Correlation between extent of osteolytic damage and metastatic burden of human breast cancer metastasis in nude mice: Real-time PCR quantitation

Orthotopic or intracardiac injection of human breast cancer cell lines into immunocompromised mice allows study of the molecular basis of breast cancer metastasis. We have established a quantitative real-time PCR approach to analyze metastatic spread of human breast cancer cells inoculated into nude mice via these routes. We employed MDA-MB-231 human breast cancer cells genetically tagged with a bacterial β-galactosidase (Lac-Z) retroviral vector, enabling their detection by TaqMan® real-time PCR. PCR detection was linear, specific, more sensitive than conventional PCR, and could be used to directly quantitate metastatic burden in bone and soft organs. Attesting to the sensitivity and specificity of the PCR detection strategy, as few as several hundred metastatic MDA-MB-231 cells were detectable in 100 μm segments of paraffin-embedded lung tissue, and only in samples adjacent to sections that scored positive by histological detection. Moreover, the measured real-time PCR metastatic burden in the bone environment (mouse hind-limbs, n=48) displayed a high correlation to the degree of osteolytic damage observed by high resolution X-ray analysis (r 2=0.972). Such a direct linear relationship to tumor burden and bone damage substantiates the so-called `vicious cycle' hypothesis in which metastatic tumor cells promote the release of factors from the bone which continue to stimulate the tumor cells. The technique provides a useful tool for molecular and cellular analysis of human breast cancer metastasis to bone and soft organs, can easily be extended to other cell/marker/organ systems, and should also find application in preclinical assessment of anti-metastatic modalities.

Experimental study into the correlation between the incremental forming and the nature of springback in automotive steels

Bending in a V-die has been well covered in the literature and the results have been used to indicate the out-come of bending in cold roll forming. However, recent work comparing springback between roll forming and single step bending has found lower springback in the roll forming process compared to single step bending. Roll forming is an incremental bending process and in this study a V-section was formed in a single operation and in multiple steps and the springback determined. The springback in V-die forming was significantly reduced by incremental forming. This suggests that the lower springback determined in roll forming compared to single step bending may be related to the incremental nature of the roll forming process.

Fracture modelling of DP780 sheets using a hybrid experimental-numerical method and two-dimensional digital image correlation

This paper is concerned with the construction of fracture envelopes of DP780 sheets using two methods: a hybrid experimental-numerical method; two-dimensional digital image correlation (2D-DIC). For the hybrid method, four types of ductile fracture tests were carried out covering a wide range of stress states on specimens: with a central hole; two symmetric circular notches; flat grooved; and diagonally double-notched. Based on the fracture strain and loading paths identified with finite element simulation, a fracture envelope was obtained by employing the three-parameter modified Mohr-Coulomb fracture model. In addition, the fracture surface strain was directly measured using 2D-DIC. Loading histories of each test were extracted from a surface element of a three dimensional finite element model. The comparison of fracture envelopes constructed by the two methods reveals that there is little difference. Thus, it can be concluded that 2D-DIC is applicable to fracture modelling of DP780 sheets despite the assumption of the plane stress condition even after necking

The correlation between stacking fault energy and the work hardening behaviour of high-mn twinning induced plasticity steel tested at various temperatures

High-Mn Twinning Induced Plasticity (TWIP) steels have superior mechanical properties, which make them promising materials in automotive industry to improve the passenger safety and the fuel consumption. The TWIP steels are characterized by high work hardening rates due to continuous mechanical twin formation during the deformation. Mechanical twinning is a unique deformation mode, which is highly governed by the stacking fault energy (SFE). The composition of steel alloy was Fe-18Mn-0.6C-1Al (wt.%) with SFE of about 25-30 mJ/m2 at room temperature. The SFE ensures the mechanical twinning to be the main deformation mechanism at room temperature. The microstructure, mechanical properties, work hardening behaviour and SFE of the steel was studied at the temperature range of ambient ≤T[°C]≤ 400°C. The mechanical properties were determined using Instron tensile testing machine with 30kN load cell and strain rate of 10-3s-1 and the work hardening behaviour curves were generated using true stress and true strain data. The microstructure after deformation at different temperatures was examined using Zeiss Supra 55VP SEM. It was found that an increase in the deformation temperature raised the SFE resulting in the deterioration of the mechanical twinning that led to decrease not only in the strength but also in the total strain of the steel. A correlation between the temperature, the SFE, the mechanical twinning, the mechanical properties and the work hardening rate was also found. © (2014) Trans Tech Publications, Switzerland.

What is so ‘primitive’ about ‘primitive democracy’? Comparing the ancient Middle East and classical Athens

This chapter seeks to delve deeper into the ancient history of democracy than is normally permitted, back to a time preceding the developments of classical Athens, when the earliest signs of organized society and complex governmental systems emerged across the ancient Middle East. It then seeks to compare and contrast these ancient Middle Eastern examples with those of classical Athens and to offer new insights into, and questions about, the nature and history of democracy. Building on some recent work (Fleming, 2004; Isakhan, 2007a; Keane, 2009: 78–155), this chapter also hopes to move the discussion beyond the phrase usually associated with ancient Middle Eastern democracies, that of ‘primitive democracy’. This chapter also argues that, while the Middle Eastern experiments were less rigid and formalized, they were in no measurable sense more ‘primitive’ than the later example offered by classical Athens. However, this essay also cautiously notes that, while not all of the elements which made ancient Athens significant occurred in the same way and at the same time in the ancient Middle East, all of them did exist at varying times and in varying guises across these earlier civilizations. To demonstrate this thesis, the remainder of the chapter utilizes several of the key criteria by which we commonly measure Athenian democracy – the functioning of its assembly, the mechanisms of justice and of the law, the varying voting and elective procedures, the rights and freedoms of the citizens, and the systematic exclusion of ‘non-citizens’ – and discusses precedents and parallels drawn from the extant evidence concerning the ancient Middle East.

Testing slope homogeneity in large panels with serial correlation

Pesaran and Yamagata (Pesaran, M.H., Yamagata, T., Testing slope homogeneity in large panels, Journal of Econometrics 142, 50-93, 2008) propose a test for slope homogeneity in large panels, which has become very popular in the literature. However, the test cannot deal with the practically relevant case of heteroskedastic and/serially correlated errors. The present note proposes a generalized test that accommodates both features. © 2013 Elsevier B.V.

Optimisation of nonlinear motion cueing algorithm based on genetic algorithm

Motion cueing algorithms (MCAs) are playing a significant role in driving simulators, aiming to deliver the most accurate human sensation to the simulator drivers compared with a real vehicle driver, without exceeding the physical limitations of the simulator. This paper provides the optimisation design of an MCA for a vehicle simulator, in order to find the most suitable washout algorithm parameters, while respecting all motion platform physical limitations, and minimising human perception error between real and simulator driver. One of the main limitations of the classical washout filters is that it is attuned by the worst-case scenario tuning method. This is based on trial and error, and is effected by driving and programmers experience, making this the most significant obstacle to full motion platform utilisation. This leads to inflexibility of the structure, production of false cues and makes the resulting simulator fail to suit all circumstances. In addition, the classical method does not take minimisation of human perception error and physical constraints into account. Production of motion cues and the impact of different parameters of classical washout filters on motion cues remain inaccessible for designers for this reason. The aim of this paper is to provide an optimisation method for tuning the MCA parameters, based on nonlinear filtering and genetic algorithms. This is done by taking vestibular sensation error into account between real and simulated cases, as well as main dynamic limitations, tilt coordination and correlation coefficient. Three additional compensatory linear blocks are integrated into the MCA, to be tuned in order to modify the performance of the filters successfully. The proposed optimised MCA is implemented in MATLAB/Simulink software packages. The results generated using the proposed method show increased performance in terms of human sensation, reference shape tracking and exploiting the platform more efficiently without reaching the motion limitations.