Smooth-car mixed models for spatial count data

Penalized splines (P-splines) and individual random effects are used for the analysis of spatial count data. P-splines are represented as mixed models to give a unified approach to the model estimation procedure. First, a model where the spatial variation is modelled by a two-dimensional P-spline at the centroids of the areas or regions is considered. In addition, individual area-effects are incorporated as random effects to account for individual variation among regions. Finally, the model is extended by considering a conditional autoregressive (CAR) structure for the random effects, these are the so called “Smooth-CAR” models, with the aim of separating the large-scale geographical trend, and local spatial correlation. The methodology proposed is applied to the analysis of lip cancer incidence rates in Scotland

P-spline anova-type interaction models for spatio-temporal smoothing

In recent years, spatial and spatio-temporal modelling have become an important area of research in many fields (epidemiology, environmental studies, disease mapping, ...). However, most of the models developed are constrained by the large amounts of data available. We propose the use of Penalized splines (P-splines) in a mixed model framework for smoothing spatio-temporal data. Our approach allows the consideration of interaction terms which can be decomposed as a sum of smooth functions similarly as an ANOVA decomposition. The properties of the bases used for regression allow the use of algorithms that can handle large amount of data. We show that imposing the same constraints as in a factorial design it is possible to avoid identifiability problems. We illustrate the methodology for Europe ozone levels in the period 1999-2005

Smooth-car mixed models for spatial count data

Penalized splines (P-splines) and individual random effects are used for the analysis of spatial count data. P-splines are represented as mixed models to give a unified approach to the model estimation procedure. First, a model where the spatial variation is modelled by a two-dimensional P-spline at the centroids of the areas or regions is considered. In addition, individual area-effects are incorporated as random effects to account for individual variation among regions. Finally, the model is extended by considering a conditional autoregressive (CAR) structure for the random effects, these are the so called “Smooth-CAR” models, with the aim of separating the large-scale geographical trend, and local spatial correlation. The methodology proposed is applied to the analysis of lip cancer incidence rates in Scotland.Mixed models, P-splines, Overdispersion, Negative Binomial, PQL, CAR models, Scottish lip cancer data

Seasonal modulation mixed models for time series forecasting

We propose an extension of a seasonal modulation smooth model with P-splines for times series data using a mixed model formulation. A smooth trend with seasonality decomposition can be estimated simultaneously. We extend the model to consider the forecasting of new future observations in the mixed model framework. Two different approaches are used for forecasting in the context of mixed models, and the equivalence of both methods is shown. The methodology is illustrated with monthly sulphur dioxide (SO2) levels in a selection of monitoring sites in Europe from January 1990 to December 2001.This research was funded by the Spanish Ministry of Science and Innovation (projects MTM2008-02901, and MTM2011-28285-C02-02). The research of Dae-Jin Lee was also funded by an NIH grant for the Superfund Metal Mixtures, Biomarkers and Neurodevelopment project 1PA2ES016454-01A2

Generic Lightlike Submanifolds of an Indefinite Cosymplectic Manifold

Lightlike geometry has its applications in general relativity, particularly in black hole theory. Indeed, it is known that lightlike hypersurfaces are examples of physical models of Killing horizons in general relativity (Galloway, 2007). In this paper, we introduce the definition of generic lightlike submanifolds of an indefinite cosymplectic manifold. We investigate new results on a class of generic lightlike submanifolds of an indefinite cosymplectic manifold

A Basic Inequality for the Tanaka-Webster Connection

For submanifolds tangent to the structure vector field in Sasakian space forms, we establish a Chen's basic inequality between the main intrinsic invariants of the submanifold (namely, its pseudosectional curvature and pseudosectional curvature on one side) and the main extrinsic invariant (namely, squared pseudomean curvature on the other side) with respect to the Tanaka-Webster connection. Moreover, involving the pseudo-Ricci curvature and the squared pseudo-mean curvature, we obtain a basic inequality for submanifolds of a Sasakian space form tangent to the structure vector field in terms of the Tanaka-Webster connection

Folding machineries displayed on a cation-exchanger for the concerted refolding of cysteine- or proline-rich proteins

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>has been most widely used for the production of valuable recombinant proteins. However, over-production of heterologous proteins in <it>E. coli </it>frequently leads to their misfolding and aggregation yielding inclusion bodies. Previous attempts to refold the inclusion bodies into bioactive forms usually result in poor recovery and account for the major cost in industrial production of desired proteins from recombinant <it>E. coli</it>. Here, we describe the successful use of the immobilized folding machineries for <it>in vitro </it>refolding with the examples of high yield refolding of a ribonuclease A (RNase A) and cyclohexanone monooxygenase (CHMO).</p> <p>Results</p> <p>We have generated refolding-facilitating media immobilized with three folding machineries, mini-chaperone (a monomeric apical domain consisting of residues 191–345 of GroEL) and two foldases (DsbA and human peptidyl-prolyl <it>cis-trans </it>isomerase) by mimicking oxidative refolding chromatography. For efficient and simple purification and immobilization simultaneously, folding machineries were fused with the positively-charged consecutive 10-arginine tag at their C-terminal. The immobilized folding machineries were fully functional when assayed in a batch mode. When the refolding-facilitating matrices were applied to the refolding of denatured and reduced RNase A and CHMO, both of which contain many cysteine and proline residues, RNase A and CHMO were recovered in 73% and 53% yield of soluble protein with full enzyme activity, respectively.</p> <p>Conclusion</p> <p>The refolding-facilitating media presented here could be a cost-efficient platform and should be applicable to refold a wide range of <it>E. coli </it>inclusion bodies in high yield with biological function.</p