A personal historic perspective on the role of chloride in skeletal and cardiac muscle

During the early decades of the last century, skeletal muscle was held to be impermeable to chloride ions. This theory, based on shaky grounds, was famously falsified by Boyle and Conway in 1941. Two decades later and onwards, the larger part of the resting conductance of skeletal muscle was found to be due to chloride ions, sensitive to the chemical environment, and to be time‐and‐voltage dependent. So, much of the groundwork for the physiological role of chloride ions in skeletal muscle was laid before the game‐changing discovery of chloride channels. The early history of the role of chloride in cardiac muscle, and work on the relative permeability to foreign anions of different muscles are also here covered from a personal perspective

An Enhanced Features Extractor for a Portfolio of Constraint Solvers

Recent research has shown that a single arbitrarily efficient solver can be significantly outperformed by a portfolio of possibly slower on-average solvers. The solver selection is usually done by means of (un)supervised learning techniques which exploit features extracted from the problem specification. In this paper we present an useful and flexible framework that is able to extract an extensive set of features from a Constraint (Satisfaction/Optimization) Problem defined in possibly different modeling languages: MiniZinc, FlatZinc or XCSP. We also report some empirical results showing that the performances that can be obtained using these features are effective and competitive with state of the art CSP portfolio techniques

Milieu-adopted in vitro and in vivo differentiation of mesenchymal tissues derived from different adult human CD34-negative progenitor cell clones

Adult mesenchymal stem cells with multilineage differentiation potentially exist in the bone marrow, but have also been isolated from the peripheral blood. The differentiation of stem cells after leaving their niches depends predominately on the local milieu and its new microenvironment, and is facilitated by soluble factors but also by the close cell-cell interaction in a three-dimensional tissue or organ system. We have isolated CD34-negative, mesenchymal stem cell lines from human bone marrow and peripheral blood and generated monoclonal cell populations after immortalization with the SV40 large T-antigen. The cultivation of those adult stem cell clones in an especially designed in vitro environment, including self-constructed glass capillaries with defined growth conditions, leads to the spontaneous establishment of pleomorphic three-dimensional cell aggregates ( spheroids) from the monoclonal cell population, which consist of cells with an osteoblast phenotype and areas of mineralization along with well-vascularized tissue areas. Modifications of the culture conditions favored areas of bone-like calcifications. After the transplantation of the at least partly mineralized human spheroids into different murine soft tissue sites but also a dorsal skinfold chamber, no further bone formation could be observed, but angiogenesis and neovessel formation prevailed instead, enabling the transplanted cells and cell aggregates to survive. This study provides evidence that even monoclonal adult human CD34-negative stem cells from the bone marrow as well as peripheral blood can potentially differentiate into different mesenchymal tissues depending on the local milieu and responding to the needs within the microenvironment. Copyright (C) 2005 S. Karger AG, Basel

Visualization of leukocyte transendothelial and interstitial migration using reflected light oblique transillumination in intravital video microscopy

Dynamic visualization of the intravascular events leading to the extravasation of leukocytes into tissues by intravital microscopy has significantly expanded our understanding of the underlying molecular processes. In contrast, the detailed observation of leukocyte transendothelial and interstitial migration in vivo has been hampered by the poor image contrast of cells within turbid media that is obtainable by conventional brightfield microscopy. Here we present a microscopic method, termed reflected light oblique transillumination microscopy, that makes use of the optical interference phenomena generated by oblique transillumination to visualize subtle gradients of refractive indices within tissues for enhanced image contrast. Using the mouse cremaster muscle, we demonstrate that this technique makes possible the reliable quantification of extravasated leukocytes as well as the characterization of morphological phenomena of leukocyte transendothelial and interstitial migration

Keep Rollin' - Whole-Body Motion Control and Planning for Wheeled Quadrupedal Robots

We show dynamic locomotion strategies for wheeled quadrupedal robots, which combine the advantages of both walking and driving. The developed optimization framework tightly integrates the additional degrees of freedom introduced by the wheels. Our approach relies on a zero-moment point based motion optimization which continuously updates reference trajectories. The reference motions are tracked by a hierarchical whole-body controller which computes optimal generalized accelerations and contact forces by solving a sequence of prioritized tasks including the nonholonomic rolling constraints. Our approach has been tested on ANYmal, a quadrupedal robot that is fully torque-controlled including the non-steerable wheels attached to its legs. We conducted experiments on flat and inclined terrains as well as over steps, whereby we show that integrating the wheels into the motion control and planning framework results in intuitive motion trajectories, which enable more robust and dynamic locomotion compared to other wheeled-legged robots. Moreover, with a speed of 4 m/s and a reduction of the cost of transport by 83 % we prove the superiority of wheeled-legged robots compared to their legged counterparts.Comment: IEEE Robotics and Automation Letter

MO-ParamILS: A Multi-objective Automatic Algorithm Configuration Framework

International audienceAutomated algorithm configuration procedures play an increasingly important role in the development and application of algorithms for a wide range of computationally challenging problems. Until very recently, these configuration procedures were limited to optimising a single performance objective, such as the running time or solution quality achieved by the algorithm being configured. However, in many applications there is more than one performance objective of interest. This gives rise to the multi-objective automatic algorithm configuration problem, which involves finding a Pareto set of configurations of a given target algorithm that characterises trade-offs between multiple performance objectives. In this work, we introduce MO-ParamILS, a multi-objective extension of the state-of-the-art single-objective algorithm configuration framework ParamILS, and demonstrate that it produces good results on several challenging bi-objective algorithm configuration scenarios compared to a base-line obtained from using a state-of-the-art single-objective algorithm configurator

Analysis of algorithm components and parameters : some case studies

Modern high-performing algorithms are usually highly parameterised, and can be configured either manually or by an automatic algorithm configurator. The algorithm performance dataset obtained after the configuration step can be used to gain insights into how different algorithm parameters influence algorithm performance. This can be done by a number of analysis methods that exploit the idea of learning prediction models from an algorithm performance dataset and then using them for the data analysis on the importance of variables. In this paper, we demonstrate the complementary usage of three methods along this line, namely forward selection, fANOVA and ablation analysis with surrogates on three case studies, each of which represents some special situations that the analyses can fall into. By these examples, we illustrate how to interpret analysis results and discuss the advantage of combining different analysis methods.Postprin