| 1. |
- Hillier, Ladeana W, et al.
(författare)
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Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
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Tidskriftsartikel (refereegranskat)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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| 2. |
- Aspholm-Hurtig, Marina, et al.
(författare)
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Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin.
- 2004
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 305:5683, s. 519-22
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Tidskriftsartikel (refereegranskat)abstract
- Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Antoni, V., et al.
(författare)
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Turbulence and anomalous transport in magnetized plasmas : Hints from the reversed field pinch configuration
- 2004
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Ingår i: Contributions to Plasma Physics. - : Wiley. - 0863-1042 .- 1521-3986. ; 44:06-maj, s. 458-464
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Tidskriftsartikel (refereegranskat)abstract
- The properties of plasma turbulence in the outer region of the Reversed Field Pinch experiments RFX and EXTRAP-T2R are reviewed. The statistical properties of fluctuations in the range of scales relevant for transport are presented. The observation of coherent structures emerging from the background turbulence and their interpretation in terms of vortices is reported. The interplay between these structures and the mean ExB flow of the plasma is demonstrated with emphasis to the action on the preferential rotation direction. The effect on the particle transport induced by the background turbulence and by the structures is discussed. Finally the methods tested to control turbulence and to mitigate the related transport are illustrated and discussed.
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| 7. |
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| 8. |
- Bower, K. N., et al.
(författare)
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ACE-2 HILLCLOUD. An overview of the ACE-2 ground-based cloud experiment
- 2000
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Ingår i: Tellus. Series B: Chemical and Physical Meteorology. - : Stockholm University Press. - 0280-6509. ; 52:2, s. 750-778
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Tidskriftsartikel (refereegranskat)abstract
- The ACE-2 HILLCLOUD experiment was carried out on the island of Tenerife in June-July 1997 to investigate the interaction of the boundary layer aerosol with a hill cap cloud forming over a ridge to the north-east of the island. The cloud was used as a natural flow through reactor to investigate the dependence of the cloud microphysics and chemistry on the characteristics of the aerosols and trace gases entering cloud, and to simultaneously study the influence of the physical and chemical processes occurring within the cloud on the size distribution, chemical and hygroscopic properties of the aerosol exiting cloud. 5 major ground base sites were used, measuring trace gases and aerosols upwind and downwind of the cloud, and cloud microphysics and chemistry and interstitial aerosol and gases within the cloud on the hill. 8 intensive measurement periods or runs were undertaken during cloud events, (nocturnally for seven of the eight runs) and were carried out in a wide range of airmass conditions from clean maritime to polluted continental. Polluted air was characterised by higher than average concentrations of ozone (> 50 ppbv), fine and accumulation mode aerosols (> 3000 and > 1500 cm -3 , respectively) and higher aerosol mass loadings. Cloud droplet number concentrations N, increased from 50 cm -3 in background maritime air to > 2500 cm -3 in aged polluted continental air, a concentration much higher than had previously been detected. Surprisingly, N was seen to vary almost linearly with aerosol number across this range. The droplet aerosol analyser (DAA) measured higher droplet numbers than the corrected forward scattering spectrometer probe (FSSP) in the most polluted air, but at other times there was good agreement (FSSP = 0.95 DAA with an r 2 = 0.89 for N < 1200 cm -3 ). Background ammonia gas concentrations were around 0.3 ppbv even in air originating over the ocean, another unexpected but important result for the region. NO 2 was present in background concentrations of typically 15 pptv to 100 pptv and NO 3 . (the nitrate radical) was observed at night throughout. Calculations suggest NO 3 . losses were mainly by reaction with DMS to produce nitric acid. Low concentrations of SO 2 (~30 pptv), HNO 3 and HCl were always present. HNO 3 concentrations were higher in polluted episodes and calculations implied that these exceeded those which could be accounted for by NO 2 oxidation. It is presumed that nitric and hydrochloric acids were present as a result of outgassing from aerosol, the HNO 3 from nitrate rich aerosol transported into the region from upwind of Tenerife, and HCl from sea salt aerosol newly formed at the sea surface. The oxidants hydrogen peroxide and ozone were abundant (i.e., were well in excess over SO 2 throughout the experiment). Occasions of significant aerosol growth following cloud processing were observed, particularly in cleaner cases. Observations and modelling suggested this was due mainly to the take up of nitric acid, hydrochloric acid and ammonia by the smallest activated aerosol particles. On a few occasions a small contribution was made by the in-cloud oxidation of S(IV). The implications of these results from HILLCLOUD for the climatologically more important stratocumulus Marine Boundary Layer (MBL) clouds are considered.
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| 9. |
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| 10. |
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| 11. |
- Craig, Cora L, et al.
(författare)
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International physical activity questionnaire : 12-country reliability and validity
- 2003
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Ingår i: Medicine & Science in Sports & Exercise. - 0195-9131 .- 1530-0315. ; 35:8, s. 1381-1395
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Physical inactivity is a global concern, but diverse physical activity measures in use prevent international comparisons. The International Physical Activity Questionnaire (IPAQ) was developed as an instrument for cross-national monitoring of physical activity and inactivity.METHODS: Between 1997 and 1998, an International Consensus Group developed four long and four short forms of the IPAQ instruments (administered by telephone interview or self-administration, with two alternate reference periods, either the "last 7 d" or a "usual week" of recalled physical activity). During 2000, 14 centers from 12 countries collected reliability and/or validity data on at least two of the eight IPAQ instruments. Test-retest repeatability was assessed within the same week. Concurrent (inter-method) validity was assessed at the same administration, and criterion IPAQ validity was assessed against the CSA (now MTI) accelerometer. Spearman's correlation coefficients are reported, based on the total reported physical activity.RESULTS: Overall, the IPAQ questionnaires produced repeatable data (Spearman's rho clustered around 0.8), with comparable data from short and long forms. Criterion validity had a median rho of about 0.30, which was comparable to most other self-report validation studies. The "usual week" and "last 7 d" reference periods performed similarly, and the reliability of telephone administration was similar to the self-administered mode.CONCLUSIONS: The IPAQ instruments have acceptable measurement properties, at least as good as other established self-reports. Considering the diverse samples in this study, IPAQ has reasonable measurement properties for monitoring population levels of physical activity among 18- to 65-yr-old adults in diverse settings. The short IPAQ form "last 7 d recall" is recommended for national monitoring and the long form for research requiring more detailed assessment.
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| 12. |
- James, Stefan, et al.
(författare)
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N-Terminal Pro–Brain Natriuretic Peptide and Other Risk Markers for the Separate Prediction of Mortality and Subsequent Myocardial Infarction in Patients With Unstable Coronary Artery Disease : A Global Utilization of Strategies To Open occluded arteries (GUSTO)-IV Substudy
- 2003
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 108:3, s. 275-281
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Biochemical markers are useful for prediction of cardiac events in patients with non-ST-segment-elevation acute coronary syndrome (ACS). The associations between N-terminal pro-brain natriuretic peptide (NT-proBNP) and other biochemical and clinical risk indicators, as well as their prognostic value concerning the individual end points of death and myocardial infarction (MI), were elucidated in a large cohort of ACS patients. METHODS AND RESULTS: NT-proBNP, troponin T, and C-reactive protein (CRP) were analyzed in blood samples obtained at a median of 9.5 hours from symptom onset in 6809 of 7800 ACS patients in the Global Utilization of Strategies To Open occluded arteries-IV (GUSTO-IV) trial. Levels of NT-proBNP were correlated independently with age, female gender, low body weight, diabetes, renal dysfunction, history of MI, heart failure, heart rate, ongoing myocardial damage, and time since onset of ischemia. Increasing quartiles of NT-proBNP were related to short- and long-term mortality that reached 1.8%, 3.9%, 7.7%, and 19.2%, (P<0.001), respectively, at 1 year. Levels of troponin T, CRP, heart rate, and creatinine clearance, in addition to ST-segment depression, were also correlated independently with 1-year mortality, but NT-proBNP was the marker with the strongest relation. In contrast, only troponin T, creatinine clearance, and ST-segment depression were independently related to future MI. The combination of NT-proBNP and creatinine clearance provided the best prediction, with a 1-year mortality of 25.7% with both markers in the top quartile vs 0.3% with both markers in the bottom quartile. CONCLUSIONS: The use of NT-proBNP appears to add critical prognostic insight to the assessment of patients with ACS.
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| 13. |
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| 14. |
- Spolaore, M., et al.
(författare)
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Vortex-induced diffusivity in reversed field pinch plasmas
- 2004
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 93:21
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Tidskriftsartikel (refereegranskat)abstract
- Coherent structures identified in two reversed field pinch experiments are interpreted as a dynamic balance of dipolar and monopolar vortices growing and evolving under the effect of the ExB flow shear. For the first time their contribution to the anomalous transport has been estimated in fusion related plasmas, showing that they can account for up to 50% of the total plasma diffusivity. The experimental findings indicate that the diffusion coefficient associated with the coherent structures depends on the relative population of the two types of vortices and is minimum when the two populations are equal. An interpretative model is proposed to explain this feature.
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| 15. |
- Tong, Longyu, et al.
(författare)
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Photo-dissociation of hydrogen passivated dopants in gallium arsenide
- 2002
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Ingår i: Nuclear Instruments and Methods in Physics Research Section B. - 0168-583X .- 1872-9584. ; 186:1-4, s. 234-239
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Tidskriftsartikel (refereegranskat)abstract
- A theoretical and experimental study of the photo-dissociation mechanisms of hydrogen passivated n- and p-type dopants in gallium arsenide is presented. The photo-induced dissociation of the Si Ga-H complex has been observed for relatively low photon energies (3.48 eV), whereas the photo-dissociation of C As-H is not observed for photon energies up to 5.58 eV. This fundamental difference in the photo-dissociation behavior between the two dopants is explained in terms of the localized excitation energies about the Si-H and C-H bonds.
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| 16. |
- Axelson, Jan, et al.
(författare)
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Runic bibliography for 1999
- 2001
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Ingår i: Nytt om runer: Meldingsblad om runeforskning. - 0801-3756. ; 15(2000), s. 41-55
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 17. |
- Axelson, Jan, et al.
(författare)
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Runic bibliography for 2000
- 2003
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Ingår i: Nytt om runer: Meldingsblad om runeforskning. - 0801-3756. ; 16(2001), s. 42-54
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 18. |
- Axelson, Jan, et al.
(författare)
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Runic bibliography for 2001
- 2004
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Ingår i: Nytt om runer: Meldingsblad om runeforskning. - 0801-3756. ; 17(2002), s. 47-66
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 19. |
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Box, George E.P., et al.
(författare)
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Performance Evaluation of Dynamic Monitoring Systems : The Waterfall Chart
- 2003
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Ingår i: Quality Engineering. - 0898-2112 .- 1532-4222. ; 16:2, s. 183-191
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Tidskriftsartikel (refereegranskat)abstract
- Computers are increasingly employed to monitor the performance of complex systems. An important issue is how to evaluate the performance of such monitors. In this article we introduce a three-dimensional representation that we call a "waterfall chart" of the probability of an alarm as a function of time and the condition of the system. It combines and shows the conceptual relationship between the cumulative distribution function of the run length and the power function. The value of this tool is illustrated with an application to Page's one-sided Cusum algorithm. However, it can be applied in general for any monitoring system.
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| 24. |
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| 25. |
- Cecconello, Marco, et al.
(författare)
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Current profile modification experiments in EXTRAP T2R
- 2004
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 0741-3335 .- 1361-6587. ; 46:1, s. 145-161
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Tidskriftsartikel (refereegranskat)abstract
- Pulsed poloidal current drive (PPCD) experiments have been conducted in the resistive shell EXTRAP T2R reversed-field pinch experiment. During the current profile modification phase, the fluctuation level of the m = 1 internally resonant tearing modes decreases, and the velocity of these modes increases. The m = 0 modes are not affected during PPCD, although termination occurs with a burst in the m = 0 amplitude. The PPCD phase is characterized by an increase in the central electron temperature (up to 380 eV) and in the soft x-ray signal. Spectroscopic observations confirm an increase in the central electron temperature. During PPCD, the plasma poloidal beta increases to 14%, and the estimated energy confinement time doubles, reaching 380 mus. The reduction in the fluctuation level and the corresponding increase in the energy confinement time are qualitatively consistent with a reduction in parallel transport along stochastic magnetic field lines.
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| 26. |
- Djoussé, Luc, et al.
(författare)
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Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16.
- 2004
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Ingår i: Neurogenetics. - : Springer Science and Business Media LLC. - 1364-6745 .- 1364-6753. ; 5:2, s. 109-14
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Tidskriftsartikel (refereegranskat)abstract
- Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the HD gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: MSX1 (Drosophila homeo box homologue 1, formerly known as homeo box 7, HOX7), Delta2642 (within the HD coding sequence), and BJ56 ( D4S127). Suggestive evidence for an association was seen between MSX1 alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model P value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the MSX1 genotype. Individuals with MSX1 genotype 3/3 tended to have younger AO. No association was found between Delta2642 (P=0.44) and BJ56 (P=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker.
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| 27. |
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| 28. |
- Eriksson, Marcus, et al.
(författare)
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Inherent Shutdown Capabilities in Accelerator-driven Systems
- 2002
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Ingår i: Annals of Nuclear Energy. - 0306-4549 .- 1873-2100. ; 29:14, s. 1689-1706
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Tidskriftsartikel (refereegranskat)abstract
- The applicability for inherent shutdown mechanisms in accelerator-driven systems (ADS) has been investigated. We study the role of reactivity feedbacks. The benefits, in terms of dynamics performance, for enhancing the Doppler effect are examined. Given the performance characteristics of source-driven systems, it is necessary to manage the neutron source in order to achieve inherent shutdown. The shutdown system must be capable of halting the external source before excessive temperatures are obtained. We evaluate methods, based on the analysis of unprotected accidents, to accomplish such means. Pre-concepted designs for self-actuated shutdown of the external source suggested. We investigate time responses and evaluate methods to improve the performance of the safety system. It is shown that maximum beam output must be limited by fundamental means in order to protect against accident initiators that appear to be achievable in source driven systems. Utilizing an appropriate burnup control strategy plays a key role in that effort.
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| 29. |
- Eriksson, Marcus, et al.
(författare)
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Safety Analysis of Na and Pb-Bi Coolants in Response to Beam Instabilities
- 2003
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Ingår i: UTILISATION AND RELIABILITY OF HIGH POWER PROTON ACCELERATORS, WORKSHOP PROCEEDINGS. - 9264102116 ; , s. 227-236
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Konferensbidrag (refereegranskat)abstract
- A comparative safety study has been performed on sodium vs. lead/bismuth as coolant for accelerator-driven systems. Transient studies are performed for a beam overpower event. We examine a fuel type of recent interest in the research on minor actinide burners, i.e. uranium-free oxide fuel. A strong positive void coefficient is calculated for both sodium and lead/bismuth. This is attributed to the high fraction of americium in the fuel. It is shown that the lead/bismuth-cooled reactor features twice the grace time with respect to fuel or cladding damage compared to the sodium-cooled reactor of comparable core size and power rating. This accounts to the difference in void reactivity contribution and to the low boiling point of sodium. For improved safety features the general objective is to reduce the coolant void reactivity effect. An important safety issue is the high void worth that could possibly drive the system to prompt criticality.
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| 30. |
- Fluckey, James D, et al.
(författare)
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Insulin facilitation of muscle protein synthesis following resistance exercise in hindlimb suspended rats is independent of a rapamycin-sensitive pathway
- 2004
-
Ingår i: American Journal of Physiology - Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 287:6, s. E1070-E1075
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Tidskriftsartikel (refereegranskat)abstract
- Hindlimb suspension (HS) results in rapid losses of muscle mass, which may in part be explained by attenuated rates of protein synthesis. Mammalian target of rapamycin (mTOR) regulates protein synthesis and has been implicated as a potential mediator of the muscle mass decrement with HS. This study examined the effect of resistance exercise, a muscle hypertrophy stimulant, on rates of protein synthesis after 4 days of HS in mature male Sprague-Dawley rats. Flywheel resistance exercise (2 sets x 25 repetitions) was conducted on days 2 and 4 of HS (HSRE). Sixteen hours after the last exercise bout, soleus muscles were assessed for in vitro rates of protein synthesis, with and without insulin (signaling agonist) and/or rapamycin (mTOR inhibitor). Results demonstrated that soleus mass was reduced (P < 0.05) with HS, but this loss of mass was not observed (P > 0.05) with HSRE. Muscle protein synthesis was diminished (P < 0.05) with HS, with or without insulin. HSRE also had reduced rates of synthesis without insulin; however, insulin administration yielded higher (P < 0.05) rates in HSRE compared with HS or control. Rapamycin diminished protein synthesis in all groups (P < 0.05), but insulin rescued synthesis rates in HS and HSRE to levels similar to insulin alone for each group, suggesting that alternate signaling pathways develop to increase protein synthesis with HS. These results demonstrate that the capacity for an augmented anabolic response to resistance exercise is maintained after 4 days of HS and is independent of a rapamycin-sensitive pathway.
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| 31. |
- Godl, Klaus, et al.
(författare)
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The N terminus of the MUC2 mucin forms trimers that are held together within a trypsin-resistant core fragment.
- 2002
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Ingår i: The Journal of biological chemistry. - 0021-9258 .- 1083-351X. ; 277:49, s. 47248-56
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Tidskriftsartikel (refereegranskat)abstract
- The N terminus of the human MUC2 mucin (amino acids 1-1397) has been expressed as a recombinant tagged protein in Chinese hamster ovary cells. The intracellular form was found to be an endoglycosidase H-sensitive monomer, whereas the secreted form was an oligomer that gave monomers upon disulfide bond reduction. The secreted MUC2 N terminus contained a trypsin-resistant core fragment. Edman sequencing and mass spectrometry of the peptides obtained localized this core fragment to the C-terminal end of the recombinant protein. This core retained its oligomeric nature with an apparent mass of approximately 240 kDa. Upon reduction, peptides of approximately 85 kDa were found, suggesting that the N terminus forms trimers. This interpretation was also supported by gel electrophoresis and gel filtration of the intact MUC2 N terminus. Electron microscopy revealed three globular domains each linked via an extended and flexible region to a central part in a trefoil-like manner. Immunostaining with gold-labeled antibodies localized the N-terminal end to the three globular structures, and the antibodies directed against the Myc and green fluorescent protein tags attached at the C terminus localized these to the stalk side of the central trefoil. The N terminus of the MUC2 mucin is thus assembled into trimers that contain proteolytically stable parts, suggesting that MUC2 can only be partly degraded by intestinal proteases and thus is able to maintain a mucin network protecting the intestine.
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| 32. |
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| 33. |
- Hartman, Thomas, 1957-, et al.
(författare)
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Allocative Efficiency in Branch Banking
- 2001
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Ingår i: European Journal of Operational Research. - 0377-2217 .- 1872-6860. ; 134:2, s. 232-242
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Tidskriftsartikel (refereegranskat)abstract
- Bank branch efficiency and organization change is analyzed using data from 50 savings bank branches in Sweden. First, technical and allocative efficiencies are analyzed, using non-priced and priced inputs. Secondly, by grouping the branches according to their organizational designation, efficiency is examined by level of service. Trends in performance over two time periods are also analyzed.
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| 34. |
- Helgesson, Johan, et al.
(författare)
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Finite Size scaling and the nuclear liquid-gas phase transition
- 2003
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Konferensbidrag (refereegranskat)abstract
- Recent analyses of multifragmentation data in terms of Fisher's model have led to the estimate of the coexistence curve of finite nuclear matter as well as of the location of the critical point. In order to extrapolate those results to infinite nuclear matter, finite size effects have to be taken into account. Guided by the finite size behavior of the three-dimensional Ising model, we propose a modified Fisher Droplet model expression that incorporates surface and correlation length effects.
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| 35. |
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| 36. |
- Jacobson, Peter, 1962, et al.
(författare)
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Melanocortin 4 receptor sequence variations are seldom a cause of human obesity: the Swedish Obese Subjects, the HERITAGE Family Study, and a Memphis cohort.
- 2002
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 87:10, s. 4442-6
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of mutations within and in the flanking regions of the gene encoding the melanocortin 4 receptor was investigated in severely obese and normal-weight subjects from the Swedish Obese Subjects study, the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family study, and a Memphis cohort. A total of 433 white and 95 black subjects (94% females) were screened for mutations by direct sequencing. Three previously described missense variants and nine novel (three missense, six silent) variants were detected. None of them showed significant association with obesity or related phenotypes. In addition, two novel deletions were found in two heterozygous obese women: a -65_-64delTG mutation within the 5' noncoding region and a 171delC frameshift mutation predicted to result in a truncated nonfunctional receptor. No pathogenic mutations were found among obese blacks or nonobese controls. Furthermore, none of the null mutations found in other populations was present in this sample. In conclusion, our results do not support the prevailing notion that sequence variation in the melanocortin 4 receptor gene is a frequent cause of human obesity.
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| 37. |
- James, Stefan K., et al.
(författare)
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Activation of the inflammation, coagulation, and fibrinolysis systems, without influence of abciximab infusion in patients with non-ST–elevation acute coronary syndromes treated with dalteparin : a GUSTO IV substudy
- 2004
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 147:2, s. 267-274
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn acute coronary syndromes, the inflammation and the coagulation systems are activated, implying an impaired outcome. In addition to platelet inhibition, recent evidence suggests that the glycoprotein IIb/IIIa receptor inhibitor abciximab attenuates inflammation and coagulation activity.MethodsThe Swedish Global Utilization of Strategies To open Occluded arteries-IV (GUSTO-IV) substudy included 404 patients with non-ST–elevation acute coronary syndromes. In addition to aspirin and dalteparin, all patients were randomized to receive abciximab infusion for 24 hours or 48 hours or corresponding placebo without early coronary revascularization. Plasma samples were obtained at baseline and 24, 48, and 72 hours.ResultsThe median levels of the coagulation markers thrombin/antithrombin complex and soluble fibrin increased significantly from 3.1 to 3.7 ug/L (baseline to peak; P <.001) and from 20 to 23 nmol/L (P <.001), respectively. The fibrinolysis marker, tissue plasminogen-activator, also increased its median levels, from 11.7 to 17.5 ug/L (P <.001), whereas the median level of plasminogen-activator-inhibitor was unchanged. The inflammatory markers interleukin-6, C-reactive protein, and fibrinogen also increased their median levels (5.4–7.8 ng/L, P <.001; 4.4–8.7 mg/L, P <.001; 3.3–3.9 g/L, P <.001). However, there were no differences in median levels or in changes of median levels of any marker at any point between the placebo group and any of the abciximab groups.ConclusionsIn non-ST–elevation acute coronary syndrome, there was a simultaneous activation of the inflammation, coagulation, and fibrinolysis systems, despite aspirin and dalteparin treatment. Prolonged treatment with abciximab had no influence of the activation of these systems.Unstable coronary artery disease (CAD) intricately involves inflammatory mediators in the development of an atherosclerotic plaque and in thrombus formation by platelet aggregation.1 Acute phase elevation of inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and fibrinogen are important predictors of the short- and long-term prognosis in unstable CAD.2, 3 and 4 Activation of the coagulation and fibrinolysis systems, as demonstrated with elevated markers of thrombin generation, thrombin activity, and fibrin turnover, also have been found in the acute phase of unstable CAD and are associated with an adverse outcome.5, 6 and 7 Glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors potently inhibit platelet aggregation and reduce the incidence of ischemic events in patients undergoing percutaneuos coronary interventions8, 9 and 10 and in patients with unstable CAD.11 The GP IIb/IIIa inhibitor abciximab, in addition to its antithrombotic effect, also suppresses the rise in levels of inflammatory markers after percutaneous coronary interventions.12 This anti-inflammatory effect might be related to abciximab's cross-reaction with other integrin receptors.13 Furthermore, by inhibiting platelet aggregation, abciximab might also attenuate the coagulation and fibrinolysis activation as shown in vitro and in vivo.14 and 15The Global Utilization of Strategies To Open occluded arteries in acute coronary syndromes (GUSTO IV-ACS) trial unexpectedly failed to show any benefit of abciximab treatment in a high risk ACS population not undergoing early coronary revascularization.16 In the GUSTO IV-ACS low-molecular weight heparin substudy,17 dalteparin was used as the anticoagulant. Dalteparin, which is an inhibitor of the coagulation cascade, mainly by inhibition of factor Xa and less of factor IIa, has previously been shown to reduce the generation and activity of thrombin in unstable coronary disease.18 There is evidence that a combination of abciximab and a low-molecular-weight heparin have additive effects on the lag-time to platelet aggregation,19 and there are several theoretical advantages with the combination treatment. There was still no significant reduction in clinical events with abciximab in combination with dalteparin.17 The aim of this Swedish substudy of GUSTO IV-ACS was to evaluate the influence of abciximab infusion on markers on inflammation, coagulation, and fibrinolysis in patients with unstable CAD treated with aspirin and subcutaneous dalteparin.
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| 38. |
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| 39. |
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| 40. |
- Julenius, Karin, et al.
(författare)
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Coupling of ligand binding and dimerization of helix-loop-helix peptides: Spectroscopic and sedimentation analyses of calbindin D-9k EF-hands
- 2002
-
Ingår i: Proteins. - : Wiley. - 0887-3585. ; 47:3, s. 323-333
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Tidskriftsartikel (refereegranskat)abstract
- Isolated Ca2+-binding EF-hand peptides have a tendency to dimerize. This study is an attempt to account for the coupled equilibria of Ca2+-binding and peptide association for two EF-hands with strikingly different loop sequence and net charge. We have studied each of the two separate EF-hand fragments from calbindin D-9k. A series of Ca2+-titrations at different peptide concentrations were monitored by CD and fluorescence spectroscopy. All data were fitted simultaneously to both a complete model of all possible equilibrium intermediates and a reduced model not including dimerization in the absence of Ca2+. Analytical ultracentrifugation shows that the peptides may occur as monomers or dimers depending on the solution conditions. Our results show strikingly different behavior for the two EF-hands. The fragment containing the N-terminal EF-hand shows a strong tendency to dimerize in the Ca2+-bound state. The average Ca2+-affinity is 3.5 orders of magnitude lower than for the intact protein. We observe a large apparent cooperativity of Ca2+ binding for the overall process from Ca2+-free monomer to fully loaded dimer, showing that a Ca2+-free EF-hand folds upon dimerization to a Ca2+-bound EF-hand, thereby presenting a preformed binding site to the second Ca2+-ion. The C-terminal EF-hand shows a much smaller tendency to dimerize, which may be related to its larger net negative charge. In spite of the differences in dimerization behavior, the Ca2+ affinities of both EF-hand fragments are similar and in the range IgK = 4.6-5.3.
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| 41. |
- Kullander, Klas, et al.
(författare)
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Role of EphA4 and EphrinB3 in local neuronal circuits that control walking
- 2003
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 299:5614, s. 1889-1892
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Tidskriftsartikel (refereegranskat)abstract
- Local circuits in the spinal cord that generate locomotion are termed central pattern generators (CPGs). These provide coordinated bilateral control over the normal limb alternation that underlies walking. The molecules that organize the mammalian CPG are unknown. Isolated spinal cords from mice lacking either the EphA4 receptor or its ligand ephrinB3 have lost left-right limb alternation and instead exhibit synchrony. We identified EphA4-positive neurons as an excitatory component of the locomotor CPG. Our study shows that dramatic locomotor changes can occur as a consequence of local genetic rewiring and identifies genes required for the development of normal locomotor behavior.
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| 42. |
- Li, Jian-Liang, et al.
(författare)
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A genome scan for modifiers of age at onset in Huntington disease : The HD MAPS study.
- 2003
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 73:3, s. 682-7
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Tidskriftsartikel (refereegranskat)abstract
- Huntington disease (HD) is caused by the expansion of a CAG repeat within the coding region of a novel gene on 4p16.3. Although the variation in age at onset is partly explained by the size of the expanded repeat, the unexplained variation in age at onset is strongly heritable (h2=0.56), which suggests that other genes modify the age at onset of HD. To identify these modifier loci, we performed a 10-cM density genomewide scan in 629 affected sibling pairs (295 pedigrees and 695 individuals), using ages at onset adjusted for the expanded and normal CAG repeat sizes. Because all those studied were HD affected, estimates of allele sharing identical by descent at and around the HD locus were adjusted by a positionally weighted method to correct for the increased allele sharing at 4p. Suggestive evidence for linkage was found at 4p16 (LOD=1.93), 6p21-23 (LOD=2.29), and 6q24-26 (LOD=2.28), which may be useful for investigation of genes that modify age at onset of HD.
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| 43. |
- Lidell, Martin, 1970, et al.
(författare)
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The recombinant C-terminus of the human MUC2 mucin forms dimers in Chinese-hamster ovary cells and heterodimers with full-length MUC2 in LS 174T cells.
- 2003
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Ingår i: The Biochemical journal. - 0264-6021. ; 372:Pt 2, s. 335-45
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Tidskriftsartikel (refereegranskat)abstract
- The entire cDNA corresponding to the C-terminal cysteine-rich domain of the human MUC2 apomucin, after the serine- and threonine-rich tandem repeat, was expressed in Chinese-hamster ovary-K1 cells and in the human colon carcinoma cell line, LS 174T. The C-terminus was expressed as a fusion protein with the green fluorescent protein and mycTag sequences and the murine immunoglobulin kappa-chain signal sequence to direct the protein to the secretory pathway. Pulse-chase studies showed a rapid conversion of the C-terminal monomer into a dimer in both Chinese-hamster ovary-K1 and LS 174T cells. Disulphide-bond-stabilized dimers secreted into the media of both cell lines had a higher apparent molecular mass compared with the intracellular forms. The MUC2 C-terminus was purified from the spent culture medium and visualized by molecular electron microscopy. The dimer nature of the molecule was visible clearly and revealed that each monomer was attached to the other by a large globular domain. Gold-labelled antibodies against the mycTag or green fluorescent protein revealed that these were localized to the ends opposite to the parts responsible for the dimerization. The C-terminus expressed in LS 174T cells formed heterodimers with the full-length wild-type MUC2, but not with the MUC5AC mucin, normally expressed in LS 174T cells. The homodimers of the MUC2 C-termini were secreted continuously from the LS 174T cells, but no wild-type MUC2 secretion has been observed from these cells. This suggests that the information for sorting the MUC2 mucin into the regulated secretory pathway in cells having this ability is present in parts other than the C-terminus of MUC2.
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