of the feedstock wires in a direct current arc, combined with primary and secondary atomisation processes under the action of a high velocity atomising gas. The high frequency arc voltage variations during electric arc spraying of Fe-0·8C have been investigated and arc voltage fluctuations related to atomisation events occurring at the wire tips during spraying. A simple analytical model has been proposed which allows the diameter of primary droplets produced by atomisation to be calculated from the wire feedrate and the average time period for material removal, which was obtained from the voltage traces. Primary droplets were then assumed to undergo secondary atomisation according to correlations from the literature, and resulting droplet diameters were compared with diameters measured by experiment. Despite uncertainties in some of the thermophysical data and dynamic conditions during atomisation, predicted droplet diameters were in good agreement with experimental mass mean droplet diameters obtained under a range of atomising gas pressures, arc voltages and wire feedrates

Oxidation during electric arc spray forming of steel

Twin wire electric arc spraying is being developed as a technique to form thick steel deposits for rapid production tooling by robotically manipulating several arc guns over a ceramic pattern. Even though nitrogen atomising gas is used to spray the steel, entrainment of oxygen from the surrounding atmosphere of the large extraction booth results in deposits that are high in oxide and substantially lower in carbon than the original steel feedstock wire. The amount of oxidation and carbon loss can be reduced if spraying is carried out in a smaller, enclosed chamber. Under chamber spraying conditions, controlled additions of oxygen to the nitrogen atomising gas leads to an increase in deposition temperatures, better bonding with the substrate, a coarser microstructure, a decrease in deposit hardness and increased deposit brittleness through intersplat delamination and oxide cracking. Differences in substrate shape, gun manipulation and oxygen entry point into the spray between chamber and spraying in a booth using a robot also alters the balance of oxidation and carbon loss processes. Oxidation during the spraying of thick steel deposits can happen in three main ways: (1) primary droplets in-flight prior to deposition; (2) incorporation of secondary droplets generated by splashing; (3) at the deposit top surface. © 2006 Elsevier B.V. All rights reserved

Droplet splashing during arc spraying of steel and the effect on deposit microstructure

The mechanism by which droplet deposition occurs is important when filling substrate features for the electric arc spray forming of steel tooling. Particle image velocimetry and high-speed video imaging techniques have been used to observe droplet deposition, particularly with regard to the behavior of droplets originating from splashing. Droplet splashing on deposition has been seen to be significant, and splash droplets form a large proportion of the overspray. The splash droplets are smaller and, when first created, move slower than the parent droplet. When spraying into deep features, the lateral and upward movement of splash droplets acts as a mechanism for deposit formation onto surfaces in shadow from the main spray. Microstructural study has shown that oxidation of the splash droplets before redeposition leads to a deposit with a high fraction of oxide. Simultaneous growth of deposit formed directly from the spray, and from splash droplets, results in a banded microstructure containing elongated macropores. A mechanism for such microstructural evolution is proposed

Arc Sprayed Steel: Microstructure in Severe Substrate Features

The effect of severe substrate topography on the microstructure of thermally sprayed coatings has been relatively neglected, but is critical in controlling the performance of thick electric arc sprayed steel shells for rapid tooling applications. This paper shows how the spray angle and the atomizing gas pressure control the distribution of porosity and oxide in steel sprayed in and around cylindrical holes of different diameter and depth. Droplet splashing and the secondary deposition of splash droplets caused systematic variations in microstructure. In particular, the origin of the phenomenon of "bridging," the premature closure of features, has been revealed by microstructural analysis and explained in terms of the trajectories of droplets. The filling of features with higher-quality material can be aided by using a low atomizing gas pressure, reducing the oxygen partial pressure of the surrounding atmosphere and careful selection of the spray angle. © ASM International 2009

A particle image velocimetry investigation of in-flight and deposition behaviour of steel droplets during electric arc sprayforming

Gas and Fe-0.8 wt.% C droplet dynamics during electric arc spraying have been characterised using particle image velocimetry (PIV). This study has shown that the flow of N-2 atomising gas was well-collimated, with an exit velocity of 255 m s(-1), decaying to 75 m s(-1) at an axial distance of 150 rum, where the jet diameter was similar to50 mm. The presence of atomised steel droplets increased spray divergence. Droplet mode velocity measurements equalled the gas-only velocity measurement of similar to 120 m s(-1) at an axial distance of 95 mm, and then further increased to 135 m s(-1) at 150 mm. Close to the substrate, droplet splashing dominated the flow field with upward and then lateral flow of splashed droplets. In the presence of a vertical step feature, the flow field became complex, with some splash droplets having trajectories that caused secondary deposition on the vertical step wall. (C) 2004 Elsevier B.V. All rights reserved

The velocity and temperature of steel droplets during electric arc spraying

The average dynamic and thermal behaviour of electric arc sprayed Fe-0.8wt.%C droplets has been investigated using a laser based time of flight velocimeter system (Laser2Focus - L2F) and a two-colour pyrometry system (In-flight Particle Pyrometer - IPP) respectively. Radial and axial variations of the spray velocity and temperature have been investigated, together with their dependence on atomising gas type, arc voltage, atomising gas pressure, and wire feed rate. Under all conditions, the average spray temperature was significantly above the steel liquidus temperature indicating most droplets were fully molten. Once projected away from the region of atomisation, the droplet spray typically cooled at ∼1 °C mm-1 and ∼105 °C s-1 and typical axial velocities were 100 m s-1. Because of asymmetry in the arc itself and the resulting differences in the melting behaviour of the wires, the spray exhibited asymmetric radial variations of both velocity and temperature about the spray cone axis. The presence of oxygen in the atomising gas had a significant effect in increasing spray temperature via exothermic oxidation of the steel droplets. Processing maps have been constructed in which the variation of average spray velocity and temperature with arc voltage, gas pressure and wire feed rate have been fitted to a series of simple polynomial expressions. These maps have been explained in terms of the heat and momentum transfer processes occurring during atomisation and subsequent droplet flight. © 2005 Elsevier B.V. All rights reserved

Characterisation of electric arc spray formed Ni superalloy IN718

Nickel superalloy IN718 has been electric arc spray formed under a range of processing conditions as small diameter ring preforms. Top surface deposition temperature has been measured using an infrared thermal imaging video camera. The as-sprayed microstructure has been investigated by a combination of optical microscopy, image analysis and electron probe microanalysis, and characterised by the through thickness variation in porosity, grain morphology and microsegregation behaviour. Low top surface temperature preforms had an unfused splat microstructure with intersplat porosity. Intermediate temperature preforms had banded unfused and fused splat micro structures with some cross-splat columnar grains and low levels of porosity. High temperature preforms had banded unfused/fused splat and equiaxed grains. The extent of microsegregation depended upon the manufacturing temperature. (C) 2002 Elsevier Science B.V. All rights reserved

Development of an electric arc sprayed self lubricating coating

Electric are sprayed coatings with a disperse lubricating phase have potential for use in a variety of industrial applications as bearing materials including low friction coatings for drill string joints in the oil industry to reduce casing wear and lower drilling torque. This paper describes the optimisation of electric are spray parameters for Fe-0.06wt.%C that will subsequently be used as a self-lubricating coating matrix.The effect of electric are spray parameters on the microstructure of a Fe-0.06wt.%C matrix has been characterised in terms of deposition rate, temperature during manufacture, porosity and microhardness. It has been shown that the local coating temperature during directly affects the final coating porosity, grain size, grain morphology and microhardness. The most effective parameter in controlling coating temperature was the coating deposition rate. The Fe0.06wt.%C coating microstructure was primary equiaxed ferrite with a dispersion of spherodised Fe3C particles formed from the in-situ tempering of the as-sprayed martensite or bainite during spraying. A fuller analytical treatment of these phenomena is given elsewhere ((13)). Fe-0.06wt.%C powder particles microstructure was primarily bainitic or martensitic. A small number of Fe-0.06wt.%C powder particles showed a dendritic phase which has been proposed as retained austenite because of austenite stabilisation by fine grains and the N-2 atmosphere, or an unidentified nitride layer

The electric arc spray manufacture of rapid production tooling: A case study

The manufacture of tooling using the electric are spray process to spray steel directly onto a master pattern offers substantial reductions in the lead times required to make complex tooling for polymer injection moulding and other applications. The process of spray forming is fast, efficient, and low cost, and has been shown to be dimensionally accurate with proper control over the residual stresses that develop during spraying. Poor dimensional control because of high internal stresses in thick are sprayed steel coatings is well known, but these problems can be avoided by the use of correct spraying conditions.This paper describes the STD SPRAYFORM process for the manufacture of tooling for the polymer injection moulding of a component for a leading company in the U.S. The steps in the spray forming process, both before and after spraying, are described. The spray forming route competed directly with a traditional method for toolmaking and considerably reduced the lead time from order to completion. The tooling produced by spray forming has been operating commercially in production in the U.S. and has to date produced in the region of half a million parts without appreciable wear. The incorporation of contoured cooling channels during spraying has enabled plastic injection moulding cycle times to be decreased by 15%