Patients with ALS show highly correlated progression rates in left and right limb muscles.

ObjectiveAmyotrophic lateral sclerosis (ALS) progresses at different rates between patients, making clinical trial design difficult and dependent on large cohorts of patients. Currently, there are few data showing whether the left and right limbs progress at the same or different rates. This study addresses rates of decline in specific muscle groups of patients with ALS and assesses whether there is a relationship between left and right muscles in the same patient, regardless of overall progression.MethodsA large cohort of patients was used to assess decline in muscle strength in right and left limbs over time using 2 different methods: The Tufts Quantitative Neuromuscular Exam and Accurate Test of Limb Isometric Strength protocol. Then advanced linear regression statistical methods were applied to assess progression rates in each limb.ResultsThis report shows that linearized progression models can predict general slopes of decline with good accuracy. Critically, the data demonstrate that while overall decline is variable, there is a high degree of correlation between left and right muscle decline in ALS. This implies that irrespective of which muscle starts declining soonest or latest, their rates of decline following onset are more consistent.ConclusionsFirst, this study demonstrates a high degree of power when using unilateral treatment approaches to detect a slowing in disease progression in smaller groups of patients, thus allowing for paired statistical tests. These findings will be useful in transplantation trials that use muscle decline to track disease progression in ALS. Second, these findings discuss methods, such as tactical selection of muscle groups, which can improve the power efficiency of all ALS clinical trials

Fast Algorithms for the Simulation of Electromagnetic Metal Forming

Despite the comprehensive understanding of the modeling and numerical simulation of electromagnetic metal forming that has recently been gained, the simulation of real forming situations is still a challenging task due to the large computational resources required. A bottleneck is the computation of the electromagnetic fields, since 100.000 up to several million unknowns are required to represent the geometry of a typical forming device. The purpose of this article is to present new techniques to speed up the simulation of electromagnetic metal forming with particular emphasis on the computation of the electromagnetic fields. An acceleration of the electromagnetic field computation is a significant step towards a virtual design of electromagnetic forming processes

Fully-coupled 3D Simulation of Electromagnetic Forming

Electromagnetic metal forming is a contact-free high-speed forming process in which strain rates of more than 103 s^(-1) are achieved. The deformation of the workpiece is driven by a material body force, the Lorentz force, that results from the interaction of a pulsed magnetic field with eddy currents induced in the workpiece by the magnetic field itself. The purpose of this work is to present a fully-coupled 3D simulation of the process. For the mechanical structure a thermoelastic, viscoplastic, electromagnetic material model is relevant, which is incorporated in a large-deformation dynamic formulation. The evolution of the electromagnetic fields is governed by Maxwell s equations under quasistatic conditions. Their numerical solution in 3D requires particular arrangements due to a reduced regularity at material interfaces. Hence, Nédélec elements are employed. Coupling between the thermomechanical and electromagnetic subsystems takes the form of the Lorentz force, the electromotive intensity, and the current geometry of the workpiece. A staggered scheme based on a Lagrangian mesh for the workpiece and an ALE formulation for the electromagnetic field is utilized to solve the coupled system, guaranteeing the efficiency and accuracy of the data transfer between the two meshes

Development of Multi Field Software Solutions and their Application for the Optimization of Electromagnetic High Speed Forming processes

The simulation of complex processes in engineering solids involving coupled mechanical and non-mechanical fields represents a challenge to physicists, mathematicians, and engineers. Both, the formulation of such models and their numerical implementation involve a great number of difficulties. Electromagnetic forming is one example of such a process, whose modelling and simulation requires a coupled electromagnetic-thermomechanical model. The purpose of this contribution is to discuss some key issues associated with the modelling and simulation of electromagnetic metal forming (EF) and the corresponding development of a finite-element-based simulation tool for EF. In particular, the modelling is based on a thermodynamically-consistent electromagnetic-thermoelastoviscoplastic material and field model in which the energy and momentum balance are coupled to the quasi-static form of Maxwell s equations via the electromotive intensity and Lorentz force, respectively. On the algorithmic side, questions like the choice of meshes, the element formulation, the numerical treatment of nonlinearities, possible model simplifications, different discretisation strategies, realisation of the non-linear coupling etc. are discussed for the presented software solution. Such issues are investigated with the help of benchmark simulations that have been developed for this purpose. Finally, as an example of an application of the developed software tool, a computer aided manufacturing (CAM) problem is considered. Here, the size of the tool coil and the peak value of the current in the tool coil circuit are optimised in order to achieve the prescribed work-piece form within the given tolerance

On the effect of current pulses on the material behavior during electromagnetic metal forming

Electromagnetic sheet metal forming (EMF) is an example of a high-speed forming process driven by the dynamics of a coupled electromagnetic-mechanical system. Basic physical processes involved in EMF, such as e.g. inelastic and hardening behavior or inertia, have been considered in previous works [1, 2]. The purpose of the current work is the investigation of temperature development during EMF and a possible reduction in the yield stress due to electric currents. While thermoelastic and viscoplastic effects are well-understood in this context [3], the possible influence of electric currents on dislocation motion, generally referred to as the electro-plastic effect [4, 5], is still an unresolved issue. In agreement with previous works [e.g., 6], it is concluded here that such an effect is at most of second-order and can most likely be safely neglected in the modeling and simulation of industrial EMF

Modeling and Simulation of 3D EMF Processes

A recent interest in potential industrial applications of electromagnetic forming processes has inspired a demand for adequate simulation tools. Aiming at the virtual design of industrial applications, the purpose of this work is to develop algorithmic formulations particularly suitable to reduce the enormous computational cost inherent to 3D simulations. These formulations comprise a carefully chosen discretization, highly accurate methods for data transfer between electromagnetic and mechanical subsystems, an efficient solid shell formulation, and a termination criterion for the electromagnetic field computation. As a result the simulation time is reduced by about one order of magnitude

Modular termination verification for non-blocking concurrency

© Springer-Verlag Berlin Heidelberg 2016.We present Total-TaDA, a program logic for verifying the total correctness of concurrent programs: that such programs both terminate and produce the correct result. With Total-TaDA, we can specify constraints on a thread’s concurrent environment that are necessary to guarantee termination. This allows us to verify total correctness for nonblocking algorithms, e.g. a counter and a stack. Our specifications can express lock- and wait-freedom. More generally, they can express that one operation cannot impede the progress of another, a new non-blocking property we call non-impedance. Moreover, our approach is modular. We can verify the operations of a module independently, and build up modules on top of each other

Simultaneous laser-driven x-ray and two-photon fluorescence imaging of atomizing sprays

In this Letter, we report for the first time, to the best of our knowledge, the possibility of visualizing an atomizing spray by simultaneously recording x-ray absorption and two-photon laser-induced fluorescence imaging. This unique illumination/detection scheme is made possible due to the use of soft x rays emitted from a laser-driven x-ray source. An 800 mJ laser pulse of 38 fs duration is used to generate an x-ray beam with up to 4 × 108 photons ranging from 1 to 10 keV, allowing projection radiography of water jets generated by an automotive port fuel injector. In addition, a fraction of the laser pulse (∼10mJ) is employed to form a light sheet and to induce two-photon fluorescence in a dye added to the water. The resulting high-contrast fluorescence images provide fine details of the spray structure, with reduced blur from multiple light scattering, while the integrated liquid mass is extracted from the x-ray radiography. In this proof of principle, we show that the combination of these two highly complementary techniques, in both the visible and soft x-ray regimes, is very promising for future characterization of challenging spray, as well as for further understanding of the physics of liquid atomization

Verifying object-oriented programs with higher-order separation logic in Coq

We present a shallow Coq embedding of a higher-order separation logic with nested triples for an object-oriented programming language. Moreover, we develop novel specification and proof patterns for reasoning in higher-order separation logic with nested triples about programs that use interfaces and interface inheritance. In particular, we show how to use the higher-order features of the Coq formalisation to specify and reason modularly about programs that (1) depend on some unknown code satisfying a specification or that (2) return objects conforming to a certain specification. All of our results have been formally verified in the interactive theorem prover Coq