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We used Wang–Landau density of states Monte Carlo to study a binary Lennard-Jones glass-forming mixture in bulk and films between noninteracting walls. Thermodynamic properties are calculated using two different ensembles and film data are compared with the bulk. Bulk properties are in good agreement with previous simulations. We confirm the formation of a glass using various properties, e.g., energy, heat capacity, and pressure with temperature. We find a change in slope in the energy per particle and pressure as a function of temperature. We do not find any defined crystal structure. A higher glass transition temperature is found for the film. [ABSTRACT FROM AUTHOR]

We performed molecular dynamics simulations of the low-molecular weight organic glass former ortho-terphenyl in bulk and freestanding films. The main motivation is to provide molecular insight into the confinement effect without explicit interfaces. Based on earlier models of ortho-terphenyl we developed an atomistic model for bulk simulations. The model reproduces literature data both from simulations and experiments starting from specific volume and diffusivity to mean square displacement and radial distribution functions. After characterizing the bulk model we form freestanding films by the elongation and expansion method. These films give us the opportunity to study the dynamical heterogeneity near the glass transition through in-plane mobility and reorientation dynamics. We finally compare the model in bulk and under confinement. We found qualitatively a lower glass transition temperature for the freestanding film compared to the bulk. [ABSTRACT FROM AUTHOR]

The computational study of soft materials under confinement for bio- and nanotechnology still poses significant challenges but has come a long way in the last decade. It is possible to realistically model and understand the fundamental mechanisms which are at play if soft materials are confined to nanometer dimensions. Here, we present several recent examples of such studies. Thin polymer films are abundantly used as friction modifiers or steric stabilizers. We show how systematic modeling can shed light on the interplay between entropic and energetic interactions. Thin glassy films are critical for the success of nanolithography. For that we have to understand the effect of confinement on the glass transition behavior in order to guarantee the stability and integrity of the lithographic masks. Simulations aim to understand the fundamental differences in the densities of states of glass formers in bulk and under confinement. With the advent of bionanotechnology the structure and phase behavior of lipid membranes as models for cellular membranes at the nano scale length is of importance due to implications in understanding the role of the lipids in biochemical membrane processes. [ABSTRACT FROM AUTHOR]

Drug discovery and development is a costly and time-consuming endeavor (Calcoen et al. Nat Rev Drug Discov 14(3):161-162, 2015; The truly staggering cost of inventing new drugs. Forbes. http://www.forbes.com/sites/matthewherper/2012/02/10/the-truly-staggering-cost-of-inventing-new-drugs/, 2012; Scannell et al. Nat Rev Drug Discov 11(3):191-200, 2012). Over the last two decades, computational tools and in silico models to predict ADMET (Adsorption, Distribution, Metabolism, Excretion, and Toxicity) profiles of molecules have been incorporated into the drug discovery process mainly in an effort to avoid late-stage failures due to poor pharmacokinetics and toxicity. It is now widely recognized that ADMET issues should be addressed as early as possible in drug discovery. Here, we describe in detail how ADMET models can be developed and applied using a commercially available package, ADMET Predictor™ 7.2 (ADMET Predictor v7.2. Simulations Plus, Inc., Lancaster, CA, USA).

Purpose: Classical pharmacology allows the use and development of conventional phytomedicine faster and more economically than conventional drugs. This approach should be tested for their efficacy in terms of complementarity and disease control. The purpose of this study was to determine the molecular mechanisms by which nimbolide, a triterpenoid found in the well-known medicinal plant Azadirachta indica, controls glioblastoma growth., Experimental Design: Using in vitro signaling, anchorage-independent growth, kinase assays, and xenograft models, we investigated the mechanisms of its growth inhibition in glioblastoma., Results: We show that nimbolide or an ethanol soluble fraction of A. indica leaves (Azt) that contains nimbolide as the principal cytotoxic agent is highly cytotoxic against glioblastoma multiforme in vitro and in vivo. Azt caused cell-cycle arrest, most prominently at the G1-S stage in glioblastoma multiforme cells expressing EGFRvIII, an oncogene present in about 20% to 25% of glioblastoma multiformes. Azt/nimbolide directly inhibited CDK4/CDK6 kinase activity leading to hypophosphorylation of the retinoblastoma protein, cell-cycle arrest at G1-S, and cell death. Independent of retinoblastoma hypophosphorylation, Azt also significantly reduced proliferative and survival advantage of glioblastoma multiforme cells in vitro and in tumor xenografts by downregulating Bcl2 and blocking growth factor-induced phosphorylation of Akt, extracellular signal-regulated kinase 1/2, and STAT3. These effects were specific because Azt did not affect mTOR or other cell-cycle regulators. In vivo, Azt completely prevented initiation and inhibited progression of glioblastoma multiforme growth., Conclusions: Our preclinical findings demonstrate nimbolide as a potent anti-glioma agent that blocks cell cycle and inhibits glioma growth in vitro and in vivo.