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  • Klintman, Marie, et al. (författare)
  • The Prognostic Value of Mitotic Activity Index (MAI), Phosphohistone H3 (PPH3), Cyclin B1, Cyclin A, and Ki67, Alone and in Combinations, in Node-Negative Premenopausal Breast Cancer
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Proliferation, either as the main common denominator in genetic profiles, or in the form of single factors such as Ki67, is recommended for clinical use especially in estrogen receptor-positive (ER) patients. However, due to high costs of genetic profiles and lack of reproducibility for Ki67, studies on other proliferation factors are warranted. The aim of the present study was to evaluate the prognostic value of the proliferation factors mitotic activity index (MAI), phosphohistone H3 (PPH3), cyclin B1, cyclin A and Ki67, alone and in combinations. In 222 consecutive premenopausal node-negative breast cancer patients (87% without adjuvant medical treatment), MAI was assessed on whole tissue sections (predefined cut-off >= 10 mitoses), and PPH3, cyclin B1, cyclin A, and Ki67 on tissue microarray (predefined cut-offs 7th decile). In univariable analysis (high versus low) the strongest prognostic proliferation factor for 10-year distant disease-free survival was MAI (Hazard Ratio (HR)=3.3, 95% Confidence Interval (CI): 1.8-6.1), followed by PPH3, cyclin A, Ki67, and cyclin B1. A combination variable, with patients with MAI and/or cyclin A high defined as high-risk, had even stronger prognostic value (HR=4.2, 95% CI: 2.2-7). When stratifying for ER-status, MAI was a significant prognostic factor in ER-positive patients only (HR=7.0, 95% CI: 3.1-16). Stratified for histological grade, MAI added prognostic value in grade 2 (HR=7.2, 95% CI: 3.1-38) and grade 1 patients. In multivariable analysis including HER2, age, adjuvant medical treatment, ER, and one proliferation factor at a time, only MAI (HR=2.7, 95% CI: 1.1-6.7), and cyclin A (HR=2.7, 95% CI: 1.2-6.0) remained independently prognostic. In conclusion this study confirms the strong prognostic value of all proliferation factors, especially MAI and cyclin A, in all patients, and more specifically in ER-positive patients, and patients with histological grade 2 and 1. Additionally, by combining two proliferation factors, an even stronger prognostic value may be found.
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  • Poschke, Isabel C., et al. (författare)
  • The Outcome of Ex Vivo TIL Expansion Is Highly Influenced by Spatial Heterogeneity of the Tumor T-Cell Repertoire and Differences in Intrinsic In Vitro Growth Capacity between T-Cell Clones
  • 2020
  • Ingår i: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 26:16, s. 4289-4301
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: During our efforts to develop tumor-infiltrating lymphocyte (TIL) therapy to counter the devastating recurrence rate in patients with primary resectable pancreatic ductal adenocarcinoma (PDA), we found that PDA TILs can readily be expanded in vitro and that the majority of resulting TIL cultures show reactivity against the autologous tumor. However, the fraction of tumor-reactive T cells is low. We investigated to which extent this was related to the in vitro expansion. Experimental Design: We compared the clonal composition of TIL preparations before and after in vitro expansion using T-cell receptor (TCR) deep sequencing. Our findings for PDA were benchmarked to experiments with melanoma TILs. Results: We found that the TIL TCR repertoire changes dramatically during in vitro expansion, leading to loss of tumor-dominant T-cell clones and overgrowth by newly emerging T-cell clones that are barely detectable in the tumor. These changes are primarily driven by differences in the intrinsic in vitro expansion capacity of T-cell clones. Single-cell experiments showed an association between poor proliferative capacity and expression of markers related to antigen experience and dysfunction. Furthermore, we found that spatial heterogeneity of the TIL repertoire resulted in TCR repertoires that are greatly divergent between TIL cultures derived from distant tumor samples of the same patient. Conclusions: Culture-induced changes in clonal composition are likely to affect tumor reactivity of TIL preparations. TCR deep sequencing provides important insights into the factors that govern the outcome of in vitro TIL expansion and thereby a path toward optimization of the production of TIL preparations with high therapeutic efficacy.
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  • Simule, Audrone, et al. (författare)
  • In situ sediment investigation in a lake influenced by mining activity
  • 2006
  • Konferensbidrag (populärvet., debatt m.m.)abstract
    • The investigation of the sediments in the lake Hörntrasket was part of the project aimed to find the reason for the reduction of the lake fauna. Earlier investigations have showed elevated concentrations of some of the metals in the lake water.One of the goals of our part of the project was to explain reasons for high metal content in the lake water. We had three hyphotesis: pollution from the mining industry, release from natural sources such as bedrocks and release from the lake sediments. The profile of bioavailable concentrations of the 12 heavy metals in the sediment pore water were determined using in situ sediment probe deployed in the spring season in the four sites in lake. The bioavailable metal pollution in lake sediment, situated in mining area, was relatively low.
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  • Wikman, Maria, et al. (författare)
  • Applying biotin-streptavidin binding for iscom (immunostimulating complex) association of recombinant immunogens
  • 2005
  • Ingår i: Biotechnology and applied biochemistry. - 0885-4513 .- 1470-8744. ; 41, s. 163-174
  • Tidskriftsartikel (refereegranskat)abstract
    • We have previously reported strategies for Escherichia coli production of recombinant immunogens fused to hydrophobic peptide or lipid tags to improve their capacity to be incorporated into an adjuvant formulation. In the present study, we have explored the strong interaction between biotin and SA (streptavidin) (K-D approximate to 10(-15) M) to couple recombinant immunogens to iscoms (immunostimulating complexes). Two different concepts were evaluated. In the first concept, a His(6)-tagged SA fusion protein (His(6)-SA) was bound to Ni2+-loaded iscom matrix (iscom without associated protein), and biotinylated immunogens were thereafter associated with the SA-coated iscoms. The immunogens were either biotinylated in vivo on E. coli expression or double biotinylated in vivo and in vitro. In the second concept, the recombinant immunogens were expressed as SA fusion proteins, which were directly bound to a biotinylated iscom matrix. A 53-amino-acid malaria peptide (M), derived from the central repeat region of the Plasmodium faiciparum blood-stage antigen Pf155/RESA, and a 232-amino-acid segment (SRS2') from the central region (from Pro-97 to Lys-328) of the major surface antigen NcSRS2 of the protozoan parasite Neospora caninum, served as model immunogens in the present study. All fusion proteins generated were found to be efficiently expressed and could be recovered to high purity using affinity chromatography. The association between the different immunogen-containing fusion proteins and the corresponding iscom matrix was demonstrated by analytical ultracentrifugation in a sucrose density gradient. However, some fusion proteins were, to a certain extent, also found to associate unspecifically with a regular iscom matrix. Furthermore, selected iscom fractions were demonstrated to induce high-titre antigen-specific antibody responses on immunization of mice. For the particular target immunogen SRS2', the induced antibodies demonstrated reactivity to the native antigen NcSRS2. We believe that the presented concepts offer convenient methods to achieve efficient adjuvant association of recombinant immunogens, and the advantages and disadvantages of the two concepts are discussed.
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  • Andersson, M. G., et al. (författare)
  • Separated by a common language : Awareness of term usage differences between languages and disciplines in biopreparedness
  • 2013
  • Ingår i: Biosecurity and bioterrorism. - : Mary Ann Liebert Inc. - 1538-7135 .- 1557-850X. ; 11:SUPPL. 1, s. S276-S285
  • Tidskriftsartikel (refereegranskat)abstract
    • Preparedness for bioterrorism is based on communication between people in organizations who are educated and trained in several disciplines, including law enforcement, health, and science. Various backgrounds, cultures, and vocabularies generate difficulties in understanding and interpretating terms and concepts, which may impair communication. This is especially true in emergency situations, in which the need for clarity and consistency is vital. The EU project AniBioThreat initiated methods and made a rough estimate of the terms and concepts that are crucial for an incident, and a pilot database with key terms and definitions has been constructed. Analysis of collected terms and sources has shown that many of the participating organizations use various international standards in their area of expertise. The same term often represents different concepts in the standards from different sectors, or, alternatively, different terms were used to represent the same or similar concepts. The use of conflicting terminology can be problematic for decision makers and communicators in planning and prevention or when handling an incident. Since the CBRN area has roots in multiple disciplines, each with its own evolving terminology, it may not be realistic to achieve unequivocal communication through a standardized vocabulary and joint definitions for words from common language. We suggest that a communication strategy should include awareness of alternative definitions and ontologies and the ability to talk and write without relying on the implicit knowledge underlying specialized jargon. Consequently, cross-disciplinary communication skills should be part of training of personnel in the CBRN field. In addition, a searchable repository of terms and definitions from relevant organizations and authorities would be a valuable addition to existing glossaries for improving awareness concerning bioterrorism prevention planning. © 2013, Mary Ann Liebert, Inc.
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  • Axelsson, Magnus A. B., et al. (författare)
  • Retrospective identification of new psychoactive substances in patient samples submitted for clinical drug analysis
  • 2022
  • Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7835 .- 1742-7843. ; 131:5, s. 420-434
  • Tidskriftsartikel (refereegranskat)abstract
    • New psychoactive substances (NPS) are life threatening through unpredictable toxicity and limited analytical options for clinicians. We present the retrospective identification of NPS in raw data from a liquid chromatography-high resolution mass spectrometry (LC-HRMS)-based multidrug panel analysis on 14 367 clinical oral fluid samples requested during 2019 mainly by psychiatric and addiction care clinics. Retrospectively analysed NPS included 48 notified originally in 2019 by the European Union Early Warning System (EU EWS) and 28 frequently reported in Sweden. Of 88 included NPS, 34 (mitragynine, flualprazolam, 3F/4F-α-P(i)HP, etizolam, 4F-MDMB-BINACA, cyproheptadine, 5F-MDMB-PICA, isotonitazene, isohexedrone, MDPEP, N-ethylpentedrone, tianeptine, flubromazolam, 4′-methylhexedrone, α-P(i)HP, eutylone, mephedrone, N-ethylhexedrone, 5F-MDMB-PINACA, ADB-BUTINACA, 3-methoxy PCP, 4F-furanylfentanyl, 4F-isobuturylfentanyl, acrylfentanyl, furanylfentanyl, clonazolam, norfludiazepam, 3F-phenmetrazine, 3-MMC, 4-methylpentedrone, BMDP, ethylphenidate, methylone and α-PVP) were identified as 219 findings in 84 patients. Eight NPS notified in 2019 were identified, five before EWS release. NPS occurred in 1.20% of all samples and 1.53% of samples containing traditional drugs, and in 1.87% of all patients and 2.88% of patients using traditional drugs. NPS use was more common in men and polydrug users. Legal (not scheduled) NPS were more used than comparable illegal ones. Retrospective identification could be useful when prioritizing NPS for clinical routine analysis and when studying NPS epidemiology. © 2022 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.
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  • Bjartell, A., et al. (författare)
  • Time-resolved fluorescence imaging (TRFI) for direct immunofluorescence of PSA and alpha-1-antichymotrypsin in prostatic tissue sections
  • 1999
  • Ingår i: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1365-7852 .- 1476-5608. ; 2:3, s. 140-147
  • Tidskriftsartikel (refereegranskat)abstract
    • We have developed a direct immunofluorescence technique utilising chelates of the lanthanide ions europium and terbium conjugated to monoclonal IgGs (Mabs) against prostate-specific antigen (PSA) and alpha-1- antichymotrypsin (ACT) for the detection and quantification on the same tissue section. Strong signals without disturbance from tissue autofluorescence were demonstrated in paraffin sections of ten benign and six malignant prostate tissue specimens. The signal intensity increased linearly with the amount of labelled Mab until epitope saturation began. The highest concentrations of bound IgG in tissue sections were 27.3 fmol/pixel for ACT and 7.2 for PSA. Time-resolved fluorescence imaging (TRFI) offers an attractive method for histochemical studies based on specific and quantitative detection of fluorescent lanthanide chelates.
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  • Cabrita, Rita, et al. (författare)
  • Tertiary lymphoid structures improve immunotherapy and survival in melanoma
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 577:7791, s. 561-565
  • Tidskriftsartikel (refereegranskat)abstract
    • Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota2,3. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored. Here we use clinical samples of metastatic melanomas to investigate the role of B cells in antitumour responses, and find that the co-occurrence of tumour-associated CD8+ T cells and CD20+ B cells is associated with improved survival, independently of other clinical variables. Immunofluorescence staining of CXCR5 and CXCL13 in combination with CD20 reveals the formation of tertiary lymphoid structures in these CD8+CD20+ tumours. We derived a gene signature associated with tertiary lymphoid structures, which predicted clinical outcomes in cohorts of patients treated with immune checkpoint blockade. Furthermore, B-cell-rich tumours were accompanied by increased levels of TCF7+ naive and/or memory T cells. This was corroborated by digital spatial-profiling data, in which T cells in tumours without tertiary lymphoid structures had a dysfunctional molecular phenotype. Our results indicate that tertiary lymphoid structures have a key role in the immune microenvironment in melanoma, by conferring distinct T cell phenotypes. Therapeutic strategies to induce the formation of tertiary lymphoid structures should be explored to improve responses to cancer immunotherapy.
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  • Cabrita, Rita, et al. (författare)
  • Tertiary lymphoid structures improve immunotherapy and survival in melanoma.
  • 2020
  • Ingår i: Nature. - : Nature Publishing Group. - 1476-4687 .- 0028-0836. ; 577:7791, s. 561-565
  • Tidskriftsartikel (refereegranskat)abstract
    • Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota2,3. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored. Here we use clinical samples of metastatic melanomas to investigate the role of B cells in antitumour responses, and find that the co-occurrence of tumour-associated CD8+ T cells and CD20+ B cells is associated with improved survival, independently of other clinical variables. Immunofluorescence staining of CXCR5 and CXCL13 in combination with CD20 reveals the formation of tertiary lymphoid structures in these CD8+CD20+ tumours. We derived a gene signature associated with tertiary lymphoid structures, which predicted clinical outcomes in cohorts of patients treated with immune checkpoint blockade. Furthermore, B-cell-rich tumours were accompanied by increased levels of TCF7+ naive and/or memory T cells. This was corroborated by digital spatial-profiling data, in which T cells in tumours without tertiary lymphoid structures had a dysfunctional molecular phenotype. Our results indicate that tertiary lymphoid structures have a key role in the immune microenvironment in melanoma, by conferring distinct T cell phenotypes. Therapeutic strategies to induce the formation of tertiary lymphoid structures should be explored to improve responses to cancer immunotherapy.
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  • Carlos, Diaz-Gil, et al. (författare)
  • Spatio-temporal composition and dynamics of zooplankton in the Kalmar Sound (western Baltic Sea) in 2009-2010
  • 2014
  • Ingår i: Boreal Environment Research. - 1239-6095 .- 1797-2469. ; 19:4, s. 323-335
  • Tidskriftsartikel (refereegranskat)abstract
    • In pelagic food webs, zooplankton is the link between lower and higher trophic levels. It is thus essential to know how the zooplankton community structure varies with its environment. We investigated the seasonal and spatial variation in the zooplankton diversity and community structure during two consecutive years in the Kalmar Sound, along the Swedish east coast, an area with a strong bathymetric gradient and of high ecological importance for e.g. commercial fish species. Two zooplankton communities were identified in the area: a coastal/estuarine community in the south and an open-water community in the north. They were separated mainly by differing salinity and temperature conditions. Biodiversity increased from spring to autumn and was higher in the open waters.
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  • Eilertsen, M.E, et al. (författare)
  • The Voices of Cancer-Bereaved Siblings : A Nation-Wide Long-Term Follow-up
  • 2018
  • Ingår i: Pediatric blood & cancer. - : Wiley. - 1545-5009. ; , s. 555-556
  • Konferensbidrag (refereegranskat)abstract
    • Background/Objectives: Siblings face many challenges and the aim of this paper is to explore bereaved siblings’ memories and experiences of their brother's or sister's illness and death.Design/Methods: In this nationwide Swedish study 174 of 240 (73 %) bereaved siblings participated and 70 % responded to two open‐ended questions on siblings’ positive and negative memories and experiences of illness and death. The data were analyzed using systematic text condensation.Results: The bereaved siblings’ responses were categorized into four different themes: endurance vs. vulnerability; family cohesion vs. family conflicts; growth vs. stagnation; professional support vs. lack of professional support. Endurance was expressed as the influence that the ill siblings’ willpower, good mood and stamina had on the healthy siblings, whereas vulnerability was expressed as the feeling of emptiness and loneliness. Family cohesion was expressed as the bonds being strengthened between family members, whereas family conflicts often led siblings to feel invisible and unacknowledged. In the third theme, most siblings expressed feeling that they grew as individuals in the process of their brother's or sister's illness and death, whereas others experienced stagnation because of the physical and mental distress they bore throughout this time, often feeling forgotten. In the last theme, most siblings perceived support by physicians and staff at the hospital as being warm, kind and honest, while some siblings had negative experiences.Conclusions: Our study shows that bereaved siblings can have positive memories and experiences, even though the death of a sibling is a distressing situation. The significance of the positive buffering effect on the bereaved siblings’ own endurance, personal growth, family cohesion and social support should be noted. The knowledge acquired by listening to the voices of bereaved siblings can be valuable in showing healthcare professionals the importance of supporting siblings of children with cancer throughout the cancer trajectory and afterwards into bereavement.
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  • Jönsson, Göran B, et al. (författare)
  • The retinoblastoma gene undergoes rearrangements in BRCA1-deficient basal-like breast cancer.
  • 2012
  • Ingår i: Cancer Research. - 1538-7445. ; 72:16, s. 4028-4036
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast tumors from BRCA1 germ line mutation carriers typically exhibit features of the basal-like molecular subtype. However, the specific genes recurrently mutated as a consequence of BRCA1 dysfunction have not been fully elucidated. In this study, we utilized gene expression profiling to molecularly subtype 577 breast tumors, including 72 breast tumors from BRCA1/2 mutation carriers. Focusing on the RB1 locus, we analyzed 33 BRCA1-mutated, 36 BRCA2-mutated and 48 non-BRCA1/2-mutated breast tumors using a custom-designed high-density oligomicroarray covering the RB1 gene. We found a strong association between the basal-like subtype and BRCA1-mutated breast tumors and the luminal B subtype and BRCA2-mutated breast tumors. RB1 was identified as a major target for genomic disruption in tumors arising in BRCA1 mutation carriers and in sporadic tumors with BRCA1 promoter-methylation, but rarely in other breast cancers. Homozygous deletions, intragenic breaks, or microdeletions were found in 33% of BRCA1-mutant tumors, 36% of BRCA1 promoter-methylated basal-like tumors, 13% of non-BRCA1 deficient basal-like tumors, and 3% of BRCA2-mutated tumors. In conclusion, RB1 was frequently inactivated by gross gene disruption in BRCA1-related hereditary breast cancer and BRCA1-methylated sporadic basal-like breast cancer, but rarely in BRCA2-hereditary breast cancer and non-BRCA1-deficient sporadic breast cancers. Together, our findings demonstrate the existence of genetic heterogeneity within the basal-like breast cancer subtype that is based upon BRCA1-status.
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  • Kozyatnyk, Ivan, et al. (författare)
  • Evaluation of barrier materials for removing pollutants from groundwater rich in natural organic matter
  • 2014
  • Ingår i: Water Science and Technology. - : IWA Publishing. - 0273-1223 .- 1996-9732. ; 70:1, s. 32-39
  • Tidskriftsartikel (refereegranskat)abstract
    • Permeable barriers are used for passive remediation of groundwater and can be constructed from a range of materials. The optimal material depends on the types of contaminants and physicochemical parameters present at the site, as well as the hydraulic conductivity, environmental safety, availability, cost and long-term stability of the material itself. The aim of the presented study was to test a number of materials for their ability to remove heavy metals and organic pollutants from groundwater with a high (140 mg L-1) content of natural organic matter (NOM). The following materials were included in the study: sand, peat, fly ash, iron powder, lignin and combinations thereof. Polluted water was fed into glass columns loaded with each sorbent and the contaminant removal efficiency of the material was evaluated through chemical analysis of the percolate. Materials based on fly ash and zero-valent iron were found to be the most effective for heavy metal removal, while fly ash and peat were the most effective for removing aliphatic compounds. Filtration through lignin and peat led to leaching of NOM. Although the leaching decreased over time, it remained high throughout the experiments. The results indicate that remediation of contaminated land at disused industrial sites is a complex task that often requires the use of mixed materials or a minimum of two sequential barriers.
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  • Krause-Jensen, D, et al. (författare)
  • Nordic Blue Carbon Ecosystems: Status and Outlook
  • 2022
  • Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 9
  • Forskningsöversikt (refereegranskat)abstract
    • Vegetated coastal and marine habitats in the Nordic region include salt marshes, eelgrass meadows and, in particular, brown macroalgae (kelp forests and rockweed beds). Such habitats contribute to storage of organic carbon (Blue Carbon – BC) and support coastal protection, biodiversity and water quality. Protection and restoration of these habitats therefore have the potential to deliver climate change mitigation and co-benefits. Here we present the existing knowledge on Nordic BC habitats in terms of habitat area, C-stocks and sequestration rates, co-benefits, policies and management status to inspire a coherent Nordic BC roadmap. The area extent of BC habitats in the region is incompletely assessed, but available information sums up to 1,440 km2 salt marshes, 1,861 (potentially 2,735) km2 seagrass meadows, and 16,532 km2 (potentially 130,735 km2, including coarse Greenland estimates) brown macroalgae, yielding a total of 19,833 (potentially 134,910) km2. Saltmarshes and seagrass meadows have experienced major declines over the past century, while macroalgal trends are more diverse. Based on limited salt marsh data, sediment C-stocks average 3,311 g Corg m-2 (top 40-100 cm) and sequestration rates average 142 g Corg m-2 yr-1. Eelgrass C-stocks average 2,414 g Corg m-2 (top 25 cm) and initial data for sequestration rates range 5-33 g Corg m-2, quantified for one Greenland site and one short term restoration. For Nordic brown macroalgae, peer-reviewed estimates of sediment C-stock and sequestration are lacking. Overall, the review reveals substantial Nordic BC-stocks, but highlights that evidence is still insufficient to provide a robust estimate of all Nordic BC-stocks and sequestration rates. Needed are better quantification of habitat area, C-stocks and fluxes, particularly for macroalgae, as well as identification of target areas for BC management. The review also points to directives and regulations protecting Nordic marine vegetation, and local restoration initiatives with potential to increase C-sequestration but underlines that increased coordination at national and Nordic scales and across sectors is needed. We propose a Nordic BC roadmap for science and management to maximize the potential of BC habitats to mitigate climate change and support coastal protection, biodiversity and additional ecosystem functions.
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26.
  • Lilja, H, et al. (författare)
  • Prostate-specific antigen in serum occurs predominantly in complex with alpha 1-antichymotrypsin
  • 1991
  • Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 37:9, s. 25-1618
  • Tidskriftsartikel (refereegranskat)abstract
    • Immunologic measurements of the serum concentration of prostate-specific antigen (PSA), an abundant prostatic-secreted serine proteinase, are frequently used to monitor patients with prostate cancer, though it has not been ascertained whether this immunoreactivity represents a PSA zymogen, the active proteinase, or PSA complexed to extracellular proteinase inhibitors. To characterize the PSA immunoreactivity in serum, we used monoclonal antibodies produced against PSA and a polyclonal rabbit IgG against alpha 1-antichymotrypsin in the design of three noncompetitive PSA assays: assay T, which detected PSA both when present as the active proteinase and when complexed to alpha 1-antichymotrypsin; assay F, which recognized the active proteinase but most poorly detected PSA complexed to alpha 1-antichymotrypsin; and assay C, which was specific for PSA complexed to alpha 1-antichymotrypsin. We used the three assays to measure PSA immunoreactivity in 64 patients' sera and in the effluent after gel chromatography of sera from four patients. This identified an 80- to 90-kDa complex between PSA and alpha 1-antichymotrypsin as the predominant fraction of the PSA immunoreactivity in blood plasma; an immunoreactive 25- to 40-kDa compound was the minor fraction.
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27.
  • Lundwall, Åke, et al. (författare)
  • Chemical characterization of the predominant proteins secreted by mouse seminal vesicles
  • 1997
  • Ingår i: Eur J Biochem. ; 249:1, s. 39-44
  • Tidskriftsartikel (refereegranskat)abstract
    • Mouse seminal vesicles secrete four major protein components with estimated molecular masses of 95, 38, 17, and 16 kDa. Amino acid sequencing revealed that the 95-kDa component represents a protein with an unknown structure, while the 38-kDa component was identified as semenoclotin, the 17-kDa component as seminal-vesicle-secreted protein IV, and the 16-kDa component as seminal-vesicle-secreted protein V. Semenoclotin and the 95-kDa component were readily cross-linked by transglutaminase, suggesting that the two proteins are involved in the formation of the mouse copulatory plug. Treatment of mouse seminal vesicle fluid with human prostate-specific antigen rapidly degraded semenoclotin, indicating a structural resemblance of this protein to human semenogelins, despite the vast difference in primary structure. As previously reported for other seminal-vesicle-secreted proteins, the semenoclotin transcripts are shown to be under androgen control.
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28.
  • Lövgren, Anna, et al. (författare)
  • Associations between screening for functional jaw disturbances and patient reported outcomes on jaw limitations and oral behaviors
  • 2023
  • Ingår i: Journal of Evidence-Based Dental Practice. - : Elsevier. - 1532-3382 .- 1532-3390. ; 23:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Temporomandibular disorders (TMDs) is a collective term for pain and functional disturbances related to the jaw muscles and the temporomandibular joint. In contrast to screening for orofacial pain, knowledge is limited on the association between patient-reported outcomes and screening for joint-related functional jaw disturbances. Therefore, our aim was to evaluate the association between a screening question for functional jaw disturbances, and disease-specific outcome measures for functional jaw limitations and oral behaviors.Methods: This study included 299 individuals (201 women; 20-69 years, median 37.0) in a general population sample from Västerbotten, Northern Sweden in 2014. A single screening question for functional jaw disturbances “Does your jaw lock or become stuck once a week or more?” was used to categorize individuals as cases or controls. Patient-reported outcomes on functional jaw disturbances were assessed with the 20-item jaw functional limitation scale (JFLS-20) and oral behaviors with the 21-item Oral Behaviors Checklist (OBC-21).Results: The strongest predictive probability to have a positive screening outcome was functional jaw limitations related to mobility (AUCboot=0.78, 95 CI:0.71-0.86, P <.001), followed by limitations related to communication (AUCboot = 0.74, 95 CI:0.63-0.80, P <.001) and mastication (AUCboot = 0.73, 95 CI:0.66-0.81, P <.001). The frequency of oral behaviors was not significantly associated with a positive screening outcome (AUCboot = 0.65, 95 CI:0.55-0.72, P =.223).Conclusions: Self-reported functional limitations, but not oral behaviors, are strongly associated with a single screening question for frequent functional jaw disturbances. This finding provides support for incorporating a question on jaw catching/locking once a week or more in screening instruments for TMDs.
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30.
  • Pettersson, K, et al. (författare)
  • Free and complexed prostate-specific antigen (PSA) : in vitro stability, epitope map, and development of immunofluorometric assays for specific and sensitive detection of free PSA and PSA-alpha 1-antichymotrypsin complex
  • 1995
  • Ingår i: Clinical Chemistry. - 0009-9147. ; 41:10, s. 8-1480
  • Tidskriftsartikel (refereegranskat)abstract
    • Generation of 15 monoclonal antibodies (MAbs) allowed construction of epitope maps and specific two-site immunofluorometric assays for free prostate-specific antigen (PSA) and PSA complexed with alpha 1-antichymotrypsin (ACT). Close correlation of PSA concentrations obtained with the use of different assays of free PSA suggested extensive similarity in immunodetection of free PSA in serum. Assays of the PSA-ACT complex overestimated the concentration of PSA-ACT in serum because of nonspecific adsorbance of ACT or cathepsin G-complexed ACT to the solid phase. This interference was substantially decreased in the presence of heparin. In studying the stability of purified PSA and PSA-ACT complexes formed in vitro, we found that the free PSA was stable during storage for 4 weeks at 35 degrees C, whereas PSA-ACT complexes largely dissociated in these conditions. The instability of PSA-ACT complexes was counteracted by storage at low temperatures, by adjusting the pH of the storage buffer between 6.8 and 7.4, and through addition of 100-1000-fold molar excess of native ACT. The ease of calibration and the accuracy of free PSA assays in comparison with assays of the PSA-ACT complex suggest that measurements of free to total PSA most accurately reflect the inverse of the proportion of PSA complexed to ACT in serum.
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31.
  • Ramstedt, Madeleine, 1975- (författare)
  • Chemical Processes at the Water-Manganite (γ-MnOOH) Interface
  • 2004
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The chemistry of mineral surfaces is of great importance in many different areas including natural processes occurring in oceans, rivers, lakes and soils. Manganese (hydr)oxides are one important group to these natural processes, and the thermodynamically most stable trivalent manganese (hydr)oxide, manganit (γ-MnOOH), is studied in this thesis. This thesis summarises six papers in which the surface chemistry of synthetic manganite has been investigated with respect to surface acid-base properties, dissolution, and adsorption of Cd(II) and the herbicide N-(phosphonomethyl)glycine (glyphosate, PMG). In these papers, a wide range of analysis techniques were used, including X-ray photoelectron spectroscopy (XPS), extended X-ray absorption fine structure (EXAFS) spectroscopy, Fourier transform infra-red (FTIR) spectroscopy, atomic force microscopy (AFM), scanning electron microscopy (SEM), X-ray diffraction (XRD), potentiometry, electrophoretic mobility measurements and wet chemical techniques, in order to obtain a more complete understanding of the different processes occurring at the manganite-water interface. From the combined use of these techniques, a 1-pKa acid-base model was established that is valid at pH>6. The model includes a Na+ interaction with the surface: =MnOH2+½ --> =MnOH-½ + H+ log β0 (intr.) = -8.20 = -pHiep =MnOH2+½ + Na+ --> =MnOHNa+½ + H+ log β0 (intr.) = -9.64 At pH<6 the manganite crystals dissolve and disproportionate into pyrolusite (β-MnO2) and Mn(II)-ions in solution according to: 2 γ-MnOOH + 2H+ --> β-MnO2 + Mn2+ + 2H2O log K0 = 7.61 ± 0.10 The adsorption and co-adsorption of Cd(II) and glyphosate at the manganite surface was studied at pH>6. Cd(II) adsorption displays an adsorption edge at pH~8.5. Glyphosate adsorbs over the entire pH range, but the adsorption decreases with increasing pH. When the two substances are co-adsorbed, the adsorption of Cd(II) is increased at low pH but decreased at high pH. The adsorption of glyphosate is increased in the entire pH range in the presence of Cd(II). From XPS, FTIR and EXAFS it was found that glyphosate and Cd(II) form inner sphere complexes. The binary Cd(II)-surface complex is bonded by edge sharing of Mn and Cd octahedra on the (010) plane of manganite. Glyphosate forms inner-sphere complexes through an interaction between the phosphonate group and the manganite surface. The largest fraction of this binary glyphosate complex is protonated throughout the pH range. A ternary surface complex is also present, and its structure is explained as type B ternary surface complex (surface-glyphosate-Cd(II)). The chelating rings between the Cd(II) and glyphosate, found in aqueous complexes, are maintained at the surface, and the ternary complex is bound to the surface through the phosphonate group of the ligand.
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32.
  • Tishelman, Carol, et al. (författare)
  • Are the most distressing concerns of patients with inoperable lung cancer adequatley assessed? A mixed-methods analysis
  • 2010
  • Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 28:11, s. 1942-1949
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Standardized questionnaires for patient-reported outcomes are generally composed of specified predetermined items, although other areas may also cause patients distress. We therefore studied reports of what was most distressing for 343 patients with inoperable lung cancer (LC) at six time points during the first year postdiagnosis and how these concerns were assessed by three quality-of-life and symptom questionnaires.Patients and Methods Qualitative analysis of patients' responses to the question “What do you find most distressing at present?” generated 20 categories, with 17 under the dimensions of “bodily distress,” “life situation with LC,” and “iatrogenic distress.” Descriptive and inferential statistical analyses were conducted.Results The majority of statements reported as most distressing related to somatic and psychosocial problems, with 26% of patients reporting an overarching form of distress instead of specific problems at some time point. Twenty-seven percent reported some facet of their contact with the health care system as causing them most distress. While 55% to 59% of concerns reported as most distressing were clearly assessed by the European Organisation for Research and Treatment for Cancer Quality of Life Questionnaire Core-30 and Lung Cancer Module instruments, the Memorial Symptom Assessment Scale, and the modified Distress Screening Tool, iatrogenic distress is not specifically targeted by any of the three instruments examined.Conclusion Using this approach, several distressing issues were found to be commonly reported by this patient group but were not assessed by standardized questionnaires. This highlights the need to carefully consider choice of instrument in relation to study objectives and characteristics of the sample investigated and to consider complementary means of assessment in clinical practice.
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33.
  • Wang, C., et al. (författare)
  • Injection of solid biomass products into the blast furnace and its potential effects on an integrated steel plant
  • 2014
  • Ingår i: Energy Procedia. - : Elsevier BV. - 1876-6102. ; , s. 2184-2187
  • Konferensbidrag (refereegranskat)abstract
    • This study is to investigate different types of biomass products' injection into the blast furnace (BF) to replace pulverized coal injection (PCI). The biomass products covered in the study are charcoal, torrefied material and wood pellets on the basis of Swedish forests. The modelling work has been performed in a specialized BF model. The modelling results show that charcoal has the significant effects on the BF operation. PCI can be replaced fully by charcoal, and only limited amount of torrefied material and wood pellets can be injected into BF. For the studied BF, the annual CO2 emission reduction potential from the replaced amount of PCI when injecting charcoal, torrefied material and wood pellets are about 1140 kton, 260 kton and 230 kton, respectively. In addition, a possible energy saving can be achieved for charcoal injection. A slightly higher P content in the hot metal may occur when injecting torrefied material.
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34.
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35.
  • Wänman, Magnus, et al. (författare)
  • The PerioGene North Study Uncovers Serum Proteins Related to Periodontitis
  • 2024
  • Ingår i: Journal of Dental Research. - : Sage Publications. - 0022-0345 .- 1544-0591. ; 103:10, s. 999-1007
  • Tidskriftsartikel (refereegranskat)abstract
    • The sequalae of periodontitis include irreversible degradation of tooth-supporting structures and circulatory spread of inflammatory mediators. However, the serum protein profile in periodontitis is not well described, which is partly attributable to the limited number of studies based on large and well-characterized periodontitis cohorts. This study aims to identify novel, circulating inflammation-related proteins associated with periodontitis within the PerioGene North case-control study, which includes 478 cases with severe periodontitis and 509 periodontally healthy controls. The serum concentrations of high-sensitivity C-reactive protein (hs-CRP) and a panel of 45 inflammation-related proteins were analyzed using targeted proteomics. A distinguishable serum protein profile was evident in periodontitis cases. The protein pattern could separate cases from controls with a sensitivity of 0.81 and specificity of 0.81 (area under the curve = 0.87). Adjusted levels for hs-CRP and 24 of the 45 proteins were different between cases and controls. High levels of hs-CRP and matrix metalloproteinase-12, and low levels of epidermal growth factor (EGF) and oxidized low-density lipoprotein receptor 1 (OLR-1) were detected among the cases. Furthermore, the levels of C-C motif chemokine-19, granulocyte colony-stimulating factor-3 (CSF-3), interleukin-7 (IL-7), and hs-CRP were significantly higher in cases with a high degree of gingival inflammation. The levels of CSF-3 and tumor necrosis factor ligand superfamily member-10 TNFSF-10 were higher in cases with many deep periodontal pockets. The PerioGene North study includes detailed clinical periodontal data and uncovers a distinct serum protein profile in periodontitis. The findings of lower EGF and OLR-1 among the cases are highlighted, as this has not been presented before. The role of EGF and OLR-1 in periodontitis pathogenesis and as possible future biomarkers should be further explored.
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