MR Elastography-Based Assessment of Matrix Remodeling at Lesion Sites Associated With Clinical Severity in a Model of Multiple Sclerosis

Magnetic resonance imaging (MRI) with gadolinium based contrast agents (GBCA) is routinely used in the clinic to visualize lesions in multiple sclerosis (MS). Although GBCA reveal endothelial permeability, they fail to expose other aspects of lesion formation such as the magnitude of inflammation or tissue changes occurring at sites of blood-brain barrier (BBB) disruption. Moreover, evidence pointing to potential side effects of GBCA has been increasing. Thus, there is an urgent need to develop GBCA-independent imaging tools to monitor pathology in MS. Using MR-elastography (MRE), we previously demonstrated in both MS and the animal model experimental autoimmune encephalomyelitis (EAE) that inflammation was associated with a reduction of brain stiffness. Now, using the relapsing-remitting EAE model, we show that the cerebellum-a region with predominant inflammation in this model-is especially prone to loss of stiffness. We also demonstrate that, contrary to GBCA-MRI, reduction of brain stiffness correlates with clinical disability and is associated with enhanced expression of the extracellular matrix protein fibronectin (FN). Further, we show that FN is largely expressed by activated astrocytes at acute lesions, and reflects the magnitude of tissue remodeling at sites of BBB breakdown. Therefore, MRE could emerge as a safe tool suitable to monitor disease activity in MS

Equi-biaxial tension tests on magneto-rheological elastomers

A bespoke test rig has been designed to facilitate testing of magneto-rheological (MR) elastomers (MREs) under equi-biaxial tension using a standard universal test machine. Tests were performed up to 10% strain on both isotropic and anisotropic MREs with and without the application of an external magnetic field. Assumptions regarding the material's response were used to analyse stress–strain results in the two stretching directions. The assumptions have been verified previously by uniaxial tension tests and by simulations of the magnetic flux distribution performed using a commercial multi-physics finite element software. The MR effect, which is defined as the increase in tangent modulus at a given strain, has been studied versus engineering strain. The latter was measured optically in the experiments using a digital image correlation system. Relative MR effects up to 74% were found when the particle alignment of anisotropic MREs was oriented parallel to an applied magnetic induction of just 67.5 mT

Reliability and validity in comparative studies of software prediction models

Empirical studies on software prediction models do not converge with respect to the question "which prediction model is best?" The reason for this lack of convergence is poorly understood. In this simulation study, we have examined a frequently used research procedure comprising three main ingredients: a single data sample, an accuracy indicator, and cross validation. Typically, these empirical studies compare a machine learning model with a regression model. In our study, we use simulation and compare a machine learning and a regression model. The results suggest that it is the research procedure itself that is unreliable. This lack of reliability may strongly contribute to the lack of convergence. Our findings thus cast some doubt on the conclusions of any study of competing software prediction models that used this research procedure as a basis of model comparison. Thus, we need to develop more reliable research procedures before we can have confidence in the conclusions of comparative studies of software prediction models

A novel class of microRNA-recognition elements that function only within open reading frames.

MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3' side rather than the 5' seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences of miRNAs that target CDS versus the 3' UTR and suggest that CDS-targeted miRNAs may use a translational quality-control-related mechanism to regulate translation in mammalian cells

Family Environment Variables as Predictors of School Absenteeism Severity at Multiple Levels: Ensemble and Classification and Regression Tree Analysis

School attendance problems, including school absenteeism, are common to many students worldwide, and frameworks to better understand these heterogeneous students include multiple classes or tiers of intertwined risk factors as well as interventions. Recent studies have thus examined risk factors at varying levels of absenteeism severity to demarcate distinctions among these tiers. Prior studies in this regard have focused more on demographic and academic variables and less on family environment risk factors that are endemic to this population. The present study utilized ensemble and classification and regression tree analysis to identify potential family environment risk factors among youth (i.e., children and adolescents) at different levels of school absenteeism severity (i.e., 1 + %, 3 + %, 5 + %, 10 + %). Higher levels of absenteeism were also examined on an exploratory basis. Participants included 341 youth aged 5–17 years (M = 12.2; SD = 3.3) and their families from an outpatient therapy clinic (68.3%) and community (31.7%) setting, the latter from a family court and truancy diversion program cohort. Family environment risk factors tended to be more circumscribed and informative at higher levels of absenteeism, with greater diversity at lower levels. Higher levels of absenteeism appear more closely related to lower achievement orientation, active-recreational orientation, cohesion, and expressiveness, though several nuanced results were found as well. Absenteeism severity levels of 10–15% may be associated more with qualitative changes in family functioning. These data may support a Tier 2-Tier 3 distinction in this regard and may indicate the need for specific family-based intervention goals at higher levels of absenteeism severity

The Sloan Lens ACS Survey. X. Stellar, Dynamical, and Total Mass Correlations of Massive Early-type Galaxies

We use stellar masses, photometry, lensing, and velocity dispersions to investigate empirical correlations for the final sample of 73 early-type lens galaxies (ETGs) from the SLACS survey. The traditional correlations (Fundamental Plane [FP] and its projections) are consistent with those found for non-lens galaxies, supporting the thesis that SLACS lens galaxies are representative of massive ETGs. The addition of strong lensing estimates of the total mass allows us to gain further insights into their internal structure: i) the mean slope of the total mass density profile is = 2.078+/-0.027 with an intrinsic scatter of 0.16+/-0.02; ii) gamma' correlates with effective radius and central mass density, in the sense that denser galaxies have steeper profiles; iii) the dark matter fraction within reff/2 is a monotonically increasing function of galaxy mass and size; iv) the dimensional mass M_dim is proportional to the total mass, and both increase more rapidly than stellar mass M*; v) the Mass Plane (MP), obtained by replacing surface brightness with surface mass density in the FP, is found to be tighter and closer to the virial relation than the FP and the M*P, indicating that the scatter of those relations is dominated by stellar population effects; vi) we construct the Fundamental Hyper-Plane by adding stellar masses to the MP and find the M* coefficient to be consistent with zero and no residual intrinsic scatter. Our results demonstrate that the dynamical structure of ETGs is not scale invariant and that it is fully specified by the total mass, r_eff, and sigma. Although the basic trends can be explained qualitatively in terms of varying star formation efficiency as a function of halo mass and as the result of dry and wet mergers, reproducing quantitatively the observed correlations and their tightness may be a significant challenge for galaxy formation models.Comment: 16 pages, 9 figures; submitted to ApJ after responding to the referee comment