Can one predict DNA transcription start sites by studying bubbles?

It has been speculated that bubble formation of several base pairs due to thermal fluctuations is indicatory for biologically active sites. Recent evidence, based on experiments and molecular dynamics simulations using the Peyrard-Bishop-Dauxois model, seems to point in this direction. However, sufficiently large bubbles appear only seldom, which makes an accurate calculation difficult even for minimal models. In this Letter, we introduce a new method that is orders of magnitude faster than molecular dynamics. Using this method, we show that the present evidence is unsubstantiated.     

One-pot four-component synthesis of 4-hydrazinothiazoles: novel scaffolds for drug discovery

One pot ring synthesis of novel 4-hydrazinothiazoles through sequential four-component route employing carbonyl compounds, aminoguanidine, isothiocyanates, and α-haloketones was accomplished under mild reaction conditions. Base-assisted eliminative aromatization in the [4+1] ring synthesis shed light on interesting leaving group propensities of amine versus hydrazine resulting in the exclusive formation of the title compounds with immense potential as scaffolds for drug discovery. Hydrazone deprotection was effected by acylation which subsequently provided a new set of diacylated molecular systems with a wider scope as chemical handles in the design of thiazolyl drug candidates.     

Heck reaction with 3-fluoro-3-buten-2-one

3-Fluoro-3-buten-2-one (2) is readily prepared from 1-fluoro-1-chloro-2-methoxy-2-methylcyclopropane (1) in 82% yield by heating the cyclopropane in aqueous quinoline solution. Ketone 2 reacts with aryl iodides (3) in a Heck reaction catalyzed by Pd(OAc)₂ to give Z-3-fluorobenzalacetones (4) in 36-86% yield.     

Enhancing exchange bias with diluted antiferromagnets

The exchange bias H(E) of coupled polycrystalline films of antiferromagnetic CoO and ferromagnetic Co was significantly enhanced by the systematic substitution of nonmagnetic Mg for Co in CoO. Samples in which either Co or Co(1-x)Mg(x)O were deposited first were investigated at temperatures from 10 to 300 K. With Co(1-x)Mg(x)O on the bottom, the increased interfacial uncompensated spin density of the single antiferromagnetic domain Co(1x)Mg(x)O crystallites produced the enhanced H(E). With Co on the bottom, a thin interfacial oxide layer was primarily responsible for the strongly increased H(E).     

Hybrid density functional theory with specific reaction parameter: hydrogen abstraction reaction of fluoromethane by the hydroxyl radical

Three potential energy surfaces with specific reaction parameters are developed and tested for the OH + CH(3)F --> H(2)O + CH(2)F reaction. The goal of this work is to determine surfaces that provide calculated reaction rate constants that are comparable to the experimental data. The potential energy surfaces are constructed using hybrid and hybrid meta density functional theory methods, and the levels of electronic structure theory used in this study are mPW1PW91, B1B95, and mPW1B95 in conjunction with the 6-31+G(d,p) basis set. The reaction rate constants are calculated over the range 200-1,500 K using variational transition state theory with multidimensional tunneling contributions. New specific-reaction-parameter Hartree-Fock contributions are determined, and the hybrid density functional theory methods with these new contributions (35.5 +/- 1.2% for mPW1PW91, 36.6 +/- 1.2% for B1B95, and 40.7 +/- 1.2% for mPW1B95, respectively) reproduce accurate rate constants over an extended temperature range. On these potential energy surfaces, the classical barrier height for the hydrogen abstraction reaction is determined to be 3.4-3.8 kcal/mol, with a best estimate value of 3.6 kcal/mol.     

Tailored xerogel-based sensor arrays and artificial neural networks yield improved O2 detection accuracy and precision

The objective of this research is to develop arrays of tuned chemical sensors wherein each sensor element responds to a particular target analyte in a unique manner. By creating sol-gel-derived xerogels that are co-doped with two luminophores at a range of molar ratios, we can form suites of sensor elements that can exhibit a continuum of response profiles. We trained an artificial neural network (ANN) to "learn" to identify the optical outputs from these xerogel-based sensor arrays. By using the ANN in concert with our tailored sensor arrays we obtained a 5-10 fold improvement in accuracy and precision for quantifying O2 in unknown samples. We also explored the response characteristics of these types of sensor elements after they had been contacted with rat plasma/blood. Contact with plasma/blood caused approximately 15% of the luminophore molecules within the xerogels to become non-responsive to O2. This behavior is consistent with rat albumin blocking certain pore sub-populations within the mesoporous xerogel matrix thereby limiting O2 access to the luminophores.     

The use of liquid membranes in the multi-residue extraction of stilbenes in a variety of biological matrices and their detection with LC-ES-MS

Supported liquid membrane (SLM) has been used as a sample preparation method in the simultaneous extraction of a mixture of three stilbene compounds in cow's milk, urine, bovine kidney and liver tissues matrices. The stilbene compounds analysed included, dienestrol, diethylstilbestrol and hexestrol. The liquid membrane used for trapping these compounds consisted of 5% tri-n-octylphosphine oxide (TOPO) dissolved in di-n-hexylether/n-undecane (1:1). The extraction efficiencies obtained after enrichment of 1 ng/L stilbenes in variety of biological matrices of milk, urine, liver, kidney and water, ranged from 60 - 70%, 71 - 86%, 69 - 80%, 63 - 7A% and 72 - 93% respectively. The detection limits obtained from urine extraction were 2.1 ng/L, 1.3 ng/L and 3.0 ng/L; from liver and kidney tissues were 2.9 ng/L, 1.6 ng/L and 3.8 ng/L and from milk was 3.2 ng/L, 2.5 ng/L and 4.3 ng/L for hexestrol, dienestrol and diethylstilbestrol respectively.     

Beurling Zeta Functions, Generalised Primes, and Fractal Membranes

We study generalised prime systems , with tending to infinity) and the associated Beurling zeta function . Under appropriate assumptions, we establish various analytic properties of , including its analytic continuation, and we characterise the existence of a suitable generalised functional equation. In particular, we examine the relationship between a counterpart of the Prime Number Theorem (with error term) and the properties of the analytic continuation of . Further we study ‘well-behaved’ g-prime systems, namely, systems for which both the prime and integer counting function are asymptotically well-behaved. Finally, we show that there exists a natural correspondence between generalised prime systems and suitable orders on . Some of the above results are relevant to the second author’s theory of ‘fractal membranes’, whose spectral partition functions are given by Beurling-type zeta functions, as well as to joint work of that author and R. Nest on zeta functions attached to quasicrystals.The work of M. L. Lapidus was partially supported by the U. S. National Science Foundation under grant DMS-0070497.