Evaluation of the strain-line patterns in a human left ventricle: A simulation study

The aim of this paper is to emphasise the role of the primary strain-line patterns in a human left ventricle (LV) within the complex system that is the heart. In particular, a protocol is proposed for the measurement of the principal strain lines (PSL) in the walls of the LV; this protocol is tested by means of a computational model which resembles a human LV. When the analysis is focused on the epicardial surface, PSL can be used to derive information on the directions of muscle fibres during the entire cardiac cycle, not only the systolic phase. © 2013 Taylor & Francis

influence of the parameterization in the interval solution of elastic beams

We are going to analyze the interval solution of an elastic beam under uncertain boundary conditions. Boundary conditions are defined as rotational springs presenting interval stiffness. Developments occur according to the interval analysis theory, which is affected, at the same time, by the overestimation of interval limits (also known as overbounding, because of the propagation of the uncertainty in the model). We suggest a method which aims to reduce such an overestimation in the uncertain solution. This method consists in a reparameterization of the closed form Euler-Bernoulli solution and set intersection

miRNAs as Influencers of Cell-Cell Communication in Tumor Microenvironment

microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level, inducing the degradation of the target mRNA or translational repression. MiRNAs are involved in the control of a multiplicity of biological processes, and their absence or altered expression has been associated with a variety of human diseases, including cancer. Recently, extracellular miRNAs (ECmiRNAs) have been described as mediators of intercellular communication in multiple contexts, including tumor microenvironment. Cancer cells cooperate with stromal cells and elements of the extracellular matrix (ECM) to establish a comfortable niche to grow, to evade the immune system, and to expand. Within the tumor microenvironment, cells release ECmiRNAs and other factors in order to influence and hijack the physiological processes of surrounding cells, fostering tumor progression. Here, we discuss the role of miRNAs in the pathogenesis of multicomplex diseases, such as Alzheimer's disease, obesity, and cancer, focusing on the contribution of both intracellular miRNAs, and of released ECmiRNAs in the establishment and development of cancer niche. We also review growing evidence suggesting the use of miRNAs as novel targets or potential tools for therapeutic applications

Left atrial trajectory impairment in hypertrophic cardiomyopathy disclosed by geometric morphometrics and parallel transport

The analysis of full Left Atrium (LA) deformation and whole LA deformational trajectory in time has been poorly investigated and, to the best of our knowledge, seldom discussed in patients with Hypertrophic Cardiomyopathy. Therefore, we considered 22 patients with Hypertrophic Cardiomyopathy (HCM) and 46 healthy subjects, investigated them by three-dimensional Speckle Tracking Echocardiography, and studied the derived landmark clouds via Geometric Morphometrics with Parallel Transport. Trajectory shape and trajectory size were different in Controls versus HCM and their classification powers had high AUC (Area Under the Receiving Operator Characteristic Curve) and accuracy. The two trajectories were much different at the transition between LA conduit and booster pump functions. Full shape and deformation analyses with trajectory analysis enabled a straightforward perception of pathophysiological consequences of HCM condition on LA functioning. It might be worthwhile to apply these techniques to look for novel pathophysiological approaches that may better define atrio-ventricular interaction

Local and Global Energies for Shape Analysis in Medical Imaging

In a previous contribution a new Riemannian shape space, named TPS space, was introduced to perform statistics on shape data. This space was endowed with a Rie-mannian metric and a flat connection, with torsion, compatible with the given metric. This connection allows the definition of a Parallel Transport of the deformation compatible with the threefold decomposition in spherical, deviatoric and non affine components. Such a Parallel Transport also conserves the-energy, strictly related to the total elastic strain energy stored by the body in the original deformation. New machinery is here presented in order to calculate the bending energy on the body only (body bending energy) in order to restrict it exclusively within physical boundaries of objects involved in the deformation analysis. The novelty of this new procedure resides in the fact that we propose a new metric to conserve during the TPS direct transport. This allows transporting the shape change more coherently with the mechanical meaning of the deformation. The geometry of the TPS Space is then further developed in order to better represent the relationship between the-energy, the strain energy and the so called bending-energy densities

Seeing the wood through the trees. Combining shape information from different landmark configurations

The geometric morphometric (GM) analysis of complex anatomical structures is an ever more powerful tool to study biological variability, adaptation and evolution. Here, we propose a new method (combinland), developed in R, meant to combine the morphological information contained in different landmark coordinate sets into a single dataset, under a GM context. combinland builds a common ordination space taking into account the entire shape information encoded in the starting configurations. We applied combinland to a Primate case study including 133 skulls belonging to 14 species. On each specimen, we simulated photo acquisitions converting the 3D landmark sets into six 2D configurations along standard anatomical views. The application of combinland shows statistically negligible differences in the ordination space compared to that of the original 3D objects, in contrast to a previous method meant to address the same issue. Hence, we argue combinland allows to correctly retrieve 3D-quality statistical information from 2D landmark configurations. This makes combinland a viable alternative when the extraction of 3D models is not possible, recommended, or too expensive, and to make full use of disparate sources (and views) of morphological information regarding the same specimens. The code and examples for the application of combinland are available in the Arothron R package

The TPS Direct Transport: a new method for transporting deformations in the Size-and-shape Space

Modern shape analysis allows the fine comparison of shape changes occurring between different objects. Very often the classic machineries of Generalized Procrustes Analysis and Principal Component Analysis are used in order to contrast the shape change occurring among configurations represented by homologous landmarks. However, if size and shape data are structured in different groups thus constituting different morphological trajectories, a data centering is needed if one wants to compare solely the deformation representing the trajectories. To do that, inter-individual variation must be filtered out. This maneuver is rarely applied in studies using simulated or real data. A geometrical procedure named Parallel Transport, that can be based on various connection types, is necessary to perform such kind of data centering. Usually, the Levi Civita connection is used for interpolation of curves in a Riemannian space. It can also be used to transport a deformation. We demonstrate that this procedure does not preserve some important characters of the deformation, even in the affine case. We propose a novel procedure called `TPS Direct Transport' which is able to perfectly transport deformation in the affine case and to better approximate non affine deformation in comparison to existing tools. We recommend to center shape data using the methods described here when the differences in deformation rather than in shape are under study

The decomposition of deformation: new metrics to enhance shape analysis in medical imaging

In landmarks-based Shape Analysis size is measured, in most cases, with Centroid Size. Changes in shape are decomposed in affine and non affine components. Furthermore the non affine component can be in turn decomposed in a series of local deformations (partial warps). If the extent of deformation between two shapes is small, the difference between centroid size and m-Volume increment is barely appreciable. In medical imaging applied to soft tissues bodies can undergo very large deformations, involving large changes in size. The cardiac example, analyzed in the present paper, shows changes in m-Volume that can reach the 60%. We show here that standard Geometric Morphometrics tools (landmarks, Thin Plate Spline, and related decomposition of the deformation) can be generalized to better describe the very large deformations of biological tissues, without losing a synthetic description. In particular, the classical decomposition of the space tangent to the shape space in affine and non affine components is enriched to include also the change in size, in order to give a complete description of the tangent space to the size-and-shape space. The proposed generalization is formulated by means of a new Riemannian metric describing the change in size as change in m-Volume rather than change in Centroid Size. This leads to a redefinition of some aspects of the Kendall’s size-and-shape space without losing Kendall’s original formulation. This new formulation is discussed by means of simulated examples using 2D and 3D platonic shapes as well as a real example from clinical 3D echocardiographic data. We demonstrate that our decomposition based approaches discriminate very effectively healthy subjects from patients affected by Hypertrophic Cardiomyopathy

Thymic development beyond β-selection requires phosphatidylinositol 3-kinase activation by CXCR4

T cell development requires phosphatidylinositol 3-kinase (PI3K) signaling with contributions from both the class IA, p110δ, and class IB, p110γ catalytic subunits. However, the receptors on immature T cells by which each of these PI3Ks are activated have not been identified, nor has the mechanism behind their functional redundancy in the thymus. Here, we show that PI3K signaling from the preTCR requires p110δ, but not p110γ. Mice deficient for the class IB regulatory subunit p101 demonstrated the requirement for p101 in T cell development, implicating G protein–coupled receptor signaling in β-selection. We found evidence of a role for CXCR4 using small molecule antagonists in an in vitro model of β-selection and demonstrated a requirement for CXCR4 during thymic development in CXCR4-deficient embryos. Finally, we demonstrate that CXCL12, the ligand for CXCR4, allows for Notch-dependent differentiation of DN3 thymocytes in the absence of supporting stromal cells. These findings establish a role for CXCR4-mediated PI3K signaling that, together with signals from Notch and the preTCR, contributes to continued T cell development beyond β-selection