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- Dahl, F, et al.
(författare)
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Imaging single DNA molecules for high precision NIPT
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 4549-
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Tidskriftsartikel (refereegranskat)abstract
- Cell-free DNA analysis is becoming adopted for first line aneuploidy screening, however for most healthcare programs, cost and workflow complexity is limiting adoption of the test. We report a novel cost effective method, the Vanadis NIPT assay, designed for high precision digitally-enabled measurement of chromosomal aneuploidies in maternal plasma. Reducing NIPT assay complexity is achieved by using novel molecular probe technology that specifically label target chromosomes combined with a new readout format using a nanofilter to enrich single molecules for imaging and counting without DNA amplification, microarrays or sequencing. The primary objective of this study was to assess the Vanadis NIPT assay with respect to analytical precision and clinical feasibility. Analysis of reference DNA samples indicate that samples which are challenging to analyze with low fetal-fraction can be readily detected with a limit of detection determined at <2% fetal-fraction. In total of 286 clinical samples were analysed and 30 out of 30 pregnancies affected by trisomy 21 were classified correctly. This method has the potential to make cost effective NIPT more widely available with more women benefiting from superior detection and false positive rates.
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- Nilsson, K O, et al.
(författare)
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Improved final height in girls with Turner's syndrome treated with growth hormone and oxandrolone.
- 1996
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 81, s. 635-
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Tidskriftsartikel (refereegranskat)abstract
- The spontaneous growth process in Turner's syndrome is characterized by a progressive decline in height velocity during childhood and no pubertal growth spurt. Therefore, therapy aimed at improving height during childhood as well as increasing final height is desirable for most girls with Turner's syndrome. Forty-five girls with Turner's syndrome, 9-16 yr of age (mean age, 12.2 yr), were allocated to three study groups. Group 1 (n = 13) was initially treated with oxandrolone alone; after 1 yr of treatment, GH without (group 1a; n = 6) or with (group 1b; n = 7) ethinyl estradiol was added. Group 2 (n = 17) was treated with GH plus oxandrolone. Group 3 (n = 15) was treated with GH, oxandrolone, and ethinyl estradiol. The dosage were: GH, 0.1 IU/kg.day; oxandrolone, 0.05 mg/kg.day; and ethinyl estradiol, 100 ng/kg.day. A height of 150 cm or more was achieved in 61%, 75%, and 60% of the girls in groups 1, 2, and 3, respectively. The most impressive increase in height was seen in group 2. In this group the mean final height was 154.2 cm (SD = 6.6), which is equivalent to a mean net gain of 8.5 cm (SD = 4.6) over the projected final height. In group 3, in which ethinyl estradiol was included from the start of therapy, the initially good height velocity decelerated after 1-2 yr of treatment. Their mean final height was 151.1 (SD = 4.6) cm, equivalent to a mean net gain of 3.0 cm (SD = 3.8). A similar growth-decelerating effect of ethinyl estradiol was seen in group 1b. We conclude that in girls with Turner's syndrome who are older than 9 yr of age, treatment with GH in combination with oxandrolone results in significant growth acceleration, imitating that in normal puberty, leading to a more favorable height during childhood. This mode of treatment also results in a significantly increased final height, permitting a great number of the girls to attain a final height of more than 150 cm. However, early addition of estrogen decelerates the height velocity and reduces the gain in height.
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- Alm, Erik, 1980-, et al.
(författare)
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Vibrational overtone combination spectroscopy (VOCSY)—a new way of using IR and NIR data
- 2007
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 388:1, s. 179-188
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Tidskriftsartikel (refereegranskat)abstract
- This work explores a novel method for rearranging 1st order (one-way) infra-red (IR) and/or near infra-red (NIR) ordinary spectra into a representation suitable for multi-way modelling and analysis. The method is based on the fact that the fundamental IR absorption and the first, second, and consecutive overtones of NIR absorptions represent identical chemical information. It is therefore possible to rearrange these overtone regions of the vectors comprising an IR and NIR spectrum into a matrix where the fundamental, 1st, 2nd, and consecutive overtones of the spectrum are arranged as either rows or columns in a matrix, resulting in a true three-way tensor of data for several samples. This tensorization facilitates explorative analysis and modelling with multi-way methods, for example parallel factor analysis (PARAFAC), N-way partial least squares (N-PLS), and Tucker models. The vibrational overtone combination spectroscopy (VOCSY) arrangement is shown to benefit from the “order advantage”, producing more robust, stable, and interpretable models than, for example, the traditional PLS modelling method. The proposed method also opens the field of NIR for true peak decomposition—a feature unique to the method because the latent factors acquired using PARAFAC can represent pure spectral components whereas latent factors in principal component analysis (PCA) and PLS usually do not.
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- Andersson, S O, et al.
(författare)
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Prevalence of lower urinary tract symptoms in men aged 45-79 years : a population-based study of 40,000 Swedish men
- 2004
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Ingår i: BJU International. - Karolinska Inst, Natl Inst Environm Med, SE-17177 Stockholm, Sweden. Univ Hosp Orebro, Dept Urol, Orebro, Sweden. Univ Hosp Orebro, Ctr Assessment Med Technol, Orebro, Sweden. Vasteras Hosp, Dept Urol, Vasteras, Sweden. : WILEY. - 1464-4096 .- 1464-410X. ; 94:3, s. 327-331
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To estimate the age-specific prevalence and severity of lower urinary tract symptoms (LUTS) among Swedish men, the intercorrelations between different symptoms, and to assess quality of life and health-seeking behaviour among men with LUTS. SUBJECTS AND METHODS In 1997, an International Prostate Symptom Score (IPSS) questionnaire, together with other questions about lifestyle, was mailed to all men aged 45-79 years living in two counties in Sweden; the analyses included 39 928 men. RESULTS Overall, 18.5% and 4.8% of the men were moderately and severely symptomatic; the prevalence of at least one symptom was 83%. LUTS were strongly age-dependent, with 1.8% of severe symptoms among men aged 45-49 years and increasing to 9.7% among those 75-79 years old. Frequent urination was the most common symptom among men aged <70 years and nocturia among those aged >70 years. Symptoms like hesitancy, poor flow and intermittency were highly correlated with each other (Spearman coefficients 0.56-0.60). There was a high correlation between the IPSS and a poor score for quality of life resulting from the bothersomeness of LUTS (r = 0.70). Among symptomatic subjects, 36% reported a poor quality of life (fairly bad, very bad or terrible). Only 29% of symptomatic subjects (IPSS >7) reported that they had been diagnosed previously for their urinary problems, and only 11% received medication for that. CONCLUSION Although the prevalence of LUTS in Sweden is high, the percentage of men whose quality of life is substantially affected is much lower.
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- Curbis, F., et al.
(författare)
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Prospects for longitudinal phase-space measurements at the MAX IV linac
- 2014
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Ingår i: IPAC 2014 : Proceedings of the 5th International Particle Accelerator Conference - Proceedings of the 5th International Particle Accelerator Conference. - 9783954501328 ; , s. 3665-3667
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Konferensbidrag (refereegranskat)abstract
- Knowing the longitudinal phase space of an electron beam is one of the most important and crucial issues in short-pulses linacs. To achieve this task expensive and rather complicated setups (like transverse deflecting cavities) are usually implemented. The MAX IV linac is a 3GeV accelerator which will be used to inject into two rings and to drive a short pulse facility. Nevertheless, a more deep understanding of the beam quality would be useful especially in view of an upgrade as FEL driver. Another interesting aspect is to evaluate how the double-achromat bunch compressors are performing. We are studying how to implement off-phase acceleration: one part of the linac will be set at zero-crossing phase and the following transfer line could be used as energy spectrometer to retrieve the bunch profile. In the present configuration of the MAX IV linac this procedure will allow to check the bunch length after the first bunch compressor. Since it is work in progress, in this contribution we present a sketch of the measurement and the feasibility of the method will be explored by means of simulations.
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- Karlberg, O., et al.
(författare)
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Characterization of longitudinal wakefields in the MAX IV linac
- 2014
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Ingår i: IPAC 2014 : Proceedings of the 5th International Particle Accelerator Conference - Proceedings of the 5th International Particle Accelerator Conference. - 9783954501328 ; , s. 3050-3052
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Konferensbidrag (refereegranskat)abstract
- In the second part of 2014, the 3 GeV linac at the MAX IV laboratory will enter its commissioning stage. Equipped with two guns, the linac will act as a full energy injector for the two storage rings and at the same time provide high brightness pulses to a Short Pulse Facility (SPF). Compression in the linac is done in two double achromats with fixed R56 that relies upon the RF phase introduced energy chirp, which in this case is strongly enhanced by the longitudinal wakefields. Since the longitudinal wakefields play a major role in the compression and bunch shaping they need to be carefully investigated during the commissioning. In this proceeding we will discuss a measurement technique that will be used during commissioning to characterize the longitudinal wakefields in the MAX IV linac and their precise effects on e.g. the bunch shape and the energy spread. Predictions obtained from particle tracking will be presented.
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| 21. |
- Karlberg, O, et al.
(författare)
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The dual origin of the yeast mitochondrial proteome
- 2000
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Ingår i: YEAST. - : JOHN WILEY & SONS LTD. - 0749-503X. ; 17:3, s. 170-187
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Tidskriftsartikel (refereegranskat)abstract
- We propose a scheme for the origin of mitochondria based on phylogenetic reconstructions with more than 400 yeast nuclear genes that encode mitochondrial proteins. Half of the yeast mitochondrial proteins have no discernable bacterial homologues, while on
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| 23. |
- Klemedtsson, Leif, 1953, et al.
(författare)
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Bayesian calibration method used to elucidate carbon turnover in forest on drained organic soil
- 2008
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Ingår i: Biogeochemistry. - : Springer Science and Business Media LLC. - 0168-2563 .- 1573-515X. ; 89:1, s. 61-79
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Tidskriftsartikel (refereegranskat)abstract
- Depending on the balance between sink and source processes for C, drained organic forest soil ecosystems can be in balance or act as net sinks or sources of CO2 to the atmosphere. In order to study the effect of groundwater level and soil temperature on C-flux, the CoupModel was calibrated (climate data, groundwater levels, soil CO2 flux, net ecosystem fluxes of CO2-exchange, sensible heat flux and latent heat flux, forest production etc.) for a drained forest in Sweden. Bayesian calibration techniques were used to elucidate how different parameters and variables were interlinked in C-circulation. The calibrated model reproduced abiotic and biotic variables reasonably well except for root respiration, which was largely underestimated. Bayesian calibration reduced the uncertainties in the model and highlighted the fact that calibrations should be performed with a high number of parameters instead of specific parameter values.
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| 24. |
- Lindgren, Anders E. G., et al.
(författare)
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PARP Inhibitor with Selectivity Toward ADP-Ribosyltransferase ARTD3/PARP3
- 2013
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Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 8:8, s. 1698-1703
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Tidskriftsartikel (refereegranskat)abstract
- Inhibiting ADP-ribosyl transferases with PARP-inhibitors is considered a promising strategy for the treatment of many cancers and ischemia, but most of the cellular targets are poorly characterized. Here, we describe an inhibitor of ADP-ribosyltransferase-3/poly(ADP-ribose) polymerase-3 (ARTD3), a regulator of DNA repair and mitotic progression. In vitro profiling against 12, members of the enzyme family suggests selectivity for ARTD3, and crystal structures illustrate the molecular basis for inhibitor selectivity. The compound is active in cells, where it elicits ARTD3-specific effects at submicromolar concentration. Our results show that by targeting the nicotinamide binding site, selective inhibition can be achieved among the closest relatives of the validated clinical target, ADP-ribosyltransferase-1/poly(ADP-ribose) polymerase-1.
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