Modelling ties in the sign test.

If ties occur in the sign test, the procedure recommended by Coakley and Heise (1996, Biometrics 52, 1242-1251) is the asymptotic uniformly most powerful nonrandomised test due to Putter (1955, Annals of Mathematical Statistics 26, 368-386). It may be shown that this is a consequence of how the probability of a tie is modelled. Other models with different optimal procedures can be constructed.

The chemistry of pseudomonic acid. 18. Heterocyclic replacement of the alpha,beta-unsaturated ester: synthesis, molecular modeling, and antibacterial activity.

The electronic requirements around the C1-C3 region of pseudomonic acid analogues were investigated. Synthetic routes were developed to access a range of compounds where the alpha, beta-unsaturated ester moiety had been replaced by a 5-membered ring heterocycle. The inhibition of isoleucyl tRNA synthetase from Staphylococcus aureus NCTC 6571 was determined as was the minimum inhibitory concentration (MIC) of the test compounds against that organism. Compounds possessing a region of electrostatic potential corresponding to that of the carbonyl group in the alpha, beta-unsaturated ester, and a low-energy unoccupied molecular orbital in the region corresponding to the double bond, were found to have IC50 values of 0.7-5.3 ng mL-1. However the MIC values of these compounds were in the range 2.0-8.0 micrograms mL-1, reflecting their poorer penetration into the bacterial cell.

Organophosphorus residues in wool grease resulting from specified on-farm lice and flystrike control treatments.

OBJECTIVE: To investigate wool organophosphorus concentrations resulting from a range of farm pesticide application methods. DESIGN: Random sampling of wool for pesticide residues and on-farm interviews to determine associated treatments. PROCEDURE: Tasmanian fleece wool lots were sampled at random and tested for organophosphorus residues. The grower was identified and the pesticide treatments applied to the sheep were ascertained by on-farm interview. RESULTS: The residue concentrations showed a large variation that was not accounted for by differences in treatments by growers. Organophosphorus concentrations were proportional to the number of treatments applied, and inversely related to the time between pesticide application and the subsequent shearing, and were significantly influenced by the method of application. After allowing for the time of application, plunge dipping resulted in pesticide residue concentrations 2 to 2.5 times greater than shower dipping, using spray races or hand jetting, and the use of these methods caused larger residues than the use of jetting races. CONCLUSIONS: We recommend that plunge or shower dipping should not be used more than 7 weeks after shearing, nor at higher concentration than the standard dose rate used for lice control, whereas jetting may be satisfactory for up to 7 months after shearing, provided only one application is administered.

How order affects the sign test.

In carrying out the sign test, the order in which the subject receives the treatments may be important. We examine Gart's test and show it is equivalent to a score test under a product binomial model. If equal numbers of subjects receive each treatment order, then we suggest our form of Gart's test rather than the sign test should be used routinely.

Perceptual characteristics of binary, trinary, and quaternary odor mixtures consisting of unpleasant constituents.

Among the most obnoxious stimuli that the population at large is exposed to during everyday life are odorous emissions from sewage treatment plants. Such emissions are complex and contain many different types of odorants that vary in quantity depending upon the contents and efficiency of treatment processes. Because little is known about how individual odorants in complex mixtures affect the perception of each other, it is difficult to develop mathematical models that can predict the pleasantness, strength, and quality characteristics of an emission at different distances from a source. In the present study, the interactions of the four major types of odorants emitted by treatment plants worldwide, namely, hydrogen sulphide, isovaleric acid, butanethiol, and skatole, were investigated by measuring the perceived intensity of individual odorants alone and in mixtures, and the overall perceived intensity, unpleasantness, and qualities of mixtures. In addition, models for predicting odor strength were investigated. The results indicated that (i) the perceived odor intensity (odor strength) of mixtures of the odorants was equal or greater than that of any of the individual constituents, but less than the sum of their intensities. However, as the number of components in a mixture increased, the intensity of the most dominant component provided a good approximation of the intensity of the mixture. (ii) The vector model of intensity summation also satisfactorily predicted the odor intensity of mixtures containing two, three, or four of the odorants investigated. (iii) In no instance was the intensity of one odorant enhanced by another, i.e., no synergistic interactions occurred; the greater the number of odorants in a mixture, the greater was the degree of suppression of the individual constituents. (iv) The greater the number of constituents in a mixture the more difficult it became to identify individual constituents. (v) Hydrogen sulphide was the least frequently suppressed constituent, and isovaleric acid and skatole were the most frequently suppressed constituents in mixtures. (vi) The unpleasantness of mixtures was usually greater than that of the individual constituents, indicating that models used for predicting complaint levels in communities affected by sewage odor and based on assumptions related to a single odorant, e.g., hydrogen sulphide, will underestimate the number of complaints. Even mixtures with low but above threshold concentrations of these odorants are likely to generate complaints.

Nonparametric comparison of two histograms.

Scholz and Stephens (1987, Journal of the American Statistical Association 82, 918-924) proposed a nonparametric k-sample Anderson-Darling statistic for grouped data. This note demonstrates that a partition-of-chi 2 method may give a more powerful nonparametric test, particularly when alternatives other than location shift are important. A taste-test example provides motivation.

The effect of ion implantation on cellular adhesion.

As there are only a finite number of materials suitable for orthopaedic reconstruction, considerable effort has been devoted recently to investigating ways of altering the surface chemistry of prosthetic materials without altering their bulk properties. Ion beam implantation is one such technique which is appropriate for orthopaedic reconstructive materials. This paper investigates the early effect of ion beam modification on cellular attachment of bone derived cells using a prototype device which measures the strength of attachment of individual cells to a silicon substratum. The results point to several conclusions. (1) There is no evidence that ion beam implantation with nitrogen, phosphorus, manganese or magnesium produces increased adhesion of human bone derived cells. (2) Surface etching with hydrofluoric acid, electron bombardment and thermal oxidation increases the strength of attachment between cells and substrata. (3) There is a correlation between wettability and rate of cellular attachment to oxygen implanted substrata during the first 2 h after cellular seeding. However, the increase in cellular attachment cannot be entirely explained by the change in critical surface tension or via increased fibronectin attachment to the substrata.

Disease clustering in time.

Tango (1984, Biometrics 40, 15-26) proposed a clustering index for testing for clusters of disease in time. A test based on this clustering index was shown to compare favourably with other statistical tests. In this article we show that Pearson's X2 and its components perform well in testing for clusters of disease in time. The rth of these components identifies a departure from uniformity in moments up to the rth and so helps describe the alternative, if any, to uniformity.

The screening of selected microorganisms for use as models of mammalian drug metabolism.

Fifty fungi and two Streptomyces species were screened for their ability to metabolise the probe substrates aminopyrine, diazepam, testosterone, theophylline and warfarin. The metabolism of the 14C-labelled substrates by whole growing cells was compared with that by rat liver microsomes using TLC-autoradiography. Testosterone, warfarin and diazepam were readily metabolised by most microorganisms, and aminopyrine and theophylline were only metabolised by a few. A relationship between substrate lipophilicity and number of microorganisms able to biotransform the substrate was observed, lipophilic substrates being favoured for metabolism, analagous to mammalian cytochrome P-450. A wide variety of metabolites were produced by the screened cultures, with a significant number co-chromatographing with mammalian metabolites. Most microorganisms appeared to exhibit cytochrome P-450-type oxidative reactions such as hydroxylation and N-demethylation, similar to mammalian hepatic microsomal cytochrome P-450 systems.

Optimal determination of most probable numbers.

Choosing the design of a dilution series experiment on the basis of availability of most probable number tables can result in a non-optimal design. Similarly, certain tables and/or rules for declaring dilution series results 'improbable' do not always give optimal decisions. Further, tables of most probable number confidence intervals are not all based on the same assumptions and give different intervals--which should be used? The aim of this article is to draw microbiologists' attention to these issues and to suggest practical solutions.

Aryl acylamidase from Rhodococcus erythropolis NCIB 12273.

A Rhodococcus erythropolis strain was isolated from soil on the basis of its ability to use acetaminophen as the sole source of both carbon and energy for growth. When grown in a complex medium containing an anilide inducer compound, the bacterium exhibited aryl acylamidase (EC 3.5.1.13) activity. This activity was not subject to carbon or nitrogen repression by the growth medium constituents as the enzyme was present throughout the exponential growth phase. The anilide was converted to the corresponding aniline, which was not further degraded. The enzyme was partially purified by a variety of methods including a batch ion exchange procedure, column ion exchange chromatography and hydrophobic interaction chromatography. The enzyme had a maximum activity at around pH 8.0 and had a Km for acetaminophen of 0.11 mM. Electrochemical assays of aryl acylamidase activity are described. The enzyme is suitable for use as a reagent in the clinical diagnostic measurement of acetaminophen.

Purification, crystallisation and preliminary X-ray diffraction characterisation of methanol dehydrogenase from Methylosinus trichosporium OB3b.

Methanol dehydrogenase was purified from the obligate methanotroph, Methylosinus trichosporium OB3b, in two steps from disrupted biomass by aqueous two-phase partition and ion-exchange chromatography. Copartitioning of a cytochrome c was dependent upon the pH at which aqueous partition was carried out. The native enzyme has a Mr of 120,000, as determined by gel filtration chromatography, and consists of two identical subunits. The purified enzyme contained four electrophoretically distinct isoenzymes, with pI values of 6.3, 6.58, 6.63 and 6.88. The native enzyme has been crystallised in a form suitable for high-resolution X-ray crystallographic studies. The crystals diffract to better than 0.19 nm spacing and are relatively stable to irradiation with X-rays. The space group is P6(1)22 (or P6(5)22) with cell dimensions a = b = 10.21 nm, c = 29.32 nm and the crystal probably contains a single monomer in the asymmetric unit.

Studies on 6 alpha-substituted penicillins. II. Synthesis and structure-activity relationships of 6 beta-(2-aryl-2-sulfoacetamido)-6 alpha-methoxy penicillanic acids.

The synthesis and antibacterial activity of 6 alpha-methoxysulbenicillin analogues (2) are described. Structure-activity studies of these derivatives bearing hydrophilic substituents in the phenyl ring led to the identification of disodium 6 beta-[D-2-(3,4-dihydroxyphenyl)-2-sulfoacetamido]-6 alpha-methoxypenicillanate (2m) as a compound with potent activity against Pseudomonas aeruginosa including beta-lactamase producing strains. Additional substitution of 2m gave derivatives 2p, 2q, 2r, with a further improvement in activity against Gram-negative bacteria.

Preparation and structure-activity relationships of some 6 alpha-substituted penicillins.

The influence on the antibacterial activity of introducing a 6 alpha-methoxy group into carbenicillin, and various 6 alpha-substituents into sulbenicillin and piperacillin was examined. Further variations of the side chain aryl group were examined in the 6 alpha-methoxy substituted series. This led to the identification of disodium 6 beta-(D,L-2-carboxy-2-thien-3-ylacetamido)-6 alpha-methoxypenicillanate (5b) as a beta-lactamase stable derivative with useful activity against Enterobacteriaceae, and disodium 6 beta-[D-2-(4-aminophenyl)-2-sulfoacetamido]-6 alpha-methoxypenicillanate (6e) with slightly lower activity against the Enterobacteriaceae but more active against Pseudomonas aeruginosa.

Insulin responsiveness in non-fa/fa and fa/fa Zucker rats: effects of adipocyte size.

Epididymal adipose tissue from non-fa/fa (lean) and fa/fa (obese) 14.5-week-old Zucker rats was used to study the influence of insulin and genotype on uptake of glucose and palmitate into adipocytes of different sizes. After incubation with radioactive substrate, adipocytes were inactivated and fixed by addition of osmium tetroxide; fixed adipocytes were isolated and separated by screening on the basis of size. Rates of substrate uptake into triacylglycerols were measured in adipocytes of each of ten size categories. Uptake rates of both glucose and palmitate increased as adipocyte size increased. Insulin had no effect on glucose uptake per adipocyte for fa/fa rats but had a highly significant (P less than 0.01) stimulatory effect on that for non-fa/fa rats. This stimulation became significantly greater with increasing adipocyte size. When insulin was included in the incubation media, glucose uptake rates were similar between similar sizes of adipocytes from non-fa/fa and fa/fa rats. Absence of insulin from the incubation media, however, resulted in lower rates of glucose uptake by adipocytes from non-fa/fa rats. Glucose uptake was maximal in adipocytes from fa/fa rats, even in the absence of insulin. Net uptake of palmitate into triacylglycerols was not influenced by insulin; a significant interaction was observed, however, between adipocyte size and genotype. Large adipocytes from fa/fa rats had greater rates of palmitate uptake than did adipocytes of similar size from non-fa/fa rats. The reverse was true for adipocytes less than 125 micron in diameter. The results of this study show that response to insulin of adipocytes of difference sizes varies with adipocyte size and with genotype.

New findings in methane-utilizing bacteria highlight their importance in the biosphere and their commercial potential.

Recent results, showing that the ubiquitous methane-utilizing bacteria (methanotrophs) can partially oxidize and, in some cases, extensively metabolize complex organic compounds, call for a reappraisal of their role in the cycling of elements in the biosphere. Possible environmental implications and opportunities for industrial exploitation are discussed.