| 1. |
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| 2. |
- Betancourt, Lazaro Hiram, et al.
(författare)
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The human melanoma proteome atlas-Defining the molecular pathology
- 2021
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Ingår i: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 11:7, s. 1-20
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Tidskriftsartikel (refereegranskat)abstract
- The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in-depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma. The data generated by global proteomic experiments covered 72% of the proteins identified in the recently reported high stringency blueprint of the human proteome. This study contributes to the NIH Cancer Moonshot initiative combining detailed histopathological presentation with the molecular characterization for 505 melanoma tumor samples, localized in 26 organs from 232 patients.
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| 3. |
- Trupp, Miles, et al.
(författare)
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Metabolite and peptide levels in plasma and CSF differentiating healthy controls from patients with newly diagnosed Parkinson's disease
- 2014
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Ingår i: Journal of Parkinson's Disease. - : Taylor & Francis. - 1877-7171 .- 1877-718X. ; 4:3, s. 549-560
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Tidskriftsartikel (refereegranskat)abstract
- Background: Parkinson's disease (PD) is a progressive, multi-focal neurodegenerative disease for which there is no effective disease modifying treatment. A critical requirement for designing successful clinical trials is the development of robust and reproducible biomarkers identifying PD in preclinical stages. Objective: To investigate the potential for a cluster of biomarkers visualized with multiple analytical platforms to provide a clinically useful tool. Methods: Gas Chromatography-Mass Spectrometry (GC-TOFMS) based metabolomics and immunoassay-based protein/peptide analyses on samples from patients with PD diagnosed in Northern Sweden. Low molecular weight compounds from both plasma and cerebrospinal fluid (CSF) from 20 healthy subjects (controls) and 20 PD patients at the time of diagnosis (baseline) were analyzed. Results: In plasma, we found a significant increase in several amino acids and a decrease in C16-C18 saturated and unsaturated fatty acids in patients as compared to control subjects. We also observed an increase in plasma levels of pyroglutamate and 2-oxoisocaproate (ketoleucine) that may be indicative of increased metabolic stress in patients. In CSF, there was a generally lower level of metabolites in PD as compared to controls, with a specific decrease in 3-hydroxyisovaleric acid, tryptophan and creatinine. Multivariate analysis and modeling of metabolites indicates that while the PD samples can be separated from control samples, the list of detected compounds will need to be expanded in order to define a robust predictive model. CSF biomarker immunoassays of candidate peptide/protein biomarkers revealed a significant decrease in the levels of A beta-38 and A beta-42, and an increase in soluble APP alpha in CSF of patients. Furthermore, these peptides showed significant correlations to each other, and positive correlations to the CSF levels of several 5- and 6-carbon sugars. However, combining these metabolites and proteins/peptides into a single model did not significantly improve the statistical analysis. Conclusions: Together, this metabolomics study has detected significant alterations in plasma and CSF levels of a cluster of amino acids, fatty acids and sugars based on clinical diagnosis and levels of known protein and peptide biomarkers.
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| 4. |
- Adman, Per, et al.
(författare)
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171 forskare: ”Vi vuxna bör också klimatprotestera”
- 2019
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Ingår i: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
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| 5. |
- Ahlman, Stefan, 1973, et al.
(författare)
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Methodology for systems analysis of sustainable wastewater management - assessment for an urban catchment in Vasastaden, Göteborg.
- 2004
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Ingår i: Proceedings of the 5th International Conference on Sustainable Techniques and Strategies in Urban Water Management (NOVATECH'2004). June 6-10 2004. ; , s. 457-464
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Konferensbidrag (refereegranskat)abstract
- This paper presents a methodology, i.e. a scheme of methods and principles to be used in systems analysis of alternative wastewater systems. The methodology is tested in a case study for an urban catchment where three different system structures for management of wastewater were compared: a combined sewer system, a conventional separate sewer system, and a source controlled separate system. The outcome of the step-by-step methodology is an overall assessment of the sustainability in each of the studied systems, which can be used as support in a decision-making process. The tools and methods have also proven to be useful in evaluation of different scenarios, especially in relation to source control.
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| 6. |
- Ahlman, Stefan, 1973, et al.
(författare)
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Modelling non-structural Best Management Practices - focus on reductions in stormwater pollution
- 2005
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Ingår i: Water Science and Technology. ; 52:5, s. 9-16
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes a modelling approach for evaluating the efficiency of different non-structural best management practises for stormwater management. A scenario with a set of source reduction practices was simulated using the substance flow model SEWSYS for an urban catchment in the city of Göteborg, Sweden. The scenario is based on a hypothetical control program that includes prevention, education and regulations. The simulation shows relatively high reductions of copper and PAH, 77 % and 50 %, respectively. The reduction in copper is mainly due to less copper roof corrosion and brake wear, while reduced road wear has the greatest effect for PAH. An important result from this study is that the non-structural BMPs applied did not give a sufficient reduction in pollution to meet the desirable environmental quality criteria. To meet these criteria, additional BMPs must be implemented, preferably a combination of both non-structural and structural measures.
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| 7. |
- Ahlman, Stefan, 1973, et al.
(författare)
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Systemanalys Vasastaden Göteborg - Avloppsvattensystemet
- 2004
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna rapport beskriver en metod för systemanalys av avloppshanteringen i Vasastaden,Göteborg. Metoden ger ett beslutsunderlag för vilket system eller vilkenkombination av system som ger bäst resultat utifrån miljöaspekter, återföring av näringsämnen, ekonomi och risker. I denna rapport har inte organisations- och brukaraspekter behandlats men det är fullt möjligt att inkludera dessa aspekter i metoden. Metoden kan fånga upp eventuella flaskhalsar i systemen, samtidigt som den belyser risken av att göra fel antaganden så att ett nytt system inte ger den utveckling som vi vill.Analysen för Vasastaden omfattar det nuvarande avloppssystemet som i huvudsak är ett kombinerat system, ett konventionell duplikatsystem och ett duplikatsystem med sorterat dagvatten samt ett svartvattensystem med antingen rörtransport till central behandlingsanläggning eller lokalt omhändertagande med lastbiltransport till central behandlingsanläggning.Med hjälp av en modell för substansflödesanalys har emissionerna av näringsämnen,metaller och organiska föroreningar till mark, vatten och slam beräknats. Resultatet av substansflödesanalysen har använts som indata till bedömning av miljöeffekter för vatten, sediment och avloppsslam. Kostnader för att anlägga, driva och underhålla systemen har beräknats med en framtagen Excel-modell. Risker och robusthet för systemen har analyserats utifrån tekniska och hygieniska aspekter. I riskanalysen har hänsyn tagits till de boende, fastighetsägarna och de kommunala förvaltningarna. I en scenariostudie konstateras att vi måste spänna bågen hårdare för att nå våra uppsatta mål kring recipientskydd och näringsåterföring. Det kan innebära både teknisk utveckling, lagstiftning eller påverkan på tillverkare och brukargrupper. Scenariostudien visar också på var vi får störst resultat när vi påverkar källorna. I en känslighetsanalys visas vad som händer i systemen när vi börjar vrida på källparametrarnaoch hur långt man teoretiskt kan komma med rimliga bedömningar av framtida förändringar i samhället. Vidare belyses vad brukarna kan påverka och vilka åtgärder som generellt ger snabbast resultat. Det handlar också om att påverka människor och deras beteende. Brukarna måste vara mer insatta om hur va-systemen fungerar och de problem som finns samt ha förtroende för systemen. Fastighetsägarna måste sköta sina tak och eventuella lokala anläggningar.Metoden utgår i mycket hög grad från de verkliga lokala förutsättningarna, och kräver mycket indata men kan ge pålitliga svar. Läkemedelsrester är inte med i analysen eftersom utgångspunkten är de ämnen för vilka gränsvärden har satts i Naturvårdsverkets Aktionsplan. Att metallgränsvärdena underskrids är ingen garanti för att lantbrukarna accepterar återföring av slammet till jordbruket. Den oro för läkemedelsrester mm vilken ligger till grund för dagens slamstopp, fångas alltså inte upp i denna analys, eftersom läkemedelsrester mm. inte är med. Systemförändringar av det slag som studerats för Vasastaden kräver i verklighetenatt beslut tas om en samlad strategi för hela Göteborg. Metoden bedöms lämplig att skala upp till hela Göteborg, som underlag för framtida strategibeslut.
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| 8. |
- Alveteg, Mattias, et al.
(författare)
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Vad räknas som belägg för studenters måluppfyllelse?
- 2018
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Ingår i: 10:e Pedagogiska Inspirationskonferensen 2018. - 2003-3761 .- 2003-377X. ; 10
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Konferensbidrag (refereegranskat)abstract
- Universitetskanslerämbetet (UKÄ) ställer numera krav på svenska lärosäten att vi ska utvärdera oss själva. Vi på LTH bör då gemensamt försöka hitta sätt att uppfylla UKÄs krav som även ger de verktyg vi själva behöver för att förbättra våra utbildningars kvalitét.Hur tar vi reda på våra utbildningars styrkor och svagheter och vad vi kan göra för att förbättra dem ytterligare? Ett sätt är att undersöka hur väl studenterna uppfyller examensmålen. Vad som ska räknas som belägg för studenters måluppfyllelse är dock svårt, av flera olika skäl. Vår rekommendation blir att triangulera olika typer av belägg samt att tydligt involvera institutionerna i arbetet.
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| 9. |
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| 10. |
- Bech-Hanssen, Odd, 1956, et al.
(författare)
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Pressure reflection in the pulmonary circulation in patients with severe mitral regurgitation indicates adverse postoperative outcome.
- 2013
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Ingår i: European Journal Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 44:6, s. 1037-1044
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Severe pulmonary hypertension (PH) is a known risk factor in valvular surgery. In the present study, we hypothesized that the assessment of pressure reflection (PR) in the pulmonary circulation, indicating increased pulmonary vascular resistance, might improve the identification of patients with increased morbidity and mortality following surgery for severe mitral regurgitation. METHODS: A total of 103 patients without atrial fibrillation were divided into three groups: Group 1 (n = 48), patients without PR; Group 2 (n = 36), patients with PR and pulmonary artery systolic pressure (PASP) ≤60 mmHg and Group 3 (n = 19), patients with PR and PASP >60 mmHg. Three variables related to PR were selected: the acceleration time in the right ventricular outflow tract (RVOT), the interval between peak velocity in the RVOT and peak tricuspid regurgitant jet velocity and the right ventricular pressure increase after peak RVOT velocity. RESULTS: There were no differences between groups in age, ejection fraction, need for coronary bypass grafting or creatinine. Patients with PR (Groups 2 and 3) had more use of vasoactive drugs (overall P < 0.0001, Group 1 vs Group 2 P = 0.018). The proportion of patients with >24 h in the intensive care unit was 27% in Group 1, 54% in Group 2 and 84% in Group 3 (overall P < 0.0001, Group 1 vs Group 2 P = 0.006). The in-hospital mortality in patients without PR (n = 49) was 0% compared with 10.9% in patients with PR (P = 0.029). CONCLUSIONS: Echocardiography assessment of PR in the pulmonary circulation and severe PH may identify patients with adverse outcome following mitral surgery.
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| 11. |
- Bergmann, Olaf, et al.
(författare)
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Dynamics of Cell Generation and Turnover in the Human Heart.
- 2015
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Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 161:7, s. 1566-1575
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of cell generation to physiological heart growth and maintenance in humans has been difficult to establish and has remained controversial. We report that the full complement of cardiomyocytes is established perinataly and remains stable over the human lifespan, whereas the numbers of both endothelial and mesenchymal cells increase substantially from birth to early adulthood. Analysis of the integration of nuclear bomb test-derived (14)C revealed a high turnover rate of endothelial cells throughout life (>15% per year) and more limited renewal of mesenchymal cells (<4% per year in adulthood). Cardiomyocyte exchange is highest in early childhood and decreases gradually throughout life to <1% per year in adulthood, with similar turnover rates in the major subdivisions of the myocardium. We provide an integrated model of cell generation and turnover in the human heart. VIDEO ABSTRACT.
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| 12. |
- Betancourt, Lazaro Hiram, et al.
(författare)
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Improved survival prognostication of node-positive malignant melanoma patients utilizing shotgun proteomics guided by histopathological characterization and genomic data
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Metastatic melanoma is one of the most common deadly cancers, and robust biomarkers are still needed, e.g. to predict survival and treatment efficiency. Here, protein expression analysis of one hundred eleven melanoma lymph node metastases using high resolution mass spectrometry is coupled with in-depth histopathology analysis, clinical data and genomics profiles. This broad view of protein expression allowed to identify novel candidate protein markers that improved prediction of survival in melanoma patients. Some of the prognostic proteins have not been reported in the context of melanoma before, and few of them exhibit unexpected relationship to survival, which likely reflects the limitations of current knowledge on melanoma and shows the potential of proteomics in clinical cancer research.
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| 13. |
- Dahlin, Sandra, et al.
(författare)
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Effect of biofuel- and lube oil-originated sulfur and phosphorus on the performance of Cu-SSZ-13 and V2O5-WO3/TiO2 SCR catalysts
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Two different SCR catalysts, V2O5-WO3/TiO2 and Cu-SSZ-13, were exposed to biodiesel exhausts generated by a diesel burner. The effect of phosphorus and sulfur on the SCR performance of these catalysts was investigated by doping the fuel with P-, S-, or P+S-containing compounds. Elemental analyses showed that both catalysts captured phosphorus while only Cu-SSZ-13 captured sulfur. High molar P/V ratios, up to almost 3, were observed for V2O5-WO3/TiO2, while the highest P/Cu ratios observed were slightly above 1 for the Cu-SSZ-13 catalyst. Although the V2O5-WO3/TiO2 catalyst captured more P than did the Cu-SSZ-13 catalyst, a higher degree of deactivation was observed for the latter, especially at low temperatures. For both catalysts, phosphorus exposure resulted in suppression of the SCR performance over the entire temperature range. Sulfur exposure, on the other hand, resulted in deactivation of the Cu-SSZ-13 catalyst mainly at temperatures below 300-350 ºC. The use of an oxidation catalyst upstream of the SCR catalyst during the exhaust-exposure could protect the SCR catalyst from phosphorus poisoning. The results in this work will improve the 2 understanding of chemical deactivation of SCR catalysts and aid in developing durable aftertreatment systems.
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| 14. |
- Fermuller, C, et al.
(författare)
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Uncertainty in visual processes predicts geometrical optical illusions
- 2004
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Ingår i: Vision Research. - : Elsevier BV. - 1878-5646 .- 0042-6989. ; 44:7, s. 727-749
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Tidskriftsartikel (refereegranskat)abstract
- It is proposed in this paper that many geometrical optical illusions, as well as illusory patterns due to motion signals in line drawings. are due to the statistics of visual computations. The interpretation of image patterns is preceded by a step where image features such as lines, intersections of lines, or local image movement must be derived. However, there are many sources of noise or uncertainty in the formation and processing of images, and they cause problems in the estimation of these features; in particular, they cause bias. As a result, the locations of features are perceived erroneously and the appearance of the patterns is altered. The bias occurs with any visual processing of line features; under average conditions it is not large enough to be noticeable, but illusory patterns are Such that the bias is highly pronounced. Thus, the broader message of this paper is that there is a general uncertainty principle which governs the workings of vision systems, and optical illusions are an artifact of this principle.
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| 15. |
- Gil, Jeovanis, et al.
(författare)
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Clinical protein science in translational medicine targeting malignant melanoma
- 2019
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Ingår i: Cell Biology and Toxicology. - : Springer Science and Business Media LLC. - 0742-2091 .- 1573-6822. ; 35:4, s. 293-332
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Tidskriftsartikel (refereegranskat)abstract
- Melanoma of the skin is the sixth most common type of cancer in Europe and accounts for 3.4% of all diagnosed cancers. More alarming is the degree of recurrence that occurs with approximately 20% of patients lethally relapsing following treatment. Malignant melanoma is a highly aggressive skin cancer and metastases rapidly extend to the regional lymph nodes (stage 3) and to distal organs (stage 4). Targeted oncotherapy is one of the standard treatment for progressive stage 4 melanoma, and BRAF inhibitors (e.g. vemurafenib, dabrafenib) combined with MEK inhibitor (e.g. trametinib) can effectively counter BRAFV600E-mutated melanomas. Compared to conventional chemotherapy, targeted BRAFV600E inhibition achieves a significantly higher response rate. After a period of cancer control, however, most responsive patients develop resistance to the therapy and lethal progression. The many underlying factors potentially causing resistance to BRAF inhibitors have been extensively studied. Nevertheless, the remaining unsolved clinical questions necessitate alternative research approaches to address the molecular mechanisms underlying metastatic and treatment-resistant melanoma. In broader terms, proteomics can address clinical questions far beyond the reach of genomics, by measuring, i.e. the relative abundance of protein products, post-translational modifications (PTMs), protein localisation, turnover, protein interactions and protein function. More specifically, proteomic analysis of body fluids and tissues in a given medical and clinical setting can aid in the identification of cancer biomarkers and novel therapeutic targets. Achieving this goal requires the development of a robust and reproducible clinical proteomic platform that encompasses automated biobanking of patient samples, tissue sectioning and histological examination, efficient protein extraction, enzymatic digestion, mass spectrometry–based quantitative protein analysis by label-free or labelling technologies and/or enrichment of peptides with specific PTMs. By combining data from, e.g. phosphoproteomics and acetylomics, the protein expression profiles of different melanoma stages can provide a solid framework for understanding the biology and progression of the disease. When complemented by proteogenomics, customised protein sequence databases generated from patient-specific genomic and transcriptomic data aid in interpreting clinical proteomic biomarker data to provide a deeper and more comprehensive molecular characterisation of cellular functions underlying disease progression. In parallel to a streamlined, patient-centric, clinical proteomic pipeline, mass spectrometry–based imaging can aid in interrogating the spatial distribution of drugs and drug metabolites within tissues at single-cell resolution. These developments are an important advancement in studying drug action and efficacy in vivo and will aid in the development of more effective and safer strategies for the treatment of melanoma. A collaborative effort of gargantuan proportions between academia and healthcare professionals has led to the initiation, establishment and development of a cutting-edge cancer research centre with a specialisation in melanoma and lung cancer. The primary research focus of the European Cancer Moonshot Lund Center is to understand the impact that drugs have on cancer at an individualised and personalised level. Simultaneously, the centre increases awareness of the relentless battle against cancer and attracts global interest in the exceptional research performed at the centre.
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| 16. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Lindberg, Ann-Sofie, 1972-, et al.
(författare)
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Multivariate statistical assessment of predictors of firefighters' muscular and aerobic work capacity
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Physical capacity has previously been deemed important for firefighters physical work capacity, and aerobic fitness, muscular strength, and muscular endurance are the most frequently investigated parameters of importance. Traditionally, bivariate and multivariate linear regression statistics have been used to study relationships between physical capacities and work capacities among firefighters. An alternative way to handle datasets consisting of numerous correlated variables is to use multivariate projection analyses, such as Orthogonal Projection to Latent Structures. The first aim of the present study was to evaluate the prediction and predictive power of field and laboratory tests, respectively, on firefighters’ physical work capacity on selected work tasks. Also, to study if valid predictions could be achieved without anthropometric data. The second aim was to externally validate selected models. The third aim was to validate selected models on firefighters’ and on civilians’. A total of 38 (26 men and 12 women) + 90 (38 men and 52 women) subjects were included in the models and the external validation, respectively. The best prediction (R2) and predictive power (Q2) of Stairs, Pulling, Demolition, Terrain, and Rescue work capacities included field tests (R2 = 0.73 to 0.84, Q2 = 0.68 to 0.82). The best external validation was for Stairs work capacity (R2 = 0.80) and worst for Demolition work capacity (R2 = 0.40). In conclusion, field and laboratory tests could equally well predict physical work capacities for firefighting work tasks, and models excluding anthropometric data were valid. The predictive power was satisfactory for all included work tasks except Demolition.
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| 22. |
- Malm, Christer, et al.
(författare)
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Evaluation of 2-D DIGE for skeletal muscle: Protocol and repeatability
- 2008
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Ingår i: The Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa Healthcare. - 0036-5513 .- 1502-7686. ; 68:8, s. 793-800
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Tidskriftsartikel (refereegranskat)abstract
- Proteomic analysis has the potential to yield vast amounts of data. The available proteomic methods have been hampered by methodological errors in quantification due to large gel-to-gel variations. The inclusion of an internal standard greatly reduces this variation, and therefore the purpose of this investigation was: 1) to develop a sample preparation protocol for human skeletal muscle for two-dimensional differentiated gel electrophoresis (DIGE) and 2) to investigate the repeatability of one particular system, the Ettan™ DIGE. To test repeatability, nine aliquots from the same homogenate were labelled with three different CyDye™ dyes (Cy2, Cy3, Cy5). Samples were run on 1824 cm gels, scanned with a Typhoon™ 9410 laser scanner and analysed in the DeCyder™ software. When selecting spots appearing only in triplicate (n = 1314), the mean error was 1.7 % (SD: 10.5 %; 95 % CI: 1.1-2.4 %). When setting the significance level to 99 %, no false-positive changes in protein volume ratios were detected. In the protocol presented here, only 0.5 mg tissue was used and separation of >2500 distinct protein spots in the pH range 3-11 and MW 10-200 kDa. Changes in protein abundance of <20 % could be detected. The method is especially useful when comparing muscle proteins between different conditions; for example, healthy and diseased tissue, before and after treatment or different exercise protocols.
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| 23. |
- Malm, Carl Johan, et al.
(författare)
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Small calibre biosynthetic bacterial cellulose blood vessels: 13-months patency in a sheep model.
- 2012
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 46:1, s. 57-62
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objectives. Many patients in need of bypass surgery lack graft material and current synthetic alternatives have poor performance. A 4 mm vascular graft composed of bacterial cellulose (BC) was developed and tested in pilot study in a large animal model. Design. BC is a biopolymer made by the bacteria acetobacter xylinum. BC grafts (n = 16) with 4 cm length and 4 mm internal diameter were implanted bilaterally in the carotid arteries of eight sheep. No long-term antithrombotic therapy was administered. Patency was assessed with ultrasound. Histology, immunohistochemistry, and electron microscopy were performed after explantation. Results. Fifty percent of the grafts occluded within two weeks. One animal died with patent grafts after 14 days. In the three remaining animals 5/6 grafts were patent after nine months. Two animals were followed 13 months after implantation with 3/4 grafts patent at explantation. All patent grafts had confluent endothelial-like cells. Conclusions. Biosynthetic small calibre vascular grafts made from BC can be patent for up to 13 months in sheep carotid arteries. BC is a potential material for small calibre grafts but patency in animal models needs to be improved before clinical studies can be planned.
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| 24. |
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| 25. |
- Malm, Henrik, et al.
(författare)
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Adaptive enhancement and noise reduction in very low light-level video
- 2007
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Ingår i: 11th International Conference on Computer Vision, 2007. - 1550-5499. - 9781424416318 ; , s. 1395-1402
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Konferensbidrag (refereegranskat)abstract
- A general methodology for noise reduction and contrast enhancement in very noisy image data with low dynamic range is presented. Video footage recorded in very dim light is especially targeted. Smoothing kernels that automatically adapt to the local spatio-temporal intensity structure in the image sequences are constructed in order to preserve and enhance fine spatial detail and prevent motion blur. In color image data, the chromaticity is restored and demosaicing of raw RGB input data is performed simultaneously with the noise reduction. The method is very general, contains few user-defined parameters and has been developed for efficient parallel computation using a GPU. The technique has been applied to image sequences with various degrees of darkness and noise levels, and results from some of these tests, and comparisons to other methods, are presented. The present work has been inspired by research on vision in nocturnal animals, particularly the spatial and temporal visual summation that allows these animals to see in dim light.
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| 26. |
- Malm, Henrik, et al.
(författare)
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Biologically inspired enhancement of dim light video
- 2012
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Ingår i: Frontiers in Sensing: From Biology to Engineering. - Vienna : Springer Vienna. - 9783211997499 - 9783211997482 ; , s. 71-85
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Bokkapitel (refereegranskat)abstract
- In this chapter a technology for the enhancement of video data obtained at low light levels is presented. The method was inspired by the way in which nocturnal animals adaptively sum intensities, spatially and temporally, to improve vision at night. Due to the low photon count under these conditions the visual input is dark and unreliable, which leads to noisy low contrast images. The noise becomes very apparent when we try to enhance the contrast and, by this, amplify the intensities in the darkest regions of the images. By constructing spatio-temporal smoothing kernels that automatically adapt to the three dimensional intensity structure at every point, the noise can be considerably reduced, with fine spatial detail being preserved and enhanced without added motion blur. For color image data, the chromaticity is restored and demosaicing of raw RGB input data can be performed simultaneously with the noise reduction. The method is a very generally applicable one, contains only few user-defined parameters and has been developed for efficient parallel computation using a graphics processing unit (GPU). The technique has been applied to image sequences with various degrees of darkness and noise levels. Results from some of these tests, and comparisons to related work, are presented here.
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| 27. |
- Malm, Helene, et al.
(författare)
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CTLA4ig induces long-term graft survival of allogeneic skin grafts and totally inhibits T-cell proliferation in LFA-1-deficient mice.
- 2002
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Ingår i: Transplantation. - 1534-6080. ; 73:2, s. 293-297
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It was recently shown that some strains of mice are capable of rejecting transplants independently of B7 and CD40L signaling and that this rejection is mediated by CD8(+) T cells. LFA-1 is known to be important for CD8(+) T cell activation and cytotoxicity. Therefore, blockade of LFA-1 could be important in overcoming costimulation blockade, CD8(+) T-cell-mediated, resistant rejection. The purpose of this study was to define the effect of combined blockade of the LFA-1 and B7 costimulation pathways on the alloimmune response in mice. METHODS: Allogeneic skin transplantation was performed using BALB/c mice as donors and C57BL/6J wild-type or LFA-1-deficient (CD11a(-/-)) mice as recipients. CTLA4Ig or anti-LFA-1 was administered either as an induction or a prolonged therapy. Mixed lymphocyte reactions were conducted to study the effect of CTLA4Ig on T-cell proliferation in CD11a(-/-) mice. RESULTS AND CONCLUSIONS: Administration of CTLA4Ig completely inhibits CD11a(-/-) T-cell proliferation in response to alloantigens and significantly improved skin allograft survival in CD11a(-/-) mice. Prolonged treatment of wild-type recipient mice with CTLA4Ig and anti-LFA-1 increased median survival time to 45.5 days compared with 16 days after induction therapy, but it was not sufficient to induce indefinite allograft survival in this model.
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| 28. |
- Malm, Henrik, et al.
(författare)
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Extensions of plane-based calibration to the case of translational motion in a robot vision setting
- 2006
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Ingår i: IEEE Transactions on Robotics. - 1941-0468. ; 22:2, s. 322-333
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper, a technique for calibrating a camera using a planar calibration object with known metric structure, when the camera (or the calibration plane) undergoes pure translational motion, is presented. The study is an extension of the standard formulation of plane-based camera calibration where the translational case is considered as degenerate. We derive a flexible and straightforward way of using different amounts of knowledge of the translational motion for the calibration task. The theory is mainly applicable in a robot vision setting, and the calculation of the hand-eye orientation and the special case of stereo head calibration are also being addressed. Results of experiments on both computer-generated and real image data are presented. The paper covers the most useful instances of applying the technique to a real system and discusses the degenerate cases that needs to be considered. The paper also presents a method for calculating the infinite homography between the two image planes in a stereo head, using the homographies estimated between the calibration plane and the image planes. Its possible usage and usefulness for simultaneous calibration of the two cameras in the stereo head are discussed and illustrated using experiments.
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| 29. |
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| 30. |
- Malm, Henrik, et al.
(författare)
-
Motion dependent spatiotemporal smoothing for noise reduction in very dim light image sequences
- 2006
-
Ingår i: Proceedings - International Conference on Pattern Recognition. - 1051-4651. ; 3, s. 954-959
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Konferensbidrag (refereegranskat)abstract
- A new method for noise reduction using spatiotemporal smoothing is presented in this paper. The method is developed especially for reducing the noise that arises when acquiring video sequences with a camera under very dim light conditions. The work is inspired by research on the vision of nocturnal animals and the adaptive spatial and temporal summation that is prevalent in the visual systems of these animals. From analysis using the so-called structure tensor in the three-dimensional spatiotemporal space, motion segmentation and global ego-motion estimation, Gaussian shaped smoothing kernels are oriented mainly in the direction of the motion and in spatially homogeneous directions. In static areas, smoothing along the temporal dimension is favoured for maximum preservation of structure. The technique has been applied to various dim light image sequences and results of these experiments are presented here.
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| 31. |
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| 32. |
- Malm, Henrik, et al.
(författare)
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Self-calibration from Image Derivatives for Active Vision Systems
- 2002
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Ingår i: Proceedings of the 7th International Conference on Control, Automation, Robotics and Vision, ICARCV 2002. - 9810474806 ; , s. 1116-1121
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Konferensbidrag (refereegranskat)abstract
- In this paper we show how to calibrate a camera, mounted on a robot, with respect to the intrinsic camera parameters when the so-called hand-eye transformation between the robot hand and the camera is unknown. The calibration is based directly on the spatial and temporal derivatives in an image sequence and do not need any matching and tracking of features or a reference object. The calibration is to be performed on an active robot vision system where the motion of the robot hand can be controlled. A minimum of 3 non co-planar translations of the robot hand are needed for the calculation. In conjunction with the intrinsic camera calibration the orientation of the camera, with respect to the robot hand, is calculated. The position of the camera can then also be obtained. At each stage only the image derivatives and the known motion of the robot hand are used. For the full, intrinsic and extrinsic, calibration a total of 5 distinct motions are used. The algorithm has been tested in extensive experiments with respect to e.g. noise sensitivity.
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| 33. |
- Malm, Henrik, et al.
(författare)
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Simplified Intrinsic Camera Calibration and Hand-Eye Calibration for Robot Vision
- 2003
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Ingår i: IEEE International Conference on Intelligent Robots and Systems. - 0780378601 ; 1, s. 1037-1043
-
Konferensbidrag (refereegranskat)abstract
- In this paper we investigate how intrinsic camera calibration and hand-eye calibration can be performed on a robot vision system using the simplest possible motions and a planar calibration object The standard methods on plane-based camera calibration are extended with theory on how to use pure translational motions for the intrinsic calibration and we see how hand-eye calibration can be performed within the same framework. The calibration of two cameras in a stereo head configuration is shown to be an interesting application of the developed theory. Results of experiments on a real robot vision system are presented.
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| 34. |
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| 35. |
- Malm, Henrik
(författare)
-
Studies in Robotic Vision, Optical Illusions and Nonlinear Diffusion Filtering
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is divided into three parts, which all deal with computational analysis and processing of images. However, the settings are quite diverse.They range from robotic camera sensors, over human perception, to physical measurement setups. In spite of this diversity, common theoretical ideas and computational aspects are applied which ties the three different parts closer together. The first part of the thesis deals with calibration methods for robotic vision. Both the estimation of the intrinsic parameters of the applied camera model, intrinsic camera calibration, and the estimation of the orientation and position of the camera in relation to the end-effector of the robot, hand-eye calibration, are discussed. Two different methods are presented. The first one explores the constraints that arise when calibrating a single camera or a stereo head configuration using a planar calibration object, while performing translational or general motions. The other one uses estimations of the spatial and temporal intensity derivatives in an image sequence for direct computation of the unknown parameters. The second part of the thesis discusses a new framework for explaining a number of geometrical optical illusions. It is proposed that noise, that enters into the visual process at different stages, causes the estimation of different features in the observed image to be biased. Different types of error models are discussed and illusions that are best explained by each particular model are presented. The discussion is not restricted to the human visual system and highlights the importance of analyzing the influence of noise and uncertainty in any visual process. The third and final part of the thesis propose the use of nonlinear diffusion filtering to process images obtained by planar laser-induced fluorescence (PLIF) spectroscopy. In particular, the images in the present application are PLIF images of turbulent flames in combustion processes. Solving a nonlinear diffusion equation using an image of this type as initial value, makes succeeding extraction of interesting quantities, such as the length of the flame boundary, an easy task. An analysis of the properties of nonlinear diffusion filtering in general, and for the present application in particular, is given.
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| 36. |
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| 37. |
- Malm, Johan, et al.
(författare)
-
Developments in biobanking workflow standardization providing sample integrity and stability
- 2013
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 95:SI, s. 38-45
-
Tidskriftsartikel (refereegranskat)abstract
- Recommendations and outlines for standardization in biobanking processes are presented by a research team with long-term experience in clinical studies. These processes have important bearing on the use of samples in developing assays. These measurements are useful to document states of health and disease that are beneficial for academic research, commercial healthcare, drug development industry and government regulating agencies. There is a need for increasing awareness within proteomic and genomic communities regarding the basic concepts of collecting, storing and utilizing clinical samples. Quality control and sample suitability for analysis need to be documented and validated to ensure data integrity and establish contexts for interpretation of results. Standardized methods in proteomics and genomics are required to be practiced throughout the community allowing datasets to be comparable and shared for analysis. For example, sample processing of thousands of clinical samples, performed in 384 high-density sample tube systems in a fully automated workflow, preserves sample content and is presented showing validation criteria. Large studies will be accompanied by biological and molecular information with corresponding clinical records from patients and healthy donors. These developments position biobanks of human patient samples as an increasingly recognized major asset in disease research, future drug development and within patient care. Biological significance: The current manuscript is of major relevance to the proteomic and genomic fields, as it outlines the standardization aspects of biobanking and the requirements that are needed to run future clinical studies that will benefit the patients where OMICS science will play a major role. A global view of the field is given where best practice and conventional acceptances are presented along with ongoing large-scale biobanking projects. The authors represent broadly stakeholders that cover the academic, pharma, biotech and healthcare fields with extensive experience and deliveries. This contribution will be a milestone paper to the proteomic and genomic scientists to present data in the future that will have impact to the life science area.This article is part of a Special Issue entitled: Standardization and Quality Control in Proteomics.
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| 38. |
- Malm, Johan, et al.
(författare)
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Semi-automated biobank sample processing with a 384 high density sample tube robot used in cancer and cardiovascular studies.
- 2015
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Ingår i: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 4:1
-
Tidskriftsartikel (refereegranskat)abstract
- In the postgenomic era, it has become evident that analysis of genetic and protein expression changes alone is not sufficient to understand most disease processes in e.g. cardiovascular and cancer disease. Biobanking has been identified as an important area for development and discovery of better diagnostic tools and new treatment modalities. Biobanks are developed in order to integrate the collection of clinical samples from both healthy individuals and patients and provide valuable information that will make possible improved patient care. Modern healthcare developments are intimately linked to information based on studies of patient samples from biobank archives in large scale studies. Today biobanks form important national, as well as international, networks that share and combine global resources.
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| 39. |
- Malm, Johan, et al.
(författare)
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Stardardization Developments for Large Scale Biobanks in Smoking Related Diseases - A Model System for Blood Sample Processing and Storage
- 2013
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Ingår i: Translational Respiratory Medicine. - : Springer Science and Business Media LLC. - 2213-0802. ; 1
-
Tidskriftsartikel (refereegranskat)abstract
- Biobank samples stored in biobanks give researchers and respiratory healthcare institutions access to datasets of analytes valuable for both diagnostic and research practices. The usefulness of these samples in clinical decision-making is highly dependent on their quality and integrity. New procedures that better preserve sample integrity and reduce degradation are being developed to meet the needs of both present and future biobanking. Hereby we present an automatic sample workflow scheme that is designed to handle high numbers of blood samples. Blood fractions are aliquoted, heat sealed using novel technology, and stored in 384 tube high-density sample arrays. The newly developed 384 biobank rack system is especially suited for preserving identical small aliquots. This technology development allows rapid access to a given sample in the frozen archive while maintaining individual sample integrity with sample tube confinement and quality management. We provide data on robotic processing of clinical samples at -80°C, following initial processing, analysis and shipping between laboratories throughout Europe. Subsequent to unpacking, re-sorting, and storage at these sites, the samples have been returned for analysis. Biomarker analysis of 13 common tests in the clinical chemistry unit of the hospital provides evidence of qualitative and stable logistics using the 384-sample tube system.
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| 40. |
- Malm, J., et al.
(författare)
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The Swedish Malignant Middle cerebral artery Infarction Study : long-term results from a prospective study of hemicraniectomy combined with standardized neurointensive care
- 2006
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Ingår i: Acta Neurologica Scandinavica. - Copenhagen : Munksgaard. - 0001-6314 .- 1600-0404. ; 113:1, s. 25-30
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Hemicraniectomy in patients with malignant middle cerebral artery (mMCA) infarct may be life-saving. The long-term prognosis is unknown.Methods: Patients with mMCA infarct treated with hemicraniectomy between 1998 and 2002 at three hospitals were included. The criterion for surgical intervention was if the patients deteriorated from awake to being responding to painful stimuli only. All patients were followed for at least 1 year. Outcome was defined as alive/dead, walkers/non-walkers or modified Rankin Scale (mRS) score ≤2.Results: Thirty patients were included (median age at stroke onset 49 years, range 17–67 years). Fourteen patients had mMCA infarct on the left side and 16 patients on the right side. Fourteen patients had pupil dilatation before surgery. Hemicraniectomy was performed at a median of 52 h (range 13–235 h) after stroke onset. Nine patients died within 1 month after surgery because of cerebral herniation (n = 6), myocardial infarction (n = 1) or intensive care complications (n = 2). No further deaths occurred during follow-up, which was at median 3.4 years after surgery. Status for the 21 survivors at the last follow-up was: mRS 2 or less (n = 6) and mRS 3–5 (n = 15). The oldest patient with mRS 2 or less was 53 years at stroke onset. Thirteen patients (43%) could walk without substantial aid.Conclusion: The long-term survival after mMCA infarction treated with hemicraniectomy seems to be favourable if the patient survives the acute phase. The outcome as measured with mRS may be better among younger patients.
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| 41. |
- Malm, Linus, 1980-, et al.
(författare)
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Predicting amyloid aggregation rates of proteins using multivariate analysis
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Several diseases have been linked to the presence of extracellular protein deposits of β-rich aggregates, known as amyloid fibrils. The formation of these fibrils and their precursors has been identified as key players in the development of these diseases. It is therefore desirable to gain a deeper understanding of the mechanism of amyloid aggregation.In this study we have used multivariate analysis to elucidate the most important physicochemical and structural factors of amino acids that are important for the amyloid aggregation. We used a combination of principal component analysis, orthogonal partial least squares and auto- and cross-covariance to investigate a database consisting of amyloid aggregation rate measurements of 77 AcP mutants.Our results show that changes in hydrophobic patterns, charge and β-sheet propensity is common for mutants with the largest changes in amyloid propensity. In addition, we can also, with reasonable accuracy, predict the amyloid aggregation rate of a test set of AcP mutants that were not used to create the initial aggregation model. Thus, the multivariate approach used in this study is shown to be powerful tools to extract important factors of protein amyloid aggregation that are hidden in the growing pool of available experimental data of amyloid aggregation.
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| 42. |
- Malm, Linus, 1980-
(författare)
-
Size determination of hyaluronan and multivariate analysis of amyloid prone proteins
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background.The extracellular matrix surrounds all cells within our bodies. The glycosaminoglycan hyaluronan is a major component in the extracellular matrix. Despite its structural simplicity it has been shown to be involved in several important functions. It is a lubricant and shock absorber, as well as an important player in inflammation and tumor invasion. Many of its functions are closely related to its size and concentration in tissues. Therefore methods for measuring these properties are of great importance to properly understand the role that hyaluronan play in different events. Proteins are found both inside and outside cells, and they have a wide variety of functions. The protein structure and function is determined by the properties of their building blocks, the amino acids. Several diseases have been linked to changes in the amino acid sequence of certain proteins by mutations, causing the proteins to form extracellular deposits of structures called amyloid aggregates. The aim of this thesis is to investigate the function of hyaluronan in cell cultures, develop new methods for size determination hyaluronan and to use multivariate methods to provide prediction and better understanding of factors driving protein amyloid aggregation. Methods.Cardiomyocytes and fibroblast were cultured and stimulated by different growth factors. Hyaluronan was purified and its size and concentration were measured. Crosstalk between cardiomyocytes and fibroblast were investigated and gene expression of hyaluronan synthases was determined. A new method for size measurement of hyaluronan was developed. The amyloid aggregation rate of different mutants of acylphosphatase was predicted by multivariate analysis. Results. Cardiomyocytes stimulated by PDGF-BB produced hyaluronan. Cardiomyocytes could induce fibroblast to increase its hyaluronan production, through an unknown soluble factor. The cardiomyocyte gene expression changed when stimulated by hyaluronan. GEMMA was presented as a new method for size determination of hyaluronan. Amyloid aggregation of different acylphosphatase mutants could be predicted using a multivariate regression model of the physicochemical and structural properties of the amino acid sequence. Conclusion. It was shown that cardiomyocytes are not only able to produce hyaluronan, but also induce an increased hyaluronan production in other cells. GEMMA was proven suitable for size determination of hyaluronan at very low concentrations. Multivariate analysis showed that hydrophobic patterns and charge where the most important factors for amyloid aggregation of acylphosphatase.
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| 43. |
- Malm, Thomas, et al.
(författare)
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Tonga, totem och tabu
- 2014
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Ingår i: Vetenskapssocieteten i Lund. Årsbok 2014. - 0349-053X. - 9789198055122 ; , s. 118-135
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Bokkapitel (refereegranskat)
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| 44. |
- Mesilov, Vitaly, et al.
(författare)
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Impact of Biodiesel-Based Phosphorus and Sulfur on Copper Speciation of Cu-SSZ-13 Catalysts : XAFS Scanning during H-2-TPR
- 2022
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 126:7, s. 3385-3396
-
Tidskriftsartikel (refereegranskat)abstract
- Biodiesel is a promising renewable fuel, which may help to limit our dependence on fossil fuels. However, the presence of contaminants in biodiesel can affect the Cu speciation of the Cu-SSZ-13 selective catalytic reduction (SCR) catalyst, resulting in its deactivation and decreased durability. In situ Cu K-edge X-ray absorption fine structure (XAFS) scanning during a temperature-programmed reduction in hydrogen (H-2-TPR) has been applied here for the analysis of Cu speciation in Cu-SSZ-13 catalysts aged using pure and contaminated biodiesel fuels. XAFS data were analyzed using the multivariate curve resolution alternating least-squares (MCR-ALS) method. While only reduction from Cu-II to Cu-I was observed at temperatures below 500 degrees C for the catalyst aged using pure biodiesel, a one-step reduction of Cu-II to Cu-0 at temperatures between 400 and 500 degrees C was found for the catalyst aged using P-doped biodiesel. The transformation of isolated CuII species to Cu-II clusters was suggested for the catalyst as a result of aging using P-doped biodiesel. The catalyst aged using S-doped biodiesel showed mainly the reduction of isolated Cu-II to Cu-I, which was inhibited as compared to that observed for the catalyst aged using pure biodiesel. The reduction of the catalyst aged using P+S-doped biodiesel led to the reduction of Cu-II to both Cu-I and Cu-0. The phosphorus was responsible for the formation of Cu-II clusters during aging of the catalyst using P+S-doped biodiesel. This study reveals that the presence of phosphorus in biofuels should be strictly regulated to avoid major changes in the Cu speciation of Cu-SSZ-13 catalysts.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Nilsson, C. L., et al.
(författare)
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Chromosome 19 Annotations with Disease Speciation: A First Report from the Global Research Consortium
- 2013
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:1, s. 134-149
-
Tidskriftsartikel (refereegranskat)abstract
- A first research development progress report of the Chromosome 19 Consortium with members from Sweden, Norway, Spain, United States, China and India, a part of the Chromosome-centric Human Proteome Project (C-HPP) global initiative, is presented (http://www.c-hpp.org). From the chromosome 19 peptide-targeted library constituting 6159 peptides, a pilot study was conducted using a subset with 125 isotope-labeled peptides. We applied an annotation strategy with triple quadrupole, ESI-Qtrap, and MALDI mass spectrometry platforms, comparing the quality of data within and in between these instrumental set-ups. LC–MS conditions were outlined by multiplex assay developments, followed by MRM assay developments. SRM was applied to biobank samples, quantifying kallikrein 3 (prostate specific antigen) in plasma from prostate cancer patients. The antibody production has been initiated for more than 1200 genes from the entire chromosome 19, and the progress developments are presented. We developed a dedicated transcript microarray to serve as the mRNA identifier by screening cancer cell lines. NAPPA protein arrays were built to align with the transcript data with the Chromosome 19 NAPPA chip, dedicated to 90 proteins, as the first development delivery. We have introduced an IT-infrastructure utilizing a LIMS system that serves as the key interface for the research teams to share and explore data generated within the project. The cross-site data repository will form the basis for sample processing, including biological samples as well as patient samples from national Biobanks.
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| 49. |
- Nilsson, Henrik, et al.
(författare)
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Trauma-afflicted refugees' experiences of participating in physical activity and exercise treatment : a qualitative study based on focus group discussions
- 2019
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Ingår i: European Journal of Psychotraumatology. - : Informa UK Limited. - 2000-8198 .- 2000-8066. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Refugees with prolonged and repeated experiences of trauma, often in combination with post-migration living difficulties, are subjected to severe levels of stress and stress-related ill health, including post-traumatic stress disorder (PTSD). Physical activity (PA) is well-established as an effective stress reliever. However, the effect of PA and exercise has received scarce attention in the context of PTSD, and particularly in the field of refugees’ health.Objective: The objective of this study was to explore the experience of participation in PA and exercise as part of the treatment for trauma-afflicted refugees.Method: An explorative qualitative research design was used. Six focus group discussions were conducted with 33 female and male participants that had experience of group-based PA and exercise treatment. The gathered data was analysed by qualitative content analysis.Results: The analysis resulted in one over-arching theme reflecting the participants overall experience of PA and exercise as a process of building resilience. Participants experienced improvements in both physical and mental health domains. Increased self-awareness and self-confidence were seen as additional important benefits, and the interruption of daily stressors provided a sense of relief and recovery. The treatment group settings were experienced as becoming a vehicle for overcoming social fear and isolation, which also carried an empowering and strength-building impact over to participants’ family life and social relationships. Treatment characteristics were experienced as highly supportive and often referred to as the basis of other positive experiences and perceived health benefits.Conclusions: The result of this study outlines a detailed account of trauma-afflicted refugees’ experiences and preferences of PA and exercise-based treatment from a broad range of perspectives. These findings provide a starting point for future research in this field and indicate a particular need for both research and intervention development to include the real-life impact of participating in such treatments.
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| 50. |
- Oderup, Cecilia, et al.
(författare)
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Costimulation Blockade-Induced Cardiac Allograft Tolerance: Inhibition of T Cell Expansion and Accumulation of Intragraft cD4+Foxp3+ T Cells.
- 2006
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 1534-6080 .- 0041-1337. ; 82:11, s. 1493-1500
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Tidskriftsartikel (refereegranskat)abstract
- Background. Previous studies have demonstrated that anti-CD40L or anti-B7 requires the presence of CD4(+)CD25(+) regulatory T cells (Treg) to induce antigen specific hyporesponsiveness. Other tolerance strategies involving Treg have shown a dependency on interleukin (IL)-10. The objective of this study was to investigate the role of CD4(+)CD25(+) Treg and IL-10 when treating transplant recipients with cytotoxic T lymphocyte-associated antigen (CTLA)-4 immunoglobulin (Ig), anti-CD40L, and anti-lymphocyte function-associated antigen (LFA)-1. Methods. Recombinase activating gene-deficient (Rag1(-/-)) mice were transplanted with BALB/c hearts and adoptively transferred with IL-10(-/-) CD4(+) T cells, CD4(+)CD25(-) T cells or CD4(+)CD25(-)CD103(-) T cells and treated with costimulation blockade. Intragraft T cells from C57BL/6 recipients were analyzed for the expression of the Foxp3 protein after tolerance induction. Results. Mice reconstituted with IL-10(-/-) CD4(+) T cells, CD4(+)CD25(-) T cells or CD4(+)CD25(-) CD103(-) T cells and treated with costimulation blockade accepted allografts permanently. Analysis of cells from recipient mice adoptively transferred with CD4(+)CD25(-) T cells contained a population of CD4(low)CD25(+) T cells 100 days after transplantation. Costimulation blockade partially prevented the homeostatic proliferation of CD4(+)CD25(-)CD103(-) T cells in Rag-1(-/-) recipients. Accepted allografts contained an elevated number of CD4(+)Foxp3(+) T cells. Conclusions. These results indicate that T-cell derived IL-10 is not essential for induction of graft acceptance in mice treated with costimulation blockade, but that treatment limits T-cell expansion in the recipients. The results further indicate that tolerance is maintained by intragraft CD4(+)Foxp3(+) T cells.
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