| 1. |
- Adcox, K, et al.
(författare)
-
PHENIX detector overview
- 2003
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 469-479
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Tidskriftsartikel (refereegranskat)abstract
- The PHENIX detector is designed to perform a broad study of A-A, p-A, and p-p collisions to investigate nuclear matter under extreme conditions. A wide variety of probes, sensitive to all timescales, are used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon. Designing for the needs of the heavy-ion and polarized-proton programs has produced a detector with unparalleled capabilities. PHENIX measures electron and muon pairs, photons, and hadrons with excellent energy and momentum resolution. The detector consists of a large number of subsystems that are discussed in other papers in this volume. The overall design parameters of the detector are presented. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 2. |
- Adler, SS, et al.
(författare)
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PHENIX on-line systems
- 2003
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 560-592
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Tidskriftsartikel (refereegranskat)abstract
- The PHENIX On-Line system takes signals from the Front End Modules (FEM) on each detector subsystem for the purpose of generating events for physics analysis. Processing of event data begins when the Data Collection Modules (DCM) receive data via fiber-optic links from the FEMs. The DCMs format and zero suppress the data and generate data packets. These packets go to the Event Builders (EvB) that assemble the events in final form. The Level-1 trigger (LVL1) generates a decision for each beam crossing and eliminates uninteresting events. The FEMs carry out all detector processing of the data so that it is delivered to the DCMs using a standard format. The FEMs also provide buffering for LVL1 trigger processing and DCM data collection. This is carried out using an architecture that is pipelined and deadtimeless. All of this is controlled by the Master Timing System (MTS) that distributes the RHIC clocks. A Level-2 trigger (LVL2) gives additional discrimination. A description of the components and operation of the PHENIX On-Line system is given and the solution to a number of electronic infrastructure problems are discussed. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 3. |
- Bower, K. N., et al.
(författare)
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ACE-2 HILLCLOUD. An overview of the ACE-2 ground-based cloud experiment
- 2000
-
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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| 4. |
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| 5. |
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| 6. |
- Cho, Eunyoung, et al.
(författare)
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Alcohol intake and colorectal cancer : a pooled analysis of 8 cohort studies
- 2004
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Ingår i: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819 .- 1539-3704. ; 140:8, s. 603-613
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epidemiologic studies have generally reported positive associations between alcohol consumption and risk for colorectal cancer. However, findings related to specific alcoholic beverages or different anatomic sites in the large bowel have been inconsistent. OBJECTIVE: To examine the relationship of total alcohol intake and intake from specific beverages to the incidence of colorectal cancer and to evaluate whether other potential risk factors modify the association. DESIGN: Pooled analysis of primary data from 8 cohort studies in 5 countries. SETTING: North America and Europe. PARTICIPANTS: 489,979 women and men with no history of cancer other than nonmelanoma skin cancer at baseline. MEASUREMENTS: Alcohol intake was assessed in each study at baseline by using a validated food-frequency questionnaire. RESULTS: During a maximum of 6 to 16 years of follow-up across the studies, 4687 cases of colorectal cancer were documented. In categorical analyses, increased risk for colorectal cancer was limited to persons with an alcohol intake of 30 g/d or greater (approximately > or =2 drinks/d), a consumption level reported by 4% of women and 13% of men. Compared with nondrinkers, the pooled multivariate relative risks were 1.16 (95% CI, 0.99 to 1.36) for persons who consumed 30 to less than 45 g/d and 1.41 (CI, 1.16 to 1.72) for those who consumed 45 g/d or greater. No significant heterogeneity by study or sex was observed. The association was evident for cancer of the proximal colon, distal colon, and rectum. No clear difference in relative risks was found among specific alcoholic beverages. LIMITATIONS: The study included only one measure of alcohol consumption at baseline and could not investigate lifetime alcohol consumption, alcohol consumption at younger ages, or changes in alcohol consumption during follow-up. It also could not examine drinking patterns or duration of alcohol use. CONCLUSIONS: A single determination of alcohol intake correlated with a modest relative elevation in colorectal cancer rate, mainly at the highest levels of alcohol intake.
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| 7. |
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| 8. |
- Cordon, O, et al.
(författare)
-
Ten years of genetic fuzzy systems : current framework and new trends
- 2004
-
Ingår i: Fuzzy sets and systems (Print). - 0165-0114 .- 1872-6801. ; 141:1, s. 5-31
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Forskningsöversikt (refereegranskat)abstract
- Fuzzy systems have demonstrated their ability to solve different kinds of problems in various application domains. Currently, there is an increasing interest to augment fuzzy systems with learning and adaptation capabilities. Two of the most successful approaches to hybridise fuzzy systems with learning and adaptation methods have been made in the realm of soft computing. Neural fuzzy systems and genetic fuzzy systems hybridise the approximate reasoning method of fuzzy systems with the learning capabilities of neural networks and evolutionary algorithms. The objective of this paper is to provide an account of genetic fuzzy systems, with special attention to genetic fuzzy rule-based systems. After a brief introduction to models and applications of genetic fuzzy systems, the field is overviewed, new trends are identified, a critical evaluation of genetic fuzzy systems for fuzzy knowledge extraction is elaborated, and open questions that remain to be addressed in the future are raised. The paper also includes some of the key references required to quickly access implementation details of genetic fuzzy systems.
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| 9. |
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| 10. |
- Frank, Rupert L., et al.
(författare)
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On the scattering theory of the Laplacian with a periodic boundary condition. II. Additional channels of scattering
- 2004
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Ingår i: Documenta Mathematica. - 1431-0635 .- 1431-0643. ; 9:1, s. 57-77
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Tidskriftsartikel (refereegranskat)abstract
- We study spectral and scattering properties of the Laplacian H (σ) = -Δ in L2(ℝ+2) corresponding to the boundary condition ∂u/∂ν + σu = 0 for a wide class of periodic functions σ. For non-negative σ we prove that H(σ) is unitarily equivalent to the Neumann Laplacian H(0). In general, there appear additional channels of scattering which are analyzed in detail.
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| 11. |
- Giele, Walter, et al.
(författare)
-
The QCD / SM working group: Summary report
- 2002
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Ingår i: Physics at TeV colliders. Proceedings, Euro Summer School, Les Houches, France, May 21-June 1, 2001. ; , s. 275-426, s. 275-426
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 12. |
- Hampel, H, et al.
(författare)
-
Core biological marker candidates of Alzheimer's disease - perspectives for diagnosis, prediction of outcome and reflection of biological activity.
- 2004
-
Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 111:3, s. 247-72
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Forskningsöversikt (refereegranskat)abstract
- Alzheimer's disease (AD) is a complex neurodegenerative dementing illness. Over the past few years, however, remarkable advances have taken place in understanding both the genetic and molecular biology with the intracellular processing of amyloid and tau and the changes leading to the pathologic formation of extracellular amyloid plaques and the intraneuronal aggregation of hyperphosphorylated tau into neurofibrillary tangles. This progress in our understanding of the molecular pathology has set the stage for clinically meaningful advances in the development of biomarkers. Emerging diagnostic methods that are based on biochemical and imaging biomarkers of disease specific pathology hold the potential to provide effective measures of natural history (marker of disease that is predictive of outcome), biological activity (such as magnitude and frequency of response correlating with drug potency) and markers of surrogate endpoints (single or composite marker that accounts for clinical benefit of the therapy). Markers of biological activity should be also evaluated regarding their value to reflect disease progression, heterogeneity of the clinical population, for early decision making and characterization of new treatments. We focussed on the current status of core analytes which provide reasonable evidence for association with key mechanisms of pathogenesis or neurodegeneration in AD. In addition, feasibility was important, such as availability of a validated assay for the biological measure in question, with properties that included high precision and reliability of measurement, reagents and standards well described. On this basis we reviewed the body of literature that has examined CSF total tau (t-tau) and beta-amyloid 1-42 (Abeta(1-42)), phosphorylated tau (p-tau) and beta-amyloid-antibodies as diagnostic tests for AD versus clinically representative comparison groups. Measurement of t-tau and Abeta(1-42) in the CSF seems useful to discriminate early and incipient AD from age-associated memory-impairment, depression, and some secondary dementias. First studies showed that measurement of p-tau proteins significantly improves early and differential diagnosis, as well as disease prediction in subjects at risk for AD and comes closest to fulfilling proposed criteria of a biological marker for AD. However, the nature of the majority of reported findings are still preliminary and retrospective. General issues for biomarkers have to be adequately addressed, such as sensitivity of the method, frequency of assessments, stability of the method, standardization of methods and dynamic range. There is still a partial lack of comparison patient populations that must be addressed in future studies. International dementia networks have been recently established to advance the establishment of core biomarker candidates of AD as potential surrogate endpoints for clinical trials and their clinical use for predictive and diagnostic purposes.
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| 13. |
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| 14. |
- James, Helen F, et al.
(författare)
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Pseudopodoces humilis, a misclassified terrestrial tit (Paridae) of the Tibetan Plateau: evolutionary consequences of shifting adaptive zones
- 2003
-
Ingår i: Ibis. - 0019-1019 .- 1474-919X. ; 145:2, s. 185-202
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Tidskriftsartikel (refereegranskat)abstract
- Pseudopodoces humilis (Hume's Ground-Jay) is a small passerine bird that inhabits the high rocky steppes of the Tibetan (Qinghai–Xizang) Plateau. Although it was long classified as a small species of ground jay (Podoces), two previous anatomical studies cast doubt on its assignment to the Corvidae (crows and jays). We studied the evolutionary relationships of Pseudopodoces using three independent datasets drawn from comparative osteology, the nuclear c-myc gene, and the mitochondrial cytochrome b gene. All three datasets agree on the placement of Pseudopodoces in the family Paridae (tits and chickadees). The cytochrome b data further suggest that Pseudopodoces may be closest to the Great Tit Parus major species group. Pseudopodoces is the only species of parid whose distribution is limited to treeless terrain. Its evolutionary relationships were long obscured by adaptations to open habitat, including pale, cryptic plumage; a long, decurved bill for probing in crevices among rocks or in the ground; and long legs for terrestrial locomotion. Despite these accommodations to a novel adaptive zone, its evolutionary affinity with the Paridae is clearly expressed in comparative osteology and genetics, and is supported by its habit of nesting in cavities.
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| 15. |
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| 16. |
- Korsgren, Magnus, et al.
(författare)
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Role of macrophage migration inhibitory factor (MIF) in allergic and endotoxin-induced airway inflammation in mice
- 2000
-
Ingår i: Mediators of Inflammation. - : Hindawi Limited. - 0962-9351 .- 1466-1861. ; 9:1, s. 15-23
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Tidskriftsartikel (refereegranskat)abstract
- Macrophage migration inhibitory factor (MIF) has recently been forwarded as a critical regulator of inflammatory conditions, and it has been hypothesized that MIF may have a role in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). Hence, we examined effects of MIF immunoneutralization on the development of allergen-induced eosinophilic inflammation as well as on lipopolysaccharide (LPS)-induced neutrophilic inflammation in lungs of mice. Anti-MIF serum validated with respect to MIF neutralizing capacity or normal rabbit serum (NRS) was administered i.p. repeatedly during allergen aerosol exposure of ovalbumin (OVA)-immunized mice in an established model of allergic asthma, or once before instillation of a minimal dose of LPS into the airways of mice, a tentative model of COPD. Anti-MIF treatment did not affect the induced lung tissue eosinophilia or the cellular composition of bronchoalveolar lavage fluid (BALF) in the asthma model. Likewise, anti-MIF treatment did not affect the LPS-induced neutrophilia in lung tissue, BALF, or blood, nor did it reduce BALF levels of tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-1alpha (MIP-1alpha). The present data suggest that MIF is not critically important for allergen-induced eosinophilic, and LPS-induced neutrophilic responses in lungs of mice. These findings do not support a role of MIF inhibition in the treatment of inflammatory respiratory diseases.
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| 17. |
- Kvien, TK, et al.
(författare)
-
Long term efficacy and safety of cyclosporin versus parenteral old in early rheumatoid arthritis: a three year study of radiographic progression, renal function, and arterial hypertension
- 2002
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 61:6, s. 511-516
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare the three year safety and efficacy of cyclosporin and parenteral gold in the treatment of early, active, severe rheumatoid arthritis (RA), and to study the reversibility of cyclosporin associated renal dysfunction in patients who discontinued cyclosporin treatment. Methods: The patients continued to receive cyclosporin or parenteral gold in an 18 month open extension to an 18 month randomised, parallel group study. The main efficacy variable was blinded evaluation of radiographic progression of joint damage, Safety variables included serum creatinine, calculated creatinine clearance, and blood pressure. Results: Radiographic progression during follow up was similar in both groups. About 60% of the patients in the intention to treat groups (n=272) and about half of the patients in the completer groups (n=114) had definite radiographic progression in joint damage (increases >6 in the Larsen-Dale score), and about one in three also had substantial progression (>18 increase in Larsen-Dale score). Both systolic and diastolic blood pressure were significantly increased in the cyclosporin group compared with the gold group, and 12/139 (9%) versus 3/139 (2%) (p=0.03) had notably raised blood pressure. The mean serum creatinine increased by 28% at the treatment end point in the cyclosporin group as compared with 7% in the gold group, The mean calculated creatinine clearance was reduced by 16% and increased by 1% in the cyclosporin and gold groups, respectively, at the end of the study. At the final follow up visit after discontinuation of cyclosporin (at least three months after treatment was stopped) the mean serum creatinine was increased by 15% and creatinine clearance reduced by 16%. Sustained increases in serum creatinine at this post-treatment end point were mostly seen in patients with a raised serum creatinine during treatment of at least 50%. Conclusion: Three year changes in radiographic damage during cyclosporin and parenteral gold were similar in patients with early, active RA. Abnormal renal function and raised blood pressure were often seen in the cyclosporin treated patients.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Nielsen, Michael L., et al.
(författare)
-
Physicochemical properties determining the detection probability of tryptic peptides in Fourier transform mass spectrometry. A correlation study
- 2004
-
Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 76:19, s. 5872-5877
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Tidskriftsartikel (refereegranskat)abstract
- Sequence verification and mapping of posttranslational modifications require nearly 100% sequence coverage in the "bottom-up" protein analysis. Even in favorable cases, routine liquid chromatography-mass spectrometry detects from protein digests peptides covering 50-90% of the sequence. Here we investigated the reasons for limited peptide detection, considering various physicochemical aspects of peptide behavior in liquid chromatography-Fourier transform mass spectrometry (LC-FTMS). No overall correlation was found between the detection probability and peptide mass. In agreement with literature data, the signal increased with peptide hydrophobicity. Surprisingly, the pI values exhibited an opposite trend, with more acidic tryptic peptides detected with higher probability. A mixture of synthesized peptides of similar masses confirmed the hydrophobicity dependence but showed strong positive correlation between pI and signal response. An explanation of this paradoxal behavior was found through the observation that more acidic tryptic peptide lengths tend to be longer. Longer peptides tend to acquire higher average charge state in positive mode electrospray ionization than more basic but shorter counterparts. The induced-current detection in FTMS favors ions in higher charge states, thus providing the observed pI-FTMS signal anticorrelation.
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| 23. |
- Perris, C, et al.
(författare)
-
Assessment of dysfunctional working models of self and others in schizophrenic patients : a summary of data collected in nine nations. International Research Group.
- 2000
-
Ingår i: Acta Psychiatrica Scandinavica. - 0001-690X .- 1600-0447. ; 102:5, s. 336-41
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the cross-cultural feasibility of a new scale for assessing dysfunctional working models of self and others, and to evaluate its discriminative power.METHOD: Schizophrenic patients (N=351), non-psychotic patients (N= 86) and non-clinical subjects (N= 511) collected in 10 centres completed the DWM-S. Current psychopathology was assessed by means of the BPRS.RESULTS: Alpha coefficients were high in all samples. Mean scores on the DWM-S appeared to be comparable in all countries, suggesting cross-national generalizability. No significant correlation was found with sex, age, levels of psychopathology and duration of illness. Discriminant analyses showed that more than 70% of the schizophrenic patients are correctly classified.CONCLUSION: The DWM-S is an easily administered self-report instrument which allows to pinpoint internal dysfunctional working models of self and others in various types of patients. It is a useful tool for case conceptualization, especially when psychotherapeutic interventions are part of the treatment programme.
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| 24. |
- Persson, Camilla, et al.
(författare)
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Site-selective regulation of platelet-derived growth factor beta receptor tyrosine phosphorylation by T-cell protein tyrosine phosphatase
- 2004
-
Ingår i: Molecular and Cellular Biology. - 0270-7306 .- 1098-5549. ; 24:5, s. 2190-2201
-
Tidskriftsartikel (refereegranskat)abstract
- The platelet-derived growth factor (PDGF) beta receptor mediates mitogenic and chemotactic signals. Like other tyrosine kinase receptors, the PDGF beta receptor is negatively regulated by protein tyrosine phosphatases (PTPs). To explore whether T-cell PTP (TC-PTP) negatively regulates the PDGF beta receptor, we compared PDGF beta receptor tyrosine phosphorylation in wild-type and TC-PTP knockout (ko) mouse embryos. PDGF beta receptors were hyperphosphorylated in TC-PTP ko embryos. Fivefold-higher ligand-induced receptor phosphorylation was observed in TC-PTP ko mouse embryo fibroblasts (MEFs) as well. Reexpression of TC-PTP partly abolished this difference. As determined with site-specific phosphotyrosine antibodies, the extent of hyperphosphorylation varied among different autophosphorylation sites. The phospholipase Cgamma1 binding site Y1021, previously implicated in chemotaxis, displayed the largest increase in phosphorylation. The increase in Y1021 phosphorylation was accompanied by increased phospholipase Cgamma1 activity and migratory hyperresponsiveness to PDGF. PDGF beta receptor tyrosine phosphorylation in PTP-1B ko MEFs but not in PTPepsilon ko MEFs was also higher than that in control cells. This increase occurred with a site distribution different from that seen after TC-PTP depletion. PDGF-induced migration was not increased in PTP-1B ko cells. In summary, our findings identify TC-PTP as a previously unrecognized negative regulator of PDGF beta receptor signaling and support the general notion that PTPs display site selectivity in their action on tyrosine kinase receptors.
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| 25. |
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| 26. |
- Polívka, Tomáš, et al.
(författare)
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Direct observation of the S1 level of the carotenoid spheroidene using near-infrared femtosecond spectroscopy
- 2001
-
Ingår i: Ultrafast Phenomena XII. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 9783642625121 - 9783642565465 ; 66, s. 668-670
-
Bokkapitel (refereegranskat)abstract
- In this work, we have determined the energy of the S1 state of the carotenoid spheroidene. The energy of this state is 13,400 ± 90 cm-1 at both 293 K and 186 K, showing that there is no temperature-induced shift of the S1 level. A discrepancy of about 800 cm-1 between the S1 energy determined here and that obtained from previous fluorescence and resonance Raman measurements is explained in terms of the different conformational species co-existing in the S1 excited state.
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| 27. |
- Polívka, Tornáš, et al.
(författare)
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Near-infrared time-resolved study of the S-1 state dynamics of the carotenoid spheroidene
- 2001
-
Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 105:5, s. 1072-1080
-
Tidskriftsartikel (refereegranskat)abstract
- Using a novel experimental approach based on near-infrared femtosecond absorption spectroscopy, we have determined the energy of the S-1 state of the carotenoid spheroidene. The energy of this state is 13 400 +/- 90 cm(-1) at both 293 and 186 K, showing that there is no temperature-induced shift of the S-1 level. A discrepancy of about 800 cm(-1) between the S-1 energy determined here and that obtained from previous fluorescence and resonance Raman measurements is explained in terms of the different conformational species coexisting in the S-1 excited state. Measurements of kinetics in the near-infrared region revealed that at least three relaxation processes take place after excitation of spheroidene into its S-2 state. Ultrafast S-2 --> S-1 internal conversion occurs within the first 300 fs, followed by vibrational cooling in the SI state, which occurs on a time scale of similar to 700 fs. The S-1 lifetime is 8 ps at 293 K, in good agreement with previous measurements of the S-1 --> S-N transition. A somewhat longer S-1 lifetime of 9.5 ps is observed at 186 K.
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| 28. |
- Schäfer, Karsten, et al.
(författare)
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X-ray structures of the maltose-maltodextrin binding protein of the thermoacidophilic bacterium Alicyclobacillus acidocaldarius provide insight into acid stability of proteins
- 2004
-
Ingår i: Journal of Molecular Cell Biology. - : Elsevier BV. - 1674-2788 .- 1759-4685 .- 0022-2836. ; 335:1, s. 261-274
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Tidskriftsartikel (refereegranskat)abstract
- Maltose-binding proteins act as primary receptors in bacterial transport and chemotaxis systems. We report here crystal structures of the thermoacidostable maltose-binding protein from Alicyclobacillus acidocaldarius, and explore its modes of binding to maltose and maltotriose. Further, comparison with the structures of related proteins from Escherichia coli (a mesophile), and two hyperthermophiles (Pyrococcus furiosus and Thermococcus litoralis) allows an investigation of the basis of thermo- and acidostability in this family of proteins.The thermoacidophilic protein has fewer charged residues than the other three structures, which is compensated by an increase in the number of polar residues. Although the content of acidic and basic residues is approximately equal, more basic residues are exposed on its surface whereas most acidic residues are buried in the interior. As a consequence, this protein has a highly positive surface charge. Fewer salt bridges are buried than in the other MBP structures, but the number exposed on its surface does not appear to be unusual. These features appear to be correlated with the acidostability of the A. acidocaldarius protein rather than its thermostability. An analysis of cavities within the proteins shows that the extremophile proteins are more closely packed than the mesophilic one. Proline content is slightly higher in the hyperthermophiles and thermoacidophiles than in mesophiles, and this amino acid is more common at the second position of beta-turns, properties that are also probably related to thermostability. Secondary structural content does not vary greatly in the different structures, and so is not a contributing factor.
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| 29. |
- Sharov, Andrei A, et al.
(författare)
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Noggin overexpression inhibits eyelid opening by altering epidermal apoptosis and differentiation.
- 2003
-
Ingår i: The EMBO journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 22:12, s. 2992-3003
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Tidskriftsartikel (refereegranskat)abstract
- Contact of developing sensory organs with the external environment is established via the formation of openings in the skin. During eye development, eyelids first grow, fuse and finally reopen, thus providing access for visual information to the retina. Here, we show that eyelid opening is strongly inhibited in transgenic mice overexpressing the bone morphogenetic protein (BMP) antagonist noggin from the keratin 5 (K5) promoter in the epidermis. In wild-type mice, enhanced expression of the kinase-inactive form of BMPR-IB mediated by an adenovirus vector also inhibits eyelid opening. Noggin overexpression leads to reduction of apoptosis and retardation of cell differentiation in the eyelid epithelium, which is associated with downregulation of expression of the apoptotic receptors (Fas, p55 kDa TNFR), Id3 protein and keratinocyte differentiation markers (loricrin, involucrin). BMP-4, but not EGF or TGF-alpha, accelerates opening of the eyelid explants isolated from K5-Noggin transgenic mice when cultured ex vivo. These data suggest that the BMP signaling pathway plays an important role in regulation of genetic programs of eyelid opening and skin remodeling during the final steps of eye morphogenesis.
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| 30. |
- Sjöberg, Rickard L, et al.
(författare)
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Limited disclosure of sexual abuse in children whose experiences were documented by videotape.
- 2002
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 159:2
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The authors describe obstacles to children's disclosure of their sexual abuse experiences.METHOD: Ten children's descriptions of 102 incidents of sexual abuse and the process of disclosing these incidents during police interviews were studied. Children's self-reports of the abuse were compared to videotapes of the incidents made by the lone perpetrator.RESULTS: There was a significant tendency among the children to deny or belittle their experiences. Some children simply did not want to disclose their experiences, some had difficulties remembering them, and one child lacked adequate concepts to understand and describe them.CONCLUSIONS: Failure by children to disclose their experiences of sexual abuse might have diverse explanations. Professionals will most likely never be able to identify all cases of sexual abuse on the basis of children's narratives.
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| 31. |
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| 32. |
- Wolfraim, Lawrence A, et al.
(författare)
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Loss of Smad3 in acute T-cell lymphoblastic leukemia
- 2004
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 351:6, s. 552-559
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The receptors for transforming growth factor β (TGF-β) and their signaling intermediates make up an important tumor-suppressor pathway. The role of one of these intermediates - Smad3 - in the pathogenesis of lymphoid neoplasia is unknown. METHODS: We measured Smad3 messenger RNA (mRNA) and protein in leukemia cells obtained at diagnosis from 19 children with acute leukemia, including 10 with T-cell acute lymphoblastic leukemia (ALL), 7 with pre-B-cell ALL, and 2 with acute nonlymphoblastic leukemia (ANLL). All nine exons of the SMAD3 gene (MADH3) were sequenced. Mice in which one or both alleles of Smad3 were inactivated were used to evaluate the role of Smad3 in the response of normal T cells to TGF-β and in the susceptibility to spontaneous leukemogenesis in mice in which both alleles of the tumor suppressor p27Kip1 were deleted. RESULTS: Smad3 protein was absent in T-cell ALL but present in pre-B-cell ALL and ANLL. No mutations were found in the MADH3 gene in T-cell ALL, and Smad3 mRNA was present in T-cell ALL and normal T cells at similar levels. In mice, the loss of one allele for Smad3 impairs the inhibitory effect of TGF-β on the proliferation of normal T cells and works in tandem with the homozygous inactivation of p27Kip1 to promote T-cell leukemogenesis. CONCLUSIONS: Loss of Smad3 protein is a specific feature of pediatric T-cell ALL. A reduction in Smad3 expression and the loss of p27Kip1 work synergistically to promote T-cell leukemogenesis in mice.
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