The unphysical nature of the SL(2,R) symmetry and its associated condensates in Yang-Mills theories

BRST cohomology methods are used to explain the origin of the SL(2,R) symmetry in Yang-Mills theories. Clear evidence is provided for the unphysical nature of this symmetry. This is obtained from the analysis of a local functional of mass dimension two and constitutes a no-go statement for giving a physical meaning to condensates associated with the symmetry breaking of SL(2,R).Comment: 5 pages (revtex4), final version to appear in Phys. Rev.

Scaling and finte-size-scaling in the two dimensional random-coupling Ising ferromagnet

It is shown by Monte Carlo method that the finite size scaling (FSS) holds in the two dimensional random-coupled Ising ferromagnet. It is also demonstrated that the form of universal FSS function constructed via novel FSS scheme depends on the strength of the random coupling for strongly disordered cases. Monte Carlo measurements of thermodynamic (infinite volume limit) data of the correlation length ($\xi$) up to $\xi \simeq 200$ along with measurements of the fourth order cumulant ratio (Binder's ratio) at criticality are reported and analyzed in view of two competing scenarios. It is demonstrated that the data are almost exclusively consistent with the scenario of weak universality.Comment: 9 pages, 4figuer

Critical behavior of weakly-disordered anisotropic systems in two dimensions

The critical behavior of two-dimensional (2D) anisotropic systems with weak quenched disorder described by the so-called generalized Ashkin-Teller model (GATM) is studied. In the critical region this model is shown to be described by a multifermion field theory similar to the Gross-Neveu model with a few independent quartic coupling constants. Renormalization group calculations are used to obtain the temperature dependence near the critical point of some thermodynamic quantities and the large distance behavior of the two-spin correlation function. The equation of state at criticality is also obtained in this framework. We find that random models described by the GATM belong to the same universality class as that of the two-dimensional Ising model. The critical exponent $\nu$ of the correlation length for the 3- and 4-state random-bond Potts models is also calculated in a 3-loop approximation. We show that this exponent is given by an apparently convergent series in $\epsilon=c-\frac{1}{2}$ (with $c$ the central charge of the Potts model) and that the numerical values of $\nu$ are very close to that of the 2D Ising model. This work therefore supports the conjecture (valid only approximately for the 3- and 4-state Potts models) of a superuniversality for the 2D disordered models with discrete symmetries.Comment: REVTeX, 24 pages, to appear in Phys.Rev.

Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction

BACKGROUND: Myocardial fibrosis is a hallmark of cardiac remodeling and functionally involved in heart failure development, a leading cause of deaths worldwide. Clinically, no therapeutic strategy is available that specifically attenuates maladaptive responses of cardiac fibroblasts, the effector cells of fibrosis in the heart. Therefore, our aim was to develop novel antifibrotic therapeutics based on naturally derived substance library screens for the treatment of cardiac fibrosis. METHODS: Antifibrotic drug candidates were identified by functional screening of 480 chemically diverse natural compounds in primary human cardiac fibroblasts, subsequent validation, and mechanistic in vitro and in vivo studies. Hits were analyzed for dose-dependent inhibition of proliferation of human cardiac fibroblasts, modulation of apoptosis, and extracellular matrix expression. In vitro findings were confirmed in vivo with an angiotensin II–mediated murine model of cardiac fibrosis in both preventive and therapeutic settings, as well as in the Dahl salt-sensitive rat model. To investigate the mechanism underlying the antifibrotic potential of the lead compounds, treatment-dependent changes in the noncoding RNAome in primary human cardiac fibroblasts were analyzed by RNA deep sequencing. RESULTS: High-throughput natural compound library screening identified 15 substances with antiproliferative effects in human cardiac fibroblasts. Using multiple in vitro fibrosis assays and stringent selection algorithms, we identified the steroid bufalin (from Chinese toad venom) and the alkaloid lycorine (from Amaryllidaceae species) to be effective antifibrotic molecules both in vitro and in vivo, leading to improvement in diastolic function in 2 hypertension-dependent rodent models of cardiac fibrosis. Administration at effective doses did not change plasma damage markers or the morphology of kidney and liver, providing the first toxicological safety data. Using next-generation sequencing, we identified the conserved microRNA 671-5p and downstream the antifibrotic selenoprotein P1 as common effectors of the antifibrotic compounds. CONCLUSIONS: We identified the molecules bufalin and lycorine as drug candidates for therapeutic applications in cardiac fibrosis and diastolic dysfunction

Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction

BACKGROUND: Myocardial fibrosis is a hallmark of cardiac remodeling and functionally involved in heart failure development, a leading cause of deaths worldwide. Clinically, no therapeutic strategy is available that specifically attenuates maladaptive responses of cardiac fibroblasts, the effector cells of fibrosis in the heart. Therefore, our aim was to develop novel antifibrotic therapeutics based on naturally derived substance library screens for the treatment of cardiac fibrosis. METHODS: Antifibrotic drug candidates were identified by functional screening of 480 chemically diverse natural compounds in primary human cardiac fibroblasts, subsequent validation, and mechanistic in vitro and in vivo studies. Hits were analyzed for dose-dependent inhibition of proliferation of human cardiac fibroblasts, modulation of apoptosis, and extracellular matrix expression. In vitro findings were confirmed in vivo with an angiotensin II–mediated murine model of cardiac fibrosis in both preventive and therapeutic settings, as well as in the Dahl salt-sensitive rat model. To investigate the mechanism underlying the antifibrotic potential of the lead compounds, treatment-dependent changes in the noncoding RNAome in primary human cardiac fibroblasts were analyzed by RNA deep sequencing. RESULTS: High-throughput natural compound library screening identified 15 substances with antiproliferative effects in human cardiac fibroblasts. Using multiple in vitro fibrosis assays and stringent selection algorithms, we identified the steroid bufalin (from Chinese toad venom) and the alkaloid lycorine (from Amaryllidaceae species) to be effective antifibrotic molecules both in vitro and in vivo, leading to improvement in diastolic function in 2 hypertension-dependent rodent models of cardiac fibrosis. Administration at effective doses did not change plasma damage markers or the morphology of kidney and liver, providing the first toxicological safety data. Using next-generation sequencing, we identified the conserved microRNA 671-5p and downstream the antifibrotic selenoprotein P1 as common effectors of the antifibrotic compounds. CONCLUSIONS: We identified the molecules bufalin and lycorine as drug candidates for therapeutic applications in cardiac fibrosis and diastolic dysfunction