Computer based screening of compound databases: 1. Preselection of benzamidine-based thrombin inhibitors

We present a computational protocol which uses the known three-dimensional structure of a target enzyme to identify possible ligands from databases of compounds with low molecular weight. This is accomplished by first mapping the essential interactions in the binding site with the program GRID. The resulting regions of favorable interaction between target and ligand are translated into a database query, and with UNITY a flexible 3D database search is performed. The feasibility of this approach is calibrated with thrombin as the target. Our results show that the resulting hit lists are enriched with thrombin inhibitors compared to the total database.     

Characterisation of botulinum toxins type C, D, E, and F by matrix-assisted laser desorption ionisation and electrospray mass spectrometry

In a follow-up of the earlier characterisation of botulinum toxins type A and B (BTxA and BTxB) by mass spectrometry (MS), types C, D, E, and F (BTxC, BTxD, BTxE, BTxF) were now investigated. Botulinum toxins are extremely neurotoxic bacterial toxins, likely to be used as biological warfare agent. Biologically active BTxC, BTxD, BTxE, and BTxF are comprised of a protein complex of the respective neurotoxins with non-toxic non-haemagglutinin (NTNH) and, sometimes, specific haemagglutinins (HA). These protein complexes were observed in mass spectrometric identification. The BTxC complex, from Clostridium botulinum strain 003-9, consisted of a 'type C1 and D mosaic' toxin similar to that of type C strain 6813, a non-toxic non-hemagglutinating and a 33 kDa hemagglutinating (HA-33) component similar to those of strain C-Stockholm, and an exoenzyme C3 of which the sequence was in full agreement with the known genetic sequence of strain 003-9. The BTxD complex, from C. botulinum strain CB-16, consisted of a neurotoxin with the observed sequence identical with that of type D strain BVD/-3 and of an NTNH with the observed sequence identical with that of type C strain C-Yoichi. Remarkably, the observed protein sequence of CB-16 NTNH differed by one amino acid from the known gene sequence: L859 instead of F859. The BTxE complex, from a C. botulinum isolated from herring sprats, consisted of the neurotoxin with an observed sequence identical with that from strain NCTC 11219 and an NTNH similar to that from type E strain Mashike (1 amino acid difference with observed sequence). BTxF, from C. botulinum strain Langeland (NCTC 10281), consisted of the neurotoxin and an NTNH; observed sequences from both proteins were in agreement with the gene sequence known from strain Langeland. As with BTxA and BTxB, matrix-assisted laser desorption/ionisation (MALDI) MS provided provisional identification from trypsin digest peptide maps and liquid chromatography-electrospray (tandem) mass spectrometry (LC-ES MS) afforded unequivocal identification from amino acid sequence information of digest peptides obtained in trypsin digestion.     

Using a process-centered approach to minimize the effort of compliance

 The complexity of different quality standards can, in principle, be covered by different approaches and strategies. In-depth process mapping of quality control (QC) work streams was used by the analytical laboratories of Lonza AG to show up the principle differences in being compliant to different quality systems. The results identified two main drivers for all necessary actions: process-related activities and infrastructure-related activities. In addition, a clear indication of the economic impact of these driving forces was gained, which led the laboratories to decide on a process-oriented approach. This approach has the advantage of being able to reflect the different demands of different quality assurance (QA) regulations within the same QC organizational structure. Following the process helps avoid unnecessary efforts in analytical work and represents a very economical approach, at the same time, providing high flexibility to react to different QA or customer demands. Received: 5 July 2002 Accepted: 12 November 2002 Acknowledgements The process-oriented approach resulted from many, very challenging discussions for which I would like to thank the staff of my organization (Analytics & QC), especially, the QA staff and the LIMS team. Presented at Analytica Conference, 23–26 April 2002, Munich, Germany Correspondence to B. Ciommer     

Controlled enzyme-immobilisation on capillaries for microreactors for peptide mapping

In the present paper, the covalent immobilisation of the digesting enzyme trypsin has been achieved through photo-immobilisation on a portion of a silica capillary, thus leading to the construction of a capillary electrophoretic (CE)-microreactor for peptide mapping. The CE-microreactor is characterised by being a single piece, thus ensuring no fluidic or electrical leakage. The enzyme was immobilised with a surface density of 15.8 g/cm², the stability was high (80% after 38 days) and the rate of conversion was 0.2 ng/s. On-line protein mapping was tested with proteins of different dimensions, showing competitiveness in terms of time (completed map within 15 min) and exhaustive maps of small proteins. The results of the CE-microreactor and the potential to immobilise biocomponents easily on a desired portion of the capillary indicate further developments towards the construction of a variety of miniaturised enzymatic screening devices for high-throughput screening analysis.     

Real-time sensing and three-dimensional display of far outdoor scenes based on asymmetric integral imaging

A new asymmetric integral imaging (AII) system for real-time pickup and three-dimensional (3-D) display of far outdoor scenes based on dynamic-pixel-mapping (DPM) is proposed. DPM is a digital process to transform the elemental images captured with a lens array into the perspective-variant object images (POIs) whose structures are matched with those of display lenses, where the orders of pixels in each POI are reversely mapped, and then capture a set of virtual elemental images (EIs) at the specific depth planes from the back-propagated POIs. This DPM enables an asymmetrical use of pickup and display lens arrays, allowing the long-ranged pickup of far outdoor scenes and their resolution-enhanced 3-D reconstruction. Experiments with a pair of pickup and display lens arrays whose pitches and focal lengths are given by 7.5 mm, 30 mm and 1.2 mm, 8 mm, respectively, show that the effective pickup-range and resolution of the proposed system have been increased up to 6 m and 1600×1600 pixels, respectively, from 0.064 m and 480×480 pixels of the conventional systems employing the same pickup and display lens arrays. In addition, experiments with an implemented test bed confirms that the proposed system can provide real-time 3-D images in 25 frames per second.     

Bounds for the fundamental solutions of elliptic and parabolic equations

It is shown that any elloptic or parabolic operator in nondivergence form with measurable coefficients has a global fundamental solution verifying certain pointwise bounds.     

Studies on defect formation in femtosecond laser-irradiated PMMA and PDMS

We report here our results on the spectroscopic and elemental analysis of femtosecond (fs) laser-modified regions in polymers of polymethylmethacrylate (PMMA) and polydimethylsiloxane (PDMS) in the context of defect formation and emission in the visible region. Different physical and chemical models are used to explain the changes in modified regions. We found that the emission intensity, recorded from the fs-modified regions of polymers, decreased over time to a constant value. We also demonstrate that these materials are suitable for the preparation of the microstructures en route for light guiding applications. The fs laser-irradiated regions exhibited paramagnetic behavior as was confirmed from electron spin resonance studies through the formation of peroxide-type free radicals. Raman mapping was performed in the modified regions which consisted of defects and found that the modulations in intensity are predominant in the central portion of the structure compared to edges. Elemental analysis has been performed in the modified regions using field emission scanning electron microscope instrument and energy-dispersive X-ray absorption spectroscopy to estimate the percentage contents of individual elements which resulted in defect formation such as paramagnetic and optical centers.     

Strong Convergence Theorems for the Generalized Viscosity Implicit Rules of Asymptotically Nonexpansive Mappings in the Intermediate Sense in Hilbert Spaces

Abstract

The aim of this paper is to introduce the generalized viscosity implicit rules of one asymptotically nonexpansive mapping in the intermediate sense in Hilbert spaces. We obtain some strong convergence theorems under certain assumptions imposed on the parameters. We also give a numerical example to support our main results. The results obtained in this paper improve and extend many recent ones in this culture.     

Multi-objective optimal design of feedback controls for dynamical systems with hybrid simple cell mapping algorithm

This paper presents a study of multi-objective optimal design of full state feedback controls. The goal of the design is to minimize several conflicting performance objective functions at the same time. The simple cell mapping method with a hybrid algorithm is used to find the multi-objective optimal design solutions. The multi-objective optimal design comes in a set of gains representing various compromises of the control system. Examples of regulation and tracking controls are presented to validate the control design.     

A screw dislocation near a non-elliptical piezoelectric inhomogeneity with internal uniform electroelastic field

Conformal mapping and analytic continuation are employed to prove the existence of an internal uniform electroelastic field inside a non-elliptical piezoelectric inhomogeneity interacting with a screw dislocation. We focus specifically on the case when the piezoelectric matrix surrounding the inhomogeneity is subjected to uniform remote anti-plane mechanical and in-plane electrical loading and a constraint is imposed between the remote loading and the screw dislocation. The constraint can be expressed in a relatively simple decoupled form by utilizing orthogonality relationships between two corresponding eigenvectors. The internal uniform electroelastic field is found to be independent of the presence of the screw dislocation; moreover, it can be expressed in decoupled form.