| 1. |
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| 2. |
- Danielsson, Christian, et al.
(författare)
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Exploration of human, rat, and rabbit embryonic cardiomyocytes suggests K-channel block as a common teratogenic mechanism
- 2013
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP): Policy B. - 0008-6363 .- 1755-3245. ; 97:1, s. 23-32
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Tidskriftsartikel (refereegranskat)abstract
- Several drugs blocking the rapidly activating potassium (K-r) channel cause malformations (including cardiac defects) and embryonic death in animal teratology studies. In humans, these drugs have an established risk for acquired long-QT syndrome and arrhythmia. Recently, associations between cardiac defects and spontaneous abortions have been reported for drugs widely used in pregnancy (e.g. antidepressants), with long-QT syndrome risk. To investigate whether a common embryonic adverse-effect mechanism exists in the human, rat, and rabbit embryos, we made a comparative study of embryonic cardiomyocytes from all three species. less thanbrgreater than less thanbrgreater thanPatch-clamp and quantitative-mRNA measurements of K-r and slowly activating K (K-s) channels were performed on human, rat, and rabbit primary cardiomyocytes and cardiac samples from different embryo-foetal stages. The K-r channel was present when the heart started to beat in all species, but was, in contrast to human and rabbit, lost in rats in late organogenesis. The specific K-r-channel blocker E-4031 prolonged the action potential in a species- and development-dependent fashion, consistent with the observed K-r-channel expression pattern and reported sensitive periods of developmental toxicity. E-4031 also increased the QT interval and induced 2:1 atrio-ventricular block in multi-electrode array electrographic recordings of rat embryos. The K-s channel was expressed in human and rat throughout the embryo-foetal period but not in rabbit. less thanbrgreater than less thanbrgreater thanThis first comparison of mRNA expression, potassium currents, and action-potential characteristics, with and without a specific K-r-channel blocker in human, rat, and rabbit embryos provides evidence of K-r-channel inhibition as a common mechanism for embryonic malformations and death.
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| 3. |
- Andersson, Sandra, et al.
(författare)
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The Transcriptomic and Proteomic Landscapes of Bone Marrow and Secondary Lymphoid Tissues
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12, s. e115911-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The sequencing of the human genome has opened doors for global gene expression profiling, and the immense amount of data will lay an important ground for future studies of normal and diseased tissues. The Human Protein Atlas project aims to systematically map the human gene and protein expression landscape in a multitude of normal healthy tissues as well as cancers, enabling the characterization of both housekeeping genes and genes that display a tissue-specific expression pattern. This article focuses on identifying and describing genes with an elevated expression in four lymphohematopoietic tissue types (bone marrow, lymph node, spleen and appendix), based on the Human Protein Atlas-strategy that combines high throughput transcriptomics with affinity-based proteomics. Results: An enriched or enhanced expression in one or more of the lymphohematopoietic tissues, compared to other tissue-types, was seen for 693 out of 20,050 genes, and the highest levels of expression were found in bone marrow for neutrophilic and erythrocytic genes. A majority of these genes were found to constitute well-characterized genes with known functions in lymphatic or hematopoietic cells, while others are not previously studied, as exemplified by C19ORF59. Conclusions: In this paper we present a strategy of combining next generation RNA-sequencing with in situ affinity-based proteomics in order to identify and describe new gene targets for further research on lymphatic or hematopoietic cells and tissues. The results constitute lists of genes with enriched or enhanced expression in the four lymphohematopoietic tissues, exemplified also on protein level with immunohistochemical images.
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| 4. |
- Anselm, Jonas, et al.
(författare)
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Bannlys alla politiska beslut som ger mer klimatutsläpp
- 2014
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Ingår i: Dagens Nyheter.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Torftig valdebatt. Dagspolitiken klarar inte att hantera ödesfrågan om klimatet, vilket oroar oss. Vi föreslår därför ett ”utsläppsmoratorium”: inga beslut får tas som ökar utsläppen av växthusgaser. Principen måste kopplas till mål om exempelvis förnybar energi och grön infrastruktur, skriver 23 forskare och debattörer.
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| 5. |
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| 6. |
- Bornefalk, Hans, et al.
(författare)
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Design considerations to overcome cross talk in a photon counting silicon strip detector for computed tomography
- 2010
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 621:1-3, s. 371-378
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Tidskriftsartikel (refereegranskat)abstract
- This article presents a Monte Carlo simulation of the detector energy response in the presence of pileup in a segmented silicon microstrip detector designed for high flux spectral computed tomography with sub-millimeter pixel size. Currents induced on the collection electrode of a pixel segment are explicitly modeled and signals emanating from events in neighboring pixels are superimposed together with electronic noise before the entire pulse train is processed by a model of the readout electronics to obtain the detector energy response function. The article shows how the lower threshold and the time constant of the electronic filters need to be set in order to minimize the detrimental influence of cross talk from neighboring pixel segments, an issue that is aggravated by the sub-millimeter pixel size and the proposed segmented detector design. (C) 2010 Elsevier B.V. All rights reserved.
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| 7. |
- Bornefalk, Hans, et al.
(författare)
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Effect of Temperature Variation on the Energy Response of a Photon Counting Silicon CT Detector
- 2013
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Ingår i: IEEE Transactions on Nuclear Science. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9499 .- 1558-1578. ; 60:2, s. 1442-1449
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Tidskriftsartikel (refereegranskat)abstract
- The effect of temperature variation on pulse height determination accuracy is determined for a photon counting multibin silicon detector developed for spectral CT. Theoretical predictions of the temperature coefficient of the gain and offset are similar to values derived from synchrotron radiation measurements in a temperature controlled environment. By means of statistical modeling, we conclude that temperature changes affect all channels equally and with separate effects on gain and threshold offset. The combined effect of a 1 degrees C temperature increase is to decrease the detected energy by 0.1 keV for events depositing 30 keV. For the electronic noise, no statistically significant temperature effect was discernible in the data set, although theory predicts a weak dependence. The method is applicable to all x-ray detectors operating in pulse mode.
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| 8. |
- Bornefalk, Hans, et al.
(författare)
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Image quality in photon counting-mode detector systems
- 2013
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Patent (populärvet., debatt m.m.)abstract
- The current invention applies to photon counting silicon x-ray detectors with energy discriminating capabilities and applications in x-ray imaging systems. The overall image quality produced by such a system is improved by the presented novel methods for optimally using the energy information in Compton events and making selective use of counts induced from charges collected in neighboring pixels. The pile-up problem during high-flux imaging regimes is reduced by a novel method for signal reset, which improves the count efficiency by reducing the risk of losing event due to signal pile-up in the read out electronics chain.
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| 9. |
- Bornefalk, Hans, et al.
(författare)
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Simulation study of an energy sensitive photon counting silicon strip detector for computed tomography : identifying strengths and weaknesses and developing work-arounds
- 2010
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Ingår i: MEDICAL IMAGING 2010. - : SPIE. - 9780819480231
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Konferensbidrag (refereegranskat)abstract
- We model the effect of signal pile-up on the energy resolution of a photon counting silicon detector designed for high flux spectral CT with sub-millimeter pixel size. Various design parameters, such as bias voltage, lower threshold level for discarding of electronic noise and the entire electronic read out chain are modeled and realistic parameter settings are determined. We explicitly model the currents induced on the collection electrodes of a pixel and superimpose signals emanating from events in neighboring pixels, either due to charge sharing or signals induced during charge collection. Electronic noise is added to the pulse train before feeding it through a model of the read out electronics where the pulse height spectrum is saved to yield the detector energy response function. The main result of this study is that a lower threshold of 5 keV and a rather long time constant of the shaping filter (tau(0) = 30 ns) are needed to discard induced pulses from events in neighboring pixels. These induction currents occur even if no charge is being deposited in the analyzed pixel from the event in the neighboring pixel. There is also only a limited gain in energy resolution by increasing the bias voltage to 1000 V from 600 V. We show that with these settings the resulting energy resolution, as measured by the FWHM/E of the photo peak, is 5% at 70 keV.
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| 10. |
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| 11. |
- Danielsson, Patrik, et al.
(författare)
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The prevalence of chronic obstructive pulmonary disease in Uppsala, Sweden - the Burden of Obstructive Lung Disease (BOLD) study : cross-sectional population-based study
- 2012
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Ingår i: Clinical Respiratory Journal. - 1752-6981 .- 1752-699X. ; 6:2, s. 120-127
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To estimate chronic obstructive pulmonary disease (COPD) prevalence in Uppsala and the impact of risk factors on disease prevalence using the standardised methods of the Burden of Obstructive Lung Disease (BOLD) study initiative. Methods: Randomly selected participants, aged 40 years or more (n = 548) responded to a questionnaire regarding smoking habits, respiratory symptoms, medical history, and exposure to airway irritants. Spirometry, with a post-bronchodilator test, was performed and COPD defined as post-bronchodilatory forced expiratory volume in 1 s (FEV(1) )/forced vital capacity (FVC) < 0.70 or FEV(1) /FVC < lower limit of normality (LLN). Circulatory inflammatory markers were measured. Results: COPD prevalence was 16.2%, which was the fourth lowest prevalence of COPD, compared with 12 other BOLD centres. Main risk factors for COPD were increasing age [odds ratio (OR) = 2.08 per 10 years] and smoking (OR = 1.33 per 10 pack years). Higher education was protective (OR = 0.70 per 5 years). Previous tuberculosis was an almost significant risk factor for COPD (P = 0.08). Subjects with COPD reported more respiratory symptoms but only 29% had previous doctor diagnosed COPD, asthma, chronic bronchitis or emphysema. Participants with COPD had higher levels of C-reactive protein (P = 0.01), but no difference was observed in interleukin 6 (IL-6) levels. Using LLN instead of the fixed FEV(1) /FVC ratio reduced the prevalence of COPD to 10%. Conclusion: COPD prevalence in Uppsala was similar to other BOLD centres in high-income countries. Apart from known COPD risk factors (age, smoking, lower educational level), a history of tuberculosis may be associated with COPD even in high-income countries. COPD remains under-diagnosed, as only 29% of subjects with COPD had a previously diagnosed lung disorder.
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| 12. |
- Jauhiainen, Alexandra, 1981, et al.
(författare)
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Distinct cytoplasmic and nuclear functions of the stress induced protein DDIT3/CHOP/GADD153
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- DDIT3, also known as GADD153 or CHOP, encodes a basic leucine zipper transcription factor of the dimer forming C/EBP family. DDIT3 is known as a key regulator of cellular stress response, but its target genes and functions are not well characterized. Here, we applied a genome wide microarray based expression analysis to identify DDIT3 target genes and functions. By analyzing cells carrying tamoxifen inducible DDIT3 expression constructs we show distinct gene expression profiles for cells with cytoplasmic and nuclear localized DDIT3. Of 175 target genes identified only 3 were regulated by DDIT3 in both cellular localizations. More than two thirds of the genes were downregulated, supporting a role for DDIT3 as a dominant negative factor that could act by either cytoplasmic or nuclear sequestration of dimer forming transcription factor partners. Functional annotation of target genes showed cell migration, proliferation and apoptosis/survival as the most affected categories. Cytoplasmic DDIT3 affected more migration associated genes, while nuclear DDIT3 regulated more cell cycle controlling genes. Cell culture experiments confirmed that cytoplasmic DDIT3 inhibited migration, while nuclear DDIT3 caused a G1 cell cycle arrest. Promoters of target genes showed no common sequence motifs, reflecting that DDIT3 forms heterodimers with several alternative transcription factors that bind to different motifs. We conclude that expression of cytoplasmic DDIT3 regulated 94 genes. Nuclear translocation of DDIT3 regulated 81 additional genes linked to functions already affected by cytoplasmic DDIT3. Characterization of DDIT3 regulated functions helps understanding its role in stress response and involvement in cancer and degenerative disorders.
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| 13. |
- Ramberg, Christina, 1962-, et al.
(författare)
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Preliminära skiljedomar
- 2013
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Ingår i: Juridisk Tidskrift. - 1100-7761. ; :2, s. 452-455
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 14. |
- Xu, Cheng, et al.
(författare)
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Energy resolution of a segmented silicon strip detector for photon-counting spectral CT
- 2013
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 715, s. 11-17
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the energy resolution of a segmented silicon strip detector for photon-counting spectral computed tomography (CT). The detector response to different monochromatic photon energies and various photon fluxes was characterized at the Elettra synchrotron. An RMS energy resolution of 1.50 keV has been demonstrated for 22 keV photons at zero flux, and it deteriorated as a function of input count rate at a rate of 5.1 eV mm(2)/Mcps. The charge sharing effect has been evaluated. The results show that around 11.1% of the interacting photons experience charge sharing for 22 keV photons and 15.3% for 30 keV.
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| 15. |
- Xu, Cheng, et al.
(författare)
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Evaluation of a Second-Generation Ultra-Fast Energy-Resolved ASIC for Photon-Counting Spectral CT
- 2013
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Ingår i: IEEE Transactions on Nuclear Science. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9499 .- 1558-1578. ; 60:1, s. 437-445
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Tidskriftsartikel (refereegranskat)abstract
- A second-generation ultra-fast energy-resolved application specific integrated circuit (ASIC) has been developed for photon-counting spectral computed tomography (CT). The energy resolution, threshold dispersion and gain of the ASIC were characterized with synchrotron radiation at Diamond Light Source. The standard deviation of threshold offsets at zero keV is 0.89 keV. An RMS energy resolution of 1.09 keV has been demonstrated for 15 keV photon energy at a count rate of 40 kcps, and it deteriorates at a rate of 0.29 keV/Mcps with the increase of output cout rate. The count rate performance of the ASIC has also been evaluated with 120 kV polychromatic x-rays produced by a tungsten anode tube and the results are presented.
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| 16. |
- Xu, Cheng, et al.
(författare)
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Evaluation of an ultra-fast photon-counting energy-resolved ASIC for spectral CT
- 2012
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Ingår i: Progress in Biomedical Optics and Imaging - Proceedings of SPIE. - : SPIE - International Society for Optical Engineering. - 9780819489623 ; , s. 83130Y-
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Konferensbidrag (refereegranskat)abstract
- We have developed an ultra-fast photon-counting energy-resolved application specific integrated circuit (ASIC) for spectral computed tomography (CT). A comprehensive characterization has been carried out to investigate the performance of the ASIC in terms of energy resolution under different photon flux rates and the count rate linearity in photon-counting mode. An energy resolution of 4.7 % has been achieved for 59.5 keV low flux photons. The count rate performance of the ASIC was measured with 120 kVp polychromatic x-rays. The results indicate that the count rate linearity can be kept for a flux rate up to 150 Mphotons s -1 mm -2 with retained energy information, and this value is increased to be 250 Mphotons s -1 mm -2 in photon-counting mode.
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| 17. |
- Xu, Cheng, et al.
(författare)
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Performance characterization of a silicon strip detector for spectral computed tomography utilizing a laser testing system
- 2011
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Ingår i: MEDICAL IMAGING 2011. - : SPIE. - 9780819485038 - 0819485039
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Konferensbidrag (refereegranskat)abstract
- A new silicon strip detector with sub-millimeter pixel size operated in single photon-counting mode has been developed for use in spectral computed tomography (CT). An ultra fast application specific integrated circuit (ASIC) specially designed for fast photon-counting application is used to process the pulses and sort them into eight energy bins. This report characterizes the ASIC and detector in terms of thermal noise (0.77 keV RMS), energy resolution when electron-hole pairs are generated in the detector diode (1.5 keV RMS) and Poissonian count rate with retained count rate linearity and energy resolution (200 Mcps.mm(-2)). The performance of the photon-counting detector has been tested using a picosecond pulsed laser system to inject energy into the detector, simulating x-ray interactions. The laser testing results indicate a good energy-discriminating capability of the detector, assigning the pulses to higher and higher energy bins as the intensity of the laser pulses are increased.
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| 18. |
- Xu, Cheng, et al.
(författare)
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Preliminary evaluation of a silicon strip detector for photon-counting spectral CT
- 2012
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 677, s. 45-51
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Tidskriftsartikel (refereegranskat)abstract
- An edge-on silicon strip detector designed for photon-counting spectral computed tomography (CT) is presented. Progress on the development of an application specific integrated circuit (ASIC) to process the pulses and sort them into energy bins is reported upon. The ASIC and detector are evaluated in terms of electronic noise, energy resolution, count rate linearity under high-frequency periodic pulses, threshold variation and gain. The high-frequency periodic pulses are injected both by means of an external pulse generator and a pulsed laser illuminating the silicon diode. The pulsed laser system has similar to 100 ps pulse width and thus generates near instantaneous pulses in the diode, thus mimicking real X-ray conversions. The evaluation shows a low thermal noise level of 0.77 key RMS, an energy resolution of 1.5 keV RMS when electron-hole pairs are generated in the detector diode by the laser injection. The test results furthermore indicate a good energy-discriminating capability of the detector with the thresholds spread out, assigning the external pulses to higher and higher energy bins as the pulse intensity is increased.
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