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  • 1.
    Hammar, Petter
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Walldén, Mats
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Fange, David
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Baltekin, Özden
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Ullman, Gustaf
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Persson, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Leroy, Prune
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Elf, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Transcription factor dissociation measurements using single molecule chase in living cellsManuscript (preprint) (Other academic)
  • 2.
    Hammar, Petter
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Walldén, Mats
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Fange, David
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Persson, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Baltekin, Özden
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ullman, Gustaf
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Leroy, Prune
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Elf, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Direct measurement of transcription factor dissociation excludes a simple operator occupancy model for gene regulation2014In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, no 4, p. 405-+Article in journal (Refereed)
    Abstract [en]

    Transcription factors mediate gene regulation by site-specific binding to chromosomal operators. It is commonly assumed that the level of repression is determined solely by the equilibrium binding of a repressor to its operator. However, this assumption has not been possible to test in living cells. Here we have developed a single-molecule chase assay to measure how long an individual transcription factor molecule remains bound at a specific chromosomal operator site. We find that the lac repressor dimer stays bound on average 5 min at the native lac operator in Escherichia coli and that a stronger operator results in a slower dissociation rate but a similar association rate. Our findings do not support the simple equilibrium model. The discrepancy with this model can, for example, be accounted for by considering that transcription initiation drives the system out of equilibrium. Such effects need to be considered when predicting gene activity from transcription factor binding strengths.

  • 3. Svalkvist, A.
    et al.
    Johnsson, A. A.
    Vikgren, J.
    Hakansson, M.
    Ullman, Gustaf
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Boijsen, M.
    Fisichella, V.
    Flinck, A.
    Molnar, D.
    Mansson, L. G.
    Bath, M.
    Evaluation of an improved method of simulating lung nodules in chest tomosynthesis2012In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 53, no 8, p. 874-884Article in journal (Refereed)
    Abstract [en]

    Background: Simulated pathology is a valuable complement to clinical images in studies aiming at evaluating an imaging technique. In order for a study using simulated pathology to be valid, it is important that the simulated pathology in a realistic way reflect the characteristics of real pathology. Purpose: To perform a thorough evaluation of a nodule simulation method for chest tomosynthesis, comparing the detection rate and appearance of the artificial nodules with those of real nodules in an observer performance experiment. Material and Methods: A cohort consisting of 64 patients, 38 patients with a total of 129 identified pulmonary nodules and 26 patients without identified pulmonary nodules, was used in the study. Simulated nodules, matching the real clinically found pulmonary nodules by size, attenuation, and location, were created and randomly inserted into the tomosynthesis section images of the patients. Three thoracic radiologists and one radiology resident reviewed the images in an observer performance study divided into two parts. The first part included nodule detection and the second part included rating of the visual appearance of the nodules. The results were evaluated using a modified receiver-operating characteristic (ROC) analysis. Results: The sensitivities for real and simulated nodules were comparable, as the area under the modified ROC curve (AUC) was close to 0.5 for all observers (range, 0.43-0.55). Even though the ratings of visual appearance for real and simulated nodules overlapped considerably, the statistical analysis revealed that the observers to were able to separate simulated nodules from real nodules (AUC values range 0.70-0.74). Conclusion: The simulation method can be used to create artificial lung nodules that have similar detectability as real nodules in chest tomosynthesis, although experienced thoracic radiologists may be able to distinguish them from real nodules.

  • 4.
    Ullman, Gustaf
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computational Science.
    Walldén, Mats
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Marklund, Erik G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mahmutovic, Anel
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Razinkov, Ivan
    Elf, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    High-throughput gene expression analysis at the level of single proteins using a microfluidic turbidostat and automated cell tracking2013In: Philosophical Transactions of the Royal Society of London. Biological Sciences, ISSN 0962-8436, E-ISSN 1471-2970, Vol. 368, no 1611, p. 20120025:1-8Article in journal (Refereed)
  • 5.
    Walldén, Mats
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Fange, David
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Gustaf, Ullman
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Marklund, Erik G
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Elf, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Fluctuations in replication initiation determine the generation time and size distributions of E. coli cellsManuscript (preprint) (Other academic)
1 - 5 of 5
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