The Development of Linear Distance Functions for Distribution Analysis

The general method of estimating the road mileage between points identified only by their co-ordinates is to proportionately inflate the straight-line distance between them. We present the traditional single-region model and extend this to a generalized multi-region format. The inflating parameters are derived and various statistical tests carried out to evaluate the models. It is shown that, on average, the multi-region approach gives better mileage estimates for all types of distribution analysis. For specific problems, which are discussed, the single-region model is shown to produce results which are unacceptable for the planning of distribution networks.     

A Simple Heuristic to Facilitate Course Timetabling

A common class of problem in the area of course timetabling is the scheduling of optional subjects so that each member of the class is able to attend as many as possible of his preferred options without clashes. A simple heuristic framework is described which produces near-optimal solutions very quickly. Various decision rules are tested on actual course data and the best available policies are identified.     

Fluorinated carbohydrates—IX The mass spectra of deoxyfluorohexopyranose derivatives

The mass spectra of some deoxyfluorohexopyranose acetates bearing the fluorine substituent at positions 2,3,4, or 6 were determind. The fragmentation pathways were analogous with those for hexopyranose acetates, except that the cleavage of bonds between carbon atoms was hindered by the attachment of a fluorine substituent to one of the carbon atoms.     

Discovery of a novel ligand that modulates the protein–protein interactions of the AAA+ superfamily oncoprotein reptin

Developing approaches to discover protein–protein interactions (PPIs) remains a fundamental challenge. A chemical biology platform is applied here to identify novel PPIs for the AAA+ superfamily oncoprotein reptin. An in silico screen coupled with chemical optimization provided Liddean, a nucleotide-mimetic which modulates reptin''s oligomerization status, protein-binding activity and global conformation. Combinatorial peptide phage library screening of Liddean-bound reptin with next generation sequencing identified interaction motifs including a novel reptin docking site on the p53 tumor suppressor protein. Proximity ligation assays demonstrated that endogenous reptin forms a predominantly cytoplasmic complex with its paralog pontin in cancer cells and Liddean promotes a shift of this complex to the nucleus. An emerging view of PPIs in higher eukaryotes is that they occur through a striking diversity of linear peptide motifs. The discovery of a compound that alters reptin''s protein interaction landscape potentially leads to novel avenues for therapeutic development.     

In‐Situ and Ex‐Situ Microscopic Study of Gas Phase Propylene Polymerization over a High Activity TiCl4‐MgCl2 Heterogeneous Ziegler‐Natta Catalyst

In‐situ gas phase poly(propylene) (PP) formation over a high activity TiCl₄‐MgCl₂‐supported Ziegler‐Natta catalyst has been studied by video microscopy combined with ex‐situ light microscopy, SEM, high‐resolution TEM, and STEM/PEELS/EDX for the first time. In‐situ observation revealed rapid formation of poly(propylene) beads 9–10 μm in size (< 1/30 s) as well as growth of significant amounts of polymer within local regions. Catalyst particles containing 2–5 nm‐sized MgCl₂ crystalline domains are subjected to transformations during catalysis that form PP/catalyst aggregated structures of 30–50 μm in size.     

Rapid catalytic oxidation of CO to CO(2) - On the development of a new approach to on-line oxygen isotope analysis of organic matter

A new approach to on-line oxygen isotope analysis has been developed which utilises existing elemental analyser and mass spectrometry technology to produce a sample of carbon dioxide gas for oxygen isotople analysis. The method relies on on-line high temperature pyrolysis of the sample over a carbon source followed by a rapid, non-contributive partial catalytic oxidation over nickel powder at between 550 and 600 degrees C. Initial results demonstrate both good precision (better than 0.2 per thousand) and accuracy for both cellulose and silver nitrate samples. Copyright 1999 John Wiley & Sons, Ltd.     

Novel small-molecule inhibitors of arylamine N-acetyltransferases: drug discovery by high-throughput screening

Arylamine N-acetyltransferases (NATs) are a family of enzymes found in eukaryotes and prokaryotes. While the precise endogenous function of NAT remains unknown for most organisms, recent evidence has shown that the expression of human NAT1 is up-regulated in estrogen receptor positive breast cancer. Additionally, NAT in mycobacteria is required for mycobacterial cell wall biosynthesis and survival of the organisms within macrophage. It is therefore important to develop small molecule inhibitors of NATs as molecular tools to study the function of NATs in various organisms. Such inhibitors may also prove useful in future drug design, for example in the development of anti tubercular agents. We describe a high-throughput screen of a proprietary library of 5016 drug-like compounds against three prokaryotic NAT enzymes and two eukaryotic NAT enzymes.     

Impurity identification and determination for the peptide hormone angiotensin I by liquid chromatography–high-resolution tandem mass spectrometry and the metrological impact on value assignments by amino acid analysis

It is common practice to quantify the mass concentration of a peptide solution through quantitative determination of selected chemically stable amino acids produced following complete hydrolysis of the parent peptide. This is because there is generally an insufficient quantity of material available to allow for the obvious alternative of a direct purity analysis characterization of the parent peptide, and the subsequent constitution of a calibration solution. However, selected accurately characterized pure peptide reference materials are required to establish reference points for the dissemination of metrologically traceable measurements and to develop reference measurement systems for laboratory medicine. In principle, purity assignment of a peptide can be performed by using the so-called mass balance approach, by employing a range of analytical techniques to obtain an estimate of the mass fraction content of all impurities present in the intact peptide, and by utilizing the difference from the theoretical limit value to assign the mass fraction content of the main peptide. Liquid chromatography–high-resolution tandem mass spectrometry (LC-hrMS/MS) is a key technique for the detection, identification, and determination of structurally related impurities present in a peptide material, and experiments characterizing the model peptide hormone angiotensin I (ANG I) are described in the present work. Degradation products that were generated from ANG I after storage at elevated temperatures were screened. The formation of peptide fragments such as ANG II or ANG III was determined by comparison of measured mass values with calculated mass values. The use of a data-dependent acquisition technique enabled the detection and structural characterization of ANG II and other peptide fragments as major impurities in the same LC-hrMS/MS analysis run. Subsequent quantification using external calibration allowed the mass fraction of the major impurities in a candidate reference material to be estimated as 10.4 mg/g. Failure to correct for these impurities would lead to a 1 % error in the determination of the concentration of the peptide in solution by amino acid analysis techniques.

Editorial for Focus Issue on Enabling Science and Technology for High-Speed Optical Communications

<正>Fiber optics underpins the communications infrastructure for the information society today. Cables consisting of hair-like fibers speed data around the globe in the form of rapid pulses of light. Modern telecom