| 1. |
- Carlsson, Göran, et al.
(författare)
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Kostmann syndrome or infantile genetic agranulocytosis, part two : Understanding the underlying genetic defects in severe congenital neutropenia
- 2007
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 96:6, s. 813-819
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Forskningsöversikt (refereegranskat)abstract
- Congenital neutropenia in man was first reported 50 years ago by the Swedish paediatrician Rolf Kostmann. He coined the term 'infantile genetic agranulocytosis' for this condition, which is now known as Kostmann syndrome. Recent studies have revealed mutations in ELA-2, encoding the neutrophil granule protease, neutrophil elastase, in autosomal dominant neutropenia, and mutations in HAX-1, encoding an anti-apoptotic protein, in autosomal recessive neutropenia. Conclusion: Future studies should aim to clarify the mechanisms underlying the evolution of secondary malignancies in these patients.
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| 2. |
- Ding, Yuan C, et al.
(författare)
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A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
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| 3. |
- Klein, Christoph, et al.
(författare)
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HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease)
- 2007
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:1, s. 86-92
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Tidskriftsartikel (refereegranskat)abstract
- Autosomal recessive severe congenital neutropenia (SCN) constitutes a primary immunodeficiency syndrome associated with increased apoptosis in myeloid cells, yet the underlying genetic defect remains unknown. Using a positional cloning approach and candidate gene evaluation, we identified a recurrent homozygous germline mutation in HAX1 in three pedigrees. After further molecular screening of individuals with SCN, we identified 19 additional affected individuals with homozygous HAX1 mutations, including three belonging to the original pedigree described by Kostmann. HAX1 encodes the mitochondrial protein HAX1, which has been assigned functions in signal transduction and cytoskeletal control. Here, we show that HAX1 is critical for maintaining the inner mitochondrial membrane potential and protecting against apoptosis in myeloid cells. Our findings suggest that HAX1 is a major regulator of myeloid homeostasis and underline the significance of genetic control of apoptosis in neutrophil development.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Alm, Jan, 1947-
(författare)
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Dyslexia: Relevance of Concepts, Validity of Measurements, and Cognitive Functions
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The thesis opens with an exposition of different uses of the term dyslexia. In that context its conceptual relevance is discussed. The empirical studies investigate a) different aspects of validity of cognitive and achievement instruments often used in diagnostic assessment of dyslexia, b) different cognitive profiles for adults with dyslexia, and c) the relationship between cognitive and achievement measures.Study I demonstrated the factor structure of the Swedish WAIS-R to be in close agreement with results of comparable analyses on normal and clinical groups in many countries world-wide, giving strong support for the construct validity of the Swedish WAIS-R for a group of adults diagnosed with dyslexia. The results from the three-factor solution were interpreted in terms of theoretical constructs, notably those posited by Carroll (1993) and Horn (1989).The cognitive profiles of a sample of Swedish adults diagnosed with dyslexia—when using the three factors, the ACID profile, and the four-category Bannatyne profile—all resemble closely the profiles observed for a wide array of U.S. samples of children and adults diagnosed with dyslexia or learning disabilities. Gender differences on Digit Symbol, favoring females, were substantial in magnitude for the present sample, consistent with a bulk of research on gender differences for samples of normal individuals and of those identified with learning problems.In Study II, factor analysis of nine Swedish achievement tests often used for dyslexia assessment yielded five meaningful factors in a group of adults diagnosed with dyslexia. Factors appeared to measure decoding, visual speed, reading comprehension, reading fluency, and phonological ability. The relationship between the five achievement factors and WAIS-R variables was subsequently examined. The Visual Speed and Reading Comprehension factors each correlated significantly with four of six global WAIS-R scores (two of three IQs and two of three factor scores). Visual Speed tended to correlate significantly with nonverbal scores and Reading Comprehension with verbal scores. Although the Phonological Ability factor did not correlate significantly with any verbal or nonverbal global score, it did correlate significantly with the Freedom from Distractibility factor and with all its component subtests—Digit Span, Arithmetic, and Digit Symbol. Decoding (technical reading skill) showed no significant relationship to any WAIS-R variable studied. More surprisingly, the Reading Fluency factor failed to show significant relationships to the WAIS-R.Study III examined the validity of The Word Chain Test, a frequently used instrument in Swedish screening and diagnostic assessments of dyslexia. Different sources of validity evidence were evaluated. In summary, the results failed to support validity both for the WRI-index and the Wordchain subtest, suggesting that the instrument seems to be of questionable value in screening or diagnostic assessment of dyslexia.
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| 10. |
- Antoniou, Antonis C., et al.
(författare)
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Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2011
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
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Tidskriftsartikel (refereegranskat)abstract
- Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
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| 11. |
- Arridge, Christopher S., et al.
(författare)
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Uranus Pathfinder : exploring the origins and evolution of Ice Giant planets
- 2012
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 753-791
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Tidskriftsartikel (refereegranskat)abstract
- The "Ice Giants" Uranus and Neptune are a different class of planet compared to Jupiter and Saturn. Studying these objects is important for furthering our understanding of the formation and evolution of the planets, and unravelling the fundamental physical and chemical processes in the Solar System. The importance of filling these gaps in our knowledge of the Solar System is particularly acute when trying to apply our understanding to the numerous planetary systems that have been discovered around other stars. The Uranus Pathfinder (UP) mission thus represents the quintessential aspects of the objectives of the European planetary community as expressed in ESA's Cosmic Vision 2015-2025. UP was proposed to the European Space Agency's M3 call for medium-class missions in 2010 and proposed to be the first orbiter of an Ice Giant planet. As the most accessible Ice Giant within the M-class mission envelope Uranus was identified as the mission target. Although not selected for this call the UP mission concept provides a baseline framework for the exploration of Uranus with existing low-cost platforms and underlines the need to develop power sources suitable for the outer Solar System. The UP science case is based around exploring the origins, evolution, and processes at work in Ice Giant planetary systems. Three broad themes were identified: (1) Uranus as an Ice Giant, (2) An Ice Giant planetary system, and (3) An asymmetric magnetosphere. Due to the long interplanetary transfer from Earth to Uranus a significant cruise-phase science theme was also developed. The UP mission concept calls for the use of a Mars Express/Rosetta-type platform to launch on a Soyuz-Fregat in 2021 and entering into an eccentric polar orbit around Uranus in the 2036-2037 timeframe. The science payload has a strong heritage in Europe and beyond and requires no significant technology developments.
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| 12. |
- Blix Germundsson, Lisa, et al.
(författare)
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Participatory ex-ante impact assessment for interactive research and development in agriculture and food systems
- 2024
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Ingår i: Impact Assessment and Project Appraisal. - Abingdon : Taylor & Francis. - 1461-5517 .- 1471-5465. ; , s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Drawing upon literature from both impact assessment of development projects and agricul-tural research, the aim of this article is to analyse the pilot testing of a new multi-dimensional assessment framework for defining and evaluating the societal impact of agricultural research and corresponding education. The research approach involves an action research effort of pilot testing in three case studies from three different countries. The framework assumes a systems view, understands impact as socially embedded, and adopts the concepts of contribution and productive interactions rather than cause-and-effect attribution. The emerging experiences include developing both project-specific and universal indicators; gauging impacts at different levels and sustainability dimensions; handling the issues of attribution and time frame; and the role of stakeholder involvement. The results have the potential to support the development of a new role for impact assessment, by enabling principal actors in research and higher educa-tion institutions to take responsibility for contributing to concrete and demonstrable sustain-ability changes in society. © 2024 The Author(s).
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| 13. |
- Bobbio, Emanuele, et al.
(författare)
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Association between central haemodynamics and renal function in advanced heart failure: a nationwide study from Sweden.
- 2022
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Ingår i: ESC heart failure. - : Wiley. - 2055-5822. ; 9:4, s. 2654-2663
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Tidskriftsartikel (refereegranskat)abstract
- Renal dysfunction in patients with heart failure (HF) has traditionally been attributed to declining cardiac output and renal hypoperfusion. However, other central haemodynamic aberrations may contribute to impaired kidney function. This study assessed the relationship between invasive central haemodynamic measurements from right-heart catheterizations and measured glomerular filtration rate (mGFR) in advanced HF.All patients referred for heart transplantation work-up in Sweden between 1988 and 2019 were identified through the Scandiatransplant organ-exchange organization database. Invasive haemodynamic variables and mGFR were retrieved retrospectively. A total of 1001 subjects (49±13years; 24% female) were eligible for the study. Analysis of covariance adjusted for age, sex, and centre revealed that higher right atrial pressure (RAP) displayed the strongest relationship with impaired GFR [β coefficient -0.59; 95% confidence interval (CI) -0.69 to -0.48; P<0.001], followed by lower mean arterial pressure (MAP) (β coefficient 0.29; 95% CI 0.14-0.37; P<0.001), and finally reduced cardiac index (β coefficient 3.51; 95% CI 2.14-4.84; P<0.003). A combination of high RAP and low MAP was associated with markedly worse mGFR than any other RAP/MAP profile, and high renal perfusion pressure (RPP, MAP minus RAP) was associated with superior renal function irrespective of the degree of cardiac output.In patients with advanced HF, high RAP contributed more to impaired GFR than low MAP. A higher RPP was more closely related to GFR than was high cardiac index.
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| 14. |
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| 15. |
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| 16. |
- Eriksson, Daniel, et al.
(författare)
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Health-related quality of life across all stages of autosomal dominant polycystic kidney disease
- 2017
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 32:12, s. 2106-2111
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A limited number of studies have assessed health-related quality of life (HRQoL) in autosomal dominant polycystic kidney disease (ADPKD). Results to date have been conflicting and studies have generally focused on patients with later stages of the disease. This study aimed to assess HRQoL in ADPKD across all stages of the disease, from patients with early chronic kidney disease (CKD) to patients with end-stage renal disease.METHODS: A study involving cross-sectional patient-reported outcomes and retrospective clinical data was undertaken April-December 2014 in Denmark, Finland, Norway and Sweden. Patients were enrolled into four mutually exclusive stages of the disease: CKD stages 1-3; CKD stages 4-5; transplant recipients; and dialysis patients.RESULTS: Overall HRQoL was generally highest in patients with CKD stages 1-3, followed by transplant recipients, patients with CKD stages 4-5 and patients on dialysis. Progressive disease predominately had an impact on physical health, whereas mental health showed less variation between stages of the disease. A substantial loss in quality of life was observed as patients progressed to CKD stages 4-5.CONCLUSIONS: Later stages of ADPKD are associated with reduced physical health. The value of early treatment interventions that can delay progression of the disease should be considered.
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| 17. |
- Eriksson, Daniel, et al.
(författare)
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Real-world costs of autosomal dominant polycystic kidney disease in the Nordics
- 2017
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is limited real-world data on the economic burden of patients with autosomal dominant polycystic kidney disease (ADPKD). The objective of this study was to estimate the annual direct and indirect costs of patients with ADPKD by severity of the disease: chronic kidney disease (CKD) stages 1-3; CKD stages 4-5; transplant recipients; and maintenance dialysis patients. Methods: A retrospective study of ADPKD patients was undertaken April-December 2014 in Denmark, Finland, Norway and Sweden. Data on medical resource utilisation were extracted from medical charts and patients were asked to complete a self-administered questionnaire. Results: A total of 266 patients were contacted, 243 (91%) of whom provided consent to participate in the study. Results showed that the economic burden of ADPKD was substantial at all levels of the disease. Lost wages due to reduced productivity were large in absolute terms across all disease strata. Mean total annual costs were highest in dialysis patients, driven by maintenance dialysis care, while the use of immunosuppressants was the main cost component for transplant care. Costs were twice as high in patients with CKD stages 4-5 compared to CKD stages 1-3. Conclusions: Costs associated with ADPKD are significant and the progression of the disease is associated with an increased frequency and intensity of medical resource utilisation. Interventions that can slow the progression of the disease have the potential to lead to substantial reductions in costs for the treatment of ADPKD.
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| 18. |
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| 19. |
- Fredrikson, Mats, et al.
(författare)
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Forskningsresultaten inom KBT är otvetydiga : Replik
- 2009
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Ingår i: Läkartidningen. - Stockholm : Sveriges läkarförbund. - 0023-7205 .- 1652-7518. ; 106:18-19, s. 1294-1296
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 20. |
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| 21. |
- Fredrikson, Mats, et al.
(författare)
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Regeringens storsatsning mot psykisk ohälsa äventyrar patientsäkerheten
- 2009
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Ingår i: Läkartidningen. - Stockholm : Sveriges läkarförbund. - 0023-7205 .- 1652-7518. ; 106:13, s. 946-947
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Regeringens rehabiliteringsgaranti kan få förödande konsekvenser för tilltron till kognitiv beteendeterapi som behandlingsmetod och för den enskilda patienten som tror sig få KBT av en kompetent behandlare. Orsaken är regeringens lågt ställda krav på behandlarnas kompetens. Rehabiliteringsgarantin bör omformuleras, anser nio KBT-företrädare.
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| 22. |
- Han, Hongya, et al.
(författare)
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Human 15-lipoxygenase-1 is a regulator of dendritic-cell spreading and podosome formation
- 2017
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Ingår i: The FASEB Journal. - : FEDERATION AMER SOC EXP BIOL. - 0892-6638 .- 1530-6860. ; 31:2, s. 491-504
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DCs) involved in proinflammatory immune responses derive mainly from peripheral monocytes, and the cells subsequently mature and migrate into the inflammatory micromilieu. Here we report that suppressing of 15-lipoxygenase-1 led to a substantial reduction in DC spreading and podosome formation in vitro. The surface expression of CD83 was significantly lower in both sh-15-lipoxygenase-1 (15-LOX-1)-transduced cells and DCs cultivated in the presence of a novel specific 15-LOX-1 inhibitor. The T-cell response against tetanus-pulsed DCs was only affected to a minor extent on inhibition of 15-LOX-1. In contrast, endocytosis and migration ability of DCs were significantly suppressed on 15-LOX-1 inhibition. The expression of 15-LOX-1 in DCs was also demonstrated in affected human skin in atopic and contact dermatitis, showing that the enzyme is indeed expressed in inflammatory diseases in vivo. This study demonstrated that inhibiting 15-LOX-1 led to an impaired podosome formation in DCs, and consequently suppressed antigen uptake and migration capacity. These results indicated that 15-LOX-1 is a potential target for inhibiting the trafficking of DCs to lymphoid organs and inflamed tissues and decreasing the inflammatory response attenuating symptoms of certain immunologic and inflammatory disorders such as dermatitis.-Han, H., Liang, X., Ekberg, M., Kritikou, J. S., Brunnstro " m, angstrom., Pelcman, B., Matl, M., Miao, X., Andersson, M., Yuan, X., Schain, F., Parvin, S., Melin, E., Sjoberg, J., Xu, D., Westerberg, L. S., Bjorkholm, M., Claesson, H.- E. Human 15-lipoxygenase- 1 is a regulator of dendritic-cell spreading and podosome formation.
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| 23. |
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| 24. |
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| 25. |
- Hemmingsson, Tomas, et al.
(författare)
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The association between cognitive ability measured at ages 18-20 and coronary heart disease in middle age among men : a prospective study using the Swedish 1969 conscription cohort.
- 2007
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Ingår i: Social Science and Medicine. - : Elsevier BV. - 0277-9536 .- 1873-5347. ; 65:7, s. 1410-1419
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Tidskriftsartikel (refereegranskat)abstract
- An association between childhood cognitive ability measured with IQ-tests and coronary heart disease (CHD) incidence has been reported recently. It is not clear from those studies to what extent the increased relative risk associated with lower cognitive ability may be explained by CHD risk factors. This study aims to investigate the association between cognitive ability measured at age 18-20 and incidence of CHD, acute myocardial infarction (AMI), and stroke among middle aged men adjusting for risk factors for CHD over the life course. Data on cognitive ability, and other risk factors for CHD (height, parental cardiovascular diseases (CVD) mortality, blood pressure, smoking, risky use of alcohol, BMI), were collected from 49,321 men, born in 1949-51, at conscription for compulsory military training in 1969/70 in Sweden. Information on socioeconomic factors in childhood (socioeconomic position and crowded housing) and adulthood (education, socioeconomic position, and income), as well as information on mortality and morbidity, was collected through national registers. Cognitive ability showed an inverse and graded association with CHD incidence. Adjustment for indicators of poor childhood circumstances, behavioural factors measured in late adolescence, and adult social circumstances strongly attenuated the increased risks of CHD and AMI. The contribution from adult social circumstances, after adjustment from all other factors, was very small. After adjustment for all risk factors no significantly increased relative risk was seen for stroke incidence. After adjustment for risk factors over the life course, the risk of CHD and AMI associated with cognitive ability decreased substantially, and was of borderline significance. Given the results from this study it is unlikely that cognitive ability is a risk factor on its own for CHD, AMI and stroke among men below 54 years of age.
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| 26. |
- Hultgren, Anders, et al.
(författare)
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Asymmetric Limit Cycles in an Industrially Applied Controlled Resonant Converter
- 2009
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Konferensbidrag (refereegranskat)abstract
- An industrially applied LCC power converter is modelled as a hybrid system. It is found that the hybrid system given a parameter set up and different initial conditions has three different limit cycles, one unstable and two asymmetric stable limit cycles. Effects of the asymmetric limit cycles are considered.
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| 27. |
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| 28. |
- Hultgren, Anders, et al.
(författare)
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Limit cycle control of an industrially applied resonant converter modelled as a hybrid system
- 2011
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Ingår i: 2011 IEEE International Symposium on Circuits and Systems (ISCAS). - Rio de Janeiro : IEEE. - 9781424494736 ; , s. 1916-1919
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Konferensbidrag (refereegranskat)abstract
- Limit cycle control of an industrially applied high power, high voltage resonant power converter is modelled as a hybrid system. It is found that the hybrid system with three continuous states and one logic state given a parameter set up and different initial conditions has a rich solution set indicating possible problems in the industrial application. The solution set are one central closed trajectory and two asymmetric types of limit cycles.
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| 29. |
- Hultgren, Anders, et al.
(författare)
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Limit Cycles in an Industrially Applied Hybrid System
- 2010
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Ingår i: 2010 11th International Workshop on 11th IEEE Workshop on Variable Structure Systems. - Mexico city : IEEE. - 9781424458295 ; , s. 277-282
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Konferensbidrag (refereegranskat)abstract
- An industrially applied LCC power converter is modelled as a hybrid system. It is found that the hybrid system with three continuous states and one logic state given a parameter set up and different initial conditions has among other solutions one central closed trajectory and two types of limit cycles, on the left and the right side. The other solutions are indicated.
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| 30. |
- Ihrmark, Katarina, et al.
(författare)
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Comparative Molecular Evolution of Trichoderma Chitinases in Response to Mycoparasitic Interactions
- 2010
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Ingår i: Evolutionary Bioinformatics. - 1176-9343. ; 6, s. 1-25
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Tidskriftsartikel (refereegranskat)abstract
- Certain species of the fungal genus Trichoderma are potent mycoparasites and are used for biological control of fungal diseases on agricultural crops. In Trichoderma, whole-genome sequencing reveal between 20 and 36 different genes encoding chitinases, hydrolytic enzymes that are involved in the mycoparasitic attack. Sequences of Trichoderma chitinase genes chi18-5, chi18-13, chi18-15 and chi18-17, which all exhibit specific expression during mycoparasitism-related conditions, were determined from up to 13 different taxa and studied with regard to their evolutionary patterns. Two of them, chi18-13 and chi18-17, are members of the B1/B2 chitinase subgroup that have expanded significantly in paralog number in mycoparasitic Hypocrea atroviridis and H. virens. Chi18-13 contains two codons that evolve under positive selection and seven groups of co-evolving sites. Chi18-15 displays a unique codon-usage and contains five codons that evolve under positive selection and three groups of co-evolving sites. Regions of high amino acid variability are preferentially localized to substrate-or product side of the catalytic clefts. Differences in amino acid diversity/conservation patterns between different Trichoderma clades are observed. These observations show that Trichoderma chitinases chi18-13 and chi18-15 evolve in a manner consistent with rapid co-evolutionary interactions and identifies putative target regions involved in determining substrate-specificity.
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| 31. |
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| 32. |
- Lapinlampi, Niina, et al.
(författare)
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Common data elements and data management : Remedy to cure underpowered preclinical studies
- 2017
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Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211. ; 129, s. 87-90
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Tidskriftsartikel (refereegranskat)abstract
- Lack of translation of data obtained in preclinical trials to clinic has kindled researchers to develop new methodologies to increase the power and reproducibility of preclinical studies. One approach relates to harmonization of data collection and analysis, and has been used for a long time in clinical studies testing anti-seizure drugs. EPITARGET is a European Union FP7-funded research consortium composed of 18 partners from 9 countries. Its main research objective is to identify biomarkers and develop treatments for epileptogenesis. As the first step of harmonization of procedures between laboratories, EPITARGET established working groups for designing project-tailored common data elements (CDEs) and case report forms (CRFs) to be used in data collection and analysis. Eight major modules of CRFs were developed, presenting >1000 data points for each animal. EPITARGET presents the first single-project effort for harmonization of preclinical data collection and analysis in epilepsy research. EPITARGET is also anticipating the future challenges and requirements in a larger-scale preclinical harmonization of epilepsy studies, including training, data management expertise, cost, location, data safety and continuity of data repositories during and after funding period, and incentives motivating for the use of CDEs.
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| 33. |
- Liu, Yan, et al.
(författare)
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Long crack behavior in a thermal barrier coating upon thermal shock loading
- 2005
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Ingår i: Journal of Thermal Spray Technology. - : Springer Science and Business Media LLC. - 1544-1016 .- 1059-9630 .- 0000-0000. ; 14:2, s. 258-263
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Tidskriftsartikel (refereegranskat)abstract
- The behavior of macroscopic long cracks in the ceramic top coat of a thermal barrier coating (TBC) system subjected to thermal shock loading and the influence of the cracks on the coating durability were investigated experimentally and numerically. Thermal shock testing was conducted until coating failure. Comparisons were made with coating samples without macroscopic cracks. The experimental results revealed that the presence of macroscopic cracks reduces the life of the TBC. The finite-element method, with a fracture mechanics approach, was applied to analyze preexisting long cracks, and the calculations correlate well with the experimental findings. It was found that the life of the coating is reduced with crack length as well as with maximum cycle temperature. It was also found that the stress-intensity factors for long cracks are initially high and decrease with the number of temperature cycles, which indicates that rapid crack growth occurs during the first number of cycles.
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| 34. |
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| 35. |
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| 36. |
- Melin, Jan, et al.
(författare)
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A third dose SARS-CoV-2 BNT162b2 mRNA vaccine results in improved immune response in hemodialysis patients
- 2022
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Ingår i: Upsala Journal of Medical Sciences. - : Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 127:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The hemodialysis (HD) population has been a vulnerable group during the coronavirus disease 2019 (COVID-19) pandemic. Advanced chronic kidney disease with uremia is associated with weaker immune response to infections and an attenuated response to vaccines. The aim of this study was to study the humoral and cellular response to the second and third doses of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) BNT162b2 mRNA vaccine in HD patients and to follow the response over time.Methods: The patients received their first two vaccine doses from 28 December 2020 within a 4-week interval and the third dose in September 2021 and were followed-up for humoral and cellular immune response at 1) 7-15 weeks and 2) 6-8 months after dose two (no t-cell reactivity measured), and 3) 3 weeks and 4) 3 months after dose three. Fifty patients were initially enrolled, and 40 patients were followed during the entire study. Levels of COVID-19 (SARS-CoV-2) IgG antibody against the Spike antigen (anti-S) and T-cell reactivity testing against the Spike protein using Enzyme-Linked ImmunoSpot (ELISPOT) technology were evaluated.Results: IgG antibodies to anti-S were detected in 35 (88%) of the 40 patients 7-15 weeks after vaccine dose two, 31 (78%) were positive, and 4 (10%) borderline. The median anti-S titer was 606 Abbott Units/milliliter (AU/mL) (interquartile range [IQR] 134-1,712). Three months after the third dose, anti-S was detected in 38 (95%) of 40 patients (P < 0.01 compared to after dose two), and the median anti-S titer was 9,910 AU/mL (IQR 2,325-26,975). Cellular reactivity was detected in 22 (55%), 34 (85%), and 28 (71%) of the 40 patients, and the median T-cell response was 9.5 (IQR 3.5-80), 51.5 (14.8-132), and 19.5 (8.8-54.2) units, respectively, for 6-8 months after dose two, 3 weeks, and 3 months after dose three.Conclusions: Our data show that a third dose of SARS-CoV-2 BNT162b2 mRNA vaccine gives a robust and improved immunological response in HD patients, but a few patients did not develop any anti-S response during the entire study, indicating the importance to monitor the vaccine response since those who do not respond could now be given monoclonal antibodies if they contract a COVID-19 infection or in the future antivirals.
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| 37. |
- Melin, Jan, et al.
(författare)
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Bedside BNP as a marker of overhydration in hemodialysis patients
- 2017
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 28:Suppl., s. 878-878
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundManagement of hydration status in dialysis patients is a great challenge to nephrologists, and new tools to understand the hydration status (HS) are needed. The aim of this study was to investigate the usefulness of brain natriuretic peptide (BNP), analyzed bedside, as a marker of overhydration (OH) in hemodialysis (HD) patients.MethodsWe investigated the distribution of BNP, measured by Alere Triage® BNP Test, and analyzed the correlation between BNP and HS, defined by bioimpedance spectroscopy (BIS) in 64 HD patients. We assumed there would be a difference in HS between patients with high levels of BNP (h-BNP) and low levels of BNP (l-BNP) and choose an arbitrary cut off of 500 ng/ml, and then differences between the groups were tested for significance. HS, blood pressure (BP) and heart rate was measured, and BNP analyzed, before one mid-week dialysis session. Blood samples were also drawn for analysis of NT-proBNP and inflammatory markers. Demographic data, comorbidities, lab values and nutritional status were collected from medical records.ResultsA positive correlation was found between BNP and OH (r = 0.4), although many severely overhydrated patients had normal or just slightly elevated BNP. BNP levels were above 500 in 38 % (n=24) of the participants. The level of OH before dialysis was higher in the h-BNP group than in the l-BNP group. There was no difference in BP before or after dialysis, but patients in the h-BNP group were older, had lower muscle strength and lower Hemoglobin and Albumin levels compared to the l-BNP group.ConclusionA normal BNP does not rule out OH as defined by BIS in HD patients, on the other hand euvolemia was rare in patients with elevated BNP. This suggests that BNP might serve as a marker of OH in a subgroup of old and frail patients. In a further study we aim to investigate if the relationship between BNP, when elevated, and OH is reproducible at an individual level.
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| 39. |
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| 40. |
- Melin, Jan, et al.
(författare)
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Humoral and cellular response to SARS-CoV-2 BNT162b2 mRNA vaccine in hemodialysis patients
- 2021
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Ingår i: BMC Immunology. - : BioMed Central (BMC). - 1471-2172. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Hemodialysis (HD) patients have an increased risk of acquiring infections due to many health care contacts and may, in addition, have a suboptimal response to vaccination and a high mortality from Covid-19 infection. Methods In 50 HD patients (mean age 69.4 years, 62% men) administration of SARS-CoV-2BNT162b2 mRNA vaccine began in Dec 2020 and the immune response was evaluated 7-15 weeks after the last dose. Levels of Covid-19 (SARS-CoV-2) IgG antibody against the nucleocapsid antigen (anti-N) and the Spike antigen (anti-S) and T-cell reactivity testing against the Spike protein using ELISPOT technology were evaluated. Results Out of 50 patients, anti-S IgG antibodies indicating a vaccine effect or previous Covid-19 infection, were detected in 37 (74%), 5 (10%) had a borderline response and 8 (16%) were negative after two doses of vaccine. T-cell responses were detected in 29 (58%). Of the 37 patients with anti-S antibodies, 25 (68%) had a measurable T-cell response. 2 (40%) out of 5 patients with borderline anti-S and 2 (25%) without anti-S had a concomitant T-cell response. Twenty-seven (54%) had both an antibody and T-cell response. IgG antibodies to anti-N indicating a previous Covid-19 disease were detected in 7 (14%) patients. Conclusions Most HD patients develop a B- and/or T-cell response after vaccination against Covid-19 but approx. 20% had a limited immunological response. T-cell reactivity against Covid-19 was only present in a few of the anti-S antibody negative patients.
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| 41. |
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| 42. |
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| 43. |
- Melin, Jan, et al.
(författare)
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Ischemia-induced renal expression of hyaluronan and CD44 in diabetic rats.
- 2006
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Ingår i: Nephron. Experimental nephrology. - : S. Karger AG. - 1660-2129. ; 103:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Unilateral renal ischemia during 30 min causes severe, non-reversible renal damage in diabetic (DM) rats, but not in nondiabetic rats. Hyaluronan (HA) is a glycosaminglycan involved in various forms of renal injury. We examined the role of HA and CD44, a major receptor for HA, in the development of postischemic renal injury in DM rats. METHODS: The left renal artery of streptozotocin diabetic Wistar rats was clamped for 30 min. The HA content in the kidneys was measured. A biotinylated HA-binding probe was used to localize HA. Inflammatory cells and other cells expressing CD44 were identified by immunohistochemistry. RESULTS: In ischemic DM kidneys the renal HA-content started to increase already after 24 h and significantly so after 1-8 weeks after ischemia/reperfusion (I/R). The relative water content of the kidneys increased in parallel. HA started to appear in the cortex of ischemic DM kidneys 1 week after I/R. In contrast, the non-DM ischemic kidneys showed no increase of HA and water content after 1-8 weeks after I/R. The tubular cells in the cortex and outer medulla demonstrated increased staining for CD44. In the same compartments the increased numbers of infiltrating inflammatory cells also expressed CD44. CONCLUSION: HA-accumulation in the renal cortex might contribute to the renal damage seen after transient ischemia in DM rats by promoting inflammation through interaction between HA and CD44 expressing inflammatory cells. Furthermore, HA accumulation may contribute to an interstitial renal edema.
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| 44. |
- Melin, Jan, 1965
(författare)
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Measurements and Analyses of the Performancs of Laboratory Fume Hoods
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- When working with health-hazardous substances or unpleasant airborne pollutants, it is important to have ventilation systems that are designed and operated to protect persons working in the laboratory. In laboratory applications, the fume hood is the most commonly used item of protective equipment. This thesis is concerned with the air-handling aspects of the protective function of laboratory fume hoods. In order to be certain that a laboratory fume hood is providing adequate protection, so that users are not exposed to health-hazardous substances, it is necessary to check its performance. There are a number of ways of doing this, but the most commonly employed method for quantitative evaluation of fume hood performance is to meter a tracer gas inside the fume hood and measure the outward leakage with an IR analyser. Measurements presented in the thesis show that outward leakage from a fume hood has a very rapid, pulsed characteristic. Since the IR analysers that are normally used when checking the performance of a fume hood do not have sufficiently rapid response, this means that the recorded outward leakage does not fully reflect the actual leakage. In the thesis, theoretical relationships are presented that describe the inertia of IR analysers, and calculations for short-duration pulses and normal instrument time constants show that the gas concentration recorded by the instruments differ considerably from the true gas concentration. The thesis describes two methods of determining the actual characteristic of the outward leakage from a fume hood. One method is based on a derived relationship that estimates the true gas concentration on the basis of the recorded concentration. The other way of determining the actual outward leakage process is to use a newly developed instrument with negligible inertia. The measurements that were made with this instrument clearly show that the outward leakage from a fume hood is pulsed, and that the pulses are of considerably shorter duration and have higher peak values than had previously been possible to record with traditional IR instruments. In the thesis, results are also presented from measurements with the aim of determining how fast the flow needs to be adjusted after the position of the hood sash is changed in order to prevent outward leakage. These measurements indicate that the air flow rate should be adjusted and stabilized within 3-4 seconds in order to avoid outward leakage. Further, in order to investigate whether flow variations in the exhaust air system could affect the performance of a fume hood, measurements were made in a test room. The results show that if there are oscillations in the exhaust air system while someone is in front of the fume hood, unstable air flow through the hood occurs, sufficient to create outward leakage.
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| 46. |
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| 47. |
- Melin, Jan, 1966-
(författare)
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Renal Ischemia/Reperfusion Injury in Diabetes : Experimental Studies in the Rat
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diabetes mellitus (DM) is one of the leading causes of end stage renal failure. An increased susceptibility to renal ischemia/reperfusion (I/R)-injury was found in DM rats. Unilateral renal ischemia for as short as 20 minutes led to an irreversible progressive injury in DM kidneys, whereas the injury in non-DM kidneys was almost reversible. The renal I/R injury was characterized by anuria, infiltration of inflammatory cells, tubular atrophy, dilation of the remaining tubuli and tubulointerstitial fibrosis. Necrotic areas were found in the inner parts of the outer medulla and in the papilla. The renal medulla was the most vulnerable part of the kidney. This was seen both by the extent of fibrosis four and eight weeks after I/R and by the presence of TUNEL-positive (apoptotic) cells 6h after ischemia. Increased accumulation of HA and enhanced CD44 expression was seen after I/R in DM kidneys.Treatment with long acting insulin 7-14 days before I/R, decreased the number of apoptotic cells in the renal medulla and protected renal function and morphology after the insult, while insulin treatment after the injury did not have any protective effect. Short acting insulin given 2-6 hours before I/R partially protected renal function but did not improve the morphological picture.Treatment with the angiotensin II receptor type 1 blocker candesartan, the PAF-antagonist UR-12670, the immunosuppressive agents tacrolimus and cyclosporin A, or prednisolone did not improve the outcome of the renal I/R injury in DM. Injection of cobalt protoporphyrin (CoPP) intraperitoneally in order to induce an over-expression of heme oxygenase-1 (HO-1) resulted in a trend towards a better function in DM kidneys after I/R. However, the induction of HO-1 by intraperitoneal CoPP injection was not achieved in all rats, when examined by western blot.In conclusion, unilateral renal I/R leads to a severe progressive injury in DM kidneys. Insulin treatment before ischemia, but not after, reduces the renal injury in DM rats. Studies using a more reliable administration of CoPP are required to decide if induction of HO-1 protects against renal I/R injury in DM.
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