| 1. |
- Andrés, E., et al.
(författare)
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Observation of high-energy neutrinos using Čerenkov detectors embedded deep in Antarctic ice
- 2001
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 410:6827, s. 441-443
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Tidskriftsartikel (refereegranskat)abstract
- Neutrinos are elementary particles that carry no electric charge and have little mass. As they interact only weakly with other particles, they can penetrate enormous amounts of matter, and therefore have the potential to directly convey astrophysical information from the edge of the Universe and from deep inside the most cataclysmic high-energy regions. The neutrino's great penetrating power, however, also makes this particle difficult to detect. Underground detectors have observed low-energy neutrinos from the Sun and a nearby supernova2, as well as neutrinos generated in the Earth's atmosphere. But the very low fluxes of high-energy neutrinos from cosmic sources can be observed only by much larger, expandable detectors in, for example, deep water3,4 or ice5. Here we report the detection of upwardly propagating atmospheric neutrinos by the ice-based Antarctic muon and neutrino detector array (AMANDA). These results establish a technology with which to build a kilometre-scale neutrino observatory necessary for astrophysical observations1.
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| 2. |
- Andrés, E., et al.
(författare)
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Recent results from AMANDA
- 2001
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Ingår i: International Journal of Modern Physics A. - 0217-751X .- 1793-656X. ; 16:1C, s. 1013-1015
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Tidskriftsartikel (refereegranskat)abstract
- We present results based on data taken in 1997 with the 302-PMT Antarctic Muon and Neutrino Detector Array-B10 ("AMANDA-B10") array. Atmospheric neutrinos created in the northern hemisphere are observed indirectly through their charged current interactions which produce relativistic, Cherenkov-light-emitting upgoing muons in the South Pole ice cap. The reconstructed angular distribution of these events is in good agreement with expectation and demonstrates the viability of this ice-based device as a neutrino telescope.
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| 3. |
- Andres, E., et al.
(författare)
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Results from the AMANDA high energy neutrino detector
- 2000
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Ingår i: Nuclear physics B, Proceedings supplements. - : Elsevier. - 0920-5632 .- 1873-3832. ; 91:1-3, s. 423-430
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Tidskriftsartikel (refereegranskat)abstract
- This paper briefly summarizes the search for astronomical sources of high-energy neutrinos using the AMANDA-B10 detector. The complete data set from 1997 was analyzed. For Eμ > 10 TeV, the detector exceeds 10,000 m2 in effective area between declinations of 25 and 90 degrees. Neutrinos generated in the atmosphere by cosmic ray interactions were used to verify the overall sensitivity of the detector. The absolute pointing accuracy and angular resolution has been confirmed by the analysis of coincident events between the SPASE air shower array and the AMANDA detector. Preliminary flux limits from point source candidates are presented. For declinations larger than +45 degrees, our results compare favorably to existing limits for sources in the Southern sky. We also present the current status of the searches for high energy neutrino emission from diffusely distributed sources, GRBs, and WIMPs from the center of the earth.
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| 4. |
- Bai, X., et al.
(författare)
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Status of the Neutrino Telescope AMANDA : Monopoles and WIMPS
- 2001
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Ingår i: Dark Matter in Astro- and Particle Physics. - Berlin, Heidelberg : Springer. - 9783642626081 ; , s. 699-706
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Konferensbidrag (refereegranskat)abstract
- The neutrino telescope AMANDA has been set up at the geographical South Pole as first step to a neutrino telescope of the scale of one cubic kilometer, which is the canonical size for a detector sensitive to neutrinos from Active Galactic Nuclei (AGN), Gamma Ray Bursts (GRB) and Topological Defects (TD). The location and depth in which the detector is installed is given by the requirement to detect neutrinos by the Cherenkov light produced by their reaction products and to keep the background due to atmospheric muons as small as possible. However, a detector optimized for this purpose is also capable to detect the bright Cherenkov light from relativistic Monopoles and neutrino signals from regions with high gravitational potential, where WIMPS are accumulated and possibly annihilate. Both hypothetical particles might contribute to the amount of dark matter. Therefore here a report about the status of the experiment (autumn 2000) and about the status of the search for these particles with the AMANDA B10 sub-detector is given.
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| 5. |
- Edsjö, Joakim, et al.
(författare)
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WIMP searches with AMANDA-B10
- 2001
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Ingår i: The Identification Of Dark Matter. - : World Scientific. - 9789810246020 ; , s. 499-505
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Andres, E., et al.
(författare)
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The AMANDA neutrino telescope : Principle of operation and first results
- 2000
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Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 13:1, s. 1-20
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Tidskriftsartikel (refereegranskat)abstract
- AMANDA is a high-energy neutrino telescope presently under construction at the geographical South Pole. In the Antarctic summer 1995/96, an array of 80 optical modules (OMs) arranged on 4 strings (AMANDA-B4) was deployed at depths between 1.5 and 2 km. In this paper we describe the design and performance of the AMANDA-B4 prototype, based on data collected between February and November 1996. Monte Carlo simulations of the detector response to down-going atmospheric muon tracks show that the global behavior of the detector is understood. We describe the data analysis method and present first results on atmospheric muon reconstruction and separation of neutrino candidates. The AMANDA array was upgraded with 216 OMs on 6 new strings in 1996/97 (AMANDA-B10), and 122 additional OMs on 3 strings in 1997/98.
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| 7. |
- Wischnewski, R., et al.
(författare)
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The AMANDA neutrino detector : Status report
- 2000
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Ingår i: Nuclear physics B, Proceedings supplements. - 0920-5632 .- 1873-3832. ; 85:1-3, s. 141-145
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Tidskriftsartikel (refereegranskat)abstract
- The first stage of the AMANDA High Energy Neutrino Detector at the South Pole, the 302 PMT array AMANDA-B10, is taking data since 1997. We describe results on atmospheric neutrinos, limits on indirect WIMP detection, seasonal muon flux variation, relativistic monopole flux limits, a search for gravitational collapse neutrinos, and a depth scan of the optical ice properties. The next stage 19-string detector AMANDA-II with ∼650 PMTs will be completed in spring 2000.
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| 8. |
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| 9. |
- Wilson, A. N., et al.
(författare)
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Magnetic dipole bands in 190Hg : First evidence of excitations across the Z = 82 sub-shell in Hg nuclei
- 2001
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 505:1-4, s. 6-14
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Tidskriftsartikel (refereegranskat)abstract
- An experiment aimed at studying high-spin states in 190Hg was performed with the Eurogam II array. The data have revealed the presence of cascades of magnetic dipole transitions with some unexpected properties. Unlike the MI bands previously observed in the heavier Hg isotopes, these structures have extremely large B(M1)/B(E2) ratios, The observation of a third dipole band with much lower B(M1)/B(E2) values in the same spin/excitation energy regime suggests that the bands may represent configurations occurring in different minima in the potential energy surface. Configuration-dependent Cranked Nilsson-Strutinsky calculations predict the presence of a minimum in the nuclear potential energy surface at a deformation of ε ≅ 0.2, γ ≅ -90°, occurring when a proton is excited across the Z = 82 shell-gap into an h9/2 orbital. It is suggested that the bands exhibiting anomalously large B(M1)/B(E2) ratios may be associated with this minimum.
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| 10. |
- Bergström, A., et al.
(författare)
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Physical activity and risk of renal cell cancer
- 2001
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Ingår i: International Journal of Cancer. - New York, USA : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 92:1, s. 155-157
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Tidskriftsartikel (refereegranskat)abstract
- The relation between physical activity and renal cell cancer is unclear. High occupational physical activity has been associated with a decreased risk of renal cell cancer among men-but not among women-in two previous studies, while no association has been found for leisure time physical activity. Our aim was to investigate the association between occupational and leisure time physical activity in a prospective cohort of 17,241 Swedish twins. Information on physical activity and a wide range of potential confounding factors was obtained through a mailed questionnaire. During follow-up from 1967 through 1997 we identified 102 cases of renal cell cancer. We found no evidence of an inverse association between either occupational or leisure time physical activity and risk of renal cell cancer in this prospective cohort.
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| 11. |
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| 12. |
- Bergström, A., et al.
(författare)
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Birth weight and risk of renal cell cancer
- 2001
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Ingår i: Kidney International. - Malden, USA : Blackwell Publishing. - 0085-2538 .- 1523-1755. ; 59:3, s. 1110-1113
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prenatal period has been suggested to be important for future cancer risk. Conditions in utero are also important for the development of the kidney, and birth weight, a marker of fetal nutrition and growth, is linearly correlated with the number of nephrons and the structural and functional unit of the kidney. An association between birth weight and renal cell cancer, the major form of kidney cancer, is biologically plausible, but has never been studied.Methods: We conducted a population-based, case-controlled study in Sweden of men and women aged 20 to 79 years. We collected self-reported information on categories of birth weight from 648 patients with newly diagnosed renal cell cancer and from 900 frequency-matched control subjects. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as estimates of the relative risks.Results: An increased risk of renal cell cancer was observed among men with a birth weight of > or =3500 g (adjusted OR = 1.3, 95% CI, 1.0 to 1.8) compared with men with a birth weight between 3000 and 3499 g, especially in the subgroup without hypertension or diabetes (adjusted OR = 1.8, 95% CI, 1.2 to 2.6). No clear association among men with a birth weight <3000 g or among women was found.Conclusions: Our study shows that conditions in utero, reflected by birth weight, might affect the risk of renal cell cancer in adulthood. It is unclear why no association was found among women. Further studies, based on weight from birth certificates, are needed to clarify this relationship.
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| 13. |
- Bergström, A., et al.
(författare)
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Obesity and renal cell cancer : a quantitative review
- 2001
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Ingår i: British Journal of Cancer. - London, United Kingdom : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 85:7, s. 984-990
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Forskningsöversikt (refereegranskat)abstract
- Obesity has been associated with an increased risk of renal cell cancer among women, while the evidence for men is considered weaker. We conducted a quantitative summary analysis to evaluate the existing evidence that obesity increases the risk of renal cell cancer both among men and women. We identified all studies examining body weight in relation to kidney cancer, available in MEDLINE from 1966 to 1998. The quantitative summary analysis was limited to studies assessing obesity as body mass index (BMI, kg m(-2)), or equivalent. The risk estimates and the confidence intervals were extracted from the individual studies, and a mixed effect weighted regression model was used. We identified 22 unique studies on each sex, and the quantitative analysis included 14 studies on men and women, respectively. The summary relative risk estimate was 1.07 (95% CI 1.05-1.09) per unit of increase in BMI (corresponding to 3 kg body weight increase for a subject of average height). We found no evidence of effect modification by sex. Our quantitative summary shows that increased BMI is equally strongly associated with an increased risk of renal cell cancer among men and women.
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| 14. |
- Bergström, A, et al.
(författare)
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Overweight as an avoidable cause of cancer in Europe
- 2001
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Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 91:3, s. 421-30
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Tidskriftsartikel (refereegranskat)abstract
- There is growing evidence that excess body weight increases the risk of cancer at several sites, including kidney, endometrium, colon, prostate, gallbladder and breast in post-menopausal women. The proportion of all cancers attributable to overweight has, however, never been systematically estimated. We reviewed the epidemiological literature and quantitatively summarised, by meta-analysis, the relationship between excess weight and the risk of developing cancer at the 6 sites listed above. Estimates were then combined with sex-specific estimates of the prevalence of overweight [body mass index (BMI) 25-29 kg/m(2)] and obesity (BMI > or = 30 kg/m(2)) in each country in the European Union to obtain the proportion of cancers attributable to excess weight. Overall, excess body mass accounts for 5% of all cancers in the European Union, 3% in men and 6% in women, corresponding to 27,000 male and 45,000 female cancer cases yearly. The attributable proportion varied, in men, between 2.1% for Greece and 4.9% for Germany and, in women, between 3.9% for Denmark and 8.8% for Spain. The highest attributable proportions were obtained for cancers of the endometrium (39%), kidney (25% in both sexes) and gallbladder (25% in men and 24% in women). The largest number of attributable cases was for colon cancer (21,500 annual cases), followed by endometrium (14,000 cases) and breast (12,800 cases). Some 36,000 cases could be avoided by halving the prevalence of overweight and obese people in Europe.
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| 15. |
- Bergström, Christel A S, et al.
(författare)
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Absorption classification of oral drugs based on molecular surface properties
- 2003
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 46:4, s. 558-570
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate whether easily calculated and comprehended molecular surface properties can predict drug solubility and permeability with sufficient accuracy to allow theoretical absorption classification of drug molecules. For this purpose, structurally diverse, orally administered model drugs were selected from the World Health Organization (WHO)'s list of essential drugs. The solubility and permeability of the drugs were determined using well-established in vitro methods in highly accurate experimental settings. Descriptors for molecular surface area were generated from low-energy conformations obtained by conformational analysis using molecular mechanics calculations. Correlations between the calculated molecular surface area descriptors, on one hand, and solubility and permeability, on the other, were established with multivariate data analysis (partial least squares projection to latent structures (PLS)) using training and test sets. The obtained models were challenged with external test sets. Both solubility and permeability of the druglike molecules could be predicted with high accuracy from the calculated molecular surface properties alone. The established correlations were used to perform a theoretical biopharmaceutical classification of the WHO-listed drugs into six classes, resulting in a correct prediction for 87% of the essential drugs. An external test set consisting of Food and Drug Administration (FDA) standard compounds for biopharmaceutical classification was predicted with 77% accuracy. We conclude that PLS models of easily comprehended molecular surface properties can be used to rapidly provide absorption profiles of druglike molecules early on in drug discovery.
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| 16. |
- Bergström, J, et al.
(författare)
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Ethyl glucuronide concentrations in two successive urinary voids from drinking drivers : Relationship to creatinine content and blood and urine ethanol concentrations
- 2003
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Ingår i: Forensic Science International. - 0379-0738 .- 1872-6283. ; 133:1-2, s. 86-94
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Tidskriftsartikel (refereegranskat)abstract
- The concentrations of alcohol in blood (BAC) and two successive urine voids (UAC) from 100 drunk drivers were compared with the concentration of ethyl glucuronide (EtG), a minor metabolite of ethanol in urine, and the urinary creatinine content as an indicator of dilution. The subjects consisted of 87 men with mean age 42.2 ▒ 14.2 years (▒standard deviation, S.D.) and 13 women with mean age 42.5 ▒ 14.4 years. Ethanol was measured in blood and urine by headspace gas chromatography (GC) and EtG was determined in urine by liquid chromatography-mass spectrometry (LC-MS). The mean UAC was 2.53 ▒ 1.15g/l for first void compared with 2.35 ▒ 1.17g/l for second void, decreasing by 0.18 ▒ 0.24g/l on average (P < 0.001 in paired t-test). The ratios of UAC/BAC were 1.35 ▒ 0.25 for first void and 1.20 ▒ 0.16 for second void and the difference of 0.15 ▒ 0.27 was statistically significant (P < 0.001). The UAC/BAC ratio was not correlated with creatinine content of the urine specimens, whereas the concentration of urinary EtG was positively correlated with creatinine (r=0.64 for first void and r=0.62 for second void). The UAC was not correlated with urinary EtG directly (r=-0.03 for first void and r=0.08 for second void) but after adjusting for the relative dilution of the specimens (EtG/creatinine ratio) statistically significant positive correlations were obtained (r=0.58 for first void and r=0.57 for second void). The dilution of the urine, as reflected in creatinine content, is important to consider when EtG measurements are interpreted. The excretion of EtG in urine, like glucuronide conjugates of other drugs, is influenced by diuresis. EtG represents a sensitive and specific marker of acute alcohol ingestion with applications in clinical and forensic medicine. ⌐ 2003 Elsevier Science Ireland Ltd. All rights reserved.
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| 17. |
- Challis, K, et al.
(författare)
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Gestational diabetes mellitus and fetal death in Mozambique: an incident case-referent study
- 2002
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 81:6, s. 560-563
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Tidskriftsartikel (refereegranskat)abstract
- Background. Third trimester fetal death is a common problem in Mozambique, occurring in approximately 5% of parturient women. Objective. To elucidate the magnitude of the gestational diabetes mellitus problem, and to estimate its prevalence in a group of women with unexplained late fetal deaths and in women with live fetuses (referents). Methods. An incident case-referent study of 109 pregnant Mozambican women with fetal deaths and 110 women delivering liveborns, regarding fasting B-glucose, oral glucose tolerance test and glycosylated hemoglobin. Result. The difference in gestational diabetes mellitus prevalence in the two groups is not significant. The prevalence of gestational diabetes mellitus was high in both groups: 11% and 7%, respectively.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Ljungman, Christer, et al.
(författare)
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A multivariate analysis of factors affecting patency of femoropopliteal and femorodistal bypass grafting
- 2000
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Ingår i: VASA. - 0301-1526 .- 1664-2872. ; 29:3, s. 215-220
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The most important factors that determine the outcome after femoropopliteal and femorodistal arterial reconstruction are still controversial. This report analysis the factors that determine the early and late patency of distal arterial reconstruction. PATIENTS AND METHODS: A retrospective analysis of patency after femorodistal arterial reconstruction with a new method for evaluation of angiographic runoff was performed for 336 arterial reconstructions. The different pre-, per- and postoperative risk factors were analysed in a Cox proportional hazards model. RESULT: The patency was significantly better for vein grafts in comparison to composite grafts and prosthetic grafts. It was 74% for vein, 46% for composite and 43% for prosthetic reconstructions, respectively, at 12 months after arterial reconstruction. The cumulative life table patency rate in extremities with good, intermediate and poor runoff was 62, 30 and 10%, respectively at 36 months. The patency rates for extremities operated on for claudication was significantly better than for extremities operated on for critical ischaemia. The multivariate analysis of different factors in a Cox analysis revealed that only the status of distal runoff, the graft material and the site of the distal anastomosis independently and significantly influenced the patency rates. CONCLUSIONS: A new model for evaluation of distal runoff proved to predict the patency rate of femoropopliteal and femorodistal arterial reconstructions reasonably well in this retrospective analysis.
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| 22. |
- Wassgren, A.-B., et al.
(författare)
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Sex Pheromone of the Pine Sawfly Macrodiprion nemoralis (Hymenoptera : Diprionidae) : Identification of (2S,3R,7R,9S)-3,7,9-Trimethyl-2-tridecanol as the Precursor for the Active Pheromone Acetate
- 2000
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Ingår i: Die Naturwissenschaften. - : Springer Science and Business Media LLC. - 0028-1042 .- 1432-1904. ; 87:1, s. 24-29
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Tidskriftsartikel (refereegranskat)abstract
- The main component of the sex pheromone precursor in females of Macrodiprion nemoralis was identified as a threo-3,7,9-trimethyl-2-tridecanol isomer, approximately 800 pg per female, by gas chromatography-mass spectrometry. Comparison of mass spectrometric ion chromatograms showed that the natural compound in the female extract has the same retention time and mass spectrum as one of the two synthetic threo peaks. The acetate of the synthetic 16-isomer mixture caught a large number of males in the field, confirming the structure of the active pheromone. Comparison of gas chromatograms of the natural female extract with the eight synthetic threo stereoisomers showed that the pheromone is the (2S,3R,7R,9S)-stereoisomer of 3,7,9-trimethyl-2-tridecyl acetate.
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| 23. |
- Andersson, Irene, 1978, et al.
(författare)
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Reduced sympathetic responsiveness as well as plasma and tissue noradrenaline concentration in growth hormone transgenic mice
- 2004
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Ingår i: Acta Physiol Scand. - 0001-6772. ; 182:4, s. 369-78
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Acromegaly [overproduction of growth hormone (GH)] and GH deficiency have both been associated with alterations in autonomic nervous system function. The aim of this study was to investigate autonomic nervous system influence on heart rate (HR) in transgenic mice overexpressing bovine GH (bGH). METHODS: HR and HR variability (HRV) were measured in conscious young (8-13 weeks) and old (5-6 months) female bGH and control mice using telemetry. HR control was studied using antagonists and an agonist of adrenergic and muscarinic receptors. Noradrenaline was measured in plasma, heart and kidney using high performance liquid chromatography. RESULTS: Average 24 h resting HR did not differ between bGH and control mice. After saline injection and after muscarinic blockade with methylscopolamine HR increase was blunted (in old) or absent (in young) bGH mice compared with control mice (P < 0.05). Phenylephrine caused a baroreflex mediated decrease in HR from around 550 to 300-350 beats min(-1), not different between bGH and control mice. Time- and frequency-domain measures of HRV were reduced in old bGH compared with control mice (P < 0.05). Noradrenaline concentrations were reduced by 25-49% in plasma and tissue of bGH compared with control mice (P < 0.05). CONCLUSION: The current study suggests reduced autonomic modulation of HR in bGH transgenic mice. Thus, GH appears to have marked effects on autonomic tone, reducing sympathetic nervous system function possibly via reduced noradrenaline stores.
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| 24. |
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| 25. |
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| 26. |
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| 27. |
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| 28. |
- Bergström, Christel A S, et al.
(författare)
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Accuracy of calculated pH-dependent aqueous drug solubility.
- 2004
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Ingår i: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987. ; 22:5, s. 387-98
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate the extent to which the Henderson-Hasselbalch (HH) relationship can be used to predict the pH-dependent aqueous solubility of cationic drugs. The pH-dependent solubility for 25 amines, carrying a single positive charge, was determined with a small-scale shake flask method. Each sample was prepared as a suspension in 150 mM phosphate buffer. The pH-dependent solubility curves were obtained using at least 10 different pH values. The intrinsic solubility, the solubility at the pKa and the solubility at pH values reflecting the pH of the bulk and acid microclimate in the human small intestine (pH 7.4 and 6.5, respectively) were determined for all compounds. The experimental study revealed a large diversity in slope, from -0.5 (celiprolol) to -8.6 (hydralazine) in the linear pH-dependent solubility interval, which is in sharp contrast to the slope of -1 assumed by the HH equation. In addition, a large variation in the range of solubility between the completely uncharged and completely charged drug species was observed. The range for disopyramide was only 1.1 log units, whereas that for amiodarone was greater than 6.3 log units, pointing at the compound specific response to counter-ion effects. In conclusion, the investigated cationic drugs displayed compound specific pH-dependent solubility profiles, indicating that that the HH equation in many cases will only give rough estimations of the pH-dependent solubility of drugs in divalent buffer systems.
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| 29. |
- Bergström, Christel A. S., 1973-
(författare)
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Computational and Experimental Models for the Prediction of Intestinal Drug Solubility and Absorption
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- New effective experimental techniques in medicinal chemistry and pharmacology have resulted in a vast increase in the number of pharmacologically interesting compounds. However, the number of new drugs undergoing clinical trial has not augmented at the same pace, which in part has been attributed to poor absorption of the compounds.The main objective of this thesis was to investigate whether computer-based models devised from calculated molecular descriptors can be used to predict aqueous drug solubility, an important property influencing the absorption process. For this purpose, both experimental and computational studies were performed. A new small-scale shake flask method for experimental solubility determination of crystalline compounds was devised. This method was used to experimentally determine solubility values used for the computational model development and to investigate the pH-dependent solubility of drugs. In the computer-based studies, rapidly calculated molecular descriptors were used to predict aqueous solubility and the melting point, a solid state characteristic of importance for the solubility. To predict the absorption process, drug permeability across the intestinal epithelium was also modeled.The results show that high quality solubility data of crystalline compounds can be obtained by the small-scale shake flask method in a microtiter plate format. The experimentally determined pH-dependent solubility profiles deviated largely from the profiles predicted by a traditionally used relationship, highlighting the risk of data extrapolation. The in silico solubility models identified the non-polar surface area and partitioned total surface areas as potential new molecular descriptors for solubility. General solubility models of high accuracy were obtained when combining the surface area descriptors with descriptors for electron distribution, connectivity, flexibility and polarity. The used descriptors proved to be related to the solvation of the molecule rather than to solid state properties. The surface area descriptors were also valid for permeability predictions, and the use of the solubility and permeability models in concert resulted in an excellent theoretical absorption classification. To summarize, the experimental and computational models devised in this thesis are improved absorption screening tools applicable to the lead optimization in the drug discovery process.
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| 30. |
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| 31. |
- Bergström, Christel A S, et al.
(författare)
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Global and local computational models for aqueous solubility prediction of drug-like molecules.
- 2004
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Ingår i: Journal of chemical information and computer sciences. - : American Chemical Society (ACS). - 0095-2338 .- 1520-5142. ; 44:4, s. 1477-88
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to develop in silico protocols for the prediction of aqueous drug solubility. For this purpose, high quality solubility data of 85 drug-like compounds covering the total drug-like space as identified with the ChemGPS methodology were used. Two-dimensional molecular descriptors describing electron distribution, lipophilicity, flexibility, and size were calculated by Molconn-Z and Selma. Global minimum energy conformers were obtained by Monte Carlo simulations in MacroModel and three-dimensional descriptors of molecular surface area properties were calculated by Marea. PLS models were obtained by use of training and test sets. Both a global drug solubility model (R(2) = 0.80, RMSE(te) = 0.83) and subset specific models (after dividing the 85 compounds into acids, bases, ampholytes, and nonproteolytes) were generated. Furthermore, the final models were successful in predicting the solubility values of external test sets taken from the literature. The results showed that homologous series and subsets can be predicted with high accuracy from easily comprehensible models, whereas consensus modeling might be needed to predict the aqueous drug solubility of datasets with large structural diversity.
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| 32. |
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| 33. |
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| 34. |
- Bergström, Fredrik, et al.
(författare)
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Dimers of dipyrrometheneboron difluoride (BODIPY) with light spectroscopic applications in chemistry and biology.
- 2002
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Ingår i: Journal of the American Chemical Society. - 0002-7863 .- 1520-5126. ; 124:2, s. 196-204
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Tidskriftsartikel (refereegranskat)abstract
- A ground-state dimer (denoted D(I)) exhibiting a strong absorption maximum at 477 nm (epsilon = 97 000 M(-1)cm(-1)) can form between adjacent BODIPY groups attached to mutant forms of the protein, plasminogen activator inhibitor type 1 (PAI-1). No fluorescence from excited D(I) was detected. A locally high concentration of BODIPY groups was also achieved by doping lipid phases (micelles, vesicles) with BODIPY-labeled lipids. In addition to an absorption band located at about 480 nm, a new weak absorption band is also observed at ca. 570 nm. Both bands are ascribed to the formation of BODIPY dimers of different conformation (D(I) and D(II)). Contrary to D(I) in PAI-1, the D(II) aggregates absorbing at 570 nm are emitting light observed as a broad band centered at about 630 nm. The integrated absorption band of D(I) is about twice that of the monomer, which is compatible with exciton coupling within a dimer. The Förster radius of electronic energy transfer between a BODIPY excited monomer and the ground-state dimer (D(I)()) is 57 +/- 2 A. A simple model of exciton coupling suggests that in D(I) two BODIPY groups are stacked on top of each other in a sandwich-like configuration with parallel electronic transition dipoles. For D(II) the model suggests that the S(0) --> S(1) transition dipoles are colinear. An explanation for the previously reported (J. Am. Chem. Soc. 1994, 116, 7801) exceptional light spectroscopic properties of BODIPY is also presented. These are ascribed to the extraordinary electric properties of the BODIPY chromophore. First, changes of the permanent electric dipole moment (Delta(mu) approximately -0.05 D) and polarizability (-26 x 10(-40) C m(2) V(-1)) between the ground and the first excited states are small. Second, the S(0) <--> S(1) electronic transition dipole moments are perpendicular to Delta(mu).
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| 39. |
- Bergström, Mats, et al.
(författare)
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PET imaging of adrenal cortical tumors with the 11beta-hydroxylase tracer 11C-metomidate
- 2000
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Ingår i: Journal of Nuclear Medicine. - 0161-5505 .- 1535-5667. ; 41:2, s. 275-282
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the study was to evaluate PET with the tracer 11C-metomidate as a method to identify adrenal cortical lesions.METHODS:PET with 11C-metomidate was performed in 15 patients with unilateral adrenal mass confirmed by CT. All patients subsequently underwent surgery, except 2 who underwent biopsy only. The lesions were histopathologically examined and diagnosed as adrenal cortical adenoma (n = 6; 3 nonfunctioning), adrenocortical carcinoma (n = 2), and nodular hyperplasia (n = 1). The remaining were noncortical lesions, including 1 pheochromocytoma, 1 myelolipoma, 2 adrenal cysts, and 2 metastases.RESULTS:All cortical lesions were easily identified because of exceedingly high uptake of 11C-metomidate, whereas the noncortical lesions showed very low uptake. High uptake was also seen in normal adrenal glands and in the stomach. The uptake was intermediate in the liver and low in other abdominal organs. Images obtained immediately after tracer injection displayed high uptake in the renal cortex and spleen. The tracer uptake in the cortical lesions increased throughout the examination. For quantitative evaluation of tracer binding in individual lesions, a model with the splenic radioactivity concentration assigned to represent nonspecific uptake was applied. Values derived with this method, however, did show the same specificity as the simpler standardized uptake value concept, with similar difference observed for cortical versus noncortical lesions.CONCLUSION:PET with 11C-metomidate has the potential to be an attractive method for the characterization of adrenal masses with the ability to discriminate lesions of adrenal cortical origin from noncortical lesions.
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| 41. |
- Dedinaite, A, et al.
(författare)
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Polyelectrolyte-surfactant layers: Adsorption of preformed aggregates versus adsorption of surfactant to preadsorbed polyelectrolyte
- 2000
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Ingår i: Langmuir. - 0743-7463 .- 1520-5827. ; 16, s. 5257-5266
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Tidskriftsartikel (refereegranskat)abstract
- The character of adsorbed layers containing both polyelectrolyte and surfactant depends on the type of polyelectrolyte used and the surfactant concentrations, as demonstrated by several recent studies. However, the layer properties also depend on the experimental pathway. This shows that the adsorbed layers can be trapped in quasi-equilibrium states, and that the true equilibrium state is only reached over experimentally inaccessible time scales. This has to be kept in mind when comparing different results reported in the literature. The present article highlights these effects using a system consisting of a highly charged cationic polyelectrolyte and an anionic surfactant. The adsorbed layer properties were determined using mainly surface force measurements and AFM imaging. We also present some new small angle neutron scattering data for bulk complexes formed between the polyelectrolyte and the surfactant, which demonstrates the presence of a characteristic correlation length of about 37-39 Å. A similar characteristic length-scale is also observed in some of the adsorbed layers, both employing the AFM and the surface force apparatus.
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| 43. |
- Eeg-Olofsson, O, et al.
(författare)
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Herpesviral DNA in brain tissue from patients with temporal lobe epilepsy.
- 2004
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 109:3, s. 169-74
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Presence of DNA from six herpesviruses were examined in brain tissue from patients operated for temporal lobe epilepsy. MATERIAL AND METHODS: A total of 19 Canadian patients (I) with a median age of 22 years, 17 Swedish patients (II) with a median age of 14 years and a reference group comprising 12 individuals were studied. Presence of herpesviral DNA was detected by nested polymerase chain reaction. RESULTS: Of three children with Rasmussen's encephalitis, Cytomegalovirus (CMV) DNA was found in two, and human herpesvirus type 6 DNA in two. In six children with ganglioglioma, Epstein-Barr virus (EBV) was detected in four. CMV DNA was found significantly more in group I compared with II, while the reverse occurred with EBV DNA. Malformations of cortical development were found significantly more in group II compared with I. CONCLUSION: Detection of DNA from some herpesviruses in epileptic brain tissue may possibly be associated with distinct clinical conditions, but factors such as age and malformations of cortical development should also be considered.
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| 44. |
- Engel, Jörgen, 1942, et al.
(författare)
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Neonatal herpes simplex virus type 1 brain infection affects the development of sensorimotor gating in rats.
- 2000
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Ingår i: Brain research. - 0006-8993. ; 863:1-2, s. 233-40
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Tidskriftsartikel (refereegranskat)abstract
- The effect of neonatal brain infection of herpes simplex virus type 1 (HSV-1) on the development of sensorimotor function in the rat was investigated using an acoustic startle paradigm. Intracerebral inoculation of HSV-1 at day 2 after birth, but not at day 4, caused a significant delay in the development of prepulse inhibition of acoustic startle. A decrease in prepulse inhibition was shown at 37, 46 and 58 days of age in these rats compared to control rats. No evidence was obtained for other behavioural dysfunctions such as differences in sensorimotor reactivity, sensorimotor response habituation, spontaneous locomotor activity, rearing activity or stereotyped behaviour. Prepulse inhibition of acoustic startle is an accepted model of sensorimotor gating in the CNS, a function which has been shown diminished in schizophrenic persons. The present results suggest that early viral infections during a neurone-susceptible period may contribute to the development of this deficit.
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| 50. |
- Kapilashrami, A, et al.
(författare)
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Drying of oil-in-water emulsions on hydrophobic and hydrophilic substrates
- 2004
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Ingår i: Colloids and Surfaces A. - 0927-7757 .- 1873-4359. ; 233, s. 155-161
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the effect of the hydrophobic/hydrophilic character of the substrates on the drying behaviour of dilute silicone oil-in-water (o/w) emulsions by light microscopy and ellipsometry. The poly(dimethylsiloxane) (PDMS) emulsion droplets, which are stabilised by a triblock PEO/PPO/PEO copolymer, form a close-packed structure containing domains of hexagonally packed droplets on the hydrophilic substrate. We find that the hydrophilic substrate does not destabilise the emulsion droplets; the close-packed structures are very stable and coalesce very slowly only when most of the water has evaporated. This is supported by ellipsometry measurements, which showed that the emulsion droplets do not adsorb to the hydrophilic substrate. The hydrophobic substrate, on the other hand, destabilises the emulsion and we observed a significant increase in the coalescence rate. Ellipsometry measurements suggest that destabilisation is promoted by the strong interaction between the emulsion droplets and the hydrophobic substrate. We also find that the emulsion undergoes dewetting followed by a release of oil and rewetting of the substrate when the o/w emulsion film reaches a critical thickness on the hydrophobic substrate
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