Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy

It is generally believed that increase in adult contractile cardiac mass can be accomplished only by hypertrophy of existing myocytes. Documentation of myocardial regeneration in acute stress has challenged this dogma and led to the proposition that myocyte renewal is fundamental to cardiac homeostasis. Here we report that in human aortic stenosis, increased cardiac mass results from a combination of myocyte hypertrophy and hyperplasia. Intense new myocyte formation results from the differentiation of stem-like cells committed to the myocyte lineage. These cells express stem cell markers and telomerase. Their number increased >13-fold in aortic stenosis. The finding of cell clusters with stem cells making the transition to cardiogenic and myocyte precursors, as well as very primitive myocytes that turn into terminally differentiated myocytes, provides a link between cardiac stem cells and myocyte differentiation. Growth and differentiation of these primitive cells was markedly enhanced in hypertrophy, consistent with activation of a restricted number of stem cells that, through symmetrical cell division, generate asynchronously differentiating progeny. These clusters strongly support the existence of cardiac stem cells that amplify and commit to the myocyte lineage in response to increased workload. Their presence is consistent with the notion that myocyte hyperplasia significantly contributes to cardiac hypertrophy and accounts for the subpopulation of cycling myocytes

Instability of axion inflation in the regime of strong backreaction

openIn axion-U(1) inflation models, in the limit of strong coupling between the inflaton and the gauge field, one helicity mode of the gauge field undergoes exponential enhancement. This amplification, governed by the inflaton velocity, leads to a delayed backreaction of the gauge field on the inflaton motion, resulting in oscillations in the inflaton velocity. In this thesis we conduct an analytical examination of the evolution equation, relaxing certain assumptions typically found in the literature. Additionally, we explore the numerical effects of a time-delayed friction term within a single-field inflation model.In axion-U(1) inflation models, in the limit of strong coupling between the inflaton and the gauge field, one helicity mode of the gauge field undergoes exponential enhancement. This amplification, governed by the inflaton velocity, leads to a delayed backreaction of the gauge field on the inflaton motion, resulting in oscillations in the inflaton velocity. In this thesis we conduct an analytical examination of the evolution equation, relaxing certain assumptions typically found in the literature. Additionally, we explore the numerical effects of a time-delayed friction term within a single-field inflation model

Biomimetic poly(glycerol sebacate) (PGS) membranes for cardiac patch application

Abstract In this study biomimetic poly(glycerol sebacate) PGS matrix was developed for cardiac patch application. The rationale was that such matrices would provide conducive environment for the seeded cells at the interphase with PGS. From the microstructural standpoint, PGS was fabricated into dense films and porous PGS scaffolds. From the biological aspect, biomimetic PGS membranes were developed via covalently binding peptides Tyr-Ile-Gly-Ser-Arg (YIGSR) and Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP), corresponding to the epitope sequences of laminin and fibronectin, respectively onto the surface. To improve and enhance homogenous binding of peptides onto the PGS surface, chemical modification of its surface was carried out. A sequential regime of alkaline hydrolysis with 0.01 M NaOH for 5 min and acidification with 0.01 M HCl for 25 s was optimal. More COOH chemical group was exposed without causing deleterious effect on the bulk properties of the polymer as revealed by the physicochemical analysis carried out. HPLC analysis, chemical imaging and ToF-SIMS were able to establish the successful homogenous functionalization of PGS membranes with the peptides. Finally, the developed biomimetic membranes supported the adhesion and growth of rat and human cardiac progenitor cells

Proximal Estimation and Inference

We build a unifying convex analysis framework characterizing the statistical properties of a large class of penalized estimators, both under a regular and an irregular design. Our framework interprets penalized estimators as proximal estimators, defined by a proximal operator applied to a corresponding initial estimator. We characterize the asymptotic properties of proximal estimators, showing that their asymptotic distribution follows a closed-form formula depending only on (i) the asymptotic distribution of the initial estimator, (ii) the estimator's limit penalty subgradient and (iii) the inner product defining the associated proximal operator. In parallel, we characterize the Oracle features of proximal estimators from the properties of their penalty's subgradients. We exploit our approach to systematically cover linear regression settings with a regular or irregular design. For these settings, we build new $\sqrt{n}-$consistent, asymptotically normal Ridgeless-type proximal estimators, which feature the Oracle property and are shown to perform satisfactorily in practically relevant Monte Carlo settings