| 1. |
- Almstedt, Karin, 1980-, et al.
(författare)
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Unfolding a folding disease: folding, misfolding and aggregation of the marble brain syndrome-associated mutant H107Y of human carbonic anhydrase II
- 2004
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Ingår i: Journal of Molecular Biology. - Oxford : Elsevier. - 0022-2836 .- 1089-8638. ; 342:2, s. 619-633
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Tidskriftsartikel (refereegranskat)abstract
- Most loss-of-function diseases are caused by aberrant folding of important proteins. These proteins often misfold due to mutations. The disease marble brain syndrome (MBS), known also as carbonic anhydrase II deficiency syndrome (CADS), can manifest in carriers of point mutations in the human carbonic anhydrase II (HCA II) gene. One mutation associated with MBS entails the His107Tyr substitution. Here, we demonstrate that this mutation is a remarkably destabilizing folding mutation. The loss-of-function is clearly a folding defect, since the mutant shows 64% of CO2 hydration activity compared to that of the wild-type at low temperature where the mutant is folded. On the contrary, its stability towards thermal and guanidine hydrochloride (GuHCl) denaturation is highly compromised. Using activity assays, CD, fluorescence, NMR, cross-linking, aggregation measurements and molecular modeling, we have mapped the properties of this remarkable mutant. Loss of enzymatic activity had a midpoint temperature of denaturation (Tm) of 16 °C for the mutant compared to 55 °C for the wild-type protein. GuHCl-denaturation (at 4 °C) showed that the native state of the mutant was destabilized by 9.2 kcal/mol. The mutant unfolds through at least two equilibrium intermediates; one novel intermediate that we have termed the molten globule light state and, after further denaturation, the classical molten globule state is populated. Under physiological conditions (neutral pH; 37 °C), the His107Tyr mutant will populate the molten globule light state, likely due to novel interactions between Tyr107 and the surroundings of the critical residue Ser29 that destabilize the native conformation. This intermediate binds the hydrophobic dye 8-anilino-1-naphthalene sulfonic acid (ANS) but not as strong as the molten globule state, and near-UV CD reveals the presence of significant tertiary structure. Notably, this intermediate is not as prone to aggregation as the classical molten globule. As a proof of concept for an intervention strategy with small molecules, we showed that binding of the CA inhibitor acetazolamide increases the stability of the native state of the mutant by 2.9 kcal/mol in accordance with its strong affinity. Acetazolamide shifts the Tm to 34 °C that protects from misfolding and will enable a substantial fraction of the enzyme pool to survive physiological conditions.
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| 2. |
- Hedenas, Henrik, et al.
(författare)
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Changes Versus Homeostasis in Alpine and Sub-Alpine Vegetation Over Three Decades in the Sub-Arctic
- 2012
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Ingår i: Ambio. - : Springer Verlag (Germany). - 0044-7447 .- 1654-7209. ; 41, s. 187-196
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Tidskriftsartikel (refereegranskat)abstract
- Plant species distributions are expected to shift and diversity is expected to decline as a result of global climate change, particularly in the Arctic where climate warming is amplified. We have recorded the changes in richness and abundance of vascular plants at Abisko, sub-Arctic Sweden, by re-sampling five studies consisting of seven datasets; one in the mountain birch forest and six at open sites. The oldest study was initiated in 1977–1979 and the latest in 1992. Total species number increased at all sites except for the birch forest site where richness decreased. We found no general pattern in how composition of vascular plants has changed over time. Three species, Calamagrostis lapponica, Carex vaginata and Salix reticulata, showed an overall increase in cover/frequency, while two Equisetum taxa decreased. Instead, we showed that the magnitude and direction of changes in species richness and composition differ among sites.
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| 3. |
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| 4. |
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| 5. |
- Ericsson, Per, et al.
(författare)
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Characterization of particulate emissions and methodology for oxidation of particulates from non-diesel combustion systems
- 2008
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Ingår i: SAE Technical Paper. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191.
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Tidskriftsartikel (refereegranskat)abstract
- Tailpipe particulate emissions, i.e., particle number, size distribution and total mass, from a series of four-cylinder engines with 2L displacement and power output of approximately 150 hp have been measured. The engines were in their respective vehicle installation, all midsize vehicles from various manufacturers, and represented different combustion concepts, i.e., port- and direct-injected vehicles and E5 and E85 fuels. The results are compared to post-Euro V emission standards for gasoline and biofuels using diesel as reference. The results show that the type of combustion and fuel significantly affect the particulate formation. In general, direct-injected engines show high particle numbers and mass compared to port-injected engines. The particulate number and total mass can be reduced by using biofuels, e.g., ethanol mixes, instead of gasoline. Moreover, an experimental procedure and setup facilitating precise studies of oxidation of particulates in realistic filter structures by well-controlled gas flow (composition and temperature) and sample (particulate load and temperature) conditions has been developed. The results from this method have been verified by using commercial soot as reference.
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| 6. |
- Fadeel, Bengt, et al.
(författare)
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Kostmann disease and other forms of severe congenital neutropenia
- 2021
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Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 110:11, s. 2912-2920
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Tidskriftsartikel (refereegranskat)abstract
- Congenital neutropenia with autosomal recessive inheritance was first described by the Swedish paediatrician Rolf Kostmann who coined the term ‘infantile genetic agranulocytosis’. The condition is now commonly referred to as Kostmann disease. These patients display a maturation arrest of the myelopoiesis in the bone marrow and reduced neutrophil numbers and suffer from recurrent, often life-threatening infections. The molecular mechanism underlying congenital neutropenia has been intensively investigated, and mutations in genes that impinge on programmed cell death have been identified. The present review provides an overview of these studies.
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| 7. |
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| 8. |
- Lindehammer, Sabina, et al.
(författare)
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Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk
- 2008
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 45:4, s. 231-5
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.
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| 9. |
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| 10. |
- Ruiz-Pavon, Lorena, et al.
(författare)
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Functionally important amino acids in the Arabidopsis thylakoid phosphate transporter: Homology modeling and site-directed mutagenesis
- 2010
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Ingår i: Biochemistry. - : American Chemical Society. - 0006-2960 .- 1520-4995. ; 49:30, s. 6430-6439
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Tidskriftsartikel (refereegranskat)abstract
- The anion transporter 1 (ANTR1) from Arabidopsis thaliana, homologous to the mammalian members of the solute carrier 17 (SLC17) family, is located in the chloroplast thylakoid membrane. When expressed heterologously in Escherichia coli, ANTR1 mediates a Na+-dependent active transport of inorganic phosphate (Pi). The aim of this study was to identify amino acid residues involved in Pi binding and translocation by ANTR1 and in the Na+ dependence of its activity. A three-dimensional structural model of ANTR1 was constructed using the crystal structure of glycerol 3-phosphate/phosphate antiporter from E. coli as a template. Based on this model and multiple sequence alignments, five highly conserved residues in plant ANTRs and mammalian SLC17 homologues have been selected for site-directed mutagenesis, namely, Arg-120, Ser-124, and Arg-201 inside the putative translocation pathway and Arg-228 and Asp-382 exposed at the cytoplasmic surface of the protein. The activities of the wild-type and mutant proteins have been analyzed using expression in E. coli and radioactive Pi transport assays and compared with bacterial cells carrying an empty plasmid. The results from Pi- and Na+-dependent kinetics indicate the following: (i) Arg-120 and Arg-201 may be important for binding and translocation of the substrate; (ii) Ser-124 may function as a transient binding site for Na+ ions in close proximity to the periplasmic side; (iii) Arg-228 and Asp-382 may participate in interactions associated with protein conformational changes required for full transport activity. Functional characterization of ANTR1 should provide useful insights into the function of other plant and mammalian SLC17 homologous transporters.
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| 11. |
- Sundín, Anders, et al.
(författare)
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Radioimmunolocalization of hepatic metastases and subcutaneous xenografts from a human colonic cancer in the nude rat : Aspects of tumour implantation site and mode of antibody administration
- 1993
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 32:7-8, s. 877-885
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Tidskriftsartikel (refereegranskat)abstract
- Antibody localization was analyzed following intraperitoneal (i.p.) or intravenous (i.v.) injection of the 125I-labelled anti-CEA-MAb I-38S1 in 44 nude rats, in order to evaluate the influence of tumour implantation site and the route of MAb administration. The animals were xenografted with a human colonic cancer (LS 174 T), either in the form of hepatic metastases, subcutaneous (s.c.) tumours or both. Tissue measurements, 4 days after MAb injection, showed better uptake for hepatic than for s.c. tumours, irrespective of the route of antibody administration. Antibody accumulation per g liver metastases was not size dependent for noduli weighing between 4 and 1,110 mg. MAb excretion evaluated in 20 animals and blood activity studied in 11 rats were equivalent 24-96 h following i.p. and i.v. injection. Dissimilar autoradiographic patterns were seen in hepatic metastases with predominantly peripherally located clusters following i.p. and more homogeneously distributed grains after i.v. MAb administration. The results indicate that tumour implantation site has a quantitative, and the route of administration at least a qualitative impact on the tumour accretion of anti-CEA MAb I-38S1 in the present xenograft model.
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| 12. |
- Agardh, Daniel, et al.
(författare)
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Prediction of silent celiac disease at diagnosis of childhood type 1 diabetes by tissue transglutaminase autoantibodies and HLA
- 2001
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X. ; 2:2, s. 58-65
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aims were to estimate the diagnostic sensitivity and specificity of autoantibodies to tissue transglutaminase (IgA- and IgG-tTG), gliadin (AGA) and endomysium (EMA) in relation to human leukocyte antigen (HLA)-DQB1 alleles to identify silent celiac disease at diagnosis of type 1 diabetes. Methods: IgA- and IgG-tTG were measured in radioligand binding assays in 165 type 1 diabetic patients. Data on HLA-DQB1 were available for 148 patients and on both AGA and EMA for 164 patients. For patients considered positive for AGA or EMA, or both, an intestinal biopsy was suggested. HLA-DQB1 typing was carried out by polymerase chain reaction and hybridization with allele specific probes. Results: Three patients, left out from further study of antibodies, but not from HLA-DQB1 analysis, had treated celiac disease at diagnosis. Out of the other 162 type 1 diabetic patients tested, nine had IgA-tTG, six IgG-tTG, eight EMA, and 11 AGA. Biopsy was suggested for nine patients, of whom six showed villous atrophy, one did not and two refused to participate. Thus, silent celiac disease was probable in 8/162 and biopsy-verified in 6/162, where five patients were AGA-positive and six either EMA-, IgA-tTG- or IgG-tTG-positive. Of the 11 patients with celiac disease (three with treated and eight with silent celiac disease), 10 were HLA-DQB1-typed, of whom 65% (13/20) had the DQB1*02 allele, compared with 36% (100/276; p = 0.011) of those without celiac disease. IgA-tTG levels were higher in patients having either *02 or *0302 (0.6; −1.3–112.4 RU) compared with those not having these alleles (0.4; −0.7–3.4 RU; p = 0.023). Conclusion: IgA-tTG are HLA-DQB1*02-associated autoantibodies with high sensitivity and specificity for silent celiac disease at diagnosis of type 1 diabetes.
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| 13. |
- Ahlner, Alexandra, et al.
(författare)
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PINT: a software for integration of peak volumes and extraction of relaxation rates
- 2013
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Ingår i: Journal of Biomolecular NMR. - : Springer Verlag (Germany). - 0925-2738 .- 1573-5001. ; 56:3, s. 191-202
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Tidskriftsartikel (refereegranskat)abstract
- We present the software Peak INTegration (PINT), designed to perform integration of peaks in NMR spectra. The program is very simple to run, yet powerful enough to handle complicated spectra. Peaks are integrated by fitting predefined line shapes to experimental data and the fitting can be customized to deal with, for instance, heavily overlapped peaks. The results can be inspected visually, which facilitates systematic optimization of the line shape fitting. Finally, integrated peak volumes can be used to extract parameters such as relaxation rates and information about low populated states. The utility of PINT is demonstrated by applications to the 59 residue SH3 domain of the yeast protein Abp1p and the 289 residue kinase domain of murine EphB2.
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| 14. |
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| 15. |
- Almazan, Nerea Martin, et al.
(författare)
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Influenza-A mediated pre-existing immunity levels to SARS-CoV-2 could predict early COVID-19 outbreak dynamics
- 2023
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Ingår i: iScience. - : CELL PRESS. - 2589-0042. ; 26:12
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Tidskriftsartikel (refereegranskat)abstract
- Susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is highly variable and could be mediated by a cross-protective pre-immunity. We identified 14 cross-reactive peptides between SARS-CoV-2 and influenza A H1N1, H3N2, and human herpesvirus (HHV)-6A/B with potential relevance. The H1N1 peptide NGVEGF was identical to a peptide in the most critical receptor binding motif in SARS-CoV-2 spike protein that interacts with the angiotensin converting enzyme 2 receptor. About 62%-73% of COVID-19-negative blood donors in Stockholm had antibodies to this peptide in the early pre-vaccination phase of the pandemic. Seasonal flu vaccination enhanced neutralizing capacity to SARS-CoV-2 and T cell immunity to this peptide. Mathematical modeling taking the estimated pre -immunity levels to flu into account could fully predict pre-Omicron SARS-CoV-2 outbreaks in Stockholm and India. This cross-immunity provides mechanistic explanations to the epidemiological observation that influenza vaccination protected people against early SARS-CoV-2 infections and implies that flu-mediated cross-protective immunity significantly dampened the first SARS-CoV-2 outbreaks.
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| 16. |
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| 17. |
- Andersson, J., et al.
(författare)
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Worse survival for TP53 (p53)-mutated breast cancer patients receiving adjuvant CMF
- 2005
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Ingår i: Ann Oncol. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 16:5, s. 743-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: TP53 has been described as a prognostic factor in many malignancies, including breast cancer. Whether it also might be a predictive factor with reference to chemo- and endocrine therapy is more controversial. PATIENTS AND METHODS: We investigated relapse-free (RFS), breast cancer-corrected (BCCS) and overall survival (OS) related to TP53 status in node-positive breast cancer patients that had received polychemotherapy [cyclophosphamide, methotrexate, 5-fluorouracil (CMF)] and/or endocrine therapy (tamoxifen). Sequence analyses of the whole TP53 coding region was performed in 376 patients operated on for primary breast cancer with axillary lymph node metastases between 1984 and 1989 (median follow-up time 84 months). RESULTS: TP53 mutations were found in 105 patients (28%). We found 90 (82%) of the 110 mutations in the more frequently analysed exons 5-8, while the other 20 (18%) were located in exons 3-4 and 9-10, respectively. Univariate analyses showed TP53 to be a significant prognostic factor with regard to RFS, BCCS and OS in patients who received adjuvant CMF. CONCLUSIONS: TP53 mutations might induce resistance to certain modalities of breast cancer therapy. Sequence-determined TP53 mutation was of negative prognostic value in the total patient population and in the CMF treated patients.
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| 18. |
- Andersson, Lars Gustaf, et al.
(författare)
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Rifbjerg!
- 2003
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Ingår i: Finns en plats på jorden. - 9163145928
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Analysis of the poem "Rifbjerg!" by Danish writer Klaus Rifbjerg
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| 19. |
- Arnell, Magnus, et al.
(författare)
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Modellering av avloppsreningsverk för multikriteriebedömning av prestanda och miljöpåverkan
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Genom att använda detaljerade dynamiska modeller och kombinera resultat från årslånga simuleringar av ARV (såväl vatten- som slamlinjer) med livscykelanalys kan olika driftstrategier utvecklas och utvärderas utifrån en bred uppsättning hållbarhetskriterier fö att maximera resursutvinning och energieffektivitet samtidigt som vattenkvalitén bibehålls och driftskostnaderna kontrolleras. Metodiken har tillämpats vid en omfattande fallstudie av Käppalaverket.
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| 20. |
- ARNELL, MAGNUS
(författare)
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Performance Assessment of Wastewater Treatment Plants : Multi-Objective Analysis Using Plant-Wide Models
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- As the knowledge about anthropogenic impacts of climate change has grown, the awareness of the contributions from treatment of wastewater has widened the scope for wastewater treatment plants (WWTPs). Not only shall ever stricter effluent constraints be met, but also energy efficiency be increased, greenhouse gases mitigated and resources recovered. All under a constant pressure on costs. The main objective of this research has been to develop a plant-wide modelling tool to evaluate the performance of operational strategies for multiple objectives at the plant and for off-site environmental impact. The plant-wide model platform Benchmark Simulation Model no. 2 (BSM2) has been modified to improve the evaluation of energy efficiency and include greenhouse gas emissions. Furthermore, the plant-wide process model has been coupled to a life cycle analysis (LCA) model for evaluation of global environmental impact. For energy evaluation, a dynamic aeration system model has been adapted and implemented. The aeration model includes oxygen transfer efficiency, dynamic pressure in the distribution system and non-linear behaviour of blower performance. To allow for modelling of energy recovery via anaerobic co-digestion the digestion model of BSM2 was updated with a flexible co-digestion model allowing for dynamic co-substrate feeds. A feasible procedure for substrate characterisation was proposed. Emissions of the greenhouse gases CO2, CH4 and N2O were considered. The bioprocess model in BSM2 was updated with two-step nitrification, four-step denitrification and nitrifier denitrification to capture N2O production. Fugitive emissions of the three gases were included from digestion, cogeneration and sludge storage. The models were tested in case studies for the three areas of development: aeration, co-digestion and greenhouse gas production. They failed to reject the hypothesis that dynamic process models are required to assess the highly variable operations of wastewater treatment plants. All parts were combined in a case study of the Käppala WWTP in Lidingö, Sweden, for comparison of operational strategies and evaluation of stricter effluent constraints. The averaged model outputs were exported to an LCA model to include off-site production of input goods and impact of discharged residues and wastes. The results reveal trade-offs between water quality, energy efficiency, greenhouse gas emissions and abiotic depletion of elemental and fossil resources. The developed tool is generally applicable for WWTPs and the simulation results from this type of combined models create a good basis for decision support.
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| 21. |
- Asad, Samina, et al.
(författare)
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HTR1A a Novel Type 1 Diabetes Susceptibility Gene on Chromosome 5p13-q13
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: We have previously performed a genome-wide linkage study in Scandinavian Type 1 diabetes (T1D) families. In the Swedish families, we detected suggestive linkage (LOD less than= 2.2) to the chromosome 5p13-q13 region. The aim of our study was to investigate the linked region in search for possible T1D susceptibility genes. Methodology/Principal Findings: Microsatellites were genotyped in the Scandinavian families to fine-map the previously linked region. Further, SNPs were genotyped in Swedish and Danish families as well as Swedish sporadic cases. In the Swedish families we detected genome-wide significant linkage to the 5-hydroxytryptamine receptor 1A (HTR1A) gene (LOD 3.98, pless than9.8x10(-6)). Markers tagging two separate genes; the ring finger protein 180 (RNF180) and HTR1A showed association to T1D in the Swedish and Danish families (pless than0.002, pless than0.001 respectively). The association was not confirmed in sporadic cases. Conditional analysis indicates that the primary association was to HTR1A. Quantitative PCR show that transcripts of both HTR1A and RNF180 are present in human islets of Langerhans. Moreover, immunohistochemical analysis confirmed the presence of the 5-HTR1A protein in isolated human islets of Langerhans as well as in sections of human pancreas. Conclusions: We have identified and confirmed the association of both HTR1A and RFN180, two genes in high linkage disequilibrium (LD) to T1D in two separate family materials. As both HTR1A and RFN180 were expressed at the mRNA level and HTR1A as protein in human islets of Langerhans, we suggest that HTR1A may affect T1D susceptibility by modulating the initial autoimmune attack or either islet regeneration, insulin release, or both.
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| 22. |
- Austrell, Per Erik, et al.
(författare)
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Survey of Design Methods and Material Characteristics in Rubber Engineering
- 1999
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The unique properties of elastomeric materials are taken advantage of in many engineering applications. Elastomeric units are used as couplings or mountings between stiff structures. Examples of these are shock absorbers, vibration insulators, flexible joints, seals and suspensions.The development of computers and of analysis programs in this area has given engineers a new tool for the design of elastomeric components. Computer simulation by finite element analysis has become increasingly important, allowing the mechanical behavior of products with for complex geometries, as well as loading cases of different kinds to be evaluated. Computer simulations enable both static and dynamic aspects to be analyzed. These matters have been recognized by the manufacturers of rubber products and by their customers. The benefits are shorter time for product development and also quality improvements.However, the possibilities available for finding less complicated technical solutions at lower cost with the use of elastomers, has not been fully utilized. Rubber components could be employed more frequently in design if engineers were more familiar with materials of this sort.Part of the problem lies in education and in the dissemination of information. Engineers working in the design area tend to not be very familiar with elastomeric materials and their properties. The offerings of courses on the mechanics of polymers at schools and universities are very limited. Skillful engineers in this field have usually acquired their knowledge through many years of experience and not formal education.Moreover, the complicated nature of the material behavior involved makes it difficult to devise general design rules and design tools. Only recently have computers and analysis programs become powerful enough for the analysis of nonlinear elastic problems involving large strains.It is essential, if one is to become competitive in high-tech applications, to possess a thorough knowledge of computer methods, material models and test methods available.There has likewise been a lack of relevant data for the computer analysis of elastomeric materials. The design tools employed rely on the material models available and on the test data required for the calibration of these models. In many cases, the only information available for analysis is a value for the hardness of the rubber in question. The wide variety of rubber compounds is also a problem. The characterization of different materials is costly and time-consuming. There is thus a need for simple and reliable methods to characterize the different vulcanizates.
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| 23. |
- Babu Moparthi, Satish, et al.
(författare)
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Differential conformational modulations of MreB folding upon interactions with GroEL/ES and TRiC chaperonin components
- 2016
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 6:28386
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Tidskriftsartikel (refereegranskat)abstract
- Here, we study and compare the mechanisms of action of the GroEL/GroES and the TRiC chaperonin systems on MreB client protein variants extracted from E. coli. MreB is a homologue to actin in prokaryotes. Single-molecule fluorescence correlation spectroscopy (FCS) and time-resolved fluorescence polarization anisotropy report the binding interaction of folding MreB with GroEL, GroES and TRiC. Fluorescence resonance energy transfer (FRET) measurements on MreB variants quantified molecular distance changes occurring during conformational rearrangements within folding MreB bound to chaperonins. We observed that the MreB structure is rearranged by a binding-induced expansion mechanism in TRiC, GroEL and GroES. These results are quantitatively comparable to the structural rearrangements found during the interaction of beta-actin with GroEL and TRiC, indicating that the mechanism of chaperonins is conserved during evolution. The chaperonin-bound MreB is also significantly compacted after addition of AMP-PNP for both the GroEL/ES and TRiC systems. Most importantly, our results showed that GroES may act as an unfoldase by inducing a dramatic initial expansion of MreB (even more than for GroEL) implicating a role for MreB folding, allowing us to suggest a delivery mechanism for GroES to GroEL in prokaryotes.
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| 24. |
- Babu Moparthi, Satish, et al.
(författare)
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Transient conformational remodeling of folding proteins by GroES - Individually and in concert with GroEL
- 2014
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Ingår i: Journal of chemical biology. - : Springer Berlin/Heidelberg. - 1864-6158 .- 1864-6166. ; 7:1, s. 1-15
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Forskningsöversikt (refereegranskat)abstract
- The commonly accepted dogma of the bacterial GroE chaperonin system entails protein folding mediated by cycles of several ATP-dependent sequential steps where GroEL interacts with the folding client protein. In contrast, we herein report GroES-mediated dynamic remodeling (expansion and compression) of two different protein substrates during folding: the endogenous substrate MreB and carbonic anhydrase (HCAII), a well-characterized protein folding model. GroES was also found to influence GroEL binding induced unfolding and compression of the client protein underlining the synergistic activity of both chaperonins, even in the absence of ATP. This previously unidentified activity by GroES should have important implications for understanding the chaperonin mechanism and cellular stress response. Our findings necessitate a revision of the GroEL/ES mechanism.
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| 25. |
- Baca, Dejan, et al.
(författare)
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A Novel Security-Enhanced Agile Software Development Process Applied in an Industrial Setting
- 2015
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Ingår i: ARES Conference International Conference on Availability, Reliability and Security 2015. - : IEEE. - 9781467365901
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Konferensbidrag (refereegranskat)abstract
- A security-enhanced agile software development process, SEAP, is introduced in the development of a mobile money transfer system at Ericsson Corp. A specific characteristic of SEAP is that it includes a security group consisting of four different competences, i.e., Security manager, security architect, security master and penetration tester. Another significant feature of SEAP is an integrated risk analysis process. In analyzing risks in the development of the mobile money transfer system, a general finding was that SEAP either solves risks that were previously postponed or solves a larger proportion of the risks in a timely manner. The previous software development process, i.e., The baseline process of the comparison outlined in this paper, required 2.7 employee hours spent for every risk identified in the analysis process compared to, on the average, 1.5 hours for the SEAP. The baseline development process left 50% of the risks unattended in the software version being developed, while SEAP reduced that figure to 22%. Furthermore, SEAP increased the proportion of risks that were corrected from 12.5% to 67.1%, i.e., More than a five times increment. This is important, since an early correction may avoid severe attacks in the future. The security competence in SEAP accounts for 5% of the personnel cost in the mobile money transfer system project. As a comparison, the corresponding figure, i.e., For security, was 1% in the previous development process.
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