One Question,Multiple Answers: Biochemical and Biophysical Screening Methods Retrieve Deviating Fragment Hit Lists

Fragment‐based lead discovery is gaining momentum in drug development. Typically, a hierarchical cascade of several screening techniques is consulted to identify fragment hits which are then analyzed by crystallography. Because crystal structures with bound fragments are essential for the subsequent hit‐to‐lead‐to‐drug optimization, the screening process should distinguish reliably between binders and non‐binders. We therefore investigated whether different screening methods would reveal similar collections of putative binders. First we used a biochemical assay to identify fragments that bind to endothiapepsin, a surrogate for disease‐relevant aspartic proteases. In a comprehensive screening approach, we then evaluated our 361‐entry library by using a reporter‐displacement assay, saturation‐transfer difference NMR, native mass spectrometry, thermophoresis, and a thermal shift assay. While the combined results of these screening methods retrieve 10 of the 11 crystal structures originally predicted by the biochemical assay, the mutual overlap of individual hit lists is surprisingly low, highlighting that each technique operates on different biophysical principles and conditions.     

A novel DCT domain CRT-based watermarking scheme for image authentication surviving JPEG compression

Digital watermarking techniques have been proposed for copyright protection and authentication of multimedia data. In this paper, we propose a novel Chinese Remainder Theorem (CRT)-based technique for digital watermarking in the Discrete Cosine Transform (DCT) domain that is robust to several common attacks. We compared the performance of the proposed technique with recently proposed Singular Value Decomposition (SVD)-based and spatial CRT-based watermarking schemes. Experimental results have shown that the proposed technique successfully makes the watermark perceptually invisible and has better robustness to common image manipulation techniques such as JPEG compression, brightening and sharpening effects compared to the spatial domain-based CRT scheme. The proposed scheme is able to achieve a Tamper Assessment Function (TAF) value of less than 10% when the watermarked image undergoes JPEG compression between a range of 50 to 70%, where as, the spatial CRT-based scheme produce TAF value of more than 35% and the SVD-based scheme produces TAF value between 10 to 40% depending on the host image, for the same range of compression. When the watermark capacity is doubled, the proposed technique is still able to maintain imperceptibility and low TAF values, for most of the attacks.     

Analysis and Convenient Formulas for Elasto-Plastic Contacts of Nominally Flat Surfaces: Average Gap,Contact Area Ratio,and Plastically Deformed Volume

Interaction of nominally flat engineering surfaces that leads to a large contact area exists in many mechanical systems. Considering periodic similarity of surface geometry, a numerical three-dimensional elasto-plastic contact model can be used to simulate the contact behaviors of two nominally flat surfaces with the assistance of the continuous convolution and Fourier transform (CC-FT) algorithm. This model utilizes the analytical frequency response functions (FRF) of elastic/plastic responses of materials and provides contact performance results, including the average surface gap, the contact area ratio, and the volume of plastically deformed material, which may be defined as performance variables. Following the digital filtration technology, rough surfaces can be numerically generated with specified autocorrelation length and the first four orders of statistical moments. A group of contact simulations are conducted with various working conditions. The effects of topographic and material properties on the contact behaviors are discussed. With a multi-variables regression method, empirical formulas are developed for the performance variables as functions of surface statistical characteristics, material properties, a hardening parameter, and the applied load in terms of pressure.     

Cracking due to Localized Hot Shock

Results are presented for the cracking to be expected when a sudden temperature increase is applied over a localized region on a surface of a brittle solid. A localized temperature increase is applied to the surface of a body whose interior is initially at uniform temperature. A three-part analysis is conducted: (i) for the evolving temperature distribution, (ii) for the evolving thermal stresses induced by the nonuniform temperature field, and (iii) for stress intensity factors of cracks oriented either parallel to or perpendicular to the surface and initiated at times when the stresses are critical. Plane-strain and axisymmetric versions of the problems are considered. For the plane-strain problem, the complete trajectory of the crack is determined under the assumption that its tip advances maintaining a pure mode I field at all times. Conditions for excluding cracking due to localized hot shock are given.     

Immunochromatographic lateral-flow test strip for the rapid detection of added bovine rennet whey in milk and milk powder

An immunochromatographic lateral-flow test dipstick test was developed for the fast detection of bovine rennet whey in liquid milk and milk powder. The test is based on the binding of casein glycomacropeptide (cGMP) by two specific anti-bovine κ-casein monoclonal antibodies and has a visual detection limit of around 15 ng mL^?1 for cGMP and 1% (v/v) for rennet whey in milk using standards and spiked samples. The dipstick performance was evaluated in a collaborative trial using skim milk powder and raw, pasteurized and UHT milk. The suitability of the dipstick was demonstrated in comparison with gel permeation-high performance liquid chromotography and a colorimetric method, by analysing 60 raw milk samples collected from farms in Brazil. The dipstick results correlated well with the HPLC results and were more reliable than those obtained with the colorimetric method. The dipstick test correctly identified all raw milk samples with a rennet whey content above 4%.     

Position control of an experimental robotic arm driven by artificial muscles based on shape memory alloys

This paper presents a study on the potential application of artificial muscles based on shape memory alloys as linear robotic actuators. An extended discussion on various control techniques and ways of biologically inspired muscle arrangements is presented. A two DOF experimental robotic arm was built and used to test the performance of the proposed artificial muscle configurations, and a biologically inspired control strategy using a rule-base concept was developed and tested using the two DOF experimental robotic arm.     

Reversible lesions of the nucleus of the solitary tract attenuate the memory-modulating effects of posttraining epinephrine.

Male rats implanted with cannula tips placed above the nucleus of the solitary tract (NTS) were trained to obtain food pellets placed in 2 arms of a Y-maze and then given a footshock in 1 arm of the maze. Ss then received bilateral injections of lidocaine or buffer into the NTS and peripheral injections of saline or epinephrine (0.01 or 0.05 mg/kg, intraperitoneally [ip]). Two tests were given 24 and 48 hrs after training to assess retention in the presence and absence of contextual cues (the stainless steel floor) associated with the footshock training trial. Epinephrine (0.05 mg/kg) produced a significant enhancement in retention, which was attenuated by injections of lidocaine into the NTS. These findings indicate that the NTS is involved in mediating the memory-modulating effects of peripheral epinephrine and that such effects are initiated at least in part by activation of vagal afferents projecting to the NTS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An investigation of drum granulation of post-pyrolysis washed biochar

Biochar, unwashed and washed with a solution of Triton and hydrogen peroxide, was wet drum granulated using molasses binder solutions. Unwashed biochar was very hydrophobic and granulation proceeded through forming liquid marbles and layering. Washing reduced the hydrophobicity of the biochar. The effectiveness of the wash depended on the biochar source; it significantly reduced the hydrophobicity of biochar from woodchips and moderately reduced the hydrophobicity of biochar from flower digestate. Therefore, washed biochar from woodchips was granulated using a hydrophilic mechanism, while washed biochar from digestate was granulated according to a combination mechanism of liquid marbles collapsing and then coalescing. The change in granulation mechanism produced stronger and denser granules with higher yields of granules in the 1–4 mm optimal size range. Washing and then granulating biochar created a product that could be further tailored for optimal soil amendment.