Exploration of the Neuronal Subtype Specificity of an Ethanol Responsive Gene: Glycogen Synthase Kinase 3 Beta (Gsk3b)

Exploration of the Neuronal Subtype Specificity of an Ethanol Responsive Gene: Glycogen Synthase Kinase 3 Beta (Gsk3b) Dalton Huey, Depts. of Bioinformatics, Biology & Chemistry, A. van der Vaart, G. M. Harris, and M. F. Miles, with Dr. Sarah Golding, Dept. of Biology Previous work done in our laboratory revealed that Glycogen Synthase Kinase 3 Beta (Gsk3b) functions as a hub gene in a network of genes regulated by acute ethanol in the medial prefrontal cortex (mPFC) across a mouse genetic panel. Adult mice treated with acute ethanol showed increased phosphorylation of GSK3B on the Ser9 residue in prefrontal cortex. Subsequent viral-mediated overexpression of Gsk3bin mouse mPFC caused an increase in ethanol consumption and pharmacological inhibition of GSK3B decreased ethanol consumption. However, it is unknown what neuron subtypes are driving this change in behavior. Here, we provide evidence that deletion of Gsk3bin Camk2a+ glutamatergic neurons of the mPFC results in a decrease in ethanol consumption in both continuous and intermittent access drinking paradigms. Furthermore, we have recently designed and validated a plasmid for Cre-dependent overexpression of Gsk3b, along with a Cre-dependent reporter as a control. These plasmids are planned for use in conjunction with different Cre drivers for viral-mediated expression in any cell type. Dissection of the neural circuitry of this ethanol responsive pathway can lead to a better assessment of Gsk3bas a potential target for the treatment of alcohol use disorders. Work supported by grants R01A027581 and P50AA022537 to MFM.https://scholarscompass.vcu.edu/uresposters/1313/thumbnail.jp

Modeling association between DNA copy number and gene expression with constrained piecewise linear regression splines

DNA copy number and mRNA expression are widely used data types in cancer studies, which combined provide more insight than separately. Whereas in existing literature the form of the relationship between these two types of markers is fixed a priori, in this paper we model their association. We employ piecewise linear regression splines (PLRS), which combine good interpretation with sufficient flexibility to identify any plausible type of relationship. The specification of the model leads to estimation and model selection in a constrained, nonstandard setting. We provide methodology for testing the effect of DNA on mRNA and choosing the appropriate model. Furthermore, we present a novel approach to obtain reliable confidence bands for constrained PLRS, which incorporates model uncertainty. The procedures are applied to colorectal and breast cancer data. Common assumptions are found to be potentially misleading for biologically relevant genes. More flexible models may bring more insight in the interaction between the two markers.Comment: Published in at http://dx.doi.org/10.1214/12-AOAS605 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Three-Dimensional Time-Resolved Trajectories from Laboratory Insect Swarms

Aggregations of animals display complex and dynamic behaviour, both at the individual level and on the level of the group as a whole. Often, this behaviour is collective, so that the group exhibits properties that are distinct from those of the individuals. In insect swarms, the motion of individuals is typically convoluted, and swarms display neither net polarization nor correlation. The swarms themselves, however, remain nearly stationary and maintain their cohesion even in noisy natural environments. This behaviour stands in contrast with other forms of collective animal behaviour, such as flocking, schooling, or herding, where the motion of individuals is more coordinated, and thus swarms provide a powerful way to study the underpinnings of collective behaviour as distinct from global order. Here, we provide a data set of three-dimensional, time-resolved trajectories, including positions, velocities, and accelerations, of individual insects in laboratory insect swarms. The data can be used to study the collective as a whole as well as the dynamics and behaviour of individuals within the swarm

Citizen engagement in spatial planning, shaping places together

This paper explores the roles and practices of collective citizen engagement in spatial planning. Drawing on a selection of core articles in planning scholarship, it investigates how citizens (re-)shape urban places by responding to perceived flaws in how spatial planning addresses societal challenges. Formal planning interventions are often spatially and socially selective, ineffective, or even non-existent due to a lack of institutional capacities and resources. Consequently, citizens take on roles that they consider as missing, underperformed or ineffective. The paper shows that this results in a variety of practices complementary to, independent from, or opposing formal planning actors and interventions. Five dilemmas citizens face are identified, highlighting the tensions that surface on exclusion, participation, and governmental responsibilities when citizens claim their role in urban governance

Inelastic tunneling in a double quantum dot coupled to a bosonic environment

Coupling a quantum system to a bosonic environment always give rise to inelastic processes, which reduce the coherency of the system. We measure energy dependent rates for inelastic tunneling processes in a fully controllable two-level system of a double quantum dot. The emission and absorption rates are well repro-duced by Einstein's coefficients, which relate to the spontaneous emission rate. The inelastic tunneling rate can be comparable to the elastic tunneling rate if the boson occupation number becomes large. In the specific semiconductor double dot, the energy dependence of the inelastic rate suggests that acoustic phonons are coupled to the double dot piezoelectrically.Comment: 6 pages, 4 figure

What Does It Mean for an Organisation to Be Intelligent? Measuring intellectual bandwidth for value creation

The importance of electronic collaboration has risen as successful organisations recognize that they need to convert their intellectual resources into goods and services their customers will value. The shift from personal computing to interpersonal or collaborative computing has given rise to ways of working that may bring about better and more effective use of intellectual resources. Current efforts in managing knowledge have concentrated on producing, sharing and storing knowledge while business problems require the use of these intellectual resources to create value. This paper draws upon Nunamaker et. al.'s (2001) Intellectual Bandwidth Model to measure an organization's potential to create value. Following an analysis of initial data collected at the Netherlands branch of Cap-Gemini Ernst & Young, conclusions are drawn with respect to what it means for an organisation to be intelligent and how such organisations can create value through the use of information and collaboration technologies to increase its intellectual bandwidth

Derivation of the Statistical Distribution of the Mass Peak Centroids of Mass Spectrometers Employing Analog-to-Digital Converters and Electron Multipliers

The statistical distribution of mass peak centroids recorded on mass spectrometers employing analog-to-digital converters (ADCs) and electron multipliers is derived from the first principles of the data generation process. The resulting Gaussian model is discussed and is validated with experimental data and with Monte Carlo simulations

Sequential Data-Adaptive Bandwidth Selection by Cross-Validation for Nonparametric Prediction

We consider the problem of bandwidth selection by cross-validation from a sequential point of view in a nonparametric regression model. Having in mind that in applications one often aims at estimation, prediction and change detection simultaneously, we investigate that approach for sequential kernel smoothers in order to base these tasks on a single statistic. We provide uniform weak laws of large numbers and weak consistency results for the cross-validated bandwidth. Extensions to weakly dependent error terms are discussed as well. The errors may be {\alpha}-mixing or L2-near epoch dependent, which guarantees that the uniform convergence of the cross validation sum and the consistency of the cross-validated bandwidth hold true for a large class of time series. The method is illustrated by analyzing photovoltaic data.Comment: 26 page

Bayesian recovery of the initial condition for the heat equation

We study a Bayesian approach to recovering the initial condition for the heat equation from noisy observations of the solution at a later time. We consider a class of prior distributions indexed by a parameter quantifying "smoothness" and show that the corresponding posterior distributions contract around the true parameter at a rate that depends on the smoothness of the true initial condition and the smoothness and scale of the prior. Correct combinations of these characteristics lead to the optimal minimax rate. One type of priors leads to a rate-adaptive Bayesian procedure. The frequentist coverage of credible sets is shown to depend on the combination of the prior and true parameter as well, with smoother priors leading to zero coverage and rougher priors to (extremely) conservative results. In the latter case credible sets are much larger than frequentist confidence sets, in that the ratio of diameters diverges to infinity. The results are numerically illustrated by a simulated data example.Comment: 17 pages, 4 figures. Published in Comm. Statist. Theory Methods. This version differs from the original in pagination and typographic detail. arXiv admin note: text overlap with arXiv:1103.269