lly WNBA Draft Profile: Versatile forward Satou Sabally can provide instant impact By sports.yahoo.com Published On :: Thu, 09 Apr 2020 20:42:49 GMT Athletic forward Satou Sabally is preparing to take the leap to the WNBA level following three productive seasons at Oregon. As a junior, she averaged 16.2 points and 6.9 rebounds per game while helping the Ducks sweep the Pac-12 regular season and tournament titles. At 6-foot-4, she also drained 45 3-pointers for Oregon in 2019-20 while notching a career-best average of 2.3 assists per game. Full Article video Sports
lly Stanford's Tara VanDerveer on Haley Jones' versatile freshman year: 'It was really incredible' By sports.yahoo.com Published On :: Fri, 08 May 2020 16:17:17 GMT During Friday's "Pac-12 Perspective," Stanford head coach Tara VanDerveer spoke about Haley Jones' positionless game and how the Cardinal used the dynamic freshman in 2019-20. Download and listen wherever you get your podcasts. Full Article video Sports
lly Practical Locally Private Heavy Hitters By Published On :: 2020 We present new practical local differentially private heavy hitters algorithms achieving optimal or near-optimal worst-case error and running time -- TreeHist and Bitstogram. In both algorithms, server running time is $ ilde O(n)$ and user running time is $ ilde O(1)$, hence improving on the prior state-of-the-art result of Bassily and Smith [STOC 2015] requiring $O(n^{5/2})$ server time and $O(n^{3/2})$ user time. With a typically large number of participants in local algorithms (in the millions), this reduction in time complexity, in particular at the user side, is crucial for making locally private heavy hitters algorithms usable in practice. We implemented Algorithm TreeHist to verify our theoretical analysis and compared its performance with the performance of Google's RAPPOR code. Full Article
lly Robust Asynchronous Stochastic Gradient-Push: Asymptotically Optimal and Network-Independent Performance for Strongly Convex Functions By Published On :: 2020 We consider the standard model of distributed optimization of a sum of functions $F(mathbf z) = sum_{i=1}^n f_i(mathbf z)$, where node $i$ in a network holds the function $f_i(mathbf z)$. We allow for a harsh network model characterized by asynchronous updates, message delays, unpredictable message losses, and directed communication among nodes. In this setting, we analyze a modification of the Gradient-Push method for distributed optimization, assuming that (i) node $i$ is capable of generating gradients of its function $f_i(mathbf z)$ corrupted by zero-mean bounded-support additive noise at each step, (ii) $F(mathbf z)$ is strongly convex, and (iii) each $f_i(mathbf z)$ has Lipschitz gradients. We show that our proposed method asymptotically performs as well as the best bounds on centralized gradient descent that takes steps in the direction of the sum of the noisy gradients of all the functions $f_1(mathbf z), ldots, f_n(mathbf z)$ at each step. Full Article
lly Recent developments in complex and spatially correlated functional data By projecteuclid.org Published On :: Mon, 04 May 2020 04:00 EDT Israel Martínez-Hernández, Marc G. Genton. Source: Brazilian Journal of Probability and Statistics, Volume 34, Number 2, 204--229.Abstract: As high-dimensional and high-frequency data are being collected on a large scale, the development of new statistical models is being pushed forward. Functional data analysis provides the required statistical methods to deal with large-scale and complex data by assuming that data are continuous functions, for example, realizations of a continuous process (curves) or continuous random field (surfaces), and that each curve or surface is considered as a single observation. Here, we provide an overview of functional data analysis when data are complex and spatially correlated. We provide definitions and estimators of the first and second moments of the corresponding functional random variable. We present two main approaches: The first assumes that data are realizations of a functional random field, that is, each observation is a curve with a spatial component. We call them spatial functional data . The second approach assumes that data are continuous deterministic fields observed over time. In this case, one observation is a surface or manifold, and we call them surface time series . For these two approaches, we describe software available for the statistical analysis. We also present a data illustration, using a high-resolution wind speed simulated dataset, as an example of the two approaches. The functional data approach offers a new paradigm of data analysis, where the continuous processes or random fields are considered as a single entity. We consider this approach to be very valuable in the context of big data. Full Article
lly Spatially adaptive Bayesian image reconstruction through locally-modulated Markov random field models By projecteuclid.org Published On :: Mon, 10 Jun 2019 04:04 EDT Salem M. Al-Gezeri, Robert G. Aykroyd. Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 3, 498--519.Abstract: The use of Markov random field (MRF) models has proven to be a fruitful approach in a wide range of image processing applications. It allows local texture information to be incorporated in a systematic and unified way and allows statistical inference theory to be applied giving rise to novel output summaries and enhanced image interpretation. A great advantage of such low-level approaches is that they lead to flexible models, which can be applied to a wide range of imaging problems without the need for significant modification. This paper proposes and explores the use of conditional MRF models for situations where multiple images are to be processed simultaneously, or where only a single image is to be reconstructed and a sequential approach is taken. Although the coupling of image intensity values is a special case of our approach, the main extension over previous proposals is to allow the direct coupling of other properties, such as smoothness or texture. This is achieved using a local modulating function which adjusts the influence of global smoothing without the need for a fully inhomogeneous prior model. Several modulating functions are considered and a detailed simulation study, motivated by remote sensing applications in archaeological geophysics, of conditional reconstruction is presented. The results demonstrate that a substantial improvement in the quality of the image reconstruction, in terms of errors and residuals, can be achieved using this approach, especially at locations with rapid changes in the underlying intensity. Full Article
lly Fully grown : why a stagnant economy is a sign of success By dal.novanet.ca Published On :: Fri, 1 May 2020 19:34:09 -0300 Author: Vollrath, Dietrich, author.Callnumber: HC 110 E44 V65 2020ISBN: 9780226666006 hardcover Full Article
lly Can $p$-values be meaningfully interpreted without random sampling? By projecteuclid.org Published On :: Thu, 26 Mar 2020 22:02 EDT Norbert Hirschauer, Sven Grüner, Oliver Mußhoff, Claudia Becker, Antje Jantsch. Source: Statistics Surveys, Volume 14, 71--91.Abstract: Besides the inferential errors that abound in the interpretation of $p$-values, the probabilistic pre-conditions (i.e. random sampling or equivalent) for using them at all are not often met by observational studies in the social sciences. This paper systematizes different sampling designs and discusses the restrictive requirements of data collection that are the indispensable prerequisite for using $p$-values. Full Article
lly A Distributionally Robust Area Under Curve Maximization Model. (arXiv:2002.07345v2 [math.OC] UPDATED) By arxiv.org Published On :: Area under ROC curve (AUC) is a widely used performance measure for classification models. We propose two new distributionally robust AUC maximization models (DR-AUC) that rely on the Kantorovich metric and approximate the AUC with the hinge loss function. We consider the two cases with respectively fixed and variable support for the worst-case distribution. We use duality theory to reformulate the DR-AUC models and derive tractable convex optimization problems. The numerical experiments show that the proposed DR-AUC models -- benchmarked with the standard deterministic AUC and the support vector machine models - perform better in general and in particular improve the worst-case out-of-sample performance over the majority of the considered datasets, thereby showing their robustness. The results are particularly encouraging since our numerical experiments are conducted with training sets of small size which have been known to be conducive to low out-of-sample performance. Full Article
lly A Locally Adaptive Interpretable Regression. (arXiv:2005.03350v1 [stat.ML]) By arxiv.org Published On :: Machine learning models with both good predictability and high interpretability are crucial for decision support systems. Linear regression is one of the most interpretable prediction models. However, the linearity in a simple linear regression worsens its predictability. In this work, we introduce a locally adaptive interpretable regression (LoAIR). In LoAIR, a metamodel parameterized by neural networks predicts percentile of a Gaussian distribution for the regression coefficients for a rapid adaptation. Our experimental results on public benchmark datasets show that our model not only achieves comparable or better predictive performance than the other state-of-the-art baselines but also discovers some interesting relationships between input and target variables such as a parabolic relationship between CO2 emissions and Gross National Product (GNP). Therefore, LoAIR is a step towards bridging the gap between econometrics, statistics, and machine learning by improving the predictive ability of linear regression without depreciating its interpretability. Full Article
lly On a computationally-scalable sparse formulation of the multidimensional and non-stationary maximum entropy principle. (arXiv:2005.03253v1 [stat.CO]) By arxiv.org Published On :: Data-driven modelling and computational predictions based on maximum entropy principle (MaxEnt-principle) aim at finding as-simple-as-possible - but not simpler then necessary - models that allow to avoid the data overfitting problem. We derive a multivariate non-parametric and non-stationary formulation of the MaxEnt-principle and show that its solution can be approximated through a numerical maximisation of the sparse constrained optimization problem with regularization. Application of the resulting algorithm to popular financial benchmarks reveals memoryless models allowing for simple and qualitative descriptions of the major stock market indexes data. We compare the obtained MaxEnt-models to the heteroschedastic models from the computational econometrics (GARCH, GARCH-GJR, MS-GARCH, GARCH-PML4) in terms of the model fit, complexity and prediction quality. We compare the resulting model log-likelihoods, the values of the Bayesian Information Criterion, posterior model probabilities, the quality of the data autocorrelation function fits as well as the Value-at-Risk prediction quality. We show that all of the considered seven major financial benchmark time series (DJI, SPX, FTSE, STOXX, SMI, HSI and N225) are better described by conditionally memoryless MaxEnt-models with nonstationary regime-switching than by the common econometric models with finite memory. This analysis also reveals a sparse network of statistically-significant temporal relations for the positive and negative latent variance changes among different markets. The code is provided for open access. Full Article
lly Post treatments of anaerobically treated effluents By dal.novanet.ca Published On :: Fri, 1 May 2020 19:44:43 -0300 Callnumber: OnlineISBN: 9781780409740 Full Article
lly Implants in the aesthetic zone : a guide for treatment of the partially edentulous patient By dal.novanet.ca Published On :: Fri, 1 May 2020 19:44:43 -0300 Callnumber: OnlineISBN: 9783319726014 (electronic bk.) Full Article
lly Atlas of sexually transmitted diseases : clinical aspects and differential diagnosis By dal.novanet.ca Published On :: Fri, 1 May 2020 19:44:43 -0300 Callnumber: OnlineISBN: 9783319574707 (electronic bk.) Full Article
lly Projected spline estimation of the nonparametric function in high-dimensional partially linear models for massive data By projecteuclid.org Published On :: Fri, 02 Aug 2019 22:04 EDT Heng Lian, Kaifeng Zhao, Shaogao Lv. Source: The Annals of Statistics, Volume 47, Number 5, 2922--2949.Abstract: In this paper, we consider the local asymptotics of the nonparametric function in a partially linear model, within the framework of the divide-and-conquer estimation. Unlike the fixed-dimensional setting in which the parametric part does not affect the nonparametric part, the high-dimensional setting makes the issue more complicated. In particular, when a sparsity-inducing penalty such as lasso is used to make the estimation of the linear part feasible, the bias introduced will propagate to the nonparametric part. We propose a novel approach for estimation of the nonparametric function and establish the local asymptotics of the estimator. The result is useful for massive data with possibly different linear coefficients in each subpopulation but common nonparametric function. Some numerical illustrations are also presented. Full Article
lly Semiparametrically point-optimal hybrid rank tests for unit roots By projecteuclid.org Published On :: Fri, 02 Aug 2019 22:04 EDT Bo Zhou, Ramon van den Akker, Bas J. M. Werker. Source: The Annals of Statistics, Volume 47, Number 5, 2601--2638.Abstract: We propose a new class of unit root tests that exploits invariance properties in the Locally Asymptotically Brownian Functional limit experiment associated to the unit root model. The invariance structures naturally suggest tests that are based on the ranks of the increments of the observations, their average and an assumed reference density for the innovations. The tests are semiparametric in the sense that they are valid, that is, have the correct (asymptotic) size, irrespective of the true innovation density. For a correctly specified reference density, our test is point-optimal and nearly efficient. For arbitrary reference densities, we establish a Chernoff–Savage-type result, that is, our test performs as well as commonly used tests under Gaussian innovations but has improved power under other, for example, fat-tailed or skewed, innovation distributions. To avoid nonparametric estimation, we propose a simplified version of our test that exhibits the same asymptotic properties, except for the Chernoff–Savage result that we are only able to demonstrate by means of simulations. Full Article
lly Cross validation for locally stationary processes By projecteuclid.org Published On :: Wed, 22 May 2019 04:01 EDT Stefan Richter, Rainer Dahlhaus. Source: The Annals of Statistics, Volume 47, Number 4, 2145--2173.Abstract: We propose an adaptive bandwidth selector via cross validation for local M-estimators in locally stationary processes. We prove asymptotic optimality of the procedure under mild conditions on the underlying parameter curves. The results are applicable to a wide range of locally stationary processes such linear and nonlinear processes. A simulation study shows that the method works fairly well also in misspecified situations. Full Article
lly Statistical inference for partially observed branching processes with application to cell lineage tracking of in vivo hematopoiesis By projecteuclid.org Published On :: Wed, 27 Nov 2019 22:01 EST Jason Xu, Samson Koelle, Peter Guttorp, Chuanfeng Wu, Cynthia Dunbar, Janis L. Abkowitz, Vladimir N. Minin. Source: The Annals of Applied Statistics, Volume 13, Number 4, 2091--2119.Abstract: Single-cell lineage tracking strategies enabled by recent experimental technologies have produced significant insights into cell fate decisions, but lack the quantitative framework necessary for rigorous statistical analysis of mechanistic models describing cell division and differentiation. In this paper, we develop such a framework with corresponding moment-based parameter estimation techniques for continuous-time, multi-type branching processes. Such processes provide a probabilistic model of how cells divide and differentiate, and we apply our method to study hematopoiesis , the mechanism of blood cell production. We derive closed-form expressions for higher moments in a general class of such models. These analytical results allow us to efficiently estimate parameters of much richer statistical models of hematopoiesis than those used in previous statistical studies. To our knowledge, the method provides the first rate inference procedure for fitting such models to time series data generated from cellular barcoding experiments. After validating the methodology in simulation studies, we apply our estimator to hematopoietic lineage tracking data from rhesus macaques. Our analysis provides a more complete understanding of cell fate decisions during hematopoiesis in nonhuman primates, which may be more relevant to human biology and clinical strategies than previous findings from murine studies. For example, in addition to previously estimated hematopoietic stem cell self-renewal rate, we are able to estimate fate decision probabilities and to compare structurally distinct models of hematopoiesis using cross validation. These estimates of fate decision probabilities and our model selection results should help biologists compare competing hypotheses about how progenitor cells differentiate. The methodology is transferrable to a large class of stochastic compartmental and multi-type branching models, commonly used in studies of cancer progression, epidemiology and many other fields. Full Article
lly On the probability distribution of the local times of diagonally operator-self-similar Gaussian fields with stationary increments By projecteuclid.org Published On :: Fri, 31 Jan 2020 04:06 EST Kamran Kalbasi, Thomas Mountford. Source: Bernoulli, Volume 26, Number 2, 1504--1534.Abstract: In this paper, we study the local times of vector-valued Gaussian fields that are ‘diagonally operator-self-similar’ and whose increments are stationary. Denoting the local time of such a Gaussian field around the spatial origin and over the temporal unit hypercube by $Z$, we show that there exists $lambdain(0,1)$ such that under some quite weak conditions, $lim_{n ightarrow+infty}frac{sqrt[n]{mathbb{E}(Z^{n})}}{n^{lambda}}$ and $lim_{x ightarrow+infty}frac{-logmathbb{P}(Z>x)}{x^{frac{1}{lambda}}}$ both exist and are strictly positive (possibly $+infty$). Moreover, we show that if the underlying Gaussian field is ‘strongly locally nondeterministic’, the above limits will be finite as well. These results are then applied to establish similar statements for the intersection local times of diagonally operator-self-similar Gaussian fields with stationary increments. Full Article
lly Stochastic differential equations with a fractionally filtered delay: A semimartingale model for long-range dependent processes By projecteuclid.org Published On :: Fri, 31 Jan 2020 04:06 EST Richard A. Davis, Mikkel Slot Nielsen, Victor Rohde. Source: Bernoulli, Volume 26, Number 2, 799--827.Abstract: In this paper, we introduce a model, the stochastic fractional delay differential equation (SFDDE), which is based on the linear stochastic delay differential equation and produces stationary processes with hyperbolically decaying autocovariance functions. The model departs from the usual way of incorporating this type of long-range dependence into a short-memory model as it is obtained by applying a fractional filter to the drift term rather than to the noise term. The advantages of this approach are that the corresponding long-range dependent solutions are semimartingales and the local behavior of the sample paths is unaffected by the degree of long memory. We prove existence and uniqueness of solutions to the SFDDEs and study their spectral densities and autocovariance functions. Moreover, we define a subclass of SFDDEs which we study in detail and relate to the well-known fractionally integrated CARMA processes. Finally, we consider the task of simulating from the defining SFDDEs. Full Article
lly A new method for obtaining sharp compound Poisson approximation error estimates for sums of locally dependent random variables By projecteuclid.org Published On :: Thu, 05 Aug 2010 15:41 EDT Michael V. Boutsikas, Eutichia VaggelatouSource: Bernoulli, Volume 16, Number 2, 301--330.Abstract: Let X 1 , X 2 , …, X n be a sequence of independent or locally dependent random variables taking values in ℤ + . In this paper, we derive sharp bounds, via a new probabilistic method, for the total variation distance between the distribution of the sum ∑ i =1 n X i and an appropriate Poisson or compound Poisson distribution. These bounds include a factor which depends on the smoothness of the approximating Poisson or compound Poisson distribution. This “smoothness factor” is of order O( σ −2 ), according to a heuristic argument, where σ 2 denotes the variance of the approximating distribution. In this way, we offer sharp error estimates for a large range of values of the parameters. Finally, specific examples concerning appearances of rare runs in sequences of Bernoulli trials are presented by way of illustration. Full Article
lly Bayesian Functional Forecasting with Locally-Autoregressive Dependent Processes By projecteuclid.org Published On :: Thu, 19 Dec 2019 22:10 EST Guillaume Kon Kam King, Antonio Canale, Matteo Ruggiero. Source: Bayesian Analysis, Volume 14, Number 4, 1121--1141.Abstract: Motivated by the problem of forecasting demand and offer curves, we introduce a class of nonparametric dynamic models with locally-autoregressive behaviour, and provide a full inferential strategy for forecasting time series of piecewise-constant non-decreasing functions over arbitrary time horizons. The model is induced by a non Markovian system of interacting particles whose evolution is governed by a resampling step and a drift mechanism. The former is based on a global interaction and accounts for the volatility of the functional time series, while the latter is determined by a neighbourhood-based interaction with the past curves and accounts for local trend behaviours, separating these from pure noise. We discuss the implementation of the model for functional forecasting by combining a population Monte Carlo and a semi-automatic learning approach to approximate Bayesian computation which require limited tuning. We validate the inference method with a simulation study, and carry out predictive inference on a real dataset on the Italian natural gas market. Full Article
lly Bayes Factors for Partially Observed Stochastic Epidemic Models By projecteuclid.org Published On :: Tue, 11 Jun 2019 04:00 EDT Muteb Alharthi, Theodore Kypraios, Philip D. O’Neill. Source: Bayesian Analysis, Volume 14, Number 3, 927--956.Abstract: We consider the problem of model choice for stochastic epidemic models given partial observation of a disease outbreak through time. Our main focus is on the use of Bayes factors. Although Bayes factors have appeared in the epidemic modelling literature before, they can be hard to compute and little attention has been given to fundamental questions concerning their utility. In this paper we derive analytic expressions for Bayes factors given complete observation through time, which suggest practical guidelines for model choice problems. We adapt the power posterior method for computing Bayes factors so as to account for missing data and apply this approach to partially observed epidemics. For comparison, we also explore the use of a deviance information criterion for missing data scenarios. The methods are illustrated via examples involving both simulated and real data. Full Article
lly Conditionally Conjugate Mean-Field Variational Bayes for Logistic Models By projecteuclid.org Published On :: Fri, 11 Oct 2019 04:03 EDT Daniele Durante, Tommaso Rigon. Source: Statistical Science, Volume 34, Number 3, 472--485.Abstract: Variational Bayes (VB) is a common strategy for approximate Bayesian inference, but simple methods are only available for specific classes of models including, in particular, representations having conditionally conjugate constructions within an exponential family. Models with logit components are an apparently notable exception to this class, due to the absence of conjugacy among the logistic likelihood and the Gaussian priors for the coefficients in the linear predictor. To facilitate approximate inference within this widely used class of models, Jaakkola and Jordan ( Stat. Comput. 10 (2000) 25–37) proposed a simple variational approach which relies on a family of tangent quadratic lower bounds of the logistic log-likelihood, thus restoring conjugacy between these approximate bounds and the Gaussian priors. This strategy is still implemented successfully, but few attempts have been made to formally understand the reasons underlying its excellent performance. Following a review on VB for logistic models, we cover this gap by providing a formal connection between the above bound and a recent Pólya-gamma data augmentation for logistic regression. Such a result places the computational methods associated with the aforementioned bounds within the framework of variational inference for conditionally conjugate exponential family models, thereby allowing recent advances for this class to be inherited also by the methods relying on Jaakkola and Jordan ( Stat. Comput. 10 (2000) 25–37). Full Article
lly How can the smoker and the nonsmoker be equally free in the same place? George Bernard Shaw / Biman Mullick. By search.wellcomelibrary.org Published On :: [London?], [199-?] Full Article
lly Danny Smith from No Human Being Is Illegal (in all our glory). Collaged photograph by Deborah Kelly and collaborators, 2014-2018. By search.wellcomelibrary.org Published On :: [London], 2019. Full Article
lly These Clark Booties Are Actually Comfortable Enough to Wear All Day—and They’re on Sale By www.health.com Published On :: Sun, 08 Dec 2019 09:36:02 -0500 You can save 50% right now. Full Article
lly The Comfy Sneakers That Kate Middleton, Kelly Ripa, and More Celebs Love Are on Sale at Amazon By www.health.com Published On :: Mon, 02 Dec 2019 17:12:09 -0500 Keep your feet comfy and your wallet fat. Full Article
lly Pax6, Tbr2, and Tbr1 Are Expressed Sequentially by Radial Glia, Intermediate Progenitor Cells, and Postmitotic Neurons in Developing Neocortex By www.jneurosci.org Published On :: 2005-01-05 Chris EnglundJan 5, 2005; 25:247-251BRIEF COMMUNICATION Full Article
lly Mary Elizabeth Williams: The clumsy, beautiful Rally to Restore Sanity By www.salon.com Published On :: Full Article
lly The quest for financial integration in Europe and globally By www.bis.org Published On :: 2019-09-12T15:45:00Z Speech by Mr Agustín Carstens, General Manager of the BIS, at the Eurofi Financial Forum, Helsinki, 12 September 2019. Full Article
lly The Right Temporoparietal Junction Is Causally Associated with Embodied Perspective-taking By www.jneurosci.org Published On :: 2020-04-08T09:30:18-07:00 A prominent theory claims that the right temporoparietal junction (rTPJ) is especially associated with embodied processes relevant to perspective-taking. In the present study, we use high-definition transcranial direct current stimulation to provide evidence that the rTPJ is causally associated with the embodied processes underpinning perspective-taking. Eighty-eight young human adults were stratified to receive either rTPJ or dorsomedial PFC anodal high-definition transcranial direct current stimulation in a sham-controlled, double-blind, repeated-measures design. Perspective-tracking (line-of-sight) and perspective-taking (embodied rotation) were assessed using a visuo-spatial perspective-taking task that required understanding what another person could see or how they see it, respectively. Embodied processing was manipulated by positioning the participant in a manner congruent or incongruent with the orientation of an avatar on the screen. As perspective-taking, but not perspective-tracking, is influenced by bodily position, this allows the investigation of the specific causal role for the rTPJ in embodied processing. Crucially, anodal stimulation to the rTPJ increased the effect of bodily position during perspective-taking, whereas no such effects were identified during perspective-tracking, thereby providing evidence for a causal role for the rTPJ in the embodied component of perspective-taking. Stimulation to the dorsomedial PFC had no effect on perspective-tracking or taking. Therefore, the present study provides support for theories postulating that the rTPJ is causally involved in embodied cognitive processing relevant to social functioning. SIGNIFICANCE STATEMENT The ability to understand another's perspective is a fundamental component of social functioning. Adopting another perspective is thought to involve both embodied and nonembodied processes. The present study used high-definition transcranial direct current stimulation (HD-tDCS) and provided causal evidence that the right temporoparietal junction is involved specifically in the embodied component of perspective-taking. Specifically, HD-tDCS to the right temporoparietal junction, but not another hub of the social brain (dorsomedial PFC), increased the effect of body position during perspective-taking, but not tracking. This is the first causal evidence that HD-tDCS can modulate social embodied processing in a site-specific and task-specific manner. Full Article
lly {beta}4-Nicotinic Receptors Are Critically Involved in Reward-Related Behaviors and Self-Regulation of Nicotine Reinforcement By www.jneurosci.org Published On :: 2020-04-22T09:29:41-07:00 Nicotine addiction, through smoking, is the principal cause of preventable mortality worldwide. Human genome-wide association studies have linked polymorphisms in the CHRNA5-CHRNA3-CHRNB4 gene cluster, coding for the α5, α3, and β4 nicotinic acetylcholine receptor (nAChR) subunits, to nicotine addiction. β4*nAChRs have been implicated in nicotine withdrawal, aversion, and reinforcement. Here we show that β4*nAChRs also are involved in non-nicotine-mediated responses that may predispose to addiction-related behaviors. β4 knock-out (KO) male mice show increased novelty-induced locomotor activity, lower baseline anxiety, and motivational deficits in operant conditioning for palatable food rewards and in reward-based Go/No-go tasks. To further explore reward deficits we used intracranial self-administration (ICSA) by directly injecting nicotine into the ventral tegmental area (VTA) in mice. We found that, at low nicotine doses, β4KO self-administer less than wild-type (WT) mice. Conversely, at high nicotine doses, this was reversed and β4KO self-administered more than WT mice, whereas β4-overexpressing mice avoided nicotine injections. Viral expression of β4 subunits in medial habenula (MHb), interpeduncular nucleus (IPN), and VTA of β4KO mice revealed dose- and region-dependent differences: β4*nAChRs in the VTA potentiated nicotine-mediated rewarding effects at all doses, whereas β4*nAChRs in the MHb-IPN pathway, limited VTA-ICSA at high nicotine doses. Together, our findings indicate that the lack of functional β4*nAChRs result in deficits in reward sensitivity including increased ICSA at high doses of nicotine that is restored by re-expression of β4*nAChRs in the MHb-IPN. These data indicate that β4 is a critical modulator of reward-related behaviors. SIGNIFICANCE STATEMENT Human genetic studies have provided strong evidence for a relationship between variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster and nicotine addiction. Yet, little is known about the role of β4 nicotinic acetylcholine receptor (nAChR) subunit encoded by this cluster. We investigated the implication of β4*nAChRs in anxiety-, food reward- and nicotine reward-related behaviors. Deletion of the β4 subunit gene resulted in an addiction-related phenotype characterized by low anxiety, high novelty-induced response, lack of sensitivity to palatable food rewards and increased intracranial nicotine self-administration at high doses. Lentiviral vector-induced re-expression of the β4 subunit into either the MHb or IPN restored a "stop" signal on nicotine self-administration. These results suggest that β4*nAChRs provide a promising novel drug target for smoking cessation. Full Article
lly The Frog Motor Nerve Terminal Has Very Brief Action Potentials and Three Electrical Regions Predicted to Differentially Control Transmitter Release By www.jneurosci.org Published On :: 2020-04-29T09:30:19-07:00 The action potential (AP) waveform controls the opening of voltage-gated calcium channels and contributes to the driving force for calcium ion flux that triggers neurotransmission at presynaptic nerve terminals. Although the frog neuromuscular junction (NMJ) has long been a model synapse for the study of neurotransmission, its presynaptic AP waveform has never been directly studied, and thus the AP waveform shape and propagation through this long presynaptic nerve terminal are unknown. Using a fast voltage-sensitive dye, we have imaged the AP waveform from the presynaptic terminal of male and female frog NMJs and shown that the AP is very brief in duration and actively propagated along the entire length of the terminal. Furthermore, based on measured AP waveforms at different regions along the length of the nerve terminal, we show that the terminal is divided into three distinct electrical regions: A beginning region immediately after the last node of Ranvier where the AP is broadest, a middle region with a relatively consistent AP duration, and an end region near the tip of nerve terminal branches where the AP is briefer. We hypothesize that these measured changes in the AP waveform along the length of the motor nerve terminal may explain the proximal-distal gradient in transmitter release previously reported at the frog NMJ. SIGNIFICANCE STATEMENT The AP waveform plays an essential role in determining the behavior of neurotransmission at the presynaptic terminal. Although the frog NMJ is a model synapse for the study of synaptic transmission, there are many unknowns centered around the shape and propagation of its presynaptic AP waveform. Here, we demonstrate that the presynaptic terminal of the frog NMJ has a very brief AP waveform and that the motor nerve terminal contains three distinct electrical regions. We propose that the changes in the AP waveform as it propagates along the terminal can explain the proximal-distal gradient in transmitter release seen in electrophysiological studies. Full Article
lly Virtually Celebrate Peak Bloom With Ten Fun Facts About Cherry Blossoms By www.smithsonianmag.com Published On :: Wed, 04 Mar 2020 16:21:37 +0000 The National Cherry Blossom Festival has moved online due to the novel coronavirus pandemic Full Article
lly willy wonka original psychedelic boat trip [2m39s] By www.youtube.com Published On :: willy wonka original psychedelic boat trip, with gene wilder Full Article
lly Rats May Be Genetically Adapted to New York Living By www.smithsonianmag.com Published On :: Fri, 13 Mar 2020 20:51:54 +0000 Perhaps it was not just a massive slice that made Pizza Rat a true New Yorker Full Article
lly Ten Museums You Can Virtually Visit By www.smithsonianmag.com Published On :: Fri, 20 Mar 2020 11:00:00 +0000 Museums are closing their doors amid the coronavirus crisis, but many offer digital exhibitions visitors can browse from the comfort of home Full Article
lly Neanderthals Really Liked Seafood By www.smithsonianmag.com Published On :: Mon, 30 Mar 2020 13:00:00 +0000 A rare cache of aquatic animal remains suggests that like early humans, Neanderthals were exploiting marine resources Full Article
lly Hollywood's 'Golden Age' Saw Massive Dip in Female Film Representation By www.smithsonianmag.com Published On :: Fri, 03 Apr 2020 11:30:00 +0000 A new study ties the ousting of women directors, actors, producers and screenwriters to the rise of entertainment studios Full Article
lly Explore the World Virtually With These Rare, Centuries-Old Globes By www.smithsonianmag.com Published On :: Mon, 06 Apr 2020 18:20:16 +0000 Visitors can get up close and personal with augmented reality versions of historic globes recently digitized by the British Library Full Article
lly EDWARD ACZEL: DO I REALLY HAVE TO COMMUNICATE WITH YOU? PT1 [5m09s] By www.youtube.com Published On :: Edward Aczel reluctantly presents his shambles of a show, 'Do I Really Have To Communicate With You?'. Winner of the Malcolm Hardee Award for [...] Full Article
lly The Best Rally Crashes & Accidents 2011....... (No Music) [9m37s] By www.youtube.com Published On :: All different rally crashes from around the globe/web with just the sounds of the cars and spectators! None of this silly music people keep masking [...] Full Article
lly How to Virtually Explore the Smithsonian From Your Living Room By www.smithsonianmag.com Published On :: Wed, 18 Mar 2020 13:24:05 +0000 Tour a gallery of presidential portraits, print a 3-D model of a fossil or volunteer to transcribe historical documents Full Article
lly RCMP say grass fires near Sweetgrass First Nation were intentionally set By www.cbc.ca Published On :: Fri, 8 May 2020 11:42:09 EDT RCMP say they were first called about the fires at 10 p.m. CST on May 7. Full Article News/Canada/Saskatchewan
lly Closing arguments presented at trial of Regina man accused of sexually assaulting 14-year-old By www.cbc.ca Published On :: Fri, 8 May 2020 17:28:37 EDT Closing arguments were presented at the trial of Phillip Lionel Levac on Friday at Regina Court of Queen's Bench. Full Article News/Canada/Saskatchewan
lly Ford government's blue licence plates officially scrapped, 'Yours to Discover' is back By www.cbc.ca Published On :: Wed, 6 May 2020 13:18:34 EDT The premier’s office confirmed the news in an email statement, blaming visibility issues under "very specific lighting conditions." Full Article News/Canada/Toronto
lly Thunder Bay Border Cats strike out as 2020 Northwoods League baseball season officially delayed By www.cbc.ca Published On :: Thu, 7 May 2020 15:29:02 EDT The Northwoods League announced Thursday that its 2020 season will not begin on May 26, as originally scheduled, due to the COVID-19 pandemic. Full Article News/Canada/Thunder Bay