| 1. |
- Uhlén, Mathias, et al.
(författare)
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A human protein atlas for normal and cancer tissues based on antibody proteomics
- 2005
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 4:12, s. 1920-1932
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Tidskriftsartikel (refereegranskat)abstract
- Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, similar to 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.
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| 2. |
- Brattås, Per Ludvik, et al.
(författare)
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TRIM28 Controls a Gene Regulatory Network Based on Endogenous Retroviruses in Human Neural Progenitor Cells
- 2017
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 18:1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Endogenous retroviruses (ERVs), which make up 8% of the human genome, have been proposed to participate in the control of gene regulatory networks. In this study, we find a region- and developmental stage-specific expression pattern of ERVs in the developing human brain, which is linked to a transcriptional network based on ERVs. We demonstrate that almost 10,000, primarily primate-specific, ERVs act as docking platforms for the co-repressor protein TRIM28 in human neural progenitor cells, which results in the establishment of local heterochromatin. Thereby, TRIM28 represses ERVs and consequently regulates the expression of neighboring genes. These results uncover a gene regulatory network based on ERVs that participates in control of gene expression of protein-coding transcripts important for brain development.
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| 3. |
- Allan, James, et al.
(författare)
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Frontiers, Challenges, and Opportunities for Information Retrieval – Report from SWIRL 2012, The Second Strategic Workshop on Information Retrieval in Lorne
- 2012
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Ingår i: SIGIR Forum. - : ACM. - 0163-5840. ; 46:1, s. 2-32
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Tidskriftsartikel (refereegranskat)abstract
- During a three-day workshop in February 2012, 45 Information Retrieval researchers met to discuss long-range challenges and opportunities within the field. The result of the workshop is a diverse set of research directions, project ideas, and challenge areas. This report describes the workshop format, provides summaries of broad themes that emerged, includes brief descriptions of all the ideas, and provides detailed discussion of six proposals that were voted "most interesting" by the participants. Key themes include the need to: move beyond ranked lists of documents to support richer dialog and presentation, represent the context of search and searchers, provide richer support for information seeking, enable retrieval of a wide range of structured and unstructured content, and develop new evaluation methodologies.
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| 4. |
- Bernsel, Andreas, et al.
(författare)
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Prediction of membrane-protein topology from first principles
- 2008
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 105:20, s. 7177-7181
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Tidskriftsartikel (refereegranskat)abstract
- The current best membrane-protein topology-prediction methods are typically based on sequence statistics and contain hundreds of parameters that are optimized on known topologies of membrane proteins. However, because the insertion of transmembrane helices into the membrane is the outcome of molecular interactions among protein, lipids and water, it should be possible to predict topology by methods based directly on physical data, as proposed >20 years ago by Kyte and Doolittle. Here, we present two simple topology-prediction methods using a recently published experimental scale of position-specific amino acid contributions to the free energy of membrane insertion that perform on a par with the current best statistics-based topology predictors. This result suggests that prediction of membrane-protein topology and structure directly from first principles is an attainable goal, given the recently improved understanding of peptide recognition by the translocon.
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| 5. |
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| 6. |
- Cossarizza, A., et al.
(författare)
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Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
- 2019
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
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Tidskriftsartikel (refereegranskat)abstract
- These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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| 7. |
- Falk, Anders
(författare)
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Sacred Games - Becoming Gods : Priming digital game ethics
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The point of departure for my research is a perceived breach and resulting dissonance between how digital games and other parts of society that are similar in form, enact certain aspects of life. This shift was made especially clear in massive multiplayer games in 2004 with the release of World of Warcraft, the design of which panders to cultural weak points, rather than attempting to mimic them. Digital games are far-reaching. In February 2019, ‘Apex Legends’ reached over 10 million players in less than 72 hours. Nonetheless, the idea of games as separate from the ‘real’ is persisting. Digital games have become a cyclopean gathering of liminality, and there are still no form-based ethics emerging, from either industry or society. Even though society is now undergoing the same abstracting digitisation, that has been a base for game design for a long time, there is a continuing separation in the knowledge applying to games or ‘reality’. The purpose of this thesis is to explore different ontological, epistemological, and ethical understandings of digital games as media, technology, modes of experience, and form. This is undertaken by using the situated and reality producing grating1 of technoscience, together with an eclectic range of concepts such as media as a message, agential reality, liminal phases, anticipation, and ergon. The research delineates a primer for applied studies within the rhizomatic structure of digital games, digitisation, technoscience, and media-technology. In accordance with this aim, the thesis has a fragmented, non-linear, and mosaic approach. This licentiate thesis is a compilation of three papers with a complementary introduction and an epilogue.
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| 8. |
- Falk, Julia, 1989-
(författare)
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En andlig terra incognita : spiritismen i det sena 1800-talets Stockholm
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation analyses the role that spiritism played in Stockholm, Sweden, during the late 19th century, more specifically between the years 1887–1902. Spiritism was an international movement grounded in the belief that spirits of dead people existed and that it was possible to communicate with them. While spiritism in Sweden was a Christian movement, its followers claimed to be using scientific methods. It is this tension between scientific ambitions on the one hand, and the combined belief in Christianity and spiritism on the other, that is investigated in this dissertation. The source material consists primarily of a spiritistic periodical, notes from spiritistic seances, and three debates about spiritism. The theoretical framework is based on the sociologist Thomas Gieryn's concept of boundary-work, specifically David Hess's extension of it and his concept of the Self and both negative and positive Others. The study concludes that spiritists constructed science as both a positive and a negative Other, meaning that they wanted to be associated with science, while also stressing that they were doing something beyond science. In relation to this image of science as both a positive and a negative Other spiritists could construct their Self as a kind of scientific pioneer. The study also identifies a similar relationship to Christianity: spiritists emphasised their faith in a Christian God, used Christian symbols, and practised Christian rituals, but they also created their own belief system and criticized the church. Their approaches to Christianity and science were not, however, entirely similar. They did not turn to Christian institutions for acceptance, but rather strived to become part of the scientific community. These differences are interpreted as part of a larger shift in social status and position of science and Christianity.This dissertation has also identified a change in how spiritism was depicted in the press by its critics. At the beginning of the period, criticism against spiritism was mostly based on accusations of spiritists being imposters and their critics wanted nothing to do with them. As theories about the unconscious spread, however, the approach towards spiritism changed. Spiritistic phenomenon could now be investigated by scientists who wanted to learn more about the unconscious, even though they did not accept the spiritists explanations that spirits were behind them. By analysing both the spiritists’ relationship to science and Christianity and how spiritism was discussed in the press, this dissertation demonstrates that the belief in spiritism was an integrated part of Stockholm’s cultural landscape in the late 19th century.
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| 9. |
- Hennerdal, Aron, et al.
(författare)
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Internal duplications in alpha-helical membrane protein topologies are common but the nonduplicated forms are rare
- 2010
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Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 19:12, s. 2305-2318
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Tidskriftsartikel (refereegranskat)abstract
- Many alpha-helical membrane proteins contain internal symmetries, indicating that they might have evolved through a gene duplication and fusion event Here, we have characterized internal duplications among membrane proteins of known structure and in three complete genomes We found that the majority of large transmembrane (TM) proteins contain an internal duplication The duplications found showed a large variability both in the number of TM-segments included and in their orientation Surprisingly, an approximately equal number of antiparallel duplications and parallel duplications were found However, of all 11 superfamilies with an internal duplication, only for one, the AcrB Multidrug Efflux Pump, the duplicated unit could be found in its nonduplicated form An evolutionary analysis of the AcrB homologs indicates that several independent fusions have occurred, including the fusion of the SecD and SecF proteins into the 12-TM-protein SecDF in Brucella and Staphylococcus aureus In one additional case, the Vitamin B-12 transporter-like ABC transporters, the protein had undergone an additional fusion to form protein with 20 TM-helices in several bacterial genomes Finally, homologs to all human membrane proteins were used to detect the presence of duplicated and nonduplicated proteins This confirmed that only in rare cases can homologs with different duplication status be found, although internal symmetry is frequent among these proteins One possible explanation is that it is frequent that duplication and fusion events happen simultaneously and that there is almost always a strong selective advantage for the fused form
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| 10. |
- Karlsson, Per Erik, et al.
(författare)
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The vulnerability of northern European vegetation to ozone damage in a changing climate An assessment based on current knowledge
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The potential vulnerability of vegetation at northern latitudes to ozone damage was assessed based on current knowledge with regard to air ozone concentrations and leaf ozone uptake as well as to plant traits affecting ozone tolerance. The focus was on the northern European arctic, alpine and northern boreal vegetation zones, with a special focus on high-altitude vegetation. In particular, we analysed if there are increasing risks for ozone impacts on northern vegetation due to high spring ozone concentrations in relation to climate change induced shifts such as e.g. an earlier start of the growing season. The ozone concentrations in these regions are characterized by the influence of a combination of conditions caused by high latitudes and high altitudes. Ozone concentrations increase with altitude and the difference in ozone concentrations between day and night are smaller at high-altitude and high-latitude sites. Summer periods with long daylight conditions potentially promote the leaf ozone uptake through the open stomata. The aims of this report were: • To assess the current state of knowledge regarding the potential vulnerability of far northern vegetation to ozone damage, today and in the future • To provide advice for policy implications regarding necessary ozone precursor emission abatement • To provide advice for future research and monitoring of ozone impacts on the vegetation at northern latitudes Ongoing environmental changes affecting far northern latitude ecosystems were reviewed. Current and novel methods were described for how to estimate the time of year during which the ozone exposure for vegetation should be accumulated. Time trends for ozone concentrations at northern latitudes were analysed. Ozone episodes with high concentrations at far northern latitudes were described. Source attributions of northern ozone concentrations were analysed. Environmental conditions at far northern latitudes that might be important for ozone damage were evaluated. Plant traits that can influence the ozone vulnerability were discussed. Current experimental results for ozone injury on northern plant species were evaluated. Future scenarios for ozone impact on northern vegetation were discussed. Some important results from the analyses are described below. At high altitudes and high latitudes, the ozone concentrations are relatively similar during day- and night-time. Furthermore, at high latitudes, the long daylight duration during the summer has the potential to increase the duration of the daily period with plant gas exchange and leaf ozone uptake. Therefore, the absorption of ozone through the stomata may potentially be higher at northern latitudes. However, measurements of light intensity and quality at northern sites in combination with a simple calculation example illustrated that this probably was not the case, since the potential added ozone uptake in the early morning and late evening at northern sites may be cancelled out by a lower ozone uptake in the middle of the day, as compared to southern sites. Both data on budburst and data on ecosystem CO2 exchange as well as meteorological observations show that there has been a development towards an earlier start of the growing season during the year, with approximately 0.5 – 1 day per year. Thus, there is clear evidence for an earlier start of the growing season, which is likely to continue. However, the timing of the spring ozone maximum is also shifted towards earlier in the year. There is presently no evidence for an increasing overlap between the growing season and the ozone peak. Despite this, there is a potential for increased ozone uptake to vegetation in spring due to the earlier growing start of vegetation and increased uptake of ozone to vegetation in May. The impact of this on the accumulated phytotoxic ozone dose for northern vegetation needs to be investigated further. The overall conclusions about the present and near future ozone vulnerability of northern vegetation were: • There remain uncertainties regarding to what extent northern vegetation is affected by ozone exposure. • According to current knowledge, we could not find evidence that expected changes in ozone concentrations and climate would make the northern arctic, alpine and subalpine vegetation substantially more vulnerable to ozone than other types of European vegetation. • The risk of significant and lasting negative impact of the current exposure to ozone on northern boreal forests is most likely not greater than for boreonemoral and nemoral forests in southern Fennoscandia. • However, peak ozone concentrations occurring in spring and early summer may affect vegetation at northern latitudes in Fennoscandia since the start of the growing season in the future may occur earlier during the year. The policy implications that can be derived from these conclusions were: • The current state of knowledge implies that ecosystems in the far north are not more susceptible to ozone than vegetation in other parts of Europe. Hence, we cannot advocate for a stronger reduction of ozone precursors emissions based exclusively on the ozone sensitivity of vegetation in the far north. • Policies designed to reduce emissions of ozone precursors to protect vegetation in other parts of Europe as well as in the entire northern hemisphere are likely to suffice to protect vegetation in northern Fennoscandia. There are important remaining knowledge gaps. Our conclusions are based on important, but limited observations. Experimental evidence from investigations specifically designed to study ozone sensitivity of high-altitude vegetation in northern Europe are to a large extent lacking. It is recommended that further experimental research is undertaken to directly compare the ozone sensitivity of plants of high-latitude/high-altitude origin with that of plants (species, genotypes) representative of regions of the southern part of the Nordic region. This research should include the characteristics of the high-latitude climate and other conditions. A specific research question is if the new ozone critical levels for European vegetation based on PODYSPEC (Mapping Manual, 2017) are correct, both regarding calculation methodology as well as impact assessments? In particular, there is a lack of information about the degree of stomata closure during nights in high-latitude area plants. This is important for the modelling of ozone uptake (dry deposition) in these areas and requires coordinated measurement campaigns in close cooperation with modelers. Further research questions may be related to the future development of the northern regions – e.g. oil and gas extraction including flaring, shipping, more tourism and climate change – how will that affect the ozone exposure of in the northern vegetation? Do future ozone precursor emission scenarios describe this correctly? Will warm and dry summers like 2018 become more frequent in connection with climate change, and how will this affect ozone impacts on vegetation? There are currently very few, long term ozone monitoring stations in the arctic and alpine vegetation zones, in particular at high altitudes. Given the expected increase in anthropogenic activities in these areas in combination with climate change, it is strongly recommended to increase the number of high-altitude ozone monitoring sites in these regions.
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