Open-Source Browser-Based Tools for Structure-Based Computer-Aided Drug Discovery

We here outline the importance of open-source, accessible tools for computer-aided drug discovery (CADD). We begin with a discussion of drug discovery in general to provide context for a subsequent discussion of structure-based CADD applied to small-molecule ligand discovery. Next, we identify usability challenges common to many open-source CADD tools. To address these challenges, we propose a browser-based approach to CADD tool deployment in which CADD calculations run in modern web browsers on users’ local computers. The browser app approach eliminates the need for user-initiated download and installation, ensures broad operating system compatibility, enables easy updates, and provides a user-friendly graphical user interface. Unlike server apps—which run calculations “in the cloud” rather than on users’ local computers—browser apps do not require users to upload proprietary information to a third-party (remote) server. They also eliminate the need for the difficult-to-maintain computer infrastructure required to run user-initiated calculations remotely. We conclude by describing some CADD browser apps developed in our lab, which illustrate the utility of this approach. Aside from introducing readers to these specific tools, we are hopeful that this review highlights the need for additional browser-compatible, user-friendly CADD software.     

Flexible active matrix addressed displays manufactured by printing and coating techniques

A flexible electrochromic active matrix addressed display, including 8 × 8 pixels, is demonstrated by using solution processing based on standard printing and coating manufacturing techniques. Each organic electrochromic display (OECD) pixel and its corresponding organic electrochemical transistor (OECT) are located on different sides of the flexible PET substrate. Electronic vias generated through the plastic substrate connects each OECD pixel with one addressing OECT. When comparing this display with actively addressed OECDs with all its components located on the same side, the present approach based on this electronic via substrate provides an enhanced pixel resolution and a relatively more simplified manufacturing process. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012     

Synthesis and anti-leukaemic activity of pyrrolo[3,2,1-hi]indole-1,2-diones,pyrrolo[3,2,1-ij]quinoline-1,2-diones and other polycyclic isatin derivatives

To further expand the structure–cytotoxic activity relationships of isatin derivatives and to reduce flexibility in substituent groups at nitrogen, 20 analogues incorporating a ring system between the N1 and C7 atoms of isatin were prepared using a variety of synthetic strategies. This yielded pyrroloindole-, pyrroloquinoline-, pyrroloacridine-, pyrrolophenanthridine- and benzopyrrolophenanthridine-based systems with embedded isatin moieties, the latter possessing a novel carbon skeleton. These compounds were subsequently assessed for their in vitro cytotoxicity against human U937 lymphoma cells, with the brominated pyrroloacridine dione 27 showing the most promising activity (IC₅₀ 3.01 μM) after 24 h.     

Transformation of macromonomers into ring‐opening polymerization macroinitiators: A detailed initiation efficiency study

In the present study, n‐butyl acrylate macromonomer (BAMM) (M_n = 1900 g mol^?1; PDI = 1.96) has been synthesized via a high‐temperature polymerization process. Subsequently, the olefinic termini of the BAMM have been transformed into a diol via a dihydroxylation process using KMnO₄ as an oxidizing agent. The OH‐terminated macroinitiator pBA(OH)₂ has subsequently been employed for the ring‐opening polymerization (ROP) of ε‐caprolactone via various catalytic systems, that is, organo‐(1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene), metal (tin(II) 2‐ethylhexanoate), and enzymatic catalysis (Novozym® 435). The obtained pBA‐b‐pCL block copolymers and the initiation efficiency of the BAMM macroinitiator have been investigated via size exclusion chromatography (SEC), electrospray ionization–mass spectrometry (ESI‐MS) hyphenated with SEC and liquid chromatography at the critical conditions of both poly(ε‐caprolactone) (pCL) and pBA. The in vitro enzyme catalysis (eROP) approach proved to be the most efficient catalysis system due to minor transesterification side reactions during the polymerization process. However, side reactions such as transesterifications occur in each catalytic system and—while they cannot be suppressed—they can be minimized. The species generated during the eROP process include the desired block copolymer pBA‐b‐pCL as main species as well as pCL homopolymer and residual macroinitiator pBA(OH)₂. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Contribution a L'etude de melanges susceptibles de former des microemulsions selon leurs compositions,par la definition de leurs comportements dielectriques a 9,455 GHz

The dielectric studies of four components mixtures are rarely made on a great deal of concentrations. The authors propose a dielectric behavior study of mixtures made with toluene-water-butanol-SDS, from specific mappings of permittivities which are plotted on pseudo ternary diagrams at 9.455 GHz. They draw different conclusions to know how at 9.455 GHz the variations of real and imaginary parts of permittivity involve the concentration of each component and the structure of the mixture.These conclusions will be perfected by studies made at other frequencies and by spectral analysis of each mixture.     

Wavelet filtering to study mixing in 2D isotropic turbulence

This paper presents the application of coherent vortex simulation (CVS) filtering, based on an orthogonal wavelet decomposition of vorticity, to study mixing in 2D homogeneous isotropic turbulent flows. The Eulerian and Lagrangian dynamics of the flow are studied by comparing the evolution of a passive scalar and of particles advected by the coherent and incoherent velocity fields, respectively. The former is responsible for strong mixing and produces the same anomalous diffusion as the total flow, due to transport by the coherent vortices, while mixing in the latter is much weaker and corresponds to classical diffusion.     

The Yamabe problem for almost Hermitian manifolds

The conformal class of a Hermitian metric g on a compact almost complex manifold (M^2m, J) consists entirely of metrics that are Hermitian with respect to J. For each one of these metrics, we may define a J-twisted version of the Ricci curvature, the J-Ricci curvature, and its corresponding trace, the J-scalar curvature s^J. We ask if the conformal class of g carries a metric with constant s^J, an almost Hermitian version of the usual Yamabe problem posed for the scalar curvature s. We answer our question in the affirmative. In fact, we show that (2m−1)s^J−s=2(2m−1)W(ω, ω), where W is the Weyl tensor and ω is the fundamental form of g. Using techniques developed for the solution of the problem for s, we construct an almost Hermitian Yamabe functional and its corresponding conformal invariant. This invariant is bounded from above by a constant that only depends on the dimension of M, and when it is strictly less than the universal bound, the problem has a solution that minimizes the almost complex Yamabe functional. By the relation above, we see that when W (ω, ω) is negative at least one point, or identically zero, our problem has a solution that minimizes the almost Hermitian Yamabe functional, and the universal bound is reached only in the case of the standard 6-sphere equipped with a suitable almost complex structure. When W(ω, ω) is non-negative and not identically zero, we prove that the conformal invariant is strictly less than the universal bound, thus solving the problem for this type of manifolds as well. We discuss some applications.     

Symmetric and Rees algebras of Koszul cycles and their Gröbner bases

In this paper we study the symmetric algebra S(E _i ) and Rees algebra R(E _i ) of the modules E _i of i-cycles of the Koszul complex associated with the sequence of indeterminates of a polynomial ring . For i=2 and i=n–2 we show that is a d-sequence on S(E _i ) and R(E _i ) and we determine Gröbner bases and Sagbi bases related to these algebras. Mathematics Subject Classification (2000):13A30, 13D02, 13H10, 13P10The second author is grateful to the National Natural Science Foundation of China for support.Part of this work was made while the third author was visiting the Fachbereich Mathematik und Informatik der Universität Essen, to which he would like to thank for its hospitality.     

A note on extremal metrics of non-constant scalar curvature

By working in ? ⁿ with potentials of the forma logu + s(u), u the square of the distant to the origin, we obtain extremal Kähler metrics of nonconstant scalar curvature on the blow-up of ? ⁿ at \(\vec 0\) . We then show that these metrics can be completed at ∞ by adding a ?? ^n?1, and reobtain the extremal Kähler metrics of non-constant scalar curvature constructed by Calabi on the blow-up of ?? ⁿ at one point. A similar construction produces this type of metrics on other bundles over ?? ^{n ? 1}.