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  • 1
    Publication Date: 2021-09-29
    Description: To understand and predict large, complex, and chaotic systems, Earth scientists build simulators from physical laws. Simulators generalize better to new scenarios, require fewer tunable parameters, and are more interpretable than nonphysical deep learning, but procedures for obtaining their derivatives with respect to their inputs are often unavailable. These missing derivatives limit the application of many important tools for forecasting, model tuning, sensitivity analysis, or subgrid‐scale parametrization. Here, we propose to overcome this limitation with deep emulator networks that learn to calculate the missing derivatives. By training directly on simulation data without analyzing source code or equations, this approach supports simulators in any programming language on any hardware without specialized routines for each case. To demonstrate the effectiveness of our approach, we train emulators on complete or partial system states of the chaotic Lorenz‐96 simulator and evaluate the accuracy of their dynamics and derivatives as a function of integration time and training data set size. We further demonstrate that emulator‐derived derivatives enable accurate 4D‐Var data assimilation and closed‐loop training of parametrizations. These results provide a basis for further combining the parsimony and generality of physical models with the power and flexibility of machine learning.
    Description: Plain Language Summary: Many Earth science simulators are implemented as monolithic programs that calculate changes in the state of a system over time. In many cases, using or improving these simulators also requires the derivatives of their outputs with respect to inputs, which describe how future states depend on past states. These derivatives can be difficult or costly to compute. Several recent studies have applied deep learning (DL) to simulation data to construct emulators of their dynamics. Here, we use the fact that DL models can be easily and automatically differentiated to obtain approximate derivatives of the original simulator and test this idea on a simple and common chaotic model of the atmosphere. We verify in several experiments that the emulator derivatives, which require neither additional training nor extensive postprocessing to obtain, can indeed be used as a valid substitute for the derivatives of the simulator.
    Description: Key Points: Deep learning models trained on simulation data can learn the dynamics of Earth science simulators. Deep learning models also learn the input–output derivatives of the state‐update function, which are unavailable for many simulators. We show on Lorenz‐96 that these learned derivatives can be used directly for data assimilation and parametrization tuning.
    Keywords: 550 ; machine learning ; deep learning ; data assimilation ; parametrization tuning ; model Jacobians ; Lorenz‐96
    Type: map
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  • 2
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Dp71 is a non-muscle product of the Duchenne muscular dystrophy gene. It consists of the cysteine-rich and C-terminal domains of dystrophin. We have generated transgenic mdx mice which do not have dystrophin but express Dp71 in their muscle. In these mice, Dp71 was localized to the plasma membrane ...
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Theory of computing systems 24 (1991), S. 295-321 
    ISSN: 1433-0490
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract We present new techniques for mapping computations onto hypercubes. Our methods speed up classical implementations of grid and tree communications by a factor of Θ(n), wheren is the number of hypercube dimensions. The speedups are asymptotically the best possible. We obtain these speedups by mapping each edge of the guest graph onto short, edge-disjoint paths in the hypercube such that the maximum congestion on any hypercube edge isO(1). These multiple-path embeddings can be used to reduce communication time for large grid-based scientific computations, to increase tolerance to link faults, and for fast routing of large messages. We also develop a general technique for deriving multiple-path embeddings from multiple-copy embeddings. Multiple-copy embeddings are one-to-one maps of independent copies of the guest graph within the hypercube. We present an efficient multiple-copy embedding of the cube-connected-cycles network within the hypercube. This embedding is used to derive efficient multiple-path embeddings of trees and butterfly networks in hypercubes.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Theory of computing systems 23 (1990), S. 61-77 
    ISSN: 1433-0490
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract We present optimal embeddings of three genres of butterfly-like graphs in the (boolean) hypercube; each embedding is specified via a linear-time algorithm. Our first embedding finds an instance of the FFT graph as a subgraph of the smallest hypercube that is big enough to hold it; thus, we embed then-level FFT graph, which has (n+1)2 n vertices, in the (n+⌈log2(n+1)⌉)-dimensional hypercube, with unit dilation. This embedding yields a mapping of the pipelined FFT algorithm on the hypercube architecture, which is optimal in all resources (time, processor utilization, load balancing, etc.) and which is on-line in the sense that inputs can be added to the transform even during the computation. Second, we find optimal embeddings of then-level butterfly graph and then-level cube-connected cycles graph, each of which hasn2 n vertices, in the (n+⌈log2 n⌉)-dimensional hypercube. These embeddings, too, have optimal dilation, congestion, and expansion. The dilation is 1+(n mod 2), which is best possible. Our embeddings indicate that these two bounded-degree approximations to the hypercube do not have any communication power that is not already present in the hypercube.
    Type of Medium: Electronic Resource
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  • 5
    Publication Date: 2017-06-05
    Description: Epilepsy is a common neurological disease, manifested in unprovoked recurrent seizures. Epileptogenesis may develop due to genetic or pharmacological origins or following injury, but it remains unclear how the unaffected brain escapes this susceptibility to seizures. Here, we report that dynamic changes in forebrain microRNA (miR)-211 in the mouse brain shift the threshold for spontaneous and pharmacologically induced seizures alongside changes in the cholinergic pathway genes, implicating this miR in the avoidance of seizures. We identified miR-211 as a putative attenuator of cholinergic-mediated seizures by intersecting forebrain miR profiles that were Argonaute precipitated, synaptic vesicle target enriched, or differentially expressed under pilocarpine-induced seizures, and validated TGFBR2 and the nicotinic antiinflammatory acetylcholine receptor nAChRa7 as murine and human miR-211 targets, respectively. To explore the link between miR-211 and epilepsy, we engineered dTg-211 mice with doxycycline-suppressible forebrain overexpression of miR-211. These mice reacted to doxycycline exposure by spontaneous electrocorticography-documented nonconvulsive seizures, accompanied by forebrain accumulation of the convulsive seizures mediating miR-134. RNA sequencing demonstrated in doxycycline-treated dTg-211 cortices overrepresentation of synaptic activity, Ca2+ transmembrane transport, TGFBR2 signaling, and cholinergic synapse pathways. Additionally, a cholinergic dysregulated mouse model overexpressing a miR refractory acetylcholinesterase-R splice variant showed a parallel propensity for convulsions, miR-211 decreases, and miR-134 elevation. Our findings demonstrate that in mice, dynamic miR-211 decreases induce hypersynchronization and nonconvulsive and convulsive seizures, accompanied by expression changes in cholinergic and TGFBR2 pathways as well as in miR-134. Realizing the importance of miR-211 dynamics opens new venues for translational diagnosis of and interference with epilepsy.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 6
    Publication Date: 2008-06-15
    Print ISSN: 1097-6256
    Electronic ISSN: 1546-1726
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 7
    Publication Date: 1994-12-01
    Print ISSN: 1061-4036
    Electronic ISSN: 1546-1718
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 8
    Publication Date: 2020-09-17
    Description: Mechanistic modeling in neuroscience aims to explain observed phenomena in terms of underlying causes. However, determining which model parameters agree with complex and stochastic neural data presents a significant challenge. We address this challenge with a machine learning tool which uses deep neural density estimators—trained using model simulations—to carry out Bayesian inference and retrieve the full space of parameters compatible with raw data or selected data features. Our method is scalable in parameters and data features and can rapidly analyze new data after initial training. We demonstrate the power and flexibility of our approach on receptive fields, ion channels, and Hodgkin–Huxley models. We also characterize the space of circuit configurations giving rise to rhythmic activity in the crustacean stomatogastric ganglion, and use these results to derive hypotheses for underlying compensation mechanisms. Our approach will help close the gap between data-driven and theory-driven models of neural dynamics.
    Electronic ISSN: 2050-084X
    Topics: Biology , Medicine , Natural Sciences in General
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  • 9
    Publication Date: 2013-01-22
    Description: Action Potential (APs) patterns of sensory cortex neurons encode a variety of stimulus features, but how can a neuron change the feature to which it responds? Here, we show that in vivo a spike-timing-dependent plasticity (STDP) protocol—consisting of pairing a postsynaptic AP with visually driven presynaptic inputs—modifies a neurons' AP-response in a bidirectional way that depends on the relative AP-timing during pairing. Whereas postsynaptic APs repeatedly following presynaptic activation can convert subthreshold into suprathreshold responses, APs repeatedly preceding presynaptic activation reduce AP responses to visual stimulation. These changes were paralleled by restructuring of the neurons response to surround stimulus locations and membrane-potential time-course. Computational simulations could reproduce the observed subthreshold voltage changes only when presynaptic temporal jitter was included. Together this shows that STDP rules can modify output patterns of sensory neurons and the timing of single-APs plays a crucial role in sensory coding and plasticity.
    Electronic ISSN: 2050-084X
    Topics: Biology , Medicine , Natural Sciences in General
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  • 10
    Publication Date: 2020-06-03
    Description: Stereotypic behavior (SB) is common in emotional stress-involved psychiatric disorders and is often attributed to glutamatergic impairments, but the underlying molecular mechanisms are unknown. Given the neuro-modulatory role of acetylcholine, we sought behavioral-transcriptomic links in SB using TgR transgenic mice with impaired cholinergic transmission due to over-expression of the stress-inducible soluble ‘readthrough’ acetylcholinesterase-R splice variant AChE-R. TgR mice showed impaired organization of behavior, performance errors in a serial maze test, escape-like locomotion, intensified reaction to pilocarpine and reduced rearing in unfamiliar situations. Small-RNA sequencing revealed 36 differentially expressed (DE) microRNAs in TgR mice hippocampi, 8 of which target more than 5 cholinergic transcripts. Moreover, compared to FVB/N mice, TgR prefrontal cortices displayed individually variable changes in over 400 DE mRNA transcripts, primarily acetylcholine and glutamate-related. Furthermore, TgR brains presented c-fos over-expression in motor behavior-regulating brain regions and immune-labeled AChE-R excess in the basal ganglia, limbic brain nuclei and the brain stem, indicating a link with the observed behavioral phenotypes. Our findings demonstrate association of stress-induced SB to previously unknown microRNA-mediated perturbations of cholinergic/glutamatergic networks and underscore new therapeutic strategies for correcting stereotypic behaviors.
    Electronic ISSN: 2218-273X
    Topics: Biology
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