| 1. |
- Hedenas, Henrik, et al.
(author)
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Changes Versus Homeostasis in Alpine and Sub-Alpine Vegetation Over Three Decades in the Sub-Arctic
- 2012
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In: Ambio. - : Springer Verlag (Germany). - 0044-7447 .- 1654-7209. ; 41, s. 187-196
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Journal article (peer-reviewed)abstract
- Plant species distributions are expected to shift and diversity is expected to decline as a result of global climate change, particularly in the Arctic where climate warming is amplified. We have recorded the changes in richness and abundance of vascular plants at Abisko, sub-Arctic Sweden, by re-sampling five studies consisting of seven datasets; one in the mountain birch forest and six at open sites. The oldest study was initiated in 1977–1979 and the latest in 1992. Total species number increased at all sites except for the birch forest site where richness decreased. We found no general pattern in how composition of vascular plants has changed over time. Three species, Calamagrostis lapponica, Carex vaginata and Salix reticulata, showed an overall increase in cover/frequency, while two Equisetum taxa decreased. Instead, we showed that the magnitude and direction of changes in species richness and composition differ among sites.
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| 2. |
- Ahlberg, Ernst, et al.
(author)
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Using conformal prediction to prioritize compound synthesis in drug discovery
- 2017
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In: Proceedings of Machine Learning Research. - Stockholm : Machine Learning Research. ; , s. 174-184
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Conference paper (peer-reviewed)abstract
- The choice of how much money and resources to spend to understand certain problems is of high interest in many areas. This work illustrates how computational models can be more tightly coupled with experiments to generate decision data at lower cost without reducing the quality of the decision. Several different strategies are explored to illustrate the trade off between lowering costs and quality in decisions.AUC is used as a performance metric and the number of objects that can be learnt from is constrained. Some of the strategies described reach AUC values over 0.9 and outperforms strategies that are more random. The strategies that use conformal predictor p-values show varying results, although some are top performing.The application studied is taken from the drug discovery process. In the early stages of this process compounds, that potentially could become marketed drugs, are being routinely tested in experimental assays to understand the distribution and interactions in humans.
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| 3. |
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| 4. |
- Atar, Dan, et al.
(author)
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Rationale and Design of the 'MITOCARE' Study: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of TRO40303 for the Reduction of Reperfusion Injury in Patients Undergoing Percutaneous Coronary Intervention for Acute Myocardial Infarction
- 2012
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In: Cardiology. - : S. Karger AG. - 1421-9751 .- 0008-6312. ; 123:4, s. 201-207
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Journal article (peer-reviewed)abstract
- Treatment of acute ST-elevation myocardial infarction (STEMI) by reperfusion using percutaneous coronary intervention (PCI) or thrombolysis has provided clinical benefits; however, it also induces considerable cell death. This process is called reperfusion injury. The continuing high rates of mortality and heart failure after acute myocardial infarction (AMI) emphasize the need for improved strategies to limit reperfusion injury and improve clinical outcomes. The objective of this study is to assess safety and efficacy of TRO40303 in limiting reperfusion injury in patients treated for STEMI. TRO40303 targets the mitochondrial permeability transition pore, a promising target for the prevention of reperfusion injury. This multicenter, double-blind study will randomize patients with STEMI to TRO40303 or placebo administered just before balloon inflation or thromboaspiration during PCI. The primary outcome measure will be reduction in infarct size (assessed as plasma creatine kinase and troponin I area under the curve over 3 days). The main secondary endpoint will be infarct size normalized to the myocardium at risk (expressed by the myocardial salvage index assessed by cardiac magnetic resonance). The study is being financed under an EU-FP7 grant and conducted under the auspices of the MITOCARE research consortium, which includes experts from clinical and basic research centers, as well as commercial enterprises, throughout Europe. Results from this study will contribute to a better understanding of the complex pathophysiology underlying myocardial injury after STEMI. The present paper describes the rationale, design and the methods of the trial. Copyright (c) 2012 S. Karger AG, Basel
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| 5. |
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| 6. |
- Carlsson, Karin, et al.
(author)
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Effects on the conformation of FVIIa by sTF and Ca(2+) binding : Studies of fluorescence resonance energy transfer and quenching
- 2011
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In: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier. - 0006-291X .- 1090-2104. ; 413:4, s. 545-549
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Journal article (peer-reviewed)abstract
- The apparent length of FVIIa in buffer solution was estimated by a FRET analysis. Two fluorescent probes, fluorescein linked to an inhibitor (FPR-chloromethyl ketone) and a rhodamine derivative (tetramethylrhodamine-5-maleimide), were covalently attached to FVIIa. The binding site of fluorescein was in the PD whereas rhodamine was positioned in the Gla domain, thus allowing a length measure over approximately the whole extension of the protein. From the FRET measurements the distances between the two probes were determined to 61.4 for free FVIIa and 65.5 Å for FVIIa bound to the soluble TF (sTF). Thus, the apparent distance from the FRET analysis was shown to increase with 4 Å upon formation of a complex with sTF in solution. However, by considering how protein dynamics, based on recently published molecular dynamics simulations of FVIIa and sTF:FVIIa (Ohkubo et al., 2010 J. Thromb. Haemost. 8, 1044-1053), can influence the apparent fluorescence signal our calculations indicated that the global average conformation of active-site inhibited FVIIa is nearly unaltered upon ligation to sTF. Moreover, it is known that Ca2+ binding leads to activation of FVIIa, and we have for the first time demonstrated conformational changes in the environment of the active site upon Ca2+ binding by direct measurements, previously suggested based on indirect measurements (Persson & Petersen, 1995 Eur. J. Biochem. 234, 293-300). Interestingly, this Ca2+-induced conformational change can be noted even in the presence of an inhibitor. By forming the sTF:FVIIa complex the conformational change of the active site is further developed, leading to a more inaccessible active-site located probe.
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| 7. |
- Carlsson, Lars, et al.
(author)
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Modifications to p-Values of conformal predictors
- 2015
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In: Statistical learning and data sciences. - Cham : Springer. - 9783319170909 - 9783319170916 ; , s. 251-259
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Conference paper (peer-reviewed)abstract
- The original definition of a p-value in a conformal predictor can sometimes lead to too conservative prediction regions when the number of training or calibration examples is small. The situation can be improved by using a modification to define an approximate p-value. Two modified p-values are presented that converges to the original p-value as the number of training or calibration examples goes to infinity. Numerical experiments empirically support the use of a p-value we call the interpolated p-value for conformal prediction. The interpolated p-value seems to be producing prediction sets that have an error rate which corresponds well to the prescribed significance level.
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| 8. |
- Carlsson, Per, et al.
(author)
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High-speed imaging of biomass particles heated with a laser
- 2013
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In: Journal of Analytical and Applied Pyrolysis. - : Elsevier BV. - 0165-2370 .- 1873-250X. ; 103, s. 278-286
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Journal article (peer-reviewed)abstract
- In this work two types of lignocellulosic biomass particles, European spruce and American hardwood (particle sizes from 100 μm to 500 μm) were pyrolysed with a continuous wave 2 W Nd:YAG laser. Simultaneously a high-speed camera was used to capture the behavior of the biomass particle as it was heated for about 0.1 s. Cover glasses were used as a sample holder which allowed for light microscope studies after the heating. Since the cover glasses are not initially heated by the laser, vapors from the biomass particle are quenched on the glass within about 1 particle diameter from the initial particle. Image processing was used to track the contour of the biomass particle and the enclosed area of the contour was calculated for each frame.The main observations are: There is a significant difference between how much surface energy is needed to pyrolyses the spruce (about 75% more) compared to the hardwood. The oil-like substance which appeared on the glass during the experiment is solid at room temperature and shows different levels of transparency. A fraction of this substance is water soluble. A brownish coat is seen on the unreacted biomass. The biomass showed insignificant swelling as it was heated. The biomass particle appears to melt and boil at the front that is formed between the laser beam and the biomass particle. The part of the particle that is not subjected to the laser beam seems to be unaffected.
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| 9. |
- Carlsson, Per-Inge, 1959-, et al.
(author)
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GJB2 (Connexin 26) gene mutations among hearing-impaired persons in a Swedish cohort
- 2012
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In: Acta Oto-Laryngologica. - London, United Kingdom : Informa Healthcare. - 0001-6489 .- 1651-2251. ; 132:12, s. 1301-1305
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Journal article (peer-reviewed)abstract
- Conclusion: The most common mutation in the Swedish population was Connexin 26 (C×26) 35delG, which indicates that the percentage of Swedish persons with C×26 mutations and polymorphisms in the GJB2 gene among non-syndromic hearing-impaired (HI) persons is comparable to the rest of Europe. The results strongly support a Swedish policy to offer all children with diagnosed hearing impairment genetic tests for the C×26 35delG mutation.Objectives: The aim of the present study was to search for mutations in the GBJ2 gene among Swedish persons with non-syndromic hearing impairment to further clarify how common these mutations are in Sweden, one of the northernmost countries in Europe.Methods: Seventy-nine patients with non-syndromic hearing impairment participated in the study. For 87% of the participants, a pure tone audiogram showed a severe or profound hearing impairment. Dried blood spots on filter paper, taken at 3-5 days of age in the Swedish nationwide neonatal screening programme for congenital disorders and saved in a biobank, were used for the molecular genetic analyses.Results: The total number of subjects with one or two pathologic mutations or a mutation of unknown consequence found in the GJB2 gene was 28 of 79 (35%). Nineteen (19) persons (24%) were homozygotes for the 35delG mutation.
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| 10. |
- Engblom, Henrik, et al.
(author)
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Peak oxygen uptake in relation to total heart volume discriminates heart failure patients from healthy volunteers and athletes
- 2010
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In: Journal of Cardiovascular Magnetic Resonance. - 1097-6647 .- 1532-429X. ; 12
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Journal article (peer-reviewed)abstract
- Background: An early sign of heart failure (HF) is a decreased cardiac reserve or inability to adequately increase cardiac output during exercise. Under normal circumstances maximal cardiac output is closely related to peak oxygen uptake (VO(2)peak) which has previously been shown to be closely related to total heart volume (THV). Thus, the aim of this study was to derive a VO(2)peak/THV ratio and to test the hypothesis that this ratio can be used to distinguish patients with HF from healthy volunteers and endurance athletes. Thirty-one patients with HF of different etiologies were retrospectively included and 131 control subjects (60 healthy volunteers and 71 athletes) were prospectively enrolled. Peak oxygen uptake was determined by maximal exercise test and THV was determined by cardiovascular magnetic resonance. The VO(2)peak/THV ratio was then derived and tested. Results: Peak oxygen uptake was strongly correlated to THV (r(2) = 0.74, p < 0.001) in the control subjects, but not for the patients (r(2) = 0.0002, p = 0.95). The VO(2)peak/THV ratio differed significantly between control subjects and patients, even in patients with normal ejection fraction and after normalizing for hemoglobin levels (p < 0.001). In a multivariate analysis the VO(2)peak/THV ratio was the only independent predictor of presence of HF (p < 0.001). Conclusions: The VO(2)peak/THV ratio can be used to distinguish patients with clinically diagnosed HF from healthy volunteers and athletes, even in patients with preserved systolic left ventricular function and after normalizing for hemoglobin levels.
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