The multivariate least trimmed squares estimator.

In this paper we introduce the least trimmed squares estimator for multivariate regression. We give three equivalent formulations of the estimator and obtain its breakdown point. A fast algorithm for its computation is proposed. We prove Fisher-consistency at the multivariate regression model with elliptically symmetric error distribution and derive the influence function. Simulations investigate the finite-sample efficiency and robustness of the estimator. To increase the efficiency of the estimator, we also consider a one-step reweighted version, as well as multivariate generalizations of one-step GM-estimators.Model; Data; Distribution; Simulation;

High-Breakdown Robust Multivariate Methods

When applying a statistical method in practice it often occurs that some observations deviate from the usual assumptions. However, many classical methods are sensitive to outliers. The goal of robust statistics is to develop methods that are robust against the possibility that one or several unannounced outliers may occur anywhere in the data. These methods then allow to detect outlying observations by their residuals from a robust fit. We focus on high-breakdown methods, which can deal with a substantial fraction of outliers in the data. We give an overview of recent high-breakdown robust methods for multivariate settings such as covariance estimation, multiple and multivariate regression, discriminant analysis, principal components and multivariate calibration.Comment: Published in at http://dx.doi.org/10.1214/088342307000000087 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

Regulation of Chandelier Cell Cartridge and Bouton Development via DOCK7-Mediated ErbB4 Activation

Chandelier cells (ChCs), typified by their unique axonal morphology, are the most distinct interneurons present in cortical circuits. Via their distinctive axonal terminals, called cartridges, these cells selectively target the axon initial segment of pyramidal cells and control action potential initiation; however, the mechanisms that govern the characteristic ChC axonal structure have remained elusive. Here, by employing an in utero electroporation-based method that enables genetic labeling and manipulation of ChCs in vivo, we identify DOCK7, a member of the DOCK180 family, as a molecule essential for ChC cartridge and bouton development. Furthermore, we present evidence that DOCK7 functions as a cytoplasmic activator of the schizophrenia-associated ErbB4 receptor tyrosine kinase and that DOCK7 modulates ErbB4 activity to control ChC cartridge and bouton development. Thus, our findings define DOCK7 and ErbB4 as key components of a pathway that controls the morphological differentiation of ChCs, with implications for the pathogenesis of schizophrenia

Introduction: Mass media effects and the political agenda: Assessing its scope and conditions

Do the mass media influence the issue priorities of politicians? This question has been present in the literature on the media and political agenda-setting since the mid-1970s when scholars first addressed it within the broader agenda-setting research. While only eighteen empirical pieces examined this topic until the mid-2000s (Walgrave & Van Aelst, 2006), in the last decade the number of studies on the media and the political agenda has expanded considerably (Van Aelst & Walgrave, 2016). In fact, in the last ten years (2005–2015), more than thirty studies focused on the media’s political agenda-setting power. The research now features a wider geographical scope, richer datasets, and more contingent factors have been investigated in detail. Studying the relationship between the media agenda and the political agenda has therefore become a flourishing subfield in political communication. In addition, it connects a community of political scientists interested in factors that influence public policy with communication scholars who work on the political influence of the mass media.info:eu-repo/semantics/acceptedVersio

Sulfur analysis of Bolu-Mengen lignite before and after microbiological treatment using reductive pyrolysis and gas chromatography/mass spectrometry

Atmospheric pressure-temperature programmed reduction coupled with on-line mass spectrometry (AP-TPR/MS) is used for the first time on microbiologically treated coal samples as a technique to monitor the degree of desulfurization of the various sulfur functionalities. The experimental procedure enables the identification of both organic and inorganic sulfur species present in the coal matrix. A better insight in the degradation of the coal matrix and the accompanying processes during the AP-TPR experiment is obtained by a quantitative differentiation of the sulfur. The determination of the sulfur balance for the reductive pyrolysis gives an overview of the side reactions and their relative contribution in the total process. The volatile sulfur species are unambiguously identified using AP-TPR off-line coupled with gas chromatography/mass spectrometry (GC/MS). In this way, fundamental mechanisms and reactions that occur during the reductive pyrolysis could be quantified, explaining the differences in AP-TPR recoveries. Therefore, this study gives a clearer view on the possibilities and limitations of AP-TPR as a technique to monitor sulfur functionalities in coal

Ras signaling mechanisms underlying impaired GluR1-dependent plasticity associated with fragile X syndrome

Fragile X syndrome, caused by the loss of FMR1 gene function and loss of fragile X mental retardation protein (FMRP), is the most commonly inherited form of mental retardation. The syndrome is characterized by associative learning deficits, reduced risk of cancer, dendritic spine dysmorphogenesis, and facial dysmorphism. However, the molecular mechanism that links loss of function of FMR1 to the learning disability remains unclear. Here, we report an examination of small GTPase Ras signaling and synaptic AMPA receptor (AMPA-R) trafficking in cultured slices and intact brains of wild-type and FMR1 knock-out mice. In FMR1 knock-out mice, synaptic delivery of GluR1-, but not GluR2L- and GluR4-containing AMPA-Rs is impaired, resulting in a selective loss of GluR1- dependent long-term synaptic potentiation (LTP). Although Ras activity is upregulated, its downstream MEK (extracellular signal-regulated kinase kinase)-ERK (extracellular signal-regulated kinase) signaling appears normal, and phosphoinositide 3-kinase (PI3K)-protein kinase B (PKB; or Akt) signaling is compromised in FMR1 knock-out mice. Enhancing Ras-PI3K-PKB signaling restores synaptic delivery of GluR1-containing AMPA-Rs and normal LTP in FMR1 knock-out mice. These results suggest aberrant Ras signaling as a novel mechanism for fragile X syndrome and indicate manipulating Ras-PI3K-PKB signaling to be a potentially effective approach for treating patients with fragile X syndrome

Propagation of outliers in multivariate data

We investigate the performance of robust estimates of multivariate location under nonstandard data contamination models such as componentwise outliers (i.e., contamination in each variable is independent from the other variables). This model brings up a possible new source of statistical error that we call "propagation of outliers." This source of error is unusual in the sense that it is generated by the data processing itself and takes place after the data has been collected. We define and derive the influence function of robust multivariate location estimates under flexible contamination models and use it to investigate the effect of propagation of outliers. Furthermore, we show that standard high-breakdown affine equivariant estimators propagate outliers and therefore show poor breakdown behavior under componentwise contamination when the dimension $d$ is high.Comment: Published in at http://dx.doi.org/10.1214/07-AOS588 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

TGF-beta/Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis

The mechanisms by which TGF-beta promotes lung adenocarcinoma (ADC) metastasis are largely unknown. Here, we report that in lung ADC cells, TGF-beta potently induces expression of DOCK4, but not other DOCK family members, via the Smad pathway and that DOCK4 induction mediates TGF-beta's prometastatic effects by enhancing tumor cell extravasation. TGF-beta-induced DOCK4 stimulates lung ADC cell protrusion, motility, and invasion without affecting epithelial-to-mesenchymal transition. These processes, which are fundamental to tumor cell extravasation, are driven by DOCK4-mediated Rac1 activation, unveiling a novel link between TGF-beta and Rac1. Thus, our findings uncover the atypical Rac1 activator DOCK4 as a key component of the TGF-beta/Smad pathway that promotes lung ADC cell extravasation and metastasis

The junctional multidomain protein AF-6 is a binding partner of the Rap1A GTPase and associates with the actin cytoskeletal regulator profilin

The AF-6 protein is a multidomain protein that contains two potential Ras-binding domains within its N terminus. Because of this feature, AF-6 has been isolated in both two-hybrid and biochemical approaches and is postulated to be a potential Ras-effector protein, Herein, we show that it is specifically the first Ras-binding domain of AF-6 that mediates this interaction and that the Ras-related Rap1A protein can associate with this motif even more efficiently than the oncogenic Ha-, K-, and N-Ras GTPases. We further demonstrate that both Ras and Rap1 interact with full-length AF-6 in vivo in mammalian cells and that a fraction of Rap1 colocalizes with AF-6 at the membrane. Dominant active Rap1A, in contrast to Ras, when introduced into epithelial MDCK and MCF-7 cells, does not perturb AF-6-specific residency in cell-cell adhesion complexes. In a pursuit to gain further understanding of the role of AF-6 in junctions, we identified profilin as an AF-6-binding protein. Profilin activates monomeric actin units for subsequent polymerization steps at barbed ends of actin filaments and has been shown to participate in cortical actin assembly. To our knowledge, AF-6 is the only integral component in cell-cell junctions discovered thus far that interacts with profilin and thus could modulate actin modeling proximal to adhesion complexes

Dual role for DOCK7 in tangential migration of interneuron precursors in the postnatal forebrain

Throughout life, stem cells in the ventricular-subventricular zone generate neuroblasts that migrate via the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into local interneurons. Although progress has been made toward identifying extracellular factors that guide the migration of these cells, little is known about the intracellular mechanisms that govern the dynamic reshaping of the neuroblasts' morphology required for their migration along the RMS. In this study, we identify DOCK7, a member of the DOCK180-family, as a molecule essential for tangential neuroblast migration in the postnatal mouse forebrain. DOCK7 regulates the migration of these cells by controlling both leading process (LP) extension and somal translocation via distinct pathways. It controls LP stability/growth via a Rac-dependent pathway, likely by modulating microtubule networks while also regulating F-actin remodeling at the cell rear to promote somal translocation via a previously unrecognized myosin phosphatase-RhoA-interacting protein-dependent pathway. The coordinated action of both pathways is required to ensure efficient neuroblast migration along the RMS