In the past two years the US LARP program carried out five tests on a quadrupole magnet aimed at the high luminosity upgrade of Large Hadron Collider (HiLumi-LHC). The 1-meter long, 120 mm bore Nb Sn IR quadrupole magnet (HQ) with a short sample gradient of 219 T/m at 1.9 K and a conductor peak field of 15 T is part of the US LHC Accelerator Research Program (LARP). In a series of tests, carried out at 4.4 K, the magnet reached a maximum "short-sample" performance of 86%. The tests exposed several shortcomings that are now being addressed in a Research & Development program. This paper summarizes the magnet test results, reveals findings, R&D actions and future improvements.
Making high-quality dopamine (DA)-producing cells for basic biological or small molecule screening studies is critical for the development of novel therapeutics for disorders of the ventral midbrain. Currently, many ventral midbrain assays have low signal-to-noise ratio due to low levels of cellular DA and the rate-limiting enzyme of DA synthesis, tyrosine hydroxylase (TH), hampering discovery efforts. Using intensively characterized ventral midbrain cells derived from human skin, which demonstrate calcium pacemaking activity and classical electrophysiological properties, we show that an L-type calcium agonist can significantly increase TH protein levels and DA content and release. Live calcium imaging suggests that it is the immediate influx of calcium occurring simultaneously in all cells that drives this effect. Genome-wide expression profiling suggests that L-type calcium channel stimulation has a significant effect on specific genes related to DA synthesis and affects expression of L-type calcium receptor subunits from the CACNA1 and CACNA2D families. Together, our findings provide an advance in the ability to increase DA and TH levels to improve the accuracy of disease modeling and small molecule screening for disorders of the ventral midbrain, including Parkinson's disease. K E Y W O R D S cell biology, induced pluripotent stem cells (iPSCs), nervous system, neural differentiation, neural induction Malvin Jefri and Scott Bell are co-first authors.
The large range of length scales present within accelerator magnets suggests the incorporation of a hierarchical structure into computational models. Evaluation of the strain state present within the superconducting filaments is necessary in order to determine the critical current of based magnets. As part of an ongoing investigation at LBNL, a three-dimensional nonlinear multiscale model is developed to investigate the behavior of strands. The strain state in the superconducting filaments is examined by simulating a cool down from reaction to 4.2 K. The effects of strand geometry on the final strain state are also explored. The validity of the model is tested through the comparison of the predicted moduli to experimental tangent measurements.
Spiking neuronal networks are usually simulated with one of three main schemes: the classical time-driven and event-driven schemes, and the more recent hybrid scheme. All three schemes evolve the state of a neuron through a series of checkpoints: equally spaced in the first scheme and determined neuron-wise by spike events in the latter two. The time-driven and the hybrid scheme determine whether the membrane potential of a neuron crosses a threshold at the end of the time interval between consecutive checkpoints. Threshold crossing can, however, occur within the interval even if this test is negative. Spikes can therefore be missed. The present work offers an alternative geometric point of view on neuronal dynamics, and derives, implements, and benchmarks a method for perfect retrospective spike detection. This method can be applied to neuron models with affine or linear subthreshold dynamics. The idea behind the method is to propagate the threshold with a time-inverted dynamics, testing whether the threshold crosses the neuron state to be evolved, rather than vice versa. Algebraically this translates into a set of inequalities necessary and sufficient for threshold crossing. This test is slower than the imperfect one, but can be optimized in several ways. Comparison confirms earlier results that the imperfect tests rarely miss spikes (less than a fraction 1/108 of missed spikes) in biologically relevant settings.
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