8 research outputs found
Adaptive Bayesian Beamforming for Imaging by Marginalizing the Speed of Sound
Imaging methods based on array signal processing often require a fixed
propagation speed of the medium, or speed of sound (SoS) for methods based on
acoustic signals. The resolution of the images formed using these methods is
strongly affected by the assumed SoS, which, due to multipath, nonlinear
propagation, and non-uniform mediums, is challenging at best to select. In this
letter, we propose a Bayesian approach to marginalize the influence of the SoS
on beamformers for imaging. We adapt Bayesian direction-of-arrival estimation
to an imaging setting and integrate a popular minimum variance beamformer over
the posterior of the SoS. To solve the Bayesian integral efficiently, we use
numerical Gauss quadrature. We apply our beamforming approach to shallow water
sonar imaging where multipath and nonlinear propagation is abundant. We compare
against the minimum variance distortionless response (MVDR) beamformer and
demonstrate that its Bayesian counterpart achieves improved range and azimuthal
resolution while effectively suppressing multipath artifacts
Linear Convergence of Black-Box Variational Inference: Should We Stick the Landing?
We prove that black-box variational inference (BBVI) with control variates,
particularly the sticking-the-landing (STL) estimator, converges at a geometric
(traditionally called "linear") rate under perfect variational family
specification. In particular, we prove a quadratic bound on the gradient
variance of the STL estimator, one which encompasses misspecified variational
families. Combined with previous works on the quadratic variance condition,
this directly implies convergence of BBVI with the use of projected stochastic
gradient descent. We also improve existing analysis on the regular closed-form
entropy gradient estimators, which enables comparison against the STL estimator
and provides explicit non-asymptotic complexity guarantees for both
The Behavior and Convergence of Local Bayesian Optimization
A recent development in Bayesian optimization is the use of local
optimization strategies, which can deliver strong empirical performance on
high-dimensional problems compared to traditional global strategies. The "folk
wisdom" in the literature is that the focus on local optimization sidesteps the
curse of dimensionality; however, little is known concretely about the expected
behavior or convergence of Bayesian local optimization routines. We first study
the behavior of the local approach, and find that the statistics of individual
local solutions of Gaussian process sample paths are surprisingly good compared
to what we would expect to recover from global methods. We then present the
first rigorous analysis of such a Bayesian local optimization algorithm
recently proposed by M\"uller et al. (2021), and derive convergence rates in
both the noisy and noiseless settings.Comment: 25 page
Practical and Matching Gradient Variance Bounds for Black-Box Variational Bayesian Inference
Understanding the gradient variance of black-box variational inference (BBVI)
is a crucial step for establishing its convergence and developing algorithmic
improvements. However, existing studies have yet to show that the gradient
variance of BBVI satisfies the conditions used to study the convergence of
stochastic gradient descent (SGD), the workhorse of BBVI. In this work, we show
that BBVI satisfies a matching bound corresponding to the condition used
in the SGD literature when applied to smooth and quadratically-growing
log-likelihoods. Our results generalize to nonlinear covariance
parameterizations widely used in the practice of BBVI. Furthermore, we show
that the variance of the mean-field parameterization has provably superior
dimensional dependence.Comment: Accepted to ICML'23 for live oral presentatio
Black-Box Variational Inference Converges
We provide the first convergence guarantee for full black-box variational
inference (BBVI), also known as Monte Carlo variational inference. While
preliminary investigations worked on simplified versions of BBVI (e.g., bounded
domain, bounded support, only optimizing for the scale, and such), our setup
does not need any such algorithmic modifications. Our results hold for
log-smooth posterior densities with and without strong log-concavity and the
location-scale variational family. Also, our analysis reveals that certain
algorithm design choices commonly employed in practice, particularly, nonlinear
parameterizations of the scale of the variational approximation, can result in
suboptimal convergence rates. Fortunately, running BBVI with proximal
stochastic gradient descent fixes these limitations, and thus achieves the
strongest known convergence rate guarantees. We evaluate this theoretical
insight by comparing proximal SGD against other standard implementations of
BBVI on large-scale Bayesian inference problems.Comment: under revie
New insights in the pathogenesis of alcohol-related liver disease: The metabolic, immunologic, and neurologic pathways☆
Alcohol-related liver disease (ALD) became an important health issue worldwide. Following chronic alcohol consumption, the development of ALD might be caused by metabolic and immunologic factors, such as reactive oxygen species (ROS) and pro-inflammatory cytokines. For example, hepatic cytochrome P450 2E1 enzyme increases ROS production and stimulates de novo lipogenesis after alcohol exposure. In addition, damage- and pathogen-associated molecular patterns stimulate their specific receptors in non-parenchymal cells, including Kupffer cells, hepatic stellate cells (HSCs), and lymphocytes, which result in hepatocyte death and infiltration of pro-inflammatory cells (e.g., neutrophils and macrophages) in the liver. Moreover, our studies have suggested the novel involvement of neurologic signaling pathways (e.g., endocannabinoid and glutamate) through the metabolic synapse between hepatocytes and HSCs in the development of alcohol-related hepatic steatosis. Additionally, agouti-related protein and beta2-adrenergic receptors aggravate hepatic steatosis. Furthermore, organ-crosstalk has emerged as a critical issue in ALD. Chronic alcohol consumption induces dysbiosis and barrier disruption in the gut, leading to endotoxin leakage into the portal circulation, or lipolysis-mediated transport of triglycerides from the adipose tissue to the liver. In summary, this review addresses multiple pathogeneses of ALD, provides novel neurologic signaling pathways, and emphasizes the importance of organ-crosstalk in the development of ALD
Ginsenoside F2 Restrains Hepatic Steatosis and Inflammation by Altering the Binding Affinity of Liver X Receptor Coregulators
Background: Ginsenoside F2 (GF2), the protopanaxadiol-type constituent in Panax ginseng, has been reported to attenuate metabolic dysfunction-associated steatotic liver disease (MASLD). However, the mechanism of action is not fully understood. Here, this study investigates the molecular mechanism by which GF2 regulates MASLD progression through liver X receptor (LXR). Methods: To demonstrate the effect of GF2 on LXR activity, computational modeling of protein-ligand binding, Time-resolved fluorescence resonance energy transfer (TR-FRET) assay for LXR cofactor recruitment, and luciferase reporter assay were performed. LXR agonist T0901317 was used for LXR activation in hepatocytes and macrophages. MASLD was induced by high-fat diet (HFD) feeding with or without GF2 administration in WT and LXRα−/− mice. Results: Computational modeling showed that GF2 had a high affinity with LXRα. LXRE-luciferase reporter assay with amino acid substitution at the predicted ligand binding site revealed that the S264 residue of LXRα was the crucial interaction site of GF2. TR-FRET assay demonstrated that GF2 suppressed LXRα activity by favoring the binding of corepressors to LXRα while inhibiting the accessibility of coactivators. In vitro, GF2 treatments reduced T0901317-induced fat accumulation and pro-inflammatory cytokine expression in hepatocytes and macrophages, respectively. Consistently, GF2 administration ameliorated hepatic steatohepatitis and improved glucose or insulin tolerance in WT but not in LXRα−/− mice. Conclusion: GF2 alters the binding affinities of LXRα coregulators, thereby interrupting hepatic steatosis and inflammation in macrophages. Therefore, we propose that GF2 might be a potential therapeutic agent for the intervention in patients with MASLD.11Nsciescopuskc
xCT-mediated glutamate excretion in white adipocytes stimulates interferon-γ production by natural killer cells in obesity
Summary: Obesity-mediated hypoxic stress underlies inflammation, including interferon (IFN)-γ production by natural killer (NK) cells in white adipose tissue. However, the effects of obesity on NK cell IFN-γ production remain obscure. Here, we show that hypoxia promotes xCT-mediated glutamate excretion and C-X-C motif chemokine ligand 12 (CXCL12) expression in white adipocytes, resulting in CXCR4+ NK cell recruitment. Interestingly, this spatial proximity between adipocytes and NK cells induces IFN-γ production in NK cells by stimulating metabotropic glutamate receptor 5 (mGluR5). IFN-γ then triggers inflammatory activation of macrophages and augments xCT and CXCL12 expression in adipocytes, forming a bidirectional pathway. Genetic or pharmacological inhibition of xCT, mGluR5, or IFN-γ receptor in adipocytes or NK cells alleviates obesity-related metabolic disorders in mice. Consistently, patients with obesity showed elevated levels of glutamate/mGluR5 and CXCL12/CXCR4 axes, suggesting that a bidirectional pathway between adipocytes and NK cells could be a viable therapeutic target in obesity-related metabolic disorders