Probing the nature of three-centered hydrogen bonds in minor-groove ligand-DNA interactions: the contribution of fluorine hydrogen bonds to complex stability

Double-stranded DNA sequences have been prepared in which single atoms (the O2-carbonyls of selected thymines) have been replaced by fluorine or methyl. To maintain normal Watson-Crick hydrogen bonding with the complementary purines, these analogue derivatives have been prepared as C-nucleosides. The O2-carbonyls of interest for this study are those involved in a bifurcated (or three-centered) hydrogen bond with the minor groove binding ligand 4',6-diamidino-2-phenylindole (DAPI). TM studies of the duplexes illustrate that the DNA duplexes are destabilized when fluorine or methyl replaces one or both of the minor groove O2-carbonyls, which can in part be explained by changes in minor groove hydration. In the presence of DAPI, most of the duplexes exhibit an increased TM due to the presence of DAPI bound in the minor groove. The extent of helix overstabilization negatively correlates with the presence of one or both methyl groups in the minor groove, suggesting that ligand binding is weakened in the presence of the non-carbonyl functional groups. The presence of single fluorine appears to promote helix stabilization, and native-like stabilization occurs when both fluorines are present. KD values quantitate binding effects between DAPI and the native and analogue sequences. Sequences with one or both methyl groups exhibit very poor binding with DAPI, while those containing a single fluorine behave essentially like native carbonyl-containing sequences. With both fluorines present, KD values were observed to increase by a moderate 3-fold at 100 mM NaCl and somewhat more at 200 mM NaCl. Binding affinities with both methyl groups present were 500-1000-fold weaker than native. The results suggest that organofluorines can function as hydrogen-bond acceptors, at least in the bifurcated interaction that contributes to minor groove binding by DAPI.     

A class of small molecules that inhibit TNFalpha-induced survival and death pathways via prevention of interactions between TNFalphaRI, TRADD, and RIP1

Small-molecule library screening to find compounds that inhibit TNFalpha-induced, but not interleukin 1beta (IL-1beta)-induced, intercellular adhesion molecule 1 (ICAM-1) expression in lung epithelial cells identified a class of triazoloquinoxalines. These compounds not only inhibited the TNFalpha-induced nuclear factor kappaB (NFkappaB) survival pathway but also blocked death-pathway activation. Such dual activity makes them unique against other known NFkappaB-pathway inhibitors that inhibit only a subset of TNFalpha signals leading to increased TNFalpha-induced cytotoxicity. Interestingly, these compounds inhibited association of TNFalpha receptor (TNFalphaR) I with TNFalphaR-associated death domain protein (TRADD) and receptor interacting protein 1 (RIP1), the initial intracellular signaling event following TNFalpha stimulation. Further study showed that they blocked ligand-dependent internalization of the TNFalpha-TNFalphaR complex, thereby inhibiting most of the TNFalpha-induced cellular responses. Thus, compounds with a triazoloquinoxaline scaffold could be a valuable tool to investigate small molecule-based anti-TNFalpha therapies.     

Shear wave speed recovery using moving interference patterns obtained in sonoelastography experiments

Two new experiments were created to characterize the elasticity of soft tissue using sonoelastography. In both experiments the spectral variance image displayed on a GE LOGIC 700 ultrasound machine shows a moving interference pattern that travels at a very small fraction of the shear wave speed. The goal of this paper is to devise and test algorithms to calculate the speed of the moving interference pattern using the arrival times of these same patterns. A geometric optics expansion is used to obtain Eikonal equations relating the moving interference pattern arrival times to the moving interference pattern speed and then to the shear wave speed. A cross-correlation procedure is employed to find the arrival times; and an inverse Eikonal solver called the level curve method computes the speed of the interference pattern. The algorithm is tested on data from a phantom experiment performed at the University of Rochester Center for Biomedical Ultrasound.     

Secondary ion yields produced by keV atomic and polyatomic ion impacts on a self-assembled monolayer surface

A suite of keV polyatomic or 'cluster' projectiles was used to bombard unoxidized and oxidized self-assembled monolayer surfaces. Negative secondary ion yields, collected at the limit of single ion impacts, were measured and compared for both molecular and fragment ions. In contrast to targets that are orders of magnitude thicker than the penetration range of the primary ions, secondary ion yields from polyatomic projectile impacts on self-assembled monolayers show little to no enhancement when compared with monatomic projectiles at the same velocity. This unusual trend is most likely due to the structural arrangement and bonding characteristics of the monolayer molecules with the Au(111). Copyright 1999 John Wiley & Sons, Ltd.     

Multi-gigabit WDM optical networking for next generation avionics system communications

It is envisaged that photonic networking will play a significant role in improving performance and reliability in both civil and military avionics systems. Of all the available photonic multiplexing technologies, wavelength-division multiplexing (WDM) has been the primary focus of attention within mainstream telecommunications offering increased throughput at a reasonable cost, with scope for enhanced routing flexibility, connectivity and network survivability. A direct mapping of techniques and devices from the maturing telecommunications sector is, however, not possible because of the stringent requirements of systems operating in the hostile aerospace environment. This paper gives an outline of these requirements and discusses, in detail, the design and development of a multi-gigabit, broadband optical WDM network architecture, specifically for use on aerospace platforms. The paper will also discuss a key element in the system, the arrayed-waveguide grating (AWG) wavelength multiplexing component, which has been designed to allow operation over the full military temperature specification without environmental conditioning.     

Combinatorial Isols and the Arithmetic of Dekker Semirings

In his long and illuminating paper [1] Joe Barback defined and showed to be non‐vacuous a class of infinite regressive isols he has termed “complete y torre” (CT) isols. These particular isols a enjoy a property that Barback has since labelled combinatoriality. In [2], he provides a list of properties characterizing the combinatoria isols. In Section 2 of our paper, we extend this list of characterizations to include the fact that an infinite regressive isol X is combinatorial if and only if its associated Dekker semiring D (X) satisfies all those Π₂ sentences of the anguage L_N for isol theory that are true in the set ω of natural numbers. (Moreover, with X combinatorial, the interpretations in D(X)of the various function and relation symbols of L_N via the “lifting ” to D(X) of their Σ₁ definitions in ω coincide with their interpretations via isolic extension.) We also note in Section 2 that Π₂(L)‐correctness, for semirings D(X), cannot be improved to Π ₃(L)‐correctness, no matter how many additional properties we succeed in attaching to a combinatoria isol; there is a fixed (L) sentence that blocks such extension. (Here L is the usual basic first‐order language for arithmetic.) In Section 3, we provide a proof of the existence of combinatorial isols that does not involve verification of the extremely strong properties that characterize Barback's CT isols.     

Existence and uniqueness results for the non-autonomous coagulation and multiple-fragmentation equation

An initial-value problem modelling coagulation and fragmentation processes is studied. The results of earlier papers are extended to models where either one or both of the rates of coagulation and fragmentation depend on time. An abstract integral equation, involving the solution operator to the linear fragmentation part, is investigated via the contraction mapping principle. A unique global, non-negative, mass-conserving solution to this abstract equation is shown to exist. The latter solution is used to generate a global, non-negative, mass-conserving solution to the original non-autonomous coagulation and multiple-fragmentation equation. © 1998 B. G. Teubner Stuttgart–John Wiley & Sons Ltd.     

Movement of drops on a solid surface due to a contact angle gradient

Experimental results on the motion of liquid drops on horizontal surfaces resulting from a contact angle gradient are presented. Silicon surfaces were modified using dodecyltrichlorosilane to generate the gradient. Water drops with initial diameters of 0.31 ‐ 0.5 mm (15 ‐ 65 nl) were placed on the surface, their movement videotaped, and subsequently analyzed. To characterize the gradient surface the static contact angle was measured along the surface.     

Chemical tuning of positive and negative magnetoresistances, and superconductivity in 1222-type ruthenocuprates

A remarkable variety of conducting states has been found in RuSr2(R2-xCex)Cu2O10-delta ruthenocuprates by tuning the properties of the magnetic CuO2 and RuO2 layers through small changes in the chemistry of the (R,Ce)2O2-delta slab. Both the R3+ cation size and the charge transfer determined by the R/Ce ratio and the oxygen deficiency delta are important controlling parameters that tune ground-state properties from positive magnetoresistive to negative magnetoresistive to superconducting.