| 1. |
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| 2. |
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| 3. |
- Hollman, Gunilla, 1953-, et al.
(författare)
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Quality of life in patients with familial hypercholesterolaemia
- 2002
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 251:4, s. 331-337
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. The primary aim of this study was to analyse quality of life in adult patients with familial hypercholesterolaemia (FH), a genetic disorder with increased risk of coronary heart disease (CHD). Secondary aims were to find explanatory factors for quality of life and anxiety.Design. A descriptive cross-sectional design was used.Setting. Outpatients from lipid clinics at two university hospitals in Sweden were included. Patients with heterozygous FH and a randomly selected control group participated by filling out questionnaires.Subjects. Two hundred and eighty patients with heterozygous FH above 18 years of age were asked, and 212 of whom 185 were free of overt CHD, participated. Of a control group of 2980 persons 1485 were included for comparison.Methods. We used Likert-type questionnaires: the Quality of Life Index (QLI) consisting of four subscales, the Hospital Anxiety and Depression Scale (HAD), the Mastery Scale measuring coping and a questionnaire on health and lipids constructed for FH patients.Results. Patients with FH were significantly more satisfied with overall quality of life 21.8 ± 0.3 (SEM) vs. controls 21.1 ± 0.1 and this was also the case in three of four subscales, all differences P < 0.05. Anxiety about getting CHD was expressed amongst 86% of the patients with FH.Conclusions. Quality of life amongst patients with FH was at least as good as in controls but they were worried about getting CHD.
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| 4. |
- Kofoed Damm, Jesper, et al.
(författare)
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Pharmacologically relevant doses of valproate upregulate CD20 expression in three diffuse large B-cell lymphoma patients in vivo.
- 2015
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Ingår i: Experimental hematology & oncology. - : Springer Science and Business Media LLC. - 2162-3619. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic code modifications by histone deacetylase inhibitors (HDACi) have been proposed as potential new therapies for lymphoid malignancies. Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoma for which standard first line treatment is the chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) combined with the monoclonal anti-CD20 antibody rituximab (R-CHOP). The HDACi valproate, which has for long been utilized in anti-convulsive therapy, has been shown to sensitize to chemotherapy in vitro. Valproate upregulates expression of CD20 in lymphoma cell lines; therefore, 48 hour pre-treatment with valproate before first line R-CHOP in DLBCL stages II-IV is evaluated in the phase I clinical trial VALFRID; Valproate as First line therapy in combination with Rituximab and CHOP in Diffuse large B-cell lymphoma.
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| 5. |
- Landegren, Ulf, et al.
(författare)
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Molecular tools for a molecular medicine : analyzing genes, transcripts and proteins using padlock and proximity probes
- 2004
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Ingår i: Journal of Molecular Recognition. - : Wiley. - 0952-3499 .- 1099-1352. ; 17:3, s. 194-7
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Tidskriftsartikel (refereegranskat)abstract
- Procedures and reagents are needed to specifically detect all the macromolecules that are being identified in the course of genome projects. We discuss how this challenge may be met using a set of ligation-based reagents termed padlock probes and proximity ligation probes. These probes include elements with affinity for specific nucleic acid and protein molecules, respectively, along with unique identifier DNA sequence elements that encode the identity of the recognized target molecules. The information content of DNA strands that form in the detection reactions are recorded after amplification, allowing the recognized target molecules to be identified. The procedures permit highly specific solution-phase or localized analyses of large sets of target molecules as required in future molecular analyses.
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| 6. |
- Landegren, Ulf, et al.
(författare)
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Padlock and proximity probes for in situ and array-based analyses : tools for the post genomic era
- 2003
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Ingår i: Comparative and functional genomics. - : Hindawi Limited. - 1531-6912 .- 1532-6268. ; 4:5, s. 525-30
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Tidskriftsartikel (refereegranskat)abstract
- Highly specific high-throughput assays will be required to take full advantage of the accumulating information about the macromolecular composition of cells and tissues, in order to characterize biological systems in health and disease. We discuss the general problem of detection specificity and present the approach our group has taken, involving the reformatting of analogue biological information to digital reporter segments of genetic information via a series of DNA ligation assays. The assays enable extensive, coordinated analyses of the numbers and locations of genes, transcripts and protein.
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| 7. |
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| 8. |
- McGinn, Steven, et al.
(författare)
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New Technologies for DNA analysis-A review of the READNA Project.
- 2016
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Ingår i: New Biotechnology. - : Elsevier BV. - 1876-4347 .- 1871-6784.
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Forskningsöversikt (refereegranskat)abstract
- The REvolutionary Approaches and Devices for Nucleic Acid analysis (READNA) project received funding from the European Commission for 4 1/2 years. The objectives of the project revolved around technological developments in nucleic acid analysis. The project partners have discovered, created and developed a huge body of insights into nucleic acid analysis, ranging from improvements and implementation of current technologies to the most promising sequencing technologies that constitute a 3(rd) and 4(th) generation of sequencing methods with nanopores and in situ sequencing, respectively.
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| 9. |
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| 10. |
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| 11. |
- Nilsson, Mats, et al.
(författare)
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Real-time monitoring of rolling-circle amplification using a modified molecular beacon design
- 2002
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 30:14, s. e66-
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Tidskriftsartikel (refereegranskat)abstract
- We describe a method to monitor rolling-circle replication of circular oligonucleotides in dual-color and in real-time using molecular beacons. The method can be used to study the kinetics of the polymerization reaction and to amplify and quantify circularized oligonucleotide probes in a rolling-circle amplification (RCA) reaction. Modified molecular beacons were made of 2'-O-Me-RNA to prevent 3' exonucleolytic degradation by the polymerase used. Moreover, the complement of one of the stem sequences of the molecular beacon was included in the RCA products to avoid fluorescence quenching due to inter-molecular hybridization of neighboring molecular beacons hybridizing to the concatemeric polymerization product. The method allows highly accurate quantification of circularized DNA over a broad concentration range by relating the signal from the test DNA circle to an internal reference DNA circle reporting in a distinct fluorescence color.
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| 12. |
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| 13. |
- Zieba, Agata, et al.
(författare)
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Molecular tools for companion diagnostics
- 2012
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Ingår i: New Biotechnology. - : Elsevier BV. - 1871-6784 .- 1876-4347. ; 29:6, s. 634-640
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Forskningsöversikt (refereegranskat)abstract
- The heterogeneous nature of cancer results in highly variable therapeutic responses even among patients with identical stages and grades of a malignancy. The move towards personalised medicine in cancer therapy has therefore been motivated by a need to customise therapy according to molecular features of individual tumours. Companion diagnostics serves to support early drug development, it can provide surrogate markers in clinical trials, and also guide selection of individual therapies and monitoring of responses in routine clinical care. The era of companion diagnostics can be said to have begun with the introduction of the HercepTest - a first-of-a-kind diagnostic tool developed by DakoCytomation in 1998 to select patients for therapy with the anticancer drug Herceptin (trastuzumab). Herceptin and the paired test proved that companion diagnostics can help guide patient-tailored therapies. We will discuss herein technologies to analyse companion diagnostics markers at the level of DNA, RNA or protein, focusing on a series of methods developed in our laboratory that can facilitate drug development and help stratify patients for therapy.
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| 14. |
- Andersson, Anton, et al.
(författare)
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A holistic and experimentally-based view on recycling of off-gas dust within the integrated steel plant
- 2018
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Ingår i: Metals. - Basel : MDPI AG. - 2075-4701. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- Ore-based ironmaking generates a variety of residues, including slags and fines such as dust and sludges. Recycling of these residues within the integrated steel plant or in other applications is essential from a raw-material efficiency perspective. The main recycling route of off-gas dust is to the blast furnace (BF) via sinter, cold-bonded briquettes and tuyere injection. However, solely relying on the BF for recycling implicates that certain residues cannot be recycled in order to avoid build-up of unwanted elements, such as zinc. By introducing a holistic view on recycling where recycling via other process routes, such as the desulfurization (deS) station and the basic oxygen furnace (BOF), landfilling can be avoided. In the present study, process integration analyses were utilized to determine the most efficient recycling routes for off-gas dust that are currently not recycled within the integrated steel plants of Sweden. The feasibility of recycling was studied in experiments conducted in laboratory, pilot, and full-scale trials in the BF, deS station, and BOF. The process integration analyses suggested that recycling to the BF should be maximized before considering the deS station and BOF. The experiments indicated that the amount of residue that are not recycled could be minimized.
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| 15. |
- Andréasson, S, et al.
(författare)
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Medical laboratory technologists' perception of professional self. A study of Swedish MLTs employed in clinical chemistry
- 1992
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Ingår i: Scandinavian Journal of Caring Sciences. - 0283-9318 .- 1471-6712. ; 6:2, s. 67-74
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Tidskriftsartikel (refereegranskat)abstract
- The subjective perception of professional self was studied for a sample of Medical Laboratory Technologists (MLTs) employed in Clinical Chemistry in Sweden. The sample (N = 488) consisted of a randomized tenth of members of their trade union. A mailed questionnaire with 21 items concerning self-description compared with peers in a seven-point Likert type scale was completed by 332 (68%). There was no significant overall difference concerning the four principal types of workplace: Clinical Chemistry, Blood Serology, Primary Care and Clinical Chemistry/Blood Serology. The main difference was found between those in managerial posts (N = 72) and the other MLTs (N = 260). Factor analysis showed three principal components, labelled Professionalism, Work Ethic, and Empathy, but also a different composition of variables of the components for the manager group compared with the non-manager group.
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| 16. |
- Andrén, Mats, et al.
(författare)
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Att lära sig språk
- 2013
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Ingår i: Språket, människan och världen. - Lund : Studentlitteratur AB. - 9789144083391
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Bokkapitel (populärvet., debatt m.m.)
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| 17. |
- Andrén, Mats, et al.
(författare)
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Att lära sig språk
- 2013
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Ingår i: Språket, människan och världen : människans språk 1-2 - människans språk 1-2. - Lund : Studentlitteratur AB. - 9789144083391 ; , s. 73-89
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Bokkapitel (populärvet., debatt m.m.)
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| 18. |
- Andrén, Mats, et al.
(författare)
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On the lower limit of gesture
- 2014
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Ingår i: Visible Utterance in Action.
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Bokkapitel (refereegranskat)abstract
- Where, if, and how, should researchers draw the limit between gesture proper and semiotically less complex forms of bodily conduct that do not quite qualify as gesture? This is the question of a lower limit of gesture (Andrén 2010). In accord with a comparative semiotic approach (Kendon 2008) I suggest that the question is best understood, not as a binary distinction between gesture and non-gesture, but as a matter of several different semiotic properties that can vary independently of each other. This involves, in particular, different levels of representational complexity and communicative explicitness. These semiotic properties are both conceptually explicated and applied to empirical examples in this paper, eventually leading me to propose a family resemblance conception of gesture.
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| 19. |
- Bergemalm, Daniel, 1977-, et al.
(författare)
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Systemic Inflammation in Preclinical Ulcerative Colitis
- 2021
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Ingår i: Gastroenterology. - : AGA Institute. - 0016-5085 .- 1528-0012. ; 161:5, s. 1526-1539.e9
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored.Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1β, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.
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| 20. |
- Bergh, Gösta, et al.
(författare)
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Altered expression of the retinoblastoma tumor-suppressor gene in leukemic cell lines inhibits induction of differentiation but not G1-accumulation
- 1997
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Ingår i: Blood. - 1528-0020. ; 89:8, s. 2938-2950
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Tidskriftsartikel (refereegranskat)abstract
- The retinoblastoma tumor-suppressor gene, RB, has been implicated in tumor suppression, in regulation of the cell cycle, and in mediating cell differentiation. RB is necessary for hematopoiesis in mice, and aberrant RB-expression is associated with the progress and prognosis of leukemia. We have used antisense oligonucleotides, established clones stably expressing an antisense RB construct, and also established clones over expressing the retinoblastoma protein (pRb) to study the role of RB expression in monocytic differentiation induced by all-trans retinoic acid (ATRA) or 1-alpha-25-dihyroxycholecalciferol (Vit D3) in the monoblastic cell line U-937 and erythroid differentiation induced by transforming growth factor beta1 (TGFbeta1) and hemin in the erythroleukemic cell line K562. A reduction in pRb production in antisense RB-transfected U-937 clones was shown. Antisense oligonucleotides as well as expression of the antisense RB construct suppressed differentiation responses to ATRA or Vit D3, as judged by the capability to reduce nitro blue tetrazolium, by the appearance of monocyte-related cell surface antigens and by morphologic criteria. K562 cells showed decreased differentiation response to TGFbeta1, but not to hemin, when incubated with antisense oligonucleotides. U-937 antisense RB-transfected cells were also suppressed in their ability to upregulate levels of hypophosphorylated pRb when induced to differentiate. Although U-937 cells incubated with antisense oligonucleotides and clones expressing the antisense RB construct were hampered in their ability to differentiate on incubation with ATRA or Vit D3, the induced G0/G1-accumulation was similar to differentiating control cells treated with ATRA or Vit D3. Intriguingly, U-937 clones overexpressing RB were also inhibited in their differentiation response to ATRA or Vit D3 but not inhibited in their ability to respond with G0/G1 accumulation when induced with these substances. The results indicate that pRb plays a role in induced differentiation of U-937 cells as well as K562 cells involving mechanisms that, at least partially, are distinct from those inducing G1 accumulation.
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| 21. |
- Ceballos, Eva, et al.
(författare)
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c-Myc antagonizes the effect of p53 on apoptosis and p21WAF1 transactivation in K562 leukemia cells
- 2000
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 19, s. 2194-2204
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Tidskriftsartikel (refereegranskat)abstract
- c-myc protooncogene positively regulates cell proliferation and overexpression of c-myc is found in many solid tumors and leukemias. In the present study we used the K562 human myeloid leukemia cell line as a model to study the functional interaction between c-Myc and p53. Using two different methods, we generated K562 transfectant cell lines with conditional expression of either c-Myc or p53. The cells expressed the p53Vall35 mutant, which adopts a wild-type conformation at 32 degrees C, while c-Myc induction was achieved with a zinc-inducible expression vector. We found that p53 in wild-type conformation induces growth arrest and apoptosis of K562. Expression of c-Myc significantly attenuated apoptosis and impaired the transcriptional activity of p53 on p21WAF1, Bax and cytomegalovirus promoters. The impairment of p21WAF1 transactivation by c-Myc was confirmed by transfection of a c-Myc-estrogen receptor fusion protein and by induction of c-myc by zinc in transfected cells. Also, p53-mediated up-regulation of p21WAF1 mRNA protein were significantly reduced by c-Myc, while Bax levels were unaffected. Consistently, c-Myc increased cyclin-dependent kinase 2 activity in K562 cells expressing p53 in wild-type conformation. These results suggest that c-Myc overexpression may antagonize the pro-apoptotic function of p53, thus providing a molecular mechanism for the frequently observed deregulation of c-myc in human cancer.
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| 22. |
- Chylicki, Kristina, et al.
(författare)
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Characterization of the molecular mechanisms for p53-mediated differentiation
- 2000
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Ingår i: Cell Growth and Differentiation. - 1044-9523. ; 11:11, s. 561-571
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Tidskriftsartikel (refereegranskat)abstract
- The p53 tumor suppressor protein can induce both apoptosis and cell cycle arrest. Moreover, we and others have shown previously that p53 is a potent mediator of differentiation. For example, expression of ptsp53, a temperature-inducible form of p53, induces differentiation of leukemic monoblastic U-937 cells. The functions of p53 have for long been believed to be dependent on the transactivating capacity of p53. However, recent data show that both p53-induced cell cycle arrest and apoptosis can be induced independently of p53-mediated transcriptional activation, indicating alternative pathways for p53-induced apoptosis and cell cycle arrest. The bcl-2 proto-oncogene contributes to the development of certain malignancies, probably by inhibition of apoptosis. Interestingly, Bcl-2 has been shown to inhibit p53-mediated apoptosis as well as p53-mediated transcriptional activation. Asking whether Bcl-2 would interfere with the p53-mediated differentiation of U-937 cells, we stably transfected bcl-2 to U-937 cells inducibly expressing p53. Although the established Bcl-2-expressing clones were resistant to p53-mediated apoptosis, we did not observe any interference of Bcl-2 with the p53-mediated differentiation, suggesting separable pathways for p53 in mediating apoptosis and differentiation of U-937 cells. Neither did expression of Bcl-2 interfere with p53-induced expression of endogenous p21, suggesting that p53-induced differentiation might be dependent on the transcriptional activity of p53. To further investigate whether the p53-mediated differentiation of U-937 cells depends on the transcriptional activity of p53, we overexpressed transactivation-deficient p53, a transcriptionally inactive p53 mutant in these cells. However, in contrast to the effects of wild-type p53, expression of trans-activation-deficient p53 did neither induce signs of apoptosis nor of differentiation in U-937 cells. Our results indicate that the transcriptional activity of p53 is essential both for p53-mediated apoptosis and differentiation of U-937 cells.
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| 23. |
- Cöster, Mathias, 1969-, et al.
(författare)
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Digital Transformation : Understanding Business Goals, Risks, Processes, and Decisions
- 2023
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Även om digitalisering är långt ifrån ett nytt koncept, antar många att det räcker med att bara införa automation och informationssystem i olika former för att effektivisera deras organisations verksamhet. Denna missuppfattning kan ofta leda till oordning och kostsamma misstag. Digital transformation: Att förstå affärsmål, risker, processer och beslut visar hur man undviker sådana problem genom att noggrant överväga vad ett företag verkligen behöver.Till skillnad från många andra böcker om digital transformation, uppehåller sig författarna inte vid databasdesign eller detaljerna för att implementera informationssystem. Istället betonar de vikten av en tydlig förståelse för alla aspekter av en organisation för att effektivt kunna implementera och hantera digitala system, från affärsmål och strategier till att strukturera information och fatta beslut, riskbedömningar, projektledning, organisera och upphandla tjänster och Produkter.Den här boken är organiserad i elva kapitel och bygger på exempel från hela världen och kommer att vara av intresse för universitetsstudenter inom företagsekonomi, management, informationssystem och datavetenskap, såväl som praktiker som vill bättre förstå hur man hanterar digital transformation i sin egen organisation.
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| 24. |
- de Oliveira, Felipe Marques Souza
(författare)
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Development and Application of Proximity Assays for Proteome Analysis in Medicine
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Along with proteins, a myriad of different molecular biomarkers, such as post-translational modifications and autoantibodies, could be used in an attempt to improve disease detection and progression. In this thesis, I build on several iterations of the proximity ligation assay to develop and apply new adaptable methods to facilitate detection of proteins, autoantibodies and post-translational modifications.In paper I, we present an adaptation of the solid-phase proximity ligation assay (SP-PLA) for the detection of post-translational modification of proteins (PTMs). The assay was adapted for the detection of two of the most commons PTMs present in proteins, glycosylation and phosphorylation, offering the encouraging prospect of using detection of PTMs in a diagnostic or prognostic capacity. In paper II, we developed a variant of the proximity ligation assay using micro titer plate for detection and quantification of protein using optical density as readout in the fluorometer, termed PLARCA. With a detection limit considerably lower than ELISA, PLARCA detected femtomolar levels of these proteins in patient samples.In paper III, we aim to compare detection values of samples collected from earlobe capillary, venous plasma, as well as capillary plasma stored in dried plasma spots (DPS) assessed with a 92-plex inflammation panel using multiplex proximity extension assay (PEA). Despite the high variability in protein measurements between the three sample sources, we were able to conclude that earlobe capillary sampling is a suitable less invasive alternative, to venipuncture.In paper IV, we describe the application of PLARCA and proximity extension assay (PEA) for the detection of GAD65 autoantibodies (GADA). Thus, offering highly sensitive and specific autoimmunity detection.
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| 25. |
- Ehinger, Mats, et al.
(författare)
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Expression of the p53 tumor suppressor gene induces differentiation and promotes induction of differentiation by 1,25-dihydroxycholecalciferol in leukemic U-937 cells
- 1996
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Ingår i: Blood. - 1528-0020. ; 87:3, s. 1064-1074
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Tidskriftsartikel (refereegranskat)abstract
- Leukemic U-937 cells, which lack normal p53, were stably transfected with a temperature-sensitive mutant of p53 to investigate the consequences for growth and differentiation. On induction of wild-type p53 activity at the permissive temperature, some of these cells underwent maturation as judged by the capacity for oxidative burst and the appearance of monocyte related cell surface molecules. Moreover, wild-type p53-expressing cells were more sensitive than p53-negative control cells to induction of differentiation by 1,25-dihydroxycholecalciferol; a twofold to fourfold increase of the fraction of cells showing signs of terminal maturation was observed when wild-type p53-expressing cells were incubated with 1,25-dihydroxycholecalciferol at concentrations that only slightly affected control cells. Whereas wild-type p53 activity per se induced maturation of certain cells, other underwent cell death judging from the reduced capability to exclude trypan blue and the appearance of fragmented DNA in flow cytometric analysis. The p53-induced cell death could be inhibited by incubation with 1,25-dihydroxy-cholecalciferol, but not all-trans retinoic acid. Thus, 1,25-dihydroxycholecalciferol, seemed to increase the survival of wild-type p53-expressing cells and to cooperate with wild-type p53 to induce differentiation. The data imply that p53-mediated maturation in U-937 cells depends on optimal regulation of signals for differentiation, survival and proliferation, and suggest a role for p53 in the differentiation induction of leukemic cells.
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| 26. |
- Ehinger, Mats, et al.
(författare)
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Involvement of the tumor suppressor gene p53 in tumor necrosis factor-induced differentiation of the leukemic cell line K562
- 1995
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Ingår i: Cell Growth and Differentiation. - 1044-9523. ; 6:1, s. 9-17
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Tidskriftsartikel (refereegranskat)abstract
- The cDNA of the human wild-type p53 tumor suppressor gene was constitutively overexpressed in the leukemic cell line K562 (which lacks detectable amounts of p53 protein) in order to investigate the consequences for growth and differentiation. Several stable clones were established by transfection of the expression vector pc53SN3. Expression of p53 protein was characterized by biosynthetic labeling and immunoprecipitation with the monoclonal antibodies pAb 1801 (reacting with wild-type and mutant human p53), pAb 240 (reacting with mutant human p53) and pAb 1620 (reacting with wild-type human p53). All clones which were 1801+, 240-, 1620- or 1801+, 240-, 1620+ were defined as "wild-type-like p53-expressing" clones. Our results show that expression of p53 protein is compatible with continuous proliferation of K562 cells. The growth characteristics of wild-type-like p53-expressing clones did not differ from that of control clones. However, the former were more sensitive than p53-negative control clones to growth inhibition by tumor necrosis factor (TNF), a cytokine with a potential role in growth and differentiation of myeloid leukemic cells. In addition, a 2- to 4-fold increase of the amount of hemoglobin, a marker of erythroid differentiation, was observed when wild-type-like p53 protein-expressing clones were incubated with TNF. This suggests that differentiation is the mechanism responsible for the increased TNF sensitivity of these clones. Our results support a role for p53 in mediating growth inhibitory and differentiation inducing signals by TNF.
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| 27. |
- Ehinger, Mats, et al.
(författare)
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p53-dependent and -independent differentiation of leukemic U-937 cells : relationship to cell cycle control
- 1998
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Ingår i: Experimental Hematology. - 1873-2399. ; 26:11, s. 52-1043
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Tidskriftsartikel (refereegranskat)abstract
- Observations based on overexpression of the suppressor gene p53 or interference with endogenous p53 support a role for p53 in mediating not only growth inhibition and apoptosis but also differentiation. The aim of this study was to characterize the mechanisms of p53-dependent differentiation in the monoblastic leukemia cell line U-937. These cells were transfected with a mutant of the p53 gene expressing wild-type p53 at a permissive temperature. The results showed that wild-type p53 and interferon (IFN)-gamma were able to work synergistically to promote differentiation. This cooperative response was not associated with early G1 arrest of the cell cycle, indicating that p53 can mediate differentiation by mechanisms other than those used for mediating G1 arrest. The differentiation response to transfected p53 with or without INF-gamma was inhibited by cyclic adenosine monophosphate (cAMP)-inducing agents (dibutyryl cyclic adenosine 3':5'-monophosphate, forskolin, and 3-isobutyl-1-methylxanthine) in a dose-dependent manner. In contrast, the differentiation response of p53-negative U-937 cells to 1,25-dihydroxychole-calciferol or all-trans retinoic acid was enhanced by cAMP-inducing agents at optimal concentrations and inhibited at higher concentrations. In addition, 1,25-dihydroxycholecalciferol-mediated differentiation could be achieved in cells arrested in G1 by concomitant incubation with cAMP-inducing agents, indicating that differentiation can occur in the absence of proliferation. In conclusion, the results of this study indicate that p53-dependent and -independent differentiation can occur independently of cell cycle regulation.
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| 28. |
- Foldemo, Annica, 1953-, et al.
(författare)
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Quality of life and burden in parents of outpatients with schizophrenia
- 2005
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Ingår i: Social Psychiatry and Psychiatric Epidemiology. - : Springer Science and Business Media LLC. - 0933-7954 .- 1433-9285. ; 40:2, s. 133-138
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSince the late 1950s, several studies have reported the burden faced by families living with a mentally ill relative. These studies have pointed out the importance of a progressive mental health service, focusing not only on the treatment of the patients, but also on the needs of the relatives. The aims of the present study were to compare the quality of life of parents of outpatients with schizophrenia with a randomly selected reference group and the relation between quality of life and burden on the parents.SubjectsThe sample comprised all parents (n=38) of outpatients with schizophrenia at an outpatient clinic in 2001, where the patients had contact at least once a week with both parents and staff. The parents were compared with a reference group (n=698).MethodsThe self-rating scale Quality of Life Index (QLI) was used to assess quality of life in both groups. In the case of the parents, semistructured interviews were supplemented by the data collection to assess the degree of burden with the Burden Assessment Scale (BAS). The outpatients were also interviewed to assess their global function with the Global Assessment of Functioning scale (GAF) and the Clinical Global Impression scale (CGI).ResultsThe parents were significantly less satisfied with their overall quality of life (p<0.05). There was a correlation between lower overall quality of life and higher perceived burden r=0.58 (p<0.01). There was also a correlation between lower values on the family subscale and social subscale within the QLI and higher subjective burden r=0.54 (p<0.01) and r=0.52 (p<0.01), respectively.ConclusionThese results indicate that caregiving has an influence on the family situation and on the quality of life of parents. These findings suggest that the professions working with the parents must have an approach focusing not only on the care given to the ill daughter or son, but also on the parents’ situation.
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| 29. |
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| 30. |
- Fredriksson, Simon, et al.
(författare)
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Protein detection using proximity-dependent DNA ligation assays
- 2002
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 20:5, s. 473-477
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Tidskriftsartikel (refereegranskat)abstract
- The advent of in vitro DNA amplification has enabled rapid acquisition of genomic information. We present here an analogous technique for protein detection, in which the coordinated and proximal binding of a target protein by two DNA aptamers promotes ligation of oligonucleotides linked to each aptamer affinity probe. The ligation of two such proximity probes gives rise to an amplifiable DNA sequence that reflects the identity and amount of the target protein. This proximity ligation assay detects zeptomole (40 x 10(-21) mol) amounts of the cytokine platelet-derived growth factor (PDGF) without washes or separations, and the mechanism can be generalized to other forms of protein analysis.
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| 31. |
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| 32. |
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Gullberg, Mats, et al.
(författare)
-
Cytokine detection by antibody-based proximity ligation
- 2004
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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. ; 101:22, s. 8420-4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Efficient and precise detection techniques, along with extensive repertoires of specific binding reagents, will be needed to meet the challenges of proteome analyses. The recently established proximity ligation mechanism enables sensitive high-capacity protein measurements by converting the detection of specific proteins to the analysis of DNA sequences. Proximity probes containing oligonucleotide extensions are designed to bind pairwise to target proteins and to form amplifiable tag sequences by ligation when brought in proximity. In our previous report, both the ligatable arms and the protein binders were DNA molecules. We now generalize the method by providing simple and convenient protocols to convert any polyclonal antibodies or matched pair of monoclonal antibodies to proximity probe sets through the attachment of oligonucleotide sequences. Sufficient reagent for >100,000 proximity ligation assays can be prepared from 1 microg of antibody. The technique is applied to measure cytokines in a homogenous test format with femtomolar detection sensitivities in 1-microl samples, and we exemplify its utility in situations when only minute sample amounts are available.
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| 37. |
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| 38. |
- Gullberg, Mats, 1953-
(författare)
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Health care professionals' self description
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the present thesis was to survey and analyse professional self of health care professionals, focusing on perceptions of self, and on their attitudes towards aspects of sense of responsibility.Studies were accomplished with quantitative techniques using questionnaires and/or instruments. A total of 803 respondents was included, and the first study (I) presented the development of the PSDF and comprised 30 registered nurses. The next study (II) examined results from 332 medical laboratory technologists who answered the PSDF. In the third study (III) 68 occupational therapists responded to the PSDF. The fourth study (IV) was a six-year follow-up of 43 registered nurses from the beginning of their training to three years after graduation, and they responded to the PSDF, the SRF and to the Form for ranked sources of encouragement. The fifth study (V) comprised four professional groups from a university hospital in Sweden (physicians, physiotherapists, registered nurses and enrolled nurses), and 312 responded to the set of forms (the PSDF, the SRF, and the Form for ranked sources of encouragement).The main theoretical approach was based on symbolic interactionism, where the self is a significant notion. Concepts on attitude, sense of responsibility and encouragement were important.The results showed that there are components of self description that is 'specific to one professional group, but also components that uncover similarities. Three important components of professional self were outlined; professional conduct, work ability and empathy. Important issues were also encouragement for work done, which influences the professional self, and that the positive attitudes to sense of responsibility showed similarities with characteristics of professional self.In conclusion, two propositions were addressed: that professionals' self description is composed of three meaningful dimensions; professional conduct, work ability and empathy, and that the professional self can be improved throughdevelopment of intrinsic attitudes and behaviours.
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| 39. |
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| 40. |
- Gullberg, Mats, 1971-
(författare)
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Proximity Ligation as a Universal Protein Detection Tool
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Among the great challenges in biology are the precise quantification of specific sets of proteins and analyses of their patterns of interaction on a much larger scale than is possible today.This thesis presents a novel protein detection technique - proximity ligation - and reports the development and application of a nucleic acid amplification technique, RCA. Proximity ligation converts information about the presence or co-localization of specific proteins to unique sets of nucleic acid sequences. For detection of target proteins or protein complexes the coincident binding by pairs or triplets of specific protein-binding reagents are required. Oligonucleotide-extensions attached to those binding reagents are joined by a DNA ligase and subsequently analyzed by standard molecular genetic techniques. The technique is shown to sensitively detect an assortment of proteins using different types of binders converted to proximity probes, including SELEX aptamers and mono- and polyclonal antibodies. I discuss factors important for using the technique to analyze many proteins simultaneously.Quantification of target molecules requires precise amplification and detection. I show how rolling circle amplification, RCA, can be used for precise quantification of circular templates using modified molecular beacons with real-time detection. The combination of proximity-probe templated circularization and RCA results in a sensitive method with high selectivity, capable of visualizing individual immobilized proteins. This technique is used for localized detection of a set of individual proteins and protein complexes at sub-cellular resolution.
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| 41. |
- Gullberg, Mats T, et al.
(författare)
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Ability to solve problems, professionalism, management, empathy, and working capacity in occupational therapy : The Professional Self Description Form
- 1994
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Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; :8, s. 173-178
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Tidskriftsartikel (refereegranskat)abstract
- The majority of occupational therapists in Sweden previously worked on large occupational therapy wards. Health care policy has changed over the years and the system has been reorganized accordingly. The employment situation for occupational therapists has also changed. This paper focuses on the perception of professional self among occupational therapists. The objective was to explore the professional self and to suggest components important to the occupational therapist profession. The Professional Self Description Form (PSDF) was used for the exploration of self. The 19 items in the PSDF cover areas relevant to professional functioning and activity. Sixty-eight employed occupational therapists participated. The results of the PSDF were subjected to factor analysis and five factors were obtained; Ability to solve problems, Professionalism, Management, Empathy, and Working capacity. We believe that these five factors can function as improving domains of the role of the professional occupational therapist in Sweden
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| 42. |
- Gullberg, Mats T., et al.
(författare)
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Reference values for the Quality of Life Index in the general Swedish population 18-80 years of age
- 2010
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Ingår i: Quality of Life Research. - : Springer Science and Business Media LLC. - 0962-9343 .- 1573-2649. ; 19:5, s. 751-760
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim in the present study was to establish underlying dimensions of quality of life in Sweden, measured by QLI, and to obtain reference values among a representative sample between 18 and 80 years of age from the general Swedish population. METHOD: A total of 1,680 randomly selected persons completed the questionnaire (57% response rate). All data were coded and entered into the statistical software. Factor analysis, maximum-likelihood method with oblique rotation, was employed to explore and reveal underlying dimensions of the QLI. To describe QLI total and subscale reference values for different age groups and men and women, respectively, means and 95% CI as well as medians and quartiles were used. For comparisons related to demographic and background variables, parametric and non-parametric analyses were used (alpha=0.01). All data were analysed using SPSS 14.0 statistical software. RESULTS: Four underlying dimensions emerged: Family and friends, Health and functioning, Social and economic and Psychological/spiritual. Mean values for the total QLI and the four subscales ranged between 17.2 and 23.7 (possible range=0.0-30.0). CONCLUSIONS: The overall QLI and subscale scores correspond with those presented by other researchers. Population-based measures of generic quality of life and underlying dimensions are important considering the gain when results from specific patient groups are viewed.
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| 43. |
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| 44. |
- Götherström, Christine, et al.
(författare)
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Development of a tool for measuring the concept of good care among patients and staff in relation to Swedish legislation
- 1995
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Ingår i: International Journal of Nursing Studies. - 0020-7489 .- 1873-491X. ; 32:3, s. 277-87
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Tidskriftsartikel (refereegranskat)abstract
- An instrument for measuring the concept of good care, in relation to the Swedish Health and Medical Services Act, has been developed and tested in short-term care. The instrument comprises 14 statements on good care. The construct validity was estimated by factor analysis based on the results from 240 patients. Five factors explained 62% of the variance of the 14 variables and covered the following areas: information, security, accessibility, continuity, and influence and respect. Patients (n = 240) and registered nurses (n = 57) showed differences in estimations of the concept of good care on all factors. There were only minor differences, however, within the patient group and the nursing group, respectively, on comparing the two samples. The instrument needs further testing in different care conditions.
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| 45. |
- Hindström, Mats, et al.
(författare)
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Strategi för formellt skydd av skog i Gävleborgs län. D. 3, Skogliga värdetrakter i Gävleborgs län
- 2006
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Värdetraktsanalys - skogliga värdetrakter i Gävleborgs län.Med värdetrakt avses ett landskapsavsnitt med särskilt höga ekologiska bevarandevärden.Länsstyelsen har analyserat den geografiska fördelningen i länet av kända värdekärnor.De kända värdekärnona består av tre olika kategorier:nyckelbiotoper,naturreservat och nationalparker samt områden som Länsstyrelsen inventerat och hittat höga skogliga naturvärden.
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| 46. |
- Jarvius, Malin, et al.
(författare)
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In situ detection of phosphorylated platelet-derived growth factor receptor beta using a generalized proximity ligation method
- 2007
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 6:9, s. 1500-1509
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Tidskriftsartikel (refereegranskat)abstract
- Improved methods are needed for in situ characterization of post-translational modifications in cell lines and tissues. For example, it is desirable to monitor the phosphorylation status of individual receptor tyrosine kinases in samples from human tumors treated with inhibitors to evaluate therapeutic responses. Unfortunately the leading methods for observing the dynamics of tissue post-translational modifications in situ, immunohistochemistry and immunofluorescence, exhibit limited sensitivity and selectivity. Proximity ligation assay is a novel method that offers improved selectivity through the requirement of dual recognition and increased sensitivity by including DNA amplification as a component of detection of the target molecule. Here we therefore established a generalized in situ proximity ligation assay to investigate phosphorylation of platelet-derived growth factor receptor β (PDGFRβ) in cells stimulated with platelet-derived growth factor BB. Antibodies specific for immunoglobulins from different species, modified by attachment of DNA strands, were used as secondary proximity probes together with a pair of primary antibodies from the corresponding species. Dual recognition of receptors and phosphorylated sites by the primary antibodies in combination with the secondary proximity probes was used to generate circular DNA strands; this was followed by signal amplification by replicating the DNA circles via rolling circle amplification. We detected tyrosine phosphorylated PDGFRβ in human embryonic kidney cells stably overexpressing human influenza hemagglutinin-tagged human PDGFRβ in porcine aortic endothelial cells transfected with the β-receptor, but not in cells transfected with the α-receptor, and also in immortalized human foreskin fibroblasts, BJ hTert, endogenously expressing the PDGFRβ. We furthermore visualized tyrosine phosphorylated PDGFRβ in tissue sections from fresh frozen human scar tissue undergoing wound healing. The method should be of great value to study signal transduction, screen for effects of pharmacological agents, and enhance the diagnostic potential in histopathology.
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| 47. |
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| 48. |
- Liu, Yanling, et al.
(författare)
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Western Blotting via Proximity Ligation for High Performance Protein Analysis
- 2011
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 10:11, s. O111.011031-
-
Tidskriftsartikel (refereegranskat)abstract
- Western blotting is a powerful and widely used method, but limitations in detection sensitivity and specificity, and dependence upon high quality antibodies to detect targeted proteins, are hurdles to overcome. The in situ proximity ligation assay, based on dual antibody recognition and powerful localized signal amplification, offers increased detection sensitivity and specificity, along with an ability to identify complex targets such as phosphorylated or interacting proteins. Here we have applied the in situ proximity ligation assay mechanism in Western blotting. This combination allowed the use of isothermal rolling circle amplification of DNA molecules formed in target-specific ligation reaction, for 16-fold or greater increase in detection sensitivity. The increased specificity because of dual antibody recognition ensured highly selective assays, detecting the specific band when combinations of two cross-reactive antitubulin antibodies were used (i.e. both producing distinct nonspecific bands in traditional Western blotting). We also demonstrated detection of phosphorylated platelet-derived growth factor receptor beta by proximity ligation with one antibody directed against the receptor and another directed against the phosphorylated tyrosine residue. This avoided the need for stripping and re-probing the membrane or aligning two separate traditional blots. We demonstrate that the high-performance in situ proximity ligation-based Western blotting described herein is compatible with detection via enhanced chemiluminescence and fluorescence detection systems, and can thus be readily employed in any laboratory.
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| 49. |
- Lundin, Per, 1971-
(författare)
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Bilsamhället : Ideologi, expertis och regelskapande i efterkrigstidens Sverige
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During the 1950s the number of cars in Sweden increased almost fivefold and the country attained the highest level of car ownership per capita in Europe. The rise and establishment of mass motoring was dramatically illustrated by the violent encounter between the car and the city. Despite the fact that congestion as well as road accidents were well-known, everyday occurrences, they reached previously unimagined heights through the growth of mass motoring. In this doctoral thesis Per Lundin focuses on the emergence of a group of planning experts as the key advocates of the idea of the “car society” as the solution to these problems. By fully adapting society to the car it would be possible to eliminate congestion and road accidents, thus affirming the continuing advance of the car. This ideal, which originated in the United States, became the goal and the dream of these experts.The general question addressed by Lundin is to what extent the actions and the ideologies of the experts interacted with the advent of mass motoring and the extensive urban building during the post-war period. In order to answer this question Lundin analyzes, firstly how the planning experts laid claim to the problems of congestion and road accidents, thereby restating them as exclusive planning problems, secondly how guidelines and standards for a car-conscious planning of cities and communities were developed based on the formulation of this problem and thirdly how, and to what extent, the guidelines and standards concerned were implemented in the town planning process.In the thesis Lundin argues that the dreams about a post-war Swedish society entirely adapted to the car by and large were realized. One important explanation of the fact that the physical adaptation of cities and societies to the car could proceed so quickly, on such a large scale and in similar forms all over the country, is found in the planning rules developed by the experts. The rules were the embodiment of the untroubled and unreflecting dreams nourished by the planning experts of the 1950s and the 1960s. Through the rules these ideological conceptions were reinforced and disseminated in a manner almost unable to stop. As the rules quickly were integrated with the planning instruments of administrative bodies locally, regionally and nationally, they set the tone for the extensive urban renewal of the following decades.
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| 50. |
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