Biomechanical Properties of Land Based and Shallow Water Wait: A Comparative Review of Literature

Aquatic locomotion exercises are frequently used in rehabilitation and cross-training for land-based athletes. Hydrostatic pressure, thermal conductivity and drag force affect a person\u27s ability to move; therefore, it is important to understand differences of biomechanical gait in water vs land. This review investigated biomechanical differences between shallow water and land-based exercises. PubMed, Google Scholar, SPORTDiscus and Scopus were searched; 33 studies included walking forward (27), backward (6) and running (6). Electromyographic amplitude was similar or less in submaximal intensity during aquatic gait, in comparison to on land. At maximal intensities, however, the amplitude was similar (n=5) or higher (n=4) in water than on land. Kinetic variables (i.e. ground reaction force, lower extremity joint moments) were reduced in water (about 30-35%), while kinematic variables varied between shallow water and land-based exercise. The research highlighted in this review provides a strong foundation for improving rehabilitation and research practices associated with aquatic activities

Merging cloned alloy models with colorful refactorings

Likewise to code, clone-and-own is a common way to create variants of a model, to explore the impact of different features while exploring the design of a software system. Previously, we have introduced Colorful Alloy, an extension of the popular Alloy language and toolkit to support feature-oriented design, where model elements can be annotated with feature expressions and further highlighted with different colors to ease understanding. In this paper we propose a catalog of refactorings for Colorful Alloy models, and show how they can be used to iteratively merge cloned Alloy models into a single feature-annotated colorful model, where the commonalities and differences between the different clones are easily perceived, and more efficient aggregated analyses can be performed.This work is financed by the ERDF — European Regional Development Fund through the Operational Programme for Competitiveness and Internationalisation – COMPETE 2020 Programme and by National Funds through the Portuguese funding agency, FCT – Fundação para a Ciência e a Tecnologia within project PTDC/CCI-INF/29583/2017 – POCI-01-0145-FEDER-029583

Antitumor activity from antigen-specific CD8 T cells generated in vivo from genetically engineered human hematopoietic stem cells

The goal of cancer immunotherapy is the generation of an effective, stable, and self-renewing antitumor T-cell population. One such approach involves the use of high-affinity cancer-specific T-cell receptors in gene-therapy protocols. Here, we present the generation of functional tumor-specific human T cells in vivo from genetically modified human hematopoietic stem cells (hHSC) using a human/mouse chimera model. Transduced hHSC expressing an HLA-A*0201–restricted melanoma-specific T-cell receptor were introduced into humanized mice, resulting in the generation of a sizeable melanoma-specific naïve CD8^+ T-cell population. Following tumor challenge, these transgenic CD8^+ T cells, in the absence of additional manipulation, limited and cleared human melanoma tumors in vivo. Furthermore, the genetically enhanced T cells underwent proper thymic selection, because we did not observe any responses against non–HLA-matched tumors, and no killing of any kind occurred in the absence of a human thymus. Finally, the transduced hHSC established long-term bone marrow engraftment. These studies present a potential therapeutic approach and an important tool to understand better and to optimize the human immune response to melanoma and, potentially, to other types of cancer

Experimental Investigation and Large-Eddy Simulation of the Turbulent Flow past a Smooth and Rigid Hemisphere

Computations carried out on the German Federal Top-Level Computer SuperMUC at LRZ Munich under the contract number pr84na.International audienceThe objective of the present paper is to provide a detailed experimental and numerical investigation on the turbulent flow past a hemispherical obstacle (diameter D). For this purpose, the bluff body is exposed to a thick turbulent boundary layer of the thickness δ = D/2 at Re = 50,000. In the experiment this boundary layer thickness is achieved by specific fences placed in the upstream region of the wind tunnel. A detailed measurement of the upstream flow conditions by laser-Doppler and hot-film probes allows to mimic the inflow conditions for the complementary large-eddy simulation of the flow field using a synthetic turbulence inflow generator. These clearly defined boundary and operating conditions are the prerequisites for a combined experimental and numerical investigation of the flow field relying on the laser-Doppler anemometry and a finite-volume Navier-Stokes solver for block-structured curvilinear grids. The results comprise an analysis on the unsteady flow features observed in the vicinity of the hemisphere as well as a detailed discussion of the time-averaged flow field. The latter includes the mean velocity field as well as the Reynolds stresses. Owing to the proper description of the oncoming flow and supplementary numerical studies guaranteeing the choice of an appropriate grid and subgrid-scale model, the results of the measurements and the prediction are found to be in close agreement

Crosstalk between Medulloblastoma Cells and Endothelium Triggers a Strong Chemotactic Signal Recruiting T Lymphocytes to the Tumor Microenvironment

Cancer cells can live and grow if they succeed in creating a favorable niche that often includes elements from the immune system. While T lymphocytes play an important role in the host response to tumor growth, the mechanism of their trafficking to the tumor remains poorly understood. We show here that T lymphocytes consistently infiltrate the primary brain cancer, medulloblastoma. We demonstrate, both in vitro and in vivo, that these T lymphocytes are attracted to tumor deposits only after the tumor cells have interacted with tumor vascular endothelium. Macrophage Migration Inhibitory Factor (MIF)” is the key chemokine molecule secreted by tumor cells which induces the tumor vascular endothelial cells to secrete the potent T lymphocyte attractant “Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES).” This in turn creates a chemotactic gradient for RANTES-receptor bearing T lymphocytes. Manipulation of this pathway could have important therapeutic implications

Endothelial Progenitor Cells (EPCs) as Gene Carrier System for Rat Model of Human Glioma

Due to their unique property to migrate to pathological lesions, stem cells are used as a delivery vehicle for therapeutic genes to tumors, especially for glioma. It is critically important to track the movement, localization, engraftment efficiency and functional capability or expression of transgenes of selected cell populations following transplantation. The purposes of this study were to investigate whether 1) intravenously administered, genetically transformed cord blood derived EPCs can carry human sodium iodide symporter (hNIS) to the sites of tumors in rat orthotopic model of human glioma and express transgene products, and 2) whether accumulation of these administered EPCs can be tracked by different in vivo imaging modalities.Collected EPCs were cultured and transduced to carry hNIS. Cellular viability, differential capacity and Tc-99m uptake were determined. Five to ten million EPCs were intravenously administered and Tc-99-SPECT images were acquired on day 8, to determine the accumulation of EPCs and expression of transgenes (increase activity of Tc-99m) in the tumors. Immunohistochemistry was performed to determine endothelial cell markers and hNIS positive cells in the tumors. Transduced EPCs were also magnetically labeled and accumulation of cells was confirmed by MRI and histochemistry. SPECT analysis showed increased activity of Tc-99m in the tumors that received transduced EPCs, indicative of the expression of transgene (hNIS). Activity of Tc-99m in the tumors was also dependent on the number of administered transduced EPCs. MRI showed the accumulation of magnetically labeled EPCs. Immunohistochemical analysis showed iron and hNIS positive and, human CD31 and vWF positive cells in the tumors.EPC was able to carry and express hNIS in glioma following IV administration. SPECT detected migration of EPCs and expression of the hNIS gene. EPCs can be used as gene carrier/delivery system for glioma therapy as well as imaging probes

A nonlinear Lagrangian particle model for grains assemblies including grain relative rotations

International audienceWe formulate a discrete Lagrangian model for a set of interacting grains, which is purely elastic. The considered degrees of freedom for each grain include placement of barycenter and rotation. Further, we limit the study to the case of planar systems. A representative grain radius is introduced to express the deformation energy to be associated to relative displacements and rotations of interacting grains. We distinguish inter‐grains elongation/compression energy from inter‐grains shear and rotations energies, and we consider an exact finite kinematics in which grain rotations are independent of grain displacements. The equilibrium configurations of the grain assembly are calculated by minimization of deformation energy for selected imposed displacements and rotations at the boundaries. Behaviours of grain assemblies arranged in regular patterns, without and with defects, and similar mechanical properties are simulated. The values of shear, rotation, and compression elastic moduli are varied to investigate the shapes and thicknesses of the layers where deformation energy, relative displacement, and rotations are concentrated. It is found that these concentration bands are close to the boundaries and in correspondence of grain voids. The obtained results question the possibility of introducing a first gradient continuum models for granular media and justify the development of both numerical and theoretical methods for including frictional, plasticity, and damage phenomena in the proposed model

Imaging Long-Term Fate of Intramyocardially Implanted Mesenchymal Stem Cells in a Porcine Myocardial Infarction Model

The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [18F]FEAU to monitor the long-term (up to 5 months) spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC) and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [18F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33–35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC–associated [18F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [18F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months) of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI