Modelling mutagenicity using properties calculated by computational chemistry

The recent advances in combinatorial chemistry and high throughput screening technologies have led to an explosion in the numbers of possible therapeutic candidates being produced at the early stages of drug discovery. This rapid increase in the number of chemicals to be classified results in a greater need for alternative methods for the prediction of toxicity. Most QSAR models for mutagenicity have been constructed for congeneric series. The prediction requirements of the pharmaceutical industry, however, cover quite diverse chemical structures. This paper reports a study of mutagenicity data for a diverse set of 90 compounds. Good discriminant models have been built for this data set using properties calculated by the techniques of computational chemistry. Jack-knifed (leave one out) predictions for these models are of the order of 85%.     

Identifying and quantifying short-lived fission products from thermal fission of HEU using portable HPGe detectors

Due to the emerging potential for trafficking of special nuclear material, research programs are investigating current capabilities of commercially available portable gamma ray detection systems. Presented in this paper are the results of three different portable high-purity germanium (HPGe) detectors used to identify short-lived fission products generated from thermal neutron interrogation of small samples of highly enriched uranium. Samples were irradiated at the Washington State University Nuclear Radiation Center’s 1 MW TRIGA reactor. The three portable, HPGe detectors used were the ORTEC MicroDetective [1], the ORTEC Detective [2], and the Canberra Falcon [3]. Canberra’s GENIE-2000 software was used to analyze the spectral data collected from each detector. Ultimately, these three portable detectors were able to identify a large range of fission products showing potential for material discrimination.     

Searching for multiobjective preventive maintenance schedules: Combining preferences with evolutionary algorithms

Heavy industry maintenance facilities at aircraft service centers or railroad yards must contend with scheduling preventive maintenance tasks to ensure critical equipment remains available. The workforce that performs these tasks are often high-paid, which means the task scheduling should minimize worker idle time. Idle time can always be minimized by reducing the workforce. However, all preventive maintenance tasks should be completed as quickly as possible to make equipment available. This means the completion time should be also minimized. Unfortunately, a small workforce cannot complete many maintenance tasks per hour. Hence, there is a tradeoff: should the workforce be small to reduce idle time or should it be large so more maintenance can be performed each hour? A cost effective schedule should strike some balance between a minimum schedule and a minimum size workforce.     

An expedient conversion of α-amino acids into Weinreb amides using COMU® as a coupling agent

The use of COMU®, as a non-hazardous partner, in the coupling of N-protected α-amino acids to N-methoxy-N-methylamine to afford the corresponding Weinreb amides is discussed. From a practical point of view the reaction can be monitored visually by virtue of the colour change associated with the conversion of substrates (yellow) into the products (orange). As the by-products of the reaction are conveniently water-soluble the products are isolated relatively pure and with minimal racemisation. These factors coupled with the short reaction time make this a very useful procedure.     

Construction of Equivalent Stochastic Differential Equation Models

Abstract

It is shown how different but equivalent Itô stochastic differential equation models of random dynamical systems can be constructed. Advantages and disadvantages of the different models are described. Stochastic differential equation models are derived for problems in chemistry, textile engineering, and epidemiology. Computational comparisons are made between the different stochastic models.     

Metal-ion Binding to Host Defense Peptide Piscidin 3 Observed in Phospholipid Bilayers by Magic Angle Spinning Solid-state NMR

Cationic antimicrobial peptides (AMPs) are essential components of the innate immune system. They have attracted interest as novel compounds with the potential to treat infections associated with multi-drug resistant bacteria. In this study, we investigate piscidin 3 (P3), an AMP that was first discovered in the mast cells of hybrid striped bass. Prior studies showed that P3 is less active than its homolog piscidin 1 (P1) against planktonic bacteria. However, P3 has the advantage of being less toxic to mammalian cells and more active on biofilms and persister cells. Both P1 and P3 cross bacterial membranes and co-localize with intracellular DNA but P3 is more condensing to DNA while P1 is more membrane active. Recently, we showed that both peptides coordinate Cu²⁺ through an amino-terminal copper and nickel (ATCUN) motif. We also demonstrated that the bactericidal effects of P3 are linked to its ability to form radicals that nick DNA in the presence of Cu²⁺. Since metal binding and membrane crossing by P3 is biologically important, we apply in this study solid-state NMR spectroscopy to uniformly ¹³C-¹⁵N-labeled peptide samples to structurally characterize the ATCUN motif of P3 bound to bilayers and coordinated to Ni²⁺ and Cu²⁺. These experiments are supplemented with density functional theory calculations. Taken together, these studies refine the arrangement of not only the backbone but also side chain atoms of an AMP simultaneously bound to metal ions and phospholipid bilayers.     

Ultrasonic sensor to characterize wood pulp during refining

A novel sensor concept has been developed for measuring the degree of refining, the water retention value (WRV), and the weight percentage of wood pulp during the refining process. The measurement time is less than 5 min and the sensor can operate in a slip-stream of the process line or as an at-line instrument. The degree of refining and the WRV are determined from settling measurements. The settling of a pulp suspension (with a weight percentage less than 0.5 wt%) is observed, after the mixer, which keeps the pulp uniformly distributed, is turned off. The attenuation of ultrasound as a function of time is recorded and these data show a peak at a time designated as the "peak time." The peak time T increases with the degree of refining, as demonstrated by measuring pulp samples with known degrees of refining. The WRV can be determined using the relative peak time, defined as the ratio T(2)/T(1), where T(1) is an initial peak time and T(2) is the value after additional refining. This method offers an alternative WRV test for the industry to the current time-consuming method.     

Application of tests of chi-square type

Some recent results on the theory of chi-square tests are given. Remarks of practical character on the use of these tests are made, reflecting on a large number of applied papers.Translated from Zapiski Nauchnykh Seminarov Leningradskogo Otdeleniya Matematicheskogo Instituta im. V. A. Steklova AN SSSR, Vol. 158, pp. 49–71, 1987.     

Ab initio theory of hydrogen bonding in vitamin B6

Ab initio MO computations have been carried out for the crystalline form of the B₆ vitamin, pyridoxinium chloride. In the crystal, the pyridoxine is protonized to pyridoxinium, with the formation of a hydrogen bond N? H⁺ ? Cl^?. For an isolated molecule, the calculations predict a single potential well, with H⁺ placed close to Cl^? at the minimum. When neighboring molecules are included in the calculations, a double well is formed, and the lower minimum occurs for the proton placed near the experimentally observed position, in the vicinity of the N atom. Mulliken populations, which depend on the proton position, are described.     

The variation of a stable path is stable

Summary Let X(t) be a separable symmetric stable process of index . Let P be a finite partition of [0,1], and a collection of partitions. The variation of a path X(t) is defined in three ways in terms of the sum collection . Under certain conditions on and on the parameters and , the distribution of the variation is shown to be a stable law. Under other conditions the distribution of the variational sum converges to a stable distribution.The author wishes to thank Prof. J. Chover for several helpful suggestions.