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- Feroci, M., et al.
(författare)
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The Large Observatory for X-ray Timing (LOFT)
- 2012
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Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 34:2, s. 415-444
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Tidskriftsartikel (refereegranskat)abstract
- High-time-resolution X-ray observations of compact objects provide direct access to strong-field gravity, to the equation of state of ultradense matter and to black hole masses and spins. A 10 m(2)-class instrument in combination with good spectral resolution is required to exploit the relevant diagnostics and answer two of the fundamental questions of the European Space Agency (ESA) Cosmic Vision Theme "Matter under extreme conditions", namely: does matter orbiting close to the event horizon follow the predictions of general relativity? What is the equation of state of matter in neutron stars? The Large Observatory For X-ray Timing (LOFT), selected by ESA as one of the four Cosmic Vision M3 candidate missions to undergo an assessment phase, will revolutionise the study of collapsed objects in our galaxy and of the brightest supermassive black holes in active galactic nuclei. Thanks to an innovative design and the development of large-area monolithic silicon drift detectors, the Large Area Detector (LAD) on board LOFT will achieve an effective area of similar to 12 m(2) (more than an order of magnitude larger than any spaceborne predecessor) in the 2-30 keV range (up to 50 keV in expanded mode), yet still fits a conventional platform and small/medium-class launcher. With this large area and a spectral resolution of < 260 eV, LOFT will yield unprecedented information on strongly curved spacetimes and matter under extreme conditions of pressure and magnetic field strength.
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| 5. |
- Berglund, Jonas, et al.
(författare)
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Novel origins of copy number variation in the dog genome
- 2012
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X .- 1474-7596. ; 13:8, s. R73-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Copy number variants (CNVs) account for substantial variation between genomes and are a major source of normal and pathogenic phenotypic differences. The dog is an ideal model to investigate mutational mechanisms that generate CNVs as its genome lacks a functional ortholog of the PRDM9 gene implicated in recombination and CNV formation in humans. Here we comprehensively assay CNVs using high-density array comparative genomic hybridization in 50 dogs from 17 dog breeds and 3 gray wolves. RESULTS: We use a stringent new method to identify a total of 430 high-confidence CNV loci, which range in size from 9 kb to 1.6 Mb and span 26.4 Mb, or 1.08%, of the assayed dog genome, overlapping 413 annotated genes. Of CNVs observed in each breed, 98% are also observed in multiple breeds. CNVs predicted to disrupt gene function are significantly less common than expected by chance. We identify a significant overrepresentation of peaks of GC content, previously shown to be enriched in dog recombination hotspots, in the vicinity of CNV breakpoints. CONCLUSIONS: A number of the CNVs identified by this study are candidates for generating breed-specific phenotypes. Purifying selection seems to be a major factor shaping structural variation in the dog genome, suggesting that many CNVs are deleterious. Localized peaks of GC content appear to be novel sites of CNV formation in the dog genome by non-allelic homologous recombination, potentially activated by the loss of PRDM9. These sequence features may have driven genome instability and chromosomal rearrangements throughout canid evolution.
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| 7. |
- Hellevuo, Heidi, et al.
(författare)
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Deeper chest compression - More complications for cardiac arrest patients?
- 2013
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 84:6, s. 760-765
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Tidskriftsartikel (refereegranskat)abstract
- Aim of the study: Sternal and rib fractures are frequent complications caused by chest compressions during cardiopulmonary resuscitation (CPR). This study aimed to investigate the potential association of CPR-related thoracic and abdominal injuries and compression depth measured with an accelerometer. Methods: We analysed the autopsy records, CT scans or chest radiographs of 170 adult patients, suffering in-hospital cardiac arrest at the Tampere University Hospital during the period 2009-2011 to investigate possible association of chest compressions and iatrogenic injuries. The quality of manual compressions during CPR was recorded on a Philips, HeartStart MRx Q-CPR (TM)-defibrillator. Results: Patients were 110 males and 60 females. Injuries were found in 36% of male and 23% of female patients. Among male patients CPR-related injuries were associated with deeper mean - and peak compression depths (p < 0.05). No such association was observed in women. The frequency of injuries in mean compression depth categories <5, 5-6 and >6 cm, was 28%, 27% and 49% (p = 0.06). Of all patients 27% sustained rib fractures, 11% sternal fracture and eight patients had haematomas/ruptures in the myocardium. In addition, we observed one laceration of the stomach without bleeding, one ruptured spleen, one mediastinal haemorrhage and two pneumothoraxes. Conclusion: The number of iatrogenic injuries in male patients was associated with chest compressions during cardiopulmonary resuscitation increased as the measured compression depth exceeded 6 cm. While there is an increased risk of complications with deeper compressions it is important to realize that the injuries were by and large not fatal.
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| 14. |
- Koski, Timo, et al.
(författare)
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Clustering by Adaptive Local Search with multiple search operators
- 2000
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Ingår i: Pattern Analysis and Applications. - : Springer Science and Business Media LLC. - 1433-7541 .- 1433-755X. ; 3:4, s. 348-357
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Tidskriftsartikel (refereegranskat)abstract
- Local Search (LS) has proven to be an efficient optimisation technique in clustering applications and in the minimisation of stochastic complexity of a data set. In the present paper, we propose two ways of organising LS in these contexts, the Multi-operator Local Search (MOLS) and the Adaptive Multi-Operator Local Search (AMOLS), and compare their performance to single operator (random swap) LS method and repeated GLA (Generalised Lloyd Algorithm). Both of the proposed methods use several different LS operators to solve the problem. MOLS applies the operators cyclically in the same order, whereas AMOLS adapts itself to favour the operators which manage to improve the result more frequently. We use a large database of binary vectors representing strains of bacteria belonging to the family Enterobacteriaceae and a binary image as our test materials. The new techniques turn out to be very promising in these tests.
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| 18. |
- Marttila, S, et al.
(författare)
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Number of sons contributes to ageing-associated inflammation
- 2015
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 8631-
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Tidskriftsartikel (refereegranskat)abstract
- The rate of inflammation increases in elderly individuals, a phenomenon called inflammaging and is associated with degenerative diseases. However, the causes of inflammaging and the origin of the associated inflammatory mediators have remained enigmatic. We show herein that there is a positive correlation between the number of sons born and C-reactive protein concentrations in 90-year-old women. This association is influenced by HLA genetics known to regulate the immune response against HY antigens.
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| 20. |
- Mirtti, Tuomas, et al.
(författare)
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Nuclear Stat5a/b predicts early recurrence and prostate cancer-specific death in patients treated by radical prostatectomy
- 2013
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Ingår i: Human Pathology. - : Elsevier BV. - 0046-8177 .- 1532-8392. ; 44:3, s. 310-319
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent need for reliable markers to identify patients whose prostate cancer (PCa) will recur after initial therapy and progress to lethal disease. Gleason score (GS) is considered the most accurate predictive marker for disease-specific mortality after primary treatment of localized PCa. Most PCas cluster into groups of GS 6 and 7 with considerable variation in the disease recurrence and disease-specific death. In preclinical PCa models, Stat5a/b promotes PCa growth and progression. Stat5a/b is critical for PCa cell viability in vitro and for tumor growth in vivo and promotes metastatic dissemination of cancer in nude mice. Here, we analyzed the predictive value of high nuclear Stat5a/b protein levels in 2 cohorts of PCas: Material I (n = 562) PCas treated by radical prostatectomy (RP), and Material II (n = 106) PCas treated by deferred palliative therapy. In intermediate GS PCas treated by radical prostatectomy, high levels of nuclear Stat5a/b predicted both early recurrence (univariable analysis; P < .0001, multivariable analysis; HR = 1.82, P = .017) and early PCa-specific death (univariable analysis; P = .028). In addition, high nuclear Stat5a/b predicted early disease recurrence in both univariable (P < .0001) and multivariable (HR = 1.61; P = .012) analysis in the entire cohort of patients treated by RP regardless of the GS. Patients treated by deferred palliative therapy, elevated nuclear Stat5a/b expression was associated with early PCa-specific death by univariable Cox regression analysis (HR. = 1.59; 95% CI = [1.04, 2.44]; P = .034). If confirmed in future prospective studies, nuclear Stat5a/b may become a useful independent predictive marker of recurrence of lethal PCa after RP for intermediate GS PCas. (c) 2013 Elsevier Inc. All rights reserved.
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| 21. |
- Nevalainen, H., et al.
(författare)
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Firing of coal and biomass and their mixtures in 50 kW and 12 MW circulating fluidized beds - Phenomenon study and comparison of scales
- 2007
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Ingår i: Fuel. - : Elsevier BV. - 0016-2361. ; 86:14, s. 2043-2051
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Tidskriftsartikel (refereegranskat)abstract
- The combustion dynamics of coal, wood chips and their mixture is investigated. Load change capability and the effect of the individual control variables, for example the mixture ratio of different fuels, on pilot-scale CFB boiler dynamics were also studied. Disturbances in fuel feeding cause fluctuations in the flue gas concentrations. Changes in the heating value are possible due to varying moisture content of the fuel. Both these disturbances affect the instantaneous firing rate in a boiler. Also the characteristics of the fuels have to be taken into consideration when designing boiler control systems. When co-firing two fuels with clearly distinct combustion characteristics, direct assumptions based on each fuel's characteristies cannot be made about combustion behaviour of their mixture. Combustion experiments with coal and wood chips and their co-firing were carried out in a pilot-scale CFB reactor (VTT) and a large-scale CFB boiler (Chalmers). A comparison of the combustion in the two different size reactors, provides information about scaling. The combustion responses due to changes in the fuel feeding of the two circulating fluidized beds are analyzed by a dynamic model. (c) 2007 Elsevier Ltd. All rights reserved.
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| 26. |
- Patel, Jayendra Z., et al.
(författare)
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Chiral 1,3,4-Oxadiazol-2-ones as Highly Selective FAAH Inhibitors
- 2013
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 56:21, s. 8484-8496
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, identification of chiral 1,3,4-oxadiazol-2-ones as potent and selective FAAH inhibitors has been described. The separated enantiomers showed clear differences in the potency and selectivity toward both FAAH and MAGL. Additionally, the importance of the chirality on the inhibitory activity and selectivity was proven by the simplification approach by removing a methyl group at the 3-position of the 1,3,4-oxadiazol-2-one ring. The most potent compound of the series, the S-enantiomer of 3-(1-(4-isobutylphenyl)ethyl)-5-methoxy-1,3,4-oxadiazol-2(3H)-one (JZP-327A, Si), inhibited human recombinant FAAH (hrFAAH) in the low nanomolar range (IC50 = 11 mu M), whereas its corresponding R-enantiomer 52 showed only moderate inhibition toward hrFAAH (IC50 = 0.24 mu M). In contrast to hrFAAH, R-enantiomer 52 was more potent in inhibiting the activity of hrMAGL compared to S-enantiomer 51 (IC50 = 4.0 mu M and 16% inhibition at 10 mu M, respectively). The FAAH selectivity of the compound Si over the supposed main off-targets, MAGL and COX, was found to be >900-fold. In addition, activity-based protein profiling (ABPP) indicated high selectivity over other serine hydrolases. Finally, the selected Senantiomers 51, 53, and 55 were shown to be tight binding, slowly reversible inhibitors of the hrFAAH.
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