Sensitization of MCF7 Cells with High Notch1 Activity by Cisplatin and Histone Deacetylase Inhibitors Applied Together

Histone deacetylase inhibitors (HDIs) are promising anti-cancer agents that inhibit proliferation of many types of cancer cells including breast carcinoma (BC) cells. In the present study, we investigated the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two HDIs, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), in luminal-like BC cells. The type of drug–drug interaction between CDDP and HDIs was determined by isobolographic analysis. MCF7 cells were genetically modified to express differential levels of Notch1 activity. The cytotoxic effect of SAHA or VPA was higher on cells with decreased Notch1 activity and lower for cells with increased Notch1 activity than native BC cells. The isobolographic analysis demonstrated that combinations of CDDP with SAHA or VPA at a fixed ratio of 1:1 exerted additive or additive with tendency toward synergism interactions. Therefore, treatment of CDDP with HDIs could be used to optimize a combined therapy based on CDDP against Notch1-altered luminal BC. In conclusion, the combined therapy of HDIs and CDDP may be a promising therapeutic tool in the treatment of luminal-type BC with altered Notch1 activity.     

Preparation and characterization of proton‐exchange hybrid membranes

Two types of composite were prepared, based on a thermoplastic polymer, polyvinylidene fluoride (PVDF), and an elastomer, ethylene‐propylene‐diene terpolymer (EPDM), respectively. We obtained both series by addition of an inorganic proton‐conducting antimonic acid derivative (HSb) and polystyrene crosslinked with a small percentage of divinylbenzene (PS‐co‐DVB). From these composites, membranes were obtained and subjected to a heterogeneous‐phase sulfonation reaction with chlorosulfonic acid. All experimental materials were characterized from a morphological and electrical point of view, by means of techniques such as differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), non‐isothermal crystallization and complex impedance analysis. Copyright © 2005 Society of Chemical Industry     

Ionomer composites based on sepiolite/hydrogenated poly(styrene butadiene) block copolymer systems

Ionomeric composites based on sepiolite and hydrogenated poly(styrene butadiene) block copolymer were obtained and characterized from a microstructural and electrical point of view. Before blending, because of the high silanol group concentration in the sepiolite, the latter could be organophilized with suitable coupling agents. The resulting materials were easily processed into thin films or membranes 0.2–0.4 mm thick, their conductivity in some cases approaching 10^?1 S/cm. Their suitability for film formation and good electrical properties indicate potential applications as electrolytes in polymer fuel cells. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 3512–3519, 2002     

An expert PID controller uses refined ziegler and nichols rules and fuzzy logic ideas

This article proposes a scheme for the on-line adjustment of three mode controller settings based on experimental measurements of closed-loop performance. It uses a recently developed heuristic tuning procedure to identify estimated process parameters. This method may give rise to conflicting estimates. Fuzzy Set theory is applied to manage the situation in terms of a fuzzy conjunction to combine the various estimates. PID control was chosen because of its wide use in the industrial environment due to driving simplicity and robustness. The article shows design, development, and computer simulation aspects.     

Optimization techniques for curved path computing

Participating media with an inhomogeneous index of refraction make light follow curved paths. Simulating this in a global illumination environment has usually been neglected due to the complexity of the calculations involved, sacrificing accurate physical simulations for efficient visual results. This paper aims to simulate non-linear media in a more reasonable time than previous works without losing physical correctness. Accuracy is achieved by solving the Eikonal equation of geometrical optics, which describes the path followed by a light beam that traverses a non-linear medium. This equation is used in the context of a photon mapping extension.     

Total Energy Shaping Control of Mechanical Systems: Simplifying the Matching Equations Via Coordinate Changes

Total energy shaping is a controller design methodology that achieves (asymptotic) stabilization of mechanical systems endowing the closed-loop system with a Lagrangian or Hamiltonian structure with a desired energy function - that qualifies as Lyapunov function for the desired equilibrium. The success of the method relies on the possibility of solving two PDEs which identify the kinetic and potential energy functions that can be assigned to the closed loop. Particularly troublesome is the partial differential equation (PDE) associated to the kinetic energy which is nonlinear and inhomogeneous and the solution, that defines the desired inertia matrix, must be positive-definite. In this note, we prove that we can eliminate or simplify the forcing term in this PDE by modifying the target dynamics and introducing a change of coordinates in the original system. Furthermore, it is shown that, in the particular case of transformation to the Lagrangian coordinates, the possibility of simplifying the PDEs is determined by the interaction between the Coriolis and centrifugal forces and the actuation structure. The examples of pendulum on a cart and Furuta's pendulum are used to illustrate the results.     

Thermodynamic compatibility of sepiolite-filled poly(vinylidene fluoride)-polystyrene blends

Summary Inverse gas chromatography (IGC) and differential scanning calorimetry (DSC) were used to investigate the effect produced by sepiolite on the thermodynamical compatibility of poly(vinylidene fluoride)-polystyrene blends. Polymer-polymer interaction parameters were calculated from the retention data, for various polar and non-polar probes in pure and mixed stationary phases of these polymers, using sepiolite as solid support, as well as from melting point depression analysis of the sepiolite filled blends. Both techniques give us positive values of the interaction parameters, in accordance with the non-compatibility of these blends; However negative values of the interaction parameters were obtained for polystyrene-rich blends (_PS 85 wt%) and high sepiolite loadings, indicating that sepiolite acts as a compatibilizing agent for the system PVF₂/PS.     

Differential Action of Connexin Hemichannel and Pannexin Channel Therapeutics for Potential Treatment of Retinal Diseases

Dysregulation of retinal function in the early stages of light-induced retinal degeneration involves pannexins and connexins. These two types of proteins may contribute to channels that release ATP, leading to activation of the inflammasome pathway, spread of inflammation and retinal dysfunction. However, the effect of pannexin channel block alone or block of both pannexin channels and connexin hemichannels in parallel on retinal activity in vivo is unknown. In this study, the pannexin channel blocker probenecid and the connexin hemichannel blocker tonabersat were used in the light-damaged rat retina. Retinal function was evaluated using electroretinography (ERG), retinal structure was analyzed using optical coherence tomography (OCT) imaging and the tissue response to light-induced injury was assessed immunohistochemically with antibodies against glial fibrillary acidic protein (GFAP), Ionized calcium binding adaptor molecule 1 (Iba-1) and Connexin43 (Cx43). Probenecid did not further enhance the therapeutic effect of connexin hemichannel block in this model, but on its own improved activity of certain inner retina neurons. The therapeutic benefit of blocking connexin hemichannels was further evaluated by comparing these data against results from our previously published studies that also used the light-damaged rat retina model. The analysis showed that treatment with tonabersat alone was better than probenecid alone at restoring retinal function in the light-damaged retina model. The results assist in the interpretation of the differential action of connexin hemichannel and pannexin channel therapeutics for potential treatment of retinal diseases.