Are nuclei withN∼43 deformed?

The level schemes of⁷⁵Se and⁷⁹Kr have been established through gamma ray and conversion electron spectroscopy following⁷⁵As (p, nγ ^?e) and⁷⁹Br (p, nγe^?) reactions. The data on these nuclei and the nuclei in the neighbourhood of this mass region are discussed and evidence is presented to show that the nuclei withN～43 are deformed.     

Intensified biochip system using chemiluminescence for the detection of Bacillus globigii spores

This paper reports the first intensified biochip system for chemiluminescence detection and the feasibility of using this system for the analysis of biological warfare agents is demonstrated. An enzyme-linked immunosorbent assay targeting Bacillus globigii spores, a surrogate species for Bacillus anthracis, using a chemiluminescent alkaline phosphatase substrate is combined with a compact intensified biochip detection system. The enzymatic amplification was found to be an attractive method for detection of low spore concentrations when combined with the intensified biochip device. This system was capable of detecting approximately 1 × 10⁵ Bacillus globigii spores. Moreover, the chemiluminescence method, combined with the self-contained biochip design, allows for a simple, compact system that does not require laser excitation and is readily adaptable to field use. Figure Schematic diagram of the miniature biochip detection system     

The SAMPL6 SAMPLing challenge: assessing the reliability and efficiency of binding free energy calculations

Journal of Computer-Aided Molecular Design - Approaches for computing small molecule binding free energies based on molecular simulations are now regularly being employed by academic and industry...     

Review of Chemometrics Applied to Spectroscopy: 1985-95, Part 2

INTRODUCTION

Before beginning Part 2 of this review, a caveat noted by Deming and Palasota is brought to the reader's attention: [1] “Press et al. [2] have emphasized that data ‘consist of numbers, of course. But these numbers are fed into the computer, not produced by it. These are numbers to be treated with considerable respect, never to be tampered with, nor subjected to a numerical process whose character you do not completely understand. You are well advised to acquire reverence for data that is rather diferent fiom the “sporty” attitude which is sometimes allowable, or even commendable, in other numerical tasks.’ Yet by and large within chemometrics, preprocessing often seems to be carried out with little understanding of its fundamental efect on the structure of the data.”     

On the use of orientational restraints and symmetry corrections in alchemical free energy calculations

Alchemical free energy calculations are becoming a useful tool for calculating absolute binding free energies of small molecule ligands to proteins. Here, we find that the presence of multiple metastable ligand orientations can cause convergence problems when distance restraints alone are used. We demonstrate that the use of orientational restraints can greatly accelerate the convergence of these calculations. However, even with this acceleration, we find that sufficient sampling requires substantially longer simulations than are used in many published protocols. To further accelerate convergence, we introduce a new method of configuration space decomposition by orientation which reduces required simulation lengths by at least a factor of 5 in the cases examined. Our method is easily parallelizable, well suited for cases where a ligand cocrystal structure is not available, and can utilize initial orientations generated by docking packages.     

The SAMPL4 host–guest blind prediction challenge: an overview

Prospective validation of methods for computing binding affinities can help assess their predictive power and thus set reasonable expectations for their performance in drug design applications. Supramolecular host–guest systems are excellent model systems for testing such affinity prediction methods, because their small size and limited conformational flexibility, relative to proteins, allows higher throughput and better numerical convergence. The SAMPL4 prediction challenge therefore included a series of host–guest systems, based on two hosts, cucurbit[7]uril and octa-acid. Binding affinities in aqueous solution were measured experimentally for a total of 23 guest molecules. Participants submitted 35 sets of computational predictions for these host–guest systems, based on methods ranging from simple docking, to extensive free energy simulations, to quantum mechanical calculations. Over half of the predictions provided better correlations with experiment than two simple null models, but most methods underperformed the null models in terms of root mean squared error and linear regression slope. Interestingly, the overall performance across all SAMPL4 submissions was similar to that for the prior SAMPL3 host–guest challenge, although the experimentalists took steps to simplify the current challenge. While some methods performed fairly consistently across both hosts, no single approach emerged as consistent top performer, and the nonsystematic nature of the various submissions made it impossible to draw definitive conclusions regarding the best choices of energy models or sampling algorithms. Salt effects emerged as an issue in the calculation of absolute binding affinities of cucurbit[7]uril-guest systems, but were not expected to affect the relative affinities significantly. Useful directions for future rounds of the challenge might involve encouraging participants to carry out some calculations that replicate each others’ studies, and to systematically explore parameter options.     

Synthesis,Characterization, and Structure of Some New Substituted 5,6-Fused Ring Pyridazines

Pyridazines are an important class of heterocyclic compounds as a result of their materials and commercial applications. The synthesis of 5,6-fused ring pyridazines 2a–h from 1,2-diacylcyclopentadienes (fulvenes) 1a–h is described herein. This route was quite general, and features an efficient and convenient two-step synthesis of a series of 5,6-fused ring 1,2-disubstituted pyridazines using enolized 1,2-disubstituted fulvenes in a methanolic solution of hydrazine. Full characterization of newly formed fulvene 1e and pyridazines 2a–h are reported. Single-crystal X-ray analysis confirms the molecular structure of pyridazine 2f, which displayed the expected pyridazine fused to the cyclopentadienyl moiety. Adding to their real world capabilities in electronic devices, compounds 2a–h display reasonably high stability in solution and in air at room temperature.

Predicting hydration free energies using all-atom molecular dynamics simulations and multiple starting conformations

Molecular dynamics simulations in explicit solvent were applied to predict the hydration free energies for 23 small organic molecules in blind SAMPL2 test. We found good agreement with experimental results, with an RMS error of 2.82 kcal/mol over the whole set and 1.86 kcal/mol over all the molecules except several hydroxyl-rich compounds where we find evidence for a systematic error in the force field. We tested two different solvent models, TIP3P and TIP4P-Ew, and obtained very similar hydration free energies for these two models; the RMS difference was 0.64 kcal/mol. We found that preferred conformation of the carboxylic acids in water differs from that in vacuum. Surprisingly, this conformational change is not adequately sampled on simulation timescales, so we apply an umbrella sampling technique to include free energies associated with the conformational change. Overall, the results of this test reveal that the force field parameters for some groups of molecules (such as hydroxyl-rich compounds) still need to be improved, but for most compounds, accuracy was consistent with that seen in our previous tests.     

Finite-bandwidth Kramers-Kronig relations for acoustic group velocity and attenuation derivative applied to encapsulated microbubble suspensions

Kramers-Kronig (KK) analyses of experimental data are complicated by the conflict between the inherently bandlimited data and the requirement of KK integrals for a complete infinite spectrum of input information. For data exhibiting localized extrema, KK relations can provide accurate transforms over finite bandwidths due to the local-weighting properties of the KK kernel. Recently, acoustic KK relations have been derived for the determination of the group velocity (cg) and the derivative of the attenuation coefficient (alpha') (components of the derivative of the acoustic complex wave number). These relations are applicable to bandlimited data exhibiting resonant features without extrapolation or unmeasured parameters. In contrast to twice-subtracted finite-bandwidth KK predictions for phase velocity and attenuation coefficient (components of the undifferentiated wave number), these more recently derived relations for cg and alpha' provide stricter tests of causal consistency because the resulting shapes are invariant with respect to subtraction constants. The integrals in these relations can be formulated so that they only require the phase velocity and attenuation coefficient data without differentiation. Using experimental data from suspensions of encapsulated microbubbles, the finite-bandwidth KK predictions for cg and alpha' are found to provide an accurate mapping of the primary wave number quantities onto their derivatives.     

The time-domain signature of negative acoustic group velocity in microsphere suspensions

In the wake of recent reports of superluminal acoustic group velocities in sonic and ultrasonic regions of the acoustic spectrum, this paper describes the time-domain manifestation of such group velocities through simulations of the linear propagation of ultrasonic wave packets in a suspension of elastic microspheres. Conditions under which arbitrarily large and negative group velocities can be observed as the speed of a peak in the envelope of an acoustic pulse are described. Propagation simulations demonstrate the physical signature of negative group velocities, as well as the causal compliance of the superluminal acoustic pulses examined in this work.