2-Hydroxyestradiol Overcomes Mesenchymal Stem Cells-Mediated Platinum Chemoresistance in Ovarian Cancer Cells in an ERK-Independent Fashion

Ovarian cancer (OC) is the second most common type of gynecological malignancy. Platinum (Pt)-based chemotherapy is the standard of care for OC, but toxicity and acquired chemoresistance has proven challenging. Recently, we reported that sensitivity to platinum was significantly reduced in a co-culture of OC cells with MSC. To discover compounds capable of restoring platinum sensitivity, we screened a number of candidates and monitored ability to induce PARP cleavage. Moreover, we monitored platinum uptake and expression of ABC transporters in OC cells. Our results showed that 2-hydroxyestradiol (2HE2), a metabolite of estradiol, and dasatinib, an Abl/Src kinase inhibitor, were significantly effective in overcoming MSC-mediated platinum drug resistance. Dasatinib activity was dependent on ERK1/2 activation, whereas 2HE2 was independent of the activation of ERK1/2. MSC-mediated platinum drug resistance was accompanied by reduced intracellular platinum concentrations in OC cells. Moreover, MSC co-cultured with OC cells resulted in downregulation of the expression of cellular transporters required for platinum uptake and efflux. Exposure to 2HE2 and other modulators resulted in an increase in intracellular platinum concentrations. Thus, 2HE2 and dasatinib might act as sensitizers to restore platinum drug sensitivity to OC cells and thus to limit TME-mediated chemoresistance in OC.     

Dielectric Properties of Colossal-Dielectric-Constant Na1/2La1/2Cu3Ti4O12 Ceramics Prepared by Spark Plasma Sintering

In the current study, we report on the dielectric behavior of colossal-dielectric-constant Na_1/2La_1/2Cu₃Ti₄O₁₂ (NLCTO) ceramics prepared by mechanochemical synthesis and spark plasma sintering (SPS) at 850 °C, 900 °C, and 925 °C for 10 min. X-ray powder diffraction analysis showed that all the ceramics have a cubic phase. Scanning electron microscope observations revealed an increase in the average grain size from 175 to 300 nm with an increase in the sintering temperature. SPS NLCTO ceramics showed a room-temperature colossal dielectric constant (>10³) and a comparatively high dielectric loss (>0.1) over most of the studied frequency range (1 Hz–40 MHz). Two relaxation peaks were observed in the spectra of the electrical modulus and attributed to the response of grain and grain boundary. According to the Nyquist plots of complex impedance, the SPS NLCTO ceramics have semiconductor grains surrounded by electrically resistive grain boundaries. The colossal dielectric constant of SPS NLCTO ceramics was attributed to the internal barrier layer capacitance (IBLC) effect. The high dielectric loss is thought to be due to the low resistivity of the grain boundary of SPS NLCTO.     

Influence of ligand-bridged substitution on the exchange coupling constant of chromium-wheels host complexes: a density functional theory study

Designing and introducing novel wheel-shaped supramolecular as host complexes with new magnetic properties is the theme of the day. So in this study, new eight binuclear chromium (III) complexes, as models of real chromium-wheel host complexes, were designed based on changing of bridged-ligands and exchange coupling constants (J) of them were calculated using the broken symmetry density functional theory approach. Substitution of fluorine ligand in fluoro-bridged model [Cr₂F(tBuCO₂)₂(H₂O)₂(OH)₄]^?1 by halogen anions (Cl^?, Br^? and I^? ) decreased the antiferromagnetic exchange coupling between Cr(III) centres such that by going from F^? to I^? the J values became more positive. In the case of hydroxo-bridged model [Cr₂OH(tBuCO₂)₂(H₂O)₂(OH)₄]^?1, replacement of hydroxyl by methoxy anion (OMe^?) strengthened the antiferromagnetic property of the complex but substitution by sulfanide (SH^?) and amide (NH₂^?) anions weakened it and changed the nature of complexes to ferromagnetic. Because of their different magnetic properties, these new investigated complexes can be suggested as interesting synthetic targets. Also, the J value changes due to ligand substitution were evaluated and it was found that the Cr–X bond strength and partial charges of involved atoms were the most effective factors on it.     

Electron Acceleration by Beating of Two Intense Cross-Focused Hollow Gaussian Laser Beams in Plasma

This paper presents propagation of two cross-focused intense hollow Gaussian laser beams(HGBs) in collisionless plasma and its effect on the generation of electron plasma wave(EPW) and electron acceleration process,when relativistic and ponderomotive nonlinearities are simultaneously operative. Nonlinear differential equations have been set up for beamwidth of laser beams, power of generated EPW, and energy gain by electrons using WKB and paraxial approximations. Numerical simulations have been carried out to investigate the effect of typical laser-plasma parameters on the focusing of laser beams in plasmas and further its effect on power of excited EPW and acceleration of electrons. It is observed that focusing of two laser beams in plasma increases for higher order of hollow Gaussian beams,which significantly enhanced the power of generated EPW and energy gain. The amplitude of EPW and energy gain by electrons is found to enhance with an increase in the intensity of laser beams and plasma density. This study will be useful to plasma beat wave accelerator and in other applications requiring multiple laser beams.     

Performance enhancement of the power penalty in DWDM FSO communication using DPPM and OOK modulation

This paper presents the design and performance enhancement of the power penalty (PP) in a dense wavelength division multiplexing based on free space optical communication (FSOC) link using digital pulse position modulation (DPPM) and on–off keying (OOK) modulation. Such a system has a high performance, low cost, robust and power efficient, reliable, excessive flexibility, and higher data rate for access networks. The system performance is evaluated for an 8-channel wavelength-division-multiplexing for hybrid fiber FSOC system at 2.5 Gbps on widely accepted modulation schemes under various atmospheric turbulence (AT) regimes conditions. The performance of system is introduced in terms of PP, bit-error rate (BER), transmission distance and the average received optical power. The numerical results shows that the improvement of the PP using DPPM modulation of 0.2–3.0 dB for weak turbulence (WT) regimes for BER of 10^?6 and above 20, 25 dB for strong turbulence (ST) regimes are reported for BER of 10^?6 and 10^?9, as respectively (depending on the AT level). Further, we develop of improvement the PP caused by multiple-access interference about 6.686 dB which is predicted for target BER of 10^?9 in WT and 1 dB at target BER of 10^?6 in ST when the 8 user are active on the system of optical network units. Additionally, the optical power budget and margin losses of a system are calculated with different link length. The proposed approach of DPPM merges superiority with higher enhancement of PP about 0.8 dB for BER equal 10^?9 at FSO link length l_fso?=?2000 m compared to OOK at 1 dB for WT. An improvement of 2 dB is observed using the DPPM scheme over an OOK due to capability of detect pulses under background noise conditions with increased receiver sensitivity.     

Improved results on robust exponential stability criteria for neutral-type delayed neural networks

In this paper, we investigate the problem of robust global exponential stability analysis for a class of neutral-type neural networks. The interval time-varying delays allow for both slow and fast time-varying delays. The values of the time-varying uncertain parameters are assumed to be bounded within given compact sets. Improved global exponential stability condition is derived by employing new Lyapunov-Krasovskii functional and the integral inequality. The developed nominal and robust stability criteria is delay-dependent and characterized by linear-matrix inequalities (LMIs). The developed results are less conservative than previous published ones in the literature, which are illustrated by representative numerical examples.     

High-field magnetoresistance and magnetothermal e.m.f. in many-valley semiconductors with ellipsoidal energy surface

Thermomagnetic coefficients appropriate to a many-valley model of a semiconductor of the n -Germanium type are evaluated in the framework of the density matrix formalism developed earlier. These coefficients are determined for arbitrary values of the magnetic field, within the effective mass approximation. The phonon-drag contribution is not included in this work. An application is made to the four-ellipsoidal model of n-Ge under the conditions where elastic-acoustic phonon scattering is the predominant mechanism of scattering and the high-temperature limit of the phonon distribution is valid. The thermoelectric power (magneto-Seebeck effect) is found to increase with increasing values of the magnetic field except for a small region of low magnetic field values where it decreases in the longitudinal configuration only.     

Processing parameters and transport properties of vacuum evaporated CdSe thin films

Semiconducting thin films of cadmium selenide have been grown by conventional thermal evaporation technique on glass substrate. Films evaporated at substrate temperature equal 523 K are stoichiometric and homogeneous. Effect of various growth parameters like rate of deposition and substrate temperature on the electrical properties has been studied in details. Also, the annealed at 673 K under vacuum for 1 h films have been analyzed for resistivity and Hall effect.     

Fractality feature in incompressible three-dimensional magnetohydrodynamic turbulence

Direct Numerical Simulation (DNS) of decaying isotropic 3D magnetohydrodynamic (MHD) turbulence based on the 10243-modes in a periodic box is used to study the statistical properties of turbulence. In this paper, the presence of intermittency in MHD turbulence is investigated through the analysis of the Probability Distribution Function (PDF) for Elsässer fields and total energy fluctuations. We observe that the PDFs of the Elsässer fields fluctuations display a strong non-Gaussian behavior at small scale, which can be ascribed to multifractality feature, while the PDFs of the total energy fluctuations have the same shape over all observed scales and are monofractal. The PDFs have stretched exponential tail and satisfy the function P(|δX|) ～ exp(?A|δX| ^μ ). Numerically, we extract the exponent μ and find that it is constant for monofractal behavior as the length scale varies. To check the notion of self-similarity in the respective fluctuation, we apply the compensated structure functions.     

3D-pharmacophore study molecular docking and synthesis of pyrido[2,3-d]pyrimidine-4(1H) dione derivatives with in vitro potential anticancer and antioxidant activities

Some poly functionalized heterocyclic-compounds containing pyridine-moieties were readily assembled by combining differently functionalized pyridopyrimidine-6-carbonitrile derivatives 1a,b with different electrophilic and nucleophilic reagents via short synthetic routes. The structures of the prepared derivatives were ascertained from their-spectral-and elemental analyses. Some of the synthesized compounds were tested as plausible antitumor agents. Most of those tested compounds likes 7 , 9 , 10 , 11a showed cytotoxic potencies against different tumor cell lines. In addition, the assessments for their antioxidant activities have also been done and compound 9 exhibited the highest antioxidant activity while compounds 7 and 10 showed moderate activities. Finally, molecular docking studies were carried out which favorably indicated a high support for the experimental-results.