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.     

Effect of Ag nanoparticle addition and ultrasonic treatment on a stable TiO2 nanofluid

Nanoparticles, when homogeneously dispersed in a base fluid, e.g. water, ethylene glycol etc. are commonly known as nanofluids. Nanofluids have gained attention in the scientific community for their enhanced thermal properties. One of the major problems in using nanofluids as a heat transfer medium for commercial applications is that, in most of the closed circuit industrial cooling processes, the cooling fluid has to be replaced after several cycles of cooling operation because of an increased presence of contaminants. If nanofluids were used as a coolant, it would be very hard to separate the nanoparticles from the waste fluid. The present work is aimed at the separation and recycling of nanoparticles from fluid waste by means of quick settling of titanium dioxide nanoparticles using silver nanoparticles along with ultrasonic treatment. It is observed that with increasing silver concentration and time of ultrasonication, the stability of the dispersion decreases. There is a value for both the silver concentration and ultrasonication time above which the settling time decreases drastically.     

L-shell/subshell ionization of Au,Pb and Bi by low energy proton impact

Proton induced X-ray emission has been used to measureL-subshell and total ionization cross-sections of Au, Pb and Bi in the energy range of 200–350 keV. The ionization cross-sections have been extracted using the X-ray spectra and other quantities like fluorescence yields, transition probabilities, relative widths and Coster-Krönig fraction etc. involved in the process. The results have been compared with the cross-sections measured before and discussed in the light of known theories regarding the ion-atom collisions.     

Performance of a 80 W copper vapor laser with “alignment free” unstable CAT-EYE resonator and other configurations using intra-cavity apertures

Performance of a kinetically enhanced copper vapor laser (KE-CVL) with various stable/unstable “alignment free” CAT-EYE resonator configurations are presented here in this paper. The laser used in the experiment was a 45 mm bore (∼2 l discharge volume) kinetically enhanced copper vapor laser developed in our laboratory and capable of generating maximum power of ∼80 W (at ∼9.8 kHz). The efficiency of the laser was ∼1.4% and beam divergence of ∼3.5 mrad in a plane-plane standard multimode cavity. For the first time performance of unstable CAT-EYE resonator is demonstrated with a CVL/KE-CVL. On using unstable CAT-EYE resonator the divergence of the laser beam reduced to ∼0.22 mrad (∼20-fold reduction as compared to conventional plane-plane cavity), ∼40 W output power and with excellent misalignment tolerance. The laser output power was found to be within ∼5% drift/decline with misalignment angle of about 4 mrad between the mirrors. This is a significant improvement in comparison to standard conventional unstable resonator (M ∼ 50) CVL where ∼0.5 mrad divergence is achieved with power drift/decline of about 45% at ∼4 mrad misalignment angle.Off-axis unstable CAT-EYE unstable resonator was also demonstrated for the first time with further reduction in beam divergence to ∼0.13 mrad and with output power of ∼28 W. The misalignment tolerance was found to be highest in case of off-axis unstable CAT-EYE resonator with decline/drift in laser power of only ∼10% for misalignment angle as high as ∼8 mrad. Performance with intra-cavity apertures in plane-plane type CAT-EYE resonator for transverse mode control is also presented for the first time in CVLs. It is observed that the laser beam divergence reduces significantly to 1.25 mrad (a factor of 2) on using an aperture of ∼3.5 mm at the CAT-EYE reflector as compared to its normal (R = F = d) configuration without aperture. In case of stable CAT-EYE resonator the average beam divergence reduces from 8 mrad to 4 mrad (factor of 2) on using intra-cavity aperture of about 3 mm. It was also observed that high misalignment tolerance was retained on using intra-cavity apertures in almost all the CAT-EYE resonators. Use of intra-cavity mesh was also demonstrated for the first time with stable CAT-EYE resonator for improving the beam focus-ability. Average beam divergence was reduced by a factor of 2.5 (from 8 mrad to 3 mrad) on using intra-cavity mesh. These new configurations in CAT-EYE resonators in KE-CVLs are found to be effective in improving and controlling the laser beam divergence significantly with additional characteristic of high misalignment tolerance.     

A cosmological study in massive gravity theory

A detailed study of the various cosmological aspects in massive gravity theory has been presented in the present work. For the homogeneous and isotropic FLRW model, the deceleration parameter has been evaluated, and, it has been examined whether there is any transition from deceleration to acceleration in recent past, or not. With the proper choice of the free parameters, it has been shown that the massive gravity theory is equivalent to Einstein gravity with a modified Newtonian gravitational constant together with a negative cosmological constant. Also, in this context, it has been examined whether the emergent scenario is possible, or not, in massive gravity theory. Finally, we have done a cosmographic analysis in massive gravity theory.     

Emergent Universe in Einstein-Gauss-Bonnet Theory

In this work, Emergent Universe scenario has been developed in Einstein-Gauss-Bonnet (EGB) theory. The universe is chosen as homogeneous and isotropic FRW model and the matter in the universe has two components—the first one is a perfect fluid with barotropic equation of state p=ω ρ (ω, a constant) and the other component is a real or phantom (or tachyonic) scalar field. Various possibilities for the existence of emergent scenario has been discussed and the results are compared with those in Einstein gravity.     

Kinetics of unusual photoinduced currents in the solid state of some ferrocene derivatives

Kinetics of change in photoinduced currents (during illumination and after switching off light source) in the solid state of some ferrocene derivatives, namely, ferrocenecarboxylic acid, acetylferrocene, ferrocenecarbaldehyde, hydroxymethyl ferrocene have been studied in dry nitrogen gas atmosphere. Unusual/anomalous photocurrent versus time profiles were observed in some ferrocene derivatives at certain cell temperatures. The kinetics of current changes under photoexcitation and after switching off the light source have been observed to be complicated in nature. Temperature-dependent behavior of the studied kinetics indicates that charge carrier trapping/detrapping and recombination processes are significantly temperature dependent. These processes have an important role in causing the temperature dependent unusual/anomalous photocurrent versus time profiles in the ferrocene derivatives studied.     

Coulomb screening in graphene with topological defects

We analyze the screening of an external Coulomb charge in gapless graphene cone, which is taken as a prototype of a topological defect. In the subcritical regime, the induced charge is calculated using both the Green’s function and the Friedel sum rule. The dependence of the polarization charge on the Coulomb strength obtained from the Green’s function clearly shows the effect of the conical defect and indicates that the critical charge itself depends on the sample topology. Similar analysis using the Friedel sum rule indicates that the two results agree for low values of the Coulomb charge but differ for the higher strengths, especially in the presence of the conical defect. For a given subcritical charge, the transport cross-section has a higher value in the presence of the conical defect. In the supercritical regime we show that the coefficient of the power law tail of polarization charge density can be expressed as a summation of functions which vary log periodically with the distance from the Coulomb impurity. The period of variation depends on the conical defect. In the presence of the conical defect, the Fano resonances begin to appear in the transport cross-section for a lower value of the Coulomb charge. For both sub and supercritical regime we derive the dependence of LDOS on the conical defect. The effects of generalized boundary condition on the physical observables are also discussed.     

Optimization of ultrasound-assisted extraction of phenolic compounds from Sesamum indicum

Abstract

Effective extraction of phyto-biomolecules insures retaining maximum functionality along with higher recovery. In this study, ultrasound-solvent assisted extraction (USAE) was employed for optimal extraction of phyto-biomolecules from Sesamum indicum (sesame) leaves using the approach of Response Surface Methodology (RSM). The optimized condition of 200?W power, 59% methanol concentration with 1:14?g/mL solid–liquid ratio and 15?min of extraction time yielded 367.39?±?1.85?mg GAE/100?g of total phenolic content, 96.72?±?3.27% of free radical scavenging activity and 81.20?±?2.87% of iron chelating activity respectively. The extract consist of essential phytocomponents like gallic acid, chlorogenic acid, and quercetin with lipid peroxidation activities of >50% over incubation time of 48?h. Also, showed antimicrobial activity against various Gram’s negative and positive food borne pathogens. The results of this study implied the importance of USAE for effective and optimum recovery of phyto-biomolecules from Sesame leaves with retained functional properties.