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Träfflista för sökning "WFRF:(Rasmuson J) srt2:(2005-2009)"

Sökning: WFRF:(Rasmuson J) > (2005-2009)

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1.
  • Gracin, Sandra, 1968- (författare)
  • Solubility and polymorphism of molecular compounds
  • 2005
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis deals with the controlled crystallization of small organic molecules and is focused on solubility and polymorphism. The solubility was determined for phenylacetic acid, p-hydroxyphenylacetic acid, p-aminophenylacetic acid, p-hydroxybenzoic acid and ibuprofen in both water and in a range of organic solvents. Data is discussed from the standpoint of molecular aspects of solute – solvent interactions and by estimated solid phase activity. It was shown that better understanding could be acquired by making a qualitative analysis of the molecular interactions in the solution and the crystal structure of the compounds in question. Solubility predictions that are carried out by the UNIFAC method are not sufficiently accurate to serve as a basis for a reliable design of a crystallization process or selection of a suitable solvent since they deviate more than 15% from experimental values. The reason for the discrepancies are related to uncertainties in the prediction of activity coefficients by UNIFAC, as well as, difficulties in the estimation of the activity of the solid state. p-Aminobenzoic acid (PABA) has been crystallized from thirteen different solvents either by slow cooling, after which the product is allowed to mature in suspension, or by rapid cooling followed by immediate isolation. Two different polymorphs have been crystallized. The system is found to be enantiotropic with the transition temperature of 25 °C, below which the β-form is the stable polymorph. The α-form was obtained from all solvents by both methods. The β-form is obtained only in carefully controlled conditions from water and ethyl acetate, well below the transition temperature. Often the α-form appears concomitantly. It is shown in this work that sonication significantly reduces the induction time for nucleation. The β-form crystallizes more reproducibly and at higher cooling rates when controlled sonication is used. In addition sonication is found to selectively favor the appearance of one of the polymorphs. Producing the pure β-form was possible even above the transition temperature where other crystallization techniques were only capable of producing the stable α-form. The α-form structure is based on centro symmetric dimers formed by association of carboxylic acid groups. It is suggested that the preference for nucleation of the α-polymorph is related to the formation of dimers in the supersaturated solution. Only at the condition where the formation of dimers is reduced sufficiently, (i.e. in the polar solvents or when sonication is applied) the nucleation of the β-form is favored.
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2.
  • Hung, Rayjean J, et al. (författare)
  • A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25
  • 2008
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 452:7187, s. 633-637
  • Tidskriftsartikel (refereegranskat)abstract
    • Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 x 10(-10)). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 x 10(-20) overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines, and they bind to N'-nitrosonornicotine and potential lung carcinogens. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets.
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4.
  • Linseisen, Jakob, et al. (författare)
  • Fruit and vegetable consumption and lung cancer risk: Updated information from the European Prospective Investigation into Cancer and Nutrition (EPIC)
  • 2007
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 121:5, s. 1103-1114
  • Tidskriftsartikel (refereegranskat)abstract
    • The association of fruit and vegetable consumption and lung cancer incidence was evaluated using the most recent data from the European Prospective Investigation into Cancer and Nutrition (EPIC), applying a refined statistical approach (calibration) to account for measurement error potentially introduced by using food frequency questionnaire data. Between 1992 and 2000, detailed information on diet and life-style of 478,590 individuals participating in EPIC was collected. During a median follow-up of 6.4 years, 1,126 lung cancer cases were observed. Multivariate Cox proportional hazard models were applied for statistical evaluation. In the whole study population, fruit consumption was significantly inversely associated with lung cancer risk while no association was found for vegetable consumption. In current smokers, however, lung cancer risk significantly decreased with higher vegetable consumption; this association became more pronounced after calibration, the hazard ratio (HR) being 0.78 (95% CI 0.620.98) per 100 g increase in daily vegetable consumption. In comparison, the HR per 100 g fruit was 0.92 (0.85-0.99) in the entire cohort and 0.90 (0.81-0.99) in smokers. Exclusion of cases diagnosed during the first 2 years of follow-up strengthened these associations, the HR being 0.71 (0.55-0.94) for vegetables (smokers) and 0.86 (0.78-0.95) for fruit (entire cohort). Cancer incidence decreased with higher consumption of apples and pears (entire cohort) as well as root vegetables (smokers). In addition to an overall inverse association with fruit intake, the results of this evaluation add evidence for a significant inverse association of vegetable consumption and lung cancer incidence in smokers. (C) 2007 Wiley-Liss, Inc.
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5.
  • Menvielle, Gwenn, et al. (författare)
  • The role of smoking and diet in explaining educational inequalities in lung cancer incidence.
  • 2009
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 101:5, s. 321-330
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Studies in many countries have reported higher lung cancer incidence and mortality in individuals with lower socioeconomic status. METHODS: To investigate the role of smoking in these inequalities, we used data from 391,251 participants in the European Prospective Investigation into Cancer and Nutrition study, a cohort of individuals in 10 European countries. We collected information on smoking (history and quantity), fruit and vegetable consumption, and education through questionnaires at study entry and gathered data on lung cancer incidence for a mean of 8.4 years. Socioeconomic status was defined as the highest attained level of education, and participants were grouped by sex and region of residence (Northern Europe, Germany, or Southern Europe). Relative indices of inequality (RIIs) of lung cancer risk unadjusted and adjusted for smoking were estimated using Cox regression models. Additional analyses were performed by histological type. RESULTS: During the study period, 939 men and 692 women developed lung cancer. Inequalities in lung cancer risk (RII(men) = 3.62, 95% confidence interval [CI] = 2.77 to 4.73, 117 vs 52 per 100,000 person-years for lowest vs highest education level; RII(women) = 2.39, 95% CI = 1.77 to 3.21, 46 vs 25 per 100,000 person-years) decreased after adjustment for smoking but remained statistically significant (RII(men) = 2.29, 95% CI = 1.75 to 3.01; RII(women) = 1.59, 95% CI = 1.18 to 2.13). Large RIIs were observed among men and women in Northern European countries and among men in Germany, but inequalities in lung cancer risk were reverse (RIIs < 1) among women in Southern European countries. Inequalities differed by histological type. Adjustment for smoking reduced inequalities similarly for all histological types and among men and women in all regions. In all analysis, further adjustment for fruit and vegetable consumption did not change the estimates. CONCLUSION: Self-reported smoking consistently explains approximately 50% of the inequalities in lung cancer risk due to differences in education.
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7.
  • Ståhl, Marie (författare)
  • Process modeling of semibatch reaction crystallization
  • 2005
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis aims at increasing the fundamental understanding of reaction crystallization by modeling, simulations and parameter estimation. Benzoic acid is used as the model compound. A population balance model of single-feed semi-batch reaction crystallization is developed, accounting for chemical reaction, mixing, nucleation, growth, and growth rate dispersion. The model is evaluated by comparing the results with data from previously published semi-batch experiments. Two different mechanistic mixing models are used to describe mixing: the engulfment model with mesomixing and the segregated feed model. When the engulfment mixing model is used, the semi-batch model correctly captures the variation in weight mean size with varying agitation rate, feed point location, reactant concentration, feed pipe diameter, and total feed time. However, at scaling-up, a decrease in weight mean size with increasing crystallizer volume is predicted, which is not found experimentally. When the segregated feed model is used to describe mixing, the results are unsatisfactory. The crystallization kinetics have a great impact on the performance of the model, influencing both the final mean size, and the predicted influence of changes in the processing conditions. The kinetics of nucleation and growth are determined from T-mixer experiments. Three population balance models of increasing complexity are developed and used in parameter estimations by non-linear optimization. The T-mixer model accounts for nucleation, growth and growth rate dispersion. Five or six kinetic parameters are estimated using data from 14 experiments at 8 different initial supersaturation levels. Depending on the assumptions in the model, different kinetics are estimated. The main differences are found in the nucleation and growth rate constants. The T-mixer kinetics yields unsatisfactory results in the semi-batch simulations, with a predicted mean size that is significantly smaller than the experimental and a less pronounced influence of processing conditions that are related to mesomixing. An attempt is made to model aging of benzoic acid precipitates formed at high supersaturation. A model of Ostwald ripening gives a reasonably good description of the changes in the size distribution, provided that the observed shape change during aging is accounted for. However, significant deviations remain, in particular, the broadening of the aged size distribution is more pronounced in the experiments than in the simulations. There are indications that the observed aging might be caused by kinetic ripening, driven by a transformation to a more regular shape or a less strained crystal, rather than by Ostwald ripening.
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8.
  • Westin, K. J., et al. (författare)
  • Nucleation of calcium carbonate in presence of citric acid, DTPA, EDTA and pyromellitic acid
  • 2005
  • Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 282:2, s. 370-379
  • Tidskriftsartikel (refereegranskat)abstract
    • The influence of four calcium complexing additives, i.e., citric acid (CIT), diethylenetriaminepentaacetic acid (DTPA), ethylenediaminetetraacetic acid (EDTA) and pyromellitic acid (PMA), and their concentration on the induction time of calcium carbonate nucleation has been studied. The experiments were performed by rapidly mixing a sodium carbonate solution and a calcium chloride solution of various concentrations. The induction time was obtained by recording the white light absorption of the solution. Chemical speciation was used to estimate the initial thermodynamic driving force of each experiment. The induction time was found to increase with additive concentration. The effect varies from one additive to another. CIT causes the greatest increase in induction time and PMA the least. Using classical nucleation theory the experimental data were evaluated in terms of the interfacial energy. fit pure water a value of 37.8 mJ m(-2) was obtained, showing good agreement with other works. CIT DTPA and EDTA caused a notable increase of the interfacial energy at a concentration of 0.5 mmol l(-1). PMA does not appear to have any effect at all on the interfacial energy. Different mechanisms for the influence of the additives on the measured induction time and on the estimated interfacial energy are discussed.
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10.
  • Zhou, Guang-Qian, et al. (författare)
  • The Drosophila ortholog of the endolysosomal membrane protein, endolyn, regulates cell proliferation.
  • 2006
  • Ingår i: J Cell Biochem. - 0730-2312. ; 99:5, s. 1380-96
  • Tidskriftsartikel (refereegranskat)abstract
    • Endolyn (CD164) is a sialomucin that regulates the proliferation, adhesion, and migration of human haematopoietic stem and progenitor cells. This molecule is predominately localized in endocytotic compartments, where it may contribute to endolysosomal biogenesis and trafficking. In order to more closely define the function of endolyn from an evolutionary view-point, we first analyzed endolyn orthologs in species ranging from insects, fish, and birds to mammals. The predicted molecular structures of the endolyn orthologs from these species are well conserved, particularly with respect to significant O-linked glycosylation of the extracellular domain, and the high degree of amino acid similarities within their transmembrane and cytoplasmic domains, with the latter possessing the lysosomal target signal, YXXphi. Focusing on Drosophila, our studies showed that the subcellular distribution of endolyn in non-polarized Drosophila S2 cells resembles that of its human counterpart in hematopoietic cells, with its predominant localization being within intracellular vesicles, while a small fraction occurs on the cell surface. Both Y --> A and L --> A mutations in the YHTL motif perturbed the normal subcellular distribution of Drosophila endolyn. Interestingly, embryonic and early larval development was often arrested in endolyn-deficient Drosophila mutants. This may partly be due to the role of endolyn in regulating cell proliferation, since knock-down of endolyn expression in S2 cells resulted in up to 50% inhibition of cell growth, with a proportion of cells undergoing apoptosis. Taken together, these results demonstrate that endolyn is an evolutionarily conserved sialomucin fundamentally involved in cell proliferation in both the human and Drosophila melanogaster. 2006 Wiley-Liss, Inc.
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