Switching Principal Component Analysis for Modeling Means and Covariance Changes Over Time

Many psychological theories predict that cognitions, affect, action tendencies, and other variables change across time in mean level as well as in covariance structure. Often such changes are rather abrupt, because they are caused by sudden events. To capture such changes, one may repeatedly measure the variables under study for a single individual and examine whether the resulting multivariate time series contains a number of phases with different means and covariance structures. The latter task is challenging, however. First, in many cases, it is unknown how many phases there are and when new phases start. Second, often a rather large number of variables is involved, complicating the interpretation of the covariance pattern within each phase. To take up this challenge, we present switching principal component analysis (PCA). Switching PCA detects phases of consecutive observations or time points (in single subject data) with similar means and/or covariation structures, and performs a PCA per phase to yield insight into its covariance structure. An algorithm for fitting switching PCA solutions as well as a model selection procedure are presented and evaluated in a simulation study. Finally, we analyze empirical data on cardiorespiratory recordings

Central Sensitisation and functioning in patients with chronic low back pain: protocol for a cross-sectional and cohort study

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Small Rho GTPase-mediated actin dynamics at endothelial adherens junctions

VE-cadherin-based cell-cell junctions form the major restrictive barrier of the endothelium to plasma proteins and blood cells. The function of VE-cadherin and the actin cytoskeleton are intimately linked. Vascular permeability factors and adherent leukocytes signal through small Rho GTPases to tightly regulate actin cytoskeletal rearrangements in order to open and re-assemble endothelial cell-cell junctions in a rapid and controlled manner. The Rho GTPases are activated by guanine nucleotide exchange factors (GEFs), conferring specificity and context-dependent control of cell-cell junctions. Although the molecular mechanisms that couple cadherins to actin filaments are beginning to be elucidated, specific stimulus-dependent regulation of the actin cytoskeleton at VE-cadherin-based junctions remains unexplained. Accumulating evidence has suggested that depending on the vascular permeability factor and on the subcellular localization of GEFs, cell-cell junction dynamics and organization are differentially regulated by one specific Rho GTPase. In this Commentary, we focus on new insights how the junctional actin cytoskeleton is specifically and locally regulated by Rho GTPases and GEFs in the endotheliu

Comparison of Methods for Adjusting Incorrect Assignments of Items to Subtests Oblique Multiple Group Method Versus Confirmatory Common Factor Method

A common question in test evaluation is whether an a priori assignment of items to subtests is supported by empirical data. If the analysis results indicate the assignment of items to subtests under study is not supported by data, the assignment is often adjusted. In this study the authors compare two methods on the quality of their suggestions to adjust incorrect assignments of items to subtests. The confirmatory common factor (CCF) method is often used in practice. However, previous research reported rather poor quality of the suggested adjustments. Therefore, the CCF method is compared with a less often used but promising method, the oblique multiple group (OMG) method. The authors compared both methods with a simulation study taken under various conditions. For each method, several adjustment procedures were studied. The best adjustment procedure within the OMG method performed better than or highly comparable to the procedures within the CCF method

Phosphorylation at endothelial cell-cell junctions: Implications for VE-cadherin function

Endothelial cell-cell junctions are strictly regulated in order to control the barrier function of endothelium. Vascular endothelial (VE)-cadherin is one of the proteins that is crucial in this process. It has been reported that phosphorylation events control the function of VE-cadherin. This review summarizes the role of VE-cadherin phosphorylation in the regulation of endothelial cell-cell junctions and highlights how this affects vascular permeability and leukocyte extravasation

Leukocytes Crossing the Endothelium: A Matter of Communication

Leukocytes cross the endothelial vessel wall in a process called transendothelial migration (TEM). The purpose of leukocyte TEM is to clear the causing agents of inflammation in underlying tissues, for example, bacteria and viruses. During TEM, endothelial cells initiate signals that attract and guide leukocytes to sites of tissue damage. Leukocytes react by attaching to these sites and signal their readiness to move back to endothelial cells. Endothelial cells in turn respond by facilitating the passage of leukocytes while retaining overall integrity. In this review, we present recent findings in the field and we have endeavored to synthesize a coherent picture of the intricate interplay between endothelial cells and leukocytes during TE

The Empirical Verification of an Assignment of Items to Subtests:The Oblique Multiple Group Method Versus the Confirmatory Common Factor Method

This study compares two confirmatory factor analysis methods on their ability to verify whether correct assignments of items to subtests are supported by the data. The confirmatory common factor (CCF) method is used most often and defines nonzero loadings so that they correspond to the assignment of items to subtests. Another method is the oblique multiple group (OMG) method, which defines subtests as unweighted sums of the scores on all items assigned to the subtest, and (corrected) correlations are used to verify the assignment. A simulation study compares both methods, accounting for the influence of model error and the amount of unique variance. The CCF and OMG methods show similar behavior with relatively small amounts of unique variance and low interfactor correlations. However, at high amounts of unique variance and high interfactor correlations, the CCF detected correct assignments more often, whereas the OMG was better at detecting incorrect assignments

The Potential of Mesenchymal Stromal Cells in Neuroblastoma Therapy for Delivery of Anti-Cancer Agents and Hematopoietic Recovery

Neuroblastoma is one of the most common pediatric cancers and a major cause of cancer-related death in infancy. Conventional therapies including high-dose chemotherapy, stem cell transplantation, and immunotherapy approach a limit in the treatment of high-risk neuroblastoma and prevention of relapse. In the last two decades, research unraveled a potential use of mesenchymal stromal cells in tumor therapy, as tumor-selective delivery vehicles for therapeutic compounds and oncolytic viruses and by means of supporting hematopoietic stem cell transplantation. Based on pre-clinical and clinical advances in neuroblastoma and other malignancies, we assess both the strong potential and the associated risks of using mesenchymal stromal cells in the therapy for neuroblastoma. Furthermore, we examine feasibility and safety aspects and discuss future directions for harnessing the advantageous properties of mesenchymal stromal cells for the advancement of therapy success

The tyrosine phosphatase SHP2 regulates recovery of endothelial adherens junctions through control of beta-catenin phosphorylation

Impaired endothelial barrier function results in a persistent increase in endothelial permeability and vascular leakage. Repair of a dysfunctional endothelial barrier requires controlled restoration of adherens junctions, comprising vascular endothelial (VE)-cadherin and associated beta-, gamma-, alpha-, and p120-catenins. Little is known about the mechanisms by which recovery of VE-cadherin-mediated cell-cell junctions is regulated. Using the inflammatory mediator thrombin, we demonstrate an important role for the Src homology 2-domain containing tyrosine phosphatase (SHP2) in mediating recovery of the VE-cadherin-controlled endothelial barrier. Using SHP2 substrate-trapping mutants and an in vitro phosphatase activity assay, we validate beta-catenin as a bona fide SHP2 substrate. SHP2 silencing and SHP2 inhibition both result in delayed recovery of endothelial barrier function after thrombin stimulation. Moreover, on thrombin challenge, we find prolonged elevation in tyrosine phosphorylation levels of VE-cadherin-associated beta-catenin in SHP2-depleted cells. No disassembly of the VE-cadherin complex is observed throughout the thrombin response. Using fluorescence recovery after photobleaching, we show that loss of SHP2 reduces the mobility of VE-cadherin at recovered cell-cell junctions. In conclusion, our data show that the SHP2 phosphatase plays an important role in the recovery of disrupted endothelial cell-cell junctions by dephosphorylating VE-cadherin-associated beta-catenin and promoting the mobility of VE-cadherin at the plasma membran