Structural characterisation of bisintercalation in higher-order DNA at a junction-like quadruplex

We report the single-crystal X-ray structure for the complex of the bisacridine bis-(9-aminooctyl(2-(dimethylaminoethyl)acridine-4-carboxamide)) with the oligonucleotide d(CGTACG)2 to a resolution of 2.4 Å. Solution studies with closed circular DNA show this compound to be a bisintercalating threading agent, but so far we have no crystallographic or NMR structural data conforming to the model of contiguous intercalation within the same duplex. Here, with the hexameric duplex d(CGTACG), the DNA is observed to undergo a terminal cytosine base exchange to yield an unusual guanine quadruplex intercalation site through which the bisacridine threads its octamethylene linker to fuse two DNA duplexes. The 4-carboxamide side-chains form anchoring hydrogen-bonding interactions with guanine O6 atoms on each side of the quadruplex. This higher-order DNA structure provides insight into an unexpected property of bisintercalating threading agents, and suggests the idea of targeting such compounds specifically at four-way DNA junctions.

Regularization of Descriptor Systems by Derivative and Proportional State Feedback

For linear multivariable time-invariant continuous or discrete-time singular systems it is customary to use a proportional feedback control in order to achieve a desired closed loop behaviour. Derivative feedback is rarely considered. This paper examines how derivative feedback in descriptor systems can be used to alter the structure of the system pencil under various controllability conditions. It is shown that derivative and proportional feedback controls can be constructed such that the closed loop system has a given form and is also regular and has index at most 1. This property ensures the solvability of the resulting system of dynamic-algebraic equations. The construction procedures used to establish the theory are based only on orthogonal matrix decompositions and can therefore be implemented in a numerically stable way. The problem of pole placement with derivative feedback alone and in combination with proportional state feedback is also investigated. A computational algorithm for improving the “conditioning” of the regularized closed loop system is derived.

Entrepreneurial opportunities, implicit contracts and market making for complex consumer goods

This article extends the theory of entrepreneurial opportunity exploitation, outlining how under certain conditions, opportunity exploitation is dependent on market making innovations. Where adverse selection and moral hazard characterize markets, consumers are likely to withdraw regardless of product quality. In order to overcome consumer resistance, entrepreneurs must signal credible commitments. But because consumers purchase without fully specifying requirements, entrepreneurs' commitments take the partial form of implicit contracts, creating strong mutual commitments to repeated transactions. These commitments enable novel markets to function, but introduce additional costs. This article illustrates the theory with the historic case of Singer in sewing machines

Synthesis, characterization, crystal structure, and DNA-binding of ruthenium(II) complexes of heterocyclic nitrogen ligands resulting from a benzimidazole-based quinazoline derivative

The reaction of cis-[RuCl2(dmso)(4)] with [6-(2-pyridinyl)-5,6-dihydrobenzimidazo[1,2-c] quinazoline] (L) afforded in pure form a blue ruthenium(II) complex, [Ru(L-1)(2)] (1), where the original L changed to [2-(1H-benzoimidazol-2-yl)-phenyl]-pyridin-2-ylmethylene-amine (HL1). Treatment of RuCl3 center dot 3H(2)O with L in dry tetrahydrofuran in inert atmosphere led to a green ruthenium(II) complex, trans-[RuCl2(L-2)(2)] (2), where L was oxidized in situ to the neutral species 6-pyridin-yl-benzo[4,5]imidazo[1,2-c] quinazoline (L-2). Complex 2 was also obtained from the reaction of RuCl3 center dot 3H(2)O with L-2 in dry ethanol. Complexes 1 and 2 have been characterized by physico-chemical and spectroscopic tools, and 1 has been structurally characterized by single-crystal X-ray crystallography. The electrochemical behavior of the complexes shows the Ru(III)/Ru(II) couple at different potentials with quasi-reversible voltammograms. The interaction of these complexes with calf thymus DNA by using absorption and emission spectral studies allowed determination of the binding constant K-b and the linear Stern-Volmer quenching constant K-SV

Climate determinism revisited: multiple equilibria in a complex climate model

Multiple equilibria in a coupled ocean–atmosphere–sea ice general circulation model (GCM) of an aquaplanet with many degrees of freedom are studied. Three different stable states are found for exactly the same set of parameters and external forcings: a cold state in which a polar sea ice cap extends into the midlatitudes; a warm state, which is ice free; and a completely sea ice–covered “snowball” state. Although low-order energy balance models of the climate are known to exhibit intransitivity (i.e., more than one climate state for a given set of governing equations), the results reported here are the first to demonstrate that this is a property of a complex coupled climate model with a consistent set of equations representing the 3D dynamics of the ocean and atmosphere. The coupled model notably includes atmospheric synoptic systems, large-scale circulation of the ocean, a fully active hydrological cycle, sea ice, and a seasonal cycle. There are no flux adjustments, with the system being solely forced by incoming solar radiation at the top of the atmosphere. It is demonstrated that the multiple equilibria owe their existence to the presence of meridional structure in ocean heat transport: namely, a large heat transport out of the tropics and a relatively weak high-latitude transport. The associated large midlatitude convergence of ocean heat transport leads to a preferred latitude at which the sea ice edge can rest. The mechanism operates in two very different ocean circulation regimes, suggesting that the stabilization of the large ice cap could be a robust feature of the climate system. Finally, the role of ocean heat convergence in permitting multiple equilibria is further explored in simpler models: an atmospheric GCM coupled to a slab mixed layer ocean and an energy balance model

High Resolution Melt (HRM) analysis is an efficient tool to genotype EMS mutants in complex crop genomes

Background: Targeted Induced Loci Lesions IN Genomes (TILLING) is increasingly being used to generate and identify mutations in target genes of crop genomes. TILLING populations of several thousand lines have been generated in a number of crop species including Brassica rapa. Genetic analysis of mutants identified by TILLING requires an efficient, high-throughput and cost effective genotyping method to track the mutations through numerous generations. High resolution melt (HRM) analysis has been used in a number of systems to identify single nucleotide polymorphisms (SNPs) and insertion/deletions (IN/DELs) enabling the genotyping of different types of samples. HRM is ideally suited to high-throughput genotyping of multiple TILLING mutants in complex crop genomes. To date it has been used to identify mutants and genotype single mutations. The aim of this study was to determine if HRM can facilitate downstream analysis of multiple mutant lines identified by TILLING in order to characterise allelic series of EMS induced mutations in target genes across a number of generations in complex crop genomes. Results: We demonstrate that HRM can be used to genotype allelic series of mutations in two genes, BraA.CAX1a and BraA.MET1.a in Brassica rapa. We analysed 12 mutations in BraA.CAX1.a and five in BraA.MET1.a over two generations including a back-cross to the wild-type. Using a commercially available HRM kit and the Lightscanner™ system we were able to detect mutations in heterozygous and homozygous states for both genes. Conclusions: Using HRM genotyping on TILLING derived mutants, it is possible to generate an allelic series of mutations within multiple target genes rapidly. Lines suitable for phenotypic analysis can be isolated approximately 8-9 months (3 generations) from receiving M3 seed of Brassica rapa from the RevGenUK TILLING service.

Accounting for complex investment transactions

This case study exposes students to complex investment transactions. You must document the following: (1) apply the appropriate accounting literature along with its provisions and justify the order of its application; (2) identify and interpret key facts to classify the given investments and relations; (3) discuss the choice of key assumptions that are central to the analysis; (4) interpret the nature of all investment relations with Holdings; discuss all Owner level and below relations; (5) discuss how accounting for varied levels of influence impact the items reported on/off the face of investors’ financial statements; (6) from DT’s perspective, discuss the potential positives and negatives of its arrangement with Owner with respect to Holdings; and (7) after analyzing additional facts, discuss the nature of the relations of Simon and Herb III with Owner.

A simple method for integrating a complex model into an ensemble data assimilation system using MPI

This paper details a strategy for modifying the source code of a complex model so that the model may be used in a data assimilation context, {and gives the standards for implementing a data assimilation code to use such a model}. The strategy relies on keeping the model separate from any data assimilation code, and coupling the two through the use of Message Passing Interface (MPI) {functionality}. This strategy limits the changes necessary to the model and as such is rapid to program, at the expense of ultimate performance. The implementation technique is applied in different models with state dimension up to $2.7 \times 10^8$. The overheads added by using this implementation strategy in a coupled ocean-atmosphere climate model are shown to be an order of magnitude smaller than the addition of correlated stochastic random errors necessary for some nonlinear data assimilation techniques.