OptiDock: virtual HTS of combinatorial libraries by efficient sampling of binding modes in product space

Products from combinatorial libraries generally share a common core structure that can be exploited to improve the efficiency of virtual high-throughput screening (vHTS). In general, it is more efficient to find a method that scales with the total number of reagents (Sigma growth) rather with the number of products (Pi growth). The OptiDock methodology described herein entails selecting a diverse but representative subset of compounds that span the structural space encompassed by the full library. These compounds are docked individually using the FlexX program (Rarey, M.; Kramer, B.; Lengauer, T.; Klebe, G. J. Mol. Biol. 1995, 251, 470-489) to define distinct docking modes in terms of reference placements for combinatorial core atoms. Thereafter, substituents in R-cores (consisting of the core structure substituted at a single variation site) are docked, keeping the core atoms fixed at the coordinates dictated by each reference placement. Interaction energies are calculated for each docked R-core with respect to the target protein, and energies for whole compounds are calculated by finding the reference core placement for which the sum of corresponding R-core energies is most negative. The use of diverse whole compounds to define binding modes is a key advantage of the protocol over other combinatorial docking programs. As a result, OptiDock returns better-scoring conformers than does serially applied FlexX. OptiDock is also better able to find a viable docked pose for each library member than are other combinatorial approaches.     

Visual spatial memory is enhanced in female rats (but inhibited in males) by dietary soy phytoestrogens

Background  

In learning and memory tasks, requiring visual spatial memory (VSM), males exhibit superior performance to females (a difference attributed to the hormonal influence of estrogen). This study examined the influence of phytoestrogens (estrogen-like plant compounds) on VSM, utilizing radial arm-maze methods to examine varying aspects of memory. Additionally, brain phytoestrogen, calbindin (CALB), and cyclooxygenase-2 (COX-2) levels were determined.     

A technique for the in situ phase calibration of in-duct axial microphone arrays

In aeroengine noise experiments in-duct microphone arrays are often used to make detailed measurements of the sound field transmitted along the duct. The individual microphones in the array must be calibrated with respect to magnitude, and often more critically with respect to phase. Calibration is difficult to perform in situ due to the presence of the duct. This paper presents a technique to allow in situ phase calibration of axial microphone arrays. It relies on the observation that the measured cross-spectral pressure matrix at the array has a Hermitian Töplitz form in the case where the propagating duct modes are mutually incoherent. Using this property a system of equations can be written which, when solved, allows the phase calibration factors to be obtained. The technique is verified experimentally using a no-flow laboratory rig by comparing the phase calibration factors obtained with those measured in free-field conditions. The accuracy of the phase calibration factors obtained by the technique is limited by the degree of deviation of the measured cross-spectral matrix from Töplitz behaviour. In the experimental results shown this is less than 15° at duct frequencies below ka=25. The technique is a robust and rapid method for calibrating in-duct axial microphone arrays.     

The application of homotopy analysis method to solve nonlinear differential equation governing Jeffery–Hamel flow

In this paper Jeffery–Hamel flow has been studied and its nonlinear ordinary differential equation has been solved through homotopy analysis method (HAM). The obtained solution in comparison with the numerical ones represents a remarkable accuracy. The results also indicate that HAM can provide us with a convenient way to control and adjust the convergence region.     

Neuromodulation by soy diets or equol: Anti-depressive &; anti-obesity-like influences,age- &; hormone-dependent effects

Background  

Soy-derived isoflavones potentially protect against obesity and depression. In five different studies we examined the influence of soy-containing diets or equol injections on depression, serotonin levels, body weight gain (BW) and white adipose tissue (WAT) deposition in female Long-Evans rats at various stages of life [rats were intact, ovariectomized or experienced natural ovarian failure (NOF)].     

Estimation of the far-field directivity of broadband aeroengine fan noise using an in-duct axial microphone array

This paper presents a measurement technique for estimating the far-field directivity of the sound radiated from a duct using measurements of acoustic pressure made inside the duct. The technique is restricted to broadband, multi-mode sound fields whose directivity patterns are axi-symmetric, and whose modes are mutually uncorrelated. The technique uses a transfer function to relate the output from an in-duct axial beamformer to measurements of the far-field polar directivity. A transfer function for a hollow cylindrical duct with no flow is derived, and investigated in detail. Transfer functions for practical cases concerning aeroengine exhausts are also presented. The transfer function is shown to be insensitive to the mode-amplitude distribution inside the duct, and hence can be used to predict the directivity in practice where the noise source distribution is unknown. The technique is then validated using a no-flow facility, and is shown to be able to predict variations in the far-field directivity pattern and also estimate the far-field sound pressure levels to within 2 dB. It is suggested that the proposed technique will be especially useful for fan rig experiments, where direct measurement of directivity, for example by use of an anechoic chamber, is impossible.     

The physics of diamond

The accurate measurement of the thermal conductivity of metals still poses considerable experimental difficulty. The reasons for this, and the main ways in which the problem has been approached, are summarized. A detailed examination of the development in technique and methods of measurement shows that while most of the steady-state methods introduced over 50 years ago are still being improved, the emphasis in the last few years has been on the development of methods which give more rapid results, particularly at high temperatures.