Insights into the mechanims underlyng the antiproliferative potential of a Co(II) coordination compound bearing 1,10-Phenanthroline-5,6-Dione: DNA and protein interaction studies

The very high antiproliferative activity of [Co(Cl)(H2O)(phendione)(2)][BF4] (phendione is 1,10-phenanthroline-5,6-dione) against three human tumor cell lines (half-maximal inhibitory concentration below 1 mu M) and its slight selectivity for the colorectal tumor cell line compared with healthy human fibroblasts led us to explore the mechanisms of action underlying this promising antitumor potential. As previously shown by our group, this complex induces cell cycle arrest in S phase and subsequent cell death by apoptosis and it also reduces the expression of proteins typically upregulated in tumors. In the present work, we demonstrate that [Co(Cl)(phendione)(2)(H2O)][BF4] (1) does not reduce the viability of nontumorigenic breast epithelial cells by more than 85 % at 1 mu M, (2) promotes the upregulation of proapoptotic Bax and cell-cycle-related p21, and (3) induces release of lactate dehydrogenase, which is partially reversed by ursodeoxycholic acid. DNA interaction studies were performed to uncover the genotoxicity of the complex and demonstrate that even though it displays K (b) (+/- A standard error of the mean) of (3.48 +/- A 0.03) x 10(5) M-1 and is able to produce double-strand breaks in a concentration-dependent manner, it does not exert any clastogenic effect ex vivo, ruling out DNA as a major cellular target for the complex. Steady-state and time-resolved fluorescence spectroscopy studies are indicative of a strong and specific interaction of the complex with human serum albumin, involving one binding site, at a distance of approximately 1.5 nm for the Trp214 indole side chain with log K (b) similar to 4.7, thus suggesting that this complex can be efficiently transported by albumin in the blood plasma.

Three-dimensial patchy lattice model: Ring formation and phase separation

We investigate the structural and thermodynamic properties of a model of particles with 2 patches of type A and 10 patches of type B. Particles are placed on the sites of a face centered cubic lattice with the patches oriented along the nearest neighbor directions. The competition between the self- assembly of chains, rings, and networks on the phase diagram is investigated by carrying out a systematic investigation of this class of models, using an extension ofWertheim's theory for associating fluids and Monte Carlo numerical simulations. We varied the ratio r epsilon(AB)/epsilon(AA) of the interaction between patches A and B, epsilon(AB), and between A patches, epsilon(AA) (epsilon(BB) is set to theta) as well as the relative position of the A patches, i.e., the angle. between the (lattice) directions of the A patches. We found that both r and theta (60 degrees, 90 degrees, or 120 degrees) have a profound effect on the phase diagram. In the empty fluid regime (r < 1/2) the phase diagram is reentrant with a closed miscibility loop. The region around the lower critical point exhibits unusual structural and thermodynamic behavior determined by the presence of relatively short rings. The agreement between the results of theory and simulation is excellent for theta = 120 degrees but deteriorates as. decreases, revealing the need for new theoretical approaches to describe the structure and thermodynamics of systems dominated by small rings. (C) 2014 AIP Publishing LLC.

Three-Dimensional patchy lattice model for empty fluids

The phase diagram of a simple model with two patches of type A and ten patches of type B (2A10B) on the face centred cubic lattice has been calculated by simulations and theory. Assuming that there is no interaction between the B patches the behavior of the system can be described in terms of the ratio of the AB and AA interactions, r. Our results show that, similarly to what happens for related off-lattice and two-dimensional lattice models, the liquid-vapor phase equilibria exhibit reentrant behavior for some values of the interaction parameters. However, for the model studied here the liquid-vapor phase equilibria occur for values of r lower than 1/3, a threshold value which was previously thought to be universal for 2AnB models. In addition, the theory predicts that below r = 1/3 (and above a new condensation threshold which is < 1/3) the reentrant liquid-vapor equilibria are so extreme that it exhibits a closed loop with a lower critical point, a very unusual behavior in single-component systems. An order-disorder transition is also observed at higher densities than the liquid-vapor equilibria, which shows that the liquid-vapor reentrancy occurs in an equilibrium region of the phase diagram. These findings may have implications in the understanding of the condensation of dipolar hard spheres given the analogy between that system and the 2AnB models considered here.

Two-loop stability of a complex singlet extended Standard Model

Motivated by the dark matter and the baryon asymmetry problems, we analyze a complex singlet extension of the Standard Model with a Z(2) symmetry (which provides a dark matter candidate). After a detailed two-loop calculation of the renormalization group equations for the new scalar sector, we study the radiative stability of the model up to a high energy scale (with the constraint that the 126 GeV Higgs boson found at the LHC is in the spectrum) and find it requires the existence of a new scalar state mixing with the Higgs with a mass larger than 140 GeV. This bound is not very sensitive to the cutoff scale as long as the latter is larger than 10(10) GeV. We then include all experimental and observational constraints/measurements from collider data, from dark matter direct detection experiments, and from the Planck satellite and in addition force stability at least up to the grand unified theory scale, to find that the lower bound is raised to about 170 GeV, while the dark matter particle must be heavier than about 50 GeV.

Railway vehicle modelling for the vehicle-track interaction compatibility analysis

Railway vehicle homologation, with respect to running dynamics, is addressed via dedicated norms. The results required, such as, accelerations and/or wheel-rail contact forces, obtained from experimental tests or simulations, must be available. Multibody dynamics allows the modelling of railway vehicles and their representation in real operations conditions, being the realism of the multibody models greatly influenced by the modelling assumptions. In this paper, two alternative multibody models of the Light Rail Vehicle 2000 (LRV) are constructed and simulated in a realistic railway track scenarios. The vehicle-track interaction compatibility analysis consists of two stages: the use of the simplified method described in the norm "UIC 518-Testing and Approval of Railway Vehicles from the Point of View of their Dynamic Behaviour-Safety-Track Fatigue-Running Behaviour" for decision making; and, visualization inspection of the vehicle motion with respect to the track via dedicated tools for understanding the mechanisms involved.

Algebraic structure for interaction on mixed models

Binary operations on commutative Jordan algebras, CJA, can be used to study interactions between sets of factors belonging to a pair of models in which one nests the other. It should be noted that from two CJA we can, through these binary operations, build CJA. So when we nest the treatments from one model in each treatment of another model, we can study the interactions between sets of factors of the first and the second models.