Characterization of the binding site for inhibitors of the HPV11 E1-E2 protein interaction on the E2 transactivation domain by photoaffinity labeling and mass spectrometry

An indandione-containing class of inhibitors abrogates DNA replication of human papillomavirus (HPV) types 6 and 11 by binding reversibly to the transactivation domain (TAD) of the viral E2 protein and inhibiting its interaction with the viral E1 helicase. To locate the binding site of this class of protein-protein interaction inhibitors, a benzophenone derivative was used to generate an irreversibly labeled E2-TAD polypeptide. The single site of covalent modification of the E2-TAD was identified by proteolytic digestions using trypsin, LysC, and V8 proteases and characterization of the resulting peptides by LC-MS procedures. Through this methodology, the benzophenone attachment point was located at the terminal methyl of residue Met101. Evidence further pinpointed the site of photoaffinity attachment to the terminal carbon atom, which is significant in providing a definitive example of the ability to locate photoinduced cross-linking to a polypeptide with atomic resolution using solely mass spectrometric detection. The location of the inhibitor binding site vis-à-vis the Glu39 and Glu100 residues sensitive to mutation for HPV 11 E2-TAD is discussed in relation to the crystal structure of the E2-TAD from the related HPV type 16.     

Impact of the Nanoscale Gap Morphology on the Plasmon Coupling in Asymmetric Nanoparticle Dimer Antennas

Coupling of plasmon resonances in metallic gap antennas is of interest for a wide range of applications due to the highly localized strong electric fields supported by these structures, and their high sensitivity to alterations of their structure, geometry, and environment. Morphological alterations of asymmetric nanoparticle dimer antennas with (sub)‐nanometer size gaps are assigned to changes of their optical response in correlative dark‐field spectroscopy and high‐resolution transmission electron microscopy (HR‐TEM) investigations. This multimodal approach to investigate individual dimer structures clearly demonstrates that the coupling of the plasmon modes, in addition to well‐known parameters such as the particle geometry and the gap size, is also affected by the relative alignment of both nanoparticles. The investigations corroborate that the alignment of the gap forming facets, and with that the gap area, is crucial for their scattering properties. The impact of a flat versus a rounded gap structure on the optical properties of equivalent dimers becomes stronger with decreasing gap size. These results hint at a higher confinement of the electric field in the gap and possibly a different onset of quantum transport effects for flat and rounded gap antennas in corresponding structures for very narrow gaps.     

Mining association rules for the quality improvement of the production process

Academics and practitioners have a common interest in the continuing development of methods and computer applications that support or perform knowledge-intensive engineering tasks. Operations management dysfunctions and lost production time are problems of enormous magnitude that impact the performance and quality of industrial systems as well as their cost of production. Association rule mining is a data mining technique used to find out useful and invaluable information from huge databases. This work develops a better conceptual base for improving the application of association rule mining methods to extract knowledge on operations and information management. The emphasis of the paper is on the improvement of the operations processes. The application example details an industrial experiment in which association rule mining is used to analyze the manufacturing process of a fully integrated provider of drilling products. The study reports some new interesting results with data mining and knowledge discovery techniques applied to a drill production process. Experiment’s results on real-life data sets show that the proposed approach is useful in finding effective knowledge associated to dysfunctions causes.     

Kinetic Facility Location

We present a deterministic kinetic data structure for the facility location problem that maintains a subset of the moving points as facilities such that, at any point of time, the accumulated cost for the whole point set is at most a constant factor larger than the optimal cost. In our scenario, each point can change its status between client and facility and moves continuously along a known trajectory in a d-dimensional Euclidean space, where d is a constant.     

S-Ribosylhomocysteine analogues modified at the ribosyl C-4 position

4-C-Alkyl/aryl-S-ribosylhomocysteine (SRH) analogues were prepared by coupling of homocysteine with 4-substituted ribofuranose derivatives. The diastereoselective incorporation of the methyl substituent into the 4 position of the ribose ring was accomplished by the addition of methylmagnesium bromide to the protected ribitol-4-ulose yielding the 4-C-methylribitol in 85% yield as single 4R diastereomer. The 4-C hexyl, octyl, vinyl, and aryl ribitols were prepared analogously. Chelation controlled addition of a carbanion to ketones from the Si-face was responsible for the observed stereochemical outcome. Oxidation of the primary alcohol of the 4-C ribitols with catalytic amounts of tetrapropylammonium perruthenate in the presence of N-methylmorpholine N-oxide produced 4-C-alkylribono-1,4-lactones in high yields. Mesylation of the latter compounds at the 5-hydroxyl position and treatment with a protected homocysteine thiolate afforded protected 4-C-alkyl/aryl-SRH analogues as the lactones. Reduction with lithium triethylborohydride and successive global deprotections with TFA afforded 4-C-alkyl/aryl SRH analogues. These analogues might impede the S-ribosylhomocysteinase(LuxS)-catalyzed reaction by preventing β-elimination of a homocysteine molecule, and thus depleting the production of quorum sensing signaling molecule AI-2.     

Interface reactions between rutile coatings and molten aluminium or AlSi7Mg0.6 alloy

Rutile coatings deposited on corundum substrates are considered as promising functional elements improving the efficiency of the filtration of oxide inclusions out of aluminium melts. This contribution describes the reactions between rutile and two kinds of the aluminium melts and discusses the consequences of these reactions for the filtration process. It was found that the contact of rutile coatings with molten aluminium leads to the formation of a corundum layer at the solid/liquid interface. The exposure of the rutile coatings to molten AlSi7Mg0.6 alloy produces an interface layer of MgTiO₃. The interface layers possess defined orientation relationship to rutile which is characteristic for locally heteroepitaxial growth. The density functional theory calculations revealed that the TiO₂/α-Al₂O₃ and TiO₂/MgTiO₃ interfaces with the orientation relationships observed experimentally have low interface energies. The mechanisms of the interface layer formation and the impact of these layers on the degradation of the rutile coatings are discussed.     

Industrial applications of product design through the inversion of latent variable models

A methodology, presented by Jaeckle and MacGregor [C.M. Jaeckle and J.F. MacGregor, Product Design Through Multivariate Statistical Analysis of Process Data, AIChE J. 44 (5) (1998) 1105–1118.], for finding a window of process operating conditions within which a product with specified quality characteristics can be produced is applied to two industrial polymerization processes. The approach uses historical data available on the process operating conditions and on the corresponding product quality for a range of existing product grades. Latent variable models — built using the existing data — are inverted to obtain a window of operating conditions, which are not only capable of yielding the desired product but are also consistent with past operating procedures and constraints. A semi-batch emulsion polymerization process for manufacturing various grades of a copolymer latex, and a batch solution polymerization process for manufacturing a range of polymer resins are considered.     

Influence of organic and colloidal fouling on the removal of sulphamethoxazole by nanofiltration membranes.

This study investigated the effects of organic and colloidal fouling on the removal of a representative micropollutant sulphamethoxazole by two commercially available NF membranes. Alginate, bovine serum albumin and colloidal silica were selected as model foulants to simulate hydrophilic and hydrophobic organic fractions, and colloidal matter that are often found in treated effluent and surface water. Membrane fouling was related to the membrane and foulant characteristics and subsequently the separation behaviour of the micropollutant sulphamethoxazole under different solution pH. On the basis of these results, it was confirmed that membrane fouling is strongly dependent on both the foulant and membrane characteristics. The complex relationship among retention mechanisms, fouling mechanisms and the effects of fouling on retention was systematically delineated. Of the three model foulants selected for this study, colloidal fouling resulted in the most significant reduction in retention of sulphamethoxazole as well as inorganic salts, while flux decline as a result of colloidal fouling was quite moderate. Reduction in retention caused by fouling was attributed to a phenomenon known as cake-enhance concentration polarisation, which was a predominant mechanism of colloidal fouling. In addition, the reported results suggested that the effect of fouling on retention is also membrane pore size dependent.