Analytic and bootstrap approximations of prediction errors under a multivariate fay-herriot model

A Multivariate Fay-Herriot model is used to aid the prediction of small area parameters of dependent variables with sample data aggregated to area level. The empirical best linear unbiased predictor of the parameter vector is used, and an approximation of the elements of the mean cross product error matrix is obtained by an extension of the results of Prasad and Rao (1990) to the multiparameter case. Three different bootstrap approximations of those elements are introduced, and a simulation study is developed in order to compare the efficiency of all presented approximations, including a comparison under lack of normality. Further, the number of replications needed for the bootstrap procedures to get stabilized are studied

MicroRNA-222 regulates muscle alternative splicing through Rbm24 during differentiation of skeletal muscle cells

A number of microRNAs have been shown to regulate skeletal muscle development and differentiation. MicroRNA-222 is downregulated during myogenic differentiation and its overexpression leads to alteration of muscle differentiation process and specialized structures. By using RNA-induced silencing complex (RISC) pulldown followed by RNA sequencing, combined with in silico microRNA target prediction, we have identified two new targets of microRNA-222 involved in the regulation of myogenic differentiation, Ahnak and Rbm24. Specifically, the RNA-binding protein Rbm24 is a major regulator of muscle-specific alternative splicing and its downregulation by microRNA-222 results in defective exon inclusion impairing the production of muscle-specific isoforms of Coro6, Fxr1 and NACA transcripts. Reconstitution of normal levels of Rbm24 in cells overexpressing microRNA-222 rescues muscle-specific splicing. In conclusion, we have identified a new function of microRNA-222 leading to alteration of myogenic differentiation at the level of alternative splicing, and we provide evidence that this effect is mediated by Rbm24 protei

Testing the goodness of fit of a hilbertian autoregressive model

The presented methodology for testing the goodness-of-fit of an Autoregressive Hilbertian model (ARH(1) model) provides an infinite-dimensional formulation of the approach proposed in Koul and Stute (1999), based on empirical process marked by residuals. Applying a central and functional central limit result for Hilbert-valued martingale difference sequences, the asymptotic behavior of the formulated H-valued empirical process, also indexed by H, is obtained under the null hypothesis. The limiting process is H-valued generalized (i.e., indexed by H) Wiener process, leading to an asymptotically distribution free test. Consistency is also analyzed. The case of misspecified autocorrelation operator of the ARH(1) process is addressed as well. Beyond the Euclidean setting, this approach allows to implement goodness of fit testing in the context of manifold and spherical functional autoregressive processes

Bootstrap Selection of the Smoothing Parameter in Nonparametric Hazard Rate Estimation

An asymptotic representation of the mean weighted integrated squared error for the kernel based estimator of the hazard rate in the presence of right censored samples is obtained for different bootstrap resampiing methods. As a consequence, a new bandwidth selector based n the bootstrap is introduced. Very satisfactory simulations results are obtained in comparison to the cross-validation selector for different models, using WARPed, i.e. binned versions of the estimators

Blue Stragglers in Galactic Open Clusters and the Integrated Spectral Energy Distributions

Synthetic integrated spectral properties of the old Galactic open clusters are studies in this work, where twenty-seven Galactic open clusters of ages >= 1Gyr are selected as the working sample. Based on the photometric observations of these open clusters, synthetic integrated spectrum has been made for the stellar population of each cluster. The effects of blue straggler stars (BSSs) on the conventional simple stellar population (SSP) model are analyzed on an individual cluster base. It is shown that the BSSs, whose holding positions in the color-magnitude diagrams (CMDs) cannot be predicted by the current single-star evolution theory, present significant modifications to the integrated properties of theoretical SSP model. The synthesized integrated spectral energy distributions (ISEDs) of our sample clusters are dramatically different from the SSPs based on isochrone only. The BSSs corrected ISEDs of stellar populations show systematic enhancements towards shorter wavelength in the spectra. When measured with wide-band colors in unresolvable conditions, the age of a stellar population can be seriously under-estimated by the conventional SSP model. Therefore, considering the common existence of BSS component in real stellar populations, a considerable amount of alternations on the conventional ISEDs should be expected when applying the technique of evolutionary population synthesis (EPS) to more complicated stellar systems.Comment: 45 pages, 21 figures Accepted for publication in ApJ (Feburary 1, 2005 issue

miRNA-126 Orchestrates an Oncogenic Program in B Cell Precursor Acute Lymphoblastic Leukemia

MicroRNA (miRNA)-126 is a known regulator of hematopoietic stem cell quiescence. We engineered murine hematopoiesis to express miRNA-126 across all differentiation stages. Thirty percent of mice developed monoclonal B cell leukemia, which was prevented or regressed when a tetracycline-repressible miRNA-126 cassette was switched off. Regression was accompanied by upregulation of cell-cycle regulators and B cell differentiation genes, and downregulation of oncogenic signaling pathways. Expression of dominant-negative p53 delayed blast clearance upon miRNA-126 switch-off, highlighting the relevance of p53 inhibition in miRNA-126 addiction. Forced miRNA-126 expression in mouse and human progenitors reduced p53 transcriptional activity through regulation of multiple p53-related targets. miRNA-126 is highly expressed in a subset of human B-ALL, and antagonizing miRNA-126 in ALL xenograft models triggered apoptosis and reduced disease burden

Role of the human concentrative nucleoside transporter (hCNT1) in the cytotoxic action of 5[Prime]-deoxy-5-fluorouridine, an active intermediate metabolite of capecitabine, a novel oral anticancer drug.

We attempt to identify the plasma membrane transporter involved in the uptake of 5'-deoxy-5-fluorouridine (5'-DFUR), an intermediate metabolite of capecitabine. This novel oral fluoropyrimidine is used in cancer treatments and is a direct precursor of the cytostatic agent 5'-fluorouracil. We also examine the role of the transporter in 5'-DFUR cytotoxicity. The human concentrative nucleoside transporter (hCNT1) was cloned from human fetal liver and expressed in Xenopus laevis oocytes. The two-electrode voltage-clamp technique was used to demonstrate that 5'-DFUR, but not capecitabine or 5'-FU, is an hCNT1 substrate. Then, hCNT1 was heterologously expressed in the mammalian cell line Chinese hamster ovary-K1. Functional expression was demonstrated by monitoring transport of radiolabeled substrates and by using a monospecific polyclonal antibody generated against the transporter. hCNT1-expressing cells were more sensitive to 5'-DFUR than vector-transfected or wild-type cells. The sensitivity of the three cell types to other agents such as cisplatin or 5'-FU was identical. In conclusion, this study shows that 1) the pharmacological profile of a nucleoside transporter can be determined by an electrophysiological approach; 2) the hCNT1 transporter is involved in 5'-DFUR uptake; and 3) hCNT1 expression may increase cell sensitivity to 5'-DFUR treatment. This study also reports for the first time the generation of an antibody against hCNT1, which may be useful in the elucidation of the relationship between hCNT1 expression and tumor response to capecitabine treatmen

Forecasting binary longitudinal data by a functional PC-ARIMA model

In order to forecast time evolution of a binary response variable from a related continuous time series a functional logit model is proposed. The estimation of this model from discrete time observations of the predictor is solved by using functional principal component analysis and ARIMA modelling of the associated discrete time series of principal components. The proposed model is applied to forecast the risk of drought from El Niño phenomenon.Projects MTM2007-63793 from Dirección General de Investigación, Ministerio de Educación y Ciencia, Spain and P06-FQM-01470 from Consejería de Innovación Ciencia y Empresa, Junta de Andalucía, Spai

Infrared composition of the Large Magellanic Cloud

The evolution of galaxies and the history of star formation in the Universe are among the most important topics in today's astrophysics. Especially, the role of small, irregular galaxies in the star-formation history of the Universe is not yet clear. Using the data from the AKARI IRC survey of the Large Magellanic Cloud at 3.2, 7, 11, 15, and 24 {\mu}m wavelengths, i.e., at the mid- and near-infrared, we have constructed a multiwavelength catalog containing data from a cross-correlation with a number of other databases at different wavelengths. We present the separation of different classes of stars in the LMC in color-color, and color-magnitude, diagrams, and analyze their contribution to the total LMC flux, related to point sources at different infrared wavelengths