The synthesis of symmetrical and unsymmetrical P1/P1' cyclic ureas as HIV protease inhibitors

Cyclic urea SD146, a potent HIV protease inhibitor bearing a flat resistance profile, possessed poor solubility and bioavailability, which precluded further development of the compound. In an effort to improve upon the pharmacokinetic profile of the compound, several analogs modified at the P1/P1' residues were prepared and evaluated. Several of those compounds displayed significant improvement of physical properties.     

Approximate similarity search for online multimedia services on distributed CPU–GPU platforms

Similarity search in high-dimensional spaces is a pivotal operation for several database applications, including online content-based multimedia services. With the increasing popularity of multimedia applications, these services are facing new challenges regarding (1) the very large and growing volumes of data to be indexed/searched and (2) the necessity of reducing the response times as observed by end-users. In addition, the nature of the interactions between users and online services creates fluctuating query request rates throughout execution, which requires a similarity search engine to adapt to better use the computation platform and minimize response times. In this work, we address these challenges with Hypercurves, a flexible framework for answering approximate k-nearest neighbor (kNN) queries for very large multimedia databases. Hypercurves executes in hybrid CPU–GPU environments and is able to attain massive query-processing rates through the cooperative use of these devices. Hypercurves also changes its CPU–GPU task partitioning dynamically according to the observed load, aiming for optimal response times. In our empirical evaluation, dynamic task partitioning reduced query response times by approximately 50 % compared to the best static task partition. Due to a probabilistic proof of equivalence to the sequential kNN algorithm, the CPU–GPU execution of Hypercurves in distributed (multi-node) environments can be aggressively optimized, attaining superlinear scalability while still guaranteeing, with high probability, results at least as good as those from the sequential algorithm.     

Effect of elemental sulfur in the crosslinking reaction of poly(vinyl chloride) with tetramethyl thiuram disulfide

The effect of elemental sulfur (S₈) and tetramethyl thiuram disulfide (TMTD) on the chemical crosslinking of PVC is studied. The tensile strength, elongation at break, and gel content of crosslinked and uncrosslinked PVC molded samples, cured at different times in hot air, are evaluated. It was found that crosslinking PVC with TMTD improves its mechanical properties, and adding S₈ produces a slight improvement. Also, the S₈ presence accelerated the PVC/TMTD crosslinking reaction when the crosslinking reaction was carried out under shear forces, but not when the curing was done in hot air, where the S₈ retards the process.     

Analysis of surface integrity for minimum quantity lubricant—MQL in grinding

The quality of machined components is currently of high interest, for the market demands mechanical components of increasingly high performance, not only from the standpoint of functionality but also from that of safety. Components produced through operations involving the removal of material display surface irregularities resulting not only from the action of the tool itself, but also from other factors that contribute to their superficial texture. This texture can exert a decisive influence on the application and performance of the machined component. This article analyzes the behavior of the minimum quantity lubricant (MQL) technique and compares it with the conventional cooling method. To this end, an optimized fluid application method was devised using a specially designed nozzle, by the authors, through which a minimum amount of oil is sprayed in a compressed air flow, thus meeting environmental requirements. This paper, therefore, explores and discusses the concept of the MQL in the grinding process. The performance of the MQL technique in the grinding process was evaluated based on an analysis of the surface integrity (roughness, residual stress, microstructure and microhardness). The results presented here are expected to lead to technological and ecological gains in the grinding process using MQL.     

A Bayesian approach to estimate the marginal loss distributions in operational risk management

One of the main problems in operational risk management is the lack of loss data, which affects the parameter estimates of the marginal distributions of the losses. The principal reason is that financial institutions only started to collect operational loss data a few years ago, due to the relatively recent definition of this type of risk. Considering this drawback, the employment of Bayesian methods and simulation tools could be a natural solution to the problem. The use of Bayesian methods allows us to integrate the scarce and, sometimes, inaccurate quantitative data collected by the bank with prior information provided by experts. An original proposal is a Bayesian approach for modelling operational risk and for calculating the capital required to cover the estimated risks. Besides this methodological innovation a computational scheme, based on Markov chain Monte Carlo simulations, is required. In particular, the application of the MCMC method to estimate the parameters of the marginals shows advantages in terms of a reduction of capital charge according to different choices of the marginal loss distributions.     

Classification of Fuzzy Mathematical Morphologies Based on Concepts of Inclusion Measure and Duality

Mathematical morphology was originally conceived as a set theoretic approach for the processing of binary images. Extensions of classical binary morphology to gray-scale morphology include approaches based on fuzzy set theory. This paper discusses and compares several well-known and new approaches towards gray-scale and fuzzy mathematical morphology. We show in particular that a certain approach to fuzzy mathematical morphology ultimately depends on the choice of a fuzzy inclusion measure and on a notion of duality. This fact gives rise to a clearly defined scheme for classifying fuzzy mathematical morphologies. The umbra and the level set approach, an extension of the threshold approach to gray-scale mathematical morphology, can also be embedded in this scheme since they can be identified with certain fuzzy approaches.

Plasmon hybridization engineering in self-organized anisotropic metasurfaces

Nano Research - The engineering of self-organized plasmonic metasurfaces is demonstrated using a maskless technique with defocused ion-beam sputtering and kinetically controlled deposition. The...     

Force-clamp spectroscopy with a small dithering of AFM tip, and its application to explore the energy landscape of single avidin-biotin complex

We have recently developed a new method for directly measuring the spring constant of single molecules and molecular complexes on a real-time basis [L.A. Chtcheglova, G.T. Shubeita, S.K. Sekatskii, G. Dietler, Biophys. J. 86 (2004) 1177]. The technique combines standard force spectroscopy with a small dithering of tip. Changes in the amplitude of the oscillations are measured as a function of the pulling-off force to yield the spring constant of the complex. In this report, we present the first results of combination of this approach with the force-clamp spectroscopy. The standard atomic-force microscope has been supplemented with an electronic unit, which is capable of realizing an arbitrary force function, and permits the force-loading regime to be interrupted at any time. Using this method, the time needed to rupture a single bond can be measured as a function of the force that is required to maintain the complex in a stretched condition. The energy landscape of the avidin-biotin complex is explored and discussed.