Novel 5-oxo-hexahydroquinoline derivatives: design, synthesis, in vitro P-glycoprotein-mediated multidrug resistance reversal profile and molecular dynamics simulation study

Overexpression of the efflux pump P-glycoprotein (P-gp) is one of the important mechanisms of multidrug resistance (MDR) in many tumor cells. In this study, 26 novel 5-oxo-hexahydroquinoline derivatives containing different nitrophenyl moieties at C-4 and various carboxamide substituents at C-3 were designed, synthesized and evaluated for their ability to inhibit P-gp by measuring the amount of rhodamine 123 (Rh123) accumulation in uterine sarcoma cells that overexpress P-gp (MES-SA/Dx5) using flow cytometry. The effect of compounds with highest MDR reversal activities was further evaluated by measuring the alterations of MES-SA/Dx5 cells' sensitivity to doxorubicin (DXR) using MTT assay. The results of both biological assays indicated that compounds bearing 2-nitrophenyl at C-4 position and compounds with 4-chlorophenyl carboxamide at C-3 demonstrated the highest activities in resistant cells, while they were devoid of any effect in parental nonresistant MES-SA cells. One of the active derivatives, 5c, significantly increased intracellular Rh123 at 100 mu M, and it also significantly reduced the IC50 of DXR by 70.1% and 88.7% at 10 and 25 mu M, respectively, in MES-SA/Dx5 cells. The toxicity of synthesized compounds against HEK293 as a noncancer cell line was also investigated. All tested derivatives except for 2c compound showed no cytotoxicity. A molecular dynamics simulation study was also performed to investigate the possible binding site of 5c in complex with human P-gp, which showed that this compound formed 11 average H-bonds with Ser909, Thr911, Arg547, Arg543 and Ser474 residues of P-gp. A good agreement was found between the results of the computational and experimental studies. The findings of this study show that some 5-oxo-hexahydroquinoline derivatives could serve as promising candidates for the discovery of new agents for P-gp-mediated MDR reversal

Effect of the Heterogeneity of Metamaterials on Casimir-Lifshitz Interaction

The Casimir-Lifshitz interaction between metamaterials is studied using a model that takes into account the structural heterogeneity of the dielectric and magnetic properties of the bodies. A recently developed perturbation theory for the Casimir-Lifshitz interaction between arbitrary material bodies is generalized to include non-uniform magnetic permeability profiles, and used to study the interaction between the magneto-dielectric heterostructures within the leading order. The metamaterials are modeled as two dimensional arrays of domains with varying permittivity and permeability. In the case of two semi-infinite bodies with flat boundaries, the patterned structure of the material properties is found to cause the normal Casimir-Lifshitz force to develop an oscillatory behavior when the distance between the two bodies is comparable to the wavelength of the patterned features in the metamaterials. The non-uniformity also leads to the emergence of lateral Casimir-Lifshitz forces, which tend to strengthen as the gap size becomes smaller. Our results suggest that the recent studies on Casimir-Lifshitz forces between metamaterials, which have been performed with the aim of examining the possibility of observing the repulsive force, should be revisited to include the effect of the patterned structure at the wavelength of several hundred nanometers that coincides with the relevant gap size in the experiments.Comment: 9 pages, 13 figures. Rewriting equations (10) and (12) and increasing the size of the lettering/numeral in figure

Interpretation of the large-deformation high-spin bands in select A=158-168 nuclei

The high-spin rotational bands in Hf-168 and the triaxial bands in Lu nuclei are analyzed using the configuration-constrained cranked Nilsson-Strutinsky (CNS) model. Special attention is given to the up-sloping extruder orbitals. The relative alignment between the bands which appear to correspond to triaxial shape is also considered, including the yrast ultrahigh-spin band in Er-158. This comparison suggests that the latter band is formed from rotation around the intermediate axis. In addition, the standard approximations of the CNS approach are investigated, indicating that the errors which are introduced by the neglect of off-shell matrix elements and the cutoff at nine oscillator shells (N-max = 8) are essentially negligible compared to other uncertainties. On the other hand, the full inclusion of the hexadecapole degree of freedom is more significant; for example it leads to a decrease of the total energy of similar to 500 keV in the triaxial superdeformed (TSD) region of Hf-168

An enhanced physics-based model to estimate the displacement of piezoelectric actuators

Piezoelectric actuators are the foremost actuators in the area of nanopositioning. However, the sensors employed to measure the actuator displacement are expensive and difficult, if not impossible, to use. Mathematical models can map the easy-to-measure electrical signals to the displacements of the actuators as the displacement sensors are replaced with the models. In addition, these models can be used in model-based control system design. Two main groups of mathematical models are used for this purpose: black box and physics-based models. As an advantage, the latter has a much smaller number of parameters reducing computational demand in real-time applications. However, physics-based models suffer from (1) the relatively low accuracy of the models and (2) non-standard and ad-hoc parameter identification methods. In this research, to improve the model accuracy, mathematical structure of a well-known physics-based model, the Voigt model, is enhanced by adding two complementary terms inspired by another model, the Preisach model. Then, a standard method based on the evolutionary algorithms is proposed to identify the model’s parameters. The proposed ideas are substantiated to increase the applicability and accuracy of the model, and they are easily extendable to other physics-based models of piezoelectric actuators. The newly proposed enhanced structure of the Voigt model doubles the estimation accuracy of the original model and results in accuracies comparable with black box models.Narges Miri, Morteza Mohammadzaheri and Lei Che

Lagrangian perturbation theory for a superfluid immersed in an elastic neutron star crust

The inner crust of mature neutron stars, where an elastic lattice of neutron-rich nuclei coexists with a neutron superfluid, impacts on a range of astrophysical phenomena. The presence of the superfluid is key to our understanding of pulsar glitches, and is expected to affect the thermal conductivity and hence the evolution of the surface temperature. The coupling between crust and superfluid must also be accounted for in studies of neutron star dynamics, discussions of global oscillations and associated instabilities. In this paper we develop Lagrangian perturbation theory for this problem, paying attention to key issues like superfluid entrainment, potential vortex pinning, dissipative mutual friction and the star's magnetic field. We also discuss the nature of the core-crust interface. The results provide a theoretical foundation for a range of interesting astrophysical applications.Comment: 13 pages, no figures, to appear in MNRA

Neurocognitive outcome after preterm birth: Interest of the follow-up and the systematic evaluation

ObjectivePreterm children can experience cognitive and behavioral difficulties being able to be responsible for school difficulties going to the academic failure. The aim of this study was to assess the cognitive process while insisting on the early screening from the preschool age.MethodsThe data arise from the study of files and from the neuropsychological evaluations realized with the premature children followed in a regular way to the service. The premature children with or without motor disabilities more 4 and a half-years, old deficit integrated pre-school and ordinary school were included. The children with severe disabilities in upper limbs and the children having a mental deficiency were excluded.Results30 middle-aged children 7 years 5 months have been included. The prematurity is between 27–34. The born term has an effect on the performances in particular on attention and visuo-spatial capacities.ConclusionThe prematurity is a risk factor of the school future of the child. There is specially a negative impact on visuo-spatial and visuo-motor processes and those children present social and behavioral difficulties. It is mandatory to include the neuropsychological evaluation in any follow-up of premature child thanks to tests validated in the Tunisian context. It remains of great importance to identify effective interventions to improve the long-term neurocognitive outcomes

Experimental Measurement of the Berry Curvature from Anomalous Transport

Geometrical properties of energy bands underlie fascinating phenomena in a wide-range of systems, including solid-state materials, ultracold gases and photonics. Most famously, local geometrical characteristics like the Berry curvature can be related to global topological invariants such as those classifying quantum Hall states or topological insulators. Regardless of the band topology, however, any non-zero Berry curvature can have important consequences, such as in the semi-classical evolution of a wave packet. Here, we experimentally demonstrate for the first time that wave packet dynamics can be used to directly map out the Berry curvature. To this end, we use optical pulses in two coupled fibre loops to study the discrete time-evolution of a wave packet in a 1D geometrical "charge" pump, where the Berry curvature leads to an anomalous displacement of the wave packet under pumping. This is both the first direct observation of Berry curvature effects in an optical system, and, more generally, the proof-of-principle demonstration that semi-classical dynamics can serve as a high-resolution tool for mapping out geometrical properties

Star Formation in the Interacting Pair NGC7733/34

The problem of star formation within the interacting pair NGC7733/34 has been studied, based on the UBVRI photometry of the source. The distribution of the colors of selected regions within the galaxies is used to infer an estimate for the age distribution of the star forming regions. The results seem to indicate the presence of numerous extended young star-forming regions in the disk of one of the two galaxies, NGC 7733, with ages in the range of $10^6$--$10^8$ yr. However, there exist no evidence for any violent star formation activity, in the past $10^8$ yr, in the nuclei of the two galaxies. The pair seems to be a merger bound system with the brightest, youngest, site of star forming activity lying at the disk interface.Comment: Accepted for publication in Astronomical Journa