Regulatory T cells expressing CD19-targeted chimeric antigen receptor restore homeostasis in Systemic Lupus Erythematosus.

Systemic Lupus Erythematosus (SLE) is a progressive disease leading to immune-mediated tissue damage, associated with an alteration of lymphoid organs. Therapeutic strategies involving regulatory T (Treg) lymphocytes, which physiologically quench autoimmunity and support long-term immune tolerance, are considered, as conventional treatment often fails. We describe here a therapeutic strategy based on Tregs overexpressing FoxP3 and harboring anti-CD19 CAR (Fox19CAR-Tregs). Fox19CAR-Tregs efficiently suppress proliferation and activity of B cells in vitro, which are relevant for SLE pathogenesis. In an humanized mouse model of SLE, a single infusion of Fox19CAR-Tregs restricts autoantibody generation, delay lymphopenia (a key feature of SLE) and restore the human immune system composition in lymphoid organs, without detectable toxicity. Although a short survival, SLE target organs appear to be protected. In summary, Fox19CAR-Tregs can break the vicious cycle leading to autoimmunity and persistent tissue damage, representing an efficacious and safe strategy allowing restoration of homeostasis in SLE.

Finite element simulation of the braiding process.

Braiding is one of the most common technique employed for the manufacture of fabrics and ropes. It is also commonly used to produce near-net shaped preforms for advanced fibre reinforced composites. This paper presents an explicit finite element approach to create and simulate the braiding process for the virtual manufacture of 2D braids. The process starts from the definition of an analytical function which describes the movement of the carriers on a braiding track plate. Models of idealised Maypole-type braiding machines are built and used to shape virtual yarns into braids. This procedure can be used in a parameter control fashion, to optimise or to create virtual braided structures, which can serve as input for other structural analyses. It is emphasised that multiple cylinders are required for the modelling of a multifilament yarn to achieve better correlation with the experimental results. A parametric study is presented to investigate the effect of the number of virtual cylinders to represent a real yarn and the shape of the final braid. Excellent correlation was found between the virtual models and the experimental results when comparing the braid angle and yarn width.

Theory of the deformation of aligned polyethylene.

Solitons are proposed as the agents of plastic and viscoelastic deformation in aligned polyethylene. Interactions between straight, parallel molecules are mapped rigorously onto the Frenkel-Kontorova model. It is shown that these molecular interactions distribute an applied load between molecules, with a characteristic transfer length equal to the soliton width. Load transfer leads to the introduction of tensile and compressive solitons at the chain ends to mark the onset of plasticity at a well-defined yield stress, which is much less than the theoretical pull-out stress. Interaction energies between solitons and an equation of motion for solitons are derived. The equation of motion is based on Langevin dynamics and the fluctuation-dissipation theorem and it leads to the rigorous definition of an effective mass for solitons. It forms the basis of a soliton dynamics in direct analogy to dislocation dynamics. Close parallels are drawn between solitons in aligned polymers and dislocations in crystals, including the configurational force on a soliton. The origins of the strain rate and temperature dependencies of the viscoelastic behaviour are discussed in terms of the formation energy of solitons. A failure mechanism is proposed involving soliton condensation under a tensile load.

Reliability of heart rate measures during walking before and after running maximal efforts.

Previous studies on HR recovery (HRR) measures have utilized the supine and the seated postures. However, the most common recovery mode in sport and clinical settings after running exercise is active walking. The aim of the current study was to examine the reliability of HR measures during walking (4 km · h(-1)) before and following a maximal test. Twelve endurance athletes performed an incremental running test on 2 days separated by 48 h. Absolute (coefficient of variation, CV, %) and relative [Intraclass correlation coefficient, (ICC)] reliability of time domain and non-linear measures of HR variability (HRV) from 3 min recordings, and HRR parameters over 5 min were assessed. Moderate to very high reliability was identified for most HRV indices with short-term components of time domain and non-linear HRV measures demonstrating the greatest reliability before (CV: 12-22%; ICC: 0.73-0.92) and after exercise (CV: 14-32%; ICC: 0.78-0.91). Most HRR indices and parameters of HRR kinetics demonstrated high to very high reliability with HR values at a given point and the asymptotic value of HR being the most reliable (CV: 2.5-10.6%; ICC: 0.81-0.97). These findings demonstrate these measures as reliable tools for the assessment of autonomic control of HR during walking before and after maximal efforts.