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Sökning: WFRF:(Jorgensen P. M.) > (2005-2009)

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1.
  • Aamodt, K., et al. (författare)
  • The ALICE experiment at the CERN LHC
  • 2008
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08002
  • Forskningsöversikt (refereegranskat)abstract
    • ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries, Its overall dimensions are 16 x 16 x 26 m(3) with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.
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2.
  • Abat, E., et al. (författare)
  • Study of the response of the ATLAS central calorimeter to pions of energies from 3 to 9 GeV
  • 2009
  • Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002 .- 1872-9576. ; 607:2, s. 372-386
  • Tidskriftsartikel (refereegranskat)abstract
    • A fully instrumented slice of the ATLAS central detector was exposed to test beams from the SPS (Super Proton Synchrotron) at CERN in 2004. in this paper, the response of the central calorimeters to pions with energies in the range between 3 and 9 GeV is presented. The linearity and the resolution of the combined calorimetry (electromagnetic and hadronic calorimeters) was measured and compared to the prediction of a detector simulation program using the toolkit Geant 4. (C) 2009 Elsevier B.V. All rights reserved.
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3.
  • Emerging Risk Factors, Collaboration, et al. (författare)
  • The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases
  • 2007
  • Ingår i: Eur J Epidemiol. - 0393-2990. ; 22:12, s. 839-69
  • Tidskriftsartikel (refereegranskat)abstract
    • Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.
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5.
  • Villa, Luisa L., et al. (författare)
  • Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions
  • 2007
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 356:19, s. 1915-1927
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Human papillomavirus types 16 (HPV-16) and 18 (HPV-18) cause approximately 70% of cervical cancers worldwide. A phase 3 trial was conducted to evaluate a quadrivalent vaccine against HPV types 6, 11, 16, and 18 (HPV-6/11/16/18) for the prevention of high-grade cervical lesions associated with HPV-16 and HPV-18. METHODS: In this randomized, double-blind trial, we assigned 12,167 women between the ages of 15 and 26 years to receive three doses of either HPV-6/11/16/18 vaccine or placebo, administered at day 1, month 2, and month 6. The primary analysis was performed for a per-protocol susceptible population that included 5305 women in the vaccine group and 5260 in the placebo group who had no virologic evidence of infection with HPV-16 or HPV-18 through 1 month after the third dose (month 7). The primary composite end point was cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical cancer related to HPV-16 or HPV-18. RESULTS: Subjects were followed for an average of 3 years after receiving the first dose of vaccine or placebo. Vaccine efficacy for the prevention of the primary composite end point was 98% (95.89% confidence interval [CI], 86 to 100) in the per-protocol susceptible population and 44% (95% CI, 26 to 58) in an intention-to-treat population of all women who had undergone randomization (those with or without previous infection). The estimated vaccine efficacy against all high-grade cervical lesions, regardless of causal HPV type, in this intention-to-treat population was 17% (95% CI, 1 to 31). CONCLUSIONS: In young women who had not been previously infected with HPV-16 or HPV-18, those in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group.
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6.
  • Tuskan, G A, et al. (författare)
  • The genome of black cottonwood, Populus trichocarpa (Torr. & Gray).
  • 2006
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 313:5793, s. 1596-604
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport.
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7.
  • Mikkelsen, T N, et al. (författare)
  • Experimental design of multifactor climate change experiments with elevated CO2, warming and drought: the CLIMAITE project
  • 2008
  • Ingår i: Functional Ecology. - : Wiley. - 1365-2435 .- 0269-8463. ; 22:1, s. 185-195
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent findings indicate that the interactions among CO2, temperature and water can be substantial, and that the combined effects on the biological systems of several factors may not be predicted from experiments with one or a few factors. Therefore realistic multifactorial experiments involving a larger set of main factors are needed. We describe a new Danish climate change-related field scale experiment, CLIMAITE, in a heath/grassland ecosystem. CLIMAITE is a full factorial combination of elevated CO2, elevated temperature and prolonged summer drought. The manipulations are intended to mimic anticipated major environmental changes at the site by year 2075 as closely as possible. The impacts on ecosystem processes and functioning (at ecophysiological levels, through responses by individuals and communities to ecosystem-level responses) are investigated simultaneously. The increase of [CO2] closely corresponds with the scenarios for year 2075, while the warming treatment is at the lower end of the predictions and seems to be the most difficult treatment to increase without unwanted side effects on the other variables. The drought treatment follows predictions of increased frequency of drought periods in summer. The combination of the treatments does not create new unwanted side effects on the treatments relative to the treatments alone.
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8.
  • Helgadottir, Anna, et al. (författare)
  • The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm
  • 2008
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 217-224
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD)(1-4) and type 2 diabetes (T2D)(5-7), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.
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9.
  • Welch, J., et al. (författare)
  • The Allen Telescope Array: The First Widefield, Panchromatic, Snapshot Radio Camera for Radio Astronomy and SETI
  • 2009
  • Ingår i: Proceedings of the IEEE. - 1558-2256 .- 0018-9219. ; 97:8, s. 1438-1447
  • Tidskriftsartikel (refereegranskat)abstract
    • The first 42 elements of the Allen Telescope Array (ATA-42) are beginning to deliver data at the Hat Creek Radio Observatory in northern California. Scientists and engineers are actively exploiting all of the flexibility designed into this innovative instrument for simultaneously conducting surveys of the astrophysical sky and conducting searches for distant technological civilizations. This paper summarizes the design elements of the ATA, the cost savings made possible by the use of commercial off-the-shelf components, and the cost/performance tradeoffs that eventually enabled this first snapshot radio camera. The fundamental scientific program of this new telescope is varied and exciting; some of the first astronomical results will be discussed.
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10.
  • Zeggini, Eleftheria, et al. (författare)
  • Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
  • 2008
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:5, s. 638-645
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
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11.
  • Kruger, T, et al. (författare)
  • Xenobiotic activity in serum and sperm chromatin integrity in European and inuit populations
  • 2008
  • Ingår i: Molecular Reproduction and Development. - : Wiley. - 1040-452X .- 1098-2795. ; 75:4, s. 669-680
  • Tidskriftsartikel (refereegranskat)abstract
    • Lipophilic persistent organic pollutants (POPs) are ubiquitous in the environment and suspected to interfere with hormone activities and reproduction. In previous studies we demonstrated that POP exposure can affect sperm DNA integrity and differences between Inuits and Europeans in sperm DNA integrity and xenobiotic activity were observed. The aim of this study was to investigate possible relations between human sperm chromatin integrity and the xenobiotic serum activity of lipophilic POPs assessed as effects on the estrogen (ER), androgen (AR), and/or aryl hydrocarbon (AhR) receptors. Human sperm chromatin integrity was assessed as DNA fragmentation index (%DFI) and high DNA stainability (%HDS) using the flow cytometric sperm chromatin structure assay (SCSA). Xenobiotic receptor activities were determined using chemically activated luciferase gene expression (CALUX) assay. The study included 53 Greenlandic Inuits and 247 Europeans (Sweden, Warsaw (Poland) and Kharkiv (Ukraine)). A heterogeneous pattern of correlations was found. For Inuits, ER and AhR activities and %DFI were inversely correlated, whereas a positive correlation between AR activity and %DFI was found for Europeans. In contrast, no correlation between receptor activities and %HDS was observed for Inuits but for Europeans positive and negative correlations were observed between ER and AR activities and %HDS, respectively. We suggest that the different patterns of xenobiotic serum activities, in combination with diet associated factors and/or genetics, might be connected to the observed differences in sperm chromatin integrity between the Inuits and Europeans. Mol. Reprod. Dev. (c) 2007 Wiley-Liss, Inc.
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13.
  • Stronati, A., et al. (författare)
  • Relationships between sperm DNA fragmentation, sperm apoptotic markers and serum levels of CB-153 and p,p '-DDE in European and Inuit populations
  • 2006
  • Ingår i: Reproduction. - : Bioscientifica. - 1470-1626 .- 1741-7899. ; 132:6, s. 949-958
  • Tidskriftsartikel (refereegranskat)abstract
    • Persistent organochlorine pollutants (POPs) are suspected to interfere with hormone activity and the normal homeostasis of spermatogenesis. We investigated the relationships between sperm DNA fragmentation, apoptotic markers identified on ejaculated spermatozoa and POP levels in the blood of 652 adult males (200 Inuits from Greenland, 166 Swedish, 134 Polish and 152 Ukrainian). Serum levels of 2, 2', 4, 4', 5, 5'-hexachlorobiphenyl (CB-153), as a proxy of the total POP burden, and of 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE), as a proxy of the total DDT exposure were determined. Sperm DNA fragmentation was measured by using the TUNEL assay, whereas immunofluorescence methods were utilized for detecting proapoptotic (Fas) and anti-apoptotic (Bcl-xL) markers. Both TUNEL assay and apoptotic markers were statistically differed across the four populations. No correlation between neither sperm DNA fragmentation nor apoptotic sperm parameters and the large variations in POPs exposure was observed for the separate study groups. However, considering the European populations taken together, we showed that both %TUNEL positivity and Bcl-xL were related to CB-153 serum levels, whereas our study failed to demonstrate any relations between DDE and %TUNEL positivity and apoptotic sperm biomarkers (Fas and Bcl-xL) in any region or overall regions. These results suggest that CB-153 and related chemicals might alter sperm DNA integrity and Bcl-xL levels in European adult males, but not in the highly exposed Inuit men. Additional issues (genetic background, lifestyle habits and characterization of total xeno-hormonal activities) need to he investigated in order to fully assess the population variations observed.
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14.
  • Bjornvold, M., et al. (författare)
  • FOXP3 polymorphisms in type 1 diabetes and coeliac disease
  • 2006
  • Ingår i: J Autoimmun. - : Elsevier BV. - 0896-8411. ; 27:2, s. 140-4
  • Tidskriftsartikel (refereegranskat)abstract
    • The FOXP3 gene encodes a transcription factor thought to be essential for the development and function of T regulatory cells. Two previous studies have tested common polymorphisms in FOXP3 for association with type 1 diabetes (T1D) with conflicting results. The aim of our study was to see whether there is any evidence of association between the FOXP3 polymorphisms previously reported to be associated with T1D, in a Caucasian population regarding T1D and coeliac disease (CD). We further looked for evidence of interaction between FOXP3 polymorphisms and HLA-DR3 in conferring susceptibility to T1D. Initially, we analysed two microsatellites in the FOXP3 gene in 363 T1D nuclear families. Our results indicated an association between FOXP3 and T1D (global p=0.004) and a possible interaction between FOXP3 and the HLA-DR3-DQ2 susceptibility haplotype. We then genotyped an additional independent set of 826 T1D patients and 1459 controls as well as one CD dataset consisting of 325 families. A similar tendency was revealed in the CD family material (pnc=0.055 for the associated allele). On the other hand, we were unable to reproduce our initial findings in the T1D case-control dataset (global p=0.6). Our results suggest that the tested FOXP3 markers do not have any major impact on susceptibility for these diseases.
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15.
  • Gloster, Tracey M., et al. (författare)
  • Characterization and three-dimensional structures of two distinct bacterial xyloglucanases from families GH5 and GH12
  • 2007
  • Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 282:26, s. 19177-19189
  • Tidskriftsartikel (refereegranskat)abstract
    • The plant cell wall is a complex material in which the cellulose microfibrils are embedded within a mesh of other polysaccharides, some of which are loosely termed hemicellulose. One such hemicellulose is xyloglucan, which displays a beta-1,4-linked D-glucose backbone substituted with xylose, galactose, and occasionally fucose moieties. Both xyloglucan and the enzymes responsible for its modification and degradation are finding increasing prominence, reflecting both the drive for enzymatic biomass conversion, their role in detergent applications, and the utility of modified xyloglucans for cellulose fiber modification. Here we present the enzymatic characterization and three-dimensional structures in ligand free and xyloglucan- oligosaccharide complexed forms of two distinct xyloglucanases from glycoside hydrolase families GH5 and GH12. The enzymes, Paenibacillus pabuli XG5 and Bacillus licheniformis XG12, both display open active center grooves grafted upon their respective (beta/alpha)(8) and beta-jelly roll folds, in which the side chain decorations of xyloglucan may be accommodated. For the beta-jelly roll enzyme topology of GH12, binding of xylosyl and pendant galactosyl moieties is tolerated, but the enzymeis similarly competent in the degradation of unbranched glucans. In the case of the (beta/alpha)(8) GH5 enzyme, kinetically productive interactions are made with both xylose and galactose substituents, as reflected in both a high specific activity on xyloglucan and the kinetics of a series of aryl glycosides. The differential strategies for the accommodation of the side chains of xyloglucan presumably facilitate the action of these microbial hydrolases in milieus where diverse and differently substituted substrates may be encountered.
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  • Hammar, N., et al. (författare)
  • Migration and differences in dietary habits : a cross sectional study of Finnish twins in Sweden
  • 2009
  • Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; Oct 17
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To compare dietary habits between Finnish twin migrants to Sweden and their co-twins always living in Finland, and to analyse how migration influenced food consumption patterns in the migrants. Subjects/Methods: Same-sexed twin pairs born in Finland below 75 years of age, with at least one twin migrating to Sweden(n=1083 pairs). Dietary habits were assessed by a food frequency questionnaire included in a comprehensive mailed questionnaire (response rate 71%). For 76 male twin pairs, information was also collected by a dietary history interview inquiring the habitual diet during the previous year. Results: Migrant twins in Sweden had a lower intake of typical Finnish foods like dark bread and berries, and an increased consumption of fresh fruit compared with co-twins living in Finland. The migrants consumed less potatoes and more rice and pasta. Sweet pastries were consumed less often by the migrants and they also tended to more often cut out visible fat of meat and on the other hand add salt to dishes. Among men the migrants had a lower alcohol intake than their co-twins living in Finland. Conclusions: Migration from Finland to Sweden is associated with differences in the food pattern that reflect population differences in eating habits between the two countries. The differences include a reduced consumption of typical Finnish foods like dark bread and berries and are of bidirectional nature from the point of view of cardiovascular health.
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  • Kongsted, Jacob, et al. (författare)
  • Coupled cluster calculations of the optical rotation of S-propylene oxide in gas phase and solution
  • 2005
  • Ingår i: Chemical Physics Letters. - : Elsevier BV. - 0009-2614. ; 401:4-6, s. 385-392
  • Tidskriftsartikel (refereegranskat)abstract
    • We present ab initio calculations of the optical rotation of S-propylene oxide in both gas phase and solution using the coupled cluster methodology combined with a dielectric continuum description of the solvent. The coupled cluster calculations are performed using the CCS, CC2, CCSD and CC3 methods. None of the presented gas phase results are in accord with the experimental sign of the optical rotation at 355 nm. Thereby, the experimental sign change between the gas phase and the cyclohexane,solution optical rotation at 355 nm is not reproduced theoretically. The vibrational effects are considered to be significant and may be of crucial importance in order to bring accordance between the calculated and the experimentally established sign of the gas phase optical rotation at 355 nm. (C) 2004 Elsevier B.V. All rights reserved.
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  • Paterson, M. J., et al. (författare)
  • Benchmarking two-photon absorption with CC3 quadratic response theory, and comparison with density-functional response theory
  • 2006
  • Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 124:5, s. 425-430
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a detailed study of the effects of electron correlation on two-photon absorption calculated by coupled cluster quadratic response theory. The hierarchy of coupled cluster models CCS, CC2, CCSD, and CC3 has been used to investigate the effects of electron correlation on the two-photon absorption cross sections of formaldehyde (CH2O), diacetylene (C4H2), and water (H2O). In particular, the effects of triple excitations on two-photon transition cross sections are determined for the first time. In addition, we present a detailed comparison of the coupled cluster results with those obtained from Hartree-Fock and density-functional response theories. We have investigated the local-density approximation, the pure Becke-Lee-Yang-Parr (BLYP) functional, the hybrid Becke-3-parameter-Lee-Yang-Parr (B3LYP), and the Coulomb-attenuated B3LYP (CAM-B3LYP) functionals. Our results show that the CAM-B3LYP functional, when used in conjuction with a one-particle basis-set containing diffuse functions, has much promise; however, care must still be exercised for diffuse Rydberg-type states.
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27.
  • Thomsen, J, et al. (författare)
  • Optical Doppler tomography for monitoring vascularization during photodynamic therapy of skin cancer lesions
  • 2008
  • Ingår i: BIOPHOTONICS: PHOTONIC SOLUTIONS FOR BETTER HEALTH CARE. - : SPIE. - 1996-756X .- 0277-786X. - 9780819471895 ; 6991
  • Konferensbidrag (refereegranskat)abstract
    • We investigate vascular changes during Photodynamic therapy (PDT) of skin tumors using optical Doppler tomography (ODT). The effect of vascular shut down on tumor destruction is currently not known, and to optimize treatment it is relevant to investigate this issue further. Optical Doppler tomography is capable of measuring blood flow in biological tissue down to 1-2 mm with sub-mm/s velocity sensitivity and micrometer spatial resolution making it suitable for blood flow measurements in the skin. We demonstrate the ability of detecting blood flow in the human skin using non-interstitial ODT to preserve the non-invasiveness. In general a very limited blood flow activity was observed in normal skin and around skin tumors making monitoring of changes difficult. We suggest solutions to a number of practical issues such as sampling errors and natural fluctuations in flow activity for future work.
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