| 1. |
- Hedström, Brita, et al.
(author)
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Visby Innerstad : En användningsplan
- 1973
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Reports (pop. science, debate, etc.)abstract
- Sedan lång tid föreligger i stort sett enighet om att bevara innerstadens bebyggelse och att anpassa eventuella nytillskott till det redan bestående. Med den inställningen har förändringsprocessen både dämpats och mildrats men ändå inte bragts att avstanna. Förändringar sker ständigt om det också huvudsakligen i smått: de många synbart så anspråkslösa byggnadsåtgärderna adderar efterhand ihop sig till något större och mer genomgripande. Långsamt, nästan omärkligt, ändrar innerstaden sitt ansikte.Ändå är det inte själva husen som förändrats mest utan användningen av dem. Ur funktionell synpunkt har 1950 - och 60-talen har varit något av en omstörtning i innerstadens historia: den har förlorat nästan hälften av de boende, en stor del av detaljhandeln och praktiskt taget helt sin gamla roll som skolcentrum. I gengäld har ytterstaden vuxit ut till ett sammanhängande kilometerbrett bälte. Till stor del av denna funktionella förändring en följd av beslutet att bevara innerstadens bebyggelse. Vad som inte fått plats inom den gamla ramen har etablerats utandör den.Föreliggande arbete vill ge en översiktlig bild av förändringsförloppen, sedda i ett långt tidsperspektiv men med tonvikt på dagsläget. Bebyggelsen tas upp till utförlig granskning men också användningen av den. Det är just samspelet mellan husen och de funtkioner, de fyller, som kan sägas utgöra bokens huvudtema. I de flesta fall är detta sammanhang hus-användning alldeles konfliktfritt och föranleder därför inte heller någon diskussion. Vad som behandlas är de relativt få problematiska fallen, hus som borde rustas upp för att fylla sin uppgift, hus som är olämpligt nyttjade eller inte använda alls. En serie sådana fall tas upp till systematisk genomgång; samtidigt berörs också de trafik - och miljömässiga konsekvenserna. Bokens syfte är alltså klart: den ger ett underlag av fakta för arbetet med att jämka samman byggnader och användningsformer. I den meningen kan skriften kallas en anvädningsplan för Visby innanför murarna.Arkitekturskolanas arbete har bedrivitis parallellt med den kommunala Innerstadskommitténs verksamhet. Något organiserat samarbete har inte förekommit med de informella kontakterna har varit både täta och goda. Att likheterna mellan Innerstadskommittén och Arkitekturskolans slutsatser blivit så pass stora, kan tillskrivas en gemensam helhetssyn.En av Arkitekturskolans elever, arkitekt Lars-Ingvar Larsson, har tidigare självständigt genomfört en undersökning av förändringar i innerstaden 1945-70- Denna studie publicerats separat och bör uppfattas som ett komplement till den hör föreliggande.Förutom de i innehållsförteckningen nämnda har ytterligare några aktivt medverkat i arbetet. Studiet av trafikfrågorna i innerstaden, i hamnen och öster om ringmuren leddes av Åke Claesson, I fältstudier och diskussioner medverkande Göran Månsson.Arkitekturskolan har fått god hjälp av ett antal initierade personer i Visby. Särskild tacksamhet är vi skyldiga byggnadsnämnden ordförande Henning Jacobson, kommunalrådet C B Stenström, stadsarkitekten Måns Hagbergm f. länsbostadsdorektören Åke Malmberg och landsantikvarien Gunnar Svahnström. I boken publiceringskostnaderna har ekonomiskt bidrag lämnats av Gotlands kommun och Riksantikvarieämbetet.Boken har redigerats av Sture Balgård och Ann Mari Westerlind med hjälp av Henrik O Andersson, Bo Ek, Göran Lindahl, Fredrik von Platen, John Sjöström Gunnar Westerlind och Hans Wetterfors.Skeppsholmen, Stockholm, sommaren 1973.Arkitekturskolans lärare och elever.
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| 2. |
- Buus, Terkild Brink, et al.
(author)
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Single-cell heterogeneity in Sézary syndrome
- 2018
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In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 2:16, s. 2115-2126
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Journal article (peer-reviewed)abstract
- Sezary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) with a median life expectancy of less than 4 years. Although initial treatment responses are often good, the vast majority of patients with SS fail to respond to ongoing therapy. We hypothesize that malignant T cells are highly heterogeneous and harbor subpopulations of SS cells that are both sensitive and resistant to treatment. Here, we investigate the presence of single-cell heterogeneity and resistance to histone deacetylase inhibitors (HDACi) within primary malignant T cells from patients with SS. Using single-cell RNA sequencing and flow cytometry, we find that malignant T cells from all investigated patients with SS display a high degree of single-cell heterogeneity at both the mRNA and protein levels. We show that this heterogeneity divides the malignant cells into distinct subpopulations that can be isolated by their expression of different surface antigens. Finally, we show that treatment with HDACi (suberanilohydroxamic acid and romidepsin) selectively eliminates some subpopulations while leaving other subpopulations largely unaffected. In conclusion, we show that patients with SS display a high degree of single-cell heterogeneity within the malignant T-cell population, and that distinct subpopulations of malignant T cells carry HDACi resistance. Our data point to the importance of understanding the heterogeneous nature of malignant SS cells in each individual patient to design combinational and new therapies to counter drug resistance and treatment failure.
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| 3. |
- Larsson Lindahl, Marianne, et al.
(author)
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Case management in aftercare of involuntarily committed patients with substance abuse. A randomized trial.
- 2013
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In: Nordic Journal of Psychiatry. - : Informa UK Limited. - 1502-4725 .- 0803-9488. ; 67:3, s. 197-203
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Journal article (peer-reviewed)abstract
- Objective: Case management has since the 1970s been widely used to co-ordinate services for mental health patients. The methodology has expanded to support patients in many different types of conditions. This study is one of very few randomized trials on case management in a European setting. It examined the impact of case management on substance abuse and use of service after discharge from court-ordered institutional care. Methods: Court-ordered patients with substance abuse (n = 36) were randomly assigned to either strengths based case management or treatment-as-usual during 6 months in aftercare. Data was collected at intake, at conclusion of intervention and at 6 month's follow-up with a follow-up rate of 94%. Results: Case management interventions were well received by the patients with no drop-out during intervention. Patients with the support of a case manager seemed to sustain abstinence in a higher degree compared with treatment-as-usual but no differences were detected in regard to use of care. A subgroup analysis showed that patients with a continuous drug abuse did have access to care from both social welfare and hospital care systems. Conclusions: Case management may be useful in order to retain abstinence in aftercare following court-ordered treatment. The social welfare and hospital care systems seem to provide care irrespective of case manager intervention. The study design, interventions and assessments instruments were well received by patients but needs to be replicated with a larger population. Clinical implications: The 100% retention in the case management support group indicates that patients were satisfied with this type of intervention and the methodology seems to be useful in order to retain abstinence.
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| 4. |
- Nyblom, Maria, et al.
(author)
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Crystal Structure of Na+, K+-ATPase in the Na+-Bound State
- 2013
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 342:6154, s. 123-127
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Journal article (peer-reviewed)abstract
- The Na+, K+-adenosine triphosphatase (ATPase) maintains the electrochemical gradients of Na+ and K+ across the plasma membrane-a prerequisite for electrical excitability and secondary transport. Hitherto, structural information has been limited to K+-bound or ouabain-blocked forms. We present the crystal structure of a Na+-bound Na+, K+-ATPase as determined at 4.3 angstrom resolution. Compared with the K+-bound form, large conformational changes are observed in the a subunit whereas the beta and gamma subunit structures are maintained. The locations of the three Na+ sites are indicated with the unique site III at the recently suggested IIIb, as further supported by electrophysiological studies on leak currents. Extracellular release of the third Na+ from IIIb through IIIa, followed by exchange of Na+ for K+ at sites I and II, is suggested.
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| 5. |
- Ohlsson, Lars, et al.
(author)
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Increased level of circulating cell-free mitochondrial DNA due to a single bout of strenuous physical exercise
- 2020
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In: European Journal of Applied Physiology. - : Springer. - 1439-6319 .- 1439-6327. ; 120, s. 897-905
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Journal article (peer-reviewed)abstract
- Purpose Physical exercise is reported to affect the immune response in various ways. Thus, the levels of pro-inflammatory cytokines as well as the abundance of circulating leukocytes are changed. In this study, the occurence of circulating cell-free mitochondrial DNA (cfmtDNA) and nuclear DNA (nDNA) was investigated in connection with a single bout of strenuous physical exercise. Methods Healthy volunteers performed a controlled ergo-spirometry cycle test and venous blood samples were taken at different time-points to analyze the concentration of blood components before, during and after the test. The number of circulating leukocytes was measured, as well as secretion of the soluble urokinase activator receptor (suPAR). Results Cf-mtDNA significantly increased during exercise, compared to baseline values and after 30 and 90 min of rest. Circulating leukocytes increased during exercise, but returned to baseline levels afterwards. Surface expression of the urokinase plasminogen activating receptor (uPAR) on neutrophils decreased significantly during exercise. The concentration of suPAR tended to increase during exercise but only significantly after 90 min of rest. Conclusion Increased concentration of cf-mtDNA indicates that cell damage takes place during high intensity training. Hypoxia and tissue damage are likely causes of cf-mtDNA from muscle cells. The levels of cf-mtDNA remain high during the initial rest, due to the decreasing numbers of leukocytes normally clearing the plasma from cf-mtDNA. The increased levels of suPAR further emphasize that strenuous physical exercise causes a reaction similar to inflammation. Further studies are needed to detect the source of increased cf-mtDNA and the corresponding increase of suPAR liberation.
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| 6. |
- Paulsen, Peter Aasted, et al.
(author)
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The C-terminal cavity of the Na,K-ATPase analyzed by docking and electrophysiology
- 2013
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In: Molecular membrane biology. - : Informa UK Limited. - 0968-7688 .- 1464-5203. ; 30:2, s. 195-205
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Journal article (peer-reviewed)abstract
- The Na,K-ATPase is essential to all animals, since it maintains the electrochemical gradients that energize the plasma membrane. Naturally occurring inhibitors of the pump from plants have been used pharmaceutically in cardiac treatment for centuries. The inhibitors block the pump by binding on its extracellular side and thereby locking it. To explore the possibilities for designing an alternative way of targeting the pump function, we have examined the structural requirements for binding to a pocket that accommodates the two C-terminal residues, YY, in the crystal structures of the pump. To cover the sample space of two residues, we first performed docking studies with the 400 possible dipeptides. For validation of the in silico predictions, pumps with 13 dipeptide sequences replacing the C-terminal YY were expressed in Xenopus laevis oocytes and examined with electrophysiology. Our data show a significant correlation between the docking scores from two different methods and the experimentally determined sodium affinities, which strengthens the previous hypothesis that sodium binding is coupled to docking of the C-terminus. From the dipeptides that dock the best and better than wild-type YY, it may therefore be possible to develop specific drugs targeting a previously unexplored binding pocket in the sodium pump.
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