Subtle Recognition of 14-Base Pair DNA Sequences via Threading Polyintercalation

ABSTRACT: Small molecules that bind DNA in a sequence-specific manner could act as antibiotic, antiviral, or anticancer agents because of their potential ability to manipulate gene expression. Our laboratory has developed threading poly-intercalators based on 1,4,5,8-naphthalene diimide (NDI) units connected in a head-to-tail fashion by flexible peptide linkers. Previously, a threading tetraintercalator composed of alternating minor−major−minor groove-binding modules was shown to bind specifically to a 14 bp DNA sequence with a dissociation half-life of 16 days [Holman, G. G., et al. (2011) Nat. Chem. 3, 875−881]. Herein are described new NDI-based tetraintercalators with a different major groove-binding module and a reversed N to C directionality of one of the minor groove-binding modules. DNase I footprinting and kinetic analyses revealed that these new tetraintercalators are able to discriminate, by as much as 30-fold, 14 bp DNA binding sites that differ by 1 or 2 bp. Relative affinities were found to correlate strongly with dissociation rates, while overall C2 symmetry in the DNA-binding molecule appeared to contribute to enhanced association rates

Simultaneous determination of time and space-dependent coefficients in a parabolic equation

This paper investigates a couple of inverse problems of simultaneously determining time and space dependent coefficients in the parabolic heat equation using initial and boundary conditions of the direct problem and overdetermination conditions. The measurement data represented by these overdetermination conditions ensure that these inverse problems have unique solutions. However, the problems are still ill-posed since small errors in the input data cause large errors in the output solution. To overcome this instability we employ the Tikhonov regularization method. The finite-difference method (FDM) is employed as a direct solver which is fed iteratively in a nonlinear minimization routine. Both exact and noisy data are inverted. Numerical results for a few benchmark test examples are presented, discussed and assessed with respect to the FDM mesh size discretisation, the level of noise with which the input data is contaminated, and the chosen regularization parameters

Status, Vision, and Challenges of an Intelligent Distributed Engine Control Architecture

A Distributed Engine Control Working Group (DECWG) consisting of the Department of Defense (DoD), the National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) and industry has been formed to examine the current and future requirements of propulsion engine systems. The scope of this study will include an assessment of the paradigm shift from centralized engine control architecture to an architecture based on distributed control utilizing open system standards. Included will be a description of the work begun in the 1990's, which continues today, followed by the identification of the remaining technical challenges which present barriers to on-engine distributed control

Liquidness: Conceptualising water within boating tourism

This paper discusses the elemental materialities of water mobilities, bringing the agentive qualities of water to the centre of theoretical discussion of tourism. Analysing data collected through qualitative interviews with, and participant observation of, British boating tourists, the analysis of watery materialities and the corresponding tourist assemblages are presented across water bodies: on inland waterways and in coastal areas. Examining the mobilities of the water materialities and the cooperation between water, boat and the tourist, we propose the concept of water-boat-human assemblage for examining boating tourism in terms of liquid relationships. The paper also introduces the notion of liquidness: the relational conglomerate between mobilities, materialities and practices as an analytical category for theorising water tourism

The Atlantic salmon genome provides insights into rediploidization

The whole-genome duplication 80 million years ago of the common ancestor of salmonids (salmonid-specific fourth vertebrate whole-genome duplication, Ss4R) provides unique opportunities to learn about the evolutionary fate of a duplicated vertebrate genome in 70 extant lineages. Here we present a high-quality genome assembly for Atlantic salmon (Salmo salar), and show that large genomic reorganizations, coinciding with bursts of transposon-mediated repeat expansions, were crucial for the post-Ss4R rediploidization process. Comparisons of duplicate gene expression patterns across a wide range of tissues with orthologous genes from a pre-Ss4R outgroup unexpectedly demonstrate far more instances of neofunctionalization than subfunctionalization. Surprisingly, we find that genes that were retained as duplicates after the teleost-specific whole-genome duplication 320 million years ago were not more likely to be retained after the Ss4R, and that the duplicate retention was not influenced to a great extent by the nature of the predicted protein interactions of the gene products. Finally, we demonstrate that the Atlantic salmon assembly can serve as a reference sequence for the study of other salmonids for a range of purposes.publishedVersio