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Ullman, Gustaf
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Publications (5 of 5) Show all publications
Hammar, P., Walldén, M., Fange, D., Persson, F., Baltekin, Ö., Ullman, G., . . . Elf, J. (2014). Direct measurement of transcription factor dissociation excludes a simple operator occupancy model for gene regulation [Letter to the editor]. Nature Genetics, 46(4), 405-+
Open this publication in new window or tab >>Direct measurement of transcription factor dissociation excludes a simple operator occupancy model for gene regulation
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2014 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, no 4, p. 405-+Article in journal, Letter (Refereed) Published
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.

National Category
Cell Biology Bioinformatics and Systems Biology
Identifiers
urn:nbn:se:uu:diva-225087 (URN)10.1038/ng.2905 (DOI)000334510100020 ()
Note

Hammar and Walldén contributed equally to this work.

Available from: 2014-06-13 Created: 2014-05-27 Last updated: 2017-12-05Bibliographically approved
Ullman, G., Walldén, M., Marklund, E. G., Mahmutovic, A., Razinkov, I. & Elf, J. (2013). High-throughput gene expression analysis at the level of single proteins using a microfluidic turbidostat and automated cell tracking. Philosophical Transactions of the Royal Society of London. Biological Sciences, 368(1611), 20120025:1-8
Open this publication in new window or tab >>High-throughput gene expression analysis at the level of single proteins using a microfluidic turbidostat and automated cell tracking
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2013 (English)In: 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) Published
National Category
Bioinformatics and Systems Biology
Identifiers
urn:nbn:se:uu:diva-193001 (URN)10.1098/rstb.2012.0025 (DOI)000312828900003 ()
External cooperation:
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eSSENCE
Available from: 2012-12-24 Created: 2013-01-28 Last updated: 2017-12-06Bibliographically approved
Svalkvist, A., Johnsson, A. A., Vikgren, J., Hakansson, M., Ullman, G., Boijsen, M., . . . Bath, M. (2012). Evaluation of an improved method of simulating lung nodules in chest tomosynthesis. Acta Radiologica, 53(8), 874-884
Open this publication in new window or tab >>Evaluation of an improved method of simulating lung nodules in chest tomosynthesis
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2012 (English)In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 53, no 8, p. 874-884Article in journal (Refereed) Published
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.

Keywords
Adults, Digital radiography, Lung, Observer performance, Technology assessments, Thorax, Artificial organs, Biological organs, Diseases, Pathology, Radiology, Visualization, Tomography
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-186731 (URN)10.1258/ar.2012.120230 (DOI)000310820000009 ()
Available from: 2012-11-29 Created: 2012-11-29 Last updated: 2017-12-07Bibliographically approved
Walldén, M., Fange, D., Gustaf, U., Marklund, E. G. & Elf, J. Fluctuations in replication initiation determine the generation time and size distributions of E. coli cells.
Open this publication in new window or tab >>Fluctuations in replication initiation determine the generation time and size distributions of E. coli cells
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(English)Manuscript (preprint) (Other academic)
National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-235544 (URN)
Available from: 2014-11-05 Created: 2014-11-05 Last updated: 2015-02-03Bibliographically approved
Hammar, P., Walldén, M., Fange, D., Baltekin, Ö., Ullman, G., Persson, F., . . . Elf, J.Transcription factor dissociation measurements using single molecule chase in living cells.
Open this publication in new window or tab >>Transcription factor dissociation measurements using single molecule chase in living cells
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(English)Manuscript (preprint) (Other academic)
Keywords
Escherichia coli, Gene regulation, Transcription factor, single molecule imaging
National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-198801 (URN)
Available from: 2013-04-25 Created: 2013-04-25 Last updated: 2014-11-05Bibliographically approved
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