| 1. |
- Beyer, J., et al.
(författare)
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Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer
- 2013
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 24:4, s. 878-888
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Forskningsöversikt (refereegranskat)abstract
- In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, similar to 50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.
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| 2. |
- Tandstad, T., et al.
(författare)
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Treatment of stage I seminoma, with one course of adjuvant carboplatin or surveillance, risk-adapted recommendations implementing patient autonomy: a report from the Swedish and Norwegian Testicular Cancer Group (SWENOTECA)
- 2016
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:7, s. 1299-1304
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Tidskriftsartikel (refereegranskat)abstract
- A total of 1118 patients with clinical stage I seminoma one course of adjuvant carboplatin or managed by surveillance were included. Stromal invasion of rete testis and tumor size > 4 cm are confirmed as risk factors predicting relapse. Relapse rates following one course of adjuvant carboplatin is high and there is need to explore more effective adjuvant treatment options in patients with seminoma.The purpose of the protocol was to reduce the treatment burden in clinical stage I (CSI) seminoma by offering risk-adapted treatment. The protocol aimed to prospectively validate the proposed risk factors for relapse, stromal invasion of the rete testis and tumor diameter > 4 cm, and to evaluate the efficacy of one course of adjuvant carboplatin. From 2007 to 2010, 897 patients were included in a prospective, population-based, risk-adapted treatment protocol implementing one course of adjuvant carboplatin AUC7 (>n = 469) or surveillance (>n = 422). In addition, results from 221 patients receiving carboplatin between 2004 and 2007 are reported. At a median follow-up of 5.6 years, 69 relapses have occurred. Stromal invasion of the rete testis [hazard ratio (HR) 1.9, >P = 0.011] and tumor diameter > 4 cm (HR 2.7, >P < 0.001) were identified as risk factors predicting relapse. In patients without risk factors, the relapse rate (RR) was 4.0% for patients managed by surveillance and 2.2% in patients receiving adjuvant carboplatin. In patients with one or two risk factors, the RR was 15.5% in patients managed by surveillance and 9.3% in patients receiving adjuvant carboplatin. We found no increased RR in patients receiving carboplatin < 7 x AUC compared with that in patients receiving a parts per thousand yen7 x AUC. Stromal invasion in the rete testis and tumor diameter > 4 cm are risk factors for relapse in CSI seminoma. Patients without risk factors have a low RR and adjuvant therapy is not justified in these patients. The efficacy of adjuvant carboplatin is relatively low and there is need to explore more effective adjuvant treatment options in patients with high-risk seminoma. The data do not support the concept of a steep dose response for adjuvant carboplatin.
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| 3. |
- Lindell, Lina, 1977-, et al.
(författare)
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Journey to the destination: a circular tourism economy : a training program for the hospitality industry to facilitate a transition towards increased circularity in the South Baltic Region
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Being aware of the extent of the tourism industry and that it is ever growing, which is also encouraged in many individual countries by the national and regional governments, it is evident that the tourism industry is an essential target group for introducing circular concepts and implementing circular solutions. Yet, this sector has so far received little attention in the literature and initiatives on circularity.Circular Economy (CE) goes beyond “green” or “environmental”, it includes all aspects of a community and challenges us to create solutions that are completely different from what we are used to. It also invites us to open up and interact with other stakeholders and the general public.In your hands is the first training material in circular economy specifically developed for small to medium sized companies of the tourism industry in the South Baltic Region. It is a small but important step in the direction towards circularity and a wellbeing society. Through this work we have shown that despite cultural challenges and regional differences there is a shared, common interest in making tourism more sustainable and even to work together towards a transformation of the hospitality industry. This common vision has been stronger than the challenges we faced in making this work and this is what will ensure the continued growing awareness on circularity and its integration in different sectors in our communities. In this work we have featured some of the groundbreaking experts in this field, and some of the first good practices from our regions. They are all courageous pioneers in a field that with time will become the norm. In fact, in the 10th Annual Forum of the EU strategy for the Baltic Sea Region (12-13/6/2019, Gdansk, Poland), CE was highlighted as the pathway to reach prosperity and wellbeing in the Baltic Sea Region.
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| 4. |
- Bushlya, V., et al.
(författare)
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On chemical and diffusional interactions between PCBN and superalloy Inconel 718 : Imitational experiments
- 2019
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Ingår i: Journal of the European Ceramic Society. - : Elsevier BV. - 0955-2219. ; 39:8, s. 2658-2665
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Tidskriftsartikel (refereegranskat)abstract
- During a metal cutting process, chemical wear can become the dominant mechanism of tool degradation under the high temperatures and contact pressures that arise between the tool and the metal workpiece. This study focuses on the chemical and diffusional interactions between superalloy Inconel 718 and cubic boron nitride (cBN) tool material with and without TiC binder. It covers thermodynamic modeling and experimental tests in the pressure range of 0.1 Pa to 2.5 GPa at temperatures up to 1600 °C. The methods used include diffusion couples under both vacuum and high pressure, transmission electron microscopy (TEM) analysis and in-situ synchrotron observations. It is shown that cBN is prone to diffusional dissolution in the metal and to reactions with niobium, molybdenum, and chromium from Inconel 718. Adding TiC binder changes the overall degradation process because it is less susceptible to these interaction mechanisms.
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| 5. |
- Gerdtsson, Axel, et al.
(författare)
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Validation of a prediction model for post-chemotherapy fibrosis in nonseminoma patients
- 2023
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Ingår i: Bju International. - 1464-4096 .- 1464-410X. ; 132:3, s. 329-336
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Tidskriftsartikel (refereegranskat)abstract
- Objective To validate Vergouwe's prediction model using the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) RETROP database and to define its clinical utility. Materials and methods Vergouwe's prediction model for benign histopathology in post-chemotherapy retroperitoneal lymph node dissection (PCRPLND) uses the following variables: presence of teratoma in orchiectomy specimen; pre-chemotherapy level of alphafetoprotein; b-Human chorionic gonadotropin and lactate dehydrogenase; and lymph node size pre- and postchemotherapy. Our validation cohort consisted of patients included in RETROP, a prospective population-based database of patients in Sweden and Norway with metastatic nonseminoma, who underwent PC-RPLND in the period 2007-2014. Discrimination and calibration analyses were used to validate Vergouwe's prediction model results. Calibration plots were created and a Hosmer-Lemeshow test was calculated. Clinical utility, expressed as opt-out net benefit (NBopt-out), was analysed using decision curve analysis. Results Overall, 284 patients were included in the analysis, of whom 130 (46%) had benign histology after PC-RPLND. Discrimination analysis showed good reproducibility, with an area under the receiver-operating characteristic curve (AUC) of 0.82 (95% confidence interval 0.77-0.87) compared to Vergouwe's prediction model (AUC between 0.77 and 0.84). Calibration was acceptable with no recalibration. Using a prediction threshold of 70% for benign histopathology, NBopt-out was 0.098. Using the model and this threshold, 61 patients would have been spared surgery. However, only 51 of 61 were correctly classified as benign. Conclusions The model was externally validated with good reproducibility. In a clinical setting, the model may identify patients with a high chance of benign histopathology, thereby sparing patients of surgery. However, meticulous follow-up is required.
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| 6. |
- Jönsson, A C, et al.
(författare)
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Secondary prevention and lifestyle indices after stroke in a long-term perspective
- 2018
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; , s. 227-234
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To describe the long-term perspective regarding prevalence of risk factors, secondary stroke prevention, and lifestyle indices after stroke.METHODS: From a population-based one-year cohort (n = 416), we performed an observational study of 145 survivors at 16 months and 10 years after stroke (age 27-97 years) regarding secondary prevention including reaching acceptable treatment goals; nutritional status with focus on underweight; and the lifestyle indices: living situation, level of dependence, and self-assessed health condition.RESULTS: Ten years after stroke, 50% of the subjects with hypertension diagnosis and 55% of those without hypertension diagnosis were within the blood pressure goal <140/90 compared with 32% (P = .008) and 37% (N.S.) at 16 months. Acceptable HbA1c levels among subjects with diabetes mellitus diagnosis increased from 35% to 45% (N.S.). Among those without diabetes diagnosis, satisfactory HbA1c levels decreased from 98% to 79% (P < .001). Underweight increased from 9% to 17% (P = .019). Among patients with cerebral infarction, the prevalence of atrial fibrillation increased from 22% to 29% (P = .004), and treatment with oral anticoagulants from 75% to 78% (N.S.). Acceptable LDL cholesterol levels increased from 59% to 80% (P = .033) among subjects on lipid lowering treatment, and from 18% to 40% among untreated (P = .010). At 10 years, 90% still lived in their own home. Health condition was reported as good/very good/excellent by 65%. Age, female sex, and living situation were associated with intensity of secondary prevention measures and underweight.CONCLUSIONS: The proportion of individuals within treatment goals improved over time, but secondary prevention still needed additional consideration 10 years after stroke.
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| 7. |
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| 8. |
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| 9. |
- Ståhl, H., et al.
(författare)
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Respiration and sequestering of organic carbon in shelf sediments of the oligotrophic northern Aegean Sea
- 2004
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Ingår i: Marine Ecology-Progress Series. ; 269, s. 33-48
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Tidskriftsartikel (refereegranskat)abstract
- Respiration and sequestering of organic carbon was investigated in northern Aegean Sea sediments (NE Mediterranean). Benthic total carbonate (C-T, also called SigmaCO(2) or dissolved inorganic carbon, DIC) fluxes and O-2 uptake rates were measured in situ using a benthic lander. Dissolved organic carbon (DOC) fluxes were calculated from pore water gradients, taking into account the influence of biodiffusion/bioirrigation. Macrofaunal biomass was determined in the sediment collected by the chambers of the benthic lander. Chl a distributions were used as a tracer of high-quality sedimentary organic carbon. The measured benthic C-T fluxes were positively correlated with the O-2 uptake rates. The obtained average apparent respiration ratio (C-T flux:O-2 flux) of 0.90 +/- 0.36 suggests a clear dominance of aerobic respiration in these organic carbon-poor shelf sediments. The C-T efflux, the 02 uptake rate, and the DOC flux were significantly higher in spring than in fall at 2 of the stations. The Black Sea water, which enters the Aegean Sea in the study area, did not influence benthic respiration rates or organic carbon sequestering rates. A strong positive correlation between both the C-T and O-2 fluxes and the mean chl a concentration in surficial sediment suggests that benthic respiration, to a large extent, was controlled by the availability of labile phytodetrital organic matter. There was no influence of macrofaunal biomass (dry weight) on C-T fluxes or oxygen uptake rates. The calculated benthic DOC fluxes made up 7.2 to 27 % (average 14 +/- 8.1 %) of the C-T fluxes, indicating that their contribution to the overall recycling of organic carbon in these sediments was important. The organic carbon burial efficiency ranged from 0.1 to 5.3 %, but at Stn KA1 it was considerably higher (average 4%) than at the other stations (average 0.3%). Except for this station, the obtained burial efficiencies were very low compared to other sediments with similar accumulation rates. The average burial flux of organic carbon corresponded to less than 1 % of the annual mean primary production (PP) for the Aegean Sea at Stn KA1, and to less than 0.1 % of PP at the other stations.
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| 10. |
- Anderberg, A. A., et al.
(författare)
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Maesaceae, a new primuloid family in the order Ericales s.l.
- 2000
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Ingår i: Taxon. - Vienna, Austria : IAPT. - 0040-0262 .- 1996-8175. ; 49:2, s. 183-187
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Tidskriftsartikel (refereegranskat)abstract
- Evidence from morphology and molecular sequence data from three chloroplast genes, rbcL, ndhF, and atpB, have shown that the genus Maesa constitutes an evolutionary lineage separate from the other three primuloid families, Theophrastaceae, Myrsinaceae, and Primulaceae. The new family Maesaceae is here formally recognised, its taxonomic status being changed from a subfamily of Myrsinaceae. The new family comprises a single genus, Maesa Forssk., with some 100 species of trees or shrubs; it is diagnosed by characters such as flower pedicels with two bracteoles, a semi-inferior ovary, and indehiscent fruits with many seeds. A key to the major groups of primuloid taxa is presented.
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| 11. |
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| 12. |
- Bäck, A., et al.
(författare)
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Walking the tightrope-perspectives on local politicians' role in implementing a national social care policy on evidence-based practice
- 2016
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Ingår i: International Journal of Mental Health Systems. - : BioMed Central Ltd.. - 1752-4458. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite national policy recommending evidence-based practice (EBP), its application in social care has been limited. While local politicians can affect the process, little is known about their knowledge, attitudes and roles regarding EBP. The aim here is twofold: to explore the role of local politicians in the implementation of EBP in social care from both their own and a management perspective; and to examine factors politicians perceive as affecting their decisions and actions concerning the implementation of EBP policy. Methods: Local politicians (N=13) and managers (N=22) in social care were interviewed. Qualitative thematic analysis with both inductive and deductive codes was used. Results: Politicians were rather uninformed regarding EBP and national policy. The factors limiting their actions were, beside the lack of awareness, lack of ability to question existing working methods, and a need for support in the steering of EBP. Thus, personal interest played a significant part in what role the politicians assumed. This resulted in some politicians taking a more active role in steering EBP while others were not involved. From the managers' perspective, a more active steering by politicians was desired. Setting budget and objectives, as well as active follow-up of work processes and outcomes, were identified as means to affect the implementation of EBP. However, the politicians seemed unaware of the facilitating effects of these actions. Conclusions: Local politicians had a possibility to facilitate the implementation of EBP, but their role was unclear. Personal interest played a big part in determining what role was taken. The results imply that social care politicians might need support in the development of their steering of EBP. Moving the responsibility for EBP facilitation upwards in the political structure could be an important step in developing EBP in social care.
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| 13. |
- Franzén, Lovisa, et al.
(författare)
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Spatially resolved transcriptomics of human and mouse fibrotic lung
- 2022
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 60
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by progressive and irreversible scarring of the lung tissue. Development of new efficacious and safe treatments is hampered by limited understanding of disease pathogenesis, lack of predictive preclinical models, and narrow therapeutic index of candidate drugs targeting complex biologies. Here, we tackle these aspects by generating spatially resolved transcriptomic maps of fibrotic lungs from clinical samples and a preclinical mouse model. We utilized the Visium platform to study parenchyma biopsies from four healthy lungs and regions of varying fibrotic severity from four IPF patient lungs. By mapping single cell RNA-seq data spatially, we were able to detect distinct fibroblast populations in different regions of the lesioned IPF lung, as well as the presence of various immune cell populations. To study lung fibrosis preclinically in vivo, the bleomycin mouse model is the most widely used alternative, although its translatability to human disease is disputed. Visium data from mouse lungs collected at two time points following bleomycin administration were generated, which allowed us to characterize the fibrotic lesions and inflammatory areas in their spatiotemporal context. In addition, mass spectrometry imaging was performed on adjacent tissue sections to provide paired spatial metabolomics. Herein, we have generated spatial maps of the lung fibrosis transcriptome from IPF lung biopsies and bleomycin-injured mouse lungs, providing an extensive resource to probe disease pathogenesis and animal model translatability.
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| 14. |
- Hedén Ståhl, Christina, 1972, et al.
(författare)
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Glycaemic control and excess risk of ischaemic and haemorrhagic stroke in patients with type 1 diabetes: a cohort study of 33 453 patients
- 2017
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Ingår i: Journal of internal medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 281:3, s. 261-272
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To estimate the excess risk of stroke in relation to glycaemic control in patients with type 1 diabetes. METHODS: In this prospective, matched cohort study, we identified patients with type 1 diabetes, aged >/=18 years, who were registered in the Swedish National Diabetes Register from 1998-2011 and five control subjects for each case from the general population, matched for age, sex and county of residence. The risks of all strokes, ischaemic stroke and haemorrhagic stroke were estimated using Cox hazard regression. RESULTS: Of 33 453 type 1 diabetes patients [mean age, 35.5 (SD 14.4) years; mean follow-up, 7.9 (SD 4.3) years; and mean diabetes duration, 20.2 years (SD 14.6)], 762 (2.3%) were diagnosed with stroke compared with 1122 (0.7%) of 159 924 control subjects [mean follow-up, 8.2 (SD 4.3) years]. The overall multiple-adjusted hazard ratios (HRs) for type 1 diabetes patients versus control subjects were 3.29 (95% CI: 2.96-3.66) and 2.49 (95% CI: 1.96-3.16) for ischaemic and haemorrhagic stroke, respectively. The risk of ischaemic and haemorrhagic stroke incrementally increased with increasing HbA1c; the risk of ischaemic stroke was significantly increased with HbA1c within target [/=9.7% (>/=83 mmol mol-1 ), there was a markedly increased risk of both ischaemic and haemorrhagic stroke, with multiple-adjusted HRs of 7.94 (95% CI: 6.29-10.03) and 8.17 (95% CI 5.00-13.35), respectively. CONCLUSIONS: Individuals with type 1 diabetes have an increased risk of ischaemic and haemorrhagic stroke, increasing markedly with poor glycaemic control.
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| 15. |
- Hedén Ståhl, Christina, 1972, et al.
(författare)
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Long-term excess risk of stroke in people with Type 2 diabetes in Sweden according to blood pressure level: a population-based case-control study
- 2017
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Ingår i: Diabetic medicine : a journal of the British Diabetic Association. - : Wiley. - 1464-5491 .- 0742-3071. ; 34:4, s. 522-530
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To estimate the risk of stroke in people with Type 2 diabetes with different blood pressure levels compared with the risk in the general population in Sweden. METHODS: This prospective case-control study included 408 076 people with Type 2 diabetes, aged >/=18 years, and free of prior stroke, registered in the Swedish National Diabetes Register 1998-2011. Age- and sex-matched control subjects (n=1 913 507) without stroke from the general population were included. Stroke diagnoses were retrieved using International Classification of Disease codes from the Swedish patient and death registers. Cox hazard ratios and 95% confidence intervals (CIs) were estimated at six different blood pressure levels. RESULTS: During a median follow-up of 4 years, 19 548 (4.8%) people with Type 2 diabetes and 61 690 (3.2%) without diabetes were diagnosed with stroke, corresponding to an adjusted hazard ratio of 1.43 (95% CI 1.41-1.46) for people with Type 2 diabetes as a group. Compared with people without diabetes, the risk of stroke for people with Type 2 diabetes with different blood pressure levels was significantly higher, starting at blood pressure levels >130/80 mmHg. Hazard ratios for stroke were 1.20 (95% CI 1.16-1.24), 1.47 (95% CI 1.43-1.50), and 1.97 (95% CI 1.90-2.03) for blood pressure categories of 130-139/80-89 mmHg, 140-159/90-99 mmHg and >/=160/>/=100 mmHg, respectively, after adjustment for age, sex, diabetes duration, being born in Sweden, maximum education level and baseline comorbidities. CONCLUSIONS: People with Type 2 diabetes and blood pressure < 130/80 mmHg had a risk of stroke similar to that of the general population. This article is protected by copyright. All rights reserved.
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| 16. |
- Jakobsson, Martin, et al.
(författare)
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Ryder Glacier in northwest Greenland is shielded from warm Atlantic water by a bathymetric sill
- 2020
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Ingår i: Communications Earth & Environment. - : Springer Science and Business Media LLC. - 2662-4435. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- The processes controlling advance and retreat of outlet glaciers in fjords draining the Greenland Ice Sheet remain poorly known, undermining assessments of their dynamics and associated sea-level rise in a warming climate. Mass loss of the Greenland Ice Sheet has increased six-fold over the last four decades, with discharge and melt from outlet glaciers comprising key components of this loss. Here we acquired oceanographic data and multibeam bathymetry in the previously uncharted Sherard Osborn Fjord in northwest Greenland where Ryder Glacier drains into the Arctic Ocean. Our data show that warmer subsurface water of Atlantic origin enters the fjord, but Ryder Glacier’s floating tongue at its present location is partly protected from the inflow by a bathymetric sill located in the innermost fjord. This reduces under-ice melting of the glacier, providing insight into Ryder Glacier’s dynamics and its vulnerability to inflow of Atlantic warmer water.
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| 17. |
- Karpman, D, et al.
(författare)
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Platelet activation in hemolytic uremic syndrome
- 2006
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Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag. - 0094-6176 .- 1098-9064. ; 32:2, s. 128-145
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Tidskriftsartikel (refereegranskat)abstract
- Platelet consumption in platelet-fibrin aggregates leading to thrombocytopenia and small vessel obstruction are major features of the hemolytic uremic syndrome (HUS). Although thrombocytopenia has been correlated to poor prognosis, the mechanisms by which thrombocytopenia develops in HUS have not been completely elucidated. However, plausible explanations have been platelet contact with thrombogenic surfaces and/or direct contact with an aggregating agent. This article summarizes several mechanisms of platelet activation, interactions with leukocytes, chemokine release, complement activation, and antimicrobial defense. Specific mechanisms are outlined by which platelets may be activated, leading to thrombocytopenia during HUS. In diarrhea-associated HUS Shiga toxin has been shown to injure the endothelium, thus exposing the subendothelium, releasing tissue factor, and rendering the vessel wall prothrombotic. Shiga toxin also binds to and activates platelets. The toxin may activate endothelial cells and platelets simultaneously. In atypical HUS the alternative complement pathway is activated because of mutations in complement regulatory proteins. Mutated factor H does not bind to endothelium and platelets efficiently, enabling complement activation on these cells. In thrombotic thrombocytopenic purpura, intravascular platelet clotting Occurs due to dysfunction of the von Willebrand factor (VWF)-cleaving protease ADAMTS13. Thrombi are formed by binding of platelets to ultralarge VWF multimers.
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| 18. |
- Kronqvist, Nina
(författare)
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Staphylococcal surface display in directed evolution
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Engineered affinity proteins have together with naturally derived antibodies becomeindispensable tools in many areas of life-science and with the increasing number ofapplications, the need for high-throughput methods for generation of such different affinityproteins is evident. Today, combinatorial protein engineering is the most successful strategy toisolate novel non-immunoglobulin affinity proteins. In this approach, generally termed directedevolution, high-complexity combinatorial libraries are created from which affinity proteins areisolated using an appropriate selection method, thus circumventing the need for detailedknowledge of the protein structure or the binding mechanism, often necessary in more rationalapproaches. Since the introduction of the phage display technology that pioneered the field ofcombinatorial engineering, several alternative selection systems have been developed for thispurpose.This thesis describes the development of a novel selection system based onstaphylococcal surface display and its implementation in directed evolution approaches. In thefirst study, the transformation efficiency to the gram-positive bacteria Staphylococcus carnosus wassuccessfully improved around 10,000-fold to a level that would allow cell surface display ofcomplex combinatorial protein libraries. In two separate studies, the staphylococcal displaysystem was investigated for the applicability in both de novo selection and affinity maturation ofaffibody molecules. First, using a pre-selection strategy with one round of phage display, ahigh-complexity affibody library was displayed on staphylococcal cells. Using fluorescenceactivatedcell sorting, binders with sub-nanomolar affinity to tumor necrosis factor-alpha(TNF-α) were isolated. Second, a combined approach using phage display for de novo selectionof first-generation affibody binders and staphylococcal display in a subsequent affinitymaturation selection was applied to generate binders with low nanomolar affinity to the humanepidermal growth factor receptor-3 (ErbB3). Moreover, in an additional study, thestaphylococcal surface display system was improved by the introduction of a protease 3Ccleavage sequence in the displayed fusion products in order to facilitate straightforwardproduction of soluble proteins for further downstream characterization.Altogether, the presented studies demonstrate that the staphylococcal selection systemindeed is a powerful tool for selection and characterization of novel affinity proteins and couldbecome an attractive alternative to existing selection techniques.
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| 19. |
- Laakso, S.V.A., et al.
(författare)
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Too Sharp for its Own Good – Tool Edge Deformation Mechanisms in the Initial Stages of Metal Cutting
- 2017
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Ingår i: Procedia Manufacturing. - : Elsevier BV. - 2351-9789. ; 11, s. 449-456
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 Metal cutting simulations have become an important part of cutting tool design and the research in the field in general. One of the most important aspects of modeling is the accuracy of the tool geometry. 3D microscopy is used for measuring the tool edge radius with good accuracy. However, especially with sharp tools, i.e. small tool edge radii, the measurements, no matter how accurate, are not much of a use, since the initial wear, or deformation is so fast in the first 1-30 seconds into the cutting, that the tool geometry is significantly different than the one measured from the new tool. The average tool life is often set to 15 minutes. Therefore, the cutting simulations that only predict the tool behavior in the first seconds of its lifetime are not very useful in predicting the process variables throughout the tool life. Simulations with creep and elastic-plastic material model however, can predict the initial deformation of the tool. This tool shape can be then used in rigid tool model to predict the process variables in the steady wear region of the tool life. This paper presents simulation model for predicting the initial tool edge deformation for WC-10%Co tool while machining AISI 304 stainless steel. The novelty in this approach is the simultaneous coupled calculation of contact surface temperature and stress and change of the tool shape.
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| 20. |
- Magnusson, Maria K, 1972, et al.
(författare)
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Adenovirus 5 vector genetically re-targeted by an Affibody molecule with specificity for tumor antigen HER2/neu.
- 2007
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Ingår i: Cancer gene therapy. - : Springer Science and Business Media LLC. - 0929-1903 .- 1476-5500. ; 14:5, s. 468-79
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Tidskriftsartikel (refereegranskat)abstract
- In order to use adenovirus (Ad) type 5 (Ad5) for cancer gene therapy, Ad needs to be de-targeted from its native receptors and re-targeted to a tumor antigen. A limiting factor for this has been to find a ligand that (i) binds a relevant target, (ii) is able to fold correctly in the reducing environment of the cytoplasm and (iii) when incorporated at an optimal position on the virion results in a virus with a low physical particle to plaque-forming units ratio to diminish the viral load to be administered to a future patient. Here, we present a solution to these problems by producing a genetically re-targeted Ad with a tandem repeat of the HER2/neu reactive Affibody molecule (ZH) in the HI-loop of a Coxsackie B virus and Ad receptor (CAR) binding ablated fiber genetically modified to contain sequences for flexible linkers between the ZH and the knob sequences. ZH is an Affibody molecule specific for the extracellular domain of human epidermal growth factor receptor 2 (HER2/neu) that is overexpressed in inter alia breast and ovarian carcinomas. The virus presented here exhibits near wild-type growth characteristics, infects cells via HER2/neu instead of CAR and represents an important step toward the development of genetically re-targeted adenoviruses with clinical relevance.
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| 21. |
- Martinsson, T, et al.
(författare)
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Tumorigenicity of SEWA murine tumor cells correlates with degree of c-myc amplification
- 1988
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Ingår i: Oncogene. - : Nature Publishing Group. - 0950-9232 .- 1476-5594. ; 3:4, s. 437-441
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown that cells of the SEWA mouse tumor contain amplified copies of the proto-oncogene c-myc in the aberrant chromosomal structures of double minutes (DMs), homogeneously staining regions (HSRs) and C-bandless chromosomes (CMs). DMs, and to a lesser degree CMs, tend to disappear from the cells grown in vitro and again reappear after transfer back in vivo, as if DNA amplification confers a growth advantage upon the tumor cells. We have now isolated five in vitro clones that exhibit different degrees of c-myc amplification. When we inoculated cells of the different clones into compatible hosts, we found that there was a positive correlation between degree of c-myc amplification, level of c-myc RNA, and tumorigenicity. Our results lend further support to the idea that gene amplification contributes to the higher malignant phenotype, and to progression of tumors.
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| 22. |
- Massier, Lucas, et al.
(författare)
-
An integrated single cell and spatial transcriptomic map of human white adipose tissue
- 2023
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Single-cell studies of human white adipose tissue (WAT) provide insights into the specialized cell types in the tissue. Here the authors combine publicly available and newly generated high-resolution and bulk transcriptomic results from multiple human datasets to provide a comprehensive cellular map of white adipose tissue. To date, single-cell studies of human white adipose tissue (WAT) have been based on small cohort sizes and no cellular consensus nomenclature exists. Herein, we performed a comprehensive meta-analysis of publicly available and newly generated single-cell, single-nucleus, and spatial transcriptomic results from human subcutaneous, omental, and perivascular WAT. Our high-resolution map is built on data from ten studies and allowed us to robustly identify >60 subpopulations of adipocytes, fibroblast and adipogenic progenitors, vascular, and immune cells. Using these results, we deconvolved spatial and bulk transcriptomic data from nine additional cohorts to provide spatial and clinical dimensions to the map. This identified cell-cell interactions as well as relationships between specific cell subtypes and insulin resistance, dyslipidemia, adipocyte volume, and lipolysis upon long-term weight changes. Altogether, our meta-map provides a rich resource defining the cellular and microarchitectural landscape of human WAT and describes the associations between specific cell types and metabolic states.
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| 23. |
- Sandén, Emma, et al.
(författare)
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Aberrant immunostaining pattern of the CD24 glycoprotein in clinical samples and experimental models of pediatric medulloblastomas
- 2015
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Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 123:1, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- The CD24 glycoprotein is a mediator of neuronal proliferation, differentiation and immune suppression in the normal CNS, and a proposed cancer biomarker in multiple peripheral tumor types. We performed a comparative analysis of CD24 gene expression in a large cohort of pediatric and adult brain tumors (n = 813), and further characterized protein expression in tissue sections (n = 39), primary brain tumor cultures (n = 12) and a novel orthotopic group 3 medulloblastoma xenograft model. Increased CD24 gene expression was demonstrated in ependymomas, medulloblastomas, anaplastic astrocytomas and glioblastomas, although medulloblastomas displayed higher expression than all other tumor entities. Preferential expression of CD24 in medulloblastomas was confirmed at protein level by immunostaining and computerized image analysis of cryosections. Morphologies and immunophenotyping of CD24(+) cells in tissue sections tentatively suggested disparate functions in different tumor subsets. Notably, protein staining of medulloblastoma cells was associated with prominent cytoplasmic and membranous granules, enabling rapid and robust identification of medulloblastoma cells in clinical tissue samples, as well as in experimental model systems. In conclusion, our results implicate CD24 as a clinically and experimentally useful medulloblastoma immunomarker. Although our results encourage further functional studies of CD24 as a potential molecular target in subsets of brain tumors, the promiscuous expression of CD24 in vivo highlights the importance of specificity in the future design of such targeted treatment.
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| 24. |
- Ståhl, Olof, et al.
(författare)
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Risk of Birth Abnormalities in the Offspring of Men With a History of Cancer: A Cohort Study Using Danish and Swedish National Registries.
- 2011
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 103, s. 398-406
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Tidskriftsartikel (refereegranskat)abstract
- Background The potential mutagenic effects of cancer therapies and the growing number of young male cancer survivors have given rise to concern about the health of their offspring. Methods We identified all singleton children born alive in Denmark between 1994 and 2004 and in Sweden between 1994 and 2005 (n = 1 777 765). Of the 8670 children with a paternal history of cancer, 8162 were conceived naturally and 508 were conceived using assisted reproductive technologies (ARTs) (in vitro fertilization or intracytoplasmatic sperm injection). Of the 1 769 0795 children without a paternal history of cancer, 25 926 were conceived using ARTs. Associations between paternal history of cancer and risk of adverse birth outcomes of children conceived naturally or by ARTs were investigated using log-linear binomial models, yielding risk ratios (RRs) with 95% confidence intervals (CIs). All statistical tests were two-sided. Results The offspring of male cancer survivors were more likely to have major congenital abnormalities than the offspring of fathers with no history of cancer (RR = 1.17, 95% CI = 1.05 to 1.31, P = .0043, 3.7% vs 3.2%). However, the mode of conception (natural conception or ARTs) did not modify the association between paternal history of cancer and risk of congenital abnormalities (natural conception, RR = 1.17, 95% CI = 1.04 to 1.31; ARTs, RR = 1.22, 95% CI = 0.80 to 1.87, P(interaction) = .84). Conclusion We observed a statistically significant but modest increase in the risk of major congenital abnormalities among offspring of males with a history of cancer, independent of the mode of conception.
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| 25. |
- Tandstad, T., et al.
(författare)
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One course of adjuvant BEP in clinical stage I nonseminoma mature and expanded results from the SWENOTECA group
- 2014
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 25:11, s. 2167-2172
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Tidskriftsartikel (refereegranskat)abstract
- The SWENOTECA group treated 517 clinical stage I nonseminoma patients with one course of adjuvant BEP in a prospective study. The median follow-up is 7.9 years. One course of adjuvant BEP reduced the risk of relapse by over 90%. The relapse rates were 1.6% in low-risk disease and 3.2% in high-risk disease. One course of adjuvant BEP should be considered a standard adjuvant treatment option.SWENOTECA has since 1998 offered patients with clinical stage I (CS I) nonseminoma, adjuvant chemotherapy with one course of bleomycin, etoposide and cisplatin (BEP). The aim has been to reduce the risk of relapse, sparing patients the need of toxic salvage treatment. Initial results on 312 patients treated with one course of adjuvant BEP, with a median follow-up of 4.5 years, have been previously published. We now report mature and expanded results. In a prospective, binational, population-based risk-adapted treatment protocol, 517 Norwegian and Swedish patients with CS I nonseminoma received one course of adjuvant BEP. Patients with lymphovascular invasion (LVI) in the primary testicular tumor were recommended one course of adjuvant BEP. Patients without LVI could choose between surveillance and one course of adjuvant BEP. Data for patients receiving one course of BEP are presented in this study. At a median follow-up of 7.9 years, 12 relapses have occurred, all with IGCCC good prognosis. The latest relapse occurred 3.3 years after adjuvant treatment. The relapse rate at 5 years was 3.2% for patients with LVI and 1.6% for patients without LVI. Five-year cause-specific survival was 100%. The updated and expanded results confirm a low relapse rate following one course of adjuvant BEP in CS I nonseminoma. One course of adjuvant BEP should be considered a standard treatment in CS I nonseminoma with LVI. For patients with CS I nonseminoma without LVI, one course of adjuvant BEP is also a treatment option.
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| 26. |
- Wikman, Maria, et al.
(författare)
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Applying biotin-streptavidin binding for iscom (immunostimulating complex) association of recombinant immunogens
- 2005
-
Ingår i: Biotechnology and applied biochemistry. - 0885-4513 .- 1470-8744. ; 41, s. 163-174
-
Tidskriftsartikel (refereegranskat)abstract
- We have previously reported strategies for Escherichia coli production of recombinant immunogens fused to hydrophobic peptide or lipid tags to improve their capacity to be incorporated into an adjuvant formulation. In the present study, we have explored the strong interaction between biotin and SA (streptavidin) (K-D approximate to 10(-15) M) to couple recombinant immunogens to iscoms (immunostimulating complexes). Two different concepts were evaluated. In the first concept, a His(6)-tagged SA fusion protein (His(6)-SA) was bound to Ni2+-loaded iscom matrix (iscom without associated protein), and biotinylated immunogens were thereafter associated with the SA-coated iscoms. The immunogens were either biotinylated in vivo on E. coli expression or double biotinylated in vivo and in vitro. In the second concept, the recombinant immunogens were expressed as SA fusion proteins, which were directly bound to a biotinylated iscom matrix. A 53-amino-acid malaria peptide (M), derived from the central repeat region of the Plasmodium faiciparum blood-stage antigen Pf155/RESA, and a 232-amino-acid segment (SRS2') from the central region (from Pro-97 to Lys-328) of the major surface antigen NcSRS2 of the protozoan parasite Neospora caninum, served as model immunogens in the present study. All fusion proteins generated were found to be efficiently expressed and could be recovered to high purity using affinity chromatography. The association between the different immunogen-containing fusion proteins and the corresponding iscom matrix was demonstrated by analytical ultracentrifugation in a sucrose density gradient. However, some fusion proteins were, to a certain extent, also found to associate unspecifically with a regular iscom matrix. Furthermore, selected iscom fractions were demonstrated to induce high-titre antigen-specific antibody responses on immunization of mice. For the particular target immunogen SRS2', the induced antibodies demonstrated reactivity to the native antigen NcSRS2. We believe that the presented concepts offer convenient methods to achieve efficient adjuvant association of recombinant immunogens, and the advantages and disadvantages of the two concepts are discussed.
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| 27. |
- Wikman, Maria, et al.
(författare)
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General strategies for efficient adjuvant incorporation of recombinant subunit immunogens
- 2005
-
Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 23:17-18, s. 2331-2335
-
Tidskriftsartikel (refereegranskat)abstract
- We have previously reported strategies for Escherichia coli production of recombinant immunogens fused to hydrophobic peptides or lipid tags to improve their capacity to be incorporated into an adjuvant formulation, e.g., immunostimulating complexes (iscoms). Recently, we also explored the strong interaction between biotin and streptavidin to achieve iscom association of recombinant immunogens. Plasmodium falciparum, Toxoplasma gondii and Neospora caninum antigens have served as model immunogens in the different studies. Generated fusion proteins have been found to be successfully incorporated into iscoms and high-titer antigen-specific antibody responses have been obtained upon immunization of mice. We believe that the different concepts presented, utilizing either hydrophobic peptide or lipid tags, or the recently explored biotin-streptavidin principle, offer convenient methods to achieve efficient adjuvant incorporation of recombinant immunogens.
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| 28. |
- Agaton, C., et al.
(författare)
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Affinity proteomics for systematic protein profiling of chromosome 21 gene products in human tissues
- 2003
-
Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 2, s. 405-
-
Tidskriftsartikel (refereegranskat)abstract
- Here we show that an affinity proteomics strategy using affinity-purified antibodies raised against recombinant human protein fragments can be used for chromosome-wide protein profiling. The approach is based on affinity reagents raised toward bioinformatics-designed protein epitope signature tags corresponding to unique regions of individual gene loci. The genes of human chromosome 21 identified by the genome efforts were investigated, and the success rates for de novo cloning, protein production, and antibody generation were 85, 76, and 56%, respectively. Using human tissue arrays, a systematic profiling of protein expression and subcellular localization was undertaken for the putative gene products. The results suggest that this affinity proteomics strategy can be used to produce a proteome atlas, describing distribution and expression of proteins in normal tissues as well as in common cancers and other forms of diseased tissues.
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| 29. |
- Agmell, M., et al.
(författare)
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Modeling subsurface deformation induced by machining of Inconel 718
- 2017
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Ingår i: Machining Science and Technology. - : Informa UK Limited. - 1091-0344 .- 1532-2483. ; 21:1, s. 103-120
-
Tidskriftsartikel (refereegranskat)abstract
- Traditionally, the development and optimization of the machining process with regards to the subsurface deformation are done through experimental method which is often expensive and time consuming. This article presents the development of a finite element model based on an updated Lagrangian formulation. The numerical model is able to predict the depth of subsurface deformation induced in the high- speed machining of Inconel 718 by use of a whisker-reinforced ceramic tool. The effect that the different cutting parameters and tool microgeometries has on subsurface deformation will be investigated both numerically and experimentally. This research article also addresses the temperature distribution in the workpiece and the connection it could have on the wear of the cutting tool. The correlation of the numerical and experimental investigations for the subsurface deformation has been measured by the use of the coefficient of determination, R2. This confirms that the finite element model developed here is able to simulate this type of machining process with sufficient accuracy.
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| 30. |
- Agmell, Mathias, et al.
(författare)
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The Influence the Uncut Chip Thickness has on the Stagnation Point in Orthogonal Cutting
- 2017
-
Ingår i: 16th CIRP Conference on Modelling of Machining Operations (16th CIRP CMMO). - : Elsevier BV. - 2212-8271. - 9781510842762 ; 58, s. 13-18
-
Konferensbidrag (refereegranskat)abstract
- The effect of cutting data on the stagnation zone of a machining operation is of great interest since it governs the material flow around the cutting edge. The material flow has a significant influence on the mechanical properties of the machined surface. This paper presents a numerical model that is able to determine the effect that the uncut chip thickness has on the stagnation zone and the connection between the stagnation zone and the deformation layer in the machined subsurface.
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| 31. |
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| 32. |
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| 33. |
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| 34. |
- Arvola Orlander, A., et al.
(författare)
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Towards an Understanding of Diffractive Readings of Narratives in the Field of Science Education
- 2018
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Ingår i: Cultural, Social and Political Prespectives in Science Education. - Cham, Switzerland : Springer International Publishing AG. - 1879-7229 .- 1879-7237. - 9783319611907 ; , s. 139-152
-
Bokkapitel (refereegranskat)abstract
- In this chapter we seek to challenge the positivistic and traditional way of doing research in the field of science education by turning to posthuman approaches to analyse our data. Feeling trapped in doing research where objects are regarded as having inherent boundaries and fixed properties, we have read data with and through a feminist materialist lens. We are curious to understand how posthuman approaches to explore ways of doing research can be mobilized using Karen Barad’s and Donna Haraway’s theories of diffractive reading. Our aim has been to open up the data to diffract it for new images and thereby to trouble the human centred and objective perspectives of doing research. Instead of taking a distance from our objects of research the diffractive reading has meant that we have infiltrated with our data, a student text and an excerpt from a classroom observation. We have allowed the data to influence us as well as the other way around and thus regarded the research objects as equivalent to ourselves in terms of agency. What came out of this way to tackle our research material is partly a different view of ourselves as scientists and the research objects as having agency, a more intrinsic, emotionally influenced and embodied view. We have got hold of our prejudices and exposed them instead of trying to pretend that they do not exist. Thereby we have taken ethical responsibility in this transparency as well as when seeing the “object” as equally active and meaning making as ourselves. Emotions have been brought to the surface and been used, since we cannot pretend that we are a mind without a body as the Cartesian thought stipulates and which natural science is still leaning on. We think that using the diffractive reading tool from a material feminist perspective has given us insights that would not have been possible to get when taking the anthropocentric and positivistic perspective. It has also proven to be a more honest and thereby more ethical alternative compared to the positivistic version. We have got a better scientific description of the world, a view from somewhere that Haraway asks for (1991).
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| 35. |
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| 36. |
- Behboudi, A, et al.
(författare)
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Functional significance of absence : The chromosomal segment harboring the Tp53 gene is missing in the T55 rat radiation hybrid mapping panel
- 2002
-
Ingår i: Genomics. - : Academic Press. - 0888-7543 .- 1089-8646. ; 79:6, s. 844-848
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Tidskriftsartikel (refereegranskat)abstract
- The T55 rat radiation hybrid (RH) mapping panel has been reported to retain the entire rat genome at retention frequencies between 22% and 37%. However, we found that a small segment of rat chromosome 10 harboring at least four different genes, including Tp53, was completely absent from the panel (retention frequency = 0%). Two other markers located in the vicinity exhibited much reduced retention (2–6%). RH clones are generated by transferring highly fragmented DNA into a recipient cell. There might be a strong selection against the transfer and retention of chromosome segments harboring an intact Tp53, as the action of this gene might prevent proliferation and establishment of the RH clone. Our finding further suggests that unexpected low retention or absence of chromosome segments in an RH panel may represent indications that the segments harbor genes with important functions in cell proliferation control.
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| 37. |
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| 38. |
- Bruder, Carl E G, et al.
(författare)
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Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles
- 2008
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 82:3, s. 763-71
-
Tidskriftsartikel (refereegranskat)abstract
- The exploration of copy-number variation (CNV), notably of somatic cells, is an understudied aspect of genome biology. Any differences in the genetic makeup between twins derived from the same zygote represent an irrefutable example of somatic mosaicism. We studied 19 pairs of monozygotic twins with either concordant or discordant phenotype by using two platforms for genome-wide CNV analyses and showed that CNVs exist within pairs in both groups. These findings have an impact on our views of genotypic and phenotypic diversity in monozygotic twins and suggest that CNV analysis in phenotypically discordant monozygotic twins may provide a powerful tool for identifying disease-predisposition loci. Our results also imply that caution should be exercised when interpreting disease causality of de novo CNVs found in patients based on analysis of a single tissue in routine disease-related DNA diagnostics.
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| 39. |
- Buckley, Patrick G, et al.
(författare)
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A full-coverage, high-resolution human chromosome 22 genomic microarrayfor clinical and research applications
- 2002
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 11:25, s. 3221-3229
-
Tidskriftsartikel (refereegranskat)abstract
- We have constructed the first comprehensive microarray representing a human chromosome for analysis of DNA copy number variation. This chromosome 22 array covers 34.7 Mb, representing 1.1% of the genome, with an average resolution of 75 kb. To demonstrate the utility of the array, we have applied it to profile acral melanoma, dermatofibrosarcoma, DiGeorge syndrome and neurofibromatosis 2. We accurately diagnosed homozygous/heterozygous deletions, amplifications/gains, IGLV/IGLC locus instability, and breakpoints of an imbalanced translocation. We further identified the 14-3-3 eta isoform as a candidate tumor suppressor in glioblastoma. Two significant methodological advances in array construction were also developed and validated. These include a strictly sequence defined, repeat-free, and non-redundant strategy for array preparation. This approach allows an increase in array resolution and analysis of any locus; disregarding common repeats, genomic clone availability and sequence redundancy. In addition, we report that the application of phi29 DNA polymerase is advantageous in microarray preparation. A broad spectrum of issues in medical research and diagnostics can be approached using the array. This well annotated and gene-rich autosome contains numerous uncharacterized disease genes. It is therefore crucial to associate these genes to specific 22q-related conditions and this array will be instrumental towards this goal. Furthermore, comprehensive epigenetic profiling of 22q-located genes and high-resolution analysis of replication timing across the entire chromosome can be studied using our array.
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| 40. |
- Buckley, Patrick G., et al.
(författare)
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Identification of genetic aberrations on chromosome 22 outside the NF2 locus in schwannomatosis and neurofibromatosis type 2
- 2005
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 26:6, s. 540-9
-
Tidskriftsartikel (refereegranskat)abstract
- Schwannomatosis is characterized by multiple peripheral and cranial nerve schwannomas that occur in the absence of bilateral 8th cranial nerve schwannomas. The latter is the main diagnostic criterion of neurofibromatosis type 2 (NF2), which is a related but distinct disorder. The genetic factors underlying the differences between schwannomatosis and NF2 are poorly understood, although available evidence implicates chromosome 22 as the primary location of the gene(s) of interest. To investigate this, we comprehensively profiled the DNA copy number in samples from sporadic and familial schwannomatosis, NF2, and a large cohort of normal controls. Using a tiling-path chromosome 22 genomic array, we identified two candidate regions of copy number variation, which were further characterized by a PCR-based array with higher resolution. The latter approach allows the detection of minute alterations in total genomic DNA, with as little as 1.5 kb per measurement point of nonredundant sequence on the array. In DNA derived from peripheral blood from a schwannomatosis patient and a sporadic schwannoma sample, we detected rearrangements of the immunoglobulin lambda (IGL) locus, which is unlikely to be due to a B-cell specific somatic recombination of IGL. Analysis of normal controls indicated that these IGL rearrangements were restricted to schwannomatosis/schwannoma samples. In the second candidate region spanning GSTT1 and CABIN1 genes, we observed a frequent copy number polymorphism at the GSTT1 locus. We further describe missense mutations in the CABIN1 gene that are specific to samples from schwannomatosis and NF2 and make this gene a plausible candidate for contributing to the pathogenesis of these disorders.
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| 41. |
- Buechler, Daniela, et al.
(författare)
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A Critical Mapping of Practice-Based Research as Evidenced by Swedish Architectural Theses
- 2011
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Ingår i: International Journal of Art & Design Education. - : Wiley. - 1476-8062. ; 30:2, s. 318-327
-
Tidskriftsartikel (refereegranskat)abstract
- This article presents an investigation that was funded by the Swedish Institute into the role of creative practice in architectural research as evidenced in Swedish doctoral theses. The sample was mapped and analysed in terms of clusters of interest, approaches, cultures of knowledge and uses of creative practice. This allowed the identification of the ontological, epistemological and methodological attitudes of the researchers, and hence a glimpse of their implicit worldview. The authors claim that the relationship between worldview and research actions in emerging areas of research such as architecture is often under-scrutinised, resulting in a disjunction between aims and strategies for action. Architectural research in which creative practices make an essential contribution to the aims, might represent something new in academic research. The investigators therefore focused on identifying cases in which creative practice was or was claimed to be integrated in an essential way into the research process. There were two principal conclusions. The first was that the mere presence of practice was not necessarily an indicator of so-called arts-based research. The second was that cases of arts-based research that could be regarded as a new paradigm as opposed to a variant of existing paradigms are less common than is claimed by the researchers themselves. As a result, this article makes a contribution to the debate on whether so-called practice-based research should be regarded as a distinct new paradigm.
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| 42. |
- Cano, F., et al.
(författare)
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Partial protection to respiratory syncytial virus (RSV) elicited in mice by intranasal immunization using live staphylococci with surface-displayed RSV-peptides
- 2000
-
Ingår i: Vaccine. - 0264-410X .- 1873-2518. ; 18:24, s. 2743-2752
-
Tidskriftsartikel (refereegranskat)abstract
- A live bacterial vaccine-delivery system based on the food-grade bacterium Staphylococcus carnosus was used for delivery of peptides from the G glycoprotein of human respiratory syncytial virus, subtype A (RSV-A). Three peptides, corresponding to the G protein amino acids, 144-159 (denoted G5), 190-203 (G9) and 171-188 (G4 S), the latter with four cysteine residues substituted for serines, were expressed by recombinant means as surface-exposed on three different bacteria, and their surface accessibility on the bacteria was verified by fluorescence-activated cell sorting (FACS). Intranasal immunization of mice with the live recombinant staphylococci elicited significant anti-peptide as well as anti-virus serum IgG responses of balanced IgG1/IgG2a isotype profiles, and upon viral challenge with 10(5) tissue culture infectious doses(50) (TCID50), lung protection was demonstrated for approximately half of the mice in the G9 and G4 S immunization groups. To our knowledge, this is the first study in which protective immunity to a viral pathogen has been evoked using food-grade bacteria as vaccine-delivery vehicles.
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| 43. |
- Collentine, D., et al.
(författare)
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Catch : Decision support for stakeholders in catchment areas
- 2002
-
Ingår i: Water Policy. - 1366-7017 .- 1996-9759. ; 4:5, s. 447-463
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Forskningsöversikt (refereegranskat)abstract
- Policy proposals for the management of water resources need to take into account two emerging themes: public involvement in the development of resource use policy and water management on a catchment level. The CATCH-model, a decision support system for catchment-based water management, builds on the use of 'discourse and deliberation' within stakeholder groups to define relevant socio-economic parameters and the relationships between these parameters. The sets of matrices that describe these parameters and their interrelation serve as the basis for evaluation of alternative management strategies and evaluation of specific measures for improving water quality. © 2002 Elsevier Science Ltd. All rights reserved.
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| 44. |
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| 45. |
- Danielsson, Marcus, 1985-
(författare)
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Mosaic loss of chromosome Y : methods for detection and consequences for affected leukocytes and men
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It has been known for centuries that men live shorter lives than women, but until recently, the biological mechanisms driving this sex bias has been poorly understood. Mosaic loss of chromosome Y (mLOY) refers to chromosome Y aneuploidy, a male specific and the most common somatic mutation in human blood cells. Known risk factors include age, smoking and genetic predisposition. Men with mLOY carry a fraction of blood cells without the Y chromosome, due to its loss from hematopoietic progenitor cells during life. Hence, in a single cell LOY is a binary event causing the absence of almost 2% of the male haploid nuclear genome. When measured in bulk samples, it is present as a continuous mosaicism affecting a fraction of cells. A paper published in 1963 demonstrated that mLOY is frequent in cells of the hematopoietic system in aging men, but it was long viewed as a neutral event. In contrast, recent discoveries demonstrate that mLOY in blood is associated with various forms of cancer, autoimmune conditions, Alzheimer’s disease, cardiovascular events, diabetes as well as age-related macular degeneration. Studies support the hypothesis that mLOY in leukocytes may exacerbate disease processes in other organs. Thus, given the associations with several common diseases, mLOY in blood cells could help explain reduced male longevity.A main aim and a long term goal of the work presented in this thesis is the development of novel methods for improved mLOY detection. Focus here is exploration of analytes such as DNA, RNA and proteins, including studies of bulk samples as well as single cell approaches. Among the evaluated methods are SNP-arrays, ddPCR, WGS, RNA-seq and CITE-seq. Furthermore, a novel method called SPARC was developed for co-detection of the transcriptome and a panel of 92 proteins in single cells. Future methods with clinical utility for mLOY should, in addition to robust detection, be able to simultaneously discriminate mLOY in different types of immune cells. The latter builds on recent results showing cell type specificity with regard to disease associations. To meet these needs, single cell analyses using mLOY associated cell surface proteins have been pursued and proof-of-concept established. Implementation of mLOY screening in general populations has the potential to identify men with increased risk for various disease. It could be envisioned that further medical examination of men affected with mLOY would enable earlier diagnoses of ongoing disease processes as well as serving to guide targeted interventions.
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| 46. |
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| 47. |
- Ellen, MacEachen, et al.
(författare)
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Systematic review of qualitative literature on occupational health and safety legislation and regulatory enforcement planning and implementation
- 2016
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : SCANDINAVIAN JOURNAL WORK ENVIRONMENT & HEALTH. - 0355-3140 .- 1795-990X. ; 42:1
-
Forskningsöversikt (refereegranskat)abstract
- Objective The ability of occupational health and safety (OHS) legislation and regulatory enforcement to prevent workplace injuries and illnesses is contingent on political, economic, and organizational conditions. This systematic review of qualitative research articles considers how OHS legislation and regulatory enforcement are planned and implemented. Methods A comprehensive search of peer-reviewed, English-language articles published between 1990 and 2013 yielded 11 947 articles. We identified 34 qualitative articles as relevant, 18 of which passed our quality assessment and proceeded to meta-ethnographic synthesis. Results The synthesis yielded four main themes: OHS regulation formation, regulation challenges, inspector organization, and worker representation in OHS. It illuminates how OHS legislation can be based on normative suppositions about worker and employer behavior and shaped by economic and political resources of parties. It also shows how implementation of OHS legislation is affected by "general duty" law, agency coordination, resourcing of inspectorates, and ability of workers to participate in the system. Conclusions The review identifies methodological gaps and promising areas for further research in "grey" zones of legislation implementation.
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| 48. |
- Erickson, Andrew, et al.
(författare)
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The spatial landscape of clonal somatic mutations in benign and malignant tissue
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Defining the transition from benign to malignant tissue is fundamental to improve early diagnosis of cancer. Here, we provide an unsupervised approach to study spatial genome integrity in situ to gain molecular insight into clonal relationships. We employed spatially resolved transcriptomics to infer spatial copy number variations in >120 000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of an unsupervised approach to capture the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.
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| 49. |
- Fleetwood, Filippa, et al.
(författare)
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An engineered autotransporter-based surface expression vector enables efficient display of Affibody molecules on OmpT-negative E. coli as well as protease-mediated secretion in OmpT-positive strains
- 2014
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Ingår i: Microbial Cell Factories. - : Springer Science and Business Media LLC. - 1475-2859. ; 13, s. 179-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cell display technologies (e.g. bacterial display) are attractive in directed evolution as they provide the option to use flow-cytometric cell sorting for selection from combinatorial libraries. The aim of this study was to engineer and investigate an expression vector system with dual functionalities: i) recombinant display of Affibody libraries on Escherichia coli for directed evolution and ii) small scale secreted production of candidate affinity proteins, allowing initial downstream characterizations prior to subcloning. Autotransporters form a class of surface proteins in Gram-negative bacteria that have potential for efficient translocation and tethering of recombinant passenger proteins to the outer membrane. We engineered a bacterial display vector based on the E. coli AIDA-I autotransporter for anchoring to the bacterial surface. Potential advantages of employing autotransporters combined with E. coli as host include: high surface expression level, high transformation frequency, alternative promoter systems available, efficient translocation to the outer membrane and tolerance for large multi-domain passenger proteins. Results: The new vector was designed to comprise an expression cassette encoding for an Affibody molecule, three albumin binding domains for monitoring of surface expression levels, an Outer membrane Protease T (OmpT) recognition site for potential protease-mediated secretion of displayed affinity proteins and a histidine-tag for purification. A panel of vectors with different promoters were generated and evaluated, and suitable cultivation conditions were investigated. The results demonstrated a high surface expression level of the different evaluated Affibody molecules, high correlation between target binding and surface expression level, high signal-to-background ratio, efficient secretion and purification of binders in OmpT-positive hosts as well as tight regulation of surface expression for the titratable promoters. Importantly, a mock selection using FACS from a 1: 100,000 background yielded around 20,000-fold enrichment in a single round and high viability of the isolated bacteria after sorting. Conclusions: The new expression vectors are promising for combinatorial engineering of Affibody molecules and the strategy for small-scale production of soluble recombinant proteins has the potential to increase throughput of the entire discovery process.
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- Goetsch, L., et al.
(författare)
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Influence of administration dose and route on the immunogenicity and protective efficacy of BBG2Na, a recombinant respiratory syncytial virus subunit vaccine candidate
- 2000
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Ingår i: Vaccine. - 0264-410X .- 1873-2518. ; 18:24, s. 2735-2742
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Tidskriftsartikel (refereegranskat)abstract
- The immunogenicity and protective efficacy of BBG2Na, a novel recombinant respiratory syncytial virus subunit vaccine candidate, was assessed in BALB/c mice under various conditions of dose, administration route and number of immunisations. A single intra-peritoneal (i.p.) dose of 2 mu g, or two doses of 0.2 mu g, were sufficient to induce elevated RSV-A serum antibodies and sterilising lung protective immunity. Serum antibody titres were significantly boosted following second immunisations, but not a third. Of three routes of immunisation, i.p. induced the highest RSV-A antibody titres, followed in efficacy by the intramuscular (i.m.) and subcutaneous (s.c.) routes. Nonetheless, all three routes induced comparable and sterilising lung protection. In contrast, upper respiratory tract protection was observed only after i.p. vaccination, although significant viral titre reductions were evident following i.m. or s.c. immunisations. Interestingly, Pepscan analyses indicated that antibody epitope usage was highest in i.p. and lowest in i.m. immunised mice, respectively. Nonetheless, all routes resulted in antibody responses to known lung protective epitopes (protectopes). Thus, the prevention of serious lower respiratory tract disease, the principle goal of a RSV vaccine, but not URT infection, is dose dependent but unlikely to be influenced by the route of BBG2Na administration.
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