edu Partnering to Reduce Achievement Gaps in New Mexico By feedproxy.google.com Published On :: Thu, 31 May 2018 00:00:00 +0000 A school leader outlines how research findings on reducing achievement gaps are reflected in practice at her New Mexico school. Full Article New_Mexico
edu Plaintiffs say education-funding lawsuit still necessary By feedproxy.google.com Published On :: Tue, 28 Apr 2020 00:00:00 +0000 Full Article New_Mexico
edu Michigan Administrator Tapped to Oversee Federal Special Education Programs By feedproxy.google.com Published On :: Thu, 11 Oct 2018 00:00:00 +0000 Laurie VanderPloeg, a longtime special education administrator, will take over the office of special education programs starting in November. Full Article Michigan
edu Educational Opportunities and Performance in Michigan By feedproxy.google.com Published On :: Wed, 16 Jan 2019 00:00:00 +0000 This Quality Counts 2019 Highlights Report captures all the data you need to assess your state's performance on key educational outcomes. Full Article Michigan
edu Educational Opportunities and Performance in Michigan By feedproxy.google.com Published On :: Tue, 21 Jan 2020 00:00:00 +0000 This Quality Counts 2020 Highlights Report captures all the data you need to assess your state's performance on key educational outcomes. Full Article Michigan
edu Could Testing Wreck Civics Education? By feedproxy.google.com Published On :: Tue, 17 Sep 2019 00:00:00 +0000 As civic education undergoes a renaissance in schools, educators are looking beyond standardized tests to determine whether the lessons empower students to embrace civic behaviors, like voting or volunteering. Full Article Illinois
edu AASA Selects Illinois Educator as Superintendent of the Year By feedproxy.google.com Published On :: Tue, 27 Feb 2018 00:00:00 +0000 David Schuler, the superintendent of Township High School District 214 in Arlington Heights, Ill., has been named 2018 National Superintendent of the Year. Full Article Illinois
edu For Educators Vying for State Office, Teachers' Union Offers 'Soup to Nuts' Campaign Training By feedproxy.google.com Published On :: Wed, 05 Sep 2018 00:00:00 +0000 In the aftermath of this spring's teacher protests, more educators are running for state office—and the National Education Association is seizing on the political moment. Full Article Illinois
edu How 3 States Are Digging In on Civics Education By feedproxy.google.com Published On :: Wed, 26 Jun 2019 00:00:00 +0000 As growing numbers of states jump on the civics-learning bandwagon, a coalition of 90 national groups warns that some strategies are better than others. Here's a look at three states working toward a comprehensive approach to the topic. Full Article Illinois
edu Educational Opportunities and Performance in Illinois By feedproxy.google.com Published On :: Wed, 16 Jan 2019 00:00:00 +0000 This Quality Counts 2019 Highlights Report captures all the data you need to assess your state's performance on key educational outcomes. Full Article Illinois
edu Educational Opportunities and Performance in Illinois By feedproxy.google.com Published On :: Tue, 21 Jan 2020 00:00:00 +0000 This Quality Counts 2020 Highlights Report captures all the data you need to assess your state's performance on key educational outcomes. Full Article Illinois
edu NHL postpones 2020 international schedule By sports.yahoo.com Published On :: Fri, 08 May 2020 13:22:55 GMT The Bruins, Predators, Avalanche, and Blue Jackets were set to play games in Mannheim, Bern, Prague, and Helsinki. Full Article article Sports
edu Missouri Governor Struggles to Oust State Education Chief By feedproxy.google.com Published On :: Wed, 22 Nov 2017 00:00:00 +0000 Margie Vandeven, the state education chief, is appointed by an appointed board, which is still split on whether to fire Vandeven. Full Article Missouri
edu Educational Opportunities and Performance in Missouri By feedproxy.google.com Published On :: Wed, 16 Jan 2019 00:00:00 +0000 This Quality Counts 2019 Highlights Report captures all the data you need to assess your state's performance on key educational outcomes. Full Article Missouri
edu Educational Opportunities and Performance in Missouri By feedproxy.google.com Published On :: Tue, 21 Jan 2020 00:00:00 +0000 This Quality Counts 2020 Highlights Report captures all the data you need to assess your state's performance on key educational outcomes. Full Article Missouri
edu Missouri teachers virtually educate students about pandemic By feedproxy.google.com Published On :: Mon, 04 May 2020 00:00:00 +0000 Full Article Missouri
edu Health education news / editor: Michael Jacob ; reporter: Ruth Garland. By search.wellcomelibrary.org Published On :: London : Health Education Council, 1985. Full Article
edu National transportation safety board public forum on alcohol and drug safety education. By search.wellcomelibrary.org Published On :: Springfield, Virginia : National Technical Information Service, 1986. Full Article
edu The nature and treatment of nonopiate abuse : a review of the literature. Volume 2 / Wynne Associates for Division of Research, National Institute on Drug Abuse, Alcohol, Drug Abuse and Mental Health Administration, Department of Health, Education and Wel By search.wellcomelibrary.org Published On :: Washington, D.C. : Wynne Associates, 1974. Full Article
edu Swimming upstream : trends and prospects in education for health / Margaret Whitehead. By search.wellcomelibrary.org Published On :: London : King's Fund Institute, 1989. Full Article
edu O problema do abuso de drogas prevenção através investigação, pesquisa e educação / Murillo de Macedo Pereira, Vera Kühn de Macedo Pereira. By search.wellcomelibrary.org Published On :: São Paulo : Governo do Estado de Sao Paulo, Secretaria da Segurança Pública, 1975. Full Article
edu A general drift estimation procedure for stochastic differential equations with additive fractional noise By projecteuclid.org Published On :: Tue, 25 Feb 2020 22:00 EST Fabien Panloup, Samy Tindel, Maylis Varvenne. Source: Electronic Journal of Statistics, Volume 14, Number 1, 1075--1136.Abstract: In this paper we consider the drift estimation problem for a general differential equation driven by an additive multidimensional fractional Brownian motion, under ergodic assumptions on the drift coefficient. Our estimation procedure is based on the identification of the invariant measure, and we provide consistency results as well as some information about the convergence rate. We also give some examples of coefficients for which the identifiability assumption for the invariant measure is satisfied. Full Article
edu Reduction problems and deformation approaches to nonstationary covariance functions over spheres By projecteuclid.org Published On :: Tue, 11 Feb 2020 22:03 EST Emilio Porcu, Rachid Senoussi, Enner Mendoza, Moreno Bevilacqua. Source: Electronic Journal of Statistics, Volume 14, Number 1, 890--916.Abstract: The paper considers reduction problems and deformation approaches for nonstationary covariance functions on the $(d-1)$-dimensional spheres, $mathbb{S}^{d-1}$, embedded in the $d$-dimensional Euclidean space. Given a covariance function $C$ on $mathbb{S}^{d-1}$, we chase a pair $(R,Psi)$, for a function $R:[-1,+1] o mathbb{R}$ and a smooth bijection $Psi$, such that $C$ can be reduced to a geodesically isotropic one: $C(mathbf{x},mathbf{y})=R(langle Psi (mathbf{x}),Psi (mathbf{y}) angle )$, with $langle cdot ,cdot angle $ denoting the dot product. The problem finds motivation in recent statistical literature devoted to the analysis of global phenomena, defined typically over the sphere of $mathbb{R}^{3}$. The application domains considered in the manuscript makes the problem mathematically challenging. We show the uniqueness of the representation in the reduction problem. Then, under some regularity assumptions, we provide an inversion formula to recover the bijection $Psi$, when it exists, for a given $C$. We also give sufficient conditions for reducibility. Full Article
edu Online Sufficient Dimension Reduction Through Sliced Inverse Regression By Published On :: 2020 Sliced inverse regression is an effective paradigm that achieves the goal of dimension reduction through replacing high dimensional covariates with a small number of linear combinations. It does not impose parametric assumptions on the dependence structure. More importantly, such a reduction of dimension is sufficient in that it does not cause loss of information. In this paper, we adapt the stationary sliced inverse regression to cope with the rapidly changing environments. We propose to implement sliced inverse regression in an online fashion. This online learner consists of two steps. In the first step we construct an online estimate for the kernel matrix; in the second step we propose two online algorithms, one is motivated by the perturbation method and the other is originated from the gradient descent optimization, to perform online singular value decomposition. The theoretical properties of this online learner are established. We demonstrate the numerical performance of this online learner through simulations and real world applications. All numerical studies confirm that this online learner performs as well as the batch learner. Full Article
edu The Maximum Separation Subspace in Sufficient Dimension Reduction with Categorical Response By Published On :: 2020 Sufficient dimension reduction (SDR) is a very useful concept for exploratory analysis and data visualization in regression, especially when the number of covariates is large. Many SDR methods have been proposed for regression with a continuous response, where the central subspace (CS) is the target of estimation. Various conditions, such as the linearity condition and the constant covariance condition, are imposed so that these methods can estimate at least a portion of the CS. In this paper we study SDR for regression and discriminant analysis with categorical response. Motivated by the exploratory analysis and data visualization aspects of SDR, we propose a new geometric framework to reformulate the SDR problem in terms of manifold optimization and introduce a new concept called Maximum Separation Subspace (MASES). The MASES naturally preserves the “sufficiency” in SDR without imposing additional conditions on the predictor distribution, and directly inspires a semi-parametric estimator. Numerical studies show MASES exhibits superior performance as compared with competing SDR methods in specific settings. Full Article
edu Bayesian hypothesis testing: Redux By projecteuclid.org Published On :: Mon, 26 Aug 2019 04:00 EDT Hedibert F. Lopes, Nicholas G. Polson. Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 4, 745--755.Abstract: Bayesian hypothesis testing is re-examined from the perspective of an a priori assessment of the test statistic distribution under the alternative. By assessing the distribution of an observable test statistic, rather than prior parameter values, we revisit the seminal paper of Edwards, Lindman and Savage ( Psychol. Rev. 70 (1963) 193–242). There are a number of important take-aways from comparing the Bayesian paradigm via Bayes factors to frequentist ones. We provide examples where evidence for a Bayesian strikingly supports the null, but leads to rejection under a classical test. Finally, we conclude with directions for future research. Full Article
edu A survey of cross-validation procedures for model selection By projecteuclid.org Published On :: Thu, 05 Aug 2010 15:41 EDT Sylvain Arlot, Alain CelisseSource: Statist. Surv., Volume 4, 40--79.Abstract: Used to estimate the risk of an estimator or to perform model selection, cross-validation is a widespread strategy because of its simplicity and its (apparent) universality. Many results exist on model selection performances of cross-validation procedures. This survey intends to relate these results to the most recent advances of model selection theory, with a particular emphasis on distinguishing empirical statements from rigorous theoretical results. As a conclusion, guidelines are provided for choosing the best cross-validation procedure according to the particular features of the problem in hand. Full Article
edu Risk-Aware Energy Scheduling for Edge Computing with Microgrid: A Multi-Agent Deep Reinforcement Learning Approach. (arXiv:2003.02157v2 [physics.soc-ph] UPDATED) By arxiv.org Published On :: In recent years, multi-access edge computing (MEC) is a key enabler for handling the massive expansion of Internet of Things (IoT) applications and services. However, energy consumption of a MEC network depends on volatile tasks that induces risk for energy demand estimations. As an energy supplier, a microgrid can facilitate seamless energy supply. However, the risk associated with energy supply is also increased due to unpredictable energy generation from renewable and non-renewable sources. Especially, the risk of energy shortfall is involved with uncertainties in both energy consumption and generation. In this paper, we study a risk-aware energy scheduling problem for a microgrid-powered MEC network. First, we formulate an optimization problem considering the conditional value-at-risk (CVaR) measurement for both energy consumption and generation, where the objective is to minimize the loss of energy shortfall of the MEC networks and we show this problem is an NP-hard problem. Second, we analyze our formulated problem using a multi-agent stochastic game that ensures the joint policy Nash equilibrium, and show the convergence of the proposed model. Third, we derive the solution by applying a multi-agent deep reinforcement learning (MADRL)-based asynchronous advantage actor-critic (A3C) algorithm with shared neural networks. This method mitigates the curse of dimensionality of the state space and chooses the best policy among the agents for the proposed problem. Finally, the experimental results establish a significant performance gain by considering CVaR for high accuracy energy scheduling of the proposed model than both the single and random agent models. Full Article
edu Deep Learning on Point Clouds for False Positive Reduction at Nodule Detection in Chest CT Scans. (arXiv:2005.03654v1 [eess.IV]) By arxiv.org Published On :: The paper focuses on a novel approach for false-positive reduction (FPR) of nodule candidates in Computer-aided detection (CADe) system after suspicious lesions proposing stage. Unlike common decisions in medical image analysis, the proposed approach considers input data not as 2d or 3d image, but as a point cloud and uses deep learning models for point clouds. We found out that models for point clouds require less memory and are faster on both training and inference than traditional CNN 3D, achieves better performance and does not impose restrictions on the size of the input image, thereby the size of the nodule candidate. We propose an algorithm for transforming 3d CT scan data to point cloud. In some cases, the volume of the nodule candidate can be much smaller than the surrounding context, for example, in the case of subpleural localization of the nodule. Therefore, we developed an algorithm for sampling points from a point cloud constructed from a 3D image of the candidate region. The algorithm guarantees to capture both context and candidate information as part of the point cloud of the nodule candidate. An experiment with creating a dataset from an open LIDC-IDRI database for a feature of the FPR task was accurately designed, set up and described in detail. The data augmentation technique was applied to avoid overfitting and as an upsampling method. Experiments are conducted with PointNet, PointNet++ and DGCNN. We show that the proposed approach outperforms baseline CNN 3D models and demonstrates 85.98 FROC versus 77.26 FROC for baseline models. Full Article
edu Reducing Communication in Graph Neural Network Training. (arXiv:2005.03300v1 [cs.LG]) By arxiv.org Published On :: Graph Neural Networks (GNNs) are powerful and flexible neural networks that use the naturally sparse connectivity information of the data. GNNs represent this connectivity as sparse matrices, which have lower arithmetic intensity and thus higher communication costs compared to dense matrices, making GNNs harder to scale to high concurrencies than convolutional or fully-connected neural networks. We present a family of parallel algorithms for training GNNs. These algorithms are based on their counterparts in dense and sparse linear algebra, but they had not been previously applied to GNN training. We show that they can asymptotically reduce communication compared to existing parallel GNN training methods. We implement a promising and practical version that is based on 2D sparse-dense matrix multiplication using torch.distributed. Our implementation parallelizes over GPU-equipped clusters. We train GNNs on up to a hundred GPUs on datasets that include a protein network with over a billion edges. Full Article
edu Model Reduction and Neural Networks for Parametric PDEs. (arXiv:2005.03180v1 [math.NA]) By arxiv.org Published On :: We develop a general framework for data-driven approximation of input-output maps between infinite-dimensional spaces. The proposed approach is motivated by the recent successes of neural networks and deep learning, in combination with ideas from model reduction. This combination results in a neural network approximation which, in principle, is defined on infinite-dimensional spaces and, in practice, is robust to the dimension of finite-dimensional approximations of these spaces required for computation. For a class of input-output maps, and suitably chosen probability measures on the inputs, we prove convergence of the proposed approximation methodology. Numerically we demonstrate the effectiveness of the method on a class of parametric elliptic PDE problems, showing convergence and robustness of the approximation scheme with respect to the size of the discretization, and compare our method with existing algorithms from the literature. Full Article
edu The Scientific basis of oral health education By dal.novanet.ca Published On :: Fri, 1 May 2020 19:44:43 -0300 Author: Levine, R. S., Dr., author.Callnumber: OnlineISBN: 9783319982076 (electronic bk.) Full Article
edu Salt, fat and sugar reduction : sensory approaches for nutritional reformulation of foods and beverages By dal.novanet.ca Published On :: Fri, 1 May 2020 19:44:43 -0300 Author: O'Sullivan, Maurice G., authorCallnumber: OnlineISBN: 9780128226124 (electronic bk.) Full Article
edu Mayo Clinic strategies to reduce burnout : 12 actions to create the ideal workplace By dal.novanet.ca Published On :: Fri, 1 May 2020 19:44:43 -0300 Author: Swensen, Stephen J., author.Callnumber: OnlineISBN: 9780190848996 electronic book Full Article
edu Handbook of geotechnical testing : basic theory, procedures and comparison of standards By dal.novanet.ca Published On :: Fri, 1 May 2020 19:44:43 -0300 Author: Li, Yanrong (Writer on geology), author.Callnumber: OnlineISBN: 0429323743 electronic book Full Article
edu Domestic Gag Rule Reduces Contraceptive Access For Nearly 370,000... By www.prweb.com Published On :: According to data released by Power to Decide, an estimated 369,960 New Jersey women of reproductive age (13-44) in need of publicly funded contraception live in counties impacted by the...(PRWeb April 09, 2020)Read the full story at https://www.prweb.com/releases/domestic_gag_rule_reduces_contraceptive_access_for_nearly_370_000_women_living_in_new_jersey/prweb17040987.htm Full Article
edu TFisher: A powerful truncation and weighting procedure for combining $p$-values By projecteuclid.org Published On :: Wed, 15 Apr 2020 22:05 EDT Hong Zhang, Tiejun Tong, John Landers, Zheyang Wu. Source: The Annals of Applied Statistics, Volume 14, Number 1, 178--201.Abstract: The $p$-value combination approach is an important statistical strategy for testing global hypotheses with broad applications in signal detection, meta-analysis, data integration, etc. In this paper we extend the classic Fisher’s combination method to a unified family of statistics, called TFisher, which allows a general truncation-and-weighting scheme of input $p$-values. TFisher can significantly improve statistical power over the Fisher and related truncation-only methods for detecting both rare and dense “signals.” To address wide applications, analytical calculations for TFisher’s size and power are deduced under any two continuous distributions in the null and the alternative hypotheses. The corresponding omnibus test (oTFisher) and its size calculation are also provided for data-adaptive analysis. We study the asymptotic optimal parameters of truncation and weighting based on Bahadur efficiency (BE). A new asymptotic measure, called the asymptotic power efficiency (APE), is also proposed for better reflecting the statistics’ performance in real data analysis. Interestingly, under the Gaussian mixture model in the signal detection problem, both BE and APE indicate that the soft-thresholding scheme is the best, the truncation and weighting parameters should be equal. By simulations of various signal patterns, we systematically compare the power of statistics within TFisher family as well as some rare-signal-optimal tests. We illustrate the use of TFisher in an exome-sequencing analysis for detecting novel genes of amyotrophic lateral sclerosis. Relevant computation has been implemented into an R package TFisher published on the Comprehensive R Archive Network to cater for applications. Full Article
edu Subspace perspective on canonical correlation analysis: Dimension reduction and minimax rates By projecteuclid.org Published On :: Tue, 26 Nov 2019 04:00 EST Zhuang Ma, Xiaodong Li. Source: Bernoulli, Volume 26, Number 1, 432--470.Abstract: Canonical correlation analysis (CCA) is a fundamental statistical tool for exploring the correlation structure between two sets of random variables. In this paper, motivated by the recent success of applying CCA to learn low dimensional representations of high dimensional objects, we propose two losses based on the principal angles between the model spaces spanned by the sample canonical variates and their population correspondents, respectively. We further characterize the non-asymptotic error bounds for the estimation risks under the proposed error metrics, which reveal how the performance of sample CCA depends adaptively on key quantities including the dimensions, the sample size, the condition number of the covariance matrices and particularly the population canonical correlation coefficients. The optimality of our uniform upper bounds is also justified by lower-bound analysis based on stringent and localized parameter spaces. To the best of our knowledge, for the first time our paper separates $p_{1}$ and $p_{2}$ for the first order term in the upper bounds without assuming the residual correlations are zeros. More significantly, our paper derives $(1-lambda_{k}^{2})(1-lambda_{k+1}^{2})/(lambda_{k}-lambda_{k+1})^{2}$ for the first time in the non-asymptotic CCA estimation convergence rates, which is essential to understand the behavior of CCA when the leading canonical correlation coefficients are close to $1$. Full Article
edu Calibration Procedures for Approximate Bayesian Credible Sets By projecteuclid.org Published On :: Thu, 19 Dec 2019 22:10 EST Jeong Eun Lee, Geoff K. Nicholls, Robin J. Ryder. Source: Bayesian Analysis, Volume 14, Number 4, 1245--1269.Abstract: We develop and apply two calibration procedures for checking the coverage of approximate Bayesian credible sets, including intervals estimated using Monte Carlo methods. The user has an ideal prior and likelihood, but generates a credible set for an approximate posterior based on some approximate prior and likelihood. We estimate the realised posterior coverage achieved by the approximate credible set. This is the coverage of the unknown “true” parameter if the data are a realisation of the user’s ideal observation model conditioned on the parameter, and the parameter is a draw from the user’s ideal prior. In one approach we estimate the posterior coverage at the data by making a semi-parametric logistic regression of binary coverage outcomes on simulated data against summary statistics evaluated on simulated data. In another we use Importance Sampling from the approximate posterior, windowing simulated data to fall close to the observed data. We illustrate our methods on four examples. Full Article
edu A Bayesian Nonparametric Multiple Testing Procedure for Comparing Several Treatments Against a Control By projecteuclid.org Published On :: Fri, 31 May 2019 22:05 EDT Luis Gutiérrez, Andrés F. Barrientos, Jorge González, Daniel Taylor-Rodríguez. Source: Bayesian Analysis, Volume 14, Number 2, 649--675.Abstract: We propose a Bayesian nonparametric strategy to test for differences between a control group and several treatment regimes. Most of the existing tests for this type of comparison are based on the differences between location parameters. In contrast, our approach identifies differences across the entire distribution, avoids strong modeling assumptions over the distributions for each treatment, and accounts for multiple testing through the prior distribution on the space of hypotheses. The proposal is compared to other commonly used hypothesis testing procedures under simulated scenarios. Two real applications are also analyzed with the proposed methodology. Full Article
edu A Kernel Regression Procedure in the 3D Shape Space with an Application to Online Sales of Children’s Wear By projecteuclid.org Published On :: Thu, 18 Jul 2019 22:01 EDT Gregorio Quintana-Ortí, Amelia Simó. Source: Statistical Science, Volume 34, Number 2, 236--252.Abstract: This paper is focused on kernel regression when the response variable is the shape of a 3D object represented by a configuration matrix of landmarks. Regression methods on this shape space are not trivial because this space has a complex finite-dimensional Riemannian manifold structure (non-Euclidean). Papers about it are scarce in the literature, the majority of them are restricted to the case of a single explanatory variable, and many of them are based on the approximated tangent space. In this paper, there are several methodological innovations. The first one is the adaptation of the general method for kernel regression analysis in manifold-valued data to the three-dimensional case of Kendall’s shape space. The second one is its generalization to the multivariate case and the addressing of the curse-of-dimensionality problem. Finally, we propose bootstrap confidence intervals for prediction. A simulation study is carried out to check the goodness of the procedure, and a comparison with a current approach is performed. Then, it is applied to a 3D database obtained from an anthropometric survey of the Spanish child population with a potential application to online sales of children’s wear. Full Article
edu The Joyful Reduction of Uncertainty: Music Perception as a Window to Predictive Neuronal Processing By www.jneurosci.org Published On :: 2020-04-01T09:30:19-07:00 Full Article
edu Wintrust Financial Corporation Announces Fourth Quarter and Year-to-Date 2019 Earnings Release Schedule By www.snl.com Published On :: Tue, 24 Dec 2019 00:11:00 GMT To view more press releases, please visit http://www.snl.com/irweblinkx/news.aspx?iid=1024452. Full Article
edu Wintrust Financial Corporation Announces First Quarter 2020 Earnings Release Schedule By www.snl.com Published On :: Thu, 16 Apr 2020 22:51:00 GMT To view more press releases, please visit http://www.snl.com/irweblinkx/news.aspx?iid=1024452. Full Article
edu Services for Shangukeidí clan mother scheduled By www.sealaskaheritage.org Published On :: Full Article
edu Noncoding Microdeletion in Mouse Hgf Disrupts Neural Crest Migration into the Stria Vascularis, Reduces the Endocochlear Potential, and Suggests the Neuropathology for Human Nonsyndromic Deafness DFNB39 By www.jneurosci.org Published On :: 2020-04-08T09:30:18-07:00 Hepatocyte growth factor (HGF) is a multifunctional protein that signals through the MET receptor. HGF stimulates cell proliferation, cell dispersion, neuronal survival, and wound healing. In the inner ear, levels of HGF must be fine-tuned for normal hearing. In mice, a deficiency of HGF expression limited to the auditory system, or an overexpression of HGF, causes neurosensory deafness. In humans, noncoding variants in HGF are associated with nonsyndromic deafness DFNB39. However, the mechanism by which these noncoding variants causes deafness was unknown. Here, we reveal the cause of this deafness using a mouse model engineered with a noncoding intronic 10 bp deletion (del10) in Hgf. Male and female mice homozygous for del10 exhibit moderate-to-profound hearing loss at 4 weeks of age as measured by tone burst auditory brainstem responses. The wild type (WT) 80 mV endocochlear potential was significantly reduced in homozygous del10 mice compared with WT littermates. In normal cochlea, endocochlear potentials are dependent on ion homeostasis mediated by the stria vascularis (SV). Previous studies showed that developmental incorporation of neural crest cells into the SV depends on signaling from HGF/MET. We show by immunohistochemistry that, in del10 homozygotes, neural crest cells fail to infiltrate the developing SV intermediate layer. Phenotyping and RNAseq analyses reveal no other significant abnormalities in other tissues. We conclude that, in the inner ear, the noncoding del10 mutation in Hgf leads to developmental defects of the SV and consequently dysfunctional ion homeostasis and a reduction in the EP, recapitulating human DFNB39 nonsyndromic deafness. SIGNIFICANCE STATEMENT Hereditary deafness is a common, clinically and genetically heterogeneous neurosensory disorder. Previously, we reported that human deafness DFNB39 is associated with noncoding variants in the 3'UTR of a short isoform of HGF encoding hepatocyte growth factor. For normal hearing, HGF levels must be fine-tuned as an excess or deficiency of HGF cause deafness in mouse. Using a Hgf mutant mouse with a small 10 bp deletion recapitulating a human DFNB39 noncoding variant, we demonstrate that neural crest cells fail to migrate into the stria vascularis intermediate layer, resulting in a significantly reduced endocochlear potential, the driving force for sound transduction by inner ear hair cells. HGF-associated deafness is a neurocristopathy but, unlike many other neurocristopathies, it is not syndromic. Full Article
edu Treatment with Mesenchymal-Derived Extracellular Vesicles Reduces Injury-Related Pathology in Pyramidal Neurons of Monkey Perilesional Ventral Premotor Cortex By www.jneurosci.org Published On :: 2020-04-22T09:29:41-07:00 Functional recovery after cortical injury, such as stroke, is associated with neural circuit reorganization, but the underlying mechanisms and efficacy of therapeutic interventions promoting neural plasticity in primates are not well understood. Bone marrow mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), which mediate cell-to-cell inflammatory and trophic signaling, are thought be viable therapeutic targets. We recently showed, in aged female rhesus monkeys, that systemic administration of MSC-EVs enhances recovery of function after injury of the primary motor cortex, likely through enhancing plasticity in perilesional motor and premotor cortices. Here, using in vitro whole-cell patch-clamp recording and intracellular filling in acute slices of ventral premotor cortex (vPMC) from rhesus monkeys (Macaca mulatta) of either sex, we demonstrate that MSC-EVs reduce injury-related physiological and morphologic changes in perilesional layer 3 pyramidal neurons. At 14-16 weeks after injury, vPMC neurons from both vehicle- and EV-treated lesioned monkeys exhibited significant hyperexcitability and predominance of inhibitory synaptic currents, compared with neurons from nonlesioned control brains. However, compared with vehicle-treated monkeys, neurons from EV-treated monkeys showed lower firing rates, greater spike frequency adaptation, and excitatory:inhibitory ratio. Further, EV treatment was associated with greater apical dendritic branching complexity, spine density, and inhibition, indicative of enhanced dendritic plasticity and filtering of signals integrated at the soma. Importantly, the degree of EV-mediated reduction of injury-related pathology in vPMC was significantly correlated with measures of behavioral recovery. These data show that EV treatment dampens injury-related hyperexcitability and restores excitatory:inhibitory balance in vPMC, thereby normalizing activity within cortical networks for motor function. SIGNIFICANCE STATEMENT Neuronal plasticity can facilitate recovery of function after cortical injury, but the underlying mechanisms and efficacy of therapeutic interventions promoting this plasticity in primates are not well understood. Our recent work has shown that intravenous infusions of mesenchymal-derived extracellular vesicles (EVs) that are involved in cell-to-cell inflammatory and trophic signaling can enhance recovery of motor function after injury in monkey primary motor cortex. This study shows that this EV-mediated enhancement of recovery is associated with amelioration of injury-related hyperexcitability and restoration of excitatory-inhibitory balance in perilesional ventral premotor cortex. These findings demonstrate the efficacy of mesenchymal EVs as a therapeutic to reduce injury-related pathologic changes in the physiology and structure of premotor pyramidal neurons and support recovery of function. Full Article
edu Deletion of Voltage-Gated Calcium Channels in Astrocytes during Demyelination Reduces Brain Inflammation and Promotes Myelin Regeneration in Mice By www.jneurosci.org Published On :: 2020-04-22T09:29:41-07:00 To determine whether Cav1.2 voltage-gated Ca2+ channels contribute to astrocyte activation, we generated an inducible conditional knock-out mouse in which the Cav1.2 α subunit was deleted in GFAP-positive astrocytes. This astrocytic Cav1.2 knock-out mouse was tested in the cuprizone model of myelin injury and repair which causes astrocyte and microglia activation in the absence of a lymphocytic response. Deletion of Cav1.2 channels in GFAP-positive astrocytes during cuprizone-induced demyelination leads to a significant reduction in the degree of astrocyte and microglia activation and proliferation in mice of either sex. Concomitantly, the production of proinflammatory factors such as TNFα, IL1β and TGFβ1 was significantly decreased in the corpus callosum and cortex of Cav1.2 knock-out mice through demyelination. Furthermore, this mild inflammatory environment promotes oligodendrocyte progenitor cells maturation and myelin regeneration across the remyelination phase of the cuprizone model. Similar results were found in animals treated with nimodipine, a Cav1.2 Ca2+ channel inhibitor with high affinity to the CNS. Mice of either sex injected with nimodipine during the demyelination stage of the cuprizone treatment displayed a reduced number of reactive astrocytes and showed a faster and more efficient brain remyelination. Together, these results indicate that Cav1.2 Ca2+ channels play a crucial role in the induction and proliferation of reactive astrocytes during demyelination; and that attenuation of astrocytic voltage-gated Ca2+ influx may be an effective therapy to reduce brain inflammation and promote myelin recovery in demyelinating diseases. SIGNIFICANCE STATEMENT Reducing voltage-gated Ca2+ influx in astrocytes during brain demyelination significantly attenuates brain inflammation and astrocyte reactivity. Furthermore, these changes promote myelin restoration and oligodendrocyte maturation throughout remyelination. Full Article
edu Reward-Based Improvements in Motor Control Are Driven by Multiple Error-Reducing Mechanisms By www.jneurosci.org Published On :: 2020-04-29T09:30:19-07:00 Reward has a remarkable ability to invigorate motor behavior, enabling individuals to select and execute actions with greater precision and speed. However, if reward is to be exploited in applied settings, such as rehabilitation, a thorough understanding of its underlying mechanisms is required. In a series of experiments, we first demonstrate that reward simultaneously improves the selection and execution components of a reaching movement. Specifically, reward promoted the selection of the correct action in the presence of distractors, while also improving execution through increased speed and maintenance of accuracy. These results led to a shift in the speed-accuracy functions for both selection and execution. In addition, punishment had a similar impact on action selection and execution, although it enhanced execution performance across all trials within a block, that is, its impact was noncontingent to trial value. Although the reward-driven enhancement of movement execution has been proposed to occur through enhanced feedback control, an untested possibility is that it is also driven by increased arm stiffness, an energy-consuming process that enhances limb stability. Computational analysis revealed that reward led to both an increase in feedback correction in the middle of the movement and a reduction in motor noise near the target. In line with our hypothesis, we provide novel evidence that this noise reduction is driven by a reward-dependent increase in arm stiffness. Therefore, reward drives multiple error-reduction mechanisms which enable individuals to invigorate motor performance without compromising accuracy. SIGNIFICANCE STATEMENT While reward is well-known for enhancing motor performance, how the nervous system generates these improvements is unclear. Despite recent work indicating that reward leads to enhanced feedback control, an untested possibility is that it also increases arm stiffness. We demonstrate that reward simultaneously improves the selection and execution components of a reaching movement. Furthermore, we show that punishment has a similar positive impact on performance. Importantly, by combining computational and biomechanical approaches, we show that reward leads to both improved feedback correction and an increase in stiffness. Therefore, reward drives multiple error-reduction mechanisms which enable individuals to invigorate performance without compromising accuracy. This work suggests that stiffness control plays a vital, and underappreciated, role in the reward-based imporvemenets in motor control. Full Article
edu Asia-Pacific campaign targets reduced food losses By www.fao.org Published On :: Thu, 29 Aug 2013 00:00:00 GMT FAO and its partners have launched an initiative aimed at cutting food waste across the Asia-Pacific region. Save Food Asia-Pacific Campaign targets losses both straight after harvest and between the market and people’s plates. FAO estimates that reducing global food waste by just one quarter would be sufficient to feed the 870 million people suffering from chronic hunger in the world. [...] Full Article