In silico design of peptidic inhibitors targeting estrogen receptor alpha dimer interface

Human estrogen receptor alpha (ERα), which acts as a biomarker and as a therapeutic target for breast cancers, is activated by agonist ligands and co-activator proteins. Selective estrogen receptor modulators (SERM) act as antagonists in specific tissues and tamoxifen, a SERM, has served as a drug for decades for ERα-positive breast cancers. However, the ligand-selective and tissue-specific response of ERα biological activity and the resistance to tamoxifen treatment in advanced stages of ERα-positive breast cancers underscores the need to find a ligand-independent inhibitor for ERα. Here we present a ligand-independent approach of inhibiting ERα transactivation targeting its dimerization-a key process of ERα biological activity. Using in silico techniques, we first elucidated the hydrogen bond interactions involved in dimerization and identified three interfacial sequence motifs, where sequence I (DKITD) and sequence II (QQQHQRLAQ) of one monomer form hydrogen bonding with sequence II and sequence I of the second monomer, respectively, and sequence III (LSHIRHMSNK) hydrogen bonds with the same from the second monomer. Studying the structural stability and the binding affinity of the peptides derived from these sequence motifs, we found that an extended and ARG mutated version (LQQQHQQLAQ) of sequence II can act as a suitable template for designing peptidic inhibitors. It provides additional structural stability and interacts more strongly with ERα dimer interface groove formed by helices 9 and 10/11 and prevent ERα dimerization. Our result provides a novel therapeutic designing pipeline for ligand-independent inhibition of ERα.     

Experimental gravity induced coexistence curve of methyl fluoride near the critical point

Abstract

The top part of the coexistence curve of methyl fluoride in the critical region has been determined first by direct observation of the disappearance of the meniscus of the fluid situated in a high-pressure light scattering cell and subsequently from the measured maximum depolarization ratio of an appreciable number of isochores close to the critical point. The experimental data obtained from direct observations yield a coexistence curve which nearly coincides with that found recently from pVT measurements. However, the data obtained from light scattering experiments describe a gravity induced coexistence curve which lies above the previous one and which shows a minimum at the critical point. The complete experimental data have been used to evaluate the critical parameters p_c, ρ_c and T_c and the critical exponent β.     

On symmetries,reductions, conservation laws and conserved quantities of optical solitons with inter-modal dispersion

This paper studies the compressional dispersive Alfvén (CDA) waves where Noether symmetries will be calculated from which the corresponding conservation laws will be obtained via Noether's theorem. Furthermore, one case of double reduction is performed via the association of a conserved vector with a Noether symmetry (with zero gauge). The conserved quantities of optical solitons in the presence of intermodal dispersion that is governed by the perturbed nonlinear Schrödinger's equation with Kerr law nonlinearity. The invariance-multiplier method is adopted to carry out the analysis, from which the conserved densities are then retrieved. Finally, the conserved quantities are obtained using the 1-soliton solution of the governing equation.     

Dynamics of Relativistic Solitons Due to Pseudo Sine-Gordon Equation

This paper is a review of some of the most important concepts and phenomena for relativistic solitons. The Sine-Gordon equation and the pseudo Sine-Gordon equations are studied in this context. A final discussion is conducted in the for soliton in more than one spatial dimensions.     

Exact interior solutions in 2+1-dimensional spacetime

An exact formulation of two-dimensional chiral hydrodynamics with diffeomorphism and conformal anomalies is provided. The constitutive relation involving the stress tensor is computed. It reveals a one parameter class of solutions which is a new result. For a particular value of this parameter, the results found in the gradient expansion scheme are reproduced. Moreover, the constitutive relation is analogous to the corresponding relation for an ideal fluid, appropriately modified to include the chirality property, which has also been derived here.     

Neutrino emissivity of quark matter at finite temperatures

We evaluate the emissivity rates for d-decay and s-decay by exactly solving the angular integrals involved and without assuming the degeneracy of electrons. We have also studied the effects of QCD coupling constant as well as the s-quark mass on the emissivity rates. We find that these parameters are important in determining the threshold and extinction densities for d- and s-decays.