Targeting oncogenic protein-protein interactions by diversity oriented synthesis and combinatorial chemistry approaches

We are currently witnessing a decline in the development of efficient new anticancer drugs, despite the salient efforts made on all fronts of cancer drug discovery. This trend presumably relates to the substantial heterogeneity and the inherent biological complexity of cancer, which hinder drug development success. Protein-protein interactions (PPIs) are key players in numerous cellular processes and aberrant interruption of this complex network provides a basis for various disease states, including cancer. Thus, it is now believed that cancer drug discovery, in addition to the design of single-targeted bioactive compounds, should also incorporate diversity-oriented synthesis (DOS) and other combinatorial strategies in order to exploit the ability of multi-functional scaffolds to modulate multiple protein-protein interactions (biological hubs). Throughout the review, we highlight the chemistry driven approaches to access diversity space for the discovery of small molecules that disrupt oncogenic PPIs, namely the p53-Mdm2, Bcl-2/Bcl-xL-BH3, Myc-Max, and p53-Mdmx/Mdm2 interactions.     

Special issue on global flow instability and control

This special issue is intended to provide a snapshot of current research in the area of ??Global Flow Instability and Control??. The original papers, and to a certain extent the topic itself, are intimately linked with the series of symposia by the same name that were held in Crete, Greece, between 2001 and 2009. As members of the organizing committees of the Crete symposia, we invited all past participants to contribute, and all papers were reviewed following the strict standards of the journal. This preface gives a brief historical account of events that have shaped ideas in the field over the past decade, followed by a synopsis of the papers published herein.     

Efficient Lagrangian scalar tracking method for reactive local mass transport simulation through porous media

Mass transfer in the presence of chemical reactions for flows through porous media is of interest to many disciplines. The Lattice Boltzmann method (LBM) is particularly attractive in such cases due to the ease with which it handles complicated boundary conditions. However, useful Lagrangian information (such as solute survival distance, effective diffusivity, collision frequency) is challenging to obtain from the LBM. In this paper, we present a straightforward and efficient Lagrangian methodology (Lagrangian scalar tracking, LST) for performing solute transport simulations in the presence of heterogeneous, first‐order, irreversible reactions, based on a velocity field obtained from LBM. The hybrid LST/LBM technique tracks passive mass markers that have two contributions to their movement: convective (obtained through interpolation of a previously obtained velocity field) and Brownian. Various Schmidt number solutes and different solute release modes can be modeled with a single solvent flow field using this method. Moreover, the mass markers can have a range of reaction rate coefficients. This allows for the exploration of the whole spectrum of first‐order heterogeneous reaction rates with just a single simulation. In order to show the applicability of the LST/LBM scheme, results from a case study are presented in which the consumption of oxygen and/or nutrients within a porous bone tissue engineering scaffold is modeled under flow perfusion culturing conditions. Although the reactive LST methodology described in this paper compliments the LBM, it can also be used with any other flow simulation that can generate the velocity field. Copyright © 2010 John Wiley & Sons, Ltd.     

Photonic nanojets as three-dimensional optical atom traps: A theoretical study

We show that an efficient three-dimensional optical atom trap can be achieved by light scattered off a dielectric microsphere. Namely, under suitable conditions, a plane wave incident on a polymer sphere produces a focal point in the forward scattering direction known as photonic nanojet. The photonic nanojet is formed at a distance of a few micrometers away from the surface of the sphere wherein the Casimir–Polder interaction felt by an atom is negligible compared to the optical and gravitational potentials. When many polymer spheres are brought together so as to form a linear chain, a one-dimensional periodic optical lattice filled with cold atoms is possible since interference between the incident and scattered beams is minimal when the spheres are not too close.     

A Numerical Method for 2-D Bed Morphology Calculations

A fully coupled two-dimensional sub-critical and/or supercritical, free-surface flow numerical model is developed to calculate bed variations in alluvial channels. Vertically averaged free-surface flow equations in conjunction with sediment transport equation are numerically solved using an explicit finite-volume scheme in integral form. The capabilities of the proposed method are first demonstrated by analyzing supercritical flow in an expansion channel. Thereafter, one and two-dimensional applications referring to aggradation and scouring are reported. For each of these test cases, computed results compare satisfactorily with measurements as well as with other numerical solutions. The method is stable, reliable and accurate, although time consuming, handling a variety of sediment transport equations with rapid changes of sediment transport at the boundaries.     

A new family of octanuclear Mn complexes with a rod-like topology

Three new octanuclear compounds were prepared from reactions of [Mn(O₂CR)₂]·2H₂O (R = Et or Ph) with the diols 1,3-propanediol (pdH₂) or 2-methyl-1,3-propanediol (mpdH₂) in the presence of NaN₃. All three compounds [Mn₈(N₃)₄(O₂CR)₆(L)₄(py)₆] (L = pd²⁻, R = Et 1; L = mpd²⁻, R = Et 2; L = pd²⁻, R = Ph 3) (py = pyridine) possess a novel near-planar, rod-like topology. Dc and ac magnetic susceptibility studies in the 2–300 K range for complexes 1 and 2 revealed the presence of dominant antiferromagnetic exchange interactions, leading to diamagnetic ground spin states.     

Time distribution of adsorption entropy of gases on heterogeneous surfaces by reversed-flow gas chromatography

The reversed-flow gas chromatography (RF-GC) technique has been applied to measure the adsorption entropy over time, when gaseous pentane is adsorbed on the surface of two solids (gamma-alumina and a silica supported rhodium catalyst) at 393.15 and 413.15K, respectively. Utilizing experimental chromatographic data, this novel methodology also permits the simultaneous measurement of the local adsorption energy, epsilon, local equilibrium adsorbed concentration, c(s)(*), and local adsorption isotherm, theta(p, T, epsilon) in a time resolved way. In contrast with other inverse gas chromatographic methods, which determine the standard entropy at zero surface coverage, the present method operates over a wide range of surface coverage taking into account not only the adsorbate-adsorbent interaction, but also the adsorbate-adsorbate interaction. One of the most interesting observations of the present work is the fact that the interaction of n-pentane is spontaneous on the Rh/SiO(2) catalyst for a very short time interval compared to that on gamma-Al(2)O(3). This can explain the different kinetic behavior of each particular gas-solid system, and it can be attributed to the fact that large amounts of n-C(5)H(12) are present on the active sites of the Rh/SiO(2) catalyst compared to those on gamma-Al(2)O(3), as the local equilibrium adsorbed concentration values, c(s)(*), indicate.     

Sign of the refractive index in lossy metamaterials

One of the criteria for determining the existence of negative index of refraction in artificial electromagnetic structures (metamaterials) is the occurrence of opposite directions of the group and phase velocities. In this work, we study specific examples of metamaterials where we show that the above criterion does not hold when losses are taken into account and dominate the interaction of light with the metamaterial. The structure are three-dimensional superlattices of consisting of plasmonic and polaritonic particles and are studied by a rigorous multiple-scattering theory and effective-medium approximation.