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Diffusion Copulas: Identification and Estimation. (arXiv:2005.03513v1 [econ.EM])

We propose a new semiparametric approach for modelling nonlinear univariate diffusions, where the observed process is a nonparametric transformation of an underlying parametric diffusion (UPD). This modelling strategy yields a general class of semiparametric Markov diffusion models with parametric dynamic copulas and nonparametric marginal distributions. We provide primitive conditions for the identification of the UPD parameters together with the unknown transformations from discrete samples. Likelihood-based estimators of both parametric and nonparametric components are developed and we analyze the asymptotic properties of these. Kernel-based drift and diffusion estimators are also proposed and shown to be normally distributed in large samples. A simulation study investigates the finite sample performance of our estimators in the context of modelling US short-term interest rates. We also present a simple application of the proposed method for modelling the CBOE volatility index data.




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Transfer Learning for sEMG-based Hand Gesture Classification using Deep Learning in a Master-Slave Architecture. (arXiv:2005.03460v1 [eess.SP])

Recent advancements in diagnostic learning and development of gesture-based human machine interfaces have driven surface electromyography (sEMG) towards significant importance. Analysis of hand gestures requires an accurate assessment of sEMG signals. The proposed work presents a novel sequential master-slave architecture consisting of deep neural networks (DNNs) for classification of signs from the Indian sign language using signals recorded from multiple sEMG channels. The performance of the master-slave network is augmented by leveraging additional synthetic feature data generated by long short term memory networks. Performance of the proposed network is compared to that of a conventional DNN prior to and after the addition of synthetic data. Up to 14% improvement is observed in the conventional DNN and up to 9% improvement in master-slave network on addition of synthetic data with an average accuracy value of 93.5% asserting the suitability of the proposed approach.




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Distributional Robustness of K-class Estimators and the PULSE. (arXiv:2005.03353v1 [econ.EM])

In causal settings, such as instrumental variable settings, it is well known that estimators based on ordinary least squares (OLS) can yield biased and non-consistent estimates of the causal parameters. This is partially overcome by two-stage least squares (TSLS) estimators. These are, under weak assumptions, consistent but do not have desirable finite sample properties: in many models, for example, they do not have finite moments. The set of K-class estimators can be seen as a non-linear interpolation between OLS and TSLS and are known to have improved finite sample properties. Recently, in causal discovery, invariance properties such as the moment criterion which TSLS estimators leverage have been exploited for causal structure learning: e.g., in cases, where the causal parameter is not identifiable, some structure of the non-zero components may be identified, and coverage guarantees are available. Subsequently, anchor regression has been proposed to trade-off invariance and predictability. The resulting estimator is shown to have optimal predictive performance under bounded shift interventions. In this paper, we show that the concepts of anchor regression and K-class estimators are closely related. Establishing this connection comes with two benefits: (1) It enables us to prove robustness properties for existing K-class estimators when considering distributional shifts. And, (2), we propose a novel estimator in instrumental variable settings by minimizing the mean squared prediction error subject to the constraint that the estimator lies in an asymptotically valid confidence region of the causal parameter. We call this estimator PULSE (p-uncorrelated least squares estimator) and show that it can be computed efficiently, even though the underlying optimization problem is non-convex. We further prove that it is consistent.




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Training and Classification using a Restricted Boltzmann Machine on the D-Wave 2000Q. (arXiv:2005.03247v1 [cs.LG])

Restricted Boltzmann Machine (RBM) is an energy based, undirected graphical model. It is commonly used for unsupervised and supervised machine learning. Typically, RBM is trained using contrastive divergence (CD). However, training with CD is slow and does not estimate exact gradient of log-likelihood cost function. In this work, the model expectation of gradient learning for RBM has been calculated using a quantum annealer (D-Wave 2000Q), which is much faster than Markov chain Monte Carlo (MCMC) used in CD. Training and classification results are compared with CD. The classification accuracy results indicate similar performance of both methods. Image reconstruction as well as log-likelihood calculations are used to compare the performance of quantum and classical algorithms for RBM training. It is shown that the samples obtained from quantum annealer can be used to train a RBM on a 64-bit `bars and stripes' data set with classification performance similar to a RBM trained with CD. Though training based on CD showed improved learning performance, training using a quantum annealer eliminates computationally expensive MCMC steps of CD.




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Classification of pediatric pneumonia using chest X-rays by functional regression. (arXiv:2005.03243v1 [stat.AP])

An accurate and prompt diagnosis of pediatric pneumonia is imperative for successful treatment intervention. One approach to diagnose pneumonia cases is using radiographic data. In this article, we propose a novel parsimonious scalar-on-image classification model adopting the ideas of functional data analysis. Our main idea is to treat images as functional measurements and exploit underlying covariance structures to select basis functions; these bases are then used in approximating both image profiles and corresponding regression coefficient. We re-express the regression model into a standard generalized linear model where the functional principal component scores are treated as covariates. We apply the method to (1) classify pneumonia against healthy and viral against bacterial pneumonia patients, and (2) test the null effect about the association between images and responses. Extensive simulation studies show excellent numerical performance in terms of classification, hypothesis testing, and efficient computation.




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Wintrobe's atlas of clinical hematology

9781605476148 hardcover




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Uflacker's atlas of vascular anatomy

Uflacker, Andre, author.
9781496356017 (hardback)




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Rapid Recovery in Total Joint Arthroplasty

9783030412234 978-3-030-41223-4




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Plastic waste and recycling : environmental impact, societal issues, prevention, and solutions

9780128178812 (electronic bk.)




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Machine learning in aquaculture : hunger classification of Lates calcarifer

Mohd Razman, Mohd Azraai, author
9789811522376 (electronic bk.)




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Drying atlas : drying kinetics and quality of agricultural products

Mühlbauer, Werner, author
9780128181638 (electronic bk.)




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Corrosion atlas case studies

9780128187616 electronic publication




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Atlas of ulcers in systemic sclerosis : diagnosis and management

9783319984773 (electronic bk.)




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Atlas of sexually transmitted diseases : clinical aspects and differential diagnosis

9783319574707 (electronic bk.)




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Atlas of mohs and frozen section cutaneous pathology

9783319748474 978-3-319-74847-4




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Atlas of male genital dermatology

Hall, Anthony, author.
9783319997506 (electronic bk.)




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Atlas of Lymphatic System in Cancer

Gantsev, Shamil. author. aut http://id.loc.gov/vocabulary/relators/aut
9783030409678 978-3-030-40967-8




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Atlas of Lasers and Lights in Dermatology

Cannarozzo, Giovanni. author.
9783030312329




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Anatomical chart company atlas of pathophysiology

Atlas of pathophysiology.
9781496370921




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A latent discrete Markov random field approach to identifying and classifying historical forest communities based on spatial multivariate tree species counts

Stephen Berg, Jun Zhu, Murray K. Clayton, Monika E. Shea, David J. Mladenoff.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2312--2340.

Abstract:
The Wisconsin Public Land Survey database describes historical forest composition at high spatial resolution and is of interest in ecological studies of forest composition in Wisconsin just prior to significant Euro-American settlement. For such studies it is useful to identify recurring subpopulations of tree species known as communities, but standard clustering approaches for subpopulation identification do not account for dependence between spatially nearby observations. Here, we develop and fit a latent discrete Markov random field model for the purpose of identifying and classifying historical forest communities based on spatially referenced multivariate tree species counts across Wisconsin. We show empirically for the actual dataset and through simulation that our latent Markov random field modeling approach improves prediction and parameter estimation performance. For model fitting we introduce a new stochastic approximation algorithm which enables computationally efficient estimation and classification of large amounts of spatial multivariate count data.




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Robust elastic net estimators for variable selection and identification of proteomic biomarkers

Gabriela V. Cohen Freue, David Kepplinger, Matías Salibián-Barrera, Ezequiel Smucler.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2065--2090.

Abstract:
In large-scale quantitative proteomic studies, scientists measure the abundance of thousands of proteins from the human proteome in search of novel biomarkers for a given disease. Penalized regression estimators can be used to identify potential biomarkers among a large set of molecular features measured. Yet, the performance and statistical properties of these estimators depend on the loss and penalty functions used to define them. Motivated by a real plasma proteomic biomarkers study, we propose a new class of penalized robust estimators based on the elastic net penalty, which can be tuned to keep groups of correlated variables together in the selected model and maintain robustness against possible outliers. We also propose an efficient algorithm to compute our robust penalized estimators and derive a data-driven method to select the penalty term. Our robust penalized estimators have very good robustness properties and are also consistent under certain regularity conditions. Numerical results show that our robust estimators compare favorably to other robust penalized estimators. Using our proposed methodology for the analysis of the proteomics data, we identify new potentially relevant biomarkers of cardiac allograft vasculopathy that are not found with nonrobust alternatives. The selected model is validated in a new set of 52 test samples and achieves an area under the receiver operating characteristic (AUC) of 0.85.




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Incorporating conditional dependence in latent class models for probabilistic record linkage: Does it matter?

Huiping Xu, Xiaochun Li, Changyu Shen, Siu L. Hui, Shaun Grannis.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1753--1790.

Abstract:
The conditional independence assumption of the Felligi and Sunter (FS) model in probabilistic record linkage is often violated when matching real-world data. Ignoring conditional dependence has been shown to seriously bias parameter estimates. However, in record linkage, the ultimate goal is to inform the match status of record pairs and therefore, record linkage algorithms should be evaluated in terms of matching accuracy. In the literature, more flexible models have been proposed to relax the conditional independence assumption, but few studies have assessed whether such accommodations improve matching accuracy. In this paper, we show that incorporating the conditional dependence appropriately yields comparable or improved matching accuracy than the FS model using three real-world data linkage examples. Through a simulation study, we further investigate when conditional dependence models provide improved matching accuracy. Our study shows that the FS model is generally robust to the conditional independence assumption and provides comparable matching accuracy as the more complex conditional dependence models. However, when the match prevalence approaches 0% or 100% and conditional dependence exists in the dominating class, it is necessary to address conditional dependence as the FS model produces suboptimal matching accuracy. The need to address conditional dependence becomes less important when highly discriminating fields are used. Our simulation study also shows that conditional dependence models with misspecified dependence structure could produce less accurate record matching than the FS model and therefore we caution against the blind use of conditional dependence models.




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Network classification with applications to brain connectomics

Jesús D. Arroyo Relión, Daniel Kessler, Elizaveta Levina, Stephan F. Taylor.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1648--1677.

Abstract:
While statistical analysis of a single network has received a lot of attention in recent years, with a focus on social networks, analysis of a sample of networks presents its own challenges which require a different set of analytic tools. Here we study the problem of classification of networks with labeled nodes, motivated by applications in neuroimaging. Brain networks are constructed from imaging data to represent functional connectivity between regions of the brain, and previous work has shown the potential of such networks to distinguish between various brain disorders, giving rise to a network classification problem. Existing approaches tend to either treat all edge weights as a long vector, ignoring the network structure, or focus on graph topology as represented by summary measures while ignoring the edge weights. Our goal is to design a classification method that uses both the individual edge information and the network structure of the data in a computationally efficient way, and that can produce a parsimonious and interpretable representation of differences in brain connectivity patterns between classes. We propose a graph classification method that uses edge weights as predictors but incorporates the network nature of the data via penalties that promote sparsity in the number of nodes, in addition to the usual sparsity penalties that encourage selection of edges. We implement the method via efficient convex optimization and provide a detailed analysis of data from two fMRI studies of schizophrenia.




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The classification permutation test: A flexible approach to testing for covariate imbalance in observational studies

Johann Gagnon-Bartsch, Yotam Shem-Tov.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1464--1483.

Abstract:
The gold standard for identifying causal relationships is a randomized controlled experiment. In many applications in the social sciences and medicine, the researcher does not control the assignment mechanism and instead may rely upon natural experiments or matching methods as a substitute to experimental randomization. The standard testable implication of random assignment is covariate balance between the treated and control units. Covariate balance is commonly used to validate the claim of as good as random assignment. We propose a new nonparametric test of covariate balance. Our Classification Permutation Test (CPT) is based on a combination of classification methods (e.g., random forests) with Fisherian permutation inference. We revisit four real data examples and present Monte Carlo power simulations to demonstrate the applicability of the CPT relative to other nonparametric tests of equality of multivariate distributions.




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Optimal functional supervised classification with separation condition

Sébastien Gadat, Sébastien Gerchinovitz, Clément Marteau.

Source: Bernoulli, Volume 26, Number 3, 1797--1831.

Abstract:
We consider the binary supervised classification problem with the Gaussian functional model introduced in ( Math. Methods Statist. 22 (2013) 213–225). Taking advantage of the Gaussian structure, we design a natural plug-in classifier and derive a family of upper bounds on its worst-case excess risk over Sobolev spaces. These bounds are parametrized by a separation distance quantifying the difficulty of the problem, and are proved to be optimal (up to logarithmic factors) through matching minimax lower bounds. Using the recent works of (In Advances in Neural Information Processing Systems (2014) 3437–3445 Curran Associates) and ( Ann. Statist. 44 (2016) 982–1009), we also derive a logarithmic lower bound showing that the popular $k$-nearest neighbors classifier is far from optimality in this specific functional setting.




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A new McKean–Vlasov stochastic interpretation of the parabolic–parabolic Keller–Segel model: The one-dimensional case

Denis Talay, Milica Tomašević.

Source: Bernoulli, Volume 26, Number 2, 1323--1353.

Abstract:
In this paper, we analyze a stochastic interpretation of the one-dimensional parabolic–parabolic Keller–Segel system without cut-off. It involves an original type of McKean–Vlasov interaction kernel. At the particle level, each particle interacts with all the past of each other particle by means of a time integrated functional involving a singular kernel. At the mean-field level studied here, the McKean–Vlasov limit process interacts with all the past time marginals of its probability distribution in a similarly singular way. We prove that the parabolic–parabolic Keller–Segel system in the whole Euclidean space and the corresponding McKean–Vlasov stochastic differential equation are well-posed for any values of the parameters of the model.




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Prediction and estimation consistency of sparse multi-class penalized optimal scoring

Irina Gaynanova.

Source: Bernoulli, Volume 26, Number 1, 286--322.

Abstract:
Sparse linear discriminant analysis via penalized optimal scoring is a successful tool for classification in high-dimensional settings. While the variable selection consistency of sparse optimal scoring has been established, the corresponding prediction and estimation consistency results have been lacking. We bridge this gap by providing probabilistic bounds on out-of-sample prediction error and estimation error of multi-class penalized optimal scoring allowing for diverging number of classes.




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Glass stereoscopic slides of Gallipoli, May 1915 / photographed by Charles Snodgrass Ryan




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Implicit Copulas from Bayesian Regularized Regression Smoothers

Nadja Klein, Michael Stanley Smith.

Source: Bayesian Analysis, Volume 14, Number 4, 1143--1171.

Abstract:
We show how to extract the implicit copula of a response vector from a Bayesian regularized regression smoother with Gaussian disturbances. The copula can be used to compare smoothers that employ different shrinkage priors and function bases. We illustrate with three popular choices of shrinkage priors—a pairwise prior, the horseshoe prior and a g prior augmented with a point mass as employed for Bayesian variable selection—and both univariate and multivariate function bases. The implicit copulas are high-dimensional, have flexible dependence structures that are far from that of a Gaussian copula, and are unavailable in closed form. However, we show how they can be evaluated by first constructing a Gaussian copula conditional on the regularization parameters, and then integrating over these. Combined with non-parametric margins the regularized smoothers can be used to model the distribution of non-Gaussian univariate responses conditional on the covariates. Efficient Markov chain Monte Carlo schemes for evaluating the copula are given for this case. Using both simulated and real data, we show how such copula smoothing models can improve the quality of resulting function estimates and predictive distributions.




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Extrinsic Gaussian Processes for Regression and Classification on Manifolds

Lizhen Lin, Niu Mu, Pokman Cheung, David Dunson.

Source: Bayesian Analysis, Volume 14, Number 3, 907--926.

Abstract:
Gaussian processes (GPs) are very widely used for modeling of unknown functions or surfaces in applications ranging from regression to classification to spatial processes. Although there is an increasingly vast literature on applications, methods, theory and algorithms related to GPs, the overwhelming majority of this literature focuses on the case in which the input domain corresponds to a Euclidean space. However, particularly in recent years with the increasing collection of complex data, it is commonly the case that the input domain does not have such a simple form. For example, it is common for the inputs to be restricted to a non-Euclidean manifold, a case which forms the motivation for this article. In particular, we propose a general extrinsic framework for GP modeling on manifolds, which relies on embedding of the manifold into a Euclidean space and then constructing extrinsic kernels for GPs on their images. These extrinsic Gaussian processes (eGPs) are used as prior distributions for unknown functions in Bayesian inferences. Our approach is simple and general, and we show that the eGPs inherit fine theoretical properties from GP models in Euclidean spaces. We consider applications of our models to regression and classification problems with predictors lying in a large class of manifolds, including spheres, planar shape spaces, a space of positive definite matrices, and Grassmannians. Our models can be readily used by practitioners in biological sciences for various regression and classification problems, such as disease diagnosis or detection. Our work is also likely to have impact in spatial statistics when spatial locations are on the sphere or other geometric spaces.




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Bayes Factor Testing of Multiple Intraclass Correlations

Joris Mulder, Jean-Paul Fox.

Source: Bayesian Analysis, Volume 14, Number 2, 521--552.

Abstract:
The intraclass correlation plays a central role in modeling hierarchically structured data, such as educational data, panel data, or group-randomized trial data. It represents relevant information concerning the between-group and within-group variation. Methods for Bayesian hypothesis tests concerning the intraclass correlation are proposed to improve decision making in hierarchical data analysis and to assess the grouping effect across different group categories. Estimation and testing methods for the intraclass correlation coefficient are proposed under a marginal modeling framework where the random effects are integrated out. A class of stretched beta priors is proposed on the intraclass correlations, which is equivalent to shifted $F$ priors for the between groups variances. Through a parameter expansion it is shown that this prior is conditionally conjugate under the marginal model yielding efficient posterior computation. A special improper case results in accurate coverage rates of the credible intervals even for minimal sample size and when the true intraclass correlation equals zero. Bayes factor tests are proposed for testing multiple precise and order hypotheses on intraclass correlations. These tests can be used when prior information about the intraclass correlations is available or absent. For the noninformative case, a generalized fractional Bayes approach is developed. The method enables testing the presence and strength of grouped data structures without introducing random effects. The methodology is applied to a large-scale survey study on international mathematics achievement at fourth grade to test the heterogeneity in the clustering of students in schools across countries and assessment cycles.




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Lasso Meets Horseshoe: A Survey

Anindya Bhadra, Jyotishka Datta, Nicholas G. Polson, Brandon Willard.

Source: Statistical Science, Volume 34, Number 3, 405--427.

Abstract:
The goal of this paper is to contrast and survey the major advances in two of the most commonly used high-dimensional techniques, namely, the Lasso and horseshoe regularization. Lasso is a gold standard for predictor selection while horseshoe is a state-of-the-art Bayesian estimator for sparse signals. Lasso is fast and scalable and uses convex optimization whilst the horseshoe is nonconvex. Our novel perspective focuses on three aspects: (i) theoretical optimality in high-dimensional inference for the Gaussian sparse model and beyond, (ii) efficiency and scalability of computation and (iii) methodological development and performance.




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Elle est classe, elle ne fume pas / Biman Mullick.

London (33 Stillness Road, London SE23 1NG) : Cleanair, [1989?]




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Elle est classe, elle ne fume pas / Biman Mullick.

London (33 Stillness Rd, SE23 1NG) : Cleanair, [198-?]




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The 2019 Victoria’s Secret Fashion Show Is Canceled After Facing Backlash for Lack of Body Diversity

The reaction on social media has been fierce.




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Experience-Dependent Plasticity of Binocular Responses in the Primary Visual Cortex of the Mouse

Joshua A. Gordon
May 15, 1996; 16:3274-3286
Articles




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Las monedas digitales de bancos centrales podrían afectar a los pagos, la política monetaria y la estabilidad financiera

Spanish version of Press release about CPMI and the Markets Committee issuing a report on "Central bank digital currencies" (12 March 2018)




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Basilea III: Finalización de las reformas poscrisis

Spanish translation of "Basel III: Finalising post-crisis reforms", December 2017.




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La confianza es el eslabón perdido en las criptomonedas actuales, según el BPI

Spanish translation of the Press Release on the pre-release of two special chapters of the Annual Economic Report of the BIS, 17 June 2018. Trust is the missing link in today's cryptocurrencies - Cryptocurrencies' model of generating trust limits their potential to replace conventional money, the Bank for International Settlements (BIS) writes in its Annual Economic Report (AER), a new title launched this year.




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El Comité de Basilea finaliza sus principios sobre pruebas de tensión, analiza fórmulas para acabar con prácticas de arbitraje regulatorio, aprueba la lista anual de G-SIB y debate sobre el coeficiente de apalancamiento, los criptoacti

Spanish translation of press release - the Basel Committee on Banking Supervision is finalising stress-testing principles, reviews ways to stop regulatory arbitrage behaviour, agrees on annual G-SIB list, discusses leverage ratio, crypto-assets, market risk framework and implementation, 20 September 2018.




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Las divergencias se amplían en los mercados: Informe Trimestral del BPI

Spanish translation of the BIS press release about the BIS Quarterly Review, September 2018




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Oportunidades y riesgos de la entrada de las big tech en el sector financiero

Spanish version of BIS Press Release - Big tech in finance: opportunities and risks, 23 June 2019




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Donations Dropped 11% at Nation's Biggest Charities Last Year




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Alaska Native Sisterhood civil rights leader Amy Hallingstad--a glimpse to 1947




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SHI to sponsor lecture on totem parks of Southeast Alaska




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Bold steps to pump coronavirus rescue funds down the last mile

Op-ed by Agustín Carstens published in the Financial Times on 29 March 2020.




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Rapid Release of Ca2+ from Endoplasmic Reticulum Mediated by Na+/Ca2+ Exchange

Phototransduction in Drosophila is mediated by phospholipase C (PLC) and Ca2+-permeable TRP channels, but the function of endoplasmic reticulum (ER) Ca2+ stores in this important model for Ca2+ signaling remains obscure. We therefore expressed a low affinity Ca2+ indicator (ER-GCaMP6-150) in the ER, and measured its fluorescence both in dissociated ommatidia and in vivo from intact flies of both sexes. Blue excitation light induced a rapid (tau ~0.8 s), PLC-dependent decrease in fluorescence, representing depletion of ER Ca2+ stores, followed by a slower decay, typically reaching ~50% of initial dark-adapted levels, with significant depletion occurring under natural levels of illumination. The ER stores refilled in the dark within 100–200 s. Both rapid and slow store depletion were largely unaffected in InsP3 receptor mutants, but were much reduced in trp mutants. Strikingly, rapid (but not slow) depletion of ER stores was blocked by removing external Na+ and in mutants of the Na+/Ca2+ exchanger, CalX, which we immuno-localized to ER membranes in addition to its established localization in the plasma membrane. Conversely, overexpression of calx greatly enhanced rapid depletion. These results indicate that rapid store depletion is mediated by Na+/Ca2+ exchange across the ER membrane induced by Na+ influx via the light-sensitive channels. Although too slow to be involved in channel activation, this Na+/Ca2+ exchange-dependent release explains the decades-old observation of a light-induced rise in cytosolic Ca2+ in photoreceptors exposed to Ca2+-free solutions.

SIGNIFICANCE STATEMENT Phototransduction in Drosophila is mediated by phospholipase C, which activates TRP cation channels by an unknown mechanism. Despite much speculation, it is unknown whether endoplasmic reticulum (ER) Ca2+ stores play any role. We therefore engineered flies expressing a genetically encoded Ca2+ indicator in the photoreceptor ER. Although NCX Na+/Ca2+ exchangers are classically believed to operate only at the plasma membrane, we demonstrate a rapid light-induced depletion of ER Ca2+ stores mediated by Na+/Ca2+ exchange across the ER membrane. This NCX-dependent release was too slow to be involved in channel activation, but explains the decades-old observation of a light-induced rise in cytosolic Ca2+ in photoreceptors bathed in Ca2+-free solutions.




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Emotional Stress Induces Structural Plasticity in Bergmann Glial Cells via an AC5-CPEB3-GluA1 Pathway

Stress alters brain function by modifying the structure and function of neurons and astrocytes. The fine processes of astrocytes are critical for the clearance of neurotransmitters during synaptic transmission. Thus, experience-dependent remodeling of glial processes is anticipated to alter the output of neural circuits. However, the molecular mechanisms that underlie glial structural plasticity are not known. Here we show that a single exposure of male and female mice to an acute stress produced a long-lasting retraction of the lateral processes of cerebellar Bergmann glial cells. These cells express the GluA1 subunit of AMPA-type glutamate receptors, and GluA1 knockdown is known to shorten the length of glial processes. We found that stress reduced the level of GluA1 protein and AMPA receptor-mediated currents in Bergmann glial cells, and these effects were absent in mice devoid of CPEB3, a protein that binds to GluA1 mRNA and regulates GluA1 protein synthesis. Administration of a β-adrenergic receptor blocker attenuated the reduction in GluA1, and deletion of adenylate cyclase 5 prevented GluA1 suppression. Therefore, stress suppresses GluA1 protein synthesis via an adrenergic/adenylyl cyclase/CPEB3 pathway, and reduces the length of astrocyte lateral processes. Our results identify a novel mechanism for GluA1 subunit plasticity in non-neuronal cells and suggest a previously unappreciated role for AMPA receptors in stress-induced astrocytic remodeling.

SIGNIFICANCE STATEMENT Astrocytes play important roles in synaptic transmission by extending fine processes around synapses. In this study, we showed that a single exposure to an acute stress triggered a retraction of lateral/fine processes in mouse cerebellar astrocytes. These astrocytes express GluA1, a glutamate receptor subunit known to lengthen astrocyte processes. We showed that astrocytic structural changes are associated with a reduction of GluA1 protein levels. This requires activation of β-adrenergic receptors and is triggered by noradrenaline released during stress. We identified adenylyl cyclase 5, an enzyme that elevates cAMP levels, as a downstream effector and found that lowering GluA1 levels depends on CPEB3 proteins that bind to GluA1 mRNA. Therefore, stress regulates GluA1 protein synthesis via an adrenergic/adenylyl cyclase/CPEB3 pathway in astrocytes and remodels their fine processes.




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Neurog2 Acts as a Classical Proneural Gene in the Ventromedial Hypothalamus and Is Required for the Early Phase of Neurogenesis

The tuberal hypothalamus is comprised of the dorsomedial, ventromedial, and arcuate nuclei, as well as parts of the lateral hypothalamic area, and it governs a wide range of physiologies. During neurogenesis, tuberal hypothalamic neurons are thought to be born in a dorsal-to-ventral and outside-in pattern, although the accuracy of this description has been questioned over the years. Moreover, the intrinsic factors that control the timing of neurogenesis in this region are poorly characterized. Proneural genes, including Achate-scute-like 1 (Ascl1) and Neurogenin 3 (Neurog3) are widely expressed in hypothalamic progenitors and contribute to lineage commitment and subtype-specific neuronal identifies, but the potential role of Neurogenin 2 (Neurog2) remains unexplored. Birthdating in male and female mice showed that tuberal hypothalamic neurogenesis begins as early as E9.5 in the lateral hypothalamic and arcuate and rapidly expands to dorsomedial and ventromedial neurons by E10.5, peaking throughout the region by E11.5. We confirmed an outside-in trend, except for neurons born at E9.5, and uncovered a rostrocaudal progression but did not confirm a dorsal-ventral patterning to tuberal hypothalamic neuronal birth. In the absence of Neurog2, neurogenesis stalls, with a significant reduction in early-born BrdU+ cells but no change at later time points. Further, the loss of Ascl1 yielded a similar delay in neuronal birth, suggesting that Ascl1 cannot rescue the loss of Neurog2 and that these proneural genes act independently in the tuberal hypothalamus. Together, our findings show that Neurog2 functions as a classical proneural gene to regulate the temporal progression of tuberal hypothalamic neurogenesis.

SIGNIFICANCE STATEMENT Here, we investigated the general timing and pattern of neurogenesis within the tuberal hypothalamus. Our results confirmed an outside-in trend of neurogenesis and uncovered a rostrocaudal progression. We also showed that Neurog2 acts as a classical proneural gene and is responsible for regulating the birth of early-born neurons within the ventromedial hypothalamus, acting independently of Ascl1. In addition, we revealed a role for Neurog2 in cell fate specification and differentiation of ventromedial -specific neurons. Last, Neurog2 does not have cross-inhibitory effects on Neurog1, Neurog3, and Ascl1. These findings are the first to reveal a role for Neurog2 in hypothalamic development.




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The Last Beekeepers of San Antonio Tecómitl, Mexico

What does William Shakespeare have in common with Mexican beekeeper Francisco Lenin Bartolo Reyes? Both men understand the importance of the honey bee, a small but invaluable ally of the human race.