Elevated expression of Runx2 as a key parameter in the etiology of osteosarcoma

To understand the molecular etiology of osteosarcoma, we isolated and characterized a human osteosarcoma cell line (OS1). OS1 cells have high osteogenic potential in differentiation induction media. Molecular analysis reveals OS1 cells express the pocket protein pRB and the runt-related transcription factor Runx2. Strikingly, Runx2 is expressed at higher levels in OS1 cells than in human fetal osteoblasts. Both pRB and Runx2 have growth suppressive potential in osteoblasts and are key factors controlling competency for osteoblast differentiation. The high levels of Runx2 clearly suggest osteosarcomas may form from committed osteoblasts that have bypassed growth restrictions normally imposed by Runx2. Interestingly, OS1 cells do not exhibit p53 expression and thus lack a functional p53/p21 DNA damage response pathway as has been observed for other osteosarcoma cell types. Absence of this pathway predicts genomic instability and/or vulnerability to secondary mutations that may counteract the anti-proliferative activity of Runx2 that is normally observed in osteoblasts. We conclude OS1 cells provide a valuable cell culture model to examine molecular events that are responsible for the pathologic conversion of phenotypically normal osteoblast precursors into osteosarcoma cells.

Plasma parameter characterization of a reflex plasma source operating in oxygen

A reflex discharge plasma, obtained as a hybrid between a Penning discharge plasma (PDP) and a hollow-cathode discharge (HCD) plasma, is analysed as a possible direction-current, high-density plasma source. The experiment is run in oxygen at pressures of 10 mTorr and 1 mTorr, and for discharge currents of 100 to 200 mA. Although the gas pressure is considerably lower than those used in HCDs, the hollow-cathode effect (HCE) occurs for current levels higher than 100 mA and leads to plasma densities comparable with those obtained using inductive plasma sources. The presence of a constant magnetic field leads to the enhancement of electron emission from cathodes under ion bombardment, and to the decreasing of the ion loss by diffusion to the wall.

Parameter studies of fibre laser micro-welding of AISI 316L using Taguchi method

This paper discusses the application of the Taguchi experimental design approach in optimizing the key process parameters for micro-welding of thin AISI 316L foil using the 100W CW fibre laser. A L16 Taguchi experiment was conducted to systematically understand how the power, scanning velocity, focus position, gas flow rate and type of shielding gas affect the bead dimensions. The welds produced in the L16 Taguchi experiment was mainly of austenite cellular-dendrite structure with an average grain size of 5µm. An exact penetration weld with the largest penetration to fusion width ratio was obtained. Among those process parameters, the interaction between power and scanning velocity presented the strongest effect to the penetration to fusion width ratio and the power was found to be the predominantly important factor that drives the interaction with other factors to appreciably affect the bead dimensions.

Parameter study on laser welding of nitinol wire by Taguchi method

A L27 Taguchi experiment was done to investigate the effect of laser power, welding time, laser mode (CW and two pulsed modes), focus position, and their possible interactions on the weld-bead aspect ratio of laser-welded NiTi wires by using a 100W fibre laser. The optimized parameter setting to produce the full penetrated weldment with minimum welding defects is successfully determined in the Taguchi experiment. The laser mode is found to be the most important parameter that directly controls the weld-bead aspect ratio. The focus position is the secondly important parameter for the laser welding of NiTi wires. Strong interaction between the power and focus position is found in the Taguchi experiment. The optimized weldment produced by the Taguchi experiment is mainly of columnar dendritic structure in the weld zone (WZ) with the size of 1-3µm, while the HAZ exhibits equiaxed grain structure with the size of 5-10µm. The Vickers micro-hardness test indicted that the WZ and HAZ in the weldment are softened to certain extends after fibre laser welding.

Parameter estimation and equation formulation in Business Dynamics

System Dynamics enables modelling and simulation of highly non-linear feedback systems to predict future system behaviour. Parameter estimation and equation formulation are techniques in System Dynamics, used to retrieve the values of parameters or the equations for ?ows and/or variables. These techniques are crucial for the annotations and thereafter the simulation. This paper critically examines existing and well established approaches in parameter estimation and equation formulation along with their limitations, identifying performance gaps as well as providing directions for potential future research.

Parameter Optimization on Laser Welding of NiTi Wires by Taguchi Method

In this research, a preliminary study was done to find out the initial parameter window to obtain the full-penetrated NiTi weldment. A L27 Taguchi experiment was then carried out to statistically study the effects of the welding parameters and their possible interactions on the weld bead aspect ratio (or penetration over fuse-zone width ratio), and to determine the optimized parameter settings to produce the full-penetrated weldment with desirable aspect ratio. From the statistical results in the Taguchi experiment, the laser mode was found to be the most important factor that substantially affects the aspect ratio. Strong interaction between the power and focus position was found in the Taguchi experiment. The optimized weldment was mainly of columnar dendritic structure in the weld zone (WZ), while the HAZ exhibited equiaxed grain structure. The XRD and DSC results showed that the WZ remained the B2 austenite structure without any precipitates, but with a significant decrease of phase transformation temperatures. The results in the micro-hardness and tensile tests indicated that the mechanical properties of NiTi were decreased to a certain extent after fibre laser welding.

Using CAD parameter sensitivities for stack-up tolerance allocation

Tolerance allocation is an important step in the design process. It is necessary to produce high quality components cost-effectively. However, the process of allocating tolerances can be time consuming and difficult, especially for complex models. This work demonstrates a novel CAD based approach, where the sensitivities of product dimensions to changes in the values of the feature parameters in the CAD model are computed. These are used to automatically establish the assembly response function for the product. This information has been used to automatically allocate tolerances to individual part dimensions to achieve specified tolerances on the assembly dimensions, even for tolerance allocation in more than one direction simultaneously. It is also shown how pre-existing constraints on some of the part dimensions can be represented and how situations can be identified where the required tolerance allocation is not achievable. A methodology is also presented that uses the same information to model a component with different amounts of dimensional variation to simulate the effects of tolerance stack-up. © 2014 Springer-Verlag France.

Characterisation of Passive Intermodulation in Passive RF Devices with X-parameter

A novel approach to the modelling of passive intermodulation (PIM) generation in passive components with distributed weak nonlinearities is outlined. Based upon the formalism of X-parameters, it provides a unified framework for co-design of antenna beamforming networks, filters, combiners, phase shifters and other passive and active devices containing nonlinearities at RF front-end. The effects of discontinuities and complex circuit layouts can be efficiently evaluated with the aid of the equivalent networks of the canonical nonlinear elements. The main concepts are illustrated by examples of numerical simulations of PIM generation in the transmission lines and comparison with the measurement results.

Improving parameter learning of Bayesian nets from incomplete data

This paper addresses the estimation of parameters of a Bayesian network from incomplete data. The task is usually tackled by running the Expectation-Maximization (EM) algorithm several times in order to obtain a high log-likelihood estimate. We argue that choosing the maximum log-likelihood estimate (as well as the maximum penalized log-likelihood and the maximum a posteriori estimate) has severe drawbacks, being affected both by overfitting and model uncertainty. Two ideas are discussed to overcome these issues: a maximum entropy approach and a Bayesian model averaging approach. Both ideas can be easily applied on top of EM, while the entropy idea can be also implemented in a more sophisticated way, through a dedicated non-linear solver. A vast set of experiments shows that these ideas produce significantly better estimates and inferences than the traditional and widely used maximum (penalized) log-likelihood and maximum a posteriori estimates. In particular, if EM is adopted as optimization engine, the model averaging approach is the best performing one; its performance is matched by the entropy approach when implemented using the non-linear solver. The results suggest that the applicability of these ideas is immediate (they are easy to implement and to integrate in currently available inference engines) and that they constitute a better way to learn Bayesian network parameters.