Fitting differential equation models to observed economic data—I. quasilinearization

This paper discusses the fitting of differential equation models to economic data. In particular, it treats the problem of describing the growth of capital in terms of a differential equation containing several parameters. The parameters are to be estimated on the basis of data. This estimation problem is formulated as a nonlinear boundary value problem. The rapidly convergent successive approximation method of quasilinearization is described and applied. Representative results of numerical experiments are presented, showing the effectiveness of the approach. Suggestions for additional studies are made.     

"Click-to-chelate": design and incorporation of triazole-containing metal-chelating systems into biomolecules of diagnostic and therapeutic interest

The site-specific conjugation of metal chelating systems to biologically relevant molecules is an important contemporary topic in bioinorganic and bioorganometallic chemistry. In this work, we have used the CuI-catalyzed cycloaddition of azides and terminal alkynes to synthesise novel ligand systems, in which the 1,2,3-triazole is an integral part of the metal chelating system. A diverse set of bidentate alkyne building blocks with different aliphatic and aromatic backbones and various donor groups were prepared. The bidentate alkynes were reacted with benzyl azide in the presence of a catalytic amount of CuI to form tridentate model ligands. The chelators were reacted with [ReBr3(CO)3]2- to form well-defined and stable complexes with different overall charges, structures and hydrophilicities. In all cases tridentate coordination of the ligands, including through N3 of the 1,2,3-triazole ring, was observed. The ligand systems could also be quantitatively radiolabelled with the precursor [99 mTc (H2O)3(CO)3]+ at low ligand concentrations. Similarly the alkynes were reacted with an azido thymidine derivative to form a series of compounds, which could be radiolabelled in situ to form single products. Subsequent incubation of the neutral and cationic organometallic 99 mTc thymidine derivatives with human cytosolic thymidine kinase, a key enzyme in tumour proliferation, revealed that only the neutral compounds maintained substrate activity towards the enzyme. Bioconjugation, radiolabelling and enzymatic reactions were successfully performed in a matter of hours. Thus, click chemistry provides an elegant method for rapidly functionalising a biologically relevant molecule with a variety of efficient metal chelators suitable for (radio)labelling with the M(CO)3 core (M=99 mTc, Re), to offer new potential for technetium-99 m in clinical and preclinical tracer development.     

New bimetallic compounds based on the bis(thiosemicarbazonato) motif

Zinc and copper bis(thiosemicarbazonato) complexes containing more than one metal centre have been prepared with a view to examining their application for molecular imaging. The zinc complexes are fluorescent with excitation and emission at relatively long wavelengths. The dinuclear copper complex undergoes two sequential, quasi-reversible reductions.     

Synthesis and reactivity of [18F]-N-fluorobenzenesulfonimide

A novel [18F]NF reagent and two novel radiochemical transformations have been developed: [18F]NFSi has been prepared from sodium dibenzenesulfonimide and reacted in the presence of silyl enol ethers and allylsilanes to deliver labelled fluorinated ketones and allylic fluorides respectively; the radiosynthesis of the fluorinated A ring of vitamin D3 has also been completed with success.     

Cooperative dynamic programming

A many-decision-maker dynamic-control problem under uncertainty is presented as an extension of the standard control problem. It is assumed that only one payoff function exists, identical for all decision makers. The outstanding problem is to find a sequence of several decision rules that optimally coordinate activities both across time and between decision makers. This cooperative dynamic programming problem requires the researcher to consider how to solve large numbers of systems of integral equations.     

A highly efficient procedure for 3-sulfenylation of indole-2-carboxylates

A highly efficient one-pot procedure for 3-sulfenylation of 2-carboxyindoles is described. Treatment of thiols with N-chlorosuccinimide at -78 degrees C in CH(2)Cl(2) affords sulfenyl chlorides in situ that readily react with 2-carboxyindoles to give 3-thioindoles in high yields. This new method is milder, produces less waste, and is compatible with a wide range of thiol and indole functionality. [reaction: see text]     

Biosensor for the specific detection of a single viable B. anthracis spore

A simple membrane strip-based biosensor for the detection of viable B. anthracis spores was developed and combined with a spore germination procedure as well as a nucleic acid amplification reaction to identify as little as one viable B. anthracis spore in less than 12 h. The biosensor is based on identification of a unique mRNA sequence from the anthrax toxin activator (atxA) gene encoded on the toxin plasmid, pXO1. Preliminary work relied on plasmid vectors in both E. coli and B. thuringiensis expressing the atxA gene. Once the principle was firmly established, the vaccine strain of B. anthracis was used. After inducing germination and outgrowth of spores of B. anthracis (Sterne strain), RNA was extracted from lysed cells, amplified using nucleic acid sequence-based amplification (NASBA), and rapidly identified by the biosensor. While the biosensor assay requires only 15-min assay time, the overall process takes 12 h for the detection of as little as one viable B. anthracis spore, and is shortened significantly, if larger amounts of spores are present. The biosensor is based on an oligonucleotide sandwich-hybridization assay format. It uses a membrane flow-through system with an immobilized oligonucleotide probe that hybridizes with the target sequence. Signal amplification is provided when the target sequence hybridizes to a second oligonucleotide probe that has been coupled to dye-encapsulating liposomes. The dye in the liposomes then provides a signal that can be read visually or quantified with a hand-held reflectometer. The biosensor can detect as little as 1.5 fmol of target mRNA. Specificity analysis revealed no crossreactivity with closely related species such as B. cereus, B. megaterium, B. subtilis, B. thuringiensis etc.     

"Click to chelate": synthesis and installation of metal chelates into biomolecules in a single step

Click chemistry has been employed for the assembly of novel and efficient triazole-based multidentate chelating systems while simultaneously attaching them to molecules of biological interest. The "click-to-chelate" approach offers a powerful new tool for the modification of (bio)molecules with metal chelators for potential diagnostic and therapeutic applications.     

Bacillus anthracis: toxicology, epidemiology and current rapid-detection methods

B. anthracis, the causative agent for anthrax, has been well studied for over 150 years. Due to the genetic similarities among various Bacillus species, as well as its existence in both a spore form and a vegetative state, the detection and specific identification of B. anthracis have been proven to require complex techniques and/or laborious methods. With the heightened interest in the organism as a potential biological threat agent, a large number of interesting detection technologies have recently been developed, including methods involving immunological and nucleic acid-based assay formats. The technologies range from culture-based methods to portable Total Analysis Systems based on real-time PCR. This review with 170 references provides a brief background on the toxicology and epidemiology of B. anthracis, discusses challenges associated with its detection related to genetic similarities to other species, and reviews immunological and, with greater emphasis, nucleic acid-based detection systems. Harriet A. Clancy is currently on active duty with the U.S. Army’s 3rd COSCOM (Corps Support Command)