252 research outputs found
On the flexibility of the design of Multiple Try Metropolis schemes
The Multiple Try Metropolis (MTM) method is a generalization of the classical
Metropolis-Hastings algorithm in which the next state of the chain is chosen
among a set of samples, according to normalized weights. In the literature,
several extensions have been proposed. In this work, we show and remark upon
the flexibility of the design of MTM-type methods, fulfilling the detailed
balance condition. We discuss several possibilities and show different
numerical results
Sampling constrained probability distributions using Spherical Augmentation
Statistical models with constrained probability distributions are abundant in
machine learning. Some examples include regression models with norm constraints
(e.g., Lasso), probit, many copula models, and latent Dirichlet allocation
(LDA). Bayesian inference involving probability distributions confined to
constrained domains could be quite challenging for commonly used sampling
algorithms. In this paper, we propose a novel augmentation technique that
handles a wide range of constraints by mapping the constrained domain to a
sphere in the augmented space. By moving freely on the surface of this sphere,
sampling algorithms handle constraints implicitly and generate proposals that
remain within boundaries when mapped back to the original space. Our proposed
method, called {Spherical Augmentation}, provides a mathematically natural and
computationally efficient framework for sampling from constrained probability
distributions. We show the advantages of our method over state-of-the-art
sampling algorithms, such as exact Hamiltonian Monte Carlo, using several
examples including truncated Gaussian distributions, Bayesian Lasso, Bayesian
bridge regression, reconstruction of quantized stationary Gaussian process, and
LDA for topic modeling.Comment: 41 pages, 13 figure
The proteasome cap RPT5/Rpt5p subunit prevents aggregation of unfolded ricin A chain
The plant cytotoxin ricin enters mammalian cells by receptor-mediated endocytosis, undergoing retrograde transport to the endoplasmic reticulum (ER) where its catalytic A chain (RTA) is reductively separated from the holotoxin to enter the cytosol and inactivate ribosomes. The currently accepted model is that the bulk of ER-dislocated RTA is degraded by proteasomes. We show here that the proteasome has a more complex role in ricin intoxication than previously recognised, that the previously reported increase in sensitivity of mammalian cells to ricin in the presence of proteasome inhibitors simply reflects toxicity of the inhibitors themselves, and that RTA is a very poor substrate for proteasomal degradation. Denatured RTA and casein compete for a binding site on the regulatory particle of the 26S proteasome, but their fates differ. Casein is degraded, but the mammalian 26S proteasome AAA-ATPase subunit RPT5 acts as a chaperone that prevents aggregation of denatured RTA and stimulates recovery of catalytic RTA activity in vitro. Furthermore, in vivo, the ATPase activity of Rpt5p is required for maximal toxicity of RTA dislocated from the Saccharomyces cerevisiae ER. Our results implicate RPT5/Rpt5p in the triage of substrates in which either activation (folding) or inactivation (degradation) pathways may be initiated
An Adaptive Interacting Wang-Landau Algorithm for Automatic Density Exploration
While statisticians are well-accustomed to performing exploratory analysis in
the modeling stage of an analysis, the notion of conducting preliminary
general-purpose exploratory analysis in the Monte Carlo stage (or more
generally, the model-fitting stage) of an analysis is an area which we feel
deserves much further attention. Towards this aim, this paper proposes a
general-purpose algorithm for automatic density exploration. The proposed
exploration algorithm combines and expands upon components from various
adaptive Markov chain Monte Carlo methods, with the Wang-Landau algorithm at
its heart. Additionally, the algorithm is run on interacting parallel chains --
a feature which both decreases computational cost as well as stabilizes the
algorithm, improving its ability to explore the density. Performance is studied
in several applications. Through a Bayesian variable selection example, the
authors demonstrate the convergence gains obtained with interacting chains. The
ability of the algorithm's adaptive proposal to induce mode-jumping is
illustrated through a trimodal density and a Bayesian mixture modeling
application. Lastly, through a 2D Ising model, the authors demonstrate the
ability of the algorithm to overcome the high correlations encountered in
spatial models.Comment: 33 pages, 20 figures (the supplementary materials are included as
appendices
Causal hierarchy within the thalamo-cortical network in spike and wave discharges
Background: Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges. Methodology and Principal Findings: We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1. Conclusion: Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy. © 2009 Vaudano et al
Insulin Sensitivity Measured With Euglycemic Clamp Is Independently Associated With Glomerular Filtration Rate in a Community-Based Cohort
OBJECTIVE—To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with prespecified subgroup analyses in normoglycemic individuals with normal GFR
The training and organization of Paediatric Neurology in Europe: Special report of the European Paediatric Neurology Society & Committee of National Advisors
Background: Paediatric Neurology (PN) is a discipline focused on diagnosis, comprehensive management
and research into dis
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