In this paper, we focus on the task of adapting genetic regulatory models based on gene expression data from microarrays. Our approach aims at automatic revision of qualitative regulatory models to improve their fit to expression data. We describe a type of regulatory model designed for this purpose, a method for predicting the quality of such models, and a method for adapting the models by means of genetic programming. We also report experimental results highlighting the ability of the methods to infer models on a number of artificial data sets. In closing, we contrast our results with those of alternative methods, after which we give some suggestions for future work.

Algorithms↗

PubMedDate not supplied

Protein expression signatures identified in Mytilus edulis exposed to PCBs, copper and salinity stress.

Applied to environmental toxicology, proteome analysis may be used to isolate chemical-specific protein expression signatures (PES). In this project specific PES were isolated in mussels, Mytilus edulis, from the Baltic Sea subjected in the laboratory to treatment with copper (70 ppb), Aroclor 1248 (1 ppb), and to lowered salinity. Four mussels in each treatment group were acclimated in the laboratory for 24 h before beginning the 7-day exposure. Whole body tissue was homogenized and separated using two-dimensional gel electrophoresis. The protein gels were scanned to TIFF files and compared using MELANIE II 2D gel analysis software (BioRad). Protein expression signatures including proteins induced and repressed by exposure were isolated for each treatment group. The specificity of PES due to environmental changes shows promise in bioindication, toxicity testing and in helping identify possible toxicity mechanisms.

Animals↗

PubMedDate not supplied

Male drug abuse, criminality and subcultural affiliation in a career perspective.

Degree of connection to the criminal underworld was the basis for typologic research on 698 male drug abusers; interviews as well as official records were used. Four types were distinguished: The addicted criminals seemed to resemble the groups dominant in Sweden from the 1950s to the 1970s. An early crime debut and criminal offenses in youthful years characterized their deviant careers. Drugs and criminal activities coexisted with an often very high intake of alcohol and the most difficult childhood and adolescence conditions compared to the other types. The criminal addicts had fewer recorded acts of juvenile delinquency. Their drug abuse was severe and occurred later in life, as criminality did, but tended to accelerate very rapidly. Their subcultural affiliation was probably as strong as that of the addicted criminals. A large group called low-crime addicts had a weak subgroup affiliation. The "normal" abuse pattern, with cannabis as the first substance used and a gradual shift to more severe opioid and CNS stimulant abuse, was most true of this type. Probably the drug abuse played a role in the development of the criminal pattern. Emotionally unstable addicts with little or no criminality had the best education, job situation and social relations. Multiple drug abuse and abuse of legal drugs were common. Mental ill-health was characteristic for this group. The results show that drug abusers in Sweden cannot be seen as a homogeneous group of individuals, that they do not commit crimes only in order to finance their habit, and that the history of narcotics use in Sweden, with its strong connection to a criminal subculture, is highly relevant to this sample.

Adult↗

PubMedDate not supplied

Human pharmacokinetics of iohexol. A new nonionic contrast medium.

The pharmacokinetics of iohexol, a new nonionic, water-soluble contrast medium, have been determined after intravenous injection in 20 healthy volunteers, at four different dose levels (125-500 mg I/kg). The apparent volume of distribution was 0.27 1/kg, indicating distribution in the extracellular water. The biologic half-life was 121 minutes, comparable with that of other intravascular contrast media. Iohexol was excreted completely unmetabolized in the urine, with a 100% recovery 24 hours after injection. A comparison of iohexol and chromium-51 (51Cr)-EDTA clearances indicates that iohexol is mainly excreted by glomerular filtration. The 51Cr-EDTA clearance was the same when injected separately and concomitantly with iohexol, indicating that glomerular filtration rate is not affected by iohexol. No dose dependency was observed in the investigated parameters t1/2 alpha, t1/2 beta, Vd, ClT or ClR. Iohexol pharmacokinetics are in correspondence with previously reported data on intravascular contrast media.

Adolescent↗