Visualization of Genomic Changes by Segmented Smoothing Using an L0 Penalty

Copy number variations (CNV) and allelic imbalance in tumor tissue can show strong segmentation. Their graphical presentation can be enhanced by appropriate smoothing. Existing signal and scatterplot smoothers do not respect segmentation well. We present novel algorithms that use a penalty on the norm of differences of neighboring values. Visualization is our main goal, but we compare classification performance to that of VEGA

Smoothing and forecasting mortality rates Running headline: Smoothing and forecasting mortality rates

Abstract: The prediction of future mortality rates is a problem of fundamental importance for the insurance and pensions industry. We show how the method of P -spline

Bilinear modulation models for seasonal tables of counts

We propose generalized linear models for time or age-time tables of seasonal counts, with the goal of better understanding seasonal patterns in the data. The linear predictor contains a smooth component for the trend and the product of a smooth component (the modulation) and a periodic time series of arbitrary shape (the carrier wave). To model rates, a population offset is added. Two-dimensional trends and modulation are estimated using a tensor product B-spline basis of moderate dimension. Further smoothness is ensured using difference penalties on the rows and columns of the tensor product coefficients. The optimal penalty tuning parameters are chosen based on minimization of a quasi-information criterion. Computationally efficient estimation is achieved using array regression techniques, avoiding excessively large matrices. The model is applied to female death rate in the US due to cerebrovascular diseases and respiratory diseases

Selection of tuning parameters in bridge regression models via Bayesian information criterion

We consider the bridge linear regression modeling, which can produce a sparse or non-sparse model. A crucial point in the model building process is the selection of adjusted parameters including a regularization parameter and a tuning parameter in bridge regression models. The choice of the adjusted parameters can be viewed as a model selection and evaluation problem. We propose a model selection criterion for evaluating bridge regression models in terms of Bayesian approach. This selection criterion enables us to select the adjusted parameters objectively. We investigate the effectiveness of our proposed modeling strategy through some numerical examples.Comment: 20 pages, 5 figure

Biogenesis of mitochondrial porin

We review here the present knowledge about the pathway of import and assembly of porin into mitochondria and compare it to those of other mitochondrial proteins. Porin, like all outer mitochondrial membrane proteins studied so far is made as a precursor without a cleavble lsquosignalrsquo sequence; thus targeting information must reside in the mature sequence. At least part of this information appears to be located at the amino-terminal end of the molecule. Transport into mitochondria can occur post-translationally. In a first step, the porin precursor is specifically recognized on the mitochondrial surface by a protease sensitive receptor. In a second step, porin precursor inserts partially into the outer membrane. This step is mediated by a component of the import machinery common to the import pathways of precursor proteins destined for other mitochondrial subcompartments. Finally, porin is assembled to produce the functional oligomeric form of an integral membrane protein wich is characterized by its extreme protease resistance

Prenatal parental tobacco smoking, gene specific DNA methylation, and newborns size: the Generation R study

Background: Deleterious effects of prenatal tobacco smoking on fetal growth and newborn weight are well-established. One of the proposed mechanisms underlying this relationship is alterations in epigenetic programming. We selected 506 newborns from a population-based prospective birth cohort in the Netherlands. Prenatal parental tobacco smoking was assessed using self-reporting questionnaires. Information on birth outcomes was obtained from medical records. The deoxyribonucleic acid (DNA) methylation of the growth genes IGF2DMR and H19 was measured in newborn umbilical cord white blood cells. Associations were assessed between parental tobacco smoking and DNA methylation using linear mixed models and adjusted for potential confounders. Results: The DNA methylation levels of IGF2DMR and H19 in the non-smoking group were median (90 % range), 54.0 % (44.6–62.0), and 30.0 % (25.5–34.0), in the first trimester only smoking group 52.2 % (44.5–61.1) and 30.8 % (27.1–34.1), and in the continued smoking group 51.6 % (43.9–61.3) and 30.2 % (23.7–34.8), respectively. Continued prenatal maternal smoking was inversely associated with IGF2DMR methylation (β = −1.03, 95 % CI −1.76; −0.30) in a dose-dependent manner (P-trend = 0.030). This association seemed to be slightly more profound among newborn girls (β = −1.38, 95 % CI −2.63; −0.14) than boys (β = −0.72, 95 % CI −1.68; 0.24). H19 methylation was also inversely associated continued smoking <5 cigarettes/day (β = −0.96, 95 % CI −1.78; −0.14). Moreover, the association between maternal smoking and newborns small for gestational age seems to be partially explained by IGF2DMR methylation (β = −0.095, 95 % CI −0.249; −0.018). Among non-smoking mothers, paternal tobacco smoking was not associated with IGF2DMR or H19 methylation. Conclusions: Maternal smoking is inversely associated with IGF2DMR methylation in newborns, which can be one of the underlying mechanisms through which smoking affects fetal growth

Probing Ultralate Reionization: Direct Measurements of the Mean Free Path over 5 < z < 6

The mean free path of ionizing photons, λ mfp, is a critical parameter for modeling the intergalactic medium (IGM) both during and after reionization. We present direct measurements of λ mfp from QSO spectra over the redshift range 5 < z < 6, including the first measurements at z ≃ 5.3 and 5.6. Our sample includes data from the XQR-30 VLT large program, as well as new Keck/ESI observations of QSOs near z ~ 5.5, for which we also acquire new [C II] 158 μm redshifts with ALMA. By measuring the Lyman continuum transmission profile in stacked QSO spectra, we find λmfp=9.33+2.06−1.80, 5.40+1.47−1.40, 3.31+2.74−1.34, and 0.81+0.73−0.48 pMpc at z = 5.08, 5.31, 5.65, and 5.93, respectively. Our results demonstrate that λ mfp increases steadily and rapidly with time over 5 < z < 6. Notably, we find that λ mfp deviates significantly from predictions based on a fully ionized and relaxed IGM as late as z = 5.3. By comparing our results to model predictions and indirect λ mfp constraints based on IGM Lyα opacity, we find that the evolution of λ mfp is consistent with scenarios wherein the IGM is still undergoing reionization and/or retains large fluctuations in the ionizing UV background well below redshift 6