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At least 577 records · Page 32

Demonstration of Decentralized Physics-Driven Learning

In typical artificial neural networks, neurons adjust according to global calculations of a central processor, but in the brain, neurons and synapses self-adjust based on local information. Contrastive learning algorithms have recently been proposed to train physical systems, such as fluidic, mechanical, or electrical networks, to perform machine-learning tasks from local evolution rules. However, to date, such systems have only been implemented in silico due to the engineering challenge of creating elements that autonomously evolve based on their own response to two sets of global boundary conditions. Here, we introduce and implement a physics-driven contrastive learning scheme for a network of variable resistors, using circuitry to locally compare the response of two identical networks subjected to the two different sets of boundary conditions. Using this method, our system effectively trains itself, optimizing its resistance values without the use of a central processor or external information storage. Once the system is trained for a specified allostery, regression, or classification task, the task is subsequently performed rapidly and automatically by the physical imperative to minimize power dissipation in response to the given voltage inputs. Here, we demonstrate that, unlike typical computers, such learning systems are robust to extreme damage (and thus manufacturing defects) due to their decentralized learning. Our twin-network approach is therefore readily scalable to extremely large or nonlinear networks, where its distributed nature will be an enormous advantage; a laboratory network of only 500 edges will already outpace its in silico counterpart.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Dynamics of voltage-driven oscillating insulator-metal transitions

Recent experiments demonstrated emerging alternating insulator and metal phases in Mott insulators actuated by a direct bias voltage, leading to oscillating voltage outputs with characteristic frequencies. Here, we develop a physics-based nonequilibrium model to describe the dynamics of oscillating insulator-metal phase transitions and experimentally validate it using a VO 2 device as a prototype. The oscillation frequency is shown to scale monotonically with the bias voltage and series resistance and terminate abruptly at lower and upper device-dependent limits, which are dictated by the nonequilibrium carrier dynamics. Here, we derive an approximate analytical expression for the dependence of the frequency on the device operating parameters, which yields a fundamental limit to the frequency and may be utilized to provide guidance to potential applications of insulator-metal transition materials as building blocks of brain-inspired non-von Neumann computers.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Electronegative metal dopants improve switching variability in Al 2 ⁢O 3 resistive switching devices

Resistive random-access memories are promising for nonvolatile memory and brain-inspired computing applications. High variability and low yield of these devices are key drawbacks hindering reliable training of physical neural networks. In this paper, we show that doping an oxide electrolyte, Al 2 ⁢O 3 , with electronegative metals makes resistive switching significantly more reproducible, surpassing the reproducibility requirements for obtaining reliable hardware neuromorphic circuits. Based on density functional theory calculations, the underlying mechanism is hypothesized to be the ease of creating oxygen vacancies in the vicinity of electronegative dopants due to the capture of the associated electrons by dopant midgap states and the weakening of Al-O bonds. These oxygen vacancies and vacancy clusters also bind significantly to the dopant, thereby serving as preferential sites and building blocks in the formation of conducting paths. Throughout this work, we validate this theory experimentally by implanting different dopants over a range of electronegativities in devices made of multiple alternating layers of Al 2 ⁢O 3 and WN and find superior repeatability and yield with highly electronegative metals, Au, Pt, and Pd. These devices also exhibit a gradual SET transition, enabling multibit switching that is desirable for analog computing.

36 MATERIALS SCIENCE↗

Understanding protein-complex assembly through grand canonical maximum entropy modeling

Inside a cell, heterotypic proteins assemble in inhomogeneous, crowded systems where the abundance of these proteins vary with cell types. While some protein complexes form putative structures that can be visualized with imaging, there are far more protein complexes that are yet to be solved because of their dynamic associations with one another. Nevertheless, it is possible to infer these protein complexes through a physical model. However, it is often not clear to physicists what kind of data from biology is necessary for such a modeling endeavor. Here, we aim to model these clusters of coarse-grained protein assemblies from multiple subunits through the constraints of interactions among the subunits and the chemical potential of each subunit. We obtained the constraints on the interactions among subunits from the known protein structures. We inferred the chemical potential that dictates the particle number distribution of each protein subunit from the knowledge of protein abundance from experimental data. Guided by the maximum entropy principle, we formulated an inverse statistical mechanical method to infer the distribution of particle numbers from the data of protein abundance as chemical potentials for a grand canonical multicomponent mixture. Using grand canonical Monte Carlo simulations, we captured a distribution of high-order clusters in a protein complex of succinate dehydrogenase with four known subunits. The complexity of hierarchical clusters varies with the relative protein abundance of each subunit in distinctive cell types such as lung, heart, and brain. When the crowding content increases, we observed that crowding stabilizes emergent clusters that do not exist in dilute conditions. We, therefore, proposed a testable hypothesis that the hierarchical complexity of protein clusters on a molecular scale is a plausible biomarker of predicting the phenotypes of a cell.

59 BASIC BIOLOGICAL SCIENCES↗

A lathe system for micrometre-sized cylindrical sample preparation at room and cryogenic temperatures

A simple two-spindle based lathe system for the preparation of cylindrical samples intended for X-ray tomography is presented. The setup can operate at room temperature as well as under cryogenic conditions, allowing the preparation of samples down to 20 and 50 µm in diameter, respectively, within minutes. Case studies are presented involving the preparation of a brittle biomineral brachiopod shell and cryogenically fixed soft brain tissue, and their examination by means of ptychographic X-ray computed tomography reveals the preparation method to be mainly free from causing artefacts. Since this lathe system easily yields near-cylindrical samples ideal for tomography, a usage for a wide variety of otherwise challenging specimens is anticipated, in addition to potential use as a time- and cost-saving tool prior to focused ion-beam milling. Fast sample preparation becomes especially important in relation to shorter measurement times expected in next-generation synchrotron sources.

36 MATERIALS SCIENCE↗

FTTN: Feature-Targeted Testing for Numerical Properties of NVIDIA & AMD Matrix Accelerators

While NVIDIA has been the dominant provider of GPUs for HPC and ML, now AMD has several offerings of GPUs. This encourages programmers to try out AMD GPUs for new codes and also port existing codes over. Unfortunately, without understanding the floating-point differences between these GPU types, software development or porting can introduce bugs—and currently such an understanding is lacking. The magnitude of this open question becomes clear if one imagines the the number of floating-point precision choices (FP16, FP32, etc.), floating-point formats (standard floats, brain-float, etc.), and execution units available (elementary units, matrix/tensor cores, etc.) Questions such as rounding modes and subnormal support are also important. Most of these answers are unknown today or are hard to access. We provide the first testing-guided approach that answers a significant number of these questions. We also devise tests to reveal internal information (e.g., extra bits kept) to make sure that our findings are reliable. Many of our tests employ systematically generated random-programs, others apply fast-math flags and some involve fused multiplyadd. Especially for tensor/matrix cores, the tests have nontrivial logic that we present Our testing approach is reusable for the plethora of GPUs yet to be introduced. Our findings include up to 7 ulps of difference between NVIDIA and AMD for sin and cos at FP32 precision and 3 ulp at FP64. In our study of matrix cores (NVIDIA) and tensor cores (AMD), we have extensively characterized rounding modes (truncation versus round-to-nearest), the number of extra internal bits kept (whether 3 bits are kept or not), subnormal support for inputs and outputs across four different floating-point formats and across NVIDIA A100 and AMD MI250X GPUs. We believe that this wealth of data becoming available for the first time may help avoid significant porting bugs when migrating code across these platforms.

Li, Xinyi↗

Automated Generation of Integrated Digital and Spiking Neuromorphic Machine Learning Accelerators

The growing numbers of application areas for artificial intelligence (AI) methods have led to an explosion of domain-specific accelerators that could support every new machine learning (ML) algorithm advancement, clearly highlighting the need for a capability to quickly and automatically transition from algorithm definition to hardware implementation and explore design space along a variety of SWaP (size, weight and Power). The software defined architectures (SODA) synthesizer implements a compiler-based modular infrastructure for the end-to-end generation of machine learning accelerators from high-level frameworks to hardware description language. At the same time, neuromorphic computing, by mimicking how the brain operates, promises to perform artificial intelligence tasks at efficiencies orders of magnitude higher than the current conventional tensor-processing based accelerators, as demonstrated by a variety of specialized designs leveraging Spiking Neural Networks (SNNs). Nevertheless, the mapping of an artificial neural network (ANN) to solutions supporting SNNs is still a non-trivial and very device-specific task, and completely lack the possibility to design hybrid systems that integrate conventional and spiking neural models. In this paper we discuss the support for such an integrated generation leveraging the SODA Synthesizer framework and its modular structure. In particular, we present a new MLIR dialect (part of the SODA frontend) that allows expressing spiking neural network features (e.g., available resources, spiking sequences, analog signal reading, etc.) and illustrate how it enables mapping to Spiking Neurons and deployment to the related specialized hardware (which, in the digital domain, could be generated through the other existing layers of the SODA Synthesizer). We then discuss the opportunities for even deeper integration afforded by the hardware compilation infrastructure, providing a path towards the generation of complex heterogeneous artificial intelligence systems.

Curzel, Serena↗

A Suppression-based STDP Rule Resilient to Jitter Noise in Spike Patterns for Neuromorphic Computing

Multi-spike models of synaptic plasticity, such as the triplet and suppression spike-timing-dependent plasticity (STDP) rules, exhibit better alignment with neurophysiological data in the brain compared to the pair-based STDP rule. Previous studies have empirically shown that the pair-based STDP rule can detect spatiotemporal spike patterns hidden in equally dense distractor spike trains in an unsupervised manner. However, it fails to detect spike patterns influenced by jitter noise. Given that spiking neural networks (SNNs) exhibit variability in generated spike trains in response to the same inputs, it becomes imperative to have learning rules capable of detecting spike patterns even in the presence of jitter noise. In this study, we introduce a simplified suppression-based STDP rule that demonstrates significantly enhanced tolerance to jitter in spike patterns compared to the pair-based STDP rule. Unlike the ideal suppression STDP rule, characterized by an exponential learning window and requiring high-resolution synapses, the simplified rule limits the synaptic efficacy update to a single bit at any given instant. Moreover, it employs 4-bit fixed-point synapses, facilitating straightforward implementation in neuromorphic hardware.

Gautam, Ashish [ORNL]↗

Virtual Neuron: A Neuromorphic Approach for Encoding Numbers

Neuromorphic computers perform computations by emulating the human brain and are expected to be indispensable for energy-efficient computing in the future. They are primarily used in spiking neural network-based machine learning applications. However, neuromorphic computers are unable to preprocess data for these applications. Currently, data is preprocessed on a CPU or a GPU-this incurs a significant cost of transferring data from the CPU/GPU to the neuromorphic processor and vice versa. This cost can be avoided if preprocessing is done on the neuromorphic processor. To efficiently preprocess data on a neuromorphic processor, we first need an efficient mechanism for encoding data that can lend itself to all general-purpose preprocessing operations. Current encoding approaches have limited applicability and may not be suitable for all preprocessing operations. In this paper, we present the virtual neuron as a mechanism for encoding integers and rational numbers on neuromorphic processors. We evaluate the performance of the virtual neuron on physical and simulated neuromorphic hardware and show that it can perform an addition operation using 23 nJ of energy on average using a mixed-signal, memristor-based neuromorphic processor. The virtual neuron encoding approach is the first step in preprocessing data on a neuromorphic processor.

Date, Prasanna↗

Explaining Neural Spike Activity for Simulated Bio-plausible Network through Deep Sequence Learning

With significant improvements in large-scale simulations of brain models, there is a growing need to develop tools for rapid analysis and interpreting the simulation results. In this work, we explore the potential of sequential deep learning models to understand and explain the network dynamics among the neurons extracted from a large-scale neural simulation in STACS (Simulation Tool for Asynchronous Cortical Stream). Our method employs a representative neuroscience model that abstracts the cortical dynamics with a reservoir of randomly connected spiking neurons with a low stable spike firing rate throughout the simulation duration. We subsequently analyze the spike dynamics of the simulated spiking neural network through an autoencoder model and an attention-based mechanism.

Kulkarni, Shruti↗

Modeling the Impacts of Material Properties on Oscillatory Neuron Behavior

In this study, neuromorphic computing, which mimics the functions of biological brains, offers improvements in both latency and energy efficiency over typical von Neumann computing architectures. Spiking neural networks can be especially power-efficient because they encode information temporally and can use more sparse electrical inputs. Here, we study the design of volatile memristors (variable resistors with memory) for neuronal devices, with particular consideration toward the feasibility of all-on-chip oscillation using built-in capacitance. We use circuit simulations to model the behavior of oscillator neurons with a range of realistic material properties. We find that energy inputs increase with insulating-phase resistivity, thermal conductivity, and device aspect ratio. However, we also find that the minimum capacitance needed for oscillation decreases with increasing insulating-phase resistivity, which opposes the constraints for power efficiency. Based on published data on NbO 2 , VO 2 , and EuNiO 3 , we find that existing materials can be engineered for all-on-chip spiking using their parasitic capacitance.

36 MATERIALS SCIENCE↗

MemXCT: Design, Optimization, Scaling, and Reproducibility of X-Ray Tomography Imaging

Here, this work extends our previous research entitled "MemXCT: Memory-centric X-ray CT Reconstruction with Massive Parallelization" that was originally published at SC19 conference (Hidayetoglu et al., 2019) with reproducibility of the computational imaging performance. X-ray computed tomography (XCT) is regularly used at synchrotron light sources to study the internal morphology of materials at high resolution. However, experimental constraints, such as radiation sensitivity, can result in noisy or undersampled measurements. Further, depending on the resolution, sample size and data acquisition rates, the resulting noisy dataset can be in the order of terabytes. Advanced iterative reconstruction techniques can produce high-quality images from noisy measurements, but their computational requirements have made their use an exception rather than the rule. We propose a novel memory-centric approach that avoids redundant computations at the expense of additional memory complexity. We develop a memory-centric iterative reconstruction system, MemXCT, that uses an optimized SpMV implementation with two-level pseudo-Hilbert ordering and multi-stage input buffering. We evaluate MemXCT on various supercomputer architectures involving KNL and GPU. MemXCT can reconstruct a large (11Kx11K) mouse brain tomogram in 10 seconds using 4096 KNL nodes (256K cores). The results presented in our original article at the SC19 were based on large-scale supercomputing resources. The MemXCT application was selected for the Student Cluster Competition (SCC) Reproducibility Challenge and evaluated on a variety of cloud computing resources by universities around the world in the SC20 conference. We summarize the results of the top-ranked SCC Reproducibility Challenge teams and identify the most pertinent measures for ensuring the reproducibility of our experiments in this article.

47 OTHER INSTRUMENTATION↗

Pursuing sources of heterogeneity in modeling clustered population

Abstract Researchers often have to deal with heterogeneous population with mixed regression relationships, increasingly so in the era of data explosion. In such problems, when there are many candidate predictors, it is not only of interest to identify the predictors that are associated with the outcome, but also to distinguish the true sources of heterogeneity , that is, to identify the predictors that have different effects among the clusters and thus are the true contributors to the formation of the clusters. We clarify the concepts of the source of heterogeneity that account for potential scale differences of the clusters and propose a regularized finite mixture effects regression to achieve heterogeneity pursuit and feature selection simultaneously. We develop an efficient algorithm and show that our approach can achieve both estimation and selection consistency. Simulation studies further demonstrate the effectiveness of our method under various practical scenarios. Three applications are presented, namely, an imaging genetics study for linking genetic factors and brain neuroimaging traits in Alzheimer's disease, a public health study for exploring the association between suicide risk among adolescents and their school district characteristics, and a sport analytics study for understanding how the salary levels of baseball players are associated with their performance and contractual status.

Li, Yan↗

Inference for Nonparanormal Partial Correlation via Regularized Rank-Based Nodewise Regression

Abstract Partial correlation is a common tool in studying conditional dependence for Gaussian distributed data. However, partial correlation being zero may not be equivalent to conditional independence under non-Gaussian distributions. In this paper, we propose a statistical inference procedure for partial correlations under the high-dimensional nonparanormal (NPN) model where the observed data are normally distributed after certain monotone transformations. The NPN partial correlation is the partial correlation of the normal transformed data under the NPN model, which is a more general measure of conditional dependence. We estimate the NPN partial correlations by regularized nodewise regression based on the empirical ranks of the original data. A multiple testing procedure is proposed to identify the nonzero NPN partial correlations. The proposed method can be carried out by a simple coordinate descent algorithm for lasso optimization. It is easy-to-implement and computationally more efficient compared to the existing methods for estimating NPN graphical models. Theoretical results are developed to show the asymptotic normality of the proposed estimator and to justify the proposed multiple testing procedure. Numerical simulations and a case study on brain imaging data demonstrate the utility of the proposed procedure and evaluate its performance compared to the existing methods. Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.

97 MATHEMATICS AND COMPUTING↗

Fast HARDI Uncertainty Quantification and Visualization with Spherical Sampling

In this paper, we study uncertainty quantification and visualization of orientation distribution functions (ODF), which corresponds to the diffusion profile of high angular resolution diffusion imaging (HARDI) data. The shape inclusion probability (SIP) function is the state‐of‐the‐art method for capturing the uncertainty of ODF ensembles. The current method of computing the SIP function with a volumetric basis exhibits high computational and memory costs, which can be a bottleneck to integrating uncertainty into HARDI visualization techniques and tools. We propose a novel spherical sampling framework for faster computation of the SIP function with lower memory usage and increased accuracy. In particular, we propose direct extraction of SIP isosurfaces, which represent confidence intervals indicating spatial uncertainty of HARDI glyphs, by performing spherical sampling of ODFs. Our spherical sampling approach requires much less sampling than the state‐of‐the‐art volume sampling method, thus providing significantly enhanced performance, scalability, and the ability to perform implicit ray tracing. Our experiments demonstrate that the SIP isosurfaces extracted with our spherical sampling approach can achieve up to 8164× speedup, 37282× memory reduction, and 50.2% less SIP isosurface error compared to the classical volume sampling approach. We demonstrate the efficacy of our methods through experiments on synthetic and human‐brain HARDI datasets.

97 MATHEMATICS AND COMPUTING↗

Allopregnanolone as an Adjunct Therapy to Midazolam is More Effective Than Midazolam Alone in Suppressing Soman‐Induced Status Epilepticus in Male Rats

ABSTRACT Aims Humans and animals acutely intoxicated with the organophosphate soman can develop sustained status epilepticus (SE) that rapidly becomes refractory to benzodiazepines. We compared the antiseizure efficacy of midazolam, a current standard of care treatment for OP‐induced SE, versus combined therapy with midazolam and allopregnanolone (ALLO) in a rat model of soman‐induced SE. Methods Soman‐intoxicated male rats with robust seizure behavior and high‐amplitude electroencephalographic (EEG) activity were administered midazolam (0.65 mg, i.m.) 20 min after seizure initiation and 10 min later either a second dose of midazolam or ALLO (12 or 24 mg/kg, i.m.). Seizure behavior and EEG were monitored for 4 h after treatment. Brains were collected at the end of the monitoring period for histological analyses. Results Animals receiving 2 doses of midazolam exhibited persistent SE. Sequential dosing with midazolam followed by ALLO suppressed electrographic seizure activity. The combination therapy also significantly reduced soman‐induced neurodegeneration and neuroinflammation compared to 2 doses of midazolam. High but not low dose ALLO was associated with transitory and reversible respiratory compromise during the 1 h period after dosing. Conclusions Treatment with midazolam followed by ALLO was more effective than 2 doses of midazolam in suppressing benzodiazepine‐refractory, soman‐induced SE, and in mitigating its acute neuropathological consequences.

Andrew, Peter M. [Department of Molecular Bioscien↗

Physiologically based modeling reveals different risk of respiratory depression after fentanyl overdose between adults and children

Despite a rapid increase in pediatric mortality rate from prescription and illicit opioids, there is limited research on the dose-dependent impact of opioids on respiratory depression in children, the leading cause of opioid-associated death. In this article, we extend a previously developed translational model to cover pediatric populations by incorporating age-dependent pharmacokinetic, pharmacodynamic, and physiological changes compared to adults. Our model reproduced previous perioperative clinical findings that adults and children have similar risk of respiratory depression at the same plasma fentanyl concentration when specific endpoints (minute ventilation, CO 2 tension in the blood) were used. However, our model points to a potential caveat that, in a perioperative setting, routine use of mechanical ventilation and supplemental oxygen maintained the blood and tissue oxygen partial pressures in patients and prevented the use of oxygen-related endpoints to evaluate the consequences of respiratory depression. In a community setting when such oxygenation procedures are not immediately available, our model suggests that the higher oxygen demand and reduced cerebrovascular reactivity could make children more susceptible to severe hypoxemia and brain hypoxia, even with the same plasma fentanyl concentration as adults. Our work indicates that when developing intervention strategies to protect children from opioid overdose in a community setting, these pediatric-specific factors may need to be considered.

60 APPLIED LIFE SCIENCES↗

Molecular mechanisms of metabotropic GABA B receptor function

Metabotropic γ-aminobutyric acid G protein–coupled receptors (GABA B ) represent one of the two main types of inhibitory neurotransmitter receptors in the brain. These receptors act both pre- and postsynaptically by modulating the transmission of neuronal signals and are involved in a range of neurological diseases, from alcohol addiction to epilepsy. A series of recent cryo-EM studies revealed critical details of the activation mechanism of GABA B . Structures are now available for the receptor bound to ligands with different modes of action, including antagonists, agonists, and positive allosteric modulators, and captured in different conformational states from the inactive apo to the fully active state bound to a G protein. These discoveries provide comprehensive insights into the activation of the GABA B receptor, which not only broaden our understanding of its structure, pharmacology, and physiological effects but also will ultimately facilitate the discovery of new therapeutic drugs and neuromodulators.

59 BASIC BIOLOGICAL SCIENCES↗