1,390 research outputs found

    Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation

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    Spontaneously beating engineered heart tissue (EHT) represents an advanced in vitro model for drug testing and disease modeling, but cardiomyocytes in EHTs are less mature and generate lower forces than in the adult heart. We devised a novel pacing system integrated in a setup for videooptical recording of EHT contractile function over time and investigated whether sustained electrical field stimulation improved EHT properties. EHTs were generated from neonatal rat heart cells (rEHT, n=96) or human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hEHT, n=19). Pacing with biphasic pulses was initiated on day 4 of culture. REHT continuously paced for 16-18 days at 0.5Hz developed 2.2× higher forces than nonstimulated rEHT. This was reflected by higher cardiomyocyte density in the center of EHTs, increased connexin-43 abundance as investigated by two-photon microscopy and remarkably improved sarcomere ultrastructure including regular M-bands. Further signs of tissue maturation include a rightward shift (to more physiological values) of the Ca(2+)-response curve, increased force response to isoprenaline and decreased spontaneous beating activity. Human EHTs stimulated at 2Hz in the first week and 1.5Hz thereafter developed 1.5× higher forces than nonstimulated hEHT on day 14, an ameliorated muscular network of longitudinally oriented cardiomyocytes and a higher cytoplasm-to-nucleus ratio. Taken together, continuous pacing improved structural and functional properties of rEHTs and hEHTs to an unprecedented level. Electrical stimulation appears to be an important step toward the generation of fully mature EHT

    Cauchy boundaries in linearized gravitational theory

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    We investigate the numerical stability of Cauchy evolution of linearized gravitational theory in a 3-dimensional bounded domain. Criteria of robust stability are proposed, developed into a testbed and used to study various evolution-boundary algorithms. We construct a standard explicit finite difference code which solves the unconstrained linearized Einstein equations in the 3+1 formulation and measure its stability properties under Dirichlet, Neumann and Sommerfeld boundary conditions. We demonstrate the robust stability of a specific evolution-boundary algorithm under random constraint violating initial data and random boundary data.Comment: 23 pages including 3 figures and 2 tables, revte

    Normative Multi-Agent Programs and Their Logics

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    Multi-agent systems are viewed as consisting of individual agents whose behaviors are regulated by an organization artefact. This paper presents a simplified version of a programming language that is designed to implement norm-based artefacts. Such artefacts are specified in terms of norms being enforced by monitoring, regimenting and sanctioning mechanisms. The syntax and operational semantics of the programming language are introduced and discussed. A logic is presented that can be used to specify and verify properties of programs developed in this language

    Rapid Synthesis of Sub-10 nm Hexagonal NaYF4-Based Upconverting Nanoparticles using TherminolÂź 66

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    We report a simple one-pot method for the rapid preparation of sub-10 nm pure hexagonal (ÎČ-phase) NaYF4-based upconverting nanoparticles (UCNPs). Using TherminolÂź 66 as a co-solvent, monodisperse UCNPs could be obtained in unusually short reaction times. By varying the reaction time and reaction temperature, it was possible to control precisely the particle size and crystalline phase of the UCNPs. The upconversion (UC) luminescence properties of the nanocrystals were tuned by varying the concentrations of the dopants (Nd3+ and Yb3+ sensitizer ions and Er3+ activator ions). The size and phase-purity of the as-synthesized core and core–shell nanocrystals were assessed by using complementary transmission electron microscopy, dynamic light scattering, X-ray diffraction, and small-angle X-ray scattering studies. In-depth photophysical evaluation of the UCNPs was pursued by using steady-state and time-resolved luminescence spectroscopy. An enhancement in the UC intensity was observed if the nanocrystals, doped with optimized concentrations of lanthanide sensitizer/activator ions, were further coated with an inert/active shell. This was attributed to the suppression of surface-related luminescence quenching effects

    'Return to equilibrium' for weakly coupled quantum systems: a simple polymer expansion

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    Recently, several authors studied small quantum systems weakly coupled to free boson or fermion fields at positive temperature. All the approaches we are aware of employ complex deformations of Liouvillians or Mourre theory (the infinitesimal version of the former). We present an approach based on polymer expansions of statistical mechanics. Despite the fact that our approach is elementary, our results are slightly sharper than those contained in the literature up to now. We show that, whenever the small quantum system is known to admit a Markov approximation (Pauli master equation \emph{aka} Lindblad equation) in the weak coupling limit, and the Markov approximation is exponentially mixing, then the weakly coupled system approaches a unique invariant state that is perturbatively close to its Markov approximation.Comment: 23 pages, v2-->v3: Revised version: The explanatory section 1.7 has changed and Section 3.2 has been made more explici

    Activin/nodal signaling and NANOG orchestrate human embryonic stem cell fate decisions by controlling the H3K4me3 chromatin mark.

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    Stem cells can self-renew and differentiate into multiple cell types. These characteristics are maintained by the combination of specific signaling pathways and transcription factors that cooperate to establish a unique epigenetic state. Despite the broad interest of these mechanisms, the precise molecular controls by which extracellular signals organize epigenetic marks to confer multipotency remain to be uncovered. Here, we use human embryonic stem cells (hESCs) to show that the Activin-SMAD2/3 signaling pathway cooperates with the core pluripotency factor NANOG to recruit the DPY30-COMPASS histone modifiers onto key developmental genes. Functional studies demonstrate the importance of these interactions for correct histone 3 Lys4 trimethylation and also self-renewal and differentiation. Finally, genetic studies in mice show that Dpy30 is also necessary to maintain pluripotency in the pregastrulation embryo, thereby confirming the existence of similar regulations in vivo during early embryonic development. Our results reveal the mechanisms by which extracellular factors coordinate chromatin status and cell fate decisions in hESCs.We thank Andrew Knights for the technical support and helpful discussion, and the Wellcome-Trust Sanger Institute Microarray and Next-Generation Sequencing facilities for the technical support. We also thank the Sanger Institute Mouse Genetics Projects for mouse production and genotyping. This work was supported by the European Research Council starting grant Relieve-IMDs and the Cambridge Hospitals National Institute for Health Research Biomedical Research Centre (L.V.), a British Heart Foundation Ph.D. Studentship (A.B.), a Federation of European Biochemical Societies (FEBS) long-term fellowship and EU Fp7 grant InnovaLIV (S.P.), EU Fp7 grant TissuGEN (S.M.), and Wellcome Trust grant 098051 (D.G.). A.B. conceived the research, performed and analyzed the experiments, and wrote the manuscript. P.M. computationally analyzed ChIP-seq data sets and performed statistical analyses. N.C.H., S.B., and R.A.P. provided technical support. A.G. performed embryo dissections and dysmorphology assessments. I.M. and D.B. performed teratoma assays. D.G. supervised the bioinformatics data analysis. S.P., S.M., and L.V. conceived the research and wrote the manuscript.This is the final published version. It first appeared at http://genesdev.cshlp.org/content/29/7/702.full

    Principals of the theory of light reflection and absorption by low-dimensional semiconductor objects in quantizing magnetic fields at monochromatic and pulse excitations

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    The bases of the theory of light reflection and absorption by low-dimensional semiconductor objects (quantum wells, wires and dots) at both monochromatic and pulse irradiations and at any form of light pulses are developed. The semiconductor object may be placed in a stationary quantizing magnetic field. As an example the case of normal light incidence on a quantum well surface is considered. The width of the quantum well may be comparable to the light wave length and number of energy levels of electronic excitations is arbitrary. For Fourier-components of electric fields the integral equation (similar to the Dyson-equation) and solutions of this equation for some individual cases are obtained.Comment: 14 page
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