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Data analysis for a dual-channel virus counter.

A simple algorithm is presented for quantitative analysis of simultaneous events on a dual-channel flow cytometer designed specifically for virus counting. The algorithm, which is based on matrix analysis of burst lag times, was evaluated using baculovirus samples that had previously been quantified by the plaque titer method. The results indicated statistical reliability for the algorithm, with three of six samples yielding the same value, within error, for viruses per unit volume as the plaque titer. The other three samples yielded values within a factor approximately 2, which was deemed acceptable given the limitations of the plaque titer method.

Algorithms↗

Detection of albumin unfolding preceding proteolysis using Fourier transform infrared spectroscopy and chemometric data analysis.

The hydrolysis of bovine serum albumin with protease K at 60 degrees C has been studied by means of infrared spectroscopy. Two-dimensional correlation spectroscopy (2DCoS) has been used to study spectral changes in the reaction. The use of the multivariate curve resolution-alternating least-squares method applied to infrared measurements allowed the recovery of pure infrared spectra and concentration profiles of the different species involved in the reaction. Special attention was paid to the careful inspection of residuals again using 2DCoS. In this way, a heat-induced unfolding step previous to protein hydrolysis was identified. The infrared spectra of the intermediate species showed a more disordered structure than native albumin, the decrease in alpha-helix conformation being especially noticeable. The formation of beta-sheet aggregates due to heating was detected too.

Animals↗

Specific screening for color precursors and colorants in beet and cane sugar liquors in relation to model colorants using spectrofluorometry evaluated by HPLC and multiway data analysis.

A comparison was made of the fluorophores in beet thick juice and cane final evaporator syrup, which are comparable in the production of cane and beet sugar; that is, both represent the final stage of syrup concentration prior to crystallization of sugar. To further elucidate the nature of the color components in cane and beet syrup, a series of model colorants was also prepared, consisting of mildly alkaline-degraded fructose and glucose and two Maillard type colorants, glucose--glycine and glucose--lysine. Fluorescence excitation--emission landscapes resolved into individual fluorescent components with PARAFAC modeling were used as a screening method for colorants, and the method was validated with size exclusion chromatography using a diode array UV--vis detector. Fluorophores from the model colorants were mainly located at visible wavelengths. An overall similarity in chromatograms and absorption spectra of the four model colorant samples indicated that the formation of darker color was the distinguishing characteristic, rather than different reaction products. The fluorophores obtained from the beet and cane syrups consisted of color precursor amino acids in the UV wavelength region. Tryptophan was found in both beet and cane syrups. Tyrosine as a fluorophore was resolved in only beet syrup, reflecting the higher levels of amino acids in beet processing. In the visible wavelength region, cane syrup colorant fluorophores were situated at higher wavelengths than those of beet syrup, indicating formation of darker colorants. A higher level of invert sugar in cane processing compared to beet processing was suggested as a possible explanation for the darker colorants.

Carbohydrates↗

Simultaneous investigation of indinavir nonlinear pharmacokinetics and bioavailability in healthy volunteers using stable isotope labeling technique: study design and model-independent data analysis.

Indinavir follows nonlinear pharmacokinetics upon oral administration at clinical doses. A study employing the stable isotope administration technique in a three-treatment design was conducted to identify the source of the nonlinearity and to determine the dose-dependency of systemic bioavailability. In treatment A, 400 mg of unlabeled indinavir (D0) was coadministered orally with 16 mg of a hexadeutero analogue of indinavir (D6) intravenously. In treatment B, 800 mg of D0 po was coadministered with 16 mg of D6 intravenously. In treatment C, 16 mg of iv D6 was infused concurrently with 16 mg iv of D0. Plasma concentrations of D0 and D6 were determined by an LC/MS/MS assay method. Concentrations of indinavir in plasma increased greater than dose-proportionally over the 400- to 800-mg dose range. No meaningful kinetic isotope effects were found in treatment C. Plasma concentrations of D6 were dependent on the coadministered D0-indinavir dose and were lowest in treatment C, higher in treatment A, and highest in treatment B. The bioavailability of indinavir was high (60-65%) and comparable between the 400- and 800-mg doses. There was a significant contribution of nonlinear kinetics in the systemic circulation to the observed disproportional increase in plasma concentrations following oral dosing. The high bioavailability at clinically relevant doses suggests a high degree of saturation of first-pass metabolism. These results further demonstrate that the concomitant administration technique in combination with the LC/MS/MS method can provide a realistic and reliable means of elucidating important pharmacokinetic properties of drug candidates during product development.

Adult↗

Marine eutrophication: a proposed data analysis procedure for assessing spatial trends.

A methodology for the discrimination of the different trophic levels at a spatial scale in the marine environment is proposed using spatial analysis methods and non-parametric statistics. Phytoplankton cell number, being a representative parameter to express trophic trends in the marine ecosystem is selected for the methodology development; Saronicos Gulf, Greece is used for the case study. The proposed stepwise methodology includes interpolation for assessing the spatial distribution of phytoplankton cell number, division of the Gulf into a number of quadrates, development of a scale characterising trophic levels and finally characterisation of the trophic state of each quadrate using non-parametric statistics. The advantages of this methodology and the potential applications in coastal management studies are also discussed.

Cell Count↗

Modern robust data analysis methods: measures of central tendency.

Various statistical methods, developed after 1970, offer the opportunity to substantially improve upon the power and accuracy of the conventional t test and analysis of variance methods for a wide range of commonly occurring situations. The authors briefly review some of the more fundamental problems with conventional methods based on means; provide some indication of why recent advances, based on robust measures of location (or central tendency), have practical value; and describe why modern investigations dealing with nonnormality find practical problems when comparing means, in contrast to earlier studies. Some suggestions are made about how to proceed when using modern methods.

Humans↗

Recent developments in genetic data analysis: what can they tell us about human demographic history?

Over the last decade, a number of new methods of population genetic analysis based on likelihood have been introduced. This review describes and explains the general statistical techniques that have recently been used, and discusses the underlying population genetic models. Experimental papers that use these methods to infer human demographic and phylogeographic history are reviewed. It appears that the use of likelihood has hitherto had little impact in the field of human population genetics, which is still primarily driven by more traditional approaches. However, with the current uncertainty about the effects of natural selection, population structure and ascertainment of single-nucleotide polymorphism markers, it is suggested that likelihood-based methods may have a greater impact in the future.

DNA, Satellite↗

An integrated data analysis approach to characterize genes highly expressed in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the major causes of cancer deaths worldwide. New diagnostic and therapeutic options are needed for more effective and early detection and treatment of this malignancy. We identified 703 genes that are highly expressed in HCC using DNA microarrays, and further characterized them in order to uncover novel tumor markers, oncogenes, and therapeutic targets for HCC. Using Gene Ontology annotations, genes with functions related to cell proliferation and cell cycle, chromatin, repair, and transcription were found to be significantly enriched in this list of highly expressed genes. We also identified a set of genes that encode secreted (e.g. GPC3, LCN2, and DKK1) or membrane-bound proteins (e.g. GPC3, IGSF1, and PSK-1), which may be attractive candidates for the diagnosis of HCC. A significant enrichment of genes highly expressed in HCC was found on chromosomes 1q, 6p, 8q, and 20q, and we also identified chromosomal clusters of genes highly expressed in HCC. The microarray analyses were validated by RT-PCR and PCR. This approach of integrating other biological information with gene expression in the analysis helps select aberrantly expressed genes in HCC that may be further studied for their diagnostic or therapeutic utility.

Biomarkers, Tumor↗

Data analysis.

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Colorectal Neoplasms↗

[Estimation of the incidence of diabetes in the Federal Republic of Germany based on insurance data. A secondary data analysis of a representative random sample of locally insured persons in the city of Dortmund].

All records relating to medical prescriptions and services relating to diabetes for a representative sample (n = 6478) of inhabitants of Dortmund in 1988, who were members of the Local Health Insurance in Dortmund, were analysed. 264 patients (4.08%) were receiving antidiabetic drugs during that year, 198 (3.06%) oral ones, 42 (0.65%) insulin and 24 (0.37%) both. 12.41% of all those insured over the age of 60 were on antidiabetic drugs, more women than men (5.08 vs 2.94%; P less than 0.001). The most frequently used oral antidiabetics were sulphonylurea ones (95.1%), while the proportion of biguanides was only 4.4%. On the basis of established diagnosis, regular blood sugar and HbA1 tests, as well as optic fundi examination, a further 104 persons (1.60%) are assumed to have diabetes but not treated by drugs. This sample indicates an overall prevalence of diabetes of 5.68% among the population. Relating it to the age and sex pattern of the population of the Federal Republic of Germany this corresponds to a prevalence of diagnosed diabetes of 4.82%. Thus there are probably a little less than 4 million diabetic citizens of the Federal Republic of Germany.

Age Factors↗