Electrical detection of amine ligation to a metalloporphyrin via a hybrid SOI-MOSFET

A close-packed monolayer of zinc 5,10,15,20-tetrakis(3-carboxyphenyl)porphyrin has been prepared and deposited on the thin native oxide covering the surface of an SOI-MOSFET (silicon-on-insulator metal-oxide-semiconductor field effect transistor) using Langmuir-Blodgett techniques. When the device is exposed to amine vapors in a nitrogen atmosphere, the amine coordinates to the zinc atom. The resulting change in electron distribution within the porphyrin leads to a large change in the drain current of the transistor, biased via a back gate. This change is sensitive to both the amount of amine present and the base strength of the amine. Only very small changes in drain current were observed with a monolayer of free base porphyrin or palmitic acid. After exposure to high pyridine concentrations, the device response saturates, but partially recovers after overnight exposure to flowing nitrogen gas. Interestingly, the device response is instantaneously reset by exposure to visible light, suggesting that photode-ligation occurs. An electrical model for the hybrid device that describes its response to ligand binding in terms of a change in the work function of the porphyrin monolayer has been developed. A transistor response to a few hundred attomoles of bound pyridine can be readily detected. This extreme sensitivity, coupled with the ability to reset the device using light, suggests that such systems might be useful as sensors.     

Hydra: a self regenerating high performance computing grid for drug discovery

Computer aided drug design is progressing and playing an increasingly important role in drug discovery. Computational methods are being used to evaluate larger and larger numbers of real and virtual compounds. New methods based on molecular simulations that take protein and ligand flexibility into account also contribute to an ever increasing need for compute time. Computational grids are therefore becoming a critically important tool for modern drug discovery, but can be expensive to deploy and maintain. Here, we describe the low cost implementation of a 165 node, computational grid at Anadys Pharmaceuticals. The grid makes use of the excess computing capacity of desktop computers deployed throughout the company and of outdated desktop computers which populate a central computing grid. The performance of the grid grows automatically with the size of the company and with advances in computer technology. To ensure the uniformity of the nodes in the grid, all computers are running the Linux operating system. The desktop computers run Linux inside MS Windows using coLinux as virtualization software. HYDRA has been used to optimize computational models, for virtual screening and for lead optimization.     

Combinatorial bounds on Hilbert functions of fat points in projective space

We study Hilbert functions of certain non-reduced schemes A supported at finite sets of points in , in particular, fat point schemes. We give combinatorially defined upper and lower bounds for the Hilbert function of A using nothing more than the multiplicities of the points and information about which subsets of the points are linearly dependent. When N=2, we give these bounds explicitly and we give a sufficient criterion for the upper and lower bounds to be equal. When this criterion is satisfied, we give both a simple formula for the Hilbert function and combinatorially defined upper and lower bounds on the graded Betti numbers for the ideal I_A defining A, generalizing results of Geramita et al. (2006) [16]. We obtain the exact Hilbert functions and graded Betti numbers for many families of examples, interesting combinatorially, geometrically, and algebraically. Our method works in any characteristic.     

Multiplier Ideals of General Line Arrangements in ℂ3

We consider the multiplier ideals of the ideal of a reduced union of lines through the origin in ?³. For general arrangements of lines, we calculate the multiplier ideals.     

Confinement potential in the dual monopole Nambu–Jona–Lasinio model with dual Dirac strings

Interquark confinement potential is calculated in the dual monopole Nambu–Jona–Lasinio model with dual Dirac strings suggested in [2,3] as a functional of the dual Dirac string length. The calculation is carried out by explicit integration over quantum fluctuations of a dual-vector field (monopole–antimonopole collective excitation) around the Abrikosov flux line and string shape fluctuations. The contribution of the scalar field (monopole–antimonopole collective excitation) exchange is taken into account in the tree approximation because of the London limit regime. The dominant role of quantum fluctuations for the formation of the linearly rising part of the confinement potential is argued. Received: 10 November 1998 / Revised version: 10 May 1999 / Published online: 12 August 1999     

The interaction of boronic acid-substituted viologens with pyranine: the effects of quencher charge on fluorescence quenching and glucose response

The fluorescence sensing of several monosaccharides using boronic acid-substituted viologen quenchers in combination with the fluorescent dye pyranine (HPTS) is reported. In this two-component sensing system, fluorescence quenching by the viologen is modulated by monosaccharides to provide a fluorescence signal. A series of viologen quenchers with different charges were prepared and tested for their ability both to quench the fluorescence of HPTS and to sense changes in glucose concentration in aqueous solution at pH 7.4. Both quenching efficiency and sugar sensing were found to be strongly dependent upon viologen charge. The molar ratio between HPTS and each of the viologen quenchers was varied in order to obtain an optimal ratio that provided a fairly linear fluorescence signal across a physiological glucose concentration range. Both the quenching and sugar sensing results are explained by electrostatic interaction between dye and quencher.     

The Monodromy Conjecture for hyperplane arrangements

The Monodromy Conjecture asserts that if c is a pole of the local topological zeta function of a hypersurface, then exp(2πic) is an eigenvalue of the monodromy on the cohomology of the Milnor fiber. A stronger version of the conjecture asserts that every such c is a root of the Bernstein-Sato polynomial of the hypersurface. In this note we prove the weak version of the conjecture for hyperplane arrangements. Furthermore, we reduce the strong version to the following conjecture: −n/d is always a root of the Bernstein-Sato polynomial of an indecomposable essential central hyperplane arrangement of d hyperplanes in C ⁿ .     

Orca: A Visualization Toolkit for High-Dimensional Data

Abstract

This article describes constructing interactive and dynamic linked data views using the Java programming language. The data views are designed for data that have a multivariate component. The approach to displaying data comes from earlier research on building statistical graphics based on data pipelines, in which different aspects of data processing and graphical rendering are organized conceptually into segments of a pipeline. The software design takes advantage of the object-oriented nature of the Java language to open up the data pipeline, allowing developers to have greater control over their visualization applications. Importantly, new types of data views coded to adhere to a few simple design requirements can easily be integrated with existing pipe sections. This allows access to sophisticated linking and dynamic interaction across all (new and existing) view types. Pipe segments can be accessed from data analysis packages such as Omegahat or R, providing a tight coupling of visual and numerical methods.     

Degradation of poly(β‐amino ester) gels in alcohols through transesterification: Method to conjugate drugs to polymer matrices

Poly(β amino ester) (PβAE) polymers have received growing attention in the literature, owing to their ease of synthesis, versatile co‐monomer selection, and highly tunable degradation kinetics. As such, they have shown extensive potential in many biomedical applications as well. In this work, it is demonstrated for the first time that PβAE polymers containing primary and secondary amine groups can undergo degradation by primary alcohols via transesterification mechanism. While this work emphasizes an important aspect of solvent compatibility of these networks, it also represents an interesting, simple mechanism for post synthesis drug incorporation, with riboflavin conjugation being demonstrated as a model compound. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2019–2026